STANFORD UNIVERSITY MEDICAL CENTER 
STANFORD, CALIFORNIA 94M5 
DEPARTMENT OF BIOCHEMISTRY 
PAUL BERG 
Willson Proftuor of Biochemistry 
October 13, 1977 
Dr. Donald Fredrickson 
Director 
National Institutes of Health 
5333 Westbard Avenue 
Bethesda, Maryland 
Dear Don, 
I am writing in response to your call for comments on the draft 
version of the Revised NIH Guidelines fo r Recombinant DNA Research. 
First, let me say that I am delighted that the earlier commitment 
to review and modify the Guidelines in the light of more current assess- 
ments of risks has moved ahead so expeditiously. In only that way will 
we be able to prevent the accumulation and perpetuation of unreasonable 
requirements. 
There are two recommendations in the draft version with which 1 
would like to take issue: 
1) The Introduction argues for defining recombinant DNAs as to 
whether or not they are novel, defining qovel as"those molecules consis- 
ting of segments of any DNA from different species that are not known to 
exchange DNA by natural physiological processes". "In general", the Intro- 
duction goes on, "recombinant DNA molecules formed from any combination of 
DNAs will not be considered novel when all the components are derived from 
genomes known to replicate within the organism used to propagate the recom- 
binant DNA." After that clear and definitive enough judgement why la the 
Director of the NIH asked to prepare a list of those combinations of DMAs 
(viral, extrachromosomal or chromosomal) that are not considered novel and, 
therefore, to be excluded from coverage by these Guidelines. It seems more 
logical that the Director should prepare a list of those combinations which, 
he views as novel in spite of the fact that, according to the definition, 
they are not! Isn't it administratively simpler to be explicit about the 
exceptions rather than to try to enumerate all possible combinations that 
fit the definition? Also, wouldn't it be easier to eliminate the excep- 
tions rather than make additions, as new evidence becomes available? 
So much for the wording,- now for substantive issues. What is the 
scientific justification for insisting that recombinants between polyoma 
and mouse DNA or beteween SV40 and monkey DNA are more novel then recom- 
binants between DNA from E. coll and A phage or plasmids? There la urn- 
[Appendix A — 12] 
