In 1930 Tillett and Francis (1) found that in certain infectious diseases, notably lobar pneumonia, the serum obtained from patients during the acute stage of the illness yields a precipitate in the presence of dilute solutions of the C polysaccharide of Pneumococcus. In pneumonia the precipitation test is positive during the height of the disease and becomes negative shortly after the onset of recovery. Thus the precipitating action of the serum closely parallels the clinical course of the infection. Although the particular carbohydrate used as test reagent is derived from Pneumococcus, the presence of the active substance in serum is not limited to pneumococcal diseases but occurs in a number of other infections such as acute rheumatic fever, bacterial endocarditis, and staphylococcal osteomyelitis. Ash (2) confirmed and extended these findings and showed that the "C-reactive" substance is demonstrable in sera obtained from children during the acute stage of infections due to Gram-negative bacilli of the colon-typhoid group. In view of the observations cited above it is evident that the phenomenon is associated with a variety of acute pathological conditions and is not specific with respect to the inciting agent.In 1934 Francis and Abernethy (3) published a preliminary report on the occurrence in patients during the acute stage of pneumonia of a characteristic skin reaction following the intracutaneous injection of 0.1 mg. of the C carbohydrate. They showed that the skin reaction is correlated with the precipitating action of the serum in vitro. These results were later confirmed by Finland and Dowling (4). Recently Abernethy and Francis (5) using a more highly purified preparation of the C polysaccharide corroborated the earlier work and emphasized the striking agreement between the results of the serological and cutaneous tests. In all patients in whom the disease terminated in uneventful recovery they found that both the serum and skin tests were positive during the acute febrile period and became negative shortly after crisis. With the development of complications, the capacity of the skin and serum to react may persist or reappear. Only in fatal cases have the results of the serological and cutaneous tests failed to agree. In these instances it has been observed that the skin may fail to react although the active substance can be demonstrated in the blood at the time of death.In a subsequent paper (6) Abernethy reported the results of a study of the precipitation reaction with sera obtained from experimentally infected animals. He found that the serum of monkeys (Macacus cynomolgos) acutely ill with experimentalType II Pneumo-173

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In 1930, Tillett and Francis (1) observed that the sera of individuals acutely ill with lobar pneumonia possess the capacity of precipitating a non-protein, carbohydrate fraction derived from Pneumococeus. This fraction was termed the C substance. It was shown that the precipitating action of patients' serum with the C substance is demonstrable early in the course of pneumonia, persists throughout the course of the active disease, and disappears during convalescence.Subsequent tests with sera from certain other diseases showed that the precipitation of fraction C is not limited to the sera of individuals with pneumococcus infection. The phenomenon was also demonstrated in cases of rheumatic fever, bacterial endocarditis, and lung abscess, but not in all febrile diseases. The sera of patients suffering from malaria, tuberculosis of the lungs, typhoid fever, measles, and varicella did not react with fraction C. While the exact nature of the mechanism of the precipitation reaction with C is not understood, Tillett and Francis suggested that the principles involved in the anamnestic reaction described by Cole (2) might be used to explain the phenomenon.Further studies by Tillett, Goebel, and Avery (3) on the chemical and immunological properties of the C substance showed that it is a complex polysaccharide contained within the body of the pneumococcus cell. It is species specific and is found in all pneumococci irrespective of type or virulence. It is distinct from the type specific capsular polysaccharide not only in its chemical properties but in its serological reactivity. Later, Heidelberger and Kendall (4) showed, in a study of the chemical properties of the polysaccharides of Type