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Federal Register / Vol. 47, No. 77 / Wednesday. April 21, 1982 / Notices 
It is our belief that some scientific 
experiments should require public review. 
The scientific community cannot isolate itself 
from the larger community that it serves and 
presume that an individual scientist is always 
capable of deciding that the degree of hazard 
associated with a particular experiment is 
acceptable to the public. Moreover, where 
public funds are spent, the expenditure of 
those funds carries with it an accountability 
to the public * * *. Scientists must accept 
(and we believe the majority do) the need to 
restrict certain hazardous laboratory 
practices to protect health and safety while 
realizing that these restrictions do not 
represent an infringement of their intellectuaK 
freedom * * *. If the Guidelines become only 
a voluntary code of standard practice, private 
firms will be more likely not to comply * * *. 
We would urge at the very least that the 
system of Institutional Biosafety Committees 
not be allowed to terminate. 
A number of other commentators who 
wrote in support of the Gottesman 
proposal also stressed the importance of 
maintaining the system of IBCs. The 
proposal recommended by the RAC, and 
being promulgated today, does indeed 
continue to mandate the existence and 
functions of the IBCs. Remaining 
mandated in the Guidelines are Section 
IV-D-2, “Membership and Procedures of 
the IBC” and Section IV-D-3, "Functions 
of the IBC.” 
Cloning of Toxin Genes 
One commentator wrote: 
I see no logic for singling out toxins for 
special treatment in the guidelines or for 
dividing toxin experiments into classes 
dependent on LDm. 
The Guidelines continue to single out 
experiments involving the cloning of 
toxin genes for special treatment, and to 
divide such experiments into classes 
dependent on LDso. This is done in 
Section III-A-1 and Appendix F of the 
Guidelines promulgated today. (This 
text is essentially identical to what was 
previously Section I-D-2 and Appendix 
G of the July 1, 1981, version of the 
Guidelines (46 FR 34462).) The 
development of these sections of the 
Guidelines is described in detail in the 
July 1, 1981. "Decision Document” (46 FR 
34455). It involved the deliberation of an 
expert Ad Hoc Working Group on 
Toxins, and extensive discussion at the 
RAC meeting of April 23-24, 1981, prior 
to their acceptance by NIH Director 
Donald Frederickson. I believe that 
these provisions should continue in the 
current Guidelines. 
Title of Section III-B-2 
One commentator suggested that the 
title of Section III-B-2 “should be 
expanded to include Class 4 and Class 5 
agents since these two categories are 
discussed under this section in subpart 
III. B.2.b." 
This suggestion has been taken. The 
proposed title as it appeared in the 
December 7, 1981, Federal Register was 
“IlI-B-2. Experiments in Which DNA 
from CDC Class 2 or Class 3 Agents is 
Cloned in Nonpathogenic Prokaryotic or 
Lower Eukaryotic Host- Vector 
Systems. ” This has been changed in the 
Guidelines promulgated today to also 
include Class 4 and Class 5 agents. 
Incorrect Citation of and Conclusion 
from Publication 
Two commentators cited a publication 
by Drs. Portnoy and Falkow as follows: 
Unexpected surprises still do arise as was 
seen by * * * the converting of E. coli K-12 
into a pathogen through the cloning of a 
hemolysin determinant from the wild type 
strain (Portnoy & Falkow, 1981,/. Bacterial. 
148:d,77].'' 
* * * it has been shown that K-12 can 
become significantly pathogenic under 
certain conditions. For example, a recent 
report by Portnoy and Falkow (/. Bacterial 
148:677, 1981) describes the acquisition of 
mouse lethality by K-12 as a consequence of 
receiving a cloned hemolysin determinant 
from a wild strain of E. coli. 
Looking up the paper cited, I find the 
article by Portnoy and Falkow is the 
Journal of Bacteriology 148, 877-883, 
1981, to be entitled "Virulence- 
Associated Plasmids from Yersinia 
enterocolitica and Yersinia pestis. " 
There are no experiments described in 
this paper which involve E. coli K-12, or 
the cloning of a hemolysin determinant. 
There is another paper by Dr. Stanley 
Falkow which does deal with the cloned 
hemolysin determinant in E. coli. This is 
“Haemolysin Contributes To Virulence 
of Extra-intestinal E. coli Infections” by 
R. A. Welch, E. P. Dellinger, B. Minshew 
and S. Falkow, Nature, 294, 665-667, 
1981. Data in that paper indicate that 
while virulence of “wild type” E. coli 
was enhanced considerably by 
introduction of a DNA sequence coding 
for hemolysin, only a slight increase in 
virulence was seen when E. coli K-12 
was used. Thus, the commentators are 
incorrect in citing the work as showing 
“The converting of E. coli K-12 into a 
pathogen through the cloning of a 
hemolysin determinant.” 
IV. Summary of Guideline Changes 
Immediately following this 
announcement there appears in a 
separate section of the Federal Register 
the revised NIH Guidelines for Research 
Involving Recombinant DNA Molecules, 
which are effective today. They were 
derived as follows: 
1. The last previous complete version 
of the NIH Guidelines was published in 
the Federal Register on July 1. 1981 (46 
FR 34462). 
2. Changes were made in the 
Guidelines as recommended by the RAC 
at its September 1981 meeting and 
promulgated by NIH in the Federal 
Register on October 30, 1981 (46 FR 
53980). 
Note. — a version of the Guidelines 
incorporating the October 30, 1981, changes 
into the July 1, 1981, Guidelines appeared as 
“Annex E” in the Federal Register of 
December 4, 1981 (46 FR 59398). 
3. Changes were made in the 
Guidelines as recommended in certain 
actions by the RAC at its February 1982 
meeting and promulgated by NIH in the 
Federal Register on March 29, 1982 (47 
FR 13308). 
4. As noted above in Parts II-A and 
II-B of this announcement, the RAC 
recommended, and NIH is accepting 
today, additional changes as stipulated 
in the "Gottesman” proposal which had 
been issued for public comment in the 
Federal Register on December 7, 1981 (40 
FR 59734). 
5. As noted above in Part III of this 
announcement, the title of Section III-B- 
2 is being changed, in response to a 
written comment received. 
6. The “Gottesman” proposal requires 
that “changes as necessary to reflect 
changes in Parts I-UI” of the Guidelines 
be made in Parts IV and V of the 
Guidelines. This has been done. 
7. Other changes have been made. For 
example, in Section III-B-3 of the 
Guidelines, and its subsections, the term 
“whole” animal or plant virus has been 
changed to “infectius” animal or plant 
virus to reflect more accurately the 
intent of this section. Section III-C has 
been reorganized and edited in order to 
clarify the intent of this section. 
bated; April 12, 1982. 
Bernard Tablot, 
Acting Director, National Institute of Allergy 
and Infectious Diseases, National Institutes of 
Health. 
Note. — OMB’s “Mandatory Information 
Requirements for Federal Assistance Program 
Announcements" (45 FR 39592) requires a 
statement concerning the official government 
programs contained in the Catalog of Federal 
Domestic Assistance. Normally NIH lists in 
its announcements the number and title of 
affected individual programs for the guidance 
of the public. Because the guidance in this 
notice covers not only virtually every NIH 
program but also essentially every federal 
research program in which DNA recombinant 
molecule techniques could be used, it has 
been determined to be not cost effective or in 
the public interest to attempt to list these 
programs. Such a list would likely require 
several additional pages. In addition, NIH 
could not be certain that every federal 
program would be included as many federal 
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