10510 
Federal Register / Vol. 54. No. 47 / Monday. March 13. 1989 / Notices 
Drs. W. French Anderson. R. Michael 
Blaese. and Steven Rosenberg of the National 
Institutes of Health, Bethesda, Maryland, can 
conduct experiments in which a bacterial 
gene coding for neomycin phosphotranaferase 
%vill be inserted into a portion of the tumor 
Infiltrating lymphocytes (TIL) of cancer 
patients using a retroviral vector. N2. The 
marked TIL then will be combined with 
unmarked TIL, and reinfused into the 
patients. This experiment is an addition to an 
ongoing adoptive immunotherapy protocol in 
which TIL are isolated from a patient's tumor, 
grown in culture in the presence of 
interleukin-2, and reinfused into the patient 
The marker gene will be used to detect TIL at 
various time intervals following reinfusion. 
Approval is based on the following four 
stipulations; 
1. There will be no more than 10 patients in 
the initial trial; 
Z 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 
purposes. 
B. Amendment of Section I-C of the NIH 
Guidelines 
Section I-C of the Guidelines is 
modified to read 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). 
This includes research performed by NIH 
directly. 
An individual receiving support for 
research involving recombinant DNA must be 
associated with or sponsored by an 
institution that can and does assume the 
responsibilities assigned in these Guidelines. 
■The NIH Guidelines are also applicable to 
recombinant DNA projects done abroad: 
1. If they are supported by NIH funds; or 
Z If they involve deliberate release into the 
environment or testing in humans of 
materials containing recombinant DNA 
developed with NIH funds, and if the 
Institution that developed those materials 
sponsors or participates in those projects. 
Participation includes research collaboration 
or contractual agreements, but not mere 
provision of research materials. 
If the host country has established rules for 
the conduct of recombinant DNA projects, 
then the project must be in compliance with 
those rules. If the host country does not have 
such rules, the proposed project must be 
reviewed by an NIH-approved IBC or 
equivalent review body and accepted in 
writing by an appropriate national 
governmental authority of the host country. 
The safety practices to be employed abroad 
must be reasonably consistent wnth the NIH 
Guidelines. 
C. Proposed Amendment of Section I-B 
Section I-B is modified to read as 
follows: 
In the context of these Guidelines 
recombinant DNA molecules are defined as 
either (i) molecules which are constructed 
outside living cells by joining natural or 
synthetic DNA segments to DNA molecules 
that can replicate in a living cell, or (ii) DNA 
molecules that result from the replication of 
those described in (i) above. 
Synthetic DNA segments likely to yield a 
potentially harmful polynucleotide or 
polypeptide (e.g„ a toxin or a 
phormacologic^y active agent) shall be 
considered as equivalent to their natural 
DNA counterpart. If the synthetic DNA 
segment is not expressed in vivo a ’ 
biologically active polynucleotide 
polypeptide product, it is exempt L die 
Guidelines. 
Genomic DNA of plants and bacteria that 
has acquired a transposable element even If 
the latter was donated from a recombinant 
vector no longer present is not subject to 
these Guidelines unless the tronsposon itself 
contains recombinant DNA. 
III. Correction to Notice of Actions 
Published in the Federal Register on 
October 26, 1988 (53 FR 43410) 
Two phrases were inadvertently 
dropped from Part n., D. Revision of 
Appendix C-IV. Appendix C-IV should 
read as follows: 
Any asporogenic Bacillus subtilis or 
asporogenic Bacillus licheniformis strain 
which does not revert to a sporeformer with a 
frequency greater than 10. can be used for 
cloning DNA with the exception of those 
e.xperimcnts listed below. 
For these exempt laboratory experiments. 
BLl physical containment conditions are 
recommended. 
For large-scale (LS) fermentation 
experiments, the appropriate physical 
containment conditions need be no greater 
than those for the host organism uiunodified 
by recombinant DNA techniques: the EC can 
specify higher containment if it deems 
necessary. 
OMB’s "Mandatory Information 
Requirements for Federal Assistance 
Program Announcements"(45 FR 39592) 
requires a statement concerning the 
official goverr ’ ont programs contained 
in \he Catalog Federal Domestic 
Assistance. Nonaally NIH lists in its 
announcements the number and title of 
affected individual programs for the 
guidance of the public. Because the 
guidance in this notice covers not only 
virtually every NIH program but also 
essentially every Federal research 
program in which DNA recombinant 
molecule techniques could be used, it 
has been determined to be not cost 
effective or in the public interest to 
attempt to list these programs. Such a 
list would likely require several 
additional pages. In addition, NIH could 
not be certain that every Federal 
program would be included as many 
Federal agencies, as well as private 
organizations, both national and 
international have elected to follow the 
NIH Guidelines. In lieu of the individual 
program listing, NIH invites readers to 
direct questions to the information 
address above about whether individual 
programs listed in the Catalog of 
Federal Domestic Assistance are 
afiected. 
Dated: March Z 1989. 
James B. Wyngaarden, 
Director, National Institutes of Health. 
[FR Doc. 83-5674 Filed 3-10-89; 8:45 am] 
MUJNQ CODE 4140-01-M 
[ 38 ] 
Recombinant DNA Research, Volume 14 
