UNIVERSITY OF CALIFORNIA, SAN FRANCISCO 
BERKELEY • DAVIS • IRVINE • LOS ANCELES • RIVERSIDE • SAN DIECO • SAN FRANCISCO 
SCHOOL OF MEDICINE SAN FRANCISCO, CALIFORNIA 94143 
September 22, 1978 
Director, National Institutes of Health 
Building 1, Room 124 
9000 Rockville Pike 
Bethesda, Maryland 20014 
Dear Director: 
I am writing to object to the lowering of the containment level for animal virus 
DNA experiments as described on page 33077 of the proposed revised guidelines 
for recombinant DNA research on general microbiological grounds coupled with 
concern regarding certain specific provisions. 
On general grounds, it was stated that the rationale for lowering the containment 
is"cloning the whole or any part of a virus must logically be less dangerous 
than working with the whole virus itself, which is done routinely". (Science 
201 : 600, 1978). I think that working with the whole virus can be significantly 
less dangerous than cloning the whole virus genome for three reasons: 1) whole 
virus can elicit the production of protective antibodies and 2) whole virus with 
its protein coat is subject to the "biological barrier" which can limit infection 
across species lines, and 3) whole virus is frequently eliminated from the body 
after infection. It can be argued, therefore, that the presence of animal virus 
DNA within E. coli , which may establish itself in the intestinal tract, subverts 
these normal protective devices and may be more dangerous than working with the 
virus Itself. 
My concerns regarding specific provisions are: 
1) Page 33077, Section III-A-2-a-(l)-(a)-(2)-(a) Hepatitis B 
Since it is possible that the subgenomic fragment could contain the DNA which 
codes for the protein which causes disease, it seems advisable to be more 
cautious than PI + EKI with this pathogen. 
In addition, no mention is made of hepatitis A virus in any section. 
2) Page 33077, Section III-A-2-a-(l)-(b)-(l)-a 
1) I think our ability to accurately ensure that a piece of DNA is non- 
transforming is not good enough to allow PI + EKI for these potential 
human transforming viruses. 
2) I think the requirements in the next section regarding the entire 
transforming gene and the entire virus are not stringent enough. An 
EK-2 host should be used. 
3) No provision is made for Herpes simplex types 1 and 2 which can transform 
cells in culture. 
[A-261] 
