LETT E R8

minimize the spread of such molecules
within human and other populations;
and (iii) devising guidelines to be
followed by investigators working with
potentially hazardous recombinant
DNA molecules.
Fourth, an international meeting of
involved scientists from all over the
world should be convened early in the
coming year to review scientific prog-
ress in this area and to further discuss
appropriate ways to deal with the
potential biohazards of recombinant
DNA molecules.
The above recommendations are
made with the realization (i) that
our concern is based on judgments of
potential rather than demonstrated risk
since there are few available experi-
mental data on the hazards of such
DNA molecules and (ii) that adherence
to our major recommendations will
entail postponement or possibly aban-
donment of certain types of scientifical-
ly worthwhile experiments. Moreover,
we are aware of many theoretical and
practical difficulties involved in evaluat-
ing the human hazards OI such re-
combinant DNA molecules. Nonethe-
less, our concern for the possible un-
fortunate consequences of indiscrimi-
nate application of these techniques
motivates us to urge all scientists work-
ing in this area to join us in agreeing
not to ini,tiate experiments of types
1 and 2 above until attempts have been
made to evaluate the hazards and some
resolution of the outstanding questions
has been achieved.

PAUL BERG, Chairinan

DAVID BALTIMORE
HERBERT W. BOYER
STANLEY N. COHEN

RONALD W. DAVIS
DAVID S. HOGNESS
DANIEL NATHANS

   RICHARD ROBLIN
JAMES D. WATSON
SHERMAN WEISSMAN
NORTON D. ZINDER

Corninittee on Recoinbinant DNA
Molecules Asseinbly of Life Sciences,
National Research Coiincil,
Nntiotitrl Academy of Sciences.
Wmhiiigton. D.C. 20418

References and Notes

I. S. N. Cohen. A. C. Y. Chann. H. Bover. R. B.

Potential Biohazards of

Recombinant DNA Molecules

Recent advances in techniques for
the isolation and rejoining of segments
of DNA now permit construction of
biologically active recombinant DNA
molecules in vitro. For example, DNA
restriction endonucleases, which gen-
erate DNA fragments containing co-
hesive ends especially suitable for re-
joining, have been used to create new
types of biologically functional bac-
terial plasmids carrying antibiotic re-
sistance markers (1) and to link
Xettopiis Iaevis ribosomal DNA to
DNA from a bacterial plasmid. This
latter recombinant plasmid has been
shown to replicate stably in Escherichia
coli, where it synthesizes RNA that is
complementary to x. larvis ribsomal
DNA (2). Similarly, segments of
Drosophila chromosomal DNA have
been incorporated into both plasmid
and bacteriophage DNA's to yield hy-
brid molecules that can infect and
replicate in E. coli (3).

Several groups of scientists are now
planning to use this technology to
create recombinant DNA's from a
variety of other viral, animal, and
bacterial sources. Although such experi-
ments are likely to facilitate the solu-
tion of important theoretical and prac-
tical biological problems, they would
also result in the creation of novel
types of infectious DNA elements
whose biological properties cannot be
completely predicted in advance.
There is serious concern that some of
these artificial recombinant DNA mole-
cules could prove biologically hazard-
ous. One potential hazard in current
expcriments derives from the need to
use a bacterium like E. coli to clone
the recombinant DNA molecules and
to amplify their number. Strains of
E. coli commonly reside in the human
intestinal tract,. and they are capable
of exchanging genetic information with
other types of bacteria, some of which
are pathogenic to man. Thus, new
DNA elements introduced into E. coli
might possibly become widely dis-
seminated among human, bacterial,
plant, or animal populations with un-
predictable effects.
Concern for these emerging capabili-
ties was raised by scientists attending
the 1973 Gordon Research Confer-
ence on Nucleic Acids (4), who re-
quested that the National Academy of

26 JULY 1974

Sciences give *consideration to these
matters. The undersigned members of
a committee, acting on behalf of and
with the endorsement of the Assembly
of Life Sciences of the National Re-
search Council on this matter, propose
the following recommendations.
First, and most important, that until
the potential hazards of such recom-
binant DNA molecules have been bet.ter
evaluated or until adequate methods
are developed for .preventing their
spread, scientists throughout the world
join with the members of this com-
mittee in voluntarily deferring the fol-
lowing types of experiments.
b Type I: Construction of new,
autonomously replicating bacterial plas-
mids that might result in the introduc-
tion of genetic determinants for anti-
biotic resistance or bacterial toxin
formation into bacterial strains that do
not at present carry such determinants;
or construction of new bacterial plas-
mids containing combinations of re-
sistance to clinically iiseful antibiotics
unless plasmids containing such com-
binations of antibiotic resistance de-
terminants already exist in nature.
b Type 2: Linkage of all or seg-
ments of the DNA's from oncogenic or
other animal viruses to autonomously
replicating DNA elements such as bac-
terial plasmids or other viral DNA's.
Such recombinant DNA molecules
might be more easily disseminated to
bacterial populations in humans and
other species, and thus possibly in-
crease the incidence of cancer or other
diseases.

Second, plans to link fragments of
animal DNA's to bacterial plasmid
DNA or bacteriophage DNA should be
carefully weighed in light of the fact
that many types of animal cell DNA's
contain sequences common to RNA
tumor viruses. Since joining of any
foreign DNA to a DNA replication
system creates new recombinan,t DNA
molecules whose biological properties
cannot be predicted with certainty,
such experiments should not be under-
taken lightly.
Third, the director of the National
Institutes of Health is requested to give
immediate consideration to establishing
an advisory committee charged with
(i) oversecing an experimental pro-
gram to evaluate the potential biologi-
cal and ecological hazards of the above
types of recombinant DNA molecules;
(ii 1 developing procedures which will

Helling, Pror. Nafl. Acad. Sc:i. U.S.A: 70, 3240
(1973); A. C. Y. Chang and S. N. Cohen. ibid.,
71, 1030 (1974).

2. J. F. Morrow. S. N. Cohen, A. C. Y. Chang.
H. Boyer, H. M. Goodman, R. B. Helling,

ihid.. in press.

3. D. S. Hogness, unpublished results; R. W.
Davis. unpublished results; H. W. Boyer, un-
published results.

4. M. Singer and D. Soll, Srienre 181. 1114 (1973).

303