McSweeney’s is getting into the genetic satire act. Plenty of room, folks, plenty of room. Funny piece: http://www.mcsweeneys.net/articles/congratulations-your-ineffectual-genetic-test-results-have-arrived
McSweeney’s is getting into the genetic satire act. Plenty of room, folks, plenty of room. Funny piece: http://www.mcsweeneys.net/articles/congratulations-your-ineffectual-genetic-test-results-have-arrived
Here it is, 2014, and we have “Is the will to work out genetically determined?,” by Bruce Grierson in Pacific Standard (“The Science of Society”).
The story’s protagonist is a skinny, twitchy mouse named Dean who lives in a cage in a mouse colony at UC Riverside. Dean runs on his exercise wheel incessantly—up to 31 km per night. He is the product of a breeding experiment by the biologist Ted Garland, who selected mice for the tendency to run on a wheel for 70 generations. Garland speculates that Dean is physically addicted to running—that he gets a dopamine surge that he just can’t get enough of.
Addiction theory long ago embraced the idea that behaviors such as exercise, eating, or gambling may have similar effects on the brain as dependence-forming drugs such as heroin or cocaine. I have no beef with that, beyond irritation at the tenuous link between a running captive mouse to a human junkie. What’s troubling here is the genetic determinism. My argument is about language, but it’s more than a linguistic quibble; there are significant social implications to the ways we talk and write about science. Science has the most cultural authority of any enterprise today—certainly more than the humanities or arts!. How we talk about it shapes society. Reducing a complex behavior to a single gene gives us blinders: it tends to turn social problems into molecular ones. As I’ve said before, molecular problems tend to have molecular solutions. The focus on genes and brain “wiring” tends to suggest pharmaceutical therapies.
To illustrate, Grierson writes,
File this question under “Where there’s a cause, there’s a cure.” If scientists crack the genetic code for intrinsic motivation to exercise, then its biochemical signature can, in theory, be synthesized. Why not a pill that would make us want to work out?
I have bigger genes to fry than to quibble over the misuse of “cracking the genetic code,” although it may be indicative of a naiveté about genetics that allows Grierson to swallow Garland’s suggestion about an exercise pill. Grierson continues, quoting Garland,
“One always hates to recommend yet another medication for a substantial fraction of the population,” says Garland, “but Jesus, look at how many people are already on antidepressants. Who’s to say it wouldn’t be a good thing?”
I am. First, Jesus, look at how many people are already on anti-depressants! The fact that we already over-prescribe anti-depressants, anxiolytics, ADHD drugs, statins, steroids, and antibiotics does not constitute an argument for over-prescribing yet another drug. “Bartender, another drink!” “Sir, haven’t you already had too much?” “Y’know, yer right—better make it two.”
Then, what if it doesn’t work as intended? Anatomizing our constitution into “traits” such as the desire to work out is bound to have other effects. Let’s assume Dean is just like a human as far as the presumptive workout gene is concerned. Dean is skinny and twitchy and wants to do nothing but run. Is it because he “wants to exercise” or is it because he is a neurotic mess and he takes out his anxiety on his wheel? Lots of mice in little cages run incessantly—Dean just does it more than most. His impulse to run is connected to myriad variables, genes, brain nuclei, and the reported results say nothing about mechanisms. We now know that the physiological environment influences the genes as much as the genes influence physiological environment. The reductionist logic of genetic determinism, though, promotes thinking in terms of a unidirectional flow of causation, from the “lowest” levels to the “highest.” The more we learn about gene action, the less valid that seems to become as an a priori assumption. The antiquated “master molecule” idea still permeates both science and science writing.
Further, when you try to dissect temperament into discrete behaviors this way, and design drugs that target those behaviors, side effects are sure to be massive. Jesus, look at all those anti-depressants, which decrease libido. Would this workout pill make us neurotic, anxious, jittery? Would we become depressed if we became injured or otherwise missed our workouts? Would it make us want to work out or would it make us want to take up smoking or snort heroin? In the logic of modern pharmacy, the obvious answer to side effects is…more drugs: anti-depressants, anxiolytics, anti-psychotics, etc. A workout pill, then, would mainly benefit the pharmaceutical industry. When a scientist makes a leap from a running mouse to a workout pill, he is floating a business plan, not a healthcare regimen.
And finally, what if it does work as intended? It would be a detriment to society, because, having a pill, it would remove yet another dimension of a healthy lifestyle from the realm of self-discipline, autonomy, and social well-being. It becomes another argument against rebuilding walkable neighborhoods and promoting public transportation and commuting by bicycle. A quarter-mile stroll to an exercise addict would be like a quarter-pill of codeine for a heroin junkie—unsatisfying. Not only is this putative workout pill a long, long stretch and rife with pitfalls, it is not even something worth aspiring to.
And that’s just one article. Scientific American recently ran a piece about how people who lack the “gene for underarm odor” (ABCC11) still buy deodorant (couldn’t possibly have anything to do with culture, could it?). Then there was their jaw-dropping “Jewish gene for intelligence,” which Sci Am had already taken down by the time it appeared in my Google Alert. I’d love to have heard the chewing out someone received for that bone-headed headline. Why do these articles keep appearing?
The best science writers understand and even write about how to avoid determinist language. In 2010, Ed Yong wrote an excellent analysis of how, in the 1990s, the monoamine oxidase A (MAOA) gene became mis- and oversold as “the warrior gene.” What’s wrong with a little harmless sensationalism? Plenty, says Yong. First, catchy names like “warrior gene” are bound to be misleading. They are ways of grabbing the audience, not describing the science, so they oversimplify and distort in a lazy effort to connect with a scientifically unsophisticated audience. Second, there is no such thing as a “gene for” anything interesting. Nature and nurture are inextricable. Third, slangy, catchy phrases like “warrior gene” reinforce stereotypes. The warrior gene was quickly linked to the Maori population of New Zealand. Made sense: “everyone knows” the Maoris are “war-like.” Problem was, the preliminary data didn’t hold up. In The Unnatural Nature of Science, the developmental biologist Lewis Wolpert observed that the essence of science is its ability to show how misleading “common sense” can be. Yet that is an ideal; scientists can be just as pedestrian and banal as the rest of us. Finally, Yong points out that genes do not dictate behavior. They are not mechanical switches that turn complex traits on and off. As sophisticated as modern genomics is, too many of us haven’t moved beyond the simplistic Mendelism that enabled the distinguished psychiatrist Henry H. Goddard to postulate—based on reams of data collected over many years —a single recessive gene for “feeblemindedness.” The best method in the world can’t overcome deeply entrenched preconception. As another fine science writer, David Dobbs, pithily put it in 2010, “Enough with the ‘slut gene’ already…genes ain’t traits.”
As knowledge wends from the lab bench to the public eyeball, genetic determinism seeps in at every stage. In my experience, most scientists working today have at least a reasonably sophisticated understanding of the relationship between genes and behavior. But all too often, sensationalism and increasingly greed induce them to oversell their work, boiling complex behaviors down to single genes and waving their arms about potential therapies. Then, public relations people at universities and research labs are in the business of promoting science, so when writing press releases they strive for hooks that will catch the notice of journalists. The two best hooks in biomedicine, of course, are health and wealth. The journalists, in turn, seek the largest viewership they can, which leads the less scrupulous or less talented to reach for cheap and easy metaphors. And even though many deterministic headlines cap articles that do portray the complexity of gene action, the lay reader is going to take away the message, “It’s all in my genes.”
Genetic determinism, then, is not monocausal. It has many sources, including sensationalism, ambition, poor practice, and the eternal wish for simple solutions to complex problems. Science and journalism are united by a drive toward making the complex simple. That impulse is what makes skillful practioners in either field so impressive. But in clumsier hands, the simple becomes simplistic, and I would argue that this risk is multiplied in journalism about science. Science writing is the delicate art of simplifying the complexity of efforts to simplify nature. This is where the tools of history become complementary to those of science and science journalism. Scientists and science writers strive to take the complex and make it simple. Historians take the deceptively simple and make it complicated. If science and science journalism make maps of the territory, historians are there to move back to the territory, in all its richness—to set the map back in its context.
Studying genetics and popularization over the last century or so has led me to the surprising conclusion that genetic oversell is independent of genetic knowledge. We see the same sorts of articles in 2014 as we saw in 1914. Neither gene mapping nor cloning nor high-throughput sequencing; neither cytogenetics nor pleiotropy nor DNA modification; neither the eugenics movement nor the XYY controversy nor the debacles of early gene therapy—in short, neither methods, nor concepts, nor social lessons—seem to make much of a dent in our preference for simplistic explanations and easy solutions.
Maybe we’re just wired for it.
Charles Seife’s piece over at sciamblogs the other day gave me one of those forehead-slapping, “if-it-was-a-double-helix-it-would-have-bit-me” moments. For 23andMe, the “test” or genome profile is small potatoes. The real product of 23andMe isn’t the saliva test.
It’s the database, stupid.
Think about gmail or Facebook. When you sign up for a “free” account you agree to allow them to send you targeted promotions, in the form of ads that appear in the margins. It’s hilarious how bad their algorithms are. When I rant about some bonehead right-wing politician, I start getting suggestions to follow Mitt Romney. When my wife posted wedding pictures, she got ads for wedding registries. My google profile is amazingly bad–mixed in with a few genuine interests, it lists dozens of things I have no interest in whatsoever (fishing, dolls and accessories, apartments and residential rentals) as well as things so general they say nothing meaningful about me (consumer resources, search engines). I’ve often found that reassuring. Though I know the software is bound to get better, it’s comforting at least for the moment to know that they don’t actually know me that well. I’m not naive enough to think that will last forever.
What 23andMe is really about, says Seife, is doing that same kind of profiling with your genome. Historians and anthropologists of science have long been interested in “biologization” and “medicalization.” Ugly words, useful concepts. Biomedicine tends to shift our gaze from labor to biology (and especially health). Is violence a crime or a disease? Do you identify more strongly as a carpenter, soldier, or professor, vs. as celiac, PTSD, or a breast-cancer survivor? Conceiving some corner of our world in biological terms can have profound implications. If violence is a crime, we treat it with fines, incarceration, or death. If it is an organic disease, we treat it with drugs and counseling. Conceivably, we may someday treat it with gene therapy. As Foucault pointed out, both criminalization and medicalization involve behavior modification–just in different formats. Medicalization can be more humane, but it can also strip away one’s autonomy and subtly and dangerously shift power relationships.
Every time someone sends in their little vial of spit to 23andMe, the company adds to a large-and-growing database of genomic data linked to a broad range of personal tastes and behaviors. Like Google and Facebook, they make you agree to let them send you ads based on the data they collect, which is augmented by their social-media site. It is a genomic version of Google. Welcome to the all-volunteer biological surveillance state.
Seife points out that Anne Wojcicki was married to Google co-founder Sergei Brin, that Google is a heavy investor in 23andMe, and that the price of the saliva test has been dropping steadily and is now below $100.
My cynical view is that the company has an easy end-around available for the FDA letter demanding that they halt marketing their test: give it away. It’s not marketing if they’re not selling, right? Investopedia defines marketing as “The activities of a company associated with buying and selling a product or service.” It does go on to list advertising as one key aspect of marketing, but I wonder whether they could successfully argue that promoting a free product isn’t marketing per se.
Legal definitions aside, if Seife is right, my guess is that before long genome profiling will be like web browsers and email: something almost everyone does, and that except for a few willing to pay for a premium private service, something that provides so many benefits that we tolerate its ads as a necessary trade-off of modern life.
Is this any more insidious than gmail? If we say yes, we risk running headlong into the genetic determinism this blog rails against. We have to be careful about privileging biological information over social information. If Facebook’s suggestions are laughable, they’d likely seem prescient in comparison with what they’d predict based on my genomic profile. The “genes for” most things explain tiny amounts of variance and tend to have low penetrance. Other than a few strongly Mendelian diseases, a genome profile currently says very little about you, simply because it’s based on small probabilities of uncertain precision.
But like the algorithms analyzing your social profile, those combing your genomic profile will improve, and probably at a rate faster than any of us expect. Most importantly, your genomic profile will merge with your social profile, which will greatly enhance the accuracy of both. Your social profile will become biologized–rooted in and interwoven with your DNA.
The gradual way in which 23andMe is heading toward an open-source business model may simply reflect the high cost of getting the biotech version of Google Plus off the ground. As profits increase, they can afford to drop the price. When it hits zero–when they start giving away the test–rest assured that ad revenues will then be enough to keep the shareholders happy.
Yesterday I and seemingly everyone else interested in genomes posted about the FDA letter ordering the genome diagnostics company 23andMe to stop marketing their saliva test. FDA treats the test as a “medical device, because “it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body.” The company first issued a bland, terse statement acknowledging the letter and then company president Anne Wojcicki signed a short post affirming the company’s commitment to providing reliable data, promising cooperation with FDA, and reasserting her faith that “genetic information can lead to better decisions and healthier lives.” (I say she “signed” it because of course we have no way of knowing whether she composed it and she’s no fool: surely the text was vetted by Legal.) In other words, the company followed up with a bland, less-terse response, carefully worded to reassure customers of the company’s ethical stance and core mission. Reactions to the FDA letter range from critics of the company singing “Hallelujah!” to defenders and happy customers are attacking FDA for denying the public the right to their own data. The 23andMe blog is abuzz and, hearteningly, a few sane souls there are trying to dispel misinformation.
I am doing history on the fly here. If journalism is the first draft of history, let’s take a moment to revise that first draft—to use the historian’s tools to clear up misconceptions and set the debate in context as best we can. The history of the present carries its own risks. My and other historians’ views on this will undoubtedly evolve, but I think it’s worth injecting historical perspective into debates such as these as soon as possible.
We must be clear that the FDA letter does not prohibit 23andMe from selling their test. It demands they stop marketing it. The difference may not amount to much in practice—how much can you sell if you don’t market your product?—but the distinction does help clarify what is actually at stake here. FDA is not attempting to instigate a referendum on the public’s access to their own DNA information. They are challenging the promises 23andMe seems to make. This is, in short, not a dispute about access, but about hype.
The company seems to promise self-knowledge. The ad copy for 23andMe promises to tell you what your genome “says about you.” “The more you know about your DNA,” they trumpet, “the more you know about yourself.” On one level, that’s perfectly, trivially true: your genome does have a lot to do with your metabolism, body structure, how you respond to disease agents, and so forth. The problem is, we as yet know very little about how it all works. The 23andMe marketing exploits a crucial slippage in the concept of “knowledge,” which FDA correctly finds misleading. In short, the marketing implies a colloquial notion of knowledge as a fixed and true fact, while the science behind the test is anything but.
Historians and other scholars of science have thought a lot about the concept of scientific knowledge. In 1934, Ludwik Fleck wrote about the “genesis and development of a scientific fact,” namely the Wasserman test for syphilis. It is a pioneering classic in a now-huge (and still growing) literature on how scientific facts are created. Science claims to gather facts about nature and integrate them into explanations of natural mechanisms. A moment’s reflection reveals that very few scientific facts last forever. Most, perhaps all, undergo revision and many are discarded, overthrown, or reversed. They are historical things, not universal truths. A surprisingly small amount of what I learned in science courses 20 and 30 years ago is still true. As that great philosopher of science John McPhee wrote, “science erases what was previously true” (Oranges, p. 75). Because scientists search for universal, timeless mechanisms, they easily slip into language suggesting that they discover universal, timeless truth. But there is uncertainty, contingency, malleability built into every scientific fact.
This goes double for genome information. The 23andMe product, like every genome test, provides probabilities of risk, not mechanisms. Probabilities are messy and hard to understand. They carry an almost irresistible tendency to be converted into hard facts. If you flip a coin 9 times and it comes up heads every time, you expect the next flip to come up tails. And if you get heads 49 times in a row, the next one has got to be tails, right? Even if you know intellectually that the odds are still 50:50, just like on every previous flip. You can know you have a particular gene variant, but in most cases, neither you nor anyone else knows exactly what that means. Despite the language of probability that dots the 23andMe literature, their overall message—and the one clearly picked up by many of their clientele—is one of knowledge in the colloquial sense. And that is oversell.
Human genetics has always been characterized by overstatement and hype. In the early 1900s, the rediscovery of Mendel’s laws persuaded many that they now understood how heredity works. Although every scientist acknowledged there was still much to learn, prominent students of human heredity believed they knew enough to begin eliminating human defects through marriage and sterilization laws. We now view such eugenic legislation as almost unbelievably naive. Combine that naivete with race, gender, and class prejudice and you obtain a tragically cruel and oppressive eugenics movement that resulted in the coerced sterilization of many thousands, in the US and abroad—including, of course, the Nazi sterilization law of 1933, based on the American “model sterilization law,” which culminated not only in racist forced sterilization but euthanasia.
Human-genetic hype hardly ended with the eugenics movement. In 1960s, as human diseases were finally being mapped to chromosomes, it seemed transparent that if a chromosomal error that produces an individual with an XXY constitution feminizes that individual (which it does), then an extra Y chromosome (XYY) must masculinize. Such “super-males,” data seemed to suggest, were not only taller and hairier than average, but also more aggressive and violent. It was, for a while, a fact that XYY males were prone to violent crime.
The molecular revolution in genetics produced even more hype. When recombinant DNA and gene cloning techniques made it possible to try replacing or augmenting disease genes with healthy ones, DNA cowboys hyped gene therapy far beyond existing knowledge, promising the end of genetic disease. The 1995 Orkin-Motulsky report acknowledged the promise of gene therapy but noted,
Overselling of the results of laboratory and clinical studies by investigators and their sponsors…has led to the mistaken and widespread perception that gene therapy is further developed and more successful than it actually is.
Soon after this report was published, Jesse Gelsinger died unexpectedly in a gene-therapy trial, patients in a French gene-therapy trial for adenosine deaminase (ADA) deficiency unexpectedly developed leukemia, and the gene-therapy pioneer W. French Anderson was arrested, tried, and convicted on charges of child molesting—in other words, abusing and overestimating his power over the children whose health was entrusted to him. The risks of failing to heed warnings about genetic oversell are high.
Like gene therapy, genome profiling has great promise, but the FDA letter to 23andMe is a stern reprimand to an industry that, like gene therapy and the entire history of human genetics, blurs the line between promise and genuine results.
The current controversy over commercial genome profiling has two qualities that distinguish it as particularly serious. First, unlike previous examples of overselling human genetics, it is profit-driven. The “oversell” is more literal than it has ever been. Although 23andMe presents as a concerned company dedicated to the health of their clientele, they are also—and arguably primarily—dedicated to their stockholders. In a for-profit industry, oversell is a huge temptation and that risk needs to be made transparent to consumers.
Second, the 23andMe test is being sold directly to individuals who may not have any knowledge of genetics. The tendency to convert risks into certainty is higher than ever. The knowledge they sell is a set of probabilities, and further, those probabilities are not stable. The consumer may not—indeed probably doesn’t—appreciate how much we know, how much we don’t know, and how much we don’t even know we don’t know. The company claims to be selling knowledge but in fact they are selling uncertainty.
In a characteristically insightful and clarifying post, the geneticist (and 23andMe board member) Michael Eisen doubts whether the 23andMe test will ever meet FDA’s definition of a “medical device.” It is not an MRI machine or a Wasserman test. It’s something new. Adequate regulation of products such as the 23andMe genome profile will require rethinking of what exactly the company is marketing.
Putting this controversy in context, then, illustrates another critical risk: the risk of failing to acknowledge the uncertainty underlying the science. In some sense, the more we learn, the less we know.
 Orkin, S. H., and A. Motulsky. Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy. Bethesda, MD: National Institutes of Health, 1995.
Hey honey–remember when I accidentally left the chicken coop open and they all flew away? Well I think they’ve come back home to roost!
Last summer, we did an analysis of the 23andMe commercial promoting their genetic testing service and the egotistical identity politics it both taps into and contributes to. The ad was all about how your genes were “You” and knowing about them would enable you to predict your genetic future. Genetic profiling can in some cases give robust statistical estimates of likelihood of certain genetic conditions, but it is safe to say that we rarely know what that means. And it’s presented as though we do.
Now we find that FDA is ordering 23andMe to stop marketing their tests.
The 23andMe saliva sample kit, says FDA, is a “medical device,” “intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body.
They cite the company’s claims to allow patients’ genome profiles to help them assess “health risks,” and “drug response,” and specifically as a “first step in prevention” that enables users to “take steps toward mitigating serious diseases” such as diabetes, coronary heart disease, and breast cancer.
This is not a shot over the bow–it’s the last straw. FDA has warned 23andMe repeatedly, going back to July, 2012, that they were making health claims about their product that they couldn’t back up.
The company offers two types of products: a genealogical “panel” or profile, and a health panel. The genealogical panel is popular but is apparently considered a harmless hobby, or at least outside the purview of the Public Health Service. It is not clear whether FDA (which, like the National Institutes of Health and the Centers for Disease Control) falls under the sprawling PHS will have any concerns about genealogical applications of the saliva test, but that would seem unlikely. The problem for 23andMe is that, as shown by the ad we analyzed earlier, they have been pushing the health panel very hard. Family trees are a hobby; health is where the real money is.
Direct-to-consumer medicine trails an appealing democratic, anti-authoritarian perfume that seems to make people slightly drunk. Mild intoxication can be pleasant, need not be dangerous, and sometimes can be a spur to creativity. But it can also impair your judgment. When you’ve gotta drive the kids home, you may need a couple cups of good strong regulatory coffee and a couple hours to sober up before getting behind the wheel.
A good deal of “preventive, participatory, personalized” medicine is profit-driven, and stockholders don’t necessarily have the public’s health foremost in mind. The FDA warning is a good illustration of why it’s important to balance the goal of stimulating innovation and economic growth with the goal of maximizing health. For the former, the free market can be a powerful tool. But for the latter, sometimes you need a little good old-fashioned meritocratic oversight.
Thoughtful blog post over at Nature recently by Erika Check, on a $25M set of 4 studies that will sequence the exomes of 1500 neonates, whether ill or not. Called the Genomic Sequencing and Newborn Screening Disorders program, it is essentially a pilot study for universal newborn genome sequencing. One could see such a study coming down the pike. But if this is a direction in which medicine is heading, we should be moving like a wary cat, not like a bounding puppy.
The dominant rhetoric for whole-genome screening sketches a benevolent world of preventive care and healthier lifestyles. “One can imagine a day when every newborn will have their genome sequenced at birth,” said Alan Guttmacher, director of NICHD, which co-sponsors the program with the genome Institute. In his genotopian vision, a baby’s sequence “would become a part of the electronic health record that could be used throughout the rest of the child’s life both to think about better prevention but also to be more alert to early clinical manifestations of a disease.”
But deeper in her article, Check responsibly quotes a skeptic, Stephen Kingsmore of Children’s Mercy Hospital and Clinics in Kansas City, who estimates that the program is likely to find 20 false positives for every true positive. In other words, only around 5% of what will loosely be called “disease genes” will in fact lead to disease. One of the reasons for that low rate of true positives is that many of the disease alleles we can screen for concern diseases of old people: Alzheimer’s, various cancers, and so on. Life experience plays a large and still imperfectly understood role in such diseases. Sure, we can test at birth or even before for the SNPs we know correlate with those diseases, but, Check asks, what does that really tell us?
In Guttmacher’s sunny scenario about early prevention, the parents and later the child could be regularly reminded of this individual’s elevated risk. This itself has not only direct health risks but potentially a significant inadvertent impact on the patient’s social life. Everything from the child’s temperament (is she anxious by nature?) to family situation (ill siblings? Alcoholic parent? Suicide?) to many other factors could profoundly modulate how this genetic knowledge would affect the child. Social context matters.
But such an individualized, lifelong health-maintenance program is unlikely ever to be accessible beyond medicine’s most elite customers. Personalized medicine has been around since the ancient Greeks, and, logically enough, it’s expensive. Only the rich have ever been able to afford truly individualized care. “Personalized medicine” seems to have almost as many meanings as people who use the term, but if what you mean by personalized medicine is a physician who knows you as an individual and tracks your healthcare over a significant part of your lifetime, you’re talking about elite medicine.
Medicine for the middle and lower classes tends to be much more anonymous and impersonal. Throughout medical history, the headcount–if they can afford a doctor at all–get more routinized, generalized care. Even many in that fortunate segment of the population today who have health insurance attend clinics where they do not see the same doctor every time. In any given visit, their doctor is likely to know them only by their chart. No one asks, “Has your family situation settled down yet? Are you sleeping better? How’s your new exercise program going?” What you get is a 15-minute appointment, a quick diagnosis, and, usually, a prescription. Genomic technology is unlikely to change this situation. If anything, it will enhance it.
For the hoi polloi, then, personalized medicine will likely mean personalized pharmacology. Some of those most excited about personalized medicine are biotech and pharma companies and their investors, because some of the most promising results from genomic medicine have been new drugs and tests. Should neonatal genome screening become part of routine medical care, middle and lower-class parents would likely be given a report of their child’s genome, the associated disease risks, and a recommended prophylactic drug regimen. Given an elevated risk of high cholesterol or other heart disease, for example, you might be put on statins at an early age. A SNP associated with bipolar disease or schizophrenia might prompt preventive anti-depressants or anti-psychotics. And so forth.
Such a program would be driven first by the principles of conservative medical practice. Medicine plays it safe. If there’s a risk, we minimize it. If you go to the ER with a bad gash, you’ll be put on a course of antibiotics, not because you have an infection but to prevent one. Second, it would be driven by economics. Drug companies obviously want to sell drugs. So they will use direct-to-consumer marketing and whatever other tools they have to do so. That’s their right, and in a comparatively unregulated market, arguably their duty.
But now recall Kingmore’s figure of 20 false positives for every true positive. This may sound high, but again, medical practice is conservative: we’d rather warn you of a disease you won’t get than fail to notify you of a disease you will get. False positives, in other words, are preferable to false negatives. Add to that the scanty state of our knowledge of gene-environment interactions. We are rapidly accumulating mountains of data on associations between SNPs and diseases, but we still know little about how to interpret the risks. We needn’t invoke any paranoid conspiracy theory: that kind of data is devilishly hard to acquire. Science is the art of the soluble.
If Kingmore is even in the ballpark, then, the more neonatal genome screening reaches into the population, the more unnecessary drugs people will be taking. Unnecessary medication of course can have negative effects, especially over the long term. Indeed, the long-term and developmental effects of many medications–especially psychiatric medications–are unknown.
The Genomic Sequencing and Newborn Screening Disorders program is purely an investigative study. Parents in this study won’t even be given their children’s genome reports. But the study is obviously designed to investigate the impact of widespread neonatal whole-genome screening. Currently, all 50 states administer genetic screening for phenylketonuria and other common diseases. The historian Diane Paul has written a superb history of PKU screening. It’s not hard to imagine a similar scenario playing out, with one state leading the way with a bold new program of universal newborn exome screening and, in a decade or two, all other states following its lead.
“Personalized medicine” is a term that’s used increasingly loosely. It covers a multitude of both sins and virtues, from old-fashioned preventive regimens to corporate profiteering. From here, widespread neonatal genome screening looks like an idea that will benefit shareholders more than patients.
Guest Post by Mark A. Largent
Medical advice—long under the authority of doctors and public health officials—is now freely available on the Internet, and nowhere are the effects of this trend more visible than around the issue of vaccines. The web provides easy access to the kinds of criticism of vaccines that was once available only from fringe natural-health booksellers and alternative medical providers. In an effort to counter these claims, mainstream healthcare providers offer orthodox scientific and medical information to consumers on the Internet. The result is a set of competing claims online that are nearly impossible for parents to reconcile into a coherent plan for vaccinating their children.
Reports of two court cases have recently emerged online that powerfully demonstrate how readers on either side of the debates over the safety of vaccines are armed with evidence to support wildly divergent views. Among mainstream medical providers, the widespread consensus is that there is no causal link between vaccines and autism. However, over the last several weeks, news has circulated on alternative medical sites about two federal court decisions that “confirmed … that there is a link between the MMR [measles, mumps, and rubella] vaccine, autism, and stomach disorders.” Citing court records, news reports (which have also been published in mainstream sources like the Huffington Post) purport to show “repeated admissions by drug companies and government alike that vaccines do in fact cause autism.”
Here are the facts of the cases: The federal court that hears cases of people allegedly injury by vaccines has recently decided in favor of the parents of two children who say that their children developed symptoms of autism because of the adverse side effects of vaccines. The so-called “vaccine court,” which was established by the 1986 National Childhood Vaccine Injury Act, is charged with resolving vaccine injury claims and provides compensation from a trust fund that is financed by a 75 cent excise tax on every vaccine. Vaccine manufactures are protected from lawsuits because the vaccine court hears claims and pays injured parties from the trust without ever assigning fault. The court typically pays out between $100 and $200 million per year.
In the first case, the court decided that a 10-year-old boy from California named Ryan Mojabi suffered a “severe and debilitating injury to his brain, described as Autism Spectrum Disorder” that was caused by brain swelling that occurred after he had been vaccinated with MMR. As a result, Ryan now suffers from the symptoms associated with autism. He was awarded an undisclosed amount that could total $10 million or more.
In a second case, which had been in and out of court for nearly a decade, 15-month-old Emily Moller had developed a high fever and seizures after being vaccinated with the combined vaccine against diphtheria, pertussis, and tetanus. She has been diagnosed on the autism spectrum. Late last year the case was settled, and Emily will receive an estimated $9 million in compensation.
These cases provide a tremendously powerful rhetorical weapon to those who claim that vaccines can cause autism. Reports of the cases are circulating widely on the web, and they add fuel to the online debates that confront new parents as they seek out information on vaccines. Both children had suffered from rare but documented adverse side effects from being vaccinated, and in both cases serious long-term damages are evident. It is doubtlessly unfortunate that these children were injured in the course of receiving routine vaccines, but cases like theirs are very rare, and vaccines safely protect the vast majority of children against diseases that once caused considerable death, injury, and discomfort.
How, then, did we end up in a situation where incredibly uncommon cases like Ryan’s or Emily’s have so much rhetorical power? And, what are we to make of these two cases? The problem, I submit, does not reside in the vaccines themselves, but in the fact that we have failed to have honest conversations about difficult issues related to vaccines.
Today’s concerns about vaccines can be traced to allegations that emerged in the late 1990s of a link between vaccines and autism. In Britain, a preliminary report by a research team suggested that the MMR vaccine might sometimes damage children’s digestive tracts, which in turn might lead to developmental disorders associated with autism. At about the same time, as part of an overhaul of the Food and Drug Administrative, reports emerged that a mercury-laden preservative—Thimerosal—had long been used in childhood vaccines. The symptoms of mercury poisoning share many similarities with autism and public health authorities had long warned parents of the dangers of heavy metals like mercury and lead, so parents were shocked to learn that their children had been injected with vaccines that contained mercury.
Both of the scientific controversies that alleged an association between vaccines and autism were resolved by 2004. Today, the consensus of the scientific and medical communities is that neither the MMR vaccine nor Thimerosal is responsible for the recent rapid increase in the diagnoses of autism. Instead, most authorities point to increasing awareness, relaxed diagnostic criteria, and a number of social and economic incentives for diagnoses to explain the increasing rate of diagnoses.
While the scientific controversy over the alleged link between vaccines and autism has been resolved for almost a decade now, the political controversy has continued to rage. Advocates of the claim that vaccines cause or trigger the symptoms associated with autism have developed an alternative set of news sources to provide evidence to those who believe that vaccines are unsafe and that the government and mainstream media are covering up the evidence. As the potentially complicated discussions about the merits and potential problems of the modern vaccine schedule have become confined almost entirely to the vaccines-cause-autism debate, advocates on either side of the issue promulgate irreconcilable claims.
In my 2012 book Vaccine: The Debate in Modern America, I argue that the rapid increase in the size of the vaccine schedule and Americans’ increasing concerns about vaccines were not merely coincidental. Under today’s vaccine schedule a fully vaccinated 6-year old will have received about three dozen inoculations of over 50 vaccines, most of them in the first 18 months of life. This has motivated considerable concern among parents about unintended side effects of vaccines. About 40% of American parents report that they have intentionally refused or delayed a recommended vaccine for their children, and about 1 in 8 parents have refused a state-mandated vaccine. Safety concerns about new vaccines and a widespread belief that we give too many vaccines, too early, against too many diseases are at the root of many parents’ concerns. Vaccine-anxious is the term I used for people who expressed concerns like these while generally accepting that vaccines are usually safe and effective. Elsewhere, I have argued that we ought to be very careful about mistakenly labeling vaccine-anxious people as anti-vaccinators. In terms of maintaining high levels of vaccine compliance, they are effectively “swing-voters,” and it is vital that we keep them within the fold. By mislabeling them as anti-vaccinators, we push them into the arms of those who have amassed ample evidence to support their fears about unintended side effects from vaccines.
Concerns that vaccines might cause autism are actually a proxy for a much more complex set of concerns, which I describe in the book. Some of these are practical, like how we cram as many as six vaccinations into one office visit. Others are moral, because half of childhood vaccines were researched and produced with the use of cells derived from aborted fetuses. Still others are deeply philosophical, including concerns that we have entered a realm of medical enhancements that fundamentally alter human beings. The vaccines-cause-autism proxy debate allows us to avoid actually engaging these complicated topics. It also allows many different views to gather under a single set of claims, which explains why criticisms of vaccines are launched by voices from every corner of the political spectrum.
The two cases from the vaccine court that have generated so much discussion among opponents of the modern vaccine schedule are influential only because we have failed to engage the real issues that animate the vaccines-cause-autism proxy debate. Until we do, the large and active community of people who express serious concerns about vaccines will continue amass evidence that will adversely affect the decisions of millions of vaccine-anxious parents.
Mark A. Largent is a historian of science and medicine and an Associate Dean and Associate Professor at Michigan State University. His teaching and research focus on the role of scientists and physicians in public policy debates. His most recent book, Vaccine: The Debate in Modern America (Johns Hopkins, 2012) analyzes the vaccine-autism debate and contemporary concerns about the modern vaccination schedule. He is currently completing a book on the history of Reye’s syndrome.