Federal Register / Vol. 58, No. 199 / Monday. October 18, 1993 / Notices 53817 
into Class III— E and into either Class III— 
C or III— D as well, it can be considered 
exempt from the requirements of the 
Guidelines. Changes * * 
Section 111— A— I will be moved to a 
new Section III— B— 1. New Section III— B 
is proposed to read: 
“Section III— B-Experiments That 
Require NIH (ORDA) and 1BC Approval 
Before Initiation. 
"Section Hl-B-1. Deliberate formation 
of recombinant DNA containing genes 
for the biosynthesis of toxin molecules 
lethal for vertebrates at an LDy> of less 
than 100 nanograms per kilogram body 
weight * • • 
"Section BI-B-l-(a). Experiments in 
this category cannot be initiated without 
submission of relevant information on 
the proposed experiment to NIH 
through ORDA. The containment 
conditions for such experiments will be 
determined by ORDA in consultation 
with ad hoc experts. Such experiments 
also require the approval of the IBC 
before initiation (see Section IV-C-l-b- 
OHO” 
Sections IIJ-A-2, IB- A- 3. Ill- A— 4 
will be renumbered to IB-A-1, III-A-2. 
UI-A-3 respectively. Sections IB-B, III— 
C, and IB-D will be renumbered to BI- 
C, BI-D, and BI-E respectively. 
The new Section IB-C-2 is proposed 
to read: 
"Section IB-C-2. Experiments in 
Which DNA From Human or Animal 
Pathogens (Class 2, Class 3, Class 4, or 
Class 5 Agents 111) is Cloned in 
Nonpathogenic Prokaryotic or Lower 
Eukaryotic Host- Vector Systems. 
"Section BJ-C-2-e. * ' * Many 
experiments in this category are exempt 
from the Guidelines (see Section BI-E- 
4) and BI-E-5). Experiments involving 
the formation of recombinant DNA for 
certain genes coding for molecules toxic 
for vertebrates require NIH (ORDA) 
approval (see Section IB-B-1) or must 
be carried out under NIH specified 
conditions as described in Appendix F." 
Section IV-B-5-b-(3) is proposed to 
read: 
"Section IV-B-5-b-{3). Petition NIH 
(ORDA), with concurrence of the IBC for 
approval to conduct experiments 
specified in Sections IB-A and IB-B of 
the Guidelines;” 
Section IV-C-l-b-(3H0 will be 
deleted which reads: "Approving the 
cloning of toxin genes in host-vector 
systems other than E. coli K-12 (see 
Appendix F); and)” 
Section IV-C-l-b-(3)-{g) will become 
the new Section rV-C-l-b-(3}-{f). 
The new Section IV-C-3-e is 
proposed to read: 
"Reviewing and approving 
experiments involving the cloning of 
genes encoding for toxin molecules that 
are lethal for vertebrates at an LDjo 5100 
nanograms per kilogram body weight in 
organisms other than E. coli K-12 (see 
Section IB-B-1 and Appendices F-I and 
F-D).” 
Sections IV-G-3-e and IV-C-3— b will 
be renumbered to become Sections IV- 
C-3-b and IV-C-3-c respectively. 
Section V-2 is proposed to read: 
"• • * In the cases falling under 
Sections IB-A through IB-D, this 
judgment is to be reviewed and 
approved by the IBC * • *” 
Appendix C is proposed to read: 
"Appendix C Exemptions Under 
Section IB-D-5. 
••• • • Appendix C-I. Recombinant 
DNA in Tissue Culture • * • 
"• * • Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (i) Experiments described in 
Section IB-A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section IB-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, and (iv) experiments involving 
the cloning of toxin molecule genes in 
E. coli K-12 (see Appendix F). 
• • Appendix C-fl. Experiments 
Involving E. coli K-12 Host-Vector 
Systems * * * 
"• • * Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (i) Experiments described in 
Section IB-A which require specific 
RAC review and NIH and IBC approval 
before initiation, -(ii) experiments 
described in Section IB-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 IB-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-BI. Experiments 
Involving Saccharomyces Host-Vector 
Systems • • • 
“• * * Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (i) Experiments described in 
Section IB-A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section IB-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 IB-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 
Syslems • • • 
"• • • Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (i) Experiments described in 
Section IB-A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section IB-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 may be conducted under 
containment conditions specified in 
Section IB-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. 
Extra chromosomal Elements of Cram 
Positive Organisms • • • 
“* * * Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (i) Experiments described in 
Section IB-A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section IB-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 is proposed to read: 
"Appendix F. Containment 
Conditions for Cloning of Genes Coding 
for the Biosynthesis ol 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 LDso 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 IB-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 LDso of 100 micrograms or 
more per kilogram of body weight. 
Recombinant DNA Research, Volume 18 
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