17 
greater difficulty in complying with the guidelines. Ronald Cape of 
Cetus Corp. stated, “We want to be treated both in the letter as well as 
the spirit like evei-ybody else in terms of these guidelines.” 
Procedures 
The effectiveness of the XIH guidelines does not depend upon reason- 
able standards alone. It also requires procedures to review and enforce 
compliance. It cannot be argued that the guidelines are merely ad- 
visory. The October 1977 environmental impact statement on the 1976 
guidelines states that “Xoncompliance with the guidelines will result 
in termination of funding of research grants and contracts.” Yet 
XIH’s lack of experience in regulation is indicated by the ambiguity 
of the guidelines' procedural provisions, by the guidelines’ failure to 
establish clearly the responsibilities of institutions, institutional bio- 
hazards committees and investigators, and by the absence of any men- 
tion of procedures to investigate and correct violations. While undoubt- 
edly most researchers have observed the guidelines conscientiously, it 
is equally clear that others have substituted their own judgments of 
safety for those of NIH. 
These conclusions result from the subcommittee’s investigation of 
an acknowledged violation last year by researchers at the University 
of California at San Francisco Medical School, reported originally 
in the September 30, 1977, issue of Science magazine. The case in- 
volved the unauthorized use of an EK2 plasmid vector with E. coli 
X 1776 in a P3 experiment to clone the rat insulin gene. The vector in 
question, pBR322, was submitted to XIH for certification in Decem- 
ber 1976, approximately 6 months after publication of the guidelines 
in the Federal Register. The experiment using pBR322 was conducted 
from mid- January to mid-March, 1977, at which time the organisms 
containing the recombinant DXA were destroyed. Subsequently, the 
■experiment was successfully repeated with an authorized vector. The 
^plasmid pBR322 was not certified by XIH until July 7, 1977. 
Chapter IV of the guidelines — “Permissible Experiments: E. coli 
K-12 Host- Vector Systems'’ states, “For the time being, no EK2 or 
EK3 host-vector system will be considered bona fide until the Re- 
combinant Advisory Committee has certified it.” This requirement is 
intended to insure that material used in moderate- and high-risk ex- 
periments has a very low probability of surviving and exchanging 
DXA with other organisms in a natural environment. In fact, the 
language of the section is misleading; it is the Director of XIH who 
certifies EK2 and EIv3 vectors after review and upon recommendation 
by the Recombinant Advisory Committee (RAC). Xevertheless, a Xo- 
vember 26, 1976, XIH memorandum advised all institutional bio- 
hazards committees that only one EK2 host-vector system had been 
certified, and that when others were certified, “You will be notified 
.and their availability will be announced in the ‘Xueleic Acid Recom- 
binant Scientific Memoranda.’ ” The memorandum also states that the 
institutional biohazard committees are responsible for informing re- 
searchers at their institutions of XIH policies and actions. In any 
event, on January 16, 1977, the Recombinant Advisory Committee only 
tentatively- recommended approval of pBR322 subject to the receipt 
of additional data supporting its safety ; these were submitted in early 
February. Further experimental data were requested by the committee 
[Appendix B — 277] 
