DEPARTMENT OF MICROBIOLOGY AND MOLECULAR GENETICS 
HARVARD MEDICAL SCHOOL 
25 Shattuck Street 
BOSTON. MASSACHUSETTS 02115 
29 December 1979 
Dr. Donald S. Fredrickson 
Di rector 
National Institutes of Health 
Bethesda, Maryland 20205 
Dear Dr. Fredrickson: 
I believe that you should reconsider the question of the col i 
exemption as voted for by the RAC at its September 1979 meeting. I am 
certain that both of us agree that recombinant DNA technology will generate 
interesting and exciting new results. My only qualms lie in the speed at 
which this work proceeds. Exemptions and/or lowering of containment 
increase this pace and the potential hazards involved. 
I have again read through all of the NIH sponsored risk assessement 
results. Present results in this area make me believe that we are not 
ready for the wide scale £. col i exemption as voted for at the September 
RAC meeting and recently published is the Federal Register. Many important 
questions of risk assessment have not yet been addressed as posed at the NIH 
sponsored Falmouth Risk Assessment Conference. Equally as important, results 
which are in are far from clear cut in demonstrating lack of risk. In fact, 
the Martin-Rowe polyoma virus results suggest just the opposite as is clearly 
pointed out in the article on this subject in Nature by Rosenberg and Simon 
(see Nature 282 , 20-27 December, 773-774, 1979). Likewise, the results of 
Stuart Levy on survival of supposedly 'disabled strains' of E_. col i again 
provide reason to not approve the col i exemption. Here, disabled strains 
were found to survive in humans at greater levels than predicted. This point 
was brought to your attention previously in a letter from Roy Curtis who 
developed the strains in question. It should also be mentioned that Levy's 
risk assessment studies on transfer of genetic information from disabled 
strains are far from complete since they do not consider transfer to the major 
bacterial inhabitants of the human gut - the anaerobes. The most recent 
NIH sponsored conference on risk assessment (August 1979) also suggested that 
the best test for survival and transfer be done not with disabled strains 
but with wild type since if transfer was not found in this case we could feel 
more assured that it would not occur with disabled or laboratory strains of 
col i K-12. Such studies have not been carried out. And lastly, other 
NIH sponsored risk assessment studies on survival of £. col i in sewage plants 
and in the air and on the bench top all demonstrate that the organism survives 
at higher than expected levels. Hence, the bulk of the results from NIH 
sponsored risk assessment studies suggest that we should not be lowering 
containment for this work as specified by the E_. col i exemption. 
Granting the exemption for E. col i studies will also induce many 
scientists to broaden the overall scope of their work which will in turn 
bring about more and more pressure for further exemptions for other systems 
of even greater risk. This has been the situation with previous exemptions 
granted by the RAC. Already the RAC is under such enormous pressure that 
'here-say' is accepted as fact and facts are often overlooked in the name 
of expediency. The well orchestrated letter writing campaign originating 
at the University of Wisconsin (Madison) in support of exemptions demonstrates 
the lenghts many scientists are willing to go to push for lowering or doing 
away with guidelines. This campaign is a political one which may backfire 
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