TUFTS UNIVERSITY 
Graduate Program in Urban Social and 
Environmental Policy 
September 24, 1979 
Dr. Donald S. Fredrickson 
Director 
National Institutes of Health 
Bethesda, Maryland 20205 
Dear Dr. Fredrickson: 
As you know, at the last meeting of the Recombinant DNA Advisory 
Committee, a proposal to exempt a large class of recombinant DNA experiments 
from the NIH guidelines was approved by a 10 to 4 vote with one abstention. 
I was one of the RAC members who voted against the proposal. Since I 
know you will be giving serious attention to this major action I would 
like to summarize the reasons for my vote which fall into four categories: 
(i) one area of potential risk has not been investigated experimentally; 
(ii) there are conflicting interpretations of the mouse-polyoma experiment; 
(iii) survival experiments with some debilitated strains of E.coli showed 
that survival was higher than previously expected; (iv) plasmid transfer 
experiments with debilitated and ordinary strains of E.col i have not been 
completed. 
The RAC subcommittee on risk assessment has proposed that a conference 
be held "as expeditiously as possible," to evaluate certain conditions that 
have a direct bearing on the safety of E , col i K12 host-vector systems. 
These include: 
(1) studies of hormone-producing strains of E.col i , to evaluate direct 
adverse effects. 
(2) studies to determine the possible occurence of autoantibodies 
or autoreactive cells due to the production of eukaryotic poly- 
peptides (including hormones) by bacteria that colonize higher 
organisms. 
I believe these areas of concern are in themselves of sufficient 
importance to warrant holding off the blanket exemption of E.col i K12 (with 
plasmid and phage restrictions) from the guidelines. RAC has been advised 
that experiments to answer these questions are not difficult to accomplish. 
Consequently, I feel strongly that NIH should fund the relevant studies to 
resolve this area of uncertainty. 
The mouse-polyoma experiments are a critical part of the risk 
assessment information. However, there are conflicting interpretations of 
the significance of these experiments. Professors Ethan Signer and Jonathan 
King (both of MIT)emphasize that an artificial recombinant was created in 
those experiments (bacteriophage lambda containing two copies of polyoma 
DNA) which proved to be infectious and tumorigenic to mice. This, they 
assert, shows that a new laboratory hybrid was created that was not found 
Medford, Massachusetts 02155 
617 628-5000 
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