75 
Pathogenicity depends on the complex interrelation between 
several properties of a given strain and the properties of the infected 
organism (2). For example, even pathogenic strains of E. coli (and 
other organisms) may be carried in certain parts of the intestines or 
in other parts of the body without causing disease. Their ability to 
cause disease depends on their residence in, and infection of, a very 
particular locality. Thus, in order to cause disease, they must have 
both the genetic capability for pathogenicity and a genetically determined 
ability to establish themselves in a suitable environment. 
It is difficult to conceive how K-12, itself nonpathogenic, could 
become pathogenic as a result of either spontaneous changes or changes 
brought about by manipulations in recombinant DNA experiments. After 
many years of laboratory manipulation, K-12 is highly attenuated. Its 
only known habitat is in biological laboratories. One laboratory which 
has studied the pathogenesis of E. coli infections for the past 10 years, 
reports having observed no genetic modification of K-12 which was 
sufficient to permit the strain to cause overt disease in any animal 
model studied (9). 
Even when genetic determinants known to cause pathogenicity in 
other E. coli strains were introduced into K-12, no instance of conversion 
to pathogenicity was detected, either with regard to diarrheal disease 
or urinary tract infection (8, 9). Certain genetic manipulations did 
yield K-12 that was better able to multiply within the gastrointestinal 
tract, but these organisms were usually less robust than the E. coli 
strains normally found in feces (not K-12). ~ 
This result was in contrast to that obtained with fecal E. coli strains 
(not K-12) which could be converted to pathogenic forms by" the same 
manipulations. These workers concluded that the inadvertent trans- 
formation of K-12 into a highly pathogenic form by the acquisition 
of a single fragment of foreign DNA in a recombinant DNA experiment 
was highly unlikely (9). 
The possiblity that K-12 could become pathogenic is discussed in 
detail in a paper by R. Freter (11). A relevant portion appears as 
Appendix O. 
