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Federal Register / Vol. 45, No. 85 / Wednesday, April 30, 1980 / Notices 
approval. Accordingly the following 
changes in the Guidelines are proposed: 
A. Section III-A-3-a is to be amended 
as follows: 
‘'HI-A-3-a. Purified DNA Other than 
Plasmids, Bacetriophages, and Other 
Viruses. The formation of DNA recombinants 
from cellular DNAs that have been purified 
[41] and in which the absence of harmful 
sequences has been established [3] can be 
carried out under lower containment 
conditions than used for the corresponding 
shotgun experiment [42]. The containment 
may be decreased one step in physical 
containment (P4— »P3; P3— >-P2; P2— >Pl) while 
maintaining the biological containment 
specified for the shotgun experiment, or one 
step in biological containment (HV3— *HV2; 
HV2— >HVl) while maintaining the specified 
physical containment. The institutional 
biosafety committee (IBC) must review such 
a reduction and the approval of the IBC must 
be secured before such a reduction may be 
put into effect. IBC approval is sufficient foa 
such a reduction except for any lowering of 
containment under Section III-A-3-a to 
levels below P1 + HV1, which requires prior 
NIH approval. (See Sections IV-D-l-c and 
IV-E-l-b-(3He).)” 
B. Section III-A-3-b is to be amended 
as follows: 
"HI-A-3-b. Characterized Clones of DNA 
Recombinants. When a cloned DNA 
recombinant has been rigorously 
characterized and the absence of harmful 
sequences has been established (3) 
experiments involving this recombinant DNA 
may be carried out under lower containment 
conditions. 
Institutional biosafety committees (IBCs) 
may give approval for a single-step reduction 
in physical or biological containment on 
receipt of evidence of characterization of a 
clone derived from a shotgun experiment and 
its probable freedom from harmful genes. IBC 
approval is sufficient for such a reduction 
except for any lowering of containment under 
Section III-A-3-b to levels below Pl + HVl, 
or reduction of containment levels by more 
than step, which also require prior NIH 
approval. (See Sections IV-D-l-c and IV-E- 
1— b— 3— (e).} ' 
C. Section IV-D-l-c-{3] is to be 
amended as follows: 
‘TV-D-^l-c-(3). Certain reductions of 
containment levels for characterized or 
purified DNA preparations or clones (see 
Section III— A— 3).” 
D. The Note in Section IV-D-3-b is to 
be amended as follows: (Additional 
language in Italics]. 
“Note. — Some examples of work that might 
ordinarily proceed without prior funding- 
agency approval are the initiation of a project 
at the Pi or P2 level (other than the first 
project at the Institution). Other examples are 
significant changes in hosts or vectors, in the 
donor species or the nature of the DNA 
segment selected, or in the physical location 
of the experiments. Still others are single- 
step reductions in containment level for (i) 
experiments with DNA recombinants from 
cellular DNAs that have been purified and 
are judged to be free of harmful sequences 
(See Section III-A-3-a) and for (iij clones 
that have been characterized and judged to 
be free of harmful sequences (see Section III- 
A-3-b). It should be clear, however, that the 
funding agency must be notified of IBC 
approvals even when prior agency approval 
is not required. See the Administrative 
Practices Supplement for further discussion.” 
E. Section IV-E-l-b-(3)-(e) is to be 
amended as follows: 
”IV-E-l-b-(3}-(e). Lowering containment 
levels in certain cases for characterized 
clones or purified DNA (see Sections IU-A-3- 
a and -b, and Footnotes 3 and 41);” 
14. Transfer of DNA Segments Cloned 
in Saccharomyces cerevisiae Host- 
Vector Systems to Higher Plants. Dr. 
Jane Setlow of Brookhaven National 
Laboratory, has suggested that the 
Guidelines include a general provision 
for cloning plant DNA in 
Saccharomyces cerevisiae and 
subsequently returning the cloned DNA 
to the plant. She proposes that the first 
sentence of Section III-c-7-b be 
amended to read as follows: 
“m-C-7-b. Transfer to Higher Plants. DNA 
from any nonprohibited source [Section I-D] 
which has been cloned and propagated in E. 
coli or S. cerevisiae under appropriate 
containment conditions, may be transferred 
with the E. coli or S. cerevisiae vector used 
for cloning to any higher plant organisms 
(Angiosperms and Gymnosperms) and 
propagated under conditions of physical 
containment comparable to PI and 
appropriate to the organism under study 
[2A].” 
15. Status of Variola and Whitepox 
Viruses. It was suggested at the RAC 
March &-7, 1980 meeting that any 
mention of the variola viruses in the 
Guidelines be marked with a symbol so 
that reference could be made to world 
organization policy regarding these 
viruses and worldwide efforts at 
eradication. 
Accordingly, it is proposed that 
Appendix B, Classification of 
Microorganisms on the Basis of Hazard, 
be amended so that each mention of 
Alastrim, Smallpox and Whitepox will 
be marked with a symbol. A footnote at 
the bottom of the page bearing this 
symbol will read: 
“All activities, including storage of variola 
and whitepox are restricted to the single 
national facility (World Health Organization 
(WHO) Collaborating Center for Smallpox 
Research, Center for Disease Control, in 
Atlanta).” 
16. Request for Consideration of 
Appropriate Containment Conditions. 
Dr. Paul S. Sypherd of the University of 
California, Irvine has requested 
consideration of the containment levels 
appropriate to the return of Mucor 
racemosus DNA cloned in 
Saccharomyces cerevisiae host-vector 
systems to Mucor racemosus. In 
addition, Dr. Sypherd requests 
permission to transform Mucor 
racemosus with S. cerevisiae vectors 
with or without cloned yeast sequences. 
17. Proposal to Amend Section I-D-6 
of the Guidelines. Dr. Irving Johnson of 
Lilly Research Laboratories, proposes 
that Section I-D-0 of the Guidelines be 
amended, as follows: 
A. Delete the second paragraph of 
Section I-D-6 which currently reads as 
follows: 
"We differentiate between small- and large- 
scale experiments with organisms containing 
recombinant DNAs because the probability 
of escape from containment barriers normally 
increases with increasing scale.” 
B. Amend the third paragraph of 
Section I-D-0 to read as follows 
(amended language in italics): 
“Experiments in Categories I-D-l to I-D-6 
may be excepted (4) from the prohibitions 
(and will at that time be assigned appropriate 
levels of physical and biological 
containment) provided that these 
experiments are expressly approved by the 
Director, NIH, with advice of the 
Recombinant DNA Advisory Committee after 
appropriate notice and opportunity for public 
comment. (See Section IV-E-l-b-(lHe).) 
Those experiments utilizing an E. coli K-12 
host-vector system and meeting the 
containment requirements of Section 111-0 
are excluded from these prohibitions. " 
18. Proposals to Amend Several 
Sections of Part IV, Roles and 
Responsibilities. Dr. Irving Johnson of 
Lilly Research Laboratories, haa 
proposed several amendments of Part IV 
of the Guidelines, “Roles and 
Responsibilities," as follows: 
A. Amend Section IV-E-l-b-(3)-(d) 
under Section IV-E-l-b, ‘‘Specific 
Responsibilities of the Director, NIH, " 
to read 6s follows (new language in 
italics): 
‘TV-E-l-b-(3)-(d). Authorizing, under 
procedures specified by the RAC, large-scale 
experiments (i.e., involving more than 10 
liters of culture) for recombinant DNAs that 
are rigorously characterized and free of 
harmful sequences (see Footnote 3 and 
Section I-EM3). 
Further volume increases at the approved 
containment level, e g., for industrial 
development and production purposes, of 
previously approved (by the Director of NIH) 
large-scale experiments may be subsequently 
approved by the local IBC in accordance 
with Section IV-D-3-a. The IBC will notify 
ORDA of such volume increases." 
B. Amend the second paragraph of 
Section IV-E-2, Recombinant Advisory 
Committee, to read as follows (amended 
language in italics): 
[95] 
