11 
as long a period or on as large a scale as Saccharcmyces cerevisiae , 
they have, nevertheless, been cultivated at the greater than 100,000 liter 
scale for decades without any evidence of negative effects. Moreover, 
the experiments for which exemption is requested would involve recombinant 
DNA only from demonstrated non-pathogen ic strains of other Streptcmyces . 
Dr. Clowes said he was reluctant at this time to move approval of Dr. Manis ' 
request, however, because he would like to question Streptcmyces experts on 
the interrelationships of the various Streptcmyces species. There appears 
to be seme contradiction between the data supplied by Dr. Manis and the 
positions of various Streptcmyces species on Appendix A of the NIH Guide- 
lines. He suggested Dr. Manis' request be referred to the Large-Scale 
Review Working Group for further study. 
Dr. Pramer supported Dr. Clcwes ' suggestion to obtain additional information 
frem experts on Streptcmyces . Dr. Wens ink agreed. 
Dr. Friedman asked to be excused from the discussion as he has collaborative 
arrangements with investigators at Upjohn Company. Dr. Gottesman asked 
Dr. Friedman to contribute his expertise and knowledge to the discussion; 
he would not, however, vote. 
Dr. Manis said Upjohn Company was requesting criteria for exenption, other 
than genetic exchange, for organisms traditionally used in large-scale 
experimentation in developing eemme rd al ly usable novel antibiotics. He 
suggested nonpathogenicity might be a criterion. Dr. Manis said he heped 
by this means to simplify review requirements. 
Dr. Davis said the taxcnomic criteria defining the Streptcmyces are so 
"fuzzy" that relationships between species may be close by one set of 
criteria but distant by another set. He said he would consider nonpatho- 
genicity a fundamental criterion. Safe cultivation of an organism on the 
100,000 liter scale for a decade provides more than sufficient evidence of 
norpa thoge nic i ty . 
Dr. Henry Miller of the Food and Drug Administration (FDA) said FDA has a 
great deal of experience overseeing ccnmercial uses of Streptcmyces . He 
said FDA scientists have reviewed the prcposal , and on theoretical and 
experiential grounds urge approval. He added that "the decision has the 
specific approval of Frank Young, the FDA Ccrmrissioner, vho is a former 
RAC member and a microbiologist." 
Dr. Johnson said the British Genetic Manipulation Advisory Group (GMAG) 
excluded all non-pathogenic strains of Streptcmyces five years ago. GMAG 
in essence considered manipulations involving ncrpathogenic Streptcmyces 
self-cloninq experiments. He thought the Upjohn proposal requested an 
action more limited in scope than the GMAG action, and he suggested the 
prcposal be approved. 
Dr. Gottesman said the current NIH Guidelines permit these experiments at 
the laboratory scale at Biosafety Level 1 and specify that investigators 
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