THE JOHNS HOPKINS UNIVERSITY 
SCHOOL OF MEDICINE 
725 N. WOLFE STREET 
DEPARTMENT OF MICROBIOLOGY BALTIMORE, MARYLAND 21205 
August 30, 1978 
Dr. Donald S. Frederickson 
Director, NIH 
Bethesda, MD 20014 
Dear Dr. Frederickson: 
I am responding to your request for comments on the proposed revised 
guidelines for recombinant DNA research, dated July 19, 1978. First, in 
general terms, I believe the revisions accurately reflect the experience 
with recombinant DNA of the past four years and the considered judgements 
of risk of infectious disease experts, whose input was unfortunately 
lacking initially. In rny opinion revised guidelines will allow important 
advances not possible under the present rules. Second, I find the increased 
emphasis on the responsibility of local biosafety committees in carrying out 
the guidelines a very important and appropriate change. At Johns Hopkins 
University the local comnittee has been functioning very effectively, whereas 
the need to obtain NIH approval of each project has caused delays without, I 
believe, adding to the project's safety. Another constructive change in the 
guidelines is the provision for case by case consideration of unanticipated 
situations such as development of new vectors. I hope the mechanism for 
review of these proposals can be simplified by separating out for prompt 
action those that represent relatively minor extensions of the guidelines. 
Finally, I would like to make a specific comnent on animal virus vectors. 
I served on the (American) working group that drafted the early recommendations, 
and of course approved them. However, I now notice an unintended practical 
restriction on the use of human adenovirus as a vector, namely the requirement 
that it "... be rendered unconditionally defective by deletion of at least two 
capsid genes ..." (Ill C-l-c-(l)-(a) p. 33081). Recently it has been possible 
to isolate deletion mutants of adenovirus that grow only in adenovirus-transformed 
cells, i.e., the "helper virus" is the integrated transforming segment. To allow 
this host-virus system to be used for isolating adenovirus-foreign DNA recombinants, 
I suggest that III-C-l-c-(l)-(a) be clarified to read as follows: 
[A-61] 
