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Federal Register / Vol. 44, No. 71 / Wednesday, April 11, 1979 / Notices 
that is similar to that for bacteria. 
Therefore, the procedures established 
for certification of HV systems other 
than £. coli K-12 (Section ll-D-2) will 
also apply to these fungal or similar 
lower eukaryotic host-vector systems. 
Once an HVl system is approved by 
NIH, it may be used under P2 
containment for shotgun experiments 
with phages, plasmids, and DNA from 
Class 1 prokaryotes [1] and lower 
eukaryotes that do not produce 
polypeptide toxins. [34] Other classes of 
recombinant DNA experiments with 
these MVl systems will require prior 
approval and classification by Niff. (See 
Sections I V— El— 1 — b — { 1 ) — { b ) . IV-E-l-b- 
(2)-(c). and IV-E-l-b-(3)-(b).) If HV2 or 
HV3 systems of this type are developed 
and approved by NIH, guidelines for 
their use in other types of recombinant 
DNA experiments will also be 
established. 
In addition to the experiments 
described above, the following 
experiments may be carried out without 
the eukaryotic host (Host C) having 
been approved as an HVl host: DNA 
from Host C may be inserted into a 
lambdoid phage vector or into a vector 
from a certified EK2 host-vector system 
and propagated in £. coli K-12 under the 
appropriate containment conditions (see 
Section III— A— 1— (a )— (5) J. Subsequently, 
this recombinant DNA may be returned 
to Host C and propagated there under Pi 
conditions. [43], 
Containment levels for other classes 
of experiments involving non-HVl 
systems may be expressly approved by 
the Director. NIH. (See Sections IV-E-l- 
b-(lMb). IV-E-l-b-(2)-(c). and IV-E-1- 
b-(3Hb).} 
N. Modification of Section lll-C-2, 
Invertebrate Host- Vector Systems 
Section III— C— 2 of the Guidelines is 
replaced with the following modified 
text: 
III-C-2. Invertebrate Host-vector 
systems. 
III-C-2-a. Insect viral vectors. As 
soon as information becomes available 
on the host range restrictions and on the 
infectivity. persistence, and integration 
of the viral DNA in vertebrate and 
invertebrate cells, experiments involving 
the use of insect viruses to propagate 
DNA sequences will be evaluated by 
NIH on a r.ase-by-case [45] and will be 
conducted under the recommended 
physical containment conditions (See 
Section IV— E— 1— b— (3)— (c)). 
IIl-C-2-b. Nonviral vectors. 
Organelle, plasmid, and chromosomal 
DNAs may he used as vectors. DNa 
recombinants formed between such 
vectors and host DNA. when propagated 
only in that host (or a closely related 
strain of the same species), are exempt 
from thee Guidelines (see section I-E). 
DNa recombinants formed between such 
vectors and DNA from cells other than 
the host species require Pi physical 
containment for invertebrate cells in 
culture since invertebrate cells in culture 
inherently exhibit a very high level of 
containment. Experiments which require 
the use of whole animals will be 
evaluated by NIH on a case-by case 
basis [45]. 
O. Addition of Section IU-C-l-f 
Vertebrate Host- Vector Systems — Non- 
Viral Vectors 
A new Section III— C— 1— f is added to 
the Guidelines as follows: 
III— C— 1— f. Nonviral vectors. Organelle, 
plasmid, and chromosomal DNAs may 
be used as vectors. DNA recombinants 
formed between such vectors and host 
DNA. when propagated only in that host 
(or a closely related strain of the same 
species), are exempt from these 
Guidelines (see Section I-E). DNA 
recombinants formed between such 
vectors and nonviral DNA from cells 
other than the host species require only 
Pi physical containment for cells in 
culture since vertebrate cells in tissue 
culture inherently exhibit a very high 
level of containment. Recombinants 
involving viral DNA or experimetns 
which require the use of whole animals 
will be evaluated by NIH on a case-by- 
case basis [45]. 
P. Addition of Section lil-C-6. Return of 
DNA Segments to a Higher Eukaryotic 
Host of Origin 
A new Section III— C— 6 is added to the 
Guidelines as follows: 
III— C— 6 . Return of DNA Segments to a 
Higher Eukaryotic Host of Origin. DNA 
from a higher eukaryote (Host D) may 
be inserted into a lambdoid phage 
vector or into a vector from a certified 
EK2 host-vector system and propagated 
in E. coli K-12 under the appropriate 
containment conditions [see Section III— 
A-l). Subsequently, this recombinant 
DNA may be returned to Host D and 
propagated under conditions of physical 
containment comparable to Pi and 
appropriate to the organism under studv. 
[2A] 
Dated: March 30. 1979 
Donald S Fredrrickeoo. 
Director. Sohnnal fnst'tu'cs of Health. 
IFR Doc. 7**- 11 037 Filed 4-10- ^9: &4o am) 
BILLING COOE 41 10-08-M 
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