f Written comments and inquiries con- 
cerning the Proposed Revised Guide- 
lines should be addressed to the Direc- 
tor, National Institutes of Health, Be- 
thesda. Md. 20014. All comments re- 
ceived win be available for public in- 
spection at the Director's office on 
weekdays (Federal holidays excepted! 
between the hours of 8:3,0 a.m. and 5 
pm. 
Dated: July 19. 1978. 
Donald S. Fredrickson, 
Director, 
National Institutes of Health. 
Decision or the Director, National 
Institutes or Health, To Issue Re- 
vised Guidelines for Recombinant 
DNA Research 
July 19, 1978. 
Contents 
Introduction and overview. 
Scope and applicability of guide- 
lines. 
Containment. 
Containment guidelines for covered 
experiments. 
Roles and responsibilities. 
Organization of document and ab- 
breviations used. 
I. Scope of the guidelines. 
Review of RAC proposed guidelines. 
Review of comments and NIH pro- 
posed guidelines. 
IL Containment. 
Physical containment. 
Review of RAC proposed guide- 
lines. 
Review of comments and NIH pro- 
posed guidelines. 
Biological containment. 
Review of RAC proposed guide- 
lines. 
Review of comments and NIH pro- 
posed guidelines. 
III. Containment guidelines for cov- 
ered experiments. 
Review of RAC proposed guidelines. 
Review of comments and NIH pro- 
posed guidelines (general). 
Specific considerations. 
IV. Roles and responsibilities. 
Review of RAC proposed guidelines. 
Review of comments and NIH pro- 
posed guidelines. 
Introduction and O verview 
Today, with the concurrence of the 
Secretary of Health, Education, and 
Welfare, and the Assistant Secretary 
for Health, I am proposing revisions to 
the NIH Guidelines for Recombinant 
DNA Research.! I) These Guidelines 
were first issued on June 23, 1976. The 
proposed revisions result from a con- 
tinuing process of scientific and public 
exchange similar to that of the 1976 
edition. This overview sketches the 
background for proposed revisions and 
summarizes the proposed changes. It 
references accompanying documents 
NOTICES 
and other pertinent sources of infor- 
mation. 
The probable risks and benefits of 
recombinant DNA research— the 
larger subject of which the NIH 
Guidelines are a part— have been dis- 
cussed in numerous forums since first 
addressed in 1973.(2) Congress 1 ms 
held multiple hearings cm related 
issues, including proposals to convert 
the Guidelines to Federal regula- 
tions! J) and redefine recombinant 
DNA research to narrow the range of 
experiments subject to regulation*. 
Early in 1977 the NIH Recombinant 
DNA Advisory Committee (RAC), the 
scientific and technical committee re- 
sponsible for proposing revision* to 
the Guidelines, began its task of iden- 
tifying changes needed in the Guide- 
lines and forwarded suggestions to me 
for consideration. In order that public 
comments could be heard on the RAC- 
proposed revisions, published in Sep- 
tember 1977,(4) a meeting of the Advi- 
sory Committee to the Director, NIH 
(DAC), the committee responsible for 
public oversight, was held in Decem- 
ber. The extensive record of this hear- 
ing bears witness to almost unanimous 
agreement that the original Guide- 
lines badly need updating, and sug- 
gests numerous directions in which re- 
visions might move.! 5) 
Much of the discussion at the De- 
cember 1977 meeting of the DAC af- 
firmed the need for continuous reeva- 
luation of the scientific premises un- 
derlying the original Guidelines. Since 
Asilomar,(2) growing evidence has sug- 
gested that other experts ought to 
review the concerns of the molecular 
biologists who first raised questions 
about the safety of recombinant DNA 
research. Scrutiny from experts In in- 
fectious diseases, epidemiology, viro- 
logy, botany, ecology, laboratory 
safety, and other disciplines has been 
needed. NTH sponsored a workshop for 
this purpose at Falmouth, Mass^ C 
months before the DAC meeting. 
Here, old and new Information about 
E. coli K-12— the host most used in re- 
combinant DNA experiments— was In- 
terpreted carefully. From this came a 
consensus that the chances of this 
host being convertible to an epidemic 
pathogen are negligible. 
Those attending the December DAC 
meeting also heard complaints that 
containment levels were set too strin- 
gently for recombinant DNA work on 
viruses and plants. This applied both 
to the original Guidelines and to the 
revisions proposed in September 1977. 
A decision was made to address the 
issues through workshops without 
delay. 
One of these workshops, held at 
Ascot, England, dealt specifically with 
viruses.! 7) Here, experts from several 
countries, most of whom had no stake 
in recombinant DNA experiments. 
3304 ^ 
reached an unequivocal opinion that 
the risks of cloning viral DNA in a bac- 
terium like E. coli K-12 are not great- 
er, and are usually much less, than the 
risks of handling the parent virus 
atone. They also stressed that defec- 
tive viruses pose little risk of Infection 
when used as vectors for cloning DNA 
in eukaryotic cells, since the cells 
cannot survive outside permissive labo- 
ratory conditions and the virus cannot 
escape in a viable form. A second 
working group, meeting in Bethes- 
da,(7) then reviewed the conclusions. 
It agreed that the original Guidelines 
imposed stricter containment on use 
of viral DNA or of viruses as vectors 
than could be justified by any availa- 
ble fact, and recommended changes. 
A group of agricultural scientists 
met in Washington, D.C., in March 
1978(8) to consider the containment 
conditions for incorporation of DNA 
from plant pathogens into & coti K-12 
and for use of viral and other vectors 
in plants. An important concept dis- 
cussed at this workshop is the lack of 
evidence that E. coli K-12, or any 
other strain of this bacterium, is capa- 
ble of acquiring an ecological niche In 
plants and thus infecting them. 
On April 27-28, 1978, the RAC con- 
sidered the recommendations concern- 
ing viruses and plants and agreed with 
most of them. With a few changes, 
they are a part of the proposed revi- 
sion. 
At the December 1977 hearings 
before the DAC, other aspects of the 
Guidelines evoked requests for revi- 
sions.! 5) There was overwhelming sen- 
timent for exempting from the Guide- 
lines experiments involving recombin- 
ation of DNA within the same strains 
or from pairs of organisms that trans- 
fer genes in nature. Discretion to 
exempt such experiments is not pro- 
vided in the original Guidelines; nor 
does one find there the flexibility to 
permit other experiments for purposes 
of risk assessments needed to deter- 
mine the merits of particular stand- 
ards, or how these should be revised. 
Other criticisms of the Guidelines 
stressed the delays and confusion cre- 
ated by excessive centralization of ad- 
ministrative control, and it is evident 
that implementing procedures must be 
changed. 
Certain background elements merit 
comment. Shortly after the NIH 
Guidelines were published, the British 
guidelines appeared.! 9) Subsequently 
other national guidelines have been 
issued, most recently those of the 
Soviet Union. Many international as- 
pects of DNA research and its regula- 
tion have been reviewed elsewhere.! 9) 
The December 1977 DAC meeting di- 
rected attention to instances where 
the NIH Guidelines either exclude ex- 
periments that have been conducted 
abroad or make them far more diffl- 
FEDERAL REGISTER, VOL 43, NO. 146— FRIDAY, JULY 28, 1978 
[41 
