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Federal Register / Vol. 45, No. 227 / Friday, November 21, 1980 / Notices 
1-e, III— C— 1— es— (1). and III-C-l-e-{l)-(a) 
as published in the Federal Register of 
January 31, 1980, with certain 
modifications in Section III— C— 1— e— (1 )— 
(a). 
The Director, NIH, accepted this 
recommendation and promulgated the 
following sections in the Federal 
Register of April 14, 1980: 
"Hl-C-1-e. All Viral Vectors. 
“III-C-l-e-(l). Other experiments 
involving eukaryotic virus vectors can be 
done as follows: 
“Ill-C-l-e-(l)-{a). Recombinant DNA 
molecules containing no more than two-thirds 
of the genome of any eukaryotic virus [all 
viruses form a single Family (36) being 
considered identical (50)] may be propagated 
and maintained in ceils in tissue culture using 
Pi containment. For such experiments, it 
must be shown that the cells lack helper virus 
for the specific Families of defective viruses 
being used. The DNA may contain fragments 
of the genomes of viruses from more than one 
Family but each fragment must be less than 
two-thirds of the genome." 
At its March 6-7, 1980 meeting, the 
RAC voted to defer consideration until 
the June 5-6, 1980 meeting of the new 
Sections III— C— 1— e— (1)— (b) and III-C-1- 
e— (1)— (c) as proposed in the Federal 
Register of January 31, 1980, and 
requested that a working group develop 
additional information. Accordingly, a 
working group met on May 13, 1980, 
during the annual meeting of the 
American Society for Microbiology in 
Miami Beach, Florida. The report of the 
working group was considered briefly at 
the June 5-6, 1980 RAC meeting when it 
was decided that it would be considered 
again by the RAC at its September 25- 
26, 1980 meeting. 
The Working Group discussed the 
question of the appropriate containment 
conditions for experiments involving 
recombinant DNA molecules containing 
less than two-thirds of the genome of 
any eukaryotic virus which may be 
rescued with helper virus. On the basis 
of the consensus of the virologists, the 
following recommendation was 
proposed, as a revision of Section III— C— 
1— e— (1)— (b) of the Guidelines: 
"HI-C-l-e-(l)-(b). Recombinants with less 
than two-thirds of the genome pf any 
eukaryotic virus may be rescued with helper 
virus using P2 containment if wild type 
strains of the virus are CDC Class 1 or 2 
agents, or using P3 containment if wild type 
strains of the virus are CDC Class 3 agents 
( 1 )." 
This proposal was published for 
comment in the Federal Register of 
August 21, 1980. During the thirty day 
comment period no responses were 
received. 
At the September 25-26, 1980 meeting, 
the RAC discussed this proposal again. 
Some members of the committee 
expressed concern whether the rescue of 
a defective recombinant virus with 
helper virus could result in the formation 
of a virus with an altered host 
specificity or increased pathogenicity. It 
was noted that the working group of 
virologists previously discussed this 
point, and reached the conclusion that 
the recombinant virus would pose no 
greater biohazard than the wild type 
virus used as a helper. The consensus of 
the working group was that the level of 
containment required for rescue of the 
recombinant virus should correspond to 
the same level of biohazard as the 
helper virus as determined by the CDC 
classification. 
The motion to accept the proposed 
revision of subsection III— C— 1— e— (1)— (b) 
was passed by a vote of 10 in favor, 5 
opposed, and 1 abstention. 
I accept this recommendation, and 
Section III— C— 1— e— (1)— (b) has been so 
modified. This modification justifies two 
further changes in the Guidelines. First, 
new text has been added to Section III— 
C— 1 to advise the reader of the 
relationship of the subsections of 
Sections III-C-1-a, III— C— 1— b, III-C-l-c, 
and III— C— 1— d of the Guidelines to the 
subsections of Section III-C-1-e. Also, 
Table IV of the Guidelines has been 
eliminated. 
XV. Proposed Containment For Cloning 
Between Members of the Actinomycetes 
Group 
Dr. Dean Taylor of the Smith Kline 
and French Laboratories, proposed that 
the third entry in Appendix E of the 
Guidelines be modified to read: 
P2 physical containment shall be used for 
DNA recombinants produced between 
members of the Actinomycetes group except 
for those species which are known to be 
pathogenic for man, animals, or plants. 
This proposal was made previously by 
the RAC Working Group on Prokaryotic 
Host-Vectors Other Than E. coli and 
appeared in the Federal Register, April 
13. 1979 (44 FR 22316). The RAC 
considered the proposal at its May 21- 
23. 1979 meeting and recommended to 
restrict this so that it did not include the 
entire Actinomycetes group but rather 
only the genera Streptomyces and 
Micromonospora. The Director, NIH, 
accepted this recommendation and the 
action was published in the Federal 
Register, July 20, 1979 (44 FR 42916), and 
appears as the third entry in Appendix E 
of the Guidelines. 
This proposal was published for 
comment in the Federal Register of 
August 21, 1980. During the 30 day 
comment period, no comments were 
received. 
During the RAC discussion of this 
proposal it was noted that the family of 
Actinomycetes include many genera 
that are not pathogenic for man, 
animals, or plants. The microorganisms 
in this group are mainly found in soil, 
and are of medical and industrial 
importance. They produce ninety 
percent of the antibiotics used in 
medicine. Although some members of 
the group are parasitic, most do not 
cause disease, or are marginal 
pathogens. 
A motion to restrict the proposal to 
members of the Actinomycetes group 
which are known not to be pathogenic 
for man, animals, or plants, failed by a 
vote of 3 in favor, 11 opposed, with 3 
abstentions. 
A motion to accept the proposal as 
published in the Federal Register on 
August 21, 1980, passed by a vote of 16 
in favor, 1 opposed, with 1 abstention. 
I accept this recommendation, and the 
third entry in Appendix E of the 
Guidelines has been so amended. 
XVI. Changes in Registration 
Requirements 
Dr. Maxine Singer, National Cancer 
institute, National Institutes of Health, 
proposed a series of changes in the 
administrative requirements specified 
by the Guidelines. The proposal would 
elimnate NIH review, registration, and 
approval for all experiments assigned 
containment conditions in the 
Guidelines. 
In submitting the proposal, Dr. Singer 
stated: 
When the Guidelines were first 
promulgated, many arguments appeared to 
dictate a complex system of review and 
approval prior to the initiation of 
experiments. Regardless of how one views 
the wisdom of the earlier decisions, the multi- 
level system with its emphasis on central 
review at the NIH is now clearly 
unnecessary, inhibitory, expensive, and 
conterproductive in relation to the respect 
accorded the containment recommendations. 
By now, Institutional Biosafety Committees 
have accumulated sufficient expeience with 
and knowledge of the Guidelines to operate 
as independent review groups. Safety 
Officers now function in many research 
institutions. Furthermore, the good laboratory 
practices mandated by the Guidelines have 
become routine practice in many 
laboratories. Indeed, confidence in the 
efficiacy of Guidelines has been based 
primarily on compliance by individual 
investiators within their own laboratories. 
The administrative changes that 
accompanied the revised containment levels 
for experiments with E. coli K-12 and S. 
cerevisiae earlier this year recognized that 
central review and approval were no longer 
necessaryily desirable or useful. The present 
proposal is an extension of that idea. 
In brief, the proposal eliminates central 
review, registration, and approval for all 
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