In December 1975 the Recombinant 
Advisory Committee recommended 
proposed guidelines for review and de- 
cision by the Director, NIH. To assist 
in the review, a special meeting of the 
Advisory Committee to the Director, 
NIH, was convened in February 1976. 
Members of the committee represent- 
ed not only science but such other dis- 
ciplines as law\ ethics, and consumer 
affairs. Comments received from com- 
mittee members and a number of 
public witnesses represented a wide 
range of views. A number of issues 
were referred back to the Recombin- 
ant Advisory Committee for their com- 
ments in April 1976. On the basis of all 
the comments received and the re- 
sponses of the RAC, the NIH guide- 
lines were finalized by the Director, 
NIH, and released in June 1976 along 
with an extensive “Decision docu- 
ment.” 
In 1977 the Recombinant Advisory 
Committee, in accordance with its 
mandate in the original guidelines, 
began the process of proposing revi- 
sions to them. A subcommittee of the 
RAC held open meetings in March and 
April. Following this, the proposed re- 
visions were considered and revised by 
the full committee at open meetings in 
May and June. On September 1, 1977, 
the RAC’s proposed revised guidelines 
were referred to the Director, NIH, for 
consideration and decision. 
These proposed guidelines were pub- 
lished in September for comment in 
the NIH Recombinant DNA Technical 
Bulletin. The bulletin is a new NIH 
publication that links recombinant 
DNA investigators in the United 
States and abroad with the advisory 
groups and organizations active in this 
field. To provide further opportunity 
for public comment, the proposed re- 
vised guidelines were published in the 
Federal Register on September 27, 
1977 (42 FR 49596). The revisions pro- 
posed by the RAC are described in 
detail in the following assessment, but 
the key changes can be summarized as 
follows: 
Definition. A new definition was pro- 
posed to cover only “novel recombin- 
ant DNA”— namely, DNA segments 
from species not known to exchange 
chromosomal DNA by natural physio- 
logical processes. Accordingly, a class 
of recombinant DNA, to be exempt 
from the guidelines, would have to 
appear on a list of “non-novel ex- 
changers.” 
Physical Containment. revisions 
here incorporated the philosophy and 
guidance of the report by NIH and the 
European Molecular Biology Organi- 
zation (EMBO) on the requirement of 
physical containment. A number of re- 
visions were also made in the organiza- 
tion of this section. 
Biological Containment. This sec- 
tion was expanded from the 1976 
NOTICES 
guidelines to include (l)a new nomen- 
clature— HV1, HV2, and HV3— incorpo- 
rating a variety of host-vector systems 
into the framework initially estab- 
lished for E. coll K-12; (2) a more re- 
strictive set of requirements for HV3 
host-vector systems; and (3) a new sec- 
tion describing mechanisms for certifi- 
cation of host-vector systems. 
Prohibited Experiments. A major 
recommendation would allow the Di- 
rector, NIH, to exercise discretion in 
permitting exceptions to the prohibit- 
ed experiments, as in studies of risk as- 
sessment. 
Permissible Experiments. On the 
basis of the scientific evidence on the 
safety of E. coli K-12, some categories 
of experiments were classified at lower 
containment levels. Several other cate- 
gories, however, remained the same as 
in the current guidelines. For certain 
categories, discretion was permitted by 
the investigator, and some categories 
of experiments were exempted. 
Implementation. Several changes 
were recommended in the responsibil- 
ities for the local institution. The rec- 
ommendations included requirements 
for training of research personnel, cri- 
teria for determining the need for 
medical procedures, clarification of 
membership on institutional bio- haz- 
ards committees, and the require- 
ments for a biological safety officer 
where work is being done at the P3 
and P4 levels. 
The NIH-proposed revisions 
The proposed revisions by the Re- 
combinant Advisory Committee were 
published in the Federal Register for 
comment on September 27, 1977 (42 
FR 49596), and notice of a public hear- 
ing was published in the Federal Reg- 
ister on November 22, 1977 (42 FR 
59918). In December the RAC-pro- 
posed revisions were considered by the 
Advisory Committee to the Director, 
NIH (DAC) at a hearing attended by 
scientific experts and public witnesses. 
As at the 1976 hearing of the DAC, 
the membership was augmented to 
assure that the committee's perspec- 
tives included sufficient expertise and 
opinion on relative scientific, environ- 
mental, occupational, and public 
policy issues. In addition, special ar- 
rangements for the meeting included 
inviting 12 witnesses to represent in- 
dustrial research, academic research, 
labor, and environmental groups. A 
number of others requested the oppor- 
tunity to contribute their views and 
testified at the hearing. 
Members of the Recombinant Advi- 
sory Committee attended to explain 
the proposed revisions, and members 
were present from the Federal Inter- 
agency committee on Recombinant 
DNA Research which represents all 
Federal departments and agencies 
that support or conduct such research 
33099 
or have regulatory authority in this 
area. 
Since September 1977, when the pro- 
posed revisions were published in the 
Federal Register, they have been re- 
viewed in light of the many comments 
received from the public and the scien- 
tific community. The public hearing 
provided a forum for all points of view, 
especially from the environmental per- 
spective. On the basis of the analysis 
of the hearing and the correspon- 
dence, the following general points 
emerged: 
• The recommendations by the Re- 
combinant Advisory Committee were 
generally supported. There was uni- 
versal sentiment for giving the Direc- 
tor, NIH, discretion to exempt certain 
experiments from the provisions of 
the guidelines, especially w'hen this 
would permit knowledge to be gained 
bearing on the provisions themselves. 
There was overwhelming sentiment 
for exempting from the guidelines ex- 
periments involving most “self-clon- 
ing” systems, as well as pairs of harm- 
less organisms that transfer genes in 
nature. That is, many of the experi- 
ments currently classified at the 
PI + EK1 level should be exempted 
from the guidelines. And witnesses 
from the scientific community strong- 
ly advocated further consideration of 
revisions involving work with viruses 
and plant pathogens. 
• On the basis of these suggestions, 
a “Joint United States-EMBO Work- 
shop to Assess Risks for Recombinant 
DNA Experiments Involving the Gen- 
omes of Animal, Plant, and Insect Vir- 
uses” was convened on January 26-28, 
1978, in Ascot, England. The report of 
the workshop (see appendix E) was re- 
viewed by a working group sponsored 
by NIH on April 6-7, and the recom- 
mendations from that group (see ap- 
pendix F) were referred to the Recom- 
binant Advisory Committee. The com- 
mittee, in turn, lent their endorsement 
in recommendations at a meeting held 
at NIH on April 27-29. The analysis of 
existing knowledge of viruses by the 
groups of experts indicate that the 
risks of cloning viral DNA in a bacte- 
rium like E. coli is not greater, and is 
usually much less, than the risk of 
handling the parent virus itself. 
• Further, a meeting of agricultural 
scientists was convened on March 20- 
21, 1978, under the joint sponsorship 
of the Department of Agriculture, the 
National Science Foundation, and the 
National Institutes of Health. Their 
recommendations were also reviewed 
by the Recombinant Advisory Com- 
mittee at their April meeting. It was 
the conclusion of the agricultural sci- 
entists that containment conditions 
for incorporation of DNA from plant 
pathogens into E. coli K-12 were un- 
justifiably high. 
FEDERAL REGISTER, VOL. 43, NO. 146— FRiDAY, JULY 28, 1978 
[ 60 ] 
