Federal Register / Vol. 44, No. 232 / Friday, November 30, 1979 / Notices 
69245 
containment levels of the 1978 
Guidelines. 
In accordance with this precedent, I 
propose a similar policy be followed in 
the transition from the 1978 to the new 
Guidelines. Thus an investigator using 
an Ff bacteriophage could continue at 
the stipulated containment level of the 
1978 Guidelines. For example, for the 
cloning of primate DNA in E. coli K-12, 
currently proceeding at the P3 + EK1 
containment level the experiment may 
continue using Ff bacteriophage at EK1 
but must also remain at the P3 
containment level 
I will ask the RAC to consider the use 
of Ff bacteriophages again at their next 
meeting. 
Keep National Registration and 
Oversight of These Experiments 
Some argued that Memoranda of 
Understanding and Agreement (MUA) 
covering the experiments falling under 
the “K coli K-12/P1 Recommendation" 
should continue to be sent to NIH for 
national registration and oversight of 
these experiments. 
In my decision document of July 1978, 
I wrote; 
In view of the impossiblity of Federal 
surveillance to enforce these standards 
externally. I feel it is essential to increase the 
authority and responsibility of the local 
institution . . . Primary responsibility for 
compliance with the rules must be located 
where the work is done. There it must be 
shared fully by principal investigators, those 
who work in their laboratories, institutional 
biosafety committees, and the institutional 
leaders. The NIH Office of Recombinant DNA 
Activities (ORDA) should be relieved of its 
burden of obligatory prior approval of certain 
experiments, so that it can better carry out 
along with the RAC two central functions. 
These are the continuing synthesis and 
interpretation of the Guidelines, and the 
maintenance of full communication among all 
who must use them. 
I remain committed to shifting 
responsibility to local institutions for 
adherence to uniform, sensible 
guidelines. We are dealing in this 
decision with a class of experiments 
judged to be of minimal risk. There is 
the possiblity that some aspect of some 
future experiment in this class may yield 
information relevant to safety that 
should be transmitted to all laboratories 
where similar experiments are being 
conducted. The Guidelines (Sections IV- 
D-l; IV— D — 3 — e and IV— D— &— a— (2)) still 
require that “any significant problems 
with * * * the Guidelines and 
significant research-related accidents 
and illnessess” are to be reported to 
ORDA. ORDA can then quickly notify 
all IBCs; and IBCs, having a registry of 
such experiments, can take appropriate 
actions without delay. The transmission 
to ORDA of registration of experiments 
in this class does not enhance safety or 
otherwise serve the public interest The 
relief from central data-handling for 
these experiments will leave ORDA free 
to perform other functions that are more 
likely to assure that use of recombinant 
DNA techniques is safe. 
II I-E Proposed Decision of the Director, 
NIH On The “E coli K-12/P1 
Recommendation " 
The “E. coli K-12/P1 
Recommendation," as pasrfed by the 
RAC on September 6, recommends that 
the experiments described in the 
proposal be “exempted from the 
Guidelines.” Yet it also specifies that 
“Pi containment shall be used.” In 
addition, it requires that these 
experiments be registered with the IBC 
but “with no requirement for review by 
the IBC prior to initiation of 
experiments." 
Currently, exempt experiments 
(described in Section I-E of the 
Guidelines) do not have any 
containment level specified and are not 
required to be registered with the IBC. 
Currently, experiments described in 
Part III of the Guidelines have 
containment levels specified and are 
required not only to be registered with 
the IBC but also to be approved by the' 
IBC prior to initiation of the experiment. 
(In addition, an MUA must be submitted 
to NIH for approval, although for most 
experiments the project can proceed 
upon IBC approval, without prior 
approval by NIH.) 
I believe the term “exempt 
experiment" as currently used in Section 
I-E of the Guidelines should be used 
only for experiments for which no 
containment level is specified and for 
which no registration with the IBC is 
required. Therefore, I propose not to 
accept the part of the "E. coli K-12/P1 
Recommendation" which refers to the 
described experiments as exempt. 
Instead, my proposed decision is to 
describe the experiments covered in the 
"£. coli K-12/P1 Recommendation” in a 
new Section which to be added to the 
Guidelines, called Section HI-0, as 
follows: 
m-0. Classification of Experiments Using 
the E. coli K-12 Host-Vector Systems. Most 
recombinant DNA experiments currently 
being done employ E. coli K-12 host-vector 
systems. These are the systems for which we 
have the most experience and knowledge. 
Some experiments using E. coli K-12 host- 
vector systems are prohibited (see Section I- 
D). 
Some experiments using E. coli K-12 host- 
vector systems are exempt from the 
Guidelines (see Sections I-E). 
Other experiments using E coli K-12 shall 
use PI physical containment and. except as 
specified in the last paragraph of this section, 
an EKl host-vector system (i.e., (a) the’host 
shall not contain conjugation-proficient 
plasmids or generalized transducing phages, 
and (b) lambda or lambdoid bacteriophages 
or non-conjugative plasmids shall be used as 
vectors). 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 NOT necessary. However, 
for these experiments, prior to their initiation, 
investigators must submit to their 
Institutional Biosafey Committee (IBC) a 
registration document that contains a 
description of (a) the sourcefs) 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 efficiently 
express any gene coding for a eukaryotic 
protein. 
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— ♦). 
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 
plasmids). When a non-conjugative vector is 
used, the E. ooli K-12 host may contain 
conjugation-proficient plasmids, either 
autonomous or integrated or generalized 
transducing phages. 
The first two sentences of Section III- 
0 are moved from where they appear as 
the first two sentences of Section LU-A 
in the 1978 Guidelines. 
Hie next two sentences refer to the 
fact that some experiments using K coli 
K-12 are prohibited (Section I-D) and 
that some are truly exempt from the 
Guidelines (Section I-E). The 
prohibitions override Section IH-0; the 
six prohibitions are I-D-l ("pathogenic 
organisms"), I-D-2 ("potent toxins"), I- 
D-3 ("plant pathogens"), I-D-4 
("deliberate release”), I-D-5 (“drug 
resistance trait"), and I-D-6 (“large 
scale”). 
Next in Section IH-0 comes a 
rephrasing of the “E. coli K-12/P1 
Recommendation,” setting the 
containment level as Pi + EKl for these 
experiments. Also included for these 
experiments is the requirement for 
registration with, but not prior approval 
by. the IBC, for most experiments and 
the statement that no MUA or other 
form of registration need be submitted 
to NIH. The requirement for IBC prior 
approval has been added for 
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