Tag Archives: genomics

DNA as Commodity

Here’s a riddle: In the morning I was in the soup. At noon I was in a dish. In the afternoon I was in your gas tank. And at night I am in the bank. What am I?

The answer is DNA. From a natural object emerging, some say, from a primordial soup, to a laboratory object, to a cultural object, it has become data, a special string of computer code endowed with the power to foretell disease, identify criminals, and be leveraged, like software, as a product.

from venturebeat.com

Robert Resta, a genetic counselor and always a reliable source of depressing, ironic, frightening, and amusing stories about heredity and DNA, forwards this piece, by @alexlash, from Xconomy.com on how your DNA is becoming commodified. What’s happening is interesting not for how new it is, but for the way in which the exotic is becoming commonplace. Featuring the San Francisco biotech company Invitae, the piece shows how this small but highly capitalized company is taking on giants such as Illumina, 23andMe, and Myriad in a bid to monetize your sequence—and give you a small cut.

The troubling thing is how commonplace this is all becoming. Nothing Invitae is doing is really new. They want to persuade you to donate your genome to their database, where it can be analyzed to inform you about your health, contribute to research, and be sold to other companies who might use it for anything from curing cancer to targeted advertising. Invitae CEO Randy Scott he is not bringing in new tests–only offering existing ones all in one place, an approach he calls “generic genetics.” (“Generic genomics” would be more accurate–this is about as far from Gregor Mendel as you can get with a double helix.) And he wants to include users in the process, so that if their sequence is bundled into some DNA-based product, you get a tiny royalty. Sort of like allowing ads on your blog.

For some time, historians and sociologists of science have been writing about “biological citizenship,” the idea that we’re coming to base our identity on our biological status rather than our labor. Many people today identify more as a cancer survivor, as living with depression, or as gluten-intolerant than as a carpenter, secretary, or professor.

DNA has been a big part of that shift to biological citizenship. It’s not the only thing, of course, but it’s a big one. DNA, a hypothetical Marxist historian (there are still a few!) might say, came to have “use value.” We hear every day suggestions that our genes make us who we are. Leaving aside for the moment whether they actually do—a challenge for me, as regular readers know—we believe our DNA to be the secret of life. And so, in a sense, it is.

What’s happening now is that use value is being converted into exchange value. DNA is becoming a currency. An investment account we’re all born with. What are you going to do with yours? Hide it under a mattress? Or make it work for you?

One could imagine a day when there’s a new kind of hereditary aristocracy. A group of nouveau riche whose wealth nevertheless was inherited. Those who, through no effort of their own, received a legacy of valuable SNPs (single-nucleotide polymorphisms). But it will take a go-getter to capitalize on that legacy. You’ll have to have ambition, street smarts, and at least a bit of lab smarts.

Marx also said that history was determined by the material reality of the individual. One might now say the molecular reality of the individual. But total self-awareness at the molecular level won’t lead to the end of exploitation of man by man. Indeed, it is only the beginning.

Human Theome Project

This is one of the most serious pieces ever posted on Genotopia. As the shooting at the French humor magazine Charlie Hebdo shows, satire can be dangerous business. It is also one of the most important forms of speech—both provocative and healing. We are reposting this feature, originally posted in 2011 and lightly edited, to lock arms with the staff and writers at Charlie Hebdo and with satirists everywhere. We hope it offends someone and are glad that our home address is not public.

Joe and Mary Juke are models of piety. They attend services twice a week, are active in faith-based charity organizations, and their house brims tastefully with Christian iconography and literature. They describe themselves as “fundamentalists,” although Joe is quick to emphasize, “We’re moderate fundamentalists—we don’t bomb clinics or anything.” They are planning to have a family, and they are making sure to create a pious environment for their children. They know that the setting in which a child is raised helps determine the kind of adult he or she becomes.

But for the Jukes, books, icons, and saying “Grace” are not enough. In what is being cited as a milestone in personal genomics, Joe and Mary have taken steps to ensure their baby is religious—by selecting its genes.

 photo gods-dna-church.gif

From Poor Old Spike’s photobucket


Using preimplantation genetic diagnosis (PGD), a combination of genetic screening and in vitro fertilization (IVF), Joe and Mary are loading the genetic dice for their progeny, selecting embryos that carry the traits they want in little Joe Jr. (or mini-Mary). Modern techniques allow them to select for a wide range of qualities, from avoiding hereditary diseases, to selecting eye, hair, and skin color, to shaping aspects of personality. For example, choosing a combination of half a dozen genes allows them to add a cumulative 40 points to their unborn child’s IQ. Many of these tests have been available for years, although they have only recently begun to be available to consumers. But the most striking decision in their family-planning process was to expressly select for embryos that will grow up to be religious, because they carry the allele known colloquially as the “god gene.”

“It kind of gives a whole new meaning to the phrase, “Chosen One,” Mary says.

Sequencing the human theome

The gene, which was identified statistically in twins in a study published in 2005, was recently cloned and sequenced, as reported in the online journal Nature Theology. Dubbed yhwh1, the gene correlates strongly with feelings of religious fervor. Studies show that the gene encodes a protein that is expressed in a part of the brain called Chardin’s area 86, long associated with religious activity and, strangely, anterograde amnesia. One famous patient was Guineas Phage, a virologist who suffered an injury with a pipetteman that resulted in a plastic tube being driven precisely into area 86; he spent the last two decades of his life on a constant pilgrimage along US Route 66 between Kingman and Barstow, accompanied by his wife, Winona, whom he continually left behind at gas stations.

Particular expression of religiosity in a given individual varies according to environment; what is inherited is the capacity for intense religious experience and evangelism. First described in the Amish in a classic study of the 1960s, the trait was described as an autosomal recessive with high penetrance, and was linked to a rare inherited form of dwarfism. Recent analyses have also found the trait occurring at high frequency among charismatic ministers, shamans, and suicide bombers.

The yhwh1 allele is one of the latest findings in the burgeoning field of “theomics,” which aims to identify all genes associated with the practice of preaching, as well as general feelings of spirituality. The Human Theome Project overran its projected completion date of December 21, 2012—the date, according to ABC News, the world as we know it might have come to an end. All things considered, then, researchers are content with their progress.

Here are some of the most exciting new findings of the HTP:

▪   Scientists estimate that at least 400 genes are involved with religious feelings or activity. Thus far, more than 100,000 variants have been described. Easing the task of studying these genes is the fact that they cluster into “ecclesiotypes” — groups of religion genes that tend to segregate together. A research team at Mystic University in Connecticut is coordinating an effort, called the “EccMap project,” to characterize them.

▪   The EccMap project consists of 400 trios  (deity, parent, and child) representing each of the five dominant world religions—christianism, judaishness, islamian, confusianity, and pastafar-I. Researchers say these explain 80% of genetic variation for religious belief.

▪   Polytheism is more common than had been thought. Ninety-five percent of all trios in the EccMap project have genes for at least two religions. Since phenotype is almost always monotheist, this suggests that the environment may play some role in fine-tuning religious beliefs.

▪   A related project seeks to uncover the epigenetics of evangelism, which is thought to be caused by methylation of regions of the X chromosome, a reversible process that can profoundly affect gene expression. Researchers hope this may provide therapeutic targets for drugs or gene therapy to “de-program” those who become convinced, against thousands of years of recorded history, that theirs is the only path up the spiritual mountain.

▪   A newly discovered kinase, called Bub666, is strongly correlated with atheism. It seems to be responsible for the breakdown of yhwh1, suggesting that biochemists are approaching a mechanistic explanation of religious experience.

▪   Rocker Ozzy Osborne has had his genome sequenced. Preliminary results show 85% homology with a Presbyterian minister from Des Moines.

“It’s tremendously exciting research,” said Mary Magdalene-Gohdtsdottir, a senior researcher in the University of Utah’s Department of Omics. “Just think of it: the genes for God! Isn’t that cool?” Indeed, the federal government thinks so. NIH Director Francois Colon, a molecular biologist and born-again Christian, has recently created a National Institute of the Molecular Biology of Yahweh (NIMBY), with an annual research budget of $400/year, as part of the government’s effort to support faith-based initiatives in biomedicine.


But is it science?

Some critics have called the Jukes’ actions a step toward eugenics, described in the 1920s as the “self-direction of human evolution.” They see religiosity as a gift, not something that can be ordered from a catalog. “This is an outrage,” said the Reverend Reginald S. Inkblot, of Southboro Baptist Church in Onan, Kansas. “Religion can’t be in your genes. Science can’t explain it. It’s just a part of who…you…um, are. It’s just in your…uh, yea…” He brightened and added, “If God had wanted us to be religious, he would have….oh, wait. Damn!—I mean, darn!”

Others are appalled that religion would receive scientific consideration from scientific foundations at all. Dick Dorkins, President of the atheistic Society for the Prevention of Intelligent design, Theology, Or Other Nonsense (SPITOON), calls the entire effort a “travesty.” “If I must check my brain at the church-house door,” he said in a Skype interview, “then you must check your soul at the laboratory door. Come on—be fair.

Dorkins worries that should the procedure become widespread, it could lead to nonreligious persecution. If those chosen by PGD tend to express genes such as yhwh1, scientists predict, it could lead to changes in gene frequency across the population. Dorkins envisions a dystopian scenario in which an atheistic underclass washes the wineglasses and polishes the pews for their genetic spiritual superiors. “It will be GATTACA crossed with The Ten Commandments,” Dorkins said, an audible quiver in his voice.

Evolution in religious hands

Some theologians have condemned in vitro fertilization because it normally results in the destruction of unused embryos. However, new gene therapy techniques make it possible to link a “suicide gene” to alternative forms of the desired genes in Joe’s sperm samples; thus, only sperm that carry the traits they want survive to fertilize Mary’s eggs. No embryos are destroyed in the process. This makes in vitro fertilization acceptable to many pro-life Christians.

Joe and Mary dismiss critics who say they are taking evolution into their own hands. “That’s just your theory,” says Joe. They view their decision to choose the religiosity of their unborn child as a command from above. “WWJC?,” Mary asks. “Who would Jesus clone?”

Ironically, as Biblical literalists, the Jukes dismiss Darwinian evolution as “unproven.” To them, the earth is 4,000 years old, and all the types of animals in the world today were on Noah’s Ark. They see themselves as spearheading a Crusade of believers into biomedicine.

His eye acquiring that spark of evangelism that is a tell-tale sign of heavy methylation at Xq66, Joe’s voice deepened and he intoned, “The heresy of modern science will only be righted when human evolution is safely in the hands of people who do not believe in it.”
Read more at http://scienceblog.com/76171/human-theome-project/#07U8Wl33hcVj3mjI.99

Genetic determinism: why we never learn—and why it matters

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”).

Spoiler: No.

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.

Running in place

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.

Why aren’t genome profiles free? A cynic’s view

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.

A blow for personal genome testing

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.

h/t Robert Resta, Mark Largent


Neonatal genome screening: preventive medicine or prophylactic profiteering?

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.


The gene for hubris

A recent post by Jon Entine on the Forbes website leads with a complimentary citation of my book– and then goes on to undermine its central thesis. He concludes:

Modern eugenic aspirations are not about the draconian top-down measures promoted by the Nazis and their ilk. Instead of being driven by a desire to “improve” the species, new eugenics is driven by our personal desire to be as healthy, intelligent and fit as possible—and for the opportunity of our children to be so as well. And that’s not something that should be dismissed lightly.

Well, first of all, as the recent revelations of coerced sterilization of prisoners in California shows, “draconian, top-down” measures do still occur. Genetics and reproduction are intensely potent, and wherever we find abuse of power we should be alert to the harnessing of biology in the service of tyranny.

Second, there’s more than one kind of tyranny. Besides the tyranny of an absolute ruler, perhaps the two most potent and relevant here are the tyranny of the commons and the tyranny of the marketplace. The fact that they are more subtle makes them in some ways more dangerous. The healthcare industry does much good in the world, but it is naive to treat it as wholly benign.

Further, putting human evolution in the hands of humans, means accepting long-term consequences for short-term goals. The traits we value–health, intelligence, beauty–are the result of the action of many genes interacting with each other and with a dynamic environment. The entire system is contingent, inherently unpredictable. Yet we treat it as simple and deterministic. Until now, technology has been the major obstacle to guiding human evolution. It may be that now the major obstacle is our reasoning ability, our capacity for grasping contingency and probability and change. We’re tinkering with the machinery of a system whose complexity is still unfolding before us. The probability of unforeseen consequences is 100%. The only question is how severe they will be. We will only know in retrospect.

If we now have the tools to meaningfully guide our own evolution–as eugenicists have always wanted to do–we cannot take a blithe and Panglossian attitude. We have to be alert to the risks and take them seriously. That is not traditionally science’s strong suit. The public face of science is sunny, optimistic, fun. It strides boldly into the future, laughing and making striking promises. The industries behind science and health are wealthy and politically powerful. Not everything they do is benign.

To be a critic of that public-relations machine–of hype, in other words–is not to be a critic of health or knowledge or progress. Genetic science has the potential to bring us enormous benefits in health and well-being, and as they do, I stand in line with my fellow humans for my fair share. But that science also carries huge and unforeseeable risks, the root of which, perhaps, is arrogance. It’s one whose consequences are painfully evident in the historical record.