Tag Archives: genetic diagnosis

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.

 

Is There Any Malevolence to Procreative Beneficence?

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.

 

23andMe, myself, and I

Here is the new ad from 23andMe that will begin airing shortly on cable TV*:

Genomics is going mainstream and the best news is first that it’s real simple and second that it’s all about me.

Let’s take the most obvious first: the “me” meme. Of course this relates to the company name, but the ad takes me to a new level. It makes “you” your DNA. I give them points for a couple of qualifiers — it “helps” make me who I am, one character says. But the overall message is that you are your genes.

It also exploits the meme of egocentrism. Nearly everything today seems to be all about me. Memoirs are the hottest genre of nonfiction. We have a magazine called “Self.” One of the most common themes on commercial websites is to have a “My [company name]” area, which usually just means they have your personal information to use to sell you more stuff. There’s even a “.me” internet domain, which they advertise “is all about you.” Who isn’t curious about himself? I’m the most interesting topic in the world! And 23andMe will tell me about my true inner nature for just $99.

One element of personalized medicine, then, is narcissism. Another, more noble, element is individuality. No one is more committed to his individuality than I am—but I’m also wary of its dark side: selfishness. I am struck by the single reference to future generations (“what I will pass on to my kids”). Again, this is a two-sided coin. In the Progressive era, the literature on genetic medicine emphasized family and community. There isn’t a hint of that here. On the one hand, then, the ad is free of the eugenic message of controlling human evolution. On the other, it’s relentlessly selfish. Most likely, the reason for staying away from issues such as family, community, and responsibility is that it enables them to steer way wide of abortion. This ad is about me, not my kids and not the future. That’s actually a new and rather radical development in genetics. 

A persistent theme in popular literature from the 19th century to the 21st, is that hereditary information provides certainty. This despite the fact that one of the signal insights from genomics is how uncertain its results are. Genetic medicine today is all about probabilities, and to make informed decisions based on our genetics we have to understand how probability works. The ad works against this principle, promising certainty where there is only chance. “Now, I know” says one woman. No, you don’t. Now, you have a sense of risk—not certainty. This is a dangerous over-simplification.

double helix

Simplified double helix from Watson and Crick’s 1953 paper.

This sense of simplicity is also carried in the graphics. Note how there’s hardly a double helix in it. “Your” DNA is reduced to circles, dots, and lines. They move and whirl entertainingly and there’s just enough suggestion of complexity to carry the message that you can’t understand “you” without them‚ 23andMe. If DNA becomes as central to identity as companies such as 23andMe want to make it, this ad suggests that its iconic image may fade. Even the stripped-down ribbons and bars version is simply too complex for TV.

karyotypedowns

An early karyogram (of Down syndrome) from the 1960s.

A comprehensive chromosome map from UCSF.

Screen shot from 23andMe commercial. Her “DNA” is those two colorful cylinders by her ear.

Most of the genetic “knowledge” promised is simple enough to be carried in the one- and two-syllable words that dominate mass-market media. Genetic medicine, stuffed as it is with Latinate and Greek words, is a tough sell in that market, but the ad pulls it off. At 0:21 we hear the longest word in the ad: “hemochromatosis.” The speaker pauses after the second syllable, to suggest empathy with viewers who get hung up on such terms. According to the Mayo Clinic website, hemochromatosis is indeed usually inherited, is rarely serious, is most common in men, and is the most common genetic disease in Caucasians. The ad script gives this word to a black man. Thus, one of the ad’s subtle messages is to erase racial differences—even differences supported by scientific evidence. It’s a commonplace in TV ads nowadays to feature men and women of many hues, but the 23andMe ad takes it a step further.

Another theme of the commercial is the way it suggests communities based around biological identities of health and disease. Once, our primary identities were with those who lived near us, or shared our work or hobbies or politics. But politics has become personal, our communities are digital, and our identities center around health. The sociologist Nikolas Rose calls this “biological citizenship.” The 23andMe website features forums where members who share particular mutations or risks can discuss diets, lifestyle habits, child-bearing decisions–or their pets, if they wish. They are communities based around health. The ad sends the message that race, class, and gender are no longer our defining social themes: what matters now is health and disability.

We hear so much about the importance of educating the public about their biology as a key component of contemporary personalized medicine, but in this ad that biology is reduced to bumper-sticker-like phrases about this circle “saying” I will have blue eyes and that line segment “saying” I have a risk of this or that disease. Learning about me will be fun, easy, and inexpensive. Thank goodness I can mail off a C-note, spit in a cup, and in a few weeks get a report that simplifies it all in language I can understand. The ad ends with a rainbow of people chanting “Me. Me. Me.” It’s the “Om” of the 21st century.

 

*h/t to Bob Resta for sending the link to the ad, and to Shirley Wu (@shwu) for a tweet that showed me that the hemochromatosis passage was too terse in yesterday’s version. I’d been wanting to add something about biological citizenship and Shirley’s comment suggested a way to do it.

 

 

 

Is Eugenics Ever Okay?

A flurry of eugenics-related news over the last couple of weeks demonstrates that we have to stop considering eugenics a historical period and think about it more as an ever-present theme. In my book I called it “the eugenic impulse”—not to invoke some sort of misty, mystical force but rather simply to point to something that seems deeply part of our nature. Which is not to say part of our DNA. My research convinced me of two things:

1) Mixed with the chauvinism, intolerance, and paternalistic governmentality of Progressive-era eugenics was an impulse to prevent disease and disability using state-of-the-art knowledge of heredity. 

2) Mixed with present-day impulses to prevent disease and disability using state-of-the-art knowledge of heredity is a great deal of hype motivated more by the desire for profits than by humanitarian concerns.

In short, I could not escape the conclusion that some aspects of contemporary genetic medicine—both good and bad—are indistinguishable from some aspects of Progressive-era eugenics—both good and bad.

The Science of Human Perfection is my attempt to wrestle with the question, “Is eugenics ever okay?” Because I have refused to come down on the side of the dogmatic anti-eugenicists, some pro-eugenics types, eager for recruits, have marshaled my words for their cause. At the same time, some antis have accused me of supporting the enemy. If I make the argument that modern medical genetics comes from the same rootstock as Progressive-era eugenics, they fear that anti-abortion fanatics will use my work as ammunition to repeal Roe v. Wade.

To those of you on both extremes, here’s my answer: No, eugenics is not okay. It scares the crap out of me, to be honest. But it’s happening anyway. No one—and certainly not a historian—is going to stop us from using genetic technology in the attempt to perfect the human race. The most intelligent response is to point out (and so hopefully avoid) the greatest risks.

*

For years, historians of eugenics have maintained that the term eugenics is no longer helpful. It is too loaded, they say; invariably, it invokes the Nazi past. Whatever programs in controlled breeding or self-directed evolution may be going on, it’s alarmist and a distraction, they say, to call them “eugenics.” For years, this was a reasonable and level-headed response, but it is no longer viable. Not because it’s less loaded, but because today’s historical actors are using it.

A growing number commentators from within the scientific community are arguing for a revisitation of eugenics:

“Seeing the bright side of being handicapped is like praising the virtues of extreme poverty. To be sure, there are many individuals who rise out of its inherently degrading states. But we perhaps most realistically should see it as the major origin of asocial behavior that has among its bad consequences the breeding of criminal violence.” (James Watson, “Genes and Politics,” 1997)

“We are once again practicing a sort of eugenics” (Matt Ridley, “The New Eugenics,” 2000)

In 2001, the conservative theorist Richard Lynn published Eugenics: A Reassessment, which argues just what you think it does. In 2002, researcher DJ Galton (no relation to the founder of eugenics) considered the new genetics, test-tube babies, and genetic screening and called a spade a spade: Eugenics: The Future of Human Life in the 21st Century.

“Eugenics failed because it was not scientific enough…The role of eugenics in our time is in maximizing [hereditary] information and its availability to those who need it and minimizing the temptation to use the State as the means of enforcing eugenic ideals.” (Elof Carlson, “The Eugenic World of Charles Benedict Davenport,” 2008)

“A new interest in rational discourse about eugenics…should be our goal.” (Maynard Olson, “Davenport’s Dream,” 2008)

“Soon it will be a sin of parents to have a child that carries the heavy burden of genetic disease. We are entering a world where we have to consider the quality of our children.” (Bob Edwards [creator of first test-tube baby])

“Eugenics, once discredited as part of the first wave of social authoritarian progressives that trampled free will for women, handicapped people and minorities, is attempting a 21st century comeback.” (Hank Campbell, “Genetic Literacy Project on Neo-Eugenics,” 2012)

“To a great extent we already live in the second age of eugenics.” (Razib Khan, “Eugenics, the 100 year cycle”, 2012)

The most recent is Jon Entine, who runs the Center for Genetic Literacy and writes regularly for the conservative money magazine Forbes. “Instead of being driven by a desire to ‘improve’ the species,” he writes, the “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.” (Jon Entine, “DNA Screening is Part of the New Eugenics—and That’s Okay,” 2013)

No, we are not trying to improve the species—just our children, and our children’s children, and our children’s children’s children,…

Talk of a new eugenics, then, is no longer idle hand-wringing. When our actors themselves are using the term, historians and philosophers need to take notice and help make sense of it.

*

The fact that Entine writes for Forbes, Ridley for the National Review, and Lynn for Mankind Quarterly suggests a linkage between the new eugenics and conservative ideologies. Eugenics has long had such associations. Some of the neo-eugenicists (e.g. Lynn) are ideologically linked to the old, discredited eugenic ideologies. But others (e.g., Ridley, Entine) I think are more complicated. Liberals and conservatives, of course, are a diverse lot. When critiquing neo-eugenics, we must bear in mind whether someone is writing from a position of profit-making, preservation of the social status quo, libertarian individualism, or other ideology.

Further, liberals can be eugenicists too. As Diane Paul showed years ago in “Eugenics and the Left,” political liberals were also deeply involved in eugenic schemes during the Progressive era. Most historians of eugenics agree that to a first approximation, everyone in the Progressive era was a conservative. Sterilization legislation was democratically approved, and most sterilizations were carried out in state hospitals, under at least a premise of social benefit. There may well have been a conservative slant to Progressive eugenics, but it was only a slant, and by the 1930s eugenics probably had a liberal slant.

Because of this political ecumenicalism, eugenics today makes for some strange political bedfellows. If some pro-eugenics advocates lean conservative, so do some antis. The Catholic Church—hardly a bastion of liberal fanaticism—opposes eugenics on grounds that it generally entails either abortion or embryo selection. Matt Ridley favors eugenics and is a pro-business conservative. Genetic screening can be seen as a liberal, feminist issue—an issue of women’s choice and empowerment. Or it can be seen as a tool of government social control. Finally, genetic screening and eugenics are not necessarily the same thing. The Center for Genetics and Society supports abortion and genetic screening but seeks to establish a critical biopolitics that can help shape policy to reap the benefits and avoid the risks of reproductive technologies—a position Entine constantly takes them to task over, presumably because they are not simple cheerleaders.

Eugenics, then, does not hew unswervingly toward either pole of the political spectrum. The eugenics question forces us to parse some traditionally liberal and conservative ideas in new ways. Favoring genetic technology is pro-business (conservative). Favoring prenatal genetic diagnosis with abortion is pro-choice (liberal). Fearing the power of genetic manipulation falling into the hands of totalitarian regimes: liberal. Favoring open markets and “consumer choice”: pro-business conservative. Sometimes this consumer-driven eugenics is even called “liberal eugenics.” Perhaps that’s a smokescreen, but maybe not entirely.

Political ideology, then, can’t help us make an easy decision on whether eugenics is ever okay. If the new eugenics has a conservative tilt it’s only a tilt, and there’s plenty of counterweight on the other side. Unfortunately, we’re going to have to make up our own minds.

eugenics-tree

 

To do that, we first have to accept that the eugenic train has left the station. Understood as “the self-direction of human evolution” (the slogan from the 1921 eugenics congress and for me still the most inclusive definition I’ve found), eugenics is going to happen. Is happening. Always happens. For now, it’s still mainly for elites who can afford expensive IVF and genetic screening, but the cost of those procedures is dropping rapidly and more people are gaining access to it each year. Many people are in fact currently making eugenic choices, from the wealthy who can afford prenatal genetic diagnosis with selective abortion to the Dor Yeshorim who screen for and discourage marriage between carriers of Tay-Sachs and a range of other genetic diseases. On this much, I agree with folks like Entine. Where we part company is that I’m not nearly so sanguine about it as he seems to be.

Recognizing that we are grasping the reins of human evolution as fast as we can raises two sets of concerns. First, “What if it doesn’t work?” It’s been argued for some time that our technological capacity greatly outstrips both our wisdom and our understanding. It’s often argued that genetic choices have been made since the dawn of marriage, so opposition to techniques such as embryo selection is mere technophobia. But even age-old holistic breeding practices have unpredictable, undesired effects. Sweet-tempered Laborador retrievers tend to get hip dysplasia and eye problems. Great Danes’ hearts fail. Some quarter horses are prone to connective tissue disorders or “tying up” episodes related to their highly bred musculature. The European royal families are prone to hemophilia and polydactyly. Selecting for single genes, rather than traits that involve suites of genes that have evolved together, seems likely to exacerbate such unintended consequences. The emerging science of systems biology holds that genes act—and hence evolve—in networks. Selecting for particular genes rather than complex traits disrupts those networks and is likely to have unpredictable effects.

We in fact have very little idea how the genome works. The genome is like an ecosystem, a brain, or the immune system: an immensely complex, deeply interconnected system. Altering one element or a few elements has effects that are not only unknown but in many cases unpredictable. Evolution, Darwin showed, is an immensely slow process, in which innumerable parts “negotiate” with one another to produce the best-adapted organisms in a given environment at a given time. In taking control over that process, we will be altering the “ecology” of the genome, and it’s bound to have similar effects to our impact on the environment. With great wisdom, it might be handled safely, but experience does not give one much hope for collective human wisdom.

The second concern is, “What if it does work?” What if it does indeed become possible to select traits—health, height, complexion, intelligence—without creating cruel monsters? I have enough faith in technology that I think this may eventually happen. Some unforeseen consequences will doubtless occur, but in time they will become correctable. So what do we do when this becomes possible? We need to keep in mind that this will be a tool of the upper strata of society for a good long time. The rich will do it more than the poor, and Americans and Europeans will do it more than Bangladeshis and Somalians. So it will be a way of inscribing socioeconomic status literally in our DNA. This is in fact a conservative application, because it will tend to reinforce the socioeconomic status quo.

Further, in most developed countries, it’s not government control we need to worry about; it’s corporate control and the tyranny of the marketplace. Advertisers will push certain genotypes. Ad campaigns, current styles, and the rapidly shifting current consensus on what is or is not healthy will shape people’s genetic decisions. And of course, you can’t shed your genome the way you can last year’s fashions. The concern here, then, is that the new eugenics harnesses long-term processes in the service of short-term goals.  This too will have unpredictable effects. History shows without a doubt that societies are rarely wise; we have great trouble seeing several moves ahead, planning for the future, delaying gratification, or sacrificing some of next quarter’s earnings so that we may reap greater health and happiness some time in the future. Even more troubling than failures of technology, then, are failures of morality. And glib reassurances that we are beyond Nazi-style totalitarianism do little to comfort me. The age of self-interested individualism can be just as scary as that of communal self-sacrifice.

Most critical analyses of past eugenic efforts have centered on race, class, and gender. I think that the greatest concern with the new eugenics will likely be the fourth member of the “big three”: disability. Another recent story concerns the stunning development of a method of “silencing” chromosomes. Every nucleated cell in a woman’s body uses this to turn off one of her two X chromosomes; otherwise, women would have a double dose of X chromosome genes, which would lead to lots of problems. The advance is in harnessing this technique so that it can be applied to non-sex chromosomes. Down syndrome results from an extra (third) chromosome 21. The blogs and papers have been awash lately with speculations about “shutting off” the extra chromosome 21 in embryos, to prevent Down syndrome.

The problem is that the severity of Down’s is unpredictable. A family might well be happy to have a high-functioning Down’s baby, but a severely affected child suffers greatly, as does its parents. Who would take that chance? If (when) this technique becomes widely medically available, the frequency of Down syndrome will drop, simultaneously reducing suffering among the victims and families of severe Down’s and joy and love among those close to high-functioning Down’s patients. No humane person would never wish, say, Down syndrome on a family not equipped to handle such a child. But nor would I want to live in a society lacking in people with Down syndrome, or little people, or the blind. It’s not a wish for suffering; we all suffer. But engineering our own evolution will likely have a normalizing effect. Intolerance of abnormality was, indeed, a common refrain among Progressive-era eugenicists and greater power over our genetic future is only likely to increase it. The movie GATTACA got this much right: genetic disease leads to suffering—but so does intolerance.

Gattaca-jude-law-14393222-640-412

Is eugenics ever okay? On the individual scale, of choosing not to raise a child with a debilitating disease, I think we have no moral choice but to condone it. A prospective parent talking with a genetic counselor about whether to prevent a deformed or diseased baby from being born is in fact a form of eugenics. But my research made it irrefutable that eugenics has always been simultaneously about individuals and populations. Individual choices lead to population changes—and individual choices are influenced by more than objective genetic knowledge. Although those parents’ choice is for their family rather than the race, they are simultaneously participating in the self-direction of human evolution—it is a choice that any Progressive-era eugenicist would have condoned. And, granting the right to abortion and embryo selection, that is an entirely moral choice.

But what influences that parent’s choice? The biomedical industry hides truly fantastic profits behind the cloak of “health.” Moving responsibly into this inevitable future demands that someone call out the self-interest of the diagnostics and pharmaceutical companies, the instrument-makers and laboratories, the hospitals, the advertisers, and the investors in this new age gold mine. It demands analysis of subtle forms of coercion. It demands a jaundiced eye. Skepticism isn’t Luddism, isn’t anti-choice, isn’t anti-health. It’s following the money.

Much as one might wish to do so, the genie can’t be stuffed back into the bottle. The new eugenics is here. This worries me greatly. But worry, by itself, solves nothing. The concerns it raises are too complex for either dogmatism or complacency. It comes with new, subtle kinds of coercion. Science alone cannot be our guide into this brave genetic world. The closer we come to guiding our own evolution, the more important a humanistic perspective—one that takes the long view of history and the broad view of social context—becomes in helping us make sense of it. The future is here, and, dammit, it’s complicated.

[Update 7/26/13 3:20 pm: Changed description of the Center for Genetics and Society to more accurately reflect their philosophy and agenda. H/t Alex Stern.]

Sign me up

Check out the delicious spoof over at The DNA Exchange. It’s a program for the “National Education Conference of the National Society of Genome Service Specialists.” Sponsored by the likes of “UneedaTest, Inc.,” “Twist-of-Fate, Inc.,” and “BraveNew Analytics,” the conference program features panel discussions such as “Clinical trials—a barrier to patient uptake of new genetic tests” and “Fear of genetic disease—your best marketing tool.” Breakout counseling sessions include “How To Appear To Promote Autonomy, Empower Patients, And Seem Non-Directive – But Still Increase Hospital Revenue.”

No conference is complete without awards. This one includes the Huntington Award for most TestAll tests ordered for adult onset diseases in a pediatric setting and the GATTACA award For Strongest Advocate of the TestAll! Really, Really Expanded Newborn Screening Panel.

At day’s end, conferees can hoist a few at the Uneeda Party, “an evening of food, drink, fun, and clever sales pitches” by the sponsor, “not intended to influence your choice of genetic testing laboratory.”

It’s a wonderful send-up of some troubling potential conflicts of interest that may be brewing in the genetic counseling profession. Or is it?

Human Theome Project sets sights on 2012

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.

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. Researchers plan to complete the Human Theome Project by December 21, 2012, when, according to ABC News, the world as we know it may come to an end. 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.

▪   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.

▪   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 Francis Collins, 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 momentarily and added, “If God had wanted us to be religious, he would have….oh, wait. Damn!”

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.”