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Federal Register / Vol. 47, No. 167 / Friday, August 27, 1982 / Notices 
questioned that language. It was pointed 
out that the text says “e.g.. a toxin or a 
pharmacologically active agent” and 
does not necessarily equate the two. 
Also the text is identical with that in the 
current April 21, 1982 version of the 
Guidelines. Dr. Bems said the working 
group determined that proposals to 
clone genes for certain biologically 
active polypeptides should be carefully 
evaluated, as were proposals involving 
toxins. The language of Section III-A-1 
and Appendix F have been modified to 
reflect diis intent. Dr. Bems said these 
sections specify the LDSOs that define 
"biologically active polypeptides." It 
was agreed to leave the language as 
proposed. 
Cir. Nightingale then reviewed the 
proposed changes in Section 111. She 
noted that a "caution" had been added 
to Section IIl-B-3. That caution is as 
follows: 
CAUTION: Special care ihould be used in 
the evaluation of containment levels for 
experiments which are likely to either 
enhance the pathogenicity (e.g.. insertion of a 
host oncogene) or to extend the host range 
(e.g.. introduction of novel control elements) 
of viral vectors under conditions which 
permit a productive infection. In such cases, 
serious consideration should be given to 
raising physical containment by at least one 
level 
Dr. Nightingale said this is one 
instance where new information 
suggested that a caution be added. Dr. 
Ahmed asked to whom the caution was 
addressed. Dr. Bems replied that the 
caution is addressed primarily to the 
IBC. Dr. Ahmed asked if the phrase 
"consideration by the IBC" should be 
added. He felt the caution as proposed 
appeared parenthetical: the I^ should 
be cited more explicitly. Dr. Bems did 
not accept Dr. Ahmed's suggestion as he 
felt responsibility should be incumbent 
on both the investigator and the IBC. Dr. 
Ahmed withdrew the proposal. 
Dr. Nightingale asked if Dr. Ahmed, as 
the maker of the motion, would agree to 
•trike the work "viral” in Section IIl-B- 
2-a. The language reads in part: 
* * * RecombinanI DNA experiments in 
which DNA from Class 4 agents is transferred 
into nonpathogenic prokaryotes or lower 
eukaryotes can be performed at P2 
containment after demonstration that only a 
totally and irreversibly defective fraction of 
the agent’s viral genome is present In a given 
lecombinanL 
Dr. Bems explained that currently all 
Class 4 agents classified in Appendix B 
are viruses. That situation might, 
however, change in the future, and 
deleting the word “viral" in Section III- 
B-2-a would provide greater flexibility. 
Dr. Ahmed agreed to delete the word 
"viral." 
Dr. Gottesman noted that language 
from Sections III-B-2-a and III-B-2-b of 
the April 21, 1982, Guidelines had been 
combined by the working group into a 
new Section IIl-B-2-a. In so doing, the 
working group had moved experiments 
involving a totally and irreversibly 
defective fraction of Class 4 agents into 
Section Ill-B-2-a, and delegated 
authority to the IBC to lower 
containment on experiments involving 
these agents. 
Dr. Nightingale mentioned the 
inadvertment omission in Section III-B- 
4-a of language dealing with USDA 
permits for working with Class 5 agents, 
and suggested suitable language be 
inserted analogous to that found at the 
end of Section III-B-2-b. Mr. Thornton 
asked if Dr. Ahmed would agree to 
insertion of such language in Section III- 
B-4-a. Dr. Ahmed agreed as did Dr. 
Bems. 
Dr. Nightingale then referred to 
Section Ill-C, Experiments that Require 
IBC Notice Simultaneously with 
Initiation of Experiments. The first 
sentence of this section reads as 
follows: 
Experiments not included in Section Ill-A 
Ill-B. IIl-O. and subsections of these sections 
are to be considered in Section UI-C. 
She said the working group was 
concerned with the language of this 
section. They noted that non-exempt 
experiments which might merit more 
stringent review by RAC or by the IBC 
prior to initiation of the experiment 
might not be adequately described in 
Sections III-A and III-B and. thus, 
would automatically fall into Section III- 
C. Dr. Nightingale suggested that a 
reference be added at the end of the first 
paragraph of Section Ill-C drawing the 
reader's attention to the first two 
paragraphs of Section IV-A, which 
emphasizes the responsibility of the 
institution and those associated with it. 
Dr. Nightingale said the clause 
emphasizing institutional responsibility 
in Action IV-A ought to read: 
• * * Therefore, it is the responsibility of 
the Institution and those associated with it to 
adhere to the intent of the Guidelines as well 
as to their specifics. 
The RAC agreed that the word 
"intent" should be substituted for the 
word "purpose” which was used in the 
version proposed by the working group. 
Dr. Ahmed agreed to add a reference to 
Section IV-A in Section IIl-C and to 
substitute the word "intent" for the 
word "purpose" in the language of 
Section IV-A. Dr. Berns agreed. 
Dr. Baltimore questioned why low-risk 
oncogenic viruses had been classified in 
proposed Appendix B as Class 2 agents. 
He said most are not human pathogens 
at all. and many are extremely 
innocuous. He felt that classifying low- 
risk oncogenic viruses as Class 1 agents 
and moderate-risk oncogenic viruses as 
Class 2 agents would be more 
reasonable. Dr. Berns did not agree 
completely; he felt some of the 
moderate-risk oncogenic viruses, such 
as Herpesvirus saimiri or EB virus, 
should be classified as Class 3 agents. 
Dr. Baltimore agreed that Herpesvirus 
saimiri might be classified as a Class 3 
agent but felt Rous sarcoma virus be 
classified as Class 1. Dr. Bems ageed 
that the list warranted closer looking at, 
but he did not feel that this RAC 
meeting was the appropriate time for 
such a virus by virus review. Dr. 
McKinney pointed out that P2 provides 
the investigator with physical protection 
that is desirable and necessary for 
working with these agents. 
He suggested low-risk oncogenic 
viruses should be used under Class 2 
containment conditions. Dr. Baltimore 
noted that in the current Guidelines a 
listing is given in Appendix B of low-risk 
and moderate-risk oncogenic viruses, 
but no containment relative to the 
Guidelines is specified. The proposed 
revised Guidelines include the new 
statements that low-risk oncogenic 
viruses "should be treated as Class 2 
agents" and moderate-risk oncogenic 
viruses "should be treated as Class 3 
agents." Therefore, this involves an 
increased stringency of the proposed 
revised Guidelines for these agents. 
Dr. Brill questioned the inclusion of all 
Klebsiella strains as Class 2 agents in 
Appendix B. He said Klebsiella species 
are ubiquitous. Dr. Bems point out that 
Klebsiella was classified as Class 2 in 
the original 1974 edition of the 
Classification of Etiologic Agents; the 
working group had not changed its 
classification. Dr. Holmes said he could 
suggest several modifications to 
Appendix B: he agreed with Dr. 
Richardson that Schistosoma mansoni 
should be Class 2; the Psittacosis- 
Omithosis-Trachoma group needs to be 
revised; consideration should be given 
to grouping Mycobacterium leprae with 
Mycobacterium tuberculosis. Mr. 
Thornton suggested in view of the 
number of specific concerns expressed 
concerning Appendix B that a working 
group review the list and report to the 
RAC at its next meeting. This was 
agreed to. 
Dr. Nightingale reviewed the proposed 
changes in Section IV, Roles ond 
Responsibilities. These modifications 
include: 
(1) in Section lV-B-2, language was 
inserted to the effect that the IBC's 
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