Federal Register / Vol. 46. No. 234 / Monday, December 7, 1981 / Notices 
59735 
currently require explicit RAC review 
and NIH upproval. 
1. Three of the five prohibitions (I-D- 
2, l-D-4, and l-D-5 in the current 
Guidelines) would be listed in a new 
section desi$;nated Ill-A and entitled 
"Experiments that require FAC review 
and NIH approval before initiation." 
These three prohibitions cover 
experiments involving the deliberate 
formation of recombinant DNAs 
containing genes for the biosynthesis of 
certain toxins lethal for vertebrates (I- 
D-2). the deliberate release into the 
environment of organisms containing 
recombinant DNA (l-D-4), and the 
deliberate tiansfei of a drug resistance 
trait to microorganisms that are not 
known to acquire it naturally if such 
acquisition could compromise the use of 
a drug to control disease agents in 
human or veterinary medicine or 
agriculture (1-D-S). 
2. Prohibition I-D-1 in the current 
guidelines (formation of recombinant 
DNAs derived from CDC Class 4 or 5 
organisms) would be deleted. Such 
experiments could be carried out under 
specific conditions set by the IBC, as 
described in a new section designated 
III-B and entitled "Experiments that 
require IBC approval before initiation". 
3. Prohibition I-D-6 in the current 
^ Guidelines, which covers certain large- 
scale experiments, would be eliminated: 
such experiments could proceed after 
I IBC approval (new section IIl-B-5). 
i Currently the Guidelines permit certain 
large scale experiments involving E. coli 
K-12, S. cerevisiae and B. subtilis host- 
vector systems to proceed following 
review by the local IBC (46 FR 33983). 
B. Exenptj'ons. No changes in the 
substance of this section are proposed. 
The categories of exemptions now listed 
I in Section I-E would be listed in a new 
I Section III-D. 
I C. Section II (Containment). All 
references to HV3 systems would be 
deleted. Such systems are not presently 
in use and are not required by current or 
proposed guidelines. Otherwise, the 
section would remain as is. 
D. Section III (Containment 
Guidelines for Covered Experiments). 
The complete text of Section III would 
be replaced by new text which would 
reorganize, simplify, and eliminate 
redundancy in the current Guidelines. In 
addition, signiHcanl lowering of 
containment for some classes of 
experiments is recommended. In the 
new Section 111, all experiments would 
fall into one of four classes: 
III-A. Current prohibitions: such 
experiments would require speciHc RAC 
review and NIH approval. 
IIl-B. Experiments requiring prior 
review by the IBC. These would include 
the use of recombinant D.NA molecules 
derived from or propagated in 
pathogens, non-defective animal virus 
systems, and the insertion of 
recombinant DNA into whole animals 
and plants. Many experiments which 
would be included in this section 
currently require NIH approval. 
IIl-C. Experiments requiring notice to 
the IBC simultaneously with initiation of 
the experiment. 
The proposal would change the 
procedure for reviewing recombinant 
DNA experiments involving non- 
pathogenic prokaryotes, lower 
eukaryotes, or defective animal virus 
systems. These experiments currently 
require prior review by the IBC. Under 
this proposal, investigators would not 
have to wait for IBC approval before 
initiating these experiments. In addition, 
r,ontainment requirements for 
experiments involving non-pathogenic 
prokaryotes and non-pathogenic lower 
eukaryotes would be relaxed. 
III-D. Currently exempt experiments. 
No changes in the substance of this 
section are proposed. 
E. Section IV. Changes as necessary 
to reflect changes in other sections of 
the Guidelines would be incorporated. 
F. Much material currently in 
Appendix E would be covered or 
superseded by the proposed changes in 
the Guidelines in Section III. Appendix 
D would be deleted. 
III. Changes in Current Guidelines to 
Implement Proposal 
A. Current Section I. Section I-A, 
Purpose, would remain unchanged. 
Section 1-B, Definition of 
Recombinant DNA Molecules, would be 
modified to include a statement on 
synthetic DNAs. and would read as 
follows: 
"1-B. Definition of Recombinant DNA 
Molecules. 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 D.NA segments likely to 
yield a potentially harmful 
polynucleotide or polypeptide (e.g., n 
toxin or a pharmacologically active 
agent) shall be considered as equivalent 
to their natural DNA counterpart. If the 
synthetic DNA segment is not expressed 
in vivo as a polynucleotide or 
polypeptide product, it is exempt from 
the Guidelines.” 
Section I-C. General Applicability. 
would remain unchanged. 
Section I-D. Prohibitions, would be 
deleted. (Some of this material is 
included in proposed new Section III-A). 
Section I-E, Exemptions, would be 
deleted. (This material would be 
included in proposed new Section III-D). 
B. Current Section II. Delete current 
Section Il-D-l-c and subsections II-D- 
l-c-(l) through Il-D-l-c-(5). Section II- 
D-2-b-(3) and references to HV3 in 
Section lI-D-3. 
C. Current Section III. Delete and 
replace current Section III and all 
subsections of III with the following 
text: 
"Part 111 discusses experiments 
involving recombinant DNA. These 
experiments hove been divided into four 
classes: 
"IIl-A. Experiments which retjuire 
specific RAC review and NIH approval 
before initiation of the experiment: 
"IIl-B. Experiments which require IBC 
approval before initiation of the 
experiment: 
"Ill-C. Experiments which require IBC 
notiHcation at the time of initiation of 
the experiment: 
"Ill-D. Experiments which are exempt 
from the procedures of the Guidelines. 
"If an experiment falls into both class 
Ill-A and one of the other classes, the 
rules pertaining to class III-A must be 
followed. If an experiment falls into 
class III-D and into either class III-B or 
III-C as well, it can be considered 
exempt from the requirements of the 
Guidelines. 
"Changes in containment levels from 
those specified here may not be 
instituted without the express approval 
of the Director. NIH (See Sections IV-E- 
l-b-(l), IV-E-l-b-(2), and subsections). 
"IIl-A. Experiments that Require RAC 
Review and NIH Approval Before 
Initiation. Experiments in this category 
cannot be initiated without submission 
of relevant information on the proposed 
experiment to NIH, the publication of 
the proposal in the Federal Register for 
thirty days of comment, review by the 
RAC. and specific approval by NIH. The 
containment conditions for such 
experiments will be recommended by 
RAC and set by NIH at the time of 
approval. Such experiments also require 
the approval of the IBC before initiation. 
Specific experiments already approved 
in this section and the appropriate 
containment conditions are listed in 
Appendices E and G. 
"IlI-A-1. Deliberate formation of 
recombinant DNAs containing genes for 
the biosynthesis of toxins lethal for 
vertebrates at an LDso of less than 100 
nanograms per kilogram body weight 
(e.g.. the bofuliniim toxins, tetanus toxin, 
diphtheria toxin. Shigella dysenteriae 
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