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Juggling With Genes

The Hazards of Recombinant DNA Reconsidered

By Laurie Hays

Last week a Harvard scientist won the Nobel Prize for Physics. While the scientific community applauded the award, the significance of his discoveries, for the most part, escaped the general public. Except for particular areas of research, such as possible cures for cancer, most scientists investigate such arcane aspects of general scientific problems that few laymen can comprehend the significance of their work. But recombinant DNA research, or gene splicing, associated with wild scenarios of two-headed monsters, has brought scientists and laymen together over the past three years to mull over the potential dangers of conducting such research. Scientists are straining for the opportunity to conduct experiments that are already permitted in other parts of the world. And they slowly, but surely, seem to be winning their point, despite the struggles of citizens anxious to ensure the safety of their communities and their futures.

Containment facilities for such research are springing up around the country, specially designed under guidelines specified by the National Institutes of Health (NIH), which set out in 1975 to prevent disasters that might occur if some of the research material should escape from the laboratories. Within two months, P-3 containment facilities for recombinant DNA research on the fourth floor of the Biological Laboratories will be ready for safety inspection. At about the same time these labs will be undergoing investigation, two even more sophisticated laboratories in Bethesda, Md., and Fort Dixon, Texas, idle since biological warfare research was banned in 1971, will reopen to perform similar, but potentially more dangerous, experiments to introduce and mix unrelated bacterial genes. Citizens in Amherst, Mass., have just begun a fight similar to the one Cambridge citizens waged last year to stop construction of P-3 laboratories for DNA research in Cambridge, while scientists at MIT and the University of Southern California at San Francisco surged ahead in an effort to gain time on their fellow scientists who are bogged down by the controversies raging over their work.

The controversy over recombinant DNA began in 1974 when scientists working in the field initiated a self-imposed moratorium on their research after they discovered they were working with potentially hazardous material. Since that time, review committees at the NIH have established the national guidelines to permit the kind of research which scientists hope will bring cures for cancer and for solving nutritional problems. Owing to the vastness of the field, however, the expectations are unlimited.

The desire to tinker with the most basic element of nature from the start provoked the public into a slowly waning crusade against scientists eager to commence DNA research work and receive recognition before other laboratories around the world did so first. Two summers ago the Cambridge City Council undertook the task of reviewing the controversial research planned by local universities and eventually emerged with a conditional approval of the research. The problem confronting the Council in its review--which attracted national media coverage--lay in the composition of the deciding body, a nine-member citizen's review panel, none of whom were scientists. Cambridge Mayor Alfred E. Vellucci says the Council and the review committee heard presentations by Harvard scientists George Wald, Higgins Professor of Biology emeritus, Richard N. Goldstein, assistant professor of Microbiology, and Ruth Hubbard, professor of Biology. They warned Cambridge citizens of the dangers involved in the research while Francis M. Pipkin, associate dean of the Faculty and chairman of the University's Committee on Research Policies, downplayed the potential dangers. "We didn't know who to believe," Vellucci says, adding that scientists who were "even Nobel Prize winners were arguing against each other." Because the job of the Council is to look after the public, Vellucci points to the necessity of not taking any risks which might endanger the community. "When you hear people talking about red ants, insects and possible spills and accidents, you have to go slow," Vellucci says.

Scientists would rather not go slow, however. And the discovery made last spring by a group of scientists in California involving a new gene for producing insulin angered a group of Harvard scientists who were working on the same project but who lacked the facilities to perform similar experiments, illustrating the competitive nature of the field. Scientists in the Harvard laboratories uttered bitter sentences when asked for a response to the California discovery. "The only reason we couldn't get those results was because we didn't have a P-3 facility to clone the gene," one scientist said, adding that he did not think the California discovery merited a story on the front page of The New York Times.

But the hysteria prevailing on the scientific front has gone even further than the angry words expressed here last spring. Sen. Edward M. Kennedy '54 (D-Mass.) withdrew his name last month from a bill he introduced last April which would have imposed severe penalties--up to $10,000 a day for experimentation performed which did not conform to NIH guidelines--under pressure from a number of scientific committees that paid him a visit in Washington. "That first bill excited resistance among the governing board of the American Scientists Committee of Microbiology," says DeWitt Stetton '30, deputy director of science at NIH. Stetton adds that the bill did not receive much support in the Senate and added he was glad to see it dropped. The bill is currently being revised to merely withdraw federal funding from any research projects which fail to meet the NIH guidelines and to deny patent rights to any discovery which might be performed under illegal conditions. If passed, the bill will offer the option of keeping scientists honest, but will lack any moralistic or political overtones.

On the whole, Washington's anxieties about recombinant DNA research have subsided somewhat in recent months, and NIH is preparing a revision of its original 1975 guidelines adopted at the Apilomar, Cal., conference. The revisions discussed last June at an NIH-sponsored conference in Falmouth, Mass., mostly include specific cases of DNA research which originally were classified to be performed in stricter containment facilities. "We initially over-reacted to the severe anxiety surrounding the issue," Stetton says, adding that the NIH review committee has significantly shifted its position. Quoting Mark Twain, who once said that the most dangerous thing we could do was lie in bed "because that's where the most people die," Stetton points out that the world we live in is full of risks. "It would be interesting to try and list, in order of degree, the number of dangers we live with, and if we did, I think that recombinant DNA would be about 95th," Stetton says.

Supporting this view in an Op Ed piece in The New York Times last April, Rene Dubos, a microbiologist and professor emeritus of Rockefeller University, wrote, "I now realize [however] that genetic change occurs frequently under natural conditions... I doubt that gene recombination in the laboratory will create microbes more virulent than those endlessly being created by natural processes." Dubos concludes his article by describing DNA research as "one of the most exciting areas of knowledge, with large philosophical and scientific implications for the misunderstandings of life."

While Washington remains primarily concerned with the possibilities of an accident occurring in a laboratory in the form of spills, there is still the problem of anticipating what the results of DNA experimentation will be used for. Dubos seems optimistic about the future, but Jonathan R. Beckwith, professor of Microbiology and Molecular Genetics, says that the major problem with recombinant DNA research does not consist of the health hazards but rather the uses to which future discoveries may be applied. Citing his distaste for explaining social problems with genetics, such as determining crime rates by finding the number of Y genes in males (an XYY male was once thought to be more likely to commit crimes) Beckwith believes it is more important to study the broader questions. "If scientists are given a free reign, they'll do whatever they want, and they will stop at nothing," he says. Beckwith's laboratory stopped performing recombinant DNA experiments because of his moral misgivings about the future results it could provide and because there are many other areas to be investigated, he says.

Given the pressure exerted on Kennedy to halt his first bill, it is evident that scientists, on the whole, do not react favorably to restrictions. But Beckwith believes that the imposition of some type of restrictions would not be any different from allocating federal funds. "I don't think that science proceeds freely," he says, adding that officials in Washington who review grant applications are the ones who decide what projects will survive.

Beckwith joined over 100 scientists who sent a letter to Congress two weeks ago expressing their disagreement with the misrepresentation and exaggeration of recent data purporting to show the safety of recombinant DNA research. "The NIH now finds that the guidelines it originally issued in July, 1976, for the conduct of recombinant DNA research are too restrictive and is planning to weaken them. We feel it is no longer the prerogative of the NIH to rewrite these guidelines," the letter stated.

The NIH committee, according to Stetton and Daphne Kamely, assistant to the director's office on recombinant DNA activities in Washington, will continue to review the cases, and as more experimentation proceeds, it may become possible to relax the limitations, she says.

Daniel Branton, professor of Biology and chairman of the Harvard Biohazards review committee, reiterates the need for constant reviews and, wherever it is possible, some loosening of the restrictions. "You have to make a decision detween making discoveries and applying them," Branton comments, adding that "you get into a lot of problems when you start regulating discoveries."

So, while it is necessary that Harvard's committee continue to inspect facilities and for the NIH to be constantly aware of the activities being performed in P-3 facilities, the question at hand may essentially boil down to whether or not science should be restrained. For those who are strongly opposed to the research, there must be more assurance from Washington officials that the results produced from recombinant DNA research will not be abused. But scientists performing the controversial experiments wish to proceed without limitations, and the issue will not subside until there is some compromise on both sides, which is the job left to the politicians.

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