MASSACHUSETTS INSTITUTE OF TECHNOLOGY 
77 MASSACHUSETTS AVENUE 
CAMBRIDGE, MASSACHUSETTS 02130 
DEPARTMENT Of BIOLOGY 
April 3, 1978 
Room 56-721 
PHONE: (617) 253-1000 
Dr. Donald S. Fredrickson 
Director 
Bldg. 1, Room 124 
National Institutes of Health 
Bethesda, MD 20014 
Dear Dr. Fredrickson: 
As you suggested in our conversation last week, I am writing to summarize 
the arguments in favor of giving some well-defined status in the revised NIH 
Guidelines for Recombinant DNA Research to ini vitro recombination experiments 
involving bacteria known to exchange chromosomal DNA in nature. As you know, 
the present draft revision regards these experiments as outside the purview of 
the guidelines, presumably because they do not result in novel combinations 
of genetic information and thus present no special hazard. I agree absolutely 
with the judgement of no special hazard, but I am afraid that excluding these 
experiments from the quidelines NIH will leave them in a bureaucratic limbo 
which potentially can cause difficulty for both the experimenter and NIH. 
I propose instead that the Guidelines include these experiments (including 
"self-cloning") explicitly, but in a category of experiment ("HV-0", and/or 
"P-0"?) requiring no precautions beyond the prudent bacteriological practice 
appropriate to the handling of the microbial species involved. Thus a Salmonella 
cross with E^. coli would be considered no more hazardous than Salmonella , and 
no additional precautions need be demanded by NIH. Bureaucratically, I can 
envision several possibilities. A purely pro forma MU A might be required, or 
else a simple notice of the experiments to NIH with an acknowledgment. Alterna- 
tively, all paperwork could be forgone entirely. The important point, in my 
view, is that the experiments be explicitly recognized as recombinant DNA 
(which they logically are) and explicitly be recognized as presenting no 
special hazard . 
The advantages of this explicit approach over exclusion of these experiments 
are the following: 
1. NIH will retain continuing control over them in principle, making more 
rational its intention to identify "exchangers" versus "non-exchangers" and, 
more important, lending its protection to these experiments. The latter will 
be of special importance in the event that legislation carrying a useful pre- 
emption clause is passed. 
2. NIH will immunize itself (and the investigators) from the charge 
that a potentially dangerous class of experiments has been left unregulated 
and unmonitored. After all, it should be anticipated that some highly 
pathogenic species of bacteria can be shown to be "exchangers" with E_. coli . 
[Appendix A — 270] 
