NOTICES 
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■hops, represent the first realistic ap- 
praisal of any hazards that might lie 
In the use of viral vectors or the clon- 
ing of viral DNA. Recombinant tech- 
niques offer access to ares of viral biol- 
ogy that are vitally important. Such 
studies should not be Impeded unnec- 
essarily. I have accepted the April 
1978 recommendations of the RAC In 
this area with minor amendments. 
The revised guidelines emphasize the 
current dictum that any hazards of 
working with viruses In recombinant 
DNA experiments are maximal at the 
first stage, when the virus Itself with 
Its full genomic complement is han- 
dled. 
The RAC unanimously approved 
modest changes In containment for 
plant experiments. I have also ap- 
proved them provisionally, contingent 
upon concurrence by the Department 
of Agriculture. 
A new sentence has been added to 
the guidelines giving much needed 
flexibility In the setting of contain- 
ment levels. (15) 
HOLES AITO RESPONSIBILITIES 
Two years’ experience with the 
guidelines has offered valuable tute- 
lage In the limits of external (Federal) 
control of laboratory experimentation. 
Scientists and their co-workers have 
long experimented with pathogenic or- 
ganisms, poisonous plants and ani- 
mals, and hazardous chemicals. The 
laboratory Is not among the more no- 
torious occupational settings for acci- 
dents or Illness, and damage to com- 
munity or environment by basic labo- 
ratory research is almost unknown. 
Control over the use of radioisotopes 
In the laboratory, long a Federal pre- 
serve, is not comparable to use of re- 
combinant DNA techniques; for the 
risks of using radioisotopes are calcu- 
lable and mistakes are easily meas- 
ured. Thus realistic and durable stand- 
ards can be set. Without a base for the 
setting of such standards, convention- 
al regulation Is difficult at best, and at 
worst can be preposterous. 
In the case of recombinant DNA 
technology, we are In the midst of a 
search for any risks, and thus for ap- 
plicable standards. The scientists who 
raised the possibility of risks also real- 
ized that the only effective safeguards 
lay in a maximum enhancement of the 
collective nature of the scientific proc- 
ess. The usual communications net- 
works of science had to be augmented 
and the evaluation of results and the 
reaching of consensus accelerated. 
These actions, is was reasoned, would 
help establish a set of Initial rules, and 
there was the added assumption that 
they could and should be kept up to 
date. All using the new techniques 
would sign a “memorandum of under- 
standing” to the effect that, until 
things became clearer, the basic com- 
munality of scientific Inquiry would be 
especially emphasized In any work 
with recombinant DNA techniques. 
The power of the Government to re- 
quire such discipline of its grantees 
was an attractive reason for the scien- 
tists to request Federal Intervention. 
And the Federal capacity to achieve 
the essential communication and con- 
sensus-building has been one of the 
most positive results of this experi- 
ment in adminstration. But the price 
of Fedeal Intervention Includes a 
heavy tax of formalism. In the In- 
stance of these guidelines, diverse 
pressures have made difficult the ap- 
propriate balancing of substance and 
procedure. I have already alluded to 
one of the undesirable results— a chill- 
ing Inflexibility of the original guide- 
lines — and Its proposed correction by 
revision. 
Prior NTH clearance is mandatory 
for new NIH grants and contracts In- 
volving recombinant DNA techniques 
and for all projects in P4 facilities. In 
the proposed revised guidelines, prior 
NIH clearance Is no longer required 
for changes at the P1-P3 levels. These 
changes must be approved by the In- 
stitutional biosafety committee (IBC), 
and NIH will then review the IBC ac- 
tions. This proposal reverses an Octo- 
ber 1977 issuance stating that changes 
In ongoing projects require prior NIH 
clearance. The requirement resulted In 
numerous delays In projects which 
could not be Justified on grounds of 
safety. 
The proposed guidelines would 
strengthen Institutional responsibil- 
ities and authorities In determining 
compliance. A full partnership with all 
Investigators and their institutions is 
Intended. The role of the IBC Is par- 
ticularly enhanced through delegation 
of some discretionary powers that 
were previously reserved for NIH and 
the RAC. To better meet these obliga- 
tions, an institution using P3 or P4 
containmen is required under the pro- 
posed guidelines to have a qualified bi- 
logical safety officer. 
Experience gained In the past 5 
years In explaining recombinant DNA 
technology has shown how valuable 
can be a co mmuni ty’s activities. At 
least one member of the EBC is to be a 
"public member”— Le., one who has no 
financial connection with the Institu- 
tion. Further, to ensure opportunity 
for public partlclation at the national 
level, procedural are set forth, as ex- 
plained in Part IV of the decision, that 
provide public notice and solicit com- 
ment on the major actions of NIAH. 
Another stipulation of the revised 
guidelines Is that failure of compliance 
can lead to suspension of NTH support 
for recombinant DNA research. (1 6) 
Provision Is now made for the pri- 
vate sector to register voluntarily Its 
recombinant DNA activities with NIH. 
Also, other consulting services, Includ- 
ing certification of host-vector sys- 
tems, will be provided. The service will 
be accompanied by protection of pro- 
prietary data as mandated by law. 
NIH Issued a draft environmental 
impact statement on the guidelines in 
September 1976. This was revised after 
public comment and Issued in final 
form In October 1977. It concluded 
that the activities covered by the 
guidelines had no predictable impact 
on the environment, since all the risks 
discussed were hypothetical. The EIS 
was examined by a Federal district 
court In 1978.(17) 
In parallel with the process of revis- 
ing the guidelines, NTH has conducted 
an environmental Impact assessment, 
Including an analysis of how current 
experiments supported by NIH will be 
affected by this revision. Again, the 
activities covered by the revised guide- 
lines deal only with hypothetical risks, 
and thus the assessment reveals no 
predictable Impact on the environ- 
ment. Its content is published here- 
with In a companion document. 
ORGANIZATION OF THE REMAINDER OF 
THIS DOCUMENT AND ABBREVIATIONS USED 
The Recombinant DNA Molecule 
Program Advisory Committee Is som- 
netimes referred to below as the Re- 
combinant DNA Advisory Committee 
or Recombinant Advisory Committee 
or RAC. 
The meeting of the Advisory Com- 
mittee to the Director, NIH, which 
took place in December 1977 Is some- 
times referred to below as the meeting 
of the Director’s Advisory Committee 
or of the DAC or the December 1977 
public hearing. 
The “NIH Guidelines for Research 
Involving Recombinant DNA Mole- 
cules” as issued on June 23, 1976, and 
publishes in the Federal Register on 
July 7, 1976, are sometimes referred to 
below as the original guidelines or the 
1976 guidelines or the current guide- 
lines. 
The proposed revised guidelines pre- 
pared by the RAC and published in 
the Federal Register on September 
27, 1977, are referred to below as the 
PRG-RAC. 
The proposed revised guidelines 
which are being proposed now by NIH 
are referred to below as the PRG- 
NIH. 
The remainder of this document is 
divided Into four parts corresponding 
to the four parts of the guidelines; i.e., 
I. Scope of the Guidelines; II. Contain- 
ment; III. Containment Guidelines for 
Covered Experiments; and TV. Roles 
and Responsibilities. 
Within each of these four parts 
there are two subsections; i.e.. Review 
of RAC-Proposed Guidelines and 
Review of Comments and NIH-Pro- 
posed Guidelines. The first subsection 
FEDERAL REGISTER, VOL 43, NO. 144— FRIDAY, JULY 2S, I97R 
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