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Federal Register Vol. 45, No. 73 / Monday, April 14, 1980 / Notices 
^Jh eSaccharomyces 2 mu plasmid containing 
yeast or S. commune sequences in S. 
commune. " 
During the thrity day comment period, 
no comments were received. 
The RAC at its March 6-7, 1980 
meeting discussed this item. It was 
noted mat Schizophyllum commune is a 
nonpathogenic saprophytic 
ba afdomycete which occurs widely in 
nature. The proposed experiments were 
judged to pose no hazard. The RAC by a 
vote of eighteen in favor, none opposed 
and one abstention, accepted a P2 level 
of containment for the proposed 
experiments. 
I accept this recommendation. 
1-H. Request for Consideration of 
Appropriate Containment Conditions 
In response to a request of December 
7, 1979, to clone Wangiella dermatitidis 
DNA, the following notice was 
published in the Federal Register of 
January 31, 1980: 
“Dr. Charles Jacobs of the University of 
Texas at Austin has requested permission 
from the RAC to clone Wangiella 
dermatitidis DNA in Wangiella dermatitidis 
using Saccharomyces/E. coli hybrid plasmids 
as vectors. Dr. Jacobs requests that the RAC 
assess appropriate containment conditions.” 
During the thirty day comment period, 
no comments were received. 
The RAC discussed this item during 
its March 6-7, 1980 meeting. Wangiella 
dermatitidis is a fungus which can in 
rare instances cause a deep mycosis in 
humans. It is classified by the Center for 
Disease Control as a Class 2 agent. This 
is essentially a "return to host of origin” 
type experiment. With the proviso that a 
HV2 certified Saccharomyces/E. coli 
hybrid plasmid vector be employed in 
the experiments, the RAC by a vote of 
ten in favor, none opposed and four 
abstentions recommended that the 
experiments be approved at the P3 level 
of containment. 
I accept this recommendation. 
/-/. Proposed Exemption for 
Streptococcus Mutans and 
Streptococcus Sanguis 
The following notice was published in 
the Federal Register of January 31, 1980: 
"Dr. Francis Macrina of the Virginia 
Commonwealth University has proposed that 
Streptococcus mutans and Streptococcus 
sanguis be included under the exemption 
category of Section I-EM of the Guidelines 
on the basis that these bacteria have been 
shown to exchange chromosomal DNA by 
known physiological processes. These two 
organisms would then constitute a new 
Sublist of Appendix A.” 
No comments were received during 
the thirty day comment period. 
At the March 6-7, 1980 meeting, the 
RAC discussed the data submitted by 
the investigator in support of his 
request. It was agreed that the 
documentation is good showing natural 
genetic exchange of chromosomal genes 
from Streptococcus mutans to 
Streptococcus sanguis. It was pointed 
out that the Director, NIH, had 
previously endorsed the concept of 
“one-way lists” for Appendix A (Federal 
Register, December 22, 1978, Page 
60100). The RAC recommended by a 
vote of nineteen in favor, none opposed, 
and no abstentions, that a new sublist 
be added to Appendix A of the 
Guidelines exempting recombinant DNA 
experiments invplving the one-way 
transfer of Streptococcus mutans DNA 
into Streptococcus sanguis. 
I accept this recommendation. 
I-]. Proposed Revision of Section III-C- 
I-e and Its Subsections 
The following notice appeared in the 
Federal Register of January 31, 1980: 
"The proposed revised Guidelines (44 FR 
69210), in Appendix C, cite a limited 
exemption, under Section I-E-5, for certain 
recombinant DNA experiments in tissue 
culture: 
Under exemption I-E-5 of these Revised 
Guidelines are those recombinant DNA 
molecules that are propagated and 
maintained in cells in tissue culture and that 
are derived entirely from non-viral 
components (that is, no component is derived 
from a eukaryotic virus). 
This exemption was promulgated in 
the Federal Register of July 20, 1979 (44 
FR 42914). In its original formulation (44 
FR 22314), the exemption proposed to 
include recombinant DNA molecules 
that contain no more than one-fourth o'f 
the genome of a eukaryotic virus. At its 
December 6-7, 1979 meeting, Dr. 
Wallace Rowe submitted a document 
requesting that the RAC reconsider the 
question of allowing exemption for 
tissue culture experiments involving 
recombinant molecules containing no 
more than one-fourth of the genome of a 
virus. A working group was appointed to 
make recommendations for 
consideration at the March 6-7, 1980 
meeting. It has been recommmended 
that Sections III-C-1-e, Ill-C-l-e-(l), 
III— C— 1— e— (1)— (a), and III-C-l-e-(l)-(b) 
of the Guidelines be changed and that a 
new Section III— C— 1— p— (1)— (c) be added. 
Section III— C— 1— e— (2) would remain 
unchanged. The proposed revised 
sections would read as follows: 
III-C-1-e. All Viral Vectors. 
Ill— C— 1— e— (1). Other experiments involving 
eukaryotic virus vectors can be done as 
follows: 
III— C— 1— e— (1)— (a). Recombinant DNA 
molecules containing no more than two-thirds 
of the genome of any eukaryotic virus (all 
viruses from a single Family being considered 
identical) may be propagated and maintained 
in cells in tissue culture in the absence of 
helper vurus using PI containment. 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. For such experiemnts, no MU A need 
be submitted but prior notice must be given 
to the IBC as described in Section III— O of the 
Guidelines. The IBC should handle such 
registration documents as described in 
Section III— O. 
Ill— C— 1— e— (1)— (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. 
III-C-l-e-(l)-(c). Recombinants with less 
than two-thirds of the genome of any 
eukaryotic virus may be rescued with helper 
virus using P3 containment if wild type 
strains of the helper virus are not able to 
grow in human cells. 
During the thirty day comment period 
no comments were received. 
At the March 6-7, 1980 meeting, the 
RAC discussed this proposal. In support 
of the proposal it was stated that there 
is no experimental evidence to date that 
any eukaryotic virus can dispense with 
one-third of its genetic information and 
replicate autonomously or that less than 
two-thirds of viruses from different 
Families can fully complement each 
other’s genetic composition. 
During the discussion it was 
recommened that the proposed Section 
III-C-l-e-(l)-(a) as published in the 
Federal Register on January 31, 1980 
should be further modified in two ways: 
The last two sentences of proposed 
Section III— C— 1— e— (1)— (a) should be 
deleted. (Deletion means a more 
conservative review procedure for these 
experiments). 
In the first sentence, the words “in the 
absence of helper virus” should be 
deleted. A new second sentence should 
be added as follows: "It must be shown 
that the cells lack helper virus for the 
specific Families of the defective viruses 
being used." (This change means a more 
conservative standard concerining the 
presence of helper viruses.) 
A motion that RAC accept Sections 
III-C-1-e, Ill-C-l-e-(l), as III-C-1-e- 
(l)-(a) as published in the Federal 
Register on January 31, 1980, with the 
two modifications in Section III-C-1-e- 
(l)-(a) as noted above, passed by a vote 
of thirteen in favor, three opposed, and 
five abstentions. A vote to defer 
consideration until the next RAC 
meeting of the proposed new Sections 
III— C— 1 - e — (1 )—[b) and III— C— 1— e— (1)— (c) 
as published in the Federal Register on 
January 31, 1980 passed by a vote of 
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