STANFORD UNIVERSITY MEDICAL CENTER 
DEPARTMENT OF GENETICS 
September 2 , 1978 
Donald S. Fredrickson, M.D. 
Director 
National Institutes of Health Bldg. 
Room 124 
Bethesda, MD 20014 
Dear Don: 
While the proposed revised recombinant DNA guidelines are in many respects 
an improvement over the earlier version, I believe that they are still far too 
restrictive with regard to non-U coli prokaryotic host-vector systems. Specif- 
ically, I am most concerned about the new guidelines' virtual prohibition of 
the use of non-pathogenic HVI systems other than U coli K12 without extensive 
review and explicit approval by the NIH Recombinant DNA Advisory Committee. 
As I have written previously, the HVI section of the new guidelines will 
bring to a halt a wide variety of experiments with non-U coli systems that have 
been permitted under the old guidelines; many such experiments have been going on 
several years with no indication whatsoever of hazard. Some of the experiments 
that will be halted involve the use of gene manipulation to produce medically 
important products such as antibiotics. I believe that this outcome is contrary 
to the public interest. 
The problem can be remedied by a simple sentence in the guidelines stating 
that experiments with non-pathogens that involve introduction of genes derived 
from other prokaryotic organisms within etiologic agent class I can be carried 
out under P2 (or P3 if you prefer) containment conditions. While this wording 
would establish a level of physical containment that I believe is far more strin- 
gent than necessary for safety, at least it would set forth some conditions for 
carrying out the experiments. Under the present wording, simple experiments 
involving introduction of genes from non-pathogens into other non-pathogenic non- 
U col i hosts are prohibited; it does not seem reasonable to effectively place 
such experiments, which most scientists would agree are among the safest of all, 
in the "too dangerous to be done" category — while at the same time relaxing con- 
tainment for almost all other recombinant DNA work. 
I know that you have considered this matter in the past and have decided 
against implementing my recommendation. Nevertheless, I hope that this letter 
may prompt you to give some additional thought to the incredibly inappropriate 
and inequitable wording of the HVI section of the revised guidelines. With best 
SC:TA 
DEPARTMENT OF GENETICS, STANFORD UNIVERSITY SCHOOL OF MEDICINE, STANFORD, CALIFORNIA 94305 • (415) 497-5052 
wishes 
Professor of Medicine and 
Professor of Genetics 
[A-78] 
