32 
that there is no reason that research with recombinant DNA should 
be particularly hazardous. In support of his observations, he high- 
lighted the fact that the Earth is populated with highly specialized 
and competitive organisms. Only a tiny fraction of these micro- 
organisms produce disease. Experience has shown that even these 
pathogens tend to lose their disease-producing capacity when grown 
in the laboratory. In other words, virulent organisms become non- 
virulent when cultured in the laboratory medium. If the concern is 
that a harmless organism, such as the variant of E. coli used in re- 
combinant molecule research may be converted into a pathogen, 
then one would have to assume that there is a reasonable certamty 
that some unexpected event would provide characteristics to the 
organism which would enable it to compete successfully. He pointed 
to historical evidence which indicated that the E. coli K-12 variant 
had lost its ability to colonize the human gut except under very 
unusual conditions. He also suggested that the available evidence of 
a pathogen’s success in causing a disease shows a dependence upon 
so many special conditions that it would probably even be difficult 
to deliberate^ construct a pathogen from the E. coli K-12 variant. 
Although there are other hazards to be considered, such as the 
transfer of genes from a harmless E. coli variant to some other micro- 
organism, it was Dr. Nathans’ opinion that even here the available 
evidence suggests that such recombinant molecules would not survive 
outside of the laboratory environment. 
Dr. Nathans also responded to the charge of a potential risk of 
breaching so-called “genetic barriers” against interchange between 
species. He cited the opportunities for potential migration of DNA 
units from species to species already existing in nature, and suggested 
that if such interchanges could occur they probably have been tested 
naturally under a variety of circumstances. Examples of opportu- 
nities for interchange of genetic material in nature include the existence 
of pathogens in the human body in direct contact with human cell 
contents, viral exchanges between cells of many species, the exposure 
or intimate contact of microorganisms to the contents of cells of 
enormous variety during the process of decay and decomposition, 
and the effects of long-term evolutionary selection pressures. Although 
there is no way of being absolutely certain that natural recombinant 
molecules are being formed, there is evidence which suggests that 
such events do occur and that a more careful search would probably 
enable these to be identified. This would suggest in turn that the use 
of the DNA recombinant molecule technique by man may not be 
unique in itself, although the establishment of laboratory conditions 
insuring the survival of large numbers of organisms containing such 
recombinant molecules is not strictly analogous to natural processes. 
Conservative Approach 
Dr. Nathan’s general conclusions lead him to believe that the 
NIH guidelines provide a high degree of conservatism and that 
although the possibility of some potentially harmful recombinant 
being produced cannot fee definitely excluded, the probability of such 
an event is very unlikely. He supports the conservatism of the guide- 
lines until such time as more evidence is accumulated to support a 
view that further reduces some of the uncertainties about the avail- 
able evidence on safety. 
[Appendix B — 81] 
