L

Preparation and Use of Recombinant Molecules
    Involving Animal Virus Genomes

   The construction and study-of hybrid DNA molecules offer many
potential scientific and social benefits.
associated with the work are difficult to assess and may be real,  it is
essential that investigations be re-initiated only under conditions designed
to reduce the possible risks.
new and safer vectors is clear, we believe that the study of these recom-
binant DNAs can proceed with the application of existing National Cancer
Institute guidelines for work involving oncogenic viruses.
that is likely that cellular DNAs contain nucleotide sequences similar to
those found in viral genes, including genes associated with oncogenic trans-
formation.
preparation and use of recombinant DNA molecules derived from animal
viruses and mammalian cells.

Because the possible biohazards

Although the need for the development of

We point out

Therefore the following recommendations are made for the

Biohazard Classification and Guidelines

"The National Cancer Safety Standards for Research Involving Onto-

genic Viruses" is divided into standards for control of (1)  low risk, (2)
moderate risk, and (3) high risk oncogenic viruses (see appendix). With
the exceptions noted below, we recommend that self-replicating recombinant
DNA molecules containing animal virus genomes or genome segments in
biological vectors be handled according to guidelines for moderate risk
oncogenic viruses.
that are proven not to be associated with pathogenicity may be carried out
according to the guidelines for low risk oncogenic viruses. On the other hand,
genome segments from highly pathogenic viruses, e. g. , smallpox, Lassa
virus, hemorrhagic fever agents and others listed as class 4 in "Classification
of etiologic agents on the basis of hazard" (Atlanta,  Ga. CDC Publication)
should be handled according to the guidelines for high risk oncogenic viruses.
The vast majority of experiments, however,  will fall into the moderate risk
category.

Experiments involving purified segments of viral genomes

Regulation

We recommend that facilities and practices in investigations involving

recombinaot DNAs be reviewed and approved by institutional committees which
would both advise principal investigators and certify in writing to granting
agencies that proposed studies would be done according to the specified guide-
line s.

   We also recommend that a national and/or international body review the
guidelines and classifications periodically. To facilitate this review, additional
data should be acquired; for example, it is important to assess the biological
activity of DNA injected into animals, the transfer of plasmids between bac-
terial strains in the gut, the persistence there of carrier DNAs,  and the
efficacy of the immune response in dealing with new plasmids introduced into
the gut.

M. Bishop
D. Jackson
D. Nathans
B. Roizman
J. Sambrook
A. Shatkin
D. Walker