Building better humans

The sci-fi possibilities of genetic tampering may soon become real. And there's no law against them.

Published June 27, 2000 7:00PM (EDT)

A young couple having difficulty conceiving a child undergoes tests to pinpoint the problem. As they sit in the doctor's office, awaiting the results, each wonders whose reproductive system has failed.

"There's nothing wrong with either of you," the doctor tells them, at last.

"So what's the problem?" they ask.

"You're two different species. You can't interbreed."

Science fiction? Perhaps for now. But according to the eminent physicist Freeman Dyson, this is where the human genome project will inevitably lead us. He and his Princeton colleague, molecular biologist Lee Silver, say that rapidly emerging genetic technology will ultimately split humanity into many species.

They draw their conclusion from cold, complex science, but their point is simple, and frightening: Once we figure out how to safely manipulate our genes, people will start adding and deleting them to their perceived advantage. Different sorts of humans will emerge. And it's safe to assume that each will decide that it is superior.

While anyone who watched even a minute of "Britney in Hawaii" might believe that this has already occurred, rest assured it has not.

But the development and use of genetic engineering are the subject of ferocious debate among the scientific elite. Some influential scientists, notably James D. Watson, the father of DNA research, are pushing for experiments that were once unthinkable: tampering with the human germline -- sperm and egg cells. In other words, genetically altering not only an individual, but future generations.

"Some people are going to have to have some guts and try germline therapy without completely knowing that it's going to work," Watson said at a UCLA conference in 1998. "And the other thing, because no one has the guts to say it, if we could make better human beings by knowing how to add genes (from plants or animals), why shouldn't we do it? What's wrong with it?"

Human germline engineering is prohibited in federally funded research. But there is no ban on such experiments in the private sector. Last weekend, a coalition of activists and organizations met in San Francisco to form the Exploratory Initiative on New Genetic Technologies. On Wednesday, the group will announce efforts to develop a broad movement to push for limitations on genetic technologies, including statutory bans on germline genetic engineering and human cloning.

"A ban," says Watson, "would be a disaster."

To get a glimpse of what might very well be our future, it helps to understand some boring science. All current human genetic therapy trials are called somatic: they involve genes in various parts of the body, but not the sex cells, which produce eggs and sperm. Tampering with sex cells -- producing genetic alterations that will be passed to your offspring, and their descendents -- takes genetic engineering into an entirely new technological and ethical realm.

While many experts believe that germline engineering is at least a decade away, Hamilton Smith, a Nobel laureate biochemist, sees the technology developing much more rapidly. "It might come pretty quickly," he says.

Smith knows something about the speed of technological advance. He is the director of DNA Resources for Celera Genomics Corp., which, in just nine months, produced a rough map of the human genome -- a feat that most scientists said would take years.

The pressure for germline engineering is also likely to come from another direction -- you and me. We want children better than ourselves. We certainly don't want them to suffer unnecessarily. David Baltimore, a Nobel laureate who heads the California Institute of Technology, believes that consumer demand will encourage the rapid development and utilization of germline engineering.

Genetic screening is already standard in prenatal care. It is not farfetched to imagine that prospective parents will one day turn to clinics to produce embryos that can not only be tested for genetic defects, but also "corrected." And is there any reason to think people will stop at fixing disease-causing defects? Is it such a stretch to imagine people demanding genetic enhancements -- mental, physical, behavioral?

Prominent scientists not only believe the possibility is real; they are also preparing for it. At a retreat of the premier geneticists and policy analysts last summer at the Jackson Laboratory in Bar Harbor, Maine, LeRoy Walters, director of the Kennedy Center of Ethics, gave a speech on methods for guaranteeing equal access to the enhancement of intelligence.

How close are we to being able to alter the human gene book? Germline genetic manipulation of other mammals is already occurring. Genes are routinely deleted from and added to mice for experiments. Five years ago a University of Pennsylvania researcher discovered how to alter the genes in the sperm of mice, and applied for a patent on it. In the wake of that advance, ethicists called for national and international meetings on germline engineering. Mice and humans are estimated to share 90 percent of their genomes.

The implications of germline engineering are so profound, and scary, that some leading scientists dismiss the possibility that anyone would seriously contemplate doing it. Asked Monday whether any reputable scientists are advocating germline engineering in humans, Celera founder and president J. Craig Venter said that he knew of nobody.

But in a new book, Watson, perhaps the most influential figure in biological research in the last half-century, is quoted as calling for germline engineering during a 1998 conference at UCLA. Watson co-discovered the double helix structure of DNA, the basis for all the genetics research, including the mapping of the genome. He was the first director of the publicly funded Human Genome Project, and is now president of the Cold Spring Harbor Laboratory on Long Island. On July 4, he is scheduled to receive the $100,000 Liberty Medal in Philadelphia for his life's work.

However shocking Watson's opinion might sound, he provides sound reasons for germline engineering, according to the transcript published in "Engineering the Human Germline: An Exploration of the Science and Ethics of Altering the Genes We Pass to our Children," edited by Gregory Stock and John Campbell. For one, germline engineering is more efficient than treating patients one by one. "You delete a bad gene from the gene pool, and no future generation need worry about it or undergo genetic therapy for it. Also, if a deadly infection broke out across the globe, humanity would be saved by implanting disease resistance into the germline."

Watson offers scientists a strategy for confronting the social challenges that will face germline engineering.

"I'm afraid of asking people what they think. Don't ask Congress to approve it. Just ask them for 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 or principles."

Although other nations, including Britain, Japan and China, cooperated in and contributed to the sequencing of the human genome, Watson believes that attempts to coordinate globally on the genome manipulation would retard the effort. "I think it would be a complete disaster to try and get an international agreement, he says. "I just can't imagine anything more stifling. You end up with the lowest common denominator."

As for regulating genetic engineering, he says: "I think our hope is to stay away from regulations and laws whenever possible."

Watson ridicules the notion that human genome has sanctity, or that civil rights should somehow enter the debate. "I think it's complete nonsense. I mean, what or who sanctifies? ... Evolution can just be damn cruel, and to say that we've got a perfect genome and there's some sanctity? ... Terms like sanctity remind me of animal rights. Who gave a dog a right? The word 'rights' gets very dangerous. We have women's rights, children's rights; it goes on forever.

"I'd like to give up saying rights or sanctity. Instead, say that humans have needs, and we should try as a social species to respond to those needs ... To try to give it 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 is not alone in his support for germline engineering. But in science circles there is also strong emerging opposition to such experiments, and growing support for regulation.

Last month, Eric Lander, a friend of Watson and director of the largest publicly funded genome sequencing center, at the Massachusetts Institute of Technology, called for a ban on human germline gene therapy because of our limited knowledge. The human genome, Lander says, "has been 3.5 billion years in the making. We've been able to read it for the last year or so. And we suddenly think we could write the story better?"

Lander acknowledges that there are potential benefits to germline engineering. "There is the prospect that by changing things we might put off aging, prevent cancer, improve memory." The dazzling possibilities, he says, makes it tough to recommend reining in scientists. "I find it a very difficult question," he said. "For my own part, I would have a ban in place, an absolute ban in place on human germline gene therapy. Not because I think for sure we should never cross that threshold, but because I think that is such a fateful threshold to cross that I'd like society to have to rebut that presumption some day, to have to repeal a ban when it thought it was time to ever try something like that."

Though Celera's Hamilton Smith and Lander were competitors in the race to complete the mapping of the human genome, they agree on this point. "The only thing I'm certain of is that we don't possess the knowledge to monkey with our germline," Smith says. "We don't fully understand the consequences of changes that even look like they would be good." As an example, Smith cites the single genetic mutation responsible for sickle cell disease, which has now been found to simultaneously provide resistance against malaria.

Francis Collins, the director of the National Institutes of Health Human Genome Project, also has repeatedly urged caution on germline, which he views as humans fully taking charge of their evolution. But asked Monday whether he would support a ban, he demurred, afraid that opening that door for legislation could lead to other prohibitive measures that would impede important biomedical progress.

Princeton's Dyson has his own ideas on what is to be done. In his view, the speciation of humans into different groups is inevitable -- and it would be a disaster to allow such diversification without restraint. "We must travel the high road into space, to find new worlds to match our new (genetic) capabilities," Dyson writes in "The Sun, The Genome and The Internet," published last year. "To give us room to explore the varieties of mind and body which our genome can evolve, one planet is not enough."

More sci-fi fantasy? The ravings of an aging academic? I asked Celera's Smith what he thought. He paused, and then said, "Dyson's a very smart guy. I think there's a lot to what he says for the future. It's hard to tell where mankind is going here."

By Ralph Brave

Ralph Brave is a science writer who lives in Davis, California.

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