Yale University 
New Haven, Connecticut 06510 
SCHOOL OF MEDICINE 
3 33 Cedar Street 
Department of Human Genetics 
April 21, 1978 
Dr. Donald Frederickson, Director 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Dr. Frederickson: 
The proposed revised Guidelines for Recombinant DNA Research state : 
"In general, recombinant DNA molecules formed from any combination of 
DNAs will not be considered novel when all the components are derived 
from genomes known to replicate within the organism used to propagate 
the recombinant DNA." The revision also states: "These Guidelines .. .pertain 
only to novel DNAs." 
If the above changes could be put into effect immediately, they 
would save the enormous amount of time and money now spent in processing 
M.U.A.s and inspecting laboratories in which the only relevant experiments 
involve the cloning of E. coli genes or coliphage genes in E_. coli 
itself. 
This is separate from the more complex matter of excluding recombinant 
DNAs that consist of segments of DNA from different species that are 
known to exchange chromosomal DNA by natural physiological processes. 
We understand that you now have a committee working on the list of 
"exchangers", and that this will take time. The matter of excluding 
"self-cloning", however, is quite straightforward and non-controversial; 
as chairpersons of Institutional Biohazards Committees we urge that, as 
soon as possible, you publish a directive excluding from the M.U.A. 
process all experiments in which segments of the E_. coli chromosome, or 
of phages or plasmids that normally infect E. coli , are cloned by insertion 
into vectors that are then propagated in E. coli . 
Respectfully, 
EAA:bgf 
On behalf of the Chairpersons of Institutional Biohazards Committees 
listed on the following page: 
[Appendix A — 291 ] 
