James Watson

Did you have a nice DNA Day? And how was your Human Genome Month?

If you missed those Congressionally-designated celebrations last month due to minor distractions, like a war or being laid off from your job, don't worry: The media missed the real story anyway.

Many of the newspaper, radio and television accounts of the 50th anniversary of the discovery of DNA's double helix, focused on the eccentric genius and baffling charm of co-discoverer James Watson. Meanwhile, largely unnoticed, Nobel laureate Watson, or "Honest Jim" as he likes to consider himself, celebrated in his own way: by continuing to aggressively advance his agenda for genetically re-engineering the human species -- even if that requires engaging in medical experimentation that puts lives at risk.

Some observers reflexively dismiss Watson's genetic prescriptions as the idiosyncratic ideas of a crank; wasn't that, they ask, the fellow who suggested a genetic linkage between skin color and sex drive? Or else ascribe them to Watson's desire to keep genetic research at the cutting edge. Yet while both of these hypotheses could be true, they miss the more important point: James Watson genuinely believes in a renewed eugenics, now scientifically accurate and technically powerful, and has laid out a logical, strategic framework for moving science and society in that direction.

Reviewing a recent biography of Watson, his former Harvard colleague Walter Gilbert tells the story of Watson mussing up his hair and untying his shoelaces before going into meetings with philanthropic donors. While we might still bemuse ourselves with Watson's performance as the absent-minded professor, we would also do well to keep a serious eye on his program for the human genetic sciences.

Gaining some insight into James Watson's genetic agenda is not really difficult -- all we need do is read his own words. The key requisite scientific notion to grasp is "inheritable genetic modification," most often referred to as "germline genetic engineering." When genetic therapy is attempted to cure the disease of an existing person, those genetic changes will affect only that person. But if genetic engineering is carried out on a sperm or an egg or an embryo, that genetic alteration will be present in every cell of that new person -- including their "germline," the sperm or egg cells which will then carry those modified genes forward into all future generations.

During the 1990s, after being forced out as director of the National Institutes of Health human genome research center, James Watson began explicitly advocating human germline engineering. His opening rhetorical move is to demystify, or some would say devalue, the existing human genome and the real humans that develop from them.

"I think it's complete nonsense ... saying we're sacred and should not be changed," Watson railed at a 1998 UCLA conference. "Evolution can be just damn cruel, and to say we've got a perfect genome and there's some sanctity? I'd like to know where that idea comes from because it's utter silliness ... To try to give it any more meaning than it deserves in some quasi-mystical way is for Steven Spielberg or somebody like that. It's just plain aura, up in the sky -- I mean, it's crap."

Watson then sought to pre-empt any scientific self-doubt: "We should be proud of what we're doing and not worry about destroying the genetic patrimony of the world, which is awfully cruel to too many people," he said. "We get a lot of pleasure from helping other people. That's what we're trying to do."

With the imperfect human genome cast as the cruel enemy and the scientist as the savior, one might assume that Watson is merely referring to curing genetic disorders. His recent public revelation of having a child of his own with a serious neurological disorder resulted in much of the media reporting that Watson's genetic engineering advocacy was motivated by this tragic personal experience. However much that may be the case, though, Watson doesn't stop at treating disease.

"And the other thing, because no one has the guts to say it," Watson informed the 1998 conferees, "if we could make better human beings by knowing how to add genes, why shouldn't we do it? What's wrong with it? Who is telling us not to it?"

Neo-Eugenics

Making "better human beings" differs from making human beings better by curing their diseases. Making better human beings is more closely aligned with the old eugenics vision. The previous century's eugenicists sought to breed better humans by promoting specific types. In America, state fairs held "Fitter Family Contests." In Germany, they mandated specific matings. In both countries the drive was to optimize the chances of producing the desired "Nordic" characteristics.

But that was still producing progeny the old-fashioned way, with its probabilities of failure and limitations imposed by the genetic mixture of the two individuals involved. With the new genetic technologies, the desired breed of better humans will be predictably engineered in your local fertility clinic.

But what exactly are Watson's eugenics intentions? How would he design better human beings? The germ-line intervention that he and other advocates most often mention is improvements to the immune system. There is a gene, for example, which provides absolute resistance to the AIDS virus. If it were possible to safely implant such a gene into an embryo, who would object? Or a gene that similarly protected someone against SARS or an even more deadly emerging infectious disease?

Such germ-line alterations are viewed cynically by Watson, though, as a means to other ends: the wedge that will open the door to further engineering. "I think that the acceptance of genetic enhancement," he writes in his new book, "will most likely come through efforts to prevent disease."

The range of potential genetic enhancements at this point is almost entirely a matter of speculation. But Watson is not shy about suggesting his own eugenic targets. In a British documentary on his life and work to be broadcast in the U.S. this fall, Watson announces that he'd like to genetically treat the 10 percent of children whom he considers "stupid" and prevent the birth of ugly girls. "If you really are stupid, I would call that a disease," Watson says. Furthermore, "People say it would be terrible if we made all girls pretty. I think it would be great."

But Watson doesn't want to simply stop with the existing human genetic repertoire. Remember, Watson wants to "add genes," meaning genes from outside the existing human gene pool. Just to make certain that I wasn't mistaken on this, I tracked Watson down in February at the Time Magazine "Future of Life" conference. By adding genes, were you referring to genes from other plant or animal species or even artificial genes created in the laboratory? I asked Watson. "Anything!" he spat back, and turned away as if the question were not even worthy of discussion.

Don't Ask, Don't Tell

Discussion of this agenda is something Watson is not interested in conducting, whether it's with a journalist or with Congress. "I'm afraid of asking people what they think," he admitted in 1998. "Don't ask Congress to approve it. Just ask them for the money to help their constituents. That's what they want ... . Frankly, they would care much more about having their relatives not sick than they do about ethics and principles. We can talk principles forever, but what the public actually wants is not to be sick. And if we help them not be sick, they'll be on our side."

Once again, treating genetic illness is as much a ploy as it is a therapeutic achievement: If Watson and friends keep our DNA trains running on time, the argument goes, then we'll let them proceed with germline genetic enhancements.

Not that Watson has ever put much stock in "ethics." At last month's NIH symposium honoring Watson, he was hailed for having proposed that 3 percent of the human genome project budget be devoted to exploring the ethical, legal and social implications of the research. No one, however, bothered to mention legal scholar Lori Andrews' witnessing of Watson explaining his real agenda in setting up a bioethics component of the genome project.

"I wanted a group that would talk and talk and never get anything done," Andrews quotes Watson as telling a meeting. "And if they did do something, I wanted them to get it wrong. I wanted as its head Shirley Temple Black."

Since re-engineering humans according to Watson's program arguably not only affects all future generations but at least theoretically raises the prospects of altering the species itself, some would claim that this is a choice for the global village of humanity to make, not individuals or even nations. Needless to say, this idea is repellant to Watson.

"I think it would be a complete disaster to try and get an international agreement," he asserted. "You end up with the lowest possible denominator. Agreement among all the different religious groups would be impossible. About all they'd agree upon is that they should allow us to breathe air. ... I think our hope is to stay away from regulation and laws whenever possible."

With the human genome, evolution, Congress, ethics and the international community dispatched as evil or irrelevant, the remaining obstacle to Watson's program lies within the scientific community itself: What scientist is willing to engage in germ-line engineering experimentation?

Watson used the occasion of this 50th anniversary of the double helix discovery to break through this barrier. In a just-published book, "DNA: The Secret of Life," he acknowledges the problem. "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," he writes. "The consequences would be tragic. Not only would the affected family suffer, but all of humankind would lose because science would be set back."

Human guinea pigs

As with other biomedical innovations, even if germline engineering proves successful in other primates, the same technique applied to humans would have unknown results. That's why, Watson writes, "the start of human experimentation will require resolute courage; the promise of enormous benefit won't be fulfilled except through experiments that will ultimately put some lives at risk."

"My view," he concludes, "is that, despite the risks, we should give serious consideration to germ-line gene therapy. I only hope," he plaintively appeals, "that the many biologists who share my opinion will stand tall in the debates to come and not be intimidated by the inevitable criticism ... If such work be called eugenics, then I am a eugenicist."

Rescuing the word eugenics from its pernicious past, Watson knows that inevitably the connection with Naziism will arise. But he's well prepared for this. "Here we must not fall into the absurd trap of being against everything Hitler was for," he wrote a few years ago. "Because of Hitler's use of the term Master Race, we should not feel the need to say that we never want to use genetics to make humans more capable than they are today."

The technology for human germ-line genetic engineering is considered to be some years or even decades away, though an unexpected laboratory breakthrough could accelerate its arrival. Germ-line genetic alteration of our fellow mammal, the mouse, is already a standard procedure in laboratories world-wide.

Harnessing a natural process known as "homologous recombination," scientists are able to target specific genes in order to turn them on or off. Francis Collins, director of the National Human Genome Research Institute, openly worries that when this technique advances so as to be reliable and efficient in humans, "there will be those arguing that it is time for us to take charge of our own evolution." Of course, this is precisely what James Watson is arguing we should do.

Scientists choose sides

As with most other developments in the life sciences, three camps have formed over the germ-line issue: those who join Watson's choir in favor of germline engineering, those who adamantly oppose any germline interventions, and those who believe that there may be instances in which germline engineering is justified and should be managed under some regulatory regime.

The Watsonians include Princeton biologist Lee Silver and University of Manchester bioethicist John Harris. Professor Harris, author of the book "Wonderwoman and Superman," responded to an email query that he does "not think there are any principled objections to germ line therapy or alterations." The only question for him, as for Watson, "is the level of risk of things going wrong set against the benefits."

While this group believes that the best social protection is keeping the government away from any involvement in the genetic decision-making, biologist Silver is famous for forecasting that the social result will be a genetically-enhanced class of the "GenRich" dominating the world. He and fellow Princeton physicist Freeman Dyson concur in believing that the ultimate development will be a number of distinct human species.

Such visions have helped ignite an opposition movement, which opposes any germ-line intervention as the means to assure that no such social scenario can ever come into creation. United with religious and social conservatives who oppose any manipulation of the embryo, these opponents are receiving a hearing of their views under a Bush administration with a president's bioethics council headed by Leon Kass. Progressive activists such as Judy Norsigian of the Boston Women's Health Collective and environmental writer Bill McKibben have been prominent in urging a ban on cloning, as this technology is viewed as another technique that would enable a genetically-modified human future.

Their arguments are both principled and pragmatic. As a principle, they resist a biotechnology that would deepen existing social chasms or further undermine human identity and meaning. As a practical matter, they believe there are existing alternatives to germ-line engineering that can achieve any prospective therapeutic goals.

Even University of Texas health law professor John Robertson, well-known for his advocacy of free choice in utilizing reproductive technologies, "doesn't see a strong case for doing" germ-line. Since germ-line would likely require the creation of multiple embryos, Robertson believes that the existing technique of Pre-implantation Genetic Diagnosis (PGD) can be used to screen out embryos with the genetic problem. "It's hard to see that the benefits of it are going to be so strong that they would outweigh or justify the risk of having severely affected offspring," he said in an interview.

But there are cases in which even PGD would not work, as when both parents are carriers of a gene mutation which can cause serious disease. There also will be instances, says Georgetown University bioethicist LeRoy Walters, in which parents for religious reasons do want to destroy an unwanted embryo. Walters also cites the "functioning of the human immune system so that fewer people would have allergies or autoimmune disease" as an example where germline intervention may be desirable and perhaps necessary.

In this, he represents the pragmatic approach, saying "let's take each case and look at it on its merits and try to balance benefits and harms on the basis of the best evidence we have from preclinical studies." But Walters admits to worry about social justice, about "the distribution of such an intervention and trying to avoid exacerbating the gap between the best off and the least well off in society." For this and other reasons, he favors regulation of germline rather than either an open door or a ban.

Walter's view is the dominant one in scientific and biomedical circles. In the fall of 2000, the American Association for the Advancement of Science issued the report of an expert working group on the subject calling for regulation of germline genetic experiments and technologies by "a public body...assigned responsibility to monitor and oversee research and developments" in the area. Still, the AAAS report is concerned not only about the safety issues, but that germline genetic engineering has "the potential to bring about not only a medical, but also a social revolution, for they offer us the power to mold our children in a variety of novel ways."

While the federal government currently does not fund research which involves human germline genetic engineering, neither is there any U.S. law forbidding it in the private sector. Almost every effort at instituting regulatory oversight in the life sciences has met stiff resistance, based on arguments that it would interfere with individual liberty or impede scientific advances and economic growth in the biotechnology sector. As a result, today there is no regulation of genetic testing or of the fertility industry.

Those who oppose germline engineering on principle oppose a regulatory regime which would make case by case judgments. For them, the question is not a matter of cases, but what kind of world we want to live in.

Whether that opposition or even any regulatory scheme can withstand the genetic enticements offered by James Watson is the story the human species will be living through in the years to come.