55926 Federal Register / 
submitted to the Director, NIH, for final 
review. 
5. Applications for large-scale 
experiments which are submitted by 
institutions not receiving NIH funds for 
recombinant DNA research shall be kept 
confidential (provided the institutions so 
desire) in accordance with the 
provisions of the NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules. 
These procedures may be refined or 
revised on the basis of discussion and 
action by the NIH Recombinant DNA 
Advisory Committee.” 
At the last few RAC meetings, there 
have been extensive discussions of the 
role of the RAC and NIH in the review 
of large-scale proposals submitted by 
industry. (Minutes of RAC meetings are 
available from ORDA.) At the June 1980 
meeting, the RAC passed a motion by a 
vote of seventeen to zero with one 
abstention that the following proposal 
be published in the Federal Register for 
consideration at the September, 1980 
meeting: 
The following procedures should be 
adopted for approval of requests to grow 
greater than 10 liters of organisms containing 
recombinant DNA. The RAC will determine if 
a given recombinant DNA-containing strain 
is rigorously characterized and the absence 
of harmful sequences established. Such a 
determination shall include specification of a 
containment level (P-LS). These 
determinations should not in any Way be 
construed as RAC certification of safe 
laboratory procedures for industrial scale-up. 
Adherence to the specified containment 
conditions is the responsibility of the local 
me. 
If the above proposal is accepted, it 
would have the effect of changing the 
application procedures to read as 
follows: 
"Application Procedures for Large-Scale 
Recombinant DNA Experiments 
1. For each research project proposing 
to exceed the 10-liter limit, the applicant 
shall file a request with the NIH Office 
of Recombinant DNA Activities 
(ORDA). The request should include the 
following information: 
a. The Memorandum of 
Understanding and Agreement (MUA) 
submitted to the local Institutional 
Biosafety Committee. The MUA should 
include, or have appended to it, a 
summary paragraph which describes the 
proposed project in language that is 
comprehensible to non-specialists. 
b. A statement of the rationale for 
wishing to exceed the 10-liter limit. 
c. Evidence that the recombinant 
DNAs to be employed in the research 
have been rigorously characterized and 
are free of harmful sequences. 
Vol. 45, No. 164 / Thursday, August 
d. Specification of the P-LS level 
proposed to be used as defined in the 
NIH Physical Containment 
Recommendations for Large-Scale Uses 
of Organisms Containing Recombinant 
DNA Molecules. /Federal Register, April 
11, 1980). 
2. Each request submitted to ORDA 
shall be referred to a working group of 
the NIH Recombinant DNA Advisory 
Committee for review. 
3. Following review and approval by 
the working group, each request shall be 
submitted to the entire Recombinant 
DNA Advisory Committee for review. 
4. Following review and approval by 
the RAC, each request shall be submittd 
to the Director, NIH, for final review. 
5. Applications for large-scale 
experiments which are submitted by 
institutions not receiving NIH funds for 
recombinant DNA research shall be kept 
confidential (provided the institutions so 
desire) in accordance with the provision 
of the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These procedures may be refined or 
revised on the basis of discussion and 
action by the NIH Recombinant DNA 
Advisory Committee.” 
8. Proposed changes in registration 
requirements. Dr. Maxine Singer, 
National Cancer Institute, National 
Institutes of Health, has proposed a 
series of changes in the administrative 
requirements specified by the 
Guidelines. In brief, Dr. Singer’s 
proposal eliminates NIH review, 
registration, and approval for all 
experiments assigned containment 
conditions in the Guidelines. The 
reasons for the proposed changes are 
discussed in a letter to ORDA. 
Specifically, the proposal would 
revise several sections of the 
Guidelines. The proposed revisions are 
discussed below. 
A. Section III. Section HI of the 
Guidelines would be amended to read 
as follows: 
“III. Containment Guidelines for 
Covered Experiments. 
Part HI discusses experiments covered 
by the Guidelines. The reader must first 
consult Part I, where listings are given of 
prohibited and exempt experiments. 
Containment guidelines for 
permissible experiments are given in 
Part III. For these experiments no 
registration with NIH is necessary. 
However, for these experiments, prior to 
their initiation, investigators must 
submit to their Institutional Biosafety 
Committee (IBC) a registration 
document that contains a description of 
(a) the source(8) of DNA, (b) the nature 
of the inserted DNA sequences, (c) the 
hosts and vectors to be used, (d) 
whether a deliberate attempt will be 
21, 1980 / Notices 
made to obtain expression of a foreign 
gene in the cloning vehicle and if so, 
what protein, and (e) the containment 
conditions specified by these 
Guidelines. 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 except as noted in Sections 
IU-A-3-a, HI-A-3-b, or for experiments 
where containment procedures are not 
explicitly described in these Guidelines. 
Changes from the levels specified in 
Part IH for specific experiments (or the 
assignment of levels to experiments not 
explicitly considered here) may not be 
instituted without the express approval 
of the Director, NIH. (See Sections (IV— 
E-l-b(lHa), IV-E-l-b-(l)-(b), IV-E-1- 
b— (2)— (b), IV-E-l-b-(2)-(c), and IV-E-1- 
b— (3)(b).) 
In the following classification of 
containment criteria for different kinds 
of recombinant DNAs, the stated levels 
of physical and biological containment 
are minimal for the experiment 
designated. The use of higher levels of 
biological containment 
(HV3>HV2>HVl) is encouraged if they 
are available and equally appropriate 
for the purposes of the experiment. 
Experiments involving recombinant 
DNA from Class 3 organisms [1] or from 
cells known to be infected with these 
agents may be conducted at P3 
containment in E. coli K-12 EKl hosts 
(see Section ni-O). Containment levels 
for all other expriments with Class 3 
organisms or with recombinant DNA 
which increases the virulence and host 
range of a plant pathogen beyond that 
which occurs by natural genetic 
exchange will be determined by NIH. 
(See Section IV-E-l-b-2-(e)).” 
B. Section III-O. Section III— O of the 
Guidelines would be amended to read 
as follows: 
“IH-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 £. 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). 
Experiments using E. coli K-12 host- 
vector systems and DNA from Class 3 
organisms [1] or from cells known to be 
infected with these agents will be 
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