24 
treatable with present-day antibiotics could be made resistant to that 
therapy. The introduction of genetic determinants conferring antibiotic 
resistance or combinations of antibiotic resistance into bacterial species 
not now known to contain them could compromise the effectiveness of some 
of our weapons against infection. 
For example, the beta hemolytic Streptococci and certain Pneumococci 
bacteria which can produce serious infections in man, are even today gener- 
ally killed by relatively low levels of penicillin. The inadvertent or 
even the intentional introduction of genes conferring high levels of peni- 
cillin resistance to these organisms would be most unfortunate if such a 
strain got loose in the population. 
Similarly, the transformation of relatively harmless bacteria into 
ones that can produce toxins such as diphtheria, cholera, or other entero- 
toxins would certainly seem to constitute a significant risk. 
An additional concern is that fragments of foreign DNA introduced into 
bacteria may include, in addition to the genes which the investigator has 
selected for study, other genes which he has not yet identified and which, 
if they became established in natural IS. coli populations, might release 
harmful products for man, plants, or animals. 
Another risky experiment is to introduce genes from tumor viruses into 
bacteria. In fact, it was just such an experiment that my own laboratory 
had proposed and deferred more than 3 years ago. SV40, adenovirus, and 
herpes virus can cause cancer in animals. We could learn something about 
how this occurs if we could put all or parts of these viral chromosomes 
into a simple bacterium like j£. coli . But our intestines are full of 
_E . coli , and one may ask whether it would be harmful to have IS. coli in our 
gut carrying genes from viruses that can change normal cells into cancer 
cells. 
The answer to that question is that we don't know, and moreover, the 
answer is very difficult to obtain. It is possible that such infections 
might not produce immediate symptoms, and therefore it might be years be- 
fore harmful effects of a tumor virus became evident. 
One very powerful feature of this technology is the ability to clone 
specific DNA fragments from the total DNA of plant and animal cells of di- 
verse sources. We refer to such experiments as "shotgun" experiments. 
Inasmuch as many mammalian and even lower animal-cell chromosomes are 
known to contain sequences common to tumor viruses, the indiscriminate and 
careless handling of modified bacteria produced in such experiments could 
loose carriers of carcinogenic potential. 
A particularly worrisome feature of _E. coli is its untiring promis- 
cuity. In fact, it is that very attribute that has made _E. coli a favorite 
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