ELI LILLY AND COMPANY 
INDIANAPOLIS, INDIANA A 0 2 00 
C. W. PETTINGA, Ph D. 
EXECUTIVE VICE PRESIDENT 
September 22, 1978 
Dr. Donald S. Fredrickson, Director 
National Institutes of Health 
Bethesda, Maryland 20014 
Re: Recombinant DNA Research, Proposed Revised Guidelines, 
43 Fed. Reg. 33042-33178 (July 28, 1978) 
Dear Dr. Fredrickson: 
In accordance with your letter dated July 19, 1978, 
and the above notice, we are submitting the following 
comments on behalf of Eli Lilly and Company concerning the 
Proposed Revised Guidelines for Recombinant DNA Research. 
Lilly is engaged in the research, development, production, 
and distribution of pharmaceutical, agricultural, and 
other products. It has extensive research and development 
facilities and its programs include research involving 
recombinant DNA. 
(1) l-D-6 . 10-Liter Limit on Volume . 
Recombinant DNA technology is progressing rapidly from 
a laboratory phenomenon to developmental activities. The 
necessity for conducting scale-up experiments (greater 
than 10-liter volumes) is imminent. We do not see any 
unusual biological or containment hazards in association 
with larger volume experiments. Our laboratories as well 
as other industrial research groups have had extensive 
experience in the handling of highly toxic bacterial and 
viral pathogens and hazardous chemicals. For example, 
live polio virus, L-asparaginase-producing strains of E. 
coli , various pneumococci, insulin, alkaloids, synthetic 
hormones, and barbiturates have all been safely processed 
in volumes of thousands of gallons over periods of many 
years. With careful attention to development and pro- 
duction process design, we have encountered minimal safety 
problems. We feel that Lilly should act on the basis of 
our established expertise within the context of the pro- 
posed revised guidelines. As indicated in paragraph 2 
below, we recommend that a mechanism be established for 
Lilly and other companies to share information with NIH 
(as it does with the scientific community) in a manner 
[A-272] 
