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Federal Register / Vol. 45, No. 147 / Tuesday, July 29, 1980 / Notices 
precise, will be used in Section III— C— 7— 
b. 
I-K. Request for Consideration of 
Appropriate Containment Conditions 
Dr. Paul S. Sypherd of the University 
of California, Irvine, requested in a letter 
of May 13, 1980 that the RAC evaluate 
containment conditions appropriate to 
the return of Mucor racemosus DNA 
cloned in Saccharomyces cerevisiae 
host-vector systems to Mucor 
racemosus. In Addition, Dr. Sypherd 
requested permission to transform 
Mucor racemosus with S. cerevisiae 
vectors with or without cloned S. 
cerevisiae sequences. Dr. Sypherd noted 
that Mucor species in general, and M. 
racemosus in particular, are ubiquitous. 
M. racemosus is globally distributed and 
is found in air, in soil, on fruits, and in 
animal dung. He added that M. 
racemosus is nonpathogenic and 
produces no known toxins. M. 
racemosus is not known to mate with 
other species of Mucor, and mating 
within the species occurs at a very low 
frequency under precisely defined 
conditions. A Federal Register 
announcement of Dr. Sypherd’s request 
appeared on April 30, 1980 [45 FR 28908] 
During the thirty-day comment period, 
no comments were received. 
During the discussion of this issue at 
the June 5-6, 1980 meeting, it was noted 
that certain species of Mucor can cause 
mycoses in medically compromised 
humans. It was thus suggested that the 
principal investigator be alerted to the 
pathogenic potenfial of certain Mucor 
species. 
By a vote of fourteen in favor, none 
opposed, and four abstentions, the RAC 
recommended acceptance of Dr. 
Sypherd's proposal at the P2 
containment level. 
I accept this recommendation. 
l-L. Cloning of Foot and Mouth Disease 
Virus — Stage II 
The RAC at its June 5-6, 1980 meeting 
considered the request from scientists at 
the Plum Island Animal Disease Center 
to remove clones containing sequences 
equivalent to a portion of the genome of 
the FQbt-and-Mouth Disease (FMD) 
Virus from Plum Island for further 
development at Genentech, Inc., of 
South San Francisco, California. This is 
Stage II of a cooperative recombinant 
DNA project by scientists at both 
institutions to clone segments of the 
Foot-and-Mouth Disease Virus for the 
purpose of developing a vaccine derived 
from the VP 3 protein encoded by the 
virus. Stage I of the project, involving 
the construction and analysis of a gene 
bank of plasmids containing FMD 
sequences, had been completed at Plum 
Island. In accord with the 
recommendations of the RAC at its 
December 6-7, 1679 meeting, and the 
approval of the Director, NIH, the 
investigators submitted data to 
demonstrate that the clones to be 
removed from Plum Island to Genentech, 
Inc. are noninfective, and contain 
sequences in aggregate less than the full 
genome of the FMD virus. 
Announcement that the RAC would 
review the request to remove clones 
from Plum Island and would recommend 
containment levels for the work at 
Genentech, Inc., appeared in the Federal 
Register of April 30, 1980. No comments 
were received during the thirty-day 
comment period. 
Information on the characterization of 
the inserted DNA sequences was 
provided to the RAC to support the 
RAC’s stipulation that “clones to be 
approved for removal from Plum Island 
shall not contain among them 
collectively or individually, the full 
genome of the FMD .virus.” (A full 
discussion of the RAC’s previous 
recommendations appears in 45 FR 
3552.) The RAC further considered the 
evidence presented which demonstrated 
that the clones lack infectivity. The 
hybridization and restriction analysis 
data for characterization were found 
satisfactory. 
On the basis that the 17 clones 
described in the submission were well 
characterized, lacked infectivity, and 
represent, in aggregate, only 75% of the 
FMD viral genome, a motion was passed 
to recommend approval for removal of 
these clones from Plum Island by a vote 
of twelve in favor, two opposed, and 
four abstentions. 
A motion to permit work with the 
clones at Genentech, Inc. under Pi + 
EKl conditions passed by a vote of 
eleven in favor, one opposed, and five 
abstentions. 
I accept these recommendations. 
I-M. Lowering of Containment Levels 
for Characterized Clones or Purified 
DNAs by Institutional Biosafety 
Committees 
The RAC at its March 6-7, 1980 
meeting voted nine in favor, one 
opposed, with three abstentions, that 
there be published in the Federal 
Register for comment, and brought back 
to the RAC at its June 5-6, 1980 meeting, 
proposed revisions' of the Guidelines to 
permit a single-step reduction in 
physical or biological containment for 
characterized clones or purified DNA, 
by the local Institutional Biosafety 
Compiittee (IBC), without a requirement 
for NIH approval. Accordingly, the 
following proposed changes in the 
Guidelines were published in the 
Federal Register of April 30, 1980: 
A. Section III-A-3-a is to be amended as 
follows: 
III-A-3-a. Purified DNA Other than 
Plasmids, Bacteriophages, and Other 
Viruses. The formation of DNA recombinants 
from cellular DNAs that have been purified 
[41] and in which the absence of harmful 
sequences has been established [3] can be 
carried out under lower containment 
conditions than used for the corresponding 
shotgun experiment [42], The containment 
may decrease one step in physical 
containment [P4— ►P3; P3— «P2; P2— <-Pl] while 
maintaining the biological containment 
specified for the shotgun experiment, or one 
step in biological containment [HV3— «HV2; 
HV2— >HV1] while maintaining the specified 
physical containment. The institutional 
biosafety committee (IBC) must review such 
a reduction and the approval of the IBC must 
be secured before such a reduction may be 
put into effect. IBC approval is sufficient for 
such a reduction except for any lowering of 
containment under Section III-A-3-a to 
levels below PI + HV1, which requires prior 
NIH approval. (See Sections IV-D-l-c and 
IV-E-l-b-(3)-(e).) 
B. Section Hl-A-3-b is to be amended as 
follows: 
III- A-3-b. Characterized Clones of DNA 
Recombinants. When a cloned DNA 
recombinant has been rigorously 
characterized and the absence of harmful 
sequences has been established (3) 
experiments involving this recombinant DNA 
may be carried out under lower containment 
conditions. 
Institutional biosafety committees (IBCs) 
may give approval for a single-step reduction 
in physical or biological containment on 
receipt of evidence of characterization of a 
clone derived from a shotgun experiment and 
its probable freedom from harmful genes. IBC 
approval is sufficient for such a reduction 
except for any lowering of containment under 
Section III — A — 3 — b to levels below 
P1+HV1, or reduction of containment levels 
by more than one step, which also require 
prior NIH approval. (See Sections IV-D-l-c 
and IV-E-l-b-3-(e).) 
C. Section lV-D-l-c-(3) is to be amended 
as follows: 
IV- D-l-c-(3). Certain reductions of 
containment levels for characterized or 
purified DNA preparations or clones (see 
Section III-A-3). 
D. The Note in Section IV-D-3-b is to be 
amended as follows: (Additional language in 
Italics). 
Note.— Some examples of work that might 
ordinarily proceed without prior funding- 
agency approval are the initiation of a project 
at the PI or P2 level (other than the first 
project at the institution). Other example are 
significant changes in hosts or vectors, in the 
donor species or the nature of the DNA 
segment selected, or in the physical location 
of the experiments. Still others are single- 
step reductions in containment level for (i) 
experiments with DNA recombinants from 
cellular DNAs that have been pruified and 
are judged to be free of harmful sequences 
(See Section IlI-A-3-a) and for (ii) clones 
that have been characterized and judged to 
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