IRBs: Insider control can't do what's expected. Part I: some history

We are supposedly able to sleep peacefully in the security of our homes because Institutional Review Boards (IRBs) are on guard to protect us from harm at the hands of universities' Dr Frankensteins.  But the system was built by the potential Frankensteins, so any such comfort goes the way of any belief that people can police their own ethics, especially when money is involved.  This is shown by a recent revelation in the news (the short version: scientist creates flu strain that human immune system can't fight, with IRB approval), that we'll be seeing more about in the near future.  So, get your face mask on and head under the covers if you want to sleep in peaceful bliss.

First, however, a brief history of IRBs

What protects us from mad scientists?
The idea of IRBs arose largely not from Frankenstein but from abuses, especially courtesy of the Nazis. Absolutely horrid crimes by almost any standard were committed in the name of research.  It wasn't just the Germans.  The Nuremberg Code for research, which stipulates essentially that it must involve voluntary consent, do no harm, have some benefit, and so on, was one result.

But abuses weren't patented by the Nazis.  Anatomists at least as far back as Galen did vivisection, at least on mammals and perhaps on humans.  People still object to vivisection--animal research--and if you knew what is allowed you might join them, even though the rationale is, as it has been since ancient times, that we make the animals suffer ultimately to relieve human disease.  Of course, we claim the animals aren't suffering, on various rationales (they aren't sentient, aren't conscious, aren't really suffering, .....).

The abuses before WWII didn't stop what happened afterwards. The well-documented Tuskegee study of southern black men affected by syphilis was, once revealed for its cruelty, another motivation for current IRBs.  A similar study in Guatemala and some shady doings of research in Africa because it can't be done here, all show the pressure that is needed to keep scientists under control.  Formal requirements for each research institute to form an IRB to review and approve any research done there, has led to very widely applied general standards, in principle consistent with the Nuremberg Code.  More recently up to date issues, like confidentiality in the computer-data era, have been added.

The idea is that the IRB will prevent research that violates a stated set of principles from being done in their facilities or by their employees.  Over the past few decades, everyone entering the research system has become aware (indeed, via formal training, has been made to become aware) of these rules and standards.  Every proposal must show how it adheres to them.

So, the rationale behind IRBs is unquestionably good, and much that is positive has resulted.  In broadest terms, we each know that we must pay attention to the ethical criteria for conducting research.  Of course, we are humans and the reality may not match the ideal.

From ideal to institutionalization
IRBs are committees comprised of a panel of investigators from the institution (though, even there  one can't review one's own proposals), plus administrators working for the institution, and at least one 'community' member.  The latter may be a minister, nurse, or some other outsider.

The idea is that each institution knows its own circumstances best and having its own independent IRB is better than some meddling government behemoth like, say NIH, that would make decisions from the outside (when NIH is, for example, the funder who will decide what will be funded--an obvious conflict of interest).  So those in, say, Wisconsin, know what's ethical for cheesedom, while Alabamians and San Franciscans have their own high ethical sense of self-restraint.

But this is a system run by humans, and over the decades it has become something of a System.  For example, perhaps you can imagine how a non-academic member from the community, even a minister, might be cajoled or cowed by the huge majority of insiders, the often knowingly obfuscating technological thicket of proposals, and so on.  As is also a problem for any peer review system, IRB members may or may not be anonymous, but within an institution even if they are, their identity can certainly be discovered.  They know, even if it's never said out loud, that if they scotch a proposal from someone on their campus, that person will be on the IRB in the future and could return the favor.  This can obviously be corrupting in itself, even if the IRB members take the care required to read each proposal carefully, and even if everything proposed is clearly stated.  Sometimes they do, but being on the board is a largely thankless task and how often do they not take that care?

It is not hard to see how IRBs will pay close attention to the details and insist on this or that tweak of a proposed protocol, what I call safe ethics.  They certainly do impose this sort of ethics--ethics that don't really stand in the way of what their faculty want to do.  But they may be reluctant to simply follow Nancy Reagan and just say 'no' to a major proposal.

IRB members from the administration are bureaucrats whose first instinct is to protect their institution (and, perhaps, their own jobs?).  They want to avoid public scandal and obvious abuse, but every proposal that is rejected is a proposal that can't be funded, and won't bring in overhead money and generate publications for the institution to boast about.  I have personally known of a case in a major university medical school whose administrator-member unashamedly (though privately) acknowledged discouraging their IRB from rejecting proposals because the institution wanted the overhead. You can guess whether research that ordinary people, people without a vested interest, might consider objectionable--such as unnecessary harsh experiments on hapless mice or other animals or studies that could jeopardize human confidentiality but with realistically scant likelihood to discover anything really important--is going to get a pass.  Maybe the investigator will be asked for some minor revisions.  But a lot of dicey research gets approved.

There are professional bioethicists in most large research-based universities including medical schools. They may have PhDs in ethics per se, and can be very good and perceptive people (I've trained some myself).  They write compelling, widely seen papers on their subject.  But in most cases they live directly or indirectly on grant funds.  They may get 5% or so of their salary on a grant as the project's ethicist.  Their careers, especially in medical schools, depend on bringing in external funds.  This is almost automatically corrupting.  Do you think it affords any sort of actual protection of research subjects for more than some rather formal issues like guaranteeing anonymity that usually few would object to?  How likely is it that a project's pet ethicist can say simply "No, this is wrong and you can't do it!"?  Surely it does sometimes happen, but since ethicists must make their own careers by being part of research projects, this really is an obvious case of foxes guarding hen-houses.

The Human Genome Research Institute (NHGRI) at NIH has had some fraction, we think 3%, of its research budget mandated to cover ethics related to genomic studies.  Decades of experience show that this should be re-named 'safe ethics'.  NIH does protect (where possible) against plagiarism, unethical revealing of subject identities, and that sort of thing.  But not against whole enterprises they want to fund that might be very wasteful (e.g., the funds would buy much more actual health--the 'H' in NIH--than, say, another mega-genomics study).  This is a truly and deeply ethical issue that cuts to the bone of vested interests, even in this case of the NHGRI.  If such things have ever been prohibited, we don't know of them, and they surely are the exception rather than the rule.  Even harmless research in the human rights sense, that is very costly, is an ethical affront to the competing interests of even more important things society can do with its funds.  But reports from the NIH ELSI (ethics) meetings have always been entirely consistent with the view I'm laying out here.

The truth is that in science, as in other areas of human affairs, money talks, and mutual or reciprocal interests lead to a system predominated by insider-trading.  The untold millions being spent on countless studies of humans or other animals, whose serious payoff to the society supporting them, if any, is no closer than light years away, is, in my opinion, offensive.  Peer review is not totally useless by any means, and doesn't always fund the insiders, but there are certainly major aspects of interlocking conflicts of interest in science.

Scientists are experts at hiding behind complex technical details and rhetoric, and we are as self-interested as any other group of humans.  We have our Frankensteins, who are amorally driven to study whatever interests them, rationalizing all the way that they're just innocent babes just following Nature's trail, and if what they do might be harmful (to humans, forget what it might do to mice, who can't vote) it's up to the political system, not scientists, to prevent that.  It's an age-old argument.

One must admit that having bureaucrats and real outsiders make decisions about what sort of research should be allowed, has its own problems.  Bureaucrats have careers, and often live by protecting their bailiwicks and the thicket of rules by which they wield power.  There aren't any easy answers.  And not all scientists are Frankensteins by any means, most being truly hoping to do good.  But the motivation to do whatever one wants even if, or perhaps especially if, it is edgy and has shock-value is often coin of the realm today.

Tomorrow, in Part II, we'll take a look at a most recent example, the influenza research mentioned at the beginning, of what is an abject failure at worst, and at best a questionable lack of institutional oversight of its own IRB.

Universal statins: scam....or just honest good luck for Pharma...or what?

The American Heart Association and American College of Cardiology issued new guidelines on Tuesday for reducing risk of heart disease and stroke (the first of five explanations of these new recommendations is offered here).  If you've got a 7.5% risk of heart disease or higher, as measured by their risk calculator (downloadable here), they recommend you go on statins.  This means, according to the panel, that 70 million Americans should now be considering taking these drugs.  This is perhaps 70% more than the number who now take them, and would put at least one third of all adults in the US on this drug.  For life. 

These recommendations have caused quite a ruckus, but perhaps for the wrong reasons. Before Tuesday, people were put on these drugs to lower their LDL cholesterol levels beyond a given threshold, but, confusingly to many, that threshold which we had supposed was a well-established rock-solid risk factor, has now been eliminated!  Before Tuesday, the indication for going on statins was high LDL, but the indications have now been broadened to include other risk factors such as diabetes and obesity.  So, people now taking statins wonder if they should continue, and others wonder if they need to start.  Some doctors commenting on these changes hasten to add that the most important protection against heart disease is a healthy lifestyle -- don't smoke, exercise, lose weight -- but if these can't be accomplished, statins are recommended (see Dr Harlan Krumholz on "The Newshour" on PBS, e.g.).

Wikipedia

But the new recommendation seems strange. First, a word about statins, drugs designed to control circulating lipids (fats), which confer heart-disease risks. They inhibit an enzyme called 'HMG-CoA reductase' which is expressed in liver cells as they produce cholesterol from raw ingredients and secret it into the blood stream.  Lower enzyme activity, lower circulating lipids.  But in fact, there is evidence that for some reason statins target inflammation in irritated arteries and veins, which may be what reduces risk of heart disease rather than any effect on cholesterol, so there is mystery even in the supposed reason for their supposed effectiveness.


Now, according to John Abramson and Rita Redberg in an editorial in the Thursday New York Times, statins aren't actually effective at preventing heart disease.

Statins are effective for people with known heart disease. But for people who have less than a 20 percent risk of getting heart disease in the next 10 years, statins not only fail to reduce the risk of death, but also fail even to reduce the risk of serious illness — as shown in a recent BMJ article co-written by one of us. That article shows that, based on the same data the new guidelines rely on, 140 people in this risk group would need to be treated with statins in order to prevent a single heart attack or stroke, without any overall reduction in death or serious illness.

If the recommendation is not based on evidence that everyone can agree is reliable then, where is it coming from? Partly, we think, it's a reflection of our belief that we're immortal, partly a general belief in the benefits of drug intervention.... and partly it's a reflection of the fact that some of the recommendation-makers have a vested interest in statins.

The first reason, our belief in immortality, is cultural, and of course very natural.  Few of us, even apparently those with strong religious belief in life hereafter, want to test out that belief.  Heart disease is the number 1 killer in the US and most of us don't want to die of it.

The second reason is more problematic. The most reliable way to lower heart disease risk is through diet, exercise and not smoking.  Indeed, lean, fit, non-smoking individuals whose only risk factor is high LDL are generally at low risk of heart disease.  Until this week, the purpose of statins was to lower LDL cholesterol, but that doesn't reliably lower risk of heart disease. So, are statins a good replacement for life-style?  The answer is No.

But what about the vested interest issues?  As Abramson and Redberg say:

The process by which these latest guidelines were developed gives rise to further skepticism. The group that wrote the recommendations was not sufficiently free of conflicts of interest; several of the experts on the panel have recent or current financial ties to drug makers. In addition, both the American Heart Association and the American College of Cardiology, while nonprofit entities, are heavily supported by drug companies. 

This kind of conflict of interest means that one must be highly suspicious.  One might argue that industry reps are the most knowledgeable about the benefits of their product.  If you want to know how to cure a toothache, ask a dentist, after all.  But how are we to judge the motive behind the recommendations?  Corporate-sponsored research is notoriously biased toward findings favoring their sponsor.  This doesn't mean the bias is intentional, but the evidence suggests that often it is.  At least, the corporate-sponsored research the corporate sponsors tell us about is that which favors their product, since they aren't in fact required to report all their results, and often don't.  (This is why Ben Goldacre, physician, writer and epidemiologist, started the AllTrials campaign to require that all clinical trials be registered, and all results be reported, positive and negative.)  So, when the science isn't convincing, and vested interests are involved in decision-making, it's not unreasonable to be suspicious.

Contingency and context
In addition, the related roles of context and contingency are fundamental and important to understand here.  Risk of heart disease is based on the context--genomic and environmental exposures affect the levels of statins and their consequences.  The risk in an individual is contingent on his/her situation at present, and that can change.  This seems so hard for the established system to understand!

Statins have side effects.  Risk of statin-related disease is estimated in the context of current culture.  If that culture changes, then the risks will change and by all that we know, they'll change dramatically.  If the major contexts change--better diets and so on, things we know a lot about--then the overall risk of heart disease will change.  Models can only do so well at estimating the interaction among the various factors (as the above quote suggests).  If people live healthier lives and if physicians actually pay attention to risk calculations, many may be able to go off their statins, or not start on them, as a result.

But how many will actually risk going off?  Will they keep taking, or their physicians not dare to recommend stopping, for various subjective, inertial, or even emotional reasons?  Will drug companies recommend cessation if, say, body weight goes below some value?  Will they fully advertise the fact that if other factors are favorable, to stop buying their product?  What does history--including their history--suggest to you?

And 10 years from now, how accurate will the predictions have been on which lifelong medications are now being recommended?  Will results be contingent, for example, on the current recommendations themselves?   For example, if you're on statins, will you be more likely to take that second helping of fries, feeling protected by the drug?  The Times Op-Ed puts it this way:

Perhaps more dangerous, statins provide false reassurances that may discourage patients from taking the steps that actually reduce cardiovascular disease. According to the World Health Organization, 80 percent of cardiovascular disease is caused by smoking, lack of exercise, an unhealthy diet, and other lifestyle factors. Statins give the illusion of protection to many people, who would be much better served, for example, by simply walking an extra 10 minutes per day.

These are not secret or new issues by any means, but they tend to be overlooked or minimized by a system that tries to be 'objective' based on current data.  The Op-Ed is written by respectable authors, but they are also known skeptics of the over-medicating problem, with its built-in conflicts of interest as we noted above.  So is their skepticism itself a disqualifying issue--does it mean they bias their views in a similar way to having Pharma-supported people on the panel that made the new recommendations?

Clearly, the issues are complex as so many issues related to late-onset disease are.  After all, you don't get a heart attack even at a young age like 40, unless you live to be 40.

Like second-hand smoke?  The real beneficiaries
Smokers get all sorts of diseases, because of the direct effects of the ugly weed.  But those who live in the same house also get diseases, indirectly, courtesy of their smoking cohabitant.  We have just the opposite story here.  The vendors of statins will get filthy rich as a direct result of their recommendations, whether or not they actually prevent heart disease.  And if they do, some other people--maybe the same people--will get even richer as an indirect result of the same recommendations!

If we don't die of heart disease or its associated diseases, we may live longer but that means more of us will get the slower, nastier, very expensive lingering ailments of old age.  The surgeons, retirement homes, cancer and dementia drug-makers will rake it in big-time!

We've written a few times about the subtle, surreptitious problem of competing causes, and this is another manifestation of the problem.  It's largely unavoidable that if you survive the quick-hitting earlier causes of death, you'll last and linger in service to the slower causes.  They're even more expensive.

We would not credit (nor blame) the statin-promoters for the diabolical scheming that would be involved in salivating over the indirect benefits of statin use.  That takes more perception and a longer view than most people, even scientists, usually have.  It is clear that most drug companies, not to mention the scientific research community itself, as we often write, are in for the quick kill, so to speak.

Neonicotinoids and colony collapse disorder - err on the side of caution, or just a distraction??

The cause of colony collapse disorder (CCD) in honey bees is not yet understood, but even so the European Commission decided on Monday to ban the use of neonicotinoid insecticides starting in December, for at least the next two years.  This past winter was particularly hard on bees in the US, even given the losses over the last 10 years or so since CCD was first described, with 40 to 50 percent and more decline in the bee population around the country, and the EPA is being asked to reconsider the use of these compounds in the US as well.

CCD, the sudden disappearance of worker bees from a beehive or colony, is characterized by little or no build-up of dead bees in or around the affected hives, and by the early death of adult worker bees away from the hive, leaving affected hives populated primarily by young adults.  The queen is usually still there, but without worker bees the colony can't sustain itself, and the remaining bees eventually die.

Varroa mite on honeybee larva;
Wikimedia

It's possible that a build-up of factors causes CCD. Mite and parasite infestation seems to contribute, as do viral infection and the widespread use of pesticides and fungicides, and there's some thought that the stresses involved in frequently moving hives used for pollination of commercial crops might also contribute.  Bees might be able to survive just mites or a viral infection, but if they are already weakened by one or more stressors they are more likely to succumb when more are piled on. 

A third of everything we eat depends on pollinators, so the losses are significant commercially, with the potential to become even more significant.  Many people are becoming increasingly concerned about the impact of CCD on the world food supply.  Just this spring California almond growers have had to scramble to find enough bees to pollinate their crop, after a particularly hard winter for bees, but additional crops worldwide are at risk.   

It was to prevent agricultural losses that the European Commission decided to act. “I pledge to my utmost to ensure that our bees, which are so vital to our ecosystem and contribute over 22 billion Euros [$29 billion] annually to European agriculture, are protected,” said European Union Health Commissioner Tonio Borg.

Do they or don't they?
Neonicotinoids, as we wrote in a recent post, are the newest class of insecticides in use today, and the most widely used.  They affect insect nervous systems, though are less toxic to mammals than older classes of insecticides.  Derived from nicotine and developed 2-3 decades ago, seeds are coated with these compounds and they remain within the plant as it grows, or they are sprayed on fields.

More than 30 studies have demonstrated a connection between bee deaths and neonicotinoid usage.  Two high profile studies determined that they are likely to have a negative effect on bees.  A paper published online in Science March 29, 2012 (Whitehorn et al.) reported growing evidence that neonicotinoids are involved.  Researchers exposed bees in the laboratory to levels of insecticide that mimicked what bees would encounter in the field, and found reduced growth rates and an 85% reduction in new queens produced.

A second paper published in Science at the same time  (Henry et al.) found effects of a sublethal dose of a neonicotinoid on the homing behavior of honeybees.  One of the hallmarks of CCD is that whole hives empty out, suggesting that bees might be disoriented and unable to retrace their flight paths home. 

The definitive role of neonicotinoids in CCD has not been demonstrated, but the evidence seems to be mounting.  Pesticides are at "unprecedented levels" in honeybee colonies, and because neonicotinoids are the most frequently used pesticide today, and are applied on "approximately 75 percent of the acres devoted" to the most important fruit and vegetable crops grown in the US, their role has to be considered. 

On the other hand, these compounds are in widespread use in Canada and Australia, and CCD is not nearly the problem in these countries as it is in the US and Europe, though mites are not a problem in Australia either, so it's impossible to know which essential variable in the CCD equation is missing.  Indeed, a number of studies have not shown a definitive link, or suggest other causes (e.g., this paper reporting that metals in the soil, due to vehicle exhaust, might be the cause.)  

Manufacturers maintain that neonicotinoids are safe if used as directed -- applied to seeds, in small amounts.  They will break down as the plant develops, and no longer be biologically active when pollinators are visiting the plants.  But two nicotinoids have been found in the pollen and nectar of flowers of squash plants after being applied to soil as directed, and they've been found on riverbanks as well, suggesting that the compounds aren't breaking down as supposed.

To some, there is enough evidence of the detrimental effects of neonicotinoids on bees that it is time to ban their use.  Several European countries had already done so before the European Commission banned them through the EU, and the EU ban is welcomed by many.

To others, there is insufficient evidence that these compounds are a core cause of CCD, and this ban is premature and even detrimental because it means that farmers will now have to use older insecticides, whose effects on bees have not been studied.  It's no surprise that neonicotinoid manufacturers lobbied hard against the ban and are among those most vociferously protesting it.

Win-lose or lose-lose?
The New York Times reports that worldwide sales of neonicotinoids is in the billions of dollars.  Bayer CropScience and Syngenta are two European companies that make these compounds.  The Times reports their representatives saying:

“The proposal is based on poor science and ignores a wealth of evidence from the field that these pesticides do not damage the health of bees,” John Atkin, Syngenta’s chief operating officer, said Monday in a statement. “Instead of banning these products, the commission should now take the opportunity to address the real reasons for bee health decline: disease, viruses and loss of habitat and nutrition.”

Bayer CropScience called the commission’s plan “a setback for technology, innovation and sustainability,” and warned of “crop yield losses, reduced food quality and loss of competitiveness for European agriculture.”

The view of the industry, and their interpretation of the science of CCD, and in particular the role of neonicotinoids, is of course colored by their vested interests.  But, the view of the European Commission and agribusiness is also colored by their vested interests.  They just happen to be diametrically opposed to those of the neonicotinoid industry.
 
In all of this, it is rather surprising that something that seemed to have come on suddenly just a few years ago and hence might be expected to have a rather simple, strong cause, is so hard to understand, despite many large, carefully designed studies.  A lot of the evidence we just mentioned would indeed suggest that neonicotinoids really are not the cause, or even a cause, of CCD (whether or not they should be used, based on other considerations).  Erring on the side of caution, which is what the ban is doing, may be risky because of the other costs that entails, but the problem is so serious that any chance of improving it is probably worth taking.  This is another instance of the elusive problem of identifying natural causation, and as so often happens, the evidence is largely statistical and hence difficult to interpret.

As with climate change, this has become not a strictly scientific decision but a political decision driven by business interests.  The science is rather more equivocal than with climate change, but still the approach should be the same.  When the stakes are so high, and perhaps even irreversible, the precautionary principle, erring on the side of caution, should drive decision making.  Which is just what happened with this ban.  Whether or not a two year ban is enough time to pin down the science is certainly a question, but if neonicotinoids might be part of the problem, they should be banned.

The $140 fix

In his State of the Union address to congress on Feb 12, President Obama laid out many ambitions for his next term.  It was a speech to the country and to Congress, and he stated many things he wanted to use the government for, in particular, goosing up the economy in various ways.

Like other  Presidents before him, and perhaps as is necessary given the complexity of his job and the topics he must deal with, Obama relies on lines and catch-phrases and selected data that he's been fed by advisers.  Often, as here, they represent vested interests within the Federal government.  For example, the Education secretary is bound to recommend this or that specific thing to fix our education problems.  The Energy department will recommend equally pressing needs, as will Defense and so on.

One needs to beware of the selectivity and promotional nature of factoids being cited, so as to at least be savvy about what they mean and why they're being cited--and of course to be aware that they are advocacy.  The President can only say, marionette-like, what he's told by people whose judgment he trusts, but they often do the same, passing things down the line to the primary advocates.  Just as lobbyists do provide expertise, along with their advocacy, advocacy isn't entirely self-serving.  But it can come pretty close and in a sense it's the President's, Congress's, and our responsibility to make the judgments about what is being said and what we believe are important.

Must everything we do be crass and venal?
In this context, Obama stated that the effort to 'map' the human genome has 'returned' $140 for every dollar ("--every dollar") that was spent on it.  How great!  But what does that suggest in a not very subtle way? That the science investment has value because it is good for business.  If that's the case, and apparently a great many people feel that it is, why not call it business socialism?  Or a welfare system for businesses and universities?

NIH isn't unique in playing the economy card, as well as the 'you will never get sick if you give us funds' card (and Obama repeated things NIH or others had told him along those lines, too).  It's how our system is constructed, perhaps.

Whether, when, or to what extent investment in NIH leads to a fully functional immortality is separate from the justification of funding on the grounds that it's good for business.  Obama isn't qualified to discuss whether to 'map' the human genome is the best or even a good way to remove disease from the face of the earth.  A State of the Union address may not be the place for subtle discourse.  But if we are just going to justify it on business grounds, we might as well not worry about whether, say, billions of dollars are spent on  projects that don't generate a single result, or projects that use mouse models that are totally inappropriate, or studies that grow ever larger when we know they'll find ever tinier effects, or projects that grow ever-larger research empires at the expense of intellectual freedom and the support of young scientists who could, with different distribution of resources, perhaps think more freely and have an even better chance of making discoveries that, yes, were good for the economy.

Our society perhaps simply can't be made to temper its exaggerations in support of vested interests, but we think that's a shame.  It systematically replaces substance with label, and numbs us from critical thinking.  If every word in our language must be a superlative, we'll all end up in semantic wonderland, like Lake Woebegon, all above average.

The ills, wills, and won'ts of science

Science is a rather large segment of our society, and a thoroughly human endeavor.  It's not apart from the rest of our social, economic, and political world even as it attempts to understand that world.  With thousands of universities needing students, faculty, and resources, all of us seeking prominence and recognition, the rather 'bourgeois' aspects of this social phenomenon are not unexpected. How could it be otherwise than that we'll establish hierarchies, advocacy, tribal factions competing both for ideas and funds or, more nobly, to show the others how (as we believe) the world in our area of expertise really is?

There will inevitably be pyramids of privilege and uneven wealth distribution, and in our society competition will drive this based on the widespread belief that competition (while harsh) is good for something, if not for the human soul.  In such an environment we can expect some outright cheating (pretty rare, fortunately), lots of sources of biased reporting and disingenuous 'null hypothesis' testing, dissembling, hyperbole and self-promotion.  Bureaucrats want to keep their portfolios of research projects large and richly funded.  University administrators want the overhead.  Journals want the material, and since they are businesses, the splashier the better (e.g., see this analysis of what's wrong with science publishing and how to fix it).  Ranking systems like 'impact factors' drive such bean-counting environments, naturally--how could it be otherwise?

Then there are the companies that make the instrumentation and other kinds of laboratory gear, including computers and software, that research depends on.  These companies, only naturally, will do what it takes to persuade us that their latest models are vital to success.  And what about the media?  They demand splash for their survival.  That's only natural, too.  And politicians?  They thrive on promises of health miracles, world dominance, scientific thrills, and various kinds of demagoguery by which fears are raised and their wisdom to fund research to relieve them are promised. 

So the hand-wringing and finger pointing about these problems are all only natural.  So, should we stop doing it?  We think the answer is absolutely not!  First, there will always be faults in any human endeavor, and in our type of society for a large endeavor, faults will be built (over time, by us!) into the system.  Some will corner markets better than others.  Most work will be chaff, even if there will always be amazingly insightful, skilled work that  positively contributes to knowledge.  For every Beethoven or Wordsworth,  Leonardo or Darwin, there will be a hive of drones who leave little mark on history.

Major changes rarely arise by brilliant new discoveries (the Darwins of the world), but most changes occur incrementally,  the tanker-of-science gradually changing course as fads come and go, glittering labs gradually fading as a new fad (whether good or bad) takes over.

Genome sequencing and GWAS as an example
We got many MT 'hits' last week by daring to point out that a substantial number of people are saying and writing that the payoff of GWAS and whole genome sequencing in large numbers of humans is not great and people may be tiring of it and the long-term cost commitment required, which prevents other areas (and investigators) from being funded.  There are large interests who are doing such work, and committed to it (for reasons that at least include their already vested interests, as well as various scientific rationales). They have large amounts of money, in many countries, and scientists know very well that a big project gains political investment that people will then be unwilling or unable to close down.  There are many examples, but big biobanks will be another that are just aborning.  They'll claim down the road that they are too big to fail, er, to have their funding cut. 

Of course, the focus or obsession on genes and 'omics' (large-scale, exhaustive generally hypothesis-free and  exploratory enumerations) may not fade.  Predictions that it is playing itself out by overkill or hyper-hype, may be wrong--we'll see.  Indeed, such commitments cannot fade very rapidly even if they deliver nothing at all (which isn't the case), if the hold on huge long-term funding is made.  But whether it pays off or not, there are many who feel it has co-opted too much else relative to its payoff.

This is but one example of the issues being raised about how science, The Enterprise, is being conducted these days, not by wealthy back-yard tinkerers but by a large middle class housed in large institutions.  Many worry about the faults, but of course they (and, sometimes, we) are on the cranky fringe that always exists.  Cranks can have their own agendas, including jealousy, of course.  But without at least some nudging from those who see the faults--and the faults in modern science are deep and wide--course corrections might be even harder to make, and lack of correction much costlier to the society that pays for it.

The Big Scientist Theory of Science

Samson, alpha male gorilla in Givskud Zoo

The Great, or Big Man Theory of History posits that the course of history is determined by the ways in which powerful men use their power.  Thus, history can be explained simply by understanding the men who made it.  This idea was first bruited about by the Scottish historian, Thomas Carlyle, in the 1840's ("The history of the world is but the biography of great men").   The opposite view, that society makes great men (or, makes men great), was proposed by Herbert Spencer in the mid-1800's.  And one of the most famous novels in history, War and Peace, was Tolstoy's attempt to show that the Big Man theory was wrong.  Neither view has won out, both still have their proponents.

Here we propose the Big Man Theory of Science.  Or, let's call it the Big Scientist Theory so as not to exclude women.  Perhaps in a Spencerian world, science would advance from discovery to discovery, going where the natural world takes it. The peer review system, oversight by governing bodies, and so on do, in theory, ensure that this is more or less the way science moves forward.  The tide of progress would sweep all along in its path.

But in a Carlylean world, science advances as scientists with big names and lots of money or political influence wish it to.  A scientist made a discovery, got famous, got awards, and that brought more awards.  Now Big Scientist writes visionary papers paving the way forward, makes decisions about where grant money goes, and more insidiously perhaps, but with just as much impact, makes decisions about what lesser scientists can say in their publications, s/he doesn't cite publications by lesser scientists questioning his or her work. 

Big Scientists determine the nature of the grant applications that will be written and funded for some time to come, they determine where the technological and academic investments are going to go, and so on.  They have labs full of DNA sequencers, but the human genome has been sequenced?  The next big scientific endeavor must require their use.  Big Scientist even tells people s/he knows that what s/he is proposing isn't good science, but it has to be done because the grant money must keep coming.  And science and large numbers of scientists follow, because everyone has to follow the money.

When it comes to the media, they first call the Big Scientist.  S/he then gets to expound on this or that, which again serves to set the agenda for the future, and importantly (or mainly) for future research investment.  With few if any exceptions, the Big Scientist advocates an agenda that just so happens to involve things that fit his/her interests and lab needs.
 
These are subtle and not so subtle ways that specific interests are perpetuated, and this engenders conflicts of interest that turn out to be comfortably in keeping with how science works today.  It is not a utopian vision of how things should be done, but it is the reality.  Probably in the very long run, though, it doesn't matter -- important progress will eventually be made.  Scientific ideas can outlive their sell-by date, replaced by better ideas.  But in the short and medium (and sometimes long) run, fads and influence control the momentum as Big Science run by Big Scientists turns out to be good primarily for Big Scientists.

These considerations are about science, but they are also a part of science.  Objectivity of neutral observers trying their best to falsify their ideas, is about as much a fairy tale as you'll ever hear.

The food industry trumps public health -- again

In May, 2010, the United Nations General Assembly passed a resolution on the 'Prevention and Control of non-communicable diseases' (NCDs), calling for a 'High Level' meeting of heads of state to address the issue of chronic diseases like heart disease, diabetes, respiratory diseases and cancer, largely the effects of tobacco use and alcohol abuse, poor diet, inactivity, and other lifestyle factors.  The meeting is scheduled for September 19 and 20, but according to a piece in the British Medical Journal, the prospects for this being a successful meeting aren't good.

In large part, as is turning out to be the theme of the week on MT, this has to do with industry pushing back.  Yes, the impact of non-communicable disease on morbidity and mortality, not to mention national economies, are great (as Deborah Cohen says in the piece, "One estimate is that $84bn (£51bn; €59bn) of economic output will be lost between 2005 and 2015 as a result of non-communicable diseases"), but the effects on industry of curtailing the use of sugar, salt, processed foods and so forth are of more concern to powerful industry interests.  And they are doing what they can to ensure this meeting fails.

As Cohen writes,

In the run up to the UN summit on non-communicable diseases, there are fears that industry interests might be trumping evidence based public health interventions. Will anything valuable be agreed?

The hope had been that, at the very least, with the spotlight on non-communicable diseases, the meeting would make them more visible generally, turning this into a teachable moment in terms of disease prevention.  But, pressure from the food industry is making it unlikely that governments are going to sign onto the commitment of resources for the health education campaigns that would be required to follow up.  

At a UN meeting in New York for representatives of charities and the public (called “civil society” in global health) in June—staged to allow advocates to have their say on the final political declaration [prepared before the meeting convenes]—many of the tabled speakers came from groups either representing industry or funded by industry. Speakers included representatives of the International Federation of Pharmaceutical Manufacturers and Associations, the International Food and Beverage Alliance, and the World Federation of the Sporting Goods Industry. A list of those attending the September summit on behalf of civil society also includes representatives of industry, the BMJ has learnt. GlaxoSmithKline, Sanofi-Aventis, and the Global Alcohol Consumers Group are included within the official US delegation. And drinks companies Diageo and SABMiller are coming from the UK.

And, there is conflict between the 'G77', the group of lower income states, who argue for the reduction of saturated fats in processed products, and the US, Canada, Australia, and EU, responding to pressure from the food industry.  At best, industry is willing to accept voluntary cutbacks.  

Bill Jeffery, from International Association of Consumer Food Organisations, says that the UN and WHO need to put up firewalls between their policy making processes and the alcohol and food companies “whose products stoke chronic diseases” and the drug and medical technology companies “whose fortunes rise with every diagnosed case.”

“If national leaders embrace lame vendor-friendly voluntary ‘solutions’ instead of effective regulations governing advertising, product reformulation, package labelling, government procurement, and VAT reforms, public health and national economies will strain under the burden of NCDs for generations to come,” he said.

There are political issues as well.  Money invested in NCDs is money diverted from infectious diseases and maternal and child health, and this is being resisted by many African countries, for whom NCDs are a less pressing issue, to date.

Now, whether or not it makes any material difference what the UN pronounces on this subject is a valid question. Goals put forward by such bodies are often little but words.  But, the fact that industry seems to be pushing hard to prevent even words from being put forward suggests that they at least think UN action might be more than just a document at the end of the day.

It's not that any of these interests are necessarily invalid.  The food industry has a right to profit from their products, and likewise the alcohol and tobacco industries.  A lot of people make their living working in such industries, and countless people enjoy their products.  But it is also true that food and alcohol consumption patterns lead to very large health-care bills, and we all one way or another have to foot that bill, so the industry is not the only entity with a legitimate interest in the discussions.  What the relative costs and benefits are, and who should bear them, or how, are part of the equation, or should be.  Fair apportionment could be based on item-specific taxes, behavior-based health care premiums, or whatever.  But they should be based on considering the whole situation.

The results of a meeting on preventing and reducing non-communicable diseases should concern just that, and not be derailed (or pre-railed) by other, competing interests before the results are even presented. If governments ultimately decide that industry interest trumps public health, fine (well, in our view, not fine, but governments do have to weigh competing interests), but at least it should be clear that that's what happening.  Instead, when, according to Cohen, "PepsiCo have secured the prime side-event slot at the UN meeting: a breakfast event from 8-10 am on the morning of the summit", and industry is helping mold the final product, public health interests don't t even get a clear shot.