Pte /@))- More than three years have passed since we commented upon the possible consequences of the indiscriminate use of recombinant DNA tech- niques (Science 185, p. 303, July 24, 1974). At that time there was no clear-cut evidence that recombinant DNA experiments were hazardous, but we believed that the properties and behavior of organisms with novel interspecies genetic combinations were unpredictable. Atse,—unlike ether Fields of seientific investigation, there were no accepted codes of practice to guide recombinant DNA research, These considerations led us to recommend that certain recombinant DNA experiments should be deferred until their poten- tial hazards could be better evaluated or until adequate methods for . preventing the spread of organisms carrying recombinant DNAs were $ofooea. Much has happened since 1974. Now, in virtually every nation where recombinant DNA experiments are performed there are guidelines, that were) developed by broadly representative groups with the necessary scientific expertise and experience,to guide the research. Though differing in detai 1 Gn. wnttermatronsbhy Qecspl?/ code a they agree in the essentials and,thereby, consititute a set of common prac- t guste picontieant DUA paslarth Cheol gif The world tices. “Many scientists believe that some features of the guidelines are more stringent than can be justified by the scientific evidence we now possess. Nevertheless, investigators and their institutions, aware of the debate of the past three years, have adopted the reeommended procedures gy gl | wneud Ly the Surchétiner , special equipment andcontainment facilities, in the-conduct—of—the work. A Consequently, the possibility that experimental organisms will be Ctra hazardous or released, has been markedly reduced. ‘During three years of recombinant DNA experimentation, A taberateries _throughoutthe-werld, there has been a striking change in evr assessment of tts-potential risks. Where it has been examined, organisms . modified by recombinant DNA experiments . competing with their parental ‘vectors or organisms. Furthermore, there is recent evidence that certain constructed DNA molecules, hitherto believed to be novel, can arise in Nature by.reactions akin to those used in the laboratory. Admittedly, more experience and experiments are needed to extend our know— ledge of the survival potential of a wider variety of recombinant organisms as well as the frequency and scope of naturally—-occurring interspecies genetic exchanges. But these results and the fact that there is no indication of any actual or potential harm to humans or the environment are encouraging and reassuring. . Even more reassuring is the virtually unanimous agreement of experts in infectious disease and epidemiology that strain K12, the enfeebled laboratory variant of E.coli widely used for recombinant DNA experiments, is unable to colonize normal human or animal intestinal tracts. Moreover, on the basis of recent experiments and existing data, these experts have concluded that there is little or no likelihood that strain K12 can be transformed into an infectious or pathogenic organism, or even into a human intestinal inhabitant, by the acquisition of a bit of foreign DNA. The use of genetically modified derivatives of strain K12 and vectors that are not self-transmissable or mobilizable to other bacteria, provides a further measure of safety. Hence, our initial concern that the introduc— tion and propagation of novel DNA elements on plasmids in E.coli would result in the dissemination of these new genetic combinations to other organisms and the environment was premature, and probably, unwar- ranted. On the other hand recombinant DNA methods have made possible in- pressive scientific advances. Substantial improvements and innovations in the experimental operations have both extended the utility of the tech- nique and further reduced the likelihood of disseminating living organisms carrying recombinant DNA molecules. The new insights about the structure and organization of genes in higher organisms that have emerged from such work promise important revelations . about their function in health and disease. Furthermore the recently reported isolation of the gene coding for insulin and the prospects for similar advances with genes coding for other therapeutic proteins brings closer the reality of practical benefits from recombinant DNA research. Considering the encouraging news so far — the rapid advance of scientific knowledge and the absence of any indications of actual hazards from recombinant DNA research ~ we regard the Readiterg rush to enact legislation as unwarranted and unnecessary. Creating a costly, cumber-— some bureaucracy to hd, the content and methods of scientific inquiry would be mprecedattea 1S aa te and eee inhibit rather than foster basic research on smporeant piologieas. and medical problems. This scope of governmentalintervention would be justified only if the research presents a clear and substantial threat to the public health and welfare. Ptud on Current Arrccernenlg , avh 2 But—sueh-a-clear-eno-substamtiel threat does not exist ,end-wasting-scaree- -and_therefore, poor public poltey, We believe that the provisions of p.4 Congressional bills S-1217 and HR-7897 will thwart basic biologic research and the achievement of its rewards for the public welfare. ~Alternate endings begin here- In our view the application or modification of already existing mechanisms that guard the public against known hazards is a more prudent way of dealing with any remaining anxieties about recombinant DNA research. -Ending for Version1l- The present NIH Guidelines,-ceonsttteute a conservative and satisfactory code of practice for the use of recombinant DNA methods. They apply to all seg- ments of the research community in the same way that other standard prac- tices are applicable to other forms of research whether publicly or privatly funded. Section 361 of The Public Health Service Act already Comte Department of Health, Education and Welfare (HEW) with broad authority to regulate laboratory work with disease K croorganisms. Extending HEW's authority to ensure compliance with the NIH Guidelines would assure scientists, the public) and the Government that uniform standards are being applied to work in this field. Thus we believe that the application or modification of mechanisms that already exist to guard the public against known hazards is a prudent way of dealing with any presently held anxieties about recombinant DNA research. -—Ending for Version 2- An alternative to the pending Congressional legislation is a re- examination of the assumptions and conclusions upon which their proposals are based. A panel of distinguished laymen, scientists and public officials, could make an in-depth analysis of the present status of the "recombinant DNA problem" and, taking into account our current knowledge of the risks p.5 and the existing mechanisms for dealing with potential biohazards in research and industrial laboratories, recommend the most appropriate course of action. We are confident that dispassionate analysis free of the glare of klieglights and political invective, would provide a sounder basis for action and would better serve the needs of the public and science. -Ending for Version 3-