MASSACHUSETTS INSTITUTE OF TECHNOLOGY 
77 MASSACHUSETTS AVENUE 
CAMBRIDGE, MASSACHUSETTS 021 TO 
DEPARTMENT OF BIOLOGY 
December 14, 1977 
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: 
We submit herewith a request from a group of scientists working 
on various aspects of the biology of Salmonella typhimurium for a 
clarification of the status of laboratory strains of this organism 
as hosts for recombinant DNA involving Salmonella DNA and, in some 
cases, E. coli K12 DNA. As you know, your advisory committee sug- 
gested that such experiments should be permitted under the current 
NIH guidelines. However, permission to proceed has not been forth- 
coming from your office. The appended letter has been approved 
for signature by eleven concerned scientists wishing to see this 
permission granted; they represent much of the Salmonella community 
active in molecular genetics today. 
In the letter, we have limited ourselves to the scientific 
issues: the benefits to research as we see them and our best esti- 
mate of the magnitude of the risk that might be imagined. In this 
covering letter, the undersigned wish to point out a few, more 
political, considerations. These are as follows: 
1. The guidelines as written do not explicitly forbid the 
experiments proposed. In the Federal Register (p. 27918) the 
relevant passage of the NIH Guidelines is as follows: " In general , 
the strain of any prokaryotic species used as the host is to con- 
form to the definition of Class I etiologic agents given in ref. 5 
(i.e. Agents of no or minimal hazard.***) and the plasmid and phage 
vector should not make the host more hazardous." (our emphasis). 
We submit that this language explicitly envisions that particular 
strains of species formally in other classes are permissible within 
the Guidelines provided that the particular strain presents "no 
or minimal hazard". Further, we cannot see why the phrase "In 
general" would be included were it intended to have absolute ban on 
non-Class I agents. In the appended letter we try to document the 
idea that strain LT2 of Salmonella typhimurium is not an appreciable 
hazard and thus conforms to the definition of Class I. 
[Appendix A — 127] 
