PART IV The Functions of the Spleen

(A paper written in October, 1923, and delivered, before the Bexar County Medical Society on February 21, 1924.)

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DEDICATED TO THE PEOPLE OF ITALY

    At a regular meeting of the Bexar County Medical Society held on October 23rd, 1919, at the suggestion of the author, the following memorandum was entered in the minutes of the Society:

    ''It has been my good fortune to make a discovery, which, coupled with my experience in malaria, has led me to the following conclusions:

    "That the spleen, which has so long baffled and been a puzzle to the physiologist, is given to man primarily as a defense against malaria. In other words, the spleen contains the defensive agent or hormone hostile to the malarial parasite, which enables it, first, to resist the initial invasion, thus accounting for immunization; and, second, to resist the influence of the continued residence of the parasite in the body.

    ''That its enlargement is physiological and a prima-facie evidence of a malarial invasion.

    ''The above is founded on my experience in malaria; and the discovery (which harmonizes entirely with the laws of Nature) of the fact that to the bat, whose food consists principally of blood containing the malarial parasite, which it gets from the malarial mosquito in all the different phases of evolution, Nature gave a spleen relatively 4.25 times as heavy as the spleen of man for its conservation and for its protection from the malarial parasite.''

    With a view of demonstrating the gist of the foregoing memorandum, I present this theory for your consideration and criticism, and advance it with the statement that this particular malady, known by the misnomer of "malaria," is a ''physio-pathological'' condition, in that it is so divergent from the bacterial diseases, because it is a scheme of Nature for the human being, and the human being only, to carry and diffuse. It goes without saying that it is a disease, in that it causes pathology without end, but what gives it its physiological aspect is that asexual cycle of the parasite occurs in the body of man; and then he, being provided with a special defense conserving himself against the parasite, thereby permits and insures the continuance of that particular form of life, as well as the life of himself, the host, through which it is perpetuated, and also confers on the parasite a special exemption or immunity from the phagocytes.

    In making the assertion that malaria is a "physio-pathological" condition, that assertion must be founded on, or at least harmonize with, the ordinary laws of Nature, which are a matter of common knowledge, or else it will fall flat.

    It is a matter of common knowledge that when Nature intends one creature to be preyed upon by another, she gives the creature preyed upon some defense against its enemy; for otherwise, the creature preyed upon would soon become extinct, as would also the creature it was intended to nourish. Ordinary reasoning makes this conclusive, as Nature does not defeat her own schemes.

    As the author confines his private practice exclusively to malaria and typhoid fever (the latter on account of its being so frequently associated with malaria and being such a powerful complication), it is but natural that he should give this world-wide disease a great deal of thought and concentrated attention.

    The occasion for launching this theory was brought about whilst the author was dissecting bats in the study of their anatomy, for he was particularly struck with the enormous size of the bat's spleen, as compared to the size of its other internal organs. The weight of a bat's spleen is relatively four and twenty-five hundredths times heavier than the spleen of man. This observation opened a wide field for thought, and threw a bright little beam of light, which, with reflection and study, was converted into a refulgent ray, illuminating one of Nature's mysteries.

    Considerable of the current knowledge of the physiology and anatomy of the spleen gives us valuable clues, which adapt themselves to the theory here advanced.

    Anatomically, at birth, its weight in proportion to that of the entire body, is almost the same as that observed in the adult. This would lead us to conclude that the spleen of the newly-born infant is provided with its hormone ready to defend its host, because at all times, beginning with birth, is a human being subject to infection by an infected anophele. This fact gives to the theory great force; and if it were not a fact, the theory would be just as greatly weakened.

    To quote from Gray's Anatomy, a recognized authority:

    "The arterioles terminate in capillaries which traverse the pulp in all directions; their walls become very much attenuated, lose their tubular character, and the cells of the lymphoid tissue of which they are composed become altered, presenting a branched appearance and acquiring processes which are directly connected with the processes of the sustentacular cells of the pulp. In this manner the capillary vessels terminate, and the blood flowing into them finds its way into the interstices of the reticulated tissue formed by the branched connective corpuscles of the splenic pulp. Thus the blood passing through the spleen is brought into intimate relation with the elements of the pulp, and no doubt undergoes important changes."

    Furthermore, to facilitate these changes, the splenic artery is remarkable for its large size in proportion to the dimensions of the organ, and for its tortuous course. Not only is the size of the spleen entirely in harmony with its functioning,—viz: permitting a large amount of blood to flow into it in order for it to become charged with its protecting hormone, but the fibre-elastic coat forming the framework of the spleen permits it greatly to enlarge, thus enabling it to do more work as conditions arise and demand. This fact again gives to the theory as much force as it would weaken it, if it were not so. One of the most remarkable points in the anatomy of the spleen is that the arteries scarcely anastomose in. order for the blood slowly to find its way into it, while the veins, in order to facilitate the return flow of hormonized blood, are notoriously supplied with anastomoses.

    It may be possible that the spleen destroys a certain number of infected corpuscles, allowing the leucocytes to remain, in order to remove the debris. This would account for the richness of the leucocytes in the spleen.

    There is an abundance of evidence to demonstrate that the spleen is not a blood-making organ, as no disturbance in the digestive functions follows its extirpation.

    Austin Flint, Jr., in his work entitled "Human Physiology,'' on extirpation of the spleen says:

    "There is one experimental fact that has presented itself in opposition to nearly every theory advanced with regard to the use of the spleen, which is that the organ may be removed from the living animal, and yet all the processes of life go on apparently as before. The spleen is certainly not necessary to life, nor, as far as it is known, is it essential to any of the important general functions. It has been removed from dogs and cats, and even from the human subject; and its absence is attended with no constant and definite changes in the phenomena of life.''

    In substantiation of the above, cases are on record of the congenital absence of the spleen in the human subject, in which eases no special phenomena had been observed during life. This would lead us to conclude that the spleen, having no particular functions to perform in the processes of life, was given by Nature to man and certain mammalia for protection against the particular hemameba she causes them to carry.

    And indeed it would be singularly peculiar and out of the infallible order of things in Nature, if she did not do so; as, if she did not give some protection to the human from the malarial parasite, which it is one of her schemes for the human to carry, the human would be overwhelmed by the parasite, which in turn, would be overwhelmed by the perishing of the host, and thereby Nature would defeat her own aims.

    Such a turn of affairs in Nature has not been known, at least not during our short lives. That the parasites do overwhelm the human, just as they destroy the mosquito in the cycle of sporogony by their overwhelming numbers, is a matter of common knowledge to the profession, but these are isolated cases, rather than the rule.

    That the spleen normally enlarges after each meal also supports the results of this study, as it is for the purpose of hormonizing the resultant new blood, thereby performing its function.

    A striking illustration, in support of the assertion that malaria is a "physio-pathological" condition, is seen in the manner in which Nature causes this parasite to find its normal habitat in the body of man, in that it makes its life-cycle intra-corpuscular. As soon as the sporozoit is injected into the blood of the human by the mosquito, it immediately enters the red corpuscle where it is perfectly ensconced and safe from the leucocyte.

    All of its life-cycle takes place in the red corpuscle, hence its freedom from attack by the natural defenders of the body. It is only after the period of sporolation, when the parasites (merozoits) are free in the blood-stream, that the leucocytes can, and do, attack the parasites; a large number of them, however, escape the defenders, re-enter the red corpuscles, where they are again safe from their enemies, the leucocytes, and ready again to begin their cycle of schizogony. By this phase of the evolution Nature asserts her wonderful balancing powers, which serve to perpetuate her various forms of life through the varying vicissitudes to which she causes them to be submitted.

    The asexual life of the parasite occurs in the body of the human. As it is he who furnished the "seed" (gametes) for the perpetuation of its life, and as the seed is such a powerful factor in the perpetuation of life, Nature again asserts herself by granting the gametes special immunities, in that, in the human, they are not strictly intra-corpuscular, they are not a foreign body in the eyes of the Great Force, and consequently are immune from phagocytic attack. But the "seed" has to pass on to another creature, the malarial mosquito, to undergo the true sexual evolution; and here again Nature continues the protection, as all the elements of the blood that the mosquito ingests are digested by her, except the gametes.

    It is quite understood that the mosquito is not in the least concerned about the life of the malarial parasite, as, when she bites, it is with the view of obtaining her natural food; and she is not at all concerned in the perpetuation of another form of life. This is Nature's concern, and we see how well she takes care of her work when we contemplate the enormous prevalence of malaria the world over.

    The enlargement of the spleen in malaria, which is conclusive evidence of a paludic invasion, is nothing more nor less than what is to be expected, as the said enlargement renders it more fit to perform its functions by allowing a larger quantity of blood to enter its structure. In fact, its enlargement, which is concomitant with the sporolating phase of schizogony, and its remaining enlarged for a considerable length of time without undergoing degenerative changes and then reducing itself to its normal size, give it a plain physiological significance.

    The enlargement of the spleen depends entirely on the greater or less severity of the malarial invasion. In notoriously malarial regions the splenomegalys are very common on account of the great prevalence of infected mosquitoes; and continued reinfections keep the spleen enlarged in its endeavors to perform its functions, viz., excreting its hormone, which is inimical to the malarial parasite, and neutralizing its toxins.

    The spleen being much overworked, it is but natural that it should lose the great bulk of its hormone; and the infected individual, finding himself without the protecting agency with which Nature intended him to be provided, soon lapses into serious pathology, in which the blood is first concerned, the physiology and chemistry of that tissue being so disturbed that the blood-making organs revolt at the quality of nutrition they are receiving, and endless pathology of a very severe nature usually follows.

    Its enlargement—that is, when it cannot only be readily palpated but very plainly seen in its left hypochondriac region—is due to its being overworked, with the consequent loss of its hormone. This is evidenced by the fact that the administration of the powdered spleens of animals, PROPERLY SELECTED, will cause its reduction in an astonishingly short time. The words "properly selected," have a deep significance, and their importance will be shown later on.

    The so-called ''Lord of the Universe" is no more in favor with Nature than are any of her other creatures, from the lowest to the highest; and, if we turn to the bovine family, we shall find a most perfect analogue furnishing convincing evidence in favor of the results of this study.

    In this species of mammals, Nature has seen fit to perpetuate another form of parasitic life in the red corpuscle of that creature, the disease to which it gives rise being known as babiosis, or familiarly as "tick fever," or sometimes as "malaria in cattle." Here the tick plays the same role in the bovine family that the mosquito does in the human family. This particular form of parasitic life, known as the piroplasma, thrives in the bodies of cattle, and in the bodies of cattle only, just as the plasmodia finds its normal habitat in the human being, and in the human being only. None of the domestic or the wild animals carry malaria, neither do any of the wild animals carry the piroplasma which cause the tick fever in cattle.

    An infected mosquito cannot infect an individual of the cattle species; and it is very doubtful as to whether an infected tick can convey the tick fever to man. There are many species of ticks, but only one species conveys the tick fever to cattle, just as there are many species of mosquitoes, but only one species transmits malaria to the human.

    In cattle with the tick fever the same pathological changes take place in the blood-making organs as do in the human being infected with the malarial parasite. This the author knows from actual observations in the slaughter houses. In fact, the analogy is so perfect, that if some enthusiastic student having the time and money and love for original research in the interest of mankind and science, would establish a thorough, systematic, and scientific study of babiosis, he would have plenty of material to work on, from the embryo to the adult; and the knowledge so gained would apply most fittingly to malaria in the human.

    In the tick, a cycle of evolution takes place on the part of the parasite, similar to the cycle of evolution that takes place in the body of the mosquito. In the red corpuscle of cattle, a cycle of evolution takes place similar to that of the cycle of evolution that occurs in the red corpuscle of man.

    In the parasitisms, or "physio-pathological" conditions, in both the human and the bovine families, we see how strictly Nature draws the line as to the food of her parasites, in that the piroplasma will not develop in the blood of any other creature that the infected tick may happen to be feeding upon. The tick itself finds nourishment, but the parasite does not, consequently its life's cycle is arrested, and it perishes. The mosquito finds nourishment in any kind of blood, but the malarial parasite she carries finds nourishment in human blood only. In tick-infected pastures or ranges, none of the wild animals there, such as the deer, which mingle freely with the cattle, particularly at the salt licks, acquire the tick fever, neither are any of the domestic or wild animals infected with malaria by an infected malarial mosquito.

    At first glance it would seem that, in the perpetuation of parasitic life, Nature gave the mosquito an advantage over the tick, in that it flies from host to host, while the tick hatches on the ground and has to await the coming to it of its host. Truly, the tick does not fly from host to host, as it has no wings to fly with; but, unlike the mosquito, the egg of the tick is infected before it is hatched, which makes up for the non-flight, and so most unerringly does Nature continue that particular form of parasitic life.

    When an individual of the bovine family is bitten by an infected tick, it acquires the tick fever, and, like the human being, the development of the acute form depends on the number of parasites injected, plus the condition of nutrition and environment. If it recover from the acute form, it is referred to by the cattle owner as being ''immune,'' which is very much in error, as the animal now has the disease in the chronic form, just as the human being has malaria in the chronic form after passing through an acute attack; and both the human and the bovine families are the disseminators of their respective parasites in their respective ways,—or, in other words, they are obeying the inexorable laws of Nature.

    In the body of man, malaria need not begin with the acute form in order to exhibit its chronicity; fever need never have been a necessary accompaniment of a paludic invasion. Perhaps the same condition holds good in cattle.

    If we should encounter a rosy, well-nourished individual, showing not a single trace of the cachexia, we should be inclined to think that he was in the enjoyment of good health until he tells us that at times he suffers with severe "headaches." An examination of his blood will perhaps show negative, but his migraines or hemicranias give the tell-tale periodicity, overshadowing the most unsatisfactory of diagnostic methods, the microscopic.

    If we select from a good-sized herd of cattle the healthiest, sleekest-looking animal, one that we have seen on foot in a playful mood, on post-mortem examination we shall find with but little difficulty the tell-tale enlarged spleen, and also the piroplasma in the blood from the spleen. In both instances it is by the spleen that the pathology has, at least for a time, been held in leash through the protective hormone secreted by the spleen; but, again, both are disseminators of their respective parasites, and are obeying the laws of Nature.

    The author desires to state that his observations of the spleen in cattle have been limited to animals slaughtered in this vicinity (San Antonio), such as cattle, pigs, goats, and sheep. As to other localities he has no data.

    That the chemistry of the spleen in man is identical with that of the spleens of the ordinary food animals, is evidenced by the fact that the human spleen will readily replace its exhausted condition by the administration of any of the spleens or splenic extracts of the animals mentioned, provided the spleens employed are normal.

    This was mentioned in one of the preceding paragraphs; and emphasis was laid on the words ''properly selected.'' The author has had considerable experience in the treatment of very poor Mexican children, having chronic malaria, with splenomegaly; and in several cases the ordinary spleen extract found in the drug stores was used without perceptible results.

"

Digestive System of Bat, from Larynx to Anus. Note the large spleen between the arrows."

Bat's Skull.

    Spleens from young pigs and goats were then procured in the slaughter houses, salted, and dried in the same manner that beef is dried—by being hung on a line in the sun. When dried, this parchment-like substance is pounded into a powder; and as much powder as a dime will take up, being held between the fingers at the edge, is given to the child four times a day—(this amount will weigh four or five grains). In an astonishingly short time the spleen resumes its normal size, and the pot-belly subsides.

    To secure "properly selected" spleens one must avoid the bovine spleens, as hardly one per cent of them are normal, showing the extreme prevalence of the piroplasmic infection in cattle; and it is nothing but what we ought to expect, as they live "under the open skies," or next to Nature, thereby facilitating the obedience to Nature's laws. Their higher contemporary would be as highly infected with his parasite, if he lived under the same conditions.

    It goes without saying that the powdered spleens, or splenic extract made from animals with babiosis, is even more than worthless, as the very substance desired has been exhausted in an enlarged spleen for, otherwise, it would not have been enlarged. This would account for the failures some of us have had in prescribing some of the spleen extracts found in the drug market. In order to procure the best results in the administration of spleen substance, the spleens should be removed from young pigs, sheep, or goats, and thoroughly examined by some competent veterinarian, and a long time after the animal has fed—or, better said, before feeding time, as it is then that the spleen is richest in its hormone, and begins to enlarge and expend the same in the performance of its physiological function.

    As a portion of these studies—particularly the analogue of malaria in cattle—comes under the realm of animal medicine, I desire to return thanks to Dr. Ingild Hansen, a highly learned Danish veterinarian, U. S. A., retired, for his hearty co-operation and advice.

    One of the most distressing experiences in the treatment of malaria is to encounter a patient with an idiosyncrasy against quinine. Such individuals suffer a great deal; and their health becomes seriously undermined because of their being deprived of that most valuable of therapeutic agents. If this study should arouse in the mind of some enthusiastic physiological chemist the desire to set for himself the task of isolating the hormone from the spleen, and if he should succeed, it is very much within the realm of possibility that he will not only have conferred a boon on his fellow man, but perhaps will have given to the world a therapeutic agent superior to quinine.

    It is the bat, which the author has been studying for a period of twenty-one years, that gives strong testimony in favor of the theory, and it would perhaps be fitting to quote from these studies some points having a bearing on this argument. The species studied so intensely by the author is the common free-tail bat—Nyctinomous Mexicanus—but what has been learned of this species applies to all others of the small varieties. In Mexico all the small bats are called "murcielagos mosqueteros," meaning mosquito bats,—so well and so long have the natives understood their habits.

    The enlarged photograph of a bat's skull proves it to be distinctly carnivorous. A glance at the dental formula shows the prominent canine teeth, but the molars differ from the molars of the carnivora, in that they are chopping teeth instead of grinding. The value of this provision is readily seen when we take account of the fact that the bat procures its food in the air, and, if it had to grind it like a cat or dog does, the food would fall out of its mouth and be lost. The mosquito, being a blood-sucking insect, and its abdomen being engorged with blood, affords the bat an ideal carnivorous diet.

    As it matters not to the mosquito from whom she gets blood, whether from the human or the bovine family, from the dog, coyote, deer, or what not, it does matter, and is of vital concern, to Nature, in that in the blood which the mosquito gets are different forms of parasites taken from the different creatures from whom she procures it. It is this parasitic-laden blood, with its concomitant toxins, which she causes to be wholesome to the bat; and she provided the proper protection when she gave that creature such an enormous spleen.

    It would be, indeed, strange, if Nature should have found other means than the spleen to protect the bat, when she already employs that method in some of her other creatures. This again supports the assertion that the chemistries of the spleens of man and of animals are so nearly identical. The spleen of a bat protects it from any and all of the different hemameba, and from toxine-laden blood carried by the different creatures in which they find a normal habitat, and which the mosquito ingests, in turn to be ingested by the bat.

    The studies already referred to show the bats to be remarkably free from disease, notwithstanding the fact that they live in caves with no ventilation, in the midst of their own excretions, and in an ammoniacal atmosphere created by the decomposing guano. The longevity of the bat is accounted for by the absence of a colon.

    In studying the scatology of bats, chemistry reveals the kind of food the creature subsists upon, and very conclusively shows the enormous amount of blood the bat consumes. In fact, it might be said from the figures that follow, that the bat has a selective instinct for finding the engorged mosquito. One ton (2000 pounds) of bat guano contains three pounds of iron. This is the valuable point, and these are the figures that give it a firm foundation. This estimate is founded on the fact, as will be noted in the current text books, that haemoglobin contains 0.42 per cent of iron, and blood contains 15 per cent of haemoglobin.

    With this information in hand, we find that three pounds of iron are the ferric content of 4761 pounds of liquid blood. Sixty-seven per cent of bat guano consists of chitin, and this per se contains 0.85 pound of iron, which is the ferric content of 1349 pounds of blood. Of course, this 0.85 pound of iron and the ferric content of 1349 pounds of blood it represents, must be deducted from the three pounds of iron and the 4761 pounds of blood. In order to be very conservative and to avoid any possible source of error, let us deduct 0.15 pound of iron as being derived from the ten per cent of the food of bats other than mosquitoes, small plant-sucking insects which would carry some iron from the green coloring matter of plants (chlorophyl) and which is the ferric content of 237 pounds of blood.

    Thus far we have accounted for one pound of iron and the 1587 pounds of blood it represents. We still have two pounds of iron, which is the ferric content of 3174 pounds of blood. Reduced to smaller figures, each pound of bat guano represents more than one and one-half pounds of liquid blood. More, it is said, because after the mosquito has had her fill of blood, and while at rest digesting her meal, in order to concentrate her food, she voids the liquid portion of the blood (liquor sanguinis) and, of course, this does not figure in the chemical determination of the iron content in the bat guano.

    The enormous good the bat does and the wonderful benefit it is to us almost baffles the imagination, when we contemplate the uncountable number of mosquitoes, each with its tiny droplet of blood in its tiny abdomen, that the bats must catch, in order for each pound of bat guano to represent more than a pint and a half of liquid blood. It arouses in our minds "a feeling akin to pain," with a sense of guilt, at having had for, lo, these many years, such a valued friend doing such wonderful work for us, and we unconscious of the fact.

    In the bat roost already described and which the author calls his Mitchell's Lake bat roost, approximately two tons of bat guano are gathered every year; and, as we have seen, this represents 6348 pounds of liquid blood. This however, is only the guano dropped on the inside of the roost during their resting hours, or the day, and does not take into account the guano dropped in the open by the bats during their hours of feeding, which ordinary reasoning assures us to be at least again as much. Thus we see that the tenants of this little building consume enough mosquitoes in one year to make up 12,696 pounds, or more than six and one quarter tons of liquid blood, and these astounding statements are not founded on the experiments, statements, or observations of any person, but on the solid and immovable foundations of SCIENCE.

    In conclusion, I hope you will pardon me when I digress from the subject matter to say that it has been one of the most ardent desires in my professional life to arouse the laity and create public opinion on the seriousness of this ''physio-pathological" malady, malaria, which is now regarded with so much levity; and if you are of the same opinion, and will use all of your influence and power to that end, you will add lustre and garlands of laurels to that noblest of all the professions, of which I have the honor to be an humble member.

    N. B. Since the preceding was set up in type, there has been received a lengthy resume of this paper on the spleen published in the June, 1925, issue of the Giornale di Medicina Militare, issued by the Ministry of "War at Rome, Italy. This recognition is a realization of one of the author's fondest hopes.