Federal Register / Vol. 49, No. 81 / Wednesday, April 25, 1984 / Notices 
17847 
Social Issues met at NIH on June 24. 
1983. and prepared a proposal for 
consideration by the full RAC at its 
September 19, 1983, meeting. 
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 for 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 Nil I 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 at 
its September 19, 1983, meeting. It was 
noted that the recommendations were 
based on several premises. These are: 
(1) There i9 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 langauge 
of the Guidelines as currently written is 
adequate or how the review procedures 
would function were to be discussed at 
a subsequent meeting of the working 
group. The Working Group 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, to 
discuss these issues. 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. 
1. A new Section III— A — 4 would be 
added to Section III— A, Experiments 
that Require RAC Review and NIH and 
IBC 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. 
2. Section III— B — 4 — b of Section III— B — 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 
IIl-B-4-a, the appropriate containment will 
be determined by the IBC. 
3. A footnote concerning Section III— 
B-4-b of Section III— 13 — 4, Recombinant 
DNA Experiments Involving Whole 
Animals or Plants would be added to 
Section V, Footnotes and References of 
Sections I-IV, as follows: 
For recombinant DNA experiments 
involving human subjects, see Section IU-A- 
4. 
In addition, the Working Group on 
Social and Ethical Issues suggested that 
working group composed of 9 members 
(including chair) be formed to conduct 
initial review of proposals for 
experiments involving human subjects 
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 the Food and Drug 
Administration and the Office for 
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. 
The working group proposal was 
published in the January 5, 1984, Federal 
Register (49 FR 696). No comments were 
received during the comment period. 
The RAC discussed this proposal at 
its February 6, 1984 meeting. It was 
pointed out that the phrase "or DNA 
derived from recombinant DNA" was 
included in the proposed Section III— A — 4 
to keep coverage under this Section of 
the Guidelines even if the DNA to be 
introduced into the human subject is 
first cleaved from the vector and 
therefore no longer "recombinant DNA." 
By a vote of fifteen in favor, none 
opposed, and two abstentions, the RAC 
recommended that the changes in the 
Guidelines proposed by the working 
group and published in the January 5, 
1984 Federal Register be accepted. 
I accept this recommendation. 
However, concerns have been raised 
about the intended scope of the new 
Section III— A— 4; e.g„ would this 
language be construed to cover feeding 
of bacteria containing recombinant DNA 
or the administration of vaccines 
containing recombinant DNA to human 
subjects. On checking with members of 
the Working Group on Social and 
Ethical Issues, I verified that it was their 
intent to include under Section III— A— 4 
only experiments In which the intent is 
to modify stably the genome of cells of a 
human subject and not experiments 
involving feeding of bacteria containing 
recombinant DNA or the administration 
of vaccines containing recombinant 
DNA. I am, thus, adding the following 
clarifying footnote to Section III— A — 4: 
Section III— A— 4 only covers those 
experiments In which the Intent is to modify 
stably the genome of cells of a human 
subject Other experiments Involving 
recombinant DNA in human subjects such as 
feeding of bacteria containing recombinant 
DNA or the administration of vaccines 
containing recombinant DNA are not covered 
in Section III— A— 4 of the Guidelines. 
In addition I am adding appropriate 
clarifying language to the new footnote 
concerning Section III— B — 4— b. 
II. Summary of Actions 
A. Amendment of Title of Section III 
The title of Section III of the 
Guidelines is changed from 
"Containment Guidelines for Covered 
Experiments" to “Guidelines for 
Covered Experiments.” 
B. Addition of a New Section III-A-4 
1. A new Section III-A-4 is added to 
Section III-A, Experiments that Require 
RAC Review and NIH and IBC 
Approval Before Initiation, of the 
Guidelines: 
III-A-4. Deliberate transfer of recombinant 
DNA or DNA derived from recombinant DNA 
into human subjects [21]. 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. 
2. A new footnote concerning Section 
III-A-4 is added to Section V, Footnotes 
and Reference of Sections I-IV, as 
follows; 
21. Section III-A-4 covers only those 
experiments in which the intent is to modify 
stably the genome of cells of a human 
subject. Other experiments involving 
recombinant DNA in human subjects such as 
feeding of bacteria containing recombinant 
DNA or the administration of vaccines 
containing recombinant DNA are not covered 
in Section III-A-4 of the Guidelines. 
3. Section III-B-4-b of Section III— B — 4. 
Recombinant DNA Experiments 
Involving Whole Animals or Plants, is 
modified by the addition of a footnoting 
as follows: 
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