53820 
Federal Register / VoL 58, No. 199 / Monday, October 18, 1993 / Notices 
Guidelines: (i) experiments described in 
Section IH-A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section IH-B which require 
NIH (ORDA) and IBC approval before 
initiation, (iii) experiments involving 
DNA from Class 3, 4. or 5 organisms (ll 
or cells known to be infected with these 
agents may be conducted under 
containment conditions specified in 
Section IH-C-2 with prior IBC review 
and approval, (iv) large-scale 
experiments (e.g., more than 10 liters of 
culture), and (v) experiments involving 
the cloning of toxin molecule genes in 
E. coli K-12 (see Appendix F). 
“• * * Appendix C-flL Experiments 
Involving Saccharomyces Host-Vector 
Systems * * * 
“* • * Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (i) experiments described in 
Section III— A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section EH— B which require 
NIH (ORDA) and IBC approval before 
initiation, (iii) experiments involving 
DNA from Class 3. 4, or 5 organisms [1] 
or cells known to be infected with these 
agents may be conducted under 
containment conditions specified in 
Section III-C-2 with prior IBC review 
and approval, large-scale experiments 
(e.g., more than 10 liters of culture), and 
experiments involving the cloning of 
toxin molecule genes in E. coli K-12 
(see Appendix F). 
* * * Appendix C— IV. Experiments 
Involving Bacillus subtilis Host-Vector 
Systems * • * 
* * • Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (1) Experiments described 
in Section EQ-A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section EC-B which require 
NIH (ORDA) and IBC approval before 
initiation, (iii) experiments involving 
DNA from Class 3, 4, or 5 organisms [l] 
or cells known to be infected with these 
agents maybe conducted under 
containment conditions specified in 
Section III-C-2 with prior IBC review 
and approval, large-scale experiments 
(e.g., more than 10 liters of culture), and 
experiments involving the cloning of 
toxin molecule genes in E. coli K-12 
(see Appendix F). 
“* * * Appendix C-V. 
Extrachromosomal Elements of Gram 
Positive Organisms * * * 
* * • Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (i) Experiments described in 
Section HI— A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section HI— B which require 
NIH (ORDA) and IBC approval before 
initiation, (iii) large-scale experiments 
(e.g., more than 10 liters of culture), and 
(iv) experiments Involving the cloning 
of toxin molecule genes in E. coli K-12 
(see Appendix F.)" 
Appendix F will read: 
“Appendix F. Containment 
Conditions for Cloning of Genes Coding 
for the Biosynthesis of Molecules Toxic 
for Vertebrates. 
“Appendix F-L General Information. 
“Appendix F specifies the 
containment to be used for the 
deliberate cloning of genes coding for 
the biosynthesis of molecules toxic for 
vertebrates. The cloning of genes coding 
for molecules toxic for vertebrates that 
have an LDjo of <100 nanograms per 
kilogram body weight (e.g., microbial 
toxins such as the botulinum toxins, 
tetanus toxin, diphtheria toxin, Shigella 
dysenteriae neurotoxin) are covered 
under Section Ett-B -1 of the Guidelines 
and require NIH (ORDA) and IBC 
approval before initiation. No specific 
restrictions shall apply to the cloning of 
genes if the protein specified by the 
gene has an LDjo of 100 micrograms or 
more per kilogram of body weight 
Experiments involving genes coding for 
toxin molecules with an LDjo of <100 
micrograms and >100 nanograms per 
kilogram body weight require 
registration with ORDA and IBC 
approval prior to initiating the 
experiments. A list of toxin molecules 
classified as to LDso is available from 
ORDA. Testing procedures for 
determining toxicity of toxin molecules 
not on the list are available from ORDA. 
The results of such tests shall be 
forwarded to ORDA, which will consult 
with ad hoc experts, prior to inclusion 
of the molecules on the list (see Section 
IV-C-l-b-( 2 He)) * * * 
“Appendix F-ffl. Containment 
Conditions for Cloning Toxin Molecule 
Genes in Organisms Other Than E. coli 
K- 12 . 
“Requests involving the cloning of 
genes coding for molecules toxic for 
vertebrates at an LD50 of less than 100 
nanograms per kilogram body weight in 
host-vector systems other than E. coli K- 
12 will be evaluated by NIH (ORDA) in 
consultation with ad hoc toxin experts 
(see Sections HI— B and IV— C — 1 — b(3) — (f). 
“Appendix F-4V. Specific Approvals. 
“An updated list of experiments 
involving the deliberate formation of 
recombinant DNA containing genes 
coding for toxins lethal for vertebrates at 
an LD 30 of less than 100 nanograms per 
kilogram body weight is available from 
the Office of Recombinant DNA 
Activities, National Institutes of Health, 
Building 31. Room 4B11, Bethesda, 
Maryland 20892.” 
Appendix F-TV-A through Appendix 
F-IV-K would be deleted. (A list of 
these specific approvals will be 
maintained in ORDA.] 
III. Correction to the Notice of Actions 
Published in the Federal Register on 
September 13, 1993.(58 FR 47906) 
Appendix I>-XLIX should read: 
“Appendix D-XLIX. 
“Dr. Gary J. Nabel of the University of 
Michigan Medical Center, Ann Arbor, 
Michigan, may conduct experiments on 
12 patients with AIDS to be divided into 
4 experimental groups. CD4(+) 
lymphocytes will be isolated from 
peripheral blood and transduced with 
Rev M10, a transdominant inhibitory 
mutant of the rev gene of the human 
immunodeficiency virus (HTV). 
Transduction of the rev mutant will be 
mediated either by the retrovirus vector, 
PLJ-cREV M10, or by particle-mediated 
gene transfer of plasmid DNA. Patients 
will be monitored for survival of the 
transduced CD4(+) cells by polymerase 
chain reaction and whether Rev M 10 
can confer protection against HIV 
infection to CD4(+) cells." 
OMB's “Mandatory Information 
Requirements for Federal Assistance 
Program Announcements” (45 FR 
39592) requires a statement concerning 
the official government programs 
contained in the Catalog of Federal 
Domestic Assistance. Normally NIH lists 
in its announcements the number and 
title and 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 
the Catalog of Federal Domestic 
Assistance are affected. 
Effective Date: October 7, 1993. 
Ruth L. Kirschstein, 
Acting Director, National Institutes of Health 
[FR Doc. 93-25498 Filed 10-15-93. 8:45 am) 
BILLING COO€ 4140-01-41 
[504] 
Recombinant DNA Research, Volume 18 
