Federal Register / Vol. 55, No. 177 / Wednesday. September 12, 1990 / Notices 
37565 
National Institutes of Health 
Recombinant DNA Research: Actions 
Under the Guidelines 
agency: National Institutes of Health. 
PHS, DHHS. 
action: Notice of Actions Under the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules. 
summary: This notice sets forth four 
actions to be taken by the Director, 
National Institutes of Health (NIH), 
under the May 7, 1986, NIH Guidelines 
for Research Involving Recombinant 
DNA Molecules (51 FR 16958). 
EFFECTIVE DATE: September 12. 1990. 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. Nelson A. Wivel, Director, 
Office of Recombinant DNA Activities, 
Office of Science Policy and Legislation, 
National Institutes of Health, Building 
31, Room 4B11, Bethesda, Maryland 
20892, (301) 496-9838. 
SUPPLEMENTARY INFORMATION: Today 
four actions are being promulgated 
under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These four actions were published for 
comment in the Federal Register of 
February 27, 1990 (55 FR 6954), and June 
27, 1990 (55 FR 26348), and reviewed and 
recommended for approval by the NIH 
Recombinant DNA Advisory Committee 
(RAC) at its meeting on March 30, 1990, 
and July 31, 1990. 
L Background Information and 
Dedsions on Action Under the **NIH 
Guidelines". 
A. Amendment of Appendix D-XIIl of 
the “NIH Guidelines” 
In a memorandum dated February 6, 
1990, Drs. W. French Anderson, R. 
Michael Blaese, and Steven A. 
Rosenberg of the National Institutes of 
Health requested that the patient 
number limitation be removed from the 
hunian gene transfer protocol which 
involves the transfer of the gene for 
neomycin resistance into tumor 
infiltrating lymphocytes; The current 
protocol is approved for 10 patients. No 
changes in the protocol itself are 
requested; it would continue as 
previously approved. 
This request was published for 
comment in the Federal Register of 
February 27, 1990 (55 FR 6954). 
The initial approval of Appendix D- 
XIII (54 FR 10510) was based on the 
following four stipulations: 
1. There will be no more than 10 patients in 
the initial trial; 
2. The patients selected will have a life 
expectancy of about 90 days; 
3. The patients give fully informed consent 
to participate in the trial; and 
4. The investigators will provide additional 
data before expanding the trial by adding 
patients or by inserting a gene for therapeutic 
pyrposes. 
At a meeting on March 30, 1990, the 
Human Gene Therapy Subcommittee (a 
subcommittee of the Recombinant DNA 
Advisory Committee) considered the 
request to remove the limit on the 
number of patients. The investigators 
presented an interim report on the first 
six patients who were studied. The 
subcommittee unanimously approved 
the request to remove the patient 
number limitation on the protocol 
described in appendix D^QII and 
recommended approval to the 
Recombinant DNA Advisory Conunittee. 
The Recombinant DNA Advisory 
Committee considered this amendment 
at the March 30, 1990, meeting. Again, 
the investigators presented an interim 
report on the first six patients who were 
studied. By a vote of 20 in favor. 0 
opposed, and no abstentions, the 
committee approved the motion to 
accept the recommendation of the 
subcommittee. 
Therefore, the stipulations imposed on 
appendix D-XIII will read: 
1. There will be no limitation on the 
number of patients in the continuing trial; 
2. The patients selected will have a life 
expectancy of about 90 days: 
3. The patients give fully informed consent 
to participate in the trial; and 
4. The investigators will provide additional 
data before inserting a gene for therapeutic 
purposes. 
I accept this recommendation, and 
appendix D-XUI of the NIH Guidelines 
is amended accordingly. 
B. Addition of Appendix D-XV to the 
“NIH Guidelines” 
In a memorandum dated Februeiry 12, 
1990, Drs. R. Michael Blaese and W. 
French Anderson of the National 
Institutes of Health indicated their 
intention to submit a human gene 
therapy clinical protocol to the Human 
Gene Therapy Subcommittee and the 
Recombinant DNA Advisory Committee 
for formal review and approval. The title 
of this protocol is ‘Treatment of Severe 
Combined Immunodeficiency Disease 
(SCID) Due to Adenosine Deaminase 
(ADA) Deficiency with Autologous 
Lymphocytes Transduced with a Human 
ADA Gene.” 
This request was published for 
comment in the Federal Register on 
February 27, 1990 (55 FR 6954). 
The Human Gene Therapy 
Subcommittee considered the request at 
its meeting of March 30, 1990. After 
extensive discussion, the subcommittee 
deferred approval of this protocol 
pending formulation of a response from 
the investigators to certain terms of the 
Points to Consider in the Design and 
Submission of Protocols for the Transfer 
of Recombinant DNA into the Genome 
of Human Subjects. Further, primary 
and secondary reviewers were asked to 
prepare written critiques of the protocol 
and supply the same to the 
subcommittee and to the investigators. 
This request was published for 
comment in the Federal Register on May 
7. 1990 (55 FR 18966). 
During the meeting on June 1, 1990, the 
Human Gene Therapy Subcommittee 
continued discussion of the clinical 
protocol. They recommended 
provisional approval with the following 
points to be definitively addressed at 
the next subcommittee meeting on July 
30. 1990. They are: 
1. That the consent form be revised and be 
reviewed and accepted by the Recombinant 
DNA Advisory Conunittee at its next 
meeting; 
2. That a stronger wammg with regard to 
the potential for malignancy be inserted into 
the consent form: 
3 That a stop criterion of two therapy- 
related deaths be inserted; 
4. That intraperiioneal infusions not be 
utilized without further approval by this 
committee; 
5. That proceeding to part 2B of this 
protocol would require approval by the 
Institutional Biosafety Committee and the 
Institutional Review Board. 
Recombinant DNA Research, Volume 14 
[311] 
