THE UPJOHN COMPANY 
KALAMAZOO, MICHIGAN 49001, U.S.A. 
TELEPHONE (616) 323-4000 
May 18, 1988 
Dr. William J. Gartland, Jr. 
Director, Office of Recombinant DNA Activities 
12441 Parklawn Drive 
Suite 58 
Rockville, MD 20852 
Dear Dr. Gartland: 
I wish to comment on the proposed actions under the NIH Guidelines for 
Research Involving Recombinant DNA Molecules as published in the 18 April 
1988 Federal Register. In particular I want to voice support of Dr. Joseph 
R. Fordham's proposed revisions in Section III-B-5. 
Dr. Fordham addresses a key issue in the successful commercial application 
of recombinant DNA technology to traditional fermentation processes. Namely, 
there are many organisms that have been used safely at large-scale to produce 
valuable products such as enzymes and antibiotics, but for which there 
existed no ready means for genetic manipulation until the advent of recombinant 
DNA technology. Such organisms fall into a gray area of the Guidelines, 
because although they are safe, the in vitro manipulations necessary to 
develop recombinant derivatives and the absence of demonstrable physiological 
genetic exchange preclude their categorization as exempt under sections 
III-D-1 through III-D-4 of the Guidelines. As the Guidelines are currently 
structured, the only recourse is to have NIH review under Section III-D-5 
each proposed experiment on a case-by-case basis. Eli Lilly's Cephalosporium 
acremonium proposal is an excellent example of this situation. To use 
this format for review and approval of such proposals is unnecessary and 
seems a misuse of NIH's time. Correspondingly, as Dr. Fordham points out, 
the conclusions of the Organization for Economic Cooperation and Development 
and the comments of the Office of Science and Technology Policy regarding 
low risk recombinant microorganisms support a subordinate review process 
which is consistent with the duties and responsibilities of Institutional 
Biosafety Committees. 
I support Dr. Fordham's proposal and the position that the Guidelines need 
to be modified to include specific wording that clearly places all responsi- 
bility for reviewing and setting containment of such large-scale experiments 
with the IBC. 
Jack J. Manis, Ph.D. 
Associate Director 
Bioprocess R&D 
Recombinant DNA Research, Volume 13 
[358] 
