NOTICES 
33057 
3^ HYI. However. I see no need to 
. v. : ' : ■ ex- 
plicitly. 
C r.e coir. T.enta tor thought the 
sfG-'u..ri; for HYi should be signifi- 
cantly relay 'd and that KIH approval 
should not be necessary. He proposed 
that the Guidelines sure that "wild 
type isottts cf any bacterial species 
no; known to be pathogenic to 
humans, .o domestic animals, or to ag- 
riculturally important plants may be 
used as an HYI host-vector system, 
provided that all components of re- 
combinant DNA molecules introduced 
into such a host-vector system, are de- 
nied from other prokaryotic organ- 
isms within Etiologic Agent Class 1. " I 
have rejected this suggestion since I 
believe it prudent, at least for the 
present, to have hither standards and 
to require NTH approval before a 
system may be called EY1. Seme com- 
mentators have urged that the re- 
quirement for independent confinra- 
ticn of reiet mnt phenotypic and geno- 
typic traits before certification at the 
KV3 level should also be applied at the 
HY2 level. There are two objects of 
such testing: 1' Tc determine wheth- 
er a system already approved has 
changed its characteristics before a 
new sample of it is distributed (for ex- 
ample. whether the amber mutations 
for phage systems are still present), 
anc .2 to repeat independently all the 
safety tests required before each new 
system wool.', be certified. The first 
could be done easily and is sufficient 
to confirm the safety characteristics: 
the second is cumbersome and dhfi- 
cult. It should be pom ted out that the 
RAC and .:s working groups that 
review the data on proposed EY2 sys- 
tems are. in eitect. conducting an inde- 
pendent check and know this area of 
research well. Further, the Committee 
no] esS that add :r.al experi- 
mental data be subrtutted as part of its 
review. NTH t.Iie>es these controls to 
be s ufficie nt. Consequently, the re- 
quirement for an independent check 
at the EV 2 level is deemed unneces- 
sary. 
For the ET3 level of containment, 
some objections have been raised to 
the requirement banning antibiotic-re- 
sistance markers, Antibiotic resistance 
can serve as a valuable marker in ex- 
periments with organisms bearing re- 
combinant DNA. The ban at the HY3 
level, however, is p-udent masmuth as 
organisms rendered antibiotic resis- 
tant would be less amenable to control 
should they escape from the labora- 
tory. This requirement also allows 
only a certain class cf certified 3TY2 
systems to qualify for EV3. Therefore, 
attempts to develop systems that meet 
these KV3 criteria should simulta- 
neously upgrade the HYI systems in 
use. since it is to the experimenters 
advantage to use those HY2 systems 
with the greatest likelihood of meet- 
ing HV3 criteria. 
Cc rtification. A number of commen- 
tators have urged more precise criteria 
for biological containment systems. 
They feel that criteria should be as ob- 
ject ive as possible and should be 
framed in terms o: performance. ss in 
the case of physical containment (for 
example, safety cabinets). It should be 
stressed that specific oojectivs criteria 
do exist for EK2 host-vector systems. 
These, however, do not appear in the 
Guidelines themselves, but rather as 
information in the Environmental 
Impact Statement. Appendix H. enti- 
tled ' Certificaricn of EK2 Host-Vector 
S> stems.” To insure that detailed ma- 
terial cn certification of host-vector 
systems is readily accessible, NIH will 
publish specific criteria in a standar- 
ized format in the Recombinant DNA 
Technical Bulletin. Specific instruc- 
tions concerning the type of data to be 
submitted to NIH for proposed ES2 
systems involving either plasmids or 
bacteriophage lambda in E. cc.: K-12 
are available from the NIH Office of 
Recombinant DNA Activities, and a 
statement to this effect is included in 
the FRG-NIH. 
Many problems persist for setting 
general criteria that could be applied 
to ad organisms for possible certifica- 
tion as HY2 and EY3. Eor example, 
with B. subtilis, which forms spares, 
safety would depend on nonsporulat- 
ing derivatives. Some commentators 
urged that ah new systems be certified 
with deliberate caution. ar.u that crite- 
ria and evidence should be a matter of 
public record before decisions are 
made. The B. subtilis system was cited 
as a case in point; extensive public 
analysis ar.d debate should precede 
certification. 
I agree that prior notification to the 
public in the Federal Register should 
be given when the RAC considers ap- 
plications for certification. (It should 
be noted that ai, meetings cf the RAC 
are announced in the Federal Regis- 
ter.: I also agree with the suggestion 
that the RAC snould have a more 
fixed schedule of meetings throughout 
the year so that the public and scien- 
tific communities may knew the 
schedule of everts clearly. 
The entire section (II-D-2-a> on re- 
sponsibility for certification of host- 
vector systems has been rewritten in 
the FRG-NIH to clarify this process. 
Distribution of Certified Host- Vec- 
tors. Some commentators have sug- 
gested that NIH distribute HYI sys- 
tems as well as HY2 and HV3 systems. 
Language has been placed in the 
PRG-NTK indicating that, where ap- 
propriate, HYI systems other than E. 
cc . : K-12 may be sent by NIH to inves- 
tigators. 
Concern has been expressed about 
culture contamination and how this 
problem would be addressed. The 
PRG-NIH provides that if NIH propa- 
gates any of the host strains or 
phages, it will not distribute the cul- 
ture before sending a sample to the in- 
vestigator who developed the system 
or to an appropriate contractor for 
verifies .ion that "the materiJ is free 
from contamination and unchanged in 
phenotypic properties." The FRG- 
NIH also assigns to the investigator 
the res; onsibility for "insuring the in- 
tegrity of physical containment (e.g., 
biological safety cabinets) and biologi- 
cal containment (e.g., genotypic and 
phenotypic characteristics, purity, 
etc.).” 
Distribution of certified host-vector 
systems has raised comment relating 
to the protection of proprietary infor- 
mation and patent rights, for this sec- 
tion of the Guidelines seems to man- 
date distribution ar.d might conflict 
with patent protection. NIH has care- 
fully considered such protection. Lan- 
guage has been included in the PRG- 
NIE (in sect.on IV-C) allowing PAC 
review for certification at the request 
of the private sector. The language 
notes, however, that interested indi- 
viduals should consider filing for 
patent protection before submitting 
information to PHEW. To be consist- 
ent with the institutional patent 
agreement policies of the Department 
of Health, Education, ar.d Welfare, 
support is accorded the concept of pro- 
tection of proprietary and patent 
rights within the bounds of due proc- 
ess for public review. 
III. Containment Guidelines for 
Covered UsEERjeENTS 
REVIEW OF RAC-PROPOSED GUIDELINES 
A major concern cf all individuals 
who have participated in establishing 
guidelines fer recombinant DNA re- 
search is that any guidelines that are 
drafted and adopted oe reassessed pe- 
riodically and changes made when 
warranted by new information and/or 
expei imenta: data. In keeping with 
this responsibility, the RAC compDed 
additional information pertaining to 
risk assessment in recomoinani DNA 
research. This information is in the 
following forms: 
1. Consultations with scientists with 
expertise in the areas of evolution, 
plant biology, oactenoiogy, virology, 
and human and animal infectious dis- 
eases; 
2. Reports from scientific meetings 
dealing with the potential biohazards 
of recombinant DNA research (for ex- 
ample, the Tenth Miles International 
Symposium on Recombinant Mole- 
cules— Impact on Science and Society, 
Cambridge, Mass.. June 1976; the Na- 
tional Academy of Sciences forum on 
Recombinant DNA Research. Washing- 
ton. D.C.. March 1977; Genetic Engi- 
neering for Nitrogen Fixation, Brook- 
FEPERAL REGISTER, VOL 43, NO. 144 — FRIDAY, JULY 28, 1978 
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