12 
reasons, the number of a host of organisms employed in DNA recom- 
binant research and development is very likely to increase. 
OTHER CONCERN'S 
The volume of recombinant material produced will also increase if 
commercial applications of the technique become feasible. The experi- 
ence of the biomedical and chemical industries suggests that large- 
scale production of recombinant organisms will be required in order to 
obtain useful products in sufficient quantity for marketing. Some re- 
searchers insist that special procedures and facilities could prevent es- 
cape of these organisms from an industrial laboratory, but the NIH 
Recombinant Advisory Committee has assumed that probability of es- 
cape from containment barriers ordinarily increases with scale. The 
committee recommended and NIH included in its guidelines a pro- 
duction limit on recombinants known to make harmful products of 
10 liters, which is generally adequate for experimental work. 
The limit is arbitrary, however, for there are no calculations of the 
correlation between the volume of organisms and the probability that 
some of these organisms will enter the environment. Investigations of 
potential risks associated with recombinant DNA have yet to address 
this question. 
The deliberate release of a recombinant molecule, which is contem- 
plated for various future applications of the technology, is also cause 
for concern. Although available data indicate that the accidental es- 
cape of K-12 would pose minimal risks to health or the environment, 
its behavior in a variety of natural circumstances lias not been exam- 
ined. For example, no one knows the effects of introducing K-12 con- 
taining a recombinant molecule into an environment where sewage 
treatment is inadequate or where contact with large numbers of dif- 
ferent species of bacteria is inevitable. Moreover, alternative host- 
vector systems are yet to be evaluated. Apprehensions about damage to 
complex ecosystems are reasonable, particularly if host cells common 
in the soil or water are used. For the time being, therefore, the NIH 
guidelines prohibit the deliberate release of recombinant DNA 
material. 
The long-range evolutionary effects of recombinant DNA work- 
are thus ill denned and partly philosophical. Recently published 
research by Chang and Cohen at Stanford suggests that many of the- 
DNA exchanges previously considered to be unique to laboratory ex- 
periments are duplications of natural capabilities of E. coU ; 3 but 
these data are limited and do not satisfy all participants in the debate. 
Robert Sinsheimer of the University of California at Santa Cruz has 
frequently expressed concern about disrupting the dynamic equilibria 
among competing species of organisms. In a statement submitted to 
the subcommittee he concluded : 
The possibilities of long-range environmental hazards, of short- or long-term 
effects upon basic microbiological equilibria, which are essential to many eco- 
logical concerns, remain unaffected by the new observations. 
3 Chang, Shing and Stanley N. Cohen, “In Vivo Site-Specific Genetic Recombination 
Promoted by the EcoRI Restriction Endonuclease,” Proceedings of the National Academy 
of Sciences, voL 74, No. ll r November 1977, pp. 4811-4815. 
[Appendix B — 272] 
