w t - M 4fit, /&/ ARTICLE XXIX. CELLULAR PHYSIOLOGY AND PATHOLOGY. Read before the New London County Association. BY ASH BEL WOODWARD, M. D., OF FRANKLIN, CONN. Within barely more than a quarter of a century, Cellular Phys- iology and Cellular Pathology have had their birth, and advanced to the dignity of an elaborate science. In 1838 Schleiden de- monstrated the method of the formation of the cell in vegetable structures, and that the cell is the ultimate element of which the vegetable is built up. This view Schwann at once applied to animal structures, and the investigations of these co-laborers, con- ducted as they were with wonderful clearness and precision, laid broad and deep the foundations of the science. Their success attracted other minds, and some of the keenest intellects of the present generation have since pursued the same inquiries. Thanks to their labors, the mysteries of life and disease have been largely unveiled, and we have every hope that our rapidly augmenting knowledge of the nature of disease will disclose still surer meth- ods for combatting it. It is proposed in this paper to take a brief survey of the results thus far achieved in this department of medi- cal and scientific research. In the vegetable kingdom the cellular system is unfolded with most simplicity, and it may assist us to clearer views upon our subject if we first briefly consider the nature of the vegetable cell. Let us take for instance one of the minute stinging hairs that pro- ject from the surface of the common nettle. In the field of a sufficiently powerful microscope this little hair is seen to be, not an inert fibre, but an organization instinct with life. We behold a thin wooden bag or envelope, enclosing a translucent fluid, which moves round in slow but ceaseless currents within its narrow con- fines. This nettle hair may serve as a type of the vegetable cell. 456 It consists of a clear, active, germinal fluid, enclosed in an inert cell wall or wooden case, the whole of microscopic minuteness. Of millions of such cells, variously intertwined and bound together, the structure of the nettle is built up, and as in each individual cell life inheres in the germinal fluid alone, so in their aggregation into the plant the life of the plant is lodged in the germinal fluid of the separate cells of which the plant is constituted. The harder material of the cell wall is as it were dead, but the germinal fluid is endowed with all the attributes of life. It absorbs food through the cell wall, assimilates this food for its own growth, converts it into the fabric of the cell wall, and also gives birth to new cells. It is convenient to have a single term by which to designate this living fluid, and for this purpose the word bioplasm, compounded of /?zos'life' and ttAo'O'/./o'' plasm ' has been sug- gested by Dr. Lionel S. Beale.* Not uncommon are plants consisfingof but a single cell; such are the Red Snow Plant, which under favorable conditions multi- plied in such inconceivable numbers as to suddenly redden broad tracts of artic or alpine snow'; or the different species of Oscil- laria, which, though of microscopic minuteness, may tinge the surface of whole lakes with a green hue at certain seasons of the year. Similar plants abound everywhere in nature, and perhaps present as great diversity of form and size as the kinds of ordinary vegetation, though they are generally so minute as to be indi- vidually invisible to the naked eye. These unicellular plants offer us the simplest forms of vegetable life and growth, and in not a few* of them the actual growth may be observed. The yeast plant is an instructive example. If a portion of yeast not larger than a pin's head be brought into the field of the microscope, it will be seen to consist of numerous little oval cells, very minute, and yet each an independent plant or individual, and consisting, like the cell of the nettle plant, of an hardened exterior surface enclosing a limpid germinal fluid. Now' under a higher magnify- ing power these oval yeast cells appear studded w ith little emi- nences, from one to a dozen projecting from the surface of each plant. Under a still higher power these eminences prove to be protrusions of the germinal matter, with a thin layer of cell w'all * The word protoplasm has been much used in this signification, but as Dr. Beale fitly remarks, the indefinite extension given to its meaning in recent discus- sions renders fatal its employment as a term of scientific accuracy. 457 forming round them, and still connected by a narrow channel with the germinal matter of the main body. Soon these little ' buds ' detach themselves, and new plants are born, destined to grow and multiply like the plants from which they sprang. When first de- tached, many measure less than the ToVoinr °f an in°h i'1 diameter. Reproduction is in this case a very simple affair. Portions of the germinal matter merely separate and begin an independent exist- ence. Here, as everywhere, the germinal matter or bioplasm is the vital part. It converts lifeless, inorganic matter, into active, living, growing matter like itself, which in its turn assimilates and vivifies other matter. The cell wall is an inert substance elabor- ated by the germinal matter and built up about itself.* The cell wall, however, is of the utmost importance. It constitutes the frame work of vegetable structures, imparting to them firmness and strength. Ordinary wood consists almost wholly of cell wall, that is, of an aggregation of very thick walled cells. But we must not forget that cell wall is functionless, and owes its very existence to the vital powers of bioplasm. In this bioplasm, then, we are brought face to face with the great mystery of life. But here we stop. Science cannot fathom it. She cannot say in what manner vital force is evolved from the chemical combination which she finds, nor can she account for inherent differences of power. For the best microscopes disclose no difference between the bio- plasm of the oak and that of the yeast plant, and chemistry with all her skill finds none. Yet one developes into a lowly fungus, while the other, multiplying many million fold, but ever true to itself, slowly builds up the towering oak. The bioplasm of the oak will never produce a yeast plant, neither will the yeast plant ever grow into an oak. In all situations the vegetable cell is essentially the same. But the proportion between the bioplasm, or central germinal fluid, and the cell wall may vary greatly. In the tree the cell wall be- comes very thick, and the bioplasm consequently diminishes, el- even altogether disappears in the center of the tree and some other situations where the cell is practically dead, and no longer a living, typical cell. The dimensions of vegetable cells are very * Bioplasm, in its conversion into cell wall, undergoes a marked chemical change, losing its nitrogen. Bioplasm consists of four elements, Carbon, Nitrogen, Oxy- gen and Hydrogen, while cell wall consists of only three, Carbon, Oxygen and Hydrogen. 458 various, but most of them can only be distinguished by a power- ful microscope. They generally vary from to T2Vo' °f au in diameter. Many are vastly smaller. From the vegetable kingdom to the lowest forms of animal life is but a step. The amoeba is one of the simplest forms. These little creatures, seldom reaching of an inch in diameter, can easily be found in water that has been kept moderately warm for a few days, and consist of pure germinal matter enveloped in an exceedingly thin membrane of firmer texture. This germinal mat- ter or bioplasm resembles that of the plant cell, and is endowed with similar vital powers. It assimilates dead matter, and con- verts it into its own living substance, and from time to time little portions detach themselves, as with the yeast cells, and become separate, independent organisms. It is also in constant motion, expanding and contracting, and moving from point to point, in the fluid in which it is suspended. In this power of locomotion we notice a general, though not universal, distinction between the lowest animal and vegetable organisms. Now the bioplasm of the little embryo from which is evolved the human organism, with all its complexity of structure, cannot be distinguished from the bioplasm of which the highest devel- opment is the simple amoeba. The most skillful observer would detect nothing peculiar to the bioplasm of either of the two, by which he could decide which would produce only the amoeba and which a human being.. It is simply a minute mass of perfectly colorless, living matter, in which no indications of form or struct- ure can be discovered. This embryonic bioplasm grows by the conversion of nutritious matter into its own substance, and from it, as in the amoeba, from time to time, little portions detach them, selves and grow to the size of the parent mass. From these in the same way spring other bioplasts, so that in a short time one particle of bioplasm gives rise to countless numbers of descend- ants. In accordance with some law of evolution, the bioplasts thus produced arrange themselves in the outlines of the future limbs, organs and tissues. After a time the vital activity is not confined merely to evolution of other bioplasm from the existing bioplasm, but the germinal masses begin to form an exterior de- posit of a harder texture evolved from their own substance, and which we may call 'formed material.' Just as the bioplasm of the plant deposits around itself layer upon layer of cell wall till the thick woody growth of the tree results, so the bioplasmic 459 masses of the foetus deposit around themselves ever thickening layers of ' formed material,' and the firm texture of muscles, tis- sues, nerves and bones is formed.* Young tissue consists of masses of germinal matter enveloped in extremely thin layers of formed material, that is, of a nearly continuous body of bioplasm. But as the growth proceeds, the formed material thickens, and in the fully grown tissue we have an extent of formed material dotted with little patches of bioplasm. The same may be said of mus- cles, nerves, &c. Some masses of bioplasm, however, do not deposit 'formed ma- terial ' to any extent, but continue to divide und subdivide as did the bioplasm of the embryo. Among these are the white corpus- cles of the blood, which can readily be examined if a drop of blood be pricked from the finger and placed under a sufficient power. They are colorless, spherical bodies, exhibiting movements like those of the amoeba, and multiplying by projecting small por- tions of their substance, which become detached and grow into complete corpuscles. The cell or ultimate element of animal structures consists, then, of matter in two conditions, of an interior active, living, growing, germinal matter or bioplasm, and of an external passive matter of firmer substance enveloping the bioplasm, and which we may call 'non-germinal matter' or 'formed material.' The proportion between the two varies greatly. " In the amoeba, in the white blood corpuscle, in the pus and mucous corpuscle, we have almost pure germinal matter, with a scarcely appreciable ring of formed material on its periphery; while in the old epithelial cell we have almost pure formed material with a mere point of germinal matter, constituting the nucleus near its center; and in the red blood disc we have pure, structureless formed material. In old tendon, again, the proportion of formed material is large and germinal matter small, while in young tendon the reverse proportion exists."! The size of this elementary part is also very various. The human ovum, a typical cell, varies from to T^() of an inch in diameter, while epithelial cells sometimes grow as large as and cells of morbid growth of an inch in diameter. Dr. Beale has measured particles of germinal matter less than *The analogy, however, is not complete. In vegetable cells, as we have seen, the bioplasm loses nitrogen during its conversion into cell wall, but in animal cells both bioplasm and formed material contain nitrogen. f Dr. Tyson. The Cell Doctrine, p. 112. 460 °f an in diameter, " which would not be called cells in the ordinary sense of the word, yet they are functionally such; that is, they grow, multiply by division, and under appropriate cir- cumstances assume the characters of fully formed cells." The germinal matter or bioplasm constituting the nucleus of fully formed cells varies from to of an inch in diameter. Of course, in these fully formed cells the formed material is propor- tionally very large. The life of the body evidently ultimately resides in the bioplasm of the cells. As we have seen, the embryonic nucleus is a minute mass of bioplasm, and from this embryo, growing, dividing and subdividing, spring countless multitudes of descendants, which build up the tissues of the body. The formed material deposited by the bioplasm masses about themselves, and constittiting by far the greater part of fully grown tissues, muscles, &c., giving them firmness and solidity, is comparatively dead. It can neither assim- ilate food, nor can it of itself grow.* While it has important functions, it is dependent for its maintenance, and the growth necessary to repair its constant wasting, upon the germinal mat- ter. In short, the bioplasm alone has the power of life and growth. "All active change which takes place in the tissue depends upon this bioplasm, however little there may be. If there be none, the tissue is as incapable of undergoing active changes as if it did not form a part of the body."f Bioplasm, then, is the seat of vital change, and if we would fathom the mysteries of life and disease, we must study them in their intimate manifestations in bioplasm not less than in their outward effects. We propose to glance at some of the changes occurring in bioplasm in disease. If a section be made through the epithelial cells of certain mu- cous membranes, for instance, of the fauces, the deeper layers will * " Formed material is without the property of germinating, or multiplying itself, or even maintaining itself. Yet it is exceedingly important, and as essential, in- deed, to the functions of the economy, as the germinal matter. It is in fact the portion of the cell in which alone function resides, since it is to the formed material of the muscle-cell that we owe the property of contractility, to the formed material of the nervous element that we are indebted for neurility, and to the formed matter of the epithelial cell that we owe its protective qualities; while the secretion of all glands is the formed material of the gland-cells." Dr. Tyson. The Cell Doctrine, p. 110. f Dr. Beale. Disease Germs: their Real Nature, p. 27. 461 consist of nearly pure germinal matter, or bioplasm divided into cells by extremely thin partitions of formed material. In the suc- cessive layers outward the formed material increases in thickness, till in the fully grown cells of the surface it largely exceeds the bioplasm, a surface cell consisting of a body of formed material with a little nucleus of bioplasm in its center. The growth of mucous membrane, then, is very simple. In the deeper portions we have germinal matter dividing and subdividing. The resulting cells of nearly pure bioplasm are slowly brought toward the sur- face by the exfoliation of the outer cells, and as they move outward the bioplasm of the cell gradually deposits more and more formed material about itself, till at the surface the normal epithelial cell results. In inflammation this regular growth is inter- rupted. In consequence of increased nutrition, the deeper bio- plasm masses divide and subdivide with great rapidity. So rapid is their growth, that time is wanting for the regular deposition of formed material, and soft, spongy cells reach the surface in which formed material is nearly wanting. These are precisely the char- acters of mucus given off' in slight inflammation of the throat. Under the microscope, mucus is resolved into cells of bioplasm with an exceedingly thin soft coating of formed material. If the inflammation be more severe, that is, if nutrient material be more abundantly supplied, the growth is so rapid that no formed mate- rial is deposited, and the pathological matter known as pus results. We thus see that pus is due to the too rapid growth, in conse- quence of increased nutrition, of normal bioplasm. It is pure but degraded bioplasm. To the eye it resembles ordinary bioplasm; but it can never build up tissue, and in its growth it divides and subdivides into masses of degraded bioplasm like itself. Some observers have evidently examined dead instead of living pus corpuscles. The dead pus corpuscle coagulates, and presents an appearance which might easily mislead. But the appearance of the living pus corpuscle admits of no mistake as regards its nature. It is not an aggregation of the dead particles of disinte- grating tissue, as some have concluded. Neither is it an exuda- tion poured out by the overburdened cells. Mucus and pus are simply the result of the rapid, morbid growth and multiplication of the normal bioplasm of the tissues. The process here traced in the epithelium of the mucous mem- brane of the fauces may be demonstrated of the other mucous 462 membranes. For instance, in inflammation of the bladder, the re- sults of a similar growth are seen in numerous pus corpuscles floating in the urine, and exactly similar to pus corpuscles from other localities. Inflammation is invariably attended with increase of the germinal matter of the affected region, as Dr. Beale has so clearly demonstrated in his recent works. In fevers, the changes of the germinal matter occurring generally precisely resemble those observed locally in inflammation. As Dr. Beale remarks, " the local phenomena of inflammation precisely correspond up to a certain stage with the general phenomena of fever." The rapid growth of bioplasm in all these cases appears to re- sult from increased nourishment beyond the amount necessary to maintain the normal growth. By the harmonious working of the different organs during health, pabulum is distributed to every portion of the system in quantity just sufficient to provide for growth in compensation for the incessant wasting consequent upon vital action. But the moment any organ fails of its full activity, the balance is disturbed, and disease may follow. Do the glands fail to eliminate from the system the products which it is their function to remove, or, if in consequence of imperfect oxydation, compounds are formed less highly oxydized than urea, uric acid, carbonic acid and other normal compounds, and hence less easily excreted, the blood becomes laden with improper pabalum, which nourishes the germinal matter, and favors its abnormal growth. If now free action of the skin, kidneys and bowels can be induced, these compounds are removed, and a return to a healthy state ensues. But if these organs fail to act, the bioplasm continues to increase enormously. This increase is primarily chiefly in the capillaries, for what reason it is difficult to state. Here the ger- minal matter multiplies to such an extent that the vessels become distended and obstructed, and the circulation of the blood is par- tially or wholly impeded. In inflammation these changes are restric- ted to a part of the body, while in fever they may occur through- out the entire organism, and in severe cases they do occur in every part of the body. The bioplasm of the tissues, fed from the same source as the bioplasm of the capillaries, increases rapidly. We have already traced this process in inflammation of the mucous membrane. If the diseased action be general, and the bioplasm continues to grow till the capillaries of the whole body become obstructed, death is inevitable, and the permanent obstruction of 463 the vessels ol any part of the body is sure to be followed by the death of that part. In this way boils and sloughs are produced, and if an extended area be affected, mortification may ensue. We turn now to the changes induced by the introduction into the system of infectious or contagious matter. Contagious germs have been, and are still, the subject of earnest discussion, and opinions differ widely. Certain cases, however, do not seem to admit of doubt. In gonorrhoeal inflammation there is a growth resembling ordinary pus, and not to be distinguished from it, though possessing specific contagious properties, and particles of this transferred to certain mucous surfaces absorb nourishment and multiply there. " These particles will retain their vitality for some time after their removal from the surface upon which they grew. They may even be transported long distances by the air, or they may remain for some time in moist clothes without being destroyed."* Of a similar nature are the germs of purulent opthalmia. It is an interesting fact that the pus of gonorrhoea will occasionally produce severe opthalmia. In post mortem dis- sections the operator sometimes unfortunately becomes inoculated with the pus of inflamed tissue, the minutest portion of which is sufficient to poison the whole system in a short time. The above are cases of contagion resulting from the growth of vitiated pus or germinal matter, which, once introduced into the system, grows and multiplies like ordinary pus, from which indeed it cannot be distinguished. But there exists an inherent difference in vital power, under control of which the specific poisons of each are manifested. If we bear in mind that our highest powers cannot distinguish a particle of the bioplasm of the amoeba from that destined to develope into a human being, we should not be sur- prised at our inability to distinguish between the different kinds of pus, whatever may be their differences in vital power. Diseased bioplasm may also transfer morbid action from point to point of the same system. " In bed-ridden patients the expec- toration of phthisis often marks its passage along the back of the wind pipe by rows of ulcers, ceasing at the glottis; the same se- cretion would appear sometimes to cause tubercular ulcers of the intestines. An unhealthy wound-any kind of sore-will set up an irritation or suppuration through the lymphatic vessels in the glands to which they run-that is germinal matter from the * Dr. Beale. Disease Germs: their Real Nature, p. 59. 464 wound gives rise to the formation of similar germinal matter in the gland. The explanation of the so-called sympathetic bubo of gonorrhcea is similar. In the same manner tubercle or tuberculoid matter may pass from the intestine to the mesenteric, and from the lungs to the bronchial glands. Cancerous matters also seem to prefer these channels to those of the general circulation. Pus passing into the systemic veins gives rise to purulent deposits; and in dysenteric and other intestinal ulcers, through the portal vein, it causes abscess of the liver."* To get at the nature of the germs of the various fevers is not so easy. All admit that living germs of some kind make their way into the system. These germs many believe to be vegetable fungi, and indeed it seems reasonable to attribute such an origin to ague and the other malarious fevers, which are not properly contagious diseases. But with regard to the real contagious fevers, we incline rather to accept the views of Dr. Beale, so ably put forth in his recent works. If vaccine lymph fresh from the grow- ing vescicle be examined under high powers, it will be found to contain a great number of extremely minute particles of bioplasm or germinal matter, and in these particles of bioplasm resides the active power of the lymph. For if they be allowed to subside, no effects are produced by inoculating with the supernatant fluid, while the full effects are produced by inoculating with the deposit. " f These little particles cannot be distinguished from the minute particles of pus or other germs of living germinal matter, the smallest particle of which, when supplied with its proper pabulum, will grow and multiply, giving rise to millions of little particles like itself, each having similar properties and powers." The small pox vescicle contains multitudes of minute particles of bioplasm, which as we might expect, present nothing characteristic. In the cattle plague, the blood fronj the smaller vessels, the mucous se- cretions, and the milk of infected animals are found swarming with these same minute living particles, and, as is well known, a small portion of the blood or secretions will transmit this terrible disease. If, then, in these and other contagious diseases we find the poisonous exudations abounding in minute and similar particles of living matter, and can prove that in vaccine lymph the active power resides in these particles of bioplasm, and not in the exuda- * Dr. Morris. Germinal Matter and the Contact Theory, p. 38. f Dr. Beale. 465 tions in which they are suspended, it is reasonable to infer that in all these exudations the minute living particles are the active poisonous agents. From what we have already seen of bioplasm, we can readily believe that these little particles, though to all appearance exactly similar, may yet differ vastly in inherent vital powers, and be the potent causes of very distinct contagious fevers. When these contagious particles reach the blood, changes are produced resembling those occurring in ordinary fever and inflam- mation. Those diseases are attended by increased growth of the bioplasm of the system, while in contagions we find a similar growth of foreign particles of bioplasm. These, penetrating the system, appropriate the pabulum of the blood, and increase enor- mously. Soon the capillaries become distended with them, as already shown in fever, and the capillary circulation is impeded. If the obstruction continues, serious alterations follow without the vessels. Minute particles of bioplasm make their way through the distended walls, and lodging in the tissue, rob the normal bio- plasm of its nourishment. Or, if the obstruction becomes complete, the circulation of the blood is stopped, and thus the tissues are deprived of their nourishment. In either case, or from both causes combined, the tissues and vessels will lose their vitality, and soon disintegrate. This wasting of the tissues is common to all con- tagious diseases, and may proceed to any length. The capillaries of any portion of the body may be affected, and hence any organ or portion of the body may undergo the change. If the surface affected be limited in extent, neighboring healthy vessels and lymphatics may absorb the disintegrated tissue, leaving behind a wasted and imperfect texture. This remaining tissue may very likely prove incapable of performing its normal functions, and hence local paralysis and permanent impairment of different or- gans so often follow some of these diseases. In scarlatina we recognize a frequent cause of the more or less complete destruction of delicate tissues connected with the organs of sight and hearing. But if the alterations affect any considerable portion of the body, death invariably closes the scene. Dr. Beale has recently published some studies of the alterations induced in the villi by cholera, which well repay careful examina- tion. In portions of small intestine from different cases of cholera, villi are shown in every stage of wasting. In some the wasting has but just commenced, while others are wholly shrunken up, the 466 capillaries reduced to mere lines, and the tissue disintegrated. It is plain that a villus thus disorganized cannot continue to be an organ of absorption; and if a great extent of intestinal surface be affected, as is the case in severe attacks, " the effective absorbing area will be too limited to take up the quantity of nutriment re- quired to maintain the body in a state of health and vigor. Nor should we be surprised that serious attacks generally prove fatal."* Our subject, gentlemen, is so extensive that our survey of it has doubtless appeared to you both hasty and imperfect. But we trust that our remarks will impress upon you the importance of recent investigations in this field, and of the practical aid which we may hope to receive from them in the rounds of our daily practice. It is certain that the more we know of the nature of disease, the more successfully we may hope to combat it; and in the whole range of our science we know of no investigations which have done so much to acquaint us with the real nature of morbid action as those which we have discussed to-day. *Dr. Beale. Disease Germs: their Real Nature, p. 98.