Dr. Donald S. Fredrickson 
February 12, 1976 
Page 2 
One application would be the synthesis of desired proteins (e.g. proinsulin) 
in microorganisms. Economically, I accept that this must be done in a living 
cell (i.e. chemosynthesis , ribosomal synthesis, etc. seem too complex and 
expensive). A gene for proinsulin with proper prokaryotic control signals would 
be synthesized chemically (or conceivably made as a cDNA from an mRNA once 
isolated). The defined piece of DNA could then be inserted into a plasmic or 
virus - but not destined for E. coli . I would propose the use of some micro- 
organism which has no association with man (or other animals) , which has a very 
restricted range of genetic exchange and, ideally, a very limited biological 
niche of viability. 
I would also propose the development of procedures that could be maximally 
automated so as to minimize all possible contact of such organisms with our 
biosphere . 
Another current application of great interest is the isolation (via shotgun 
techniques) of specific pieces of eukaryotic DNA. Here my objection is to the 
irreversible incorporation of any such undefined DNA into free-living ubiquitous 
bacteria. I would suggest that it would be safer - and far more potentially 
reversible - to incorporate such DNA into an animal virus against which we 
already have a viable defense - for example, cowpox. All persons and animals 
who might come in contact with such organisms could be vaccinated. If some 
hazard were perceived, all infected animals or tissue culture cells could be 
exterminated (we have coped with outbreaks of animal disease before). The 
genetic gap between prokaryotes and eukaryotes would not be bridged. 
(I presume an analogous approach could be taken for experiments within the plant 
kingdom - obviously without vaccinations). 
My thought then is to approach each desired objective in as specific (and safe) 
a manner as we can think of rather than to attempt a global approach which 
inevitably seems to leave uncovered opportunities for experiments of large 
(in my view) potential danger. 
I regret that the format of the meeting did not really permit an exploration of 
this point of view with the committee as I would be interested in their reactions 
(I did have an opportunity to discuss some of this privately with Paul Berg). 
I appreciate the difficulties you are in with respect to any modification of the 
guidelines from the Recombinant DNA Committee which has worked long and hard for 
a year; also with respect to the whole biological community, many members of 
which simply do not believe a hazard exists. Almost any stricter proposal than 
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