Federal Register / Vol. 44, No. 232 / Friday, November 30, 1979 / Notices 
69235 
Guidelines in the Federal Register of 
July 7, 1970. Key points in the history 
included: 
• The Maxine Singer-Dieter Soil letter 
[Science 181, 1114, 1973) arising from the 
Gordon Research Conference on Nucleic 
Acids of July 1973. 
• The Paul Berg et al. letter to Science 
[185, 303, 1974) calling for the NIH to 
establish an advisory committee to write 
guidelines. 
• The Asilomar conference of 
February 1975. 
• The work of the NIH Recombinant 
DNA Advisory Committee (RAC) 
through 1975, resulting in the proposed 
guidelines of December 1975. 
• The speciakmeeting of the Advisory 
Committee to the Director, NIH, on 
February 9-10, 1970, to review the 
proposed guidelines. 
• Final issuance of the NIH 
Guidelines on June 23. 1970 (published in 
the Federal Register on July 7, 1970). 
The history from the period July 1970 
to December 1978 includes the following 
key points: 
• Deliberations on revisions by the 
RAC during 1077, resulting in proposed 
revisions published for comment in the 
Federal Register on September 27, 1977 
(42 FR 49590). 
• A public hearing on the revisions, at 
the meeting of the Advisory Committee 
to the Director, NIH, December 15-18, 
1977. 
• Publication for public comment in 
the Federal Register on July 28, 1978 (43 
FR 33042) of new proposed revised 
guidelines accompanied by a detailed 
Decision Document and a detailed 
Environmental Impact Assessment. 
• A public hearing on the proposed 
revisions, chaired by the General 
Counsel of HEW, on September 15, 1978. 
• Publication of revised guidelines on 
December 22, 1978 (43 FR 00080), 
accompanied by a detailed Decision 
Document and Environmental Impact 
Assessment 
The entire history is extentively 
documented in Volumes 1-4 of 
"Recombinant DNA Research" — a series 
constituting a readily available public 
record of activities in regard to the NIH 
Guidelines. 
II. Revision of the December 1978 
Guidelines 
The December 1978 NIH Guidelines 
for Research Involving Recombinant 
DNA Molecules (43 FR 00108) include 
procedures for changing the Guidelines. 
As detailed in Section IV— El— 1— b — (1) of 
the Guidelines, this involves 
consideration of the proposed changes 
by the NIH Recombinant DNA Advisory 
Committee (RAC) with an opportunity 
for public and Federal agency comment 
and with publication in the Federal 
Register of the final decision by the 
Director, NIH. 
On April 11, 1979, there appeared in 
the Federal Register (44 FR 21730) the 
first changes in the Guidelines under 
these new procedures. There, I 
published background information on 
recommendations made by the RAC at 
their Feburary 10-17, 1979, meeting, and 
promulgated certain changes in the 
Guidelines. 
In the Federal Register on July 20, 1979 
(44 FR 42914), I published background 
information on recommendations made 
by the RAC at their May 21-23, 1979, 
meeting, and promulgated certain 
additional changes in the Guidelines. 
At the most recent RAC meeting on 
September 0-7, 1979, additional changes 
in the Guidelines were recommended. 
Parts III and IV of this announcement 
give background information on these 
recommendations and my proposed 
decision on them. Immediately following 
this announcement, there appear 
proposed revised NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules (which I will refer to as the 
November 1979 proposed Guidelines). 
These were obtained by incorporating 
into the December 1978 Guidelines all 
the changes made following the 
February 16-17, May 21-23, and 
September 6-7 RAC meetings. 
III. The "E coli K-12/P1 
Recommendation” Made by the RAC at 
the September 6-7, 1979, Meeting 
The organization of Part III of this 
announcement is as follows: 
In Section III-A, the historical 
background of the "£. coli K-12/P1 
Recommendation" is given. In summary, 
this was a recommendation that 
experiments involving propagation of 
recombinant DNA in EK1 hosts should 
be exempted from the Guidelines, but be 
carried out at the Pi level of physical 
containment, and be registered with the 
Institutional Biosafety Committee (IBC) 
without the requirement for IBC prior 
review. 
Section III— B specifies a framework 
for analyzing how a hazardous situation 
might result from these changes in the 
Guidelines, and then shows the low 
probability of each of a series of steps 
required for a harmful effect — including 
escape of E. coli K-12 in significant 
numbers from a Pi laboratory, 
implantation and persistence of E. coli 
K-12 in the human intestinal tract, 
conversion of E. coli K-12 into an 
epidemic pathogen, and transmission of 
recombinant DNA to other organisms. 
Section III— C gives my responses to 
issues raised in correspondence 
concerning the recommendation. 
Section III-D discusses alternatives 
which I considered prior to my proposed 
decision. 
Section III— E gives my proposed 
decision. In summary, these experiments 
are not to be exempted from the 
Guidelines. I proposed to accept the 
recommended containment level of Pi 
and EK1, and the requirement that these 
experiments be registered with and 
reviewed by the IBC. Prior review by the 
IBC would not be required before 
initiation of most experiments in this 
class. Prior review and approval by the 
IBC would be required, however, for 
experiments in which there is a 
deliberate attempt to have the E. coli K- 
12 efficiently express a gene coding for a 
eukaryotic protein. Registration of these 
experiments with NIH, and review of 
them by NIH, would not be required. 
III-A. Background 
Of all the recommendations arising 
from the last three meetings of the RAC, 
the one that has generated the greatest 
number of letters and the most 
discussion at the RAC meetings is a 
proposal adopted by the RAC on 
September 8, 1979, by a vote of 10 in 
favor, 4 opposed, and 1 abstention, that: 
Those recombinant DNA molecules that 
are propagated in E. coli K-12 hosts not 
containing conjugation-proficient plasmids or 
generalized transducing phages, when 
lambda or lambdoid bacteriophages or non- 
conjugative plasmids are used as vectors, are 
exempted from the Guidelines, subject to the 
prohibitions of 1-D-l through l-D-6. Prior to 
initiation of the experiments, investigators 
wishing to carry out such experiments must 
submit a registration document that contains 
(a) a description of the source(s) of DNA, (b) 
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 with no requirement for review 
by the IBC prior to initiation of experiments 
in these categories. 
(In referring to this recommendation 
during my analysis below, I will call it 
the "E. coli K-12/P1 Recommendation.”) 
At my request, the NIH Office of 
Recombinant DNA Activities (ORDA) 
has prepared a 312-page book entitled 
"Background Documents on E. coli K- 
12/Pl Recommendation.” This contains 
a history of the RAC consideration of 
this proposal at both its May 1979 and 
September 1979 meetings, and includes 
copies of all correspondence received 
and documents reviewed by the RAC at 
these meetings. This document: (i) is 
now available for public inspection at 
ORDA; (ii) can be made available (in 
whole or in part) to any requester upon 
payment of reproduction costs; and (iii) 
will be published (and subsequently 
may be purchased through the U.S. 
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