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Appendix E 
Department op Health, 
Education, and Welfare, 
Public Health Service, 
National Institutes of Health, 
Bethesda, Md. March 16, 1978. 
Dr. Donald S. Fredrickson, 
Director, National Institutes of Health, 9000 
Rockville Pike, Bethesda, Md. 
Dear Dr. Fredrickson: On January 26-28, 
1978, a joint U.S.-EMBO Workshop to 
Assess Risks for Recombinant DNA Experi- 
ments Involving the Genomes of Animal, 
Plant, and Insect Viruses was held in Ascot. 
England. The workshop was sponsored by 
the NIH at your request, in response to dis- 
cussions concerning viruses at the Director’s 
Advisory Committee meeting of December 
1977. The workshop was attended by 27 sci- 
entists from the United States, the United 
Kingdom, West Germany, Finland, France. 
Sweden, and Switzerland. The participants 
were invited because of their scientific ex- 
pertise and not as representatives of any 
government or of any policymaking group. 
The primary purpose of the meeting was 
to conduct a scientific and technical analy- 
sis of possible risks associated with cloning 
eukaryotic viral DNA segments in E. coli K- 
12 host-vector systems and with the use of 
eukaryotic viruses as cloning vectors in 
animal, plant, and insect systems. In addi- 
tion, there were general discussions of the 
possible importance of recombinant DNA 
technology for the solution of problems in 
basic and applied virology and of the classi- 
fication of viruses with respect to the 
hazard that laboratory research with them 
might pose to the laboratory worker or to 
the community. 
A report of the discussions and conclu- 
sions of the workshop is transmitted to you 
along with this letter. A draft of this report 
was sent to the members for comment and 
revision, and this final version is based on 
the replies of all the participants. In view of 
the favorable responses, we feel that this 
report will receive the support of virologists 
in general. We hope that it will be useful to 
you and the various national committees 
that are considering containment levels for 
this type of recombinant DNA research. 
Since this is the report of an international 
group, we generally avoided reference to 
any particular set of containment condi- 
tions. Rather, we anticipate that the various 
national committees will use this report as 
the scientific basis for setting the contain- 
ment conditions they feel appropriate. 
Sincerely, 
Malcolm A. Martin, 
Laboratory of Biology 
of Viruses, NIAID. 
Wallace P. Rowe, 
Laboratory of Viral Diseases, 
NIAID. 
John Tooze, 
Executive Secretary, European Molec- 
ular Biology Organization, Heidel- 
berg. 
Co-Chairmen. 
REPORT OF U.S.-EMBO WORKSHOP TO 
ASSESS RISKS FOR RECOMBINANT DNA 
EXPERIMENTS INVOLVING THE GENOMES 
OF ANIMAL, PLANT, AND INSECT VIRUSES 
This is the report of a joint U.S.- 
EMBO workshop held in Ascot, Eng- 
land, January 27-29, 1978, which was 
convened to discuss the possible risks 
of recombinant DNA experiments in- 
volving the DNAs of animal, plant, 
and insect viruses. The 27 scientists in 
attendance (see attached roster) had 
expertise in clinical infectious disease; 
public health, medical and diagnostic 
virology; the biology of virus infection; 
biochemical virology; and plant, insect, 
and veterinary viruses. Five of the par- 
ticipants are actively engaged in re- 
combinant DNA experimentation. A 
consensus statement of the discussions 
in the areas of pathogenesis and epide- 
miology of viral diseases, potential 
benefits of recombinant DNA experi- 
ments involving eukaryotic viral DNA, 
viral hazard classifications, and clon- 
ing in prokaryotic and eukaryotic sys- 
tems is presented below. The group’s 
conclusions, with respect to possible 
risks of recombinant DNA experi- 
ments involving viruses are based on 
the best available scientific data de- 
rived from publications, knowledge of 
current activities in the field of viro- 
logy, and first-hand experience in the 
virology laboratory. 
Introduction 
Viral disease is a complex process 
that involves a series of critical steps; 
these include entry of the virus parti- 
cle into the host, infection of specific 
cells at the portal of entry, replication 
of the virus in the infected cells, and 
usually, the spread of the progeny 
virus particles within the infected host 
to other susceptible cells. Depending 
upon the nature of the particular viral 
agent, the deleterious effects for the 
host, if any, may result from cytolytic 
activity, cellular transformation, 
chronic cellular dysfunction, or the 
provocation of an injurious immunolo- 
gical response. Viruses contain 5 to 150 
or more genes and their coordinated 
functioning is required for viral 
growth and, consequently, for survival 
of the virus in nature. Even though we 
do not generally understand the pre- 
cise role of each viral gene product, it 
seems clear that viral infection and 
disease production requires proper 
functioning of most, if not all, viral 
genes and, in general, is not a conse- 
quence of any single viral gene prod- 
uct. In the case of oncogenic papova- 
viruses, transforming retro- viruses 
and possibly adenoviruses, individual 
viral genes are thought to be responsi- 
ble for the transforming properties of 
the virus. 
Recombinant DNA experiments 
have already yielded new information 
about the structure and control of ex- 
pression of genes in higher organisms 
that could not have been obtained by 
conventional techniques. DNA cloning 
provides unparalleled opportunities to 
explore the basic biology of animal 
and plant viruses. Virologists will be 
able to probe more deeply into the 
control of viral gene expression and 
FEDERAL REGISTER, VOL 43, NO. 146— FRIDAY, JULY 28, 1978 
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