CARNEGIE INSTITUTION OF WASHINGTON 
Department of Embryology 
115 West University Parkway 
Baltimore, Maryland 21210 
TELEPHONE: 467-1414 
February 12, 1976 
Dr. Donald Frederickson , Director 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Dr. Frederickson: 
I wish to summarize briefly why I believe that the 
"Proposed Guidelines for Research Involving Recombinant DNA 
Molecules" are too strict and too inflexible. I refer 
specifically to the part which requires at least EK2 
biological containment for recombining plant, vertebrate 
and viral DNAs. Since there are no EK2 vectors, nor a clear 
mechanism of how EK2 will be certified when they exist, this 
requirement effectively places an indefinite moratorium on 
gene isolation research with these organisms. There are 
two ways that flexibility could be introduced without 
compromising safety. First, instead of categorically 
requiring EK2 for these experiments, give investigators a 
chance to present their experiments in detail to some 
objective committee. There are certain kinds of genes and 
certain ways of doing shotgun experiments which even the 
strictest critic might find totally acceptable to be carried 
out under EKl . If the committee is not fully satisfied with 
the safety precautions of the scientist, then they will 
require him to wait until EK2 systems are available. 
Second, make some government P4 facilities available 
with trained technicians for scientists who wish to do 
shotgun experiments. Require that the clone containing the 
gene be identified and characterized at the P4 facility. At 
that point the guidelines permit the investigator to work 
with it in his own laboratory. This is a safe way to use 
existing (EKl) systems. 
Finally, I urge you to devise methods for the review 
and revision of the rules as often as possible. 
I thank you again for the opportunity to state my 
opinions before you and the Advisory Committee. 
Sincerely yours, 

DDB : ar Donald D. Brown, M.D., Staff Member 
cc: Dr. D. Stetten Carnegie Institution of Washington 
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