APPENDIX O 
Excerpted from a paper by Rolf Prefer: Real and Imagined Dangers 
of Recombinant DNA Technology: The Need for Expert Evaluation (1977). 
To be published by the University of Michigan Press in a monograph. 
The Recombinant DNA Debate. 
II. Can E. coll become a super-pathogen capable of suddenly wiping out 
large segments of the human population ? 
The main argument to be made concerning this question is quite 
straightf onward and can be stated in a single paragraph; 
The cliaracteristics which a bacterial pathogen must have in order 
to cause disease in man or animals are exceedingly complex. While much 
remains unknown in this area, it is clear however that a given bacterium 
must possess a very large number of attributes, before it can colonize 
man and cause disease. For example, a typical pathogenic bacterium must 
be able to (i) survive in the environment (water, sewage, air, etc.) in 
order to spread from one host to the next. It must then (ii) be able 
to multiply on the body surface (skin, nose, throat) or in the intestine, 
or lung. It must (iii) have some mechanism for penetrating into the 
body, for (iv) spreading throughout the body and (v) to resist the numer- 
ous defense mechanisms of the mammalian tissue. Pathogenic bacteria must 
finally (vi) be able to produce a toxin or to othen^ise interfere with 
the host's physiology to bring about the symptoms which we recognize as 
disease. Each of these various stages requires that the bacterium possess 
a discrete and complex set of characteristics in order to survive. If 
only one of these characteristics is missing, the chain is broken and 
the bacterium will be stopped in its progress and will be unable to cause 
disease. For this reason, and fortunately for us, only very few of the 
many thousand bacterial species are capable of causing human disease, 
because only those few microbes possess the complete set of the essential 
characteristics. The new recombinant DNA technology makes it possible to 
insert into a microorganism a relatively small piece of DNA which will 
add one or ^ few new characteristics to its new microbial host. If new 
genes are inserted into an initially apathogenic, or into a specially 
"enfeebled" microorganism (as required in the NIH guidelines) , it is 
exceedingly improbable that these newly introduced characteristics in- 
cl\jde every single member of the large set of characteristics which are 
required to convert the enfeebled microorganisms into a functional patho- 
gen. 
As always in biology, there are of course exceptions to this generali- 
zation. An obvious one are pathogens such as the diphtheria bacillus, 
cholera vibrio and the pathogenic JE. coli strains which do not need to go 
through the whole sequence, but which settle on the surface of the throat 
or the intestinal wall and produce a toxin at that location. It is this 
toxin which, in turn, will enter the tissues of the body and cause 
disease. But, even with these types of pathogens, the apparent simpli- 
city of the manner in which they cause disease is highly deceptive. In 
Appendix 0--1 
