i>age 2 
be properly scrutinized. I do not think it reasonable to make public policy based 
upon as yet private communications. 
Further, the burden of the new information, as I understand it, is that E. Coli is 
a "poor" pathogen, that E_. Coli K12 is an enfeebled strain as a consequence of its 
long years of laboratory passage and that it has so far proven impossible to convert 
K12 to pathogenicity. Even if accepted as correct, the significance of such 
observations may be questioned. 
Because Eh Coli is a "poor" pathogen does not mean that it m.icht not be convertible 
to a "good" pathogen by the increment of one or a few genes. Most pathogenic 
organisms reach an equilibrium level of pathogenicity with respect to their common 
hosts, lest all hosts be killed off. Considering the ubiquitous presence of Eh Coli 
in man, it would be expected that current strains will not be highly pathogenic — 
but that does not prove they lack the potential. 
The enfeebled nature of K12 is presumably the consequence of mutation (s) introduced 
during its laboratory passage. This thought gives rise to the suspicion that 
different strains of K12 (and there any many in use) having different histories may 
not all be similarly enfeebled. Has this been studied? 
The failure to convert K12 to to pathogenicity through the introduction of certain 
plasmids or Salmonella genes is comforting but not definitive. As long as the 
detailed nature of the mutations on K12 which prevent the expression of pathogenicity 
is unknown, we cannot know how difficult the introduction of pathogenicity would be 
by the appropriate route. Most of the factors affecting pathogenicity act by 
modification of the cell surface. Some relatively simple (and thus potentially 
reversible) modification of a cell surface component in K12 could be sufficient to 
block the introduction of pathogenicity by any of the means thus far attempted. 
The potential for transfer of the recombinant plasmids from K12 to other bacterial 
species has only been studied under a limited variety of circumstances. The potential 
for such transfer in the wide variety of natural environments in which Coli is found 
has not been explored. 
Even were the statements about the reduced hazard now perceived to be associated with 
Eh Coli K12 recombinant DNA experiments to be accepted at full value, there is still 
no way to assess the absolute risk associated with these experiments. It may be less 
than it was thought to be — but the whole structure of graded risk implicit in the 
guidelines floats at some level dependent upon investigatorial confidence rather than 
documented fact. If such experiments are "less risky," because of the "float" those 
who regarded the Guidelines with derision may now regard them with greater derision 
while those who felt they were inadequate in the first place may still find them to 
be inadequate . 
At this point I would like to issue a strong caution concerning the introduction of 
new HV systems for recombinant DNA work. If, as I believe, so much uncertainty 
continues to surround research with so well-studied an organism as E. Coli , our 
ignorance with regard to any other vector, its ecological involvements, the organisms 
with which it can exchanae DNA, etc., etc. must be that much greater. I point out 
again in this regard our need to be concerned with the safety of other life forms as 
well as man. 
I believe it is also important to keep in mind that reductions, particularly in physical 
containment as from P3 to P2 will significantly increase the number of sites where 
[Appendix A — 181] 
