NOTICES 
33097 
ed over the ls»t 5 years have yielded a 
product harmful to man or the envi- 
ronment. On the other hand, many ex- 
amples of useful knowledge obtained 
through soch techniques continue to 
accumulate rapidly. 
Scientific developments 
No scientific evidence not considered 
in the promulgation of the guidelines 
has emerged to support the fears that 
the use of these techniques will create 
a harmful product. On the contrary, 
scientific information has been devel- 
oped over the part 2 years that lessens 
concern over the possible environmen- 
tal hazard. Dr. Roy Curtiss, professor 
of microbiology at the University of 
Alabama School of Medicine in Bir- 
mingham, and others have demon- 
strated that biological containment 
measures— methods developed to 
weaken bacteria u*ed in the experi- 
ments— do prevent these bacteria from 
surviving in a natural environment, 
and would do so if they escaped from 
the laboratory. 
While the probability of doing harm 
with laboratory recombination of 
genes has not been, and never will be, 
reduced to aero, we have reached a 
point where the burden of proof is 
shifting toward those who w’ould re- 
strict such activities. The eareful in- 
terpretation af evidence obtained 
before and after June 1978 has re- 
duced to Inconsequential levels the 
probabilities that E. coli K-12, the 
host most used in recombinant DNA 
experiments can be converted to an 
epidemic pathogen. Much of the rele- 
vant data and their discussion by ex- 
perts are now available in the pub- 
lished proceedings of an NIH-spon- 
sored meeting in Falmouth, Mass., on 
June 29-11. 1977 (Journal of Infec- 
tious Diseases, May 1976). 
The Falmouth conference brought 
out evidence that the risk of trans- 
forming E. coli K-12 into a pathogen 
Is minimal, either for laboratory per- 
sonnel or the public at large. Dr. Sher- 
wood Gorbach, chairman of the con- 
ference, has reported that there was 
scientific sonseMus on this matter 
among all In attendance, ineluding mi- 
crobiologists who work with disease- 
producing bacteria. 
Much of the concern expressed 
about recombinant DNA experiments 
relates to tho creation of novel organ- 
isms in the laboratory. Additional evi- 
dence, however, suggests that the re- 
combinatkme of DNA produced in the 
laboratory may be very similar to 
many that occur tn nature. If further 
work confirms and extends this evi- 
dence, then the concern about creat- 
ing novel forms of life will be put into 
a new perspective. 
Administrative developments 
Implementation of the NIH guidelines 
The current NIH guidelines provide 
not only explicit instructions about 
the conduct of experiments, but also 
an administrative framework for their 
implementation. They set out the re- 
spective responsibilties of the princi- 
pal investigator, the institution where 
the work is conducted (including the 
institutional biohazard committee), 
the NIH Recombinant DNA Advisory 
Committee (or simply "Recombinant 
Advisory Committee” or "RAC,” the 
technical body responsible for propos- 
ing the guidelines), and the NIH staff. 
The NIH Office of Recombinant 
DNA Activities (ORDA) was estab- 
lished to coordinate the administra- 
tion of NIH policies and procedures 
for safe utilization of recombinant 
DNA technology in research. Dr. Wil- 
liam Gartland is Director of ORDA. 
Over the 2 years the implementation 
of the guidelines by participants in 
this research has proceeded well. Ap- 
proximately 130 institutions where 
NIH-supported research is taking 
place have established institutional 
biohazard committees, and approxi- 
mately 350 projects are involved. 
Over the past 2 years administrative 
practices have evolved to deal with re- 
quirements of the guidelines. One of 
the requirements is a means for inter- 
pretation. The standards in the guide- 
lines are very explicit about the con- 
duct of permissible experiments. Still, 
questions of interpretation continue to 
arise and must be dealt with. Our de- 
termination to assure that the experi- 
ments comport with the standards of 
the guidelines has necessitated a 
number of administrative delays in 
acting on research protocols. 
Another area of difficult administra- 
tion has been certification of new 
host-vector systems. These represent 
microorganisms weakened by various 
methods to prevent their survival were 
they to escape from their specially 
contained environment in the labora- 
tory. Under the current guidelines, the 
Recombinant Advisory Committee 
must review all applications for new 
host-vector systems and recommend 
for certification those that meet the 
relevant criteria. 
Undoubtedly the presence of the 
guidelines and their implementation 
have caused some experiments to be 
postponed and some scientific work to 
be delayed. At the same time, NIH, 
having embarked upon this conserva- 
tive course, believes it must guarantee 
the integrity of the administrative 
safeguards and see that due process is 
observed in implementation. 
Policy issues 
Three key policy issues concerning 
recombinant DNA research have domi- 
nated NIH attention during the ad- 
ministration of the NIH Guidelines. 
They are the determination of the en- 
vironmental impact, if any. of the NIH 
Guidelines and the research conducted 
thereunder; the patenting of recom- 
binant DNA research inventions devel- 
oped under Federal support; and the 
extension of the NIH Guidelines na- 
tionally through existing regulation or 
new legislation. Discussions of these 
policy issues follow: 
National Environmental Policy Act 
( NEPA ). In accordance with the Na- 
tional Environmental Policy Act of 
1969 (NEPA), NIH undertook an envi- 
ronmental impact assessment of envi- 
ronmental effects, if any, of the origi- 
nal NIH Guidelines. A draft environ- 
mental impact statement was pub- 
lished in the Federal Register in Sep- 
tember 1976 for public review and 
comments. On the basis of the com- 
ments received, NIH published a final 
EIS in October 1977. 
During the development of the EIS, 
two suits under NEPA were brought 
against the Department. One suit, in 
the Federal District Court in New 
York, alleged that NIH failed to 
comply with NEPA by not completing 
an EIS before supporting recombinant 
DNA research and before releasing the 
original guidelines. The Government 
has answered the allegations, and the 
case is pending in New York. 
The second suit filed in the Federal 
District Court in Washington, D.C., by 
a resident of Frederick, Md., sought an 
injunction to prevent NIH from con- 
ducting a risk-assessment experiment 
at the Frederick Cancer Research 
Center without first filing an environ- 
mental impact statement. On Febru- 
ary 23, 1973, a decision was rendered 
by the U.S. District Court against the 
issuance of an injunction, and this de- 
cision was affirmed by the U.S. Court 
of Appeals on March 8, 1978. It was 
the decision of the court that recom- 
binant DNA research was beneficial, 
that the experiment under question 
was important, and that it posed no 
substantial risk. The court went on to 
state that "the Recombinant DNA Re- 
search Guidelines represent an effort 
by many scientists to evaluate the haz- 
ards and provide safe methods for 
their control. The record reflects that 
NIH has carefully considered the po- 
tential risks of this experiment under 
the guidelines and has taken the nec- 
essary precautions * * *. The EIS does 
represent a ‘hard look’ by NIH at re- 
combinant DNA research performed 
in accordance with its guidelines. It 
appears that compliance with the NIH 
guidelines will insure that no recom- 
binant DNA molecules will escape 
from the carefully controlled labora- 
tory to the environment.” 
Patent Policy. Shortly before release 
of the NIH Guidelines in June 1976, 
NIH received a letter from Stanford 
University noting that both Stanford 
and the University of California were 
FEbERAl REGISTER, VOL 43, NO. 146— FRIDAY, JULY 28, 1978 
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