19 
In the absence during- this period of the principal investigator 
on the insulin project, Howard Goodman,. Boyer was designated 
to NIH as the acting principal investigator. Goodman also asked 
Brian McCarthy, another member of the department, to be avail- 
able to advise the investigators in his laboratory. Boyer and 
McCarthy also shared responsibility for supervising the newly 
constructed P3 facility. Both knew that pBR322 had not been 
certified but claim they were unaware of its use by two post- 
doctoral fellows conducting the experiment, Axel Ullrich and 
Jonathan Shine. 
Shortly after the first of March, Goodman and Rutter dis- 
covered that pBR322 had not been certified. They attempted to 
ascertain from NIH whether certification was imminent. Finding 
that there would be a further delay, Rutter called the NIH Deputy 
Director for Science, Dewitt Stettin, between March 16 and 
March 19 to seek his advice about the continuing use of the vector. 
Rutter was advised to destroy the host organisms ; at that point 
he and Goodman decided to terminate the experiment. The 
Deputy Director did not inform the NIH Office of Recombinant 
DNA Activities (ORDA) or other officials of the call. 
In late May a member of the Rutter laboratory staff informed 
David Martin, chairman of the UCSF biohazards committee, of 
the pBR322 incident. After making a personal inquiry, Martin 
told a meeting of the committee on June 3 that researchers had 
used a vector on the advice of NIH officials who predicted its 
“imminent” certification. When certification was not forthcom- 
ing, the researchers had to destroy their work “to avoid non- 
compliance with the director's wishes, although consistent with 
the guidelines.” The committee approved a letter of complaint 
to NIH that referred to the delay in certifying pBR322 but not 
to its use. It was not until September that the full committee 
learned of the violation. 
Apart from Rutter’s call to the Deputy Director in March, no 
one at UCSF reported the incident to NIH; officials of ORDA 
and the Office of the Director did not leam about it until late 
summer when the Science reporter inquired. Even then, no in- 
vestigation was made ; rather, ORDA requested a written report 
from the new chairman of the biohazards committee, James 
Cleaver, for the purpose of answering further public inquiries 
to NIH. Although the report, dated October 25, indicated that 
the experiment continued for several weeks after the investigators 
discovered that the vector was not certified and that neither the 
biosafety committee nor NIH was fully apprised of the incident, 
NIH took no further action until prompted by the subcommit- 
tee’s investigation. On December 1, ORDA asked for a supple- 
mentary written report from the biohazards committee chairman. 
The UCSF violation occurred shortly after NIH issued procedural 
instructions for implementing the guidelines and coincided with the 
formulation of test criteria for host-vector systems. It resulted in 
part from confusion about the NIH approval process. Witnesses 
stated that NIH has since improved its publication of certification 
actions and clarified the roles of the RAC and the Director. Accord- 
[ Appendix B — 279] 
