STANFORD UNIVERSITY MEDICAL CENTER 
STANFORD, CALIFORNIA 94305 
Stanford University School of Medicine September 22, 1978 
Department of Medicine 
Dr. Donald Frederickson 
Director 
National Institutes of Health 
Bethesda, MD 20014 
Dear Don: 
I am writing to comment on the proposed new guidelines governing research with 
recombinant organisms. I appreciate the efforts which have been made to define 
and limit potential harms, and I am encouraged by the absence of harms in the 
experiments conducted thus far. I also appreciate the efforts which have been 
made to establish reasonable guidelines so that important research can continue 
without unreasonable restrictions. Nonetheless, I think there are substantial 
problems which are inadequately addressed by the proposed new guidelines. The 
following comments specifically do not address proposed modification of contain- 
ment requirements for particular types of experiments; I am skeptical about some 
of the reasons for those changes but do not consider myself qualified to criticize 
them reliably. My concerns are: 
1. Epidemiology . To date we have encouraging evidence that the techniques 
have not produced pathogenic organisms. However, the evidence is 
quite incomplete. First , the rDNA experiments which have been done to 
date have been mainly of the potentially safest types; those requiring 
more effective containment have by and large not been performed. Second , 
the published epidemiological analyses of exposed persons involve only 
a few of the active laboratories and cover brief time periods of 
exposure. We have essentially no information about the effect of 
chronic, low dose exposure to recombinant organisms. Third , virtually 
all experiments to date have been small in scale; it is entirely pos- 
sible that large scale experiments such as will occur in industry will 
create different epidemiological problems and perhaps greater risks. 
Fourth , the proposed guidelines require no formal epidemiological study 
and appear to leave health monitoring practices entirely undefined and 
voluntary at involved institutions. Therefore it seems to me that 
the guidelines' approach to the monitoring and study of the potential 
spread and effects of recombinant organisms is seriously inadequate. 
On both scientific and public policy grounds, this is a genuine 
deficiency. 
2. Public participation in decision making . I understand that recombinant 
experimentation is only one way in which potentially dangerous 
organisms can be created through laboratory experimentation or commercial 
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