BERRY 



nothing of the kind has been attempted. Should it be done ? Well 

 might we provide the answer. 



The uncertainties, the difficulties, and indeed the impossibilities 

 of scientific experimentation with human beings in most research 

 with infectious diseases forces theuseof laboratory animals. There 

 is ample precedence in the area of cold since a century ago when 

 Pasteur reported his classical work with anthrax in chickens. The 

 birds were resistant until chilled by a cold rain (Pasteur et al., 

 1878). In the intervening years the literature is adequate to prove 

 that Pasteur's observations were not isolated findings. Other animals 

 may or may not respond in modified form to infectious challenge, 

 depending upon a number of variables, but there are sufficient ex- 

 amples to leave no room to doubt that host- parasite interaction is a 

 plastic phenomenon under the pressure of certain environmental 

 changes. 



Confrontment with the established fact still leaves an enormous 

 area for elaboration. When animals are known to become more 

 susceptible to infectionj there is always the question of why. It is 

 axiomatic by now to offer certain tentative explanations. It can be 

 said, for example, that the defenses of the host have been weakened. 

 These include the humoral defense, the cellular defense, a weaken- 

 ing of the barriers to invasion, plus various combinations of them 

 all. Even if there is evidence for change in any one of the defenses, 

 it is still necessary to seek out the basis for the change. It is also 

 possible that virulence ofthe pathogen is enhanced. Without attempt- 

 ing to define virulence, agreement hopefully is assumed that it 

 comprises many facets, any one of which may become primary in a 

 particular situation. Again, it is desirable to understand the nature 

 of the virulence change whenever it plays a role. There are, in 

 addition, somewhat more elusive concepts that can be reasonably 

 offered to explain an elevation in host susceptibility. The in vivo 

 environment on which pathogen proliferation depends, be it intra- 

 cellular, extracellular, or both, can conceivably be enriched. There 

 is less direct evidence for this than one would wish, especially for 

 the bacteria, but virus multiplication is known to be iritimately 

 linked with the metabolic vigor of the parasitized cell. By contrast, 

 the host might be put in the position of heightened sensitivity to the 

 toxic manifestations of the disease state. 



