Page 20 of Attachment E 
(iii) Dr. Buija (Netherlands; Document No. 25), commenting for 
the ‘Committee in Charge of the Control of Genetic 
Manipulation” describes two projects relevant to this 
question. The goal of the first, under Professor D. Tempest, 
Laboratory of Microbiology, University of Amsterdam, is 
study of the persistence of R-plasmids, including plasmids 
used as vectors in recombinant DNA experiments, in various 
environmental conditions. The second project, under Dr. 
P.A.M. Guinne, Laboratory for Bacteriology, National In- 
stitute of Public Health, Bilthoven, is aimed at developing 
selective tests for identification of £. coli K-12 strains used in 
recombinant DNA experiments. 
(iv) Professor M. Richmond (UK; Document No. 12) comments for 
GMAG that specific programs have not been initiated in this 
area but there is much on-going research relative to the topic 
covered in this question as regards man as well as animal 
and plant populations. Examples of reports from such 
studies were included as bibliography and appendices in a 
reply from Dr. S. Falkow (USA; Document No. 22). 
(v) Dr. Falkow (together with Dr. P. Shipley) is currently 
preparing a comprehensive review on “the role of plasmid- 
mediated enterotoxins and specific adhesive properties” as 
they relate to dissemination of infection, and a copy of the 
review will be made availalbe to our Working Group when it is 
completed. 
We note that most Guidelines governing recombinant DNA research 
forbid manipulation of genes specifying toxins, despite the fact that 
analogous exchanges probably occur naturally as exemplified by the 
immunological relatedness of enteric and cholera toxins (Falkow, S., 
Lorenzini — WHO Symposium, in press). Conversely, as Dr. M. Rich- 
mond has commented (Document No. 12), it is unknown whether there 
are any likely circumstances in which recombinant DNA could add to 
the hazard intrinsic in an already infective organism. 
We conclude that in the next few years we shall learn much more 
about the natural history of plasmids, their exchange among bacterial 
species and their relationship to disease, and we anticipate that this 
new knowledge will be relevant to risk assessment in these as well as 
the bacteriophage-based systems. Knowledge to date indicates the 
safety precautions in all present Guidelines are more than sufficient to 
ensure safety (i.e. use of nontransmissible plasmids and E. coli K-12 
based systems). No doubt future results will dictate adjustment of these 
measures where appropriate. 
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