GlobalTort : Commentary from lawyers and experts on mass torts, law, insurance and science

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

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

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

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

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

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

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

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

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

Here are key excerpts:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

"Incorporating Innovative Science

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Key excerpts are set out below from the ScienceDaily article:  

***

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

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

 ****

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

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

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Do you take health insurance coverage  for granted ?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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


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


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

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

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

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

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


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


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


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

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


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

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

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


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






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


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


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


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

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

_____________________________________________________________________________

Exhaled breath condensate biomarkers in asbestos-related lung disorders.


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

Respiratory Medicine (2009)

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

PubMed ID: 19520561

Abstract

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

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

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

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

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

_____________________________________________________________________________


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


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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


--Edward R. Winstead

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

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

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

Cord Blood Can Save Lives

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

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

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

Register as a Potential Bone Marrow Donor

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

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

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

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

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

_____________________________________________________________________


• THE INFORMED PATIENT

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

• By LAURA LANDRO

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

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

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

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

Marrow Transplant Myths

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

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

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

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

Diagnosed With Leukemia

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

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

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

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

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

Advances in Matching

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

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

Ineligible Donors

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

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

• Email informedpatient@wsj.com.

Printed in The Wall Street Journal, page D1

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

1,103 ?

5,279?

9,867 ?

Drum roll please -the answer is:

5 ( I did not forget any numbers).

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

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

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

She also said:

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

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

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

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

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

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


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


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

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

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

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

_________________________________________________________________

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

****

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

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

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

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

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

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

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

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

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

***

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

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

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

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


Breakthrough in fight against mesothelioma

By Lindy Kerin for AM

AM abc.net.au/am

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

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


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

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

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

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

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

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

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

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

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

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

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

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


Two Units Of Umbilical Cord Blood Reduce Risk Of Leukemia Recurrence

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

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

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

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

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

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

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

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

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

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

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


Set out below is the abstract from the medical article.


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

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

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

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

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

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




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

Can more be done in an effective way. Absolutely !

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

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

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

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

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

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

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

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

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

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

***

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

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

________________________________________________________________


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

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

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

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

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

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

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

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

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

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


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

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


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



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


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



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

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

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


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


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


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

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

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

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

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

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

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

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

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

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

"Watson believes :

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

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

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

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

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

_______________________________________________________________

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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


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


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

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

The speech is well worth reading in full.

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

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

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

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

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

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

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

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


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


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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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


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

Ruling aids exposure defense on asbestos

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

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

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

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

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

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

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

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

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



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

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


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


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

Speakers are:

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

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

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

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

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


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

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

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

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

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

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

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

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


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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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