# Defensive Ferments of the Animal Organism/Defensive Ferments of the Animal Organism/Section 5

​Prolonged observations on a particular case of definite disease will be of the greatest importance. It would be absurd to investigate, say, a hundred ​cases of tuberculosis, of paralysis, or of dementia præcox, &c., without carefully considering the clinical aspect of each of them. Above all, one ought to make a continuous study of certain types of disease in their different stages. Thus, for instance, epilepsy ought to be observed before, during and after its onset, at the period of remission, and so on.
The normal individual also offers opportunities for such studies, on such occasions as the advent of puberty, the climacterium, &c.
All the various forms of nephritis supply another important field of research. Does the kidney play an active part in individual cases, or does it only excrete albumen that is out of harmony with the blood plasma—that is, does it, in the main, play only a passive part? The following observation illustrates a case of this kind. Serum, from a female patient suffering from nephritis gravidarum, decomposed placenta-albumen and placenta-peptone with great difficulty. The rotation of the serum was unusually high. When this serum was mixed with that of a normal pregnant patient, a change was observed in the rotation of the mixture; and the fact that this was due to a decomposition was proved by the dialysation method. Neither serum, dialysed by itself, showed any decomposites of albumen. When both sera—the one from the case of nephritis gravidarum, and the other from the normal pregnant person—were subjected ​to dialysis together, peptone appeared in the dialysate. This case evidently has to be explained as follows:—
As in every case of pregnancy, the blood was filled with substances out of harmony with the plasma—in this case, obviously, proteins. Normally, these compounds are removed by decomposition, with the help of the ferments. In the case of the female patient suffering from nephritis gravidarum the decomposition was evidently very incomplete, in consequence of which the disharmonious proteins accumulated rapidly, and had eventually to be removed by the kidneys.
This observation agrees very closely with some results obtained by Aschner, who observed that the albumen found in the urine during eclampsia is decomposed by the serum of pregnant individuals, although this is not the case when albumen is taken from a case of ordinary nephritis. It is obvious that traces of a specifically constructed albumen are quite sufficient to produce the effects of a decomposition by specifically directed ferments. Of course, we have no right to conclude, on the strength of this fact, that, because the serum of pregnancy reacts quite specifically towards particular urine-albumens, therefore all the excreted proteins belong to a particular type. The eclampsia may be coupled with an ordinary case of nephritis, or follow it.
​Each individual case of albuminuria presents analogous problems. Can the serum decompose urine-albumen, or does it disintegrate the tissues of the kidneys? Is the normal tissue of kidneys decomposed, or only pathologically altered? Let us point out, at this stage, that the determination of the power of rotation of the serum may itself be sufficient to direct us towards various important observations. May there not be a hyper- and a hypoproteinæmia? Is there any albuminuria which is based exclusively on heteroproteinæmia? Bence Jones's albuminuria and the typical albuminuria of pregnancy very likely represent such cases. It would obviously be incorrect to designate such kinds of albuminuria as being conditioned by nephritis.
In this connection we would lay stress on the fact that eclampsia, and the toxæmias of pregnancy, present us with a fruitful field for researches on their special conditions. Up to the present it would appear that the prognosis of eclampsia is the more unfavourable, according as the decomposition of the proteins disharmonious with the plasma is the less complete. It goes without saying that we must not jump to broad conclusions on the strength of these observations. We have never ventured to assert that the deciding factor in eclampsia is the insufficient decomposition of the disharmonious substances; and, ​indeed, it is quite likely that this is a secondary phenomenon. The fact, that in cases of eclampsia a disturbance may occur in the functions of the liver, deserves much attention. In two cases—the only two which have been investigated along these lines—a disturbance of the functions of the thyroid gland was also found.
A very useful field of research is also supplied by the tumours. Carcinoma, in particular, should give rise to substances that are out of harmony with the blood plasma, and so to defensive ferments. Our own experience has shown, that the serum of carcinomatous patients decomposes boiled carcinoma tissues, but not placenta. On the other hand, decomposition of carcinoma by the serum of pregnancy was never observed. According to our experience it was possible to obtain an early diagnosis of carcinoma. Moreover, the method may perhaps be of use for controlling the therapeutic methods used in cases of carcinoma, whether they be of an operative or of any other character. From a fortnight to three weeks after the disappearance of the carcinoma cells, the ferments that are directed against cancer should also disappear, if we are to judge from present experience.
Finally, we shall have to consider the diseases of metabolism, and all such phenomena as are etiologically wrapped in obscurity, as, for instance, various dermatoses, sympathetic ophthalmia, &c. Here we ​shall have to test one organ after another, until we meet with one against which defensive ferments are to be found. The exact study of the so-called nutritive disturbances of the suckling will, from this point of view, be of much interest.
Moreover, we shall certainly be in a position to determine experimentally, as well as by means of clinical observations, the best method of attacking certain poisons, such as lead, nicotine, alcohol (methyl, ethyl, &c.), ether, chloroform, morphia, &c. We shall be able to delimit primary and secondary injuries, and to shed new light upon many problems of toxicology and pharmacology.
In conclusion, we should like to summarize the researches which have been published since the appearance of the first edition of this book. We ourselves have at our disposal more than 500 cases of differential diagnosis between pregnancy and non-pregnancy. In these cases complications of all kinds were present, salpingitis, carcinoma, myoma, parametritis, tuberculosis, &c. With the exception of one uncertain case of probable abortion, no mistakes have been made in our diagnosis. In addition, forty-two cases of carcinoma have been investigated. The serum of carcinomatous patients decomposed similar carcinomatous tissues after boiling, but never tissues of placenta.
We ought to point out here, that we must never ​rely, in these investigations, upon one particular boiled organ. The great advantage of the whole method of investigation is the fact, that it is possible to make each case absolutely sure by means of control experiments. Placenta, for instance, can always be tested by means of serum from definitely non-pregnant individuals, as well as from males. Further, all kinds of organs should be subjected in turn to the action of a particular serum.
The sero-diagnosis of pregnancy has been recently employed with success by numerous scientists. While many observers agree with our point of view, that the defensive ferments which appear during pregnancy are directed against the albumen of placenta, other authors are of the opinion that no strictly specific action exists. But surely positive facts have more value than negative ones.
We are so strongly persuaded, from our own experiences, of the certainty of our methods, that we do not hesitate to demand that no one should deal with pathological cases by means of the dialysation method and the optical method, who has not given evidence of having been able to produce 100 per cent. of correct diagnoses from pregnant, and particularly from non-pregnant, individuals, using placenta as his substrate. Should the technique of the student be ​found wanting in this branch of practical application, then it is quite certain that he has not mastered the method, and no special investigations should be undertaken without such a certificate of capacity. No conscientious student should make use of a particular method without having made sure, by some means or another, that he is master of it; and the diagnosis of pregnancy supplies these means.
A further important rule is, that we must never allow current theories to mislead us. The assumption of a specific action of the defensive ferments has been established on the strength of the facts derived from experiments, but it has still to be supported by means of exhaustive investigations. Nor should any final conclusion ever be expressed in regard to a particular case, until it has been definitely determined by clinical means. It is in this respect that pregnancy offers such a sure basis. we do not know of any other condition which allows of such a clear and indubitable estimate of method. It either exists or it does not, and is never open to a discussion of "probabilities."
Valuable service is rendered to research as a whole, if every case, which gives an unexpected result in respect of its reaction, is thoroughly investigated. In the first place the dialysation tubes should be changed, or else another organ should be used. If the result always recurs, we still have to exclude the ​possibility that, in the organ used, substances are inherent which are also contained in other organs. In saying this we are thinking of such a case as the following. It may be that an individual has some diseased connective tissue in some part of his body. The supporting tissues of the organism also have their metabolism, and are quite able to give off disharmonious products into the blood, especially if they are profoundly altered or broken down. Every organ contains connective tissues, though whether they possess an organically specific structure is highly doubtful. It would certainly be of the greatest importance, if so-called failures were tested with connective tissue pure and simple, and then with the corresponding organ without its connective tissue. It would also be advisable, in the case of unexpected results, to test with the albumens of blood serum, and those of blood corpuscles. Studies of this kind will lead much more quickly to clear results than the hurried collection of data which have probably been all subject to the same source of error.
Amongst other observations which have been communicated up to the present time we shall refer to the following. Epstein found that out of thirty-seven cases of cancerous patients all but one, originating from a cachectic patient, aged 80, decomposed the coagulated albumen of carcinoma, while in no one case was the albumen of placenta ​attacked. Further, the serum of forty-seven individuals who undoubtedly had no carcinoma, but who, on the other hand, had at least partly suffered from serious illnesses resulting in general loss of strength, was tested for their action upon the tissues of carcinoma. In forty-six cases no decomposition took place. Ludke and Gambaroff also announce favourable results in regard to the diagnosis of carcinoma.
Some interesting observations of Paltauf may be quoted, as specially advocating the acceptance of ferments which are specifically directed against particular substrates. The tissue of a tumour from a woman, aged 61, was not attacked by the serum of a carcinomatous patient which decomposed carcinomatous tissues, although at the same time the coagulated tissue was decomposed by the serum of pregnancy. The pathological diagnosis was as follows: Malignant chorionic epithelioma.
Bauer draws attention to the demonstration of defensive ferments in the blood serum, in cases of endemic goitre, which are able to decompose the tissues of the thyroid gland. These ferments have also been observed, even when no goitre was present, while the clinical phenomena pointed to a disturbance of the functions of the thyroid gland. We, too, have found a decomposition of the tissues of the thyroid gland in one case of myxœdema. There is no doubt that in these diseases we are dealing, not with an ​athyreosis, as was once supposed, but with a dysthyreosis.
The symptoms in Basedow's disease are of particular interest. Here we find decomposition of the thymus gland, of the thyroid gland, and very often of the ovary, as has been established by Lampe, Papazolu, and Fuchs, on the basis of a large amount of material. No other organ was decomposed. It is interesting to note, that normal thyroid gland was decomposed only in very exceptional cases, while Basedow thyroids were always attacked.
This observation points to two possibilities in regard to the production of substances out of harmony with the plasma. Sometimes the normally constructed cell is incapable of completing the otherwise normal decomposition of particular substances, so that materials appear in the blood which still show the characteristic features of the cell, from which they originated. The decomposition is discontinued at a particular stage. A certain analogy with this kind of disturbance of cellular metabolism is presented by those anomalous cases, in which simpler products are not fully reduced. We may refer to cystinuria, alkaptonuria, pentosuria, &c. In the first case cystin, in alkaptonuria, homogentisic acid, and in the last case a pentose, are excreted in the urine. Some forms of glycosuria also belong here. The cells are unable to attack the grape sugar, because no active ​ferment is present which can act on this carbohydrate.
Further, the cause of disharmony with the blood plasma may depend upon the fact that cells of a particular kind have degenerated, in consequence of which they have a pathological structure, and give off a disharmonious kind of material, to which the blood plasma is unused.
We may also mention the experiments of Bauer and Reines, made for the purpose of clearing up the etiology of sclerodermy. The actual experiments point to a disturbance of the functions of the thyroid gland; but it is probable that other organs are affected sympathetically. In these experiments, also, it appears that certain organs are decomposed, while others are not.
Fauser, Wegener, Job. Fischer, Kafka, and others report numerous observations on cases of dementia præcox, paralysis, and melancholia. In the first-named disease defensive ferments appear against the sexual glands and the cortex of the brain. According to our ideas this means that these organs exhibit a disturbance of function, though which organ primarily discontinues its functions cannot at present be ascertained. In cases of melancholia no defensive ferments have as yet been found. In paralysis the cortex of the brain is nearly always decomposed.
These researches naturally do no more than imply ​a rapid advance into unknown territory. There are still many stages to go over again, before we can arrive at a definite picture. A serological examination must be first employed, and the clinical diagnosis, which is generally more uncertain, will be compared with it. Often later observations alone will show, whether the serological diagnosis is really correct. It will be particularly necessary to make our clinical description of individual cases as thorough as possible. The serological diagnosis of diseases of the nervous system will attain a great measure of success, when it enables us to isolate diseases, hitherto considered identical, according to the presence of particular defensive ferments, and to find that the clinical course of the disease corresponds with this. In any event, each separate case must be carefully and continuously studied.
Moreover, the above investigations are of special importance for this reason, that they definitely indicate the specific action of the defensive ferments. Fauser and Wegener report that female patients suffering from dementia præcox never decomposed testes, but only ovaries. Conversely, males only attack testicular tissue, but never the ovary. Both authors have also experimented with placenta, and, on the one hand, confirmed the sero-diagnosis of pregnancy, and on the other showed that the male serum never decomposes tissues of placenta. Of ​great importance is Wegener's communication, in which he states that, in cases of neuritis, muscle tissue is decomposed.
Finally, we may refer to the fact that experiments have been made with a view to throwing light upon the etiology of diseases of the eye, the causes of which are not yet known with certainty. Sympathetic ophthalmia provides features of particular interest. The researches carried on in this connection, by v. Hippel and Hegener, show distinctly that the defensive ferments exhibit specific activities. The number of observations is as yet too small to enable us to draw definite conclusions therefrom. In connection with these latter observations we may point out, how important it is to follow up every case, clinically, over a long period, and in no case to pay attention only to the disease which gave rise to the investigation. In particular, the further course of the disease should be followed up in all its phases. We have, in the dialysation process and in the optical method, means which allow us to test the functions of organs over long periods of time.
The observations, which we have here briefly sketched out, will certainly undergo rapid extension in various directions. Perhaps it will be found later on, that there are other explanations than those which have been developed here; and it is highly probable that some of the earlier results, which were obtained ​by means of other methods, will be brought into line with those acquired by means of the new methods. Thus the discovery, by Hermann Pfeiffer and his pupils, of the existence of toxic compounds in the urine in certain diseases and in certain conditions, should suggest to us that the products, which are formed by the defensive ferments, are also finally excreted. The comparative investigation of the dialysates, however, will have to decide whether there are direct relations of any kind between such products of decomposition and the poisonous components of the urine, and whether we are right in speaking of toxæmias that result from the decomposition of albumens.
Layout 2