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1. A study has been made of natural agglutination as exemplified by the reactions of the serum of nine animal species with a variety of bacteria.  2. End-titres are recorded, and the fact is noted that sera of different animal species show an order of agglutinating activity which is almost constant for all organisms used. Ox, pig and horse sera give consistently strong reactions, while specimens from rabbit, guinea-pig and rat react weakly or not at all. Sheep, human and cat sera occupy an intermediate position. Variations are noted, however, with different individual specimens of serum from the same species.  3. Organisms of the series tested can also be grouped in order according to their apparent susceptibility to agglutination by normal sera.  4. The serum of young animals is found to be deficient in the agglutinating principle.  5. The agglutinating effect shows a thermolability intermediate between that of complement and the immune agglutinins. Complete inactivation occurs as a rule after exposure to 60° C.–65° C. for half-an-hour. For certain strains the serum principle is inactivated at much lower temperatures.  6. Lability curves show marked irregularity. In certain cases a zone of relative inactivation is produced at a temperature of 55° C.  7. The natural agglutinating substance is found to be present in greater degree in the carbonic acid insoluble fraction of serum than in the carbonic acid soluble fraction. In this respect it differs from the immune agglutinins, which are chiefly located in the carbonic acid soluble moiety.  8. The agglutinating principle for each organism can be absorbed completely by the homologous strain, when a variable lowering of the end-titre for other unrelated organisms results. A similar lowering of activity for these organisms may be produced by treating the serum with non-specific physical absorbents. Charcoal and Kieselguhr were used to demonstrate this.  9. By the technique of double absorption it can be shown that agglutination depends on non-specific and specific factors and it is concluded that normal serum agglutinates bacteria in virtue of a twofold mechanism:  ( a ) A non-specific effect reacting in varying degree with all organisms and removable by treatment with a finely divided absorbent.  ( b ) A series of specific effects reacting as true “natural antibodies.” These specific antibody-like principles exist for a wide variety of organisms. Absorption of any one organism removes the homologous effect leaving the remainder quantitatively unimpaired.  10. The question of bacterial variation and receptor analysis in relation to the natural agglutinins is being studied and will be reported on at a later date.

Observations on the Occurrence, Characteristics and Specificity of Natural Agglutinins