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Transfer of Foreign DNA from E. coli K-12. While the conversion 
of K-12 into a pathogen by the insertion of foreign DNA fragments 
appears impossible, the foreign DNA fragment could be transmitted 
to another bacterium with which the K-12 comes in contact, including 
other strains of E. coli. Such a transmission might result in insertion 
of the foreign DNA fragment into a known pathogen, or might convert 
the recipient into a pathogen, even if the original K-12 host cell does 
not multiply and live. Transfer of plasmids or bacteriophage, the 
vectors for the foreign DNA in K-12 systems, is a complex biological 
phenomenon. (See references 2 and 24 at the end of this section, and 
also the detailed discussion in Section III-A-1 of the Guidelines.) The 
following analysis of existing information indicates that with those 
K-12 -vector systems permitted by the Guidelines, the likelihood of 
transmission is extremely remote. 
The case of plasmid vectors is considered first. Certain plasmids 
are inherently able to transfer themselves from one bacterial cell 
to another. The Guidelines do not permit the use of such plasmids 
(called "conjugative" plasmids) for recombinant DNA experiments. 
Other plasmids only transfer themselves from one bacterial cell to 
another with great difficulty or not at all, and these plasmids (non- 
conjugative) may be used in recombinant DNA experiments. 
However, a nonconjugative plasmid can be transferred much more 
readily if the cell harboring it is invaded by a conjugative plasmid. The 
conjugative plasmid confers upon the nonconjugative one the property of 
transferability. Therefore, even with a nonconjugative plasmid, the 
possiblity of transfer of the foreign DNA segment exists, though to 
a much lower extent. 
The extent can be estimated by considering the probability that 
each of the necessary events takes place. There are extensive 
experimental data permitting such estimates: the probabilities differ 
depending on the particular plasmids being considered. With certain 
K-12 plasmid systems, it has been estimated that the maximum probability 
for transmission of a nonconjugative plasmid vector from a K-12 host 
16 
cell is 1 in 10 (that is, 1 in 10, 000, 000, 000, 000, 000) K-12 surviving 
per day in the intestinal tract of warm-blooded animals (7, 8). 
The probability is even lower in sewers, sewage treatment plants, 
streams, and rivers. Most of the estimates of the probability of trans- 
fer of a nonconjugative plasmid are derived from data obtained under 
laboratory conditions. Knowledgeable experts believe that the probability 
will be even lower in natural environments, such as animal intestines 
(8). Nevertheless, the uncertainty indicates that animal and human 
feeding studies are required to verify the predictions (12). The 
extensive information on which these conclusions were based are 
summarized in reference 7. 
