NOTICES 
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DNA by known physiological processes 
are exempt from the Guidelines under 
exemption I-E-4. 
The RAC at its April 27-28. 1978, 
meeting pointed out that there are 
certain scientifically important experi- 
ments which are very safe but which 
neither fit the criteria to be exempt 
from the guidelines, nor the criteria 
for HVI certification. A new section 
III-B-2 has been added to the PRG- 
NIH to cover these cases and assign 
appropriate containment levels. In 
these experiments DNA from a pro- 
karyotic host (Host X) is cloned into 
E. coli K-12 (this situation is already 
covered in sec. III-A-l-b(2) of the 
guidelines); in the second part of the 
experiment the recombinant DNA 
(consisting of DNA sequences from 
Host X linked to an E. coli plasmid or 
bacteriophage) is returned to Host X 
and propagated there. 
Section III-C. Experiments with eu- 
karyotic host-vectors 
a number of commentators felt that 
the stringent containment conditions 
required both in the original guide- 
lines and in the PRG-KAC for intro- 
duction of recombinant DNA into 
tissue culture cells, using viruses as 
vectors. were unwarranted. The 
EMBO Standing Advisory Committee 
on Recombinant DNA. Research wrote; 
Ip. exp: ments involving the introduction 
of foreign DNA into cultured cells of ani- 
mals using DNA viruses as vectors, biologi- 
cal containment is assured by the very re- 
stricted permissive conditions for the host 
ceils: the only routes by which the recom- 
binant molecule might escape are by chance 
infection of a contaminating microorganism 
or within a viral capsid and the size of the 
recombinant molecule may well preclude its 
encapsidation • * *. For example, cloning of 
mouse DNA using polyoma virus as a vector 
and mouse cells as host should not require 
precautions more stringent than those rou- 
tine used for many years in laboratories 
s!u. ; ng polyoma virus infection of mouse 
cells ard mice. The EMBO Committee finds 
the proposals for this class of experiments 
in i e revised NIH Guidelines not suffi- 
ciently discriminating because they would 
impose unnecessarily high levels of physical 
containment for experiments with many eu- 
karyotic DNA’s. 
Discussed earlier within Part III of 
this document under the heading ‘'Re- 
combinant DNA Experiments Involv- 
ing Viral DNA" was the history of the 
"Ascot" workshop report (See App. E 
to the accompanying environmental 
impact assessment, and the report of 
the working group which met on April 
6-7. 1978 (App. F to the accompanying 
environmental impact assessment). I 
have accepted the recommendations of 
the work group and incorporated their 
suggested revision of this section 
which now becomes section III-C of 
the PRG-NIH. The result of this 
change is that section III-B-3 of the 
PRG-RAC "Experiments with Eukar- 
yotic Host-Vectors." subparts (a) "Ver- 
tebrate Host-Vector Systems." and (b) 
“Invertebrate Host-Vector Systems," 
are eliminated; substituted for it in 
the PRG-NIH is new language derived 
from the working group report which 
become section III-C "Experiments 
With Eukaryotic Host-Vectors,” sub- 
parts (1) Vertebrate Host-Vector 
System"; (2) "Invertebrate Host- 
Vector Systems in which Insect Vir- 
uses Are Used To Propagate Other 
DNA Segments", and (3) Plant Viral 
Host-Vector Systems." 
Section III-C-4. Plant Host-Vector Sys- 
tems Other Than Viruses 
Discussed earlier within Part III of 
this document under the heading "Re- 
combinant DNA Experiments Involv- 
ing DNA Prom Plants and Plant Path- 
ogens" was the Workshop on Risk As- 
sessment of Agricultural Pathogens, 
held on March 20-21, 1978. sponsored 
by USDA, NSF, and NIH. Based on 
the Workshop report (See Appendix G 
to the accompaying Environmental 
Impact Assessment), section III-D of 
the PRG-NIH has been rewritten. 
Section III-C-5. Fungal or Similar 
Lower Eukaryotic Host-Vector Sys- 
tems 
Both the 1976 Guidelines and the 
PRG-RAC used the same short para- 
graph for this section, giving little 
detail, because they noted "the devel- 
opment of these host-vector is present- 
ly in the speculative stage." Since that 
time a specific host-vector system of 
this class has been developed, i.e., Sac- 
charomyces cerevisiae (baker's yeast), 
and other similar systems may also 
soon be proposed. Accordingly, this 
section (III-C-5) of the PRG-NIH has 
been expanded to give more specific 
instructions on appropriate contain- 
ment levels. 
Section III-D. Complementary DNAs 
Since specific containment levels for 
the use of purified cDNA of viral 
mRNA are now given in section III-A- 
2-a of the PRG-NIH. a sentence has 
been added noting this at the begin- 
ning of section III-D of the PRG-NIH. 
Otherwise, the rest of this evoked no 
comments and remains identical in the 
PRG-NIH to the PRG-RAC. 
Section III-E. Synthetic DNA 
Because synthetic DNA is now ex- 
plicitly included in the PRG-NIH (as 
discussed in section I of this docu- 
ment), it was necessary to add lan- 
guage to Part III of the PRG-NIH de- 
tailing the appropriate containment 
levels for these experiments. The RAC 
at its meeting on April 27-28, 1978. ap- 
proved such language, and it has been 
inserted in the PRG-NIH as section 
III— E. 
IV. Roles and Responibilities 
REVIEW OF RAC PROPOSED GUIDELINES 
This section, as in the 1976 Guide- 
lines, provides an administrative 
framework for implementation. Modi- 
fications to the various roles and re- 
sponsibilities proposed by the RAC are 
listed below. 
Institutional Responsibilities 
Institution. Several changes were 
proposed in the PRG-RAC as com- 
pared to the 1976 Guidelines in the re- 
sponsibilities of the institution. Re- 
sponsibilities that were added or fur- 
ther detailed included: (1) a require- 
ment for insuring the training of re- 
search personnel and the use of good 
microbiological technique, and (2) a 
requirement to determine the need for 
medical procedures, with recommenda- 
tions of possible specific practices. 
Institutional Biosafety Committees. 
Membership of the committees was 
clarified by a recommendation to in- 
clude other than scientific members. 
In thePRG-RAC (section III), institu- 
tional biosafety committees (IBCs) are 
given the discretion to approve single- 
step reductions in containment levels 
for experiments with characterized 
clones and purified DNA. The I3C's 
would be required to notify the NIH 
Office of Recombinant DNA Activities 
(ORDA) of these approvals. 
Biological Safety Officer. Institu- 
tions at which P3 and P4 level recom- 
binant DNA work is conducted would 
be required to have a biological safety 
officer, whose specific roles and re- 
sponsibilities are outlined. 
Principal Investigator. The role and 
responsibilities of the principal investi- 
gator would remain basically the same 
except for the important addition of a 
requirement for training in microbio- 
logical techniques. Responsibility for 
the determination of the practices nec- 
essary for medical surveillance would 
be relocated to the institution. 
NIH Responsibilities 
Office of the Director. The responsi- 
bilities of the Director would remain 
unchanged. A sentence was added 
which clarified the Director's authori- 
ty to implement the Guidelines and to 
be the final arbiter in the interpreta- 
tion of the Guidelines. 
Recombinant Advisory Committee. 
There were no changes in the current 
responsibilities of the RAC; however, 
there were clarifications of the scope 
of some duties, for example, the certi- 
fication process. The language of the 
1976 Guidelines caused confusion 
among some concerning the certifica- 
tion of EK2 (HV2) and EK3 (HV3) 
host-vector systems. In practice, the 
certification process involved a two- 
step procedure: (1) the RAC's recom- 
mendation to the Director, NIH, that 
FEDERAL REGISTER, VOL 43, NO. 146— FRIDAY, JULY 28, 1978 
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