Should we manipulate human genes at all?

The following is an extract from DNA The Secret of Life, the new book by James Watson with Andrew Berry. The extract is titled "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 he ours.

Life, we now know, is nothing but a vast array of co-ordinated chemical reactions. The "secret" to that co-ordination 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 new-found 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 ofreckless 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.

Genetic 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 recognises only one side of our humanity.

If I see the consequences of our increasing genetic understanding and knowhow 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, co-operation 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 50 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 swathes 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 he 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.

I see only one truly rational argument for delay in the advance of human genetic enhancement. Most scientists share this uncertainty: can germ-line gene therapy ever be carried out safely? The case of Jesse Gelsinger has cast a long shadow on gene therapy in general. It's worth pointing out, though, that contrary to appearances, germ-line gene therapy should in principle be easier to accomplish safely than somatic cell therapy.

In the latter case, we are introducing genes into billions of cells, and there is always a chance, as in the recent SCID case in France, that a crucial gene or genes will be damaged in one of those cells, resulting in the nightmarish side-effect of cancer.

With germ-line gene therapy, in contrast, we are inserting DNA into a single cell, and the whole process can accordingly be much more tightly monitored. But the stakes are even higher in germ-line therapy: a failed germ-line experiment would be an unthinkable catastrophe; a human being born flawed, perhaps unimaginably so, owing to our manipulation of his or her genes. The consequences would be tragic. Not only would the affected family suffer, but all of humankind would lose because science would be set back.

When gene therapy experiments in mice run aground, no career is aborted, no funding withdrawn. But should gene improvement protocols ever lead to children with diminished rather than improved potential for life, the quest to harness the power of DNA would surely be delayed for years. We should attempt human experimentation only after we have perfected methods to introduce functional genes into our close primate relatives.

But even when monkeys and chimpanzees (an even closer match) can be safely gene-enhanced, the start of human experimentation will require resolute courage; the promise of enormous benefit won't he fulfilled except through experiments that will ultimately put lives at some risk. As it is, conventional medical procedures, especially new ones, require similar courage: brain surgery, too, may go awry, and yet patients will undergo it if its potential positives outweigh the dangers.

My view is that, despite the risks, we should give serious consideration to germ-line gene therapy. I only hope that the many biologists who share my opinion will stand tall in the debates to come and not be intimidated by the inevitable criticism.

Some of us already know the pain of being tarred with the brush once reserved for eugenicists. But that is ultimately a small price to pay to redress genetic injustice. If such work be called eugenics, then I am a eugenicist.

Over my career since the discovery of the double helix, my awe at the majesty of what evolution has installed in our every cell has been rivalled only by anguish at the cruel arbitrariness of genetic disadvantage and defect, particularly as it blights the lives of children. In the past it was the remit of natural selection - a process that is at once marvellously efficient and woefully brutal - to eliminate those deleterious genetic mutations. Today natural selection still often holds sway: a child born with Tay-Sachs who dies within a few years is, from a dispassionate biological perspective, a victim of selection against the Tay-Sachs mutation.

But now, having identified many of those mutations that have caused so much misery over the years, it is in our power to sidestep natural selection. Surely, given some form of pre-emptive diagnosis, anyone would think twice before choosing to bring a child with Tay-Sachs into the world. The baby faces the prospect of three or four long years of suffering before death comes as a merciful release.

And so if there is a paramount ethical issue attending the vast new genetic knowledge created by the Human Genome Project, in my view it is the slow pace at which what we now know is being deployed to diminish human suffering.

Leaving aside the uncertainties of gene therapy, I find the lag in embracing even the most unambiguous benefits to be utterly unconscionable. That in our medically advanced society almost no women are screened for the fragile X mutation a full decade after its discovery can attest only to ignorance or intransigence. Any woman reading these words should realise that one of the important things she can do as a potential or actual parent is to gather information on the genetic dangers facing her unborn children by looking for deleterious genes in her family line and her partner's, or, directly, in the embryo of a child she has conceived.

And let no one suggest that a woman is not entitled to this knowledge. Access to it is her right, as it is her right to act upon it. She is the one who will bear the immediate consequences.

Two years ago, my views on this subject received a very cold reception in Germany. The publication of my essay, "Ethical Implications of the Human Genome Project," in the highly respected newspaper Frankfurter Allgemeine Zeitung (FAZ), provoked a storm of criticism. Perhaps this was the editors' intent. Without my knowledge, let alone consent, the paper had given my essay a new title devised by the translator as "The Ethic of the Genome - Why We Should Not Leave the Future of the Human Race to God."

While I subscribe to no religion and make no secret of my secular views, I would never have framed my position as a provocation to those who do.

A surprisingly hostile response came from a man of science, the president of the German Federal Chamber of Medical Doctors, who accused me of "following the logic of the Nazis who differentiate between a life worth living and a life not worth living."

A day later, an editorial entitled "Unethical Offer" appeared in the same paper that had published mine. The writer, Henning Bitter, argued with self-righteous conviction that in Germany the decision to end the lives of genetically damaged foetuses would never become a private matter.

In fact, his grandstanding displayed a simple ignorance of the nation's law; in Germany today, it is solely the right of a pregnant woman, upon receipt of medical advice, to decide whether to carry her foetus to term.

The more honourable critics were those who argued openly from personal beliefs, rather than exploiting the terrifying spectre of the German past.

The respected German President, Johannes Rau, countered my views with an assertion that "value and sense are not solely based on knowledge".

As a practising Protestant, he finds truths in religious revelation while I, a scientist, depend only on observation and experimentation. I therefore must evaluate actions on the basis of my moral intuition. And I see only needless harm in denying women access to prenatal diagnosis until, as some would have it, cures exist for the defects in question.

In a less measured comment, the Protestant theologian Dietmar Mieth called my essay the "Ethics of Horror", taking issue with my assertion that greater knowledge will furnish humans better answers to ethical dilemmas. But the existence of a dilemma implies a choice to be made, and choice to my mind is better than no choice.

A woman who learns that her foetus has Tay-Sachs now faces a dilemma about what to do, but at least she has a choice, where before she had none.

Though I am sure that many German scientists agree with me, too many seem to be cowed by the political past and the religious present: except for my longtime valued friend Benno Müller-Hill, whose brave book on Nazi eugenics, Murderous Science (Tödliche Wissenschaft), still rankles the German academic establishment, no German scientist saw reason to rise to my defence.

I do not dispute the right of individuals to look to religion for a private moral compass, but I do object to the assumption of too many religious people that atheists live in a moral vacuum. Those of us who feel no need for a moral code written down in an ancient tome have, in my opinion, recourse to an innate moral intuition long ago shaped by natural selection promoting social cohesion in groups of our ancestors.

The rift between tradition and secularism first opened by the Enlightenment has, in more or less its present form, dictated biology's place in society since the Victorian period.

There are those who will continue to believe humans are creations of God, whose will we must serve, while others will continue to embrace the empirical evidence indicating that humans are the product of many millions of generations of evolutionary change.

John Scopes, the Tennessee high school teacher famously convicted in 1925 of teaching evolution, continues to be symbolically retried in the 21st century; religious fundamentalists, having their say in designing public school curricula, continue to demand that a religious story be taught as a serious alternative to Darwinism.

With its direct contradiction of religious accounts of creation, evolution represents science's most direct incursion into the religious domain and accordingly provokes the acute defensiveness that characterises creationism.

It could be that as genetic knowledge grows in centuries to come, with ever more individuals coming to understand themselves as products of random throws of the genetic dice - chance mixtures of their parents' genes and a few equally accidental mutations - a new gnosis in fact much more ancient than today's religions will come to be sanctified.

Our DNA, the instruction book of human creation, may well come to rival religious scripture as the keeper of the truth.

I may not be religious, but I still see much in scripture that is profoundly true. In the first letter to the Corinthians, for example, Paul writes:

"Though I speak with the tongues of men and of angels, but have not love,

"I have become sounding brass or a clanging cymbal.

"And though I have the gift of prophecy, and understand all mysteries and all knowledge,

"and though I have all faith, so that I could remove mountains,

"but have not love, I am nothing."

Paul has in my judgment proclaimed rightly the essence of our humanity.

Love, that impulse which promotes our caring for one another, is what has permitted our survival and success on the planet. It is this impulse that I believe will safeguard our future as we venture into uncharted genetic territory. So fundamental is it to human nature that I am sure that the capacity to love is inscribed in our DNA. A secular Paul would say that love is the greatest gift of our genes to humanity.

And if some day those particular genes, too, could be enhanced by our science, to defeat petty hatreds and violence, in what sense would our humanity be diminished?

In addition to laying out a misleadingly dismal vision of our future within the film itself, the creators of Gattaca concocted a promotional tag line aimed at the deepest prejudices against genetic knowledge: "There is no gene for the human spirit."

It remains a dangerous blind spot in our society that so many wish this were so. If the truth revealed by DNA could be accepted without fear, we should not despair for those who follow us.

Secret of Life, by James Watson with Andrew Berry. William Heinemann. 446pp, stg£20. ISBN number: 0 434 01116 9.