A Homeric view of kidney evolution: A reprint of H.W. Smith's classic essay with a new introduction

In From Fish to Philosopher (43), Homer W. Smith melds his groundbreaking physiological studies with geological and evolutionary musings to present an amazingly integrated view of how adaptation of a single organ may have contributed to the evolution of man. A condensed version of this thesis was presented in a lecture to the School of Medicine at the University of Kansas in 1943 and later published by the University of Kansas Press (Smith,41). This holistic view of how selection led to adaptation of the kidney in response to the move from salt- to freshwater, and in the example of the elasmobranchs and bony fishes back to saltwater again, is an extraordinary piece of evolutionary exposition. Knowledge has advanced since 1940 but as a work of integrative logic, and a beautiful piece of writing, it has few rivals. This essay begins with the cooling of the earth four billion years ago. The cooling of the crust produced periodic upheavals that had major effects on the earth's atmospheric conditions, which in turn led to changes in selective pressure. Smith describes how the migration from the oceans to freshwater challenged the physiology of invertebrates and protovertebrates and proposes how these pressures were dealt with through the evolution of the kidney. As upheavals drove the early freshwater-inhabiting vertebrates either back to the sea or onto the land, once again physiological barriers had to be overcome, largely by the kidney. Some of Smith's early physiological studies were conducted on the African lungfish and the changes that occur as these animals escape drought through estivation (summer sleep: the opposite of winter hibernation) in mud burrows. These animals can survive for years without food when encased in dry mud. In this state, the animal needs to adapt from a situation in which water influx and excretion are dominant processes to one in which there is absolutely no water intake and no production of urine. The lungfish therefore cyclically deals with similar physiological pressures to those faced by vertebrates in the course of evolution and musing on these changes probably contributed enormously to the thesis presented in the essay reproduced here. As a researcher investigating development of the kidney, I find this vision of evolution modifying organogenesis (and organogenesis modifying physiology) to be extremely useful. A wealth of comparative systems exist in nature that could allow us to link genetic change to developmental adaptation. One particularly useful example outlined by Smith is the aglomerular kidney's of certain marine fishes. Which of the genes postulated to be essential for glomerular development are no longer expressed during organogenesis in these animals? One such gene, WT1, is still present in the genome of the aglomerular (Marshall,38) pufferfish (Miles et al.,39), but has changes that may render it non- or partially functional. As the genomes of both glomerular (zebrafish) and aglomerular (Fugu) fish are now available, this problem is ripe for exploration. Amphibians initially live in an aqueous environment, but in many species spend large amounts of adult time terrestrially. These animals switch kidneys along with environments during metamorphosis with larval pronephroi dedicated to excreting water and adult mesonephroi dedicated to retaining it (Vize et al.,45). What developmental adaptations are associated with this transition? How do the permanently aquatic water excreting mesonephric kidneys of zebrafish differ from those of the water-retaining amphibians? Both Danio and Xenopus genomes will soon be completely sequenced and provide powerful tools for investigating such questions. Smith's essay provides a framework for thinking about how genetic change may drive physiological specialization and brings to light a wealth of interesting material and experimental possibilities. If readers enjoy this essay, they will be even more impressed by the expanded detail offered in From Fish to Philosopher (43). Other excellent works by Smith include a semifictional account of his adventures obtaining lungfish for physiological studies in Kamongo (40); an edited collected works, Homer William Smith: His Scientific and Literary Achievements (44); and the philosophical Man and His Gods (42), with a foreword by Albert Einstein. HOMER W. SMITH A reprinting from "Lectures on the Kidney," University Extension Division, University of Kansas, Lawrence Kansas (4). Seventy-odd years have elapsed since Claude Bernard first apprehended the fact that the true medium in which we live is neither air nor water, but the blood, the internal medium that bathes our muscles, glands and brain. This internal environment, as he called it, is a cosmos elaborately isolated from the external world and protected by a variety of physiological devices to the end that its composition shall remain unaffected by the sudden and sometimes severe changes that beset the other and unstable cosmos that lies outside our skins.2 During the 7 decades since Bernard formulated this concept, there has been discovered feature after feature in our milieu intérieur to which his concept of physiological regulation must be applied. Vital phenomena involve the interplay of so many physical-chemical factors that only a beginning can be made toward enumerating them. The most important one is, of course, water itself, the chief constituent of the blood and tissues; then there are the numerous inorganic salts: sodium, potassium, magnesium, calcium, chloride, phosphate and bicarbonate, the delicate and precisely balanced acid and basic components, glucose and amino acids. This list, though incomplete, is long enough to emphasize the biological importance of the mixture as a whole. The lungs serve to maintain the composition of the blood with respect to oxygen and carbon dioxide, and with this their duty ends. The responsibility for maintaining the composition of the blood in respect to other constituents devolves largely upon the kidneys. It is no exaggeration to say that the composition of the blood is determined not by what the mouth ingests but by what the kidneys keep; they are the master chemists of our internal environment, which, so to speak, they synthesize in reverse. When, among other duties, they excrete the ashes of our body fires, or remove from the blood the infinite variety of foreign substances which are constantly being absorbed from our indiscriminate gastrointestinal tracts, these excretory operations are incidental to the major task of keeping our internal environment in an ideal, balanced state. Our glands, our muscles, our bones, our tendons, even our brains, are called upon to do only one kind of physiological work, while our kidneys are called upon to perform an innumerable variety of operations. Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, without immediately endangering our survival, but when the kidneys fail to manufacture the proper kind of blood neither bone, muscle, gland nor brain can carry on. To quote Bernard again, "In proportion as we ascend the scale of living beings, the organism grows more complex, the organic units become more delicate and require a more perfected internal environment." It was the view of this physiologist that we achieve a free and independent life, mentally and physically, because of the constancy of the composition of our blood. Recognizing that we have the kind of blood we have because we have the kind of kidneys that we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself. Taken as a whole, the human kidney appears to be extraordinarily complex, but on anatomical analysis this complexity is reducible to fairly simple terms. Each of the two kidneys, which are of about the same size, is made up of slightly more than one million microscopic units, or nephrons. These nephrons are all essentially alike and consist of a filtering bed composed of a capillary tuft, or glomerulus, which drains directly into a long, elaborate tubule. These million-odd glomerular-tubular units empty into common collecting ducts which through confluent union finally deliver the urine into the pelvis of the kidney, whence it flows down the ureter into the bladder. In the two million-odd glomeruli, i.e., in the renal filtering bed where the formation of urine begins, the blood is literally spread out over a great surface by being divided among the innumerable capillary channels. The total surface of the glomerular capillary bed in the two human kidneys exceeds 1.0 square meter. Through this bed there are filtered off in each minute's time about 125 cc of water, or about 0.01 cc per square centimeter per minute, which is a rate of filtration well below that of the ordinary laboratory filters. But this capillary bed is still a filter in the ordinary laboratory sense for it permits everything in the plasma to pass through it except the blood cells, the plasma proteins and similar large molecular aggregates. To supply this 125 cc of filtrate 1,200 cc of blood are perfused each minute through the capillary bed of the glomeruli. After leaving the glomerulus the blood passes into a second set of capillaries surrounding the tubule; here an opportunity is afforded for the tubule cells to transfer various substances from blood to tubular urine, or from tubular urine back into the blood, and here is where all specific chemical operations are carried out. For as the glomerular filtrate passes down the tubules valuable substances such as glucose, sodium, chloride, amino acids, etc., are reabsorbed and returned to the blood by various processes of tubular reabsorption. At the same time certain waste products and foreign substances are taken from the blood by the tubule cells and transferred to the tubular urine. These excreted substances and such waste products and foreign compounds as are present in the original filtrate but are themselves not reabsorbed, remain in the tubular fluid to be excreted in the urine. Of all substances reabsorbed by the tubules water is reabsorbed to the greatest extent: out of the 125 cc of filtrate formed each minute, on the average 124 cc of water are reabsorbed, leaving only 1.0 cc to be excreted as urine. In consequence of this extensive reabsorption of water, such substances as are filtered through the glomeruli but are themselves not reabsorbed by the tubules appear in the final urine in a highly concentrated form.35 In requiring how the renal tubule elaborates the glomerular filtrate into urine it will be noted that this tubule is cytologically differentiated into three segments: a proximal segment, an intermediate thin segment, and a distal segment with drains into an arborized system of collecting tubules. The proximal segment appears to be a jack-of-all-trades, capable of reabsorbing valuable constituents, notably glucose and chloride, from the glomerular filtrate, and at the same time capable of transporting many waste products and foreign substances from blood to urine. On rather indirect evidence it has been inferred that the thin segment is responsible for the final reabsorption of water and the production of a highly concentrated urine. The function of the distal segment remains something of a mystery, but there are reasons to believe that it is responsible for the adjustment of the acidity of the urine, for the conservation of the alkali reserve of the blood, and perhaps for the chemical formation of ammonia. In the present stage of our knowledge it would be dangerous to be dogmatic about details, and in any case it is not my intention to discuss the finer points of renal function. We are concerned here only with the general pattern of structure and function in this nephric unit, and with the inquiry, How did our kidney come to have the architecture that it does? In pursuit of this inquiry we must digress from the structure of the kidney to the general evolutionary history of the vertebrates, which history must itself be prefaced by a brief discussion of the structure of the earth. According to the geologist the continents upon which we live are but irregular slabs of granite some 15 to 40 miles thick, floating like isolated islands upon a bed of basalt, the rock which makes up the oceanic floor. Under this bed of basalt, which is only some 700 miles thick, is a zone of semifluid magma extending to a total depth of about 1,800 miles. Innermost is a core of iron, some 4,000 miles in diameter, which is raised far above incandescent heat (6,000°C) by the enormous pressure existing at the center of the earth. It is now generally agreed by the geologist and the astronomer that the earth was separated from the sun about 2,000 million years ago through disruption of the parent body by a passing star, but the daughter planet remained molten and homogeneous for only a short time, quickly acquiring its present stratified structure as it cooled and crystallized. The continents float above the average level of the earth's crust because their granite is lighter than the basaltic bed upon which they rest; as their exposed masses weather down and the silt is deposited in the sea along their edges, the added weight of this deposit causes the plastic basalt to flow beneath the land masses and to float them higher in the air. It is these slow adjustments to maintain isostatic equilibrium between the continents and the oceanic floor that sometimes cause abrupt movements of the land.6, 21 But all the earthquakes of historic time are trivial when compared with the disturbances of the past, which have extended not over days or weeks, but millions of years. As measured, quite accurately it is now believed, by the radioactive clock within its rocks, the earth has had its present cold and semisolid form for about 1,800 million years. During this period it has been cooling and shrinking as a whole, having decreased in diameter something between 200 and 400 miles. Under the stresses resulting from this cooling process, and more particularly in consequence of the alternate fusion and solidification of the basaltic crust, this shrinking has been intermittent rather than uniform, so that at recurrent intervals of roughly 30 million years the continental masses have been wrinkled and folded into great mountain chains. During the intervening periods of geologic quiescence, the mountains raised by the preceding diastrophic movement have been largely if not entirely worn away to sea level by the slow erosion of wind and rain. Schuchert30 (1929) estimates that the total continental depth eroded in this manner since the opening of the Paleozoic exceeds 75 vertical miles, or more than 20 ranges of mountains like the present European Alps or the American Rockies. These periodic revolutions, as the geologist calls them, have made us what we are. Because they have changed the form and size of the continents and seas and at times submerged great areas of land beneath the water, because they have diverted oceanic currents, altered the dust and water vapor in the atmosphere, raised barriers to moisture-laden winds and otherwise interfered with the basal forces that control the weather, these revolutions have been accompanied by marked and protracted changes in climate over the entire surface of the earth. In general, periods of mountain building have been accompanied by marked refrigeration so that in some instances glaciers have descended to sea level in equatorial latitudes; while in the quiescent intervals, after erosion had leveled the recently formed mountains to mere hills, warm shallow seas have transgressed widely over the low-lying lands, and even Arctica and Antarctica have enjoyed a climate that was warm and humid.29 According to modern experimental biology, the vis a tergo of evolution is the production of new varieties in consequence of random mutations in the chromosomes; such of these varieties as are unfitted to survive are pruned away by natural selection, leaving the better-fitted mutants to get along as best they can. Mutation is fundamental to evolution, but mutation itself would be of little avail to modify organic pattern did not the vis a fronte of natural selection foster the survival of exotic individuals, of the new mutations, by offering them a special environment in which their are by them from genetic through with the and probably in other We may believe that in the of the final evolutionary as we it mutation and environment have balanced and we to either mutation or selection any they within certain to have one after a few million when many millions of mutations have and most of them have become we can to find among the some that are to severe changes than was the parent It is only in the development of of environment, of physiological in sense of the that we can of evolution as being rather than The that evolution has not been a process, but an intermittent In it has been a of organic specialization in marked with the great upheavals of the earth's It was probably one of these with the that the vertebrates their The more important in the history of these with special to those that have a upon the evolution of the kidney, are in of the evolution of the vertebrates in to saltwater and freshwater The irregular which have this evolutionary The time scale is such that the and time are The problem of the of the first remains more or where it was by the great of the a state. A few years ago there was of on at one that the with the the and the a common marine a similar perhaps to the of the The most important of this were that it a to that of and like it one end as it and through the But the of this the like of which no one has to the great has recently been on the that the as they first appear in the were and animals as far in from as one can This fact is in responsible for the of which has been by that the first may have been from a Paleozoic or sea To this we will one more of our in a later As we say from what the first were neither can we with any the time of their Some would this evolution to the and some to the The opening of the was marked by one of the most periods of mountain building the earth has These mountains have long since been but the to which they were is to be in the vertical miles of and through which the has the and from which the geologic its The has that the of the vertebrates of of a and internal with an for the of muscles so as to powerful of the the and muscles being made up of of of the to the of these muscles and to maintain an even as the animal itself in the and of major sense in the end of the These are such as to the organism with to it to move through the as an to live in a According to one first by and by the of the had from the sea into the or freshwater of the continents when the the of the land the of the and this the evolution of the But offered by has it that the in freshwater being literally into the and in time by the of the marine that had then to in the we it is now agreed that it was in the of the Paleozoic and not in the that the first and from them the and early were When, in and I the comparative of the kidney and on the of the of the early vertebrates the freshwater thesis as set by and we were of on But since that time the has been by and and in the of this new evidence the freshwater can no longer be the of is water, and the evolution of the kidney is essentially the of the evolution of the regulation of the water of the generally in equilibrium with the and they therefore no problem of water it may be that in the or of the vertebrates the kidney was if at concerned with the excretion of water, but with the excretion of from the evidence of comparative the marine of the had in each of the of the body a of tubules which the body or with the these tubules were probably to carry the and out of the the stage the had come to a in and the which it with the and which were themselves formed by an of the perhaps in the regulation of the composition of the blood by reabsorbing valuable substances from the or by waste products into this fluid as it out of the this rather of a and a of ducts the first to the of the Paleozoic In from the sea to and up the to the these were probably a to for but they were to have that as is by the which they soon The first vertebrates to appear in in the the and the and the the and even the later advanced were encased from to in which the form of bony or of the of times from to that some and in of the all this has out that the only of the and early fishes were the that with them the continental some of these were than the and and but they were mud and they with their as their or as do their the their may have been more than The thesis that the of the early vertebrates to them from is perhaps to I an these vertebrates had an which they could not but one which them minute of the and and one from which there was no escape though they from to physical-chemical in their new the first from the sea up in freshwater, its blood and the physical-chemical of its marine were in salts: for we may on that at the opening of either or time the sea had or of its present This might be in but it could not be without and The evolution of a internal environment, if it had not was For in the new freshwater the and proteins of the cells water pressure so that by the organism to pass from to and in to to We may that were the of water not survival in freshwater would be The first toward the of water would be to the body as far as by a not believe that the present of the vertebrates of and time was a the of freshwater rather than the and of the In the history of evolution we instances where some adaptation is carried to and and perhaps an to freshwater may have been the of and and other as would later serve to off such as had not been It that it was from certain of these that the were If we this of we must that what out to be a was to supply the fishes with for and with and other for and the with with which to about on But to the body in important changes in internal as The of the tubules had to be and these tubules had to be to into the one which still the now the evolution of the first may have been by the of the with most of the body by a few muscles had to be and in to in a powerful this on the muscles, with of the of the body beneath one or a few would to the of the and to foster the development of and as they appear in the higher The evolution of an the of which had to be in a would foster the evolution of a or which in to the The development of about the would foster the of mouth and the evolution of which, in the are first in the of But these interesting and they are from our that it was in freshwater that the first vertebrates to be in the the to be far from the of For even their best at free the early

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.