UNIVERSITY OF CALIFORNIA, BERKELEY 
BERKELEY • DAVIS • IRVINE • LOS ANGELES • RIVERSIDE • SAN DIECO • SAN FRANCISCO 
SANTA BARBARA • SANTA CRUZ 
COLLEGE OF NATURAL RESOURCES 
AGRICULTURAL EXPERIMENT STATION 
DEPARTMENT OF PLANT PATHOLOGY 
BERKELEY, CALIFORNIA 94720 
December 9, 1977 
Dr. D.S. Fredrickson, Director 
National Institutes of Health, 
Department of Health, Education and Welfare 
Bethesda, Maryland 20014 
Dear Dr. Fredrickson: 
Thank you for your letter and the copy of the draft version of the 
proposed revisions of NIH Guidelines for Recombinant DNA Research. Having 
reviewed the proposed revisions I would like to offer the following com- 
ments for consideration by you and by the Recombinant DNA. Molecule Program 
Advisory Committee at its next meeting: 
At the risk of being somewhat repetitious, but in order to retain clarity 
and perspective in my comments, I would like to state from the outset what 
I perceive to be the essential but separable potential biohazard components 
of i_n vitro DNA manipulations and some of the basic purposes of the NIH 
Guide! i nes : 
Two basic biohazard components can be distinguished: primary and 
secondary. The first include (a) the potential for converting the cloning 
host (primary host) into a pathogen or into an otherwise undesirable organism, 
and (b) the potential of such primary host to escape and become established 
into a congenial or uncongenial habitat. The secondary biohazard components 
are: (c) the "runaway" of recombinant molecules into hosts other than the 
one used for cloning (secondary hosts), and (d) the potential for such or- 
ganisms to perform as in (a) and (b). 
The Guidelines presumably aim at (i) prohibiting experiments such as those 
[Appendix A — 110] 
