Federal Register / Vol. 45, No. 85 / Wednesday, April 30, 1980 / Notices 
28907 
language should be added at the end of 
UI-C-4: 
"and (iii) negative air pressure should be 
employed in the greenhouse or growth 
chamber when infectious agents are used 
which generate airborne propagules." 
Dr. Zaitlin notes that a PI greenhouse 
or growth chamber is described in 
Section III— C— 3, Plant Viral Host-Vector 
Systems, in which there is a 
recommendation for positive air 
pressure in order to exclude insects 
which might transmit viruses. However, 
in the conditions considered in Section 
ni-C-4, i.e. Plant Host-Vector Systems 
other than Viruses, the propagules 
themselves (spores, mycelia, etc.) should 
be contained, and a negative air 
pressure would be more appropriate. 
9. Cloning of Foot and Mouth Disease 
Virus — Stage II. At the December 8-7, 
1979 meeting, the RAC considered a 
proposal submitted by investigators at 
the Plum Island Animal Disease Center 
to permit the cloning of foot and and 
mouth disease virus (FMDV) in an E. 
coli K-12 host-vector system. Since 
FMDV virus is classified as a Class 5 
agent, an exception to a prohibition of 
the Guidelines (I-D-l) was requested for 
cloning segments of the virus. Stage I of 
the proposal involves the cloning of 
double-stranded cDNA from RNA 
isolated from the virus. Subgenomic 
fragments of the viral genome are to be 
propagated in an E. coli K-12 host 
employing plasmid pBR322 as a vector. 
Clones containing FMDV sequences of 
interest would be analyzed and 
collected. The Director, NIH on 
recommendation of the RAC, approved 
on January 17, 1980 the formation of 
recombinants between fragments of 
FMDV and plasmid pBR322 as outlined 
in Stage I of the proposal. This stage is 
being carried out at the Plum Island 
Animal Disease Center. 
The second stage of the scientific plan 
is proposed to be carried out in a joint 
effort at the laboratories of Genentech, 
Inc., South San Francisco, California. 
After clones containing viral sequences 
of interest have been assayed for lack of 
infectivity, they would be transferred to 
Genentech, Inc. for detailed molecular 
characterization. An attempt would be 
made to modify clones to produce 
polypeptides of interests, specifically 
the VP» polypeptide. 
The RAC at its December 6-7, 1979 
meeting recommended that a Working 
Group of the RAC be formed to report 
back to the full RAC after examination 
of the testing data on the infectivity of 
the clones produced at Plum Island 
under Stage I, prior to their removal 
from Plum Island. The Director, NIH 
accepted this recommendation on 
January 17, 1980. As Stage I of the 
project is nearing completion, the 
investigators now propose to submit 
testing data on the infectivity of the 
clones to the RAC Working Group and 
the RAC at its June 5-6 meeting in order 
to seek approval for further stages of the 
project. The RAC will consider whether 
they recommend that the clones may be 
removed from Plum Island, and what 
they judge to be the appropriate 
containment level for work with the 
clones at Genentech, Inc. 
10. Request for an Exception to a 
Prohibition: Field Testing of Com Genes 
Put into Com (Zea mays) with an E. coli 
or S. cerevisiae Vector. Dr. Ronald 
Davis of Stanford University Medical 
Center has requested permission from 
the RAC to field test com plants (Zea 
mays) which have been transformed by 
com DNA or modified com sequences 
cloned in Escherichia coli or 
Saccharomyces cerevisiae host-vector 
systems. Approval of this request 
requires an exception to Prohibition I- 
D-4, which prohibits deliberate release 
into the environment of any organism 
containing recombinant DNA 
11. Request for Certification of a 
Bacillus subtilis Strain as the Host 
Component of an HV2 Host-Vector 
System. Dr. William F. Burke, Jr. of 
Arizona State University requests the 
RAC to certify Bacillus subtilis strain 
ASB298 as the host component of an 
HV2 host-vector system. Dr. Burke has 
supplied ORDA with a report outlining 
the construction and characteristics of 
this strain. 
12. Proposed Revision of Section III- 
C-l-e. A notice appeared in the Federal 
Register of January 31, 1980 concerning 
proposed revision of Section IH-C-l-e, 
and its subsections. It was ' 
recommended that Sections IE-C-l-e, 
III— C— 1— e — (1), III— C— 1 ~ c ~ ( 1 ) — (a), and 111— 
C-l-e(lHb) of the Guidelines be 
changed and that a new Section IH-C-1- 
e-(lHc) be added. Section ID-C-l-e-(2) 
would remain unchanged. The RAC, at 
its March 6-7, 1980 meeting, 
recommended adoption of Sections HI— 
C— 1— e, III — C — 1 c ^ ( 1 ] , and III— C— 1 — e — (1) — 
(a) as published in tne Federal Register 
of January 31, 1980, with certain 
modifications in Section IH-C-l-e-(l)- 
(a). 
The Director, NIH, accepted this 
recommendation and promulgated the 
following sections in the Federal 
Register of April 11, 1980: 
"IH-C-l-e. All Viral Vectors. 
HI-C-l-e-(l). Other experiments involving 
eukaryotic virus vectors can be done as 
follows: 
HI-C-l-e-{l)-(a). Recombinant DNA 
molecules containing no more than two-thirds 
of the genome of any eukaryotic virus [all 
viruses from a single Fanlily (36) being 
considered identical (50)] may be propagated 
and maintained in cells in tissue culture using 
Pi containment For such experiments, it 
must be shown that the calls 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 a genome.” 
_ At its March 8-7, 1980 meeting, the 
RAC voted to defer consideration until 
the June 5-6, 1980 meeting of the new 
Sections HI-C-l-e-(l}-{b) and HI-C-1- 
e-(lHc) as proposed in the Federal 
Register of January 31, 1980, and 
requested that a working group develop 
additional information. An ad hoc 
working group will meet on May 13, 1986 
during the meeting of the American 
Society for Microbiology. The report of 
the working group will be considered at 
the June 5-6, 1980 RAC meeting. 
Accordingly, the proposed revised 
Sections fil-C-l-e-(l}-(b) and HI-C-1- 
e— (1)— (c) are again published for public 
comment prior to consideration at the 
June 5-6, 1980 meeting: 
"HI-C-l-e-(l)-(b). Recombinants with less 
than two-thirds of the genome of any 
eukaryotic virus may be rescued with helper 
virus using P2 containment if wild type 
strains of the helper virus are not able to 
grow in human cells. 
IH-C-l-e-(l)-( c ). Recombinants with less 
than two-thirds of the genome of any 
eukaryote virus may be rescued with helper 
virus using P3 containment if wild type 
strains of the helper virus are able to grow in 
human cells.” 
13. Lowering of Containment Levels ' 
for Characterized Clones or Purified 1 
DNAs by ICBs. The December 1978 NIH 
Guidelines specified in Sections m-A- 
3-a, HI-A-3-b, and IV-D-3-b, 
conditions under which the local 
Institutional Biosafety Committee could, 
without NIH prior approval, give 
approval for a single step reduction in 
physical or biological containment. 
When the Guidelines were revised in 
January 1980 and Section III-A was 
changed from covering experiments with 
the E. coli K-12 host-vector system to 
covering experiments with certain HVl 
and HV2 systems, the ability of the IBC 
to grant such single step reductions 
without NIH approval was withdrawn. 
(This is discussed on page 69246 of the 
November 30, 1979 Federal Register). 
The RAC at its March 6-7, 1980 meeting 
voted 9 to 1 with 3 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 to be approved 
by the local IBC, without prior NIH 
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