128 
• The K-12 strain does not carry the surface component required 
for E. coli to establish itself in humans. Experiments have 
shown that man must ingest at least a million K-12 organisms 
to obtain even transient multiplication in the intestine (references 
30 and 31 of the Guidelines). 
There is more information about E. coli than about any other class 
of microorganism. The modern sanitation practices and sewage treat- 
ment systems that have virtually eliminated from developed countries 
the once -prevalent epidemics of intestinal pathogens, such as typhoid, 
cholera, and dysentery, would provide the same barrier against wide- 
spread dissemination of E. coli -containing recombinants. Further, 
conversion of a laboratory strain to pathogenicity is likely to require 
alterations in many genes; the chance that alteration of a single gene 
might lead to pathogenicity is extremely remote. For example, it is 
known that two separate plasmid-coded genes can, together, convert 
certain strains of E. coli into pathogens. However, these same two 
plasmids, when inserted into E. coli K-12 do not result in pathogenicity: 
the recipient K-12 is not capable of inducing disease in susceptible 
animals. Thus, not only pathogenic genes, but also the nature of the 
cell carrying those genes, is important in the determination of 
pathogenicity. 
Recognizing the ability of certain plasmid vectors to transmit 
themselves and any foreign DNA to a recipient host cell other than that 
used in the laboratory, the Guidelines do not permit use of such 
plasmids--referred to as "conjugative" plasmids. The possibility that 
nonconjugative plasmids may themselves be transferred under certain 
conditions is extensively discussed in the Guidelines (Section III-A). 
The probability of the latter transfers can be quite low; the data for 
each case are considered in the certification of EK2 and EK3 host- 
vector systems. The criteria recently adopted by the Recombinant 
Advisory Committee for the certification of EK2 host-phage and host- 
plasmid systems are included in Appendix H of the EIS. 
D. No Guidelines but NIH Consideration of 
Each Proposed Project on an Individual 
Basis Before Funding 
There were no specific comments directed exclusively to this 
Section. 
