Arch Intern Med (Chic). 1930;45(4):641-646. doi:10.1001/archinte.1930.00140100165015.
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In 1922, Zeydner and van Leeuwen1 reported the presence of an alcohol-soluble, toxic substance in the blood of twelve persons suffering from asthma, urticaria and migraine which had a definite stimulating action on smooth intestinal muscle. The method of extraction of this substance, that of Freund,2 was designed to eliminate those normal stimulating and augmentor substances which may appear in any serum during the process of clotting. When safeguarded in such a manner, this technic yielded negative results with the blood serum of normal controls, whereas a definite action was demonstrable with the serum of persons with an "allergic disposition."

The many difficulties encountered in the utilization of blood extracts with Freund's method have been emphasized by Clark and Gross,3 who showed that the substance present in normal serum has a strong stimulant action on the isolated uterus and an irregular action on the isolated intestine of the rat. This


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