The New York Times - March 22, 1998 Page 1
By GINA KOLATA LOS ANGELES -- For years, molecular biologists and geneticists have trod gingerly around the most explosive topic of the new reproductive biology: purposely making genetic changes in people that would persist for generation after generation.
There were so many technological roadblocks to the process, called germline genetic engineering, that most scientists viewed it almost as science fiction.
But now, as researchers rush past these roadblocks, a group of eminent molecular biologists and molecular geneticists met Friday on the leafy campus of the University of California at Los Angeles to confront the issue. Their goal was to discuss how, why and when germline engineering should proceed.
The scientists, leaders in the field, were meeting on their own, with no government or other mandate to issue guidelines or regulations and, in fact, no wish to restrict their work. But they said it was time for science to confront its growing powers to shape human biology.
Members of the public and even many scientists are unaware of how close science is to making germline engineering a reality, said Dr. Michael Rose, who studies the genetics of aging at the University of California at Irvine and who was a speaker at the meeting. He said the meeting would bring public attention to "one of the most important questions for the human species: the extent to which it will direct its own evolution."
It will, some day, be possible to give people genes to prevent them from developing certain diseases or to cure them of diseases that stubbornly resist treatment, like cancer or AIDS.
"I could imagine a child that never got a cold," said Dr. John Campbell, a meeting organizer who is a theoretical evolutionary biologist and professor of neurobiology at the University of California in Los Angeles. Eventually scientists may be able to add whole "cassettes" of genes that could confer enhanced intelligence or rid people of the plagues of aging.
Unlike genetic therapies being experimented with today, in which scientists try to insert genes into specific body tissues, these genetic changes could become permanent, present in sperm and egg cells and passed from generation to generation.
Germline genetic engineering "really touches the essence of who we are, what it means to be human," said Dr. Gregory Stock, a conference organizer and director of the Science, Technology and Society program at UCLA's Center for the Study of Evolution and the Origin of Life. "We are talking about intervening in the flow of genetic information from one generation to the next. We are talking about the relationship of human beings to their genetic heritage."
The speakers, drawn from the ranks of molecular biology and genetics, had the most august credentials: memberships in the National Academy of Science, a Nobel prize, editorships of leading journals. Throughout the day, one after the other, they spoke about new possibilities and powerful new tools already under development that could make human germline engineering happen.
No one could say when this new kind of genetic engineering might be put into practice. But they all agreed that seemingly insuperable technical barriers were falling year by year and many said they expected to see many techniques in use within 20 years.
For example, Campbell said as recently as 15 years ago that putting a cassette of genes together would have been a herculean task. Now it's a project for graduate students.
Of course, once genetic germline engineering becomes technically feasible, researchers would want to do animal studies to make sure the techniques are safe before trying them in people.
Today, obstacles to germline engineering are practical, not theoretical. Scientists have the ability to add desired genes -- snapping gene cassettes onto artificial chromosomes and injecting the chromosomes into newly fertilized eggs. Because every cell in the body is a descendant of that first fertilized egg, every cell would have a copy of the artificial chromosome. Artificial chromosomes, even human artificial chromosomes, have already been created and patented, the scientists reported, and companies have sprung up to exploit the technology.
Dr. Leroy Hood, chairman of the department of molecular biotechnology at the University of Washington in Seattle, said he has now developed a way to create an entire custom chromosome on a computer chip containing DNA.
But what if the artificial chromosome is faulty or what if it begins to look primitive to some future generation that wants the updated version of this genetic software? No problem, said Dr. Mario R. Capecchi, a distinguished professor of biology and human genetics at the University of Utah. Biologists already know how to make artificial chromosomes that can self destruct on command.
The lone ethicist speaking at the conference was Dr. John Fletcher, who was chief of the bioethics program at the National Institutes of Health and is now a professor of biomedical ethics at the University of Virginia. He said he had no problems in principle with giving people genes that would prevent or cure diseases.
But, he said, he is troubled by the idea of adding genes for certain complex traits like, for example, "emotional stability." However, he added, there is nothing intrinsically unethical about germline genetic engineering.
Scientists at the meeting spoke quite seriously about extending the human life span with cassettes of anti-aging genes. They also envisioned adding cassettes of anti-cancer genes and genes that would confer resistance to the AIDS virus.
The cassettes would include control regions that would turn the genes on only in the tissues where and when they are needed. Of course, they noted, no human would be treated until the methods were thoroughly tested in animals and proved safe and reliable.
Campbell described in detail how an anti-cancer gene cassette might work. He envisioned providing cells with the equivalent of a loaded gun, its trigger cocked. But the gun could only go off in certain cells and then only if a person deliberately pulled it.
For prostate cancer, for example, scientists might add a gene that would kill prostate cells on command. To control such a gene, scientists would hook it to another gene that responds to an insect hormone, ecdysone, that normally has no effect on human cells. If a man found he had prostate cancer, he would take an ecdysone pill. It would activate the suicide gene, killing his prostate cells, but leaving every other cell of his body untouched.
The cassettes eventually could be enormously sophisticated, scientists said. If you wanted to enhance the human species, Hood explained, you would add entire clusters of genes that would interact and boost or modulate each other's effects as genes do in nature.
The Human Genome Project, an ambitious effort map the entire sequence of human DNA, should reveal those gene clusters, he said, and then it would be only a matter of time before they are used in genetic engineering.
With the genome project, Hood said, "we have the tools, the data, the vision, to do systems biology the way it was never done before." And so, he added, human germline engineering is "absolutely" going to happen.
What is most amazing, said Dr. Lee Silver, a molecular geneticist at Princeton University and editor in chief of the journal Mammalian Genome, is that germline engineering, for a variety of technical reasons, should actually be easier than the more limited genetic engineering that scientists have tried thus far.
Dr. James D. Watson, director of the Cold Spring Harbor Laboratory in New York and winner of a Nobel Prize in 1962 for discovering the structure of DNA, agreed. If scientists wait for conventional genetic engineering to succeed before trying germline engineering, he said, "we might as well wait for the sun to burn out."
And, he asked, why not try germline genetic engineering when the methods are ready? "If you could cure a very serious disease, stupidity," Watson said, "that would be a great thing for the people who otherwise would be born seriously disadvantaged."