Biotech Panel Wrestles With Oversight Role

New DNA technology outpaces NIH committee's original charter as other agencies move to regulate experiments in genetics. WASHINGTON--A government panel that oversees scientific experiments involving genetically engineered organisms is grappling with an issue that could alter the way in which that science is performed. The National Institutes of Health's Recombinant DNA Advisory Committee (known as "the RAC"), was formed in 1974 after scientists recognized the need for guidelines to control the results of a new technology that allowed researchers to splice together genes to form artificial genetic hybrids in a process called recombinant DNA. But now that panel is being forced to adjust to a changing situation that threatens to undo the order that has existed for the past decade. One problem facing RAC is that the technology doesn't stand still. Biotechnologists have developed new ways to make large quantities of DNA and to introduce DNA into cells that don't involve the recombinant DNA techniques outlined in the early guidelines. Although these techniques can produce the same types of organisms whose properties raised so many concerns 16 years ago, it's not clear that NIH has the authority to oversee them. On another front, plant and animal geneticists are asking to release genetically altered organisms outside the safe confines of the laboratory, into open greenhouses and fields. Those are areas that NIH traditionally has avoided monitoring. Federal agencies like the U.S. Department of Agriculture (USDA), which is in the throes of hashing out its own guidelines, don't want the responsibility, either, and are asking NIH to redefine its jurisdiction. All this confusion has thrown scientists into a morass of incomplete and overlapping guidelines. "Befuddled scientists are constantly calling Washington," says David Mac-Kenzie, director of USDA's national biological impact assessment program, "because they don't know who to go to before doing field research." The current dilemma facing NIH is, in large part, a testimonial to its careful approach to the problem. At the dawn of the new technology, many scientists were unsure about the safety of recombinant DNA. Those fears were magnified by environmental groups who, in some cases, opposed the technology itself as well as the methods being used to protect the public. Concerned microbiologists and biochemists turned to NIH, demanding strict protocols and safeguards. On Oct. 7, 1974, under the aegis of NIH, they chartered a watchdog group that became RAC. After much tinkering it came up with a clear set of rules. All scientists at institutions receiving NIH funds must convince RAC, composed of 25 scientists, lawyers, science ethicists, and public interest representatives, that their experiments with recombinant DNA are being carried out in accord with strictly defined levels of physical and biological containment. Before long, however, it became clear that experiments with recombinant DNA weren't nearly as dangerous as first feared; most of the new organisms couldn't survive in the environment or, if they did survive, couldn't spread. Few were deemed threatening enough to merit the scrutiny of RAC. In fact, RAC's purview has shrunk to the point that today it considers only a tiny percentage of all experiments funded by NIH that involve recombinant DNA. As a result, many policy experts began to ask whether RAC had outlived its usefulness. Some predicted that the few regulatory scraps left to it - monitoring genetically altered pathogenic organisms and human gene therapy, for example - would be handed over to other federal agencies like USDA, the Environmental Protection Agency, or the Food and Drug Administration (FDA). NIH has always been uncomfortable with regulation, notes one policy expert at FDA who sees RAC as an anachronism. "It's like an old bottle of Coke," the official notes. But even so, he says, it would be very difficult politically for an NIH director to pull the plug on RAC. The debate was sharpened in January 1989, when Margaret Mellon, an environmental specialist at the National Wildlife Federation, complained before RAC that the health of people and the environment was threatened by a new generation of genetic engineering techniques not covered in RAC's guidelines. She asked RAC to expand its guidelines. "It's just clear as a bell that researchers are doing something [with the new techniques] that they haven't done before," says Mellon. "We're not just talking about replicating nature." But RAC scientists aren't so sure. "I don't think the new techniques open any new doors into the types of organisms that can be made," says biochemist Monica Riley, the chairwoman of the subcommittee asked to consider the NIH guidelines. "So the question is not `Ah, do we have a new set of potentially dangerous techniques coming down the road?' The point is that we have variations on the theme in laboratory methodology that are not technically covered." Riley says that Mellon's concerns demonstrate the need for an oversight body like RAC. Says Riley: "Are we letting some experiments fall through the cracks, and should they be covered? That's the question we were asked to consider." The main problem facing RAC, Riley says, is defining a system to determine which experiments are dangerous. She and others point out that experiments are destined to keep on falling through the cracks as long as NIH, like most government agencies, determines risk by examining the process by which organisms are created rather than the outcome of the technology. "It's clear the guidelines should be rewritten to incorporate the new methods," says subcommittee member Moselio Schaechter, a microbiologist at Tufts University. "But this would mean the guidelines would expand indefinitely," he says, as each year sees the development of new processes. The alternative, Schaechter says, "is to look at whether the final product is dangerous." RAC is still considering Mellon's complaint. Wivel says that it will be at least two more years before new guidelines can be instituted. Some scientists suggest that RAC restructure its thinking and monitor the potential danger of the organism. But the problem with looking at the product, explains Schaechter, is that it doesn't permit RAC to set limits on the origins of the organisms to be considered. Under such a policy, he notes, "a pathogenic bacteria, for example, would have to be considered under these guidelines, regardless of its origins, natural or man-made." Many scientists wonder whether it's necessary to keep an eye on such a broad array of experiments, even if NIH had the time or money to do so. Once such a review was begun, they ask, how would NIH know when to stop? "The inherent dangerousness of the organism is what's important," agrees Wivel. "But we don't want to look at all naturally occurring organisms that have been exchanging DNA for the past millennium." So far RAC has failed to come up with a hybrid set of regulations that would define all potentially dangerous, man-made organisms because of the inherent problem of defining the unknown. Paradoxically, the two categories of experiments RAC continues to scrutinize are ones defined by their product. The first includes experiments with "dangerous pathogenes or viruses," according to Riley. The other relates to human gene transfer and gene therapy experiments. "Eventually, human gene experiments will probably be taken over by the FDA," predicts W. French Anderson, one of the NIH scientists conducting the first such clinical experiments. "But not until the public is clearly comfortable with the social issues." Anderson and others realize that, at some point, NIH will transfer responsibility for most types of experiments to other government agencies. In the meantime, they say, the most important task of RAC and the federal agencies is to determine a common set of guidelines. Though many outdoor experiments fall into the domain of USDA, there is a large gray area between where NIH responsibility leaves off and where USDA monitoring picks up. Appendices to the RAC guidelines published in 1987 in the Federal Register, for example, cover some - but not all - greenhouse and field tests. "Most people doing greenhouse research don't know about the guidelines, because most scientists don't read the Federal Register," says Dan Jones, deputy director of USDA's Office of Agricultural Biotechnology. "And those guidelines have never been finalized. So people doing outdoor research don't know when their experiments are covered by NIH and when they enter the general ecosystem overseen by the USDA. They can't know, because we don't know." USDA's own Agricultural Biotechnology Research Advisory Committee recently established a working group to come up with some answers. That six-member group met earlier this month to begin to make USDA guidelines compatible with RAC's. "Because NIH doesn't want to consider plants and animals within its purview, USDA is supposed to pick up the slack," says University of Nebraska plant pathologist, Anne Vidaver, a member of the subcommittee to revise the NIH guidelines. "But it's all very fuzzy where the cutoff point is. We need procedures that are consistent among the agencies." As RAC struggles through its identity crisis, it is willing to listen to all recommendations, according to executive secretary Wivel. "What defines the true merit of RAC," he says, "is that it's constantly evolving and reconsidering its mission." Diana Morgan is a freelance science writer in Washington, D.C.

Biotech Panel Wrestles With Oversight Role

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