Potential Biohazards of Recombinant DNA Molecules Author(s): Paul Berg, David Baltimore, Herbert W. Boyer, Stanley N. Cohen, Ronald W. Davis, David S. Hogness, Daniel Nathans, Richard Roblin, James D. Watson, Sherman Weissman and Norton D. Zinder Source: Science, New Series, Vol. 185, No. 4148 (Jul. 26, 1974), p. 303 Published by: American Association for the Advancement of Science Stable URL: http://www.jstor.org/stable/1738673 Accessed: 27-08-2015 20:21 UTC

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This content downloaded from 128.163.2.206 on Thu, 27 Aug 2015 20:21:36 UTC All use subject to JSTOR Terms and Conditions LETTERS minimize the spread of such molecules within human and other populations; Potential Biohazards of Sciences give consideration to these and (iii) devising guidelines to be matters. The undersigned members of followed by investigators with Recombinant DNA Molecules working a committee, acting on behalf of and potentially hazardous recombinant with the endorsement of the DNA Recent advances in techniques for Assembly molecules. of Life Sciences of the National Re- an the isolation and rejoining of segments Fourth, international meeting of search Council on this of DNA now permit construction of matter, propose involved scientis,ts from all over the the recommendations. biologically active recombinant DNA following world should be convened early in the and most that until molecules in vitro. For example, DNA First, important, coming year to review scientific prog- the hazards of such restriction endonucleases, which gen- potential recom- ress in this area and to further discuss binant DNA molecules have been erate DNA fragments containing co- better appropriate ways to deal with the evaluated or until methods hesive ends especially suitable for re- adequate potential biohazards of recombinant are for their DNA joining, have been used to create new developed preventing molecules. scientists the world The types of biologically functional bac- spread, throughout above recommendations are with the members of this terial plasmids carrying antibiotic re- join com- made with the realization (i) that mittee in sistance markers (1) and to link voluntarily deferring the fol- our concern is based on judgments of Xenopus laevis ribosomal DNA to lowing types of experiments. potential rather than demonstrated risk - 1: Construction of DNA from a bacterial plasmid. This Type new, since there are few available experi- latter recombinant plasmid has been autonomously replicating bacterial plas- mental data on the hazards of such mids that result in the shown to replicate stably in Escherichia might introduc- DNA molecules and (ii) that adherence tion of coli where it synthesizes RNA that is genetic determinants for anti- to our major recommendations will biotic resistance or bacterial toxin complementary to X. laevis ribsomal entail postponement or possibly aban- formation into bacterial donment of DNA (2). Similarly, segments of strains that do certain types of scientifical- Drosophila chromosomal DNA have not at present carry such determinants; ly worthwhile experiments. Moreover, or we are been incorporated into both plasmid construction of new bacterial plas- aware of many theoretical and mids combinations and bacteriophage DNA's to yield hy- containing of re- practical difficulties involved in evaluat- brid molecules that can infect and sistance to clinically useful antibiotics ing the human hazards oft such re- replicate in E. coli (3). unless plasmids containing such com- combinant DNA molecules. Nonethe- Several groups of scientists are now binations of antibiotic resistance de- less, our concern for the possible un- terminants fortunate planning to use this technology to already exist in nature. consequences of indiscrimi- create recombinant DNA's from a i Type 2: Linkage of all or seg- nate application of these techniques variety of other viral, animal, and ments of the DNA's from oncogenic or motivates us to urge all scientists work- in this bacterial sources. Although such experi- other animal viruses to autonomously ing area to join us in agreeing not to ments are likely to facilitate the solu- replicating DNA elements such as bac- initiate experiments of types 1 and 2 above tion of important theoretical and prac- terial plasmids or other viral DNA's. until attempts have been made tical biological problems, they would Such recombinant DNA molecules to evaluate the hazards and some also result in the creation of novel might be more easily disseminated to resolution of the outstanding questions types of infectious DNA elements bacterial populations in humans and has been achieved. whose biological properties cannot be other species, and thus possibly in- PAUL BERG, Chairman completely predicted in advance. crease the incidence of cancer or other DAVID BALTIMORE There is serious concern that some of diseases. HERBERT W. BOYER these artificial recombinant DNA mole- Second, plans to link fragments of STANLEYN. COHEN cules could prove biologically hazard- animal DNA's to bacterial plasmid RONALDW. DAVIS ous. One potential hazard in current DNA or bacteriophage DNA should be DAVID S. HOGNESS experiments derives from the need to carefully weighed in light of the fact DANIEL NATHANS use a bacterium like E. coli to clone that many types of animal cell DNA's RICHARD ROBLIN the recombinant DNA molecules and contain sequences common to RNA JAMES D. WATSON to amplify their number. Strains of tumor viruses. Since joining of any SHERMAN WEISSMAN E. coli commonly reside in the human foreign DNA to a DNA replication NORTOND. ZINDER intestinal tract, and they are capable system creates new recombinant DNA Committee on Recombinant DNA Molecules of exchanging genetic information with molecules whose biological properties Assembly of Life Sciences, National other types of bacteria, some of which cannot be predicted with certainty, Research Council, are pathogenic to man. Thus, new such experiments should not be under- National Academy of Sciences, DNA elements introduced into E. coli taken lightly. Washington, D.C. 20418 might possibly become widely dis- Third, the director of the National References and Notes seminated among human, bacterial, Institutes of Health is requested to give plant, or animal with un- immediate consideration to 1. S. N. Cohen, A. C. Y. Chang, H. Boyer, R. B. populations establishing Helling, Proc. Natl. Acad. Sci. U.S.A. 70, 3240 predictable effects. an advisory committee with (1973); A. C. Y. Chang and S. N. Cohen, ibid., charged 1030 Concern for these an 71, (1974). emerging capabili- (i) overseeing experimental pro- 2. J. F. Morrow, S. N. Cohen, A. C. Y. Chang, ties was raised by scientists attending gram to evaluate the H. Boyer, H. M. Goodman, R. B. Helling, potential biologi- ibid., in press. the 1973 Gordon Research Confer- cal and ecological hazards of the above 3. D. S. Hogness, unpublished results; R. W. ence on Nucleic Acids (4), who re- of recombinant DNA Davis, unpublished results; H. W. Boyer, un- types molecules; published results. quested that the National Academy of (ii) developing procedures which will 4. M. Singer and D. Soll, Science 181, 1114 (1973). 26 JULY 1974 303

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