MICHAEL HEIDELBERGER 



Looking back from the present admittedly none too elevated 

 observation post, in which one must still duck occasional snipers' shots, 

 one cannot fail to be astonished that so many sound observations and 

 so many keen deductions were made in those early days. Next to 

 nothing was known of the chemical nature of antigens and antibodies, 

 the protagonists in the drama of immunity, while complement, the 

 powerful mediator of cell lysis, flitted in and out like the ghost in 

 Hamlet, between material existence and a mere "colloidal state" of 

 something else. Worse still, measurement of quantities of any of these 

 elusive unknowns could only be carried out in relative terms, such as 

 by the volume which just would kill or not kill an animal, or by the 

 dilution at which an inflamed skin area or a haze in a test tube just 

 faded out. Immunology, and the early immunochemistry as well, 

 staggered under the dictatorship of dilution and the tyranny of titer. 



Relief, happily, was just around the corner. Discovery of the 

 specific polysaccharides (2,8) in Avery's laboratory gave concrete 

 direction to the relation between chemical constitution and bacterial 

 specificity. Extension of chemical concepts to protein antigens was 

 facilitated by the imaginative and painstaking studies under Land- 

 steiner's (29) direction, in which aromatic radicals, optically active 

 acids, and amino acids were coupled to proteins through the diazo 

 reaction and their eff"ects on specificity studied. As for antibodies, 

 prolongation of the discussion as to whether these were serum globulins 

 or unknown substances adsorbed on globulins seemed futile after 

 Felton's simple method for the concentration of pneumococcus anti- 

 bodies led him to the demonstration that zinc and aluminum salts of 

 these globulins were completely precipitable by the homologous type- 

 specific polysaccharide of pneumococcus (5a). 



Though the chemistry of antigens and antibodies began to be 

 better understood, the fetters of the old, relative analytical methods re- 

 mained unbroken until Kendall and the writer (11), putting their faith 

 in the rigorous criteria of analytical chemistry, devised quantitative 

 micro methods for the accurate estimation of many antigens and anti- 

 bodies in absolute terms, that is, units of weight rather than of titer. 

 With Sia (19) they demonstrated the parallel between mouse protec- 

 tion and the amount of antibody pitrogen precipitated from anti- 

 pneumococcus type I serum by the specific polysaccharide of type I 

 pneumococcus. This was in 1930, but only in 1938 did the "brass 



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