SEPTEMBER 6-7 - MINUTES OF MEETING 
11 
Mr. Thornton said that the Risk-Assessment Subcommittee had recommended 
that there be a conference on hormone-producing strains of E. coli 
to evaluate possible adverse effects, and on the possible occurrence 
of autoantibodies or autoreactive cells due to the production of 
eukaryotic polypeptides by bacteria that colonize higher organisms. 
Dr. Krause said that NIAID will consider supporting a conference 
if the RAC so recommends. The conference would probably not take 
place until this winter. Dr. Walters observed that if the RAC 
defers action on the proposal until the results of the conference 
are available, it would not be able to act until its March, 1980 
meeting at the earliest. Dr. Novick said that he was still concerned 
about the problems of autoimmunity and active polypeptides. He said 
that he would like to hear the results of the risk-assessment program 
before the proposal is acted upon. 
Dr. Williams then proceeded to summarize sane of the data available 
on persistence, transfer, and reversion. He cited the results of 
Levy and Marshall in the Recombinant DNA Technical Bulletin. The 
experiments involve the survival of x 1776 and x 1776(pBR322) . He 
said that neither of these organisms were capable of colonizing 
germ-free mice. x 1776 did not colonize humans. In contrast, 
x 1776(pBR322) was able to survive in humans for an average of 82 
hours, but was unable to transfer its antibiotic resistance to 
other hosts. Dr. Williams explained that Dr. Freter has an explan- 
ation for these results, namely that antibiotics on the plate 
interfere with the growth of enterococci from the endogenous flora. 
Dr. Freter has conducted experiments with a number of strains of 
E. coli , including wild-type, x 1776, and x 1776 carrying plasmids. 
There is no evidence of plasmid transfer in human or mouse systems. 
Dr. Williams summarized his conclusion that concerns about polyoma 
DNA and about shotgun clones from eukaryotic sources in a variety 
of certified host-vector systems are not of consequence. The feeding 
experiments demonstrate that x 1776 and its derivatives containing plasmids 
are less able to survive in humans and mice than wild-type E. coli . He 
said that there was no evidence of transfer to bacteria of the endogenous 
flora and no evidence of mobilization of the plasmids. He said that if 
the persistence approaches zero, then the outcome is inconsequential. 
Dr. Goldstein said that he was troubled by the conclusions of Levy and 
Marshall. He cited the last sentence of the paper that states that 
since x 1776(pBR322) survives for four days, "studies looking for transfer 
of the plasmid to endogenous host bacteria become more critically important." 
Dr. Rowe had a preprint of a later manuscript from Dr. Levy, et al., and 
read from a section of the paper dealing with transfer of pBR322 to endogenous 
bacteria in the human intestinal tract. The results demonstrated an absence 
of detectable transfer of pBR322 during transit in the intestinal tract of 
human volunteers, despite survival of the K-12 strain for almost a week at 
reasonably high titers. 
[ 160 ] 
