Appendix lll-A— History of the Recombinant DNA Debate • 319 
revised Guidelines provided, for the first time, for 
voluntary registration of projects with NIH, in which 
the registrant would agree to abide only by the con- 
tainment standards of the Guidelines.*’ 
Other major changes were embodied in the new 
Guidelines. Because of the consensus that the ex- 
periments posed lower risks than originally thought, 
some types of experiments were exempted, while 
containment levels were lowered for almost all 
others. In order to provide greater tlexibility, these 
Guidelines permitted exceptions on a case-by-case 
basis, and included procedures for their change on a 
piecemeal basis without going through the whole in- 
ternal process at HEW . For major changes, the pro- 
cedure was; 1) publication of the proposed changes 
in the Federal Register at least 30 days prior to a R,\C 
meeting; 2) R.AC consideration of the proposed 
changes: and 3) publication in the Federal Register of 
the final decision of the Director, N'lH. The standard 
for all actions of the Director under the Guidelines 
was "no significant risk to health or to the environ- 
ment.’’** Lastly, the new Guidelines delegated project 
approx al to the IBCs. 
The problems posed by voluntary compliance and 
commercialization haxe continued to be addressed 
by MH. In a second major revision to the Guidelines 
on January 29. 1980, a section (Part \ I ) was added to 
specify procedures for voluntary compliance. * * On 
Iconiinuedfrom p. 3tH) 
•Subsequently. Califano sent similar letters to the Secretaries of 
.Agriculture (February 1979) and Labor (July 1979) requesting 
them to consider how their agencies' authorities could be used to 
require prixate sector rDN.A research to comply with the 
Guidelines.” 
"Minutes of the Interagency Committee on Recombinant DNA 
Research, p. 3, July 17. 1979, reprinted in Recombinant DNA Re- 
search, vol. 5. p 132. et. seq. 
’’See. l\'-F-3. 1978 Guidelines. 
“Sec. IX -E-l-b. 
■ ■ Sev eral responses to the FD.A notice had questioned the agen- 
cy s legal authority to regulate prixate rDN.A research. Conse- 
quently, Dr. Fredrickson and Dr. Donald Kennedy, then Commis- 
sioner of Food and Drugs, developed a draft supplement to the 
Guidelines, specifying procedures for voluntary compliance by in- 
dustry. It was published for comment on .Aug. 3, 1979 (44 F.R. 
45868) and incorporated as part of the proposed revised Guide- 
lines of November 30, 1979. (44 F.R. 69210, 69247). 
April 11, 1980, NIH published Physical Containment 
Recommendations for Large Scale Uses of Organisms 
Containing Recombinant DNA Molecules in the form 
of Draft Part \'II to the Guidelines.** Besides setting 
large scale containment levels, this document recom- 
mends that the institution: appoint a biological safety 
officer with specified duties; and establish a worker 
health surveillance program for work requiring a 
high (Pj) containment level. Finally, a more ad hoc re- 
quirement has been used since October 1979 for ap- 
prox'als of industrial requests for cultures up to 750 
liters (1); the approvals were conditioned on NIH 
designated observers being permitted by the com- 
panies to inspect their facilities.*'* At least one inspec- 
tion has taken place. 
On November 21, 1980, NIH adopted the third ma- 
jor revision to the Guidelines.** It contained these 
significant changes: institutions sponsoring the 
research are no longer required to register their 
projects xvith NIH pursuant to an informational docu- 
ment called a Memorandum of Understanding (MUA) 
xvhenever the containment levels are specified in the 
Guidelines; and NIH will no longer review IBC deci- 
sions on experiments for which containment levels 
are specifieid in the Guidelines. 
On November 21, 1980, NIH also promulgated 
revised application procedures for large-scale pro- 
posals. The application must include the following in- 
formation: 1) the registration document submitted to 
the local IBC; 2) the reason for wanting to exceed the 
10-1 limit; 3) evidence that the rDNA to be used was 
rigorously characterized and free of harmful se- 
quences; and 4) specification of the large-scale con- 
tainment level proposed to be used as defined in the 
NIH Physical Containment Recommendations of 
April n, 1980. 
In addition to adding part VI to the Guidelines, the most signifi- 
cant change in the January 1980 Guidelines was the addition of 
sec. III-O, which permitted most experiments using E. coli K-12 
host-vector systems to be done at the lowest containment levels. 
”45 F.R. 24968, Apr. 11, 1980. 
”44 F.R. 69251, Nov. 30, 1979. 
”45 F.R. 77372, Nov. 21, 1980. 
