50524 
Federal Register / Vol. 45, No. 147 / Tuesday, July 29, 1980 /Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research; Actions 
Under Guidelines 
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, NIH, under the 
1980 NIH Guidelines for Research 
Involving Recombinant DNA Molecules 
(45 FR 6724). 
EFFECTIVE DATE: July 29, 1980. 
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 NDA 
Molecules. These proposed actions were 
published for comment in the Federal 
Register of April 30, 1980, and reviewed 
and recommended for approval by the 
Recombinant DNA Advisory Committee 
(RAC) at its meeting on June 5-6, 1980. 
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. I am deferring action 
on one major action, recommended for 
approval by the RAC, proposing the 
field testing of corn plants ( Zea mays ) 
into which corn recombinant DNA has 
been added using an E. coli or S. 
cerevisiae vector. A final decision on 
this proposal will be reached after the 
receipt of additional information. 
Part I of this announcement provides 
background information on the actions. 
Part II provides a summary of the 
major actions. 
I. Decisions on Actions Under 
Guidelines 
I-A. Proposal To Include 
Saccharomyces Cerevisiae Hose- Vector 
Systems Under Section III-O of the 
Guidelines 
Dr. Jane Setlow of the Brookhaven 
National Laboratory, at the March 6-7, 
1980 Recombinant DNA Advisory 
Committee (RAC) meeting, proposed 
that NIH consider classifying 
experiments involving laboratory strains 
of Saccharomyces cerevisiae as host- 
vector systems under Section III-O of 
the Guidelines. Dr. Setlow advanced the 
following arguments to support this 
proposal: (1) S. cerevisiae is 
nor.pathogenic; (2) S. cerevisiae does 
not implant in the mammalian intestine; 
(3) the dilute conditions in which S. 
cerevisiae is found in nature are 
extremely unfavorable for mating; and 
(4) laboratory strains do not efficiently 
compete with wild type strains S. 
cerevisiae. She added that S. cerevisiae 
does not have a biological association 
with man. 
The RAC discussed this issue at the 
March 6-7, 1980 meeting, and agreed 
that the proposal should be published in 
the Federal Register to permit thirty 
days of comment. Accordingly, proposed 
language which would amend two 
sections of the Guidelines, appeared in 
the Federal Register of April 30, 1980 [45 
FR 28905]. This involved a proposed 
substitution for Section III-O of the 
Guidelines and a deletion in Appendix 
D, as follows: 
III-O. Classification of Experiments Using 
E. coli K-12 and Saccharomyces cerevisiae 
Host-Vector Systems. Most recombinant 
DNA experiments currently being done 
employ E. coli K-12 host-vector systems; 
others employ the S. cerevisiae host-vector 
systems. These are the systems for which we 
have the most experience and knowledge. 
Some experiments using E. coli K-12 and S. 
cerevisiae host-vector systems are prohibited 
(see Section I-D). 
Some experiments using E. coli K-12 and S. 
cerevisiae host-vector systems are exempt 
from the Guidelines (see Section I-E). 
Other experiments using E. coli K-12 or 
laboratory strains of S. cerevisiae shall use 
PI physical containment and, except as 
specified in the last paragraph of this section, 
an HV1 host-vector system [i.e., for 
experiments using E. coli K-12 (a) the E. coli 
host shall not contain conjugation-proficient 
plasmids or generalized transducing phages, 
and (b) lambda or lambdoid bacteriophages 
or non-conjugative plasmids [49] shall be 
used as vectors. For experiments in S. 
cerevisiae, laboratory strains shall be used.) 
for these experiments no Memorandum of 
Understanding and Agreement (MUA) as 
described in Section IV-D-l-c need be 
submitted, nor is any registration with NIH 
necessary. However, for these experiments, 
prior to their initiation, investigators must 
submit th their Institutional Biosafety 
Committee (IBC) a registration document that 
contains a description of (a) the source(s) of 
DNA, (b) the nature of the inserted DNA 
sequences, and (c) the hosts and vectors to be 
used. This registration document must be 
dated and signed by the investigator and filed 
only with the local IBC. The IBC shall review 
all such proposals but such review is not 
required prior to initiation of experiments. An 
exception, however, which does require prior 
review and approval by the IBC is any 
experiment in which there is a deliberate 
attempt to have the E. coli K-12 or S. 
cerevisiae efficiently express as a protein 
product the information carried in any gene 
derived from a eukaryotic organism or from 
any virus or viroid which infects a eukaryotic 
organism. 
Experiments involving the insertion into E. 
coli K-12 of DNA from prokaryotes that 
exchange genetic information with E. coli by 
known physiological processes will be 
exempted from these Guidelines if they 
appear on the “list of exchangers" set forth in 
Appendix A (see Section I— E— 4). 
For those not on the Appendix A list but 
which exchange genetic information (35) with 
E. coli, experiments may be performed with 
any E. coli K-12 vector (e g., conjugative 
plasmid). When a nonconjugative vector is 
used, the E. coli K-12 host may contain 
conjugation-proficient plasmids, either 
autonomous or integrated, or generalized 
transducing phages. 
The language “*HVl-Unmodified 
laboratory strains of Saccharomyces 
cerevisiae" would be deleted from Appendix 
D. 
During the thirty-day comment period, 
no comments were received. 
At the June 5-6, 1980 meeting, the 
RAC once again discussed this issue. It 
was noted that S. cerevisiae does not 
colonize animals, large amounts of yeast 
are regularly consumed by humans with 
no ill effects, S. cerevisiae does not 
appear to express mammalian genes, 
and the probability that genetic material 
will be transferred from or otherwise 
disseminated by laboratory strains of S. 
cerevisiae is very low. 
The RAC suggested that the language 
of the sentence of the proposed 
amended Section III-O which begins, 
“an exception, however * * might 
lead to confusion over the status of 
cloning S. cerevisiae DNA in S. 
cerevisiae. A motion that the phrase “or 
S. cerevisiae " be deleted from this 
sentence passed by a vote of fifteen in 
favor, one opposed, and three 
abstentions. The amended sentence 
would read; 
* * *An exception, however, which does 
require prior review and approval by the IBC 
is any experiment in which there is a 
deliberate attempt to have E. coli K-12 
efficiently express as a protein product the 
information carried in any gene derived from 
a eukaryotic organism or from any virus or 
viroid which infects a eukaryotic organism. 
The proposal to include S. cerevisiae 
host-vector systems under Section III-O 
of the Guidelines as published in the 
Federal Register of April 30, 1980 with 
the amendment noted above, was 
accepted by the RAC by a vote of 
fourteen in favor, two opposed, and two 
abstentions. 
I accept this recommendation. 
In addition to the deletion of reference 
to HVl S. cerevisiae in Appendix D of 
the Guidelines, reference to HV2 5. 
cerevisiae has also been deleted from 
Appendix D. Added to Appendix D, 
[141] 
