Dna: The Secret of Life

by Watson, James

  That only men were affected suggested sex linkage. The inheritance pattern was consistent with a gene likely on the X chromosome, and recessive, meaning that it was typically unexpressed in women, in whom the other (normal) copy on their second X would mask the faulty one's effect. In men, with their single X, the recessive variant was automatically expressed. By comparing the DNA of affected and unaffected members of the family, Brunner and his team duly mapped the gene to the long arm of the X chromosome. In collaboration with Xandra Breakfield at Massachusetts General Hospital, he found that the eight violent men all had a mutated – and nonfunctional – copy of a gene coding for monoamine oxidase. This protein, found in the brain, regulates levels of a class of neurotransmitters called "monoamines," which include adrenaline and serotonin.

  The monoamine oxidase story does not end with the eight violent Dutchmen. It turns out to provide an illuminating glimpse of the interaction between genes and the environment, the complex duet of nature and nurture that informs all our behavior. In 2002, Avshalom Caspi and others at London's Institute of Psychiatry examined why some boys from abusive homes grow up normal while others end up antisocial (in the technical sense of having a history of behavioral problems – not in the sense of preferring to keep company with Web pages over people or of tending to be found picking at the canapés in a lonely corner at parties). The survey revealed a genetic predictor of development: the presence or absence of a mutation in the region adjacent to the monoamine oxidase gene, the switch regulating the amount of the enzyme produced. Maltreated boys with high levels of the enzyme were less likely to become antisocial than those with low levels. In the latter case, genes and the environment conspired to predispose the boys to lives punctuated by brushes with the law. Girls are less likely to be affected because, with the gene located on the X chromosome, they must inherit two copies of the low-level version rather than one. Girls who do have two copies, however, are likely to have antisocial tendencies similar to those of affected boys. But again the causal relation is nowhere near 100 percent in either boys or girls: growing up abused and having low monoamine oxidase levels in no way guarantees a career in crime.

  Among the most surprising discoveries of a monogenic (single-gene) impact on a complex form of human behavior is what the press have dubbed the "grammar gene." As we discussed in the context of human evolution (chapter 9), in 2001 mutations detected by Tony Monaco at Oxford in the FOXP2 gene were found to impair the ability to use and process language. Not only do those so affected have difficulty articulating, but they are stymied by simple grammatical reasoning that poses no trouble for the typical four-year-old: "Every day I wug; yesterday I _____." FOXP2, remember, encodes a transcription factor – a genetic switch – that apparently plays a crucial role in brain development. Rather than exerting a simple direct behavioral impact (like that of monoamine oxidase), FOXP2 affects behavior by shaping the very organ at the center of it all. FOXP2 will prove, I believe, a model for momentous discoveries yet to be made; if I am right, many of the most important genes governing behavior will indeed turn out to be those involved in constructing that most extraordinary of organs, that still supremely inscrutable mass of matter, the human brain. These genes influence us by how they build the exquisite piece of hardware that mediates all we do.

  We are as yet in the early days of our attempts to understand the genetic underpinnings of our behavior, both that which we all have in common – human nature – and that which sets us apart, one person from another. But this is a fast-moving area of research; I'm sure that what I've written will be out-of-date by the time this book is published. The future promises a detailed genetic dissection of personality, and it is hard to imagine that what we discover will not tip the scales of the nature/nurture debate more and more in the direction of nature – a frightening thought for some, but only if we persist in being held hostage to a static, ultimately meaningless dichotomy. To find that any trait, even one with formidable political implications, has a mainly genetic basis is not to find something set immutably in stone. It is merely to understand the nature upon which nurture is ever acting, and those things we, as a society and as individuals, need to do if we are better to assist the process. Let us not allow transient political considerations to set the scientific agenda. Yes, we may uncover truths that make us uneasy in the light of our present circumstances, but it is those circumstances, not nature's truth, to which policy makers ought to address themselves. As those Irish children who packed the hedge schools understood very well, knowledge, however awkwardly acquired, is still preferable to ignorance.

  CODA

  OUR GENES AND OUR FUTURE

  "The event on which this fiction is founded has been supposed, by Dr. Darwin, and some of the physiological writers of Germany, as not of impossible occurrence."

  So begins Percy Bysshe Shelley's anonymous preface to his wife Mary Shelley's novel Frankenstein, a story whose grip on the modern imagination has exceeded by far that of anything the poet himself ever wrote. Perhaps no work since Frankenstein has so hauntingly captured the terrifying thrill of science at the point of discovering the secret of life. And probably none has dealt so profoundly with the social consequences of having appropriated such godlike power.

  The idea of animating the inanimate, and improving upon life as it occurs naturally on earth, had captured the human imagination long before the publication of Mary Shelley's work in 1818. Greek mythology tells of the sculptor Pygmalion, who successfully petitioned Aphrodite, goddess of love, to breathe life into the statue of the beautiful woman he had carved from ivory. But it was during the feverish burst of scientific progress following the Enlightenment that it first dawned upon scientists that the secret of life might be within human reach. Indeed, the Dr. Darwin to whom the preface refers is not the familiar Charles but rather his grandfather Erasmus, whose experimental use of electricity to spark life back into dead body parts fascinated his acquaintance Shelley. In retrospect we know that Dr. Darwin's exploration of what was called "galvanism" was a red herring; the secret of life remained a secret until 1953. Only with the discovery of the double helix and the ensuing genetic revolution have we had grounds for thinking that the powers held traditionally to be the exclusive property of the gods might one day be ours. Life, we now know, is nothing but a vast array of coordinated chemical reactions. The "secret" to that coordination is the breathtakingly complex set of instructions inscribed, again chemically, in our DNA.

  But we still have a long way to go on our journey toward a full understanding of how DNA does its work. In the study of human consciousness, for example, our knowledge is so rudimentary that arguments incorporating some element of vitalism persist, even as these notions have been debunked elsewhere. Nevertheless, both our understanding of life and our demonstrated ability to manipulate it are facts of our culture. Not surprisingly, then, Mary Shelley has many would-be successors: artists and scientists alike have been keen to explore the ramifications of our newfound genetic knowledge.

  Many of these efforts are shallow and betray their creators' ignorance of what is and is not biologically feasible. But one in particular stands out in my mind as raising important questions, and doing so in a stylish and compelling way. Andrew Niccols's 1997 film Gattaca carries to the present limits of our imagination the implications of a society obsessed with genetic perfection. In a future world two types of humans exist – a genetically enhanced ruling class and an underclass that lives with the imperfect genetic endowments of today's humans. Supersensitive DNA analyses ensure that the plum jobs go to the genetic elite while "in-valids" are discriminated against at every turn. Gattaca's hero is the "in-valid" Vincent (Ethan Hawke), conceived in the heat of reckless passion by a couple in the back of a car. Vincent's younger brother, Anton, is later properly engineered in the laboratory and so endowed with all the finest genetic attributes. As the two grow up, Vincent is reminded of his own inferiority every time he tries, fruitlessly, to best his little brother in swim races. Genet
ic discrimination eventually forces Vincent to accept a menial job as a porter with the Gattaca Corporation.

  At Gattaca, Vincent nurtures an impossible dream: to travel into space. But to qualify for the manned mission to Titan he must conceal his "in-valid" status. He therefore assumes the identity of the genetically elite Jerome (Jude Law), a one-time athlete, who, crippled in an accident, needs Vincent's help. Vincent buys samples of Jerome's hair and urine and uses them to secure illicit admission into the flight-training program. All seems to be going well when he encounters the statuesque Irene (Uma Thurman) and falls in love. But a week before he is to fly off into space, disaster strikes: the mission director is murdered and in the ensuing police investigation the hair of an "in-valid" is discovered at the crime scene. An eyelash Vincent has lost threatens not only to dash his desperate dream but to unjustly implicate him by DNA evidence as the director's murderer. Vincent's unmaking seems foreordained, but he evades a nightmarish genetic dragnet until another of Gattaca's directors is found to be the actual murderer. The film's ending is only semi-happy: Vincent will fly off into space but without Irene, who is found to carry certain genetic imperfections incompatible with long space missions. In real life, the two actors who play Vincent and Irene have their futures more under their personal control. Ethan Hawke and Uma Thurman later married and now live in New York City.

  Few, if any, of us would wish to imagine our descendants living under the sort of genetic tyranny suggested by Gattaca. Setting aside the question of whether the scenario foreseen is technologically feasible, we must address the central issue raised by the film: Does DNA knowledge make a genetic caste system inevitable? A world of congenital haves and have-nots? The most pessimistic commentators foresee an even worse scenario: Might we one day go so far as to breed a race of clones, condemned to servile lives mandated by their DNA? Rather than strive to fortify the weak, would we aim to make the descendants of the strong ever stronger? Most fundamentally, should we manipulate human genes at all? The answers to these questions depend very much on our views of human nature.

  Today much of the public paranoia surrounding the dangers of human genetic manipulation is inspired by a legitimate recognition of our selfish side – that aspect of our nature that evolution has hardwired to promote our own survival, if necessary at the expense of others. Critics envision a world in which genetic knowledge would be used solely to widen the gap between the privileged (those best positioned to press genetics into their own service) and the downtrodden (those whom genetics can only put at greater disadvantage). But such a view recognizes only one side of our humanity.

  If I see the consequences of our increasing genetic understanding and know-how rather differently, it is because I acknowledge the other side as well. Disposed though we might be to competition, humans are also profoundly social. Compassion for others in need or distress is as much a genetic element of our nature as the tendency to smile when we're happy. Even if some contemporary moral theorists are content to ascribe our unselfish impulses to ultimately selfish considerations – kindness to others seen as simply a conditioned way of promoting the same benefit in return – the fact remains: ours is a uniquely social species. Ever since our ancestors first teamed up to hunt a mammoth for dinner, cooperation among individuals has been at the heart of the human success story. Given the powerful evolutionary advantage of acting collectively in this way, natural selection itself has likely endowed each of us with a desire to see others (and therefore our society) do well rather than fail.

  Even those who accept that the urge to improve the lot of others is part of human nature disagree on the best way to go about it. It is a perennial subject of social and political debate. The prevailing orthodoxy holds that the best way we can help our fellow citizens is by addressing problems with their nurture. Underfed, unloved, and uneducated human beings have diminished potential to lead productive lives. But as we have seen, nurture, while greatly influential, has its limits, which reveal themselves most dramatically in cases of profound genetic disadvantage. Even with the most perfectly devised nutrition and schooling, boys with severe fragile X disease will still never be able to take care of themselves. Nor will all the extra tutoring in the world ever grant naturally slow learners a chance to get to the head of the class. If, therefore, we are serious about improving education, we cannot in good conscience ultimately limit ourselves to seeking remedies in nurture. My suspicion, however, is that education policies are too often set by politicians to whom the glib slogan "leave no child behind" appeals precisely because it is so completely unobjectionable. But children will get left behind if we continue to insist that each one has the same potential for learning.

  We do not as yet understand why some children learn faster than others, and I don't know when we will. But if we consider how many commonplace biological insights, unimaginable fifty years ago, have been made possible through the genetic revolution, the question becomes pointless. The issue rather is this: Are we prepared to embrace the undeniably vast potential of genetics to improve the human condition, individually and collectively? Most immediate, would we want the guidance of genetic information to design learning best suited to our children's individual needs? Would we in time want a pill that would allow fragile X boys to go to school with other children, or one that would allow naturally slow learners to keep pace in class with naturally fast ones? And what about the even more distant prospect of viable germ-line gene therapy? Having identified the relevant genes, would we want to exercise a future power to transform slow learners into fast ones before they are even born? We are not dealing in science fiction here: we can already give mice better memories. Is there a reason why our goal shouldn't be to do the same for humans?

  One wonders what our visceral response to such possibilities might be had human history never known the dark passage of the eugenics movement. Would we still shudder at the term "genetic enhancement"? The reality is that the idea of improving on the genes that nature has given us alarms people. When discussing our genes, we seem ready to commit what philosophers call the "naturalistic fallacy," assuming that the way nature intended it is best. By centrally heating our homes and taking antibiotics when we have an infection, we carefully steer clear of the fallacy in our daily lives, but mentions of genetic improvement have us rushing to run the "nature knows best" flag up the mast. For this reason, I think that the acceptance of genetic enhancement will most likely come about through efforts to prevent disease.

  Germ-line gene therapy has the potential for making humans resistant to the ravages of HIV. The recombinant DNA procedures that have let plant molecular geneticists breed potatoes resistant to potato viruses could equally well make humans resistant to AIDS. But should this be pursued? There are those who would argue that rather than altering people's genes, we should concentrate our efforts on treating those we can and impressing upon everyone else the dangers of promiscuous sex. But I find such a moralistic response to be profoundly immoral. Education has proven a powerful but hopelessly insufficient weapon in our war. As I write, we are entering the third decade of the worldwide AIDS crisis; our best scientific minds have been bamboozled by the virus's remarkable capacity for eluding attempts to control it. And while the spread of the disease has been slowed for the moment in the developed world, huge swaths of the planet tick away as demographic time bombs. I am filled with dread for the future of those regions, populated largely by people who are neither wealthy nor educated enough to mount an effective response. We may wishfully expect that powerful antiviral drugs or effective HIV vaccines will be produced economically enough for them to be available to everyone everywhere. But given our record in developing therapies to date, the odds against such dramatic progress occurring are high. And yet those who propose to use germ-line gene modifications to fight AIDS may, sadly, need to wait until such conventional hopes turn to despair – and global catastrophe – before being given clearance to proceed.

  All over the world government regulations now
forbid scientists from adding DNA to human germ cells. Support for these prohibitions comes from a variety of constituencies. Religious groups – who believe that to tamper with the human germ line is in effect to play God – account for much of the strong knee-jerk opposition among the general public. For their part, secular critics, as we have seen, fear a nightmarish social transformation such as that suggested in Gattaca – with natural human inequalities grotesquely amplified and any vestige of an egalitarian society erased. But though this premise makes for a good script, to me it seems no less fanciful than the notion that genetics will pave the way to Utopia.

  But even if we allow hypothetically that gene enhancement could – like any powerful technology – be applied to nefarious social ends, that only strengthens the case for our developing it. Considering the near impossibility of repressing technological progress, and the fact that much of what is now prohibited is well on its way to becoming practicable, do we dare restrain our own research community and risk allowing some culture that does not share our values to gain the upper hand? From the time the first of our ancestors fashioned a stick into a spear, the outcomes of conflicts throughout history have been dictated by technology. Hitler, we mustn't forget, was desperately pressing the physicists of the Third Reich to develop nuclear weapons. Perhaps one day, the struggle against a latter-day Hitler will hinge on our mastery of genetic technologies.