gestion of placenta depends in the Abderhalden test are essentially different from the substances obtained by immunisation of rabbits, or that they are both alike, but not enzymic in character. Further experiments along this line convinced us that the latter alternative is the correct one. We corroborated the earlier findings of Stephan and Hauptmann, that the complement plays an important part in the Abderhalden test, but also found that the specific enzymes (socalled) of Abderhalden behave, in every way, like antibody, as understood in the terminology of immunity. We also succeeded in exhausting the serum of pregnant individuals of its specific elements, and in actually sensitizing placenta-protein so as to obtain a positive ninhydrin test after the addition of fresh human or animal (male or female) serum.

Having thus convinced ourselves that the Abderhalden test did not depend on any enzyme specifically able to digest placenta-protein (since the addition of any serum favored a positive ninhydrin test, provided the serum was added to previously sensitized placenta) we concluded that the ninhydrin test is nothing but a new expression of the phenomenon which previously had been brought to light by the indicator of Bordet-Gengou, viz., hemolysis. Viewed in this light the Abderhalden test, without offering anything new on the theory or mechanism of immunity, introduces a very effective indicator of the occurrence of the reaction.

As to the mechanism of the test proper, I wish to state without going into the details of our experiments, that I have proof of the fact that in the Abderhalden test placenta is not digested, but that the amino-acids and polypeptids, which dialyse through the wall of the thimble, come from the serum. I have noted their appearance in a serum after it had been incubated with placenta-protein for some time, and under certain conditions. These dialysable products result from the digestion of the globulin in the serum by the accompanying serum protease; in other words, as a result of the autodigestion of the patient's serum.

The proteolytic ferment responsible for this auto-digestion is not specific, but is present in all fresh sera, in vivo as well as in vitro. The action of this ferment, while in the body, is arrested by the antitryptic action of serum constituents, among which are non-saturated fatty acids. The combination of any specific antibody (not of a ferment nature) with its antigen, in vitro, is also capable of removing the antitryptic inhibiting principle from the serum, setting free the protease which, in turn, digests the globulin fraction of the serum and produces dialysable substances.

Incidentally I wish to call attention to the fact that this autodigestion of serum may explain the mechanism of the phenomenon of the complement-deviation or complement-fixation, for, in each case where complement is fixed, there appear dialysable products that give a positive ninhydrin test and, vice versa, wherever the Abderhalden test is positive, the complement (as can be proved) is inactivated.

The auto-digestion of serum, induced by the removal of antitrypsin in Jobling's experiments, can be stopped by returning nonsaturated fatty acid to the serum. The auto-digestion of the serum in the Abderhalden test (which is due to the removal of the antitryptic inhibition from the serum of the patient, by the combination of serum antibody with placenta-antigen) can also be stopped by the addition of non-saturated fatty acids. According to my experiments, moreover, self-digestion of the serum results in the production of a toxic substance which appears to be identical with Friedberger's anaphylatoxin and, when occurring in vivo, is probably the cause of eclampsia. I am inclined to think from the results of some of our experiments, that here we have the clue to possible prevention of this much dreaded occasional accompaniment of child-birth.

In short, the Abderhalden reaction is specific, but depends not as Abderhalden believes, on the presence of specific enzymes, but on the presence in the blood of pregnant women of the specific antibody that combines with placenta antigen, and thus sets free the only proteolytic enzyme which is always present in the serum of every animal. When considered from this point of view, the Aberhalden test should be positive wherever the complement-deviation test is positive. I have obtained, in many instances, a positive reaction with the sera of syphilitics, using pure lipoid antigen, in which the only source of protein cleavage products was the serum of the patient. This again proves that not the substrate, but the serum itself, is digested in the Abderhalden test.

Western Pennsylvania Hospital,
Pittsburgh, Pa.

A NOTE ON THE ABSENCE OF MORPHINE FROM THE LIVER IN A CASE OF CHRONIC LAUDANUM ADDICTION

JACOB ROSENBLOOM

(Biochemical Laboratory of the Western Pennsylvania Hospital, Pittsburgh, Pa.)

There is considerable doubt regarding the nature of the transformations through which morphine may pass after its introduction into the animal body. It is possible that such morphine may be changed into oxidimorphine or some other derivative, or that a compound of morphine with cell material may be formed. However, in many cases of undoubted poisoning by opium or morphine, it has been impossible to detect this drug or alkaloid in the tissues or organs. Witthaus1 states that Lesser, in a case of post-mortem analysis, found morphine in the urine but not elsewhere in the cadaver. Lassaigne could not find morphine in the liver of a dog poisoned with 8 oz. of Sydenham's laudanum. Christison3 mentions four cases of death due to poisoning from laudanum where no trace of the poison could be detected. Woodman and Tidy could not detect any alkaloid in a case of laudanum poisoning. Haines could find no trace of morphine in the stomach in a case where 10 to 15 grains were taken. Haines also quotes the report of Surg.-Maj. Ross, who writes that in Bengal, in 1869, there were 45 fatal cases of poisoning by opium, and an analysis was made in each instance, yet in only two was opium detected in the stomach.

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The failures to detect morphine in the urine in cases of un

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doubted opium poisoning, as well as in the urine of morphinists, has also strengthened the idea that the alkaloid is modified or rendered undetectable in the system. However, Marquis after the injection of morphine into the circulation of cats, recovered from the liver 30 percent of the injected amount; and Antheaume and Mouneyrat, 10 in a case of morphine poisoning in an individual who had previously used 62 grains daily (recently 30 grains daily), but who had taken no morphine for the preceding two weeks, found morphine in large quantity in the liver.

As morphine, through its phenolic hydroxid, combines with sulfate to form a compound similar in structure to the ethereal sulfate normally contained in urine, the possibility of such a formation in the body suggests itself. Eliassow11 and Stolnikow12 have shown that the proportion of ethereal sulfates is increased under treatment with morphine. 13 The results of Rubsamen's11 experiments tend to show that a certain percentage of injected morphine disappears in the bodies of rats, and that this proportion is increased by habituation. The changes said to occur are effected by oxidation or by "pairing." There has been considerable controversy15 about these experiments, however, and the matter is still unsettled.

Babel claims that morphine is oxidized by brain pulp in vitro, Cloetta11 previously supposed that nerve tissue is vitally active in this direction. Rubsamen 14 could not verify in rats or rabbits the results of Babel's experiments. Tauber, 18 by perfusion experiments on the liver and kidney of pigs, found that these organs could not oxidize morphine, but Gerard and Ricquet1 showed that, by maceration with horse kidney pulp, morphine is oxidized to oxidimorphine and the latter is also reduced to the former.

It may be readily noted that there is considerable difference of opinion on the question of the transformation of morphine in the body. I recently obtained the liver, three hours after death, of a woman who had used large amounts of laudanum for about five years. It seemed of interest to determine whether morphine was present in this organ. A careful search for morphine by Dragendorff's process, as described by Witthaus, 20 showed that it was absent. As a control, 150 mg. of morphine sulfate were added to a liver; the same amount of morphine sulfate was isolated, proving that the technic was good. This result indicates the possibility that morphine is so changed in the body, that, under conditions as yet unknown, it cannot be recovered.

However, I have shown with Dr. S. R. Mills21 that, under certain conditions, morphine withstands decomposition in the presence of putrefying material. Ogier22 states that he has frequently failed to detect morphine in viscera, which had contained it, after putrefaction for from two weeks to one month. Tardieu23 found morphine in putrefying viscera after 45 days; Nagelvoort24 after 50 days; Marme25 after 8 weeks; Marquis26 after 2 months; Proelss27 after