16452 
Federal Register / Vol. 46, No. 46 / Thursday, March 12. 1981 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant ONA Researctt; Actions 
Under QuIdeHnes 
AOCNCv; iVational Institutes of Health. 
PHS. HHS. 
Acnosc Notice of actions under NIH 
Guidelines for Research Involving 
Recombinant ONA Molecules. 
SUtsssAAY: This notice sets forth actions 
taken by the Director, NIH. under the 
1980 NIH Cuideliaes for Research 
Involving Recombinant ONA Molecules 
(45 FR 77384). 
imcnvi OATi: March 11. 1981. 
soa PUStTHCn INFOaSSATlON COSTTACr. 
Additional information can be obtained 
from Dr. William ). Cartland. Office of 
Recombinant ONA Activities (OROA). 
National Ixutitutes of Health. Bethesda. 
Maryland 20205. (301) 496-8051. 
sueeisMCMTAjrv itssoassATiosc I am 
promulgating today several major 
actions under the NIH Guidelines for 
Research Involving Recombinant ONA 
Molecules. These proposed actiotu were 
published for comment in the Federal 
Register of November 28. 1980. and 
reviewed and recommended for 
approval by the Recombinant ONA 
Advisory Committee (RAC) at its 
meeting on fanuary 8-9, 1961. In 
accordance with Section IV-E-l-b of 
the NIH Guidelines. I find that these 
actions comply with the Guidelines and 
present no signiRcant risk to health or 
the environment. 
Part I of this announcement provides 
background Information on the actions. 
Part 0 provides a summary of the major 
actions. 
L Dedsiofu on Actions Under 
Guidelines 
t-A. Proposed Containment for 
Nonpathogens 
Dr. Winston BrilL a RAC member, 
proposed in a letter dated November 14, 
1980, that the Guidelines be amended to 
permit use of nonpathogenic 
prokaryotes and nonpathogenic lower 
eukaryotes as donors and recipients in 
recombinant DNA experiments under Pi 
containment conditions. 
The following language was published 
In the November 28. 1980 Federal 
Register (45 F*R 79386) for thirty days of 
comment: 
A A new section. III-0-2. would be added 
to the Culdelinee. as follows; 
"ID-O-2. Experiments Involving Non- 
Pathogenic Prokaryotes and Lower 
'ukaryotes. Recombinant DNA experiments 
rvolving prokaryotes and lower eukaryotes. 
nonpathogenic (2A| for man, animals, or 
plants, can be conducted under PI 
containment" 
B. A new paragraph would be added just 
before Section Ill-O begins, as follows: 
"When the reader finds that the 
contaiiunent level given for the same 
experiment is different in two different 
sections within Part IlL he may choose which 
of the two levels he wishes to use for the 
experiment" 
C The second paragraph of Section IH-B-3 
would deleted. Revised Section Ul-B-3 would 
read as follows: 
"Ul-B-3. Non-HVl Systems. Containment 
levels for other classes of experiments 
Involving non-HVl systems may be approved 
by the Director. NIH. (See Sections fV-£-l- 
b-(l)-(b). rV-E-l-MZHc). and IV-£-l-b- 
OHbir 
D. Section fV-E-l-b-2-(f) would be 
deleted. This Section currently reads as 
follows; 
"IV-£-l-b-(2)-(0. Assigning containment 
levels for experiments in whi^ both donor 
and redplant are non-pa thogenic prokaryotes 
(sec Section 10-8-3)." 
During the thirty day comment period 
eight letter* supporting this proposal 
were received. Two additional letters, 
while supporting the proposal, 
recommended that containment be set at 
P2. rather than Pi. 
The RAC discussed the proposal at 
the january 8-9. 1961 meeting. Dr. Brill 
suggested that the proposed Section III- 
0-2 be modified in two wayr (1) 
following the word “plants” would be 
added the words, "and only DNA from 
such sources,"; and (2) text would be 
added specifying that the experiments 
must be review^ with the local IBC 
with documentation that the organisms 
are not known pathogens. (Dr. Brill also 
IniUally recommend^ that containment 
for these experiments be raised from Pi 
to P2. but later said he was convinced 
by the arguments of some RAC members 
that Pi was appropriate). 
During the ensuing discussion RAC 
members opposed to the motion pointed 
out that (1) the proposal cover* an 
enormous variety of organisms, (2) 
“nonpathogenic" may be defined 
differently by different IBCs and (3) no 
restriction is placed on the type of 
vector* to be used. A substitute motion 
was advanced by Dr. Cottesman which 
would provide for an expedited review 
procedure. Under this proposal. ORDA 
would review proposals involving 
nonpathogenic prokaryotes and lower 
eukaryotes on a case-by-case basis. The 
RAC. by a vote of six in favor, eight 
opposed and two abstentions, denied 
this substitute motion. 
The RAC continued discussion of Dr. 
Brill's motion. Some RAC members felt 
the proposal as written placed a burden 
of interpreting “pathogenicity" on IBCa. 
Nonetheless, sentiment supporting an 
expedited type of procedure for dealing 
with prokaryotic and lower eukaryotic 
nonpathogens was expressed. By a vote 
of nine in favor, eight opposed, and 
three abstentions, the RAC passed Dr. 
Brill's motion, as it had appeared in the 
Federal Register, with the two changes 
suggested by Dr. Brill at the meeting. 
The substitute proposal which would 
permit ORDA to lower containment on 
proposals utilizing nonpathogenic 
prokaryotes and lower eukaryotes on a 
case-by-case basis, was again offered 
by Dr. Cottesman for consideration. The 
proposal was that if Dr. Fredrickson 
should not accept Dr. Brill's proposal, it 
was the sense of the RAC that it would 
be preferable to the status quo to at 
least make two changes: (1) extend the 
current situation allowing cloning 
between nonpathogenic prokaryotes at 
P3 to also include lower eukaryotes: and 
(2) allow lowering below P3 for 
Individual cases by ORDA rather than 
requiring RAC review. A motion to table 
this proposal failed; by a vote of eight in 
favor, eleven opposed. By a vote of 
fourteen in favor, one opposed, and 
three abstentions, the Rj\C then 
approved Dr. Cottesman's motion. 
In deciding whether to accept the 
"Brill" motion, recommended by the 
RAC by a vote of nine in favor, eight 
opposed, and three abstentions, or the 
more conservative "Cottesman" motion, 
recommended by the RAC by a vote of 
fourteen in favor, one opposed, and 
three abstentions, I note that already in 
the Guidelines the following 
experiments are permitted: 
1. Certain experiments with 
prokaryotes and lower eukaryotes are 
exempt from the Guidelines, under 
Sections l-E-3 and I-E-4. 
2. Certain experiments with 
prokaryotes and lower eukaryotes may 
be done at Pi containment under 
Guideline Sections lU-O, IIl-B-2 and 
Ul-C-6. 
3. Certain experiments with 
prokaryotes and lower eukaryotes may 
be done at P2 containment under 
Guideline Sections lII-A-l-a-{5) and 
m-A-l-b. 
Dr. Brill's proposal covers an 
enormous number of organisms, many of 
which have not been well characterized. 
‘Tilonpa thogenic" might be Interpreted 
differently by different IBCs. The 
proposal does not require use of non- 
conjugatlve plasmids. For these reasons 
I am, at present not accepting the "Brill" 
motion and instead I am accepting the 
more conservative "Cottesman" motion. 
Accordingly a new section, III-0-2, is 
added to the Guidelines as follows; 
"IH-O-2. Experiments Involving 
Prokaryotes Nonpathogenic for Man, 
(651 
