THE UPJOHN COMPANY 
Theodore Cooper, ivi L) , r'n.L) 
Kalamazoo Michigan 4900' USA Vice Chairman 
TELEPHONE ( 616 ) 323-4000 (616) 323-709 5 
January 19, 1986 
Director 
Office of Recombinant DNA Activities 
Building 31, Room 3B10 
National Institutes of Health 
Bethesda MD 20892 
Dear Sir: 
The Upjohn Company strongly supports the proposed revisions in Appendices 
CC-II, C-lll and C-IV of the National Institutes of Health Guidelines for 
Research Involving Recombinant DNA Molecules ( Federal Register, Vol. 51, 
No 24, December 19, 1986, pp 45650-45652). The revisions proposed by the 
Commissioner of the Food and Drug Administration are progressive and 
significantly clarify the appropriate containment for large-scale recombinant 
fermentation experiments. These revisions will make it easier for industry to 
engage in strategic planning. They also bring into focus the safe history of 
the fermentation industry and the generally innocuous natures of 
microorganisms used to produce antibiotics, proteins, amino acids and 
vitamins. All evidence accumulated to date on Escherichia coli K-12, Bacillus 
subtilis and Saccharamyces cerevisiae support their inclusion in the 
classification of non-pathogenic and innocuous microgranisms The 
introduction of foreign genetic information into such organisms does not 
change their natures unless the foreign DNA encodes for biosynthesis of toxic 
molecules or antibiotic resistance, as described in Sections lll-A-1 and lll-A-3 of 
the Guidelines 
Finally, the Commissioner addresses the important economic aspects of 
developing and applying recombinant DNA technology. If the United States 
is to achieve significant commercialization of this technology, the capital 
costs of large-scale recombinant processes must be competitive with both 
foreign-based recombinant process and conventional domestic ones. The 
proposed changes will help in this regard, and they will allow the United 
States to retain its role as the world's leader in biotechnology. 
The proposed changes in Appendices C-ll, C-lll and C-IV are progressive in 
both a scientific and an economic sense, and they will not put the public at 
any greater risk. We recommend their adoption. 
Sincerely, / 
< 
Theodore Cooper, M. D , Ph D. 
Vice Chairman of Board of Directors 
Recombinant DNA Research, Volume 1 1 
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