Philip Alcabes discusses myths of health, disease and risk.

Profiting from Preparedness

Don’t miss Helen Epstein’s brilliant exposé in the latest issue of The New York Review of Books. She shows how the profit motive shapes the “preparedness” industry — worth $10 billion worldwide in 2009 (the year of the Flu Pandemic That Wasn’t).

I’ve covered the profit-motivated thinking behind vaccine recommendations generally and specifically with regard to flu immunization.  Epstein’s main interest is in the role of pharmaceutical companies in promoting oseltamivir (Tamiflu®) and other neuraminidase inhibitors as public health responses to flu fears.  Her story features the brilliant work of Tom Jefferson and colleagues, and the shady behavior of the global biotech firm Roche in trying to block Jefferson et al.’s efforts to investigate the safety of neuraminidase-blocking agents.

Jefferson was lead author on the Cochrane Collaborations’ main paper on neuraminidase inhibitors for flu prevention and treatment.   But when reports of adverse effects of these drugs emerged and he and colleagues tried to re-assess the underlying reports on which the effectiveness of oseltamivir and similar drugs was based, Jefferson was stymied.  His colleague, Peter Doshi, related the story in BMJ.   The journal’s editor-in-chief, Fiona Godlee, along with Cochrane director Mike Clarke, wrote in an accompanying editorial:

The review and a linked investigation undertaken jointly by the BMJ and Channel 4 News cast doubt not only on the effectiveness and safety of oseltamivir (Tamiflu) but on the system by which drugs are evaluated, regulated, and promoted.

The take-home message is that while there is evidence that Tamiflu can be effective in treating flu, the evidence is shakier than it seems, and troubling reports point to potentially serious adverse effects.

How does a questionable medication get to be the basis (or part of the basis) for public health policy?  The answer is that the policy makers and the money makers work hand in hand.

Maryann Napoli at Center for Medical Consumers tried to point out the troubling links between WHO and big pharma last year, and Steven Novella at Science-Based Medicine brought it up around the same time.

But most of the coverage focuses on the involvement of individual scientists and/or physicians who are receiving payments or other forms of remuneration directly from drug companies.  It’s not hard to police such straightforward conflicts — and so it was easy for Margaret Chan, WHO Director-General, to say last year that “at no time, not for one second, did commercial interests enter my decision-making.”

Epstein’s great contribution is in showing that obvious conflicts of interest aren’t the main way that for-profit companies influence policy.  It’s done through stonewalling, as Jefferson encountered when he tried to examine Roche’s data.  It’s done through widely accepted collusions.

For instance, the CDC Foundation — “Helping CDC Do More, Faster” is its motto — is a nonprofit organization, created by the U.S. Congress, whose job is to

connect the Centers for Disease Control and Prevention (CDC) with private-sector organizations and individuals to build public health programs that make our world healthier and safer.

Of course, calling them “private-sector organizations” suggests that these are not-for-profits — and some, like the District of Columbia Department of Health, the Medical College of South Carolina, and UNICEF, really are.  But most of the private-sector collaborators who are linked with CDC’s policy makers by the CDC Foundation are big corporations.  They include all the giants of Pharma world:  Merck, Pfizer, Roche, Sanofi-Pasteur, etc.  (They also include some who are just giants:  Google, Dell, YUM! Brands, and IBM, to name a few.)

So when CDC’s updated flu response plan now recommends antiviral (i.e., neuraminidase-inhibitor) treatment “as soon as possible,” it’s worth asking whether this is because it has any public health value (answer:  no) or just because CDC is cozy with companies that make money when people get sick.

Vaccine Crusaders Arm for Battle

I’m not sure I want to feel sorry for Andrew Wakefield — a nudnik, possibly even a charlatan.   And although I worry that MMR vaccine, especially as part of the intense dosing schedule for childhood vaccination overall, might have bad effects on some kids’ immune systems,  I’m not categorically opposed to immunization.

Still, it’s hard to avoid wondering:  is Wakefield right when he alleges that he’s being persecuted by the vaccine industry?

Last week, I discussed the BMJ article by Brian Deer asserting that Wakefield’s research was fraudulent, and the accompanying editorial supporting immunization.  At that point, I thought that the BMJ pieces were, together,  a one-off.

I was wrong.  In fact, it looks this week like the vaccine industry has armed some of its main warriors and sent them out to do battle.

The Battle Against Anti-Vaccinationism

In the Jan. 13th issue of the New England Journal of Medicine, two powerful chiefs, Gregory Poland and Robert M. Jacobson, claim that there’s an “age-old struggle” to make vaccines available.  Their aim is to vilify the “antivaccinationists” who “have done significant harm to the public health.” [Note the use of the holy article in this phrase, to signal just how sacred these warrior-priests hold “the” public health to be.]

The Poland-Jacobson piece is pure propaganda.  Theirs is a tale of heroic struggle on the part of ever-embattled Believers against the satanic forces of Antivaccationism — who have been trying “since the 18th century” to shake people’s faith in the vaccine gospel.  And nowadays the nasty antivaccinationists are using scarily modern forms of communications, such as TV and the Internet, in order “to sway public opinion and distract attention from scientific evidence.”

Wow:  TV and the web.  Sounds satanic alright.

I guess I shouldn’t be surprised that a couple of crusaders make their own work sound salvationist.  What troubles me is that they make it sound like they’re disinterested do-good-ers.

In fact, Poland and Jacobson are in bed with Big Pharma.  Poland runs the Mayo Clinic’s Vaccine Research Group.  Although as far as I can tell, Poland and Jacobson are not currently in the direct pay of the vaccine manufacturers, they and the VRG have benefited handsomely from vaccine makers’ largesse.

For instance, Poland’s and Jacobson’s work on human papillomavirus vaccine, as they acknowledge in a 2005 Mayo Clinic Proceedings paper, was funded by Merck, and their co-workers were Merck employees.  Later, in conjunction with a continuing medical education module on meningococcal vaccine in 2009, Poland disclosed the following ties:

Sources of Funding for Research: Merck & Co, Inc, Novavax, Inc, Protein Sciences Corp; Consulting Agreements: Avianax, LLC, CSL Biotherapies, CSL Limited, Emergent Biosolutions Inc, GlaxoSmithKline, Merck & Co, Inc, Novartis Vaccines, Novavax, Inc, PowderMed Ltd

And on his disclosure form for this week’s NEJM article Poland acknowledges funding from Pfizer and Novartis for vaccine studies.

So when Poland and Jacobson write that our society “must continue to fund and publish high-quality studies to investigate concerns about vaccine safety,” they’re really talking about preserving their livelihood.  It’s very much in their interest to ensure a steady flow of such funding.

And when they say that “society must recognize that science is not a democracy in which the side with the most votes or the loudest voices gets to decide what is right,” they’re being completely disingenuous.  Because Poland and Jacobson know quite well why science is not a democracy:  in the type of research they do, it’s the big money that decides what is right.

A High Priest of Vaccine “Science”

Then there’s Paul Offit making the rounds.  Offit has been the subject of lots of attention by Age of Autism, most recently as a “denialist.” Offit probably profited somewhat from the licensing of Rota Teq vaccine, which he helped invent — although AofA’s allegation that he is therefore beholden to Merck seems unsubstantiated.

What’s obvious about Offit is that he is contemptuous of people who don’t agree with his version of truth.

Offit appeared on Lenny Lopate’s radio show in New York yesterday, and presumably will be appearing elsewhere.  His aim is to explain the “grave public health problem of vaccine avoidance.”  The “anti-vaccine movement threatens us all,” he says.  In fact, that’s the subtitle of his new book, Deadly Choices.

Where Poland and Jacobson are militant and sanctimonious, Offit sounds a note at once sentimental and officious.  It’s “tragic” that there have been measles outbreaks because of parents refusing to have their kids vaccinated, he says.  And the problem is that people just don’t understand science.  In fact, Dan Olmsted at AofA gets it quite right when he critique’s Offit’s blinkered version of science:

Anyone concerned about [possible harms of vaccination] fits Offit’s definition of anti-vaccine, because vaccines don’t cause any of them, because Paul Offit says so, a solipsism that is really quite breathtaking: “[B]ecause anti-vaccine activists today define safe as free from side effects such as autism, learning disabilities, attention deficit disorder, multiple sclerosis, diabetes, strokes, heart attacks, and blood clots — conditions that aren’t caused by vaccines — safer vaccines, using their definition, can never be made.”

I had the same reaction to Offit’s self-important — and, to my mind, unscientific — claims.  Offit shows no interest in the open inquiry that marks science.  People who don’t agree with him are uneducated, poorly informed, maybe just stupid.  And, of course, dangerous.

“Tragic” Consequences of Unbelief

On the Lopate show, Offit resorted to the now-common formula of the “tragic” consequences of parents’ belief in Andrew Wakefield.

What’s the tragedy, exactly?   It’s true that there have been outbreaks of measles in the British Isles that have been traced to parents’ refusal to have their children immunized.  An excellent review in BMJ in 2006 provided some of the data for the U.K. — including that one child died in a 2006 measles outbreak that was related to poor immunization coverage.  A few children died in Ireland in 2000.  A CDC account of a measles outbreak in California in 2008 reports that it hospitalized a few children, although none died.

It would be great if nobody ever died from an infection that could be prevented in any way.  It’s surely tragic to the parents of a child who dies from a preventable infection.   The sympathies of each of us should go out to such parents, as to those whose kids are killed by bad drivers, sports injuries, or infections for which there’s no vaccine.

But in what sense is one child’s death more of a collective “tragedy” for all of us than the other deaths that go unremarked every day?   Why is it tragic when one child dies of a vaccine-preventable infection and not when a lot of them die of poorly regulated handguns or as troops fighting wars that never endanger our leaders, only our young?

The Ramp-up of Aggression by the Vaccine Crusaders

Why are the vaccine warriors rampant now?  Perhaps the vaccine makers are terrified that the low uptake of H1N1 flu vaccine despite all the hype in 2009, along with low MMR compliance in some places (the U.K. especially), means that their profits are going to slide.  Maybe their friends, like Offit and Poland, are worried that reduced uptake of vaccines will translate into diminished research funding or fewer conferences in delicious places.

Or maybe the vaccine industry finds Wakefield so obstreperous that they can’t rest until he is destroyed. Wakefield’s no choir boy, but he might not have realized just how much control the pharmaceutical industry can exert in the U.K.

In a review essay in last week’s New York Review of Books, Simon Head points out that Big Pharma is “the only major segment of the British economy that is both world-class and an intensive user of university research,” and implies that it exerts control over both the substance and volume of U.K. research productivity, especially in medicine.  Head sees reason to believe that Pharma will “tighten its hold over scientific research in the UK” in the future.

It’s Not a War

There need be no either-or about vaccines.  If our society can live with guns and automobiles (together accounting for roughly 50,000 American deaths a year), if we tolerate alcohol, processed foods, acetaminophen, high-rise construction, and all the other things that occasionally cause harm but mostly contribute to the way of life we prefer — then we can stop calling it “tragic” when a few parents don’t have their kids immunized.

Because to call one measles death “tragic” is to further the vaccine warriors’ campaign — the campaign that pretends to be on behalf of science or healthy kids, but is really fought to protect the fortunes of vaccine makers.

The campaign protects the power of shiftless public officials who claim to be protecting the public from harm when they serve up millions of taxpayer dollars to vaccine manufacturers for barely useful vaccines (H1N1 2009), or for vaccines that are undoubtedly helpful but might be harmful in some cases and haven’t been thoroughly examined (HPV vaccine).  And who, to this day, won’t even consider the very good question that Andrew Wakefield posed in the 1990s:  is it a good idea to give kids three immunizations in a single preparation?

I had my child immunized when she was the right age for that.    But I’m not certain that absolutely everyone has to do the same.  Neither are the courts, which is why they allow exemptions from immunization for personal belief.

I don’t think measles is a menace to civilization.  I know that only a very tiny percentage of children who contract measles get dangerously sick from it, that flu vaccine doesn’t work for everyone (and isn’t an effective public health measure to stop flu outbreaks even though it can protect individuals from illness), and that varicella vaccine can make the problem of shingles worse even though it reduces the problem of chicken pox.  And so forth.

I mean that immunization is complex and fraught.  Not everyone can be expected to agree with every vaccine recommendation.   Even while some people are opposed to vaccination and refuse to immunize their kids, life will go on, and society will continue to thrive, and Paul Offit can continue to say arrogant things about “science.”

So, could someone please call off the crusade?

Mitochondrial Dysfunction: Biologizing Autistic Behavior

Marx famously opined that social phenomena — world-historic events, he called them — occur first as tragedy, then as farce.  That was in 1852.

Today, it would be closer to the truth to say that tragedy only counts if it can be diagnosed.   And diagnosis only counts if it’s biological.

That’s been the story of  the conversation about autistic children, and the implication of so-called mitochondrial dysfunction.

Deficiencies of energy metabolism have been rumored in association with the autistic picture for a while now, and emerged in the Hannah Poling case a few years ago.  They were given a boost by a small European case series (abstract here, PDF here) published in 2005 in Developmental Medicine and Child Neurology.  (The authors of the article gave their paper the deceptive title “Mitochondrial dysfunction in autism spectrum disorders:  a population-based study,” even though the research involved no population at all, just 11 kids.  But business is business.)

Another boost came this week with the publication in JAMA of a methodologically careful study of  energy metabolism in 10 California children diagnosed with autism, contrasted with 10 children drawn from a well-matched sample of comparable control children.   The new study found reduced oxidative activity in mitochondria — the tiny energy-chain entities inside cells that produce chemically based, biologically derived power for the cells’ functions.  The reduced oxidative activity was present in most of the 10 autistic children, and they showed a much-altered mean energy metabolism on several different measures.

Thus, altered energy metabolism at the cellular level has been documented in a small handful of children diagnosed with autism.  It seems not to be present in all children with autistic diagnoses.  It might be a result of autistic behavior rather than a cause, or a bystander phenomenon of some kind.  Or it might be a feature that hastens diagnosis (in the ones who have the unusual metabolic pattern, it has not been shown to precede the diagnosis) without actually playing any predisposing role.  Indeed, the authors of the JAMA paper remark that the

mitochondrial dysfunction observed in this preliminary study performed with children presenting with full syndrome autism may or may not indicate an etiological role.

But this minor and still untested finding on mitochondrial energetics, still not of any self-evident significance regarding the cause of autistic behavior, has created a major stir.  Medscape weighed in.  Business Week ran a story written by HealthDay reporter Jenifer Goodwin.  And it’s no surprise that the story has been front page news at the autism blogs, like Age of Autism and Autism Speaks.

So it seems safe to say that we’re looking at the third coming of a fact.

That some children engage with the world differently than do most kids was the first discovery, an old discovery (some think the 18th-century Wild Child of Aveyron was autistic).  It was codified in 1910 when  the psychiatrist Eugen Bleuler labeled one of the varieties of childhood schizophrenia “autistic.”  Identification.

Next came diagnosis — beginning with Hans Asperger in 1938 and Leo Kanner in 1943.   In the grip of modernity, slow acquisition of words, quirky communication, fixity of focus, failure to multitask, preoccupation with parts rather than wholes, and so on, are no longer signs of diabolical possession, thankfully.  But neither do they signal a broadened sense of what human experience is like.  They’re just signs of disease.

Diagnosis has allowed all sorts of theories to summon support:  about parenting, about the toxic environment, about thimerosal in vaccines, or about immunization itself.  Autism is the diagnosis that lets people express their misgivings about modernity.

Now we’re seeing the beginning of step 3:  biologization.

If autism is to stand up to 21st-century modernity, it has to have a biological basis.  Otherwise it will go the way of the obsolete disorders of old, like neurasthenia, hysteria, or frigidity.  The research on mitochondrial dysfunction in California won’t be the last or the only big-dollar expenditure aimed at finding a biochemical basis for the diagnosis of autism.   And there’ll be DNA studies, too.

The sad thing is that the only good way for troubled parents to get services for their children is to have the kids diagnosed, and to help to get them labeled as biologically off-kilter (Autism Speaks was one of the sponsors of the study just published in JAMA).  Get them labeled as dysfunctional, to use the term of art.

There’s no percentage in betting on need, or social disadvantage, or just plain poverty as an impetus to free up funds and services.  The need doesn’t count if there’s no dysfunction.   Your event doesn’t count as world-historic without a biological basis now.  First as tragedy, then as diagnosis, then as biology…

Autism, ADHD, obesity, addiction — each time our society is confronted with a problem it can’t solve or an irritation it can’t salve, we feed the problem into the medical establishment’s diagnosis mill.  Then we turn it over to the biologists to put some science on it.

Once the problem has a name and a diagnosis and a biological mishap to it — then we can see it.

Plague Did Not Begin in China. And Why Should Anyone Think It Did?

Nicholas Wade, the NY Times‘s science writer, jumps the gun with a story today asserting that plague began in China.  Maybe it’s understandable:  you don’t often get a front-page story if you’re a science reporter, so once in a while you take some shaky science and turn it into an international incident.

But to understand why the story is wrong means recognizing a weakness of science as it’s often practiced today.

Wade’s claim is based on two papers published this month.  A relatively well done study by Haensch et al. in PLoS Pathogens earlier in October tested human remains from well-identified plague pits — burial sites for medieval plague victims — in different parts of Europe.  Researchers amplified DNA sequences of the plague bacterium, Yersinia pestis, at specific genetic loci, and tested to see whether the DNA matched known sequences of contemporary Y. pestis genes.

The findings published in PLoS suggest that the Black Death and perhaps subsequent waves of plague in Europe were indeed caused by Y. pestis — which would tend to debunk the theory proposed by some British researchers that the Black Death was some kind of viral hemorrhagic fever outbreak.  And they suggest that there were at least two widely different Y. pestis strains involved in different parts of Europe.  Here’s a bit of the abstract:

[O]n the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route.

The main weakness here is that DNA could not be amplified from all of the plague pits the researchers studied, but after using alternative means to test the DNA debris against contemporary gene sequences the investigators concluded that the absence of genetic material reminiscent of one strain of Y. pestis was evidence that that strain was not in play in that part of Europe at the time.  Probably right, but stretching the available evidence.

It’s a common mistake, alas.  To paraphrase Karl Popper:  just because you see DNA from white swans and don’t see any DNA from black swans, doesn’t mean that black swans don’t exist.

Still, the PLoS paper is persuasive that more than one strain of the plague bacterium was circulating, and probably causing deaths, in the plague period in Europe.  Of course, it says nothing about China.

So where does the NYT reporter get his headline-grabbing story?  A paper to be published in Nature Genetics online (still embargoed at the time I’m writing, but a summary appears here) states that the sequences of plague DNA amplified from plague pit remains, as well as contemporary isolates, can be placed on a molecular clock because of the occurrence of unique mutations.  Winding the clock backward, the researchers conclude that the Ur plague organism, ancestor of all Y. pestis, came from the far east.

The molecular biology may be unimpeachable, but the inferences about history aren’t supportable by molecular evidence.  That might explain why they’re almost certainly wrong.

The problem (scientists, I hope you’re listening!) is that you may know very well what you know, but you can never know what you haven’t seen.  The hereditary tree has its roots in China.  Here is one proposed by some of the same authors in a 2004 PNAS paper:

In this set-up, isolates of Y. pestis from China seem closest to the primordial strains.

But of course, the molecular clock doesn’t take account of strains that are no longer extant.  And ones that haven’t been unearthed.  The contemporary researchers don’t see them (or don’t know how to look), so they don’t exist.

It’s a bad mistake, inferentially.  And historically.  It’s where the NYT writer goes wrong.  Almost certainly, plague did not begin in China.  It began as an enzootic infection of small mammals in the uplands of central Asia.  This is the story convincingly relayed by William H. McNeill in Plagues and Peoples a generation ago, and none of the many accounts I’ve read since then has debunked it.

Plague would have had to begin in an ecosystem in which it could circulate at moderate transmission rates with little pathogenicity among small mammals (the natural host of the bacterium).  Exactly where it started remains open to question, but it was probably in the area that is now Turkestan/Uzbekistan.  With the development of trade between that region and China, intermixing of local (central-Asian) animals with caravan-accompanying rats would have allowed Y. pestis to adapt to the latter.

Quite possibly China was the source of the first human outbreaks of plague — because the river valleys of China were settled and agricultural (therefore offering feeding opportunities for rats as well as multiple opportunities for rat-human interaction) long before Europe was.  That fact probably accounts for the biologists’ (mistaken) belief that their early samples show that Y. pestis started out in China.

But plague began as — and remains — a disease of animals.  To acknowledge that human outbreaks in China preceded the human outbreaks in Europe (the Justinian plague that began in the mid-sixth century, the Black Death that began in the 1340s, and subsequent visitations) is not the same as saying that plague originated in China.

Which it didn’t.  Plague is an animal disease from Central Asia.  Plague’s long history is the usual one:  ecosystem change, trade, animal-human interactions, alterations in climate and economic conditions, and occasional opportunities for mass human illness.   (One world, one health.)

Above all, remember that science is only capable of drawing conclusions about what scientists can observe.  Don’t be taken in by hair-raising stories.  Even in the NY Times.

Bed Bug Worry, Mosquito Mayhem

You hear a lot about bed bugs these days, here in New York City.   The bed bug infestation has become part of New York angst, the newest of our plagues.  The NY Times had its top infectious disease writer cover the recent CDC-EPA joint statement on bed bug control.  There’s even an iPhone app with GPS-enabled bed bug maps of New York and other big cities.

Early this month, a couple of friends, thinking they might splurge on a downtown hotel to celebrate their tenth wedding anniversary, were soliciting bed bug reports before choosing where to stay.  And at a family gathering last week, one young man — recently graduated from an elite college, an intellectual usually given to ironic mockery of the nuttier trends evident in the generation that still uses e-mail — told me that while he’s afraid of bees and doesn’t like mosquitoes, bed bugs really terrify him.

Bed bugs are unpleasant.  Their bites can itch.  Their feces and molted shells can set off asthma attacks or other allergies.  It’s sensible to avoid them, and get rid of them if they’re in your home.  I wrote a few months ago that it makes perfect sense that health authorities do something to limit bed bug woes.

But if you ask me what insects worry me most as a public health professional, I certainly wouldn’t say “bed bugs.”  Ticks, especially as Lyme disease spreads geographically.  Phlebotomine (sand) flies, as leishmaniasis becomes a more serious problem.  Mosquitoes, always.   Bed bugs are far from the top of my list.

The Aedes mosquitoes that carry yellow fever, dengue, rift valley fever, and chikungunya viruses, are most troubling right now.  Ae. aegyptii most of all, of course, but increasingly Ae. albopictus.

An extensive outbreak of rift valley fever in South Africa produced dozens of human cases earlier this year, and seems to be continuing among livestock.  An epidemiologist friend in Europe told me a few weeks back that he and other European disease control specialists, already concerned about dengue and yellow fever, are looking at RVF exposures in the southern part of the continent — a worrisome finding for a virus that has primarily been African.   The European Center for Disease Control is, appropriately, concerned about the establishment of Ae. albopictus in Europe.

Ditto chikungunya, which as produced 33 cases in Delhi, India, this year, possibly including an illness in the city’s mayor.

Dengue  demands control most pressingly of all.  Although the CDC is busily advising Americans not to worry (“Nearly all dengue cases reported in the 48 continental states were acquired elsewhere by travelers or immigrants,” its info page reads), there is active spread through much of the Caribbean basin — see the map at Dengue Watch, for instance.  The Mexican ministry of health reports dengue transmission in areas bordering the U.S.  There has already been an outbreak in Texas (in 2005).  And other highly industrialized countries with strong surveillance and control systems are experiencing dengue cases, including the first report of domestic transmission within France this summer.

(Hats off to Crof at H5N1, who has been following both chikungunya and dengue assiduously.)

The expansion of the range of Ae. albopictus, a secondary but by no means ignorable vector for dengue, makes the geographic extension of these pathogens worthy of concern.

With climate changing, trade routes always in flux, area spraying of insecticide disfavored because of environmental considerations, and of course mosquitoes evolving to take advantage of new niches, it seems unlikely that North Americans can go on counting on the mere improbability that virus and vector will coincide.

Mosquito control programs are in place, and U.S. authorities expend considerable effort at controlling Ae. aegyptii in Puerto Rico.  But the West Nile fever outbreak of 1999 and its subsequent extension in North America reveals the porousness of mosquito control.

Mosquitoes are much more worrisome than bed bugs.