History and science include stories of too many inhumane "experiments" undertaken by old white guys perhaps  convinced the ends would justify the means. Here's a new example uncovered through detailed research on a rather macabre - but very famous -  experiment said to prove infants are blank slates. It turns out the infant was seriously ill, and so not  a proper subject. It also appears likely the researcher made a knowingly false claim the infant was healthy and normal. Perhaps not surprisingly, the infant was a child of a woman of little means and employee of the hospital.

Real science is wonderful, but there are dark corners.   Hat Tip to Marginal Revolution for flagging the story from The Chronicle of Higher Education. 

Part of the story is set out below: 

In the famous Little Albert experiment, a nearly 9-month-old baby is shown a white rat. The rat crawls up to the baby, on him, and around him. The baby seems interested in the rat and unafraid. Later, researchers again produce the rat and place it next to the baby, but this time the rat’s presence is accompanied by a loud, startling clang — a sound the baby clearly doesn’t like. This is repeated multiple times until the baby starts to cry at the mere appearance of the rat, loud clang or no. The fear extends to other furry things like a dog and a monkey, animals that previously provoked only mild interest. The researchers have taught Little Albert to be afraid.

The experiment was conducted by John Watson in 1920 and was part of the psychologist’s attempt to prove that infants are blank slates and therefore infinitely malleable. It has been recounted in countless papers and textbooks. One of the longstanding mysteries about the experiment, the identity of Little Albert, wasapparently solved in 2010 by Hall P. Beck, a psychologist at Appalachian State University. He and his co-authors argued that Little Albert was Douglas Merritte, the son of a wet-nurse who worked at the Johns Hopkins University, where the experiment was carried out. Merritte died in 1925 at age six from convulsions brought on by hydrocephalus (also known as “water on the brain”).

Now comes another twist–one that, if accurate, would change how the Little Albert experiment is viewed and would cast a darker shadow over the career of the researcher who carried it out.

A paper published this month in the journal  History of Psychology makes the case that Little Albert was not, as Watson insisted, “healthy” and “normal.” He was probably neurologically impaired. If the baby indeed had a severe cognitive deficit, then his reactions to the white rat or the dog or the monkey may not have been typical–certainly reaching universal conclusions about human nature based on his reactions wouldn’t make sense. The entire experiment, then, would be a case of a researcher terrifying a sick baby for no valid scientific reason (not that using a healthy baby would have been ethically hunkydory).

But what makes it worse, the authors of the paper argue, is that Watson must have known that Little Albert was impaired. This would turn a cruel experiment of questionable value into a case of blatant academic fraud.

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Here's some incentive to stick with that resolution to exercise more often. Researches in Boston at Dana-Farber have made it into Nature with a new finding on another aspect of why exercise helps us live longer and feel better.  Part of the answer it turns out is that exercise stimulates production of a hormone now dubbed "irisin," and it helps to stimulate "good fat" instead of "bad fat." The short story is below; the ScienceDaily summary includes a link to the full article. 

"There has been a feeling in the field that exercise 'talks to' various tissues in the body," said Spiegelman, a professor of cell biology at Harvard Medical School. "But the question has been, how?"

According to the report, the irisin hormone has direct and "powerful effects" on adipose, or fatty, tissue -- subcutaneous deposits of white fat that store excess calories and which contribute to obesity.

When irisin levels rise through exercise -- or, in this study, when irisin was injected into mice -- the hormone switches on genes that convert white fat into "good" brown fat. This is beneficial because brown fat burns off more excess calories than does exercise alone.

Only a small amount of brown fat is found in adults, but infants have more -- an evolutionary echo of how mammals keep themselves warm while hibernating. In the wake of findings by Spiegelman and others, there has been a surge of interest in the therapeutic possibilities of increasing brown fat in adults.

Along with stimulating brown fat development, irisin was shown to improve glucose tolerance, a key measure of metabolic health, in mice fed a high-fat diet.

The discovery won't allow people will be able to skip the gym and build muscles by taking irisin supplements, Spiegelman cautioned, because the hormone doesn't appear to make muscles stronger. Experiments showed that irisin levels increase as a result of repeated bouts of prolonged exercise, but not during short-term muscle activity.

The Dana-Farber team identified irisin in a search for genes and proteins regulated by a master metabolic regulator, called PGC1-alpha, that is turned on by exercise. Spiegelman's group had discovered PGC1-alpha in previous research."

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How is that we so readily and unintentionally find images of "faces" in clouds, tree bark and myriad other locations?  Some of the answers are explained in a new paper from MIT - highlighted in ScienceDaily. In short, brain scans indicate that one part of the brain seems to have a specialty in making the initial observation, and a different portion of the brain makes a final decision on whether it's really a human face. Set out below is a key excerpt from ScienceDaily. 

"A new study from Sinha and his colleagues reveals the brain activity that underlies our ability to make that distinction. On the left side of the brain, the fusiform gyrus -- an area long associated with face recognition -- carefully calculates how "facelike" an image is. The right fusiform gyrus then appears to use that information to make a quick, categorical decision of whether the object is, indeed, a face.

This distribution of labor is one of the first known examples of the left and right sides of the brain taking on different roles in high-level visual-processing tasks, Sinha says, although hemispheric differences have been seen in other brain functions, most notably language and spatial perception."

To this layman, the study explains some of the mechanics behind the conclusions set out in Thinking Fast & Slow, a fascinating book to consider as to trial work and other aspects of life. 

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As the $1,000 genome is arriving, so are print editions of the third edition of theReference Manual on Scientific Evidence. As a reminder, the online (pdf) version can be downloaded for no charge - go here. The manual was developed by the National Academies of Science in collaboration with the Federal Judicial Center, which produced the previous edition. The web site for the National Academies of Science provides background history related to the writing of the 3rd edition. 

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 Not so many years ago, my sister was a bench scientist sequencing genes by hand. One weekend, she mentioned that she and others from Salk Labs were going to Silicon Valley to look at software touted as helping to automate gene sequencing. 

Today, the $1,000 genome actually is arriving. Stunning progress. Imagine what's ahead.

The device to make this possible is a $ 149,000 machine made by Ion Torrent. The company's latest press release is here. The story - and related offshoots -  can be found  many places, such as Genetic Engineering News, the Financial Times, and Nature. The field is burgeoning - consider this excerpt from the story in the Financial Times:

"For a decade since the completion of the $3bn international research project to decode the first human genome, the cost of DNA sequencing has been falling faster than almost any other field of technology, as new methods are introduced to read the genetic code shared by all life on Earth.

“A genome sequence for $1,000 was a pipedream just a few years ago,” said Richard Gibbs, director of the human genome sequencing centre at Baylor College of Medicine in Houston. “[It] will transform the clinical applications of sequencing.”

Baylor is one of three large US medical centres, along with Yale School of Medicine and the Broad Institute, that will receive the first Ion Proton sequencers at the end of January, said Jonathan Rothberg of Life Technologies, who invented the technology used. Deliveries to other academic and commercial customers will follow over the next few months.

Sequencing a human genome on most of the instruments working today costs $5,000 to $10,000 and takes up to a week, using optical technology to read the individual letters of DNA that are tagged with fluorescent marker. The Ion Proton machine cuts that substantially, by using semiconductor technology to read DNA directly through its chemistry.

Life Technologies will not have the $1,000 genome field to itself for long. Other gene sequencing companies, such as Illumina of the US and Oxford Nanopore of the UK, are rapidly developing competing systems – and the cost is expected to plummet further, leading some to speculate that it will become routine for every baby to have its genome read at birth.

Mr Rothberg estimates that between 5,000 and 10,000 people have had their full genome sequenced so far, almost all for research rather than medical treatment. “I believe millions or even tens of millions of people will have their personal genome read over the next decade,” he said."

There also is a remarkable back story. Guess who is one of the creators of  the company that created the new Ion Torrent machine? 

Gordon Moore. Yes, that Gordon Moore - the creator of Moore's Law on diminishing computing costs. And, on reading the Wikipedia entry, one discovers that Mr. Moore has done many other impressive things to drive science forward, including a $ 600 million donation to Caltech and creating a foundation that funds a range of science projects. 

Here's an excerpt from Nature's story this past summer:

"The latest contender in the race for the prized '$1,000 genome' has proved its mettle in a singularly appropriate way: by sequencing the genome of computer pioneer Gordon Moore.

Each Ion Torrent chip sports 1.2 million DNA-testing wells.ION TORRENT

Like the computer chips made by Intel, the company that Moore co-founded, the Ion Personal Genome Machine (PGM) exploits semiconductor technology, with its ability to deliver ever-increasing speed and lower costs — a trend predicted by 'Moore's law' some 50 years ago. When Ion Torrent of Guilford, Connecticut, part of Life Technologies in Carlsbad, California, introduced the device late last year¹, some scientists wondered whether it could live up to its promise to put a sequencer within the reach of any reasonably funded lab. Their doubts are likely to wane in the wake of the company's latest demonstration, published this week in Nature (see page 348)."

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Thinking about New Year's Resolutions? Please consider two that may actually save a human life. Both resolutions are easy to fulfill. For one, you can spread the word that cord blood donations at birth offer enormous opportunities to save lives because the blood contains life-saving stem cells. For another, you can register to become a potential bone marrow donor. Set out below are more facts on why the needs are so great and why it's easy to accomplish both resolutions. 

Cord Blood Saves Lives  

There is enormous medical value to donating cord blood and placentas when children are born. Why? Because they are chock full of pluripotent stem cells able to evolve into cells performing most any cellular role in the body. Why does that matter ? Because the cells may replace existing defective or failed cells that cause cancers and other dread diseases.  For example, read a November 15, 2009 Science Daily article about great new science in which cord blood is used to achieve tremendous results for patients who need bone marrow (stem cell) transplants to overcome leukemias and other cancer involving blood and bone marrow. Or read the full medical article. The short version of the story is as follows:

"ScienceDaily (Nov. 15, 2009) -- A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning."

Is there really a need to spread the word about the value of cord blood ? You bet - the science above is new, and so most people have no idea of the value of the cells, and are not aware of the critical needs. As a result, we are missing enormous opportunities to save lives. How do I know that ? Various ways, but one is through a holiday gathering attended by a college roommate, Dwight, a brilliant and compassionate person who is a practicing Ob Gyn. The topic came up because several former college friends gathered for the holidays, and one brought up the topic of knowing way too many people with cancer even though we are all less than 55. After various comments about cancer treatments and hopes for "cures," Dwight the Ob GynB  stated his intense frustration that many parents to be - and hospitals - pay virtually no attention to cord blood donations. The result ? Every day, thousands of people and hospitals fail to preserve and use thousands of placentas and cord blood that collectively contain billions of stem cells that could save countless lives. So, please spread the word. It takes only a few seconds, for example, to forward an email or to cut and paste some of this text into an email to your existing list of friends and neighbors.

Register as a Potential Bone Marrow Donor

For a second resolution, consider registering to become a bone marrow donor. It's easy to register with the nationally-recognized "Be the Match Foundation." Click on Be the Match or use your web browser to go to www.marrow.org. Contrary to what many people think, the need for bone marrow has not ended. To the contrary, there is a growing need for bone marrow donors, and the need is especially critical for children. Why ? Because diversity and "mixed marriages" mean that traditional ethnic lines are being crossed, thereby producing new genomes for which there are few or no matches because the existing potential donors are typically older and not so diverse. So, registering new, younger and more diverse potential donors is of critical importance for children with leukemias and other blood cancers. The Wall Street Journal covered the topic in detail;  read the full story or see the text pasted below. As a result, Mayo Clinic and others  run registration drives, as exemplified by Mayo.

Registering more potential donors also is critical because some cancer rates are soaring.  Some of the stunning numbers are that for just 2010, and for just the United States, over 65,000 people will be diagnosed with non-Hodgkins lymphoma, and another 8,000 will be diagnosed with Hodgkin's lymphoma. For too many of these patients, the only real chance for life is a bone marrow transplant.

What's involved in registering ? Not much - the registration process is simple, painless and can be done through the mail. How? First, the potential donor registers online with contact information. The mail will then bring a small packet containing a couple of cotton swabs (Q-tips) that you use to gather some fluid/skin cells from the inside of the mouth. Rub the swabs on the inside of your mouth, mail the swabs back in, make a small donation, and that's all there is to it. After that, the registration group submits the q-tips to a lab that analyzes the DNA on the swab to indicate the genomic types for which the registrant perhaps could be a donor. Please click here to go the Be The Match website and register right now to start the new year off with action that may save a life.

Isn't bone marrow donation very painful ? NO, NO, NO - that used to be true, but it's not true anymore ! The typical bone marrow donation process today involves extracting the needed marrow cells through a blood donation/filtering process that takes a few hours. In essence, a needle is inserted, blood is slowly drained out to run through a filter, and the needed cells are collected through a process known as peripheral blood stem cell (PBSC) donation. You can easily talk, watch TV, or listen to music during the process. Or you could simply reflect on probably saving a life. Go here to read more myth busting about bone marrow donation.

Hopefully you are now resolved to take action. After all, how many other actions can you take this year that might actually save a life ?

But, if you need more motivation, there is a Wikipedia article on marrow donation and the various involved groups. Or, consider the full May 27, 2009 Wall Street Journal article (below) on the critical needs.

 _____________________________________________________________________

• THE INFORMED PATIENT

• MAY 27, 2009

I. Building Diversity in Bone-Marrow Registries

• By LAURA LANDRO

Like thousands of patients battling blood cancers, Natasha Collins faces a needle-in-a-haystack search for a bone-marrow donor. But for the 26-year-old medical student with recurrent leukemia, the hunt is even more of a challenge because she is half African American and half Caucasian. 

Transplants of bone marrow, which produces new blood cells, offer a potential cure for a growing number of cancers and other diseases, but only if the patient and donor are genetically compatible. Only 30% of patients have a sibling with the same genetic makeup who can provide marrow transplants. For other people, the best chance of a match is someone of their own race or ethnicity. That poses a special problem for minorities, and the growing number of people who identify themselves as multiracial, because for these groups there is a shortage of donor volunteers. 

Some seven million people in the U.S. have signed up on a national registry to be potential bone-marrow donors. Even so, less than half the 10,000 patients who needed a transplant last year were able to find a genetic match that led to a transplant. While the odds of a white patient finding a match are 88%, the odds for most minorities can be as low as 60%. The odds of actually receiving a transplant are as low as 20% for some minorities because of other factors such as access to care in their communities. 

Now, the National Marrow Donor Program, the nonprofit group that administers the registry with partial funding from the U.S. government, is stepping up efforts to recruit donors from different ethnic backgrounds. The 21-year-old program, which recently changed the name of its registry to Be the Match, is spreading its message through social media Web sites like Facebook and MySpace. It is trying to reach a younger generation that its research shows isn't aware of the program's mission or of medical advances that make it possible to screen potential donors by testing DNA with a simple cheek swab from a kit (available online at bethematch.org).

Marrow Transplant Myths 

Be the Match also aims to shatter some myths about bone-marrow donation, such as the fear that it will hurt the donor. Traditionally, donors underwent general anesthesia so stem cells in the bone marrow could be collected from needles inserted into large bones in the back. About 20% of transplant donations are still conducted this way. 

Now, in a relatively painless procedure that doesn't require anesthesia, some 60% of transplants are performed by harvesting a donor's peripheral blood stem cells, which are cells from bone marrow that circulate in the blood stream. These can be collected by circulating the donor's blood intravenously over several hours through a machine. The procedure also delivers a greater volume of stem cells to the recipient than a traditional bone-marrow transplant. The donor's body regenerates the stem cells within a few weeks. Donor costs are typically covered by the patient's insurance or by funds from the registry and other sponsors. 

An additional 20% of transplants are performed using umbilical-cord blood cells that are donated after childbirth. This procedure, which doesn't require as close a genetic match between donor and recipient, is relatively new, and there isn't a large body of scientific evidence of its long-term effectiveness and complication rates. 

Bone-marrow transplants, first offered in the 1960s, have been used to treat leukemia, aplastic anemia, lymphomas such as Hodgkin's disease, multiple myeloma, immune-deficiency disorders and some solid tumors such as breast and ovarian cancer. Before undergoing transplants, patients typically are treated with chemotherapy and sometimes radiation to destroy their diseased marrow. The donor's healthy blood-making cells are then infused directly into the patient's bloodstream, where they help to build a new blood supply.

But for a transplant to succeed, markers known as human leukocyte antigens, or HLAs, have to match between donor and recipient. The body uses the markers to recognize which cells belong in the body and which are intruders. A close match will reduce the risk that the patient's immune cells will attack the donor's cells or that the donor's cells will attack the patient's body after the transplant. Patients inherit half their HLA markers from each parent, and each sibling has a 25% chance of matching. But it is possible to have even a dozen siblings and no match.

Diagnosed With Leukemia

I was one of the lucky ones. When I was diagnosed with a form of leukemia in 1991 and needed a transplant, both of my brothers tested as identical matches on each of six HLA markers used to determine compatibility (though five are sometimes acceptable). Because some HLA types are found more often in certain racial and ethnic groups than others, the HLA markers of a donor can be close enough to be compatible with a patient from a similar ethnic background. People with mixed backgrounds, such as African and European ancestry, for example, have unique combinations of HLA types. "As long as we create more diversity [in the population], we will need more and more donors to reflect that," says National Marrow Donor Program Chief Executive Jeffrey Chell.

Ms. Collins, the medical student, had a transplant from donated cord blood cells in May 2007, but her cancer, known as acute myelogenous leukemia, has returned. Her doctors now believe a bone-marrow transplant offers Ms. Collins the best chance of a cure. Her classmates at Yale University have held bone-marrow drives, sent emails to other medical schools to recruit donors, and created a Facebook group with over 1,000 members and a YouTube video (both accessible at www.matchnatasha.org).

Ms. Collins is now undergoing chemotherapy, which weakens her immune system. She says she is trying to keep up with her class work by studying at home. "The good news is that we've found some potential matches," she says.

The National Marrow Donor program says it is seeing results from its minority recruitment efforts. Groups such as Historically Black Colleges and Universities conducted drives that have signed up 5,000 donors in a program launched last year. The donor program is also working with Hispanic groups and Asian and Pacific Islander organizations, as well as with blood centers in states that have large Native American populations. In 2008, it signed up 440,000 new donors, just under half of whom were from diverse racial and ethnic communities. The group also is working with international registries, with a total of five million potential donors, and is signing cooperative agreements with countries like Brazil.

Studies show that there are a number of reasons why different ethnic groups don't sign up as bone marrow donors, including a lack of educational resources devoted to those communities, fear of doctors and hospitals, concern about putting personal information in a database, and cultural taboos about donating a physical part of oneself. 

In one effort to recruit Asian and Pacific Islander donors, 26-year-old acute leukemia patient Michelle Maykin founded Project Michelle, an online campaign that includes a Web site, projectmichelle.org, with blogs, photos and videos. The project has recruited more than 15,000 new donors by sponsoring bone marrow drives with the help of the national registry at Asian churches and student groups, among others. 

Advances in Matching 

Improvements in matching techniques, using DNA-based testing methods, can more precisely identify the best donor. Be the Match recently started offering an online search tool that patients and doctors can use to get an idea of how many potential matches may be in the registry. 

In the past 18 months, the registry found matches for more than 5,000 transplants, an 18% increase over the previous period. More diseases, such as sickle cell anemia, are now treated with transplants. And patients 50 and older, for whom transplants were once considered too risky, are now eligible for the treatment. That's because of new, pre-transplant chemotherapy regimens that are less toxic, and better post-transplant care to prevent infections and rejection. 

Ineligible Donors 

Some medical conditions may eliminate potential donors, such as bleeding problems or heart disease. When Christopher Bartley, a classmate of Ms. Collins at Yale Medical School who has African-American, Caucasian and Honduran roots, tried to sign up, he found that he was ineligible because he suffers from sleep apnea, which causes pauses in breathing during sleep. 

And even though the hope is that more minorities will provide matches for others in the same ethnic mix, it is also possible to find a match where there is no ethnic similarity. Victoria Namkung, a Los Angeles writer of Irish, Jewish and Korean origins, who signed up as a donor several years ago, was surprised to learn that she was the match for a Mexican-American man in Ft. Myers, Fla. Donors and recipients can communicate anonymously for the first year through the registry and then meet if they choose. Ms. Namkung says she and her recipient have met and keep in touch. The feeling of having provided him a life-saving transplant "changed my life," she says.

• Email informedpatient@wsj.com. 

Printed in The Wall Street Journal, page D1

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As year end 2011 arrives, a powerful and popular book is Thinking Fast and Slow, by 2002 Nobel Prize winner Daniel Kahneman, a research scientist focused on how our minds actually work. The Nobel Prize was for economic science, and would have been shared with a colleague but for an untimely death. The book is reviewed in depth here (the Guardian), here (NYT), here (Financial Times), and here (Economist).

In short, the book compiles lessons from many years of scientific experiments, and proves that intuition, judgments and more forms of "thinking"  are frequently produced without much (or any) conscious weighing of factors. That outcome occurs because the dominant part of our thinking process is a fast, automatic system that processes information in ways influenced by factors far more subtle than one would suspect (System 1 is the book's label).  Ideas take hold, for example, when they become familiar from repetition, regardless of whether they are correct or good ideas. Ideas also take hold when we are "primed" towards a thought, with "priming" occurring in incredibly subtle ways (e.g. young people will walk more slowly after reading a group of words related to being elderly). Our predominant "fast" thinking contrast with "slow" thinking involving, for example, math calculations and other complex tasks (System 2 thinking). Slow thinking taxes people both physically and mentally, and so the natural tendency is to reduce slow thinking and leave decisions to fast thinking.

Year end 2011 also brings evidence tending to prove the argument that political thought is now on sale, cheap. The sale arises through the U. S. Supreme Court's Citizens United decision -background here and here. The decision prohibits effective limits on the money poured into political speech. The proof of the power of the money - and tight ties to candidates - is arising now through primary elections in Iowa. There, about $2.8 million of advertising by a wealthy super PAC appears to have turned the tide against Mr. Gingrich, and in favor of Mr. Romney, as detailed by Nicholas Confessore and Jim Rutenberg in the New York Times and by The Iowa Republican web site. And the super PAC is run by former key aides to Mr. Romney. 

$2.8 million buys massive advertising. Repetition. Priming. Fast thinking. Political thought now on sale, cheap. 

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Various authors, including Tyler Cowen at Marginal Revolution, are mentioning a January 2012 book on how economics shapes the ways that science is researched and pursued.  The publisher is Harvard University Press; the page for the book includes the table of contents and a "search inside" function. And of course it's available at Amazon.  The author is Paula Stephan - she's a professor at Georgia State and prior author of an 880 page compendium of papers on science and economics 

Some of the academic reviews are set out below from the Book's webpage: 

“Paula Stephan is the undisputed authority on the economics of science and her book is a delight. Laced with dozens of revealing anecdotes about everything from transgenic mice to the competition for high h-indexes and the Nobel Prize, How Economics Shapes Science reveals the economic logic behind the workings of modern science and makes a compelling case for using incentives to rationalize our use of scarce resources.”—Charles Clotfelter, Z. Smith Reynolds Professor of Public Policy and Professor of Economics and Law, Duke University

“Paula Stephan is one of the world’s leading scholars of the economics of science. Her comprehensive analysis—as readable as it is timely—is a must read for anyone worrying about the future of science policy or the economics of universities.”—Ronald G. Ehrenberg, Irving M. Ives Professor of Industrial and Labor Relations and Economics, Cornell University

“This is a marvelous book—lucid, cogent, and lively, full of fascinating anecdotes and news about what university science costs, who pays for it, and who benefits. Paula Stephan saw science as an economic enterprise long before other economists did, and she’s written what will be the definitive book for years to come.”—Richard Freeman, Herbert Ascherman Chair in Economics, Harvard University

“This fascinating book makes senior scientists like me keenly aware of the travails that await our students and post-docs as they pursue the many years of scientific training that lead to a very uncertain career. As Paula Stephan shows, from the point of view of income and stability, our students might be better off getting MBAs. All senior scientists should read this book. It gives a sobering dose of reality to our love of science.”—Kathleen Giacomini, Professor of Bioengineering and Therapeutic Sciences, University of California San Francisco

“How do economic considerations shape what scientists do? How do scientific developments affect economic progress? In a world facing challenges like global warming and threats of economic stagnation, these are critical questions. Paula Stephan’s treatment is masterful—and readable outside the ranks of economists, too.”—Richard R. Nelson, George Blumenthal Professor Emeritus of International and Public Affairs, Business, and Law, Columbia University

“Scientific research and professional training are now inextricably linked. At the same time the perceived costs and benefits of science have skyrocketed, with governments and universities setting economic incentives in the race for productivity and prestige. Stephan’s groundbreaking economic analysis shows the complex results of these policies.”—Mara Prentiss, Mallinckrodt Professor of Physics, Harvard University

“We in Europe often invoke the U.S. science system as the frontier for us, but most of us don’t know in detail how it actually operates. With its wealth of facts and stories, and its rich multidisciplinary perspective, Paula Stephan’s book can teach us. It will help scientists understand their environment and help policy makers see what levers they have (or do not have) to direct science. No one other than Paula Stephan could write with such insight and depth.”—Reinhilde Veugelers, Professor of Managerial Economics, Strategy and Innovation, Katholieke Universiteit Leuven

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For hundreds of years, scientists assumed that only the dose made the poison, and that more was always worse. Scientists also paid scant or no attention to the timing of the dose.

Today, we know better. We know that for some substances, less is more - that is, a lower dose will or can cause more harm than a large dose - this rule seems to apply especially to endocrine disrupters. We also know that the timing of the dose matters - think thalidomide and children with malformed or missing arms and legs if their mothers took thalidomide early in a pregnancy, as described in a 2009 paper from the Proceedings of the National Academy of Science. 

ScienceDaily now brings a new example of why timing matters. In a new paper in Nature, from scientists at Salk Labs, they've shown some small part of the biology behind why timing of a dose matters in terms of receiving a dose during sleeping and non-sleeping hours. The Salk press release includes the following key excerpts: 

In a paper published last week in Nature, scientists at the Salk Institute for Biological Studies report finding that proteins that control the body's biological rhythms, known as cryptochromes, also interact with metabolic switches that are targeted by certain anti-inflammatory drugs.

The finding suggests that side effects of current drugs might be avoided by considering patients' biological rhythms when administering drugs, or by developing new drugs that target the cryptochromes.

"We knew that our sleep and wake cycle are tied to when our bodies process nutrients, but how this happened at the genetic and molecular level was a complete mystery," says Ronald M. Evans, a professor in Salk's Gene Expression Laboratory, who led the research team. "Now we've found the link between these two important systems, which could serve as a model for how other cellular processes are linked and could hold promise for better therapies."

For more information:
Nature
Authors: Katja A. Lamia, Stephanie J. Papp, Ruth T. Yu, Grant D. Barish, N. Henriette Uhlenhaut, Johan W. Jonker, Michael Downes, Ronald M. Evans
Cryptochromes mediate rhythmic repression of the glucocorticoid receptor

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Here is good news for current and future victims of dread diseases and injuries - the EU has rejected patents on embryonic stem cells. The full story is in this post on Patent Docs.  Here's the introduction: 

"The European Court of Justice (ECJ) today rendered its decision regarding the patent-eligibility of human embryonic stem cells (hESCs) in Europe, and as widely expected has heeded the recommendation of the court's advocate general that hESCs are not patent-eligible subject matter (see"European Court of Justice Considers Embryonic Stem Cell Ban").

The case began in 2004, when Greenpeace sued in German federal court over a German patent to the University of Bonn involving methods for deriving neural cells from hESCs (DE 197568664 C1).  While German laws regarding stem cell research have been characterized as the "most restrictive in Europe," such research is permitted provided that it is performed with pluripotent (rather than totipotent) cells, using cell lines imported from abroad and only cell lines that were made prior to May 2007.  Nevertheless, Greenpeace argued that claims to methods for using hESCs were "immoral and against public order," provisions of European law generally that define subject matter not eligible for patent (there is no corresponding provision under U.S. law)." 

*****

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For scientists, data is key. So, it's relevant to note that we are close to the day of commercially managed but freely accessible  DNA databases in the "cloud." Set out below are key excerpts from this article by Arik Hesseldahl at All Things Digital regarding a start-up known as DNAnexus. 

Beyond science, think also about the possibilities for litigation.  As GE might say, imagine the possibilities when data is widely and freely shared along with medical histories which are real but blinded to preserve privacy.  Thus, for example, think about the possibilities for asbestos litigation. Imagine a database with DNA analysis from all the mesothelioma pathology samples held by Dr. Victor Roggli at Duke. Or, imagine plaintiff's firms obtaining client permissions, and then collaborating to provide genomic data from all of their mesothelioma patients. Or, if the plaintiff's firms  will not take that step, imagine chapter 11 asbestos trusts requiring submission of tissue as a condition for collecting money from the trusts. Or, perhaps insurers might even break down and spend money on such an effort. They should, because finding cures for cancers ultimately will be cheaper than paying the bills that will come due when health insurance claims and tort litigation increase in waves  as global cancer rates double by 2020 and triple by 2030. 

Some key excerpts from the article on the DNA database effort by Google and DNAnexus:

"Google, he said, will collaborate with DNAnexus to provide access to a huge archive of publicly available DNA information. The archive will take over where the federal government’s National Center for Biotechnology Information (NCBI) is leaving off, after being shut down because of budget cuts.

DNAnexus and Google have teamed up to take over that database and will continue to provide access — for free — to medical researchers. It will now live in Google’s cloud, and researchers will now have a new, easy-to-use interface for accessing it. It represents the largest single dataset ever put on Google’s infrastructure by a third party.

Don’t mourn the government effort. DNA databases are probably better handled by the private sector, Sundquist says, mainly because sequencing a genome, which used to require NASA-sized multibillion-dollar budgets that only big governments can sustain, is no longer so complicated or expensive." 

***

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This post on the Patent Doc blog brings the news that legislators in Australia are seeking to amend the patent statutes to explicitly prohibit gene patents. Since the Patent Docs are lawyers for pharma, they of course highlight the fact that a committee declined to embrace the bill. But they also were objective enough to link to this article from the Australian which highlights the sponsor's intent to bring the issues forward regardless of the committee vote. According to the article in the Australian, gene patents are opposed by an array of interest groups, including advocacy groups for cancer patients and survivors.

Here in the states, the issue is moving towards the US Supreme Court as the Myriad case heads into the certiorari process. As readers may recall, the Obama Administration has wisely opposed gene patents, as described in this prior post. The district court proceedings were covered here. Complete coverage of the Myriad case is found at a great blog known as the Genomics Law Report - look at the upper right hand corner of the home page.

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Nobel Prize week started today with the prize in Medicine shared among three researchers who made fundamental discoveries about the immune system. The discoveries provided the basis for some of the transformative medicine taking hold today, such as vaccines to prevent cancer.  In short, each of the prize winners discovered a fundamental part of the immune system, and did so through studies that Tea Partiers probably would ridicule because, for example, some of the work included analyzing fruit flies. This award thus illustrates why the nations of the world need to continue to fund fundamental research in biology and related fields. Today's fruit fly findings build tomorrow's preventive and curative medicine. 

The Nobel press release is pasted below, and explains the research and outcomes: 

Press Release

2011-10-03

The Nobel Assembly at Karolinska Institutet has today decided that

The Nobel Prize in Physiology or Medicine 2011

shall be divided, with one half jointly to

Bruce A. Beutler and Jules A. Hoffmann

for their discoveries concerning the activation of innate immunity

and the other half to

Ralph M. Steinman

for his discovery of the dendritic cell and its role in adaptive immunity

Summary

This year's Nobel Laureates have revolutionized our understanding of the immune system by discovering key principles for its activation.

Scientists have long been searching for the gatekeepers of the immune response by which man and other animals defend themselves against attack by bacteria and other microorganisms. Bruce Beutler and Jules Hoffmann discovered receptor proteins that can recognize such microorganisms and activate innate immunity, the first step in the body's immune response. Ralph Steinman discovered the dendritic cells of the immune system and their unique capacity to activate and regulate adaptive immunity, the later stage of the immune response during which microorganisms are cleared from the body.

The discoveries of the three Nobel Laureates have revealed how the innate and adaptive phases of the immune response are activated and thereby provided novel insights into disease mechanisms. Their work has opened up new avenues for the development of prevention and therapy against infections, cancer, and inflammatory diseases.

Two lines of defense in the immune system

We live in a dangerous world. Pathogenic microorganisms (bacteria, virus, fungi, and parasites) threaten us continuously but we are equipped with powerful defense mechanisms (please see image below). The first line of defense, innate immunity, can destroy invading microorganisms and trigger inflammation that contributes to blocking their assault. If microorganisms break through this defense line, adaptive immunity is called into action. With its T and B cells, it produces antibodies and killer cells that destroy infected cells. After successfully combating the infectious assault, our adaptive immune system maintains an immunologic memory that allows a more rapid and powerful mobilization of defense forces next time the same microorganism attacks. These two defense lines of the immune system provide good protection against infections but they also pose a risk. If the activation threshold is too low, or if endogenous molecules can activate the system, inflammatory disease may follow.

The components of the immune system have been identified step by step during the 20^thcentury. Thanks to a series of discoveries awarded the Nobel Prize, we know, for instance, how antibodies are constructed and how T cells recognize foreign substances. However, until the work of Beutler, Hoffmann and Steinman, the mechanisms triggering the activation of innate immunity and mediating the communication between innate and adaptive immunity remained enigmatic.

Discovering the sensors of innate immunity

Jules Hoffmann made his pioneering discovery in 1996, when he and his co-workers investigated how fruit flies combat infections. They had access to flies with mutations in several different genes including Toll, a gene previously found to be involved in embryonal development by Christiane Nüsslein-Volhard (Nobel Prize 1995). When Hoffmann infected his fruit flies with bacteria or fungi, he discovered that Toll mutants died because they could not mount an effective defense. He was also able to conclude that the product of the Toll gene was involved in sensing pathogenic microorganisms and Toll activation was needed for successful defense against them.

Bruce Beutler was searching for a receptor that could bind the bacterial product, lipopolysaccharide (LPS), which can cause septic shock, a life threatening condition that involves overstimulation of the immune system. In 1998, Beutler and his colleagues discovered that mice resistant to LPS had a mutation in a gene that was quite similar to the Toll gene of the fruit fly. This Toll-like receptor (TLR) turned out to be the elusive LPS receptor. When it binds LPS, signals are activated that cause inflammation and, when LPS doses are excessive, septic shock. These findings showed that mammals and fruit flies use similar molecules to activate innate immunity when encountering pathogenic microorganisms. The sensors of innate immunity had finally been discovered.

The discoveries of Hoffmann and Beutler triggered an explosion of research in innate immunity. Around a dozen different TLRs have now been identified in humans and mice. Each one of them recognizes certain types of molecules common in microorganisms. Individuals with certain mutations in these receptors carry an increased risk of infections while other genetic variants of TLR are associated with an increased risk for chronic inflammatory diseases.

A new cell type that controls adaptive immunity

Ralph Steinman discovered, in 1973, a new cell type that he called the dendritic cell. He speculated that it could be important in the immune system and went on to test whether dendritic cells could activate T cells, a cell type that has a key role in adaptive immunity and develops an immunologic memory against many different substances. In cell culture experiments, he showed that the presence of dendritic cells resulted in vivid responses of T cells to such substances. These findings were initially met with skepticism but subsequent work by Steinman demonstrated that dendritic cells have a unique capacity to activate T cells.

Further studies by Steinman and other scientists went on to address the question of how the adaptive immune system decides whether or not it should be activated when encountering various substances. Signals arising from the innate immune response and sensed by dendritic cells were shown to control T cell activation. This makes it possible for the immune system to react towards pathogenic microorganisms while avoiding an attack on the body's own endogenous molecules.

From fundamental research to medical use

The discoveries that are awarded the 2011 Nobel Prize have provided novel insights into the activation and regulation of our immune system. They have made possible the development of new methods for preventing and treating disease, for instance with improved vaccines against infections and in attempts to stimulate the immune system to attack tumors. These discoveries also help us understand why the immune system can attack our own tissues, thus providing clues for novel treatment of inflammatory diseases.

Bruce A. Beutler was born in 1957 in Chicago, USA. He received his MD from the University of Chicago in 1981 and worked as a scientist at Rockefeller University in New York and the University of Texas in Dallas, where he discovered the LPS receptor. Since 2000 he has been professor of genetics and immunology at The Scripps Research Institute, La Jolla, USA.

Jules A. Hoffmann was born in Echternach, Luxembourg in 1941. He studied at the University of Strasbourg in France, where he obtained his PhD in 1969. After postdoctoral training at the University of Marburg, Germany, he returned to Strasbourg, where he headed a research laboratory from 1974 to 2009. He has also served as director of the Institute for Molecular Cell Biology in Strasbourg and during 2007-2008 as President of the French National Academy of Sciences.

Ralph M. Steinman was born in 1943 in Montreal, Canada, where he studied biology and chemistry at McGill University. After studying medicine at Harvard Medical School in Boston, MA, USA, he received his MD in 1968. He has been affiliated with Rockefeller University in New York since 1970, has been professor of immunology at this institution since 1988, and is also director of its Center for Immunology and Immune Diseases.

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Amazing how some of our elected representatives think their religious abstractions are an excuse to seek to take us backwards in science. Thus, this year once again sees a host of Republicans (21) - and Democrat Dan Lipinksi of Chicago - sponsor a bill that would downgrade and slow funding for research using embryonic stem cells. The current bill is here; a Hill article is here, a current announcement from the Republican "leader" is here, and here is a prior statement from Rep. Lipinski's office. Hat tip to Paul Knoepfler, a stem cell scientist who blogs, here is the main page for his blog, and here is the relevant post. 

It's a shame these purported leaders fail to read - or respect - science. Time and again, researchers have shown that induced stem cells have problems that are not found in embryonic stem cells.  (Induced stem cells (iPS cells) are the supposedly "ethical" alternative to embryonic stem cells.) Thus, for example, this past spring, the leading  science journal known as Nature published a major article detailing genomic flaws in iPS cells. The flaws include alterations in genes associated with cancer. Does this mean iPS cells can never work? No, but it means more steps and research are needed, and answers and outcomes arrive more slowly. Delay may seem ok to legislators wrapped up in their own beliefs and busy pandering to right wingers, but it's not ok for people who are suffering or dying today. 

The ScienceDaily summary of the research is here; key excerpts are set out below:

"A new study -- published in the March 3 issue of the journal Nature and led by scientists at the University of California, San Diego in collaboration with other leading stem cell research groups -- finds that the genetic material of reprogrammed cells may in fact be compromised, and suggests that extensive genetic screening of hiPSCs become standard practice before these stem cells are used clinically.

A national team of researchers, co-directed by Kun Zhang, PhD, an assistant professor of bioengineering in the UC San Diego Jacobs School of Engineering, examined 22 different hiPSC lines obtained from seven research groups that employed different methods to reprogram skin cells into pluripotent stem cells. In all of these cell lines, the researchers found protein-coding point mutations, an estimated six mutations per exome. The exome is the part of the genome that contains the genetic instructions for making proteins and other gene products.

"Every single stem cell line we looked at had mutations. Based on our best knowledge, we expected to see 10 times fewer mutations than we actually observed," said Zhang, a faculty member of the Institute for Genomic Medicine and the Institute of Engineering in Medicine, both at UC San Diego.

The findings help answer the question of whether reprogramming adult mammalian cells into hiPSCs affects the overall genome at the fundamental level of single nucleotides. They do. Zhang called the mutations "permanent genome scars."

The scientists said while some of the mutations appeared to be silent, the majority did change specific protein functions, including those in genes associated with causative effects in cancers. (emphasis added). 

"Reprogrammed stem cells provide an important new tool in the fight against human disease, but to use these cells directly in the clinic, we must ensure that they are safe and that we are able to define their structure and behavior in the most precise terms," said Lawrence S.B. Goldstein, PhD, professor in the Department of Cellular and Molecular Medicine at the UCSD School of Medicine and co-director of the study with Zhang. Goldstein is also director of the UC San Diego Stem Cell Program.

More after the jump ....

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Courtesy of this post at Marginal Revolution, here's the link to a story on progress on a computer controlled car being tested in Berlin, with apparent success.  But, of course, lawyers are probably not yet involved, much. Two interesting excerpts are:

"However, he said, that besides the technological issues, the legal challenges would be another issue that needed to be regulated: "Who will be responsible when there's an accident — the owner or the passenger of the computer-controlled car or the company that produced it?"

***

Ideally, the car will respond to orders by remote control, for example on an iPad or an iPhone. With a click or a touch, the passenger can call the car to his personal location and then order the car to drop him off at his desired destination.

"This kind of car is actually perfect for car sharing," said Rojas. "There will be no more need for owning a car — once the automobile has dropped off its passenger it will drive on to the next passenger."

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It seems obvious that athletes go faster when competing against marginally better competitors. Now it's been proven in an experiment explained here in this NYT 'Personal Best" article by science writer Gina Kolata. But there are limits, it seems, to how much faster. 

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This post by Dr. Wendy Harpham provided a link to an interesting article in Atlantic related to a new book on intense beliefs perhaps leading to death. The book, by Shelley Adler, is  Sleep Paralysis: Night-mares, Nocebos, and the Mind Body Connection. 

Wendy is always brief, and explained the story as follows:

"The Dark Side of the Placebo Effect: When Intense Belief Kills is a fascinating piece about the work of Shelley Adler, a professor at the University of California, San Francisco. She explored why otherwise healthy young men (median age 33 years old) who were immigrants from southeast Asia were dying in their sleep without any obvious cause of death. Puzzled doctors called it Sudden Unexpected Nocturnal Death Syndrome (SUNDS).

Adler "comes to a stunning conclusion: In a sense, the Hmong were killed by their belief in the spirit world, even if the mechanism of their deaths was likely an obscure genetic cardiac arrhythmia that is prevalent in southeast Asia."

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Another cool new science tool. Now scientists at Caltech and Howard Hughes are starting to be able to see inside a cell during the moment of division.  

How?  Here's the explanation from ScienceDaily: 

"Jensen's group is one of just a few in the world that uses electron cryotomography (ECT) to image biological samples. Unlike traditional electron microscopy -- for which samples must be dehydrated, embedded in plastic, sectioned, and stained -- ECT involves plunge-freezing samples so quickly that they become trapped in a near-native state within a layer of transparent, glasslike ice. A microscope can then capture high-resolution images of the sample as it is rotated, usually one degree at a time.

One limitation of ECT is that samples cannot be thicker than 500 nanometers -- otherwise the electron beam cannot penetrate the sample sufficiently. Therefore, ECT studies have focused on small bacteria and viruses. But Jensen's group wanted to extend the technique to observe eukaryotic cells, which are typically much bigger. So they located the smallest known eukaryote, Ostreococcus tauri, and imaged it with ECT."

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This New York Times article reports on initial follow-up studies on disease among firefighters who worked at the 9/11 site. The conclusion?  A decade later, it's still too early to draw conclusions. 

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Story telling with pictures is powerful, and data visualization is only getting better. Courtesy of the Marginal Revolution, consider the power of this graphic view of  a micro-finance success story. 

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Updated

The NYT now includes this Nicholas Wade article on the new science described below. The article provides history and context on the Black Death. 

________________________________________________________________________

Some parts of history increasingly involve science. Last month there was news of "museumomics" - using DNA from museum samples to look back in time by obtaining and analyzing old DNA from museum samples of Tasmanian Devils, an animal now facing a vicious cancer spread by a virus.  Now there is news from ScienceDaily of scientists finding and analyzing remnants of 600 year old human teeth in order to find and prove the pathogen responsible for "the Black Death."  

The full article is available here through the genius of freely available scientific information provided by the Proceedings of the National Academies of Science. Here are key excerpts from the ScienceDaily summary:

"Previous genetic tests indicating that the bacterium was present in medieval samples had previously been dismissed as contaminated by modern DNA or the DNA of bacteria in the soil. Above all, there was doubt because the modern plague pathogen spreads much more slowly and is less deadly than the medieval plague -- even allowing for modern medicine.

The international team of researchers has for the first time been able to decode a circular genome important for explaining the virulence of Y. pestis. It is called pPCP1 plasmid and comprises about 10,000 positions in the bacterium's DNA. The sample was taken from skeletons from a London plague cemetery. The working group in Tübingen, led by Dr. Johannes Krause used a new technique of "molecular fishing" -- enriching plague DNA fragments from tooth enamel and sequencing them using the latest technology. In this way, the fragments were connected up into a long genome sequence -- which turned out to be identical to modern-day plague pathogens. "That indicates that at least this part of the genetic information has barely changed in the past 600 years," says Krause.

The researchers were also able to show that the plague DNA from the London cemetery was indeed medieval. To do that, they examined damage to the DNA which only occurs in old DNA -- therefore excluding the possibility of modern contamination. "Without a doubt, the plague pathogen known today as Y. pestiswas also the cause of the plague in the Middle Ages," says Krause, who is well known for his DNA sequencing of ancient hominin finds, which help trace relationships between types of prehistoric man and modern humans."

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This recent Gina Kolata article in the NYT recently highlighted transformative scientific change - molecular epidemiology for bacteria and viruses. In short, it means the ability to in just a few days (or less) actually prove the source of bacterial diseases or even a virus.

How?  By using fact investigation, plus great hardware and software to sequence genomic structures, and compare them to databased genomes. Note below the stunning drops in time and price for the work. 

Consequences for litigation ? Well, it's probably not here quite yet, but think about possibilities general and specific.

On specifics, think about the next wave of illness suspected to be associated with contaminated food. (For background, see this page from the Centers for Disease Control.) Using the tools described below, the contamination perhaps will be traceable by science that may not be disputable. If that happens, the suspected source may run out of room to express doubt about the cause of an outbreak.  Instead, it may face comparison of bacteria at its facility to bacteria found in sick people. When that happens and people want compensation, there may not be any causation issues left for debate.

On a large scale, think about epidemiology in general. Defendants often argue that a bad outcome is not "scientifically proven" until large scale epidemiology confirms cause and effect in a double-blinded, long term study which correlates logically to other scientific proof . That can take months, years or decades, depending on the substance and disease at issue.  And, the study may be confounded by variables and may not yield a conclusion. See this defense side post for a long explanation of epidemiology and litigation tactics.

Plaintiff's lawyers, on the other hand, will have to think about whether they can/should bring claims if a test was not run on a given person. They can argue an inference from others, but ...

Think also about the act and expense of ordering testing. Should doctors order tests to determine the precise source, even if it seems obvious when the 20th patient has just been seen ? Should a heath insurer pay the bill ? Should/could the paying health insurer have a remedy against the source for all expenses of tests caused by the contamination? 

Key excerpts are set out below on the exponential nature of the scientific change. Read the entire article for examples of the tools in action - the examples are powerful. 

___________________________________________________ 

"It is the start of a new age in microbiology, Dr. Musser and others say. And the sort of molecular epidemiology he and his colleagues wanted to do is only a small part of it. New methods of quickly sequencing entire microbial genomes are revolutionizing the field.

The first bacterial genome was sequenced in 1995 — a triumph at the time, requiring 13 months of work. Today researchers can sequence the DNA that constitutes a micro-organism’s genome in a few days or even, with the latest equipment, a day. (Analyzing it takes a bit longer, though.) They can simultaneously get sequences of all the microbes on a tooth or in saliva or in a sample of sewage. And the cost has dropped to about $1,000 per genome, from more than $1 million.

In a recent review, Dr. David A. Relman, a professor of medicine, microbiology and immunology at Stanford, wrote that researchers had published 1,554 complete bacterial genome sequences and were working on 4,800 more. They have sequences of 2,675 virus species, and within those species they have sequences for tens of thousands of strains — 40,000 strains of flu viruses, more than 300,000 strains of H.I.V., for example.

With rapid genome sequencing, “we are able to look at the master blueprint of a microbe,” Dr. Relman said in a telephone interview. It is “like being given the operating manual for your car after you have been trying to trouble-shoot a problem with it for some time.”

Dr. Matthew K. Waldor of Harvard Medical School said the new technology “is changing all aspects of microbiology — it’s just transformative.”

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Some parts of history increasingly involve science. Last month there was news of "museumomics" - using DNA from museum samples to look back in time by obtaining and analyzing old DNA from museum samples of Tasmanian Devils, an animal now facing a vicious cancer spread by a virus.  Now there is news from ScienceDaily of scientists finding and analyzing remnants of 600 year old human teeth in order to find and prove the pathogen responsible for "the Black Death."  

The full article is available here through the genius of freely available scientific information provided by the Proceedings of the National Academies of Science. Here are key excerpts from the ScienceDaily summary:

"Previous genetic tests indicating that the bacterium was present in medieval samples had previously been dismissed as contaminated by modern DNA or the DNA of bacteria in the soil. Above all, there was doubt because the modern plague pathogen spreads much more slowly and is less deadly than the medieval plague -- even allowing for modern medicine.

The international team of researchers has for the first time been able to decode a circular genome important for explaining the virulence of Y. pestis. It is called pPCP1 plasmid and comprises about 10,000 positions in the bacterium's DNA. The sample was taken from skeletons from a London plague cemetery. The working group in Tübingen, led by Dr. Johannes Krause used a new technique of "molecular fishing" -- enriching plague DNA fragments from tooth enamel and sequencing them using the latest technology. In this way, the fragments were connected up into a long genome sequence -- which turned out to be identical to modern-day plague pathogens. "That indicates that at least this part of the genetic information has barely changed in the past 600 years," says Krause.

The researchers were also able to show that the plague DNA from the London cemetery was indeed medieval. To do that, they examined damage to the DNA which only occurs in old DNA -- therefore excluding the possibility of modern contamination. "Without a doubt, the plague pathogen known today as Y. pestiswas also the cause of the plague in the Middle Ages," says Krause, who is well known for his DNA sequencing of ancient hominin finds, which help trace relationships between types of prehistoric man and modern humans."

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Funny how things work out. This morning's first post addressed scientific research, data sharing and full disclosure as a means for corporations and governments to acquire trust, and change minds. The post was written last week and scheduled to appear this morning.

The point was further highlighted over the weekend by a series of events tied to politics and science. Specifically, John Huntsman went on national media shows to call out some other Republican candidates as "anti-science."  Why ? Because some of the candidates are following the tobacco industry tactic of proclaiming there are "issues" about science when in fact there are no real issues. Think global warming, and think evolution. He did not raise it, but also think stem cells. The raw video is here.  A YouTube version is here.  Paul Krugman then piled on with his  NYT opinion piece titled "Republicans Against Science." Even Karl Rove is offended by Mr. Perry's extreme statements, as explained here. 

Ignoring data and reality should not work. Ultimately, the tactic failed the tobacco industry. Time will tell whether the tactic works for polticians. 

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To recap before updating, A Long Swim is the name given by a friend to a 30 mile, fourteen hour swim across the English Channel to raise money for research into ALS (Lou Gehrig's disease). For his family, it is a story of a three generation journey with ALS. Incredibly, the day after the swim was completed, Nature published breakthrough findings on the root cause of ALS.  And, adding even more to the joy, the breakthrough findings were made by the Les Turner ALS Foundation research group supported by the family.  

The update is that Doug and Susan McConnell have now provided some personal perspective on the incredibly grueling nature of A Long Swim. You can read the story of the swim as told and shown by Doug's wife, Susan, on her blog - My Bionic Boyfriend. The post is titled The Things We Do for Love. And, contrast Susan's telling with Doug's telling, which is in progress. Here, he provides some understated insights into mechanics of the 30 mile journey. 

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Artist's view. The basis of amyotrophic lateral sclerosis (ALS) is a broken down protein recycling system in the neurons of the spinal cord and the brain. (Credit: © CLIPAREA.com / Fotolia)

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Update

Doug is now the 48th person over 50 to swim the Channel !! The journey was over thirty miles and 14hours. 

The ALS fundraising also is a success. It's approaching $150k. 

__________________________________________________________________________________

ALS is one of the world's miserable diseases. It's also known as Lou Gehrig's disease. More research is needed to stop the disease.

To that end, a friend from college fraternity days has embarked on a remarkable fundraiser which goes forward today: the journey is swimming the English Channel, starting in Dover today at about 1:00 (UK time).  

He is Doug McConnell, and the project is called A Long Swim. Doug's twenty-one mile journey is to honor his father (a victim),  to raise money for ALS support and research through the Les Turner ALS Foundation, and to embrace a great challenge and adventure after more than a year and a half of arduous training.

The Les Turner ALS Foundation sponsors cutting edge scientific research. For anyone so inclined, donations can me made through its web page. 

Doug's progress can be tracked online www.ais-doverstraits.co.uk. The boat accompanying him is called Sea Satin.    

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Where will science take us, and how fast ? Do legislators, courts and lawyers really need to think today about scientific changes promised for tomorrow?  

Every day, ScienceDaily brings new articles with incremental progress in many areas. And, sometimes, the world's great science journals - and free online science such as the Public Library of Science (PLoS)  - bring news of profound breakthroughs. But should we believe predictions?

For a positive answer as to the accuracy of predictions for future science, take a look back at this page and its  imbedded string of AT&T videos. Make sure to look at the embedded predictive AT & T ads from 1993 (need help remembering 1993 - the narrator is Tom Selleck). Each ad precisely predicts and portrays one or more technologies now used everywhere. So, yes, there are indeed sound reasons to read and believe current predictions of future scientific possibilities. 

Also worth looking at is this page,  with an imbedded look at the success and failure in a newspaper's 1994 prediction of the future of newspapers, and the thing we today call an Ipad, or more generically, a tablet computer. 

Kudos to Peter Kafka at All Things Digital for posting the various the past predictions and ads regarding technology, and note his credits to Richard Raucci for pointing out that an even larger collection of seven A T & T predictive videos is here on Youtube.

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The invitation/appeal pasted below also is online here. In short, it's an invitation/appeal  to be part of an expert prediction team as part of an experiment on smart people making predictions, versus using data to make predictions without judment. 

The invitation/appeal arrives with a hat tip and thanks to the Marginal Revolution, a blog focused on progress through marginal changes, to use a very short label. 

To whet your interest in the research and one of the acclaimed researchers seeking your input, set out below is Wikipedia's entry on Philip Tetlock, and his findings/view that data create better predictions than do human judgments. Then read on below to see more on the study, and the invitation itself. But,  again, the link is here to join. 

_______________________________________________________________________________

 From Wikipedia:

Philip E. Tetlock is Leonore Annenberg University Professor of Psychology at the University of Pennsylvania. He has also written several non-fiction books on politics, including Counterfactual Thought Experiments in World Politics (with Aaron Belkin; 1996) and "Expert Political Judgment: How Good Is It? How Can We Know?".

His Expert Political Judgment: How Good Is It? How Can We Know? (2005) describes a twenty-year study in which 284 experts in many fields, from professors to journalists, and with many opinions, from Marxists to free-marketeers, were asked to make 28,000 predictions^[1][2] about the future, finding that they were only slightly more accurate than chance, and worse than basic computer algorithms which was the recipient of the 2008 University of Louisville Grawemeyer Award for Ideas Improving World Order. Dr. Tetlock was awarded the Woodrow Wilson Award for best book published on government, politics, or international affairs and Robert E. Lane Award for best book in political psychology, both from American Political Science Association in 2005. Forecasters with the biggest news media profiles were especially bad. The study also compared the records of "foxes" and "hedgehogs" (two personality types identified in The Hedgehog and the Fox).^[3][4]

The Value of Statistics

Tetlock's conclusion about expert opinion is that statistics when properly used are more reliable than human judgement in every sphere of activity.^[5]

In 2000 Tetlock was awarded the NAS Award for Behavior Research Relevant to the Prevention of Nuclear War from theNational Academy of Sciences.^[6]

_______________________________________________________________________________

Philip Tetlock requests your help

Posted: 03 Aug 2011 02:28 PM PDT

 ______________________________________________________________________________

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Who says Americans are afraid of sharing genomic information, especially when it's analyzed in bits? 100,000 Kaiser Permanente patients contributed saliva for DNA analysis as to a subpart of the genome. The subpart  - telomeres - is fairly newly discovered and seems important in several ways as to how we age and how cells die (or not). Now, thanks to new technology not available three years ago, the genomic work was completed in less than 15 months, and the data is being linked to health records and California environmental data. The resulting database will be online next year. Set out below are excerpts from UCSF's online description of the project. 

_________________________________________________________________________

"The genotyping project was made possible by a two-year, $24.8 million grant awarded in September 2009 to the Kaiser Permanente RPGEH and UCSF by the National Institutes of Health. Funding for the grant came from three sources: the National Institute on Aging, the National Institute of Mental Health, and the Office of the Director.

”The completion of genotyping on this large and diverse population marks an unprecedented milestone in population-based genetics research,” said Richard J. Hodes, MD, director of the National Institute on Aging at the National Institutes of Health. “The genetic information, combined with the longitudinal clinical and health data that are already part of the Kaiser Permanente database, along with California environmental data, will create a unique and powerful resource to help answer research questions about aging, health and disease.”

To complete the genotyping project in two years, as required by the funding, Kaiser Permanente first had to build a new, high-throughput laboratory in Oakland, Calif., to extract DNA from more than 100,000 saliva samples in 15 months. The extracted DNA was transferred to UCSF’s Institute for Human Genetics, which worked with Affymetrix to create custom Axiom® arrays for genotyping 675,000 to 900,000 genetic markers – comprised of single nucleotide (SNPs) and insertion-deletion polymorphisms – across all 100,000 samples.

“This project reflects the incredible advances that have occurred in the past decade in the field of genomics and the speed and cost-effectiveness of genotyping technology,” said UCSF professor Pui-Yan Kwok, MD, PhD, who led the SNP genotyping work at UCSF. “Three years ago, we could never have undertaken a project of this size, much less completed it in only 15 months.”

Separate samples of DNA from the same 100,000 individuals were also analyzed in the laboratory of UCSF Professor Elizabeth Blackburn, PhD, who received the Nobel Prize in Physiology or Medicine in 2009 for her discovery of telomeres. The Kaiser Permanente/UCSF project will create the largest resource of telomere data available and will be the first such resource linked to health records of this number and diversity through Kaiser Permanente.

Data from the genotyping project will be processed and cataloged by RPGEH and UCSF scientists over the next year so it can be made available to researchers in late 2012."

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Regenerative medicine is now one more step down the path. Japanese scientists have now used stem cells to grow mouse teeth in a laboratory. As the cells started to thrive, the cells were put into a mold and grew into teeth. The  teeth were then successfully transplanted into the mouths of mice. ScienceDaily has the full story here - a couple of paragraphs are below to prove I'm not making this up. 

"FROM STEM CELLS TO WHOLE TOOTH UNITS

Tsuji's team removed two types of stem cells from the molar teeth of mice and grew them in the laboratory. To control the length and shape of the teeth, the cells were placed in a mold, where they grew into entire tooth units.

The entire tooth units were then transplanted into the lower jaws of one-month-old mice. They fused with the tissues and jaw bones around them after about 40 days, Tsuji said. Nerve fibers too could be detected in the new teeth.

Tsuji stressed the importance of finding the right "seed cells" for reparative therapy. In this case, entire tooth units could be grown because the stem cells were taken from molar teeth of mice -- where they later grew into enamel, dental bones and other parts that comprised a regular tooth unit.

In 2010, U.S. researchers created an artificial lung that rats used to breathe for several hours."

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As science grows, so do patent disputes - especially in the worlds of biotechnology and computers.   The Supreme Court of the United States is paying attention, and recently has created a continuing flow of patent appeals from the Federal Circuit court created thirty years ago as a specialized appellate court to hear patent appeals. Some might say the stream of appeals is in part a product of Chief Justice Roberts' desire to provide certainty for businesses (see this prior post for links to relevant articles).  Interestingly, the Supreme Court's recent path has included serial reversals of decisions of the Federal Circuit, a perhaps not surprising result.

The Supreme Court's growing interest in patents, the reversals, and even the grants of certiorari (the appeal), raise interesting questions. For example,  how cases are selected, when does the US government weigh in, and how the Court decides the cases. Some insights into these subjects are summarized in this new and highly informative post by Kevin Noonan at Patent Docs. The post summarizes a recent discussion of the patent cases by a truly learned panel.  The panel was comprised of  "former Solicitors General and Assistant Solicitors. [The panel} addressed recent Supreme Court precedent in patent law during the BIO International Convention last month.  Moderated by former Federal Circuit Chief Judge Paul Michel, the panel consisted of Seth Waxman, former Solicitor General now at Wilmer Hale; Paul Clement, another former Solicitor General now at Bancroft PLLC; and Thomas Hungar, former Assistant Solicitor General now at Gibson Dunn LLP."  

The post is well worth reading for many reasons. Among others, Mr. Noonan's post distills out the views the panel articulated on substantive issues, and the tensions and economic conflicts in patent law. The outcomes will impact the where, when and how of research, investment, and value models for scientists. The outcomes also will impact economic and life and death issues in biotechnology research as scientists and businesses search for treatments for disease, and patent issues impact that process. For example, many assume that next year the Court will here important issues on whether patents are properly obtained for describing the sequences of genes, an issue and case covered in this prior post. There, the government weighed in against such patents. 

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Lacking an influential religious right wing, Canada is a leader in stem cell research. Indeed, much of the fundamental, early proof of stem cells is credited to Canadian researchers. Here's a Canadian-centric timeline of stem cell discoveries. 

Now the Canadians have made another breakthrough stem cell discovery. Specifically, they've found and isolated the stem cell capable of generating the entire blood system.   ScienceDaily presents the summary here. The full paper is published in the prestigious journal, Science, and is here.

The lead researcher for this project, Dr. John Dick, is well-known for blood and stem cell discoveries, and cancer research.  In 2007, for example, his team made Science (and ScienceDaily) with research work that opened the door to using stem cells to create and track the leukemia process from the very beginning of that form of blood cancer.  In January, 2011, Dr. Dick's team built on that work and published in Nature this groundbreaking paper  on genetic diversity in leukemias, as summarized here by ScienceDaily. The research proved that in at least the ALL form of leukemia, the tumors are NOT all alike. That is, they are not all one malignant cell endlessly dividing to spew out exact replicas. Instead, at least in ALL leukemias, there are multiple different forms of cancer cells. This discovery helps to explain why chemotherapy sometimes fails to prevent a later relapse - the chemo wiped out one line of cancerous cells but not another. 

Finding the ultimate "parent" blood stem cell is important for multiple reasons. One is that it shows the value of new tools. The team used high volume flow cytometry to find the parent stem cell. That tool en essence screens huge volumes of cells to find a specific cell of interest. Improved versions of the tool may allow screening the blood of known of blood cancer patients to find the variant lines of cancer cells. If done post-therapy, that could help determine if every line of cancer cell has been killed. 

On finding the parent stem cell itself, the finding offers a start towards developing more forms of regenerative medicine to save the lives of cancer patients. Today's stem cell (bone marrow) transplants are the original form of regenerative medicine as the immune system is wiped out and then regenerated from the transplanted cells. The procedure imposes a significant risk of death, and a stunning burden on the body and mind of cancer patients, albeit today's patients suffer and die less than did patients transplanted in past decades. And, there is the ceaseless problem of finding donor cells, a challenge made even harder by today's increased ethnic diversity. So, for today, preserving cord blood is/should be a "no brainer" for any financially capable family, and registering to donate bone marrow is painless, easy and one of the few ways each of us can physically contribute to trying to save lives. This "New Year's resolution" post outlines the how and why of cord blood preservation and bone marrow registration, with links to relevant agencies and services.

For the future, Dr. Dick and others hope to find ways to use the parent stem cells to regenerate non-cancerous forms of the myriad forms of blood cells, and to help treat other blood diseases. Here are key excerpts from the ScienceDaily summary:

"Dr. Dick works out of UHN's Ontario Cancer Institute (OCI) -- the venerable institution where stem-cell science began in 1961 with the original discovery of Drs. James Till and Ernest McCulloch -- and McEwen Centre for Regenerative Medicine with the next generation of stem-cell scientists focused on developing better and more effective treatments for heart disease, diabetes, respiratory disease and spinal cord injury.

The 1961 Till and McCulloch discovery quickly led to using stem cells for bone marrow transplantation in leukemia patients, the most successful clinical application so far in what is now known as regenerative medicine and a therapy that is used to treat thousands of patients annually around the world.

"Ever since stem-cell science began," says Dr. Dick, "scientists have been searching for the elusive mother lode -- the single, pure stem cell that could be controlled and expanded in culture prior to transplantation into patients. Recently scientists have begun to harness the stem cells found in the umbilical cord blood; however, for many patients a single donor sample is not large enough to use. These new findings are a major step to generate sufficient quantities of stem cells to enable greater clinical use and thus move closer to realizing the promise of regenerative medicine for patients."

Along the way, scientists have indeed mapped many vital signposts regarding stem-cell subsets and specialization. Last year, Dr Dick's team reported isolating the more specialized progenitor cells that lie downstream of the stem cell. This latest discovery was enabled by hi-tech flow cytometry technology: a process that rapidly sorts, sifts and purifies millions of blood cells into meaningful bins for scientific analysis. Now, stem-cell scientists can start mapping the molecular switches that guide how "normal" stem cells behave and endure, and also characterize the core properties that distinguish them from all other blood cell types.

This discovery is the one Dr. Dick has personally been seeking ever since 1988 when he developed the first means of studying human blood stem cells by transplanting them into immune-deficient mice, research that was also published inScience. "Back then, our goal was to define single human stem cells. With advances made in technology, twenty-three years later, we have."

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This post of a few days ago focused on some groundbreaking work referred to as "museumomics" - that is, using hairs from old museum samples of animals to obtain DNA for sequencing to see what animal genomes looked like in the past. The global scope of the team was impressive, as were the bios for all of the team leaders. But, stunning is the word that comes to mind for the bio for  one of the leaders - Vanessa Hays of the Venter Institute. So, the bio for Ms. Hays is pasted below, and is online here at the J. Craig Venter Institute. The institute website is worth a browse too. 

I especially enjoyed the story of Ms. Hays  convincing Archbishop Desmond Tutu to become the first South African to allow sequencing of his genome. 

Scientist Spotlight: Meet Vanessa Hayes

Published by Laura Sheahan on 10 November 2010 in Genomic Medicine.

Geneticist Vanessa Hayes does not think small nor move slowly—from completing her post doc in six months (the US National average is 3 to 7 years) to completing the first South African Genome Project in 2010 with her goal set on defining the extent of human diversity in all populations, she is on a mission.  Just 11 years outside her post doc she has the credentials of someone who has been in science much longer. Her work and talent has taken her to remote regions of Southern Africa, all over Australia, Europe, the U.S. and now to the J. Craig Venter Institute with her appointment as Professor of Genomic Medicine at the San Diego facility.

Of Cartoons and Men…

Born and raised in South Africa, Vanessa first headed a laboratory near Cape Town to investigate genetic susceptibility to HIV/AIDS after earning a Ph.D. in 1999 in Medical Genetics at the University of Groningen, Netherlands. After three years at the University of Stellenbosch she moved to Sydney, Australia to become group leader of Cancer Genetics first at the Garvan Institute of Medical Research, and later at the Children’s Cancer Institute of Australia. During those years she began two major cancer research projects that continue today. One is a study to assess how ethnicity impacts prostate cancer risk and outcomes by genetic profiling men with and without prostate cancer from different ethnic and geographical locations (initially South Africa and Australia). “I believe in going to the extremes of phenotypic diversity to understand genotype – for example the clinical disparities of prostate cancer in Africa compared to non-African populations has not been adequately explored,” she said explaining that the genetics of ethnic diversity is one of her main research interests. “We don’t always have clear clinical definitions to describe phenotype, but genomics can help to define disease,” she added.

This cancer research then led her to what might seem like an unlikely suspect–the Tasmanian devil. The inspiration for a much beloved Looney Toons character and the largest carnivorous marsupial indigenous to Australia, Vanessa became acquainted with the devil when learning that it was a good model for human cancers. She partnered with Stephan Schuster of Pennsylvania State University to sequence the animal using next-generation (gen) sequencing, in turn establishing the then first next-gen sequencing research laboratory in Australia.  By establishing a Tasmanian devil genome, she and her team were able to define the extent of dwindling genetic diversity within the devil population as a result of an unusual infectious facial cancer. The hope is that this information and tools developed will be used for the insurance breeding program, which has been established by Australian authorities to save this iconic species from inevitable extinction within the next decade.

Putting Africa on the Genetic Map

In early 2010 Vanessa embarked on another collaborative effort with Schuster’s lab, this one to help get African populations represented in genetic databases and reap the benefits of human genomics research. The initiation of the South African Genome Project was a key step in helping to define the extent of human variation, the relevance to assessing disease risk, and the response to various medicines. The effort was conceived out of Vanessa’s frustration in earlier studies with African populations when she found a complete lack of African reference genomes and susceptibility gene array profiles in existing databases. Africa, believed to be the birthplace of mankind with the oldest populations, offers a much greater diversity than found in individuals of European decent. Another issue with the existing databases was that the little African genetic data represented in early 2010 was based on one population – the Yoruba people from Nigeria. Demonstrating that the Yoruba people are clearly not representative of the majority of the over 500 different linguistic groups in central to southern Africa, Vanessa was determined to change the face of European-driven genomic research.

Vanessa and a Bushman lady from the Southern African Kalahari desert in deep discussions about what we can read in the blood (aka genomics). This lady is one of only a few click-speaking hunter-gatherer peoples left who represent an ancient line for all modern humans. (photo credit: Chris Bennett - www.chrisbennettphoto.com)

Ingenuity and perseverance led Vanessa to knock on the door of Nobel Peace Prize recipient Archbishop Desmond Tutu. He was, she knew, a critical step needed to gain access to a potential treasure trove of South African genetic data. She made her case directly to the Archbishop in front of a room of advisors who told him not to participate in a genetic study. However, much to her surprise, Tutu agreed to be the first South African to have his genome sequenced. Vanessa believes he did so, against the advice of his advisors, because he knew the importance of this type of research to the people of his country. The Archbishop’s participation was both critical and significant as he represents not only the Bantu linguistic group to which 80% of the South African population belongs, but he is also a survivor of TB, polio, and prostate cancer. The researchers were able to correlate his genetic markers (genotype) potentially associated with disease susceptibility with his family and medical history (phenotype), providing valuable information about the Bantu people. Vanessa and her team also sequenced the complete genome and three exomes (protein-coding genes only) from four individuals representing diverse ethnic groups of what are known as the Kalahari Bushmen. Bushmen (or San) is the term for the click-speaking hunter-gatherers who inhabit the Kalahari Desert, which spans parts of Botswana, Namibia, and Angola. Her studies, published in Nature in 2010, showed that two different linguistic groups of Kalahari Bushman were as genetically divergent as Europeans and Asians. Some found this finding surprising, however, the extent of the diversity should not be surprising considering these Bushman represent the oldest living lineage of modern humans.

By this time in 2010 Vanessa decided she had reached the technological limits of her research in human genomics in her current position in Australia. She was searching for a place to expand her capabilities, particularly in next generation (gen) sequencing and bioinformatics. She was interviewing last spring in Melbourne at the Walter and Eliza Hall Institute for Medical Research where Dr. Craig Venter happened to be giving a keynote lecture. The JCVI was not on her radar at the time as she had several job offers within and outside Australia, but Craig was able to convince her to come to work with him and the team at JCVI.

Sleep is overrated

The sequencing of Archbishop Tutu was only a start to Vanessa’s plans in human genomics research. She is continuing to expand her work with indigenous groups in Africa. Much like the aspirations (and accomplishments) of her new boss, she claims a ‘modest’ goal: “To define the extent of human diversity that exists globally so we can have a true picture of variation that human genomes have and to help make sense of that variation by linking genotype to phenotype.” Phenotype cannot only mean disease conditions (associated with genes) but also evolved behaviors. For example, how the Bushmen are able to go for a week without water in the desert climate is a phenotype that may be encoded in their genes. Understanding the genetic basis for disease and behavior in different populations will certainly be a challenge, but clearly Vanessa is a person who thrives when presented with challenges.

Vanessa’s limited spare time revolves around her family, including two children — each born on different continents — who keep her busy with the latest goal to teach mom how to surf! A keen soccer player in Australia, she has turned to a new adventure since her move to San Diego, kickboxing.  She says she doesn’t get much sleep, particularly little in the past three years, but at least now she’s working mostly on U.S. time rather than two opposite time zones.

If she had time for another career, “it is hard to think of another career as I am doing exactly what I love, combining my passion for the rich-diversity of people from Southern Africa (and globally) from whom we have so much to learn, with the speed and dynamics of everyday life of 21st century science. What better place to combine these two worlds than here at JCVI.” Vanessa hopes via her new position to understand and educate others about the breadth of human genetic diversity existing in populations worldwide

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Museumomics ? Scientists using hairs from old, stuffed animals from museums to obtain historic DNA samples of a species, and then running advanced new sequencing software to compare past genomes of the species  to current genomes. And, it's not just an idea but rather it is happening now, as described below.  (Does Jurassic Park of 1993 come to mind - this is not the exact same premise, but  ...)

Tasmanian devils ? The fictional cartoon creature is real, as described here by Wikipedia. It's also an endangered species. 

The scientists ? As is so often true these days, it's a global team. As described by ScienceDaily, "[the team, led by Stephan Schuster, a professor of biochemistry and molecular biology at Penn State University; Webb Miller, a professor of biology and computer science and engineering at Penn State University; and Vanessa Hayes of the Venter Institute in San Diego, includes other scientists at institutions and universities in Australia, Denmark, and the United States. The results of the study will be published in the Proceedings of the National Academy of Sciences."   Reading the bios of the team leaders illustrates the significant depth and breadth of their knowledge. As to the reference to the Venter Institute, that is indeed a reference to the institute created Craig Venter of the Human Genome Project. 

The science? Summarized  here by ScienceDaily, it's a new science journal article on using museumomics to try to help thwart extinction of the Tasmanian devil. The point is to find genetically diverse animals before starting a breeding program. In short, pick the right breeding animals, as best we can tell, by comparing the genomes of current animals to prior generations of animals.

Implications ? Consider the litigation possibilities of studies looking backwards at the genomes of various species, including homo sapiens. For example, consider a  study of museum samples of  bald eagles and other birds. Suppose museumomics could track and show the genomic changes caused over time by  DDT.  This online article from Duke provides a simple summary of some of the impacts of DDT. The massive overall impact for eagles was described in this 1982 Science article by  James W. Grier.  DDT also caused non-genomic changes, as described in this 2009 article by Silva et al. 

Perhaps museumomics also will put an end to Fox "News" publishing stories (e.g this 2006 story) that seek to distract attention away from the reality that DDT caused massive harm. The headline from Fox ?  "Bald Eagle - DDT Myth Still Flying High." 

Read the key excerpts below to see the working scale of the museumomics as applied to the Tasmanian Devil.

 ____________________________________________________________________

"The second aspect of the project was to learn how much genetic diversity had been lost since Europeans settled Tasmania in 1803. To do this, the scientists analyzed a large number of genetic markers from an additional 175 Tasmanian devils, some of which were museum specimens from the Smithsonian in Washington, D.C. and the Natural History Museum in London. Schuster explained that this approach to genomic research, which he has named "museomics," is truly unique and brimming with potential. "Museums are treasure troves of specimens collected in the last 250 years," Schuster said. "And, in fact, we can get DNA from hair shafts of a museum specimen." Schuster explained that DNA collection from hair is virtually non-destructive; that is, museum specimens are not damaged visually in the process of removing just a few hairs. Interestingly, after analyzing the 175 individuals, the scientists learned that the genomic diversity of the Tasmanian devil, while low, has not decreased much over the last century. "This is an important finding because it means that DFTD is not to blame for any lack of genetic diversity since the disease appeared only 15 years ago," Miller explained. "It's crucial that we act as responsible stewards for the species, helping maintain what little genetic diversity it had before the DFTD epidemic struck."

Schuster also said that a significant and defining part of the team's project was the ability to generate extra-long genetic sequences using a special genome-sequencing technology that, at the time the scientists performed the research, had not yet been released publicly. "This technology, developed by Roche Diagnostics and 454 Life Sciences, allowed us to assemble a mammalian genome from scratch," Schuster said. "The longer stretches of DNA or "long reads" were particularly critical to develop a full understanding of the genetic makeup of such a unique species."

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The future is starting to arrive. The new issue of Nature (online June 26, 2011) and ScienceDaily bring the significant news that scientists have now actually fixed a disease by editing a chromosome in a mouse. In short, they researchers designed a way to target - and then edit (replace) -  a particular segment of DNA.

In short, the targeted sequence  was missing the instructions to create  blood clotting protein. The absence of the clotting protein creates the disease we call hemophilia. The "fix" involved inserting the genetic coding needed to cause the mouse body to generate the clotting factor. An engineered virus was used to find the errant section, cut it out, and then insert new instructions. It worked - the mouse now produces the clotting factor and so is no longer  a hemophiliac ! 

This is just one step down the path for science, but it is a symbolically large step.  Key quotes are set out below from ScienceDaily's summary of the full article.

ScienceDaily (June 26, 2011) — Using an innovative gene therapy technique called genome editing that hones in on the precise location of mutated DNA, scientists have treated the blood clotting disorder hemophilia in mice. This is the first time that genome editing, which precisely targets and repairs a genetic defect, has been done in a living animal and achieved clinically meaningful results.

As such, it represents an important step forward in the decades-long scientific progression of gene therapy -- developing treatments by correcting a disease-causing DNA sequence. In this new study, researchers used two versions of a genetically engineered virus (adeno-associated virus, or AAV) -- one carrying enzymes that cut DNA in an exact spot and one carrying a replacement gene to be copied into the DNA sequence. All of this occurred in the liver cells of living mice.

"Our research raises the possibility that genome editing can correct a genetic defect at a clinically meaningful level after in vivo delivery of the zinc finger nucleases," said the study leader, Katherine A. High, M.D., a hematologist and gene therapy expert at The Children's Hospital of Philadelphia. High, a Howard Hughes Medical Institute Investigator, directs the Center for Cellular and Molecular Therapeutics at Children's Hospital, and has investigated gene therapy for hemophilia for more than a decade.

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The Human Genome Project is one part of the stunning leaps in medical and biological science over the last 30 years. Today, lives are saved by what we now know and can do, and lives of course are priceless.

As if that's not enough,  now look at the eye-popping ROI numbers for the Human Genome Project. $ 796 billion and 310,000 jobs in return for a  $3.8 billion investment.  Even if we allow for some puffery or generous accounting, the numbers are stunning. The text  pasted below is just part of this excellent blog post by Donald Zuhn on Patent Docs (they are Chicago-based PhD patent lawyers for bio and pharma).

Imagine what might happen to save more lives if our nation fully invested in stem cells by having the wisdom to reject the their  purported "morality" in favor of saving lives. Imagine how many new jobs might be generated if our nation finds the courage to keep investing in science despite the screams of the deficit hawks who sat silently while Bush turned a surplus into a deficit. Imagine the economy if we as a nation supported science as well as we've supported the financial services industry. And, by the way, when was the last time you saw an investment banker save a life with her knowledge ?

_______________________________________________________________________

"Earlier this month, the Battelle Memorial Institute announced the issuance of a report concerning the economic impact of the Human Genome Project.  In the report, the research group indicated that the return on the $3.8 billion the U.S. government invested in the project between 1988 and 2003 totaled $796 billion.  The report also indicated that the project has created some 310,000 jobs (as of 2010), generating $244 billion in total personal income.  In 2010 alone, the project and associated genomics research and industry activity generated $67 billion in economic output, supported jobs that produced $20 billion in personal income, and provided $3.7 billion in federal taxes -- almost paying back the government's total investment in the project in a single year.  In addition, Battelle noted that the project had launched a "genomic revolution" that would "create significantly more jobs in the future."

The report also noted that the project led to significant breakthroughs including new forms of personalized medicine and genetics therapy, greater productivity in agriculture, and potential sources of renewable energy.  Life Technologies CEO Greg Lucier (the report was sponsored by Life Technologies' foundation) stated that "[f]rom a simple return on investment, the financial stake made in mapping the entire human genome is clearly one of the best uses of taxpayer dollars the U.S. government has ever made," adding that "[t]his project has been, and will continue to be, the kind of investment the government should foster."

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Certainty is valuable. Just ask entrepreneurs making decisions on where to invest or seeking to sell future cash flows for a multiple of earnings.

Or, ask insurers pricing risk premiums. Put aside mere money. Consider doctors or scientists seeking to predict the success of any particular treatment for any given disease. Consider the patient wondering if he or she will, for example, remain paralyzed for life, or whether stem cells may help to cure Alzheimer’s, cancers or other diseases.

Now consider the impact of the news that experiments by smart researchers at UCSD further prove the folly of depending on faux stem cells (“ induced stem cells or iPS).  The iPS cells are the faux stem cells touted by the religious right as an alternative to true stem cells from embryos. The latest research results were publicly announced last Friday, and are now moving through the news cycle. Nature’s press article is here, Andrew Pollack’s NYT article is here, and the full Nature paper is here. Key excerpts are pasted below from Nature’s press article.

Implications ? On the money side, the uncertainty plainly will slow progress in research and investment in iPS cells in particular. On the human sides, that means more patients will die or suffer while waiting even longer for answers.

The implications also are broader. The Catholic Church now faces a new set of challenges and questions as it seeks to limit science based on its “moral” view. And, right wingers will face a new set of challenges for the 2012 elections whne they argue to limit science. ____________________________________________________________________________________________________

“Cells that have been reprogrammed to grow into different types of tissue might be rejected by the body — even when they are transplanted into the individual from whom they are made, researchers report in a study published today in Nature.

The study was led by Yang Xu, a molecular biologist at the University of California, San Diego. It will shake up the regenerative-medicine field, because until now, most scientists have assumed that reprogrammed cells made from an individual's own tissue could be safely transplanted back into the same person.”

"This is a surprise; it's going to put a spanner in the works for the whole field," says Paul Fairchild, an immunologist and stem-cell biologist at the University of Oxford, UK. The latest study looked at mouse embryonic stem cells and mouse induced pluripotent stem (iPS) cells. Both types of cell are pluripotent, meaning that they can grow into many other cell varieties.”

****

“The finding comes on top of the publication of a spate of studies suggesting that iPS cells might contain more genetic abnormalities than embryonic stem cells.. The US Food and Drug Administration heard concerns about genetic mutations in iPS cells at a meeting in Bethesda, Maryland, in March.”

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Why support federally funded cancer research ? An expert article presents the case in brief, with the argument presented by George W. Sledge, Jr., MD,  who is the President of the American Society of Clinical Oncology.

The short summary? Supporting federally funded cancer research is important because it's compassionate for the 500,000 people who die of cancer each year in the US. And its important  because it's a vast and growing area of science that produces great jobs and more. Federal investment also is needed because pharma does not pay for basic science research, and we need to keep up with China, which is investing heavily in the area, as is described here. Dr. Sledge also is urging oncology and other professionals to speak out because his trip to Washington was not encouraging.  

Here's a key excerpt, followed by the text of the full article:

 "An investment in cancer research not only enhances the lives of patients, it also creates jobs and spurs economic growth. In 2007, NIH and NCI funding created over 350,000 jobs and generated more than $50 billion in economic activity. NIH and NCI contribute to local economic revitalization efforts by providing funding to universities, research institutions, and smalls businesses across the country." 

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Science beyond fiction.

Think about  that phrase. Think about the changes of the last hundred years. The last ten years. The last two years. The last week. Science is exploding, and today's fiction cannot keep pace with the fundamental daily advances in science. 

The source of the phrase ?  An EU-created group  focused  on  science and change.

The group?  FET. Future and Emerging Technologies.  FET's tagline:  "science beyond fiction."

FET's mission ? The website defines it as follows:

 "Within the EU Framework Programme for Research and Technological development, Future and Emerging Technologies (FET) is funding frontier research based on a radically new visions of what can be done and grounded in scientifically valid ideas how to make major steps towards achieving such visions.

FET acts as a pathfinder open to new ideas and opportunities, as they arise from within science or society. It aims to go beyond the conventional boundaries of Information and Communication Technology (ICT) and ventures into uncharted areas.

FET funded projects increasingly rely on fresh synergies, cross-pollination and convergence with different scientific disciplines and with the arts and humanities. This transdisciplinary and high-risk research requires new attitudes and novel organisational models in research and education. The multidisciplinary creative process that is at the heart of future and emerging technologies is a constant challenge to conventional academic boundaries."

A conference known as fet11 just finished up in Hungary, and brought together scientists, government leaders and dreamers from around Europe. Among other things, they talked about new projects, and a billion dollars of research grants.  Neelie Kroes, Vice President of the European Commission, is one of the government leaders.  Her resume is impressive:

"Biography: From February 2010 Kroes has been a Vice President of the European Commission and is leading implementation of the Digital Agenda for Europe - the EU's new comprehensive action plan to harness ICTs to drive growth and address social challenges. Kroes will be mobilising industry, national governments, other stakeholders and her colleagues to deliver on 31 pieces of legislation and 101 targets by the end of her term in 2015. At the top of the list is the EU's commitment to deliver 'broadband for all' .  Prior to her roles in Brussels, Kroes was President of Nyenrode University from 1991-2000, and served on the boards of a string of major companies such as Lucent Technologies, Volvo, and P&O Nedlloyd.  Kroes hails from the liberal VVD Party in the Netherlands, and served as a national minister of transport and telecommunications in the 1970s and 1980s. Kroes has been a Knight of the Order of the Netherlands Lion since 1981 and a Grand Officer of the Order of Orange-Nassau since 1989."

What did they decide?  This page from IPfrontline provides the following synopsis of the finalists for the grants, in alphabetical order:

 FuturICT Knowledge Accelerator and Crisis-Relief System: ICT can analyse vast amounts of data and complex situations so as to better predict natural disasters, or manage and respond to man-made disasters that cross national borders or continents.

• Graphene Science and technology for ICT and beyond: Graphene is a new substance developed by atomic and molecular scale manipulation that could replace silicon as the wonder material of the 21st century.
• Guardian Angels for a Smarter Life: tiny devices without batteries that act like autonomous personal assistants, and which can sense, compute and communicate potentially even while travelling through your bloodstream.
• The Human Brain Project: understanding the way in which the human brain works can bring the benefits of brain-related or brain-inspired developments to computing architectures, neuroscience and medicine.
• IT Future of Medicine: digital technology has the power to deliver individualised medicine, based on molecular, physiological and anatomical data collected from individual patients and processed on the basis of globally integrated medical knowledge.
• Robot Companions for Citizens: soft skinned and intelligent robots have highly developed perceptive, cognitive and emotional skills, and can help people, radically changing the way humans interact with machines.

 That's a great list of projects, andthe fet11 website is full of interesting articles and videas.   Kudos to the  EU leaders  trying to push science ahead.  Science is our future, and makes sense for reasons of business, jobs and finding solutions to help people. 

Here in the US, President Obama and others also "get" the value of science. Indeed, he's made some wonderful decisions to push science forward. Sad to say, US efforts to push science ahead face opposition vocal, headline-grabbing opposition from  misguided  tea-partiers who seek  to slash research budgets, and restrict science.   Hopefully forward-looking people will speak out with voices and numbers sufficient  to overcome the opposition. 

Hat tip to the Financial Times for covering the topic here, but it's articles are often behind barriers.

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 It feels like science fiction. But, here is the ScienceDaily summary of an experiment - and success - in robots learning altruism and cooperation. The experiment was undertaken to test "Hamilton's Rule" on why humans act altruistically. The full paper is here in PLoS.

The experiment involved researchers at the Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland,  and the  Department of Ecology and Evolution, Biophore, University of Lausanne. The Swiss researchers used  small "Alice"  robots previously developed at the University.  The robots seek out food. The robots started with 33 "genes" of code. They evolved and improved over 500 generations of robots. The authors now want to put the results to work to see if flying robots will better cooperate in swarming. 

The law side? Who knows. But this article caught my eye because somewhere an article set out  the idea that some day robots could be used to clean up debris at nuclear power plants, but current design standards make that harder because power plant designs assume human mobility and dexterity. Will it some day be negligent to design a nuclear plant without providing for robotic clean up?

Here's the conclusion from the article:

"Because the 33 genes were initially set to random values, the robots' behaviors were completely arbitrary in the first generation. However, the robots' performance rapidly increased over the 500 generations of selection (Figure 2). The level of altruism also rapidly changed over generations with the final stable level of altruism varying greatly depending on the within-group relatedness and c/b ratio (Figure 3). When the c/b value was very small (0.01), the level of altruism was very high in the populations where within-group relatedness was positive (i.e., 0.25, 0.5, 0.75, and 1.00) and close to zero when robots were unrelated (Figure 4). In the treatments with other c/b values, the level of altruism was also very low when the relatedness was close to 0 and the level of altruism also rapidly increased when the relatedness became higher than a given value. In all cases, the transition occurred when r became greater than c/b, as predicted by Hamilton's rule."

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My 54th birthday brought an unexpected present. On April 29,  2011, the DC Circuit vacated the nation-wide injunction limiting stem cell research involving federal funding, as is well-described  by Lyle Denniston at Scotusblog. The opinion is here. Thank goodness for appellate courts,  the Obama Administration pressing the appeal quickly, and true scientists supportiing the effort to overturn the injunction.

It's hard to grasp why the injunction was ever issued given the public interest factor for issuing injunctions. Delaying research is not simply an abstract issue. To say the least, stem cell research goes to the heart of diseases (e.g. cancers)  which kill thousands every day, and to profound injuries that can devastate lives. Stem cell research also is big business, and would be bigger here except that the restrictive limits push researchers outside the US. 

As it happens, ScienceDaily  this week brought news of new research papers which highlight the importance of basic and wide-ranging research to fully understand stem cells and their internal cellular components. Thus, this April 26, 2011 ScienceDaily article highlights an April 15, 2011 online paper reporting that scientists researching breast cancer recently found evidence that some breast cancer cells can go backwards to become a stem-cell like cancer cells:

ScienceDaily (Apr. 26, 2011) — Whitehead Institute researchers have discovered that a differentiated cell type found in breast tissue can spontaneously convert to a stem-cell-like state, the first time such behavior has been observed in mammalian cells. These results refute scientific dogma, which states that differentiation is a one-way path; once cells specialize, they cannot return to the flexible stem-cell state on their own.

"It may be that if one eliminates the cancer stem cells within a tumor through some targeted agent, some of the surviving non-stem tumor cells will generate new cancer stem cells through spontaneous de-differentiation," says Whitehead Founding Member Robert Weinberg. Cancer stem cells are uniquely capable of reseeding tumors at both primary and distant sites in the body.

As to the value of fundamental research, ScienceDaily noted here that one of the world's great medical journals - Cell -  includes a new paper highlighting a fundamental new discovery on the path of genetic mutations. The new paper is set out as the featured and free article of Cell's  April 29, 2011 issue, and is accompanied by a video and graphic explanations. The new knowledge arises from research lead by  University of San Francisco scientists who unraveled a genetic mystery embodied in a mutant mouse first noted by NIH researchers back in the 1940s. The mutant mouse was notable for a short, kinky  tail and a neck with an extra set of ribs. Back in the 1940s, the scientists lacked the tools needed to understand the mutation, but they kept breeding the mouse line, knowing the future should bring new analytic tools. 

As reported in Cell, the research team used today's new tools and the line of mutant mice to learn  that a cell component known as the ribosome has a heretofore unknown role in determining which proteins are produced by our cells, and how one missing protein could produce the mutations. The conclusions almost certainly apply to humans  because cells are cells. This is major science news because - until now -  the ribosome was known as simply a production machine that did not influence outcome. To learn that the ribosome may alter outcome is  fundamental and highly important new knowledge, as illustrated by Cell giving the paper so much coverage.  (Sad to day, it's far too easy to think of various newly-elected US Representatives, and envision an uninformed, budget-cutting  tea-partier deriding the research as "wasting money for over 60 years on trying to find out why some mice have kinky tails". )

Most scientists "get" the importance  of stem cells and wide-ranging research on their characteristics. Indeed, only a zealous few argue that their personal, "moral" beliefs are more important than scientific knowledge. Thus, national scientific research leaders actively opposed the injunction, and submitted evidence opposing the injunction, as described in this press release from the  University of California at San Francisco.  The comments illustrate  the point that research delays and injunctions are not abstract matters:

____________________________________________________ 

April 29, 2011

The U.S. Federal Court of Appeals has overturned an August 2010 ban on federal funding of embryonic stem cell research, paving the way for broader exploration of how stem cells function and how they can be harnessed to treat a wide range of currently incurable diseases

The ruling has been welcomed by the Obama Administration, which attempted to lift the ban in 2009, and by the nation’s top researchers in the field, including Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

“This is a victory not only for the scientists, but for the patients who are waiting for treatments and cures for terrible diseases,” Kriegstein said. “This ruling allows critical research to move forward, enabling scientists to compare human embryonic stem cells to other forms of stem cells, such as the cell lines which are derived from skin cells, and to pursue potentially life-saving therapies based on that research.”

Kriegstein said the ruling will make a significant difference for stem cell research in general, including at UCSF, where the majority of stem cell investigators receive some funding from the National Institutes of Health for their research, as well as from private sources and from the state. The ruling enables those scientists to integrate research from various funding sources, thereby more quickly addressing the causes and therapies for diseases.

Kriegstein was one of two University of California scientists to file a Declaration in September 2010 in support of the UC Board of Regents’ motion to intervene in the August lawsuit, Sherley v. Sebelius.

Sherly v. Sebelius had argued that when the Obama Administration lifted a ban on federal funding for the research in March 2009, it had violated the 1996 Dickey-Wicker Amendment which barred using taxpayer funds in research that destroyed embryos.

In response, a U.S. District Court judge temporarily ordered a ban on the use of federal money for the research until the court battle could be resolved.

The Appeals Court decision put the Dickey-Wicker question to rest, ruling that the amendment was “ambiguous” and that the NIH “seems reasonably to have concluded that although Dickey-Wicker bars funding for the destructive act of deriving an ESC (embryonic stem cell) from an embryo, it does not prohibit funding a research project in which an ESC will be used,” according to the 2-1 decision.

“I am very happy with this decision, although I am surprised that it wasn’t a unanimous vote,” Kriegstein said. “In my opinion, the evidence in favor of pursuing this research is overwhelming compared to the arguments submitted to stop the research.”

UCSF is one of two universities, along with the University of Wisconsin, that pioneered human embryonic stem cell research in the United States, beginning in the late 1990s.

UCSF has developed one of the largest programs in the nation, primarily funded by the California Institute for Regenerative Medicine, a voter-supported initiative that provided $3 billion to fund statewide research in lieu of federal funding for it. Funding from the NIH, private philanthropy and other state sources also have been critical for the program.

UCSF also launched the nation’s first stem cell PhD program in 2010, for which the first class already has been chosen and will begin in fall 2011.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For more information, visit www.ucsf.edu.

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Engineers are creating better software for managing massive amounts of information in visual form. ScienceDaily has the story on new tools created at the University of Wisconsin. Go here to see the tool in use via any of several examples, such as a journey through a real vein and really seeing plants grow. The vein video brings to mind the 1966 movie, Fantastic Voyage.  The body of science certainly has changed since then.

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News is out here and here on a paraplegic young man who is part of Geron's first clinical trial on injecting stem cells to try to aid recovery from a devastating spinal cord injury injury suffered in a car accident. There are some ironies in the story as well. Young TJ was injured on the anniversary of the birthday of actor Christopher Reeve who, as most know, became a stem cell advocate following his own devastating injuries. TJ also is part of a Baptist family leaving in the deep south, and the story recounts a religious side to the decision to proceed. Here's the science and hope part of the story:

Special teams trained

"After many delays, Geron finally persuaded the Food and Drug Administration last July to allow the company to study 10 patients. Geron spent months training special teams of doctors at seven secret sites around the country so that they could be ready to act quickly. The teams then had to wait for a patient who met the study’s strict criteria — someone who had been paralyzed from the chest down within the previous two weeks.

Surgeons planned to use specially designed equipment to infuse into the first patient’s spine about 2 million “oligodendrocyte progenitor” cells, which Geron scientists had created in the laboratory from embryonic stem cells obtained from days-old embryos left over from fertility treatments. The hope is that the cells will form a restorative sheath around the damaged spinal cord. In tests in hundreds of rats, partially paralyzed animals regained the ability to move, according to Geron."

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Lives can hang in the balance when reports are written to summarize the results of medical studies.  Sadly, some scientists do commit fraud, and others allow their conclusions to be skewed.  

A prime example of scientific fraud became public in 2000. Sadly, the fraud arose in the scientific literature on breast cancer treatments. In an editorial letter by  Dr. George W. Sledge, Jr., he explained the facts, and why "big lies" do indeed matter. He said:

"The facts of the case are straightforward. Werner Bezwoda is a South African clinical investigator who has in recent years presented 2 randomized trials comparing high-dose chemotherapy and autologous stem cell transplantation with standard-dose chemotherapy for patients with breast cancer. Both trials suggested a striking benefit of high-dose chemotherapy for both lymph node-positive and metastatic breast disease. One of these trials was considered sufficiently important to earn Dr. Bezwoda a plenary session lecture at the annual meeting of the American Society of Clinical Oncology. Because of the importance of these results, their striking positivity, and because of differences in the way in which transplant therapy was delivered, American investigators wished to examine Dr. Bezwoda's work before launching a confirmatory trial. Dr. Bezwoda's work was (after some delay) audited by a group of American physicians. The audit team discovered significant failings in Dr. Bezwoda's records, sufficient to raise the question of academic fraud. Dr. Bezwoda, in a letter, has admitted committing this fraud.^"

See Sledge GW. Why Big Lies Matter: Lessons From the Bezwoda Affair. MedGenMed 2(1), 2000. [formerly published in Medscape Women's Health eJournal 5(1), 2000]. Available at: http://www.medscape.com/viewarticle/408908.

In view of past fraud, scholars continue to worry about disclosures of financial interest information when scientific research projects and papers are sponsored by private usiness. A new article,  reported in ScienceDaily,  and published in the AMA Journal,  focuses the discussion on meta-analyses. Meta studies are in esssence massive studies created by combining data from individual studies. The researchers found that financial linterest disclosures from the individual are not being reported in many meta-analyses.

In this age of cheap information creation and storage, it seems unfortunate that disclosure are not routinely made and tracked. One hopes the funding source has no impact on the research outcome or the form of the report. But it seems unwise to depend only on hope, and better  to provide the disclosures as matter of routine. In the past, the AMA has been out in front in terms if requiring dislcosure for articles it publishes in JAMA, as is illustrated by this 2001 statement of its policy. Perhaps this new article will have a further, positive impact on disclosures.

Set out below are key excerpts from the disheartening story in the ScienceDaily summary:

 " More and more, policy decisions and what medications doctors prescribe for their patients are being driven by large "studies of studies," called meta-analyses, which statistically combine results from many individual drug trials.

Led by Dr. Brett Thombs and McGill graduate student Michelle Roseman, the team found that important declarations of financial conflicts-of-interest in individual drug trials disappeared when those studies were combined in meta-analyses. Their results will be published in the March 9 issue of the Journal of the American Medical Association (JAMA).

Roseman, the study's first author, and the rest of the team reviewed 29 recent meta-analyses on a range of drug treatments published in high-impact medical journals. Those 29 meta-analyses, or "studies of studies," included results from 509 drug trials. The team documented the funding sources and author-industry financial ties of all 509 trials and whether or not the meta-analyses noted who had funded the trials.

"Only 2 of the 29 meta-analyses even mentioned the issue of who funded the original drug trials, and even those 2 did it in very obscure places in the published articles," said Thombs, a psychologist and assistant professor in the Department of Psychiatry at McGill University. "Not one of the meta-analyses mentioned whether researchers who conducted the trials were employed by industry or personally received money from industry."

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Formaldehyde.  IARC and now EPA have deemed it a "known carcinogen."  Go here for a collection of EPA's work on formaldehyde.

The reaction? Chemical companies and others are worried.  Proof? See below from theAmerican Conference Institute - the conference presenters work hard to stay ahead of the curve.

American Conference Institute's  
2^nd National Forum on
Chemical Products Liability & Environmental Litigation
Develop cost-effective defense strategies and adapt to constantly
evolving scientific standards, technologies, and regulations
April 27 - 28, 2011 | Sutton Place Hotel | Chicago, Illinois

OVERVIEW    SPEAKER FACULTY     DOWNLOAD PDF AGENDA     REGISTER NOW    

Attend unique and cutting-edge master classes accompanying
ACI's 2^nd National Forum on Chemical Products Liability and Environmental Litigation 

Formaldehyde exposure cases are predicted to become as prolific as benzene litigation.  Recent studies have linked formaldehyde exposure to rare forms of cancer, the EPA has indicated that formaldehyde is a known human carcinogen (in its Toxicological Review of Formaldehyde Inhalation Assessment: In Support of Summary Information on the Integrated Risk Information System [IRIS] ), and a wave of litigation is all but imminent.  Prepare yourself by attending the unique master class dedicated to understanding the science of formaldehyde, exposure pathways, and possible defense scenarios.  This invaluable session, led by Lawrence Riff, a leading toxic tort litigator at Steptoe & Johnson, Dr. Jonathan Whysner, a preeminent medical toxicologist at Columbia University, and Steven Washburn, CEO of the environmental consulting firm Environ, will keep you one step ahead of the rest as this exciting field of litigation develops. 

In addition, prepare for R.E.A.C.H. requirements in the U.S.  EPA under the Obama Administration has been vigorously enhancing chemical regulations and labeling requirements.  TSCA reform is fully underway and it is only a matter of time before the stringent EU standards are mirrored in the U.S.  Attend this master class and learn to navigate the statutory framework of R.E.A.C.H. as ExxonMobil's Ted Ray and Fulbright & Jaworski's Jeff Margulies draw on parallels currently being implemented in the U.S. (CA's Green Chemistry Initiative) and abroad.

Gain the edge you need over your competition and maximize your benefit from the Chemical Products conference; attend the post-conference master classes to learn about cutting edge litigation trends and international requirements that affect companies in the U.S.

At the main conference, meet, network, and learn from the nation's leading in-house counsel from 13 of the top chemical, oil, and gas companies, includingAkzoNobel, Chevron, Dow AgroSciences, Dow Chemical Co., DuPont, ExxonMobil, Georgia Gulf Corp., Occidental Chemical, PPG Industries, Praxair, Sunoco, Shell Oil, and Solvay North America , who will participate on two separate panels tackling issues such as controlling litigation costs and resolving discovery challenges.  The esteemed in-house participants will also be joining outside counsel experts on numerous substantive panels. 

___________________________________________________________________________

How are these effects being found? Old ways and new ways. For some insights into new ways, consider this abstract from a January 2011 medical journal article on disease in exposed workers.

"Formaldehyde, classified by the IARC as carcinogenic in humans and experimental animals, is a chemical agent that is widely used in histopathology laboratories. The exposure to this substance is epidemiologically linked to cancer and to nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it provides information on several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomere fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA. The aim of this study is to compare the frequency of genotoxicity biomarkers, provided by the CBMN assay in peripheral lymphocytes and the MN test in buccal cells, between individuals occupationally exposed and non-exposed to formaldehyde and other environmental factors, namely tobacco and alcohol consumption. The sample comprised two groups: 56 individuals occupationally exposed to formaldehyde (cases) and 85 unexposed individuals (controls), from whom both peripheral blood and exfoliated epithelial cells of the oral mucosa were collected in order to measure the genetic endpoints proposed in this study. The mean level of TWA8h was 0.16 ± 0.11 ppm (<detection limit until 0.51 ppm) and the mean of ceiling values was 1.14 ± 0.74 ppm (0.18–2.93 ppm). All genotoxicity biomarkers showed significant increases in exposed workers in comparison with controls (Mann–Whitney test, p < 0.002) and the analysis of confounding factors showed that there were no differences between genders. As for age, only the mean MN frequency in lymphocytes was found significantly higher in elderly people among the exposed groups (p = 0.006), and there was also evidence of an interaction between age and gender with regards to that biomarker in those exposed. Smoking habits did not influence the frequency of the biomarkers, whereas alcohol consumption only influenced the MN frequency in lymphocytes in controls (p = 0.011), with drinkers showing higher mean values. These results provide evidence of the association between occupational exposure to formaldehyde and the presence of genotoxicity biomarkers."

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President Obama and others argue that better science will save time, money, and lives. Some doubt the argument, but it's true.  Here's a promising example that popped up this past week. It's this March 4 ScienceDaily article on successful use of ultrasound and computer algorithms to distinguish between benign and malignant masses in the breast. The new technique appears to be much easier for the woman, as well as being cheaper,faster and safer than conventional approaches.                                                                                           The method draws heavily from today's strong computer power. Key parts of the  article are pasted below, but it’s well worth a full read for both the science and some insight into the changes being brought by today’s computing power and creative thinking by a bright PhD student.

"ScienceDaily (Mar. 4, 2011) — Recent research by doctoral student Sevan Goenezen holds the promise of becoming a powerful new weapon in the fight against breast cancer. His complex computational research has led to a fast, inexpensive new method for using ultrasound and advanced algorithms to differentiate between benign and malignant tumors with a high degree of accuracy.

***

Goenezen's research offers the hope of dramatically reducing the need for invasive, uncomfortable, and stress-inducing biopsies, and perhaps even replacing mammograms. It uses a new technique to analyze images captured with a noninvasive, radiation-free ultrasound device, locate tumors, and determine if the tumor is malignant. The only required equipment is a specific type of ultrasound machine -- which generally costs around $10,000, far less than X-ray equipment -- and a common personal computer. Thanks to these new algorithms, results can be computed in less than five minutes on a high-end PC.

This new technique uses ultrasound images of breast tissue to infer the mechanical properties of the tissue as it is compressed. The structure of collagen fibers within malignant tissues is very different from the collagen fiber structure in benign tissue. This method quantifies the non-linear behavior of the tumor tissue to determine whether it is cancerous.

In a clinical study, Goenezen used this strategy to analyze 10 data sets, five of which were from patients with benign tumors, and five with malignant tumors. The system correctly diagnosed nine out of the 10 patients. The lone error was a false positive, meaning the system indicated the tumor was malignant when it was actually benign."

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After eight years of President Bush blocking and denying science, current threats to science arise from tea partiers who offer mindless budget cutting generalities,  sometimes supplemented by bible thumping.  And, some offer  tax subsidies for cheap, local manufacturing, but that is not a viable long term strategy for our nation. Why? Because more and more manufacturing will be accomplished  by robots and manufacturing  "printers" that build new devices layer by layer from digital plans. Indeed, the latter  earned the February 10, 2011 cover story on the Economist (see Print me a Stradivarius). For a more local example, get a high-tech dentist and ask to watch your next dental crown being made by a mini-machine that whirs into action based on digital images of your tooth. Or, read about it here at CAD-CAM dentistry on Wikipedia.

We were not always a manufacturing nation. Indeed, we were once agrarians. Thing changed, and our nation grew and prospered. Now, society here is changing again. We are no longer the best and cheapest to make things. So, where should we be going?  Where do we have to be going?

Forward. Through science. New knowledge, new jobs, and knowledge-based products we do not yet have or even imagine. New products such as monoclonal antibodies that block diseases. They can save lives, create jobs, and reduce health care costs.

Happily, President and Mrs. Obama "get" and support the value of science. Accordingly, the President's budget promotes science and basic research. Specifics are provided by an  OMB statement that  is here on the White House website. Some key quotes are below; hat tip to Patent Docs for flagging the statement.

 Support Biomedical Research at the National Institutes of Health. The Budget includes $32 billion for basic and applied biomedical research supported by the National Institutes of Health (NIH). Innovation in this field creates and sustains companies, products, and jobs.  Through implementation of the National Center for Advancing Translational Sciences and the Cures Acceleration Network, NIH will increase its focus on bridging the translational divide between basic science and therapeutic applications. By fostering novel collaborations among government, academia, and industry, NIH will accelerate the development of treatments for diseases and disorders that affect millions of Americans. NIH will continue to pursue the leading edge of discovery in basic cancer science, development of new cancer treatments, and prevention and early detection of cancer, focusing on recent discoveries regarding cancer genomes. For Alzheimer’s disease, NIH is partnering with the private sector to find new methods for early diagnosis and to support early drug discovery and preclinical drug development. Ongoing research into environmental factors, early detection, and novel treatments will transform our understanding and care for those with autism spectrum disorders.

Increase Investment in Research and Development and Create Transformational Technologies. For many years, the United States has been a world leader in research and development (R&D) spending, as well as in the quality and impact of that spending. The challenge is for the Nation to make private and public investments in science, research and development that will keep the U.S. as the world’s leader in innovation for decades to come. The 2012 Budget does that by providing $148 billion for R&D overall, while targeting resources to those areas most likely to directly contribute to the creation of transformational technologies that can create the businesses and jobs of the future. The Budget makes progress toward the President’s commitment to double funding for key basic research agencies: the National Science Foundation (NSF), the Department of Energy’s Office of Science, and the National Institute of Standards and Technology (NIST) laboratories. These funds will be directed at priority areas, such as clean energy technologies, advanced manufacturing technologies, and cyber security. In addition, the Budget provides $12 million in NIST for the Advanced Manufacturing Technology Consortia program, a new public-private partnership that will develop road maps for long-term industrial research needs and fund research at universities, government laboratories, and businesses directed at meeting those needs.  The Budget also funds research at the National Institutes of Health with an increased focus on translating research discovering into clinical trials. These funds will directed at priority areas, such as clean energy technologies, advanced manufacturing technologies, and cyber security. The Budget also funds research at the National Institutes of Health with an increased focus on translating research discovering into clinical trials.

 Prepare 100,000 STEM Teachers over the Next Decade. Students need to master science, technology, engineering, and mathematics (STEM) in order to thrive in the 21st Century economy. Steadily, we have seen other nations gain ground in preparing their children in these critical fields. That is why the President has set the ambitious goal of preparing 100,000 STEM teachers over the next decade, and recruiting 10,000 STEM teachers over the next two years. The Budget allocates $100 million toward that goal, including $80 million from the Department of Education dedicated to teacher pathways that successfully prepare effective STEM teachers and $20 million from the National Science Foundation (NSF) to launch a new teacher-training research program called Teacher Learning for the Future. In cooperation with the Department of Education, NSF's Teacher Learning for the Future program will fund innovative efforts that design, develop, implement, and test new teacher-training programs. These programs will be developed in conjunction with a government-wide effort to improve the impact of Federal investments in math and science education by ensuring that all programs supporting K-12 and undergraduate education adhere to consistent standards of effectiveness.

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Over the last couple of days, Chicago received 15-20 inches of snow from a massive storm spread across most of North America. For some great s images of its breadth, go here or here. For the very local view of my front entry, see above. Happily, the snow is really not a big deal for the well since our area has plenty of snow plows that work wonders if everyone has the brains to stay ofdf the roads for a day.

The storm here is a lightweight to cyclone Yasi that hit Australia with 155 mph winds. Go here for stunning images from the satellites, and more data than any one human can digest. Australia certainly has had a tough 2011 weather-wise.

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Science continues to push ahead, and a recent example illustrates some of what lies ahead.   Many  (but not all) tort law rules include some element of proof focused on the foreseeability of the harm caused by a product. That may seem simple when one is considering a shovel, for example. But when the products interact at the cellular level, the complexities are greater. And, more and more, lawyers are going to need to understand to understand chemistry and biology.

The latest example from science? Thanks to researchers at Children's Hospital Boston Informatics Program (CHIPS), there is new software aimed at predicting when drugs will disrupt the function of the reproductive system.  ScienceDaily has the full story here. Here are key excerpts:

The model, described in the March 2011 issue of Reproductive Toxicology (published online in November), used bioinformatics and public databases to profile 619 drugs already assigned to a pregnancy risk class, and whose target genes or proteins are known. For each of the genes targeted, 7426 in all, CHIP investigators Asher Schachter, MD, MMSc, MS, and Isaac Kohane, MD, PhD, crunched databases to identify genes involved in biological processes related to fetal development, looking for telltale search terms like "genesis," "develop," "differentiate" or "growth."

The researchers found that drugs targeting a large proportion of genes associated with fetal development tended to be in the higher risk classes. Based on the developmental gene profile, they created a model that showed 79 percent accuracy in predicting whether a drug would be in Class A (safest) or Class X (known teratogen).

Conclusion ? Tremendous change is ahead. Perhaps more aspiring lawyers will spend undergraduate days or other time learning biology, and much more. Who knows - maybe it will become common to see law schools focus on science, or team with other graduate schools to offer combined  programs.

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Hope

Philosophers say it's essential. Respected universities now teach positive psychology, and papers suggest it works.

Where do humans find hope ? There are, of course, multiple sources, including the mystical. But for many, genuine hope flows primarily from science.  Hope is the possibility of finding less brutal treatments to  buy more time for cancer patients. Hope is the possibility of understanding genes, epigenomes and proteins. Hope is the possibility of understanding, or at least managing, the myriad diseases which inflict so much suffering.

The tight ties between science and hope are exemplified by Dr. Jonas Salk, certainly a legendary figure in science. Although he once was leaning towards law,  Dr. Salk changed course, moved into science, and then went on to drive the creation of the polio vaccine which bears his name. In addition, Dr. Salk joined with others (such as  Frances Crick of DNA fame), to found one of the world's great research institutes, The Salk Institute for Biological Studies.  On walking into this bastion of science, located in a minimalist and stunning complex on the Pacific seacoast, the eye is drawn to an inscribed message of hope. The message is one of Dr. Salk's more famous quotes.  The message from Dr. Salk to his fellow scientists ?

"Hope lies in dreams, in imagination and in the courage of those who dare to make dreams into reality."

Let''s hope that 2011 brings a much greater voice for science, and much less attention to the religious extremists who condemn others to death and suffering by prohibiting various forms of the science that is hope.  Let's hope our nation and the world actually provide ample funds and praise for the brave,  smart and compassionate souls who work in labs, hospitals and clinics to find answers, to blunt suffering, and to provide continued life.  And, let's hope we invest in the  economic reality that  science and hope can and do create new industries and jobs.   

Is there reason for real hope that that 2011 will bring a greater voice for science ? Yes.  Increasingly, scientists are explicitly calling for speaking out on matters of science and policy. Examples? Consider this Nature editorial  which named scientist  Jane Lubchenco as Newsmaker of the Year for her role in bringing science to bear on the Gulf oil rig fiasco. Here are key excerpts:

"The United States could do with more scientists like Lubchenco, with the skills and the dedication to speak out on issues that matter. The need will be particularly acute next year, when the Republican Party takes over the US House of Representatives. Although Republicans have generally supported basic science, incoming House leaders have made it clear that they are hostile to certain areas of research. Some have pledged to hold hearings on climate science, which they argue is seriously flawed and has overstated the evidence for global warming. Adrian Smith (Republican, Nebraska) introduced the YouCut Citizen Review, which calls on the US public to search the National Science Foundation website list of peer-reviewed grants for those they consider wasteful. And Darrell Issa (Republican, California), the incoming head of the powerful Committee on Oversight and Government Reform, last year led an effort to revoke funding from the National Institutes of Health for studies of substance abuse and HIV risk in other countries (see Nature 460, 667; 2009).

Scientific leaders in the United States must stand up against such attacks. As a first step, they should try to meet with incoming House members from both parties to voice their concerns and explain the rationale behind research in controversial areas. Recognizing that all politics is local, scientists will need to make clear why climate change or HIV research matters for the communities represented by members of Congress. They should take along science-savvy business leaders and locally elected officials to help make their case.

____________________________________________________________________

Best wishes to all for a New Year of peace, joy, love and hope !

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The Economist recently teed off on the foolishness of trying to suppress embryonic stem cell research. Such a shame that church and conservative "leaders" can't figure out that their  vague abstractions are sentencing people to deaths and misery that perhaps could  be made avoidable.  

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Nature compiled this series of great images from science in 2010. My favorite, of course, is a photo of the Hartley 2 comet which streaked the Milky Way this past year, as described by Wikipedia.

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Epigenetics.

What is it? It's a part of science which is going to matter to tort lawyers. In short, it's what we presently label as the control system which can alter the instructions programmed into our genes. 

Why does it matter? Because alterations to the epigenome can alter the behavior of the genome, producing, for example, extreme changes (e.g. cancers; see this Nature article on melanomas) and more subtle changes (coloration; obesity). Of significance, the alterations are at least sometimes marked and observable at the cellular level. Imagine what these markers can do for toxic tort litigation and insurance coverage issues.

The changes wrought by epigenomic changes may be multi-generational. Examples ?  Consider  this December 2010 Nature article by Farooq Ahmed which describes in lay terms how starvation of parents appears to have altered genomes for their children.  Or take a look at this Nature article by Anna Petherick on how the contents of breast milk in mammals differ throughout nursing.  Or this Nature article on the emerging science of "nutrigenomics." For something much darker, note this Time article on research suggesting that the stresses induced by the Nazi have caused genetic changes in children of the parents who were tortured. 

For more on epignetics in general,  this Time article from late 2009 marked the first wide mapping of a part of the human epigenome by Salk Lab scientists, as reported here in Nature. Or, enjoy this January 2010 John Cloud article in Time,  titled  Why Your DNA Isn't Your Destiny. The article includes helpful illustrations.

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Nature is the source for this new article reporting success in turning stem cells into small, three dimensional structures much like the basics of human intestinal tissues. To get to that point, the researchers used various growth factors believed to be involved in signaling inside human cells. ScienceDaily has the story here.

Hard to believe some people still oppose unlimited stem cell research.  

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The holidays are here. For too many children, the days and nights will be spent in hospital beds while their bodies, their families and their doctors try to stave off or control leukemias, lymphomas and other cancers.  Their journey is daunting. Go here to read about how some cope through Beads of Courage.  The gist? Set out below  is the synopsis provided by Dr. Wendy Harpham, a doctor, blogger and long-time cancer survivor who writes brief but powerful  posts On Healthy Survivorship.

"Children make bead necklaces, where each bead represents one challenge they've overcome. So, for example, a white bead represents a chemo treatment and a red bead a transfusion. Children have beads for losing their hair, having surgery, undergoing bone-marrow biopsies, and so on."

If you have the courage, go here to see a 7 minute video of the children who earn Beads of Courage. Moved? You can click here to join the Leukemia and Lymphoma Society in asking Congress to increase funding for cancer research. Today, the National Cancer Institute's budget is $ 5 billion.  That's less than 1% of the over  well over  $ 600 billion the US  annually spends on defense even though cancer kills far more people than do wars. In fact, cancer kills 500,000 Americans each year.

Click here to read the great science the NCI would like to invest in with an addtional $ 2 billion. What better investments are possible when children are dying, and we as a society need to greatly reduce the human and financial costs of cancer? 

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 The power of widely shared information has been very much in the news this week thanks to the Manning/WikiLeak' disclosures of US government documents.  So, this seems like a good time for a new example of how much  it matters that today's scientific tools and  computers generate incredible amounts of information  which can can be shared globally in a virtual instant in open access databases filled with tens of millions of datapoints generated from locations around the world.  Here's what some scientists said with respect to recent discoveries described in this website release, which is summarized here in ScienceDaily:

"These discoveries were only possible thanks to the collaboration of a large team of scientists with expertise in different disciplines from around the world," emphasizes Dr. Melnick, "and thanks to an unusual alliance between multicenter clinical trials groups from Europe and the United States. This spirit of cooperation allowed for the collection and analysis of the massive genomic datasets required for these discoveries to be made. Working together, it will be possible to accelerate the pace of discovery and development of better treatments."

How did they make the discoveries ?

"The large-scale, international, collaborative research effort scrutinized the genomes of 750 AML patients from the United States and Europe for chemical clues to better understand how leukemia arises from normal bone marrow cells. Using computational tools to sift through millions of data points, they discovered a unique chemical signature in the genomes of patients with mutations in either of two enzymes called IDH1 and IDH2, which occur frequently in AML."

What was discovered by this global group of doctors and researchers from prestigious universities, and authors of this article in the heavyweight journal, Cancer Cell ?    An unexpected  new insight into casuation for one of the many vicious leukemias that kill tens of thousands of people every year, when counted on a global scale. And, the insight likely applies to other types of cancer.

NEW YORK (Dec. 2, 2010) — There is new hope for people with acute myelogenous leukemia (AML), a fast-growing cancer of the blood and bone marrow. Research led by Weill Cornell Medical College and published today in the online edition of the journal Cancer Cell reveals a surprising and unexpected cancer-causing mechanism. The investigators discovered that newly identified mutant enzymes in AML create a chemical poison to cause leukemia. Their findings should prove useful in treating patients by providing a molecular target against which to develop new drugs against one subset of AML as well as other cancers.

What is the signficance of the finding ?  It proves that the our genetic variations are subject to profound further epigenetic differences created, at least often, by environmental sources. Click here for the full scientific summary of the signficance of the study.

How much does environment matter? It's huge, at least in some cases.  Proof ? Read this summary of an elegantly simple but powerful experiment in which varying environments lead to to  widely different outcomes for a simple yeast with four main genetic variations.

And, to close, what did they do with the paper and the data. The paper is sitting on the web here, widely and freely accessible. And, the article materials include this link  to help others find and use all the data  in this free online resource. 

The value of setting information free for sharing ? Beyond measure, and growing every day.

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Much of our future lies in science. Accordingly, as a fan of the University of Illinois (see below) and science,  it was great to see the following news regarding the U of I taking on another  role in pushing science forward. How ?  By entering into a long-term partnership with the Science Olympiad. What is the that? It's a national program that encourages and provides real opportunities and scholarships for kids interested in science. The news is set out below, and is posted here: 

 Chicago-Based Science Education Non-Profit is Largest Team Science Competition in the United States; University of Illinois Ranked Top Ten in Science and Engineering 

CHICAGO, November 18, 2010 -- University of Illinois at Urbana-Champaign (UIUC), one of 

the leading science and engineering institutions in the United States and nationally-recognized 

Science Olympiad have announced a long-term partnership. Science Olympiad is a 27-year-old 

national science competition that focuses on student teams working together on science, 

technology, engineering and math (STEM) challenges. Aligned to the National Science Education 

Standards developed by the National Research Council, Science Olympiad’s broad scope of 

events touch every letter in STEM. 

"We are honored to partner with the University of Illinois," said Dr. Gerard Putz, Science 

Olympiad co-founder and president.  "Its commitment to the on-campus I-STEM Education 

Initiative mirrors Science Olympiad's mission to connect K-12 STEM learning, higher education 

and workforce development.  This partnership secures a rock-solid foundation for Science 

Olympiad moving forward." 

The merger will employ a three-year transition period during which I-STEM and UIUC will work 

closely with Science Olympiad to increase staffing and programs. After the 2013 National 

Tournament, Science Olympiad’s national operations will be housed on the UIUC campus, and in 

2014, the University of Illinois plans to host the 30th Anniversary of the Science Olympiad 

National Tournament. In 2010, UIUC offered 62 gold medal winners in the high school division 

of the Science Olympiad National Tournament a four-year, full-ride tuition waiver, valued at 

more than $100,000 each. 

A key highlight of the merger is the formation of the Science Olympiad Endowment at the 

University of Illinois Foundation, which will be devoted to serving the philanthropic, service- 

oriented goals of Science Olympiad. Major priorities include: 

• Awarding grants to communities for Urban and Rural Schools Initiatives 

• Awarding grants and professional development to state Science Olympiad organizations 

• Providing scholarships or fellowships to Science Olympiad Alumni Association members 

Click here to go the ScienceOlympiad website; a basic summary is set out below.

WHAT IS SCIENCE OLYMPIAD? 

Science Olympiad is an international non-profit organization devoted to improving the quality of science education, increasing student interest in science and providing recognition for outstanding achievement in science education by both students and teachers. These goals are accomplished through classroom activities, research, training workshops and the encouragement of intramural, district, regional, state and national tournaments. Science Olympiad tournaments are rigorous academic interscholastic competitions that consist of a series of team events, which students prepare for during the year. These challenging and motivational events are well balanced between the various science disciplines of biology, earth science, chemistry, physics and technology. There is also a balance between events requiring knowledge of science concepts, process skills and science applications. In addition, during the day there are open house activities that consist of science and mathematics demonstrations, activities and career counseling sessions conducted by professors and scientists at the host institution occurring concurrently with the events.

Many states and regions have organized physics, biology or chemistry competitions, but few have combined all disciplines in one large Science Olympiad. The excitement of many students from all science areas competing and cheering one another on to greater learning caused one school district to coin the phrase "intellete". When they searched for a place to house their newly won Science Olympiad State Championship trophy, the only location available was outside the principal's office in the "athlete" showcase, so they convinced the school board to build an "intellete" showcase. One of the goals of the Science Olympiad is to elevate science education and learning to a level of enthusiasm and support that is normally reserved only for varsity sports programs.

Please forgive today's boosterism for the University of Illinois and science. The roots for it lie in my University of Illinois heritage and great pride in the school. I grew up in Champaign-Urbana,  hometown of  the U of I's main campus, and lived on campus while obtaining my undergrad degree in business in 1980. ( My high school science teacher managed to make science boring for me, hence the business degree.)  The roots also run deeper. Dad was engineering professor at the U of I, and Mom was a senior administrative assistant to various senior administrators. My sister is a molecular biologist who earned her bio degree from the U of I and then moved west to work with the great researchers at Salk Labs. My brother is a U of I trained engineer/businessperson with a major international manufacturing business. 

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Just in time for Thanksgiving, a new scientific first arrives in the form of a breakthrough in cancer research tools. The gist ? Scientists have now figured out a way to transform ordinary human tissue into a  tumor growing in a dish. Result ? A strong possibility that potential cancer-treatment agents can be quickly tested and watched in the dish, with results observable in days instead of the months normally needed for animal studies. 

For people with cancer now,  days matter. That's surely one reason why the research is published  in Nature Medicine, one of the world's leading scientific journals.

Key excerpts are set out below from this summary article in ScienceDaily. The Nature Medicine abstract is here.

"Researchers at the Stanford University School of Medicine have successfully transformed normal human tissue into three-dimensional cancers in a tissue culture dish for the first time. Watching how the cells behave as they divide and invade surrounding tissue will help physicians better understand how human cancers act in the body. The new technique also provides a way to quickly and cheaply test anti-cancer drugs without requiring laboratory animals."

***

Studies of this type, which used to take months in animal models, can now occur on a time scale of days," said Paul Khavari, MD, PhD, the Carl J. Herzog Professor and chair of dermatology at Stanford. The researchers focused on epithelial cells, which line the surfaces and cavities of the body. Cancers of epithelial cells make up approximately 90 percent of all human cancers.

***

 The researchers took advantage of their new "tumor-in-a-dish" model to test 20 new experimental anti-cancer drugs. Many of these drugs cannot be easily tested in animals because they are difficult to administer and may be toxic in their current form. But Khavari and Ridky were able to quickly home in on three promising candidates that stopped the altered epithelial cells from invading through the membrane. While the drugs will still have to be optimized for testing in animals, this type of pre-screening allows researchers to narrow down the possibilities.

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In view of the current controversy about patents for simply describing a gene, it's especially interesting to read a tribute written by former students of a great scientist with a major interest in the how and why of   hematopoietic stem cells. Hematopoietic stem cells are the stem cells that create all the blood cells needed to live.  

Judging by this tribute in the scholarly journal titled Human Gene Therapy, Dr. Wolfram Ostertag was quite a scientist and inspirational leader who made profound contributions as a scientist and a leader for young scientists.  Another tribute article is here, and notes that he was first published in Science at age 21. That's akin to arguing to the Supreme Court at age 21. 

Dr. Ostertag also declined to obtain a patent for findings now used to help block AIDS. Set out below is a key excerpt from the tribute. As to his work on AZT,  it appears it was but a small part of his life's work. The entire tribute is well worth reading  to gain some insights into how and why great scientists lead.  

"Almost forgotten but highly remarkable is his important role in the discovery of the antiretroviral activity of azidothymidine (AZT) (Ostertag et al., 1974; Dube and Ostertag, 1991). Back in 1974, he found that AZT inhibits the replication of murine leukemia virus, his preferred genetic tool since the early 1970s. From an economic perspective, it may have been his greatest mistake not to have patented this discovery, which occurred many years before HIV emerged as a new plague of human existence. Work started in his department has led to the development of highly efficient genetic principles to block the entry of HIV into cells (Hildinger et al., 2001)."

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The NYT's Erik Olsen compiled this wonderful on line article explaining and compiling examples of work from  the burgeoning world of molecular animation. It's how ideas and reams of data come to life and become manageable. The article includes multiple links to great animations, and identifies leaders in the field. The videos are great; make sure to check out The Inner Life of the Cell, which will take you to, of all places, You Tube.  While  there, look at some of the other similar videos that pop up.

Animations for accidents are now courtroom staples. Imagine tomorrow when a lawyer can use a video to demonstrate how a toxin destroys cells or alters genes. Remote concepts will become far simpler when they look like Pac Men. Defendants will have to counter. 

Tomorrow's trials will be very cool.

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Wonderful news. Our government has seen the light, and now opposes patents for simply reporting the structure of genes.  Bravo for the Obama Administration. Courtesy of the NYT, here is the link to Justice's brief, filed Friday.  The NYT article is here, by Andrew Pollack. 

As I've argued before in this post, patents for reporting gene structures are improper and need to be eliminated because they are simply a report of facts. So, in my view, this policy decision is great news for cancer patients who need science to move faster. Clearing out patents inevitably will  speed up genomic research.  On the other hand, some will wring their hands, but wrongly. Scientists and businesses with a real long term interest in a science subject can apply and leverage their knowledge over years because they are experts. The news, however, is not good for raw capitalists who simply want to buy an asset (a patent), and milk it for multiples of earnings. That's not a real loss. That's the kind of short-term thinking that produced CDOs and other poor financial products.

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The promise of actually putting stem cells to work continues to draw closer.  ScienceDaily and Cell Stem Cell very cool graphics explaining the conclusion) bring the news that Karolinska Institute scientists headed up a global group of researchers who  have now used genetic fate mapping to follow some parts of the actual path of stem cell activity after traumatic injuries to the spine. The Cell Stem Cell link above connects with a very cool graphic explanation of the process. In words, Karolinska's press release explains the conclusion as follows: 

"The research group has identified a type of stem cell, called an ependymal cell, in the spinal cord. They show that these cells are inactive in the healthy spinal cord, and that the cell formation that takes place does so mainly through the division of more mature cells. When the spinal cord is injured, however, these stem cells are activated to become the dominant source of new cells.

The stem cells then give rise to cells that form scar tissue and to a type of support cell that is an important component of spinal cord functionality. The scientists also show that a certain family of mature cells known as astrocytes produce large numbers of scar-forming cells after injury.

"The stem cells have a certain positive effect following injury, but not enough for spinal cord functionality to be restored," says Jonas Frisén. "One interesting question now is whether pharmaceutical compounds can be identified to stimulate the cells to form more support cells in order to improve functional recovery after a spinal trauma."

The Karolinska Institute is a major Swedish medical center; its nonresearch activities include selecting the annual Nobel Prize winner for medicine. The Karolinska press release is here. The abstract is here.

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Scientists are now another important step down the line towards creating useful pluripotent stem cells from skin cells. This research unfortunately is required because of the embryonic stem cell research restrictions imposed by persons who think their religious abstractions are more important than saving lives. (The mind still reels at trying to understand the moral compass  of the churches and individuals who insist their abstractions are more important than the lives of other human beings.)    

The gist of the research is that Boston scientists found a way to use messenger RNA to transform  skin cells into iPSCs (induced pluripotent stem cells). This method stands in contrast to other, harsher and less efficient methods. The September 30 research was reported here in ScienceDaily. The research is published here in a prestigious journal, Cell Stem Cell, and was published on an expedited basis. The research result  is indeed great news.

Unfortunately, great news also makes for great distortion. The conservative Washington Post reported the research here under a headline suggesting that original stem cells are now moot (“Scientists overcome hurdles to stem cell alternatives”). The same article also included a strong quote from an advocate for restricting stem research, Richard M. Doerflinger of the U.S. Conference of Catholic Bishops.

As usual, Mr. Doerflinger’s opinion is a religious view, and not a scientific view. This progress is not THE answer for the future. Indeed, if one goes  deeper into the article, it makes fairly plain that this is a  positive – but far from  final step – in going around the laws imposed by moral dictators who care so little for people who might benefit from stem cell treatments. Thus, the article states:

"Rossi and other researchers, however, said that embryonic stem cells are still crucial because, among other things, they remain irreplaceable for evaluating alternatives.

The new report provides a substantial advance," said National Institutes of Health Director Francis S. Collins. "But this research in no way reduces the importance of comparing the resulting iPS cells to human embryonic stem cells. Previous research has shown that iPS cells retain some memory of their tissue of origin, which may have important implications for their use in therapeutics. To explore these important potential differences, iPS research must continue to be conducted side by side with human embryonic cell research." (emphasis added).

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For years, scientists involved in "toxic tort" cases focused mainly on the dose, and less so on the timing and volume of particular doses. Accordingly, toxic tort lawyers focused in the same places with respect to "exposure" to alleged toxins.However, the focus on overall dose can be misleading. Indeed, today, more and more science focuses on the timing of the dose, and the volume of a particular dose.

Consider, for example, DES given to pregnant mothers. The lesson learned from DES is that the adverse consequences of DES use were significantly worse when the drug was taken during the first trimester, as illustrated by this study of "DES sons."  

The same principle also applies to some medical treatments. Thus,ScienceDaily today brings an example from the treatment of lupus. For years, the standard of care was to provide intravenous steroids, followed by monthly high doses. Now, however, cellular level research is suggesting that the standard of care may we ll be wrong. Instead, the better treatment may be more frequent, high doses when the disease first appears. 

Why ? Apparently the higher, earlier doses do a better job of killing the cells causing the disease symptoms. Thus, the article explains:

"They found that pulse doses of intravenous steroids kill off the cells -- called plasmacytoid dendritic cells -- producing interferon alpha, a protein that promotes this inflammation. Oral corticosteroids given at much lower doses did not have this effect.

"Now we have the biological rationale for why pulsing is often more effective than standard therapy," said Dr. Tracey Wright, assistant professor of pediatrics at UT Southwestern and another study co-author."

 Conclusion?  Both lawyers  and scientists need to remember to test old assumptions and beliefs.

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Wow !  This article from the Howard Hughes Institute explains - and shows images from - new microscopes that can watch and record the evolution of life as cells begin dividing at moment one. This technology did not exist two years ago, but now it exists and works well.  Go here to see video of the process, and video generated from the process.

According to the article, this technology will soon be commercially available. Imagine the uses. One might be to compare the evolution of creatures with and without genetic damage. Who will need epidemiology if cause and effect can be osberved and recorded ?

Here are key excerpts:

"Using the new set-up, Keller’s team captured zebrafish development for 58 hours, generating a microscopy data set that comprises one million high-resolution images, as well as early development of a fly embryo. Reconstructing cell positions in the live fly recording by automated computer algorithms allowed the scientist to create a Digital Fly Embryo. It will be easy to implement the technique in other developing animals, he says, because the striped patterns can be adjusted during the experiments to get the maximum amount of information from the changing embryo.

Keller says that the technology will be commercially available soon, making it possible to get a systems-level understanding of how cells are behaving and interacting with each other and forming the various different tissues and organs in an organism. Multiple levels of molecular biology, such as genes and proteins, can be examined in real time in the context of the entire developing embryo."

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How will lawyers and judges ever keep up with science as we trudge along seeking certainty. ?Scientists, on the other hand, like to look ahead and theorize. Thus, the UK's Royal Society and Nature are  celebrating  the Society's  350th anniversary (really, 350 years) by hosting a July 1, 2010, conference to look forward at what science will look like in 50 years. The broad topics are pasted below, and are focused around data, careers, and measurement. (BTW, you can see great science videos here from the Society.)

One wonders what the conference speakers will foresee on the data front given Moore's law  of computing power doubling ever two years ("Moore's law describes a long-term trend in the history of computing hardware, in which the number of transistors that can be placed inexpensively on an integrated circuit has doubled approximately every two years."). Think also about giant projects, such as the data generated from atom smashing at CERN. Or, go here to read about the University of Illinois National Center for Supercomputing Applications that is working with the federal government to build the next world's larget publicy accessible computer system - Bluewaters, a petaflop system. How big is that ? " A petaflop is one quadrillion calculations per second."  Or, go here and read about how the world  of computing power looks to a computer guy who loves reading semi-annual lists of the world's 500 largest computer systems.

Set out below is a short view of the conference; go here for more specifics.

"The Tomorrow’s Giants conference is part of an exciting week of celebrations for the Royal Society’s 350th anniversary, which will include an extended Summer Science Exhibition at Southbank Centre, London. To be held on Thursday 1st July 2010, this one day conference co-hosted by the Royal Society and Nature, will bring together scientists and policymakers to gather scientists’ visions of the next 50 years looking in particular at the following three themes:

Data: The challenge of curating and supporting databases in the future and ethical concerns around the storage and management of certain types of data.

Careers: mechanisms for providing security and support for research careers.

Measuring and Assessment: the use of performance indicators and the challenge of having appropriate checks without inhibiting research.

In the lead up to the conference the Royal Society hosted regional meetings across the country in Edinburgh, Liverpool, Bath, Oxford, Cambridge, Nottingham and London. We invited over 100 scientists to share and exchange views on these issues and this Nature Network forum is an opportunity for you to add to the discussion. We’re taking your views from both the workshops and this forum to make sure that the right questions get asked at the conference next year so here is your opportunity to contribute to the discussion of the issues impacting on the shape of science in the next 10-50 years.

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Our bodies are run by proteins. Genes control the proteins produced inside our bodies. Now, researchers have  started to achieve the goal of understanding the mechanisms by which genes control the rate at which proteins are created. The rate of production  obviously is a key variable in understanding  function. So, this great new science was published in the April 16, 2010 theory section of Cell, one of the world's great science  journals. It explains a genetic subcode.

Why does this matter ? Rate of production is a key variable because too much or too little can make all the difference, and now scientists are starting to know more about how that process is regulated. Also, now we start to see, perhaps,  why the same protein can be made through different combinations of amino acids.  And, as the article says, a great pragmatic result is that the ability to "read the directions"  for rate of production may soon mean that scientists can skip time consuming lab experiments that are used today to figure out a protein's rate of production. Instead, scientists now may be able to just read the genomic instruction manual.

The article is:   Cannarozzi G et al. A Role for Codon Order in Translation Dynamics. Cell 141, 355-367, April 16, 2010. doi:10.1016/j.cell.2010.02.036. The article is available in full online at no cost.

The image above, courtesy of Cell, provides a graphic abstract of the article. The article is summarized in various places. I learned of it through a ScienceDaily article (look to the right side of this blog, and you will see a news feed for articles from ScienceDaily). The researchers are part of  ETH  Zurich ; it's online summary is worth reading in full. The key excerpts are set out below

"For this translation work, the cell follows a decoding procedure provided by the "genetic code", which tells what protein is made from a given sequence. The researchers from ETH and Swiss Institute of Bioinformatics (SIB) now identified a new sub-code that determines at which rate given products must be made by the cell. This information has several interesting implications. First, it provides novel insights into how the decoding machinery works. Secondly, and more pragmatically, it makes possible to read information about gene expression rates directly from genomic sequences, whereas up to now, this information could only be obtained through laborious and expensive experimental approaches, such as microarrays.  

"A cell must respond very quickly to injuries such as DNA damage and to potent poisons such as arsenic. The new sub-code enables us to know which genes are turned-on quickly after these insults and which are best expressed slowly. One benefit of this study is that we now can get this information using only analysis of the coding sequence", said Gina Cannarozzi, co-author of the study and Senior Research Associate at the Institute of Computational Science of ETH Zurich." 

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The BBC reported today that asbestos-related disease is the largest single cause of work-related deaths in the UK, with annual deaths at around 2,000 per year.  Why so many deaths in such a small country ? Much of the answer has to do with the amount of amphibole fiber use, according to Dr. Julian Peto, one of the world's best epidemiologists. As mentioned before, Dr. Peto and other top scientists speak next week at this Perrin conference in Las Vegas.  I'm looking forward to attending and learning more.

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 A new expert report calls for significant changes and improvements to  the clinical trial approval and implementation process as it pertains to cancer research. Why do these clinical trials matter and why is important to accomplish the changes, quickly ?

1.5 million Americans will be diagnosed with cancer this year. For too many, the only hope for life will lie in a clinical trial. For too many,  there will not be an answer, and so 500,000 Americans will die of cancer or its consequences. Some will suffer intense physical pain. Virtually all will suffer significant emotional loss, and for some, depression and worse will follow. Clinical trials are crucial to learning how to better fight and manage the various forms of cancer in order to slow the staggering human costs of cancer.

On the financial side, the numbers are huge. The overall costs of cancer were  estimated by NCI at $ 100 billion for 2006.  Those costs are also revenues for many academics, researchers and businesses. Cancer is big business, and clinical trial are an important aspect of treatment, and costs/revenues.

Beyond traditional costs and revenues, there are other costs, including tort system costs. As science continues to develop, more and more of the cancers will end as the subject of lawsuits against product manufacturers, chemical companies, premises owners and others.

Those stark realities are just some of the reasons why it's important that our nation focus on improving clinical trials for cancer treatments. Among other things, one clear need is to speed up approval processes and testing processes to more rapidly translate new science into clinical results. These and other suggested improvements are laid out in the new report  from a blue ribbon committee of scientists, with their report issued through the National Cancer Institute. A three page summary is here. The New York Times followed up with an editorial this past weekend to highlight the need for change, including more speed and more focus. For  the personal observations of a cancer survivor and doctor who is personally and professionally active in clinical trials as both a patient and an advocate, go here to Wendy Harpham's wonderful blog:  Healthy Survivors.

The entire report is important. From the three page summary,  set  out below is one part that policy makers and tort lawyers especially need to consider as to biomarkers. When and as the recommendations are followed, changes are sure to follow for tort, medical monitoring  and insurance litigation:

"Incorporating Innovative Science

Progress in the treatment of cancer patients depends on the effective incorporation of scientific advances into clinical trials. For example, to achieve the goals of targeted cancer therapy, biomarkers (predictors of a response to a particular therapeutic intervention) increasingly are being used to select which treatment strategy is most likely to benefit individual patients. To advance this field, NCI should, among other actions, mandate that biospecimens collected from patients in the course of Cooperative Group trials be submitted to standardized central biorepositories supported by a national inventory and a defined peer-review process for accessing specimens for study.

The Cooperative Groups should lead in developing and testing innovative designs for clinical trials that evaluate multiple therapies, combinations of therapies, and biomarkers. The National Institutes of Health, including NCI, should take a more systematic, multidisciplinary, and dynamic approach when developing standards for new scientific methods and technologies used in trials, to ensure appropriate and consistent use."

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Back in law school, we all heard something about the awesome power of federal judges and probably wondered what it's like to go home at the end of the day knowing you made a real difference in the world. That power was on real display this past Monday when a  federal judge in New York expeditiously exercised some of the vast  power by issuing a momentous and massive 154 page opinion on cross-motions for summary judgment. The opinion is one that will produce a massive future cascade of events.  One hopes the judge and his staff all enjoyed a well-earned respite on Monday evening. 

What happened?  Judge Robert W. Sweet  struck down the patent  claims to the BRCA 1 and 2 genes. Those two genes, if found together,  signal a materially increased risk (over 80%) of developing breast cancer.  More broadly, the rationale of the opinion suggests the same result is proper for most if not all patent claims to gene sequences.  In a careful and thorough opinion, Judge Sweet accepted the patent invalidity claims put forward a by a well- crafted consortium of plaintiffs seeking to invalidate the patents. In short,  the patents were rejected because the patents amount to a claim of rights for simply reporting the order of  the nucleotides that make up a gene, and patents are not awarded for reporting biological facts.  

Why is this a big deal? Start with the numbers. 4,382 patents are claimed in the US for the just under 24,000 genes that comprise a typical genome. See Opinion at 70. That's about 20% of all the genes.

Most of all, this opinion matters because it is a huge win for science and the free flow of information.  Simply put, the mere existence of patents creates doubts and claims that lawyers turn into delays, negotiations and lawsuits.  I've been following this case for some time, and read the main briefs, and some of the declarations. The papers present various disagreements and claims about the future of science if gene sequence patents are invalid.  But, the indisputable facts are that gene patents create delays in research. Today, delays are adverse and matter because  because science today can move so fast if allowed to do so. And, even more to the point, people with cancer cannot wait. Today, almost 1.5 million Americans are diagnosed with cancer every year. That translates into thousands of daily decisions for mothers, fathers, children and lovers who need the best possible information to make life altering decisions on how or whether to treat a particular set of facts and risks.  Patents indisputably block the fastest possible flow of information.

Congratulations to the plaintiffs and their lawyers for such a careful and well done pursuit of a massively important lawsuit that brought together a wide range of individuals and organizations.  The individual plaintiffs included both scientists blocked from further medical researchers, and breast and ovarian cancer patients unable to pay the $ 3,000 required for one of Myriad's tests to determine if they carry the BRCA genes. Organizational plaintiffs included a wide range of highly respected associations of  doctors and scientists. Numerous amicus briefs also were submitted by well-known medical groups. The plaintiffs were represented by the American Civil Liberties Union and  the Public Patent Foundation at Cardozo Law School.                       .

Defendants? Myriad Genetics and the University of Utah. Their  lawyers are from Jones Day.

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Courtesy of this article in Science Daily, there is word of a new article in Science that explains a trick some tumors use to avoid detection. The article abstract is here.   In short,  some tumors emit a protein that tricks the body into ignoring the tumor.  See below for a more precise explanation. The chart to the left shows the outcome. Go here for a larger version of the image.

 "The tumor tricks the body into thinking it is healthy tissue,” says lead author Melody Swartz, head of the Laboratory of Lymphatic and Cancer Bioengineering (LLCB) and EPFL professor. Swartz and her team set out to understand how immune tolerance is induced by tumors, allowing them to progress and spread. The researchers from EPFL concentrated their efforts on a certain protein that is normally present in healthy lymph nodes to attract T cells and program them to perform vital immune functions. They found that some tumors can secrete this protein to transform the outer layer of the tumor into lymphoid-like tissue. This outer layer then attracts and effectively re-programs the T cells to recognize the tumor as friend not foe, resulting in a tumor that goes undetected by the immune system.

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A new ScienceDaily article raises a question: can toxic tort lawyers learn from fruit flies ?

The lesson, it seems,  is that toxic tort lawyers will devote increasing amounts of energy to arguing the extent to which studies of animals - or even insects - are or should be admissible and persuasive for purposes of reaching conclusions regarding cause and effect in humans. Today, defendants are usually (not always) happy to argue that the only "credible science" is a double-blind epidemiological study that shows a relationship between exposure and harm at a relative risk at or above 2.0, or some variation of that theme, as illustrated by this simple but useful outline of some state law cases after Daubert. On the other hand, plaintiffs, especially early movers, are often (but not always) forced to place faith in other forms of science because it often takes years to create and execute a double-blind epidemiological study, if it can be done at all. 

The fruit fly teaches us that these debates will becoming increasingly informed by phylogenetics, a field of science that seeks to offers insights into the how and why of evolutionary genetic similarities and differences between various organisms. Go here for a Wikipedia explanation, or here for a free on-line lecture from iBio. (More examples of why the web is so incredible for spreading information).   

The fruit fly article illustrates the point in a general way. The gist of the article is that scientists have now proved that humans, animals and fruit flies all share a protein (TRPA-1, they call it), that  triggers a string reaction to noxious substances. This is not stunning news in the sense of teaching that we can learn from humble forms of life. After all, scientist for years have learned much from worms. That said, this phylogetics outcome is  important enough to have earned space in the March 18 issue of Nature, perhaps the world's most respected journal for interdisciplinary science.  So, maybe even toxic  tort lawyers can indeed learn from fruit flies. 

Key excerpts are set out below from the ScienceDaily article:  

***

"Chemical nociception, the detection of tissue-damaging pungent chemicals like those found in wasabi, tear gas and cigarette smoke, is triggered by a protein receptor known as TRPA1, which is found throughout the human body in the nose, mouth, skin, lungs, and GI tract. Studying the chemical sensors of Drosophila fruit flies, scientists discovered that flies use their ortholog of the human TRPA1 sensor for the same purpose.

Using a combination of behavior, physiology and phylogenetics, the scientists discovered that this defensive response to noxious compounds is an evolutionary stalwart cutting across immense time scales and linking humans, insects and many other animals back to their common ancestor over 500 million years ago, said lead author and biologist Paul Garrity.

 ****

Working with biochemist Doug Theobald, the team reconstructed TRPA1's family tree back some 700 million years using a variety of bioinformatic methods. "We discovered that a new branch split off the tree at least 500 million years ago, and that this new branch, the TRPA1 branch, appeared to have had all the features needed for chemical sensing even back then," said Garrity. "Since that time, it appears that most animals, including humans, have maintained this same ancient system for detecting reactive chemicals."

And therein lies some of the future promise of harnessing TRPA1. Because the receptor is so widely dispersed throughout the animal kingdom, it holds promise both as a target for therapeutics and deterrents. Understanding more about how the receptor works may help lead to important applications in medicine and industry."

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Do you take health insurance coverage  for granted ?

The table above lets you see the soaring numbers of annual US deaths from cancer. The data is taken from the American Cancer Society's 2009 compilation of cancer statistics.  It often costs a staggering amount of money to die peacefully of cancer.  Dying in pain is not so expensive. 

So, what are are the odd of developing cancer, and what are the consequences for obtaining health insurance ?  As to insurance, developing cancer renders you instantly uninsurable for health insurance as an individual. Want proof ? See, for example, this Blue Cross Summer 2009 application takers manual from Florida. (go to page 62 of the manual to start reading the medical underwriting guidelines that specify the over 100 diseases that bar an individual from purchasing individual  health insurance; for tumors, go to page 90).    

The odds on developing cancer ? The ACS'  detailed on line data for people in the US shows that 1 in 2 men will be diagnosed with cancer during a lifetime. The odds are  1 in 3 for women. Go here to download  ACS’s 2009 date , or go here to view an already downloaded copy; see page 19 for men, and page 20 for women. )

But those are mainly smokers, right? No, that myth is way out of date. In older populations, there are about 1/3 lung cancers, but it's a different story for new cancers. The ACS' data includes tables showing the locations for the 1.5 million new cancers in the US in 2009 (yes, really, 1. 5 million new cancers in a just a year in just the US).  Of the new cancers in 2009,   less than 15% will be lung cancers, and as any tort lawyer knows, some lung cancers are not caused by smoking.

How many people in the US are cancer survivors and are uninsurable as individuals ? Of course, we can't say for sure, but the best data indicates that between 10 and 15 million Americans are cancer survivors, as shown by the data below.  Most,  if not all of them, can never purchase individual health insurance, as shown by the Blue Cross application manual linked above.

So, those are the realities. How can a legislator in our country in good conscious choose to say "no" to making health insurance available for these 10-15 million persons who are cancer survivors?  Please, pick up the phone and ask your elected representatives to make sure that - at least - legislation is passed to stop insurers from excluding coverage for persons with pre-existing conditions. 

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Here is the online agenda for a great new asbestos litigation conference on May 3 and 4.

Why great ? Because the conference format explicitly recognizes the importance of science to where the litigation has been, and where it will go.  Thus, virtually all of the speakers are doctors and scientists, including several who are world class in anyone's book.  The conference, sponsored by Perrin Conferences,  is titled:     A Conference on Asbestos and Mesothelioma. 

Science alone of course does not result in lawsuits. Accordingly, lawyers are involved to a degree. The conference chairs are two lawyers with reputations for knowing and enjoying the science side of litigation. They are plaintiff''s counsel Shep Hoffman, founder of The Law Offices of Shepard A. Hoffman, Dallas, and defense counsel, Robert Rich, a partner of Gordon Rees, San Francisco. 

The scientist are listed below - this is by far the best overall assembled group of doctors and scientists focused on asbestos. Part of the power of this group is that it includes speakers with diverging views. And, for anyone interested in the global spread of asbestos disease, and thus some spread of the litigation, do not miss the chance to hear from Dr. Julian Peto, who is at the forefront of those looking all the way around the world. 

It will be interesting to see the level of attendance, the manner in which this conference is conducted, and whether this approach is repeated for asbestos and replicated for other areas of mass tort litigation.  In the past, most asbestos conferences that included much science were conferences sponsored by one side or the other. Thus, for many, many years,  Al Parnell and the Defense Research Institue have held an annual Asbestos Medicine conference that usually included severals doctros and scientists. The conference usually also was attended by a few plaintiff's lawyers. And, likewise, the plaintiff's bar holds periodic meetings, but typically they do not allow defense lawyers to attend.

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Remember the issues regarding DES daughters and sons said to be suffering additional diseases, and a class action settlement in the Netherlands ?  More recently,  there are some new indicators that some chemicals inflict some epigentic changes that will or may cause multigenerational disease issues.  

For a 2006 nonscience article, see this Vanity Fair article on claims that Agent Orange is causing horrible deformities in third-generation descendants of persons exposed to Agent Orange. For more science, here is a new ScienceDaily article on BPA exposure during pregnancy.

"Taylor and colleagues made this discovery by exposing fetal mice to BPA during pregnancy and examining gene expression and DNA in the uteruses of female fetuses. Results showed that BPA exposure permanently affected the uterus by decreasing regulation of gene expression. These epigenetic changes caused the mice to over-respond to estrogen throughout adulthood, long after the BPA exposure. This suggests that early exposure to BPA genetically "programmed" the uterus to be hyper-responsive to estrogen. Extreme estrogen sensitivity can lead to fertility problems, advanced puberty, altered mammary development and reproductive function, as well as a variety of hormone-related cancers. BPA has been widely used in plastics and other materials. Examples include use in water bottles, baby bottles, epoxy resins used to coat food cans, and dental sealants.

"The BPA baby bottle scare may be only the tip of the iceberg." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Remember how diethylstilbestrol (DES) caused birth defects and cancers in young women whose mothers were given such hormones during pregnancy. We'd better watch out for BPA, which seems to carry similar epigenetic risks across the generations. "

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God love smart scientists and doctors !  Back in February, this post covered some of the ground on medical treatments aimed at individual genomes. In August,  this post reported on Abbbott and Pfizer working in creating a gene chip to screen  patients with a specific type of cancer for specific genomic changes so that a clinical trial can be run using people with that specific genomic defect.  In this week of focus on health care, it is just plain wonderful to read that similar approaches are starting to produce the "miracles" needed for some of the almost 1.5 million Americans who will be diagnosed with cancer this year. 

The specifics ? Now coming on line are humane therapies - pills !-  tailored to particular changes in individual genomes. These  therapies are actually shrinking tumors, and are doing so without the incredible brutality of chemotherapy and bone marrow transplants. There are still issues and uncertainties ahead, but these types of results prove the merit to treating specific genomes. 

Here are the absolute key quotes from an article this morning in the NYT:

"The trial of PLX4032 offers a glimpse at how doctors, patients and drug developers navigate a medical frontier as more drugs tailored to the genetic profile of a cancer are being widely tested on humans for the first time.

Throughout the fall, the only two patients on the trial whose tumors continued to grow were the ones who did not have the particular gene mutation for which the drug had been designed. They were removed from the trial. By late December, tumors in the 11 patients who did have the mutation had shrunk. Those involved in the trial held their collective breath waiting to see how long the remissions would last. "

The entire article is here; addtional key excerpts on the science are pasted below. The entire article is well worth reading for the human side of the story.

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This part of the future is not yet here,  but the story pasted below illustrates part of the promise of biomarkers.....


ScienceDaily (Feb. 9, 2010) -- The earlier the doctor finds the tumor, the better the patient's chances of recovery. A new testing method aims to detect the disease in its initial stages. The technology is based on a microfluidic chip with tiny channels in which a blood sample from the patient circulates. The chip traces marker proteins which are indicative of cancer. The measured concentration of the tumor marker in the blood will help doctors to diagnose the disease at an early stage.

Similar testing systems already exist but their measurements are not very precise and they can only detect molecules that are present in the blood in large quantities. What's more, the tests have to be carried out in a laboratory, which is time-consuming and costly.


A project funded by the German Ministry of Education and Research and coordinated by the Fraunhofer FIT aims to improve matters. Biofunctionalized nanoparticles developed by research scientists at the Fraunhofer Institute for Silicate Research ISC in Würzburg are the key element in the new sensor. "We have improved the detection limit compared with the present state of the art by a factor of one hundred," explains Dr. Jörn Probst, Head of the Business Unit Life Science at the ISC. "Whereas previously a hundred molecules were needed in a certain quantity of blood to detect tumor markers, we now need only one. This means that diseases can be diagnosed much earlier than with present methods."


But how does the biosensor integrated in the chip register the few biomolecules swimming around in the blood that are indicative of a certain disease? "We have placed antibody-occupied nanoparticles on the sensor electrode which fish out the relevant proteins. For this purpose, we repeatedly pump the blood across the electrode surface. As with a river, the flow is fastest in mid-channel and the water runs more slowly near the bank. We have therefore made a sort of fishing rod using nanoparticles which registers the antibodies in the middle of the blood flow where most proteins swim by per unit of time.« If an antibody catches the matching protein, a tumor marker, the electrical charge distribution shifts and this is picked up by the electrode."

The researcher groups are now developing a first demonstrator combining four independent single-molecule-sensitive biosensors. The experts are also working on the simultaneous detection of several tumor markers, which will increase the clarity of tests. The system will be ready to enter the market in a few years' time

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The online story pasted below is noteworthy for the the conclusion that cigarette smoke residue from nicotine causes the presence of excess  "toxins" on furnishings inside buildings. It seems premature to conclude that tobacco companies will soon face property damage claims for contaminating property, but it does make one wonder. Note also the closing paragraph's reference to developing biomarkers to prove the presence of the "toxins." Biomarker science is the subject of today's second post.

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ScienceDaily (Feb. 9, 2010) -- Nicotine in third-hand smoke, the residue from tobacco smoke that clings to virtually all surfaces long after a cigarette has been extinguished, reacts with the common indoor air pollutant nitrous acid to produce dangerous carcinogens. This new potential health hazard was revealed in a multi-institutional study led by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab).

"The burning of tobacco releases nicotine in the form of a vapor that adsorbs strongly onto indoor surfaces, such as walls, floors, carpeting, drapes and furniture. Nicotine can persist on those materials for days, weeks and even months. Our study shows that when this residual nicotine reacts with ambient nitrous acid it forms carcinogenic tobacco-specific nitrosamines or TSNAs," says Hugo Destaillats, a chemist with the Indoor Environment Department of Berkeley Lab's Environmental Energy Technologies Division. "TSNAs are among the most broadly acting and potent carcinogens present in unburned tobacco and tobacco smoke."


Destaillats is the corresponding author of a paper published in the Proceedings of the National Academy of Sciences (PNAS). Co-authoring the PNAS paper with Destaillats were Mohamad Sleiman, Lara Gundel and Brett Singer, all with Berkeley Lab's Indoor Environment Department, plus James Pankow with Portland State University, and Peyton Jacob with the University of California, San Francisco.


The authors report that in laboratory tests using cellulose as a model indoor material exposed to smoke, levels of newly formed TSNAs detected on cellulose surfaces were 10 times higher than those originally present in the sample following exposure for three hours to a "high but reasonable" concentration of nitrous acid (60 parts per billion by volume). Unvented gas appliances are the main source of nitrous acid indoors. Since most vehicle engines emit some nitrous acid that can infiltrate the passenger compartments, tests were also conducted on surfaces inside the truck of a heavy smoker, including the surface of a stainless steel glove compartment. These measurements also showed substantial levels of TSNAs. In both cases, one of the major products found was a TSNA that is absent in freshly emitted tobacco smoke -- the nitrosamine known as NNA. The potent carcinogens NNN and NNK were also formed in this reaction.
"Time-course measurements revealed fast TSNA formation, up to 0.4 percent conversion of nicotine within the first hour," says lead author Sleiman. "Given the rapid sorption and persistence of high levels of nicotine on indoor surfaces, including clothing and human skin, our findings indicate that third-hand smoke represents an unappreciated health hazard through dermal exposure, dust inhalation and ingestion."


Since the most likely human exposure to these TSNAs is through either inhalation of dust or the contact of skin with carpet or clothes, third-hand smoke would seem to pose the greatest hazard to infants and toddlers. The study's findings indicate that opening a window or deploying a fan to ventilate the room while a cigarette burns does not eliminate the hazard of third-hand smoke. Smoking outdoors is not much of an improvement, as co-author Gundel explains.

"Smoking outside is better than smoking indoors but nicotine residues will stick to a smoker's skin and clothing," she says. "Those residues follow a smoker back inside and get spread everywhere. The biggest risk is to young children. Dermal uptake of the nicotine through a child's skin is likely to occur when the smoker returns and if nitrous acid is in the air, which it usually is, then TSNAs will be formed."


The dangers of mainstream and secondhand tobacco smoke have been well documented as a cause of cancer, cardiovascular disease and stroke, pulmonary disease and birth defects. Only recently, however, has the general public been made aware of the threats posed by third-hand smoke. The term was coined in a study that appeared in the January 2009 edition of the journal "Pediatrics," in which it was reported that only 65 percent of non-smokers and 43 percent of smokers surveyed agreed with the statement that "Breathing air in a room today where people smoked yesterday can harm the health of infants and children."

Anyone who has entered a confined space -- a room, an elevator, a vehicle, etc. -- where someone recently smoked, knows that the scent lingers for an extended period of time. Scientists have been aware for several years that tobacco smoke is adsorbed on surfaces where semi-volatile and non-volatile chemical constituents can undergo reactions, but reactions of residual smoke constituents with atmospheric molecules such as nitrous acid have been overlooked as a source of harmful pollutants. This is the first study to quantify the reactions of third-hand smoke with nitrous acid, according to the authors.

"Whereas the sidestream smoke of one cigarette contains at least 100 nanograms equivalent total TSNAs, our results indicate that several hundred nanograms per square meter of nitrosamines may be formed on indoor surfaces in the presence of nitrous acid," says lead-author Sleiman.


Co-author James Pankow points out that the results of this study should raise concerns about the purported safety of electronic cigarettes. Also known as "e-cigarettes," electronic cigarettes claim to provide the "smoking experience," but without the risks of cancer. A battery-powered vaporizer inside the tube of a plastic cigarette turns a solution of nicotine into a smoky mist that can be inhaled and exhaled like tobacco smoke. Since no flame is required to ignite the e-cigarette and there is no tobacco or combustion, e-cigarettes are not restricted by anti-smoking laws.






"Nicotine, the addictive substance in tobacco smoke, has until now been considered to be non-toxic in the strictest sense of the term," says Kamlesh Asotra of the University of California's Tobacco-Related Disease Research Program, which funded this study. "What we see in this study is that the reactions of residual nicotine with nitrous acid at surface interfaces are a potential cancer hazard, and these results may be just the tip of the iceberg."


The Berkeley Lab researchers are now investigating the long-term stability in an indoor environment of the TSNAs produced as a result of third-hand smoke interactions with nitrous acid. The authors are also looking into the development of biomarkers to track exposures to these TSNAs. In addition, they are conducting studies to gain a better understanding of the chemistry behind the formation of these TSNAs and to find out more about other chemicals that are being produced when third-hand smoke reacts with nitrous acid.


"We know that these residual levels of nicotine may build up over time after several smoking cycles, and we know that through the process of aging, third-hand smoke can become more toxic over time," says Destaillats. "Our work highlights the importance of third-hand smoke reactions at indoor interfaces, particularly the production of nitrosamines with potential health impacts."


In the PNAS paper, Destaillats and his co-authors suggest various ways to limit the impact of the third hand smoke health hazard, starting with the implementation of 100 percent smoke-free environments in public places and self-restrictions in residences and automobiles. In buildings where substantial smoking has occurred, replacing nicotine-laden furnishings, carpets and wallboard can significantly reduce exposures.

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Remember those controversies about biased doctors misreading reading x-rays to find asbestosis or "pleural changes consistent with exposure"  to asbestos or silica ?  New science will bring new controversies - see below for a recent article on using biomarkers in exhaled breath to find asbestosis. Here is the online source of the abstract pasted below.

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Exhaled breath condensate biomarkers in asbestos-related lung disorders.


Sharron Chow, Charlotte Campbell, Alessandra Sandrini, Paul S Thomas, Anthony R Johnson, ...Deborah H Yates show all

Respiratory Medicine (2009)

Volume: 103, Issue: 8, Pages: 1091-1097

PubMed ID: 19520561

Abstract

OBJECTIVES: Asbestos induces generation of reactive oxygen and nitrogen species in laboratory studies. Several such species can be measured non-invasively in humans in exhaled breath condensate (EBC) but few have been evaluated. This study aimed to assess oxidative stress and lung inflammation in vivo. METHODS: Eighty six men were studied: sixty subjects with asbestos-related disorders (asbestosis: 18, diffuse pleural thickening (DPT): 16, pleural plaques (PPs): 26) and twenty six age- and gender-matched normal individuals. RESULTS: Subjects with asbestosis had raised EBC markers of oxidative stress compared with normal controls [8-isoprostane (geometric mean (95% CI) 0.51 (0.17-1.51) vs 0.07 (0.04-0.13) ng/ml, p<0.01); hydrogen peroxide (13.68 (8.63-21.68) vs 5.89 (3.99-8.69) microM, p<0.05), as well as increased EBC total protein (17.27 (10.57-28.23) vs 7.62 (5.13-11.34) microg/ml, p<0.05), and fractional exhaled nitric oxide (mean+/-SD) (9.67+/-3.26 vs 7.57+/-1.89ppb; p<0.05). EBC pH was lower in subjects with asbestosis compared with subjects with DPT (7.26+/-0.31 vs 7.53+/-0.24; p<0.05). There were no significant differences in exhaled carbon monoxide, EBC total nitrogen oxides and 3-nitrotyrosine between any of the asbestos-related disorders, or between these and controls. CONCLUSION: In asbestos-related disorders, markers of inflammation and oxidative stress are significantly elevated in subjects with asbestosis compared with healthy individuals but not in pleural diseases

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From the January 26, 2010  NCI Cancer Bulletin is a story that provides the latest example of the dawning age of new science brought about by committed doctors, brilliant scientists, your donations, high speed computers and software, and the  desire  to save lives.

Recall that the Humane Genome project was announced in 1990 and completed in 2003. Now, less than seven years lateer, genomes are sequences in days.

Note that the results all will be made public at no expense.

This project illustrates why patents should not be allowed for gene sequences, a battle the ACLU and others are fighting right now.

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St. Jude, Washington University Launch Genome Project for Childhood Cancers


Researchers at St. Jude Children's Research Hospital and the Washington University School of Medicine in St. Louis have launched the Pediatric Cancer Genome Project 1 to sequence the genomes of at least 600 children with cancer over the next 3 years. The collaboration marks the first time that whole-genome sequencing will be used on a large scale to discover genetic changes driving pediatric cancers.

"This is the largest and most powerful single initiative in the 50-year history of St. Jude," the research hospital's director, Dr. William E. Evans, said at a press briefing announcing the project yesterday. "DNA is being sequenced as we speak," he added.

St. Jude has a repository of biological samples and clinical information from children who have been treated there since the 1970s. The collection represents a treasure trove of information about cancer, and it can now be scrutinized using the latest genomic technologies at a cost that continues to decline substantially over time.

"This is a new era for pediatric cancers," NIH Director Dr. Francis Collins said at the briefing. "The study represents an opportunity to discover all the ways that a good cell in an innocent child goes wrong."


The project--estimated to cost $65 million and funded by St. Jude--aims to discover the genetic origins of pediatric cancers while creating knowledge that can be used to improve the care of young people with these rare diseases. Early results could reveal new uses for available drugs, and, over the long term, lead to targeted agents for these cancers, the researchers said.

New genetic signatures for classifying and treating patients are also anticipated. Knowing that a child has a subtype with a poor prognosis would allow physicians to select aggressive treatments early in the course of the disease. Similarly, doctors could safely withhold treatments from a patient who has a better prognosis, based on a genetic profile.

"These two great NCI-designated comprehensive cancer centers are demonstrating yet again their commitment to making a difference for kids with cancer," said NCI Director Dr. John Niederhuber.

Dr. Larry J. Shapiro, dean of the Washington University School of Medicine and a pediatric geneticist, said at the briefing: "This project will provide a detailed and complete picture of the mutations in the cancer cells."

In 2008, researchers at Washington University and their colleagues published 2 the first genome sequence of a person with cancer--a woman with leukemia. They have since published 3 the genome of a second person with leukemia, and they have also sequenced dozens of additional cancer genomes using the same whole-genome approach.

The new effort will focus on leukemias, brain tumors, and sarcomas (tumors of bone, muscle, and other connective tissues). To identify genetic changes associated with cancer, the researchers will sequence DNA from both the tumor cells and normal cells of each patient.

The project complements in every way the efforts of The Cancer Genome Atlas 4 (TCGA) Research Network, which focuses on adult cancers, noted Dr. Collins. Just last week, TCGA investigators identified new subtypes 5 of brain cancer using genomic and clinical data--an example of the kind of knowledge Dr. Collins expects to come from the pediatric project.

Another genome effort in pediatric cancer is the NCI-supported childhood cancer TARGET 6 initiative, which includes St. Jude investigators as well as other childhood cancer researchers. The initial discoveries from this project are being translated to the clinic through an early stage clinical trial that is in development for a newly described 7 type of acute lymphoblastic leukemia.

What distinguishes the new project from past efforts, said Dr. Richard Wilson, director of the Genome Center at Washington University, is that this one will be "all whole-genomes all the time." Most genome studies have been limited to sets of genes or genetic markers because of the costs of sequencing DNA. Those costs have now fallen to below $100,000 for a tumor-normal combination, and the sequencing can be done in about a week, Dr. Wilson said. (See "A Conversation with Dr. Elaine Mardis 8" in this issue.)

"There is a sense of urgency to make progress here, and it has now become affordable," said Dr. Evans. "We see this effort as a marathon, and the first 3 years are really just the beginning. I am certain there will be lots of unanswered questions at the end of this period, and there will be much more work to be done."

He acknowledged the enormous challenge of managing and making sense of as much as 100 trillion pieces of data (600 cases, 2 genomes per case, and each genome will be sequenced 30 times to ensure that nothing is missed). To meet this challenge, Washington University is adding new instruments and computational power, and the researchers are confident that they are ready.

"The data storage, management, and analysis problems are substantial," Dr. Wilson said in an interview. "But this project is coming along at just the right time in terms of our technical capabilities. We've really come a long way in just the last 6 months in terms of our data production technology."

St. Jude has, in effect, been preparing for this project for 45 years by creating the tissue repository and developing a capacity for preclinical research studies. The infrastructure and resources required for follow-up studies of the genomic data, such as mouse models, already exist at St. Jude, noted Dr. Elaine Mardis, co-director of the Genome Center at Washington University. "The genome project will fill these pipelines with new information to be analyzed."

In the future, the project will include other types of alterations in cancer, such as those involving RNA and epigenetic changes, which alter the activity of genes without causing a change in DNA sequence, the researchers said.

They stressed that the results will be made publicly available through a Web site once the information has been validated. The hope is that other investigators will bring their own expertise and perspectives to the data and help move the science forward.

"We view this as creating a resource not just for our efforts but for the world," said Dr. Evans. He quoted the founder of St. Jude, the entertainer Danny Thomas, who liked to say, "To cure one child in Memphis is to cure a thousand worldwide."

"It is always a good thing if our discoveries can be amplified and leveraged elsewhere," Dr. Evans added, "and that's what has to happen." (emphasis added)


--Edward R. Winstead

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For 2010, I wish you good health, and lives full of hope, peace, joy and love.

While you are thinking about New Year's Resolutions, please consider two that may actually save some one's life. Both resolutions are easy to fulfill. For one, please spread the word that cord blood donations at birth offer enormous opportunities to save lives because the blood contains life-saving stem cells. For another, please go here to register to become a potential bone marrow donor.

Please read on for more facts on why the needs are so great and why it's easy to accomplish both resolutions.

Cord Blood Can Save Lives

There is enormous medical value to donating cord blood and placentas when children are born. Why? Because they are chock full of pluripotent stem cells able to evolve into cells performing most any cellular role in the body. Why does that matter ? Because the cells may replace existing defective or failed cells that cause cancers and other dread diseases. Go here, for example, to read a November 15, 2000 Science Daily article about great new science in which cord blood is used to achieve tremendous results for patients who need bone marrow (stem cell) transplants to overcome leukemias and other cancer involving blood and bone marrow. Or go here to download the full medical article. The short version of the story is as follows:

"ScienceDaily (Nov. 15, 2009) -- A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning."

Is there really a need to spread the word about the value of cord blood ? You bet - the science above is new, and so most people have no idea of the value of the cells, and are not aware of the critical needs. As a result, we are missing enormous opportunities to save lives. How do I know that ? Various ways, but most recently I heard it at a holiday gathering from my old roommate, Dwight, a brilliant and compassionate person who is a practicing OB GYN. The topic came up because several former college friends gathered for the holidays, and one brought up the topic of knowing way too many people with cancer even though we are all less than 55. After various comments about cancer treatments and hopes for "cures," Dwight the OB GYN stated his intense frustration that many parents to be and hospitals pay virtually no attention to cord blood donations. The result ? Every day, thousands of people and hospitals fail to preserve and use thousands of placentas and cord blood that collectively contain billions of stem cells that could save countless lives. So, please spread the word. It takes only a few seconds, for example, to forward an email or to cut and paste some of this text into an email to your existing list of friends and neighbors.

Register as a Potential Bone Marrow Donor

For a second resolution, please consider registering to become a bone marrow donor. It's easy to register with the nationally-recognized "Be the Match Foundation." Click on Be the Match or use your web browser to go to www.marrow.org. Contrary to what many people think, the need for bone marrow has not ended. To the contrary, there is a growing need for bone marrow donors, and the need is especially critical for children. Why ? Because diversity and "mixed marriages" mean that traditional ethnic lines are being crossed, thereby producing new genomes for which there are few or no matches because the existing potential donors are typically older and not so diverse. So, registering new, younger and more diverse potential donors is of critical importance for children with leukemias and other blood cancers. The Wall Street Journal covered the topic earlier this year; go here to read the full story or see the text pasted below. As a result. Mayo Clinic and others are running registration drives, as described here by Mayo.

Registering more potential donors also is critical because some cancer rates are soaring. As shown here, some of the stunning numbers are that for just 2009, and for just the United States, over 65,000 people will be diagnosed with non-Hodgkins lymphoma, and another 8,000 will be diagnosed with Hodgkin's lymphoma. For too many of these patients, the only real chance for life is a bone marrow transplant.
What's involved in registering ? Not much - the registration process is simple, painless and can be done through the mail. How? First, the potential donor registers online with contact information. The mail will then bring a small packet containing a couple of cotton swabs (Q-tips) that you use to gather some fluid/skin cells from the inside of the mouth. Rub the swabs on the inside of your mouth, mail the swabs back in, make a small donation, and that's all there is to it. After that, the registration group submits the q-tips to a lab that analyzes the DNA on the swab to indicate the genomic types for which the registrant perhaps could be a donor. Please click here to go the Be The Match website and register right now to start the new year off with action that may save a life.

Isn't bone marrow donation very painful ? NO, NO, NO - that used to be true, but it's not true anymore ! The typical bone marrow donation process today involves extracting the needed marrow cells through a blood donation/filtering process that takes a few hours. In essence, a needle is inserted, blood is slowly drained out to run through a filter, and the needed cells are collected through a process known as peripheral blood stem cell (PBSC) donation. You can easily talk, watch TV, or listen to music during the process. Or you could simply reflect on probably saving a life. Go here to read more myth busting about bone marrow donation.

Hopefully you are now resolved to take action? After all, how many other actions can you take this year that might actually save a life ?

But, if you need more motivation, here is a Wikipedia article on marrow donation and the various involved groups. Or, please read the full May 27, 2009 Wall Street Journal article below on the critical needs..

_____________________________________________________________________


• THE INFORMED PATIENT

• MAY 27, 2009
I. Building Diversity in Bone-Marrow Registries

• By LAURA LANDRO

Like thousands of patients battling blood cancers, Natasha Collins faces a needle-in-a-haystack search for a bone-marrow donor. But for the 26-year-old medical student with recurrent leukemia, the hunt is even more of a challenge because she is half African American and half Caucasian.

Transplants of bone marrow, which produces new blood cells, offer a potential cure for a growing number of cancers and other diseases, but only if the patient and donor are genetically compatible. Only 30% of patients have a sibling with the same genetic makeup who can provide marrow transplants. For other people, the best chance of a match is someone of their own race or ethnicity. That poses a special problem for minorities, and the growing number of people who identify themselves as multiracial, because for these groups there is a shortage of donor volunteers.

Some seven million people in the U.S. have signed up on a national registry to be potential bone-marrow donors. Even so, less than half the 10,000 patients who needed a transplant last year were able to find a genetic match that led to a transplant. While the odds of a white patient finding a match are 88%, the odds for most minorities can be as low as 60%. The odds of actually receiving a transplant are as low as 20% for some minorities because of other factors such as access to care in their communities.

Now, the National Marrow Donor Program, the nonprofit group that administers the registry with partial funding from the U.S. government, is stepping up efforts to recruit donors from different ethnic backgrounds. The 21-year-old program, which recently changed the name of its registry to Be the Match, is spreading its message through social media Web sites like Facebook and MySpace. It is trying to reach a younger generation that its research shows isn't aware of the program's mission or of medical advances that make it possible to screen potential donors by testing DNA with a simple cheek swab from a kit (available online at bethematch.org).

Marrow Transplant Myths

Be the Match also aims to shatter some myths about bone-marrow donation, such as the fear that it will hurt the donor. Traditionally, donors underwent general anesthesia so stem cells in the bone marrow could be collected from needles inserted into large bones in the back. About 20% of transplant donations are still conducted this way.

Now, in a relatively painless procedure that doesn't require anesthesia, some 60% of transplants are performed by harvesting a donor's peripheral blood stem cells, which are cells from bone marrow that circulate in the blood stream. These can be collected by circulating the donor's blood intravenously over several hours through a machine. The procedure also delivers a greater volume of stem cells to the recipient than a traditional bone-marrow transplant. The donor's body regenerates the stem cells within a few weeks. Donor costs are typically covered by the patient's insurance or by funds from the registry and other sponsors.

An additional 20% of transplants are performed using umbilical-cord blood cells that are donated after childbirth. This procedure, which doesn't require as close a genetic match between donor and recipient, is relatively new, and there isn't a large body of scientific evidence of its long-term effectiveness and complication rates.

Bone-marrow transplants, first offered in the 1960s, have been used to treat leukemia, aplastic anemia, lymphomas such as Hodgkin's disease, multiple myeloma, immune-deficiency disorders and some solid tumors such as breast and ovarian cancer. Before undergoing transplants, patients typically are treated with chemotherapy and sometimes radiation to destroy their diseased marrow. The donor's healthy blood-making cells are then infused directly into the patient's bloodstream, where they help to build a new blood supply.
But for a transplant to succeed, markers known as human leukocyte antigens, or HLAs, have to match between donor and recipient. The body uses the markers to recognize which cells belong in the body and which are intruders. A close match will reduce the risk that the patient's immune cells will attack the donor's cells or that the donor's cells will attack the patient's body after the transplant. Patients inherit half their HLA markers from each parent, and each sibling has a 25% chance of matching. But it is possible to have even a dozen siblings and no match.

Diagnosed With Leukemia

I was one of the lucky ones. When I was diagnosed with a form of leukemia in 1991 and needed a transplant, both of my brothers tested as identical matches on each of six HLA markers used to determine compatibility (though five are sometimes acceptable). Because some HLA types are found more often in certain racial and ethnic groups than others, the HLA markers of a donor can be close enough to be compatible with a patient from a similar ethnic background. People with mixed backgrounds, such as African and European ancestry, for example, have unique combinations of HLA types. "As long as we create more diversity [in the population], we will need more and more donors to reflect that," says National Marrow Donor Program Chief Executive Jeffrey Chell.

Ms. Collins, the medical student, had a transplant from donated cord blood cells in May 2007, but her cancer, known as acute myelogenous leukemia, has returned. Her doctors now believe a bone-marrow transplant offers Ms. Collins the best chance of a cure. Her classmates at Yale University have held bone-marrow drives, sent emails to other medical schools to recruit donors, and created a Facebook group with over 1,000 members and a YouTube video (both accessible at www.matchnatasha.org).
Ms. Collins is now undergoing chemotherapy, which weakens her immune system. She says she is trying to keep up with her class work by studying at home. "The good news is that we've found some potential matches," she says.

The National Marrow Donor program says it is seeing results from its minority recruitment efforts. Groups such as Historically Black Colleges and Universities conducted drives that have signed up 5,000 donors in a program launched last year. The donor program is also working with Hispanic groups and Asian and Pacific Islander organizations, as well as with blood centers in states that have large Native American populations. In 2008, it signed up 440,000 new donors, just under half of whom were from diverse racial and ethnic communities. The group also is working with international registries, with a total of five million potential donors, and is signing cooperative agreements with countries like Brazil.

Studies show that there are a number of reasons why different ethnic groups don't sign up as bone marrow donors, including a lack of educational resources devoted to those communities, fear of doctors and hospitals, concern about putting personal information in a database, and cultural taboos about donating a physical part of oneself.

In one effort to recruit Asian and Pacific Islander donors, 26-year-old acute leukemia patient Michelle Maykin founded Project Michelle, an online campaign that includes a Web site, projectmichelle.org, with blogs, photos and videos. The project has recruited more than 15,000 new donors by sponsoring bone marrow drives with the help of the national registry at Asian churches and student groups, among others.

Advances in Matching

Improvements in matching techniques, using DNA-based testing methods, can more precisely identify the best donor. Be the Match recently started offering an online search tool that patients and doctors can use to get an idea of how many potential matches may be in the registry.

In the past 18 months, the registry found matches for more than 5,000 transplants, an 18% increase over the previous period. More diseases, such as sickle cell anemia, are now treated with transplants. And patients 50 and older, for whom transplants were once considered too risky, are now eligible for the treatment. That's because of new, pre-transplant chemotherapy regimens that are less toxic, and better post-transplant care to prevent infections and rejection.

Ineligible Donors

Some medical conditions may eliminate potential donors, such as bleeding problems or heart disease. When Christopher Bartley, a classmate of Ms. Collins at Yale Medical School who has African-American, Caucasian and Honduran roots, tried to sign up, he found that he was ineligible because he suffers from sleep apnea, which causes pauses in breathing during sleep.

And even though the hope is that more minorities will provide matches for others in the same ethnic mix, it is also possible to find a match where there is no ethnic similarity. Victoria Namkung, a Los Angeles writer of Irish, Jewish and Korean origins, who signed up as a donor several years ago, was surprised to learn that she was the match for a Mexican-American man in Ft. Myers, Fla. Donors and recipients can communicate anonymously for the first year through the registry and then meet if they choose. Ms. Namkung says she and her recipient have met and keep in touch. The feeling of having provided him a life-saving transplant "changed my life," she says.

• Email informedpatient@wsj.com.

Printed in The Wall Street Journal, page D1

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Here's a pop quiz. Out of 83,000 or so chemicals, how many chemicals or chemical classes has EPA regulated under TSCA ?

1,103 ?

5,279?

9,867 ?

Drum roll please -the answer is:

5 ( I did not forget any numbers).

Surprised ? Me too. But that's what you learn when you read this post on the Mass Tort Defense blog and/or then go read the December 2, 2009 testimony of John Stephenson, GAO, Director, Natural Resources and Environment . He said, at 9, " In fact, since Congress passed TSCA in 1976--over 33 years
ago--EPA has issued TSCA regulations on only five existing chemicals or chemical classes.")
That result seems especially pathetic when one considers that the EU is busy implementing its comprehensive REACH program of chemical regulation, explained here by the EU.

Will things change here ? That's not my area of expertise, so I will not offer a prediction. But, the testimony also is noteworthy for its focus on how science is now focused on cellular level events and so the dependence on epidemiology is lessening. The topic was covered by Linda Birnbaum, Ph.D., Director, National Institute of Environmental Health Sciences, National Institutes of Health, andDirector, National Toxicology Program, U.S. Department of Health and Human Services. Pasted below are some key excerpts from her testimony, beginning with the conclusion:

"We are poised to move forward into an era of a new kind of toxicological testing that is less expensive and also gives us an improved understanding of the actual effects on humans. Toxicology is advancing from a mostly observational science using disease-specific models to a better predictive science focused upon a broad inclusion of target-specific, mechanism-based, biological observations. This means using alternative assays targeting the key pathways, molecular events, or processes linked to disease or injury, and incorporating them into a research and testing framework. The NTP is laying the foundation for this testing paradigm in partnership with the National Human Genome Research Institute and the EPA. They are using quantitative high throughput screening assays to test a large number of chemicals. The resulting data are being deposited into publicly accessible relational databases. Analyses of these results will set the stage for a new framework for toxicity testing. (emphasis added)

She also said:

"Environmental health science has made tremendous strides since the original passage of the Toxic Substances Control Act, or TSCA. Our understanding of chemical toxicity has been challenged by the new science of epigenetics, which is the study of changes to the packaging of the DNA molecules that influence the expression of genes, and hence the risks of diseases and altered development. Studies indicate that exposures that cause epigenetic changes can affect several generations. This new understanding heightens the need to protect people at critical times in their development when they are most vulnerable to this kind of toxicity. (emphasis added)

The concept of "windows of susceptibility" is an important area. Research has revealed the heightened vulnerability of fetal, infant and child developmental processes to disruption from relatively low doses of certain chemicals. Established first for neurodevelopmental toxicants like PCBs, and lead and other metals, this concept also applies to hormonally active agents (endocrine disrupting chemicals). In our NIEHS Breast Cancer and Environment Research Program, co-funded with the National Cancer Institute, researchers are investigating whether periods of susceptibility exist in the development of the mammary gland, when exposures to environmental agents may impact the breast and endocrine systems that can influence breast cancer risk in adulthood.
***
There are other susceptibilities to consider. For some types of chemicals and health effects, there may be excess risk from specific genes or chronic diseases. For example, the level of a person's risk of bladder cancer from smoking has been shown to depend in part on whether or not that individual's genome contains variants in specific detoxification enzymes. The existence of these subtle variations in susceptibility must be factored into overall toxicity assessments.

Scientists believe that other chemicals such as some PCBs and furans may cause cancer in a similar manner. The question for public health officials was how health standards could be adjusted to take into account the fact that people are always exposed to mixtures of dioxin-like compounds, not just one at a time.
To address this problem, a large body of work led to the development of a method to estimate toxicity of mixtures of dioxin-like compounds based upon toxic equivalency factors, or TEFs. To estimate the overall toxicity of a mixture, the contaminants' weighted contributions are added together, adjusting for the fact that some compounds are more toxic than others. The additive methodology has been tested and confirmed by studies done by the NTP, EPA, and others. TEF methodology has also been extended to other health endpoints, including reproductive and developmental, immune, and neurological.

Differences in routes of exposure must also be considered. For example, hexavalent chromium compounds have been shown to cause lung cancer in humans when inhaled, but it was not known how these compounds behaved when ingested. Hexavalent chromium was tested by the NTP because of concerns over its presence in drinking water. The NTP studies showed that a compound containing hexavalent chromium causes cancer in laboratory animals following oral administration in drinking water, confirming the need to protect people from oral routes of exposure."

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A hat tip to David Zaring at The Conglomerate for this post that covers some interesting ground regarding "risk" issue, including regulatory issues and issues regarding product liability and other tort claims. One part of the post also covers a new book on the safety - or lack of safety - of imports into the US

Of perhaps greatest interest, the post educated me to an upcoming (Dec. 6-9) seminar in Baltimore by The Society for Risk Analysis. The conference agenda is here. If you see an interesting item on the agenda, you can click through links on the left side to see detailed abstracts of presentations. Some are of potential global note as they address issues regarding the use of "sponsored" research, risks of nanoparticles (some are said to be be more toxic than asbestos fibers in some settings) and on whether formaldehyde is a carcinogen. To whet your interest, pasted below is the text of one abstract regarding sponsored research:


"M2-E 10:30 AM-Noon Research Funding and Scientific Integrity: Conflicts and Criteria


M2-E.1 10:30 Proposed consensus criteria for assessing the reliability of scientific work. Conrad, Jr. JW*; Conrad Law & Policy Counsel jamie@conradcounsel.com

Abstract: Ultimately, the merits of scientific research findings are judged by the extent to which they are reproduced by other scientists. Such replication can take years, and what constitutes replication in a given case may be disputable for some time. Consequently, the scientific community has developed a variety of shorter-term approaches for assessing scientific work. Some of these approaches are designed to evaluate the validity and significance of the work, particularly in comparison to other studies addressing the same question. (These approaches are frequently termed "weight of evidence" approaches.) Other approaches are addressed to the more limited, but still vitally important, task of evaluating the reliability of the work against concerns that the results may be the product of error or may have been consciously or unconsciously influenced by conflicting interests or biases of the investigator. Some of these latter approaches have become well-established (e.g., peer review, disclosure of competing interests); others are not yet widely accepted (e.g., public registries of proposed research, free access to underlying data). This presentation will survey the approaches being suggested and will propose a set of criteria that, if they became conventionally accepted, would allow all concerned to have confidence in the reliability of scientific work regardless of who conducted or funded it. "

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More great new science at the observable cellular level. As described below, scientists used tools to observe cellular level shapes, and then figured out a way to "staple" some proteins to better take on the needed shape to fit cellular receptors. How cool and important is this discovery? Very - the science is so good it was published in Nature this month. Go here to Science Daily for the broader whole story; excerpts are below.

Why does this relate to law? As these techniques are used to actually implement ways to "turn off" cancer, they will become the remedies sought by persons facing cancer allegedly or actually caused by particular substances.

_________________________________________________________________

"ScienceDaily (Nov. 12, 2009) -- Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed. Their discovery, published in the November 12 issue of Nature, lays the foundation for a new kind of therapy aimed directly at a critical human protein -- one of a few thousand so-called transcription factors -- that could someday be used to treat a variety of diseases, especially multiple types of cancer.

****

Based on his work as an oncologist, Bradner became deeply interested in a human protein called NOTCH. The gene encoding this protein is often damaged, or mutated, in patients with a form of blood cancer, known as T-ALL or T-cell acute lymphoblastic leukemia.

Abnormal NOTCH genes found in cancer patients remain in a state of constant activity, switched on all the time, which helps to drive the uncontrolled cell growth that fuels tumors. Similar abnormalities in NOTCH also underlie a variety of other cancers, including lung, ovarian, pancreatic and gastrointestinal cancers.

Even with this deep scientific knowledge, drugs against NOTCH -- or any other transcription factor -- have traditionally been extremely difficult, if not impossible, to develop. Most current drugs take the form of small chemicals (known as "small molecules") or larger-sized proteins, both of which have proven impractical to date for disabling transcription factors.

A few years ago, Bradner and his colleagues hatched a different idea about how to tame the runaway NOTCH protein. Looking closely at its structure as well as the structures of its partner proteins, they noticed a key protein-to-protein junction that featured a helical shape.

"We figured if we could generate a set of tiny little helices we might be able to find one that would hit the sweet spot and shut down NOTCH function," said Bradner.

Creating and testing these helices involved a team of interdisciplinary researchers, including Greg Verdine, Erving Professor of Chemistry at Harvard University and director of the Chemical Biology Initiative at Dana-Farber Cancer Institute, as well as scientists at Brigham and Women's Hospital and the Broad Institute's Chemical Biology Program, which is directed by Stuart Schreiber.

Verdine invented a drug discovery technology that uses chemical braces or "staples" to hold the shapes of different protein snippets. Without these braces, the snippets (called "peptides") would flop around, losing their three-dimensional structure and thus their biological activity. Importantly, cells can readily absorb stapled peptides, which are significantly smaller than proteins. That means the peptides can get to the right locations inside cells to alter gene regulation."

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Wondering what the Daubert case law will look like in a few years as great new science pushes past epidemiology as new machines and techniques make cause and effect more or less directly observable ? Worried about Alzheimer's perhaps being part of your future and wondering what's ahead? Wondering why nations need to invest more n fundamental science at national laboratories such as Brookhaven and Argonne ? If any of those topics are in mind, consider reading a short article that reports on a new molecular level discovery made by scientists at the storied Cold Springs Harbor Laboratory using the National Synchrotron Light Source at Brookhaven National Laboratory. For the article online, go to ScienceDaily (Nov. 13, 2009). Key excerpts are below:

"A team of scientists at Cold Spring Harbor Laboratory (CSHL) reports on Thursday their success in solving the molecular structure of a key portion of a cellular receptor implicated in Alzheimer's, Parkinson's, and other serious illnesses

***

"Without a highly detailed molecular picture of the ATD, however, efforts to rationally design inhibitors cannot proceed. Hence the importance of Furukawa's achievement: a crystal structure revealed by the powerful light source at Brookhaven National Laboratory, that shows the ATD to have a "clamshell"-like appearance that is important for its function. The results are published in a paper appearing online Thursday ahead of print in The EMBO Journal, the publication of the European Molecular Biology Organization. (emphasis added)

The team obtained structures of the ATD domain with and without zinc binding to it. Zinc is a natural ligand that docks at a spot within the "clamshell" in routine functioning of the NMDA receptor. Of much greater interest is the location and nature of a suspected binding site of a small molecule type that is known to bind the ATD and inhibit the action of the NMDA receptor.

These inhibitor molecules are members of a class of compounds called phenylethanolamines which "have high efficacy and specificity and show some promise as neuroprotective agents without side effects seen in compounds that bind at the extracellular domain of other receptors," Furukawa explains. Now that his team has solved the structure of the ATD domain of the NR2B subunit, it becomes possible to proceed with rational design of a phenylethanolamine-like compound that can precisely bind the ATD within what Furukawa and colleagues call its "clamshell cleft," based on the crystal structure they have obtained."

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Courtesy of a friend in Australia, here is a link to a story on new radiotherapy science developed in Australia that is bringing some new hope for perhaps two more years of life for persons suffering from mesothelioma. Key excerpts are as follows:


Breakthrough in fight against mesothelioma

By Lindy Kerin for AM

AM abc.net.au/am

Posted Fri Nov 13, 2009 11:11am AEDT
Updated Fri Nov 13, 2009 11:22am AEDT
A new radiation technique can improve the life expectancy for sufferers.

A new radiation technique can improve the life expectancy for sufferers. (www.sxc.hu: Adam Ciesielski, file photo)


Australian experts are offering new hope to mesothelioma sufferers, claiming a breakthrough in the treatment of the aggressive cancer.

Specialists at the Austin Health Centre in Victoria have discovered a new radiation technique which can improve the life expectancy for sufferers.

Every year, around 700 Australians find out they have mesothelioma. The deadly cancer, which attacks the lungs, is mostly caused by exposure to asbestos.

On average sufferers are given just two years to live after diagnosis.

Dr Malcolm Feigen, a Radiation Oncologist at the Austin Health Centre in Victoria, has for the past seven years been developing new techniques for treating mesothelioma, involving high doses of radiotherapy.

"Gradually with new technologies and better equipment we've been able to increase our doses and look at the results by doing PET scans before they start the radiotherapy and PET scans after they've finished to see what difference we've made," he said.

"And we've been very impressed that in most cases there's a considerable improvement in the activity of the tumour masses that we've given high doses of radiotherapy. And most patients have got through the course of treatment with no major side effects and some have had long-term benefits."

Dr Feigen says patients treated only with chemotherapy mostly have short-term benefits and then the cancer comes back.

"But with radiotherapy it doesn't come back in the same area and if we find patients early enough we may be able to stop any further developments of their disease," he said.

All up, 13 patients were involved in the pilot program.

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Are cord blood donations important ? You bet ! Great new science documents that children and others with leukemia (and perhaps other lymph cancers) may obtain cures through transplants of two units of cord blood even when there is no perfect match available. This is promising news because today's increasing diversity means that children from diverse marriages have more difficulty in finding perfect matches for marrow stem cell donations. The published medical article is in the journal Blood and can be downloaded here for personal use. Set out below is summary from Science Daily.

University of Minnesota (2009, November 15). Two Units Of Umbilical Cord Blood Reduce Risk Of Leukemia Recurrence. ScienceDaily.


Two Units Of Umbilical Cord Blood Reduce Risk Of Leukemia Recurrence

ScienceDaily (Nov. 15, 2009) -- A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning. This finding has the potential to change the current medical practice of using one unit of UCB for treatment of patients who are at high risk for recurrence of leukemia and other cancers of the blood and bone marrow.

Michael Verneris, M.D., and John Wagner, M.D., who specialize in research and treatment of children with cancer, led the research team on this breakthrough study. The results are published in the current issue of the scientific medical journal Blood. This study was funded with grants from the National Cancer Institute and the Children's Cancer Research Fund.

Verneris and his colleagues studied 177 patients treated at the University of Minnesota Medical Center, Fairview and the University of Minnesota Amplatz Children's Hospital between 1994 and 2008. The average age of the patients in this study was 16 years. Eighty-eight patients had acute lymphoblastic leukemia (ALL) and 89 had acute myeloid leukemia (AML).

"Our analysis showed that patients in first or second remission from the leukemia had a significantly lower likelihood of leukemia recurrence if they were transplanted with two UCB units than if they were transplanted with one (19 percent vs. 34 percent)," says Verneris.

"We believe our finding provides evidence that using two units of UCB for transplantation may be more effective in preventing leukemia relapse and gives hope to patients with hematological malignancies so that they may live cancer-free," he says.

Blood and marrow stem cell transplantation has been a mainstay treatment for patients with high risk leukemia and other hematological malignancies for the past 30 years. In the last decade, the blood in the placenta and umbilical cord has been collected and banked for public use. Now, UCB is routinely used throughout the world as an alternative to bone marrow transplantation.

However, because of the limited number of cells in UCB, this stem cell source has been reserved for young children and small adults. The practice of using two UCB units (from two different individuals) was pioneered at the University of Minnesota approximately 10 years ago. By using two UCB units, nearly all patients can now use this stem cell source for transplantation.

Previous research studies have also shown that about 25 to 30 percent of patients suffer leukemia relapse after transplant. The relapse or disease recurrence rates are similar regardless of whether the stem cells used for transplantation are from bone marrow, peripheral blood, or umbilical cord blood.

Verneris and his colleagues compared the outcomes of patients who were transplanted with one verses two UCB units. Forty-seven percent of the patients received one unit of UCB; the remaining patients received two units. The choice to receive one versus two units was based on the number of stem cells contained in the UCB. Since the number of stem cells needed for a successful transplant varies with the patient's weight, older patients and those who weigh more need more stem cells than infants and young children.

"Given that adult patients were more likely to receive two UCB units and that they tend to have more aggressive leukemia, we think that the lower relapse rates with two UCB units is remarkable," says Verneris. He notes that while promising, these results will have to lead to a national study comparing one verses two cord blood units in children with leukemia.

"Prior to the research done by my predecessors, the co-infusion of two UCB units had not previously been performed," says Verneris. "We now know that without this double transplantation procedure, the majority of the patients treated would have had no other reasonable treatment option for their leukemia. The fact that they had less leukemia relapse was a wonderful surprise." (emphasis added)


Set out below is the abstract from the medical article.


Relapse risk after umbilical cord blood transplantation: enhanced
graft-versus-leukemia effect in recipients of 2 units

Michael R. Verneris,1,2 Claudio G. Brunstein,2,3 Juliet Barker,2,3 Margaret L. MacMillan,1,2 Todd DeFor,1,2 David H. McKenna,4 Michael J. Burke,1 Bruce R. Blazar,1,2 Jeffrey S. Miller,2,3 Philip B. McGlave,2,3 Daniel J. Weisdorf,2,3 and John E. Wagner1,2

1Department of Pediatrics, 2Blood and Marrow Transplant Program, 3Department of Medicine, and 4Department of Laboratory Medicine and Pathology,
University of Minnesota Medical School, Minneapolis

Umbilical cord blood (UCB) transplantationis potentially curative for acute leukemia. This analysis was performed to identify risk factors associated with leukemia relapse following myeloablative UCB transplantation. Acute leukemia patients (n 177; 88 with acute lymphoblastic leukemia and 89 with acute myeloid leukemia) were treated at a single center. Patients received a UCB graft composed of either 1 (47%) or 2 (53%) partially human leukocyte antigen (HLA)-matched unit(s). Conditioning was with cyclophosphamide and total body irradiation with or
without fludarabine. The incidence of relapse was 26% (95% confidence interval [CI], 19%-33%). In multivariate analysis,relapse was higher in advanced disease patients (> third complete remission [CR3]; relative risk [RR], 3.6; P < .01), with a trend toward less relapse in recipients of 2 UCB units (RR 0.6; P .07). However, relapse was lower for CR1-2 patients who received 2 UCB units (RR 0.5; P < .03). Leukemia-free survival was 40% (95% CI, 30%-51%) and 51% (95% CI, 41%-62%) for single- and double-unit recipients, respectively (P .35). Although it is known that transplantation in CR1 and CR2 is associated with less relapse risk, this analysis reveals an enhanced graft-versus-leukemia effect in acute leukemia patients after transplantation with 2 partially HLA-matched UCB units. This trial was registered at http://clinicaltrials. gov as NCT00309842. (Blood. 2009;114: 4293-4299).

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90,000 people per year travel to Houston's MD Anderson Cancer Center for treatment. Many are children. Most will not find a cure. Some will obtain more time. Almost all will suffer to achieve those additional years or months. Some will be in agonizing treatments for many months or even years. Forty years after President Nixon acknowledged the need for the so-called war on cancer, the therapies are still barbaric. Indeed, too many treatments are still so barbaric that more people than you would know will some day die from the treatments instead of the original cancer.

The staggering 90,000 number and other harsh realities are part of Gina Kolata's latest NYT article on why changes are needed in the race to prevent, manage and cure cancers. Her latest story focuses on MD Anderson to starkly highlight part of why our nation needs health care reform in general, and why our nation needs to exponentially accelerate and improve the manner in which individuals are treated for the myriad forms of cancers. Here is the image of yesterday's powerful front page picture and story. Here is the story itself.




Much more can and should be done, now. Happily, there is some expanded support triggered by the Obama Administration's support for science as detailed here. For example, the NIH and NCI are accelerating great new programs, including the Cancer Genome Atlas with wide-spread "cloud" access to the incredible amounts of new genomic information. But, much more can and should be done. Myriad cancers are starting to surrender their secrets to the brilliant doctors, new machines, and staggeringly fast computers and software that are sequencing genes and visualizing molecules at an unprecedented pace and in ways never before accomplished. Please, stay focused on the debates over health care and demand that our nation act to devote far more resources to saving more of our nation's 500,000 annual US victims and to prevent future cancers.

Can more be done in an effective way. Absolutely !

Who says so? For one, Dr. James Watson (of the Nobel prize team regarding DNA) in this powerful 2009 NYT editorial article. In just a few paragraphs, he outlines where we've been, where we are now, and why now is the time to accelerate and move forward in new ways.

For another, this 2008 book by Dr. Guy Faguet, an experienced doctor/scientist, has much to say on the subject of what's ahead and what needs to change on cancer research and treatment. http://www.amazon.com/War-Cancer-anatomy-failure-blueprint/dp/1402036183.

Dr. Faguet makes three main points. First, the "cell kill" approach to cancer is in large measure a failure. He also explains how and why the cell kill clinical trial is so slow and so tied to outmoded reimbursement systems and short-term profit models. Second, cancer prevention deserves far more effort and attention. For example, many oncogenic chromosome changes are caused by retroviruses, and so preventive vaccines are key to prevention and warrant far more effort and money. Some remarkable reductions in cancer appear to been achieved in some nations through vaccinations to eliminate one hepatitis virus. Third, the fast arriving future is finding cancer early and applying human and workable genomic therapy instead of trying to kill cancer cells after they are widespread.

Can this be done, politically speaking ? Yes. For that subject, see Dr. Harold Varmus' book - The Art and Politics of Science.

Dr. Varmus credentials ? Nobel Prize winner as part of a team of cancer researchers, head of the NIH for the Clinton Administration, and now the leader of Memorial Sloan Kettering. http://www.amazon.com/Art-Politics-Science-Harold-Varmus/dp/0393061280/ref=sr_1_1?ie=UTF8&s=books&qid=1256563341&sr=1-1

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Here's a science follow up to yesterday's historic ruling by the Massachusetts Supreme Court regarding medical monitoring due to genome level changes. Yesterday, a story popped up that illustrates how fast and far medicine and genomics are moving thanks to incredible computer speeds and software. The gist? In 10 days, scientists sequenced an entire human genome and diagnosed a disease that had baffled the clinicians !!

The full story is here, from the Howard Hughes Medical Institute. Here are key excerpts:

"October 19, 2009 Diagnosis Emerges from Complete Sequencing of Patient's Genes

For the first time, scientists have diagnosed a genetic disease by completely sequencing all of a patient's genes. Using high-throughput DNA sequencing technology, Howard Hughes Medical Institute (HHMI) researchers successfully identified a gene mutation that was responsible for the patient's disease, but had not been suspected based on clinical observations.

Starting with DNA from a blood sample from the patient -- an infant in Turkey who was persistently dehydrated and failing to gain weight - the team found in 10 days a gene mutation known to affect electrolyte transport in the intestines and cause a condition called congenital chloride diarrhea. Doctors in Turkey confirmed the diagnosis clinically and were able to provide a treatment tailored to the disease.

***

I think in the coming years we're going see a dramatic increase in the use of this kind of technology," Lifton says. "This is going to be a very powerful technology for disease-gene discovery and clinical application." Lifton and his colleagues reported their method and diagnosis in an advanced online publication of the Proceedings of the National Academy of Sciences on October 19, 2009."

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This August 27 press release from Abbott and Pfizer exemplifies another way science is changing and will over time create new legal issues as to remedies for tort claims. The pertinent part of the press release is quoted below; the gist is that the two are undertaking a joint effort to create a diagnostic test to find persons with a specific genetic defect so that a clinical trial can be then undertaken only with patients with that particular genetic defect. Soon enough, plaintiffs will be able to have good science behind requests asking courts to order a risk -creator to pay for much more than just a traditional annual check-up.

________________________________________________________________


Des Plaines, Illinois and New York -- Abbott (NYSE: ABT) announced today that it has entered into an agreement with Pfizer Inc to develop a molecular diagnostic test intended to screen non-small cell lung cancer (NSCLC) tumors for the presence of gene rearrangements. Pfizer has developed a novel investigational agent that selectively targets cancer-causing genes implicated in the progress of many cancers. To be eligible to receive Pfizer's oral therapy, a particular genetic translocation (rearrangement) known to be found in NSCLC tumors and a wide variety of other cancers, but not in normal cells, must be present.

Under terms of the agreement, Abbott will develop a companion diagnostic test that will determine a patient's genetic status and will be used in patient selection for future clinical trials of PF-02341066.

"We are very pleased to partner with Abbott to develop a companion diagnostic test for non-small cell lung cancer and ensure its global availability for patients and physicians who need this information to make the best treatment decisions," said Garry Nicholson, General Manager, Pfizer Oncology Business Unit. "This test will allow us to focus on the patient population most likely to benefit from our NSCLC candidate. Working in close partnership with the experienced Abbott team, we are confident that we will deliver yet another application of personalized medicine to address a currently unmet medical need in NSCLC."

"Pfizer's novel compound for treating non-small cell lung cancer appears to be ideally suited to individualized therapy," said Stafford O'Kelly, head of Abbott's molecular diagnostics business. "Abbott is a leader in the development and commercialization of companion diagnostics and we're delighted to collaborate with Pfizer, a leader in cancer therapeutics, on the development of a test to identify patients who might benefit from this important compound."

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More on brain rewiring and damages potentially recoverable in current or future tort litigation. This prior post provided some fact patterns and legal issues on future damages issues as drawn from research breakthroughs described in a wonderful book on brain plasticity - The Brain That Changes Itself -- Stories of Personal Triumph from the Frontiers of Brain Science, by Dr. Norman Doidge.

Now, here's more to think about as both individuals and as tort lawyers who end up in arguments about what is "harm," how it is proved and measured, and how it is compensated. Specifically, yet more news on brain rewiring is out and indicates that stress does produce physical changes in the brain, thus providing possible evidentiary support for claims that stress is indeed a physical injury.

This August 17, 2009 NYT article by Natalie Angier summarizes new research on brain plasticity as it relates to stress. The gist is that scientists in Portugual this summer published an article in a prestigious medical journal regarding their findings on brain changes when rats were subjected to stress. The not so good news is that stress does indeed destroy brain wiring. The better news is that the brain can rewire and return to "normal" when the stress is reduced back to normal levels. Here are key quotes:

"Reporting earlier this summer in the journal Science, Nuno Sousa of the Life and Health Sciences Research Institute at the University of Minho in Portugal and his colleagues described experiments in which chronically stressed rats lost their elastic rat cunning and instead fell back on familiar routines and rote responses, like compulsively pressing a bar for food pellets they had no intention of eating.

Moreover, the rats' behavioral perturbations were reflected by a pair of complementary changes in their underlying neural circuitry. On the one hand, regions of the brain associated with executive decision-making and goal-directed behaviors had shriveled, while, conversely, brain sectors linked to habit formation had bloomed. (emphasis added).

****
But with only four weeks' vacation in a supportive setting free of bullies and Tasers, the formerly stressed rats looked just like the controls, able to innovate, discriminate and lay off the bar. Atrophied synaptic connections in the decisive regions of the prefrontal cortex resprouted, while the overgrown dendritic vines of the habit-prone sensorimotor striatum retreated."


If I were a plaintiff's lawyer, the NYT and Science article would be dropped into my bag of citations and evidence to argue for a broader range of treatment after, for example, suffering a trauma from a one time physical event or after cancer has been countered via surgery, chemotherapy or other means. As a defense lawyer, I'm probably going to argue this is not (yet) accepted science and try to keep it out of evidence under the Daubert rules. But, one might also ask what makes sense for the long term - perhaps injured people should receive some paid for r & r to get them into good patterns and a better recovery that may save money in the long run. Then we lawyers can argue about who should pay for it - the health insurer, the Comphrehensive General Liability insurer, the tort defendant or some government agency.

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More on science and tort law. Suppose medical malpractice destroys a woman's inner ear balance function to the point she can stand up only when supported by a wall or other structure. Suppose you are the insurer for the doctor - how much do you offer to compensate for her inability to work or to live any kind of a normal life? Is the offer a structured settlement worth perhaps $ 10 million over 30 years? If you are the woman, do you accept that offer? Or, do you commit yourself to an experimental but potentially highly successful new approach to restore your balance by going around the destroyed system ?


The experimental approach may well be the better alternative for both the victim and the insurer. What is it? Helping the woman's brain to rewire itself through an intensive therapy process that calls for rebuilding and rewiring the brain and balance system by routing signals up to the brain through a Rube Goldberg hat with wires connected to the tongue. In fact, as is detailed below, this technique worked and restored - fully - "the wobbler's" balance. And, the therapy subsequently has worked repeatedly for other persons with similar problems.



Or, suppose you are the disability insurer for a physician who suffers a stroke in the prime of life and loses significant bodily function. Do you pay out millions in disability over the years or pay hundreds of thousands of dollars for an intensive therapy that may restore function by once again rewiring the brain ? The latter may well be the right choice.


Suppose you are a disability insurer facing the prospect of thousands more Alzheimer's claims than the underwriters had expected. What to do - pay, take the insurance company into "run-off" or pay for "learning software" for which there is objective clinical data indicating that use of the software therapy helps to block or delay the onset of Alzheimer's by helping the brain form new links ?



For all of the above fact patterns, consider some additional questions. Suppose the issues do not arise from insurance policies and instead arise from a lawsuit seeking remedies/damages for an injury caused by negligence ? Suppose the claim is based on strict liability - does that matter? Suppose the victim smoked or took some other action plainly viewed - today - as contributory fault - does that limit the remedy or damages?

Does the insurer get to choose the option or does the insured/victim make the choice? Suppose the insured/victim chooses not to try the intense therapy despite a proven track record of success in "like" patients - should that limit the amount of damages payable ? How "like" does "like" have to be ?

Suppose the therapy is available only at one or two facilities in the US - is there an obligation to pay for the travel and hotel expenses? How nice a hotel? What about paying for food and shelter for a supporting family member? What about paying for a family member or a professional nanny to stay with children while the wife goes through therapy and is supported by her husband? What about paying a supporting family member who goes with the patient to support the patient through the intensive, months-long therapy? What happens when the victim is from country x, speaks language y, and the therapy is - for now- available only in country q where they speak language b?


Excluding the insurance company parts, the examples above are all drawn from real world situations covered in a fantastic book on brain science. The thrust of the book is that brain rewiring principles today are well-accepted and indeed proven by "brain mapping," but 30 or so years ago were considered heresy. The most basic scientific principle? Contrary to conventional medical wisdom, the brain in fact can and will rewire itself IF worked intensely by therapists who know what they are doing. Are the results purely subjective? No - they've been objectively proven by laborious "brain mapping" and by observable results.


The book? The Brain That Changes Itself -- Stories of Personal Triumph from the Frontiers of Brain Science by Dr. Norman Doidge. Who is he? A physician turned researcher who took the time to write a brilliantly readable book explaining for everyone why and how science can cause seemingly miraculous recoveries for victims of strokes, disease, traumatic accidents and even psychological traumas. The book is in part an explanation of the insights of dedicated scientists who rejected conventional thinking about the brain and proved that in fact the brain is a remarkably "plastic" organ that can change and overcome profound injuries to the brain itself. The book also explains how the brain rewires to compensate for and overcome injuries to other parts of the body. The book begins, for example, with the story alluded to above regarding the brilliant new technique for rewiring the brain of the "wobbler" injured by a physician's error. Other chapters describe how intense, out-of-the -ordinary therapies produced virtually complete recoveries for victims of strokes, some birth defects and even some mental health issues.


The book also is a must read for everyone worried about dementia in old age. Pages 70-91 describe demonstrably successful software and exercise programs being developed by a company known as Scientific Learning that has developed a program known as Fast For Word, and other software developed by Posit Science. Also significant is the description of the Aerosmith School at pages 36-44.

Conclusion? New issues lie ahead. Centers of excellence with intensive therapies can and do offer some people wonderful, life-saving opportunities not available anywhere else. Which lawyer among us is good enough to - successfully - argue to a jury why the injured person is not entitled to access the center of excellence when the requested remedy is based on sound logic and science ? And, aren't all sides better off if the intensive therapy succeeds and produces fewer overall costs ?

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Today, more on science, cancer and law. Why do I think these topics are worth writing about for tort lawyers and perhaps some policy-makers around the world? Because science brings us a fast arriving future, as is detailed below. And, if the US actually achieves health care reform and more sophisticated rules at the FDA, cures will arrive even sooner. The results for lawyers, cancer victims and persons at risk ? Over the next few years, we will see more highly specific lawsuits seeking specific kinds of medical monitoring (tests for proteins, specific types of scans) and specific leading-edge clinical treatments. You can read here a summary of the cases Phillip Morris is fighting and note that two (in New York and Massachusetts ) are medical monitoring cases seeking CT scans for certain groups of smokers. More such suits are sure to come as science moves ahead. And, damages claims are going to increase around the world as even the poorest persons from any nation seek what they will argue is the fundamental human right to funds for and access to a meaningful chance for a cure for cancer. Thus, the financial and human stakes will continue to rise for parties to litigation and national policy-makers.

To start with, consider some numbers regarding cancer. About 2,4oo hundred or so annual mesothelioma cancer deaths in the US have caused the payment of hundreds of billions of dollars in settlement payments and legal fees. The mesothelioma rate is exploding over seas, especially in Australia and Europe where amphibole use was rampant and continued far longer than it did in the US. Meanwhile, many nations are increasing the use of asbestos, including some use of chrysotile that contains amphiboles.

Now look outside asbestos and see how small mesothelioma is in the grand scheme. Per statistics from the American Cancer Society, over 1.4 million new cancers will be diagnosed this year just in the US and 4% of Americans are cancer survivors. Every two days, more people in the US die of cancer than died on 9/11/01. Mesothelioma is a modest problem in that scale (a statement which is not to minimize the horrible and almost always fatal nature of mesothelioma.)

Now, think about another form of cancer, such as non-Hodgkin's lymphoma. The annual rate used to be over 50,000 per year (in just the US) but now has climbed to well over 60,000 diagnoses per year. Please see this prior post for links to the American Cancer Society data and for Gina Kolata's prior article summarizing the slow pace of generating cures.

In view of those numbers, consider where science is on research. Ms. Kolata last week published this important new article detailing the moribund pace and utility of clinical trials for new cancer drugs. It's depressing reading as she details multiple problems, including lack of volunteers for the trials, and design flaws that require too many participants. Yet another problem - highly relevant today - is that most existing insurance reimbursement plans financially and practically discourage doctors from helping patients find and join appropriate clinical trials. So, for policy-makers and voters, here is proof that our present system is exactly backwards as it discourages clinical trials needed to find and prove cures for cancer. Thus, we now have further objective proof that our existing health care insurance system is built to generate revenues instead of cures, and so is deeply flawed for persons with serious diseases, which of course is the group that most needs health care and insurance. Hopefully a revised system will include some clever economic choice Nudges from the conservative and creative new regulatory czar, Cass Sunstein ( go here for the blog tied to the recent and wonderful book Nudge by Messrs. Sunstein and Thaler).

But, despite those flaws, is science now at a point to make real progress and actually put in place cures for at least several cancers? Some say yes. Who says so? Nobel Prize winner Dr. James Watson, one of the two leaders of the team that explained DNA's double-helix. Go here for his powerful article explaining that mapping the genome and other advances mean that science has made enough progress so that there is now a scientific tool kit that can actually work for some people with some cancers and can be applied to an increasingly wide range of cancers. Here's the opening paragraph of his article:

"THE National Cancer Institute, which has overseen American efforts on researching and combating cancers since 1971, should take on an ambitious new goal for the next decade: the development of new drugs that will provide lifelong cures for many, if not all, major cancers. Beating cancer now is a realistic ambition because, at long last, we largely know its true genetic and chemical characteristics." (emphasis added).

Go here for Dr. Wendy Harpham's full post on Dr. Watson's article, but here is Dr. Harpham's summary of his recommendations:

"Watson believes :

The new signal-blocking drugs (e.g., Herceptin) will lead only to improved lengths of survival.
Most anticancer drugs can reach their full potential only if given in combination with other drugs.
We must change F.D.A. regulations to allow testing in combination new drugs that, when given alone, have proved ineffective.

The NCI should provide funds to smaller biotech companies doing innovative work and to major research-oriented cancer centers doing low probability-high payoff projects."

Do clinical trials and science actually translate into lives saved even while science is ongoing? Yes, sometimes. Want proof ? Go to this blog (On Healthy Survivorship) to read Dr. Harpham's personal success story. She is a physic an who was forced to give up her patient treatment practice back in the early 1990s due to repeated onsets of non-Hodgkins lymphoma. Thwarted, she refocused to writing a great series of books and a blog about cancer and healthy survivorship. Today, she is a healthy survivor because of clinical trials and monoclonal antibodies, and healthy, realistic hope, as she describes in this post in particular and her blog and books in general.

Conclusion ? I'd say defense lawyers and corporations face future waves of claims based on new science and new lawsuits seeking new remedies. Specific causation and other defenses of course will continue to exist, but when the plaintiffs can invoke names of credible scientists such as Dr. Watson, the defense side will start to see one aspect of the whittling back of science as major weapon against tort claims.

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The world plainly is growing smaller and is more subject to empiric evaluation. To me, those are great trends for many reasons, including my preference for facts instead of hearsay and anecdote. So, I follow the Empirical Legal Studies blog. The following post is germane for lawyers around the world seeking to better understand the activities of the European Court of Justice.

_______________________________________________________________

from Empirical Legal Studies by Jason Czarnezki
Alec Stone Sweet and Thomas Brunell have posted three data bases, on the activities of the European Court of Justice, and the adjudication of EU law, under Articles 226 (infringement proceedings - brought by the Commission against a Member State), 230 (annulment actions in administrative law brought by individuals and companies against the EU), and 234 (preliminary references from national judges to the ECJ). They collected these data over the course of 12 years, and they are unavailable outside of the Court, which does not provide public access to them. The home for these data is the Robert Schuman Centre, the European University Institute. The datesets, accompanying codebooks, and papers providing summary analyses of the data can be found here: http://www.eu-newgov.org/datalists/deliverables_detail.asp?Project_ID=26. Since 1996, scholars have used these data in a wide variety of research projects, including doctoral dissertations, books, articles in economics, law, sociology, and political science.

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Here's a new example of changes in science causing changes in law. An article here reports the Danish government has now paid industrial compensation to some 40 women for incidents of breast cancer when they had 20-30 year careers working night shifts. The article includes a UK defense lawyer at Eversheds warning that studies by IARC and the Danish decision may put UK employer's on notice of the risk. Here are key excerpts:

"Are workers at risk of developing cancer because of their shift patterns? That is the question that will be troubling UK employers now a UN study by the International Agency for Research on Cancer (IARC) has concluded that working night shifts raises the risk of breast cancer.
The UN study found in particular that nurses and flight attendants involved in night-shift working over a period of 30 years had an increased incidence of breast cancer.

The study is not definitive - for one thing, it only looked at a limited number of occupations - and the IARC itself has called for further research. However, the Danish government has been sufficiently concerned to recognise as an industrial injury breast cancer developed after night-shift work. That finding cleared the way for compensation payments to approximately 40 women who had worked night shifts for some 20-30 years where there was no other significant factor to explain the development of the cancer.

But even though employers may not yet have the full picture, the courts have decided that it is only necessary to know that some harm is foreseeable to its workers - not the exact type of harm.

The HSE has issued no guidance in this country, and its own research into the potential link is not expected until 2011, but that is not a complete defence when an EU government is already paying out on such claims. Employers cannot ignore this research when assessing the risks to which they expose their workforce. Employers who have made such assessments and given warnings are in a better position to ward off claims."

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Here is a blog entry from one of the lawyers at the Conglomerate explaining part of the personal and moving story behind how and why Major League Baseball is commemorating this July 4 as the 70th anniversary of Lou Gehrig's still-powerful "Luckiest Man" speech. It's a great reminder and its great to see this consciousness-raising, especially in this year of debate about health care reform. Such a shame we do not yet have a cure for this insidious disease and related diseases.

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The substance of sponsored medical literature remains a controversial issue. A 2009 article by Mark S. Frankel in the ABA's SciTech lawyer raises a variant issue. The article is titled "Clinical Trials and the Financial Markets, " and is online here. The article recounts market knowledge and manipulation issues arising from leaks of information involving sponsored clinical trials and other clinical trials. The following quote caught my eye especially since the 2009 ASCO Conference ended a few weeks ago nd I was watching articles pop up online from the conference on cancer treatments. Some of the results/articles plainly did move the markets, which of course is fine so long as the information is accurate:

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Ms. Gina Kolata is back with another important but depressing New York Times article on the failure of our national policy for addressing cancer. Her series started with a late April article. I mentioned it here in a post that provided links to sources showing that more people die in the US every two days due to cancer than died on 9/11/01, and that a careful, extended study showed that the direct costs of cancer treatment are exceed by indirect costs of cancer at a ration of about 2.3 to 1 by the indirect costs.

The gist of her new article is to demonstrate that our nation fails to fund research on new ideas and instead strongly tends to fund new research in old areas. Doing so of course has its advantages in that little risk is taken, but the article also explains that taking risks and following new ideas is often how we make real progress. Indeed, just think of where we might be if Dr. Salk had been stuck thinking in conventional ways. Ironically, the later online version of the Sunday NYT includes a new article reporting on success in battling cancer in animals through some unusual techniques developed in Australia that take advantage of leaks in tumor blood vessels to deliver minicells that mark the area for treatment.

For a dramatic, detailed and easy to read example of why new thinking is a MUST for cancer, read Dr. Folkman's War. http://www.amazon.com/Dr-Folkmans-War-Angiogenesis-Struggle/dp/0375502440
The book tells the story of how a stint doing pathology and seeing tiny tumors throughout bodies ultimately caused Dr. Judah Folkman to reach the profound insight that all solid tumors need blood vessels to grow, and that something in the body must turn on and off the ability to generate blood vessels. As the book details, Dr. Folkman and his ideas were rejected and indeed even ridiculed. But after many years , his unorthodox theories ere proven correct. Research continues today into how to delay or stop tumor growth using some of the principles he developed, and some promising results have been obtained.

In short, there is much to be done to create a strong national or global strategy for solving or managing the myriad types of cancer. Indeed, I've come to the view that all the walkathons and charities are in a way counterproductive. Why? Because they implicitly send the message that cancer has to be solved through relatively modest hard-earned donations instead of through a massive national and international funding of efforts to find cures for cancers.

Finding ways to cure or manage cancer should be a priority of our government for both objective and subjective reasons. On the objective side, the direct and indirect costs of cancer are huge as detailed by the study mentioned above, and our economy needs the short term and long term jobs that new science may create (which would blue collar jobs as well because fermenting yeast to grow medicines is much like brewing beer, except even cleaner). For subjective reasons to find answers for cancer, consider that every two days, over 4,000 people will die from cancer. Our government, however, has not spent hundreds of billions of dollars a year to avenge the thousands of the thousands of "homeland" cancer deaths that occur every day.


For data for cancer for 2009, see:
http://www.cancer.org/docroot/STT/STT_0.asp

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Asbestos campaigners in the UK have embarked on a 1,200 mile bicycle trip to publicize the need for more medical research into asbestos-related cancers and to publicize asbestos issues. The trip is the subject of a blog known as "Breath-Taking Journey" and is found here. The ride is to end on July 4.

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Monday's post noted that the war on cancer is going slowly, at best. Little did I know that by the end of the day, President Obama would respond during a speech to the National Academy of Sciences by announcing a doubling of the budget for cancer research !!

Ok, ok, so the reality is that his speech was planned long before the blog post went up. But, it was still great to read the following excerpt from a White House post on the speech, and to read the following excerpt from his speech to the National Academy of Sciences:


Excerpt from Post: " Given the nature of the challenges the country faces in global economic competitiveness, energy, and health, the President will call for the U.S. to surpass its record investment in research and development, set in 1964 at the height of the space race, exceeding three percent of GDP. This goal would be met with both public and private investment."


Excerpt from Speech to the National Academy: "And that's why my administration is committed to increasing funding for the National Institutes of Health, including $6 billion to support cancer research -- part of a sustained, multi-year plan to double cancer research in our country."

That's great. In my opinion, it's still not enough money for cancer and other diseases when one considers the just under 600,000 US lives lost to cancer each year, and the hundreds of thousands of lives lost annually to other dread diseases. It is, however, great to see science becoming a national priority after so many years of neglect, if not antipathy.

The speech is well worth reading in full.

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The Friday April 24, 2009 New York Times included a thoroughly depressing article on cancer by long-time science writer Gina Kolata. The general point of the article is to document the lack of real progress on the "war on cancer."

The lack of progress is especially daunting when one considers some data on how much we spend on different wars. According to Ms. Kolata's her article, the National Cancer Institute has spent $ 105 billion on cancer since Richard Nixon announced the war on cancer in 1971. That's a paltry expenditure when one considers that 4% of Americans are cancer survivors, and detailed data showing lifetime cancer risks, such as the 1 in 8 women will develop breast cancer, and 1 in 13 men will develop lung cancer. Risks of course translate into deaths. Slightly under 600,000 people in the US will die from cancer during 2008 according to detailed statistics from the American Cancer Society. That means that every two days, more people die of cancer than died on 9/11/01. Incredibly, since 2001, we've spent spent trillions of dollars to stop the risk of a few thousand more 9/11 type deaths, but since 1971, NCI could only muster about $ 5 billion per year for diseases that take hundreds of thousands of lives per year. In my book, that's insane when considered only in terms of the human agony inflicted by cancer.

The failure to solve disease problems becomes even more incredible when one looks at the costs inflicted by disease. On that topic, consider data from an an April 27, 2009, Business Insurance article by Joanne Wojcik. Her article reports on a significant recent study on health care costs of employers. Some quotes are below, but note especially two points. In terms of costs for hospitals and drugs, cancer is the leading cause of expense. But, even those costs are exceeded by 2 to 1 by indirect costs.

"For every dollar spent on medical costs and pharmaceuticals, there is $2.30 of health-related productivity losses due to absenteeism and presenteeism, according to the study. For certain conditions, such as anxiety, employers lose as much as
$20 in productivity for every dollar they spend on medical care and pharmaceuticals.

The study, which researchers said is one of the largest to date on the subject, found that when medical and prescription drug costs are considered alone, the top five conditions driving employer health care costs are cancer, back/neck pain, coronary heart disease, chronic pain and high cholesterol.

However, when medical and drug costs and productivity losses are factored into the equation, the five costliest conditions for employers are depression, obesity, arthritis, back/neck pain and anxiety, researchers say."

BTW, this is not a lightweight study. Instead, according to Business Insurance:

"The study was conducted in two phases: The first phase used data collected between 2005 and 2006 from four employers with 57,000 employees. In the second
phase, between 2007 and 2008, researchers increased the number of employers to
10 and employees to 150,000 and investigated more subtle aspects of the relationship between the 25 targeted health problems and productivity. More than
1.1 million paid medical and pharmacy claims were included in the combined
analysis."


The article abstract is pasted below and also is available here. The same link may be used to purchase the article.


Health and Productivity as a Business Strategy: A Multiemployer Study.

Fast Track Article Journal of Occupational & Environmental Medicine. 51(4):411-428, April 2009.Loeppke, Ronald MD, MPH; Taitel, Michael PhD; Haufle, Vince MPH; Parry, Thomas PhD; Kessler, Ronald C. PhD; Jinnett, Kimberly PhD

Abstract: Objective: To explore methodological refinements in measuring
health-related lost productivity and to assess the business implications of a
full-cost approach to managing health.

Methods: Health-related lost productivity was measured among 10 employers with a total of 51,648 employee respondents using the Health and Work Performance Questionnaire combined with 1,134,281 medical and pharmacy claims. Regression analyses were used to estimate the associations of health conditions with absenteeism and presenteeism using a range of models.

Results: Health-related productivity costs are significantly greater than medical and pharmacy costs alone (on average 2.3 to 1). Chronic conditions such as depression/anxiety, obesity, arthritis, and back/neck pain are especially important causes of productivity loss. Comorbidities have significant non-additive effects on both absenteeism and presenteeism.

Executives/Managers experience as much or more monetized productivity loss
from depression and back pain as Laborers/Operators. Testimonials are reported
from participating companies on how the study helped shape their corporate
health strategies.

Conclusions: A strong link exists between health and productivity. Integrating productivity data with health data can help employers develop effective workplace health human capital investment strategies. More research is needed to understand the impacts of comorbidity and to evaluate the cost effectiveness of health and productivity interventions from an employer perspective.

(C)2009The American College of Occupational and Environmental Medicine

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The New York Times ran a Saturday article detailing growing evidence of government misconduct in the criminal prosecution of WR Grace officials. Unlike most of the ongoing superficial stories about the trial, this article includes links to the judge's opinion excluding evidence proferred by the government, plus a brief from teh Grace side that details government misconduct. The article also includes references to the students and professors following the trial through a reasonably helpful blog.

The bottom line? As is so often the case when speaking about asbestos, the opponents of industry seek to ignore scientific lines drawn for many years between types of asbestos and how asbestos is defined. The science and lines deserve respect because, at the end of the day, good decisions have to be based on science.

Please do not take me as seeking to excuse everything done by industry or insurers. I certainly agree that officers of Johns-Mansville and some other companies took inexcusable actions. Some of their insurers also have much dirty laundry.

That said, distinctions between among asbestos fiber types are very real and their "toxicities" are different by orders of magnitude. For example, crocidolite fibers are usually viewed as 5oox more potent that chrysotile fibers in terms of causing mesothelioma.


Caveat/Disclaimer: In the mid-to-late 1990s, I was part of ateam of lawyers who represented W.R. Grace in asbestos litigation. My personal opinion is that the prosecution always has been a travesty because it ignored the facts and science regarding the Libby, Montana zonolite mining facility purchased by Grace after the facility had been in operation for many years.

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Lawyers are starting to react publicly to the Illinois Supreme Court's ruling on the Lipke issue. One article is pasted below, and quotes a well-respected and veteran Chicago lawyer, Ed McCambridge, 'as saying:

'It's probably the biggest asbestos opinion in the history of the state,'' McCambridge said. ''It is clearly going to have a huge effect on how cases will be tried in this state."

Ed is more than correct. Indeed, the opinion has national implications.

Why? Under (misinterpretations) of the Lipke case decided decades ago, the absurd result was that the last few defendants left in cases in Illinois were under enormous pressure to settle. Why? Because Lipke was construed to say that the jury could only hear evidence of the alleged exposure to the products of the defendant(s) in trial. For example, assume a plaintiff with mesothelioma who spent 10 years working at the old Manville plant in Waukegan, a suburb north of Chicago. Assume he spent his 10 years shoveling the especially lethal mphibole asbestos fibers that Manvilleused in some of its products. Assume also that outside of work, he once changed car brakes and once changed a gasket on a pump. Under Lipke as misconstrued, the plaintiff could take the brake lining maker and gasket maker to trial, but the defendants could not put in evidence to prove up his work at the Manville work as the sole cause of his mesothelioma. Does that make for an absurd trial and an absurd result? You bet, but trial judges in Illinois applied the law that way for decades, thus making Illinois a favored forum for plaintiff's to bring cases against defendants with little or no actual role in causing mesothelioma.

As Ed said, the implications are huge for the trial of cases in Illinois. The implication also are national because "Illinois values" should now fall for many defendants. That matters nationally because asbestos bankruptcy "liability estimates" have for years been artificially inflated by "Illinois values." Indeed, I was personally involved in proving in a bankruptcy that the settlement values for one defendant were 8x higher in Illinois than anywhere else in the nation.
So, so long as defendants and insurers do not blow this win with bad trial tactics, Illinois values should drop. The ruling also will be germane to choice of law issues, a topic of increasing importance in asbestos litigation.

Two other observations. One wonders why it took the Illinois Supreme Court almost tow years to issue this fairly simple opinion. One also wonders why it took insurers and defendants decades to take up an asbestos verdict and get Lipke reversed. During those years, literally billions of dollars were paid out for asbestos claims filed in Illinois.


http://www.chicagolawbulletin.com/news/get_story_text.cfm?id=100003346&SessionID=2516884

Ruling aids exposure defense on asbestos

By Bethany Krajelis Law Bulletin staff writerSPRINGFIELD -- The defendant in an asbestos case should not have been barred from presenting evidence of the decedent's other exposures to the material, the Illinois Supreme Court held Thursday.

In a 5-1 ruling, the high court remanded the matter of Sally Nolan v. Weil-McLain to the Circuit Court for a new trial and overturned two appellate decisions, saying the lower courts had misinterpreted a rule created in Lipke v. Celotex Corp., 153 Ill. App. 3d (1987), to prevent defendants from introducing evidence of other exposure.

Justice Robert R.Thomas did not take part in the decision and, while Justice Thomas L. Kilbride agreed with the majority that it was an error to exclude such evidence, he disagreed that the error requires a new trial.

Nolan sued 12 defendants, including Weil-McLain, in 2001, claiming that her husband's death from mesothelioma was caused from asbestos exposure at work. The other defendants settled, leaving Weil-McLain, a manufactorer of cast-iron boilers, the only defendant at trial.
A Vermilion County jury awarded Nolan $2.3 million in 2004. The 4th District Appellate Court affirmed the lower court's ruling, relying on Lipke, Kochan v. Owens-Corning Fiberglass Corp., 242 Ill. App. 3d (1993), and Spain v. Owens-Corning Fiberglass Corp., 304 Ill. App. 3d (1999).
The Lipke court acknowledged there can be more than one proximate cause of an injury, but noted that ''the fact that plaintiff used a variety of asbestos products does not relieve defendant of liability for his injuries. Evidence of such exposure is not relevant.''
In a 26-page opinion on Nolan's claim written by Justice Charles E. Freeman, the court agreed with Weil-McClain's argument that the trial court misinteprepated Lipke in barring the defense from preventing evidence of other sources of asbestos exposure that Clarence Nolan had encountered.
''Lipke simply determined that evidence of the plaintiff's other exposures was not relevant to the specific defense raised, i.e., that the plaintiff did not have an asbestos-related disease,'' Freeman wrote. ''In the matter at bar, however, defendant wishes to offer evidence of decedent's other exposures for different purposes: to contest causation through the use of the sole proximate cause defense, which was not raised by the Lipke defendant.''
Because the Kochan court extended the Lipke rule to say that evidence of other exposure is always irrelevant, which the justices acknowledged basically makes it impossible for asbestos defendants to argue a sole proximate cause defense, the high court overruled that portion of the Kochan decision.
In overruling Kochan and Spain, the high court also relied on its decisions in Thacker v. UNR Industries Inc., 151 Ill. 2d (1992), and Leonardi v. Loyola University of Chicago, 168 Ill. 2d (1995).
And while Kilbride agreed with most of the majority opinion, he said in his dissent that the error of not allowing evidence of other exposure at trial does not merit a new trial. He noted that other evidence that was admitted did provide Weil-McLain grounds for a sole proximate cause defense.
''[A] new trial is not warranted because Weil-McLain was able to receive a fair, albeit not perfect, trial in spite of the trial court's ruling,'' Kilbride wrote.
Nolan's attorney, David A. Novoselsky, said Kilbride's dissent says it all.
''In my opinion, the defendant got a fair trial here,'' Novoselsky said. ''This jury heard all of the evidence. It's as simple as that.''

Novoselsky said he plans to recommend that his client petition for a rehearing before the high court. He said he would ask the justices to consider Kilbride's dissent.

Richard P. Godfrey, who represented Weil-McLain at oral argument, said he was pleased with Thursday's opinion and believes the ruling will have an impact on a number of other cases.

Edward J. McCambridge, the national coordinating counsel for Weil-McLain, said Thursday's opinion is not only huge for the company, but for asbestos litigation in general.
''It's probably the biggest asbestos opinion in the history of the state,'' McCambridge said. ''It is clearly going to have a huge effect on how cases will be tried in this state.''

Edward Murnane, president of the Illinois Civil Justice League, and Gregory L. Cochran, the president of the Illinois Association of Defense Trial Counsel, both said they welcome the long-awaited decision with open arms.

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The march of science continues, and so does its impact on tort litigation. For example, the American Bar Association's TIPS section is hosting an April 2-4 seminar in Phoenix that includes speakers focused on claimant specific genomes as they impact disease. The agenda is here. Plainly we are moving towards a world in which individuals and subgroups will receive more attention, and generalized tort class actions will be harder to justify, but specialized clas actions may be harder to avoid. The results probably will help some plaintiffs and some defendants.



On the subject of individualized disease and mediciane, also interesting is a very recent medical article about using individual DNA to predict the amount of blood thinner needed for particular individuals. The research is descibed in a February 18 wall Street Journal article by Keith J. Winstein. To date, the dosing process for using blood thinners apparently has involved much trial and error, but now there is apparently credible evidence that the needed dose frequently can be predicted using individual DNA, at least for one of the blood thinner drugs. The research also is described a showing that some individuals do not well with the drug due to their DNA. Thus, this would seem to be yet another example of why the FDA and the US medical system are going to have learn to work with both epidemiology and molecular biology at the same time. Double blind studies are a pretty blunt instrument when compared to personalized science regarding the drugs useful for a specific person.

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"Sponsored research" continues to be controversial. The topic will be squarely addressed next spring in a Friday March 20, 2009 session of the Defense Research Institute's annual seminar on toxic tort litigation. The full DRI seminar agenda is here, and the session is as described as follows:


Meddling with Science--Is Scientific Research
Manipulated for Purposes of Litigation or Regulation?


Plaintiffs' lawyers claim that corporations protect their profits
by suppressing or influencing scientific and medical research and
information. Defense lawyers fight what they call "junk science"
offered by plaintiffs' experts and environmental activists. Do
scientists who participate as experts in litigation tamper with
or improperly influence scientific investigation to bolster the
prosecution or defense of claims in litigation? Do corporations
underwrite research simply to cast doubt on the claims of
environmental advocates and the plaintiffs' bar, or are they
interested in legitimate research that may rebut unwarranted
claims? Two scientists at the center of this contentious dialogue
will engage in a lively debate.

Speakers are:

David Michaels, Ph.D., MPH, George Washington University
School of Public Health and Health Services, Washington, D.C.

Dennis J. Paustenbach, Ph.D., CIH, DABT, ChemRisk Inc.,
San Francisco, California

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A continuing topic of this blog is exploration of the ways that advances in science will change tort litigation tactics and may change tort law rules. The topic will be squarely addressed next spring in a Friday March 20, 2009 session of the Defense Research Institute's annual seminar on toxic tort litigation. The speaker is the well-known and always interesting Dennis Paustenbach. The full DRI seminar agenda is here, and the session is as described as follows:

Toxicogenetics and Toxicogenomics--Science
Fiction or the Future of Toxic Torts?

The genetic revolution is here and has the potential to transform
toxic tort law as we know it. From biomarkers
to DNA microarrays to individualized genetic testing, there
are technical and scientific advances being made that have
the potential to alter the way in which toxic tort causation
is established. Dr. Paustenbach will dispel the myths and
explain the realities about genomics and toxic torts.


Dennis J. Paustenbach, Ph.D., CIH, DABT, ChemRisk Inc.,
San Francisco, California

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What to do with sponsored research - take it at face value, disregard it completely, or use it subject to considering whether to reduce its weight due to the sponsorship (assuming the sponsorship is disclosed). The debate today ranges across a wide spectrum of information sources and decision-makers.

Of note yesterday, an NYT article by Reed Abelson reports that the Cleveland Clinic announced plans to make disclosure of all payments from drug companies and other sources. According to the article:

"It appears to be the first such step by a major medical center to disclose the industry relationships of individual doctors. And it comes as the nation's doctors and hospitals are under mounting pressure to address potential financial conflicts of interest that can occur when they work closely with companies to develop and research new drugs and devices.
The Cleveland Clinic's Web postings are the most recent part of a conflict-of-interest effort at the clinic after some of its leading doctors came under fire several years ago when the news media disclosed some of their financial links."

On the topic more generally, one good source for general reading is a cogent New York Times article by Adam Liptak regarding the Exxon Valdez case and its footnote 17 regarding the Court's refusal to rely on research sponsored by Exxon. Titled From One Footnote, a Debate Over the Tangles of Law, Science and Money," the article also details a like ruling by Judge Weinstein in a drug class action.

The sponsored research topic also is being aired through symposia, such as Cornell sponsoring a symposium on Empirical Legal Studies (agenda here). There also is a good blog devoted to Empirical Legal Studies.

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How should governments and courts decide/define when persons have a condition that should warrant payment of compensation through tort claims or through government agency programs ? The question is relevant in many settings, but the issues I know best relate to asbestos litigation. The question is presently the subject of discussion in a variety of jurisdictions and contexts.

Issues of this sort are under discussion in the UK. There, asbestos-related cancers are increasing significantly, and so are lawsuits seeking damages for the cancers. Paying compensation for cancer is easy to understand in many instances. However, some groups want to go further. Thus, some constituencies are urging the UK government (Britain and Wales, for this purpose) to use legislation to change recent case law so that payments may or will be paid to persons who can be deemed to have a condition known as "pleural plaques." Plaques are marks on a lining outside the lung, and the plaques are markers of past asbestos inhalation, but do not cause any impairment except, perhaps, in unique circumstances.


These issues arise because the House of Lords issued an opinion holding that common law compensation was not payable, concluding in essene that plaques do not constitute an injury. Subsequently, the UK Ministry of Justice issued a 9 July 2008 "Consultation" paper asking for views on whether the UK government should use legislation to allow or facilitate payment of compensation to persons with pleural plaques. The UK Consultation paper is a lengthy document setting out information about the issues, and five possible alternatives for government action, with a cost estimate for each of the five proposals. The government's Consultation paper is available online at: http://www.justice.gov.uk/publications/cp1408.htm.

Many papers were submitted on both sides of the issues, and the collection will be posted here as time permits. For now, I've posted online an image of the paper I submitted in opposition to the two most extreme aspects of the proposals set out in the Consultation paper.

The UK Government is expected to submit a reply to all the papers, and the reply is expected during November 2008.

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A prior post here noted that Canadian scientists recently criticized the Canadian government for continuing to support global sales of chrysotile asbestos fibers. The industry historically was very valuable for Canada in terms of jobs, taxes and revenues - the mining itself is graphically shown in a wonderful McCord Museum set of online photos of miners and the mines that show abysmal safety practices.


According to a front page Globe and Mail article on October 31, 2008, Canada took a formal position of silence this past week at proceedings under the Rotterdam convention to decide whether chrysotile asbestos fibers should be added to a list of the world's most dangerous substances and thereby banned to a large degree. In past years, Canada actively spoke against adding chrysotile to the list. The net result was the same because the convention calls for consensus, which was not achieved since nations such as Pakistan and India oppose the ban. Those nations are among many in which asbestos-cement board remains a popular building product despite hazards that may arise if good work practices are not used when the material is cut or destroyed. Cement board is a strong building material used for many roofs and walls in countries that lack trees and/or the infrastrcuture needed for lumber for use for building materials, and is flexible enough that scrpas of it were molded into a giant penguin shown here because of concerns about the asbestos in it.

This outcome is major disappointment to groups such as the International Ban Asbestos Secretariat that has worked for over a decade to obtain a global ban on asbestos fiber sales.

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The Canadian Medical Association has come out with an editorial, described here, that calls on Canada to join with other countries to further regulate "asbestsos" exports. The topic is of interest in Canada because its been a major exporter of asbestos for decades, and so the fibers produce jobs, corporate profits and tax revenue. The issue is in part caused by disputes about how safe or unsafe are the various types of asbestos fibers and their various end uses. The topic is relevant here because a recurrent issue in tort litigation no doubt will be whether and how health standards and practices in one country should effect what happens in another country or be applied in different countries.

The same issues also arise for politicans, as illustrated by the article. In the US, the issue has arisen during the US presidential election through Senator Obama has called for further and/or additional enforcement of terms intended to protect workers and "the environment" against processess that are not deemed as safe as practices in the US. Some have called it that a good idea, and others call it "protectionism." Some would say that it is short-sighted if the US and other "developed" economies do not push or "nudge" others to move towards less risky practices. Otherwise, it seems that industry is receiving a subsidy in the form of allowing it to undertake operations known not to be "safe." That said, others argue that the US should "let the free market" work and not "interfere."

Lots of room for debate in this area, and it will be interesting to see what happens.

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For some time now, I've been writing about potential changes in product liability law due to rapid changes in communication and science. In a February, 2007 article for Corporate Counsel, I addressed various changes, including the widespread availability of scientific information and its impact on information-related tort claims. The article included my prediction that "sophisticated intermediary" types of defenses would change in light of all the available information. I'll pat myself on the back and note that I was right - in a drug case in 2007, the West Virginia Supreme Court cast aside the "learned intermediary defense due to the wide availability of information to consumers. See Johnson and Johnson v. Karl, 220 W.Va. 463, 647 S.E.2d 899 (2007). The Court there said many things, including the following:

"When the learned intermediary doctrine was developed, direct-to-consumer advertising of prescription drugs was utterly unknown . . . Since the 1997 proliferation of drug advertising, only four high courts have adopted the learned intermediary doctrine . . . None of those courts gave thorough consideration to the changes that have occurred in the prescription drug industry with respect to direct-to-consumer advertising. We however, find such changes to be a significant factor in deciding this issue . . "

So, with that as background, I particularly enjoyed reading an excellent new article by Sarah (Sally) Olson of Wildman regarding the Johnson case and other additional specific examples of the Internet's effect on tort claiming. The article is titled: Net's Impact on Strict Product Laibility Law. The effects she describes include increased numbers of public consumer complaints of defects, consumer input into design, whether a company needs to monitor blogs, whether a company run blog or website will produce its own liability if a company is not accurate in what it says publicly, and various other points. Ms. Olson's article is well worth reading in full and considering how it might apply in your context.

After that, think also about reading a 2008 book titled: Stop The Presses: The Crisis and Litigation PR Desk Reference. Written by Richard Levick and Larry Smith of Levick Strategic Communications, the book's chapters 7 and * deal with blog strategies and lots of other "crisis" issues that did not exist 5 years ago in any material way. Then I'd suggest reading their chapter 9 on the impacts of media as related to increased prosecutorial activity. That's a topic I've also covered in a more limited context in a 2006 Corporate Counsel article focused on "toxic torts" and criminal prosecutions.

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Science moves much faster than does "the law," and the changes in science over time will have a profound impact on the framing and resolution of legal issues.

For a new example, consider that respected medical journals Nature and Nature Genetics this month published articles from three research teams asserting identification of one or more genes they say are materially related to an increased risk of contracting non- small cell lung cancer, which comprises about 80% of lung cancers. Having one copy of the gene is said to be a characteristic of about 50% for persons of European descent, and far lower among persons from Asia and Africa. According to the authors, inheriting one copy of the gene raises the risk by about 28%, and inheriting two copies of the gene raises the risk by 70-80%. Some of the authors suggest the gene may be tied to the tendency to smoke. The press articles indicate that the research teams made the usual prediction that tests for the two genes will be available in the future.

The implications for law in general are profound when one considers all of the societal and legal issues related to health itself, and the obligations of insurers, governments or individuals for the expenses of treating (or, some day, preventing) a non small cell tumor in the lung. Those many issues are far beyond the scope of this blog. Here, the focus will remain on the potential tort litigation issues that may flow from these studies, and the other studies that surely will follow.

For example, many asbestos claimants with "lung cancer" attibute the disease in whole or in part to inhalation of asbestos fibers and/or cigarette smoking. In such cases, what difference should it or does it make if the claimant has one or more copies of the identified genes, and has the non small cell tumor? Defendants may ask for genetic testing and if they find the presence of one or two copies of the gene said to be relevant, they may argue that their presence breaks the legal causation chain and so precludes liability. Defense counsel also may invoke Daubert principles and seek to bar expert testimony from plaintiff's experts if the testimony is not focused in persons with two copies of the gene - will that tactic be allowed to work ? How soon?

Plaintiffs' counsel, on the other hand, may be expected to argue that the "two copies" claimant is just like the "eggshell skull" plaintiff we all heard about in law school. We were taught that the general rule is that a liable defendant cannot avoid financial responsibility simply because a particular person had an especially thin skull. Will that rule continue in force in the age of genomic testing? Should it stay in force as is, or does it need modification?

Plaintiffs also may use the presence of two copies of the gene to try to meet legal standards they cannot meet today for some claimants advancing fear of cancer claims or other claims. For example, some state law opinions (e.g Havner in Texas) will for the most part refuse to permit a claim unless the plaintiff proves that there is a relative risk of a specific disease created by "exposure" to a substance that is at or exceeds 2.0. Will science over time allow plaintiffs' lawyers to meet the 2.0 standard for claimants with the "two copies" even if the 2.0 standard could not be met for a person without the two copies of the "lung cancer" gene?

These and many other issues are arriving fast. For press articles with more details on the lung cancer studies, see:

http://news.bbc.co.uk/2/hi/health/7325971.stm; http://www.latimes.com/features/health/medicine/la-sci-lung3apr03,1,483181.story

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