54 
Analogous considerations apply when bacteriophages are to be used 
as vectors for foreign DNA. Bacteriophage vectors could be spread 
either as mature bacteriophage, or in cells carrying the phage DNA 
inserted into its own chromosome or as a plasmid. The widely studied 
bacteriophage lambda might best be used to illustrate relevant con- 
siderations, since it is often employed in recombinant DNA experiments. 
Considering first its escape as a phage particle, lambda is sensitive 
to the acidity of the stomach and is likely to be destroyed there. Normal 
intestinal strains of E_. coli are usually not susceptible to infection by 
lambda, and in fact, susceptible strains are rare in nature. Further, 
11 
in at least one case, ingestion of 10 (1 00, 000, 000, 000) lambda 
particles yielded no detectable lambda in resulting feces. Lambda 
is also readily destroyed by drying in air. Dissemination of lambda 
recombinants can be minimized by use of mutant varieties of lambda 
which lack genes necessary for insertion into the host chromosome: 
with such phage the frequency of integration into the host chromosome 
-5 -6 
is reduced to 10 or 10 (1 in 100,000 to 1, 000,000). Finally, 
conversion of lambda DNA to a stable plasmid is also a relatively 
-6 
unlikely event, occurring at a frequency of about 10 
EKl containment. Considering, then, the properties of E. coli K-12, 
as well as those of the existing plasmid and bacteriophage vectors, the 
Guidelines conclude that, in the use of such host-vector systems, 
recombinant DNAs are highly unlikely to be spread by the ingestion 
or dissemination of the few hundred or thousand bacteria that might 
be involved in laboratory accidents, given standard microbiological 
practice. Therefore, these existing systems, and analogous combina- 
tions of E. coli K-12 with other vectors and bacteriophages, are judged 
to offer a moderate level of biological containment and are defined 
as EKl, the lowest level of biological containment for experiments 
with E. coli systems. Other prokaryote host-vector systems need to 
be evaluated using the same general principles as those applied to 
the E. coli K-12 situation. 
