Federal Register / Vol. 44, No. 213 / Thursday, November 1, 1979 / Notices 
63075 
proposed new sections would read as 
follows: 
Il-D-l-a. HVO. A host-vector system that 
provides no biological containment in 
comparison with naturally-occurring 
organisms of the same species. 
II-D-l-a-{l). EKO. The host is any strain of 
E. coli and vectors include plasmids and 
bacteriophages without restriction. 
II- D-l-a-(2). Other prokaryotes. Other 
prokaryotes may be used at die HVO level 
after certification by the Director, NIH, with 
advice of the Recombinant DNA Advisory 
Committee, after appropriate notice and 
opportunity for public comment. 
4. Amendment of Sections III-B-2, 
11I-C-5, and III-C-6. At its September 6- 
7, 1979 meeting, the RAC voted to 
consider at its next meeting an 
amendment of Section III-C-6 proposed 
by Dr. David Hogness of Stanford 
University to remove the requirement 
for use of certified EK2 plasmid vectors 
in certain experiments involving “return 
of DNA to host of origin.” Because the 
proposed amendment is also applicable 
to other sections of the Guidelines, all of 
the affected sections will be considered 
for amendment. The proposed 
amendment of Sections III-B-2, III-C-5, 
and III-C-6 would change the words 
“. . . may be inserted into a lambdoid 
phage vector or into a vector from a 
certified EK2 host-vector system and 
propagated . . .” to “. . . may be 
inserted into a vector and propagated 
5. Amendment of Section III-C-7-a. 
Dr. David Hogness of Stanford 
University has proposed that Section 
III-C-7-a be amended to include 
invertebrates. The current version of HI— 
C-7-a refers only to non-human 
vertebrates. The amended Section III-C- 
7-a would read as follows: 
III- C-7-a. Transfer to Non-human Animals. 
DNA from any nonprohibited source (Section 
I-D), except for greater than one quarter of a 
eukaryotic viral genome, which has been 
cloned and propagated in E. coli under PI 
conditions, may be transferred with the E. 
coli vector used for cloning to any eukaryotic 
cells in culture or to any nonhuman animal 
and propagated under conditions of physical 
containment comparable to PI and 
appropriate to the organism under study [2A]. 
Transfers to any other host will be 
considered by the RAC on a case-by-case 
basis [45]. 
6. Request to Clone Segments of Foot 
and Mouth Disease Virus. Investigators 
at the Plum Island Animal Disease 
Center have requested an exception to a 
prohibition in order to clone in E. coli K- 
12 the VP 3 protein of Foot and Mouth 
Disease (FMD) virus. This virus is an 
RNA virus belonging to the class of 
picornavirus. This disease agent is 
controlled by the United States 
Government, which has, by law, 
forbidden entry into the U.S. of the 
animal disease organism (CDC class 5 
agent). The U.S. Congress has, however, 
designated the Plum Island Animal 
Disease Center, of the U.S. Department 
of Agriculture, as the one place in the 
U.S. where this agent can be cultured. 
The Director, NIH, is authorized to 
permit exceptions to prohibuted 
experiments under Section IV-E-l-b- 
(l)-(e). 
7. Containment Standards for Large- 
Scale Research and Production. The 
Working Group on Large-Scale Research 
and Production has prepared a draft set 
of physical containment standards for 
recombinant DNA research involving 
more than 10 liters of culture. Copies of 
these draft standards are available from 
the NIH Office of Recombinant DNA 
Activities. 
Comments on the draft standards are 
invited. Comments received in timely 
fashion will be considered at the 
December RAC meeting. All comments 
received through January 10, 1980, will 
be taken into account by the Working 
Group in its preparation of a revised 
draft. The revised draft standards for 
large-scale work will be available from 
ORDA on February 1, 1980, and will be 
considered at the March RAC meeting. 
Comments on the revised draft 
standards will be considered at the 
March meeting. 
If eventually approved by the NIH 
Director, the substantive standards for 
large-scale work could be combined 
with the procedural standards 
recommended by the RAC at the 
September 1979 meeting or a 
subsequently revised version. The 
combined standards could then 
constitute an Appendix on Large-Scale 
Research and Producton to the general 
NIH Guidelines. 
8. Transfer of DNA from Anabaena to 
Klebsiella. Dr. Robert Haselkom of the 
University of Chicago has requested 
approval to transfer cloned fragments of 
Anabaena DNA into Klebsiella by 
transformation. 
9. Proposed EK2 Lambda-E. coli K-12 
Host-Vector Systems. Dr. Pierre Tiollais 
of the Institut Pasteur has requested EK2 
certification of several E. coli K-12 host- 
vector systems based on derivatives of 
bacteriophage lambda. 
10. Proposal from Risk Assessment 
Working Group. The NIAID Risk- 
Assessment Working Group has 
proposed a major change to the NIH 
Recombinant DNA Guidelines that will 
broaden the field of investigations of 
risk assessment studies and will 
accelerate the process by which such 
studies will be carried out. At the 
present time, experiments allowable 
under the Guidelines are basically 
restricted to the use of DNA from non- 
pathogenic organisms which are 
propagated in host organisms that 
possess at least a moderate degree of 
biological containment. Experiments 
which involve genes for the biosynthesis 
of toxins potent for vertebrates, DNA 
from class 3, 4, and 5 pathogens, and 
DNA from plant pathogens that may 
increase virulence or host range are 
specifically prohibited by the Guidelines 
as are experiments which may involve 
“wild type” host-vector systems. The 
design of risk assessment studies which 
now may be classified as allowable 
experiments may skew the studies 
toward negative results because of the 
absence of moieties which may confer 
hazardous qualities. Also, the results of 
such experiments may not allow 
extrapolation to assess risks of 
recombinant DNA experiments that may 
involve organisms which possess 
intrinsic hazardous qualities such as 
infectious microorganisms. On the other 
hand, it shoud be possible to measure 
more precisely the potential risk of 
recombinant DNA technology if 
experiments which fall within the 
prohibited categories were encouraged 
and carried out. While such experiments 
can be excepted from the prohibitions, 
the long process for granting exceptions 
discourages innovative research in the 
prohibited areas. The following major 
change is therefore recommended to 
encourage and stimulate relevant risk 
assessment studies that may lead to a 
more precise understanding of the 
potential hazards associated with 
recombinant DNA technology. 
The specific proposed change to the 
Guidelines is to add the following 
paragraph to the end of Section I-D: 
Experiments in Categories I-D-l, I-D-2, 1- 
D-3, 1-D-5, and experiments involving “wild 
type” hostvector systems are excepted from 
the prohibitions provided that these 
experiments are designed for risk assessment 
purposes and are conducted within the NIH 
high containment facilities located in Building 
41-T on the Bethesda campus and in Building 
550 located at the Frederick Cancer Research 
Center. The selection of laboratory practices 
and containment equipment for such 
experiments shall be approved by ORDA 
following consultation with the RAC Risk 
Assessment Subcomittee and the NIH 
Biosafety Committee. 
11. Proposed Containment for Cloning 
Tumor Virus Genes. Dr. Stuart Newman 
of New York Medical College has filed 
the following statement and proposed 
major action with ORDA: "I would like 
to point out several aspects of the 
recently reported Rowe-Martin 
tumorigenicity risk-assessment 
experiments (Israel, et al., Science, 205, 
1140, 1979) that I believe have not 
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