Bacteria in Daily Life

It is far from an easy matter to secure for experimental purposes an adequate supply of eel serum, for even a big fish weighing nearly five pounds is not capable of yielding more than about twenty-five cubic centimetres of blood, and from this only from ten to twelve cubic centimetres of serum are obtainable. Calmette has shown that not only the venom glands of reptiles contain toxic substances, but that the blood of such snakes also possesses lethal properties, only in a far less degree. Curiously, the serum of eels is no less than three times as toxic as the serum of the most vicious viper, and, moreover, produces far more discomfort and pain to the animals into which it is introduced than accompanies the injection of viper blood. In the case of viper blood its introduction is followed by no symptoms of discomfort, the animal remains quite quiet, growing more and more somnolent, a condition which is followed by an abnormal fall of temperature, ultimately ending in complete collapse, symptoms which in a much more modified degree characterise the injection of heated eel serum into animals. This heated eel serum, which we have seen is deprived of the objectionable characteristics of ordinary eel serum, produces but very transitory symptoms in animals, occasioning some degree of somnolence, and now and again a reduction in temperature, a condition from which, however, the animals rapidly recover in from two to three hours. Animals, however, treated with this heated eel serum acquire a power of resisting the lethal action of unheated or ordinary eel serum, and this artificially induced condition of immunity continues for about three days after the completion of the treatment.

The protective properties of this heated serum are not restricted to animals subsequently inoculated with eel serum, but are extended also to animals which afterwards receive injections of viper serum; but of much greater interest and importance is the remarkable fact that heated eel serum, as well as weak doses of the latter not heated but diluted with water, are capable of protecting animals from the fatal consequences of the far more potent viper venom.

It is interesting to note that, although diluted eel serum can protect an animal from so deadly a poison as viper venom, the serum of vipers is quite unable to afford any such service in the case of animals inoculated with ordinary eel serum. The full complement of protective power obtainable from this treated eel serum is only able to slowly assert itself, for it is necessary for a period of as long as twenty-four hours to elapse after its introduction to ensure the animal's system being thoroughly impregnated with it and enable it to withstand a lethal dose of viper venom.

In this respect, what may be designated treated or protective eel serum differs very markedly from anti-venomous serum, which we have seen is serum derived from animals trained up to withstand fatal does of serpent venom, for anti-venomous serum acts immediately, and at once confers immunity on an animal from the lethal effects of such venom.

The rapidity with which it acts is indeed one of the most astonishing properties of this particular anti-toxin. Thus if two cubic centimetres of anti-venomous serum be inoculated into the marginal vein of a rabbit's ear, it at once confers upon the latter complete immunity from snake poison. Immediately after the injection of the serum, venom sufficient to destroy an ordinary rabbit in a quarter of an hour may be injected with impunity into the vein of the other ear. But not only are the protective powers of this serum so remarkable in their degree, but its curative powers, a much more difficult property to establish in a substance, are extraordinarily intense, as may be gathered from the following example. Four rabbits were inoculated with a quantity of venom calculated to destroy them in the space of two hours; one of these four animals was abandoned to its fate, but the other three received, practically at the eleventh hour, viz. just fifteen minutes before the expiration of the calculated two hours' respite, an intravenous injection of a small quantity of anti-venomous serum, only amounting to one four-hundredth part of the weight of each animal respectively. The rabbit which received only the venom died at the end of two hours, whilst the other three remained in perfect health.

But although eel serum can be persuaded to part with its poisonous character and even exercise protective powers over otherwise doomed victims, it is not able to stretch forth a healing hand to the afflicted, for, when once the poison has been introduced, whether it be eel or viper blood, or the venom of snakes, it is absolutely powerless to mitigate or stop in any way the deadly progress of the toxin. Thus whilst eel blood may acquire protective properties it cannot acquire curative properties, and, therefore, treated eel serum cannot be legitimately enrolled with the anti-toxins which have been elaborated, as, for example, anti-venomous serum, for, to be worthy of such rank, a substance must be capable of wielding both protective and curative powers.

But, although eel serum may under certain conditions protect from the lethal action of serpent venom, eels are not themselves under ordinary circumstances endowed with any power to withstand the influence of this poison, for a good-sized eel will succumb to a dose of venom which is sufficient to kill a guinea-pig.

Considerable interest is attached to the fact that anti-venomous serum not only acts as an anti-toxin towards serpent venom, but also towards a poison of quite a different character, such as that present in the normal blood of eels, for this fact tends to confirm the view upheld by some authorities, that specific toxins do not necessarily only yield to specific anti-toxins, and that a particular anti-toxin may act as such towards divers toxins of varied origin and character. Calmette has brought this point out very clearly in his later investigations on the vegetable poison abrine, a very powerful toxin, furnished by the active principle of the seeds or beans of a leguminous plant common in India and South America, and frequently used, as already mentioned, by the natives in India to revenge themselves on their enemies in poisoning their cattle. Immunising serums of various kinds were selected for testing their protective action on animals poisoned with abrine, and it was found that anti-tetanic, anti-diphtheritic, anti-anthrax, and anti-cholera serums all individually exerted a decided immunising action with regard to this powerful vegetable poison. The hope is, therefore, perhaps not beyond the realm of possibility, that at some future time the complexity of drugs which now figure in the chemists' pharmacopœia may be replaced by a few substances the application of which will come within the means and understanding of all. So far we have not dealt with the artificial immunisation of an animal from the action of eel poison, but this apparently offers very little difficulty, and is accomplished by introducing very small and gradually increasing doses of eel serum into the system, care being taken to proportion the quantity given according to the weight and general condition of the animal to be immunised. A rabbit, for example, treated in the above manner, subsequently yielded a serum which was proved to possess both preventive and curative powers in respect to both eel poison, and viper venom and blood, entitling this so called anti-eel serum to take its place amongst the anti-toxins, and furnishing yet another instance of a substance exercising its immunising influence over various toxins.

This process of gradually acclimatising, as it were, animals to a particular poison by repeated doses of the same poison, recalls the old proverb, "Seek your salve where you got your sore," and brings us to a consideration of some of the primitive antecedents of a practice which, at the present time, promises to bring about so profound a revolution in the art of medicine. The modern system of inoculation has, however, arisen quite without reference to such antecedents, which latter were not based upon any scientific laws or considerations, but owed their evolution to local customs and experience handed down from age to age by tradition, and in many cases preserved through a simple faith in the superstitions which surrounded them.

To such a category must be added the curious superstitions indulged in by the native population of Tunis regarding methods of preventing hydrophobia in persons bitten by rabid animals. Dr. Loir refers to these primitive ideas on the art of healing in a report of the work carried out at the Anti-rabic Institute at Tunis, one of the many centres for the prevention of rabies by Pasteur's method which have been established in every quarter of the globe except Great Britain, the inhabitants of this "great conservative island-Empire," as a renowned foreign scientist describes it, still preferring a trip to Paris to countenancing the establishment of an anti-rabic institute in their own country. The Arab physicians in Tunis have from time immemorial sought to specially identify themselves with cures for this disease, which is so prevalent as to be a veritable scourge to the country. A much-vaunted remedy advocated by the profession consists in pounding up the charred head of a rabid dog with vinegar, and administering an emulsion of the same to the patient. The dung of camels is also highly prized as a remedy, as also the water of certain wells which the simple faith of the natives has endowed with supernatural curative properties. But the strangest prescription of all consists in broth made from lambs a year old, to which is added a peculiar kind of beetle, but in such a small quantity that the latter ingredient only equals the weight of a grain of corn. This concoction is given to the unfortunate patient twenty-three days after he has been bitten. In the urine, according to the Arabian doctors, seven small worms should be found which represent the embryos of dogs engendered by the virus in the human body, and which when once got rid of the patient recovers!

In the face of such crude traditions upheld with so much tenacity by the native population, it is surprising that the Tunisian Anti-rabic Institute has met with such a large measure of support in the shape of applicants for admission, which, on an average, number over one hundred annually. The mortality amongst those treated closely approaches the satisfactory results obtained at the Paris Institute, where the death-rate amounts to about 0·38 per cent. of the persons treated.

There is perhaps no more interesting chapter in the history and literature of medicine than might be compiled by searching out the early uses of drugs and the primitive application of methods in the art of healing, and tracing their connection, if possible, with the practices which are in vogue at the present day. In the matter of toxins and anti-toxins, or in respect to the modern theories of preventive medicine, there would appear to be a curious link between the methods based upon elaborate scientific inquiries and those which arose through simple experience and expediency.

The idea of a poison, as the old proverb above tells us, being a corrective for itself is no new idea, for we read how in ancient times, for example, the Ophiogenes of the Hellespont were renowned for their immunity to snake poison, and one account of them states particularly that they fed upon serpents, and that to this diet they probably owed their reputed magical art in withstanding the action of serpent venom. Again, a traveller in Egypt, Hasselquist, tells us how the serpent-charmers there eat serpents, making them into a kind of broth, and that invariably before starting off to catch these reptiles they partake of some of it.

In a paper by Mr. T. R. Rao on the Yánádés tribe of the Nellore district, Madras Presidency, the author mentions that these strange people have, amongst other characteristics, absolutely no fear in catching cobras, which they draw out of their holes without any alarm as to their fangs, and that they appear to protect themselves against the effects of snake-bites by swallowing the poison-sacs of snakes.

Bruce describes how he saw a serpent-charmer in Cairo who allowed himself to be bitten by a viper between the forefinger and the thumb, and made no endeavour whatever to apply remedies, neither did he exhibit the slightest anxiety as to the consequences. That this was no trick, and that the viper was really possessed of all its deadly faculties at the time it bit the man, was proved by the fact that a pelican subsequently bitten by the same animal died in thirteen minutes. Bruce also tells of a man who "with his naked hand took a viper from a number of others lying at the bottom of a tub. He put it on his head, then in his breast, and tied it about his neck like a necklace. Next it was made to bite a hen, which died in a few minutes; and, to complete the experiment, the man took it by the neck, and, beginning at the tail, ate it as one does a carrot or a stick of celery, without any seeming repugnance."

A most interesting account of snake-charmers is given by Drummond Hay, in his book on Western Barbary, in which he relates his experiences with some of these wonderful individuals belonging to the sect called Eisowy. Members of this sect, he mentions, frequently handled scorpions and poisonous reptiles without fear or hesitation, and they were never attacked by them. He was present at one of their exhibitions of feats with snakes in which they both allowed themselves to be bitten and provoked the snake to bite them. The charmer thus bitten then in his turn ate or chewed the reptile, which, he remarks, writhing with pain, bit him in the neck and hands till it was actually destroyed by the Eisowy's teeth.

In South Africa snake poison is actually taken as a protection against snake-bites, and if we turn to the Lancet of the year 1886, we shall find a letter from Mr. Alfred Bolton stating that his curiosity had been aroused by the fact that while in South Africa cattle and horses frequently died from the effect of snake-bites, the natives themselves seldom or never appeared to suffer any inconvenience from such injuries other than would follow any accident which would set up local inflammation. On inquiry he found that they were in the habit of extracting the poison gland from the snake immediately it is killed, squeezing it into their mouths and drinking the secretion, thereby apparently acquiring absolute immunity from snake-bites. So impressed was Mr. Bolton by what he observed that he adds: "I can no longer refuse to believe in the efficacy of the snake virus itself as a remedy against snake poison."

Savage tribes have learnt from bitter experience how to protect themselves from snake-bites, and it is well known that they have a method of inoculation which they employ with success. The Creoles of Surinam use an ointment as a protection against snake-bites, which is regarded as highly efficacious. It is reputed to consist principally of the pounded head of a rattlesnake, which concoction would therefore include the contents of the venom glands. This is then mixed with the juices of a certain plant, which addition probably mitigates the intensity of the venom by acting as a diluent. This substance is generally applied by making an incision in the wrist or forearm and rubbing it in, after which individuals thus treated appear to enjoy security from the venom of snake-bites.

What applies to serpent venom would also appear to hold good in regard to other poisons, such as that contained in the sting of a bee. This poison is extraordinarily tenacious of its irritant properties, and, unlike eel poison, retains its virulence even when exposed to high temperatures.

An interesting memoir on the immunity of the bee-keeper from the effects of bee poison was published a short time ago by Dr. Langer in a German scientific journal. He issued a number of circulars with questions to be answered, and sent these to more than a hundred bee-keepers in different parts of the country, with the result that a hundred and forty-four stated that they were now immune to bee poison, nine having been fortunately endowed with a natural immunity to this irritant, whilst only twenty-six out of the whole number applied to stated that they were still susceptible.

This condition of immunity to bee poison is obtained after a varying number of stings have been inflicted; in some cases thirty, at the rate of from three to four a day, are sufficient to ensure freedom from further discomfort, but the inoculations may have to be prolonged up to one hundred stings to secure complete immunity.

In experiments carried out on animals this immunity to bee poison has been also induced by repeated application of the irritant. It was formerly generally supposed that the irritant nature of a bee's sting was due to the presence of formic acid; but inasmuch as bee poison can retain its poisonous character in spite of being submitted to heat, which would effectually volatilise the formic acid present, this assumption must be abandoned, and opinion is more inclined now to regard this irritant substance as partaking of the nature of an alkaloid.

Before closing this brief review of some of the most recent discoveries which have been made in the domain of immunity, we must mention some extremely suggestive and important researches on the poison of tetanus, or lock-jaw, which have emanated from Dr. Roux's laboratory at the Institut Pasteur in Paris.

It will perhaps be remembered that Pasteur, when working at hydrophobia, experienced the greatest difficulty in exciting rabies in animals with certainty, and that it was only when the fact of its being a disease which essentially affects the nervous system of the animal was taken into account that it occurred to him to cultivate the virus in the medium for which it had seemingly the greatest affinity, viz. the nervous tissue of an animal; it was only on taking this step that he succeeded in invariably provoking rabies in the animals under experiment.

In the case of tetanus we have another disease affecting the nerve-centres of the body, and although many authentic cases have been cited in which the treatment with anti-tetanic serum has been entirely successful, a great many instances have occurred in which it has been of no avail at all, more especially when the disease has obtained a firm hold on its victim. Now Dr. Roux has not only been carrying out experiments to ascertain what is the result of directly attacking, as Pasteur did in the case of rabies, the nerve-centres of an animal with the tetanus toxin, but he has also taken another and very important step further, and has investigated, not only the action of the toxin, but also that of the anti-toxin on the nerve-centres of an animal suffering from tetanus.

In describing the cerebral inoculations which he has conducted on animals, Dr. Roux points out that the operation, in itself, is attended with no pain or even inconvenience to the animal in question, that subsequently it eats with its usual appetite, and shows no signs of discomfort.

First, as regards the infection of an animal with the tetanus virus introduced directly into the brain, it has been found that very much smaller quantities produce a fatal result than when subcutaneously inoculated. Thus, a rabbit which received two cubic centimetres of the poison under the skin took four days to succumb to tetanus, whilst one-twentieth of the quantity inoculated into the brain sufficed to kill another rabbit of the same size in less than twenty hours.

Another very instructive example of this susceptibility of the nerve-centres for certain poisons is afforded in the case of rats and the toxin of diphtheria. Rats possess a natural immunity from this substance, and can successfully withstand a dose of diphtheria poison introduced under the skin which would infallibly kill several rabbits. This state of immunity, however, entirely disappears when the toxin is brought directly in contact with nervous tissue, for a very small quantity of diphtheria poison – insufficient to cause under ordinary circumstances even a passing swelling at the seat of inoculation – will, when introduced into the brain of a rat, kill the animal.

Again, rabbits are generally credited with possessing high powers of resisting the action of morphia, a large dose of this substance introduced subcutaneously producing no result whatever. A cerebral inoculation, however, of a minute quantity of morphia causes an immediate reaction, and the animal, after remaining in a more or less dazed condition for several hours, finally succumbs to this drug. Dr. Roux is inclined to regard this difference in the susceptibility exhibited by animals to one and the same poison as being due to a good deal of the toxin, when subcutaneously introduced, failing to reach the nerve-centres, it having been destroyed or arrested in the system before it could attack them.

What is the nature of the subtle forces which may so beneficially intervene between the toxin and its victim has long been a problem which has excited the interest and ingenuity of some of the most brilliant scientific authorities of the day, and it is one which, even in the hands of men like Metchnikoff, is still awaiting a satisfactory solution!

The important point was next approached by Dr. Roux as to whether an animal, successfully trained to withstand large doses of the poison, as ordinarily introduced, could also resist it when directly inoculated into the brain. Is, in fact, the undoubted immunity to tetanus poison which may be possessed by an animal due to the nerve-centres having become insensible to this substance? The answer to this question would appear to be in the negative, for animals artificially protected from tetanus poison introduced under the skin succumbed to a small dose inoculated direct into the brain, which would otherwise have not produced even a slight passing tetanic affection of the limb where the inoculation was made. Immense numbers of experiments were made under varying conditions, but the result was fully confirmed, showing that the nerve-centres had not acquired any immunity to the poison, although the blood serum of the victims to such cerebral inoculations was proven over and over again to be endowed with strong protective properties against tetanus poison.

The endeavour was then made to, in Dr. Roux's words, "place the anti-toxin where the toxin is working," and preserve the vital force of the nervous tissue. To arrest tetanus by substituting cerebral for subcutaneous inoculations of the anti-tetanic serum was the next feat attempted. Several guinea-pigs and rabbits were inoculated subcutaneously with virulent doses of tetanus poison sufficient to kill them in about seventy hours; some were subsequently treated with anti-toxic serum introduced in the ordinary way under the skin, whilst others were inoculated with from six to seven drops of this protective serum direct into the brain. The results were extraordinarily successful. Although but a few drops of the anti-toxin were used for the cerebral inoculations, the animals survived the otherwise fatal doses they had received of the toxin; whilst out of seventeen guinea-pigs which received subcutaneous inoculations of the anti-toxin only two recovered, and the quantity of the anti-toxin employed reached as much as from ten to twenty cubic centimetres in some of the experiments, contrasting in a remarkable manner with the few drops which sufficed in the case of the cerebral inoculations.

Dr. Roux sums up this splendid result in the following modest words: "Il ne suffit pas de donner de l'anti-toxine, il faut la mettre au bon endroit."

The significance and far-reaching application of this most important discovery cannot easily be overestimated. Hitherto the preparation of an anti-toxin has been the chief point considered, but Dr. Roux and his able coadjutor, M. A. Borrel, have shown how great may be the results which attend its method of administration, and have opened up an entirely new direction for investigation.

Although the subject of immunity is not, as we have seen, by any means wholly a latter-day creation, yet its approach and consideration from a modern point of view, assisted by the resources and equipment provided by modern scientific methods, justifiably entitles the nineteenth century to claim it as its own discovery.

However brilliant and successful the labours may be of those who will follow in the future, subsequent generations will know how to venerate those great leaders of scientific thought, amongst whom we must rank Pasteur, to whose genius the world owes so great a debt of gratitude, and the vast extent of whose labours cannot be adequately measured at the present day by reason of the restricted scientific horizon which encircles public opinion in this country.