APPENDIX D TO APPENDIX C 
DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE 
PUBLIC HEALTH SERVICE 
NATIONAL INSTITUTES OF HEALTH 
BETHESDA. MARYLAND 20014 
December 23, 1975 
NATIONAL CANCER INSTITUTE 
Our Reference: 
Dear Dr. 
Your present grant appears to involve the cloning of biochemically 
produced recombinant DNA molecules. As you know, there is need 
for caution in the production and handling of agents that may be 
produced and replicated in the laboratory. This letter is written 
to emphasize the potential hazards associated with this type of 
research. 
Although the final report of the Asilomar Conference has been 
published (Science 188: 991-994, June 6, 1975), there is still 
need for more explicit guidelines as to what types of containment 
should be used in performing various types of , experiments using 
currently available vector-host systems. An NIH Program Advisory 
Committee on Recombinant DNA Molecules has been working on a set 
of guidelines for at least six months and will complete the job 
early next year. In the meantime, there are certain experiments 
that should not be done at all. These include the cloning of 
recombinant DNA's from highly pathogenic organisms (i.e.. Class 
III, IV, V etiologic agents as classified by the U.S. Department 
of Health, Education, and Welfare ["Classification of Etiologic 
Agents on the Basis of Hazard, " PHS, Center for Disease Control, 
Atlanta, Georgia (4th edition), 1974], DNA containing toxin 
genes, and large scale experiments, i.e., more than 10 liters of 
culture, using recombinant DNA*s that are able to make products 
potentially harmful to man, animals, or plants. In addition, we 
believe that no experiments that would confer on pathogenic 
organisms an extended range to resistance to therapeutically 
useful antibiotics or disinfectants should be undertaken at 
this time. 
Until v/e have more explicit guidelines and more experience in 
assessing this new type of potentially hazardous research, and 
until the proper role is determined for institutional biohazards 
Appendix C — 16 
