CHAPTER XIV

IMMUNITY ACQUIRED BY NATURAL MEANS

Immunity acquired after recovery from infective diseases.—Immunity acquired in malaria.—Humoral properties of convalescents from typhoid fever.—Preventive power of the blood of persons who have recovered from Asiatic cholera.—Antitoxic power of the blood of persons who have recovered from diphtheria.

Immunity acquired by heredity.—Absence of hereditary immunity properly so-called.—Immunity conferred by the maternal blood and by the yolk.

Immunity conferred by the milk of the mother.

[Sidenote: [454]]

It has long been known that an attack of one of many of the infective diseases brings about a refractory condition of the organism against that disease, a condition which persists for many years, and may even endure for life. Even before the microbiological era of medical science had arrived it had been fully established that a person who had recovered from small-pox might come in contact with and nurse small-pox patients without risk of contracting a second attack of the disease. The same thing has been observed purely empirically in several other infective diseases, such as whooping-cough, typhoid fever, scarlatina, mumps, etc. On the other hand it has been shown that certain infective diseases, such as fibrinous pneumonia, erysipelas, recurrent fever, and influenza, do not leave behind them the slightest trace of an immunity. It has often been observed, indeed, that after a first attack of any of these diseases there is a marked susceptibility to a second attack. Between these two extremes come the infections which are followed merely by a refractory condition of shorter duration than that which follows the diseases of the first group. The first of this intermediate group is measles, which gives rise to a relatively long immunity, then come in order bubonic plague, anthrax, cholera, etc.

[Sidenote: [455]]

It should be stated that the first attack of any of the infective diseases causes modifications more or less permanent in the organism, and is always followed by immunity. Even in erysipelas, a disease where the relapses are so frequent that certain individuals are, so to speak, predestined to re-acquire it at short intervals, an immunity is produced, but a very transient one. Since the discovery of the streptococcus of erysipelas by Fehleisen[724], this observer, and several other investigators, have inoculated it into persons affected with malignant tumours. In the course of a series of experimental cases of treatment it was noted on several occasions that after a first inoculation, followed by typical erysipelas, a period of immunity was developed, during which the introduction of the streptococcus produced no result. It has also been observed that recurrent fever, when inoculated into monkeys, sets up a very transient but real refractory condition. In fibrinous pneumonia, also, the relapses are generally separated by periods of immunity, of longer or shorter duration.

[Sidenote: [456]]

It was generally supposed that an attack of malarial fever was not only not followed by any immunity, but that a first attack predisposed the organism to a second. Facts of this kind have often been observed and cannot now be questioned. Nevertheless, an acquired immunity against malaria is developed under certain conditions. During his travels in New Guinea, Koch[725] found that in certain regions whilst most children below ten years of age are attacked by malaria, and Laveran’s parasite can be demonstrated in their blood, older children and adults are completely immune from this infection. Koch is convinced that in this instance we have an example of immunity acquired by natural means as the result of an attack of malaria at the younger age. This great observer bases his conclusion on the fact that unattacked adults, coming from districts where the children contain the parasite, do not contract malaria when they migrate to other malarial regions, whilst natives coming into these same regions from districts where malaria does not exist are soon attacked. Max Glogner[726] has attempted to explain these facts established by Koch, on the assumption that the unaffected adults simply benefit by their natural immunity and that we have here a kind of selection: the adults who are susceptible to malaria die as the result of this disease, whilst others, naturally refractory, resist and show themselves incapable of contracting the disease even in other malarial regions. Glogner in support of his view cites the case of the children of the orphanage at Samarang (Java), who for many years are subject to relapses and to malarial re-infections and are incapable of acquiring the slightest immunity. According to Koch, Glogner’s example cannot be compared with that of the children of New Guinea. In the former case, the natural course of the disease is interrupted by treatment with quinine, which must prevent immunity being set up; whilst, in the latter, the children are abandoned to their fate, and, receiving no treatment, slowly acquire a true immunity. It is evident that this acquired immunity in malaria is a complex phenomenon on which fresh researches must be made; but it cannot be questioned that, under certain conditions, it comes under the general rule and can be naturally acquired.

This general rule is that, in infective diseases, immunity is usually developed after a first attack. The acquired refractory condition is of very long duration in certain cases, but very transitory in others. To the discovery of the vaccination by attenuated micro-organisms, made by Pasteur and his collaborators, the objection was often made that many diseases, such as anthrax, might relapse. This is undoubtedly the case; the anthrax bacillus may attack the same individual several times; nevertheless the acquired immunity against this disease is very real, though the refractory condition lasts for one or a few years only, instead of persisting for a very much longer period, as in the case of typhoid fever, mumps, and small-pox. Bearing in mind the possibility of a relapse in the case of these infective maladies, attempts at artificial vaccination should never be relinquished.

[Sidenote: [457]]

Among the examples of immunity acquired by natural means must be cited that of syphilis, a very special case. It has long been known and demonstrated by numerous experiments on man, that individuals who have presented the primary symptoms of syphilis contract a marked immunity against a new infection. The syphilitic chancre does not relapse, and yet this very manifest and persistent immunity does not prevent the individual, immune against re-infection, from continuing to be ill and of being the field for the later syphilitic phenomena. This special refractory condition has done great service in establishing the etiology of certain diseases which we were justified in suspecting to be of syphilitic origin. Many clinical observers have accepted this origin for general progressive paralysis. Others deny any causal relation between the two diseases. Krafft-Ebing[727] has resolved this question by the application of the law of acquired syphilitic immunity. The inoculation of the syphilitic virus into ten persons attacked by general paralysis was followed by no chancre at the seat of inoculation and by no other primary or secondary symptom of syphilis. The patients with general paralysis present a real immunity against these symptoms; consequently general paralysis is a tardy manifestation of syphilis.

The acquired immunity against re-inoculation by the syphilitic virus is established immediately after the end of the period of incubation of the first infection, and is of lifelong duration[728]. Besides this very special and, so to speak, partial immunity, there exists in syphilis a second form of acquired immunity which is of a more general nature. According to the law known as the law of Baumès-Colles, the mother who suckles her infant, hereditarily infected with syphilis through the father only, enjoys a real anti-syphilitic immunity.

[Sidenote: [458]]

In tuberculosis the few facts of acquired immunity that have been observed present a certain analogy with those bearing on immunity in syphilis. A large number of well-observed facts demonstrate that a person who has suffered from scrofula or has manifest symptoms of tuberculosis properly so called, cannot count upon an immunity against pulmonary phthisis. It might, then, be supposed that no acquired refractory condition exists in connection with this disease. Koch[729] has clearly demonstrated, however, that tuberculous guinea-pigs, into which the bacilli of tuberculosis have been introduced subcutaneously, react against these bacilli in a very special manner. The presence of these micro-organisms immediately sets up an active inflammatory process at the point of inoculation; this brings about the expulsion of the bacilli with the exudation; a voluminous slough is developed, which, when shed, carries with it a large number of bacilli, a process followed neither by the formation of a permanent ulcer nor by hypertrophy of the neighbouring glands. As in syphilis, the animal has acquired immunity against re-infection by the tuberculous virus, which, however, in no way prevents the first inoculation from becoming generalised and setting up a fatal tuberculosis of almost all the organs. Koch’s observations, which have served as the basis of his researches on tuberculin, have been confirmed by other investigators. The reaction of the tuberculous organism against re-infection has received the name of “Koch’s phenomenon.”

Clinical medicine has afforded many data of the highest importance bearing on the establishment of an acquired immunity in many infective diseases; but a scientific study of the mechanism of this immunity could only be founded on the result of microbiological researches obtained during the recent period of scientific activity. The general conclusion to be drawn from these researches is that the immunity, acquired by natural means, is very analogous to that which is obtained artificially by vaccination by the various methods already mentioned. The phenomena observed in animals inoculated with the various known vaccines present a great resemblance to those that obtain during recovery from a disease contracted under natural conditions. To support this thesis it would be necessary for us to survey the mechanism of healing, which would carry us too far afield, the subject being far too vast to be summarised here. We must, then, content ourselves with a few remarks inserted for the instruction of the reader on this subject.

Those diseases against which no remedy exists are most suitable for furnishing us with important information on immunity acquired by natural means. We have already seen in the case of malaria to what point therapeutic treatment can modify the natural course of the phenomena. For this reason it will be useful to consider first the immunity acquired as the result of a first attack of typhoid fever. The immunity which develops in this example is both marked and persistent; the therapeutic intervention which might disturb the natural phenomena is _nil_.

[Sidenote: [459]]

As yet we do not know the mechanism of healing in typhoid fever. This disease affecting the human species exclusively (the experimental peritonitis of animals, set up by the typhoid coccobacillus, is distinguished by very marked differences), it is very difficult to find a means of studying it at all satisfactorily during the phase of recovery. Even in default of this knowledge, however, it is possible to gather some idea as to the changes which the blood plasma undergoes, not only during the course of an attack of typhoid fever, but also during and after convalescence.

Some time ago Chantemesse and Widal[730] observed that the blood serum of persons attacked by typhoid fever acquires the property of inhibiting the experimental peritonitis set up by the typhoid coccobacillus in laboratory animals. The blood of the patient becomes “preventive.” Against this conclusion the objection has been raised that in the large doses of serum employed by the above observers a protective effect can be obtained, even when using the blood of normal men, i.e. neither suffering from typhoid fever, nor having recovered from this disease. Later researches, however, have confirmed the observation made by Chantemesse and Widal. It is no doubt true that the injection of half a cubic centimetre of normal human serum into the peritoneal cavity of an untreated guinea-pig is often sufficient to render it refractory to a dose of typhoid coccobacilli fatal to the control animal. We have an ordinary protective action, such as described in Chapter X. The blood of typhoid patients is, however, capable of protecting normal animals, in doses which exhibit not the slightest protective action if normal blood be used.

[Sidenote: [460]]

The protective power of the blood serum of convalescents has been studied very carefully by Pfeiffer and Kolle[731]. In certain individuals very small quantities (0·001 c.c.) of this fluid were quite sufficient to confer on guinea-pigs an immunity against fatal typhoid peritonitis. This power was at its maximum only during the first weeks of convalescence. In one case, in which these observers were able to study the properties of the blood on two separate occasions, they found that two months after the first examination there had been a marked falling off in the acquired protective power. In a second case, where the blood was examined a year after the patient had recovered from a grave attack of typhoid fever, they found only feeble indications of this specific protective property. “Everything seems to indicate,” conclude Pfeiffer and Kolle, “that the protective typhoid substances were rapidly eliminated by the blood stream. If further researches should confirm these results, as yet few in number, we might conclude therefrom that the immunity which, after an attack of typhoid fever, persists for years, frequently even for the rest of life, would be independent of the amount of ready-prepared protective substances in the blood” (_l.c._ p. 218). The facts upon which this conclusion is based confirm the general thesis that even acquired immunity is in no way the function of any humoral property.

We know that in the protective serums there is constantly found the specific fixative (the sensibilising substance of Bordet, the intermediary body or amboceptor of Ehrlich). It was, therefore, quite natural that this substance should be sought in the blood of patients who were suffering, or had recovered, from typhoid fever. Bordet and Gengou[732] easily demonstrated, by the method described in Chapter ix, the existence of typhofixative in the blood serum of two individuals convalescing from this disease.

Widal and Le Sourd[733] extended this discovery to the blood taken during the course of the disease from typhoid fever patients. The ten cases studied by them all gave a positive result, whilst all the samples of blood from persons suffering from various other diseases possessed no typhofixative. As yet we do not know whether this substance persists for any length of time after recovery or not. In this respect we have much more information concerning another humoral property of typhoid patients,—specific agglutination. Guided by the fact that, even during the course of the disease, the blood of persons suffering from typhoid fever acquires protective properties, Widal sought to find out whether the agglutinative power of the fluids of the body appears equally early. We know that his studies gave a positive answer, and that the blood of typhoid patients may have agglutinative properties from the first day of the disease. This fact was made use of by Widal to establish the serum diagnosis of typhoid fever, a method now generally used in clinical medicine. The question which most interests us at this moment is whether this acquired agglutinative property persists for any length of time after the recovery of the patient, and whether it can be employed as the measure of immunity obtained.

[Sidenote: [461]]

In certain cases the serum was found to be fairly strongly agglutinative for a considerable period after recovery had taken place. But these cases are rare, and the agglutinative power, like the protective power of the blood, usually begins to decrease very soon after recovery. Bensaude[734] observed that the former disappeared between the 10th and 95th day of apyrexia. Widal and Sicard[735] have noted in certain of their cases the complete disappearance of the agglutinative power of the blood, which took place in one case on the 18th, in another on the 24th day of defervescence. In many convalescents, fifteen to thirty days after the commencement of apyrexia, the agglutinative power begins to be attenuated.

Previous to these researches on the protective and agglutinative properties, Stern[736] had already put the question: May we not draw some general conclusion as to the bactericidal power of the blood serum of convalescents from typhoid fever? He found that the typhoid coccobacilli did not thrive so well in the blood serum of persons in good health as in that of convalescents, in which they give abundant cultures. Widal and Sicard (_l.c._) subjected this question to a fresh examination, and showed that in this respect there exists no constant or marked difference. Thus, in ten samples of serums from individuals who had never been under the influence of the typhoid infection, four were found to be bactericidal for the typhoid coccobacillus. In twelve other samples, drawn from convalescents from typhoid fever, five exhibited a bactericidal power against the same micro-organism.

All the researches made on acquired immunity after recovery from typhoid fever demonstrate clearly that, in this case, it is impossible to attribute it to humoral modifications, which are usually more transitory than the immunity.

[Sidenote: [462]]

The immunity which follows an attack of cholera is far from being either as powerful or as prolonged as that which follows typhoid fever. Certain individuals have contracted cholera twice during the same epidemic, but such cases are exceptional, whilst acquired immunity, temporary at least, may be looked upon as the general rule. Many points in the pathogenesis of intestinal cholera are still obscure; nevertheless we are justified in affirming that this disease is a real intoxication by the cholera poison manufactured, in the small intestine of man, by Koch’s vibrios. The action of the vibrionic toxin is sufficient to set up a grave and often fatal attack of cholera; but in the majority of cases a secondary infection by the vibrio which penetrates into the intestinal wall, denuded of its epithelial layer, is associated with the action of the poison. Sometimes this micro-organism becomes generalised in the animal, and is found in the blood and in many of the organs.

The facts I have here briefly summarised may be utilised to explain certain characters which are found in the fluids of individuals who have recovered from an attack of cholera. Soon after the discovery of the tetanus and diphtheria antitoxins, and almost immediately after the demonstration of the protective power of the blood, taking advantage of the epidemic of Asiatic cholera, which developed in Europe from 1892, the new data began to be applied to that disease. We have already referred in a preceding chapter to the fact that the blood serum or the blood of those in good health and who have never had Asiatic cholera, is capable of preventing cholera peritonitis in the guinea-pig inoculated with Koch’s vibrios. In order to obtain this protective action, the injection of a pretty large dose, about half a c.c., is necessary. This property is in no sense specific, for the same blood, injected in the same doses into guinea-pigs, will protect them not only against this vibrio, but also, and indifferently, against many other bacteria, such as the typhoid coccobacillus, the _Bacillus coli_, etc.

The blood or blood serum, coming from those who have recovered from Asiatic cholera, may, on the other hand, acquire a specific protective power. It will, indeed, prevent infections by other micro-organisms; but, to obtain this effect, it is necessary to inject the same quantities of it as of the blood coming from normal individuals. On the other hand, when we wish to prevent cholera peritonitis in the guinea-pig, we need introduce minute doses only of the serum of persons who have recovered from an attack of cholera. Lazarus[737] was the first to make this interesting observation. In three cases of cholera studied by him, the serum withdrawn some time after recovery exhibited an extraordinary protective power: a decimilligramme of the blood serum of these patients was quite sufficient to prevent the death of a guinea-pig inoculated intraperitoneally with the cholera vibrio. Soon after, G. Klemperer[738] made a similar observation in two other cases that had recovered, but the blood, in his convalescents, was much less active than was that in the cases cited by Lazarus.

[Sidenote: [463]]

Issaeff[739], working in Koch’s Institute in Berlin, examined the blood of several persons who had recovered from cholera, and found that the serum had always acquired a specific protective property; this property never developed before the third week from the commencement of the disease, and had completely disappeared as early as three months after this period. Several examples studied by A. Wassermann[740] and Sobernheim[741] fully corroborate this conclusion. Our own researches[742] on twenty-four cases indicate a very great variability in the protective power of the blood of persons who had recovered from cholera. We were able to demonstrate its presence in rather more than 58 per cent. of these cases. Sometimes this power was almost as marked as in the example given by Lazarus, whilst in others it was very feeble, often even _nil_. We were unable to demonstrate any relation between the gravity of the disease and the strength of the protective power of the blood. Thus, in a moderately severe case of cholera, a very small quantity of serum (0·001 c.c.) was sufficient to protect the guinea-pig from fatal cholera peritonitis, whilst in another, an extraordinarily grave case, even a quantity of 2 c.c. was incapable of producing the same effect. In these two cases the blood had been withdrawn at the corresponding period after the commencement of the disease (seventy-third and seventy-fifth days). Sobernheim (_l.c._) found the protective power of the serum most marked in a person who had cholera vibrios in his normal dejecta, but who was always in good health and was only examined because he was living with cholera patients.

[Sidenote: [464]]

All these observations point to the fact that neither recovery from, nor immunity against, cholera can be regarded as a consequence of the protective power of the blood. This power does not manifest itself until some time after complete recovery has taken place, and then disappears too soon, that is to say at a moment when acquired immunity ought still to be maintained. On the other hand, the irregularity in the protective power of the blood indicates that this humoral property is something secondary. Since Asiatic cholera is an intoxication by the cholera toxin, we can readily understand that the protective power, resulting from the invasion of the living parts of the organism by the vibrios, should here play a part of little importance. We know already that this power is due to the presence of substances manufactured by phagocytic elements, placed in contact with vibrios. In the experimental infection of rabbits by the cholera vibrio, as demonstrated by Pfeiffer and Marx, the cells of the spleen, of the lymphatic glands, and of the bone-marrow, produce the protective substances. We have no idea of the source of these substances in Asiatic cholera in man.

Asiatic cholera, being an example of intoxication of intestinal origin, it might be supposed that the antitoxic power of the body fluids should be specially manifested after recovery has taken place. On this point our knowledge is as yet very imperfect, because it was not until after the end of the last epidemic of cholera that we learnt how to prepare the toxin. In a case of cholera (M.S.), contracted in our laboratory, the blood serum was examined to ascertain its protective power and its antitoxic activity. This fluid, withdrawn more than three weeks after the commencement of the disease, was found to be protective only in a large dose (0·5 c.c.), in which dose even the serum of normal persons is capable of producing the same effect. It was found in an experiment with suckling rabbits that the antitoxic property of the blood serum of M.S. was _nil_. It did not prevent these rabbits from dying of intestinal cholera after the absorption of the vibrios, in spite of a dose of three c.c. of serum injected some time previously.

This experiment, unique up to the present, is, of course, insufficient to enable us to affirm that recovery from Asiatic cholera may take place without the development of antitoxic power in the body fluids. That this is so is, nevertheless, probable. In other intoxications of microbial origin, certain data have been collected which point to the same conclusion. Thus, Knorr[743] observed that the blood of guinea-pigs which had recovered from tetanus did not exhibit any antitetanic power. Vincenzi[744] made a similar observation in a man who had recovered from tetanus.

[Sidenote: [465]]

[Sidenote: [466]]

We are much better informed as to the antitoxic property of the blood of persons who have recovered from diphtheria. Klemensiewicz and Escherich[745] have studied two cases of diphtheria in which the defibrinated blood withdrawn some time after recovery was found to be protective for the guinea-pig against a lethal dose of diphtheria bacilli. This fact has been confirmed by several other observers, especially by Abel[746] and Orlowski[747], the latter of whom made his researches under the direction of Escherich. In these experiments the antitoxic power of the blood was demonstrated against diphtheria toxin employed without bacilli. According to the data collected by the above authors the antitoxic property of the body fluids was not exhibited during the early days of convalescence, but was well marked in the second week after recovery. This power was maintained for a short time only, disappearing in a few months. Amongst the observations collected on this subject the most interesting is that made by Escherich. In an infant examined for the first time whilst it was still in good health, the blood was incapable of protecting the guinea-pig. Some time after this negative result had been obtained the child was attacked by a mild diphtheria, which gave rise to the development of antitoxin, for its blood when again examined exhibited a very high antitoxic power. This proves most clearly that even a slight attack of diphtheria is capable of producing antitoxic power in the body fluids. This observation may be utilised to explain the frequency of the presence of this property in the blood of persons in good health who, according to their own statements, have never had diphtheria. This fact has been established by the researches of A. Wassermann[748], Abel (_l.c._), and Orlowski. According to the last observer, the blood in one-half the children in the hospital at Gratz who had not been attacked with diphtheria was antitoxic against the diphtheria toxin, sometimes even to a higher degree than was that of the children who had recovered from this disease. Wassermann has demonstrated that in adults this antidiphtheritic power of the blood is even more frequent than in children, and that it increases with age. Nevertheless, these persons affirm that they have never had an attack of the disease. To explain this very paradoxical fact, Wassermann asked himself whether the individuals whose blood was antidiphtheritic did not owe this property to the action of pseudo-diphtheria bacilli. Although incapable of causing the disease, these bacilli might, perhaps, exert a certain immunising influence and give rise to the production of an antitoxin active against true diphtheria toxin. Researches, directed to the clearing up of this point, have not led Wassermann to reaffirm his suggestion. It must be observed that the varieties of these pseudo-diphtheria bacilli are numerous, and that some of them, perhaps, may be capable of fulfilling the function suggested by Wassermann. On the other hand, it is proved that the specific and virulent diphtheria bacillus may be found in the throat of persons in good health either without inducing diphtheria, or only giving rise to a very slight form of disease of very short duration. We must bear in mind that in persons who have not had typhoid fever, but who live among patients suffering from this disease, the blood may be very agglutinative (Foerster); that in others, unattacked by cholera but containing Koch’s vibrios in the intestine, the blood may acquire a high specific protective power (Sobernheim). It is probable that the same rule applies also to the case of diphtheria, and that, consequently, the blood of persons in good health, but containing the diphtheria bacillus in their bodies, may acquire antitoxic power.

This humoral power, once developed, may even be transmitted from the mother to the foetus and so become hereditary. Abel (_l.c._) examined the blood serum of four adult women, taking it from the placenta after parturition. Each time it was found to be distinctly antitoxic against the diphtheria toxin. Later, Fischl and Wunschheim[749], working in Chiari’s laboratory in Prague, studied the blood of new-born children from the same point of view. They showed that in the majority of cases this fluid prevents the production of a fatal disease in the guinea-pig, in spite of the injection of several lethal doses of very virulent diphtheria cultures. The blood of new-born children is equally capable of neutralising the diphtheria toxin, that is to say, of protecting animals against poisoning by this toxin. The above observers do not doubt that this antitoxic power comes directly from the maternal blood through the placental circulation. This fact appears to throw some light on the phenomena of immunity acquired by heredity.

[Sidenote: [467]]

Until quite recently we have had very vague notions as to the possibility of transmitting to descendants the immunity contracted as the result of recovery from an infective disease or after vaccination. It has long been known that natural immunity may be transmitted hereditarily. Certain families or certain races are characterised by a special insusceptibility to certain infective diseases. It must even be admitted that this innate immunity has been transmitted from generation to generation. It is quite otherwise with acquired immunity. We know that as a rule the characters acquired during life are not transmitted to descendants; it is only in special cases, in the very lowest organisms, such as the bacteria and their allies, that we may observe the conservation of certain acquired characters through an infinity of generations. The attenuation of bacteria or the absence of the formation of spores, once acquired under special conditions, may thus be transmitted to their descendants who develop and live under normal conditions.

[Sidenote: [468]]

[Sidenote: [469]]

After the discovery of anthrax vaccine by Pasteur, Chamberland and Roux, and an attempt had been made to vaccinate large flocks of sheep, it was an easy matter to investigate whether immunity acquired by the parents was transmissible to their offspring. Several observers, amongst whom I may specially cite Chauveau[750], Rossignol and Cienkowski, got together a certain number of data bearing on this question. These data showed distinctly that, in certain cases, the lambs born from vaccinated sheep presented, from birth, an undoubted resistance to the anthrax bacillus. This fact, however, was neither constant enough nor sufficiently marked to enable us to count upon the young animals being in a refractory condition, and thus avoid having to submit them to vaccination by the two Pasteur vaccines. This necessity threw into the background the researches on the hereditary transmission of acquired immunity. It was only much later that this question was again taken up on a purely theoretical basis. Ehrlich[751], to whom science is indebted for so many works of the highest importance upon immunity, again took the initiative in exact and minute researches upon the heredity of immunity, acquired as the result of vaccination against toxins. In this relation he studied the immunity of the descendants of animals immunised against phanerogamic toxins, such as ricin, abrin and robin, and later, in collaboration with Hübener[752], that of the offspring of animals vaccinated against tetanus toxin. Ehrlich proved very clearly that the antitoxic immunity acquired by the father is never transmitted to his progeny. This fact alone is quite sufficient to show that it is not a true immunity that is met with in young animals born of mothers who have acquired a refractory condition; true immunity is transmitted by the sexual elements, the spermatozoon and the ovum. Certain observers, Tizzoni[753] and his collaborators Cattani and Centanni, thought they could overthrow the rule established by Ehrlich. They believed that the male rabbit, vaccinated against rabies, was capable of transmitting its immunity to its progeny. Charrin and Gley[754] expressed the same opinion as regards animals of the male sex vaccinated against experimental pyocyanic disease. But the very precise experiments of Wernicke[755], Vaillard[756] and Remlinger[757] upon a whole series of infective diseases and intoxications, such as diphtheria, cholera peritonitis, anthrax, experimental typhoid septicaemia, etc., showed conclusively the correctness of Ehrlich’s results. Well-vaccinated males, even when hypervaccinated, never transmit their immunity to their descendants. This acquired property, like so many others, is not hereditary in the strict sense of the word. The females, on the other hand, with rare exceptions, transmit their acquired immunity to their young, but this transmission can in no way be attributed to the ovum; it is here, then, no longer a question of hereditary immunity properly so called. According to Ehrlich the female furnishes in her blood plasma the antitoxin which passes into the circulation of the foetus. In all respects this is allied to the so-called passive immunity (or antitoxic immunity of von Behring). It is due entirely to the direct introduction of antitoxin, manufactured by the cells of the maternal organism, into the body of the progeny. The living elements of the foetus play no part in it, and it is for this reason that the antitoxins and immunity in the new-born animal disappear so very rapidly,—within a few weeks after birth. Wernicke accepts the views of Ehrlich in their entirety. He found that the immunity of female guinea-pigs was transmitted to the new-born animal; but this hereditary transmission was exhausted in a single generation; it was not found in the second generation. Wernicke was able to demonstrate that the refractory condition in guinea-pigs, born of mothers vaccinated against diphtheria, persisted for three months. Vaillard found that it was retained in certain cases for an even longer period,—up to the fifth month. On one occasion he even observed the transmission of the immunity to a second generation. A female guinea-pig, born of a mother immunised against tetanus, gave birth to a young one which, when tested a month after birth with a ten times lethal dose of the toxin, contracted merely a slight tetanus.

From this fact, as well as from the fact that the immunity of the young ones born of vaccinated mothers persists longer than does that conferred by the injection of antitoxic serum, Vaillard concludes that there exists a kind of hereditary immunity which is “fixed” by the cells. He thinks that not only the antitoxins and other antibodies but also certain living elements, especially the leucocytes, are able to pass from the maternal blood into that of the foetus and to transmit to it the properties acquired by the mother. At this point we may recall the facts demonstrated by von Behring and Ransom that antitoxin persists much longer in the blood of an animal when it is introduced with the serum of the same species. (We have described these observations in