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Federal Register / Vol. 47, No. 77 / Wednesday, April 21, 1982 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research; Actions 
Under Guidelines 
AOENCY: National Institutes of Health. 
Public Health Service, HHS. 
action: Notice of actions under NIH 
guidelines for research involving 
recombinant DNA molecules. 
SUMMARY: This notice sets forth actions 
taken by the Acting Director, National 
Institute of Allergy and Infectious 
Diseases, by authority of the Director. 
National Institutes of Health, imder the 
1981 Guidelines for Research Invoving 
Recombinant DNA Molecules (46 FR 
34462). 
EFFECTIVE DATE: April 21, 1982. 
FOR FURTHER INFORMATION CONTACT; 
Additional information can be obtained 
from Dr. William Jr. Gartland, Office of 
Recombinant DNA Activities (ORDA), 
National Institutes of Health, Bethesda, 
Maryland 20205 (301) 496-6051. 
SUPPLEMENTARY INFORMATION: I am 
promulgating today a major action under 
the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
This action involves a major revision of 
the Guidelines. In accordance with 
Section IV-E-l-b of the Guidelines, I 
6nd that this action .complies with the 
Guidelines and present no significant 
risk to health or the environment. 
The structure of this announcement is 
as follows: 
L Background 
II. February 8-9, 1982, Meeting of 
Recombinant DNA Advisory Committee 
m. Analysis of Correspondence Received 
IV. Summary of Guideline Changes 
Immediately following this 
announcement, there appears in a 
separate section of the Federal Register 
the revised NIH Guidelines for Research 
Involving Recombinant DNA Molecules, 
which are effective today. 
I. Background 
Drs. David Baltimore and Allan 
Campbell proposed a major revision of 
the Guidelines (Baltimore-Campbell 
proposal) which was published for 
public comment in the Federal Register 
on March 20, 1981 (46 FR 17995) and was 
considered by the NIH Recombinant 
DNA Advisory Committee (RAC) at its 
April 1981 meeting. At the April 1981 
meeting, a Working Group on Revision 
of the Guidelines was established to 
review the Baltimore-Campbell proposal 
as well as other approaches which might 
lead to a major revision of the 
Guidelines. The Working Group met on 
June 1, 1981, and on July 9. 1981, The 
Working Group prepared a proposal for 
revising the Guidelines, a summary of its 
actions, and a document entitled 
“Evaluation of the Risks Associated 
with Recombinant DNA Research." Two 
minority reports were prepared by 
several members of the Working Group. 
The Working Group report and the 
minority reports were distributed to 
RAC members prior to the September 
1981 meeting. The document entitled 
“Evaluation of the Risks Associated 
with Recombinant DNA Research” was 
an extensive analysis with the following 
headings: 
I. History and Introduction 
II. Possible Hazards 
A. Basic Assumptions 
1. Uniqueness of Organisms Created by 
Recombinant DNA Techniques 
a. Limits of the technique 
b. Natural exchange mechanisms 
c. Counterarguments 
2. Dissemination 
a. Stability of recombinant DNA 
b. Transmission into other potential hosts 
3. Harm 
a. Breaching prokaryotic — eukaryotic 
barriers: evolutionary considerations 
b. Small pieces in large organisms 
c. Specific cases 
i. Expression of active peptides: hormones, 
toxins 
ii. Expression of cross-reacting antibodies 
iii. Animal virus cloning 
B. Human Genetic Engineering 
III. Costs 
IV. Conclusions 
A. Summary Analysis of Risks 
B. Possible Responses 
1. Maintain the Status Quo 
2. Abolish the Guidelines 
C. Recommendation 
The RAC extensively discussed the 
Working Group's report and other 
approaches to revision of the Guidelines 
at its September 1981 meeting. The RAC 
passed by a vote of 16 in favor, 3 
opposed, with 1 abstention, the elements 
of its version of a proposed revision of 
the Guidelines to be published for public 
comment. Based on these elements, NIH 
staff prepared the RAC version of 
proposed revised Guidelines (September 
1981 RAC proposal) which was 
published for public comment in the 
Federal Register of December 4, 1981 (46 
FR 59368). The relevant backgroimd 
documents were also published in the 
December 4, 1981, Federal Register 
announcement, as follow — Annex A: 
Original proposal of Drs. David 
Baltimore and Allan Campbell; Annex B: 
Documents prepared by Working Group 
on Revision of the Guidelines; Annex C: 
Minority reports of working group 
members; Annex D: Draft Minutes of 
relevant portion of September 10-11, 
1981. RAC Meeting: and Annex E: 
Current NIH Guidelines. Comments 
were due by February 2, 1982. 
The major features of the September 
1981 RAC proposal were: 
1. The Guidelines would cease to be 
mandatory and would become a 
volimtary code of standard practice. 
Requirements that institutions have an 
Institutional Biosafety Committee (IBC), 
that investigators obtain prior approval 
from the IBC before beginning certain 
experiments, that investigators obtain 
prior approval from NIH before 
beginning certain experiments, and the 
section of the Guidelines specifying that 
noncompliance with the Guidelines 
could lead to loss of NIH funds, would 
all be eliminated. 
2. Section III of the Guidelines giving 
containment levels would be greatly 
simplihed, and most experiments 
currently mandated at P2 and P3 
containment would be recommended at 
PI. 
3. The prohibitions section (I-D) of the 
Guidelines would be eliminated, 
although two of the previous 
prohibitions would be retained instead 
as admonishments. 
Dr. Susan Gottesman of the National 
Cancer Institute of the National 
Institutes of Health prepared an 
alternative proposal (Gottesman 
proposal) for a major revision of the 
Guidelines. 
The major features of this proposal 
were: 
1. The Guidelines would continue to 
be mandatory for institutions receiving 
NIH funding. Certain experiments would 
continue to require prior review by NIH, ,> 
certain experiments would continue to ^ 
require prior review by an IBC, and •.( 
certain experiments would require 
notice to an IBC simultaneously with 
initiation of the experiment. ' 
2. Section III of ^e Guidelines would 
be reorganized and simpliHed. All . 
experiments would fall into one of four , ! 
classes. Physical containment i 
requirements for some classes of 1 j 
experiments would be lowered. ^ j 
3. Three of five prohibitions (I-D-2, 1- , 
D-4 and I-D-5 in the July 1981 j 
Guidelines) would be listed in a new ^ jj 
section that would continue to require 
RAC review and NIH approval before j ' ,i 
initiation. Experiments falling under j || 
prohibition I-D-1 and I-D-6 in the July J 
1981 Guidelines could proceed after IBC | ; I 
approval. f j| 
A summary of this (Gottesman) ■ |j‘ 
proposal and changes in the July 1981 , 
Guidelines to implement the proposal ' [: 
were published for comment in the f 
Federal Register of December 7. 1981 (46 
FR 59734). Comments on this proposal d 
were due by February 1, 1982. iij 
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