Protozoology

"Protozoology (see 22.479) is that branch of zoology which is concerned with the group of animals known as the Protozoa. It is not, as its name might seem to imply, a primitive form of zoology. As a science it is comparatively young, but, owing chiefly to the practical importance of some of the animals with which it deals, it had in 1921 already become one of the largest and most cultivated fields in biology. The Protozoa are very interesting animals, from both the practical and the theoretical standpoint. Nevertheless, they are all small, and most cf them of microscopic dimensions. To the general public they are therefore invisible, and consequently unknown, except by the conspicuous results - such as diseases - which they occasionally produce. In common speech they are still nameless, though they are popularly included among" animalcules "and" microbes."But these are unscientific and unnatural groups, which comprise all microscopic creatures, both animals and plants; and consequently the Protozoa are still confused, in the popular mind, with other" microbes,"such as the Bacteria, with which they have no connexion.

It will be evident that protozoology, as an independent science, must necessarily have arisen as a comparatively late offshoot of zoology. Its history is bound up with that of the microscope, an instrument which bears much the same relaton to protozoology that the telescope does to astronomy. Before microscopes were invented no Protozoa could have been clearly visible. With the first lenses, the largest and most conspicuous of them were discovered; and as microscopes were improved, more and more minute creatures gradually became known. Out of the confusion of forms which the microscope has continued to reveal, the Protozoa have ultimately emerged as a well-defined group of animals, and, as a result, those who study these animals have slowly built up a new section of zoological science.

As an individual science protozoology only became selfconscious at a quite recent period. The name itself, though already in use between 1870 and 1880, only became current after the opening of the 10th century - that is to say, within the memory of many living zoologists. But the science was really born - though not baptized - when the first Protozoa were discovered. This far-reaching discovery was made in the latter half of the 17th century. It was made by a man who was neither zoologist nor physician, but who occupied the humble position of chamberlain to the sheriffs of the little town of Delft, in Holland - Antony van Leeuwenhoek (1632-1723), an amateur microscopist, who studied at no university, nor under any of the great professors of his day, but whose title to fame rests upon the simple and honest application of his own native genius. This remarkable man made his own microscopes, lenses and all, and turned them upon almost every object which suggested itself to his quick imagination. In the course of his work he examined the water from the leaden gutters of his house, from the well in his courtyard, and also fresh rain-water, snow-water and" the water wherein pepper had lain infused."He found that all these liquids, and many others, were not clear and empty when viewed by the microscope, but teeming with living creatures. The discovery was promptly communicated by letter to the Royal Society in London, who published a part of it in the year 1677. Some of the animals which Leeuwenhoek here described can now be identified as Protozoa, and his letter may therefore be regarded as the first page in the history of protozoology.

Leeuwenhoek, the father of protozoology, himself studied and described many Protozoa. His observations were soon repeated and confirmed by others, notably by some of the early Fellows of the Royal Societ y and his fellow-countryman Huygens, the great astronomer. But for many years protozoology made little progress, and remained essentially what it was originally, an amusement rather than a science. Although many good observations were made and recorded, they were always disjointed, and often distorted by fancy and speculation. Many good zoologists regarded with doubt and misgiving everything seen with the microscope, an attitude of mind which has not quite disappeared even in these days of perfect instruments. Even the great Linnaeus (1707-1778), who attempted to catalogue and classify all animals and plants, and thereby founded modern systematic biology, never really overcame his suspicions sufficiently to incorporate the Protozoa firmly in his system. His mental attitude is shown in the name" Chaos infusorium," with which, in 1767, he dubbed a mixed lot of questionable protozoal organisms - the term Chaos itself having been suggested, no doubt, by Ovid's" rudis indigestaque moles." But already at this period many workers were convinced that the Protozoa - or" Infusoria,"as they were then called, from their occurrence in infusions - have a real existence. The once notorious John Hill (1716-1775), in the course of his journalistic, theatrical, medical, and botanical adventures, turned his attention to microscopes; and in 1752 he described and, for the first time, scientifically named, a number of Protozoa which he had seen in infusions. Up to this time writers had been content to call them by diminutives of the names of larger and more familiar creatures, or occasionally by names suggested by comparison with some common object. We thus find the early protozoologists describing their observations upon << little" "little insects," worms, fishes,"and even reptiles," and upon " "the slipper," the sun, the trumpet, the gimlet,"or the bell animalcule." It was not until 1773 that a serious attempt was made to reduce the chaos to order by careful observation and description and classification of the "Infusoria." This notable work was done by the Danish naturalist, O. F. Muller (1730-1784); and his last book, published posthumously in 1786, is the first systematic treatise on protozoology. It is a remarkable work, full of shrewd observations, and showing astonishing insight, but containing, of course, many mistakes which were inevitable at that period. Many of the Protozoa described and sketched by Muller - mostly from observations made, as were those of Leeuwenhoek, with the aid of only a simple lens - are easily recognizable now by a protozoologist.

The circumstance that Muller was able to attempt a comprehensive systematic treatise on the Protozoa implies that a very considerable advance had taken place in biological thought since microscopic organisms were discovered. Many of the earlier workers, like the uneducated at the present day, believed in spontaneous generation. They believed, with Aristotle, that many "imperfect" animals were bred in mud, water, or decomposing matter; and so long as this view was tenable there was no reason why these misbegotten offspring of the superabundant vitality of the earth should display any particular constancy in their appearance or any fixity of form. Consequently, to attempt to describe and classify the "Infusoria" must have seemed a futile task to many men of science two hundred years ago.

Spontaneous generation, as a scientific doctrine, was not really demolished by the admirable experiments of Redi (1668), as is often supposed, for he disproved it for only the larger and more obvious animals, such as insects; and the later discovery of microscopic organisms raised the whole problem once more, but presented it in a much more difficult form. It was Redi's countryman, Spallanzani, who, a hundred years later, extended his observations to microscopic animals, and showed by means of ingenious and exact experiments that the "Infusoria" spring from living antecedents, and live, grow, and multiply like larger creatures. Spallanzani helped to lay the foundations on which Muller built, though his own work was not firmly consolidated until, a century later, the last rivets were driven in by Pasteur and Tyndall.

In the latter half of the 18th century many minor contributions were made to protozoology, and although these were continued during the early part of the next century, no considerable advance was made until about 1830, when the Berlin zoologist, C. G. Ehrenberg (1795-1876), began to publish his researches. With amazing perseverance he studied, described, and named all the "Infusoria" that he could find: and as he pursued his investigations not only at home, but also in Egypt, Arabia, Siberia, and elsewhere, the forms which he discovered were not a few. His chief contribution to protozoology was published in 1838 - a monumental folio volume of more than 550 pages, accompanied by an atlas of 64 coloured plates. This is still one of the classics of the science. It contained much that was new and much that was true, everything of note that his industrious reading could find in the works of his predecessors, and withal a mass of mistakes, to which he clung tenaciousl y - in spite of violent contradiction and criticism - to the end of his days.

Ehrenberg's most dangerous opponent was a Frenchman, Felix Dujardin (1801-1860). In 1841, with an octavo volume of some 680 pages, but only 23 plates, he undermined the foundations of the big folio, and thus overthrew, for all time, many of the favourite theories of his German antagonist. Dujardin's work is also a protozoological classic. Together with Ehrenberg's volume it marks the end of the old protozoology of the micrographers and the beginning of the new science as a special branch of zoology. Rarely does the modern worker, unless he be a historian, require to consult any earlier treatises than these.

Since the time of Dujardin only one really exhaustive work on the Protozoa as a whole has been written. This is the great monograph by O. Butschli, of Heidelberg, published in 1880-9. It is significant of the vast modern development of protozoology that up to 1921 no work on a like scale, by a single individual, had been produced. It is now, indeed, impossible for any one man even to read all that has been written on the Protozoa, and the more recent workers have had perforce to devote their attention to some particular group of these organisms, or to some special branch of protozoology. To master a detail of the science is now the work of a lifetime. No one man could in 1921 claim to be an expert in all protozoology any more than in all mathematics or all chemistry. The territory already surveyed was so vast that the most he could hope to do was to cultivate his own small holding properly.

## The Modern Science

Since the middle of the 19th century biological theory and practice have undergone profound changes; and in more recent years protozoology, with the rest of zoology, has largely changed its character. This period has seen - to note but a few of its more striking developments - the establishment of the Theory of Organic Evolution, the rise of the Cell Theory, the foundation of Histology and Cytology, and the unfolding of Physiology and Embryology and Medicine as experimental sciences. Protozoology has been profoundly influenced by all these new growths, and has itself contributed not a little to them. An attempt has been made, and has already been partly successful, first, to discover all the Protozoa there are, both living and fossil; then to investigate their structure in the minutest detail, and to ascertain how they live and develop; and finally, to understand their relations to other organisms and their place in nature. Countless monographs have been written on individual species, on the larger and smaller groups into which these can be scientifically classified, on collections made all over the world, and upon the special physiological, medical, and other problems which the Protozoa, as a whole or in part, present. But we must content ourselves here with the merest sketch of the growth and status of modern protozoology.

Before proceeding, we must note some of the peculiar difficulties which differentiate protozoology from the rest of zoology. The animals with which it deals are, speaking generally, invisible to the naked eye. Consequently, they cannot be studied and anatomized by ordinary methods. The protozoologist has first to become a master in the use of the microscope, and to learn its limitations as an instrument of research. When he has become proficient he must learn or devise methods for catching, watching, breeding and preserving those Protozoa that he wishes to study, and must thus become familiar with a peculiar and varied technique adapted to the investigation of the lives and habits of animals invisible to the unaided eye. He must then acquire the power of correctly interpreting what he sees under these peculiar conditions. If he is an efficient microscopist and a good observer, endowed with abundant patience and ingenuity, and if, at the same time, he is a good zoologist and sound philosopher, then, with experience and diligence, he may hope some day to become a good protozoologist. From the very nature of the subject, therefore, it will be obvious that it is easier to make mistakes in protozoology than in most other branches of zoology; and there can be little doubt that the writings on the Protozoa, taken as a whole, contain a larger percentage of error than those on any other group of animals. Protozoology is, indeed, still in its infancy, and learning slowly and painfully by the method of making mistakes.

Protozoology, like most other sciences, is important from two different standpoints, which may be called the theoretical and the practical. On the theoretical side we have to consider its relations to the rest of zoology, and the value of its contributions to biological philosophy; on the other side, we must consider the utility of its practical applications, which are chiefly medical. In other words, we must look at protozoology as a pure science and as an applied science. It is necessary to distinguish these two aspects, although they are inextricably blended in reality. Protozoology was actually applied in medicine before it was ready; and this led not only to great confusion but almost to the severance of Medical Protozoology from the rest of the science. But progress on the medical side has now reacted beneficially upon the pure science, by bringing to light many new facts and setting many new problems.

## The Pure Science

The theoretical importance of protozoology is not what it appeared to be fifty years ago. It has not fulfilled some of the high hopes then entertained for its future. In the earlier period the writer of an article such as this would have begun, in all probability, by declaring that the study of the Protozoa would lead to the solution of most of the outstanding general problems of biology. He would have pointed out that these animals were of the greatest importance in connexion with the two chief biological generalizations of his time - the Cell Theory and the Evolution Theory - and he would probably have ended by saying that it was only lack of detailed knowledge which prevented protozoology from answering most of the fundamental questions of biology. Yet we have now an abundance of the sort of information then regarded as requisite, and the great problems are still, for the most part, where they were. It is both interesting and instructive to inquire how this has come about.

The cell theory was first definitely formulated, in Germany, by Schleiden (1838) and Schwann (1839), and was modelled into its modern form by Max Schultze (1861): that is to say, it took shape at the time of the reformation of protozoology by Ehrenberg and Dujardin, when the science was still feeling for a foothold. According to the cell doctrine, all organisms, both animals and plants, are built up of structural units, called "cells," in much the same way as a house is built of bricks. Schultze defined "a cell" as "a little lump of protoplasm with a nucleus inside it," and this definition was generally accepted. It should be noted that this proposition, so far as the larger animals and plants are concerned, is not a "theory" at all, but a statement of fact easily verifiable by means of the microscope. The body of a rabbit or a cabbage is, for the most part, actually composed of "cells" as conceived in the definition. The "theory" was introduced when the proposition was held to apply to all organisms at all stages in their development. Dujardin had shown that the Protozoa are soft-bodied animals composed of "sarcode" - the "protoplasm" of later workers - in which no constituent "cells" are discernible. Like "cells" Protozoa contain "nuclei," but, unlike the large animals, they show no internal differentiation into cellular units. It was thus necessary to introduce some new conception if the cell theory was to become universally applicable.

The extension of the theory, so as to enable it to include the Protozoa, was made by von Siebold. Each individual protozoon, he said, is itself a "cell." It is comparable with a single one of the innumerable units of which the bodies of large animals are built. The Protozoa are "unicellular" animals, all others "multicellular." According to this doctrine, therefore, a protozoon is not comparable, as an individual, with a whole multicellular animal, but with one of the cells in its body: or, the other way about, a multicellular animal is not an individual of the same sort as a protozoon, but a colony of such individuals.

This conception appeared so plausible - owing, it must be supposed, to the backward state of protozoology and cytology at that date - that it found ready acceptance; and, in spite of the cogent objections which have been raised against it by Huxley (1853), Whitman (1893), Sedgwick (1894), Dobell (1911), and others, it has prevailed down to the present day. The cell theory is still taught to almost every beginner in biology. He is still told that he is not an individual, but a community of individuals; and that the protozoon, which he can see with his own eyes leading an individual existence, is not an individual - such as he believed himself to be - but the equivalent of one little bit of his body.

When the cell theory was being founded, another great biological generalization was just emerging - the doctrine of Organic Evolution. Charles Darwin's great work, which appeared in 1859, created a revolution in biological thinking. Although Darwin's own work, and his statement of the theory, appear to be unexceptionable, the doctrine miscalled "Darwinism" developed along extravagant lines - chiefly, as is now evident, owing to the wild speculations and dominating influence of E. Haeckel and other German writers. The "cell theory" was immediately subpoenaed to give evidence for these "Darwinists." They wrongly believed that the evolution theory required the presence of some "most primitive" and "elementary" animals - from which all the "higher" forms had been derived - on the earth at the present day; and the shaky syllables let fall by the cell theory were eagerly seized upon, interpreted, and ultimately incorporated as incontrovertible facts in the case of the "Evolutionists." "Unicellular" organisms - such as the Protozoa - thus became the startingpoint of evolutionary speculations. The Protozoa were obviously the "simplest" animals, since less was known about them than about the others; and they were clearly the "most elementary," each individual representing but one of the structural elements of which the others were composed. Their insignificant size made them the "lowest" forms on earth, and their position - according to the "theory" - at the bottom of the "Scala Naturae," made them the "most primitive." It thus became easy to show, by specious arguments and "question-begging epithets," that protozoology occupied a position of fundamental importance in biology. By studying the Protozoa the earliest stages in evolution would be revealed. The beginnings of life would be laid bare. Physiology and morphology would appear in their elemental forms, stripped of all confusing detail. And optimists were not wanting who divined that, by higher and still higher powers of the microscope, Nature's inmost secrets - such as the origin of life itself - would be divulged.

These fantastic dreams have been slowly dispelled by the "dry light" of reason. It has become clear that protozoology was placed in a false position by the devotees of the cell doctrine and the dogmatic evolutionists. Let us look at the fundamental conception of the "unicellularity" of the Protozoa from another angle, and see how it appears in the light of modern knowledge.

In the first place, it is clear that the Protozoa cannot properly be described as "unicellular." Every protozoal animal has an independent existence. It has its own peculiar structure, exercises its own proper functions, leads its own life - often, indeed, a very complex one. As an animal it is, from every standpoint, as much an "individual" as a man is. One protozoon is one whole animal, just as one man is one whole animal. From the standpoint of common sense, no less than from that of modern zoology, the whole organism is the unit of individuality. But when we examine a protozoon under the microscope we still see - as Dujardin saw - that its body is not differentiated internally into cells, as is that of a man. Its body is often surprisingly complex in structure, but it is never composed of cells. It is clear, therefore, that we can contrast the body of a man with that of a protozoon by saying that the one is cellular in structure, the other non-cellular. To call it "unicellular," and thus compare one whole animal with a minute differentiated fraction of another, is obviously absurd. It is as though a man who had only seen houses built of bricks were suddenly to encounter one constructed, all of a piece, of concrete; and then, being unable to find the familiar individual bricks in its fabric, were to declare that the concrete house is not a house - in the sense that the brick house is - but one large and peculiarly modified brick.

When once it is realized that the Protozoa are not, in any sense, "elementary" or "unicellular" animals, but a group of peculiarly constructed creatures, adapted in a special way to particular conditions of life, then it will also be realized that we have no reasons - apart from preconceived ideas derived from unsound generalizations - for believing that they represent "primitive" or "first" forms of life. That they are not "simple" we now know. It is true that they display, on the whole, less visible structural differentiation than most of the larger animals; but physiologically they are very complex. That they are able to perform all the chief functions of "higher" animals, but with fewer instruments, does not make their mechanism easier to understand; and it is thus hardly conceivable that the Protozoa can ever offer us the easiest way of approach to physiological problems. They offer us, indeed, the most difficult field in animal physiology, owing to their microscopic size and apparent simplicity of structure. As a great physiologist has well said: "Experience and reflection have shown me that, after all, the physiological world is wise in spending its strength on the study of the higher animals. And for the simple reason that in these, everything being so much more highly differentiated, the dews of the tangles come, so to speak, much more often to the surface, and may be picked up much more readily" (Michael Foster). Attempts to found a "general physiology" on the Protozoa as "cells" and "elements" are doomed to failure, for they are based upon an unsound philosophy; and the speculative and deductive efforts in this direction - such as that of Verworn in Germany - have slowly given way before the experimental and inductive methods of Jennings and others in America and elsewhere.

As a point of historic interest, it may be noted that the father of protozoology and his immediate followers had none of the extravagant later notions regarding the "unicellular" and "elementary" nature of the Protozoa. For Leeuwenhoek the Protozoa were animals like any other animals, but delightfully and marvellously little; and he thus saw more clearly and naturally than many of his later successors.

There are probably few biologists who now cherish any hopes of seeing the fundamental problems of biology solved by the study of the Protozoa, though the majority still speak and write in the optimistic language of last century. For these mental survivals there is a psychological basis, which seems worth noting before we go on to consider the true status and value of protozoology. There is a curious disposition, apparently inherent in the human mind, to suppose that by studying the most minute creatures we can come nearer to first principles. And it is the same with the study of the larger organisms. As the cytologist probes into the structure of an animal with higher and still higher powers of the microscope, he feels that he is gradually "getting to the bottom" of his problems. He feels that when his microscope has resolved the larger animals into their smallest component parts, and has revealed every detail of the smallest living thing, he will be face to face with fundamentals. It does not require much thought to realize that this is a fallacy. The deeper we delve, the more detail we discover. But it is all of the same sort: we add to the quantity and not to the quality of our knowledge. With the highest possible magnification we shall obtain no information which is qualitatively or fundamentally different from that to be derived from the study of large organisms, and their gross anatomy, with the naked eye.

The mental bias just mentioned seems to be responsible for many popular - and not a few "scientific" - notions about the Protozoa. It appears, for example, to be at the back of the unreasonable but common belief that the Protozoa are "elementary" and "primitive" animals. Although few biologists now believe in spontaneous generation, yet many are able to believe that living things must have been spontaneously generated from lifeless matter in the past; and to those who hold this belief it still appears self-evident that the organisms so generated were microscopic. Consequently, these biologists feel that the Protozoa must, in some way, be nearer than other animals to "the beginnings of life," and they find no difficulty in conceiving that the first animals were "Protozoa." In the same way, when these same biologists come to consider evolution, and the relations of living animals to one another, they find in the Protozoa the easiest starting-point for their speculations. The Protozoa are "the simplest" animals, and the human mind works most readily from simple to complex conceptions. Consequently, evolution is pictured as necessarily moving in the same direction - the simply constructed creatures coming first, and the complex developing from them. But it is surely a poor philosophy which would constrain Nature to order her infinite events in that particular sequence in which thoughts happen to follow one another most easily in the mind of man.

What, then, it may be asked, is the theoretical interest or value of protozoology? Clearly it is this. Biological theory is sound in proportion to the truth of its generalizations. When all the facts are known about all animals and plants, we shall be able to make true general propositions about them. Before we know the facts our generalizations can be but partial and premature - more or less lucky guesses, based upon incomplete knowledge. All biological theory is at present in this condition and therefore the careful study of any animal or group of animals - such as the Protozoa - will, if it yields new facts for generalization, be valuable ultimately as a contribution to biology. At present we cannot hope to do much more than collect facts, by means of accurate observation and apposite experiment. When we have collected and critically analyzed them, we can sometimes make tentative generalizations of a lesser order. But the larger and truer generalizations will come later.

It may be said that if this is all that can be expected from protozoology, then it is no more important than any other branch of zoology: there is no reason why we should study the Protozoa rather than any other group of animals. All this is quite true and reasonable; but there is also a reason why protozoology is likely to yield results of particular interest. The Protozoa are a group of animals organized on a different principle from the rest. They are, as we have just seen, non-cellular animals with peculiar lives and habits. Structurally and functionally they differ, in many ways, from all other animals. Now all the chief biological generalizations - almost all general propositions relating to such phenomena as birth, growth,.. development, sex, reproduction, heredity, variation, and death - have been derived from observations made upon the larger multicellular animals. When general ideas were formulated on such subjects the Protozoa were practically left out of account. When the more important facts about the Protozoa are firmly established, we shall be able to recast many of our biological theorems in a more satisfactory form. The Protozoa offer us, in other words, a new world of animals for generalization, and a new standpoint from which to survey our old-world zoological knowledge. The discovery of the Protozoa was to zoology what the discovery of America was to geography. But we are still, in protozoology, in the 16th century. For our knowledge of the new world we must still depend upon travellers' tales, upon reports of things ill-observed and misunderstood, marvels and myths and mysteries. But some day we shall have accurate and faithful records, and then protozoology will come into its own. As yet we are hardly on the threshold of the new biology, but for those who delight in the destruction of error and the advancement of true learning, the protozoological prospect is already full of hope.

## The Applied Science

The chief practical applications of protozoology are to medicine. Certain of the Protozoa live as parasites in the bodies of men and animals, and thereby cause diseases. Some of these are so important that they are widely known - for example, malaria and sleeping sickness - and the elucidation of such diseases is one of the most interesting and recent chapters in biology. Protozoology also has certain applications to agricultural science, because many Protozoa inhabit the soil, but their value is still doubtful.

The founder of protozoology was the first to find Protozoa inhabiting the living bodies of other and larger animals. In 1681 he described one such "animalcule" which was living in his own intestine. In 1683 he described and depicted others from the intestine of the frog. All these are recognizable, with fair certainty, at the present day. Leeuwenhoek did not suggest that these "parasites" were in any way concerned in the causation of disease, and it is probable, indeed, that the forms which he observed are not. But already at that date the "microbe" theory of disease-production was in existence, for it was guessed at long before any "microbes" were discovered; and consequently we find that, even in Leeuwenhoek's lifetime, the suggestion was put forward that his "little animals" might be the "causes" of certain disorders. We find, for example, an early fellow of the Royal Society remarking, in 1683, of a "murren" which had raged among the cattle in central Europe, and of which the cause was undiscovered: "I wish Mr. Leewenhoeck had been present at some of the dissections of these infected Animals, I am perswaded He would have discovered some strange Insect or other in them." Mr. Leeuwenhoek's successors have, on many a like occasion, fulfilled the expectations of "the ingenious Fred. Slane, M.D., and F.R.S.," but his "strange insects" they now call "Protozoa" or "Bacteria." From the time of Leeuwenhoek to the present day the parasitic Protozoa have been studied with increasing attention. Their relation to diseases has been gradually elucidated, though we are still very far from finality in our knowledge of this absorbingly interesting subject. The history of our knowledge is long, and the discoveries have followed devious ways - too devious and intricate to be more than touched upon here.

Our knowledge of protozoal diseases - diseases colloquially said to be "caused" by protozoal parasites - really begins as recently as the middle of the 19th century, when Louis Pasteur (1822-1895) began his researches on a disease of silkworms called pebrine. Applying to the investigation of this disease the genius which stamps his work on "microbes" generally, Pasteur first discovered its causes, and then deduced methods for its prevention. The "cause" he found to be a microscopic parasite, now called Nosema bombycis and classified among the Protozoa. Although Pasteur did not know that the parasite was a protozoon, his work on pebrine and other microbic diseases was of fundamental importance for protozoology, because it demonstrated the methods by which such diseases can be studied and elucidated. Pasteur's scientific principles were impeccable, and equalled only by his own practical applications of them. It is common knowledge that he founded modern bacteriology; but in so doing he also laid the foundations of medical protozoology. To the casual reader it may seem strange that the study of silkworms can have any bearing upon medicine, or could in any way contribute towards the alleviation of human suffering. But there was another practical result of Pasteur's work which everyone will immediately appreciate, since it can be expressed in pounds, shillings and pence. Before pebrine attacked the silkworms of France the silk industry yielded an annual revenue of 130,000,000 francs to the State. After the disease had raged for a dozen years the revenue had fallen to 8,000,000, and the industry was on the brink of ruin. To have discovered the causes of the disease, and to have devised, as a direct consequence, means for its control, and, as a further consequence of this, to have rehabilitated the whole silk industry - these are practical results which everyone can understand. And one has but to remember that protozoal diseases may affect man himself and his larger domesticated animals - not merely silkworms - to realize the practical possibilities of protozoology.

Towards the close of the 19th century medical protozoology became linked up with another branch of zoology - entomology, the science which deals with insects. This connexion has nothing to do with the silkworms just mentioned, but arose through the discovery of the part played by certain other insects in the causation of protozoal diseases. The discoveries in this field began, once more, with the investigation of a disease of domesticated animals; but the pioneer was not, in this case, the Frenchman Pasteur, but the Scotsman David Bruce. His work is of such importance that we must notice it at this point.

## The Work of Bruce

Some parts of Africa are the home of certain large blood-sucking flies called "tsetse." The "Fly Country" is uninhabitable except for wild animals; and long before its full significance was understood, the fly itself was recognized as a serious obstacle to the opening-up of Central Africa. Livingstone, the greatest of all African explorers, was so impressed with the fly's importance in this connexion that he put a vignette of a tsetse on the title-page of his Missionary Travels (1st ed., 1857). Live stock taken into the "Fly Country" rapidly succumbs to a disease which is called "nagana" in Zululand, where Bruce's original investigations were made. The disease was also called "tsetse-fly disease," since it was believed by the European settlers to be caused by the bite of the fly. The natives believed, however, that it was "caused by the presence of large game, the wild animals in some way contaminating the grass or drinking-water." Bruce began his work in Zululand - after an abortive attempt in 1894 - in Sept. 1895 (the month of Pasteur's death). His full report on his researches is dated May 1896. In this almost incredibly short space of time he demonstrated that nagana is caused by a protozoal blood-parasite - since named Trypanosoma brucei, after its discoverer; that the parasite lives normally in the blood of big game, without harming them; and that it is conveyed from animal to animal by the tsetse. When the fly sucks the blood of an infected animal it becomes itself infected with the trypanosomes, which are subsequently re-inoculated into other animals by the fly when it sucks their blood. If these other animals are domestic stock, such as oxen or horses, they become infected with trypanosomes, contract nagana, and die. If they are wild game, such as antelopes, they also become infected, but develop no disease. In nature the trypanosome lives in the game and the flies alternately, the fly acting as an intermediary in the spread of infection from antelope to antelope. The big game - indigenous in the country - are habituated to and proof against the infection; domestic animals - foreigners, introduced by man - are not, and when infected usually die.

Bruce thus succeeded in extracting elements of truth from both the European and the native beliefs, and was able to combine them into a true theory of the causation of nagana. At the same time he threw a flood of light on many other protozoal diseases, and suggested all sorts of possibilities concerning their causation and prevention. He forged new links between protozoology and medicine and between entomology and protozoology. It is true there were other lights and other links before. Trypanosomes were known, and known to cause diseases, before Bruce went to Zululand. Timothy Lewis and Griffith Evans had observed similar parasites in India more than a decade earlier; and Theobald Smith and Kilborne, in America, had demonstrated in 1893 that the disease of cattle known as "Texas fever" - a disease also caused by a blood-inhabiting protozoal parasite - is transmitted from beast to beast by the agency of ticks. But Bruce's work was solid, complete, and demonstrative. By clean experiments and right reasoning he contributed more to science in a few months than hundreds who have followed up his work have since been able to contribute in many years. In work of this sort it is the quality, not the quantity, that counts. Later researches have but served to enhance the magnitude and difficulty of the problem which confronted Bruce in 1895; and to find a just parallel to the masterly manner in which he solved it, we must go back to Pasteur. There is, indeed, the same simplicity, the same directness, the same insight in the work of both these men. Their works are enduring demonstrations of the method of science: they are a delight to read, and illustrate on every page the favourite maxim of Boerhaave: Simplex sigillum yeti.  The following-up of Bruce's discoveries and the working-out of details and consequences have led to the accumulation of an immense amount of new knowledge - protozoological, entomological, and medical. We can do no more than mention it here. We must, however, notice one of the first-fruits of his labours - the application of his results to the study of human diseases. This application was made mainly by Bruce himself.

A few years after he had done his great work on nagana he attacked the problem of sleeping sickness, a human disease which has depopulated large areas of Central Africa. Bruce and his collaborators were able to show that this disease is similar to nagana. It is likewise caused by a trypanosome, which is conveyed to man by the bite of a tsetse-fly, and which is capable of living in other animals. In this case the parasite had been previously seen by Forde and Dutton, and by Castellani. But its relation to human disease and the part played by the tsetse in its transmission were first clearly demonstrated through the work of Bruce.

## Malaria, and Other Diseases

We must now notice another disease, which is known by name to all - malaria, "the scourge of the tropics." This disease, as we now know, is also carried from man to man by the agency of a blood-sucking fly - in this case a mosquito, and it is also caused by a blood-inhabiting protozoal parasite, though it is one very different from that which causes nagana. Moreover, this parasite lives in men and mosquitoes only. After undergoing a peculiar development in the blood of a human being, it is sucked up with his blood by a mosquito when it feeds upon him. Provided that the mosquito is of the right sort, the parasites in the blood - if they are in the proper stage of development - undergo further remarkable changes in the mosquito's body. Thereafter the mosquito is able to infect other men with the parasites, which it injects into their blood in the process of sucking. And so the life of the parasite continues.

The foregoing is the briefest synopsis of a very complicated story, in which almost every event has been worked out in great detail. Hundreds have contributed to this work, though some of them can hardly be said to have cooperated in it. Indeed, such bitter fights have taken place among them that it has now become almost impossible to mention the names of some workers without offending others. The history of these discoveries would give an unpleasant shock to anybody simple enough to believe that men of science always labour for truth and the advancement of knowledge rather than for fame and personal gain. Fortunately the names of the leading discoverers are now known to almost everybody, and their individual achievements are no longer in dispute. Even the "general reader" is familiar with the name of Laveran, the great Frenchman who, in 1880, discovered the malarial parasites in human blood; of Patrick Manson, the founder of modern tropical medicine, who divined, in 1894, the part played by the mosquito; of Ronald Ross, who, inspired by Manson, first worked out in 1888 the complete development of the malarial parasite of birds, and thus solved the general problem; and of Grassi and his fellow-workers in Italy, who immediately confirmed Ross's work and extended and successfully applied his results to the study of malaria in man. When the 19th century ended the story was almost complete.

It will be evident that malaria, nagana, and similar diseases are not purely protozoological problems. It will also be obvious that such diseases might be stamped out and prevented by attacking either the protozoal parasites which "cause" them, or the insects which transmit them, though there could have been but little hope of success in coping with such diseases before the life-histories of the parasites were discovered. When protozoology, entomology and medicine have solved their respective parts of such problems, then many tropical regions which are now forbidden ground will become habitable for man and beast. The practical importance of protozoology in cases such as these is self-evident. The facts speak for themselves.

Malaria is a far commoner disease than nagana, and the discoveries relating to it have therefore made a far wider appeal to the public. It intrigues the public to hear that there would still be no Panama Canal but for the great discoveries in connexion with malaria. It would excite them but little to hear that some obscure tribe of Zulus could now keep cattle in places where it was previously impossible. But the advancement of science is not measured in such terms, and science values most highly those who discover and enunciate new principles. Already we can observe that the problems presented by nagana and malaria are similar, and that most of the generalizations which their solution can give us are, indeed, the same. We can see, too, that history, in the end, is generally just. Consequently, we may hazard a guess that in years to come the historian of science, in his impartial search for beginnings and great names, will not fail to note the sequence of the discoveries which we have just considered, and will apportion his praise accordingly.

The World War Period. - Medical protozoology, like many another branch of science, received a powerful stimulus from the World War of 1914-8. Not only was much of the previously acquired knowledge put into practice, but this practical application in turn revealed or emphasized the gaps, defects, and errors in many current conceptions, and so led ultimately to the prosecution of new researches and the acquisition of much new knowledge. Surveyed from the most general standpoint, the war appears to have taught us little that was new regarding malaria and the other protozoal diseases already mentioned. Its chief protozoological contribution has been to our knowledge of those Protozoa which live in the human intestine, and more especially to the elucidation of the disease called amoebic dysentery. We may therefore say a few words on this subject at this point.

The Protozoa known as "amoebae" form a large and interesting group. Most of the species live independently in such places as ponds, ditches, or the soil; but some of them live in the bodies of other animals, and one of them - called Entamoeba histolytica - was already known before the war to live in the human bowel and "cause" amoebic dysentery. The parasite was discovered by LOsch in Russia as long ago as 1875. Its real relation to dysentery, however, was not made clear, though much debated, until just before the war, when the admirable researches of two American workers in the Philippine Islands - E. L. Walker and A. W. Sellards - were published. During the war their results have been confirmed and greatly extended, chiefly by the investigations of British workers. As a consequence, we now know as much about amoebic dysentery as we do about malaria or the diseases due to trypanosomes. There are several points here which are worthy of mention.

We now know that no less than five different species of amoebae may live in the intestine of man, though only one of these - the "dysentery amoeba" already mentioned - ever does him any harm. Moreover, we now know also that amoebic dysentery is a comparatively rare disease. There are many different kinds of dysentery, and the kind due to amoebae is far from being the commonest. Before the war amoebic dysentery was generally recognized as a disease more or less restricted to the tropics, though certain other kinds of dysentery occur all over the world. The curious fact brought into prominence by the war is that the dysentery amoeba itself is very common almost everywhere. This parasite, which can cause, by its presence in the bowel, a violent and sometimes fatal form of dysentery, usually does no such thing. Very many people, in all parts of the world, are infected with it, but very few ever suffer any appreciable harm from its presence. The parasite and the person who harbours it are usually suited to one another in such a way that they can live together comfortably, oblivious of the existence of one another. There are, for instance, in the British Isles at this moment many thousands of people who are heavily infected with these disease-producing parasites, and y et enjoying perfect health.

Another curious feature of amoebic dysentery is the circumstance that it cannot be contracted from a person suffering from the disease. The people responsible for the spread of infection are those who harbour the parasite but themselves suffer no ill consequences from its presence. The explanation of these seemingly contradictory facts is really quite simple, now that we know the life-history of the amoeba and its relation to disease. It is a popular fallacy to suppose that any parasite is the sole "cause" of any disease. A disease is a joint result of many antecedent factors, and in the present case it would probably be nearer the truth to say that the person who harbours the amoeba, rather than the amoeba itself, is the "cause" of amoebic dysentery. For dysentery results only when the infected person happens to be abnormally sensitive to infection with the amoeba, and the condition is as harmful to the parasite as it is to the patient. Normally man and amoeba fit one another, and there is no trouble. Abnormally there is a misfit, and amoebic dysentery is the consequence. The disease is really an unimportant side-show in the life-history of the parasite, the result of its being planted in unsuitable soil.

The foregoing considerations will serve to show once more the value of protozoology in. the study of human diseases. What hope could there ever be of eradicating a disease such as amoebic dysentery if we remained in ignorance of the life-history of the parasites connected with it? We might cure every case of the disease - we might conceivably prevent the death of every patient who contracted it; but even if we did, it is now clear that this would have no effect whatever upon the continuance and prevalence of the disease itself. Such procedure could not possibly stamp out amoebic dysentery, or even reduce by one the annual number of cases of this disorder. This is not to say that protozoology has yet enabled us to do either of these things; but it has enabled us to formulate the problem correctly, and has shown the uselessness of expending our energies in wrong directions. Greater results will follow when our knowledge is greater and more properly and consistently applied.

It has been supposed for so long that the parasites which produce protozoal diseases are peculiar to tropical or subtropical countries that the discovery of the dysentery amoeba in Britain may seem surprising. It is really not so surprising as the circumstance that nobody, until quite recently, had thought of looking for it here. And there are many equally remarkable parallels. To mention only those diseases and parasites which we have already noted, we can now say that malaria occurs indigenously in Britain - though this was hardly suspected until recently; and that parasites closely similar to those which cause nagana and Texas fever have now been discovered in the sheep and cattle of the United Kingdom. How far these observations are of practical importance the future will show, but already they clearly indicate that protozoology may be studied with profit at home no less than abroad.

## Organization and Training of Workers

In conclusion, we shall now note very briefly what has already been done for the promotion of protozoology as a branch of science.

As a profession it still hardly exists. Most of those who have enlarged the science have been zoologists or medical men engaged in teaching other subjects and in practising their professions. Many great discoveries have been made by men who cannot be described as protozoologists. But the science has now become so vast, from the amassing of myriads of complicated details, that it can no longer be regarded as an occupation for anyone but a highly trained specialist. The amateur toying with his microscope, the ordinary zoologist or physician working in occasional vacations or leisure hours snatched from practice, can no longer expect to make any solid contributions to protozoology. In future all great advances in knowledge must come from those who are bred up as protozoologists - who not only have the necessary physical and mental gifts for this most difficult study, but who also are prepared to devote their lives and energies to it, and to it alone.

Modern science has already developed to such unwieldy proportions that it has ceased to be coherent and has burst asunder into separate segments. The day of the "scientist," with all science for his province, is gone for ever. If men of science are to escape the fate of the builders of the Tower of Babel, it can only be by conscious cooperation. Each worker must do his own special work, but must do it with due regard for his fellowlabourers in adjoining sections, and with the plan of the whole building constantly before his eyes. Protozoology must, accordingly, develop along its own lines and by the labour of protozoologists, but it must remain in touch with the rest of zoology and with medicine and with all other sciences whose collaboration is likely to be mutually beneficial. We can already observe the bad effects of non-collaboration in the modern school of protozoology which originated with Fritz Schaudinn in Berlin. Over-specialization has there led - after beginning on an admirable foundation of fact - to fantastic speculation and the promulgation of doctrines which are biologically unsound.

One of the good results of the World War was to encourage the collaboration of workers in different branches of science, and in Britain the bonds which previously existed between protozoology and medicine have been greatly strengthened. One of the most obvious conditions necessary for the continuance of this alliance is the growth of protozoology itself. Unless the protozoologists can build sc.idly, and not too slowly, they will lose their advantages. Unfortunately, no adequate provision has yet been made for the training of workers in protozoology. At present there are in Britain and elsewhere few first-rate professional protozoologists and few competent teachers, but a large number of day labourers and dabblers from other sciences. Protozoologists are still mainly recruited from other professions. The remedy for this state of affairs will be found only when protozoology is recognized as a separate science - an occupation for specialists and not for smatterers; and when encouragement is given to its development by the founding of professorships in the subject - or similar appointments - in the larger universities. These professorships must be primarily for research, and secondarily for teaching purposes. The professor must have ample time and funds for teaching himself, and for carrying out his own researches. If he is sufficiently gifted to do both these things, he will be able at the same time to teach his science to others who would follow in his footsteps. But the time has now gone when the junior demonstrator in zoology or the lecturer on general parasitology in the medical schools can expect to "take up" protozoology for a term or two and thereby profit science or himself. Unfortunately, too little had been done up to 1921 to create the necessary facilities.

A professorship in the subject, founded on the right lines, was indeed instituted in London University some years ago, but it had remained unoccupied up to 1921 since the death of its first holder in 1915. At Cambridge the Quick professorship of biology, founded later, at one time appeared likely to develop into a chair of protozoology, but these hopes were not fulfilled. An assistant professorship, chiefly devoted to protozoology, recently existed in the Imperial College of Science in London; but no further appointment was made to this post after it was vacated by its first occupant. The medical schools of Great Britain have, in some instances, lecturers in protozoology, but these are mostly medical men with other work to perform and no special knowledge of the science as a whole. The schools of tropical medicine in London and Liverpool have been more fortunate, and have been able to appoint to their staffs protozoologists who can devote their undivided attention to the subject. But here again it is chiefly the practical side of the science, as applied to medicine, that is being fostered. Rothamsted Experimental Station has a protozoologist to study the subject in its agricultural aspects, and several universities and other institutions of minor importance have members who have specialized in protozoology. Veterinary medicine in Great Britain has, however, still done little for research or instruction in protozoology.

In the British colonies and dependencies things are no better.

A chair of protozoology has recently been created in India; but as a general rule protozoological research and teaching are still being carried out under unfavourable conditions by hardworked professors of other subjects. The valuable work already done by many of these men is surely a sufficient pledge of the profits that will accrue when more adequate provisions are made.

If we turn to the United States we find that Columbia University has a professor of protozoology and Johns Hopkins an assistant professor. There is also an American professor of protozoology in the Philippines. But with these exceptions, and a few of lesser importance, protozoology is advancing in America and elsewhere by the labours of zoologists and medical men whose appointments were not primarily established for the furtherance of the science.

Recent Literature. - The most trustworthy of recent books dealing with the Protozoa as a whole are those of E. A. Minchin, An Introduction to the Study of the Protozoa (1912), and F. Doflein, Lehrbuch der Protozoenkunde (4th ed., Jena, 1916). See also D. Bruce and others (1903-1919), Reports of the Sleeping Sickness Commission, i.-xvii. (Royal Society, London); C. Dobell (1911), "The.Principles of Protistology" (Arch. f. Protistenkunde, vol. xxiii., p. 269); C. Dobell and others (1921), A Report on the Occurrence of Intestinal Protozoa in the Inhabitants of Britain (Medical Research Council, Special Report Series, No. 59, London); C. Dobell and F. W.

O'Connor (1921), The Intestinal Protozoa of Man (London); S. P. James (1920), Malaria at Home and Abroad (London); H. S. Jennings (1906), Behavior of the Lower Organisms (New York); A. Laveran and F. Mesnil (1912), Trypanosomes et Trypanosomiases  (2 ed. Paris); E. L. Walker and A. W. Sellards (1913), "Experimental Entamoebic Dysentery," Philippine Journ. Sci. (B. Trop. Med., vol. viii., p. 253). (C. Do.)