NOTICES 
60083 
so the Exemptions sections was devel- 
oped. 
In my view, the criteria given in the 
exemptions and prohibitions sections 
of the PRO defining recombinations 
similar to natural events are both con- 
servative and reasonable. It should be 
noted that the wording of prohibition 
I-D-5, "that are not known to acquire 
it naturally,” is identical to that of the 
original 1976 Guidelines. 
PROHIBITIONS— SPECIFIC COMMENTS 
Several commentators requested 
clarification of prohibition I-D-2 con- 
cerning the deliberate formation of 
potent toxins. Was it intended to cover 
only toxins for vertebrates or those 
for all species? A commentator noted 
tha,t fungi produce antibiotics that are 
potent toxins for bacteria. It is not the 
intent of this prohibition to cover such 
toxins but only potent toxins for ver- 
tebrates. Accordingly, new language 
makes it clear that "potent toxins” 
refers specifically to vertebrates. 
A number of commentators form the 
agricultural community urged that 
mechanisms be set in place for waiver 
of prohibition I-D-4, which bans delib- 
erate release into the environment of 
any organism containing recombinant 
DNA. Recognizing the need expressed 
by these commentators for more de- 
finitive standards for allowing excep- 
tions, I will refer the matter to the Re- 
combinant Advisory Committee (RAC) 
for its consideration. Indeed, in re- 
sponse to several suggestions from 
commentators, the RAC will be asked 
to address conditions under which ex- 
ceptions to various prohibited catego- 
ries of experiments may be granted. 
Another commentator urged that 
for waiver of the prohibition on delib- 
erate release into the environment, 
the Guidelines explicitly require com- 
pliance with the National Environ- 
mental Policy Act (NEPA) and any ad- 
ditional safeguards to be stipulated by 
EPA. Others urged that full Environ- 
mental Impact Statements be filed on 
most exceptions to the prohibitions. 
As I noted in my Decision accompany- 
ing the PRG on July 28, 1978, all 
waiver decisions will include a careful 
consideration of the potential environ- 
mental impact. Some decisions may be 
accompanied by a formal assessment 
or statement — a determination, howev- 
er, that can only be made on a case-by- 
case basis. In the new procedures for 
the Federal agencies under the Guide- 
lines, all agencies represented on the 
Federal Interagency Committee, in- 
cluding EPA and OSHA, will have 
nonvoting members on the RAC, and 
will thus have opportunity to partici- 
pate in all the RAC’s deliberations. In 
addition, the Federal Interagency 
Committee may be convened to discuss 
issues its members believe are impor- 
tant prior to the granting of any 
waiver. Exceptions to prohibitions also 
fall under the procedure described in 
Section IV-E-l-b-(l) of the Guidelines 
that involves at least 30 days of public 
comment. 
The standard for exceptions to pro- 
hibitions in the Guidelines was a 
source of much comment. Some com- 
mentators believe that the standard 
should be “no significant risk and a 
clear social benefit to be realized.” 
Others urged that exception to the 
prohibitions be justified only to 
permit special risk-assessment experi- 
ments. I believe that Section IV-E-l-b 
sets the appropriate standard at this 
time. This is particularly so in light of 
the new procedural protections de- 
scribed in part IV requiring public and 
Federal agency participation in such 
decisions. 
There were a number of comments 
from the private sector concerning the 
prohibition on large-scale experiments 
(I-D-6). They noted that the necessity 
for conducting scale-up experiments 
(greater than 10-liter volumes) is im- 
minent, and that, in their view, such 
experiments present no unusual haz- 
ards. I recognize the need for conduct- 
ing experiments with more than 10 
liters of culture and the extensive ex- 
perience of industry in dealing with 
larger volumes. The criteria set forth 
in the Guidelines make the prohibi- 
tion inapplicable when the recombin- 
ant DNAs are rigorously characterized 
and free of harmful DNA sequences. 
An exception to the prohibition may 
also be granted [see Guidelines, Sec- 
tion rV-E-l-b-G)-(e)] and the RAC 
will begin to consider specific stand- 
ards for exceptions. 
EXEMPTIONS — SPECIFIC COMMENTS 
In the PRG all of the prohibitions 
overrode the exemptions. There were 
suggestions that certain prohibitions 
not apply to the exemptions. It was 
recommended, for example, that the 
prohibitions relating to the deliberate 
release of recombinants into the envi- 
ronment and the deliberate transfer of 
drug resistance not apply to exempt 
experiments. In my view these prohi- 
bitions must continue to apply for the 
present. 
It was also argued that the prohibi- 
tion on large-scale experiments should 
not apply to exempt experiments. This 
prohibition, indeed, is different from 
the other five, as is explicitly noted in 
the 1976 Guidelines. In the PRG the 
language was tightened: “recombinant 
DNAs known to make harmful prod- 
ucts” was changed to “unless the re- 
combinant DNAs are rigorously char- 
acterized and are shown to be free of 
harmful genes.” For experiments in 
the exempt category that call for more 
than 10 liters of culture, it seems un- 
necessary to have the recombinant 
DNAs meet these criteria. Therefore, a 
fixed prohibition, unduly restrictive in 
these cases, no longer applies, and ex- 
periments which meet the criteria of 
the exemptions may be conducted in 
volumes of over 10 liters. The first five 
prohibitions continue to apply to all 
experiments and override the exemp- 
tions. 
A correspondent stated that the in- 
clusion of specific exemptions in the 
Guidelines is premature. It was recom- 
mended that exemptions be granted 
instead on a case-by-case basis after 
risk-assessment, NEPA compliance, 
public participation, and a finding 
based on experimental data that the 
exemption presents no significant risk 
to health or the environment. In my 
view the five classes of exemption 
listed in the PRG, as discussed in the 
accompanying Decision Document and 
Environmental Impact Assessment, 
are warranted. It is a view shared by 
the RAC and many commentators 
throughout this long period of pro- 
posed Guideline revision. All of the 
participants and observers concerned 
with the Guidelines will benefit from 
disengagement of the least potentially 
hazardous use of recombinant DNA 
techniques, so that attention may be 
focused on the areas still encompassed 
by the Guidelines. 
A witness at the September 15 hear- 
ing objected to exemption of experi- 
ments involving naked DNA, maintain- 
ing that the Rowe-Martin experiment 
showed that the ingestion of naked po- 
lyoma DNA by mice resulted in infec- 
tion. This is incorrect. In that experi- 
ment the DNA caused infection in 
mice only when injected, and then 
with much reduced ability as com- 
pared with the whole virus. It is a 
common experience that naked DNA 
molecules are fragile and difficult to 
retain intact in the laboratory. Ingest- 
ed DNA would be destroyed in the ali- 
mentary tract by stomach acid and the 
various enzymes that degrade DNA. 
The one route whereby naked DNA 
molecules might be hazardous is acci- 
dental injection, as into a laboratory 
worker. The same could be said for 
many of the chemicals used in experi- 
ments. For this reason, the use of hy- 
podermic needles in laboratory proce- 
dures is avoided whenever possible. 
Their use is specifically discouraged in 
the section of the Guidelines on Con- 
tainment. Further, Footnote 5 has 
now been expanded to recommend in- 
activation of DNA before disposal, and 
specifically refers to the, Laboratory 
Safety Monograph as a source of 
advice on acceptable methods. 
A commentator on behalf of the 
RAC’s Working Group on Prokaryotic 
Host-Vectors Other than E. Coli K-12 
proposed modification of Exemption 
I-E-3. He provided the following justi- 
fication: “Addition of the proposed 
clause [‘or which have been trans- 
FEDERAL REGISTER, VOL. 43, NO. 247— FRIDAY, DECEMBER 22, 1978 
[ 6 ] 
