Federal Register / Vol. 45. No. 85 / Wednesday, April 30, 1980 / Notices 
known [2A] to be infected with such agents, 
regardless of the host-vector system used." 
This question was presented to the 
RAC at its December 6-7, 1979 meeting 
and a working group was appointed to 
study the issue. A draft proposal of a 
revision of the Guidelines to remove 
Class 3 agents from Section I-D-l of the 
Guidelines was presented to the RAC at 
its March 6-7, 1980 meeting. 
Prior to the March 6-7, 1980 meeting, 
Dr. Clarence Kado of the University of 
California, Davis, requested the RAC to 
consider the elimination of Section I-D- 
3 of the Guidelines, which states as not 
to be initiated: 
“l-D-3. Deliberate creation by the uae of 
recombinant DNA of a plant pathogen with 
increased virulence and host range beyond 
that which occurs by natural genetic 
exchange. [2A]” 
This issue was also discussed by the 
RAC at the March 6-7, 1980 meeting. 
During the discussion, it was suggested 
that the mechanism used to remove CDC 
Class 3 agents from Section I-D-l of the 
Guidelines might be appropriate for 
removing recombinant DNA 
experiments involving certain plant 
pathogens from Section I-D-3. 
Accordingly the proposals have been 
combined. 
The purpose of the proposed changes 
is to remove recombinant DNA 
experiments with CDC Class 3 
organisms and certain recombinant 
DNA experiments with plant pathogens 
from the prohibited classes of 
experiments. The proposal would allow 
experiments with CDC Class 3 
organisms to be conducted at P3 
containment in E. coli K-12 EKl host- 
vector systems. The containment levels 
for other recombinant DNA experiments 
would be assigned by the director, NIH 
after review by the RAC. 
It is felt that reducing administrative 
procedures will increase flexibility and 
encourage the use of these techniques in 
elucidating the pathogenic process. P3 
containment, which is considered 
adequate for work with the pathogenic 
organisms themselves, should be 
adequate, or more than adequate, for 
work with E. coli K-12 containing 
recombinant DNA from these organisms. 
Changes are proposed in the 
Guidelines as follows: 
A. Section I-D-l is to be amended to 
read: 
“I-D-l. formation of recombinant DNAs 
derived from pathogenic organisms classified 
[1] as Class 4 or 5 or from cells known [2A] to 
be infected with such agents, regardless of 
the host-vector system used." 
B. Section I-D-3 is to be deleted. 
C. Section I-E is to be amended to 
read: 
"I-E. Exemptions. It must be emphasized that 
the following exemptions [4] are not meant to 
apply to experiments described in Sections 1- 
D-l to I-D-5 as being prohibited. In addition, 
any recombinant DNA molecules involving 
DNA from Class 3 organisms [1] or cells 
known to be infected with these agents, or 
any recombinant DNA molecules which 
increase the virulence and host range of a 
plant pathogen beyond that which occurs by 
natural genetic exchange, are not exempt 
unless specifically so designated by NIH 
under Section I-E-5." 
D. Section III. After the last sentence, 
“The use of higher levels of biological 
containment * * * for the purposes of 
the experiment," the following new 
paragraph is to be added: 
"Experiments involving recombinant DNA 
from Class 3 organisms (1) or from cells 
known to be infected with these agents may 
be conducted at P3 containment in E. coli K- 
12 EKl hosts (see Section III— O). Containment 
levels for all other experiments with Class 3 
organisms or with recombinant DNA which 
Increases the virulence and host range of a 
plant pathogen will be determined by NIH 
(See Section IV-E-l-b-2-e)." 
E. Section III-O. After the third 
paragraph, “Some experiments * * * are 
exempt from the Guidelines (see Section 
I-E),” the following new paragraph is to 
be added: 
“Experiments using E. coli K-12 EKl host- 
vector systems and DNA from Class 3 
organisms [1] or from cells known to be 
infected with these agents will be conducted 
at P3 containment or at a lower level as 
specified by NIH (See Section IV-3-l-b-2- 
e).“ 
F. A new Section IV-E-l-b-2-e is to 
be added as follows: 
"IV-E-l-b-2-e. Assigning containment levels 
for experiments with recombinant DNA from 
Class 3 organisms [1] and for experiments 
which increase the host-range and virulence 
of plant pathogens." 
G. Section V, footnote 2, is to be 
amended to read: 
“2. For experiments using Vesicular 
Stomatitis virus (VSV), contact the NIH 
Office of recombinant DNA Activities." 
H. Section V, footnote 38. The second 
sentence is to be amended to read: 
"(As noted in the Prohibition Section, the use 
of viruses classified [lj as Class 4 or 5 it 
prohibited.)" 
3. Proposal to Amend Portions of 
Section III-A-2-a, Viruses of 
Eukaryotes. In the 1980 Guidelines a 
level of biological containment requiring 
the use of an "HVl host and a vector 
certified for use in an HV2 system” has 
been substituted for “an EKl host and a 
vector certified for use in an EK2 
system.” This level of biological 
containment is abbreviated as “HVlCV" 
in Table HI and Footnote 40 of the 1980 
2890! 
Guidelines. At the December 6-7, 1979 
meeting of the RAC, a working group 
was appointed to review the 
appropriateness of this level of 
biological containment. The working 
group proposed that HV2 biological 
containment be required for these 
experiments. Accordingly, a proposal to 
amend portions of Section IIl-A-2-a, 
Viruses of Eukaryotes, was published in 
the Federal Register of January 31, 1980 
[45 FR 7182]. 
The RAC discussed this proposal at 
the March 6-7, 1980 meeting. During the 
discussion, the RAC agreed that the 
“CV” nomenclature was developed for 
EK host-vector systems. However the 
RAC felt that requiring the use of HV2 
systems instead of HVlCV imposed an 
unnecessarily stringent level of 
containment. 
The RAC voted to publish for 
comment in the Federal Register a 
proposal to substitute HVl for HVlCV 
in all places in the Guidelines. The 
proposal is as follows: Substitute the 
term “an HVl host-vector” for "an HVl 
host and a vector certified for use in an 
HV2 system” in Section III— A— 2— a— (1 }— 
(a}-(3)-(£>) and substitute the term "an 
HVl host-vector” for "an HVl host and 
a vector certified for use in an HV2 
system, or P3 + HVl," in Sections III-A- 
2— a— (1 )— (a )-(2}-(c) , IH-A-2-a-(l)-(b}- 
(1) -(h), III-A-2-a-(l)-(b)-(2)-(h), III-A- 
2-a-(2)-(a)-(7)-(h), III-A-2-a-(2)-(a)- 
[2) -{b), and III-A-2-a-(2)-(c)-(2)-(b). In 
Table III, whenever any one of the 
following three terms apoears, ("HVlCV 
[40]”; HVlCV [40] or P3 + HVl"; or 
“HVlCV[40] or P3 + HVl[38]") it would 
be changed to "HVl.” 
4. Proposal To Include 
Saccharomyces cerevisiae Hcst-Vector 
Systems under Section III-O of the 
Guidelines. Dr. Jane Setlow of the 
Brookhaven National Laboratory, 
proposed at the March 6-7, 1980 
meeting, that the RAC consider 
classifying under Section III-O of the 
Guidelines experiments involving 
laboratory strains of Saccharomyces 
cerevisiae as host-vector systems. Dr. 
Setlow advanced the following 
arguments to support this proposal: (1) 
S. cerevisiae is nonpathogenic; (2) it 
does not implant in the intestine; (3) the 
dilute conditions in which it is found in 
nature are extremely unfavorable for 
mating; and (4) it does not efficiently 
compete with wild type strains of S. 
cerevisiae. She noted in addition that S. 
cerevisiae does not have a biological 
association with man. Material 
supporting this proposal has been 
provided to ORDA by Dr. Setlow and is 
available upon request. The RAC 
discussed this question at the March 6- 
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