What's Behind the Rise in Food Allergies?

The incidence of food allergies in children is rising. Wheat, milk, egg, fish, peanut, walnut, shellfish and soy allergies have led to recalls of pork, turkey, cream of wheat mushroom soup, roast beef, ice cream and corn pasta in recent months. What's behind the increase in allergies?

There are at least two good hypotheses for which there's sound evidence. First, despite what our pediatrician told us, it's probably a good idea to introduce babies to e.g. cow milk sooner rather than later (see "Early Exposure to Cow's Milk Protein is Protective Against IgE-Mediated Cow's Milk Protein Allergy") and make sure they get a large enough dose to produce tolerance as it's apparently the low doses of say peanuts that lead to sensitization and allergy (see e.g. "Peanut Sensitization and Allergy: Influence of Early Life Exposure to Peanuts").

The second emerging hypothesis, another of the increasingly common "Grandma was right" sort of ideas, is that lack of sunshine is also responsible for the rise in food allergies in children. It turns out that vitamin D is crucial to a properly functioning immune system and without it you wind up with a gut full of the wrong sorts of bacteria behaving badly. (See "Potential Mechanisms for the Hypothesized Link Between Sunshine, Vitamin D, and Food Allergy in Children" and "The Role of the Gut Mucosal Immunity in the Development of Tolerance Versus Development of Allergy to Food").

And while we're on the topic of the consequences of this needless epidemic of vitamin D deficiency in the U.S. due to four decades of anti-sun/anti-reason activism you should also read: "North-South Differences in U.S. Emergency Department Visits for Acute Allergic Reactions", "Are Active Sun Exposure Habits Related to Lowering Risk of Type 2 Diabetes Mellitus in Women, a Prospective Cohort Study?" and "Vitamin D and Risk of Cognitive Decline in Elderly Persons" along with "Vitamin D: A Place in the Sun?" and "Vitamin D in Asthma: Panacea or True Promise?"

The takeaway here is that by overreacting to rare and likely uncontrollable risks we've been stampeded right into far more common and otherwise avoidable risks. So who should be liable to all of the eggshell plaintiffs manufactured out of junk science? Should it be the companies whose products would not have caused harm but for the activists or should the activists be called to account for what they have done?

Twenty Suspected Carcinogens

The American Cancer Society is calling for new research to settle the issue of whether or not twenty different agents do indeed cause the types of cancer in which they've been implicated. The twenty are:

(1) Lead and lead compounds; (2) indium phosphide (used in many flat screen TVs); (3) cobalt with tungsten carbide; titanium dioxide; (4) welding fumes; (5) refractory ceramic fibers; (6) diesel exhaust; (7) carbon black; (8) styrene oxide and styrene; (9) propylene oxide; (10) formaldehyde (does it cause leukemia?); (11) acetaldehyde; (12) formaldehyde; (13) methylene chloride; (14) trichloroethylene; (15) tetrachloroethylene; (16) chloroform; (17) PCBs; (18) DEHP (a phthalate); (19) atrazine (a herbicide and the subject of a coordinated attack by various activists groups resulting in a new EPA review); and, (20) shift work (the presumed exposure being "light at night" leading to a disruption of circadian rhythms and the most commonly associated malignancy being breast cancer).

You can find the press release here: Report Outlines Knowledge Gaps for 20 Suspected Carcinogens; and you can find the IARC report summarizing past rationale for assigning these suspected carcinogens to groups 2A - 3, the new evidence forming the basis for the recommendation that the status be updated and the sorts of epidemiological and mechanistic studies necessary to answer the question of whether they ought to be added to the list of 107 Group 1 agents known to be carcinogenic to humans, here: Identification of Research Needs to Resolve the Carcinogenicity of High-Priority IARC Carcinogens.

Which Came First, the Mutation or the Cancer?

The current paradigm, some 40 or 50 years old now, would say it was the mutation. As the first plaintiff's expert witness I ever cross examined at the courthouse said of the chemical in question "it messes with your DNA and if your DNA is messed up anything, especially cancer, can happen". By the way, for the younger set, before Daubert and Robinson/Havner that's what all too often passed for "science" in the courtroom.

Yet in the new Million Women Study of breast cancer, mutations associated with higher risk and environmental insults associated with higher risk seem to have no relation with one another such that hormone replacement therapy doesn't increase the risk of breast cancer even in women with genes predisposing them to estrogen-receptor positive disease. How can that be?

Well, here's some food for thought. Where do we come from? Bacteria, way back when. How do bacteria talk to each other? Quorum sensing (by the way, don't you wish all your teachers had been like Bonnie Bassler?) So if our stem cells want to monitor how many undifferentiated cells they need to be making and if those cells want to monitor their path to differentiation might they not do it via the same signaling pathways that their ancestors employed? If that's the case then could it be that a disruption in signaling causes runaway production of immature cells (cancer) and that the mutations only occur later? There's more than a scintilla of evidence for it.

What recruits bone marrow cells to the gut where their signaling is disrupted? Is it significant that many of the benzene workers thought to have developed leukemia as a result of exposure lived not only in the same building but were roommates? Is the parallel between the fall in cancer mortality and the rise of antibiotic use suggestive? It's something to think about anyway.

EPA Reanalyzing Dioxin Toxicity

On June 14, USEPA gave notice of a July 9, 2010 "listening session" related to its external review draft document entitled "EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments." The draft document includes new analyses on potential human effects from exposure to 2, 3, 7, 8 tetrachlorodibenzo-p-dioxin (TCDD). The draft document was also provided to EPA's Science Advisory Board for peer review.

How, and Why, Do Some Bacteria Facilitate Cancer Metastasis?

When you ask a physician or researcher how bacteria cause and/or promote cancer usually the only answer you get is "inflammation" and some hand waiving. It sort of makes sense. Lots of new and different stuff is going on, lots of new and different cells are running all around and lots of old cells are busily dividing and multiplying - surely a recipe for an accident.

But what if the bacteria are actively promoting the metastasis? That's the finding in "Bacteria Peptidoglycan Promoted Breast Cancer Cell Invasiveness and Adhesiveness by Targeting Toll-Like Receptor 2 in the Cancer Cells". Why, in the "what's in it for them" sense, would bacteria promote something that kills their host? Something to ponder over the weekend.

An Unusual Benzene/MDS Opinion

In Quillen v. Safety-Kleen Systems, Inc., 2010 WL 2044508 (E.D.Ky.) the court determined that plaintiff's expert, Dr. George Rogers, could properly attribute a case of myelodysplastic syndrome (MDS) to benzene by doing a differential diagnosis. That some courts have taken to using differential diagnosis to identify the root cause of say splenomegaly rather than to distinguish histoplasmosis induced splenomegaly from Hodgkin's disease induced splenomegaly would likely set many physicians' eyes rolling.  Yet, that's apparently what the 6th Circuit said in Hardyman v. Norfolk & Western Railway Co., 243 F.3d255 (6th Cir. 2001) and thus the thinking by the Quillen court.

The point of doing a differential diagnosis, of course, is to rule out possible causes until just one is left - it's a process of elimination. But just because every other cause of splenomegaly has been ruled out in the case of a male patient that doesn't mean that it makes sense to conclude that the cause must be the remaining possibility - a metastatic ovarian cancer. To be considered for elimination in the first place the putative cause has to be one that makes sense. In Quillen though there was no effort to demonstrate that plaintiff's experience with benzene was the sort that would make benzene a reasonably plausible cause of his MDS.

Finally, please ponder the following. In response to the defendant's objection that plaintiff's expert had not ruled out ionizing radiation  the court wrote: "Defendant points to nothing in the record demonstrating that Quillen was ever exposed to a statistically significant amount of such radiation." Somewhere an epidemiologist just fell out of her chair.

Autism/Vaccine Proponent Andrew Wakefield, Banned from Medicine in Britain

As a follow-up to our post on the death of the vaccine/autism litigation last week, we report the following news: Dr. Andrew Wakefield, the chief proponent of the now discredited junk science behind the MMR vaccine/autism link, has been banned from practicing medicine in his native UK.

Wakefield has moved to Texas and set up an autism clinic.

A brief synopsis of the whole sorry history of the MMR vaccine/autism scare is encapsulated in this prior post and comic strip which is eloquent in its brevity and accuracy.

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Final Nail In the Vaccine/Autism Coffin?

The Court of Appeals for the Federal Circuit recently drove what we hope is the last nail in the coffin of the vaccine/autism litigation. Rarely has a toxic tort had the potential to cause so much harm based on such shoddy science. The history of this tort and its shortcomings have been reported in great detail.

In short, the scientific evidence that vaccines cause autism came from a discredited article by Andrew J. Wakefield and two follow-up articles. Dr. Wakefield’s article created a public health crisis with parents, including celebrity parents Jenny McCarthy and Jim Carey, urging parents not to get their children vaccinated. As a result, formerly endemic childhood diseases which had become effectively eradicated in the developed world began to make a reemergence. Wakefield’s article was finally withdrawn from the Lancet earlier this year after 10 of the 12 co-authors disavowed it. Wakefield, himself, refuses to withdraw the article even though it was found that he committed scientific misconduct and lied in the article. The UK’s General Medical counsel’s Fitness to Practice Panel issued a judgment against him for his vaccine/autism paper. Wakefield continues to testify. Others testify based on his work.

Thankfully, the vaccine litigation was consolidated in the federal Vaccine Court pursuant to The Vaccine Act (passed in response to the health scare where the DTP vaccine was accused of causing neurological damage and in response to lawsuits, stopped being manufactured). Plaintiffs in three bellwether cases all failed on causation. The Special Masters wrote massive opinions eviscerating Wakefield and the causation theories of Plaintiffs.

Hopefully parents can now rest assured that vaccines are not a risk for autism. And, they can recognize the far greater risks to their children and society from not vaccinating.

Can't Prove a Negative: Mobile Phones and Brain Cancer

A World Heath Organization (WHO) study on cell phones and brain cancer has been published. It tracked 13,000 cell phone users over a number of years. The study showed no association between brain cancer and cell phone use. Statistically, people who used cell phones had a decreased rate of brain cancer.

Despite this, and despite every prior study showing no statistical evidence of an increased rate of brain cancer in cell phone users, the authors state that “[t]he results really don’t allow us to conclude that there is any risk associated with mobile phone use but it is also premature to say that there is no risk associated with it.”

This is true. It is just about impossible to prove a negative. This has not stopped the authors of the recently released President’s Cancer Panel from arguing for a “precautionary principle” to regulation. Their precautionary principle would have cell phones outlawed until they could be proven safe. Specifically, the panel argues that cell phones should be banned until there is no risk of cancer associated with them. The obvious question, however, is how to prove that there is no risk. Study after study finds no association but cannot prove the negative, an absolutely risk free product. All the freedoms and advances in wireless technology would be banned until a 30-year long term study showed there would be no risk. By 2040, what other life-changing technologies would we have missed?
 

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An Epidemic of Head and Neck Cancer

Cancer of the oropharynx in men is on the rise. Such cancers have traditionally been blamed on smoking and/or drinking so what accounts for its increase in a time of reduced rates of smoking and alcohol abuse? A virus; human papillomavirus (HPV). See "HPV-Associated Head and Neck Cancer: A Virus-Related Cancer Epidemic".

Remember, (1) the focus of this year's World Cancer Day was a call for greater awareness of the contribution of infectious disease to cancer; and, (2) the "age of receding panemics" never really passed - we just stopped looking for them.

 

Anti-H.pylori Therapy Cures MALT Lymphoma in H.pylori-Negative Patients. Hmmmm

We've defended a few gastric lymphoma cases in which the alleged cause was benzene exposure. The discovery that Helicobacter pylori was was the cause of most instances of the disease made the litigation go away. Nevertheless there have continued to be cases of MALT lymphoma in patients without evidence of H. pylori infection. Could their cancers have been caused by something besides a bacteria?

In "Treatment Outcome of Localized Helicobacter pylori - Negative Low-Grade Gastric MALT Lymphoma" the authors report on what happened when they treated some MALT lymphoma patients who had no evidence of H. pylori infection with anti-H.pylori antibiotics. Complete remission was achieved in each case.

The authors offer the following hypotheses about why giving people a drug to kill a particular strain of bacteria that they don't have that bacteria might nevertheless cure them of lymphoma: (1) a first cousin, H. heilmannii, might actually be the causative organism; (2) unknown bacterial agents susceptible to the antibiotics caused the lymphoma; (3) H. pylori at populations too small to be detected are still enough to cause lymphoma; and, (4) antibiotics eradicate MALT lymphoma not by simply killing H. pylori but rather by altering the resident immune system - resetting the system as it were.

Unless the answer is (3) MALT lymphoma will serve as yet another example of the fact that, save for very rare instances like pleural mesothelioma and erionite, "but for" causal attribution in cancer cases is exceedingly difficult.

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But Sometimes Causation is Really, Really, Really Easy

As we wrote yesterday, causal attribution in most toxic tort cases is hard and the discovery that life and many of its diseases are emergent rather than predetermined phenomena has made the exercise even more complex. That said, sometimes causal attribution is easy - as in the cases of falling, being shot or developing mesothelioma after exposure to erionite.

50.5% of all deaths were due to mesothelioma in one village in Turkey and of women who moved from areas without erionite to this same village 69% of all deaths were due to mesothelioma. Read about it in: "Endemic Malignant Mesothelioma: Exposure to Erionite is More Important Than Genetic Factors".

Is there any carcinogen as potent as erionite? What do these numbers suggest about the mode of action of erionite? It sure looks as though the biological insult from erionite is more akin to that of some physical trauma than from some molecular biological disruption as in the case of a genetic mutation.

Causation is Really, Really, Really Hard

Life would be so much simpler if causation were binary - e.g. stay out of the sun and never get melanoma or worship the sun and die young of skin cancer. That way we'd have real choice, the virtuous would be spared and the heedless would be plagued. It doesn't work that way, of course.

Shockingly (or not) most people who sunbathe, drink or smoke don't die of skin cancer, throat cancer or lung cancer. What gives? Maybe the numbers are wrong or maybe the statistics are just some trick of government / industry / academia / nefarious "other". Those are a few of the explanations offered up by the readers of the San Francisco Chronicle in response to its new article: "Vitamin D Levels Dip" in which the claim that sunbathing might be good for you is explored.

That biological cause and effect, even at the level of a single protein, can't be put into simple one-to-one correspondence doesn't just vex bloggers; it is profoundly troubling to researchers and it's prompting many to reexamine views about causality in biological systems that were being investigated decades ago but which fell out of favor in the modern reductionist era.

In "Order Without Design" Alexei Kurakin nicely sums up the evidence for life, and thus diseases of life, being emergent processes unexplainable by reducing the system to its parts and its inputs. Life (and its afflictions) instead seems to be a dynamic process driven essentially by economic competition for energy and materiel at the molecular level. What is the evidence for this claim? One very big piece of it is found in the amazing plasticity of proteins.

We've all been taught that proteins, especially cytokines, work like locks and keys. It's an easy to grasp metaphor and promised easy-ish cures for what ails us. Disease was the product of missing keys or broken locks. Supply the missing key, or one that worked the broken lock, and the door to good health was open again, right? Too often though it turned out that replacement keys didn't work as expected and that broken locks weren't actually broken - they were just performing other functions.

Closer examination revealed that proteins were often found far from where they were thought to do their work and were twisted and folded into completely unexpected shapes. Further investigations revealed that many if not most proteins exist not in some concrete form with concrete functionality but rather in a "disordered" state waiting to be shaped and directed not by some genetic program or external event but rather by the tides of energy and matter within the cell itself. And it is out of the ebb and flow of those tides that the organized activity of the cell emerges.

There's much more in the paper and those which it cites, of course, but for our purposes suffice it to say that the question of causation in biological systems cannot sensibly be asked, as we do in our courts, "Was chemical "X" a producing cause of Plaintiff's cancer?" Perhaps the question should be something more akin to "Given Plaintiff's condition before exposure to chemical "X"  by how much was her risk of cancer increased by that exposure?" But then that doesn't really get it either. Take mesothelioma and amphibole exposure as an example. 

It's commonly said that amphibole exposure is a risk factor for mesothelioma in humans. But if that's the case why didn't the other 95% of the workforce at say the unibestos plant in Tyler, Texas get mesothelioma? Is it that amphibole-induced mesothelioma is a purely stochastic process such that those who developed the disease were just unlucky? Or rather is it the case that causation, in the case of chronic diseases anyway, isn't generalizable? That's the takeaway - there may not be such a thing as what lawyers call "general causation".

Does Shift Work Cause Cancer?

IARC thinks so. Others have recently published papers claiming that breast cancers and melanomas are probably caused by exposure to electric lighting at night. However, a new study published in the American Journal of Epidemiology looked at 73,049 Chinese women and found no association between breast cancer and night-shift work, irrespective of frequency, duration or cumulative shift work. The authors conclude that "it may be premature to consider shift work a cause of cancer."

What if Everything You Knew About the Cause of Cancer Was Wrong?

Back in the day, a doctor from deep East Texas opined as follows about an alleged carcinogen: "It messes with your DNA and everybody knows that if your DNA gets messed up it can lead to cancer." Multimillion dollar verdicts were founded on little more than that sort of speculation.

Yet, what if that which everybody knows about cancer is wrong? The prevailing paradigm, that cancer comes from a single cell that develops a mutation and then grows out of control, is beginning to show a lot of cracks. Why do cancer outbreaks mimic those of pathogenic epidemics? Why would population mixing lead to cancer? Read about it at Carcinogenesis in "Hypothesis: Towards the Origin of Cancer Epidemics and Pathogenesis".

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Diagnosing Asbestosis

BPA: Hypotheses Begin to be Tested

In "Perinatal Exposure to Bisphenol-A and the Development of Metabolic Syndrome in CD-1 Mice", just published in the journal Endocrinology, researchers tested the claim that exposure to a typical dose of BPA (1ppb via diet) increases the risk of high-fat diet-induced obesity and glucose intolerance. The experimental data did not support the claim. Interestingly, the BPA-fed mice grew a bit quicker early in life but by adulthood were the same size and body composition as the mice not fed BPA.

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EPA Goes After BPA

The New York Times reported today that EPA is adding Bisphenol-A (“BPA”) to its list of chemicals of concern. BPA is widely used in certain plastics, notably food packaging and baby bottles. New studies of concentrations of BPA in surface water, ground water and drinking water will be required. In addition, manufacturers using BPA in their products will be required to provide test data to help evaluate effects on growth, reproduction and development in aquatic organisms and wildlife.

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"We Make Our Food Very Similar to Cocaine Now" - Gene-Jack Wang M.D.

Sometimes mass tort litigation feels a lot like being in the movie "Groundhog Day". The names and the products may change from day to day but the plaintiffs', the true believers' and the media's overarching narrative is always some aspect of the one refined in the tobacco litigation. One such narrative goes towards abrogating personal responsibility and does so by purporting to show that a product is both irresistibly addictive and insidiously malignant.

Today's vignette is thanks to a (free) paper just published in Nature Neuroscience titled "Dopamine D2 Receptors in Addiction-Like Reward Dysfunction and Compulsive Eating in Obese Rats". In the study being reported eleven rats got their fill of "bacon, sausage, cheesecake, pound cake, frosting and chocolate", eleven others got to pig out on "bacon, sausage ..." but for only one hour per day while nine other rats got nothing but "rat chow". Shockingly, the rats stuck in a cage all day with nothing to do but eat pound cake with frosting put on weight.

Various permutations of the experiment were run including some involving IHC staining with fluorescent proteins so that the now obligatory brilliantly colored photomicrographs could be produced. Some other rats considering pigging out were "punished" with electric foot shocks while yet others had "stimulating" electrodes implanted in their brains and held in place by four stainless steel skull screws.

The pound cake with frosting didn't affect life expectancy since all the rats were sacrificed two weeks after their 40 day food odyssey. However, the researchers found evidence of classic addiction response whereby reward mechanisms (pound cake with frosting makes you happy) were gradually suppressed by the body as it tried to adjust to the good times and maintain homeostasis so that more and more pound cake with frosting was needed to reproduce the initial reward level. The rat chow rats and the one hour per day bingers on the other hand lived out their 54 days in much slimmer bodies and with the normal compliment of dopamine receptors implying that living in a cage and eating rat chow is not excessively rewarding.

The quote above from Gene-Jack Wang, M.D. was found at The Situationist in its write-up of the Nature Neuroscience article. He's also quoted as saying that purified modern food makes people eat "unconsciously" and animals "eat like a drug abuser [uses drugs]". Wang is said to be the chair of the medical department at the U.S. Department of Energy's Brookhaven National Laboratory.

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Lies, Damned Lies, and P-Values

In "Odds Are, It's Wrong", Tom Siegfried lays out the argument for the proposition that much of what you read in the scientific literature is wrong because many of the claims being made rely on statistical significance. You see, an impressive sounding statement like "the association between exposure and disease was highly significant (P<0.05)" does NOT mean (a) that there's a 95% chance that the association is causal; (b) that the absence of an association can almost certainly be ruled out; nor does it necessarily mean that (c) the finding is momentous, compelling or even important. It doesn't even say that if the test were to be repeated that its results would likely hold. A P-value, the arbitrary judge of "statistical significance", won't, and can't, have anything to say about the likelihood that a given hypothesis is or is not true.

The fact of the matter is that if you have a bunch of data and can't find at least one statistically significant association it in only proves one thing - that you're not trying hard enough. The magical P-value level of 0.05 is nothing but a trade-off; a balancing act between finding associations that don't exist (false positives) and missing true associations that do (false negatives). As a result, false associations are not only possible, they're guaranteed when you have enough data and slice it enough ways.

Now, lawyers are getting into the act. And while it's bad enough that "[a] lot of scientists don't understand statistics" (Steven Goodman quote from the "Odds Are, It's Wrong" article) it gets awful when lawyers try to deploy statistics to support or rebut claims. Law review articles are littered with claims resting on nothing more than small P-values. Some purport to show that certain appellate courts are biased against accident victims; others that tort reform is good for your health. And hardly a week goes by that I don't see a brief or a pleading asserting that Texas "jurisprudence" requires an epidemiological study with a risk ratio greater than 2 and a P<0.05 before a plaintiff can recover on a toxic tort claim. 

Apparently many lawyers, especially on the defense side, either forgot or never learned that it's easy to gin up false associations that meet the greater than 2 and less than 0.05 test. In fact, that's how most categories of toxic tort claims got started. Enshrining such a test in the law would turn out to be The Full Employment Act for toxic tort lawyers.

Causal inference from epidemiological statistical analysis is a crude method that nevertheless worked well for finding big effects like that of smoking on lung cancer risk and amphibole exposure on mesothelioma risk. On more subtle effects though, at the population level or molecular level, reliance on 20th century methods has produced so much bad science of late (bad only because statistics are routinely misused and abused and not because statistics aren't powerfully effective tools when properly used) that new methods of causal analysis are beginning to replace them. And these tools can answer the question of "how likely is it that drug A caused injury B?"

To see what the future of causal proof in toxic torts will look like read: "An Introduction to Causal Inference" by Judea Pearl.

Occupational Exposure to Endotoxins: A Good Thing?

In the newest edition of the journal Cancer Causes and Control you'll find a paper titled "Endotoxin Exposure and Lung Cancer Risk: A Systematic Review and Meta-Analysis of the Published Literature on Agriculture and Cotton Textile Workers". The authors examined 28 studies of workers occupationally exposed to high levels of endotoxins and their risk of developing lung cancer. Previous studies had suggested acute and chronic lung conditions could be caused by endotoxins.

Interestingly, endotoxin exposure was consistently associated with a large and statistically significant decrease in lung cancer. Furthermore, the protective effect was strengthened as dose was increased.

Also this month, in Cancer Epidemiology, Biomarkers & Prevention, you'll find "Lower Risk of Lung Cancer After Multiple Pneumonia Diagnoses". It turns out that getting pneumonia three or more times is even better than high exposure to endotoxins if you want to avoid lung cancer.

What is it about these biological challenges to the lung that leads to significant anti-lung cancer protective effect? It's anyone's guess but perhaps keeping your immune system tuned up is part of the answer.

No Association Between Industrial-Grade Talc and Mesothelioma

A new review of available toxicological, mineralogical and epidemiological data pertaining to talc mined in northern New York by R T Vanderbilt shows no support for the claim that exposure to it causes mesothelioma. See: "Industrial-Grade Talc Exposure and the Risk of Mesothelioma" just published in Critical Reviews in Toxicology.

No Association Between Paint Fumes in the Home and Fetal Growth

See "Non-Occupational Exposure to Paint Fumes During Pregnancy and Fetal Growth in a General Population"

Though about half of the mothers surveyed said they'd been exposed to paint fumes in the home while they were pregnant the data suggested that the more fumes to which they'd remembered being exposed the lower the risk that their baby would be underweight. What? This study probably has more to say about the use of interview data as a proxy for exposure than it does about the relationship being examined.

Children Spread Disease. Who Knew?

In this recent article in JAMA(2010;303(10):943-950), the authors evaluate the impact of vaccinating children and adolescents on the incidence of influenza among non-vaccinated populations. They conclude that, if you vaccinate your children and teenagers, there is less disease among the rest of the population. Tell us something else that every parent already knew. Now, go wash your hands and come in to dinner.

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Coronary Heart Disease: Neither Degenerative Nor Man-Made?

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.

These Genes Determine Your Health: And They're Not Yours

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.

Alzheimer's: The Result of an Unnoticed, Chronic Low-Grade Infection?

Beta amyloid, aka abeta, builds up dramatically in the brains of patients with Alzheimer's. So, beta amyloid causes Alzheimer's, right? Or has something to do with causing it, right? At least it needs to be eliminated because people who don't have it don't have Alzheimer's so it must be bad somehow, right?

Maybe not. In a new report that demonstrates perfectly two (re-)emerging views about chronic diseases researchers at Massachusetts General Hospital have shown that beta amyloid is a potent antibiotic effective against fungi like Candida albicans and bacteria like Staphylococcus. They go on to hypothesize that far from being bad, beta amyloid may in fact be very good. It may well save you from brain infections that would otherwise kill you at a much younger age. An excellent write up can be found at Bloomberg and the article itself, "The Alzheimer's Disease-Associated Amyloid beta-Protein is an Antimicrobial Peptide", is at Plos One.

Oh, and those two (re-)emerging views about chronic diseases? The first is that too often scientists and physicians fall into the trap of assuming that the arrow of causation runs from biomarker to disease when in fact the body, with millions of years of fine tuning under the hood, has almost certainly some mechanism to deal with the build up of the by-products of its defenses such that fooling with that immune system, given our level of ignorance about how it works, is perilous at best. The second is that microbes, thought to have been essentially conquered 40 years ago, are in fact at the root of many if not most maladies commonly thought to be caused by man. Microbes it turns out have not been asleep over the eons nor even over the last 40 years. Almost weekly as new ways to culture and identify them are developed, new and heretofore unsuspected infections are identified. We're only beginning to understand the nature of the microbes that help us and prey upon us and so for now perhaps it's enough to consider the fact that in our own bodies they outnumber our human cells nine to one.

One last thing, isn't it interesting that many of the drugs currently being tested to determine their anti-aging potential are also potent anti-fungals? Correlation isn't, of course, causation, but it might be worth pondering.

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Review Of 2008 Articles On Toxicity Of Metal And Carbon Based Nanomaterials

Since 2007, the results of certain animal studies have fueled speculation that certain nanomaterials may behave in ways suspiciously similar to asbestos. In this article published in the journal Nanotoxicology this month, the authors report on their review of 746 articles published or pre-published in 2008 on the possible health effects of carbon- and metal-based nanomaterials. These particular types of nanomaterials are produced and used worldwide. The authors conclude: “Unfortunately, due to the large variability in materials used and methods used conflicting data are generated hampering the risk assessment.”

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World Cancer Day - Focus on the Link Between Infections and Cancer

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 

On to a Fifth Age? How About We Finish the Second?

In a 1971 paper that profoundly influenced how scientists and policy makers approached public health issues Abdel Omran set out his theory of "The Epidemiologic Transition". He hypothesized that societies went through three different ages, or phases, that defined their experience with regard to mortality and life expectancy. In the first, the "age of pestilence and famine", life expectancy is low and episodes of widespread death are common. In the second, the "age of receding pandemics", infectious diseases are overcome and life expectancy increases dramatically. Finally, in the third, the "age of degenerative and man-made diseases", diseases of aging and self-inflicted suffering becomes the predominant determinant of mortality. Eventually others, noting the dramatic increase in life expectancy due to the rapid decline in deaths due to heart attack and stroke, posited a fourth age; essentially the same as the original third age but with cardiovascular disease removed from the "degenerative disease" category.

Now in an editorial in this month's JAMA  Dr. Michael Gaziano asserts that we may be entering a fifth phase, or age, of the epidemiologic transition. We are now, he writes, entering the "age of obesity and inactivity" in which ailments due to gluttony and sloth predominate on death certificates. The editorial references two new articles in the same issue purporting to show Americans are fat and getting fatter; especially the children.

But wait a minute. The age of man-made diseases barely materialized. Certainly there have been many many cases of people suffering terribly as a result of some man-made health hazard. Look no further than the cases of mesothelioma among the men who served aboard amosite laden Navy ships. And smoking continues to exact its terrible toll. Yet if you throw all the deaths due to occupational diseases and every last lung cancer/COPD death into the same category you can't get to 10% using worst case estimates. More sober estimates put the percentage of deaths due to man-made diseases at considerably less than one. Nevertheless, this powerful meme - that most of our woes are self-inflicted and due to some failure to live in a natural way - still propels not only mass tort litigation but also much scientific and political thinking.

However, there's more than just AIDS to demonstrate that we never really saw the "disappearance" of infectious diseases. Go to www.pubmed.gov/ and do some searches on helicobacter pylori and humanpapilloma virus and you'll see just how many cancers are now being attributed to just these two organisms. Investigate mollicutes and you'll find that all sorts of microbes are suddenly being found associated with disease and they're only now being found because the technology to identify them is only now being refined.

Finally, remember to read the fascinating journey of Barry Marshall and Robin Warren from authors of an abstract rejected as one of the year's worst to winners of the Nobel Prize in Medicine for the very same work. In the end, the view, supported by the work of one of the world's preeminent public health researchers, that peptic ulcers were caused by that most modern of man-made insults, stress, only gave way to the understanding that the cause was in fact a bacteria when the evidence was irrefutable.

Does Education Cause Autism?

If a strong and consistent association between autism and a single chemical or vaccine were found in ten separate clusters around California you'd expect to read about it; and you'd expect the researchers to infer that the chemical or vaccine was, in fact, the cause of autism. But what if the only strong and consistent association wasn't between autism and exposure to some substance but was instead between autism and something complex, like "high parental education"? Well, you'd probably expect a lot of frustration; and you'd be pretty sure autism wouldn't be laid at the feet of higher education.

So what should we make of "Geographic Distribution of Autism in California: a Retrospective Birth Cohort Analysis" ? Why would the children of parents with college degrees be at a 400% increased risk of autism? Why aren't chemicals to blame?

The authors concede in interviews with Scientific American that the results tend to undermine claims that industrial pollution causes autism. Yet rather than explore the possible reasons why college-educated parents might be significantly more likely to have autistic children the authors speculate that their results may be biased. Perhaps, they suggest, the less educated aren't educated enough to take their autistic children in to be diagnosed. Or maybe, they wondered, the educated are much more likely to use some unknown household chemical which does, in fact, cause autism. Scientific American hastens to add that there's an unpublished study that shows a doubling of the risk of autism in mothers who use pet flea shampoos.

But why point to a much smaller effect allegedly to be found in an unpublished paper when a much larger effect published in a peer reviewed journal is in front of you?

First, people tend to prefer simple answers with readily implemented solutions, the blame for which, and the costs of which, get imposed on someone else. 

Second, epidemiology, at least as practised in the West, tends to be reductionist. The triumph of linking tobacco to smoking led many epidemiologists to believe, or at least to want to believe, that indeed there are simple solutions to big problems and that silver bullets are out there just waiting to be found.

Finally, it's becoming increasingly clear that all sorts of ailments, from cancer to obesity, are highly complex and result in large part, from lifestyle, cultural and economic choices. Take breast cancer for example. One of the very best ways to reduce the risk of breast cancer is for a woman to bear children and to begin doing so in her late teens or early 20s. Yet no one wants to say that putting off children to get a degree and start a career is a cause of breast cancer.

And so, for now, the search is still on for the usual suspects.

 

 

It's National Radon Action Month

The EPA says that radon, a colorless, odorless gas, is responsible for 20,000 American lung cancer deaths annually. Because January is the best time to test for the gas it has been designated "National Radon Action Month". You can read the EPA's press release here and find its radon information and testing site here.

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Bernie Goldstein States the Case for Benzene-Induced Lymphocytic Malignancies

Arguing that the target of benzene is a multipotent stem cell capable, when carrying the sort of mutations thought to be caused by benzene, of producing both myeloid and lymphoid malignancies, and that new classification systems are blurring the lines between previously thought distinct diseases, Goldstein's article concludes that  there is now sufficient evidence to attribute lymphomas to benzene exposure.

That's the same argument made years ago in benzene litigation, though with different references. So what should we make of the intervening science? What about alkylating chemotherapeutics that produced similar genotoxicity and t-AMLs but not lymphomas? What about the epi studies that show increased risk for AML but not lymphomas?

In many respects last year's benzene conference in Munich served mainly to demonstrate how little is known about leukemogenesis and how staggeringly complex is the causal web that leads to lymphoproliferative malignancies.

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Are Michigan Courts Shifting the Burden of Proof to Defendants?

One explanation for Genna v. Jackson (a new opinion out of the Michigan Court of Appeals) and Gass v. Marriott Hotel Services, Inc is that the courts thought about it and decided to shift the burden of proof regarding causation to the defendant any time a plaintiff suffers an injury that is consistent with the possible harm, as set out on a warning label or MSDS, associated with a potentially toxic material. In Genna the court reversed summary judgment in favor of the defendant in part because "[h]ere, like in Gass, defendant has not submitted any scientific evidence that the mold in her condominium could not have cause [sic] plaintiffs' injuries." In Gass the 6th Circuit noted "Defendants have offered no evidence to refute the MSDS's representation of Demand CS as a chemical which could have caused Plaintiffs' symptoms". The court later continued saying "[p]laintiffs are not required to produce expert testimony on causation where Defendants have failed to offer scientific evidence regarding the effects of Demand CS or Suspend SC."

The Genna court concluded, on the issue of causation, "[t]his is not a complicated case: the children were sick, the children were removed from the home, the mold was discovered, and the children recovered." Noting evidence that there was lots of mold and that mold in general had been reported to cause some of "the types of symptoms suffered by the children" the court concluded [i]t does not take an expert to conclude that, under these circumstances, defendant more likely than not is responsible for plaintiffs' injuries." (citing Gass). "Here, there was ample circumstantial evidence that would "facilitate reasonable inferences of causation, not mere speculation."

Under this view of an unannounced burden-shifting approach taken by these two courts it appears that in Michigan if a plaintiff develops ailments consistent with a those listed on a product's label or MSDS the jury is free to infer causation even in the absence of evidence of what dose produces those ailments and what dose plaintiff suffered and even in the absence of an expert to opine that the product in question caused the harm at issue.

Another explanation for these cases is that Michigan does not require toxic tort plaintiffs to show what some call specific causation - a concept common in cases in which causal inferences are derived from epidemiological evidence. The idea is that when dealing with an illness that has been associated with multiple causes, among which is the chemical at issue, the plaintiff must show that the putative cause was more likely than not the cause in fact of his illness.  Evidence for this view can be found in the following passage from Genna: "Defendant urges this Court to adopt the requirement that, in order to prove causation in a toxic tort case, a plaintiff must show both that the alleged toxin is capable of causing injuries like those suffered by the plaintiff in human beings subjected to the same exposure as the plaintiff, and that the toxin was the cause of the plaintiff's injury. They urge this Court to find that direct expert testimony be required to establish the causal link, not inferences. We decline to adopt this requirement. There is no published Michigan case law on the subject."

A final explanation is that more attention to Aristotle's Rhetoric is needed. As Chief Judge Boggs, dissenting in Gass wrote the problem here is the logical fallacy behind post hoc, ergo propter hoc causal inferences such as those suggested by the plaintiffs in Genna and Gass. "It is the fallacy of saying that because effect A happened at some point after alleged cause B, the alleged cause was the actual cause. Such logic has never been enough to survive summary judgment. See, e.g., Abbott v. Federal Forge, ("[P]ost hoc, ergo propter hoc is not a rule of legal causation.") 912 F.2d 867, 875 (6th Cir.1990).

Equally importantly Chief Judge Boggs understands that lay juries are in no position to judge whether there has been a breach of the duty of care without evidence of what levels are harmful and the levels to which plaintiffs were actually exposed. If you don't know the dose you can't know what risk, if any, the defendant imposed on the plaintiff. He wrote: "Thus presented, the question is whether the plaintiffs needed expert testimony in this case to prove how much chemical exposure is too much chemical exposure or to prove whether the amount of exposure actually caused the alleged harmful consequence. In my view, the majority pays too little attention to this issue, rushing from the fact of exposure and odd symptoms to the legal conclusion of fault." He continued: "As I understand it, these cases require expert testimony in complex, professional, or scientific-based negligence cases in order to limit the dangers associated with indulging the post hoc impulse: it is too easy to charge an uncommon harm to the presence of a mysterious substance. Properly credentialed expert testimony operates as a bulwark against such fallacious attribution of guilt. As in the Daubert context, our concern in applying these cases should be to "assure that the powerful engine of tort liability ... points towards the right substances and does not destroy the wrong ones." General Electric v. Joiner, 522 U.S. 136, 148-49, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997) (Breyer, J. concurring).

Whatever the explanation these cases will be a boon for Michigan toxic tort plaintiffs.

Don't Pitch the Water Softener

Have you been worrying that your water softener is significantly increasing your risk of dying from a heart attack? I didn't think so. But just because you haven't been feeling vulnerable around your water softener doesn't mean the WHO hasn't been fretting for you.

Thanks to epidemiological studies going back a decade or more (e.g. "Magnesium and Calcium in Drinking Water and Death from Acute Myocardial Infarction in Women") a worry arose that we were killing ourselves by eliminating the minerals naturally found in most drinking water. Yet subsequent studies have failed to confirm the finding including the just published "Effect of water hardness on cardiovascular mortality: an ecological time series approach". So what gives?

Well, what gives is that most of what gets published in peer reviewed journals is probably false; and when it comes to causal inferences drawn from epidemiological studies "the apparently indiscriminate indentification of particular aspects of daily life as dangerous to health" is, as witty programmers say, a feature, not a bug.

 

Sorting out Cause and Effect

We live in strange times. Though whole genomes, of an individual as well as a malignant progenitor stem cell responsible for AML, have been sequenced and though modern medical diagnositic machinery and implantable devices increasingly look like things that Gene Roddenberry would have rejected as too futuristic, the fact is that scientists know very little about how our bodies work. Take C-reactive protein for example.

Let's say you decide to study heart attacks by measuring the levels of certain proteins in the blood and then later checking to see if there's been an association between the levels measured and an adverse event like a subsequent heart attack. Bingo! People with high levels of C-reactive protein have a high risk of heart attack. Wow!

Ok, let's assume the association is strong and consistent so that the finding probably reveals something about how the body works. But what?

Too often these sorts of findings have precipitated a Whac-A-Mole reaction from the medical community whereby drugs are promptly designed and thereafter prescribed to begin whacking the protein back down to "normal" levels. Causes precede effects, right? So this must be a cause, right?

Well, what if C-reactive protein is actually part of the body's response to accumulating plaque and inflammation? What if its level correlates with risk because it's part of the body's attempt to fix whatever is broken? What if it's not a cause of heart disease but is really an effect of heart disease? Reuters is reporting on a new analysis published in Lancet indicating that at least in the case of C-reactive protein earlier assumptions had indeed confused cause and effect. The authors conclude that it is unlikely that C-reactive protein is a cause of heart disease.

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The Global Burden of Cancer

The American Cancer Society has published "The Global Burden of Cancer: Priorities for Prevention" this month in the journal Carcinogenesis. While tobacco use is discussed first and diet, obesity and lack of physical activity second, it's cancers related to chronic infections that gets the most coverage. "Persistent infection with various microbial organisms accounts for about 18 percent of cancers worldwide." Preventive approaches including the development of vaccines and lifestyle modifications are discussed in detail.

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Interstitial Fibrosis Among Farmworkers Due to Agricultural Dust

A series of lungs from California farm workers who died in accidents or from illness were examined for evidence of pneumoconiosis.   Despite being young these Hispanic farm workers had significantly more evidence of interstitial fibrosis than did non-farm workers.  A variety of analytical techniques demonstrated that those with pneumoconiosis had significant exposure to crystalline silica and aluminum silicate.

The article is "Pneumoconiosis from agricultural dust exposure among young California farmworkers".  As for the source of mineral dust exposure the authors note "most agricultural soils are composed largely of silicate materials (e.g., feldspars, mica, clay minerals) and crystalline silica (CSi) (quartz)".

New NHL Solvent Study

An important new study was recently released indicating that there is no causal association between ambient exposure to either solvents or benzene and the development of non-Hodgkin’s lymphoma (NHL). The report adds to a growing body of literature demonstrating no discernable risk for typical community benzene exposures.

Outbreak of Neurological Disorder Among Slaughterhouse Workers

Researchers from Mayo Clinic have published "An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study" in The Lancet Neurology. Workers exposed to aerosolised pig brains (ugh) developed polyradiculoneuropathy - a painful and disabling autoimmune illness. Of the 24 workers affected 17 required immunomodulatory therapies, six improved after exposure ceased and one was lost to follow up.

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Could Mammograms be the Cause of Some Breast Cancers?

In the on-going debate over when to start getting mammograms and how often to have them the assumption by many of those supporting an "early and often" policy has been that false positives lead to little more than worry and maybe a needle biopsy. Now The New York Times is reporting on a study that appears to demonstrate that young women already at heightened risk of breast cancer double that risk if they start getting mammograms early.

Five prior studies of women carrying a mutation that is thought to put them at increased risk of breast cancer were examined to determine whether low dose radiation exposures from mammograms further increased that risk. The results, which were statistically significant at a 95% confidence interval, showed that women carrying the breast cancer gene who started mammography early in life or who had five or more mammograms were more than twice as likely to develop breast cancer as women with the breast cancer gene who started getting mammogramps later and had fewer of them.

The working hypothesis is that mammography actually causes many cases of breast cancer in susceptible women. An alternate explanation, I suppose, is that about half of all breast cancers detected by mammography either aren't cancerous or were never going to develop into a malignancy.

Hopefully doctors are finally beginning to discuss the large and unsettling uncertainties associated with the diagnosis, treatment and causal attribution of poorly understood diseases like cancer.

A Biomarker of Past Benzene Exposure?

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.

Parkinson's: A Microbial Etiology?

Articles published in the last several months raise the question whether microbes found in the gut are responsible for Parkinson's disease.  In September researchers published an article titled "The Second Brain and Parkinson's disease" in which they reviewed and elaborated on emerging evidence that the enteric nervous system and the microbes that in part constitute it may, be responsible for precipitating Parkinson's disease.   Another group published "Autoimmune Disease and risk for Parkinson disease" in which they failed to find support for the hypothesis that Parkinson's is an autoimmune disorder.  Most recently in Medical Hypotheses Mark Lyte's "The Microbial Organ in the Gut as a Driver of Homeostatsis and Disease" speculates that the microbes living in our guts along with the enteric nervous system form a sort of organism within an organism that when disrupted can lead to diseases such as Parkinson's.  For more on this unfolding understanding of the role of these microorganisms in our lives see "They Are What You Eat".

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Is Non-Small Cell Lung Cancer Caused by the Measles Virus?

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.

Pericardial Mesothelioma Following Radiation Treatment

Here's a case report of pericardial mesothelioma arising twenty-four years after the patient was treated with radiation therapy to the mediastinum for nodular sclerosing Hodgkin's disease.

Two Weeks to Copenhagen

In two weeks, representatives from 192 countries will assemble in Copenhagen for the purpose of setting global limits on carbon emissions. COP15, the official name of the climate change summit, referencing the 15th Conference of the Parties under the United Nations Framework Convention on Climate Change (UNFCCC), consists of environmental ministers who meet annually. The goal of the Copenhagen summit is “to secure binding emissions targets and overcome the division between the developed and developing world.”  Apparently, despite high hopes among proponents, it appears unlikely that a deal will be reached this year.

World leaders have confirmed that time has run out to secure a legally binding agreement at the COP15.  However, the United States and Britain hope to at least hammer out an outline of  the commitments to be put in place rather than postpone the formulation of a plan for an entire year.

So what's behind the delay?  Certainly the global economic turmoil makes it difficult for politicians to agree to changes that would at least in the short term cause even further job dislocations.  More significant perhaps is an apparent waning of public interest in the issue of global warming/climate change.

Recent polling has shown a marked decrease in both the belief that climate change is occurring and that such change is due to human agency.   What's behind this significant change in public opinion?  Over at Yale Environment 360 you'll find an excellent article addressing the concern that years of increasingly dire climate predictions have resulted not in more widespread and more confidently held belief in human-caused climate change but rather "apocalypse fatigue".

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They Are What You Eat

We've written before about the dawning realization that the microbes that live in and on us can have a surprising degree of control over our lives. Today we learn that what we eat may control which microbes we host and whether we get fat or stay lean.

In a news release from Washington University titled "Junk food binge alters community of microbes in the gut in less than a day" researchers report that high fat / high sugar diets shift the distribution of bacteria in the intestines towards those bacteria which are exceedingly efficient at extracting calories from food. These super efficient microbes, once transplanted, could then cause weight gain and obesity even in mice fed a low-fat, plant-based diet. The shift towards the super efficient microbes occurred just 18 to 20 hours after the consumption of fatty/sugary foods. 

Finally, gut microbes were demonstrated to be capable of being passed from mother to offspring.

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Asbestos Fiber Dimensions and Lung Cancer Mortality

A study published last week in Occupational and Environmental Medicine estimated exposures to asbestos fibers of specific sizes of workers exposed to chrysotile using data from transmission electron microscopy (TEM) and investigated the extent to which the risk of lung cancer varies with fiber length and diameter. The study used a cohort of 3803 workers that were employed from January of 1950 and December of 1973 in manufacturing asbestos textile products. Workers’ exposures to asbestos fibers were estimated from work histories and over 3500 industrial hygiene measurements.

Fiber length and diameter were significantly associated with an increasing risk of lung cancer. Exposures to longer and thinner fibers tended to be most strongly associated with lung cancer. The results supported the investigators hypothesis that the risk of lung cancer among workers exposed to chrysotile asbestos increases with exposure to longer fibers.

A New Study on Bisphenol A and Funding for Several More

In a study just published in the Oxford Journal of Toxicological Sciences the authors report that  bisphenol A (BPA) produced no sexual developmental disorders in the laboratory animals  tested.  Pregnant rats were exposed to very low to low doses of BPA and their offspring were studied for any signs of sex morphology disruptions.  The study was funded and conducted by Reproductive Toxicology Branch of the EPA.

Interestingly, ethinyl estradiol on the other hand even at very low doses produced numerous reproductive morphological disruptions.  Ethinyl estradiol is a form of estrogen used in almost all modern formulations of the Pill.

The National Institute of Environmental Health Sciences has announced a $30 million, two-year research effort to study the health effects of exposure to bisphenol A (BPA).  The funds for this effort were appropriated to the NIEHS as part of the American Recovery and Reinvestment Act.
BPA is an organic compound that is used in the production of polycarbonate plastics and epoxy resins. According to NIEHS’ press release in “2008, NTP [National Toxicology Program] and NIEHS concluded that there is evidence from animal studies that BPA may be causing adverse effects.” The press release continues that the “innovative two-year grants provided through the Recovery Act will support human and animal studies that address many of the research gaps identified by expert scientific panels, and provide a better understanding of how this chemical may impact human health.”
 

Dihydrogen Monoxide - Another Dose Response Toxin

The maxim “the dose makes the poison” is regularly offered by defendants in toxic tort cases as a premise for the assertion that a particular dose was too small to have been toxic. To demonstrate the concept examples of toxicity due even to essential substances like water are deployed. I’ve done it myself and the retort from plaintiff’s counsel has been invariably mocking. Here are sixteen million reasons why they should reconsider.

 

Bayesian Trials 77030

John Cook at The Endeavor posted this comment by Mithat Gönen of Memorial Sloan-Kettering Cancer Center about a recent paper concerning Bayesian clinical drug trials of chemotherapeutics.

"While there are certainly some at other centers, the bulk of applied Bayesian clinical trial design in this country is largely confined to a single zip code."

That zip code is 77030 and it’s the zip code for M.D. Anderson Cancer Center. Here’s a great article about M.D. Anderson just published in the New York Times by Gina Kolata.

Bayesian decision-making approaches are proving their worth every day in a wide variety of fields and more than a few courts are starting to grasp and apply probabilistic decision rules. Expect to see more and more Bayes decision theory as courts take an increasingly modern approach to the question of causal inference in mass tort cases.

Coal Ash is Dirty Stuff, But is it Hazardous?

This question has been posed by coal ash’s recent notoriety, and the answer is without consensus. European scientists recently published a paper aimed at determining the levels of mercury in coal ash (one of coal's more dangerous components) and its potential to leach into the surrounding environment. The researchers concluded that concentrations of mercury or leaching values were not so high as to justify considering coal ash a hazardous waste by European standards. (The EPA has made a similar determination but it is being reviewed.)

Such findings, while restricted to mercury, seem to take the fire out of recent lawsuits filed by individuals affected by coal ash spills and/or disposal claiming coal ash mercury and other components are leaching into water sources at dangerous levels. While mercury, arsenic, lead and other compounds are undeniably harmful at certain exposure levels their concentration and propensity to leach are not so clear. Thus, the question of coal ash harmfulness is subject to debate and will be studied in greater detail by courts and administrative agencies grappling with this issue.

What Role Does Immunosuppresion Play in the Pathogenesis of Mesothelioma?

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.

COPD is an Independent Risk Factor for Cancer

After adjusting for smoking chronic obstructive pulmonary disease (COPD), chronic bronchitis and emphysema were associated with a doubling of the risk for lung cancer in this just published paper.  It's part of the ongoing Environment and Genetics in Lung Cancer Etiology (EAGLE) study.

Noting that a family history of chronic bronchitis and emphysema alone have been associated with lung cancer, that COPD has been associated with lung cancer in never-smokers and that COPD is thought to be responsible for 10% of all lung cancers, the authors concluded that these findings support the hypothesis that COPD alone causes lung cancer and they further conjectured that chronic inflammation is the essential mechanism in COPD/emphysema-induced lung cancer.

Why are Mesothelioma Rates Still Rising in Alberta?

The incidence rate for mesothelioma continues to rise in Alberta, Canada. This paper just published in Chronic Diseases in Canada reports a continuing and significant increase in reported cases of mesotheliomas among male Albertans and projects that the incidence of the disease may not peak for another 10 years.

An interesting issue touched upon but not worked out is the impact on current projections of past misdiagnoses. Think about what it would mean for these projections if past less refined diagnostic procedures understated the number of cases of mesothelioma; then think about what it would mean if reported cases of mesothelioma in the 1960s and 1970s were overstated.

Causation is Hard

What does it mean when an increase in cancer coincides with an increase in the ability to detect it? Nothing really, because correlation isn’t necessarily causation? Or something, because the new diagnostic technique has biased the data? Specifically, are doctors finding more cases of melanoma nowadays because they’re looking harder or are they finding more cases of melanoma because something else, maybe increased UV radiation, is causing more people to get it? Those are the questions raised by this New York Times article. Something similar happened with prostate cancer and something similar will likely happen in the future once methods of detecting cancers like mesothelioma and leukemia very early in the disease process are developed.

A Cup of Bifidobacterium Animalis Strain DN-173 010, Please

If you watch TV you’ll have noticed celebrities eager to tell you about their “digestive health”. They attribute their well being to regularity and their regularity to eating probiotics, which are live bacteria. The NYTimes also noticed and reported on the issue today. Especially of note to lawyers is the discussion of the $35 million Dannon, maker of probiotic product Activia, has agreed to pay to settle claims of mislabeling and deceptive marketing.

Interestingly, Dannon has agreed to “increase the visibility of the scientific names of the unique strains of probiotics that are in each of these products”. Pity the poor consumer who has enough trouble understanding the nutritional data already on food products – “hmmm, should I buy the yogurt with streptococcus thermophilus, lactobacillus acidophilus and a generic bifidobacterium or the one with just bifidobacterium regluaris?”

Then there’s the law of unintended consequences. The idea that certain strains of bacteria have been essentially domesticated and can be turned loose in the gut to work their magic without fear that they might mutate or disrupt an already balanced system seems overly hopeful. While the milk intolerant have been happily ingesting lactobacillus acidophilus for years and research on certain species of lactobacillus seems to support the theory that these “good” bacteria wage war in your guts against “bad” cancer-causing bacteria both directly and indirectly (e.g. by inducing intestinal epithelial cells to shore up their defenses) one wonders how long it will be before a good strain goes bad, a good strain is unmasked as a double agent or a good strain is demonstrated to have a dark side.

Specific Causation

I was part of a panel discussion last week in San Francisco about what we in the law call "specific causation" - essentially the determination, in an individual case of causal attribution, when the disease in question has been associated with certain risk factors in the general population.  It is, I think, a distinction without a difference but until courts move past 20th century science (epidemiology) and on to 21st century science (molecular biology) it's one we'll have to talk about.  Here's my PowerPoint from the seminar.

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Is Soda Raising Blood Pressure in Middle-Aged Men?

Diets high in foods with large amounts of fructose sugar such as sweetened soft drinks increased blood pressure in men, according to a study presented September 23rd that also found that a drug for gout blocked the effect. Most sugar consumption in the U.S. comes from sweetened drinks and foods high in sugar or high fructose corn syrup.  Fructose is the only common sugar known to increase uric acid levels. 

Men in the study who ate a high-fructose diet had their blood pressure rise about 5 percent after two weeks, while those who also were given a gout treatment increased less than 1 percent. Eating great amounts of fructose without the treatment also raised the risk of developing metabolic syndrome, a risk factor associated with the development of heart disease and diabetes.  The gout treatment lowered the body’s uric acid that is linked at elevated levels to high blood pressure, diabetes and heart disease.  So, it’s possible that lowering uric acid levels could become a routine practice in the future, much like lowering cholesterol.

My blood pressure was perfect until middle age when it ticked up a bit and I've not had a sugary soda in many years. The same is true for many men. Thus, I'm betting on correlation rather than causation on this one. Well, correlation and a statin that is ...

The Causes of Autism

Here's a paper that reviews current knowledge regarding the causes of autism. Note the concerns about Vitamin D deficiency. Could it be that decades of sun-o-phobia has led to more than just increases in rickets and a host of cancers?

Every Puff You Take

What is it in cigarette smoke that causes lung cancer? Tar? PNAHs? Exotic isotopes? What about bacteria and fungi? What if they're in part responsible for chronic inflammation associated with lung cancer? It turns out that when you inhale cigarette smoke you invite into your lungs a swarm of nasty germs. Here's a new article that'll introduce you to the issue and lay out the evidence.

Wouldn't it be interesting if there were similar microbes living in and on asbestos fibers? Actually ....

The 411 On An Old Healh Scare Revived by Congress

Senator Tom Harkin (D-IA), the new head of the Senate Committee on Health, Education, Labor and Pensions promised on Monday to probe deeply into any potential links between cell phone use and cancer. This issue has been extensively studied, particularly in Scandinavian countries where cell phone manufacturers such as Nokia and Ericson are headquartered. Each study to date has found no statistically significant association between cell phone use and cancer, including brain cancer.

However, there are still some who attribute brain cancer to cell phones on the theory that radio waves, a form of radiation, damage brain cells. The debate comes on the heels of the 1980's and 1990's controversy regarding the potential adverse health effects of electromagnetic fields EMFs emanating from power lines. While studies cleared EMFs they implicated population mixing likely via some sub-clinical infection as a cause of cancer in children. More on population mixing to come.

Sugar Pills More Potent Than Ever

Wired has a new article about the placebo effect and evidence that placebos are becoming more increasingly more potent.

Years ago I was thinking about going to medical school and so hung on every word from a friend's father when he talked about what he did for a living. I remembered being fascinated by his stories about sugar pills and the patients to whom he prescribed them. He said that he'd learned years before that for some patients, the ones without any objective signs of treatable illness, he did his best work by being part priest and part witch doctor.

He'd listen to their stories, affirm their suffering, advise them to live better, forgive them their faults and prescribe powerful new magic - "penta-methyl-tri-something-or-another-cis-this-and-that". And it worked. He and his pharmacist friend had to be creative though as patients would compare pills and often return to demand stronger magic citing a neighbor's far milder symptoms. So they wound up having a number of different sugar pills in varying shapes and sizes. I don't recall him saying much about color other than that one lady, upon discovering that she'd been prescribed a very large red and white pill, returned to the office to say that she wasn't nearly as sick as the doctor apparently thought she was.

So what does this have to do with mass torts? Well, particularly in the realm of adverse effects from the use of psychotropic drugs, there's a huge risk of (or opportunity for) getting the causation arrow pointed in the wrong direction especially when so little is known about the causes of mental and emotional disorders and the mechanisms by which they are alleviated. After all, trial lawyers thrive in conditions of uncertainty.

Diagnosing Mesothelioma

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?