Document 1 
THE ROCKEFELLER UNIVERSITY 
1230 YORKAVENUE NEWYORK, NEW YORK 100 21 
September 7, 1976 
Dr. Donald Fredrickson, Director 
National Institute of Health 
Bethesda, Md. 20014 
Dear Dr. Fredrickson: 
I must say that I am very happy and impressed with the 
environmental impact statement on in vitro recombinant DNA 
experiments. Particularly relevant is the argument on the 
breakdown of the homeostasis (of some kind) that occurs when 
a plasmid is added to a bacterium such that it grows more 
slowly and is often lost. This includes natural, unmodified 
plasmids such as that F agent which is maintained solely on 
basis of its conjugal potential. Also the argument that 
when one inserts or deletes a piece of DNA into plasmids or 
phage DNA, it grows more slowly. This is probably more then 
just the disruption of gene function but depends rather on 
organization of an unknown kind of the nucleotide sequences. 
The last argument which is really not referred to other than 
in the context of K-12 having been a laboratory strain for 
30 years is the deadaptation to the natural host and the 
adaptation to laboratory conditions of biological organisms. 
This principle first described and used by Pasteur in his 
attenuation of the rabies virus to make a vaccine is, as you 
know, the procedure that has been used to make all of our 
live vaccines. 
In general the statement is the most carefully and calmly 
reasoned presentation of the benefits and risks of this new 
technology and its potential effect on the environment, 
since the original Berg e^ al, letter. 
I also want to note that although like many others I 
might nitpick at the details of the guidelines, on the whole 
they represent a very solid and thoughtful piece of work. 
They should be more than sufficient, to protect everyone. I 
am sure that given experience, they will be able to become 
much less stringent. 
Appendix K — 4 
