SEPTEMBER 6-7 - MINUTES OF MEETING 
6 
Dr. Krause summarized the status of the risk-assessment program. He noted 
that a proposed plan for a risk-assessment program had been published for 
comment in the Federal Register on April 2, 1979. The plan, which will be 
implemented by NIAID, was considered by the RAC at its May meeting and has 
been reviewed by the RAC Subcommittee on Risk- Assessment. Dr. Krause 
stated that an ad hoc NIAID Vtorking Group on Risk Assessment had been 
convened on August 30, 1979 to review the state of knowledge on Protocols 
I and II proposed by the workshop on risk-assessment held at Falmouth, 
Massachusetts on June 20 and 21, 1977 (J. Infect. Dis. 137: 613-714, 
1978). Dr. Krause summarized the recommendations of the Working Group 
(Attachment II). The Working Group unanimously recommended that NIAID not 
initiate new studies on Protocol I, the colonization and transmission of 
plasmids by E. coli K-12 in the gastrointestinal tract of humans. This 
recommendation was based on review of the available data. The Working 
Group concluded that recombinant DNA experimentation using E. coli K-12 
host-vector systems is without risk when conducted in complTance with good 
microbiological laboratory practices. The Vtorking Group also recommended 
that new studies not be initiated on Protocol II, tests for transmissibility 
of plasmids of E. coli K-12 and x 1776 in germ-free mice. NIAID will instead 
rely on present contracts to provide some additional data. The Working 
Group could not foresee how recombinant DNA technology could confer pathogenic 
properties on E. coli , and it recommended that NIAID should not develop 
new experimental models to test this possibility. The Vtorking Group did 
recommend that certain studies should be conducted using wild- type _E. coli 
to test for both survival and transfer to the endogenous flora of humans. 
Finally, the Vtorking Group expressed support for the proposed exemption 
provided that Pi laboratory practices were used in conducting this and 
other categories of exempted research. 
Dr. Gottesman summarized the paper on a framework for assessing the potential 
risks of recombinant DNA experiments prepared by Dr. Sidney Brenner for 
the United Kingdom Genetic Manipulation Advisory Group. She discussed a 
generation pathway in Brenner's scheme: 
/ 
reversion of 
disabling properties 
^escape -^persistence 
V 
\ S 
^ transfer of plasmid • 
to wild-type strain 
outcome 
To reach the stage of outcome, the organism must escape, persist, and be 
capable of reverting or transferring its DNA to a wild-type strain. The 
outcome depends on the expression of the DNA and on whether a target is 
available. To reach the end of the generation tree, each of the steps has 
to occur. Dr. Brenner's scheme defines a number of factors including f, 
the fraction of total sequences that code for proteins with effective targets. 
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