NOTICES 
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Appendix C 
RESPONSES TO SOME COMMENTS ON THE 
NIH ENVIRONMENTAL IMPACT STATE- 
MENT, BY PUBLIC WITNESSES AT THE 
DAC MEETING, DECEMBER 15-16, 1977 
At the public meeting of the Adviso- 
ry Committee to the Director, NIH. 
held at the National Institutes of 
Health in December 1977, witnesses 
representing environmental groups 
commented on the "Environmental 
Impact Statement on NIH Guidelines 
for Research Involving Recombinant 
DNA Molecules,” published by NIH in 
October 1977. Some of the comments 
and responses by the Office of the Di- 
rector, NIH, are summarized below. 
Comment 1. "The environmental 
impact statement does not respond to 
the arguments that any gene, if ex- 
pressed out of its normal context, has 
the potential for being ‘harmful.’ Ap- 
pendix K59-62” (of the EIS). 
Response. Page 23 of the EIS (sec- 
tion IV-C-1) states that the “stable in- 
sertion of DNA derived from a differ- 
ent species into a cell or virus (and 
thus the progeny thereof) may change 
certain properties of the host. The 
changes may be advantageous, detri- 
mental, or neutral with regard to (a) 
the survival of the recipient species, 
(6) other forms of life that come in 
contact with the recipient, and (c) as- 
pects of the nonliving environment. 
Current knowledge does not permit ac- 
curate assessment of whether such 
changes will be advantageous, detri- 
mental, or neutral, and to what 
degree, when considering a particular 
recombinant DNA experiment.” This 
statement and subsequent elaboration 
acknowledges the commentator’s 
point — that any gene, if expressed out 
of its normal context, has a potential 
for doing harm. The EIS does not 
qualify here— does not limit itself to 
the effects of "harmful” genes, such 
as those coding for synthesis of a 
toxin. Section IV-C proceedes to dis- 
cuss ways in which hazardous agents 
might be produced. Factors such as 
survival of the host cell, survival of 
vectors, and effects of hosts or vectors 
on other forms of life are considered. 
Moreover, the guidelines classify all 
DNA that might be manipulated, so 
that some measure of containment is 
required for any recombination. Thus 
“any gene” is covered. 
Comment 2. "The EIS does not re- 
spond to the argument that while E. 
coli K-12 does not normally colonize 
the human colon, it is incorrect to 
infer that this property renders it 
harmless to humans. Appendix K62- 
64.” 
Response. The letter cited (Zimmer- 
man, Environmental Defense Fund) 
argues that E. coli K-12’s survival per 
se is not the issue— that genetic ex- 
change is. The point is covered in sec- 
tion IV-C-l-b-(2) on page 29 of the 
EIS: "When a cell or virus dies, or 
comes close to or invades the tissue of 
another living organism, the re- com- 
binant DNA may effectively enter a 
new cell. A hazardous 
situation • • • might ensue if foreign 
proteins were manufactured in this 
‘secondary’ recipient” (et seq.). Fur- 
ther treatment of the issue is present- 
ed in section VI-C, page 76, under the 
heading "Transfer of Foreign DNA 
from E. coli K-12.” The EIS does not 
infer that the demonstrated reluc- 
tance of E. coli K-12 to colonize the 
human intestine renders it entirely 
harmless. If that were so, there would 
be no guidelines as we know them, 
where experiments using this attenu- 
ated organism are classified over the 
whole range of containment possibili- 
ties. 
Comment 3. “The possibility that an 
organism containing chimeric DNA 
could possess properties exhibited by 
neither the host nor the organism is 
not considered. No response to this in 
the EIS. Appendix K65.” 
Response. Section IV-C-1 of the EIS. 
pages 23-31, describes the ways in 
which recombinant DNA experiments 
might be hazardous. Under the subti- 
tle “The effect of bacteria and viruses 
containing recombined DNA on other 
forms of life, “there are sections ex- 
plaining basic mechanisms whereby a 
recipient microorganism might be al- 
tered with regard to its pathogenicity 
or toxicity as a result of a resident re- 
combinant. “Foreign DNA inserted 
into a bacterial gene,” it is stated, 
"might so alter the microbial cell’s 
properties that it becomes harmful to 
other organisms. This might happen, 
for example, through a change in the 
growth rate and competitive advan- 
tage of the recipient microbial cell, re- 
sulting in increased virulence of a 
mildly pathogenic bacteria.” (EIS, p. 
29) The statement and those following 
it are broad enough to include the pos- 
sibility that “an organism containing 
chimeric DNA could possess properties 
exhibited by neither the host nor the 
organism” (which probably means 
"neither the foreign donor nor the 
host organism”). In other words, the 
EIS has nowhere denied this possibil- 
ity and, indeed, addressed it in a gen- 
eral way by considering the various 
mechanisms through which hazards 
might arise. 
Comment 4. “There is no adequate 
response to the criticism that the pub- 
lication of the EIS after the release of 
the guidelines negated the purpose of 
the National Environmental Policy 
Act, i.e., to secure broad public com- 
ments on the guidelines and the policy 
of expansion they assume. Appendix 
K31.” 
Response. The EIS on page 2 re- 
sponds to the above criticism as fol- 
lows: "Although NEPA assumes that 
such Federal actions will not be taken 
until the NEPA procedures are com- 
pleted, the Director of NIH concluded 
that the public interest required im- 
mediate issuance of the guidelines, 
rather than deferral for the months 
that would be required for completion 
of the NEPA process. This was be- 
cause experiments utilizing recom- 
binant DNA technology were proceed- 
ing in various laboratories throughout 
the country with only general and 
purely voluntary restrictions.” The 
statement is still valid, and it is diffi- 
cult to see how the NIH might better 
have acted in the public interest. NIH 
has pointed out elsewhere that the re- 
lease of guidelines was a positive act in 
the interest of public safety, not an 
act that could in any way be construed 
as negative or hazardous. 
Comment 5. "No response or correc- 
tion of the lack of ’classification 
system for pests and pathogens of 
plants and animals on the basis of 
their hazards to agriculture such as 
exists for etiologic agents of disease on 
the basis of their hazard to humans.’ ” 
Correspondence between Drs. John W. 
Littlefield and Peter Day, April 14, 
1977. 
Response. The EIS addresses the 
guidelines’ treatment of plant and 
animal sources of DNA on page 120, 
first paragraph. It explains that the 
analysis of potential hazards in the 
EIS is given in a general way that is 
equally applicable to persons, animals, 
and plants. The section of the guide- 
lines on plants has been expanded in 
the proposed revision. Specifications 
for plant host-vector systems provide 
safeguards in greenhouses, growth 
chambers, etc., that meet the stand- 
ards for experiments involving other 
life forms. As to a classification 
system, a workshop on risk assessment 
of agricultural pathogens, comprising 
distinguished American plant patholo- 
gists, was held on March 20-21, 1978 
(as announced on March 6 in the Fed- 
eral Register) under the sponsorship 
of the U.S. Department of Agriculture, 
the National Science Foundation, and 
the National Institutes of Health. The 
report of this workshop constitutes ap- 
pendix G. It was presented to the Re- 
combinant Advisory Committee at its 
meeting on April 27-28, 1978, and was 
unanimously endorsed with certain 
minor amendments. The recommenda- 
tions of the RAC have been adopted in 
the NIH Director’s proposed revised 
guidelines (PRG-NIH) with additional 
minor amendments to sections dealing 
with the use of plants and plant path- 
ogens in recombinant DNA research. 
Comment 6. “No response to Dr. 
Peter Albersheim’s concern over the 
use of the organism Agrobacterium tu- 
mefaciens in nitrogen-fixation work. 
Correspondence with Dr. Fredrickson, 
FEDERAL REGISTER, VOL 43, NO. 146— FRIDAY, JULY 28, 1978 
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