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
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.
We’ve been pretty serious for a while, which always makes me a little edgy. And “tattoos” or some version thereof continues to be one of the biggest search terms for this blog. So, to raise the font size of “tattoos” in the tag cloud, I’ve put together a gallery of eye candy.
In their 1994 book, The DNA Mystique, Susan Lindee and Dorothy Nelkin write that “habitual images and familiar metaphors…provide the cultural forms that make ideas communicable.” The double helix is the scientific icon of our age—much like the Bohr atom was during the Cold War. Putting it on your body identifies you with science, with biotechnology, with life. It is also just a stone beautiful image, which works in a line, say down your spine, wrapped around a biceps or ankle, or curving sinuously just about anywhere. The best collection of science-themed tattoos of course is Carl Zimmer’s “Science Tattoo Emporium.” Many of these were borrowed from his archive, so a big hat-tip (tat-hip?) to him. I have the hardcover version Science Ink prominently displayed on my coffee table. Others drawn from elsewhere around the web. Click the picture to open the original url.
John Belmont has asked a question that deserves a separate post. This is necessarily brief and should not be mistaken for a general survey of this concept, but the concept is so general that it deserves a somewhat fuller answer than I can (or should) give in the comments. Here is John’s question:
Can you discuss Savelescu’s Procreative Beneficence in the context of these new genetic screening technologies? (Screening that then often triggers definitive diagnostic testing)
It seems normal for parents to desire healthy offspring. Is it evil or morally suspect for a couple to choose healthy offspring?
In 2001, Julian Savulescu advanced a principle he calls “procreative beneficence,” which states that “couples (or single reproducers) should select the child, of the possible children they could have, who is expected to have the best life, or at least as good a life as the others, based on the relevant, available information.” It is of that species of ethical principles called “intuitive”: on the face of it, who could argue on behalf of not providing the best possible conditions for one’s child, whether they be environmental or genetic? So no, of course it’s not evil to choose healthy offspring, so long as one is morally okay with disposing of “unfit” embryos or young fetuses. But its morality is less straightforward.
Savulescu’s idea has spawned a sizable secondary literature, especially among bioethicists, most of whom have tried various tacks to destroy his principle. A full discussion and evaluation of this literature is more than I can undertake here, but i’ll provide a starter bibliography at the bottom.
Few–including Savulescu himself–deny that PB is an element of the “new eugenics.” By this is meant an “individualized” or “liberalized” (or even “commercialized”) eugenics, rather than a state-controlled eugenics. This distinction is entirely appropriate. State-controlled eugenics is part of a specific historical context, whereas I see eugenics as a trans-historical principle (what I have more colloquially called an “impulse”). The eugenic impulse goes beyond notions of “old” or “new” eugenics: eugenics is just there, manifesting in different ways in different periods. Empirically, we appear to be driven to take control of our own evolution.
On the surface, Savulescu’s principle, like arguments in favor of “new” eugenics generally, appears not to be concerned with control over human evolution. It refers only to choices about specific individuals—a couple’s (or individual’s) choices about the genome of an embryo or fetus, it doesn’t concern the well-being of the population. However, <a href=”http://www.ncbi.nlm.nih.gov/pubmed/20047587″ target=”_blank”>Elster</a> shows that procreative beneficence is impossible to fully separate from “General Procreative Beneficence”–the idea that “couples ought to select children in view of maximizing the overall expected value in the world, not just the welfare of their future child.” Most literature advocating the new eugenics treats the individual and the population as wholly distinct, yet of course what is a population but a collection of individuals? These two principles–concern for the individual and concern for the population– are by no means mutually exclusive; indeed, the thrust of my book is that they have always coexisted. It’s naive (or cynical) to act as though one can be separated from the other.
Under this view, PB is in fact an indirect means of directing the evolution of the population. My position is that state control is not what makes a practice eugenic. What makes a reproductive practice eugenic is whether it includes a decision about the welfare of the population; whether it is subject to social (including economic) pressures. If one is “merely” choosing the “best” possible child, few of us have the luxury of ignoring racial features, for example. The “best” child is the best in a particular or anticipated environment. The literature on PB that I have read does not take this fully into account.
If the “best” environment is truly adapting, shifting, and local, then we have Darwinian conditions, in which the population is “evolving itself” with no particular end. This is morally less troubling than a Spencerian goal-directedness. I make no claim to being a moral philosopher, but as a historian, it seems morally less responsible to deny parents that freedom than to allow it. In sum, I am not persuaded by moral arguments against PB.
But I have rational arguments against it. They are two: What if it doesn’t work?; and What if it does?
What if it doesn’t work? We can tinker with genomes long before we understand them, the way one can learn a few Unix commands without fully comprehending the operating system. I worry we will make bad choices. I worry we will uncouple biological systems that have evolved together for millennia. I worry that our technology outstrips our wisdom.
What if it does? I worry that corporate control–via market pressures, advertising, and so forth–may prove even more potent than government control. I worry that PB will instantiate in our very DNA ideas of normalcy that may transcend local conditions and become general principles of human perfection. I worry that it will encourage the idea that genes are all; that we can simply “dial in” the child we want; that we will rob poorly funded social programs to pay for already amply funded research programs for the elite. Historical examples do not provide a comforting set of models for human behavior in these areas.
In short, then, it may not be “evil” to choose the genetic constitution of a child, but in doing so we are making many more choices than we are aware of.
Some references on procreative beneficence:
Savulescu, J. “Procreative Beneficence: Why We Should Select the Best Children.” Bioethics 15, no. 5-6 (Oct 2001): 413-26.
Savulescu, J. “In Defence of Procreative Beneficence.” J Med Ethics 33, no. 5 (May 2007): 284-8. doi:10.1136/jme.2006.018184.
Savulescu, J., and G. Kahane. “The Moral Obligation to Create Children with the Best Chance of the Best Life.” Bioethics 23 (Jun 2009): 274-90. doi:10.1111/j.1467-8519.2008.00687.x.
Herissone-Kelly, P. “Procreative Beneficence and the Prospective Parent.” J Med Ethics 32, no. 3 (Mar 2006): 166-9. doi:10.1136/jme.2005.012369.
Bennett, R. “The Fallacy of the Principle of Procreative Beneficence.” Bioethics 23, no. 5 (Jun 2009): 265-73. doi:10.1111/j.1467-8519.2008.00655.x.
Elster, J. “Procreative Beneficence: Cui Bono?”. Bioethics 25, no. 9 (Nov 2011): 482-8. doi:10.1111/j.1467-8519.2009.01794.x.
Herissone-Kelly, P. “Reasons, Rationalities, and Procreative Beneficence: Need Hayry Stand Politely by While Savulescu and Herissone-Kelly Disagree?”. Camb Q Healthc Ethics 20, no. 2 (Apr 2011): 258-67. doi:10.1017/S0963180110000903.
Bourne, H., T. Douglas, and J. Savulescu. “Procreative Beneficence and in Vitro Gametogenesis.” Monash Bioeth Rev 30, no. 2 (Sep 2012): 29-48.
Herissone-Kelly, P. “Wrongs, Preferences, and the Selection of Children: A Critique of Rebecca Bennett’s Argument against the Principle of Procreative Beneficence.” Bioethics 26, no. 8 (Oct 2012): 447-54. doi:10.1111/j.1467-8519.2010.01870.x.
Hotke, A. “The Principle of Procreative Beneficence: Old Arguments and a New Challenge.” Bioethics (Jul 29 2012). doi:10.1111/j.1467-8519.2012.01999.x.
Bennett, R. “When Intuition Is Not Enough. Why the Principle of Procreative Beneficence Must Work Much Harder to Justify Its Eugenic Vision.” Bioethics (Jul 10 2013). doi:10.1111/bioe.12044.
A while ago, we reprinted a set of brilliant pictures of “composite photography”, a more high-tech version of a technique Francis Galton invented in the late 19th century. Here’s a different approach, less sophisticated but still interesting. The artist, Ulric Collette (who has 3 eyes, 2 noses, and 2 mouths) has digitally stitched together the faces of family members. Many are comic grotesques, but quite a few just seem to have the normal asymmetries we all have. As the artist suggests, cover first one side of a face and then the other to see how different the originals were, and then reblend them in your mind. The show’s title? Genetic Portraits.
Here are just a couple teasers. Click the link and go see them all.
H/t to Richard Nash and to fullym.com.
According to a recent study, pork appreciation could be genetic. Though the finding remains speculative, the correlation of such a high-level subjective character trait with a particular gene is already having a far-reaching impact on domestic policy.
In the study, variants of the OR7D4 gene, which encodes an odorant receptor, were correlated with a preference for pig meat. Subjects who possessed the RT allele rated the appeal of pork more highly than those who possessed a variant called WM. The gene in question responds to the steroid androstenone, which, it turns out, is present in high amounts in the muscle of male pigs. The authors simply connect the dots and suggest that the taste for pork may be mediated by this gene. The paper was published this week in the journal PLOS One.
This study represents a breakthrough in the genetics of breakfast. For years now, researchers have searched in vain for the gene for crispy potatoes, tender inside, with onions, bell peppers, salt, pepper, and a little oregano. An egg-hunt for the Over Easy Gene has flopped, the candidate-gene approach providing exactly zero gene candidates. The scientific community was buzzed, however, by the discovery of two coffee genes in the spring of 2011.
The Pork Board, American Home Fries Association, Egg Board, Florida Citrus Growers, and Coffee-Growers’ Association are joining forces and lobbying direct-to-consumer genetic testing companies such as 23AndMe to create a Breakfast Panel in their personal genomics profiles. Researchers and marketers hope to identify a genotype for the preference for an “American breakfast.” Preliminary studies suggest that a still-hypothetical “Continental” genotype shows linkage between a preference for a nice buttery croissant or currant scone with cigarette smoking, universal healthcare, promiscuous sex, and tight pants with pointy little effeminate shoes. Dick Dorkins, who heads up the personal genome sequencing effort “Project Dick,” has already assembled such a hypothetical panel and run it against his own genome. He claims that his sequence shows that he is as American as the gene for apple pie.
These findings raise the possibility of prenatal genetic diagnosis and selective abortion. The prospect of implanting only embryos genetically tailored to like Mom’s cooking may be too tempting for farsighted prospective parents to pass up. In the not-too-distant future, only “foodies” may have gastronomically adventurous children, while those for whom salt is a spice may be able to tailor their progeny to share their lack of taste. Vegetarians could become a separate caste and sent to a reservation in Northern California, where their only sustenance would be mung beans and marijuana.
This naturally has political implications. Indeed, the conservative pro-science group Freedom Control Institute issued a white paper yesterday recommending genetic screening for health, genealogy, and breakfast preference for all presidential candidates in future elections. Under their plan, a Breakfast Panel profile would be used to screen anyone seeking to occupy the highest breakfast nook in the land. Any candidate showing a Continental Breakfast Profile, with variants such as OR7D4-WM, would be ineligible to be included on primary ballots in Kansas.
The idea is not without controversy. Questions remain about where one would draw the lines around a properly free-market American breakfast. Watchdog groups decry the amount of pork in American politics, yet it seems unrealistic to do more than trim some of the fat. Presumably the sausage-links gene variant of OR7D4 would qualify one for office. But what about Canadian bacon?, asks Dorkins. Is that even bacon at all?
Then there is the whole matter of toast. Right-wing genetic hardliners insist that true Americans eat only white bread, while moderates point out that six out of the last six Presidents have eaten wheat toast. Possession of a pumpernickel variant, all sides agree, would indicate a dangerously Euro-socialist culinary constitution and should debar someone from higher office.
The dairy lobby, which so far has been left out of these discussions owing to low blood-sugar, has begun to push for social policy on the genetics of preference for milk products. Cheese, for example, has long been a political hot potato. Hardliners favor limiting candidates to cheddar and colby. Rallying around the slogan “Soft on cheese—soft on defense,” they argue that a strict “No Brie” genetic policy is a bulwark against socialized medicine. Opponents, however, accuse them of lactose intolerance, pointing out that the high correlation between the genetics of preference for hard and soft cheeses would make such a policy impractical.
Such self-styled “lactose liberals” suffered a blow last week, when a Colorado woman spilled her yogurt on President Obama. With one flick of her spoon, she disabused the President of what had been a pro-active culture stance. Within hours, the Oval Office issued the “Yoplait Doctrine,” which severed diplomatic relations with any nation producing dairy products containing live bacteria intended for sale in the United States. More than 40 countries, including India, Pakistan, Afghanistan, Germany, and even neutral Switzerland, immediately closed their American embassies.
A global food fight may be beginning that could trigger the Broccoli Clause of the 1992 Paris Convention on food policy. If invoked, all participants would be required to eat their vegetables or else be sent to their rooms without any dessert.
After months of emails, instant messages, not-so-instant messages, and dammit-downright-slow messages attempting to get his attention, Genotopia has finally secured an interview with Dick Dorkins, the professional cynic, atheist, and genomics enthusiast. Genotopia readers first met Dorkins when he commented on the discovery of a gene for thalassophilia. Best known for his work with SPITTOON, the Society for the Prevention of Intelligent-design, Theology, or Other Nonsense, Dorkins is also an outspoken advocate for personal genomics, which he champions as the true path to spiritual enlightenment. In this first part of our interview, he tells about “Project Dick,” his effort to sequence his own genome, and the breakthrough technique that has made it possible.
GT: Thanks for taking the time to sit down with us.
DD: Don’t be an ass. I’m just banging out ex cathedra ripostes in between doing things that matter.
GT: What matters?
DD: Well I do, for starters. But I’m not doing myself at the moment, if that’s what you’re implying.
GT: What are you doing then?
DD: If you must know, I’m looking at myself.
GT: In the mirror? Doesn’t that make it confusing to type?
DD: Don’t be an ass. Not my image. My self. My true self. My genome.
GT: Ah, your DNA sequence. But wait—your genome famously refused to be sequenced.
DD: That’s right, it did. But I kicked its nucleic butt and now it’s as docile as a retriever.
GT: How did you do that?
DD: Through a breakthrough technology called “nuclear sequencing.” Not as in the cell nucleus. As in Hiro-fucking-shima. You’ve heard of shotgun sequencing?
GT: Sure. Craig Venter’s technique of “blasting” the entire genome into smithereens of DNA, sequencing the fragments with high-powered automated sequencers, and stitching the pieces together using massive computing power. It’s how the Human Genome Project finished early.
DD: You’re not as dumb as you type. Well, as you know, I’ve formed a company to sequence my own genome. We call it “Project Dick.”
GT: Catchy. I like the ambiguity.
DD: I came up with it myself. Anyway, as you say, my genome was impervious to shotgun sequencing. It squinted down the barrel of Venter’s biggest ABI machine, tossed back its head and gave a bitter, defiant laugh: “Hahahaha.” There might even have been an evil “Bwa” at the beginning. We hit it with everything we had and when the smoke cleared my genome was still just sitting there smirking.
GT: Tough. What did you do?
DD: We invented machine-gun sequencing. But still, nothing. My genome wears kevlar nucleus armor. It drives an Armored Personnel Carrier. Not so surprising really, when you consider the individual it encodes. So this brilliant chap we’re collaborating with out at Stanfoo University, Will B. Rich, upped the ante, so to speak, and invented the atom bomb of DNA sequencing.
GT: How does it work?
DD: It literally destroys my DNA, atom by atom, and then reassembles it. The processing power this requires is staggering.
GT: My God.
DD: Not quite. Google.
GT: You hired Google to sequence your DNA?
DD: Hired? Don’t be an ass. Like God, Google is everywhere. We have written code that borrows computing cycles one at a time from every desktop and mobile device on the planet and uses them to assemble the sequence of my genome. In between the “A” and the question mark of your last question, your Android contributed one tiny piece of my genome. Your device is sequencing me. You are sequencing me.
GT: You’re welcome. So in a sense, Google already has all this information—about you, and, theoretically, anyone else—and you are simply tapping in and extracting it? Should we be concerned about this?
DD: Google knows. Google cares.
GT: Dick! What you’re suggesting is the exploitation for personal gain of a giant omniscient, omnipresent, celestial intelligence, privy to our every move and capable of probing into the deepest recesses of our genetic structure–and that moreover, it is in a sense voluntarily created by our desire for communication with our fellow man and our desire for really cool apps! Explain, please!
DD: Can’t. Later, at my leisure, I will try to explain it to you slowly. But it’s time for my cup of special Punjabi aceyjee tea. It has telomere-lengthening properties, don’t you know. So ciao for now.
(Check back later for Part II of our interview!)