10508 
Federal Register / Vol. 54. No. 47 / Monday, March 13. 1989 / Notices 
DEPARTMEFTT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research: Actions 
Under Guidelines 
agency: National Institutes of Health, 
PHS, DHHS. 
action: Notice of actions under NIH 
guidelines for research involving 
recombinant DNA molecules. 
summary: This notice sets forth three 
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: March 13, 1989. 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Ms. Rachel E. Levinson, Office of 
Recombinant DNA Activities, Office of 
Science Policy and Legislation, National 
Institutes of Health, Building 31, Room 
BlC34, 9000 Rockville Pike, Bethesda, 
Maryland 20892. (301) 496-9838. 
SUPPLEMENTARY INFORMATION: Today 
three actions are being promulgated 
under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These three proposed actions were 
published for comment in the Federal 
Register of September 2, 1988 (53 FR 
34246), and reviewed and recommended 
for approval by the NIH Recombinant 
DNA Advisory Committee (RAC) at its 
meeting on October 3, 1988, A transcript 
of that meeting is available from the 
Office of Recombinant DNA Activities 
at the address given above. 
In accordance with Section FV-C-l-b 
of the NIH Guidelines, these actions 
have been found to comply with the NIH 
Guidelines and to present no significant 
risk to health or to the environment 
Part I of this announcement provides 
background information and decisions 
on the actions under the NIH 
Guidelines. Part II provides a summary 
of the actions. Part HI provides a 
correction to a notice published in the 
Federal Register on October 26, 1988 (53 
FR 43410). 
L Background Information and 
Dedsioos on Actions Under the NIH 
Guidelines 
A Human Gene Transfer Proposal 
Three National Institutes of Health 
(NIH) intramural scientists. Dr. W. 
French Anderson, National Heart Lung, 
and Blood Institute, and Drs. R. Michael 
Blaese and Steven A. Rosenberg. 
National Cancer Institute, have 
submitted a proposal involving transfer 
of a bacterial gene coding for neomycin 
phosphotransferase into the cells of 
human patients. The gene is to be used 
as a marker to trace the path of "tumor 
infiltrating lymphocytes." or TIL, 
administered as pail of an ongoing 
experimental cancer treatment. 
The proposal was first received in 
June emd July 1988, by a number of 
internal NIH review committees charged 
with oversight of the safety of proposed 
experiments. Concern for safety extends 
from the patients to the health care 
personnel and the researchers. The 
institutional review boards of the two 
sponsoring institutes and the NIH 
Institutional Biosafety Committee (IBC) 
all gave “conditional approval" with 
certain stipulations. Among these 
stipulations was a requirement that the 
Recombinant DNA Advisory Committee 
(RAC) grant its approval of the same 
procedure. 
On July 29. 1988. the Human Gene 
Therapy Subcommittee of the 
Recombinant DNA Advisory Committee 
met to consider the gene transfer 
proposal and deferred approval pending 
receipt of additional data. This public 
meeting was aimounced in the Federal 
Reg;ister on June 24, 1988 (53 FR 23805). 
The Subcommittee provided specific 
questions to be answered by the 
investigators prior to the October 3, 
1988, RAC meeting. 
During a telephone conference on 
September 29. 1988. the Subcommittee 
members and consultants participating 
in the conference decided unanimously 
to defer approval of the proposal 
because the questions posed at the July 
29, 1988, meeting had not yet been 
answered by the additional data which 
had been provided. 
The October 3, 1988, public meeting of 
the RAC was announced in the 
September ^ 1988, Federal Register (53 
FR 34246). At this meeting, the RAC 
received and discussed data not made 
available previously to the Human Gene 
Therapy Subcommittee. Based on these 
data, the RAC recommended that NIH 
approve this protocol by a vote of 16 in 
favor, 5 opposed, and no abstentions. In 
addition to the RAC review, I requested 
that the entire protocol, including data 
presented at the October 3, 1988, 
meeting and any additional data 
obtained since that date, be reviewed by 
the Subcommittee at its December 9, 
1988, public meeting (53 FR 45591). 
This request was duly carried out and 
the Human Gene Therapy Subcommittee 
voted unanimously to approve the 
protocol by a vote of 12 in favor, none 
opposed, and no abstentions. 
Following that meeting, the Office of 
Recombinant DNA Activities sent a mail 
ballot to RAC members, including the 
motion approved by the Subcommittee 
and the minutes of the December 9. 1988. | 
meeting of the Human Gene Therapy ; 
Subcommittee. The results of the ballot | 
were 21 in favor, none opposed. 3 i 
abstentions. r 
The motion approved by the Subcommittee 
and the RAC is as follows: | 
i 
To approve the human gene transfer ^ 
proposal submitted by Drs. Anderson. Blaese. i 
and Rosenberg with the following | 
stipulations: i 
1. There will be no more than 10 patients in I 
the initial trial; u 
2. The patients selected will have a life I 
expectancy of about 90 days; I 
3. The patients give fully informed consent i 
to participate in the trial; and 
4 . The investigators will provide additional I 
data before expanding the trial by adding { 
patients or by inserting a gene for therapeutic 
purposes. 
Points 1 through 3 of the motion were 
adopted by the RAC at the October 3. 
1988, meeting. Point 4 of the motion was 
added by the Subcommittee on 
December 9. 1988, making explicit a 
policy that had been agreed upon at the 
October 3, 1988, RAC meeting. 
Approval to implement this proposal 
has now been recommended by: The 
Clinical Research Subpanels of both 
sponsoring institutes, the NIH 
Institutional Biosafety Committee, the [ 
NIH Recombinant DNA Advisory ! 
Committee (RAC), the Human Gene j 
Therapy Subcommittee of the RAC and j 
the Food and Drug Administration 
Vaccines and Related Biologic Products 
Advisory Committee. | 
Through data obtained in animal || 
experiments, the investigators have ! 
demonstrated to the satisfaction of the i 
above review committees that the use of | 
ampho tropically packaged retroviral i 
vectors does not pose a public health I 
risk to patients or to health care I ! 
personnel, even in the event of | 
accidential exposure to experimental | 
material. Therefore, I have determined f ! 
that this protocol does not present a risk il 1 
, to public health or to the environment 1 1 
After reviewing the relevent records 
and documentation. I accepted this 'I 
recommendation, and approval to ' 
conduct this experiment has been given .i 
to Drs. Anderson, Blaese, and Roseberg. | 
B. Amendment of Section I-C of the NIH j 
Guidelines 
Section I-C of the NIH Guidelines 
currently reads as follows: | 
The Guidelines are applicable to all 
recombinant DNA research within the United 
States or its territories which is conducted at | 
or sponsored by an Institution that receives 
any support for recombinant DNA research 
from the National Institutes of Health (NIH). 
[36] 
Recombinant DNA Research, Volume 14 
