Federal Register / Vol. 45, No. 20 / Tuesday, January 29, 1980 / Notices 
6721 
"Instructing and training staff in the 
practices and techniques required to 
ensure safety and in the procedures for 
dealing with accidents.” 
In response to the fourth comment 
given above, I note that this was 
discussed in the November 30 Decision 
Document/Environmental Impact 
Assessment under the consideration of 
the comments "Data Are Not Sufficient 
To Justify Exemption." 
In response to the fifth comment given 
above, we did not mean to imply that 
microorganisms do not escape from 
laboratories in which containment is 
practiced. Data on laboratory-acquired 
infection rates at different physical 
containment levels were given in the 
NIH Environmental Impact Statement on 
the 1976 Guidelines where it was 
pointed out that "when known 
hazardous agents are handled, the risk 
of a laboratory-acquired infection 
cannot be totally eliminated." What is 
discussed in the November 30. 1979, 
Decision Document/Environmental 
Impact Assessment is the low 
probability of E. coli K-12 escaping in 
significant numbers from a Pi 
laboratory. This, combined with the low 
probabilities of a series of other steps 
discussed in that document, leads to an 
extremely low probability of hazard 
arising from E. coli K-12 carrying 
recombinant DNA. 
In response to the sixth and seventh 
comments given above that changes are 
being made "in the absence of data from 
a risk-assessment program," or upon 
insufficient data, I must note that the 
November 30 Decision Document/ 
Environmental Impact Assessment 
discussed in detail the substantial body 
of data available on the safety of E. coli 
K-12 and specifically dealt with the 
issue of risk-assessment under the 
discussions of the comments "Delay 
Any Change in the NIH Guidelines 
Pending Many More Risk-Assessment 
Experiments," and "Data Are Not 
Sufficient to Justify Exemption” as well 
as the alternative “Make No Change In 
The Guidelines Until Many More Risk- 
Assessment Experiments Are 
Completed." I continue to believe, as I 
wrote then, that the action is fully 
supported by the data. 
IlI-B-2-d. Comments on the Time Taken 
To Promulgate the NIH Director's 
Decision on This Recommendation 
Fourteen commentators, including one 
of the four RAC members who voted 
against the "E. coli K-12/P1 
Recommendation" at the September 6, 
1979, RAC meeting, wrote against delay, 
noting that the RAC's "E. coli K-12/P1 
Recommendation" had been made in 
September 1979 but not yet promulgated. 
Comments included the following — "It is 
regrettable that these revisions have 
been delayed for further comment in 
view of the extensive period provided 
already for such comments and the 
extensive discussions by the 
Recombinant DNA Advisory Committee 
prior to its votes. T believe that the 
expense in terms of time taken from 
other fruitful activities of yourself and 
the many commentators on this issue 
was unnecessary and extremely 
wasteful." — “I am appalled at the 
interminable delays required before a 
recommendation of the RAC can be put 
into effect. The procedures required by 
the December 1978 guidelines are 
cumbersome enough without an 
additional layer of public comment, 
analysis, and justification added on. 
NIH and American biomedical scientists 
deserve better treatment and trust from 
their top health administrators." — "It is 
disheartening to find that, even after 
thorough consideration and approval by 
RAC, the E. coli K-12/P1 measure 
remains in administrative limbo.” — "The 
unnecessarily long delays in 
implementing the new guidelines have 
adversely affected the morale of 
American scientists and hampered 
progress in this highly significant area of 
research and development.” 
On the other hand, one commentator 
wrote, "I once again congratulate you on 
the exemplary way in which revision of 
these guidelines is being continued 
while still making proposals available to 
the public for scrutiny before their final 
adoption.” 
I am firmly committed to the 
procedures of the NIH Guidelines. As 
pointed out above in Section II of this 
document, procedures for revising the 
Guidelines involve certain mandatory 
“delays" including publication of the 
proposed changes in the Federal 
Register for public comment, at least 30 
days prior to a meeting of the RAC, and 
consideration of the proposed changes 
at a formal RAC meeting. For 
recommendations arising from three of 
the last four RAC meetings, there was 
no additional public comment period. 
For the recommendations made at the 
September 6-7, 1979, RAC meeting, 
however, I did issue my proposed 
decision for an additional 30-day period 
of public comment. It is my intention, 
generally, in the future, to rely, in 
formulating my final decision, on the 
comments received in the initial 
comment period, and on the 
recommendations of the RAC, without 
issuing a proposed decision for an 
additional period of public comment. 
IU-B-2-e. Ff Bacteriophages 
Three letters discussed the use of Ff 
bacteriophages. One wrote, “Nor can I 
see why other E. coli K-12 host-vector 
systems, such as those employing Ff 
bacteriophages, are not included within 
the Section IIU-O reduction." Another 
wrote, "I certainly hope that this 
proposal will be extended to the Ff 
bacteriophages in the near future." 
I discussed this in detail in my 
November 30, 1979, Decision Document/ 
Environmental Impact Assessment 
under the alternative "Include Ff 
Bacteriophages (Filamentous Single 
Strand Male Specific Bacteriophages 
such as M13 and fd) With Lambda or 
Lambdoid Bacteriophages To Be 
Permissible Under the 'E. coli K-12/P1 
Recommendation.’ ” There, I noted that I 
would “ask the RAC to consider the use 
of Ff bacteriophages again." At the 
December 1979 RAC meeting, a Working 
Group was appointed to consider this 
issue. They will report to the RAC at its 
next (March 1980) meeting. I will 
consider the recommendations of the 
RAC before taking action on inclusion of 
Ff bacteriophages within Section III— O. 
I/I-B-2-f. Requirement for IBC Prior 
Review and Approval When There Is a 
Deliberate Attempt To Have the E. coli 
K-12 Efficiently Express a Gene Coding 
for a Eukaryotic Protein 
One of the differences between the 
“£’. coli K-12/P1 Recommendation" 
made by the RAC on September 6, 1979, 
and my proposed modification of this 
recommendation to become Section III— 
O of the November 30, 1979, ‘proposed 
revised Guidelines was the addition of 
the text which states, “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." 
Four commentators wrote in 
opposition to this. One said that the 
requirement “is in my view superfluous, 
and is almost guaranteed to cause 
nuisance and confusion for investigators 
and IBC's. Many IBC's will understand 
this section to imply that they must 
require higher containment for such 
experiments, and for this the guidelines 
give no guidance or clarification. This 
requirement will expose many 
investigators to arbitrariness and 
unnecessary restrictions. . . . The 
Guidelines should clarify the intent of 
this requirement and should explicitly 
state that Pi containment is 
recommended. . . Two other 
commentators urged that this sentence 
be eliminated. One wrote, “Failing that 
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