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The Harold Varmus Papers

Letter from Herbert W. Boyer, Philip Coffino, and Harold Varmus to Daphne Kamely, National Institute of General Medical Sciences pdf (75,731 Bytes) transcript of pdf
Letter from Herbert W. Boyer, Philip Coffino, and Harold Varmus to Daphne Kamely, National Institute of General Medical Sciences
To ensure the safety of recombinant DNA research (research that, among many other results, yielded important techniques for Varmus' investigation into the origins of cancer), the National Institutes of Health in 1976 issued guidelines for the construction and operation of laboratories in which such research was conducted. The guidelines established four containment levels, setting more stringent requirement for such features as air exhaust and wastewater disposal systems with each ascending level. This directive lays out the protocol for using and cleaning a level two containment facility in Varmus and Bishop's laboratory.
Item is a photocopy.
Number of Image Pages:
1 (75,731 Bytes)
1977-05-26 (May 26, 1977)
Boyer, Herbert W.
Coffino, Philip
Varmus, Harold
Kamely, Daphne
National Institute of General Medical Sciences
Original Repository: University of California, San Francisco. Archives and Special Collections. Harold E. Varmus Papers
Reproduced with permission of the Regents of the University of California.
Medical Subject Headings (MeSH):
DNA, Recombinant
Exhibit Category:
Biographical Information
Box Number: 1
Folder Number: 11
Unique Identifier:
Document Type:
Letters (correspondence)
Physical Condition:
Series: UCSF Collections
SubSeries: Collection Number MSS 84-25
SubSubSeries: Correspondence, 1971-1984
Folder: Correspondence, 1977
May 26, 1977
Dear Dr. Kamely:
We would like to undertake a project involving recombinant DNA. Under the present NIH guidelines, this project would appear to require P4 containment. We request that the Recombinant DNA Advisory Committee review the following considerations which we feel would warrant P3 containment conditions.
We propose to use polyoma virus as a vector to clone the thymidine kinase (TK) gene of pseudorabies virus (PRV) in mouse cells. DNA of a polyoma mutant temperature sensitive in an early function (ts-a) will be purified. Restriction endonuclease(s) will be used to delete a portion of the genome that codes for late function. A PRV restriction fragment that codes for TK will be identified and purified using transfection of TK-mouse L cells to HAT resistance as an assay of activity. Recombinants of the polyoma and TK fragments will be formed using conventional procedures. TK-L cells will be infected at the restrictive temperature and cells selected in HAT medium to obtain clones that express TK activity. These cells will be shifted to the permissive temperature and closed circular DNA isolated from the Hirt supernatant.
The following considerations apply in evaluating the biohazards of the proposed experiment:
1. PRV, a herpes virus, is not known to be pathogenic for man, but is pathogenic for pigs and cattle.
2. Viral strains with highly attenuated virulence for livestock and laboratory animals have been described and will be used if available.
3. Polyoma with a deletion of late function will be used.
4. No virions will be generated.
5. A partially defined fragment of PRV DNA will be used.
6. Mouse cells are permissive for both polyoma and PRV, hence both genomes have had the opportunity to coexist in a single host before the introduction of recombinant DNA technoloqy.
In view of these considerations, we request permission to conduct this series of experiments under P3 containment conditions. This project will be conducted by the undersigned.
Sincerely yours,
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