Recombinant DNA: How Much Risk is too Much? At least three serious issues surround recombinant DNA research. The first is the extent of the actual biohazards that can result; the second is the matter of what and how much risk is necessary; the third is the issue of judicial control or public regulation of scientific work. Recombinant DNA research, sometimes described as gene-splicing, involves a group of techniques in which segments of I)NA molecules from unrelated species are incorporated into the genetic apparatus of bacteria, and the bacteria grown and propagated. For example, DNA from viruses, protozoa, insects, sea urchins, frogs, yeast, mammals and unrelated bacterial soecies have been incoroorated into Escherichia coli, and-many billions of these bacteria produced. Concern arises because certain genetic combinations might produce biohazards, such as disease producing, toxin aeneratina or drug resistant oreanisms. The first e ~ p r e ~ s i oofnconcern came about three years ago from eleven scientists engaged in this research who felt that the simplicity of the teck&ues might lead to widespread experimentation without consideration of potential dangers or~adcquatrsafeguards. They realized that, among ofher things, these techniques might be used tocreatea strainof E. coli c a ~ a b l of' e oroducine botulinum toxin or dinhtheria toxin. or to construEt streptococci or pneumococEi resistant td penicillin. They sought to alert their coworkers to these kinds of potential hazards; they asked that suchexperiments not be done, and they called for a moratorium on construction of recombinant genes containing tumor virus DNA until the implications of such work could be analyzed. [See: Science, 95,654 (February 18,1977).] This expression of concern has led to an ever-widening chorus of opposition to r-DNA research. Leading the critics are a few distinguished biologists like Nobel Laureate George Wald of the Harvard Bio-Labs. Wald is quoted as saying, "Recombinant DNA faces our society with problems unprecedented not only in the history of science but of life on the to redesign living Earth. It places in human hands the capacity oreanisms.. . . The results will be new oreanisms.~.ielf oer; pzuating and, hence, permanent. Once c r k d , they cannot he recalled." Accordine to Wald. this "reoresenh ohssiblv the largest ethical problem that science has ever h a d b face: o u r morality up to now has been to go ahead without restriction to learn all we can about nature. Restructuring nature was not part of the bargain." Although most hiologists agree that the preceding statements summarize some of the kev issues involved. manv biologists, including several of ~ o b e stature, l argue thai the dangers seen by Wald are negligible and comparable to those managed now in laboratories conducting research on communicahle diseases. Three years of agonizing discussion and dehate on this subject within the scientific community and the Natinnal Institutes of Health led to the issuance in September. 1976 of a set of euidelines for research safetv. These guidelines are without enforcement authority and a;e based on the hrlief that the risks involved aresmallcornoared with the knowledge and beneficial applications to be by the research. In essence, the NIH guidelines [Fed. Reg., 41 (176) (9 September 1976)]: a) prohibit experiments in which there is some scientific basis for anticipating that a hazard will result. h) require that r-DNA experiments for which there is a t present no evidence of hazard, hut for which it is perceived that the hazard might be potentially serious if conjectural ~
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fears prove to be real, he carried out in high level (P4) containment facilities. These facilities are designed for work with the most hazardous naturally occurring microorganisms known to man. C) require experiments associated with still lesser degrees of bvoothetical risk to be conducted in P 3 containment facilitik's, and those with unlikely hazard potential to be carried out in P2 facilities. Despite the discussions and guidelines, the debate over allowing DNA research to proceed continues. The issues will not he resolved easily. Perhans the most readilv understood and addressed of these issues is'the extent of th; real and present danger to puhlic health and safetv~osedhv r-DNA research. There can be no doubt that letbafvhses A d other deadly microorganisms can he created. Nature has nroduced oreanisms that cause everything from b~bonic'~1agueandsmallpox to Marburg hemorrhagic fever (a virus caused disease that claims nearly 100 percent of its victims). The possibility that some such deadly species can he produced in r-DNA research cannot be eliminated. ~owever;because much is known of the microbiology of microorganismsrecognized as harmful, there is good scientific basis for anticipating when a hazard might result from r-DNA experiments. By universal agreement such experiments are prohibited. For many experiments there is no evidence of a biohazard, hut there also is no certainty that there is no hazard. For these exoeriments. euidelines and containment procedures have been developk2 In effect, the euidelines are orecautions to nrotect the oublic aeainst haz>ds that are not known to exist, but t i a t migLt possibly exist. Some critics of r-DNA research contend that even if a particular recombinant DNA molecule shows no evidence of being hazardous a t present, we cannot be certain that it will not devastate life on earth some years hence. This raises the question of how much risk in siientific research should be permitted or is indeed necessary to safeguard human life against deleterious microorganisms that might appear from any origin. An examination of the benefits that can accrue (and already have accrued) from r-DNA research-benefits such as enhanced understanding of the nature, functioning and ex~ression-reeulationin eenes. the causes of antibiotii resistance in bacteria, tecbni&es that will revolutionize the nroduction of antibiotics. vitamins. vaccines and other medically useful chemicals, and the prospects of this research leading to better understanding of and control of viral and bacterial caused diseases of the present and those that might emerge in the future-greatly weakens the case of critics who insist that such research should be prohihited until zero risk can he demonstrated. Still, if such research is to continue, so will the risks, and the haunting question remains: Who will decide how much risk is too much? Considering the possible consequences of excessive risk-taking and the likelihood that afew scientists will be unable to resist the temptation to create forbidden life or to modify harmful life that exists, perhaps the time has come for some sort of comDact between science and the oublic-a compact wherein arrangements for public accoun&bility of scientific activity and essential freedom of scientific inquiry are spelled out and guaranteed. Such a compact would appear to be inevitahle, particularly in these days when major puhlic interests are a t stake in so many areas of scientific research. If developed with the eood will of the scientific communitv. W T ~ i t could be a far blessing than liability.
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Volume 54, Number 5, May 1977 1 285
