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IV. PROPOSED UPDATE OF PROGRAM TO ASSESS RISKS OF RECOMBINANT DNA RESEARCH 
When the revised Guidelines for the conduct of recombinant CNA research 
were issued in December 1978, the Secretary, DHEW (now DHHS ) , requested 
that the NIH prepare an NIH Risk Assessment Plan which, after publication 
in the Federal Register for comment and review by the RAC, would be made 
final and updated annually. This present document (tabs 1093, 1094, 1106) 
is the second proposed update. Dr. McGarrity said the objective of the 
annual update was to review information relevant to recombinant CNA risk 
assessment. 
Dr. McGarrity said he supported the concept of an annual update and thought 
it should be continued in the future. Drs. Maas, Levine, and Fedoroff agreed. 
Dr. McGarrity asked whether data from the agricultural area might also be 
evaluated and incorporated into the annual update. 
Dr. McGarrity, noting a discussion of Dr. Freter's observations in Section 
II-D, Mechanisms That Control Human and Animal Gut Flora , questioned whether 
plasmid acquisition could in some instances lead to an increased bacterial 
growth rate rather than the reduced growth rates observed. Dr. Levine 
said plasmids can apparently either enhance or decrease colonizability and 
survivability. He said some studies reported in the update are attempts 
to elucidate the basic mechanisms involved in these processes. He thought 
many of the answers show there are minimal risks associated with recombinant 
CNA research. In reading the update, he was impressed with how much progress 
there has been in the last few years in answering basic questions on coloni- 
zability and the effect of plasmids. 
Dr. Holmes pointed out that specific parameters in individual risk assess- 
ment experiments are limited; however, the complexity of variables affecting 
experiments is enormous. As an example, Dr. Holmes said he drew conclusions 
different from those reached by Dr. Levine in Section II-B, Transmission 
of Vectors from E. coli K-12 to Other Bacteria in Vivo . He thought these 
experiments show the effect of tetracycline on plasmid transmissibility. 
Dr. Levine said several letters commenting on the update had been received 
by OREA. While most reiterate the concept that risks are minimal, the 
letter from EPA points out the need for risk assessment with respect to 
intentional release into the environment. Dr. Fedoroff agreed and said 
that when RAC reviews cases of requests for release to the environment 
of genetically engineered organisms, the investigator should be asked to 
include monitoring of the dissemination of the organisms. 
Dr. Gottesman pointed out that risk assessment experiments with EL_ coli 
K-12 were relevant when they were designed and performed. Now the Guide- 
lines permit many other types of organisms to be used, so K-12 risk assess- 
ment data are less relevant. She said designing a general risk assessment 
protocol is difficult. Dr. Gottesman thought a more appropriate approach 
might be to ask investigators to add risk assessment to specific experiments 
they are doing. 
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