NOTICES 
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the revised guidelines [have] the 
intent of erring on the side of cau- 
tion.” While believing that the guide- 
lines are, and should be, deliberately 
restrictive, I agree with the criticism 
that scientists should not enter into 
an activity with the intent of erring. 
The PRG-NIH now reflects this opin- 
ion by deletion of this phrase. 
Another commentator suggested 
that the guidelines should contain lan- 
guage requiring all publications deal- 
ing with recombinant DNA activities 
to include a description of the physical 
and biological containment procedures 
used. While the PRG-NIH urges "that 
all publications dealing with recombin- 
ant DNA work include a description of 
the physical and biological contain- 
ment procedures employed,” NIH is 
not well advised to dictate to research- 
ers or editors what must be included in 
a scientific publication. 
There were several suggestions that 
the purpose of the guidelines be more 
clearly stated and that terms be more 
precisely defined. I have, therefore, 
added considerable new material to 
Part I of the PRG-NIH, renamed 
"Scope of the Guidelines,” and divided 
it into the following sections, each of 
which is discussed further below: Pur- 
pose: Definition of Recombinant DNA 
Molecules; General Applicability: Pro- 
hibitions; Exemptions; and General 
Definitions. 
Purpose 
The introduction to the 1976 guide- 
lines states that “the purpose of these 
guidelines is to recommend safeguards 
for research on recombinant DNA 
molecules.” As noted above, to elimi- 
nate "naked” recombinant DNA from 
the guidelines, the PRG-RAC pro- 
posed this passage to read that the 
purpose is to “establish procedures for 
handling organisms and viruses con- 
taining recombinant DNA molecules.” 
This proposed revision would have 
had the effect of removing from cover- 
age by the guidelines certain experi- 
ments which are prohibited by the 
1976 guidelines— for example, deliber- 
ate formation of naked recombinant 
DNA containing genes for the biosyn- 
thesis of potent toxins. I have decided 
to resolve this issue conservatively. 
The language in the PRG-NIH, there- 
fore, clearly states that the guidelines 
are intended to pertain to the con- 
struction and handling of naked re- 
combinant DNA molecules as well as 
of organisms and viruses containing 
such molecules. 
General applicability 
Many commentators urged that a 
statement of general applicability of 
the guidelines be included in an early 
part. The issues relate to (1) the appli- 
cability of the guidelines to non-NIH 
funded research with recombinant 
DNA at institutions receiving NIH 
funds for this purpose, (2) the applica- 
bility of the guidelines to NIH-sup- 
ported recombinant DNA research 
conducted in foreign countries, and (3) 
the location of responsibility for insur- 
ing compliance with the guidelines. 
Therefore, a section entitled "General 
Applicability” now appears after the 
"Purpose” section in Part I of the 
PRG-NIH. 
The existence of guidelines for re- 
combinant DNA research assumes 
their general application. Partial ad- 
herence within an institution would 
defeat the purpose of extending maxi- 
mal protection to the community. 
Thus, it would be inconsistent for NIH 
to provide funds for biomedical re- 
search activities to an institution that 
did not meet the standards of the 
guidelines in all of its recombinant 
DNA research, regardless of the 
source of funding. This principle is 
now stated explicity in the PRG-NIH, 
and we intend to consider withholding 
NIH funds as a sanction against viola- 
tion. 
Rules must be established for the 
conduct of recombinant DNA activities 
funded by NIH in other countries. 
Generally, the requirements in force 
in those countries shall apply. A 
memorandum of understanding and 
agreement (MUA) must still be filed 
with NIH, indicating specifically 
which guidelines will govern the activi- 
ties; and NIH reserves the right to 
withhold funding if the safety prac- 
tices to be employed are not compara- 
ble to the NIH guidelines. An explicit 
statement about this has been inserted 
in the PRG-NIH. 
Part IV of the PRG-NIH describes 
the responsibilities of all individuals 
and organizational entities involved in 
the conduct and review of a recombin- 
ant DNA activity. Two years of experi- 
ence with administering the NIH 
guidelines has indicated that the ulti- 
mate responsibility for insuring com- 
pliance must be borne by the institu- 
tion where the research is being done. 
This implies some discretion under 
well-defined limits for interpretation 
of common standards, and imposes a 
requirement for local expertise other 
than the investigator’s. Accordingly, 
Part I of the PRG-NIH now requires 
that an individual receiving NIH sup- 
port for recombinant DNA research be 
associated with an institution that is 
willing and able to accept the responsi- 
bilities and conditions of local gover- 
nance, described more fully in Part IV 
of the PRG-NIH. 
Definition of recombinant DNA mole- 
cules 
It became apparent from the com- 
ments received that the PRG-RAC 
definition was inadequate in that it 
did not address the handling of recom- 
binant DNA molecules containing seg- 
ments of chemically synthesized DNA. 
I have decided that the most effective 
way to achieve this objective is simply 
to include "natural or synthetic DNA” 
in the definition of a recombinant 
DNA molecule, and this has been in- 
serted in the PRG-NIH definition. A 
new section, therefore, has also been 
added to Part III of the PRG-NIH 
giving containment levels for work 
with recombinant DNA molecules con- 
taining synthetic DNA. 
I have also revised what I perceived 
to be an ambiguity in the PRG-RAC 
definition by including within the 
PRG-NIH definition language explic- 
itly stating that DNA molecules which 
result from the replication of recom- 
binant DNA molecules are subject to 
the safety provisions of the guidelines. 
Finally, no other provision of the 
PRG-RAC definition evoked as much 
comment as did the wording to ex- 
clude “non-novel” recombinant DNA 
from the standards. The ambiguity of 
such phrases as “known to exchange 
chromosomal DNA” and "by natural 
physiological processess” was strongly 
noted, and I agree with the commenta- 
tors that we must strive for a greater 
degree of clarity and objectivity. Thus, 
it has been decided to eliminate in the 
PRG-NIH the two conditions cited 
above as criteria for exemption from 
the guidelines. Staff discussions of the 
public comments made it clear that in- 
clusion of exemption provisions within 
the definition itself was not desirable. 
Several attempts at appropriate lan- 
guage did not bear careful scrutiny. 
Given this situation, and also my 
opinion that certain categories of re- 
combinant DNA experiments are 
indeed so apparently free of causing 
harm that they should not come 
under the guidelines, it was my deci- 
sion to remove the criterion of “novel- 
ty” from the definition and use it as a 
basis for the development of a new 
section entitled "Exemptions.” 
Exemptions 
The nature of the public comments 
on the PRG-RAC exclusion of nonno- 
vel exchangers can be divided into cat- 
egories — those that pertain to the pro- 
posed standards and those to the pro- 
posed process. 
The standards proposed by the 
PRG-RAC were that novel recombin- 
ant DNA’s are those consisting of "seg- 
ments of any DNA from different spe- 
cies not known to exchange chromoso- 
mal DNA by natural physiological 
processes * * * In general recombinant 
DNA molecules * * • will not be con- 
sidered novel when all the components 
are derived from genomes known to 
replicate within the organism used to 
propagate the recombinant DNA.” 
This is qualified, however, by a foot- 
note stating that the “recombinant 
DNA formed between segments of eu- 
FEDERAL REGISTER, VOl. 43, NO. 146— FRIDAY, JULY 28, 1978 
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