FREDERICK CANCER RESEARCH CENTER 
PO BOX B ■ FREDERICK. MARYLAND U SA. 21701 ■ 301 663-8000 
ffl 
Litton 
March 29, 1976 
Dr. W. Emmett Barkley, Director 
Office of Research Safety 
Office of the Director, NCI 
Building 41, Room A107 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Emmett: 
You have asked whether I have any comments on the memorandum 
concerning recombinant DNA. This memorandum was written by the 
Boston group to the Director of NIH after they had reviewed my 
summary of "The Detrick Experience as a Guid e to . . . P4 . . . ., 11 
(20 January 1976). The memorandum is clear and straightf orward , 
but, like so much of the published reports in SCIENCE and else- 
where, it leaves me with an impression that the biological hazards 
have been hastily assumed, without critical examination by enough 
microbiologists experienced in the study of infectious disease. 
In the field of infectious disease (omitting application of 
recombinant DNA research to insects and plants) , I have been trying 
to imagine the successful use of recombinant DNA that would create 
a microbiological biohazard greater than any already known. I 
cannot do so. Possibly this is because I do not understand the - 
full scope of the proved possibilities. Nevertheless, my view is 
(1) that each project should be conducted with precautions appro- 
priate for the most dangerous biological reagent used in the 
experiment (rule of the most dangerous component, as in Attachment 
II of the 29 December 1975 NIH minutes) , and (2) that an assumption 
of a resultant recombinant of even greater hazard would require a 
knowledgeable discriminating evaluation before it is accepted. 
For instance, mention has been made of an EM coli- botulinum 
toxin hybrid. It seems to me it is most unlikely that it will be 
possible to cause an aerobic vegetative cell to produce in vivo 
a toxin formerly produced in vitro by an anaerobic spore former. 
Even if such a microorganism were formed, most likely the situation 
would be as with Cl . tetani , which long has been known to be present 
in the gut of the horse without production of toxigenic effect. 
[ 508 ] 
OPERATED FOR THE NATIONAL CANCER I NSTITUTE 
BY LITTON 8IONETICS. INC 
