Federal Register / Vol. 49, No. 3 / Thursday, January 5, 1984 / Notices^ 
699 
IV. Proposal to Add a New Section III— 
A -4 to the Guidelines and to Devise 
Mechanisms to Review Proposals 
Involving Genetic Engineering in 
Humans 
At its April 11, 1983, meeting, the 
Recombinant DNA Advisory Comittee 
(RAC) endorsed a proposal to form a 
working group to comment and report to 
RAC on the “Report on the Social and 
Ethical Issues of Genetic Engineering 
with Human Beings," issued by the 
President's Commission for the Study of 
Ethical Problems in Medicine and 
Biomedical and Behavioral Research. 
The President's Commission began its 
study in September 1980 in response to a 
request of the President's Science 
Advisor. Concern has been expressed 
earlier that year by the Nation's three 
major religious associations that no 
governmental body was “exercising 
adequate oversight or control, nor 
addressing the fundamental ethical 
questions in a major way." The 
Commission's report, issued in 
November 1982, concluded that 
continuing oversight of the field is 
desirable and suggested tl at one 
possible mechanism could be revising 
the responsibilities of the RAC. 
The RAC Working Group for 
Development of Response to President's 
Commission's Report on Ethical and 
Social Issues met at NIH on June 24, 
1983, and prepared a proposal for 
consideration by the full RAC on 
September 19, 1983. 
,The working group's primary 
recommendations were: 
1. The membership of the RAC be 
modified to include adequate 
representation to deal credibly with 
these issues. 
2. Procedures should be developed for 
the coordinate consideration of 
experiments involving the use of 
recombinant DNA technology in humans 
by Institutional Review Boards (IRBs), 
the Office of Protection from Research 
Risks (OPRR), the Food and Drug 
Administration (FDA), Institutional 
Biosafety Committees (IBCs), the Office 
of Recombinant DNA Activities 
(ORDA), and the Recombinant DNA 
Advisory Committee (RAC). 
3. The NIH Guidelines for Research 
Involving Recombinant DNA Molecules 
should be reviewed for their adequacy 
and clarity in dealing with human 
experimentation. 
The RAC discussed this proposal a' 
its September 19, 1983, meeting. It was 
noted tha' the recommendations were 
based on several premises. These are: 
(1) There is currently no other national 
body that deals with ethical issues in 
the biomedical field: (2) RAC’s expertise 
would be supplemented by adding 
experts in the ethical issues of using 
human subjects: and (3) RAC would 
review proposals on a case-by-case 
basis in response to investigator- 
initiated research. RAC's review would 
supplement review by IBCs and IRBs. 
The RAC unanimously accepted the 
working group's recommendation. 
Questions such as whether the language 
of the Guidelines as currently written is 
adequate or how the review procedures 
would function were to be discussed at 
subsequent meetings of the Working 
Group. 
The Working Croup on Social and 
Ethical Issues (formerly the Working 
Group for Development of Response to 
President's Commission's Report on 
Ethical and Social Issues) met at the 
NIH on December 13, 1983. The working 
group requested that the following 
modifications to the Guidelines be 
published for comment, and be 
considered by the RAC at their February 
1984 meeting. 
A. A new Section III— A — 4 would be 
added to Section III— A. Experiments 
that Require RAC Review and NIH and 
IRC Approval Before Initiation, of the 
Guidelines: 
III— A— 4. Deliberate transfer of recombinant 
DNA or DNA derived from recombinant DNA 
into human subjects. The requirement for 
RAC review should not be considered to 
preempt any other required review of 
experiments with human subjects. IRB review 
of the proposal should be completed before 
submission to NIH. 
B. Section III— E3 — 4 — b of Section III— D — 4, 
Recombinant DNA Experiments 
Involving Whole Animals or Plants, 
would be footnoted. Section III— B — 4 — b 
reads as follows: 
III— B — 4 — b. For all experiments involving 
whole animals and plants and not covered by 
iII-B-4-a, the appropriate containment will 
be determined by the IBC. 
C. A footnote concerning Section III— 
B-4-b of Section III— B— 4, Recombinant 
DNA Experiments Involving Whole 
Animals or Plants would be added to 
Section V, Footnotes and Reference of 
Sections I-IV, as follows: 
for recombinant DNA experiments 
involving human subjects, see Section III— A— 
4. 
In addition, the Working Group on 
Social and Ethical Issues suggested that 
a working group, composed of 9 
members (including chairperson), be 
formed to conduct initial review of 
proposals submitted to the RAC. 
Individuals with expertise in basic 
science, clinical medicine, law, and 
ethics would be appointed to the 
working group. Liaison members from 
FDA and the Office of Protection from 
Research Risks would also be 
appointed. The working group might use 
as resource material reports such as 
“Splicing Life" prepared by the 
President's Commission for the Study of 
Ethical Problems in Medicine and 
Biomedical and Behavioral Research. 
V. Proposed Exemption for Certain 
Experiments Involving Nonpathogenic 
Streptomyces 
Dr. Jack Manis of The Upjohn 
Company requests that under Appendix 
C of the Guidelines that "the Director of 
NIH and the RAC consider exemption 
from the Guidelines of any 
ireacombinant DNA experiments which 
involves only non-pathogenic 
Streptomyces species and their 
indigenous plasmids and viruses.” 
Dr. Manis also requests that "the 
Director of the NIH and the RAC 
consider exempting from regulation by 
the Guidelines any scale-up of 
recombinant Streptomyces cultures 
which are derived from nonpathogenic 
streptomycetes and which use as the 
basic host organisms Streptomyces 
species which have routinely been used 
in large-scale antibiotic fermentations 
without medical or ecological incident 
(e.g., S. lincolnensis, S. fradiae. S. 
Erythreus, etc.)." 
VI. PI Growth Conditions for Plants 
Sereral inquiries concerning the 
specifications for contained growth 
conditions for plants have been 
received. In order to facilitate 
understanding of these requirements, the 
U.S. Department of Agriculture 
representative to the RAC suggested 
that language describing the 
specifications for contained growth 
conditions for plants be added to the 
Guidelines. One mechanism by which to 
include such a description in the 
Guidelines would be for Section III— B — 4 — 
b to be footnoted. 
Section III— B — 4— b reads as follows: 
II— 13 — 4— b. For all experiments involving 
whole animals and plants and not covered by 
III— B— 4 — a, the appropriate containment will 
be determined by the IBC. 
A footnote concerning Pi growth 
conditions for plants would be added to 
Section V, Footnotes and Reference of 
Section I-IV, as follows: 
If the IBC wishes to require Pi growth 
conditions for plants, this can be met by 
either (1) a limited access greenhouse, or (2) a 
plant growth chamber, which are insect- 
restrictive and in which a pest control regime 
is maintained. The greenhouse or growth 
chamber should be under positive air 
pressure unless airborne propagules are 
generated (e.g., fungal spores) in which case 
negative air pressure should be emplnved 
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