APPENDIX O 
the third section of this paper we will examine some of the various 
parameters that are involved in determining the implantation of bacteria 
into the gut, and it will become apparent that this seemingly uncom- 
plicated process has so far defied analysis because of its complexity. 
In fact, there is bacterial pathogen at all for which we can state all 
the relevant characteristics which make it different from related non- 
pathogenic species. Textbooks of medical bacteriology often mislead 
the beginning student by showing lists of "virulence factors"* for each 
pathogen, which the poor fellow may even have to memorize. After doing 
so, the student still does not understand virulence* because the known 
(and more often only "suscepted") virulence factors represent only the 
tip of the proverbial iceberg of pathogenicity. For example, "the" 
virulence factor of the diphtheria bacillus is thought to be the well 
known toxin. However, the bacterial strain which is most active in pro- 
ducing this toxin (and which is therefore used in industry for this pur- 
pose) is not highly virulent, simply because it lacks other attributes and 
therefore cannot multiply or produce toxin in the mammalian body (2). 
Closer to our problem is the example of the enteropathogenic coli strains. 
It has been shown that such strains must have distinct virulence factors, 
in order to cause diarrheal disease. One such factor, a toxin, is the 
agent that induces the diarrhea. However, the K-12 strain of coli 
was unable to produce diarrheal disease in the animal gut even when it 
carried the gene coding for this toxin, again obviously because it 
lacked other equally important but as yet unidentified virulence fac- 
tors that would enable it to surrive in the intestine (3). The reader 
should note here that the coli strains to be used for recombinant 
DNA work are all derivatives of this K-12 strain. 
When applying for admission to the bar, lawyers often fail to mention 
the fact that their heart is capable of pumping blood, that their kidney 
can purify the blood and that their stomach can digest their breakfast. 
This is surprising because, if their organs did not have these capabilities, 
the applicants would be confined to a hospital which would have to supply 
a heart-lung machine, an artificial kidney and an Intravenous feeding 
device. Consequently such applicants could not practice law with the degree 
of efficiency to which their clients would be entitled. Nevertheless 
lawyers' applications are seldom rejected on the grounds of having omitted 
such vital information for the simple reason that "it goes without saying" 
that any specialized activity of man must be supported by the myriad of 
physiologic, metabolic and other functions which are essential to the life 
of the human body. Analogously, when medical microbiologists discuss 
"virulence" mechanisms of pathogenic bacteria they rarely point out that 
these mechanisms include all the myriad of metabolic functions and struc- 
tural features which every bacterial cell must have in order to survive. 
This fact is seldom emphasized because it is not very exciting and because 
it is so obvious that it "goes without saying". Consequently, the term 
Virulence factors are those characteristics which enable a pathogenic 
microorganism to cause disease. The terms "virulence" and "pathogenicity" 
are used here synonymously and refer to the ability to cause disease. 
Appendix 0--2 
