53980 
Federal Register / Vol. 46, No. 210 / Friday. October 30, 1981 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research; Actions 
Under GuideUnes 
AGENCY; National Institutes of Health. 
PHS, HHS. 
action: Notice of actions under NIH 
Guidelines for Research Involving 
Recombinant DNA Molecules. 
summary: This notice sets forth actions 
taken by the Director, NIAID, by 
authority of the Director, NIH, under the 
1981 Guidelines for Research Involving 
Recombinant DNA Molecules (46 FR 
34462). 
EFFECTIVE DATE: October 30, 1981. 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. William J. Gartland, Office of 
Recombinant DNA Activities (ORDA). 
National Institutes of Health. Bethesda. 
Maryland 20205 (301) 496-6051. 
SUPPLEMENTARY INFORMATION: I am 
promulgating today several major 
actions under the NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules. These proposed actions were 
published for comment in the Federal 
Register of August 4, 1981, and reviewed 
and recommended for approval by the 
Recombinant DNA Advisory Committee 
(RAC) at its meeting on September 10- 
11, 1981. In accordance with Section IV- 
E-l-b of the NIH Guidelines, I find that 
these actions comply with the 
Guidelines and present no significant 
risk to health or the environment. 
Part I of this announcement provides 
background information on the actions. 
Part II provides a summary of the 
major actions. 
L Decisions On Actions Under 
Guidelines 
A. Modification of Section UI-0-2 of the 
Guidelines 
Dr. Michael j. Ross of Genentech, Inc., 
in a letter dated fuly 10, 1981, requested 
that the RAC evaluate a proposal to 
amend Section III-B-^3 of the Guidelines. 
Section III-B-3 currently specifies that 
the Director, NIH, using a case-by-case 
review process, may set containment 
levels for certain experiments involving 
non-HVl host-vector systems. Dr. Ross 
proposed that a provision be added to 
this language. The provision would 
permit cloning of DN.4. from any 
nonpathogenic species into 
nonpathogenic lower eukaryotes at the 
P3 level of containment; closing of DNA 
from any nonpathogenic species into 
nonpathogenic prokaryotes would be 
allowed at the P2 level of contaimnent. 
Data supporting the contention that the 
donor and recipient are nonpathogenic 
would be submitted to the local IBC. 
An announcement of Dr. Ross’ 
proposal appeared in the Federal 
Register of August 4, 1981 (46 FR 39771). 
During the thirty day comment period, 
no comments were received. 
The RAC evaluated Dr. Ross’ proposal 
at the September 10-11, 1981 meeting. 
During the discussion, it was noted that 
Section IU-B-3 deals only with 
prokaryotic host-vector systems. Dr. 
Ross’ proposal includes the cloning of 
DNA into nonpathogenic prokaryotes 
and also lower eukaryotes. It was 
pointed put that Section UI-0-2 could be 
modified to accommodate the proposal 
including both prokaryotes and lower 
eukaryotes. RAC recommended 
approval of the proposal by a vote of 
twelve in favor, none opposed, with no 
abstentions, with NIH to modify the 
appropriate section of the Guidelines. 
I accept this recommendation and the 
following wording is substituted for 
Section IU-0-2: “UI-0-2. Experiments 
Involving Nonpathogenic Prokaryotic 
and Lower Eukaryotic Host-Vector 
Systems. DNA from any species 
nonpathogenic for man, animal, or 
plants may be cloned into lower 
eukaryotes nonpathogenic for man. 
animal, or plants at the P3 level of 
containment [2A]. DNA from any 
species nonpathogenic for man, animaL 
or plants may be cloned into 
prokaryotes nonpathogenic for man. 
animals, or plants at the P2 level of 
containment [2A], Data supporting the 
contention that the donor and recipient 
are nonpathogenic must be submitted to 
the local IBC. Lower levels of physical 
containment may be assigned by ORDA 
on a case-by-case basis for specific 
donor-recipient combinations (see 
Section IV-E-l-b-(3)-{h)).’’ 
B. Proposed Amendment of III-C-2-a 
and lU-C-7-c of the Guidelines 
In a letter dated April 27, 1981, Dr, 
Lois Miller of the Universtiy of Idaho. 
Moscow, Idaho, submitted a proposal to 
revise Section llI-C-2-a and to add a 
new section. !II-C-7-c, to the 
Guidelines. 
The proposed revision of Section III- 
C-2-a which involves experiments with 
invertebrate viral vectors appeared as 
follows in the Federal Register of August 
4, 1981 (46 FR 39771): 
“III-C-2. Invertebrate Host-Vector 
Systems. 
“III-C-2-a. Invertebrate Viral Vectors. 
Experiments involving invertebrate 
virus vectors can be done as follows: 
“IE-C-2-a-{l). Recombinant DNA 
molecules containing no more than two- 
thirds of the genome of any invertebrate 
virus [all viruses from a single family 
(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 ceils lack helper virus for the 
specific Families of defective viruses 
being used. The DMA 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. 
’TU-C-2-a-(2). Recombinants with 
less dian two-thirds of the genome of 
any invertebrate virus may be rescued 
with helper virus using P2 containment 
unless it is classified by the GDC as a 
class 3 agent (1) in which case P3 
containment is required. 
“III-C-2-a-(3). ^periments involving 
the use of other whole or defective virus 
genomes to propagate DNA sequences 
from prokaryotic or eukaryotic 
organisms (and viruses), or as vectors to 
transform nonpermissive cells, will be 
evaluated by NIH on a case-by-case 
basis [45] and will be conducted under 
the prescribed physical and biological 
containment conditions. (See Section 
IV-E-l-b-(3)-(c).) 
“NTH will also review on a case-by- 
case basis [45] all experiments involving 
the use of virus vectors in animals and 
will prescribe the physical and 
biological containment conditions 
appropriate for such studies. (See 
Section IV-E-l-b-(3)-(c).)’’ 
Dr. Miller also proposed that a new 
Section III-C-7-c be added to the 
Guidelines as follows: 
“IIl-C-7-c. Transfer to Invertebrates. 
DNA from any non-prohibited source 
[Section I-D], except for greater than 
one quarter of a eukaryotic viral 
genome, which has been cloned and 
propagated in fi call K-12, may be 
transferred with the E. call vector used 
for cloning to any eukaryotic cells in 
culture or to any invertebrate organism 
and propagated under conditions of 
physical containment comparable to PI 
and appropriate to the organism under 
study (2A). Transfers to any other host 
will be considered by the RAC on a 
case-by-case basis (45).’’ 
No comments were received on these 
proposals. The RAC discussed the 
proposed changes in the Guidelines and 
noted that they were similar to those 
already pertaining to the use of 
vertebrate viruses as vectors. It was 
noted that Dr. Miller argues that 
employing invertebrate viral vectors 
poses no greater safety problems than 
working with vertebrate viral vectors. 
'The RAC agreed that the suggested 
changes would be consistent with the 
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