My Beautiful Genome

by Lone Frank

  “Yes,” says Leroi. “Counsyl has had an extremely positive reception in the media, which is evidence in itself that this is the way the wind is blowing. And their hundred diseases is a good beginning.” He punctuates his assessment with a slight sniff. “But you can go much further.”

  Further, to Leroi, means his notion of a GQ – if not a guarantee to look sharp and live smart, then at least a holistic look at the genome that takes all mutations into consideration. The quotient also encompasses those SNPs that do not necessarily result in a disease but may increase the risk of it. Leroi even wants to include mutations whose effect we have no idea of yet. “The principle is that you measure how many mutations an individual has and, from that, calculate the probability for a number of diseases,” he says with the tone of a mathematics lecturer. “Ultimately, you may be able to provide a good estimate of your expected lifespan.”

  It’s simple, in concept. You take a genome, sequence its twenty thousand or so genes, and count up how many mutations they carry – those mutations, that is, that might result in changes in the proteins the genes produce. Changes in proteins are potentially a really bad thing. From the knowledge geneticists already have about an organism’s proteins, you can calculate the probability that each of the – presumably thousands – of identified mutations will create a seriously disturbed protein. This is not about small, subtle variations in efficiency but about more or less shattered proteins, and thus mutations thought to be harmful.

  “Put it all together and you have the person’s total mutational load, or genetic quotient,” says Leroi, leaning back in his office chair. “Do you understand?”

  I believe so. A few researchers have even begun to do the calculations, it turns out. Carlos D. Bustamente of Stanford University, who also happens to have received a prestigious MacArthur “genius grant,” has compared a number of African and European genomes and found that Europeans have far more mutations.

  “They don’t say in the article that Africans are, therefore, genetically healthier but that, I believe, is the conclusion. Why may be more difficult to explain,” Leroi riffs.

  “It would certainly be interesting to know whether there is a connection between physical quality and mutational load,” I reply meekly.

  “Yes, yes. And, naturally, you have to study and compare large groups of people to show it. But I feel convinced that a person’s mutational load will prove to have a direct connection with that person’s general health and also with various other traits. Intelligence and physical beauty, say.”

  As for himself, Leroi is planning in silico experimentation. He wants to run computer calculations using some of the many genomes that are now freely accessible to the public and combine them to produce hypothetical offspring. “Virtual babies!” as he says with the day’s first approximation to a smile. “This will show you how much the mutational load varies, if you choose different partners, and thus say something about the extent to which it would be an advantageous choice. Both between possible partners and, eventually, between fertilized eggs that you may produce with a given partner.”

  He stubs out his cigarette and exhales the last smoke from the side of his mouth.

  “The greater the knowledge we acquire about genetics, the more important it will seem to us to know what we are passing on to our children. It will become an almost automatic part of our thinking, because we all want to maximize our options. In the beginning, people will pay for this themselves, and there will be a limited number of users, but at some point the health system will step in, because it is about limiting the burden of disease.”

  Leroi resolutely empties his coffee mug. He has to teach and doesn’t have any more time to chat.

  “My students are in their twenties, and I tell them that, when they have children, it will seem entirely normal for them to have their genome saved on their laptops. When it comes to choosing from a handful of test-tube-fertilized eggs, you’ll want to choose the one with the fewest harmful mutations. That is, the highest genetic quotient. But, as I said – you don’t choose between perfection and the opposite, you choose the least worst.”

  AFTER THIS INSTRUCTIVE conversation, I need a cup of coffee. If I were a smoker, I would probably have grabbed a cigarette with it. That was some heavy stuff to get served up in the middle of the afternoon – neo-eugenics – and without a filter.

  Ironically enough, it is only the turn of expression that is deeply provocative. For Armand Leroi is completely right that the practice is uncontroversial for most people. To get rid of unhealthy and defective children before they become children has long been a standard practice and an option we use at our pleasure. I also think Leroi has it right when he says future generations will find active choices with respect to genetics quite normal, almost natural. We are talking about generations who will grow up with easy, cheap, and direct access to genetic information, just as current generations have grown up with easy and cheap access to all sorts of information technology.

  We also know that people want to choose. We know this not just because of the many customers Counsyl has already attracted. We need only look at the development of the old, low-technology business of sperm banks. Here, there is great demand for selection. In the United States, it has become a matter of course for women or couples to choose what traits they want to try to pass on to their children by reviewing pictures and detailed descriptions of possible donors. A British outfit catering to the same urge is the London Sperm Bank, which is the largest operation of its type in the United Kingdom. According to its website, the bank offers a “sperm donor catalogue” from which individuals can chose a donor “… with the most appealing characteristics, just add it to [their] cart and complete the ‘shopping’ process.” That isn’t the case everywhere. In Denmark, until recently, opting for a sperm donor was a blind choice. A pig in a poke, where, when you decided to use a sperm donor, you knew even less about your child’s father than if you picked someone up at a bar. According to the country’s rules, it is still not legal to give people a choice, but this looks likely to change under the European Union regime. As Peter Bower, director of the European Sperm Bank in Copenhagen, put it to me, “This is where you see market growth.”

  But it’s one thing to pick from among volunteers who have signed away their sperm and another to poke at defenseless embryos to ensure their GQ is up to scratch. The dawn of Homo sapiens 2.0 will not happen without resistance and debate. In 2010, for the tenth anniversary of the mapping of the human genome, the journal Nature asked a number of prominent researchers to predict real developments over the next ten years. David Goldstein, a geneticist at Duke University, pointed to the screening of fetuses. “The identification of significant risk factors for disease is bound to substantially increase interest in embryonic and other screening programs,” he writes. “Society has largely already accepted this principle for mutations that lead inevitably to serious health conditions. Will we be so accommodating of those who want to screen out embryos that carry, say, a twentyfold increased risk for a serious but unspecified psychiatric disease?”

  Good question, Dr. Goldstein. It raises the classic debate about the extent to which boundaries should be drawn and rules should be drafted governing what future parents may be allowed to decide. What diseases make it okay to choose an abortion? Which are too minor? Are there traits beyond actual diseases that you may select for?

  At heart, these issues come down to where the power over our reproduction rights should lie, and where the balance between consideration for the individual and society should rest. The state has always tried to control human reproduction. In certain places and at certain times, it has done so quite bluntly by forbidding abortion and access to contraception, or by ordering the sterilization of selected groups. Today, we may be able to empathize with a couple who want to abort a fetus with genetic defects that will cause great suffering and pain, perhaps even premature death. But what about the less serious conditions – where do we draw the line? />
  For the time being, the debate has mostly focused on late abortion. For example, in 2008, the Danish Abortion Board, which must grant permission in all cases of late abortion, refused to allow a woman named Julie Rask Larsen to abort a fetus at week twenty, when a scan showed a missing left forearm. The board believed this was a handicap that both mother and child could live with. Rask Larsen did not agree. So, she went to England to receive her abortion.

  As people begin to consider the ramifications of our new genetic prospects, they may imagine a brutal society that embraces the crude and narrow view that humanity only has room for the perfect – a real-world Gattaca. More simply, parents may start to acquire an “erroneous” relationship with their offspring, viewing children as something they can, like any other piece of technological merchandise, order with the specifications they desire.

  A glimpse of this future came in 2009, when doctors at University College, London announced the birth of the world’s first child “designed” to be free of mutations in the BRCA-1 gene. The father of the child had seen most of his close female relatives succumb to breast and ovarian cancers because of mutations in the BRCA-1 gene and, with his wife, requested in vitro fertilization and screening of the fertilized eggs. From these eggs, the doctors selected one without BRCA-1 mutations. Voilà – the end of eternal angst and annual checkups with breast surgeons into the next generation. What could be a better motive for choosing your child’s genetics?

  But the critics were many. They argued that it was insane to abort innocent fetuses with a predisposition for disease that might never come to fruition or might do so only late in life. Especially diseases that can be treated – and perhaps, within a lifetime, cured.

  Such outcries were turned on their heads by the British bioethicist Jacob Appel, who calls for mandatory testing of fetuses for serious genetic defects, including carcinogenic mutations in the BRCA genes. “Mandatory genetic testing isn’t eugenics, it’s smart science,” reads the confrontational headline of his article on the subject. Appel offers an executive summary of this ingenuity: first, the children who are not born are spared suffering from the disease and painful treatments. Second, there are great societal savings in avoiding various expensive cures. And if you look at the problem realistically, he concludes, it is the equivalent of child abuse to choose to give birth to sick and handicapped children, when technology lets us avoid it.

  This is where he lost a lot of people. It was just too cruel, even for a philosopher.

  As Appel points out, however, Western societies today often put the welfare of the child ahead of the parents’ wishes. We don’t allow parents who are Jehovah’s Witnesses to deny their children necessary blood transfusions. Nor is it legal for members of the Christian Scientist sect to insist on praying for their children’s health instead of allowing them to be treated with antibiotics for life-threatening infections. “Child welfare laws certainly prevent a mother from intentionally exposing her daughter to an environmental toxin that produces an 80% risk of future cancer,” notes Appel. Why then should the same mother be allowed, in full knowledge, to give her daughter a carcinogenic BRCA mutation?

  In the wake of Appel’s radical stance, the editor of New Scientist, Michael LePage, tried to find some steady ground. He disagreed that gene testing should be mandatory. Instead, society should make genetic screening available to future parents, who can then choose whether to avail themselves of it. In LePage’s view, a couple shouldn’t have to go to a commercial enterprise such as Counsyl and empty their wallet to access its genetic riches. This is a public good, and the public should provide it. Those couples who get screened and discover they both carry the same mutations may then be offered the option of testing eggs fertilized in vitro and selecting the healthy ones.

  The central argument of both men is something we are not used to thinking about – namely, the sin of omission. Usually, bioethics is about forbidding or limiting the use of a new technology, and people only rarely ask whether it might be unethical not to use it. But when we have the means to avoid suffering in unborn children and do not exploit it, that is akin to standing around and watching while someone dies of a disease that can be treated by the technology available.

  It’s at this stage that the worriers truly raise the specter of a Gattaca-like existence, in which it becomes socially unacceptable to give birth to a child with a serious disease or physical handicap; socially unacceptable to choose consciously not to be screened. Wouldn’t the inevitable consequence be a miserable human community in which the imperfect and the handicapped are poorly treated?

  So far, the nightmare scenario has not happened. In practice, society does not treat the handicapped worse than it did before amniocentesis, gene tests, and legal abortion existed. On the contrary. Most would agree that both the treatment of and general attitude toward the disabled are a great deal better than they have been. It might well be that future parents who insist on their right to a sick child will encounter condemnation here and there, just as smokers and obese people presently face societal disapproval. But the condemnation of other people is something humans have always been forced to contend with – this is how morality expresses itself in everyday life. The real challenge is to secure equal opportunity for all citizens, regardless of their genetic profile.

  Still, the question remains: if it is ethically responsible to have an abortion to prevent suffering, who is to define what suffering qualifies when the measure is a genetic test? At the beginning of 2010, Britain’s Human Fertilisation and Embryology Authority made a first stab at solving the dilemma, producing a list of more than a hundred genetic illnesses for which the country’s doctors could offer to screen fetuses. A glance down the list reveals that some are far from life-threatening, such as certain forms of congenital blindness and deafness. There are also diseases that can be expressed in varying degrees, including thalassemia, which, in addition to anemia, can produce pain and much discomfort. But you can also live perfectly well with some forms of thalassemia, as does the tennis player, Pete Sampras.

  SO, HOW DO you defend aborting fetuses for this sort of minor infraction? Or something even more innocuous – sex, for example? Several companies, including the Texas-based IntelliGender and the Boston-based Acu-Gen Biolab, have marketed at-home tests that reveal a fetus’s sex after ten weeks of pregnancy. If parents can identify sex within the window when an abortion is solely their decision, what would stop them from making such a choice? Ultimately, the “right” to abortion is a political position. Once a country has decided to make abortions available, it has, in principle, opened the doors for a woman to get rid of any fetus she doesn’t want. It may be that she does not have time for a child given the demands of work and life; it may be that she has been abused by the child’s father and does not want to bear his offspring. These are perfectly legitimate grounds for making this personal choice, because abortion is about a woman’s right to make decisions about her own body, under the law. Considered this way, you can see why it is difficult to establish rules that forbid a woman from having an abortion on genetic grounds once a society has made the fundamental decision to recognize the right to either abortion or gene testing. Ethically, it makes no sense.

  But even if we come to terms with the possibilities of the present, there is always the future to fret about. When discussing whether or how to ensure we have healthy children, it seems we inevitably wind up debating the prospects for “designer” children, the notion of the gene-manipulated wunderkind. Most people shudder at this, which makes it a favorite dystopia among philosophers. Beyond the realm of Hollywood thrillers, the American intellectual Francis Fukuyama, for example, is renowned for vision of a “post-human” future, in which human beings have taken evolution into their own hands and altered human nature itself. For the worse, it is to be understood, and to a point where liberal democracy is itself in danger. In his horror script, humanity is permanently divided into an underclass of poor “naturals” and an upper class of ri
ch, superior, gene-manipulated individuals – the “created” class, you could call it. And if you believe the dystopians, this new übermenschen will consist of blond, blue-eyed, athletically gifted specimens who work as brain surgeons or theoretical physicists by day and are piano virtuosi by night. Of course, such a society of upgraded people is a utopia according to the transhumanists, a collection of philosophers, technologists, and general enthusiasts who believe we should improve humankind by any means available. Unfortunately, the resolution to this debate cannot be “To each his own.”

  It is high time to dispel this talk. There is no magic gene dust you can sprinkle over Mr. and Mrs. Smith’s fertilized eggs to upgrade their future children. The science tells us very clearly that this is naïve and unrealistic. It is based on the outdated presumption that there are identifiable genes that make the difference between tall and short, gorgeous and plain, highly gifted and mediocre. There aren’t. Just as there is no such thing as genetic or biological perfection – Armand Leroi’s formulation that the best is, in reality, “the least worst” is exactly right.

  HOW GENETIC KNOWLEDGE will affect us after we are born is quite another discussion. If all our genomes are published and publicly accessible, far more than physical disabilities will be revealed – and not necessarily to the people you’d like. Things like your psychological dispositions.