Complement-Deficient Guinea-Pig Serum
Authors: Hyde Roscoe R. 
Published: January 2023

Summary
A stock of guinea-pigs obtained from the Vermont Agricultural Experiment Station through the courtesy of Dr. F. A. Rich has shown a very marked deficiency in complement. Our results in this respect are in complete agreement with those obtained by Moore and Downing. Our evidence substantiates the claim of Coca that in these pigs the third (heat resistant or yeast absorbed) complement component is missing. The deficient serum may be activated for hemolytic tests by the addition of very small amounts of fresh human, guinea-pig, dog, cat, or rabbit serum, but not with the fresh serum of the ox, pig, duck, chicken, pigeon, sheep, frog, goat or mouse. Heated human serum is a potent activator. Certain sera have supplied as many as 5000 activating units per cubic centimeter. The deficient serum is activated in vivo by injections of the fresh or heated serum from the normal guinea-pig or man. The activation is instantaneous after intravenous injections, with subcutaneous or intraperitoneal injection the activation is from four to eighteen hours later. The animal returns to its previous non-complementing state after three or four days. Complement-deficient serum is lytic for red corpuscles provided that large quantities of sensitizing serum are used. The deficient serum becomes active under these conditions because the sensitizing serum supplied the factor which the deficient serum lacks. This factor seems to be the third or thermostable complement component, since (a) hemolytic sera that are capable of sensitizing corpuscles for the complement-deficient serum lose this power after treatment with yeast, although the hemolytic titer has not been reduced, (b) serum heated above 56°C. loses its power to react with deficient serum while it is still very potent in reactions with normal guinea-pig serum, (c) on aging, hemolytic sera become non-reactive with the deficient serum but retain the power to react with normal serum, and (d) a very potent hemolytic serum was encountered which would not sensitize corpuscles for the complement-deficient serum regardless of the number of hemolytic units added to the reaction. This evidence denies Ecker's claim to the effect that the susceptibility of the corpuscles to the lytic action of the deficient serum is due to supersensitization per se. The third complement component would seem to share certain properties usually attributed to enzymes since it brings about changes out of all proportions to the amount involved. This component although produced by a living organism, is not in itself living in the sense that it possesses independent power of growth and reproduction. It effects changes not merely by virtue of its quality but also by virtue of its quantity. The complement-deficient guinea-pig would seem to hold its own quite as well as the normal when kept under ideal conditions but succumbs more readily when the environment is adverse. The complementing condition of the deficient guinea-pig is not modified as a result of keeping the animal on a diet of grass, raw vegetables, etc. The complement-deficient condition behaves in heredity as a simple recessive Mendelian unit which gives clean-cut segregation from its normal allelomorph. The third complement component does not pass through placenta from mother to offspring. Neither does it pass from the fetus to the mother. The third component is of autochthonic origin and whether or not it is present is determined by the inherited genotypical make-up of the zygote. The recent claim of Guyer to the effect that acquired characters impress themselves on the germ plasm by way of the blood stream finds no support in light of the clear-cut lack of influence which is shown to exist between the third complement component in the blood and the gene for this character in the germ plasm of the guinea-pig.