Discretizations

Some months ago we decided to put Discretizations on hiatus while we tried to figure out what to do about the tsunami of scientific papers washing up on PubMed (which was already piled deep in the flotsam and jetsam of publish or perish) now that China, India, Korea, etc. are getting in on the fun. On the one hand we're sorely tempted to take advantage of a situation that presents us daily with awesome posting opportunities like: Hay fever causes testicular cancer! On the other hand we know that most statistically significant findings are in fact false - in no small part because "it is a habit of mankind to entrust to careless hope what they long for, and to use sovereign reason to thrust aside what they do not desire". So, rather than being a part of the problem by propagating noise and not signal we've decided to limit our Discretizations to papers that 1) report an actual observation and not just the spectre of one drawn from data dredging and statistical analysis; 2) reflect an effort to reproduce a previously reported finding (e.g. testing a hypothesis previously drawn from statistical inference but in a different population); or, 3) extend (marginally) some previously established finding. Here goes:

Your word for the day is "immunobiotics": good bacteria that can aid in the production of certain blood cells

Obesity is a risk factor for lumbar radicular pain and sciatica - and it may impair healing mechanisms

Poor folks still have (on average) poor ways (which explains a large portion of the disparity in life expectancy between those in the bottom quartile of socioeconomic status and everyone else) 

Hospital staff and visitors can spread nosocomial pathogens to nearby businesses

How does metformin help patients with diabetes? Maybe by making the gut a happier place for A. muciniphila

No evidence found to support the hypothesis that parental smoking (and the benzene exposure that goes with it) during pregnancy increases a child's risk of developing acute lymphoblastic leukemia (ALL)

Does the debate about segregating cystic fibrosis patients by lung/bronchial microbiome, going so far as to prevent some/most/all-but-one CF sufferers from attending indoor CF Foundation events, presage future debates as more and more diseases are found to have bacterial components? Here are the pros and cons of the CF debate.

As We Were Saying

It certainly appeared by the 1960s that humanity was leaving the so-called second epidemiologic tranistion. Ancient pathogens were being defeated at every turn as science went from triumph to triumph. And thus a whole generation of public health professionals committed themselves to combating man-made and degenerative diseases; by then believed to be the leading cause of human suffering.

It was sin that brought these afflictions. The sin of greed led owners to run factories demanding back-breaking work. The sin of gluttony led workers to pack on the pounds putting unnatural stresses on the back that wore it down too soon. Decades of litigation over sore backs followed and most were fought over the question of which sin was the greater. It wasn't until recently that some researchers began to wonder, and to investigate, whether or not something else was actually responsible for the epidemic of back pain that arose in the second half of the twentieth century.

That something else turns out to be an anaerobic bacteria and the proof of it would make Robert Koch proud. In more than 40% of all patients with low back pain who had signs on MRI of degenerative disc disease the bacteria was identified as being present. And when antibiotics targeted at that very bacteria were administered a big chunk of those cases resolved (versus placebo).

Not every case of lumbar pain was due to anaerobic bacteria and it also appears that sudden stress on the back may create an opportunity for the bug to exploit. Nevertheless, it's quite clear that antibiotics, rather than difficult surgery with its attendant permanent (though usually partial) disability, may be all it takes to restore sufferers of back pain to good health. The lesson here, as my colleague put it in a joint presentation we gave today, is that "we may forget to focus on germs but they never forget to focus on us."

Of Mice and Men and Their Breath

One of the longstanding disputes in toxic tort litigation revolves around whether or not animal models are good (i.e. predictive) models for assessing the likely outcome of exposures to the chemical in question. As we've written previously the 1,3 butadiene question hangs crucially upon the question of whether or not workers in SBR (styrene-butadiene rubber) plants are likely to metabolize butadiene the same way as B6C3F1mice. However, isn't there an assumption here that goes unexcavated?

Aren't we assuming that all people metabolize things like butadiene the same way? Undoubtedly. But guess what? Thanks to differences in the bacteria in their gut, their diets and likely other yet undiscovered factors, people metabolize things differently. Read all about it at: Human Breath Analysis May Support the Existence of Individual Metabolic Phenotypes

Very Little Authority For Now, But Maybe Not For Long

Two yellow pads are full of notes, diagrams, thoughts and arguments and still the answer eludes me. So, rather than continue not to post anything about all the interesting stuff going on in mass torts while I try to figure it out I'll just throw out what I've got so far over a series of posts and move on to something less difficult (and likely more interesting). On then to the question that's been bugging me for a month.

Should alternative liability, in the form of burden of proof shifting, apply in the following case: (1) a neonate contracted a Cronobacter sakazakii infection and was seriously injured; (2)  C. sakazakii is a ubiquitous pathogen and readily forms biofilms on stainless steel, inside household water pipes and upon other surfaces (3) C. sakazakii infections in neonates have also been repeatedly traced to PIFs; (4) plaintiff's experts opined that it's more likely than not that the source of C. sakazakii was the powdered infant formula (PIF) fed to the neonate; (5) PIFs are not sterile since the process of sterilization would destroy the nutritional value of the PIF; (6)  there were two or more suppliers of PIF whose product was prepared for the neonate; (7) none of the remaining PIF fed to the newborn, nor any of the lots from which they were drawn, were found to contain C. sakazakii; and, (7) the wrong complained of was a failure to warn that full term neonates, like the plaintiff, were at risk of C. sakazakii infections.

Alternate liability analysis often begins with Summers v. TiceIn that case both hunters who had fired their weapons in plaintiff's direction had been sued and both could be shown to have breached their duty to safely handle those weapons. Because it was impossible for the plaintiff to show whose buckshot was responsible for his injury, and because it was deemed just that the consequence of that impossibility fall on the culpable defendants rather than the innocent and injured plaintiff, the court held that the defendants, rather than the plaintiff, should bear the burden of proving from which shotgun the pellets had originated. Fair enough.

Here, in Burks v. Abbott Laboratories, both of the manufacturers of PIF consumed by the plaintiff had also been sued. Furthermore, neither's product bore a warning about the hazard which plaintiff claimed they had a duty to disclose. However, not all the possible sources of C. sakazakii (Mother Nature being judgment-proof) were before the court. Nevertheless, the court held, though it "located very little authority on this specific question" that  the determination of whether it was more likely than not  that the source of plaintiff's C. sakazakii infection was the defendants' PIF should be applied to the defendants collectively.

Ponder the consequences. Let's say that 51% of all C. sakazakii infections in neonates are due to PIFs even when C. sakazakii can't be isolated from the product or the lot from which it was drawn, and that 49% of all C. sakazakii infections in neonates are due to C. sakazakii found in the household water used to reconstitute the PIF or on kitchen surfaces. Also, assume the warning could fairly be said to be lacking (which in this case is not at all a given and in fact raises as many questions as stacking defendants to get to the 51% threshold - but that'll be addressed in subsequent posts).

If there's only one supplier of PIF there's no need for alternative liability so assume there are at least two. But what happens when you start dividing up the 51% among the defendants? Unless one of them was responsible for ~99% of the product the result is that you've stacked two defendants who might, but probably didn't, have something to do with plaintiff's infection and handed them all of the liability for it. Is that fair? What if there were 100 suppliers? And what's the justification for stacking defendants? Is it because they're in the same business? If so, how similar must their businesses be to permit such stacking? If in order to get to a 51% likelihood as to the source of the infection you had to stack PIF manufacturers with stainless steel kitchen appliance manufacturers (because C. sakazakii happily lives on stainless steel and creates biofilms that makes it nearly impossible to remove with household cleaning products) could you justify handing them the burden of proof by saying they were all in the food business? 

Or what about reducing defendants' liability by Mother Nature's share? Would that solve the "overdeterrence" problem? What follows from the fact that the potential for these sorts of infections, due to the nature of pathogens, is essentially binary (you get it or you don't) and not of the dose-response variety seen in typical mass tort cases?  These are the sorts of questions that have led to a lot of head scratching but so far few answers.Over the next couple of days I'll type up more of these questions and the paths down which they lead (at least the ones I've thought of and followed).

How a fact pattern like the one in Burks gets resolved is I think a very big deal. That's because an awful lot of diseases laid over the last forty years at the feet of man-made substances and bad habits turn out to have been due to pathogens all along. It also appears we're entering an era in which old scourges reemerge thanks to having evolved antibiotic resistance and new ones arise thanks to globalization.  The resulting morbidity and mortality will makesevery other mass tort pale in comparison and so far juries aren't having much trouble blaming defendants for the depredations of Mother Nature's tiniest critters. We think there's a wave of litigation coming in which plaintiffs will assert liability for facilitating the transmission of pathogenic agents. The answers to questions like those posed by Burks will be critical in determining how it all plays out. 

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The Annual Report to the Nation on the Status of Cancer (covering 1979 - 2009) is out. The good news is that overall death rates for some of the biggest killers continues to decline. The bad news is that deaths from cancers caused by infectious agents like HPV and hepatitis-C are up; doubling in some cases. Get your daughters, and sons, vaccinated.

It took several decades but the egg has now been cleared on the charges of murder by heart attack and stroke.

It also took decades to clear caffeinated coffee on all charges of murder by cancer. Now drinking 4+ cups per day has been shown to cut your risk of some cancers by half.

Many common food ingredients have been scientifically demonstrated to double or halve, and often double and halve, your risk of cancer. Click here to find out why.

The human breast milk microbiome is far more diverse than previously imagined and it's composition is impacted by factors such as obesity and Cesarean delivery. Could it be that her microbes, rather than a mother's genes, are to blame for her obese children? Could it be that it's the absence of certain breast microbes in mothers who underwent Cesarean delivery that's responsible for the increased risk of asthma in their children?

In the past, proponents of the Precautionary Principle have tended to deny that hormesis exists. As the evidence in favor of hormesis has gotten harder to ignore their narrative has changed to (1) it hasn't been shown to be the sort of general phenomenon that would permit an inference of hormesis for all toxins and (2) too little is known about the mechanism to permit its incorporation in to risk models.

Gut science: truth is stranger than fiction

A new paper by UT Southwestern Medical Center scientists presented a study which found that bacteria in your gut are competing through bacteriophages – unique predatory bacteria harboring viruses – for dominance and greater access to nutrients. While we knew that bacteria in the gut outnumber the number of cells in the body and have a huge impact on our immune system, we were unaware that they were unleashing viruses on each other. Further studies are planned to look into how to harness this fight for the betterment of us, not just the bacteria.  See a story here.

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The Painting That Served As Inspiration For Nature's "Fellow Travellers"

If you want to be staggered by the by the sheer number of bacteria that live in and on us, by the fact that different parts of our bodies are inhabited by different bacteria, by the fact that different people host different communities and that as we change (e.g. by aging) we take on new fellow travellers, read "Structure, function and diversity of the healthy human microbiome" in this week's Nature. If you want to be staggered by the effort that has gone in to the Human Microbiome Project read "A framework for human microbiome research", also in Nature. But for the back story on the really cool illustration on the journal's cover click here.

And what does all this have to do with mass torts? If you have to ask, you haven't been paying attention. :)

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 "'Hunches', even if held by experts, are not scientific knowledge."

Banning plastic grocery bags might be a very bad idea.

There's no such thing as negligent failure to generate the same hypothesis as plaintiff's future experts.

There's a very slight increased risk of lung cancer among Carolina chrysotile textile workers with 100 f-yr/ml exposure.

Apparently, the Restatement (Third) of Torts, Liability for Physical and Emotional harm, section 7's exception permitting no-duty rules when "relatively clear, categorical, bright-line rules of law" can be promulgated is big enough to drive the very big take-home truck through it. We predict dyspepsia for Michael Green. See Mary Campbell v. The Ford Motor Company.

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When it comes to lung cancer, keep your chickens close but keep your flock closer.

"They've internalized their own confusion": watch this video if you want to understand the difference between humble falsificationist evidence-based science and the authoritarian "because I say so" approach adopted by the 1st Circuit in Milward.

Antibiotic use in children less than six months old is strongly associated with the subsequent development of asthma, especially in those without a family history of asthma, and the greater the intake of antibiotics the greater the odds of developing asthma.

Attacks on randomized controlled trials (RCTs) miss the point.

A new paradigm for cancer prevention, indeed.

 

Clostridium Difficile Infections Are At Historic Highs

The CDC has a series of reports out about the growing problem of C. difficile infections contracted via health care-associated activities. The number of deaths attributable to C. difficile has increased more than seven-fold in a little over a decade and now stands at 14,000 annually.

The reports twist together a few threads we've been following for awhile now. First, chronic and often unnecessary antibiotic use in patients disrupts their normal gut microflora and provides an opportunity for C. difficile to gain a foothold and thereafter thrive. Second, these infections aren't just hospital-acquired, or nosocomial, anymore. Infected patients, especially those with diarrhea and on antibiotics transmit the pathogen to surfaces in clinics, nursing homes and doctors' offices and staff thereafter transmit it to other patients; thus they're healthcare-associated infections (HAIs). Finally, the infection is preventable.

The CDC makes the following recommendations to clinicians:

1. Prescribe and use antibiotics carefully. About 50% of all antibiotics given are not needed, unnecessarily raising the risk of C. difficile infections.

2. Test for C. difficile when patients have diarrhea while on antibiotics or within several months of taking them.

3. Isolate patients with C. difficile immediately.

4. Wear gloves and gowns when treating patients with C. difficile, even during short visits. Hand sanitizer does not kill C. difficile, and hand washing may not be sufficient.

5. Clean room surfaces with bleach or another EPA-approved, spore-killing disinfectant after a patient with C. difficile has been treated there.

6. When a patient transfers, notify the new facility if the patient has a C. difficile infection.

If you have a C. difficile case you might want to see how the healthcare provider filled out this form.

For more information try the following links:

CDC's March 2012 "Vitalsigns"

Centers for Medicare & Medicaid Services (CMS) Guidelines for Reducing the Spread of C. difficile.

Finally, there's a brand new research paper from the CDC which discusses the finding that C. difficile is an emergent disease affecting patients recently exposed to antimicrobial drugs.

 

April's "Gut" Has Some Very Interesting Articles.

Have a look at the cover and you'll see why double-dipping chip dippers are frowned upon. Elsewhere you'll find evidence that that if you want to stay lean or if you want to avoid type II diabetes you need to hold down the ratio of Firmicutes to Bacteroidetes that live in your gut. If you're looking for evidence that keeping H. pylori at bay keeps gastric MALT lymphoma away you'll find that too. There's also evidence that pancreatic cancer is associated with just a couple of bacteria found inthe saliva of those at risk of the deadly disease. Here's the link: Gut

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When Man's Designs Don't Include Nature's

Does powdered infant formula (PIF) contaminated with Cronobacter sakazakii nee Enterobacter sakazakii constitute a design defect? The district court in The Security National Bank of Sioux City, Iowa v. Abbott Laboratories thinks so.

Creating (we think) a design defect dichotomy the court distinguished between "intended design", here PIF designed to specification but without bacteria and (apparently) "unintended design" - PIF designed to specification but with bacteria. Unintended design defects sound suspiciously like manufacturing defects since the bugs are picked up in the manufacturing process but the court held otherwise. Turning defendant's argument that bacterial contamination is common in any food not specifically sold as sterile into an assertion that the PIF was thereby meant incorporate E. sakazakii the court wrote: "[a]ny assertion that Defendant's intended design included the presence of E. sakazakii strains credulity."  

Hammering away at defendant's claim that the microbial world's ancient and relentless assault on humanity and its works aren't part of the design of PIF the court continued: "the implication is clear: their product is intended to contain E. sakazakii, as well as other potentially harmful bacteria. First, if 75% of a product does not contain a bacteria and 25% of a product does, elementary statistics dictates that the 75% without the bacteria constitutes the norm while the 25% with the bacteria constitutes a deviation therefrom. Second, a common defect, such as the persistent contamination of a food product with bacteria, if generally unknown and proven harmful, should increase a manufacturer's total liability, rather than eliminate it." Finally, holding that plaintiff's proposed alternate designs of adding a biocide to the unintentionally designed but on spec PIF, or of adding water so that PIF becomes IF, the court concluded that plaintiff's design defect claims survived defendant's motion to dismiss.

So, when a food company's designs don't include E. sakazakii's does that constitute an "unintended design defect"? Even when its product is on spec? And is adding e.g. antibiotics or soaps or chlorine to PIF a valid alternate design of PIF? How about claiming that PIF can be changed to IF without somehow losing the P?

A half dozen other claims by plaintiff also survived the motion to dismiss including manufacturing defect and breach of implied warranty. Those we get but the design defect claim is a head-scratcher. Perhaps the court didn't understand that we're all in continuous contact with potentially harmful bacteria. In fact, we're full of and crawling with countless numbers of them though we only notice if say one that lives peacefully on our skin winds up in our lungs. Or maybe the court understood and is imposing a duty to incorporate nature's designs into our own. We'll let you know if further light is shed on the matter.

For more about PIF, E. sakazakii and the devastating meningitis that caused severe and permanent brain damage in plaintiff see this very informative PowerPoint from the CDC: "Enterobacter sakazakii meningitis and death associated with powdered infant formula." and last December's press release from the FDA, "Investigation of Cronobacter Bacteria Illness in Infants".

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The conjunction paradox isn't one and doesn't require new standards of proof; rather, it's evidence that the asymmetry in the law markedly favors false positives, whatever some may say.

Cancer-causing H. pylori might find its way into you by hitching a ride in food borne yeasts.

Blame for obesity: BPA vs BUG.

The evidence that hormone replacement therapy "causes" breast cancer isn't as strong as you think.

Occupational exposure to animals: evidence for a causal link with cancer mounts.

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Hydraulic Fracturing (a/k/a fracing a/k/a fracking) Roundup

Yesterday our energy partners reported on the EPA's claim of water contamination in Wyoming due to hydraulic fracturing fluids used in natural gas production. Today The New York Times is wondering whether earthquakes can be blamed on fracing. Thus it sounds like a good time to provide you some links to recent studies of the process that you may find of interest. Here goes:

Scientific American has the truth about "fracking" and thinks that engineering science has gotten ahead of safety

The comment period for New York's Supplemental Generic Environmental Impact Statement just ended and some public health advocates don't like it

Two miles underground amidst the shale and gas, where the pressures and temperatures are extreme lives a fascinating community

And some of its members traveled there via drilling muds

Finally, some public health advocates and journals tend to overlook one important aspect of the energy business - that it provides lots of high paying jobs and benefits from free laundry service to transportation to health care and often excellent pension benefits; not to mention an interesting and disciplined work environment - a big boost to socioeconomic status which bestows dramatic economic, physical and even mental health benefits that echo through succeeding generations. So let's not forget when balancing risks and benefits of fracing to add the profound public health benefits that flow from good jobs to the benefit side of the ledger.

What To Do When a Miracle Drug Is Found to be The Cause of a Host of Unexpected Maladies?

There's an epidemic of immune disorders in America.  Allergies (especially food allergies), asthma, atopy, hypersensitivity disorders including Stevens Johnson Syndrome, Crohn's disease, type1 diabetes, obesity and more are being laid at the feet of perinatal use of antibiotics.  Evidence is mounting rapidly that the use of antibiotics in newborns or their mothers disrupts the intestinal microbiota essential to a well-functioning immune system. The consequences are seen in the host of immune-related disorders which have become perhaps the most significant cause of morbidity and mortality in the United States today.  For a new primer try: Perinatal Programming of Asthma: The Role of Gut Microbiota.

So what should we make of a drug that when first administered saved a young woman, allowing her to have a family and to live to 90* and yet which (because the role that gut bacteria play in generating a healthy immune system was decades away from being known) would eventually precipitate a wave of autoimmune disease in the United States?  If antibiotics are indeed responsible for as many cases of debilitating illness as is now widely suspected, should we ban them and vilify their makers?  Should their makers be driven to ruin by our tort system to ensure that nothing like penicillin is ever unleashed on the public again?  Or should we instead finally recognize that we must take the good with the bad;  that with every advance comes risk; and, that unintended consequences, the nature and extent of which may not be known for years to come, is the price of progress?

* The First American Civilian Saved by Penicillin

The first U.S. civilian whose life was saved by penicillin died in June 1999 at the age of 90 years. In March 1942, a 33-year-old woman was hospitalized for a month with a life-threatening streptococcal infection at a New Haven, Connecticut, hospital. She was delirious, and her temperature reached almost 107 F (41.6 C). Treatments with sulfa drugs, blood transfusions, and surgery had no effect.

As a last resort, her doctors injected her with a tiny amount of an obscure experimental drug called penicillin. Her hospital chart, now at the Smithsonian Institution, indicates a sharp overnight drop in temperature; by the next day she was no longer delirious. She survived to marry, raise a family, and meet Sir Alexander Fleming, the scientist who discovered penicillin. In 1945, Fleming was awarded the Nobel Prize in Physiology and Medicine, along with Ernst Chain and Howard Florey, who helped develop penicillin into a widely available medical product.
 

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"... the only group of organisms that have been convincingly shown to cause extinction."

What are they? They're responsible for massive worldwide die-offs of frogs and other amphibians. They're killing huge numbers of bats across the United States and threatening some local populations with outright extinction. They've also been convincingly associated with bee-colony collapse disorder which has wiped out 20 - 40 percent of U.S. honeybee colonies.

But they're not all bad. They invented penicillin and make other good things like beer and bread.

So, what are they? Read all about them in the Institute of Medicine's new report: "Fungal Diseases: An Emerging Threat to Human, Animal and Plant Health: Workshop Summary". The partial quote in our blog title comes from one of the participants, Arturo Casadevall, who said "Fungi are the only group of organisms that have been convincingly shown to cause extinction." And if you want more proof that infectious disease have most certainly not been conquered (and in fact have been invisible to investigators until now) be sure to read the story of the Cryptococcus gatti epidemic that emerged on Vancouver Island and has spread to the Northwestern U.S. killing 40 and sickening over 300 so far.

 

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"The Cost to the Health of Our Microbial Ecosystems"

Gina Kolata has another good read at the NYTimes in "The New Generation of Microbe Hunters". The word, as you can see, is quickly getting out; the old ways of thinking about the determinants of human health are crumbling as the discovery that we are "super-organisms", more bacterial than human - at least from a genetic perspective, sweeps away old notions about what makes us sick, what keeps us healthy and even what (and maybe who) we are.

For other dispatches from the revolution you might want to read about just how big a deal this is, how much we know, how much remains to be understood and the promise of biotherapeutics; or maybe, since there's a little Gilgamesh in each of us, how  changing the bacteria in the gut of mice makes the rodents live significantly longer;  then there's a dysregulated microbiome and rheumatoid arthritis; new insights into how H. pylori causes gastric cancer; and gut microbes can cause cancer of the liver and breast (in mice anyway); and changing the gut microbiota to treat type 2 diabetes and, and, and ... There's a torrent of literature but that'll give you an idea what's out there and what's coming.

None of that is to say "Eureka!" they've found the answer. Likely (as it's wise to hedge bets) the causation onion has many layers still uncovered. No, the point is twofold. First, the 40 year old idea championed by public health advocates pushing what they call social, or environmental, justice - that much if not most human suffering is due to bad industrial chemicals or the bad habits inculcated in consumers by nefarious corporations bent on selling them things they don't want or need - was never sound but now it's just silly. Second, if you've been paying attention, you'll understand that an awful lot of illness and suffering has been caused by stuff nobody, we presume, ever fretted about. But who knows? Maybe somebody somewhere has the disrupted microbiome version of the Sumner Simpson Papers. Wouldn't that be something?

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A Stage in the Age of the Phage

Gina Kolata of the NYTimes has an interesting article up today discussing the German E. coli O104:H4 outbreak. It turns out that a combination of two factors, the ability of the bug to produce Shiga toxin and to form a solid and tightly adhering biofilm on the walls of the intestines, is responsible for the severity of the illnesses suffered. It also appears that contrary to original assumptions the bacteria came not from food animals but from people.

How though did E. coli O104:H4 come to acquire the ability to produce Shiga toxin? We know it's produced by E. coli O157:H7 but how did this other bug come to produce a variant of the poison? Enter the phage.

E. coli O104:H4 doesn't have genes that would allow it to make Shiga toxin and guess what? Neither does E. coli O157:H7. Instead, they come from a phage that has infected E coli. and turned it into a deadly pathogen. See "Phage on the Rampage" in Nature News.

So bacteriophages are the villains of the E. coli story, right? Well, yes, and no. It depends on the phage. Clever bioengineers have found another phage that rips E. coli O157H7 apart and they've fed it to cows. The therapy reduces the level of E. coli O157:H7 in cows and thereby reduces the risk of infection to humans. See e.g. "Application of Bacteriophages To  Control Intestinal Escherichia coli O157:H7 Levels in Ruminants" and "Oral and Rectal Administration of Bacteriophages for Control of Escherichia coli O157:H7 in Feedlot Cattle."

Phage therapy isn't just for cows. Though it's been around for decades it was largely ignored in the West and its full potential never unlocked behind the iron curtain. Now, "bacteriophage-based 'probiotic products' may provide a novel, safe and effective approach for favorably manipulating the GI tract's microflora".

A cup of live bacteria chased with a spoonful of phages - together sent into your gut daily to wage war against our ancient enemies. What a world. And because it's so far beyond the future world we imagined we can be certain that at least some of the adventures on which we'll embark will end badly. And that means mass torts will be around for the biological revolution just as it was for the industrial version.

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Community Health and the Lake Wobegon Effect

It would be nice if every community could have above average health. The problem of course is that it's not possible - by definition. But that may not stop Congress from decreeing that whenever "a greater-than-expected number of cases within a group of individuals, a geographical area, or a period of time" is found or just suspected something ought to be done about it.  OK, not doable but maybe worthwhile, right?

It's only worthwhile if you really want to find the answer. Unfortunately, the "Strengthening Protections for Children and Communities From Disease Clusters Act" doesn't want to find the answer. It only wants to find a particular answer. And that answer is, "using health protective" science, limited to alleged toxins and pollutants.

The attempt to codify ours as the Third Age of the Epidemiologic Transition, one in which man-made illnesses are allegedly our primary source of woe and the only ones for which interventions will work, is especially appalling given the staggering amount of evidence that disease clusters are almost never the result of exposure to chemicals and that infectious diseases are, as ever, the real culprits. To get some idea of just how fast and how often emergent infectious processes may set off illness (including cancer) within a community see "Truly Emerging - A New Disease Caused by a Novel Virus"

Magic Microbes

While some people still mock the idea that bacteria have abilities far beyond anything imagined and thus impact our lives in almost unbelievable ways the evidence that it is so continues to mount. Take for example today's article in the NYTimes titled "Bacteria Divide People Into 3 Types, Scientists Say". Apparently we tend to be colonized (interesting word choice for a host (no irony intended) of reasons) not by more or less of certain types from a spectrum of bugs but rather by one of three sorts of microbe societies. One can imagine the speed dating possibilities: "I'm a Bacteroides; what are you? "Oh, we can end this now. I'm a Prevotella and I just can't deal with all the Bacteroides drama." See "Enterotypes of the Human Gut Microbiome"

The authors liken the discovery of consistent patterns of bacterial colonization to blood typing. I'll bet it's far more profound than that. All Hail our Bacteroides Overlords! All kidding (I hope) aside, I was convinced last year when my son and I as part of a 5th grade science project quite inadvertently happened upon the micro-droplets on the underside of a cover slide past which we'd been watching some beasties from a puddle. In the droplet were bacteria zipping about plus a couple more that had lined up and started to push out of their little bubble of existence. Over time they organized themselves into a straight line and kept pushing outward until they reached a bigger drop whereupon the survivors of the small droplet passed through the tiny tunnel their fellows had made and escaped. Simply amazing.

Also we're learning that all bacterial infections are not created equal. In recent years parents of children with type 1 diabetes have had to wonder about whether they might accidentally have caused the illness by creating too sterile an environment. That's because of mounting evidence that children exposed to dirt and thus microbes have a lower incidence of type I diabetes - more evidence for the hygiene hypothesis. Now however come some new studies showing that simply being exposed to lots of bacteria isn't enough to help ward off type I diabetes. For example see "The Incidence of Type-1 diabetes in NOD (non-obese diabetic) Mice Is Modulated by Restricted Flora Not Germ-Free Conditions". Germ-free (gnotobiotic) mice are no more prone to type 1 diabetes than their germy cousins unless their cousins had a very particular sort of infection by B. cereus (most recently of not-so-sterile hospital wipe fame).

So what does it all mean? Nobody who's honest really knows. Beads and rattles, after all.

It's World Health Day. What are You Doing to Combat the Spread of Antimicrobial Resistance?

Following the anthrax attack after 9/11 someone I knew began keeping a bottle of Cipro on his desk. He went through it that week. Had his family on it too - more bottles at home. I distinctly remember him telling me that I really needed to get to be buds with a doctor so I could get the good stuff. I worried that I'd put my family at risk by not developing a dealer. Of course I'd never really thought about it before because I had another friend who had always had several Z-paks in her top drawer. "I just call and say I've got a fever and a red throat and he writes me a 'script'." She mainly got them for her mother because her Mom's doctor wouldn't ever give her anything; "he always just says 'it's a virus'."

Now that we have relearned that many bacteria and fungi are keen on killing us and feasting on our corpses shouldn't we be keeping our powder dry? And now that we're learning almost daily of new microscopic bugs suspected of causing cancer (See e.g. "Novel Clues on the Specific Association of Streptococcus gallolyticus subspecies gallolyticus With Colorectal Cancer") shouldn't we hold off on using antibiotics until we see the whites of their colonies cultured in a petri dish lest we make them immune to what few weapons we have?

Read all about it at the WHO's "Combat Drug Resistance" webpage.

About Serratia marcescens

Contaminated IV bags used to deliver nutrients to critically ill patients are suspected as the source of at least 19 nosocimial infections detected in a number of Alabama hospitals resulting in nine deaths. Serratia marcescens is an opportunistic pathogen responsible for an increasing number of severe hospital-acquired infections. Here are some of the newest papers on the subject:

Three newborns died and six others sickened in the NICU - healthcare workers need to wash their hands before and after handling patients (it really is appalling that after Dr. Semmelweis' work 150 years ago so many health care workers continue to ignore this most basic sanitary measure). See "Investigation of an Outbreak of Serratia marcescens in a Neonatal Intensive Care Unit"

But maybe health care workers aren't always to blame. Looks like bulk-refillable dispensers of anti-bacterial soap may actually become contaminated with bacteria. See "Bacterial Hand Contamination and Transfer After Washing With Soap From Contaminated Bulk-Refillable Dispensers".

"Outbreak of Neonatal Infection by an Endemic Clone of Serratia marcescens"

"Serratia marcescens Outbreak in a Neonatal Intensive Care Unit Related to the Exit Port of an Oscillator"

A Big Step Forward in Tracing Foodborne Illness Back to Its Source

Where pulsed-field gel electrophoresis failed to distinguish a strain of Salmonella enterica responsible for a major salmonellosis 2009-2010 outbreak from a strain isolated in a prior separate outbreak so-called next-gen DNA sequencing (NGS) has allowed researchers to pinpoint the source of the recent outbreak to a specific spice used on salami.  See Identification of a Salmonellosis Outbreak by Means of Molecular Sequencing.  Note however that traditional epidemiologic traceback techniques had lead investigators to the source of the outbreak.  NGS confirmed the outbreak and further demonstrated that endemic contamination of food facilities by pathogens can lead to the production of new strains thereby making more precise sequencing "essential to the traceback of bacterial pathogens as they emerge in the food supply."

More Media Coverage of Bacillus Cereus Lawsuits

MSNBC is reporting that another personal injury lawsuit has been filed arising out of a hospital-acquired B. cereus infection and that a number of would be plaintiffs are inquiring about their own claims. Meanwhile the difficulty in tracing the geneology of members of the bacillus family, and a new way forward, are coming into focus. See: "Bacillus Taxonomy in the Genomic Era Finds Phenotypes to be Essential Though Often Misleading".

But Why Is It So Difficult To Think Of It Again?

It being the "it" of the Goethe quote referenced in "Acne Vulgaris, Probiotics and the Gut-Brain-Skin Axis --- Back to the Future?" : "everything has been thought of before, but the difficulty is to think of it again".

Of late there has been considerable debate about a perceived stagnation in medicine. Advances came fast and furious in the first few decades of the 20th century (think antibiotics, the pill, the Salk vaccine, etc). Nowadays advances are few and what few there are seem little more than nibbles around the edges e.g. news of a treatment extending the life expectancy of patients with advanced pancreatic cancer from 24 weeks to 27 weeks made its way to the front page of the newspaper a while back. What happened to progress? Has all the low hanging fruit already been picked? Why aren't the drug companies discovering wonder drugs? Are none left to be found?

It's an old temptation that makes people think they understand the world and how it works. In 1874  Max Planck's physics professor told the future father of quantum theory not to bother with a career in physics saying "in this field, almost everything is already discovered ...". Ooops.

The peril, as Thomas Kuhn described it in "The Structure of Scientific Revolutions", is that researchers tend to get trapped within a worldview, a paradigm, that blinds them to possibilities beyond the perceived realities that they've spent their lives trying to comprehend. It's not until a scientific discipline is in crisis, a state brought about by a once elegant theory being turned into a Rube Goldberg contraption from the numerous tweaks made to explain away embarrassing inconsistencies, that blinders come off. It's only then that new ideas, or as Goethe might put it old ones thought of again, are tried.

And that, I think, is where we are today - In the middle of a crisis of medicine. The old deterministic model on which the small molecule pharma model was built i.e. add what's lacking, deplete what's in overabundance, turn off what shouldn't be on and turn on what shouldn't be off, doesn't work beyond a few now obvious exceptions.

So what old ideas are being reconsidered anew? Read the (ungated) paper on acne vulgaris referenced above. Seventy years ago a few people thought that the bacteria which live in our guts and on our skin (and maybe elsewhere) could explain the strange association between gastrointestinal illness, depression and acne vulgaris. They also thought that reforming the microbiota (terra-forming the gut or ile-forming) with different bacteria might ameliorate or even cure such complex disorders. Now there are lots of researchers opening their eyes to the possibility that most diseases are emergent phenomena far too complex to be dealt with one molecule at a time yet ones that might yield to complex cocktails of multiple drugs or, more complex yet, cocktails of bacteria, probiotics, to fight fire with fire.

If the past is any guide we're not in an era of stagnation in medicine; we're on the verge of a new age of discovery.

 

A Deadly Hospital-Acquired Infection Becomes a Products Liability Claim

In today's news is a tragic story about the parents of a two-year old boy whose death from a nosocomial (hospital-acquired) infection they blame on alcohol wipes contaminated with Bacillus cereus.  According to the complaint filed February 13th in federal court here in Houston the Kothari's son developed bacterial meningitis following an otherwise uneventful craniotomy performed at Children's Memorial Hermann Hospital for a benign arachnoid cyst.  During the course of his treatment alcohol pads and swabs were used on his surgical wounds and within days he developed a B. cereus infection (established by positive cultures from cerebrospinal fluid) and died shortly thereafter. The next month Triad, alleged to have been the manufacturer of the alcohol pads and swabs, recalled the products saying they were potentially contaminated with B. cereus. Two days later the FDA announced a recall of all such Triad pads and swabs saying that their use "could lead to life-threatening infections, especially in at risk populations, including immune suppressed and surgical patients." 

It's estimated that in the U.S. two million patients are sickened and 80,000 are killed annually by nosocomial infections. Accordingly, it's a very big problem and so has the potential to be a very big mass tort.

Yet a big part of the problem, and the biggest impediment in the past to tort claims arising from these illnesses, are the twin issues of tracing the infection to a putative source and then establishing that the bacteria cultured from the victim are the descendants of bacteria found in the defendant's products or at its manufacturing facilities. Since most bacteria responsible for nosocomial infections, including B. cereus, are ubiquitous in the environment and were, until recently, impossible to distinguish phylogenetically, establishing causation has been essentially impossible. Now, thanks to epidemiology returning to its humble origins and genetic sequencing taking giant strides forward, it may be possible to trace an infection to its origin and conclusively establish ancestry.

Unfortunately the Kothari complaint does not reveal whether or not anything beyond a post hoc ergo propter hoc inference supports their claim. One allegation is that B. cereus infections are rare in hospitals and yet the first thing that pops up on PubMed is "Bacillus cereus Bacteremia Outbreak Due to Contaminated Hospital Linens". And as to the proposition that B. cereus infection is somehow unusual and thus more likely due to something gone astray see "Bacillus cereus, a Volatile Human Pathogen". Finally, as to the claim that B. cereus meningitis in children is exceedingly rare see (ungated) "Bacillus cereus Bacteremia and Meningitis in Immunocompromised Children".

Did the hospital have a record of B. cereus infections? Were catheters employed that B. cereus could have used as an escalator to infection? Was the strain identified identical to the one that prompted the recall? Were there other sources of that strain? If so, how is one deemed more likely the cause than the other?

Efforts to identify strains of disease-causing bacteria and to trace them back to their origin have put us on the verge of being able to identify and hopefully thereupon eradicate the causes of an enormous portion of human suffering. But we're not quite there yet as demonstrated by tonight's report of the National Academy of Sciences on the 2001 anthrax attacks. B. cereus is a cousin of B. anthracis - the causative agent of anthrax. B. anthracis was long thought to be less promiscuous than its cousins and so less likely to vary widely thus making its origin easier to identify. But it ain't so. See Chapter 5.2 "Identification of the B. anthracis Strain". The very same difficulties will likely hamper any attempt to match strains of B. cereus.

Establishing a common strain of bacteria and tracing it back to a particular defendant remains a very high hurdle for any plaintiff to clear. But when the day comes that both are readily doable "Katy bar the door" because the number of deaths from cancer, heart disease, diabetes, etc being laid at the feet of infectious agents is staggering and rising every day. Worst of all, thanks to the ability of these ancient predators to evolve at a fantastic rate. there's little anyone can do to predict where and from which formerly benign little bug the next onslaught is likely to arise.

Infants on Antibiotics Experience a Big Increase in Their Risk of Developing Asthma

Even if neither parent had asthma, introducing antibiotics to a child less than six months of age produced a big increase in the risk that he or she would develop asthma five and a half years later. Do antibiotics prevent the establishment of bacteria in our gut that help us recognize good from bad in the outside world and modulate our immune system's response or do antibiotics nuke our gut microflora dysregulating our immune systems? Read all about it (free online) in "Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children" in the American Journal of Epidemiology.

Breast Implants and Cancer

I thought it was no biggie when the FDA sent out an email late Wednesday morning saying that an extraordinarily rare malignancy, anaplastic large cell lymphoma (ACLC), had been associated with breast implants. A variety of implants, mainly orthopedic devices, have long been associated with certain rare cancers. Since the site of the cancer tends to coincide with the site of complicating surgical infections it has been thought that an infectious agent was responsible. See e.g. "Soft Tissue Anaplastic Large T-Cell Lymphoma Associated With a Metallic Orthopedic Implant: Case Report and Review of the Current Literature".

A quick review of PubMed showed that concern over ACLC and breast implants had been around for years. See e.g. "Anaplastic Large-Cell Lymphoma in Women With Breast Implants" (free in JAMA) published in 2008. So I went looking for something else to post on. Then, on tonight's 10 o'clock news here in Houston, one of the local stations led off with a story about the late John O'Quinn's litigation against Dow Corning and his claims that silicone implants caused autoimmune disorders and cancer. They made it sound as though O'Quinn had had somehow been vindicated by today's FDA press release. Then they went out and found some sympathetic woman who had recently had a radical mastectomy followed by breast reconstruction and asked her what she thought about the "new report on breast implants and cancer". To her everlasting credit she said she was happy with her decision and was confident that she'd made the right one.

ACLC is not breast cancer and the odds of getting it, assuming the association is confirmed (and there is indeed an awful lot of evidence showing that in the areas around implants whether silicone or metal where infections can set in, cancers can sometimes follow) are about 1 in 900,000. The odds by the way of drowning in your bathtub are significantly higher - somewhere around 1 in 660,000.

The media could have focused on the story of the mounting evidence for a link between pathogens and cancer. Instead they seem to have resorted to a long since discredited narrative about breast implants. It's too bad because the real story is the story of our generation.

More Evidence That Exposure to Poultry Viruses and Bacteria Causes Cancer in Humans

Significant increases in mortality risk for some forms of leukemia has again been identified in a cohort of poultry workers. See "Update of Cancer and Non-Cancer Mortality in the Missouri Poultry Cohort". Given the profound changes in the demographics of the poultry industry in recent years it would be interesting to see if population mixing might have been responsible for some or all of the increased risk.

Maybe That's Why You Fell For Her. She Cooks Just The Way Your Mom's Gut Microbes Like It.

Biological causation gets more complex by the day and the simple, reductionist model of toxin in - disease out common to toxic tort cases gets more absurd by the day. Imagine what you'd have thought two years ago about this claim: the diet of a fruit fly changes the composition of the bacteria in its gut and those bacteria then change the pheromones she releases so that she will attract a male fruit fly with the same sort of bacteria in his gut resulting in a mating preference change that lasts up to 37 generations even if her offspring's diet changes along the way.

Thus, it's not just a matter of "They Are What You Eat"; it may well also be a matter of "You Are What Your Great Great Great Great Grandmother's Intestinal Bacteria Ate". See "Bacteria Can Drive the Evolution of New Species" in Nature News for the write-up and "Commensal Bacteria Play a Role in Mating Preference of Drosophila melanogaster" for the paper that heralds the discovery.

For more on the idea of a "hologenome" - i.e. the idea of thinking of "your" genetic code as consisting of the genes in your chromosomes plus those in the bacteria that live in and on you - see the following:

"Role of Microorganisms in the Evolution of Animals and Plants: the Hologenome Theory of Evolution"

"The Hologenome Theory of Evolution Contains Lamarckian Aspects Within a Darwinian Framework"

"Whole-Body Systems Approaches for Gut Microbiota-Targeted Preventive Healthcare"

Tracing For The Win

So much for SanGar Produce & Processing Company's objections to state testing procedures that detected Listeria monocytogenes in its San Antonio plant. The FDA has not only confirmed the presence of L. monocytogenes at the plant it has also confirmed that the strain found is identical to that which sicked many and killed four already immune compromised individuals.

This is what the investigation of foodborne outbreaks will produce increasingly from now on - swift and irrefutable tracing back to their origin.
 

Listeria Monocytogenes Outbreak Traced to Celery; Or Was It?

 

The Texas Department of State Health Services (DSHS) has shut down a San Antonio packager of produce for restaurants and schools following its determination that a L. monocytogenes outbreak thought to have been responsible for five deaths of immune compromised individuals originated at its facility. The company targeted for the shutdown is disputing the claim saying that its testing showed no L. monocytogenes and questioning whether the samples taken from which the bacterium was cultured were contaminated thanks to shoddy procedures by DSHS personnel. Read about it in "San Antonio Produce Plant Closed by Health Agency" in the Houston Chronicle. The DSHS news release can be found at "DSHS Orders SanGar Produce to Close, Recall Products".

L. monocytogenes contamination of ready-to-eat foods is a world-wide problem. See: "Occurrence of Listeria Monocytogenes in Ready-To-Eat Foods From Supermarkets in Southern Italy". For a recent discussion of molecular markers for detection and attribution and biomarkers for surveillance and epidemiological investigations see: "Future Challenges to Microbial Food Safety".

Toxoplasma gondii: Sheep and Goats Have a Vaccine Against It. Why Don't We?

It''s becoming apparent that Toxoplasma gondii is responsible for an awful lot of human suffering around the world. The parasitic organism causes birth defects and spontaneous abortions, neurolgical impairment, eye damage and is increasingly suspected in Alzheimer's, schizophrenia and Parkinson's.

T. gondii infects human cells and reproduces within them eventually setting up shop in cysts throughout the central nervous system, heart, muscle, bone marrow and other organs. Persons infected are infected for life. Human infection is most commonly the result of consuming un-/under-cooked cyst-bearing meat though contact with the feces of animals, especially cats, T. gondii's ultimate host, are another avenue of exposure.

While 11% of Americans are infected with the parasite, that figure rises to as high as 70% in some South American countries. The European Food Safety Authority, worried that foodborne infection by T. gondii is on the rise and is responsible for significant yet underreported and undetected diseases within the EU, has recommended Toxoplasma monitoring of lifestock. Recent estimates of the impact of T. gondii-induced disease reveal it to be "one of the most significant causes of foodborne disease worldwide."

The good news is that thanks to demand from sheep and goat producers there's a vaccine that works well in sheep and goats. The problem is that it's a live cell preparation like the Sabin vaccine discussed during oral argument in Bruesewitz, et al v. Wyeth, Inc.,So what's the problem? The problem is that while it works really well, much better than bits of a dead organism, it's more likely to cause adverse effects. Meanwhile, finding all the bits of a dead organism that prime the immune system while weeding out those that might produce harm is a terribly complicated and expensive process. Add to that the threat posed by litigation over the inevitable errors in science's slow but steady progress through trial and error and it ought not be surprising that sheep and goats get protected while human suffering due to T. gondii spreads.

For a new, free and enlightening paper on the topic see "Vaccination Against Toxoplasma gondii: An Increasing Priority for Collaborative Research?"

They're Walking, Yes Indeed, They're Talking, 'Bout You and Me

Bacteria are amazing. Each new discovery only adds to our awe. We know that bacteria talk to each other about us and now we learn that they can get up on their feet, special pili, and walk right on up catheters and other surfaces to us. There's a video of one going vertical and running off and the paper that discusses the phenomenon, "Bacteria Use Type IV Pili to Walk Upright and Detach from Surfaces" and its importance in the effort to understand biofilm formation in today's Science Magazine. Hat tip: Houston Chronicle which has a great writeup.

2010 FETTI Conference Presentation

I was out the end of last week to attend the FETTI conference in Chicago. Here's the PowerPoint from my presentation: Food-Borne Illness And a New Day for Toxic Torts

Parkinson's: Not Much Evidence for Manganese; Strong Evidence for Vitamin D Deficiency

In Tamraz v. Lincoln Electric Company, et al the 6th Circuit held that an expert could not stack speculation about mechanisms upon unseen and undetected lesions in the plaintiff to get from manganese exposure to his Parkinson's disease. Furthermore, the court ruled that you can't reasonably arrive at a causation opinion using what's erroneously called a differential diagnosis (it's more properly called simply a process of elimination) when you've no sound basis for ruling anything either in or out.

On the other hand, there's growing evidence that vitamin D deficiency is strongly associated with Parkinson's. Best of all, it makes sense. It looks like the enteric nervous system is first to be degraded in Parkinson's and that system is exquisitely sensitive to the gut mediated immune system which in turn is adversely affected by vitamin D deficiency. See: "Parkinson Disease: Could Sunlight Offer Protection from Parkinson Disease?"

Would Zombies Make Good Plaintiffs?

Before answering the question let's see if mind control is even possible. By now you're probably aware of the fact that a fungus (Cordyceps unilateralis) can zombify an ant; making it leave the colony and move to the perfect spot for the fungus to sprout out of its head and complete its life cycle. For this and other examples of hijacked brains see 10 Fascinating Cases of Mind Control.

You'll notice on that list the case of Toxoplasma gondii. It's a nasty little microbe that infects the brains of rats and tells them to find cats. Once gobbled up by a cat the T. gondii in the rat infects the new host and completes its own life cycle. Now that's unsettling. It's one thing for ants to be zombified, but rats? We've unhappily shared microbes with them before. Is there any evidence that T. gondii alters human behavior? Yep.

Is it possible that T. gondii is the cause of some cases of neuroticism, schizophrenia, depression, bipolar disorder and obsessive compulsive disorder? Yep, yep, yep, yep and yep. See "Toxoplasmosis as a Cause for Behaviour Disorders - Overview of Evidence and Mechanisms". Neuroticism? What's the evidence? See "The Diagnosis of a Personality Disorder Increases the Likelihood for Seropositivity to Toxoplasma gondii in Psychiatric Patients" and "Manipulation of Host Behaviour by Toxoplasma gondii: What is the Minimun a Proposed Proximate Mechanism Should Explain?"

So, a new client walks into your office and she's a zombie. T. gondii infections come primarily from water or improperly cooked food and your client can be shown to have been wrongly exposed. The problem however, given the fact that 30% of all humans carry T. gondii, is that while 4 of your jurors are likely to be zombies themselves the other 8 aren't. In your jurisdiction you need 10 for a verdict. How do you convice the 4 that being a zombie is a bad thing while convincing the 8 that your client isn't a monster?

What a world.

What Do Wrinkles, Rheumatoid Arthritis and Multiple Sclerosis Have in Common?

Apparently, whether you get them or not depends on the microbes that live in your gut.

It may not make sense intuitively (undoubtedly a common problem in times of crumbling paradigms) but the bacteria in your intestines may decide whether your skin responds to UV damage with wrinkles or is instead rejuvenated. See "Probiotics for Photoprotection".

Interested in how the right gut microbes suppress central nervous system inflammation and how the wrong ones cause just the sort of chronic brain and spinal cord inflammation thought to be responsible for MS? Read: "Proinflammatory T-Cell Responses to Gut Microbiota Promote Experimental Autoimmune Encephalomyelitis". Here's one of many interesting takeaways: "... mammals are colonized for life with extraordinary multitudes of indigenous bacteria, and the contributions of this enormous and diverse ecosystem to human health remain poorly understood. Recent studies have launched a revolution in biology aimed at understanding how (and more importantly, why) mammals harbor symbiotic bacteria."

Take a mouse predisposed to rheumatoid arthritis and make it germ free. No rheumatoid arthritis. Then expose it to a single microbe, the segmented filamentous bacteria, "and arthritis rapidly ensued." That was the finding of "Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells". And for a real eye opener read "Segmented Filamentous Bacteria Shape Intestinal Immunity". How could two genetically identical mice have dramatically different immune systems? By having different microbes in their guts - as in the case of B6 mice from two different vendors.

Memo to self: look into whether different sources of B6 mice might correlate with different results re: butadiene's carcinogenic potential.

Koch's Postulates Revised

Whenever epidemiological data is used to support a claim of causation in a toxic tort case a fight over causal inference invariably erupts and for the last twenty years or so that has meant an argument about whether Sir A. B. Hill's so-called causal criteria have been met. Long before Hill tried to prove that smoking causes lung cancer Robert Koch tried to find a defensible argument for the claim that microbes were the cause of anthrax. What he came up with are known as Koch's postulates and they've been around for well over one hundred years. Now, in an attempt to update them for a world in which often only bits of pathogens long gone remain an attempt to update the postulates has been published.

In "Microbe Hunting"  the author summarizes the problem of causal attribution when the responsible bacteria can't be cultured or even found and when their role in disease is the result of an incredibly complex interplay between host, uncounted trillions of microbes and the external environment. He discusses the methods for teasing out pathogens from dense webs of causation and proposes a refined set of causal criteria. It's well worth reading because if you do mass torts you'll be dealing with this issue for years to come.