Dr. Donald S. Fredrickson 
February 5 S 1976 
Page 2 
The biological containment proposals are ingenious but suffer from a fatal flaw. 
They can all be circumvented by a simple recombination event in which the 
recombinant DNA is a passive participant. And regrettably organisms capable 
of initiating and carrying out recombination with E. coli abound in man (who will 
be doing the experiments) and his environs. 
If then - as I regard as nearly inevitable - coliform (and related) organisms 
bearing recombinant DNA become established in various parts of our environment, 
what will be the consequence? I think it is unpredictable and likely highly 
dangerous. Prokaryotic and eukaryotic organisms (including man) coexist 
intimately on this planet. They interact intensely but at the phenotypic level 
of toxins and antibodies, etc. They do not, with any frequency (so far as I know), 
interact at the genetic level. Thus the prokaryotic world with its varied 
organisms, viruses, colicins, restriction factors, etc., and the eukaryotic 
world with its species, viruses, etc. have no genetic intercourse - although they 
use the same genetic code. One evident reason for this is the difference in 
control elements - promotors, initiators, terminators , etc. employed in the two 
domains which effectively appear to prevent expression of genetic material from 
one domain in the other. 
Incorporation of eukaryotic DNA with its control signals into prokaryotes on an 
appreciable scale cannot but significantly perturb the prokaryotic-eukaryotic 
interaction. By recombination events these control elements could become associ- 
ated with varied kinds of prokaryotic DNA. One can imagine that the viruses of 
prokaryotes (particularly the lysogenic species) could acquire the capacity to 
infect eukaryotes (consider the consequence for a eukaryotic cell of invasion 
by an expressible Mu- type phage - or even by a phage carrying a gene for a 
restriction enzyme). 
As another possibility, microorganisms might acquire the capacity to serve as 
reservoirs for some of the common eukaryotic viruses. 
One need not continue to spin out potential horror stories. The point is that 
we will be perturbing, in a major way, an extremely intricate ecological inter- 
action which we understand only dimly. 
A further important point, which I feel has been underestimated, is that once 
initiated, this course of action is most likely irreversible. We are concerned 
with living, self-reproducing organisms. Once set free into an appropriate 
environment I do not see how we could ever reverse the process (it may already be 
too late), should a hazard appear. The situation is thus very unlike other 
issues of hazard that have arisen such as the use of PCB or DDT or aerosol 
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