SCOTUS is often fractured these days, but yesterday managed to unanimously and correctly reject patents on genes in the Myriad case. Why? Because a gene patent simply describes a law of nature, which is the normal sequence of nucleotides in a particular gene.

The ruling happily ends Myriad's undeserved monopoly on the BRACA genes - it was merely the entity that put the very last brick in the wall after years of intense BRACA gene research by many, as observed and described in the well told story: Breakthrough: The Race to Find The Breast Cancer Gene. One suspects that other BRACA researchers (such as Mary-Claire King) are now feeling better about the intersections between law and science. James Watson (of DNA fame) probably also feels better as to science and law - he personally wrote a brief to SCOTUS on the issue.

Certainly the ruling is great news for the free flow of information (such as PLoS), and for anyone facing cancer and other diseases that are or may be caused by genetic mutations. I cheered when Judge Sweet first exercised the awesome power of a federal district judge to enjoin Mryiad's claims,  and this weekend will drink a toast to the challengers, Judge Sweet and SCOTUS (but not the Federal Circuit or the patent zealots). Kudos to the ACLU and its teammates for bringing the case. 

The ACLU's page includes a string of quotes from happy scientists and persons who have been trough cancer. Here are a few:

More broadly, the case provides a lesson about the litigation industry. Some people claim or think there is a right to patent pretty much anything, and even now are barking that SCOTUS does not "get" all the nuance and brilliance of "patent think."  It's part of why the US and the EU now have some courts full of patent litigation, and "patent thickets."  It's part of why SCOTUS keeps reversing the Federal Circuit.  It's part of why Judge Posner last year chided Apple and Motorola for patent silliness. One might observe that it's hard to feel much sympathy for businesses which themselves are patent happy but then complain bitterly when sued by patent trolls, now known as non-practicing entities. As with many types of litigation, both real and imaginary battle lines and issues are drawn, redrawn and spun, with self-interest driving the drawing. 

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Times and science change. It appears the Cleveland Clinic apparently recently brought online old editions of its own Cleveland Clinic Journal of Medicine. The materials online now incluede, for example, a 1986 case report on a cystic peritoneal mesothelioma. According to the abstract, a literature search at that time yielded 20 other case reports. See below for the abstract. 

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(Image of a lung cancer cell. Photo courtesy of National Geographic.) 

"Seeing is believing" is a phrase learned in youth. It's a phrase sometimes forgotten by word-driven lawyers. But for those who work in disease litigation and/or with clients that manufacture products, it's a phrase we need to remember. Thanks to new science, an opportunity to see and believe arises each year when the American Society of Clinical Oncology (ASCO) meets in Chicago in late May - early June.  

New science tools on display at cancer meetings are truly stunning, and cover a range of uses. Multiple groups are, for example,  visualizing prostate cancer.  Others are visualizing malignant cells that are "hidden" from chemotherapy. These processes include producing single images of the sort shown above. Now, however, the visualizing is moving into continuous monitoring at the single cell level, due to massive computing power, among other things. For example, I watched a presentation showing a week of constant visual surveillance of about 10 individual cells as they grew and divided. Visualizing cancer's development is the current point for treating physicians who want to know and see the diseases killing their patients. The step makes sense because knowing the enemy well is part of The Art of War.  

But, researchers and others are looking further ahead. Plainly, a next application will be monitoring cells visually as they are "dosed" with a "toxin." And, that process can and will be linked to monitoring the cells in terms of chemical and "omic" changes as they are dosed. The "omics" data also can be visualized. 

Much change is ahead. Lawyers and their clients can anticipate and be part of the change, or just wait for surprises. The latter, however, seems illogical since corporate America largely dislikes surprises. 

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(Photo courtesy of TGEN and its Center for Rare Childhood Disorders. Shelby Valint is the child in the center of the picture).

The power of genomics can be especially stunning when applied to children. The lesson for me was highlighted last week during a meeting at TGEN, which is the Translational Genomics Research Institute. Broadly speaking, TGEN is perhaps the foremost US-based translational genomic sequencing powerhouse, and is located in Phoenix. TGEN includes a group of researchers focusing the power of genomics on children through the Center for Rare Childhood Disorders.

The meeting included mention of  "the story of Shelby Valint, a 12-year-old Phoenix girl who was wheelchair-bound for nearly a decade due to a rare disease of unknown cause. She had difficulty walking, talking, holding her head up, swallowing, and even breathing... but the key word in that description of Shelby is "had". Scientists at the non-profit Arizona research institute TGen sequenced Shelby's genome; something they couldn't have done in a reasonable amount of time or cost just five years ago. By sifting through the unique alterations in her data they were able to provide clues to the genetic basis of her rare disorder and empower her physician to prescribe a medicine based on this new information that resulted in changes to Shelby that were nothing short of a miracle. Today, she can talk and walk, even run, and is a 7th-Grade honors student. "

What did TGEN do? Thanks to her smart and determined doctor (Dr. Vinodh Narayanan), Shelby became the first patient for TGEN's Center for Rare Childhood Disorders, and they put their analytic power to work for Shelby. They found a mutation in Shelby's DDC gene. As explained by the NIH:  "The DDC gene provides instructions for making the aromatic l-amino acid decarboxylase (AADC) enzyme, which is important in the brain and nervous system. This enzyme takes part in the pathway that produces dopamine and serotonin, which are chemical messengers that transmit signals between nerve cells (neurotransmitters)." With the defective gene identified, an existing drug was put to work to transform Shelby's life. 

The  following summary is taken from a Phoenix newspaper article in the Arizona Republic, written by Ken Alltucker: 

 "TGen mapped Shelby's genome twice. The first found no significant abnormalities. But a more powerful scan revealed what appeared to be an anomaly in a gene called DDC. 

That, combined with information from the earlier spinal tap, led Narayanan to believe the genetic anomaly blocked her ability to synthesize dopamine.

 Renee wanted results. The doctor had already treated Shelby with L-Dopa, which had too many side effects.

"For Shelby, most days were spent lying on the couch. Renee would carry Shelby in her arms, bathe her and chop up her food into tiny pieces. She could not swallow liquids without risk of choking, so the family mixed a thickening ingredient with her drinks

"She felt limp in my arms," said Renee Valint, Shelby's mother. "She felt like a rag doll.

Shelby's symptoms seemed to worsen in 2008. She began to have trouble swallowing food, and she was down to 37 pounds.

As her childhood progressed, Shelby was subjected to needles, biopsies, scans and other medical tests. Each sought to rule out a disease or condition. Each left Renee and her husband, Scott, frustrated over the lack of a clear diagnosis.

Renee and Scott watched their second-born daughter grow weaker. She would try to walk along furniture, but she would often fall down.

She was bright, her thoughts were clear, but she was trapped in a body that betrayed her."

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(Image courtesy of OHSU).

It's been done - researchers from Oregon have cloned human, embryonic stem cells. Scientific American and many others are carrying the story.

There are limits to the accomplishment - the clones are not perfect and seem unwilling to grow in utero. Nonetheless, it's quite a step. Now we wait to see how it all unfolds at the intersections between science, law, ethics and other views. 

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This morning brings a feel good story that coincides with impressive new science - bio-engineered organs. In this instance, a little girl of 21/2 is now living with a bio-engineered windpipe. In essence, doctors built a scaffold to outline the windpipe and stem cells then recruited other cells to fill in around the scaffold. The technique also is being applied to others organs. The story is here - from the NYT. Set out below are key paragraphs on the science:

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New tools make for new findings, and sometimes they are profound. An example of a new tool is NGS. Next generation sequencing is one of the factors driving molecular biology forward at an incredible pace. NGS, as it's called, comes in different flavors. The common link is that most flavors of NGS are incredibly fast and more accurate when compared to the "old" version. The new methods therefore can provide a faster, deeper and more accurate look into more parts of the genome than did the "old fashioned" sequencing that accomplished the Human Genome Project.  (The old version is known as Sanger sequencing and debuted around 1977. The Sanger technique involved running DNA through gels at relatively glacial paces - my sister used to do do some of this work way back in the 1980s). 

A new example of a profound outcome is the use of NGS to figure out that a form of epilepsy arrives from a mutation of a specific gene that regulates the brain's use of potassium. Specifically, ScienceDaily brings word that the problem lies with a gene called CNTN2. The source flaw was found by comparing genomes of "a particular Egyptian family, in which five sick children were born from the marriage of one healthy cousin to another healthy cousin."  The five children suffered from a specific epilepsy syndrome, in which different types of epileptic attacks occur. All five of the genomes were compared and a common flaw was found.

A point for lawyers? Note the sudden new knowledge. Imagine the consequences if molecular biology shows that your client's product or process is part of a process that mutates the CNTN2 gene.  That's probably not going to happen here because the mutation was on both sides of the family. But, these days, new findings can emerge that fast - no need to wait for epidemiology.

Set out below are further specifics from the article:

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By all accounts, SCOTUS did not seem interested in drinking the patent think kool-aid offered by Myriad Genetics  to try to justify its claim to patenting a gene. Justice Kagan commented that the USPTO appears "patent happy."  A patent lawyer friend previously observed that  observation also applies to many patent lawyers - as he put it, their perspective is flawed as is the judgment of a man with a hammer who sees everything as a nail. See, e.g,. here (NPR), and here (PatentlyO - detailed summary with useful links to transcript and more). 

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The Myriad case heads back to the US Supreme Court today for oral argument. My hope is that Mryriad's argument for gene patents  goes down in flames. 

The issues revolved around various aspects of efforts to patent gene testing for a particular gene. Myriad keeps shifting positions, but at various times, it has argued that its patent gives it the sole right to test a person's BRACA gene if any money is involved.  The ACLU challenged the patent, and it was struck down by a federal district court judge. The patent court (the Federal Circuit) reversed, looking at the world through it's patent-centric glasses. The US Supreme Court took cert in Myriad but then remanded after unanimously issuing the Prometheus opinion that struck down a patent involving some related but far from identical issues. On remand of Myriad, the Federal Circuit failed to get the message from its unanimous reversal in Prometheus. Therefore, it once again reversed the trial judge. 

Some members of pharma want gene patents. Many industry members, however, do not want gene patents. I'd recommend shorting Myriad. 

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 The three-dimensional electron microscopy structure of the complete Tetrahymena telomerase enzyme complex, with previously solved high-resolution structures modeled in. (Credit: Jiansen Jiang, Edward Miracco/UCLA Chemistry and Biochemistry)

The picture above shows the power of multi-disciplinary collaboration aided by the power of the Internet and the cloud. A new example arose over the last three weeks as two different groups of researchers from multiple countries and disciplines published papers showing that they had mapped the structure of telomerase, and the second set of  researchers  visualized its structure, as shown above.  

These results are pretty close to a moonshot for molecular biologists. The significance arises because telomerase is the protein understood to provide immortal life to stem cells. Perhaps that's at least part of why one of the first to see telemorase is quoted as saying: " I was so excited I could hardly breathe." 

Cancer researchers also are excited. Why?  Because most types of cancer cells hijack the telomerase protein to create their own immortality. Some also see telomerase as the cellular fountain of youth. That label is applied because it regulates the life of chromosomes. By regulating chromosomes, the protein is thought to hold a significant role in aging.

Why do the structures matter? Drug discovery is less prone to failure when the protein structures are known and visualized. New doors just opened. 

The new and collaborative findings arrived through work that it is said could not have been accomplished as recently as five years ago. And the research derived outcomes from thousands of contributors, as highlighted by the quotes below. 

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To catch a tumor cell? Well, obviously, you just line up and sort 10 million cells - per second -  from a tube of blood. The summary story is here from ScienceDaily.  The device is FDA approved - not a fantasy. And it's getting better every year. The full story is in Science Translational Medicine. 

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Change is good. 

Once upon a time (that is, back in the 50s and 60s), tired middle-aged and older persons were targeted by ads for Geritol, a "tonic" that contained lots of iron, plus 12% alcohol. The pitch was that middle-age tiredness was brought on by "iron-poor tired blood." Ultimately, the FTC went after Geritol and its makers for false advertising. As explained by Wikipedia: "Geritol was the subject of years of investigation starting in 1959 by the Federal Trade Commission (FTC). In 1965, the FTC ordered the makers of Geritol to disclose that Geritol would relieve symptoms of tiredness only in persons who suffer from iron deficiency anemia, and that the vast majority of people who experience such symptoms do not have such a deficiency. Geritol's claims were discredited in court findings as "conduct amounted to gross negligence and bordered on recklessness," ruled as a false and misleading claim, and heavily penalized with fines totaling $812,000 ($4,251,130 as of 2013), the largest FTC fine up to that date (1973). 

Fast forward to 2013. Today we actually know part of how and why blood does in fact change with age. Indeed, researchers are gaining knowledge and experiencing some success on ways to reverse the changes, as described in a press release from Lund University regarding a newly published journal article on experiments with the stem cells that generate blood. In short, the experiments are aimed at reversing epigenetic changes in which changes in blood occur as genes are switched on or off by external influences. The epigenetic changes in turn lead to a different mix of cells within blood. Now, the researchers are finding ways to undo the changes and to restore the balance of cells that was present during youth.

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Science and law intersections sometimes arise in terrible places, but the science remains key. Consider, for example, the new well-known litigation arising out of the recent death of a 14 year old girl, Anna Fournier, with known heart issues and perhaps other unknown issues. The litigation arises because she is said to have consumed two energy drinks during the prior 24 hours, and those drinks are alleged to have caused her death. 

When children die, "why" becomes a huge question for distraught parents and friends. Many wonder if "something" could or should have been done somewhere in advance, to avoid the death, or wonder if someone can see a particular reason why that particular day resulted in the death.  Answering why questions usually is not easy. Better answers often (if not always) require data. Scientific data. Valid data. The right data. And, preferably data taken by experts, quickly, before cellular level decay starts occurring. 

The importance of facts and data is on display in the litigation and the related battle for control of media and popular opinion. The most developments are covered in a cogent article from a food and beverage publication. In short, the beverage maker (Monster) is bringing out experts who are said to have been through the available data. As the story line goes, the experts say they see significant pre-existing heart problems in Ms. Fournier, but no harm caused by the energy drinks. Counsel for the plaintiff sees it differently, according to the article. And, a medical examiner made a "finding" regarding "caffeine toxicity." "According to the autopsy report and death certificate  [alleges the complaint], the cause of death was cardiac arrhythmia due to caffeine toxicity complicating mitral valve regurgitation in the setting Ehlers–Danlos syndrome.” 

Conclusion? Scientific facts matter. When bad things happen, the facts should be gathered, quickly and well, preferably by experts if time permits, and preferably through cooperative effort by all sides. But when only the plaintiff knows suit will or may be filed, the plaintiff should obtain and preserve evidence all along. 

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It's good to see the US government building on lessons learned from past investments in big science. The latest target apparently is mapping the brain, with the Obama Administration preparing to back a multi-year plan with costs around $ 3 billion. Goals include learning more about the brain-related diseases (e.g. Alzheimers, Parkinsons, and autism) to learning more about how minds work, and where controllers are found. No doubt the results also will accelerate the already cutting-edge therapies implemented for disabled persons at the world class Rehabilitation Institute of Chicago.  In fall 2012, RIC unveiled the world's first neural controlled  bionic leg. Perhaps more understanding and help for soldiers suffering from concussions and other brain traumas, including post-traumatic stress syndrome.

It's hard to imagine a better investment than fundamental science. For recent precedent, consider the Human Genome Project.  A true game-changer for science and humanity, the HGP also proved a marvelous financial investment, as previously discussed in this post about Batelle's review of the ROI. Indeed, the President cited the HGP and the Battele Study in his State of the Union speech.  The eye-popping ROI numbers for the HGP: $ 796 billion and 310,000 jobs in return for a  $3.8 billion investment.  

But what's in it for tort lawyers? The concussion litigation comes to mind. Perhaps new arguments about the design suitability of protective helmets for any sport or activity. Arguments about new bionic limbs for persons injured when buildings collapse or planes fall from the sky. 

 And other lawyers will benefit too. Think about criminal defense lawyers hiring brain experts to explain/rationalize client conduct. 

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(The image is courtesy of the Danish National Biobank.)

Recent articles about genetic investigation of the Irish potato famine lead to renewed wondering about new science bringing new tort claims arising from previously unrecognized mass torts. Similar questions also arise prospectively thanks to current  biobanking and other means for preserving anything from plants to bodily tissues and fluids. The questions are illustrated by recent advances in science, as applied to the Irish potato blight of the 19th century, along with today's accrual rules about knowledge of a claim. 

As to the potato famine, a new research article explains how the potato blight happened. As it turns out, a clever virus silenced the RNA of potatoes. According to the article, this is the first ever finding of an RNA silencing virus in which infection is promoted by "proteins produced by eukaryotic pathogens -- nucleated single- or multi-cellular organisms..." Thus, plainly new science, with ongoing investigation because forms of the blight remains with us today.

But, how do we know what was going on in potatoes back during the famine of the 1800s? Because some far-sighted plant scientists of the 19th century ground up potatoes and stored the samples in glass jars. Recently, current scientists were able to retrieve and sequence DNA extracted from those old samples stored away well more than 100 years ago. Ring up another positive outcome for museumomics, as it's called by some (and perhaps also think back to the Jurassic Park premise of DNA trapped in amber.)

Yesterday's glass jars are the historic predecessors to today's growing biobanks. Today, biobanks store, for example, cord blood, tissues and fluids. According to a January 2013 article, there now are over 600 formal biobanks in the US. No doubt the number is much higher if one were to find and count all the old freezers full of tissues stored away by pathologists. 

Of course, there apparently are limits on how far we can go backwards in time. Recent research, for example, indicates a tentative theory of 521 years as the half-life of DNA. Working backwards from that tentative finding, the authors estimated that scientists probably cannot get useable data from DNA that's older than 1.5 million years. So, maybe there are limits, but the limits certainly are broad enough to cover the last few generations of humans. Moreover, the limits may change - the half-life calculation is tentative, and amazing things recently were done with a single strand of ancient DNA.

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Will endocrine disrupters become "the next asbestos?"  Consider the following on the topic:

"Human and animal life is widely exposed to many artificial substances that interfere with the sensitively constructed hormonal system. Substances that interfere with hormones are called Endocrine Disrupting compounds/chemicals (EDC). EDCs are a truly emerging risk. There is strong evidence for negative effects on animal organisms and mounting evidence for effects on human health. Evidence is mounting that specific substances are connected to human bodily injuries."

More propaganda from a cabal of dastardly plaintiff's lawyers (humor intended) ? No. 

The preceding words on endocrine disrupters are from some of the world's largest insurers. Specifically, the words are from a project of the Emerging Risk Initiative set out on this page of the CRO Forum. More specifically, they explain: 

"Emerging Risk Initiative

"For the risk management of liability insurers it is crucial to monitor this emerging risk. A greater clarity regarding the associated costs has to be achieved.The paper gives a brief introduction to the risk and it aims at increasing awareness. A dialogue should be started taking into account risk-mitigation strategies and the involvement of all stakeholders."

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Pictured above is an old fashioned epipen. It's used to dispense a cheap drug when needed. The device is pictured because this week brought a new article on a new rectangular, "talking' epi dispensing evice known as the Auvi-Q. In my opinion, epi devices are illuminating examples of why health care costs are soaring needlessly. A  NYT article on the talking, rectangular device also seems to me to illustrate the growing problem of insipid reporting. Why, one would think, do most people  really need to pay $ 240 for a pair of talking shots that will be obsolete if not used in 18 months? And why does our market seem to not include much less expensive devices? 

Facts. In tv shows involving emergency rooms, doctors frequently ask for injection of ".2 of epi." That's epinephrine, more commonly known as adrenaline. It raises heart rate and blood pressure. It's most frequently used for the treatment of acute allergic reactions to avoid or treat the onset of anaphylactic shock. Epi works by relaxing the muscles in the airways and tightening the blood vessels.

Why do I care about this topic? I learned the lessons of epi when my middle-aged body suddenly reacted strongly and adversely (anaphylactic shock)  to bee stings that were not a problem when I was a kid. How bad? I passed out on a commuter train when I tried to stand up and exit the train a few minutes after I was stung. Thanks to decades of swimming, I'm equipped with a strong heart and so did not die, but an estimated 40-100 people do die every year from stings. Thus,  anaphylcatic shock is a big deal - a survey on frequency is here.   

Since then, I carry an epipen in summer months in Chicago when bees and wasps are out. Is the pen larger than I'd like? Yes, half as long would be much more convenient. The current pen does not fit into a hip pocket. The new device apparently solves that problem and that's a positive, but...... 

Is it hard to use an epipen - do we need a talking pen? No, it's not hard to use an epipen. In fact, I've used an epipen after being stung. Twist off the end cap, put the nose of the pen on your mid-thigh and then push in the plunger to give yourself a shot. It takes only a few seconds. And Intelliject, creator of the new device, offers this simple graphic of how to use the new rectangular device. So, why do we need a talking device, and how many languages will it speak? Maybe the makers could include SIRI in the device and get the weather too, at even higher price? 

The real problem, in my opinion? The pricing of epidevices. The new device is said to be priced at $240 for a pair of the devices, as reported by the  NYT article.  That's nuts - adrenaline is hardly novel, and apparently is produced in bulk for little cost - alibaba shows here several suppliers of forms of apparently low cost adrenaline with no lack of supply. Most of the cost apparently lies in promotion, packaging, distribution and profit.

As of 2005, a summary of a medical article reported that:  "In Dr. Simons' survey, widespread availability of epinephrine autoinjectors for emergency self-treatment of anaphylaxis in the United States, Europe, Canada and Australia contrasted with limited availability in Asia, South America and Africa. Survey results revealed the cost for epinephrine autoinjectors were reported to range from U.S. $30 to U.S. $110, and could vary 2-fold within the same country. The purchase cost in some countries is equivalent to a month's salary for many patients. " A fall 2012 medical article apparently is focused on the price increases for epi devices, but the article is behind a pay wall. Also see this abstract from Dr. Simons on epi devices.

According to Allergy Notes: 

"The wholesale price of 1 epinephrine autoinjector increased annually from $35.59 in 1986 to $87.92 in 2011 (147%). Among patients prescribed autoinjectors, only 40% of teens/adults and 60% of children less than 12 years of age had them refilled over a 6-year period. The retail price of the new "EpiPen 2-pak" that the patients often quote is more than $250 for each "pak". In August 2012, the FDA approved Auvi-Q - the first-and-only epinephrine autoinjector with audio and visual cues that guide patients and caregivers step-by-step through the injection process. No information about the price of Auvi-Q is available at this time but it is not expected to cost significantly less than EpiPen."

The price also is a big deal because epipens expire every so often - the time length is about 12 - 18 months, as described in this 2010 survey article on epinephrine use.  The price increases and design "improvement" bring to mind incredibly Dina Rasor's 1985 book on expensive Pentagon hammers and toilet seats, among others. That problem also continues today. 

In the UK, ChemistDirect sells adrenaline injections for less than $10 for a 1 ml syringe. In Canada, less than $20. And if you want epi for a horse in the US, it's also cheap - less than $ 20 per bottle. And, perhaps there's something I do not "get," but it appears CMS will only reimburse .062 cents as the cost for epi when given by a doctor under code JO171.

And, of course one wonders about other options.  What about over the counter epi devices - why are these prescription devices ?  And, if I can buy an automatic weapon without a prescription, what's so dangerous about an epi dispensing device? What would the cost be if we turn loose generic makers of epi devices? 

Back to the insipid article. The article does not ask any of the questions above. Instead, it's a lovely puff piece about how is this all working out for the inventors of the new rectangular device, a pair of twins who suffer from food allegeries and so faced  risks of anaphylcatic shock.  I admire their desire to create a device in a more convenient size, but beyond that, it's hard to see much to applaud. According to the NYT article, though, the device is now out on the market and they've pocketed a lucrative licensing deal for wrapping some plastic and a needle around a life saving drug: 

"This week, the brothers’invention —a slimmer device shaped like a smartphone —hit pharmacy shelves nationwide, the culmination of a single-minded quest that began15 years ago and ended in a $230 million licensing deal with the French pharmaceutical giant Sanofi."

Concluding thoughts? I love science and innovation, and I'm all for providing incentives and payoffs to scientists who devise new "drugs" or genomic therapies.  But it seems to me a shame to see products like this on the market, and destined to raise health insurance premiums when insurers pay for these  products that involve low science but big, artificial barriers to entry into the market.  Razor blades come to mind.   So, I can't just can see why the NYT would applaud this device when too many cannot afford to pay a $ 240 per month premium for even basic health insurance, much less the price of this device that will be obsolete in 18 months or so when the epi no longer is fresh. 

It's also too bad so many writers appear to do little more than accept spin created for media, as opposed to asking real questions and seeking out facts, and questioning the spin. Here, one might note that Sanofi this past week issued YouTube promotions and an Auvi-q press release on January 28, 2013, which follows more media releases last August . Meanwhile, the web site of the creators of the new device also includes promotional information.  And the same author also wrote last fall on epinephrine and epipens, but focused on Mylan's product offering.

Maybe more facts would change my opinion. Maybe costs to produce adrenaline are skyrocketing due to a Chinese cartel similar to the rare earths cartel, but it's sure hard to imagine a cartel on this substance. And I cannot find any evidence of large price increases for making adrenaline. It's also possible the the devices produce only a 10-15% profit if enough costs are allocated by creative bean counters to create Pentagon-like accounting. And offshore licensing fee also could help to create costs and move profits into tax havens. In sum,  I'm dubious that this product really adds anything useful except a new shape for a shot dispenser, which is hardly rocket science.  All we need is compact device that works reliably at a modest price. But the market seems to lack such a device, and instead we see prices rising dramatically for current epi devices, putting them out of reach for many and raising overall costs for no apparent good reason. 

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An ongoing reality is that government monies are key catalysts for science and new products, which in turn lead to more jobs. For example, money from the Department of Defense DARPA group was key to the creation of the internet. This page from DARPA's web site touts its leading role in the Internet and many other projects that generated products we use today.  

Similar returns arise from investing in basic molecular biology. Today we are seeing staggeringly great human and financial returns from the government investing $ 4 billion in a project modestly known referred to as the Human Genome Project. And, this past fall, scientists started publishing massive numbers of papers and data from the ENCODE project that created vast pools of new knowledge from portions of the genome we used to call "junk DNA"  (because we did not yet "get" how it worked). Humanity inevitably will reap enormous human and financial returns from these investments in basic knowledge.

A new article makes it plain that we need to add another government investment to the list of great investments in fundamental knowledge. The example involves artificial intelligence as exemplifed  by SIRI of Iphone fame. Bianca Bosker tells the story well in this Huffington Post article.

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(Image courtesy of Johns Hopkins press release and AAAS Translational Medicine/AAAS)

Stem cells. Some scoff,  but their usefulness is being proven. In this instance, researchers are now proving - in humans - that specialized stem cells can be used to generate new growth of cartilage after knee surgery. 

ScienceDaily brings the news of the research paper that provides all the science data. The ScienceDaily summary is based on a press release issued by the Johns Hopkins researchers. Key sections are quoted below. The full paper is here, but is behind a pay wall.  

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2012 ends with a new paper illustrating the power of genomics to find a likely cause of diseases such as cancer. In short, researchers were able to find and focus on a small number of families with strong histories of bowel cancer. The researchers then collected DNA and sequenced genes from the family members (the same process that helped researchers find BRACA 1 and 2).

Outcome? The researchers found two mutations strongly associated with developing malignant or non-malignant bowel tumors in the highly-effected families, and a few members of another cohort of persons with bowel cancer. They also found precancerous growths in the bowels of persons in the families with predominance of the mututations. On the other hand, the two mutations were not found in thousands of persons in the cohort of persons with bowel cancer.

Conclusion? Gene sequencing can work well when researchers obtain access to cohorts of persons with similar diseases. Sequencing also can work for screening and finding growths before they become malignant. Cohort testing also may tend to suggest that some tumors are not caused by genetic variations, and instead arise from other causes. Mass tort defendants and insurers should be thinking about the consequences of gene sequencing of cohorts of persons with similar diseases.

 The press release from Oxford is set out below in full: 

"Rare DNA faults in two genes have been strongly linked to bowel cancer by Oxford University researchers, who sequenced the genomes of people from families with a strong history of developing the disease. 

The researchers sequenced the entire DNA genomes of 20 people from families with a strong history of bowel cancer. Eight of the 20 people had developed bowel cancer, while the rest had a first-degree relative who had developed the disease. The findings are published in the journal Nature Genetics.

They found that everyone who had a faulty POLE or POLD1 gene developed bowel cancer or had a precancerous growth in the bowel.

To confirm their findings they then looked for faults in these two genes in almost 4,000 people with bowel cancer, and 6,700 people without the disease. 

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23. It's a number made special by Michael Jordan. But now 23 also has special meaning for persons facing T-cell lymphoma. The number relates to a phase 1 study of an anti-body drug conjugate. ADCs, as they are called, combine a drug with a "targeting" agent to get the drug into the desired cells. In this new study, the ADC went 23 for 26 in creating complete remissions in persons receiving the drug to treat their t-cell lymphomas.  Talk about being in the zone - those numbers are stunning. And, the other 3 persons received partial remissions. The press release is pasted below. 

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The Centers for Disease Control recently issued a report quantifying the increase in diagnosed diabetes as having doubled in 15 years (key excerpts below). The point of mentioning the data. To highlight that risk profiles change, for people and product manufacturers. Key excerpts are below. 

Increasing Prevalence of Diagnosed Diabetes — United States and Puerto Rico, 1995–2010

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This list includes some truly unique gifts for people who enjoy science. 

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(Image from NIH)

Wow. Researchers figured out a way to remove the extra copy of chromosome 21 that is the cause of Down's syndrome. ScienceDaily has the story here, a press release is here, and the full paper is here in Cell Stem Cell. 

The removal of the extra chromosome is not a cure for Down's syndrome in living people, but it may in the future help to limit disease in persons with Down's syndrome. On the broad view, this is quite a great scientific feat, and no doubt others will build on the knowledge to develop other genomic therapies.  

How was it done? "The researchers used an adeno-associated virus as a vehicle to deliver a foreign gene called TKNEO into a particular spot on chromosome 21, precisely within a gene called APP, which sits on the long arm of the chromosome.  The TKNEO transgene was chosen because of its predicted response to positive and negative selection in specific laboratory growth mediums." Amazing. 

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Western Kenya, Ugenya District. One World Futbol is the game ball. (Photo: Tiba Foundation)

A good news story about science, children, soccer balls, and people with good hearts.

Tim Jahnigen saw footage of kids in Darfur playing soccer with pieces of trash tied up with string. He felt kids deserved better, and set out to find a way to make a more or less indestructible soccer ball that's still a good soccer ball. With support from science and money from Sting, the ball was created.

The ball is made from "a type of hard foam made of ethylene-vinyl acetate, a class of material similar to that used in Crocs, the popular and durable sandals. ... Mr. Jahnigen has developed a fifth generation of the ball, which is rounder than earlier versions. He carries samples around the world to conferences, potential buyers and sponsors. For effect, he crushes them and even drives cars over them. All of them bounce and hold their shape. By his estimate, the ball can last for 30 years, eliminating the need for thousands of hand-sewn leather balls that are typically donated by relief agencies."

Now, the soccer balls are available for donation and/or purchase through One World Futbol. The donation page is here. If you buy one, the group donates another ball somewhere in the world. Or, you can pick the recipient from among a few projects. The price for two 30 year soccer balls? $39.50. 

Hat tip to Ken Belson and the NYT for telling the story, which is the source for the quote above.  

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As the US exits the confrontational world of political campaigns, it's refreshing to read a story about cooperation and support. Both emerged when lab animals, cells, and biologic samples at NYU were threatened by the conditions created by Tropical Storm Sandy. The NYT story highlights contributions and support ranging from heavy lifting to money to replacement animals and science. The story provides evidence as to why science today moves faster than politicians and lawyers. 

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Today, science is a clear winner with the re-election of President Obama. Among other good judgments on science, President Obama made a great choice in persuading a brilliant visionary and politically able scientist to run the National Cancer Institute - he is Dr. Harold Varmus, a prior winner of the Nobel Prize in medicine for breakthrough research findings on links between cancer and vaccines.

NCI has a broad vision for the future, and that vision will drive change. The broad vision is pasted below, and online here: 

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Epigenetics continues to change and shape thinking on disease processes and causation. It's an important topic for product liability lawyers - and corporate lawyers and insurers - for today and tomorrow.

A new example even shows up in the current issue of The Economist. The article highlights new research suggesting that nicotine cause epigenetic changes with multi-generational impacts. The impact? Asthma in the children and grand-children of mothers who take in nicotine. The ScienceDaily summary is here, and the paper itself is here. 

The study is in rats, and it's early yet, but the findings certainly are intriguing in an age when our children are experiencing apparent increases in some forms of asthma. The published article states the conclusion as follows:

Reading the news certainly was enough to make me wonder about a possible link between my mother's former smoking (and my former smoking), and the occasional asthma attacks suffered during soccer games by one of my otherwise athletic and apparently healthy daughters.

Imagine children and grand-children as plaintiffs against big tobacco. The distributors of disease in a stick will not be able to trot out the usual defenses. Perhaps I've missed something, but I'm not aware of a single big tobacco warning about possible harms to children or grandchildren.

Also, consider the risk and possibilities for other industries. And when thinking about warnings and foreseeability, consider the following underlined sentence from an excerpt from the Economist article: 

"ONE of biology’s hottest topics is epigenetics. The term itself covers a multitude of sins. Strictly speaking, it refers to the regulation of gene expression by the chemical modification of DNA, or of the histone proteins in which DNA is usually wrapped. This modification is either the addition of methyl groups (a carbon atom and three hydrogens) to the DNA or of acetyl groups (two carbons, three hydrogens and an oxygen) to the histones. Methylation switches genes off. Acetylation switches them on. Since, in a multicellular organism, different cells need different genes to be active, such regulation is vital.

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(Images courtesy of Nature and the 1000 Genomes project)

This week brought another example of the exponential explosion in molecular biology. The Human Genome Project began in 1990, and took 13 years to sequence one human genome - the history is here.

Now what? The 1000 Genomes project, an international collaboration, has sequenced 1092 human genomes since  the project took shape in 2008. Indeed, much data was online by 2010, but now all the cell lines and data are open access information freely accesible to any researcher. The work is formally reported in the November 1, 2012 issue of Nature.

What did they do in more detail? "By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations ....   

Look again at the change in pace. Thirteen years for 1 genome, and now about four years for 1092 genomes (with more to arrive soon). Imagine what's ahead as more and more supercomputers are built and put to work on analysis of massive databases using tomorrow's generations of sequencing and analytic software, augmented by existing pools of knowledge. Over time, quantum computing will start to arrive.  The Nobel Committee sees at least some of the possibilities ahead.  One thing is certain - research "in silico" will drive knowledge forward at exponentially faster rates. And pharma (large and small), governments and science leaders will continue to invest in science. Lawyers and clients should be thinking about the nature of Daubert hearings in five or ten years. 

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The fact pattern sounds like a law school examination. Publicly held biotech company is using clinical trials to test an anticancer drug. Biotech entity hires clinical trial company to perform part of  the clinical trial. Results are returned and appear quite promising. Biotech announces results to investors. Ten days later, biotech company finds errors in the data from clinical trial company. Biotech publicly announces that there are errors in previously released data and investors should not rely on the data. Stock price plunges by 78%. Biotech company then sues clinical trial company for errors in data. That suit is followed by securities fraud class action suits by law firms representing shareholders. Resolve all issues. 

The biotech company is Peregrine. The story has been covered by LAW360 (here and here) and others. The suit against clinical data company is here. 

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Over time, biobanks and computers will produce a relatively rapid explosion of new knowledge. A weekend article from the NYT makes the point nicely as it describes a biobanking project well underway at the American Museum of Natural History, and the related Sackler Institute for Comparative Genomics with its Ambrose Monell Cryo Collection. the The museum already holds millions of examples of nature, and some day "museumomics" no doubt will be applied to some of the specimens. Now, however, the collection also includes 70,000 frozen samples of 40,000 species, all collected since 2001.

As to computers expanding knowledge, the pace and scale are exponential. The following quote makes the point:  "Some of the data that the [computers] process comes from the genomics laboratory in the Sackler Institute, where the power of DNA sequencing has grown with astonishing speed. “Any of the students up here could do my thesis in five minutes,” Rob DeSalle, curator of the division of invertebrate zoology, said. “It may even be five seconds.”  

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Honesty and trust are keys to relationships of many kinds. A pair of news stories this week highlight practical and important issues about transparency and access to testing data regarding scientific research for medical treatments. 

On the negative side, the maker (Dendreon) of a prostate cancer vaccine (Provenge) is now under attack for perhaps having manipulated data analysis to show a false benefit. As the story goes, FDA approval was sought and obtained based on data analysis that drew a line at patient age of 71 versus 65, with that difference said to have mattered. This article provides more specifics, and seems fairly persuasive. 

In contrast, the much-fined GSK announced this week that it's going to do even more publishing of detailed research data in anonymized form, and is going to make clinical trial data available to researchers with "valid" reasons to look at the data.   A Reuters article is here, and the press release is here.  

GSK's steps seem positive for many reasons, even if the steps could go even further (e.g letting an investor service hire an expert to analyze the data.) On the litigation side, time will tell how increased transparency ties to, for example, lawsuits alleging "fraud on the FDA."  Hopefully the increased transparency will produce more collective scientific knowledge, better outcomes, and reduce litigation. 

The GSK press release strikes me as as a useful if over simple explanation, so it's pasted below in full text: 

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At first it was the PAS antigen test for prostate cancer. Now cancer biomarkers are arriving for more and more other cancers. Their arrival is logical as molecular biology continues to explode, and researchers and doctors seek to find and treat disease when the tumors are less pervasive and hopefully more manageable. There are special pressures to look for tumors such as mesothelioma, a tumor that is often lethal in a very short time, and that often leads to litigation. 

The newest mesothelioma biomarker paper is published in the New England Journal of Medicine, and is by Dr. Harvey Pass et al. The paper is summarized here.  The science appears promising and relates to a glycoprotein known as fibulin-3. 

On the legal side, the summary offers multiple points worth noting:

Today's scientific tools are now being applied to previously collected samples of blood and tumors. The past samples are not perfect research tools for multiple reasons. But, they exist and are increasingly are being tapped, along with new "fresh frozen" tumor samples that are better for genomic analysis. Overall, both the old and new samples are fueling increasingly fast-paced changes in knowledge about mesothelioma.  Set out below are a couple of key sentences on the past data collections:

"To test the idea, they measured fibulin-3 levels in stored plasma samples from 92 patients with mesothelioma, 136 people exposed to asbestos but who did not have the disease, 93 patients with effusions not caused by mesothelioma, and 43 healthy controls.

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Remember the old saying about a leopard not being able to change its spots. Well, it looks like that's going to become an obsolete saying in the days of genomics. Researchers have now used genomic sequences to find a gene change responsible for cheetahs with stripes and blotches instead of spots. The work is published in Science. An easier to read version of the story is in the New York Times.  

The researchers say the relevant gene seems to be "conserved" (common) among felids (cats), but are still working on figuring out exactly how the change happens. The outcome seems to involve a protein known as Endothelin3. That protein also exists in humans. Id.

Two points here. For lawyers, this is an easy example of genes being conserved (common) across species. That's pertinent to why it's often (not always) appropriate to extrapolate animal study data to humans. The second point comes to mind as a father of teenage girls who are often thinking about what would be "cool." Putting that hat on made me wonder if future generations of teenagers will be asking for genetic therapy to create stripes or spots instead of asking for body piercings or tattoos. I hope that's just a fanciful question for all future generations, but .... 

The abstract in Science explains the study as follows: 

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Molecular biologists continue to delve into the specifics of how "toxins" cause harm, thus creating information that someday will end up as part of toxic tort litigation. Working with funds from NIH and the Veterean's Administration, researchers at the University of South Carolina have now published findings of dioxin causing changes to the patterns of microRNA expressed in fetal mice when the mother is exposed to dioxin. The changes appear to matter biologically because microRNA regulate (control) the work of various genes, including genes related to the occurrence of cancers and other diseases. The microRNA changes found here include changes to microRNA tied to cell signaling pathways specifically known to involve diseases such as cancer. The findings thus represent a step down the path of explaining the full biology of why dioxin is "toxic." The pattern of microRNA changes also may - after more work - prove to be a means of fingerprinting a cause of harm in a particular creature.  

The paper is:  Narendra P. Singh, Udai P. Singh, Hongbing Guan, Prakash Nagarkatti, Mitzi Nagarkatti. Prenatal Exposure to TCDD Triggers Significant Modulation of microRNA Expression Profile in the Thymus That Affects Consequent Gene Expression. PLoS ONE, 2012; 7 (9): e45054 DOI: 10.1371/journal.pone.0045054. ScienceDaily also provides a summary and links. 

 A press release from the University of South Carolina explains the findings as follows:

For more on microRNA's and their roles, note the following explanations from the article: 

"The biological significance of miR generation is evident by their ability to regulate gene expression causing serious effects on various physiological, pathological, and other biological mechanisms and functions. The miRs have been shown to regulate up to 30% of the mammalian genes [3] suggesting that most cellular pathways are potentially regulated by miRs [4], [5], [6]. The effect of miRs can be of various degrees from mild to very strong. The strong effect of miRs is evident from the lethality of knockout mice that lack any of the enzymes responsible for miR production, such as Ago2, Dicer, and Drosha. Some of cellular processes regulated by miRs include apoptosis, cell growth, fat storage, insulin secretion, and cancer initiation and progression [4], [5], [6]. miRs may play a significant role in responses to xenobiotic chemicals and their role in causing various health associated problems and ailments. Fukushima et. al. have shown that exposure of rats to liver toxicants such as acetaminophen or carbon tetrachloride caused alteration in the expression of various miRs [7]. In another report, tamoxifen, a potent hepatocarcinogen, was shown to increase the expression of several miRs associated with oncogenes [8]. There are reports demonstrating that cigarette smoking can cause changes in miR expression profile [9]. It has also been shown that mothers smoking cigarettes can exhibit changes in expression levels of miRs related to growth and developmental processes [10]. Similarly, other chemicals, such as bisphenol A, have been shown to cause alteration in miR expression in vitro [11]. There are also reports suggesting that drug-metabolizing enzymes such as CYP family genes are targeted by certain miRs [6], [12]. These reports suggest that miRs may regulate the toxicity mediated by environmental chemicals.

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Remember photon torpedos in Star Trek? Now there's something new photon-wise, but even better than torpedos. The Financial Times spread the word today that UK researchers and various private industry groups from Europe and Asia unveiled yesterday a quantum computing chip structure that utilizes silicon chips and light (photons). According to the story, the processes it uses are said to be relatively compatible with existing technology and production processes. The research was unveiled this week at the British Science Festival. Here's a highlight from the FT article:

"A quantum computing device with 100 photons could in principle solve trillions of equations at the same time."

How is this relevant to lawyers? For one, the power of research "in silico" will go up and thereby add even more speed to molecular biology relevant to tort claims. The technology - when it arrives in a few more years - also will have implications for failure to warn if everything can be simulated and predicted. Am I dreaming?  Maybe a little, but consider the last statement of the FT article: 

“Just as wind tunnels are not used for aircraft designs any more but [have been] replaced by computer simulations, in the future we may be able to replace most chemistry labs with quantum computers,” says Prof O’Brien."

Set out below is the press release from the University of Bristol:

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Amazing. One small piece of DNA. Using advanced, repeating gene sequencing techniques, the researchers generated a precise genomic sequence.  The DNA belongs to a young girl. A girl who lived well over 50,000 years ago in a cave in Siberia. Scientists call her a Denisovan because that's the name of the cave. They were near relatives to Neanderthals - see here for a broader discussion in Scientific American. Now, by comparing the old and current genomes, the team can see how much we've changed from this ancient person from over 50,000 years. The answer? Not really that much change. 

The new work is by researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. The work and paper are groundbreaking because the researchers  figured out how to use a single strand of DNA to generate the sequence. What do other researchers think about the work of Matthias Meyer and others?  “Meyer and the consortium have set up the field of ancient DNA to be revolutionized—again,” says Beth Shapiro, an evolutionary biologist at the University of California, Santa Cruz, who was not part of the team. Evolutionary geneticist Sarah Tishkoff of the University of Pennsylvania agrees: “It's really going to move the field forward.”

Why does that matter? Because many more fossils include single strands pieces of old DNA. Think pieces of amber and Jurassic Park. What's next for the research team? "Back in [the lab at Max Plank in Leipzig], the mood is upbeat, as researchers pull fossil samples off the shelf to test anew with “Matthias's method.” First on the [team leader's list}: Neandertal bone samples, to try to produce a Neandertal genome to rival that of the little Denisovan girl." That is, they are going to try more museumomics. 

Why do lawyers care? Suppose the question is whether "toxins" are causing multi-generational changes to genomes. Suppose the current plaintiff has lockets of hair from her life before exposure to the toxin, and/or knows the locations for the graves of 3 or 4 generations of predecessors. We could be looking at generation to generation sequencing and comparison. Suppose the plaintiff is 65 year old woman with breast cancer, and a daughter and a granddaughter. Suppose there also are sequences for the daughter and the granddaughter.   Will that generate "proof" of a cause if breast cancer shows up in the daughter or granddaughter ? I'm sure I don't know, but it's interesting to think about the possibilities ahead. 

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Unlike asbestos and silica fibers, nanofibers are created by human designers.  All three substances, however, are proven or suspected carcinogens. 

Why carcinogenic? To borrow a phrase, size does matter, at least for some kinds of fibers. Science to date tells us that longer asbestos fibers are in general more lethal than are shorter fibers, especially for the needle-like amphibole fibers. In addition, the RJ Lee Group and Dr. Ilgren published new 2012 work indicating that width also matters, at least for crocidolite mined in Bolivia, and perhaps for other fibers. Now, the BBC reports on new research in the UK which indicates that carbon nanofibers become more carcinogenic once the length exceeds 5 micro-meters:

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Unfortunately, some science papers end up being retracted because of foul-ups or deceit. Retraction Watch keeps an eye on and writes about retracted papers. An August 22, 2012 post explains what does - and does not - happen with retracted papers on PubMed. 

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Judge Posner never lacks for an opinion. In this opinion in ATA v. Federal Express, he explains why an expert opinion on damages should not have survived a Daubert hearing. The opinion covers in some detail how to use simple regression analysis in a damages case, explains various flaws in what was done, explains confidence intervals, provides sources for educational data for judges regarding regressions, and reminds (with cites) regarding case law allowing judges to appoint their own experts. 

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(Photo courtesy of UK Mirror)

A good news story for science from the London Olympic Games. The news is that British scientists and others figured out a way to turn the London games into long term progress for science and humans. How? When the Olympics end, the labs assembled in London to check for doping during the Olympics will be turned into a new leading edge lab for molecular biology research. The story is told by the BBC and Science magazine.

The Brits are using the lab as part of their very smart move to seek a role as world leaders in molecular biology in particular and science in general. Indeed, David Cameron is personally involved in the annoucement and promotion for the new lab, as explained by the BBC:

Science has more of the technical specifics:   

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The Olympics highlight the reality that science changes, and it's a mistake to become complacent about science. To see the impact, here's a great graphic on 100 meter freestyle outcomes in Olympic history. The results highlight the impact of changes wrought by improving the science of swimming, not to mention conditioning, nutrition and weight training.

Examples of change? I can say from experience that back in the old days of the early 1970s, typical swim team coaching in Illinois included the idea of kicking very little in freestyle races, and no one was doing a dolphin kick off the blocks or coming out of turns. Today, it's relatively the opposite as swimmers use a dolphin kick off the blocks and off turns, and any observer can see that a powerful kick is a significant component of great freestyle swimming. Doc Counsilman was the main researcher and writer of the book on swimming, first in 1968 and then a whole new book in 1994. The research was conducted in pools using scuba gear, cameras and lots of work. Today, great advice is online and free, with plenty of videos and science papers to help create the next set of Olympic winners. 

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(Image courtesy of Cray Supercomputing - more than 270 Cray supercomputers are now being deployed in the Blue Waters Project ongoing at the University of Illinois Center for Supercomputing Applications - the resulting supercomputer will be one of the world's fastest, and will be used for scientific research.) 

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Two new terms for the lexicon:  In silico testing and bio-CAD design.

In vivo testing of a creature measures and observes conditions within a living creatures. In vitro testing of a creature measures and observes part of a creature within the glass of dishes and tubes. Now, in silico testing has matured to the point that an entire, existing creature has been measured, modeled and accurately operated inside a computer using algorithims and data built from over 900 traditional studies. Does the model work in ways that conform to real world observations ? Yes. The research findings were published in Cell in July - the outcome also is explained in a press release from Stanford and a ScienceDaily summary is here.  

The results ? Excellent. The abstract for the paper states the results in the understated style of science:

Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally different cellular processes and experimental measurements. Our whole-cell model accounts for all annotated gene functions and was validated against a broad range of data. The model provides insights into many previously unobserved cellular behaviors, including in vivo rates of protein-DNA association and an inverse relationship between the durations of DNA replication initiation and replication. In addition, experimental analysis directed by model predictions identified previously undetected kinetic parameters and biological functions. We conclude that comprehensive whole-cell models can be used to facilitate biological discovery." (underling added)

The press release is not understated:

"In a breakthrough effort for computational biology, the world's first complete computer model of an organism has been completed, Stanford researchers reported last week in the journal Cell.

Relevance for lawyers ?  Sooner than we may imagine, it seems there will be Daubert hearings involving findings generated from all three types of research - in vivo, in vitro and in silico. 

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The X Prize Foundation seeks to highlight progress and hopes in science and technology through extreme challenges, with prizes. One offered prize will provide glory and $10 million for a group able to sequence the genomes of 30 centenarians in 30 days for less than $1,000 per person. Ion Torrent has now announced it's entry to win the prize - entries are only now starting to appear to seek the prize first announced in 2006.  

The challenge money is offered by ExpressScripts as described here. Nominations are now open for the 100 centenarians who will become part of history by donating genomic material for sequencing. One hope is that the work will start to open the door to understand why some people are so long lived.  

Ion Torrent is a game changing enterprise. Part of its backstory is here, and ties to Gordon Moore, the creator of the famed Moore's Law on increasing computing speeds and decreasing costs. Ion Torrent's basic plan is outlined here. Amazing!

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Medical monitoring claims came and went because science in the 1980s did not have much to offer as an alternative to the annual check-up. But with molecular science exploding with new findings, medical monitoring claims have renewed vitality if used with reasonable groups and useful, additive science. Happily, costs alos are falling for possible forms of monitoring as computers and other devices make it easier to find and report on data. Indeed, a recent summary on biosensors notes  the developing efforts to find early evidence of cancers using only exhaled air - apparently some markers in the blood make their way out through the lungs. 

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"This image [of stem cells] shows that ductal and epidermal progenitors (in red) proliferate and repair an epidermal scratch wound; the sweat gland progenitors (in blue and green) show no signs of proliferation to this type of wound, but instead respond to deep glandular wounds." (Credit: Image courtesy of Rockefeller University)

Who cares about understanding stem cells in glands? Everyone should. Breasts are mammary glands. Sweat glands make it possible for us to sweat, and thus humans are able to survive in hot environments. The pituitary gland directs the flow of hormones that take us through life changes, including puberty, pregnancy, and menopause.

What's the relevance for lawyers, risk managers and others?  Increasing knowledge of cellular functions in glands may make it possible to "prove" when and how external sources damage cells, and thereby contribute to cancers and other harmful changes. With breast cancer rates rising steadily in the US and globally - as are breast cancer deaths - some women are increasingly asserting claims against some of the generators of substances which appear to be some of the causes of breast cancer. 

With all those facts in mind, it's easier to appreciate that indeed it is a big deal that molecular biologists are achieving profound gains in understanding the molecular level workings of stem cells in glands. Specifically, researchers have now found the stem cells driving creation and maintenance of sweat glands, and are observing their function, including noting the sweat glands creating tiny amounts of milk. The story is told in a ScienceDaily article built from a press release summarizing a paper just published in Cell, an important science journal. Key excerpts are below.

The study was supported by grants from the Stem Cell Research and Starr Foundation and from the National Institutes of Health. Researchers from the Université Libre de Bruxelles, in Belgium, and from St. Jude Children’s Research Hospital in Tennessee contributed to the study. (underlining added)

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(Credit - Image Courtesy of University of California - Los Angeles)

ScienceDaily brings news of a multi-disciplinary team developing yet another great new tool for scientists. It's a camera. A sensitive camera that captures images of cells. It's also a really fast camera. It's so fast it can accurately capture images of 100,000 cells per second. How fast is that? That's about 100X the best cellular camera in use today. 

The numbers are impressive, but what's the real world application and translation into science? One example is to use the camera to screen blood samples to look for cancer cells. That use can be put to work as part of making decisions about ending radiation or chemotherapy or other treatments when cancer cells are no longer found. And, of course, the camera screening could be used in to look for cancer cells before a tumor becomes clinically apparent. Tools like this ultimately can be used to avoid vast amounts of misery, and to save vast amounts of money through better decision making when cancer has manifested, and through cancer prevention. 

That's the big picture. Set out below are further specifics from the summary from ScienceDaily: 

ScienceDaily (July 6, 2012) — The ability to distinguish and isolate rare cells from among a large population of assorted cells has become increasingly important for the early detection of disease and for monitoring disease treatments. Circulating cancer tumor cells are a perfect example. Typically, there are only a handful of them among a billion healthy cells, yet they are precursors to metastasis, the spread of cancer that causes about 90 percent of cancer mortalities. Such "rogue" cells are not limited to cancer -- they also include stem cells used for regenerative medicine and other cell types.

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Next time you walk by fish for sale in a pet store, take a look at a tank full of zebrafish. Then, smile about the major contributions zebrafish are making to human health through their relative transparency, their physical structures, and their genes. Really? Absolutely!

But first, a few words about another little known part of science - Cold Spring Harbor. While reading the press release, note its mention that the annual zebrafish research conference was first held at Cold Spring Harbor. CSH, as its known, is a revered research institute among molecular biologists - its main history page runs quickly through just some of its many important places in the history of genetics and molecular biology. CSH was led at one point by James Watson of DNA fame, and his seminal work was first announced at a CSH conference. CSH also was a research home to Barbara McClintock, a cell genetics researcher who won a Nobel Prize in physiology  - in 1983 - for work she did at Cold Spring Harbor in 1944. Thus, almost forty years later she alone was honored for discovering transposons, which are the so-called jumping genes involved in genetic mutations. Sadly, the history of CHS is not all positive - it also was the early 1900s home to misguided eugenics work. On the brighter side, cancer research fundamentals also was occurring at CSH back in the early 1900s. The CSH history page explains:

"In 1916, Clarence Little—studying the genetics of cancer in mice—discovered that Japanese “waltzing” mice, but not other mouse strains, were susceptible to transplanted sarcomas (connective tissue cancers). In 1928, E. Carleton MacDowell discovered a strain of mice predisposed to spontaneous leukemia. Subsequent breeding experiments led to the development of mice with increased susceptibility or resistance to the cancer. MacDowell's work is a cornerstone of modern cancer research."

Returning to the zebrafish and genetics, the ScienceDaily summary was created from just part of the materials released by the Genetics Society of America in connection with the 2012 International Zebrafish Development Conference, held June 20-24 in Madison, Wisconsin. For those of us who missed the conference announcement, some background from the press release is set out below. 

ABOUT THE INTERNATIONAL CONFERENCE ON ZEBRAFISH GENETICS AND DEVELOPMENT: The zebrafish emerged as a major model system in 1994 with the first international conference at Cold Spring Harbor with 350 participants. This year the zebrafish community celebrates its 10th biennial international conference with more than 900 participants in Madison, WI. Studies using the zebrafish as a model system have allowed us to understand the genetic control of early development that underlie many human diseases. For more information about the conference, see http://www.zebrafishgenetics.org//

Now to specifics. Set out below is one excerpt from a ScienceDaily summary of several specific examples of using zebrafish genes in research to improve human health - in this instance, the genetics of leukemias and lymphomas: 

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Another back story to the June 4 post on important new work on proteins that bind to mRNA. The back story is the umbrella research group -  the European Molecular Biology Laboratory, a striking example of why molecular biology is racing forward (and why the U.S. acts foolishly when there are cuts to funding for fundamental research in molecular biology.) The EMBL web site tells the story of its creation and ongoing work - excerpted below are portions of pages here, and here. One can also follow EMBL on Facebook - its pages actually are informative. 

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A back story. Yesterday's post covered an important new research arising from work with "HeLa" cells. The new work brings to mind an important book on medical research history, money and racial barriers - The Immortal Life of Henrietta Lacks. The well told story was investigated and written by Rebecca Skloot - she provides a useful web site related to the book and story.  In short, the book tells the story of a black woman's awful journey through a cervical cancer, and her treatment at the then-segregated Johns Hopkins hospital. More of the story goes to  myriad later events as Mrs. Lack's cell line became a global standard, but with much misunderstanding and failure to communicate as to how that happened and who reaped financial rewards from her suffering. Mrs. Lack's cancer ultimately became the first immortal line of cells available for study, and so HeLa cell lines are ubiquitous today in research. Oprah Winfrey is overseeing creation of a cable tv movie based on the book, and Ms. Skloot penned a summary for Ms. Winfrey's web site. 

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New libraries of molecular knowledge continue to appear as molecular biology races forward. The May 3, 2012 issue of Cell brings a new paper reporting that European researchers searched for and appear to have found all proteins that bind to mRNA. This important work arises from a comprehensive study of proliferating HeLa cells. The findings include 860 proteins, with new discovery of over 300 proteins. Defining the universe of proteins is an important step in understanding the workings of our cells and genomes. A press release provides additional color and links; the work is part of the ongoing efforts of the European Molecular Biology Laboratory. 

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How did we end up generally adopting a 95% confidence level? A post at Empirical Legal Studies explains that the answer lies in a paper:  The Adoption of Significance Tests by the Scientific Community: An Empirical Analysis, by David A. Gully (Columbia--Engineering). The paper discusses the adoption of the 0.05 standard. The abstract explains the history as follows:

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The popular press says that a Pakistani doctor was given a 33 year jail term for telling the CIA where to find Bin Laden. It's actually more complicated and involves misleading the public - and children - using fake science regarding immunizations through a plan created by the CIA and the doctor. Kevin Jon Heller has the story at Opinio Juris.  

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Throwing away life. That may be the result of failing to preserve umbilical cords and placentas. 

New studies continue to investigate and find opportunities to harvest pluripotent stem cells from umbilical cords and placentas. The latest study is summarized by ScienceDaily and online at Stem Cells Translational Medicine. 

The key point?   Saving tissue at birth may some day help save a life. Some day not so far off, we amy see legal issues over whether preservation of tissue should be paid for by insurance - or a medical monitoring fund - as a prophylactic tool for persons with significant genetic risks. Others will want to privately fund the preservation as a hedge against diseases that may be become curable through stem cells. Set out below are key excerpts from the ScienceDaily summary:

The current report demonstrates that placental stem cells have much broader therapeutic potential than bone-marrow transplants, because they are pluripotent -- i.e. able to differentiate into many different cell types -- and they also generate growth factors that help in tissue repair. These cells are shown to integrate into different tissues when transplanted into mice, but like cord blood stem cells, and in contrast to embryonic pluripotent stem cells, they do not form tumor-like structures in mice. 

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An example of a local impact from big science and computers.  Due to birth problems with a bleeding brain and apnea, seven year old Selena Schuster faces big challenges in speaking, as described in the Orland Prairie. But,  now she's getting a a "new voice" - and better speech skills - using an Ipad and a special speech program on the tablet. The overall program is described here at Apraxia-KIDS.  

Results? According to her Mom, they are seeing real progress after she received the device in January. She has advanced to 3 and 4 word sentences instead of 2 words. And it's helping her feel better about trying to speak, and being more outward. 

Investing in science - it matters, globally and locally. 

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Opinio Juris includes multiple posts related to a timely seminar on medical tourism. This topic is going to grow, for many reasons, especially if SCOTUS (not wisely) votes to knock out the health care legislation that is so vital to many, including people with pre-existing conditions. 

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How do genomes change due to environmental forces? A new paper published in the April 5, 2012 issue of Nature sheds some light, and finds an example indicating that change happens the same way even if in different locations at different times. The conclusions are drawn from  a team of researchers sequencing and comparing the genomes of various colonies of the pictured fish - a stickleback -  that moved from the salty ocean to various fresh water locations.  (photo courtesy fo Stanford University). Some specific observations are pasted below from the article summary from ScienceDaily. The bigger picture point  is that scientists found the same groups of changes in different colonies.

With that in mind,  suppose there is litigation about disease in persons living around a "toxic" location. This study of the stickleback suggests that in due time, it will be possible to compare the genomes of colonies of people living near the site, and control groups who do not live near the site. Plaintiff's lawyers will argue that causation has been proved if comparative genomics shows that the persons living near the site all have similar changes to DNA or similar epigentic changes to their DNA.. 

Now go a step further. Suppose there are genomic studies of several groups of people who live by similar "toxic" sites, such as, for example, oil wells in Ecuador. Suppose those persons all show the same changes to DNA which are part of the pathways to cancer, or changes in regulatory microRNA.  Suppose those changes are not found in other "colonies" of Ecuadorians. Conclusion?

In this age of sequencing a genome for $1,000 (or less) , new things are possible. That's why next week I'll be in London to speak about science and tort law at a forward-looking litigation conference sponsored by Perrin Conferences. Join us if you can - it should be interesting!  

Set out below are key quotes on the stickleback research:

"For their latest study, Kingsley, scientists from the Broad Institute of MIT and Harvard, and an international team of collaborators started by sequencing the genome of an Alaskan freshwater stickleback to serve as a standard for comparison. That was an achievement in itself, yielding the first complete stickleback genome sequence.Next, the team followed suit with the genomes of twenty additional sticklebacks from around the world, including ten ocean stickleback varieties found around North America, Europe, and Japan, as well as the genomes of ten freshwater relatives from nearby freshwater locations. They then analyzed the sequences to identify DNA regions that changed whenever the fish made the move from salt water to fresh.

The researchers found 147 "reused" regions in the fish's genome. That suggests that each time the fish left the sea, variants in this same group of genes helped remodel the fish into forms that were better suited to fresh water, Kingsley says.

So what are these genes? The reused regions include the key armor genes that Kingsley and colleagues previously identified, and many others involved in metabolism, developmental signaling, and behavioral interactions between animals. The study highlights some genes in which alterations likely aid fish adapting to life in a less salty environment. These genes, which are in the WNT family that helps orchestrates embryonic development, adjust the size of small tubes in the kidney that are involved in conserving salt. Freshwater fishes tend to lose salt to their environment, so they need longer tubes to recapture it from the fluid filtered by the kidneys instead of excreting it in their urine.

The stickleback sequences also allowed the researchers to tackle one of the most contentious issues in evolutionary biology. Researchers have battled over what type of genetic changes spur evolution. Some scientists argue for changes to the coding sections of the genome, the portions that cells read to make proteins. More influential, other researchers contend, are alterations to regulatory DNA, which controls the activity of genes. "Here, it isn't either-or," says Kingsley. The team's analysis suggests that both kinds of changes occurred during stickleback evolution, but regulatory changes were about four times as common. "We finally get an idea of the relative contributions of both mechanisms, to a whole range of traits that have evolved in the wild," says Kingsley.

Using genome sequences to analyze the sticklebacks' natural evolutionary experiments "is showing us the genetic mechanism through which animals adapt to different environments," says Kingsley. With this approach, "we can find the key genes that control evolutionary change, helping to bridge the gap between alterations in DNA base pairs and the appearance of new traits in natural populations."

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Our brains do amazing things without conscious direction. For example, specific portions of our brains are programmed to quickly search for and recognize faces. Our perceptions also are shaped - instantly - by other inputs, including events prior to seeing an image, and events in tandem with seeing an image - such as smelling wine. The wine glass or faces experiment illustrated above is the subject of new work - here - that looks deep into the brain for the technical answers on brain function. For a wonderful general account of the workings of our brains, read Thinking, Fast and Slow by Nobel Prize winner Daniel Kahneman, a psychiatrist. The book should be required reading for law students and lawyers, especially trial lawyers. Why? Because he explains both System 1 - automatic, "fast" thinking, and System 2 - the much more difficult process of reasoning and doing "slow" thinking. Messages to jurors - or any audience - need to be considered in light of both processes. 

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With increasing frequency, researchers are figuring out how and why nature does what it does. A springtime example makes several points in a memorable way as scientists explain early blooming. 

 In a new article summarized in ScienceDaily and published in Nature, researchers explain hwo they uncovered the molecular level events that warmth triggers in flowers. The findings explain why flowers bloom "early" when warmth is present. In short, a plant gene generates a substance that will bind to receptor cells when it's warm outside, but will not bind when it's cool. ("With warm air, a control gene, called PIF4, activates the flowering pathway, but at lower temperatures the gene is unable to act. What is striking is that temperature alone is able to exert such specific and precise control on the activity of PIF4," said Dr Phil Wigge.")  

Understanding molecular pathways is critical to knowing how and why nature does what it does. Knowing why flowers bloom may seem trivial in one sense. But, as the researchers pointed out, global warming means there will be increasing importance to understanding what crops are likely to do as temperatures rise. Fundamental research does matter.

The findings in flowers rather elegantly highlight two other big picture points relevant to the intersections between law and science. First, the findings about the internal influence of temperature highlights the reality that external environment does matter in terms of the course of cellular-level outcomes. Indeed, the findings illustrate that multiple factors at work in how and why our cells do what they do, and the factors go beyond DNA. Second, the findings highlight that small differences do matter, to cells. And that small difference makes all the difference at the results level. The fact that small differences can matter seems a good point to remember the next time sometime  is ridiculing EPA for worrying about and regulating "low-level" exposures to substances. 

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It's difficult to create positives from death. But, when a loved one is dying, positives are possible when there is the presence of mind to donate tissues for scientific research. A recent example arises from a new study of the portions of the brains of children who suffered from autism, and died young. The mRNA of their  brain tissues were compared to the same tissues of other children who died young. Important differences were found, and provide new insights into the autism disease process. The new study is published in the free, full online access library known as the Public Library of Science - Genetics. 

This example of progress from tissue donation provides a moment for thought:  Have you registered with your Secretary of State to be an organ donor ? Have you told your family members that you wish to donate tissues for research? 

Note also that scientific papers sometimes include a very human touch. The study authors thoughtfully included this note: 

"We thank all parents for the donation of brain tissue from their loved ones. Tissue for this study was provided by the NICHD Brain and Tissue Bank for Developmental Disorders, the Brain and Tissue Bank for Developmental Disorders, Autism Tissue Program, and Harvard Brain Tissue Resource Center. Additional acknowledgements are listed in Text S1."

The study citations and credits - below - also illustrate the free flow of knowledge, the power of collaboration, and investment in fundamental research: 

"Citation: Chow ML, Pramparo T, Winn ME, Barnes CC, Li H-R, et al. (2012) Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages. PLoS Genet 8(3): e1002592. doi:10.1371/journal.pgen.1002592

Editor: Greg Gibson, Georgia Institute of Technology, United States of America

Received: September 27, 2011; Accepted: January 22, 2012; Published: March 22, 2012

Copyright: © 2012 Chow et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This research was supported by Cure Autism Now, the Simons Foundation, The Peter Emch Family Foundation, Autism Speaks, The Thursday Club Juniors, the Rady Children's Hospital of San Diego, and the UCSD-NIH Autism Center of Excellence (P50-MH081755). NJS and MEW are funded in part by part by the following National Institutes of Health research grants: U19 AG023122-01, R01 MH078151-01A1, N01 MH22005, U01 DA024417-01, UL1 RR025774, RC2 DA029475, R01 AG031224, U54 NS056883, as well as grants from the Price Foundation and Scripps Genomic Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

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Quite an idea - a breast implant that would help reduce the probability of a recurrence of breast cancer. ScienceDaily brings word that scientists at Brown University are at work using nanoscale materials to create an implant with a "rough" surface that so far appears to impede cells from generating VEGF - which is vascular endothelial growth factor. In short, it's a protein that promotes blood vessel growth, and most tumors need many blood vessels. So far, a 23 nanometer "bump" shows encouraging signs of deterring cancer cells from attaching and growing. This is early stage work, but quite an idea to turn a medical repair into a process that may also help a person avoid a recurrence of breast cancer. 

(The image is courtesy of Brown's press release.)

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The opinion in Prometheus continues to frustrate those in the patent bar who think the Federal Circuit deserves deference, for some unexplained reason - an example is here. A smart friend who is a patent lawyer reminded me of the maxim: "When you only have a hammer, everything looks like a nail." 

Others consider the outcome not surprising and very desirable for patients and research.  For example, consider the excerpts below from a Law.com article by Jan Wolfe:

"The U.S. Supreme Court delved into one hypothetical after another during oral arguments last December in Mayo Collaborative Services v. Prometheus Laboratories. The justices debated would-be patents involving fireplaces, chicken feed, and people whose fingers change color when they take aspirin. Always quick with a retort, and even an alternative hypo of his own, was Stephen Shapiro of Mayer Brown, who scored a landmark win for Mayo this week along with Jonathan Singer of Fish & Richardson.

The Supreme Court handed down a 9-0 decision on Tuesday throwing out Prometheus's patents for a diagnostic test for determining how thiopurine drugs are metabolized within the body. The case, which came out the opposite way in two different trips to the U.S. Court of Appeals for the Federal Circuit, has been closely watched because of its impact on the burgeoning field of personalized medicine. The justices concluded that Prometheus's patents "claim the underlying laws of nature themselves" and therefore must be deemed invalid.

Fish & Richardson's Singer told us the win "feels fantastic after seven and a half years of hard work." He's been pressing Mayo's case as lead counsel since 2004, when Prometheus sued for infringement after Mayo developed its own diagnostic test. A district court judge ruled for Prometheus in 2005, but the court later changed course and invalidated the two Prometheus patents. In 2009 the Federal Circuit reversed. The Supreme Court ordered the Federal Circuit to reconsider in light of the high court's opinion in Bilski v. Kappos, but the Federal Circuit again ruled for Prometheus in 2010. All the while, the Mayo team stuck to its guns. "If you read the district court opinion, and the Supreme Court's opinion, you'll find them very similar in terms of the arguments we made," Singer told us. 

Mayo's Federal Circuit briefs highlighted that Mayo halted crucial research because of Prometheus' infringement claims. That history colored the litigation, Singer said, likely shaping both press coverage and the policy arguments eventually adopted by the Supreme Court. "You can appreciate the effect it has on a trier-of-fact when doctors have to stop their research," he said. "These particular patents had a startling effect not just on commercial competition, but also on patient care. That's what this case is really about."

The unanimous ruling that Prometheus's test is not patentable subject matter "is a big surprise for a whole lot of people," said Herbert Hovenkamp, who wrote an amicus brief for Mayo in the case on behalf of nine law professors. He said that at oral argument Justice Stephen Breyer, who wrote the majority opinion, seemed a bit more inclined to agree with the U.S. government than with Mayo. The U.S. Solicitor General had argued that Prometheus's test could be patentable subject matter, but that the patents are invalid because they were anticipated."
 

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Many know of Gordon Moore thanks to his famous "law"  and his role as a founder if Intel, but as I recently learned, there's much more to the Gordon Moore story.  In 1965, Mr. Moore articulated Moore's Law that every year, society would see much faster computers because 2x the numbers of transistors could be pushed into integrated circuits. The rule was later updated to 18 months, and today, every three years.

Before co-founding Intel, Mr. Moore was a co-founder of Fairchild Semiconductor's integrated circuit business. The business was focused on the then-novel idea of using silicon to fabricate integrate circuit devices. 

Here are some facts most do not know about Mr. Moore.  He and his wife, Betty, are massive donors to and investors in science. Courtesy of Wikipedia:

 "In 2001, Moore and his wife donated $600 million to Caltech, the largest gift ever to an institution of higher education. He said that he wants the gift to be used to keep Caltech at the forefront of research and technology. Moore was chairman of Caltech's board of trustees from 1994 to 2000, and continues as a trustee today. In 2002, he received the Bower Award for Business Leadership. In 2003, he was elected a Fellow of the American Association for the Advancement of Science."

But that's only part of the story. The Gordon and Betty Moore Foundation is online here with a low key but informative website. Go here to look at year by year gifts - they range from small to incredible, and cover a broad range of science. The Foundation explains its work and mission as "creating positive outcomes for future generations."

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This NYT article by John Markoff explains part of the story on why we are now sequencing entire genomes for hundreds of dollars, and why a full sequence will soon cost far less. For another part of the story, read here on Ion Torrent. The story brings home the power of science when coupled with great new devices coupled with massive computers sorting through massive amounts of data. Note, for example, the article's point that new, industrial strength digital cameras will create a 10X increase in genome processing speed, allowing this company to sequence 100,000 genomes in year, instead of 10,000. 

Sequencing genomes alone will not drive all the answers we need. There is more to be done to correlate original DNA with environmentally-induced changes to the epigenetic system that regulates the actual function of DNA - those changes are part of the development of cancers and other diseases. But scientists today are light years ahead of 10 years ago, and will move further and faster if government budgets are preserved for investment in the fundamental research that drives molecular biology.

Investing in fundamental research is key. Society did well from investing in the race to the moon. Far more benefits will flow from investing in understanding our complex bodies. The original race to sequence one genome cost $ 3.8 billion, and is calculated to have generated 310,000 jobs, not to mention knowledge gained or lives saved. And, as pointed out by the article, the genome sequencing business and science are racing forward at an even faster pace.

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Epigenetics matter - a lot. It's chemistry in way - it's about external factors creating reactions that cause sections of your DNA to do more - or less - than it would normally do.

Here's a dramatically simple new example reported in Cell Metabolism and covered by ScienceDaily. Exercise (or caffeine) change the operation of some sections of your DNA. Consider the simple example below, and then imagine the findings when agencies use new science to test the epigentic impacts of various "toxins."  So far, the US has only regulated 5 substances under TSCA - really, 5, out of 83,000 or so chemicals. Imagine what's ahead. 

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Imagine growing hamburgers. No cows. Just meat growing in a lab. Or a meat factory.

The vision is real. In fact, the first hamburger is growing now, and should be ready for cooking in the fall. A celebrity chef may be asked to cook it. The story is here on the science being developed by researchers in the Netherlands. They see the process as taking another 15-20 years to result in true hamburger "factories." The news was publicized in connection with the 2012 annual meeting of the American Association for the Advancement of Science, held this year in Vancouver. 

The possibilities are interesting - but far from certain -  when one considers world population growth, the risks of pesticides, and the resources involved in raising cattle.  

Hat tip to Marginal Revolution for flagging the topic and articles. 

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Epigenetics and toxins are subjects of ever-increasing research and findings demonstrating harms to offspring, especially when a fetus is exposed to a toxin while in utero. In short, the timing of exposure can really matter. A new study is the first to link genetics and epigenetics with exposure to a flame retardant chemical. In short, the exposure of mother mice can result in harms in offspring.  A possible human analog involves clear cell vaginal  cancers suffered by "DES daughters and grand-daughters"  after DES was consumed during pregnancy by a mother or

grandmother.  

On the flame retardant, set out below are key excerpts from ScienceDaily's

summary of the new research paper and related press release materials:  

"The research was published online February 16 in the journal Human Molecular Genetics. It will be presented during a symposium on Feb. 18, at the annual meeting of the American Association for the Advancement of Science (AAAS) by Janine LaSalle, a professor in the Department of Medical Microbiology and Immunology in the UC Davis School of Medicine and the UC Davis Genome Center.

"This study highlights the interaction between epigenetics and the effects of early exposure to flame retardants," said Janine LaSalle, the study's senior author and a researcher affiliated with the UC Davis MIND Institute. "Our experiments with wild-type and mutant mice indicate that exposure to flame retardants presents an independent risk of neurodevelopmental deficits associated with reduced sociability and learning."

Epigenetics describes the heritable changes in gene expression caused by mechanisms other than those in the DNA sequence. One such mechanism is DNA methylation, in which genes are silenced when their activation no longer is required. DNA methylation is essential for normal development. The researchers chose a mouse that was genetically and epigenetically susceptible to social behavioral deficits in order to understand the potential effect of this environmental pollutant on genetically susceptible humans.

LaSalle and her colleagues examined the effects of the chemical BDE-47 (Tetrabromodiphenl ether), a member of the class of flame retardants called polybrominated diphenylethers, or PBDEs. PBDEs have been used in a wide range of products, including electronics, bedding, carpeting and furniture. They have been shown to persist in the environment and accumulate in living organisms, and toxicological testing has found that they may cause liver toxicity, thyroid toxicity and neurodevelopmental toxicity, according to the U.S. Environmental Protection Agency. BDE-47 is the PBDE found at highest concentrations in human blood and breast milk, raising concerns about its potential neurotoxic effects during pregnancy and neonatal development.

******

Rett syndrome is causally linked to defects in the methyl-CpG-binding protein 2 gene MECP2 situated on the X chromosome. Mutations in MECP2 result in a nonfunctional MeCP2 protein, which is required for normal brain development. The researchers evaluated the effects of exposure to BDE-47 on mice genetically engineered to have mutations in MECP2 and their offspring, or pups. The genetically engineered Mecp2 mother mice, or dams, were bred with non-mutant wild-type males. The dams were monitored for 10 weeks -- for four weeks prior to conception, three weeks during gestation and three weeks of lactation. They were then compared with a control group of normal, unexposed dams and pups over several generations and hundreds of mice.

The study found that that the weights of the pups of the lactating BDE-47-exposed dams were diminished when compared with the controls, as were their survival rates. To assess the effects of the flame retardant exposure on the pups and their genotypes, the researchers placed them through more than 10 cognitive, social and physical tests."

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The front page of the NYT this morning is dominated by a mosaic picture of 60 people who form a chain of 60 lives and 30 kidney transplants driven by domino chains of linked donations. The story by Kevin Sack is a remarkable tale and vividly illustrates the goodness of many people. The story focuses on a donation chain set in motion by the National Kidney Registry, a non-profit driven by a couple with a daughter who at one time needed a kidney transplant. 

The heart-warming and remarkable story deserves a leisurely Sunday morning read to nurture faith in mankind. And, after the feel good part, consider the story's subtle but clear lessons on the human and financial gains resulting from investing money and time in collaborative, creative and passion-driven teams bringing to fruition the power of science in this new age of individualized medicine. Specifically, the chain of paired donations - and thus cures  - was driven by:

• scientific tests able to distinguish among people at incredible levels of detail in order to vastly reduce the rate of transplant rejection, and thus make the best use the limited resource of donated kidneys, 
• a father with passion, money and skills in differential equations and computers - with help from others, he built programs able to quickly find and identify potential matches based on the scientific testing tied to the individualized blood types and antibodies of both donors and patients in need, and
• a physician creative enough to see the possibility of donation chains that would cross over the usual boundaries of families and friends to become an essentially unbounded chain,

The investment outcomes are fabulous. The story focuses on one particular chain of 60 people and 30 kidneys, but there are many more successful chains. The results are online at the web site. Read the full story and imagine the suffering avoided and the lives restored.

And, the investment also produces a fabulous financial return. So, the next time someone suggests cutting science budgets, follow Nancy Reagan's advice to "just say no" and then point the speaker  to the following numbers quoted from Mr. Sack's article: 

"Domino chains, which were first attempted in 2005 at Johns Hopkins, seek to increase the number of people who can be helped by living donors. In 2010, chains and other forms of paired exchanges resulted in 429 transplants. Computer models suggest that an additional 2,000 to 4,000 transplants could be achieved each year if Americans knew more about such programs and if there were a nationwide pool of all eligible donors and recipients.

Such transplants ultimately save money as well as lives. The federal Medicare program, which pays most treatment costs for chronic kidney disease, saves an estimated $500,000 to $1 million each time a patient is removed from dialysis through a live donor transplant (the operations typically cost $100,000 to $200,000). Coverage for kidney disease costs the government more than $30 billion a year, about 6 percent of the Medicare budget."

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People  sometimes take science in the wrong direction. In that vein,  consider a blog post from  Jennifer K. Wagner at the University of Pennsylvania’s Center for the Integration of Genetic Healthcare Technologies. Ms. Wagner's post explains that North Carolina is close to paying $ 50,000 of compensation to persons who are still alive and were subjected to involuntary sterilization. The post covers interesting ground and covers similar issues in other states - here's an excerpt: 

"Charmaine S. Fuller Cooper, Executive Director of NC Justice for Sterilization Victims Foundation presented (pdf) the Task Force in April 2011 with the history of NC’s eugenics program, explaining that North Carolina adopted its first sterilization law in 1919, its second in 1929, and its third in 1933. North Carolina did not abolish its eugenics board until 1977. The involuntary sterilization law, however, was not repealed until 2003. Don Akin, State Center for Health Statistics, presented (pdf) the Task Force with estimates of how many of the >7,500 individuals sterilized through the program were expected to still be alive, calculating roughly 40% of the victims (~2,900 victims) would have survived to the year 2010, but placing a “realistic” estimate at 1,500-2,000 surviving victims."

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The world cannot afford major diseases, and should be investing heavily in science. Yet, in the US, we see "budget hawks" blindly arguing for across the board budget cuts that would further reduce research budgets already too low. How can anyone in good conscience suggest that nations cut budgets focused on research of major diseases? And, when will politicians stop posturing over political footballs and focus instead on real needs, such as encouraging science and facilitating faster, better clinical trials for promising new treatments (statement of ASCO)

The points are highlighted by the possibility that there is now a major breakthrough in Alzheimer's research. The news is out in a ScienceDaily summary of a new study published on Thursday in Science, a world class journal.

The news is big, as indicated by the article being published online on February 9, after being received on December 9, 2011. That's fast for a journal.  The story also is on Huffington Post, in Scientific American (excellent summary), the BBC, and the Wall Street Journal. The news also is key because the active agent - Bexarotene- already is approved for use in coping with a form of cancer, might be  "only" $1,200 per month and is under study in various trials for cancer issues. 

Translating this research into the clinic is of course not a sure thing and will take time. But, if it works at all well, consider the potential benefits in human misery avoided, and economic savings. Scientific research is key for our collective futures and deserves vastly more financial support than it receives today. Set out below are key excerpts from the ScienceDaily summary: 

"ScienceDaily (Feb. 9, 2012) — Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journalScience, show that use of a drug in mice appears to quickly reverse the pathological, cognitive and memory deficits caused by the onset of Alzheimer's. The results point to the significant potential that the medication, bexarotene, has to help the roughly 5.4 million Americans suffering from the progressive brain disease.

Bexarotene has been approved for the treatment of cancer by the U.S. Food and Drug Administration for more than a decade. These experiments explored whether the medication might also be used to help patients with Alzheimer's disease, and the results were more than promising.

Alzheimer's disease arises in large part from the body's inability to clear naturally-occurring amyloid beta from the brain. In 2008 Case Western Reserve researcher Gary Landreth, PhD, professor of neurosciences, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. Landreth, a professor of neurosciences in the university's medical school, is the senior author of this study as well.

Landreth and his colleagues chose to explore the effectiveness of bexarotene for increasing ApoE expression. The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors (RXR), which control how much ApoE is produced.

In particular, the researchers were struck by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of Alzheimer's disease. The present view of the scientific community is that small soluble forms of amyloid beta cause the memory impairments seen in animal models and humans with the disease. Within six hours of administering bexarotene, however, soluble amyloid levels fell by 25 percent; even more impressive, the effect lasted as long as three days. Finally, this shift was correlated with rapid improvement in a broad range of behaviors in three different mouse models of Alzheimer's.

One example of the improved behaviors involved the typical nesting instinct of the mice. When Alzheimer's-diseased mice encountered material suited for nesting -- in this case, tissue paper -- they did nothing to create a space to nest. This reaction demonstrated that they had lost the ability to associate the tissue paper with the opportunity to nest. Just 72 hours after the bexarotene treatment, however, the mice began to use the paper to make nests. Administration of the drug also improved the ability of the mice to sense and respond to odors.

Bexarotene treatment also worked quickly to stimulate the removal of amyloid plaques from the brain. The plaques are compacted aggregates of amyloid that form in the brain and are the pathological hallmark of Alzheimer's disease. Researchers found that more than half of the plaques had been cleared within 72 hours. Ultimately, the reduction totaled 75 percent. It appears that the bexarotene reprogrammed the brain's immune cells to "eat" or phagocytose the amyloid deposits. This observation demonstrated that the drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and reverses the pathological features of the disease in mice."

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Tuesday was an especially  good day for science in the US.

One positive was the Administration announcing an additional  $ 50 million of funding (still far from enough) for research on Alzheimers. Happily, the Administration and far-sighted legislators continue to invest in science instead of caving in to short-sighted budget hawks who fail to appreciate the human and economic value of investing in science. Investing in science should be a no brainer, as proved by the stunning gains in knowledge and jobs achieved from projects such as the race to the moon (Freakonomics quorum on ROI) and investing just under $ 4 billion in the Human Genome Project ($ 796 billion and 310,000 jobs in return for a  $3.8 billion investment. )

The President also directly boosted science in general by hosting the administration's second  White House science fair for young students. The serious and not so serious events included the President trying out a marsh mellow cannon (video here) developed by 14 year old Joey Hudy, one of the students.  The cannon uses pressurized air to shoot marsh mellows up to 175 feet. On the more serious side, the Science Fair press release details a range of Administration actions supporting science. Key excerpts are below:

"[President Obama will be hosting] the second White House Science Fair celebrating the student winners of a broad range of science, technology, engineering and math (STEM) competitions from across the country. The President will also announce key additional steps that the Administration and its partners are taking to prepare 100,000 effective math and science teachers and to meet the urgent need to train one million additional STEM graduates over the next decade.

“When students excel in math and science, they help America compete for the jobs and industries of the future,” said President Obama. “That’s why I’m proud to celebrate outstanding students at the White House Science Fair, and to announce new steps my Administration and its partners are taking to help more young people succeed in these critical subjects."

The President hosted the first-ever White House Science Fair in late 2010, fulfilling a commitment he made at the launch of his Educate to Innovate campaign to inspire boys and girls to excel in math and science. Over the past year, the President met with the three young women who won the Google Science Fair, met a student robotics team on his bus tour through North Carolina and Virginia, and made a surprise appearance at the New York City Science Fair. The second White House Science Fair will include over 100 students from over 45 states, representing over 40 different STEM competitions that recognize the talents of America’s next generation of scientists, engineers, inventors and innovators. More than 30 student teams will have the opportunity to exhibit their projects this year, almost twice as many as the first White House Science Fair. The President will view exhibits of the student work, ranging from breakthrough research to new inventions, followed by remarks to an audience of students, science educators and business leaders on the importance of STEM education to the country’s economic future. For a sampling of the exhibits that the President will see, as well as more information on all the students, competitions and organizations being honored, click here."

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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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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.

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"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 ?

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"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