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Federal Register / Vol. 46, No. 126 / Wednesday. July 1, 1961 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research; Actiorts 
Under Guidelines 
AGENCY: National Institutes of Health. 
PHS, DHHS. 
ACTION: Notice of Actions under NTH 
Guidelines for Research Involving 
Recombinant DNA Molecules. 
SUMMARY: This notice sets forth actions 
taken by the Director, NIH, under the 
November 1980 NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules (45 FR 77384). 
EFFECTIVE DATE: July 1, 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 March 20. 1981, and 
reviewed and recommended for 
approval by the Recombinant DNA 
Advisory Committee (RAC) at its 
meeting on April 23-24, 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. 
Following this announcement, there 
appears in a separate section of the 
Federal Register the revised NIH 
Guidelines for Research Involving 
Recombinant DNA Molecules. These 
revised Guidelines differ from the ‘ 
version of the Guidelines promulgated 
on November 21, 1980 (45 FR 77384) by 
incorporating within them both the 
changes in the Guidelines which were 
recommended at the RAC meeting of 
January 8-9, 1961, and promulgated on 
March 12. 1981 (46 FR 16452), and the 
changes in the Guidelines which were 
recommended at the RAC meeting of 
April 23-24, 1981, and which are 
discussed in this announcement. 
I. Revision of Guidelines for 
Recombinant DNA Experiments 
Involving Escherichia Coli K-12 and 
Saccharomyces Cervisiae Host- Vector 
Systems 
Containment requirements and 
administrative procedures for the 
conduct of most recombinant DNA 
experiments involving EKl Escherichia 
coli strain k-12 and laboratory strain 
Saccharomyces cerevisiae host-vector 
systems have been specified in Section 
III-O of the Guidelines. The 
chairpersons of Institutional Biosafety 
Committees, at a meeting in 
Washington, D.C. on November 24-25, 
1980, passed by a large majority a 
resolution that experiments currently 
covered by Section IIl-O should be 
made exempt from the Guidelines. The 
chairpersons felt that the risks 
associated with these experiments are 
negligible, and that exemption of 
experiments currently covered by 
Section IIl-O would reduce paperwork 
by approximately 90%. 
This proposal was discussed by the 
RAC at its meeting on January 8-9, 1981. 
In “straw votes" at the meeting, an 
overwhelming majority of RAC 
members favored doing something to 
reduce materially or eliminate the 
paperwork and reporting functions for 
experiments covered by Section III-O; 
about half the RAC members felt serious 
consideration should be given to 
exempting entirely from the Guidelines 
experiments currently covered by 
Section III-O. The RAC requested that a 
series of options be developed and 
published for comment in the Federal 
Register. Accordingly, a series of 
options was published for comment in 
the Federal Register of March 20, 1981 
(46 FR 17994), and considered at the 
April 23-24, 1981 meeting of the RAC. 
Three major options were published 
for comment. Option A would have 
allowed review by an institutional 
official rather than requiring review by 
the IBC of experiments currently 
covered by Section III-O. Option B 
would have eliminated the registration 
and review requirements for 
experiments currently covered under 
Section III-O. Option C would have 
exempted from the Guidelines 
experiments currently covered by 
Section III-O. Under each of these three 
major options a series of suboptions 
was proposed for alternative ways of 
treating certain types of experiments 
which were already being treated 
differently from the majority of 
experiments under Section III-O. These 
are experiments involving the cloning in 
E. coli K-12 of DNA from Class 3 GDC 
agents, and experiments involving a 
deliberate attempt to have E. coli K-12 
efficiently express a eukaryotic gene. 
Under Option C, additional suboptions 
were proposed regarding biological and 
physical containment, and large-scale 
experiments (i.e., greater than 10 liters 
of culture). 
During the 30 day comment period, 
only one commentator responded 
referring to the proposed changes as 
“* * * an attempt to bring the 
Guidelines into a state of consistency 
with present evaluations of the potential 
for hazard in recombinant DNA 
experiments. As I see that evaluation, 
there is widespread agreement that 
experiments involving E. coli K-12 or S. 
cerevisiae host-vector systems will not 
generate harmful organisms. * * *" One 
commentator, who wrote after the 
comment period, was opposed to the 
proposed changes "until adequate risk 
assessment studies have been 
performed.” The RAC discussed the 
proposed changes at its meeting on 
April 23. Dr. Edward Adelberg, 
Chairman, Yale University Institutional 
Biosafety Committee, summarized the 
concerns of the chairpersons of IBCs at 
their meeting in November 1980. He said 
that the chairpersons voted heavily in 
favor of an exemption for these 
experiments, but noted that any one of 
the three proposed options would 
greatly reduce what was considered 
unnecessary paperwork. The RAC then 
discussed in detail the various options 
and suboptions. 
After a series of motions and 
amendments, the RAC by a vote of 13 in 
favor, 8 opposed, with no abstentions, 
passed Option C with Suboptions C-l-b, 
C-2-a, C-3-a, C-4-b as modified at the 
meeting, and C-5-b. Under the 
recommendation passed by the RAC, 
experiments currently covered by 
Section III-O would be removed from 
Section III-O. These experiments would 
be exempted under Section I-E-5. The 
exemption would apply to all 
nonprohibited experiments which use 
either E. coli K-12 or laboratory strains 
of Saccharomyces cerevisiae as the 
host-vector system with the following 
provisos: 
• The exemption would be qualified 
with the statement that “(a) the E. coli 
host shall not contain conjugation 
proficient plasmids or generalized 
transducing phages, and (b) lambda or 
lambdoid or Ff bacteriophages or non- 
conjugative plasmids (49) shall be used 
as vectors.” This qualification would 
then be qualified by the statement that 
experiments “involving the insertion 
into E. coli K-12 of DNA from 
prokaryotes that exchange genetic 
information (35) with E. coli may be 
performed with any E. coli K-12 vector 
(e.g., conjugative plasmid). When a non- 
conjugative vector is used, the E. coli K- 
12 host may contain conjugation- 
proficient plasmids either autonomous 
or integrated, or generalized transducing 
phages.” 
• Language would be added to the 
Guidelines to explicitly'make 
[142] 

