UNIVERSITY OF CALIFORNIA, BERKELEY 
BERKELEY • DAVIS • IRVINE • I.OS ANGELES • RIVERSIDE • SAN DIEGO • SAX FRANCISCO 
BERKELEY, CALIFORNIA 91720 
COLLEGE OF NATURAL RESOURCES 
AGRICULTURAL EXPERIMENT STATION . *11/1 1 Q7Q 
DEPARTMENT OF PLANT PATHOLOGY Apri I 14, 19/0 
Dr. Donald Frederikson, Director 
National Institutes of Health 
Bethesda, MD 
Dear Dr. Frederikson: 
In an earlier letter (dated Dec. 9, 1977) I had written to you concerning 
the proposed revisions of the NIH Guidelines. Since then I have given additional 
thought to the points which I raised and feel rather strongly that they should 
be brought to the attention of the RAC Committee, something which my first 
letter apparently did not accomplish. Accordingly, I am submitting a new sum- 
mary letter to you and to individual members of the Committee for consideration 
at the next available opportunity. 
General comments: 
It is clear that the basic revisions proposed are meaningful and overdue. 
The original stringency has already caused much unnecessary delay in certain 
areas of research. This I have had the ill fortune to experience personally. 
However, if the Guidelines are to be respected and followed by scientists they 
should take into account, in my view, (i) the comparative biosafety of in vivo 
and in vitro methods of accomplishing particular experimental goals (e.g., the 
construction of a particular strain particularly in gram-negative procaryotes), 
and (ii) the possible indirect consequences of over-regulating the in vitro 
over the in vivo method. The latter, of course, being "natural" and not having 
caused any serious biosafety problems to my knowledge after 25 years of use, 
should hot be regulated. 
Specific comments: 
(1) La Jolla Working Group Draft--Recommendation III . This recommendation pro- 
poses to deregulate self-cloning (which I fully support) whenever the vector is 
indigenous to (found in nature in) the host used. It is implicit that self- 
cloning using non-indigenous vectors will not be deregulated. This distinction 
I do not support because I consider it largely arbitrary, wasteful and almost 
meaningless. It suggests, for example, that all ColEl derivatives are less 
safe as vectors in Enterobacteria other than E. col i or in other hosts in which 
they may yet be shown to replicate. An indigenous vector must certainly be less 
well -adapted to the laboratory host than to its natural one--therefore less 
likely to perpetrate the recombinant molecules stably in the former case than in 
the latter. 
[Appendix A — 279] 
