Mass Torts: State of the Art : Mass Torts Lawyer & Attorney : Vorys, Sater, Seymour & Pease Law Firm : Toxic Torts & Wrongful Death

In "On to a Fifth Age? How About We Finish the Second?" we discussed a JAMA editorial wherein Dr. Michael Gaziano asserted we may be entering a fifth age of the so-called epidemiologic transition. These transitions are claimed to be changes in the primary causes of morbidity and mortality and Dr. Gaziano opined that we are moving into an era in which obesity and inactivity will drive preventable illness. We discussed the origin of the idea of epidemiologic transitions and questioned  whether we'd ever finished the second age which would have required the conquest of infectious diseases.

The so-called third age was supposed to be the "age of degenerative and man-made diseases" but it keeps turning out that many illnesses thought to be due to wear and tear, lifestyle or pollutants actually have an infectious disease process at their core. Now there's growing evidence that coronary heart diseases (CHD) may in many cases have more to do with a number of infections, including influenza, than with lifestyle or the environment.

Here's a link to a letter published in the Reflections section of The Lancet: Infectious Diseases that nicely summarizes the pre-1970 thinking that pointed to infections as the cause of CHD, the subsequent predominating narrative of chronic diseases not being caused by infections, and the new evidence that chronic diseases are in fact often caused by previously undetected infectious processes: "Inflammation as the Cause of Coronary Heart Disease". And here's a link to a written debate about "this nascent field associating chronic diseases with infections" from 2002 with the author of the recent Lancet paper cited above: "Debate on the Paper by Maria Ines Reinert Azambuja & Bruce B. Duncan".

Given the enormous renewed interest in infections as a possible cause of chronic illness and the ease with which scientists can now find traces of bacterial, fungal and viral DNA (or RNA) at the scene of the suspected microbial crime it's fair to assume that we'll be seeing many more such stories in the future.

• Email This
• Print
• Comments

Mitochondrial DNA, or mtDNA, is increasingly assayed for early evidence of a disease which will eventually become manifest. Take a sample, amplify the DNA, examine it and look for change - makes sense, right? Your genes are the ones you're born with, right? And if they've changed that can't be good, right?

Well, it turns out that you, or your mitochondria at least, evolve or mutate within the course of your lifetime - and it's perfectly normal. We may have started out with Mom's mitochondria but it looks like by the time we're adults mitochondria in different parts of the body don't just express different genes, they have different genes. That's the conclusion of "Heteroplasmic Mitochondrial DNA Mutations in Normal and Tumour Cells" just published in Nature.

There's a great write-up of the findings at TheScientist.com and it makes two very important points for those of us dealing with litigation involving mtDNA biomarkers.

1) "we have to keep in mind [that] some of the changes we see may not really be [disease-related] mutations." - quote from author Nickolas Papadopoulos

2) "there's a big question mark about how early this increase in mtDNA variation appears in the blood. If it's only apparent once the cancer is well established then it isn't much use as a biomarker." - email from molecular biologist Ian Holt to The Scientist

• Email This
• Print
• Comments

The genes belong to bacteria living in your gut. They, along with their fellow microbes in and on "your" body outnumber human cells 10 to 1. But their genes collectively outnumber yours 150 to 1. These findings are just part of what you'll find in "A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing"  published in Nature and free online.

The authors conclude that  this catalogue of bacterial genes found in the human gut "will lead to a much more complete understanding of human biology than the one we presently have." I think it's fair to say that the realization that the microbes we host have so much control over our lives will lead to a revolution in how we think of ourselves and how we prevent, diagnose and treat conditions like obesity, diabetes and cancer.

• Email This
• Print
• Comments

You can read about a new vaccine based therapy for mesothelioma that is both safe and, in some at least, effective in "Consolidative Dendritic Cell-Based Immunotherapy Elicits Cytotoxicity Against Malignant Mesothelioma"

• Email This
• Print
• Comments

In May of 2006 PLOS One published an excellent paper summarizing the evidence that the reductionist approach embraced by medicine over the last century or so had done about as much as it could and was actually hindering further advances. You can find a free copy of that paper, "The Limits of Reductionism in Medicine: Could Systems Biology Offer An Alternative?" at PLOS One.

Modern medicine, the authors wrote, tends to assume (a) that each disease has a single cause; (b) that any deviation from homeostasis requires beating down levels of whatever is up and pumping up levels of whatever is down; (c) that a risk factor for disease in one person is a risk factor for disease in another person; and, (d) that in the case of multiple disease states they can each be treated separately rather than cumulatively. While this approach has been quite successful, particularly for certain diseases, the view of the body and its functions as a bunch of disconnected parts to be dealt with by hyperspecialized parts doctors is beginning to give way to a view that a deeper understanding of disease will occur only when when the complex systems governing the whole organism are understood.

Now there's another paper advancing this idea that afflictions of the body are more than just the sum of their signs and symptoms. In "Systems Biology as a Paradigm Shift in Clinical Research" available free at Oxford Journal of Nephrology Dialysis Transplantation. In particular the authors note the failed promise of biomarker identification to uncover either the causes of illness or effective treatments.

"Simply stated, molecules in a living cell are involved in networks of interactions that regulate the cell's basic functions ... [d]isruption of a partner in these interactions does not result in linear and definable effects but rather in global and often unpredicted perturbations of the whole network." The authors conclude with an overview of the systems biology approach and its promise particularly with regard to understanding and treating chronic diseases.

• Email This
• Print
• Comments

At least that may be the case for parasitic worms, also known as helminths. In the review article "Parasitic Helminths: New Weapons against Immunological Disorders" its authors discuss the recent literature supporting the hygiene hypothesis - the idea that the modern hygienic lifestyles of children deprive them of the immune system priming necessary to provide protection later on against diseases like diabetes, allergies, arthritis, Crohn's disease and cancers like Hodgkin's. Later in the article they turn to the evidence showing that one especially unhygienic aspect of an infestation, the helminths laying eggs in your body, is especially good for you.

So what does this have to do with mass torts? Well, a number of ailments attributed to chemicals, diet or drugs may in fact have their roots in our having rather suddenly and dramatically distanced ourselves from the microbiological environment that shaped us over the eons. Thanks to the elucidation of the molecular pathways responsible it may now be possible to identify those plaintiffs whose unmatured immune systems are the real culprits.

• Email This
• Print
• Comments

In an article just published in Diagnostic Cytopathology, "Podoplanin is a Useful Marker for Identifying Mesothelioma in Malignant Effusions", the authors conclude that calretinin plus podoplanin (part of an immunohistochemical staining panel) would significantly improve the specificity of pleural effusion diagnostics in suspected cases of malignant pleural mesothelioma (MPM). In other words, the suggested technique would do a better job of differentiating MPM from adenocarcinomas of the ovary, lung and breast.

As more and more putative mesothelioma cases have been filed, particularly by women plaintiffs with de minimis or even nonexistant amphibole exposures, battles over diagnosis have become more common. On the other hand, plaintiffs' counsel are now seeking to tie adenocarcinoma of the ovary to asbestos exposure. Perhaps both then are just new new levels in the never ending Whac-A-Mole game that is asbestos litigation.

• Email This
• Print
• Comments
• Trackbacks

Reuters Health is reporting on a new study in the Journal of Investigative Dermatology in which British researchers publish the results of their study on Vitamin D deficiency and sunshine. The short version is: you were made to be exposed to sunlight, you can get sick without it but moderation, as in all things, is the key.

There's a lot more of interest in this study available free online at Nature.

• Email This
• Print
• Comments

Tomorrow, February 4, is World Cancer Day and the International Union Against Cancer (UICC) is calling for greater awareness of the contribution of infectious disease to cancer cases around the world. "Cancer can be prevented too" is the theme of the effort. According to the press release the campaign is backed by a new scientific report: Protection Against Cancer Causing Infections which focuses on the nine known infections that can lead to cancer.

There's already a highly effective vaccine against human papillomavirus that prevents cervical cancer, a dreadful disease that took the life of one of my law school classmates within a year of her graduation, though it's still not widely given for a variety of reasons associated with culture and values. There's also a vaccine to protect against hepatitis B virus which causes a staggering number of cases of liver cancer worldwide yet it too is grossly underutilized. For more on World Cancer Day 2010 try these links: UICC World Cancer Campaign, World Health Organization,  European Hospital and this book: Infections Causing Human Cancer 

• Email This
• Print
• Comments

"If there is one thing the history of evolution has taught us it's that life will not be contained. Life breaks free, expands to new territory, and crashes through barriers, painfully, maybe even dangerously." -Dr. Ian Malcom, Jurassic Park

That's the quote that came to mind when I read the story about infectious cancer in Tasmanian devils from The New York Times. It's about a cell that became "malignant" and then set out on its own to be parasitic on others of the species. So far, only one similar case has been found - that of canine transmissible venereal tumor in dogs. But then, how long have researchers been looking for cells that left the multicellular super organism of which they were once a part to set up shop and find a new way of growing and propagating?

The dogmatic view that chronic diseases like cancer must be due to chemicals or behavior is now yielding to an older view that many of our woes are instead due to a nature red in tooth and claw.

• Email This
• Print
• Comments

The LATimes is reporting on a new study finding that neuroticism and extraversion in patients suffering from major depressive disorder are respectively alleviated and enhanced in patients taking Paxil. As compared to those taking placebos, Paxil patients not only experienced longer lasting relief from depression they also saw significant positive personality changes becoming less neurotic and more outgoing. "That is a dramatic change," said Robert McCrae, a leading researcher on personality, now retired. "If you were these patients or someone in their family, you'd notice a difference."
 

• Email This
• Print
• Comments

Despite decades of emphasis on putative man-made carcinogens, and a corresponding tendency to dismiss nature's brutish side as a possible cause of cancer, the case for viruses in causing human cancers has only gotten stronger. In "Human tumor-associated viruses and new insights into the molecular mechanisms of cancer" the roll of Epstein-Barr virus (EBV), human papillomavirus (HPV), hepatitis B and C (HBV and HCV respectively), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) in a significant percentage of human cancers is discussed along with insights into molecular biological mechanisms and some very interesting thoughts about how these insights might reveal other heretofore unsuspected viral-induced cancers, novel treatments and public health strategies to reduce cancer by preventing viral infections.

• Email This
• Print
• Comments

In their paper "Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the functional analysis of separated alleles in yeast, in human lung cells" Billet et al hypothesize that benzene-induced leukemia is the result of one or more mutations in the tumor suppressor gene known as TP53. They then report on their efforts to identify mutations in TP53 caused by benzene or its metabolites. It turns out that of the mutations linked to benzene exposure it is those in which guanine is substituted for adenine (A>G) that produce a pattern similar to that seen in benzene-induced acute myelogenous leukemia.

The authors conclude by suggesting that such an A>G transition could be "a fingerprint of benzene" that might help identify cases of AML produced by very low levels of past benzene exposure.

• Email This
• Print
• Comments

Why is the rate of lung cancer among nonsmokers increasing? In this paper published in Experimental Lung Research the authors not only found measles virus antigens in 83% of non-small cell lung cancer cases, they found that infection with the virus resulted in an excess of a protein typically seen in excess among lung cancer patients.

• Email This
• Print
• Comments

It was only a matter of time before molecular biological methods allowing screening for past potentially toxic exposures were developed.  In "DNA Double Strand Breaks by Asbestos, Silica and Titanium dioxide: Possible Biomarker of Carcinogenic Potential?' the authors from NIOSH, Health Effects Laboratory Branch, report that crocidolite was much more likely to produce  DNA double strand breaks leading to a molecule that can be detected by fluorescent antibody.  What this will mean for mass torts is anyone's guess but its implications for cases involving medical monitoring claims or mesothelioma claims where the plaintiff has failed to identify any amphobile exposures are obvious.

Interestingly, while similar effects were seen for crystalline silica and titanium dioxide, they were significantly less pronounced than that induced by crocidolite.

• Email This
• Print
• Comments

In this paper the authors, including Arnold Brody, report that carbon nanotubes are responsible for inflammation on the pleural surface of mice following a brief exposure.  A subsequent immune response lead to areas of pleural fibrosis.  Non-fiber shaped carbon nanoparticles failed to produce a similar outcome suggesting that the fibrous tube structure may be an important aspect of this phenomenon.  The authors suggest minimizing inhalation of nanotubes until longer term assessments are completed.

• Email This
• Print
• Comments

This is cool: BioGene.

Hat tip: OpenHelix.

• Email This
• Print
• Comments

A Japanese man who was diagnosed with advanced malignant pleural mesothelioma is disease-free more than two years after being treated with a mushroom extract containing agaricus blazei Murill Kyowa and a modified form of acupuncture. The authors, who note that the patient had undergone debulking and chemotherapy but thereafter, as is typically the case, fared poorly, conjecture that his remarkable recovery may be due to “some immunological reactions of the host to the tumor” induced by either or both of the alternative treatments. The free paper was published in the Journal of Medical Case Reports.

• Email This
• Print
• Comments

Although the precise mechansim for mesothioma is currently unknown, one study has postulated that immunosupression plays a role in the pathogenesis of this cancer. Mesothelioma in an HIV/AIDS patient without history of asbestos exposure: possible role for immunosuppression in mesothelioma: a case report, involved the study was of 41-year-old man who had asthma, HIV with progression to AIDS in the past 3 years, and a 20-pack year smoking history, was diagnosed with malignant mesothelioma.  This individual had no occupational history of asbestos exposure but did have a brief history of assisting in the demolition of a house over an 8-hour period a year before his diagnosis but it was unknown if he was exposed to asbestos during that work.

The authors of the study noted that the polyoma virus SV-40 has been implicated as a participant in some cases of mesothelioma. Studies have postulated that since the virus inactivates anti-tumor genes such as retinoblastoma, it promotes immunosuppression that may lead to enhanced susceptibility to mesothelioma. Similar to SV-40 virus, HIV is also an oncovirus and therefore capable of inducing cancer. Because HIV suppresses the immune system the authors think that HIV increases the susceptible to mesothelioma.

The authors also noted that transplant patients are immunosuppressed due to administration of drugs to prevent transplant organ rejection and elderly patients undergo physiologic immunosenescence which is characterized by reduced immune responses. Mesothelioma has been reported in transplant patients, without notable asbestos exposure, and mesotheliomas are classically reported in elderly patients.

The study notes that mesothelioma may be more prevalent in SV-40 virus-infected patients, HIV/AIDS patients, organ transplant patients, and elderly patients, than in the general population. The study concludes the development of mesothelioma in patients with HIV/AIDS, SV-40 infection, organ transplant, or advanced age suggests that chronic immunosuppression enhances susceptibility to mesothelioma.

• Email This
• Print
• Comments

US EPA has been working on a risk assessment of trichloroethylene (TCE) for some time now. Here’s a link to the EPA Issue Papers through 2005. Now a comprehensive review of the issues has been published in Critical Reviews in Toxicology. The article is entitled “Trichloroethylene risk assessment: A review and commentary” and it provides an excellent overview of the developing molecular biological and molecular epidemiological approach to causal attribution and risk; one we’re sure to see increasingly in asbestos, benzene and other mass tort litigation.

• Email This
• Print
• Comments

There are some interesting articles in the scientific literature about a war of which you've likely never heard. It's the one going on inside your body. A war pitting microbe against microbe. A conflict in which chemical warfare, the secretion of toxins, may well result in collateral damage - with the collateral damagee being you and the damage being cancer. More about that in the coming days but for now, here's an article about colon cancer risk and some of the bacteria working night and day to keep you from developing it. Here's the link.

• Email This
• Print
• Comments

Immortalized cells in a patient suffering from glioblastoma multiforme showed signs of infection by the SV40 virus. link. Further evidence of an alternate cause, particularly among who received the polio vaccine when it was contaminated with SV40, in brain cancer cases.

For the latest on the SV40 / mesothelioma debate see this article noting that both asbestos and SV40 cause calretinin (you remember - calretinin- from all those mesothelioma immunohistochemistry path reports you're always reading) to rush to the defense of mesothelial cells eventually, perhaps, exhausting some ill defined mechanism and leading to mesothelioma.

• Email This
• Print
• Comments

Lots of things cause aneuploidy but does that mean they cause cancer? Could it be that it's actually protective?

Nat Rev Mol Cell Biol. 2009 Jul;10(7):478-87. Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis

• Email This
• Print
• Comments

Here's an another article for the health conscious suggesting that Golden Delicious apples contain a chemical that inhibits the growth of a bacterium called helicobacter pylori (h. pylori).  H. pylori is known to cause MALT lymphoma and stomach cancer and is increasingly suspected as a causative agent in a host of other cancers often the subject of mass tort litigation.

Though IARC declared h. pylori a Class I human carcinogen for gastric cancer in 1994, unflinching efforts to demonstrate links between h. pylori and neoplasms as diverse as colon cancer and lymphoma commenced only recently.  

In another post on this topic I’ll discuss the big drum that always gets beat in mass tort cases, epidemiology, and how it fared in elucidating the real cause of gastric cancer.  Teaser: When it came to finding the real cause, h. pylori, epidemiology produced an epic failure.

See "Carotenoids with Anti-Helicobacter Pylori Activity from Golden Delicious Apple"

• Email This
• Print
• Comments

Chronic beryllium disease may result from very low levels of exposure to beryllium which occurred decades before any manifestation of the illness. The mechanism is thought to be a delayed immune response triggered by unknown environmental and genetic factors but at its heart due to sensitization to beryllium.

In this paper the authors present a history of the disease and current knowledge of its molecular biochemical mechanisms. They conclude that the current very low OSHA exposure limits still do not protect workers and suggest screening methodologies to identify those at risk.

• Email This
• Print
• Comments

Bloomberg is reporting in "Prostate Cancer’s Worst Form Linked to Gene-Influencing Virus" that a virus linked to the most aggressive form of prostate cancer, the XMRV virus, may insert itself in a cell's genome setting up shop next to genes coding for cell growth and thereby leading to uncontrolled growth.

Daily the 20th century scientist's belief that nature is benign yields to the wisdom:

Tho' Nature, red in tooth and claw
With ravine, shriek'd against his creed
 

  - In Memoriam A.H.H. - Alfred, Lord Tennyson

• Email This
• Print
• Comments

In the hormone replacement therapy litigation there's obviously a fight over whether estrogen caused the plaintiff's breast cancer. Is the demarcation simply a line between those breast cancers fueled by estrogen and those that aren't? If so, are there alternate causes of estrogen-fueled breast cancers?

What about human papillomavirus? It's been identified as the cause of cervical as well as head and neck cancers. Now HPV has been suggested as a cause of breast cancer.  http://www.nature.com/bjc/journal/vaop/ncurrent/full/6605282a.html

But is HPV a cause independent of estrogen or does estrogen facilitate whatever HPV does that leads to breast cancer? And if it's the latter, how do you sort out causation?

• Email This
• Print
• Comments

The idea that fungi, bacteria, viruses, etc. invade much more complex organisms and force them to do their bidding is not new but the extent of the control they can exert is just now beginning to be revealed.

For a good discussion of one method by which an organism invades another to create something new see this article - though perhaps the title of it needs to be altered slightly to read "how endosymbosis is changing life on earth".

But for a really interesting read about one life form hijacking another see this story about zombie ants.  Hat tip www.MycoRant.com.

And what does this have to do with mass torts?  1) Again, there's increasing evidence of a paradigm shift in the thinking about causes of cancer and a number of infectious disease processes are being associated with cancers seen in toxic tort cases; and, 2) infectious disease, maybe including those that decades later result in cancer, may soon be among the most massive of mass torts.

• Email This
• Print
• Comments

Here's a link to the program and abstract book: http://www.tum-benzenesymposium.de/AbstractBook_FINAL_082509.pdf

Given the current state of benzene litigation among the most interesting presentations will be those pertaining to (1) latency (whether attributable cases drop dramatically after 10 years or so); (2) disease endpoints (just AML, just certain subtypes of AML, or NHL, MM and even ALL); (3) molecular biology/epidemiology (biomarkers and pathways) for assessing past exposures; and, (4) risk assessment.

Details to follow.

• Email This
• Print
• Comments

Or would a better title be something like "Back to the Future"? When I got out of law school I worked on more PAHs, nitrosamine and butadiene cases than dust cases. Some early and fairly primitive epi studies had suggested causal associations with brain cancers in southeast Texas but the litigation never really went anywhere - or at least it didn't turn into the next asbestos. There were a few bladder cancer cases that got interesting but the literature on glioblastoma pretty uniformly concluded that it had no known etiology and the brain cancer cases died out.

See: Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology. You'll have to register (and pay) to get more than the abstract.

• Email This
• Print
• Comments

From bisphenol-A to benzene some researchers are claiming that some toxic substances not only don't have a no observable effect level (NOEL) but also that the shape of the dose response curve for these substances at low levels is supralinear.  What that all means is that the bane of any toxic tort litigator, the linear dose response assumption implying that even one molecule poses some risk, understates the actual risk associated with very low levels of exposure.

In "Evidence That Humans Metabolize Benzene via Two Pathways" by Rappaport, et al. hypothesize that at low levels of benzene exposure (less than one ppm) humans metabolize  the aromatic molecule much more efficiently than at higher levels due to some as-yet unidentified metabolic pathway.  Consequently "true leukemia risks" from exposure to benzene at what are considered acceptable ambient levels may instead pose significantly greater risks than are currently contemplated by regulators, according to the authors.

• Email This
• Print
• Comments

Distinguishing a mesothelioma from a lung adenocarcinoma is critical in asbestos malignancies. Over time, diagnoses made on the basis of morphology and the presence of asbestos bodies gave way to immunohistochemistry. Immunohistochemical staining panels keep changing and debates often rage over whether say a positive calretinen, etc. and negative CEA, etc. is enough or whether they merely show for example an adenoma of mesothelial origin. Now there's a new paper out discussing the use of epigenetic (your genes aren't so deterministic after all) profiles. Its title is "Differentiation of lung adenocarcinoma, pleural mesothelioma, and nonmalignant pulmonary tissues using DNA methylation profiles" and you can buy a copy of it there.

Of course all these new methodologies raise the obvious question of "What happens when you try to draw causal inferences about a case diagnosed today from epidemiological research conducted at a time long before these diagnostic techniques existed?" Will these then be, at least with regard to the litigation, distinctions without a difference?

• Email This
• Print
• Comments

One contemporary narrative goes like this: most cancers are preventable because most cancers are the result of man’s disregard for “nature”; whether due to pollution or ad campaign-induced bad habits like eating too much. But what if it turns out that a group of microbes that set up shop in our bodies are the real cause of many if not most cancers? 

Lung cancer has been the injury at issue in a number of mass tort cases.  A host of recently published papers indicates that human papillomavirus may trail only cigarette smoking as the leading cause of lung cancer.  See "Incidence of Human Papilloma Virus in Lung Cancer" and "The Role of Human Papilloma Virus in Lung Cancer: A Review of the Evidence"

Human papillomavirus has been associated with lung cancer in numerous studies though there is considerable debate as to whether the correlation is coincidental or causative. The first article reviews the literature and argues for a causative role for HPV in lung cancer. The second article suggests a biologically plausible mechanism for the production of lung cancer by human papillomavirus.

• Email This
• Print
• Comments
• Trackbacks