12 
itu st notify their IBC simultaneously with initiation of these experiments. 
At the large-scale level, IBC approval nust be obtained before initiation 
of the proaedure. Dr. Manis ' request, therefore, deals primarily with the 
issue of whether investigators must consult their IBC before they initiate 
these types of large-scale processes. Dr. Gottesman expressed discomfort 
with a request to approve a blanket exemption for these organisms. 
Dr. Gottesrran said she had several questions on the St reptorry ces . For 
exanple, vhat is known about the mechanism of pathogenicity? What might 
influence the behavior of nopathogens? What is the frequency of genetic 
transfer? Is there any ecological concern about introducing novel anti- 
biotic synthetic ability into an organism? She thought discussions with 
S trep tomyces experts would be useful. 
Dr. Manis said he had been unable to demonstrate genetic exchange with 
Streptcrnyces lincolnensis or Streptcmyces fradiae or between those two 
strains . 
Dr. Davis asked whether Streptcmyces lincolnensis and Streptcmyces fradiae 
could be placed on a sublist of Appendix A of the NIH Guidelines. 
Dr. Gottesman said organisms are added to Appendix A when data demonstrate 
genetic exchange between the organisms. If the organisms exchange genetic 
material in the laboratory, such exchange is assumed to occur in nature. 
No genetic exchange has been shewn with Streptcmyces lincolnensis and 
Streptcmyces fradiae , hewever, so they cannot be included on Appendix A. 
Dr. Friedman said he saw no reason to change the current NIH Guidelines 
vhich require IBC appro/al before scale-up of such experiments. 
Dr. Manis said Upjchn Company was requesting the flexibility in determining 
large-scale containment procedures accorded E. coli and S. cerevisiae host- 
vector systems be accorded to procedures involving Streptomyces lincolnensis 
and Streptcmyces fradiae . 
Dr. Robert McKinney of the NIH Division of Safety, the Chair of the RAC 
Large-Scale Review Working Group, said the NIH Guidelines provide sufficient 
flexibility to proceed at the large-scale level. 
Dr. Gottesman said Dr. Manis' request should be referred to the Large-Scale 
Review Working Group for consideration. 
Mr. Vein Houghton, the Chair of Schering Corporation’s Institutional Biosafety 
Committee (IBC), supported the opinion that these cases should be evaluated 
by the IBCs. 
No motion was offered on the proposal , and Mr. Mitchell suggested RAC 
proceed to the next agenda item. 
[ 132 ] 
