Statement by June E. Osborn, M. D. Professor of Medical Microbiology 
and Pediatrics, University of Wisconsin-Madison 
September 15, 1978 
My purpose in making a comment concerning the revised guidelines for 
recombinant DNA research is to support the general direction of 
proposed changes, rather than to comment on specific provisions. I 
am a pediatrician who specializes in infectious diseases and also a 
microbiologist whose primary focus has been mechanisms of pathogenesis 
of microorganisms. As such I have been concerned from the outset of 
the recombinant DNA debate with the relative lack of recourse to the 
substantial fund of knowledge concerning known pathogenetic mechanisms 
of genuinely virulent organisms. The inference has sometimes been 
that pathogenetic mechanisms of microbes are generally unknown and 
mysterious and that, once pathogenic, organisms are uniformly so 
in an all-or-none fashion. As I read the revised guidelines 1 was 
therefore pleased to note that the proposed changes move substantially 
toward a thoroughly rational, cautious approach to facilitating 
advances in research under conditions of sensible containment. 
Perhaps some consideration of known facts about pathogens will amplify 
my first point: that the revised guidelines are sensible in their 
emphasis on the human host who would be the initial biologic target 
of an inadvertently released vector. A healthy adult who is not 
undergoing antimicrobial or immunosuppressive therapy is usually an 
effective barrier even against pathogenic miotoorganisms that have 
been millenla in the making. For instance the meningococcus - which 
can produce meningitis and/or overwhelming sepsis - is far more 
commonly carried by a substantial fraction of the population as a 
harmless component of the throat flora in the winter months. More 
pertinently, "virulent" E. coll organisms - not even the weakened 
strains about which much debate has centered * are poor pathogens 
at best; and while certain bacterial products made by some strains 
are thought to augment their potential Invasiveness, the vast 
majority of instances of serious E. coli disease occur in infants 
or in hosts with immunologic or anatomic predisposition. 
My second point is complementary to the first: even the most 
virulent of microorganisms has a "dosage" threshold below which 
its mechanism of pathogenesis fails. When persons are bitten by 
a demonstrably rabid wolf, less than half proceed to get rabies; 
and the presumed reason for the others' failure to become ill is 
a dosage effect. It has been shown experimentally that 20,000,000 
virulent group A streptococci are required in order to establish 
a pharyngitis in human volunteers; and a million coagulase positive 
staphylococci can be Injected into healthy human skin without causing 
disease (whereas the presence of an inert foreign body such as a 
suture in that skin suddenly allows 100 staph to establish purulent 
infection - again emphasizing the importance of the host's role in 
successful pathogenesis by microorganisms). 
Insofar as mechanisms of pathogenesis are concerned, much again is 
known about the established pathogens of man. Group A streptococci 
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