# Defensive Ferments of the Animal Organism/Defensive Ferments of the Animal Organism/Section 4

​Of course, the mere fact, that it has been found possible to found a sero-diagnosis of pregnancy on the principles described above, would not give us the right to speak of a sero-diagnosis of the functions of organs. Further research, based on these principles as well as on the methods described, has, however, given us results which entitle us fairly to presume, that a new road has already been found for the development of our knowledge of the structure and metabolism of cells, under normal and pathological conditions.
As, meanwhile, our knowledge of the physical and chemical properties of the complicated constituents of the cell, and the products of its metabolism, is still very scanty, while in addition the disharmonious components of the plasma only appear in minute quantities, we are not in a position to seek them out by direct means. We have, therefore, to hit upon indirect means, and to find out whether a particular blood serum has ferments at its disposal, which are ​able to decompose the substrate peculiar to a particular organ. In a certain sense we give the serum a definite question to answer, when we add all kinds of organs to it, and observe which, or how many, of them are decomposed by it. If we find a decomposition, then we infer a somewhat abnormal activity of the cells of the corresponding organ. We presume that substances have been passed out, primarily from the cells of the organ in question, which have not vet been made sufficiently harmonious with the plasma, and that they still exhibit characteristic features peculiar to the cells in question.
In the future we shall undoubtedly avoid using whole organs and tissues for our researches, but shall select particular types of cells; and we shall have to be particularly careful in deciding, whether the tissue used is normal or modified. It is quite conceivable that, in certain diseases, only those tissues are decomposed which have been modified in a particular manner. In such a case the diseased tissue would be altered in such a way, that the substances that are out of harmony with the plasma would be more or less in disharmony with the cells of the normal organ; by which we mean, that compounds and decomposites would appear, which have completely disharmonious activities. And indeed, it would be possible to imagine that products would be formed that are out of harmony with the entire body, ​because the whole organ has become similarly disharmonious.
The fact that the animal organism replies to the invasion of disharmonious substances—which, either taking their origin from the metabolism of certain cells of its organs, or being normal constituents of the cells, pass directly into the blood plasma—by means of specifically directed ferments, is of the greatest importance to physiology as well as to pathology.
Up to the present we have only been able to distinguish three different proteolytic ferments, namely, pepsin, trypsin, and erepsin. In addition to these, we may perhaps reckon as proteolytic the ferments of rennet, and of fibrin. Strictly speaking, erepsin must be excluded, because it is principally directed against the products of decomposition of albumen. Our experience of the defensive ferments induces the supposition that trypsin, for instance, is not uniform in its nature. Of course, it may be possible that there are ferments which, just as a master-key can open various kinds of locks, are able to decompose very different substrates, when these belong to the same type of compound. But it is more likely that, in trypsin, ferments of different kinds are combined, and that in the blood the different components each act separately.
The defensive ferments are, as we have already ​pointed out, reagents acting on the characteristic, typical structure of the components of definite kinds of cells. We may illustrate this idea by an example. A great sensation was caused at one time bv the observation, that there were unicellular organisms which apparently showed signs of intelligence. It could be seen under the microscope how the uni-cellular organism, called Vampyrella spirogyræ, hurried from one alea thread to another, until it stopped at a particular kind of alga in order to use it as food. However many kinds of alga were offered to it, it would always pick out the same kind. This phenomenon, which seems so amazing at first sight, may doubtless be explained in the following way: Every living being has ferments at its disposal which, as Emil Fischer pointed out, may be compared with keys, and the substrate, against which they are directed, with locks. Just as a particular key generally unlocks and locks only a particular lock, so can particular ferments only decompose or reconstruct substrates of a particular constitution.
The Vampyrella spirogyræ, then, hurries from alga to alga, bearing with it ferments, by means of which it intends to convert nutriment into a suitable form. It is always trying to effect an entry by means of its "keys," and it only succeeds in certain cases, namely, when the key fits the lock, which is to say, when the cell-wall of the particular alga is of ​such a structure, that the decomposition can be effected by means of the ferments it possesses. A breach is made into the cell-wall; its contents are laid bare, and can then be utilized as nutriment.
This unicellular organism shows us, then, that the various algæ have a very different cell structure. The defensive ferments prove the same thing, and provide us with knowledge which we should be unable at present to arrive at by any other means.
Exhaustive researches are now in progress, which seek to ascertain whether the separate kinds of cells of an organism have the command of specifically directed ferments. We know that every cell requires ferments for the purpose of breaking up the food that is brought to it, or of constructing new compounds out of it. Further, we know that the cell is able to disintegrate parts of its own contents, and to replace them by new material. Is it not probable that specific activities are indicated in this case also? In the course of our experiments in this direction peptones were produced from certain cells, and the decomposition of these peptones by the corresponding cell ferments was then attempted. As a matter of fact, juices obtained from certain organs by extraction or maceration decomposed only peptones or albumen from the corresponding tissues; that is to say, extracted thyroid juice broke down peptones obtained from that organ, but not liver peptones ​(E. Abderhalclen, A. Fodor, and E. Schiff). The kidneys alone were exceptional, their ferments attacking peptones originating from the most different organs. In all probability this result points to a new function of the kidney, namely, the duty of intercepting all disharmonious substances of a complicated nature, which have been brought to it by the blood, but have escaped the action of the defensive ferments of the blood. The kidney decomposes these, and by so doing renders them useful to the organism. The observations we have quoted suggest the possibility, that the kidneys may be instrumental in supplying defensive ferments to the blood. It would be very interesting to determine the contents of diseased kidneys in respect of ferments, and to find out whether they are still able to perform their duties. By such studies new points of view might be supplied, which would give us a better understanding of the particular diseases affecting this organ. Moreover, exhaustive studies on the specificity of the ferments of cells as such should enable us to prove that each kind of cell has its own structure. We shall also be able, by means of the dialysation process and of the optical method, to make a much better study of cell ferments than has hitherto been the case.
The number of problems, that arise from the facts we have brought forward, is so immense that we shall content ourselves with drawing attention to only a ​few of them. In the first place it would be desirable to find out where the defensive ferments arise, and whether they can be met with inside the individual cells themselves. It is, for instance, conceivable that the walls of the intestine, and perhaps also the cells of the liver, are always provided with definite ferments for the purpose of further reducing substances which, though insufficiently decomposed, pass through the gut epithelium; and it is very probable that the leucocytes play an important part in this connection. They circulate rapidly through the whole organism. They are to be looked on as protective organs, which, to use a metaphor, overlook everything with a view to finding out whether order prevails. Some products are eliminated by being absorbed into the body of the leucocytes (phagocytosis); others are attacked by their ferments, and so broken up, and deprived of their characteristic structure. Finally, as mentioned before, the separate organs have to be considered, particularly the kidneys.
But the most important advantage of the methods we have described is, that they will enable us to study the reciprocal dependence of individual organs. Suppose, for instance, we remove the thyroid gland; we then anticipate that another organ, some of whose functions depend on this gland, will have its metabolism interfered with, and will in consequence give ​off disharmonious material. The failure of this organ is followed by that of a second, which was accustomed to obtain secretions from the first, and thus we are led to the discovery of wheels within wheels.
Or it may be that investigation of a large material shows that certain dys-functions were attributed, on the basis of our earlier experience, to disease of a particular organ, when all the time it was functioning quite normally. For instance, the following case is quite conceivable. Let us suppose that a very definite function of organ B depends upon organ A. The latter may work quite normally, although B is so modified that it passes into the blood constituents of its own cells. Let us suppose that it is these products against which the secretion, originating from organ A, is directed; then it finds the substances, which it ought to affect within organ B, already in the blood. It combines with these substances, and in consequence never reaches organ B. We then observe the same phenomena as would result if organ A were diseased. The dialysation process and the optical method would, in this case, give the apparently astounding result, that defensive ferments are present in the blood serum which are directed against the components of organ B, whilst those which correspond to the components of organ A would, against all expectation, be entirely absent. ​Organ A only appears to refuse to work because, as the result of a primary dys-function of organ B, the secretions are unable to achieve their aim in the proper place. They are caught up too soon.
We must not forget to mention, that it is, perhaps, more often than we imagine, that substances which are out of harmony with the plasma circulate in the blood. We are thinking particularly of disintegration of the form-elements of the blood. That ferments, directed against the components of the red blood corpuscles, can be found in animals that are apparently quite normal, is shown by the fact that, amongst horses and cattle, about 40 per cent. of cases investigated gave a decomposition of albumen which originated from the form-elements (E. Abderhalden and A. Weil).
The following experiments supply a striking indication of the probable cause of this phenomenon. Blood was taken from a rabbit. The serum neither decomposed any organ that was free from blood, nor any organ that contained blood—traces of blood being quite sufficient. Without any further treatment, blood was again taken from the animal after two days, and again the serum gave no decomposition with any organ free from blood. On the other hand, the reaction gave positive results with all organs that contained blood. It was certainly not the albumen of the organs that was decomposed, but the blood ​contained in the tissue. The appearance of defensive ferments, after the extraction of blood, is without doubt to be ascribed to the destruction of red blood corpuscles that results therefrom. Is it not possible that the absorption of plugs of fibrin that occlude the walls of the vessels may be connected with defensive ferments, and may not the latter also have a share in the organization of thrombi?
Defensive ferments, which decompose the albumen of blood corpuscles, may be produced by means of injections of hæmolytic blood, and herein lies a source of error which should never be underestimated. Only organs that are absolutely free from blood give conclusive results. Defensive ferments, which decompose the albumen of blood corpuscles, are frequently met with in carcinoma. Any extravasation of blood into the tissues, however slight, will give rise to this kind of defensive ferments.
Within the domain of pathology there is no field which would not lend itself to researches based on the methods we have described. We will call attention to some. In the first place we can try, by means of defensive ferments directed against certain kinds of cells, to discover those organs which are giving off substances that are out of harmony with the blood or the plasma. This would be the case, when a particular organ fails to complete its otherwise normal metabolism. But it is also possible that ​decomposites, or secretions, are formed, which are in themselves disharmonious. The future must teach us whether quantitative conditions are decisive or not, but it is at least possible that a secretion of quite normal composition may act disharmoniously with the plasma, when it passes into the blood in too large quantities.
In pathological cases, too, we shall be able, by following up a particular disease, to determine the nature of the reciprocal relations in which different organs stand towards each other. It may be noticed, perhaps, that at the beginning only one organ shows signs of dys-function, that another then follows suit, and so on. We shall also be able to make therapeutical studies. If a therapeutical measure should result in the disappearance of the defensive ferments, the therapy would have to be estimated otherwise than if this were not the case.
A large field of study is presented by all cases of degeneration, such as muscular and nervous degenerations, as well as by processes which result in the formation of decaying products of every kind, such as putrefaction of tissues, or absorption of exudates, of extravasations of blood, or of thrombi, &c.
The infectious diseases obviously supply us with an extensive field of study. On the one hand we shall have to decide whether defensive ferments exist that are directed against specific micro-organisms, ​and, further, whether the tissue attacked is decomposed by blood serum. Either the micro-organisms will be able to decompose the tissue—their nutritive medium—in a manner harmonious with themselves and disharmonious with the body, and so produce decomposites out of harmony with the plasma, or else the injured tissue will be altered in such a way as to be no longer able to continue the normal processes of its metabolism. A mass of observations are waiting to be made in this direction.
We may point out that it has been ascertained that, in cases of miliary tuberculosis, defensive ferments exist which are directed against tubercle bacilli. It seems that the serum of cattle suffering from tuberculosis is able to decompose the bovine type only. Caseated lung tissues were not decomposed by the serum of animals which suffered from miliary tuberculosis, but only of those which exhibited caseous pneumonia. These experiments, which were performed with the assistance of Andryewsky, on cattle and cows, are an inducement to further studies.
We may take this opportunity of pointing out, that the dialysation process for the demonstration of defensive ferments offers the great advantage of toxilogically testing the products of decomposition. We may use the dialysate, which must, of course, contain the products of decomposition, either directly, or after complete concentration at a low temperature and ​decreased pressure, for all kinds of experiments on animals. It is a pity that hardly any investigations have been made in this direction.
Once we have demonstrated the existence of ferments directed against particular micro-organisms, then the question naturally arises, what influence is attributable to the defensive ferments in a special case. They may act defensively. But it is also possible that it is they which first produce the poisonous substances, when decomposing disharmonious material. The ferment is unable to "know" what will be the result, when it breaks down a particular substrate. It may be that the attacked substrate is quite harmless to the organism, and that injurious substances first appear during decomposition.
If further researches show that the organism defends itself successfully by means of definite ferments, then a road is marked out for therapy to follow. By the direct addition of the necessary micro-organisms, or of certain parts of them, we shall produce defensive ferments which are directed against them, and try to transmit these with the serum. We can determine, exactly, the moment when the defensive ferments appear. A particularly fine basis for experiments seems to be supplied by thromboses, which one might be able to attack effectively by means of properly directed ferments, and so bring about their absorption.
​The following observation is important. If albumen is injected into the circulation of an animal for the first time, defensive ferments are found to appear, in the case of intravenous injection, at the end of about one day. If the injection is repeated, say, a month after the defensive ferments have disappeared, then the ferments reappear very much earlier. (Abderhalden and Schiff.) May it not be that immunity partly rests upon the fact that an organism is able to set free its defensive ferments quicker than usual?
Syphilis, also, may certainly be studied from the standpoint we have laid down. We have to consider the affected tissue on the one hand, and the spirochæte on the other, as substrates.
It is also clear that we may suspect the presence, in the serum, of defensive ferments which are able to reduce fats, carbohydrates, nucleo-proteids, &c. The demonstration of proteolytic defensive ferments represents only one special case. We have selected this case because, up to the present, no methods exist for satisfactorily demonstrating lipolytic or amylolytic ferments—in short, those ferments which are directed against the particular constituents we have mentioned—unless one has rather large quantities of serum at one's disposal. We are, meanwhile, engaged in extending our researches to other ferments.
With regard to the infectious diseases, we should ​like to discuss more closely what is, in our conception, the relation of the micro-organisms to the cell complex of the host.
Let us return for a moment to the conception we developed at the commencement of this work, according to which the organism, under normal conditions, represents a whole closed in itself. We have already pointed out that the harmony of all the processes going on within the whole complex is perturbed, as soon as disharmonious kinds of cells settle inside it; that is, species of cells which have their own metabolism, and their own specific structure. On the one hand these cells have to be fed, and on the other they give off the products of their metabolism, and perhaps also secretions of various kinds, to the exterior. In order to be able to make use of the nutritive material supplied by the host, which is at first disharmonious with their cells, they also must possess ferments which will make the food accessible. It is conceivable that the substances belonging to the host are first absorbed by the cells, and then transformed in their interior, but it is more likely that the invaders give off ferments externally, which decompose the nutritive media around them, and prepare it in that way for absorption. The resulting decomposites are then taken up by the cell. A reconstruction must be made in any case, and especially when the substances are intended, for the building of new cells. ​Experiments which have been carried on with different so-called toxins have shown, without any doubt, that splitting agents are present in them. These experiments, however, do not make it absolutely certain that the micro-organisms secrete ferments, because it is difficult to decide whether the so-called toxins of the trade represent uniform products, and particularly whether they always contain secretions only. As a preliminary condition, then, for the possibility of the existence of micro-organisms amidst a particular complex of cells foreign to them, we require the presence of ferments which enable them to build up the food they require from substances that are in harmony with the cells and the blood of their host. In this case the relations between the configuration of the ferments and that of the substrates are no doubt expressed in their most distinctive form. How often may not a micro-organism penetrate into an organism and die out, only because it is unable to feed on the nutritive medium supplied, while in other cases it is able to settle down because the substrates presented to it can be rendered accessible by its ferments. If all the substances are used up, and none of the same kind are supplied anew by the host at the proper place, then the conditions of its existence are withdrawn from the micro-organism, and it must either perish or find a new "pasture." It may also happen in many cases that ​the cells of the host catch the secreted ferments of the micro-organism, or render them inactive in some other way, and in this manner either increase the difficulties of existence for the invaders, or else completely destroy them.
How sensitive individual organisms are, in regard to these nutritive substrates, is shown, by numerous laboratory observations on the cultivation of the most varied micro-organisms. We know that many of them only thrive, when very definite substrates are offered to them. The fact, that an alteration of the nutritive medium deprives certain organisms of their means of existence, is shown in the clearest manner by the observation that an infection with trichophyton fungi cures itself at the time of puberty. Evidently the cells of the skin become so modified, at the onset of sexual maturity, that the substrate of the host—the components of the skin—can no longer act as a means of subsistence for the fungus. From this point of view we may well imagine that medicines and other therapeutical means effect a curative action, without directly attacking particular kinds of cells which may be living as parasites in the animal organism, for they need only to destroy the conditions of existence required by the organism in question by means of a modification of its nutritive substrate. It is imaginable that certain means do modify certain cells to such an extent, that their ​components can no longer be considered as supplying nutritive material for the organism that lives in them.
The fact that the cells which are out of harmony with the body are dependent upon nutritive material of the most varied nature for the opportunity of extending their existence, and more particularly for maintaining their species, gives us an insight into the kind of influence exercised by these parasites on the host. In the first place they may act injuriously by the simple removal of nutritive substrates, while, in addition, the preparatory decomposition of the nutritive material may give rise to by-products which are harmful to the organism. We can well imagine that particular cells have ferments at their disposal, which decompose particular substrates in a thoroughly characteristic fashion, and so, for instance, produce stages of decomposition which are quite out of harmony with the cells of the host. The same substrate may be decomposed in the most various ways, right clown to its simplest structural units. The idea of an atypic decomposition of substances in harmony with the body, cells, and plasma, by ferments of disharmonious cells, suggests the possibility that micro-organisms, though not actually themselves passing into the circulation substances that are directly poisonous, may act injuriously, simply from the fact that, by means of fermentative decompositions, they form products out of the material ​of the host, which seriously affect the metabolism of the latter. It is certainly not necessary in every case that the poisonous substance, the so-called toxin, should originate in the cell of the micro-organism itself; it is just as likely that it is formed, outside the cell, by ferments given off by the latter. When we introduce substances out of harmony with the species or the plasma, we have similarly to reckon with the presence of stages of decomposition, which may be disharmonious with the organism, and capable of producing injurious effects. In this case the disharmonious substrate is the cause of the appearance of a substance, that is disharmonious both in structure and configuration. In cases of invasion by bacteria, we have, on the contrary, a destruction of generally harmonious substances, yet the decomposition is brought about by ferments which are probably of a different kind. The cause of the appearance of disharmonious decomposites is thus to be explained, not by the substrate, but by the nature of the ferments. It is possible that, in time, we may succeed in tracking down in the organism these ferment-like agents that are given off by parasites. For the time being we must be satisfied with being able to point to the possibility of a decomposition of this kind being a cause of injury.
Disharmonious cells may also act injuriously upon the organism, owing to their decomposition inside the ​body. The death of a cell of this kind results in the appearance, within the circulation, of substances which are disharmonious. We can make a comparison between a case of this kind and the parenteral injection of substances out of harmony with the body and the plasma; for, in this case, the organism will surely defend itself against the very disharmonious substrate, by depriving the substrate of its specific structure by means of an extensive decomposition. We should then be presented with conditions entirely analogous with the parenteral injection of various substances, or with the invasion, into the circulation, of chorionic cells which are out of harmony with the blood plasma, and the resulting reaction would be entirely similar. But here, too, during decomposition, it may happen that the organism will produce decomposites which are naturally injurious, so that, in any given case, it would mainly depend on whether the intermediate products appeared only in small quantities and were promptly reduced, or whether, conversely, the power of decomposition possessed by the organism is inhibited—either because the decomposites cannot be further reduced or be rejected, or because the ferments necessary for further reduction are not present in sufficient quantity. We can well imagine that the decomposition of the bodies of dead micro-organisms, without the direct participation of the microbes themselves, will give rise to various ​disturbances; and we might certainly expect secondary disturbances in the harmonic processes of the whole metabolism of the host, without the micro-organisms as such exerting any direct action.
Finally, we have to consider yet another possibility, that certain micro-organisms produce poisonous substances within themselves, and give them off externally. It is, at present, very problematical, what view we are to take of these substances. Are they substances which play a part in the metabolism of the micro-organisms themselves, or are we dealing with agents which, when passed to the exterior, affect the nutritive medium in some way or another, that is, by either decomposing or reconstituting it? It is quite conceivable that certain micro-organisms have agencies at their disposal, which are able to modify particular nutritive cultures in a particular way. Many pathological observations have proved, that certain micro-organisms require a so-called mixed infection, that is, that certain bacteria alter the cell substance of the host in such a way, that some other kind of bacterium finds conditions favourable for its existence. It seems that this is also the case with some kinds of tumours, such as sarcoma and carcinoma, where a preparation of the medium by certain substances is of great importance. In the future we shall be compelled to appreciate all these possibilities. If we could succeed in limiting more precisely the ​conditions under which certain bacteria can exist, mainly on the basis of more exact studies on the composition of the medium, then we should undoubtedly be in a position to employ more objective therapeutic methods. Further, it would be possible to formulate a conception of the injurious activities of certain kinds of bacteria more clearly than we can at present. Unfortunately, it would scarcely be possible to make use of direct methods in this case, unless we were to succeed in cultivating individual micro-organisms on substrates the composition of which we were thoroughly acquainted with. Our progress in the field of the chemistry of the different kinds of cell units, and of their nutritive bases, has brought us nearer to this objective, but a large part of the road lies before us yet, before we shall obtain such an exact knowledge of the composition of certain albuminous substances, such as phosphatides and nucleoproteids, &c., as to be able to properly appreciate differences of configuration, as well as differences of structure. Once we have advanced so far, we shall be able to replace our present conception of "disposition" by definite facts.
The train of thought we have been pursuing is only intended to show that, in considering the question of the injuries which bacteria may inflict on their host, we must not only consider the bacteria as such, but must realize that their entire metabolism is of ​pre-eminent importance. It is not the bacteria alone, and the so-called toxins, that have to be considered in the whole question of immunity reactions, but most probably the intermediate products of their metabolism, as well as certain decomposites which are, at any rate partly, formed quite outside the cells in question. And, above all, ve have to consider the structure of the organism. The host directs its struggle, not only against the living micro-organism, but also against the particles which appear with the decay of the dead organism, and more particularly against the intermediate products which originate during the preparation of the nutritive medium. The organism attacks every point with its ferments, and tries to decompose or reconstruct anything that is disharmonious with its structure or configuration, or even its physical properties. The more it succeeds in this respect, the more does it deprive the micro-organisms of the conditions required for their existence, and protect its own cells against the injurious action of these substances.
We come, then, to the conclusion, that at least one part of the means of defence, possessed by an organism against infections of any kind, depends on its power of liberating ferments, which attack the disharmonious substances—be they by-products or end-products of metabolism, or products of cellular disintegration—and deprive them as quickly as ​possible of those specific properties which are out of harmony with the host. Of course, other processes come into play in this connection. The decomposites are oxidized, reduced, methylated, acetylated, benzolated, &c., and are also, without any doubt, coupled in very different ways with various compounds. The defensive ferments prepare the disharmonious material in a proper manner, so that the individual cells of the body may attack it in their own specific way. The ferments remain unaltered during all these processes. They enter temporarily into combination with the substrate to be altered. Once the decomposition is completed, the ferment is again ready to initiate new reactions—mostly decompositions. An over-production of ferments, in response to an invasion of disharmonious bodies, is therefore unnecessary. The importance we ascribe to these means of defence of the organism against the invasion of disharmonious substances may, however, be objected to on the ground that little is gained by demonstrating the existence of ferments in the blood plasma, and by agreeing that they play an important part in connection with infectious diseases, so long as the ferments themselves are not known by us. We know nothing of their structure, their nature, or their special modes of action; and only become aware of their existence through their activities. The fact, that they are ​specifically directed against particular substrates, makes it possible for us to demonstrate their existence, and the knowledge, that ferments play an important part amongst the means of defence of the animal organism against disharmonious substances, indicates this much progress, that we are enabled thereby to follow up, experimentally, phenomena which we meet with under normal conditions in the individual cells of the body. With the help of the ferments the cell is continuously remodelling in a suitable manner the food, which the blood brings to it still in harmony with the plasma, either by way of completing a further decomposition, or of setting up a synthesis. The ferments are the tools of the cells, by means of which fuel is brought into a suitable form, the structure of the cell is completed, and various substances are prepared, which, as secretions, have a more or less definite part to play throughout the organism. If the organism liberates defensive ferments, then its cells effect nothing actually new. A normal process is simply allocated to a specific case. The ferments are adapted to the new kind of substrate, and, if necessary, passed out into the circulation. So that this form of defence against disharmonious substances, which the cell utilizes, may be ranked directly with the normal processes of cellular metabolism an—idea which has always dominated the researches of Paul ​Ehrlich. At the same time, a careful analysis of the processes effected by the ferments gives us the chance of determining, with more certainty than has hitherto been the case, what is the nature of the injuries set up by the presence of cells that are out of harmony with the body. Sometimes the parasite takes an active part, sometimes only a passive one, while at other times its influence is extremely varied.
The proof, that ferments play an important part in the means of defence of animal cells against disharmonious substances, opens up new paths for experimental research. It may be long before the true nature of ferments is elucidated; nevertheless, we shall always be getting nearer to the possibility of excluding the second unknown—the substrate. The more we extend our knowledge of the composition and structure of the food material, and of the components of the cells, the more do we find ourselves in a position to make use of substrates of a known structure, which enable us to investigate the ferments in a much surer manner, and to determine exactly how they decompose a particular product. We shall be able to get hold of individual decomposites, and study their properties, so as gradually to penetrate into the mysteries of the effects of infectious diseases, as well as into the principles of immunity.
There is scarcely, in the whole domain of biology, a more stimulating task than that of finding ​out how the organism defends itself when disharmonious substances introduce a disturbing element into its metabolism, so delicately poised and harmonized even in its finest details. In these problems the most varied hypotheses regarding cellular metabolism are to be met with. The more the biologist enlarges the limits of his researches, and the more he follows up all general phenomena, the more may he venture to hope that he will gain new means and new lines for the study of special processes. The appearance of the defensive ferments in the animal organism, when it is invaded by substances that are out of harmony either with its body, with its blood, or even with some of its cells, gives us an insight into many problems of pathology, and particularly into those of immunity. Every approximation of fields of thought that are at first sight dissimilar, arising out of observations which allow us to presume common reactions and common processes, must be met with approval. It will then be possible that, by an exchange of results based on very different methods and hypotheses, we shall acquire a wide outlook over the fundamental properties of cells of different origin.
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