Читать книгу The Body at Work: A Treatise on the Principles of Physiology - Alex Hill - Страница 6

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Protoplasm was defined by Huxley as “the physical basis of life.” It is the material substance which lives. There is no life in anything which does not consist of, or is not supported upon, or permeated by a system of filaments of protoplasm. Huxley’s definition indissolubly links in thought protoplasm and life. But it is doubtful whether the definition is in any sense axiomatic. The adjective “physical” has too narrow a range. If the biologist could say to the chemist, “Here is a substance which was alive. If I could restore to it the energy which it has lost, if I could impart to it the movement which I recognize as life, it would again be alive,” he would offer the chemist a substance susceptible to the methods of his science, something which he could analyse. If, approaching the physicist with a group of chemical products, he could say, “Into these protoplasm broke up on dying. I cannot assure you that while it was alive they were combined into molecules within your meaning of the term. There may be no such ‘substance’ as protoplasm in the sense in which you understand the word, but so long as this mass lived these various familiar compounds were bound together in a supermolecular form. Death was their falling apart. If I could cause them to recombine, they would be alive,” he would give the physicist a problem within the range of his methods. The physicist could devise a method for measuring these units. The science which can weigh an electron, the thousandth part of an atom, need not fear failure in its attempt to gauge the size of units of structure composed of groups of heavy molecules, albumins, globulins, and other proteins,[1] with the inclusion, perhaps, of fats, sugars, inorganic salts. But herein lies the biologist’s dilemma. He cannot assert that there exists a homogeneous substance, protoplasm. He cannot assert that there exists a definite tectonic grouping of heterogeneous substances which, so long as it is maintained, constitutes a physical basis capable, and alone capable, of exhibiting the phenomena of life. Protoplasm is still a hypothetical substance—a name. Truly, in the absence of nitrogen-containing compounds of very complicated chemical constitution there is no life. All living things yield on chemical analysis approximately the same nitrogenous substances. No one can say whether the capacity for living is dependent upon the molecular—that is to say, the chemical—constitution of the basis, or whether it is dependent upon the arrangement of its molecules, its form. It is even open to question whether instability, the capacity for incessant change, both in chemical composition and in form, be not the condition which differentiates living matter from dead. “Physical basis” is too hard a term for this elusive concept of the matter which exhibits life.

If it were possible by a process of elimination to ascertain the substances which must be present in protoplasm, the physiologist might formulate a reasonable hypothesis as to the nature of this “basis.” But there is no part of any living thing, or, at any rate, no part which is not microscopic in its dimensions, which can be pointed out as protoplasm and nothing besides. It is impossible to isolate anything which can be described as pure protoplasm. Nor is it possible, by comparing various tissues which are acknowledged to be rich in protoplasm, to ascertain what chemical substances are common to them all.

If it were feasible, by analysing a number of specimens of protoplasm, to make sure that, although x is absent from one, y from another, and z from a third, some one thing, P, is always present, then P might be regarded as the physical basis, even though it were evident that P alone was not protoplasm. Protoplasm would be P combined with either x, y, or z. Globulins and albumins and other proteins are always present, but in varying proportions; but it is impossible to make certain that either of these chemical substances is more important than the rest. Nor is it possible to assert of either that it is essential.

Chemically, protoplasm is a mixture of substances, chiefly proteid, in a condition in which it is capable of manifesting the phenomena of life. But whether it be more complex and of heavier molecule than either globulin, nucleo-protein, albumin, fibrin, or any other of the nitrogenous compounds which take its place when it is dead; or whether it be as simple as either of these, but differ from them all in its instability, in the constant flux of its atoms, which causes it at one time to incline towards one of them, at another time to another, are questions which cannot at present be answered.

The uncertainty as to the chemical nature of protoplasm is responsible for an unfortunate irregularity in the use of the term. It is ex hypothesi the most active, the most living part of an animal cell. If the cell has a nucleus and an envelope, the protoplasm must lie in the space between the two. This part of the cell is therefore often termed, without qualification, the “cell-protoplasm.” Frequently the abuse of the word is carried still further. Young cells, leucocytes, nerve-cells, etc., which have no envelope, consist of a nucleus embedded in soft cell-substance. The latter is termed its protoplasm. The cell is described as consisting of nucleus and protoplasm, the term assuming an anatomical signification. Not only is such a use of the term bad, because it indicates a confusion of thought, but it brings with it a train of ambiguities. What are the limits of the protoplasm? If the cell-body be firmer towards its exterior than it is within, is the denser substance protoplasm, or is it not? It has not the qualities which are attributed to protoplasm in so marked a degree as has the substance which it surrounds. Hence a distinction is made. The one is “ectoplasm,” the other “endoplasm.” Within the cell-body are many collections, often in the form of granules, of substances which have not the protoplasmic attributes. They constitute the “deuteroplasm” of certain cytologists. But these enclosed substances may be as far removed from protoplasm as starch grains. It is absurd to use the termination “plasm” for such well-defined products of cell activity as these. The subject is, unfortunately, obscured by conflicting terms. Nomenclatures which were invented with the object of giving definiteness to our ideas have served but to perplex them. The term “protoplasm” should be reserved as a synonym for the substance which is most alive, the substance in which chemical change is most active, the substance which has in the highest degree a potentiality of growth. Anatomical distinctions are better expressed in anatomical terms. We shall treat of such distinctions when considering the organization of the cell.

In the meantime it may be well to consider the attributes which appear to belong to this most living substance. Its chemical composition can be inferred only from the compounds found on analysis to be present in a mass of organized substance which there is reason for thinking was rich in protoplasm while it was alive. The compounds found vary within certain limits. The quantity of water associated with these compounds is still more variable. Water is essential to the existence of protoplasm. Its power of combining with water in variable quantities is one of its characteristics. Tissue rich in protoplasm yields on an average about 75 per cent. of water. Part of the protoplasm within a cell holds more water associated with it, part less.

Closely associated with its power of holding water is its tendency to assume an architectural form. In large vegetable cells, such as those of the hairs within the flowers of Tradescantia, the protoplasm may be seen, under the microscope, arranged in threads containing granules which are incessantly streaming up and down them. The spaces between the threads are filled with water. Such mobile protoplasm cannot be said to have a structural form. But in the greater number of cells, and especially in animal cells, the protoplasm is disposed in a network, with usually a tendency for the strands of the network to set in lines. In attempting to define these very variable networks, the microscopist is obliged to speak with caution. He finds it very difficult to distinguish between appearances which he is justified in regarding as inherent in the cell-substance, whether alive or dead, and appearances which he may have induced by the action of reagents whilst preparing the tissue for examination. Rarely can he assert that he sees a network in a living cell. When examining a dead cell, he is bound to recognize that the preservatives and hardening reagents which he used may have caused the proteins to coagulate in a particular pattern. If he obtains the same pattern with several different methods, he infers that the appearance which he sees is that of a structure existing in the living cell; but he is never quite sure that it is not an arrangement produced by reagents after death.

The tendency of protoplasm to dispose itself in the form of a network or sponge-work is of the greatest interest in its bearing upon the theory of its activity in effecting chemical change. The body itself, as we shall find later, is a network of tissues enclosing lymph. The lymph in the tissue-spaces contains foods and waste products in solution. The tissues are constantly taking from it the former, and discharging into it the latter. Every cell is, microscopically, a tissue. The strands of its protoplasm are perpetually sorting foods from its cell-juice, adding to its cell-juice waste products. By diffusion, foods, including oxygen, pass from lymph to cell; waste products, including carbonic acid, pass from cell to lymph. If water be added to gum, the gum swells. The mixture is homogeneous. Diffusion takes place slowly through the mucilage. When water is taken up by protoplasm, the protoplasm swells; but the mixture is not homogeneous. The protoplasm expands as a wet sponge expands, although the relation of the enclosing reticulum to the water which it encloses is far more complicated. It is, as it were, a sponge made of gum. Some water is combined with the protoplasm; the remainder fills its spaces. There is an active surface relation between the free water and the protoplasmic threads. As water rises in a capillary tube, as it passes from the inside to the outside of a flannel shirt, so it circulates within the cell.

Irritability is a property commonly attributed to protoplasm, but it is a little doubtful whether there be not again some danger of an illogical use of terms. An amœba, one of the unicellular organisms found in ponds, has the power of moving. If a piece of a water-plant—the stalk of duck-weed is a suitable object—be examined with the microscope, these little animals are usually to be found upon its surface. They feed upon algæ more minute than themselves. When they come in contact with something suitable for food, their body-substance flows around it. The food is coagulated. So much of it as is digestible is digested; the remainder is extruded. Constantly parts of the body-substance are protruded, other parts retracted, in the search for food. Such movement is a response to stimulus. Stimuli received at one part of the body-substance are transmitted to another. The body-substance is irritable. It acknowledges stimuli; it conducts them. But if the amœbæ are watched until, owing to lack of oxygen or other cause, they die, their irritability comes to an end. It is a phenomenon of life. Again the physiologist is in a dilemma. Either protoplasm is not protoplasm when death has supervened, or protoplasm is not irritable as such. It is somewhat paradoxical to ascribe to the physical basis of life a property which depends upon its being alive.

Yet the influence on protoplasm of anæsthetics makes it difficult to understand how it can be either physically or chemically a substance which loses its form or changes its constitution whenever it ceases to display the usual evidences of its existence. Chloroform and similar agents suspend irritability. Yet irritability returns as their influence passes off. They appear to hold it in check without—at any rate visibly—changing the nature of the irritable substance.

All parts of the minute body-substance of an amœba are equally irritable. In higher animals irritability is concentrated in the nervous system. The form of irritability to which consciousness is adjunct is restricted to the cortex of the great brain.

Chloroform and similar agents are termed “anæsthetics” because they abolish the irritability of the cortex of the great brain, before their effects upon other parts of the nervous system are sufficiently pronounced to endanger the working of the animal machine. Pain ceases to be felt before the dose of anæsthetic is sufficient to suspend the irritability of the centres of reflex action. All protoplasm, whether animal or vegetable, is susceptible to the influence of these agents. They cause it to enter into a state which resembles death in all respects save the impossibility of revival. There is a great demand in the Paris flower-market for white lilac in the winter. The plant cannot be forced until after a period of rest. By withholding water and placing the bushes in a cool, shady place, horticulturists endeavour to send them prematurely into their winter sleep. Recently it has been found that from three to four weeks can be gained by placing the bushes for a couple of days in an atmosphere charged with the vapour of ether. Some change of state is evidently produced in protoplasm by anæsthetics. It ceases to be capable of receiving or transmitting stimuli. But we cannot picture the change as being sufficiently pronounced to justify the hypothesis that so long as it is irritable protoplasm is a complex substance which is resolved, as it loses its irritability, into simpler compounds familiar to the chemist. Perhaps it would be more correct to say, we cannot picture these chemical substances as reuniting into protoplasm when the effect of the anæsthetic passes off. Rather are we driven to think of living matter as a mixture of many substances in a state of molecular interchange, and to suppose that the activity of this interchange is diminished by anæsthetics.

Chemical activity is a property of protoplasm. In its network combinations and decompositions are effected more extensive in range than any which a chemist can cause to occur in his laboratory. From ammonia, carbonic acid, and water, a plant makes albumin. A chemist cannot make albumin, no matter how complex may be the nitrogenous substances which he endeavours to cause to combine. Albumin is resolved by animals into water, carbonic acid, and urea. Cells of the gastric glands set a problem which puzzles the chemist by making hydrochloric acid from sodic chloride without the intervention of a “stronger” acid. Many other illustrations of the same kind might be cited. Although the tissues of animals act chiefly as destroying agents, their protoplasm is not without constructive power. There is apparently no limit to the capacity for synthesis of plants. The chemistry of living things may be divided into two provinces, absolutely antagonistic in the series of reactions which they comprise. The one series is constructive, synthetic; the other destructive, analytical. Construction involves the locking up of energy. It is endothermal. Destruction results in the setting free of energy. It is exothermal. To accomplish synthesis energy must be added. Plants obtain it from the sun’s rays. Animals disperse energy, set free by the analysis of substances formed in plants, in maintaining their bodies’ warmth and movement.

The chemistry of the laboratory and the chemistry of protoplasm present certain contrasting features. A chemist reaches the compound which he wishes to form by effecting a series of interchanges. For example, he wishes to form uric acid by uniting a nucleus contained in lactic acid with urea. First he introduces chlorine and ammonia into the molecule of lactic acid. He makes trichlorlactamide. Then he heats (supplies energy to) a mixture of trichlorlactamide and urea. Two of the chlorine atoms carry off hydrogen atoms from the urea. A third leaves the trichlorlactamide with its ammonia. Water also breaks away. Uric acid remains.

Trichlorlactamide	Urea	Uric Acid
CCl₃CH.OH.CO.NH₂+	2(NH₂)₂CO=	C₅H₄N₄O₃	+NH₄Cl	+2HCl	+H₂O.

In this example the trichlorlactamide may be said to exchange its chlorine and ammonia for urea. When he planned the reaction, the chemist foresaw what would happen. He knew that if he weakened the grip of the lact radicle upon them, chlorine and hydrogen, chlorine and ammonia, oxygen and hydrogen, would take the opportunity of getting away together. The lact radicle and urea would be left with dangling arms, which must “satisfy their affinities” by linking up. It would be rash to assert that any reaction is impossible to Nature’s chemistry; but it may safely be said that the reactions which protoplasm effects are, so far as we know them, of a different type from this laboratory example. Uric acid is the chief excrement of birds. It is made in the liver. If the liver is shut off from the circulation, lactate of ammonia is excreted in the place of uric acid. It is therefore, in all probability, lactate of ammonia which the liver transforms into uric acid. We cannot pretend to say how this is done, although an empirical formula for the change might be drafted easily enough.

Lactate of ammonia has the formula NH₄C₃H₅O₃. Uric acid, C₅H₄N₄O₃, contains a much higher percentage of nitrogen. It could be produced from lactate of ammonia by the condensation of the nitrogen-containing nucleus and the addition of a sufficient amount of oxygen to complete the oxidation of the superfluous carbon and hydrogen into carbonic acid and water. It is of little interest to count the number of atoms concerned in this process. If a bird be fed upon urea, or even upon various salts of ammonia, its liver will change them into uric acid. Lactate of ammonia is the nitrogen-containing compound with which the liver has normally to deal. It can handle almost any other combination of nitrogen with equal ease. In the protoplasm of the liver the atoms in the molecule of lactate of ammonia are rearranged. The molecules are condensed; water is set free; oxidation occurs. It seems almost as if molecules, when in contact with protoplasm, lose their individuality. Their atoms fall into new groups. Chains which the chemist finds so difficult to break—chains from which he can remove a link only by insinuating another and a stronger—are, when in contact with protoplasm, groups of isolated links. The links rearrange themselves. They join into new circlets, larger, smaller, more open, closer. As grains of sand on a metal plate group themselves in harmony with the vibrations caused in the plate by drawing a violin bow across it, so the atoms answer to the forces which set protoplasm vibrating. There is no waste of force. The chemist may need to enclose sawdust and lime in a crucible heated in an electric furnace if he wishes to compel them to combine as carbide. He supplies energy enormously in excess of the amount which the new compound will lock up. Under the influence of protoplasm the reactions which occur are exactly proportional to the amount of energy supplied. Or, if it be a reaction by means of which energy is set free, it occurs spontaneously. No energy is absorbed in setting it going. All the energy liberated is effective. The chemist very frequently needs to heat a substance in order to cause it to decompose, even though it be falling from a less stable to a more stable state.

Vital chemistry and mineral chemistry are so widely different in their methods that one is tempted to think of them as different in kind. We find it very difficult to look at both from the same point of view. Men’s minds are preoccupied with the things that they have to do for themselves. The chemistry of the laboratory is seen as a science circumscribed by the laboratory walls. If it were possible to stand outside, it would be evident that it is only a part of the science of molecular change. Matter changes its state under the influence of force. Many rearrangements are effected by the chemist which do not occur in nature. He has an almost infinite range of action. Yet many of the rearrangements of matter and force which are occurring in the dandelion on his window-sill (if the fumes of sulphuretted hydrogen have not killed it) he is unable to reproduce. It is largely a question of waste. Nature works with greater precision than the chemist; but the chemist could do all that Nature does if he had but the same control of force.

We have spoken of the reactions which occur in protoplasm as divisible into two great series—the one ascending, constructive, endothermal; the other descending, destructive, exothermal. In the one series energy is locked up; in the other series it is set free. Synthesis and analysis are names applied to the two series respectively. Synthesis is characteristic of plants, although analysis is also perpetually occurring. Plants fix carbon from the air and liberate oxygen. They also respire, setting free carbonic acid. Analysis is characteristic of animals, although synthesis is not excluded.

Of the chemical processes which occur in plants very little is known. Few halting-places between raw materials and finished products can be marked. The final products are sugars and starches, oils, proteins, and a vast number of other substances—alkaloids, glucosides, etc. Condensation, dehydration, and deoxidation are the methods by which the synthesis of these compounds is accomplished. These methods are adopted simultaneously in varying degree. The large group of bodies known as sugars and starches are, with few exceptions, built on the C₆H₆ model; in fruit-sugar, C₆H₁₂O₆, six atoms of carbon are linked to one another and to six molecules of water. The formula of starch is (C₆H₁₀O₅)ₙ. Not only has water been removed from the molecule, but an unknown number of molecules have been linked together. This condensation and dehydration is effected whenever sugar carried in cell-sap is deposited as starch in seeds or tubers. These compounds are hexatomic. The chemist pictures them as made by the union in the first place of six atoms. As small drops unite to form larger ones, so small molecules, under the direction of the protoplasm of plants, close together.

The reactions which characterize animal protoplasm are of a different kind. They belong to the descending series. Close molecules are unfolded. Water is incorporated with them. Hydrogen and carbon are oxidized into water and carbonic acid. The conversion into sugar of glycogen or of starch may be taken as an illustration of expansion. Starch, (C₆H₁₀O₅)ₙ, becomes maltose, C₁₂H₂₂O₁₁, and then dextrose, C₆H₁₂O₆. The grouped molecule of starch opens out. The breaking of the double molecule of maltose into two molecules of dextrose is a further illustration of progress towards simplicity. Hydration, union with H₂O, accompanies this expansion. Hydrolysis is the secret of almost all digestive acts. Starch is hydrolysed into sugar, fat hydrolysed into glycerin and fatty acid, proteins hydrolysed into peptones.

All the chemical transformations which protoplasm is able to accomplish are of the nature of fermentations. The term fermentation was first applied to the effervescence which occurs in grape-juice when its sugar is being converted into alcohol, carbonic acid gas, and certain substances which appear in relatively small quantities. It was discovered later that the yeast which effects this change is a unicellular plant. The term “fermentation” was extended to the production of vinegar from alcohol, and eventually to all such reactions as are carried out by living organisms, or by the secretions or products of living organisms, without the destruction of the agent which is effective in the process. A ferment is an organic body which brings about changes in other bodies without itself undergoing change. At the end of the process, however prolonged, there is as much ferment as there was at the beginning, and its chemical nature is the same. Rennin has been made to curdle nearly a million times its weight of milk, pepsin to digest half a million times its weight of fibrin. As the ferment is not consumed, there is no relation, except one of speed, between the ferment and the quantity of fermentable substance which it is able to transform. We said that a ferment is an organic body. It is necessary to introduce the qualification “organic,” because certain reactions termed “catalyses” which occur in mineral chemistry resemble fermentations in respect of the non-destruction of the agent which serves as intermediary. If a solution of cane-sugar containing a very small quantity of sulphuric acid is boiled, the cane-sugar is “inverted.” It is changed into a mixture of fruit-sugar and levulose. The ferment invertin of the gastric juice and of intestinal juice produces a similar effect; and just as invertin remains unchanged, so also the sulphuric acid is found in the mixture unchanged in nature and in amount after an unlimited inversion of cane-sugar. Great stress was formerly laid upon the similarity between fermentation and catalysis. It has now been shown that catalytic actions are not necessarily of the same nature as fermentation, although the results and, as far as is visible, the means are similar. For example, finely divided platinum (or, better, palladium) causes an indefinite quantity of oxygen and hydrogen to unite. The reaction comes within the category of catalyses. But it is widely different from a fermentation. The metal causes hydrogen to condense, and actually absorbs it into its surface layer. In the liquid form hydrogen cannot resist combination with oxygen. This may be termed a “physical phenomenon,” adopting the common distinction between chemistry and physics. There is no reason for thinking that fermentations can be explained in so simple a way. They may, however, be grouped under the designation “catalyses.” As the initial conditions and final results are similar, it is inevitable that fermentations and catalyses should obey the same “laws” as to mass action, speed, effect of accumulation of products of action, and the like; but it does not follow that invertin and sulphuric acid produce their effects in the same way. Fermentations are instances of catalysis, but all catalytic actions are not fermentations.

So far from dwelling upon the resemblance between fermentation and the catalysis of mineral chemistry, chemists nowadays incline to regard fermentation as essentially a reaction of life. It is very difficult, when attempting to present ideas which are new to thought, to adapt, without ambiguity, existing words. It would be absurd to talk of a substance removed from yeast or bacteria or blood-corpuscles by a process which involves cooling with liquid air, grinding with powdered glass, solution in water, precipitation with absolute alcohol, and resolution in water, as alive. Yet, unlike any known mineral product, it is easily killed. Ferments are not destroyed by cold, but their activity is arrested. They are most active at about the body temperature. Their activity is annihilated by heating them, in solution, to the temperature at which albumin coagulates—a little over 50° C. Although they are not alive, their behaviour very closely resembles that of living matter. They can be obtained only from living things. They produce their effects even though they are present in almost infinitely small quantity. It is impracticable to make a chemical analysis of a ferment, owing, in the first place, to the very small amount available for analysis, and, in the second place, because of the impossibility, with existing methods, of obtaining a ferment pure. The amount of ferment present in even a great mass of yeast, or in many pounds of salivary gland or pancreas, is extremely small. However prepared, it is always accompanied with proteid substances. It is impossible to say whether ferments, like proteins, have heavy nitrogen-containing molecules. The fact that they are not diffusible suggests that they have.

It would be straining language to term fermentation a phenomenon of life; worse, to define life as a sequence of fermentations. Yet it is safe to say that all the chemical changes carried out by living organisms are fermentations. Fermentation and the chemistry of life are almost synonymous terms.

A very large number of ferments are already known. Each has its own specific work to do: “To every fermentable substance is fitted a ferment, as a key to a lock.” It will be understood, from what has been already said regarding our inability to determine the composition of any ferment, that we cannot say whether or not these various ferments differ one from another in chemical constitution. They are classified according to their action, and not according to their nature. Those which build up are termed “synaptases” (συνάπτω, I unite); those which decompose, or hydrolyse, “diastases” (διάστασις, separation). The termination “ase” is added to the name of the substance upon which the ferment acts, except in cases in which other terms have already become so general as not to be displaceable: amylase, hydrolysing starch; sucrase, inverting cane-sugar; protease, hydrolysing proteins. Unfortunately, there is little uniformity in this nomenclature; amylopsin, invertin, pepsin, are terms used as often as those terminating in “ase.” As a distinguishing termination, “in” or “sin” is less desirable than “ase,” owing to the fact that it has been appropriated already as the termination of the names of albuminoids—e.g., gelatin, chondrin, mucin.

The various ferments are substances which protoplasm sets aside for specific purposes. Primitively, contact with the substance to be fermented determined the nature of the ferment assigned to the task. There are reasons for thinking that protoplasm still retains its power of making a suitable response; cases may be cited in which the lock presented to protoplasm shapes the wards of the key. In such cases the fermentable substance provokes the formation of the ferment. But, for the most part, in situations where particular ferments are regularly needed, protoplasm has acquired the habit of making such ferments and no others. The cells of salivary glands accumulate ptyalin, the cells of gastric glands accumulate pepsin, during the intervals between meals.

The capacity of protoplasm for producing a new ferment when it is needed is shown by such examples as the following: Blood-plasm contains a variety of proteid substances. If a solution of white of egg be added to it, the mixture is clear and uniform. Yet egg-albumin is treated by the blood as a foreign body, a poison. When injected into the veins of a living animal, some of it is excreted by the kidneys, some destroyed in the blood-stream. If several successive doses of egg-albumin are injected into an animal (it is most convenient to inject it into the peritoneal cavity), the power of the blood to destroy the intruder is greatly increased. If now a specimen of blood be taken, and the plasma or serum mixed with egg-albumin, the mixture is no longer clear. The egg-albumin is precipitated. The blood of the animal thus “prepared” has developed a ferment, termed a “precipitin,” which throws down egg-albumin. If instead of egg-albumin, which, although a foreign body, is comparatively innocent, a substance which is distinctly poisonous, toxic, be injected into an animal, the first dose, if a large one, will prove fatal. If, however, the first dose be small, and succeeding doses progressively larger, the animal acquires the power of tolerating a quantity of the poison much larger than would have proved fatal in the first instance. A classical example of this, because it afforded an opportunity of directly observing under the microscope the difference between “unprepared” blood and blood from an immune animal, is the acquisition by a mammal of the power of tolerating the injection of the blood of an eel. Eel’s blood contains a toxin which destroys the red blood-corpuscles of a mammal. The dissolution of the blood-corpuscles may be watched with the microscope. If successively increasing doses of serum of eel’s blood be injected into the body of a rabbit, the rabbit acquires the power of resisting the toxin. Further than this, the serum of the immune rabbit injected into a rabbit which has not been prepared confers immunity upon the latter. If the blood of the prepared animal be mixed with the blood of an unprepared rabbit and with eel’s serum, and the mixture examined under the microscope, it will be seen that red blood-corpuscles are no longer dissolved. The immune serum is able to save the blood-corpuscles of the unprepared blood from destruction. During its course of preparation the rabbit developed an antitoxin.

If germs of diphtheria are injected into the blood of a horse, the first injections give rise to marked febrile symptoms. After a number of injections the horse becomes completely tolerant of the virus. Not only does its blood develop sufficient antitoxin to protect it against the toxin of diphtheria, however large may be the quantity injected into its system, but the serum of the prepared horse, when injected beneath the skin of a child suffering from diphtheria, carries with it sufficient antitoxin to destroy the toxin which has gained admission to the child’s blood.

Many more instances might be cited of this capacity of developing “antibodies” of protoplasm. The leucocytes of the blood are incessantly adapting their chemistry to the needs of the economy. All the tissues, it may be supposed, possess the power of developing resistant ferments; but the leucocytes (Fig. 4) are the undifferentiated cells, the maids-of-all-work. They have not specialized as makers of ptyalin or makers of pepsin. They are not completely given up to lifting weights, like muscles, or carrying messages, like nerves.

Bacteria are the world’s scavengers. To them ultimately belongs the task of reducing organic matter to the salts which plants reorganize. The cycle of life would be broken if bacteria were suppressed. No sooner has an animal fallen than these little agents commence their beneficent task of resolving its carcass into air and soil. Birds and insects may interrupt their work. They may steal portions of the derelict, use them for fuel, or patch them between their own ribs. But they, too, will soon lie breathless on the ground; and the bacteria are always ready to finish their interrupted task. Why should they wait until the slight change occurs, important to us, but of little consequence to them, which marks the transition of living protoplasm into dead proteins? There is nothing in the constitution of protoplasm which makes it harder to break up than protein. There is no quality inherent in living matter which makes it resistant of decay. We resent the officiousness which prompts bacteria to obtain entrance into the ship while it is still under full sail, with a view to commencing the work of demolition. Deep in our minds lies the conviction that it is contrary to the rules of Nature. We are especially annoyed at the many ruses bacteria adopt to disguise their personalities. The bacteria of the soil we can keep at a proper distance. But bacteria of the stream, bacteria of milk, bacteria of the breath that would betray us with a kiss! It is hard to recognize that they are fairly and squarely playing their part. Birds and insects we can beat off with our hands. Our invisible enemies are everywhere. They are constantly insinuating themselves through scratches in the skin, through abrasions in the mouth, through surfaces of the intestine left unprotected owing to the desquamation of its epithelium. But if we are constantly open to attack, we are policed by myriads of zealous leucocytes, ever ready to reduce the invaders to impotence. The germs which have found entrance fire off a toxin. The leucocytes reply with an antitoxin. There is absolutely no limit to the power of protoplasm to protect itself, if only it be not taken by surprise. It can resist any organic poison if it is allowed a sufficient time to produce the antipoison. The ferment of pancreatic juice, trypsin, is a poison which is unlikely to find its way into the blood. When injected it produces disastrous results owing to its immense activity in digesting proteins. An animal “prepared” by the injection of successive doses of trypsin develops an antitrypsin. Injection of pancreatic juice no longer does it any harm. Tapeworms which live in the intestines are bathed in pancreatic juice; they are constantly exposed to its digestive action. They are not digested, because they secrete an antibody which prevents the development of the activity of trypsin. It is not in this case, strictly speaking, antitrypsin. It is antikinase, a substance which, if extracted from the bodies of tapeworms and added to pancreatic juice, renders it incapable of digesting albumin. The antikinase does not destroy trypsin, but destroys kinase, the co-operation of which is essential to its activity.

Not only has protoplasm the power of meeting with an antiferment any ferment which might prove prejudicial to its own integrity; but after it has been once attacked it continues to defend the vulnerable spot. Its tactics are, it must be confessed, somewhat like those of the dusky warrior who, during his first lessons in the art of boxing, made a point of covering with his fist the place where he had just been hit; but even its power of remembering its last injury is of supreme value to the human race. Before the age of sanitary science, and even, in certain backward communities, in these days of its beneficent rule, conditions producing disease were not necessarily set right as soon as the epidemic was over. The close-packed inhabitants of a ghetto were continuously exposed to germs of typhoid fever, small-pox, whooping-cough. But after their protoplasm had once responded to the need for the production of an antigerm, it either continued for many years to keep a stock in hand, or it kept the recipe within easy reach. The memory of protoplasm is amazing. It is commonly said that vaccination is an absolute protection for seven years. There is no doubt but that the immunity from small-pox which it induces, if gradually lessening, lasts for life. The disease, if it attacks a person who has been vaccinated in infancy, is relatively harmless.

Inoculation, vaccination, is the boxing-master’s method of utilizing the self-protective instinct of the dusky warrior. Knowing that his pupil will for a long while continue to cover an injured spot, he asks himself: “Where is he most likely, when it comes to a serious contest, to be hit?” Then he gives him a gentle tap in that particular place. Does he need to know how to defend himself against small-pox? Give him cow-pox. Is he likely to receive a knock-down blow from typhoid fever? Just show him what it feels like to have a gentle shake. Educate his protoplasm to make antityphoid ferment, by giving him the typhoid germ in such an attenuated form that it cannot do him any harm.

The chemistry of protoplasm is a science which is growing rapidly, or, to speak less arrogantly and more correctly, our knowledge of the ways of protoplasm, the Chemist, has greatly increased during the last few years. We can but watch protoplasm at work. Our experiments, so called, are but windows which we open in the walls of his laboratory. We cannot take the work out of his hands. The methods of mineral chemistry are useless in this search for knowledge. And, naturally, the longer we watch, the more details do we discover in what seemed at first a generalized procedure. We recognize that several manipulations are required in the carrying out of a reaction which hitherto we believed to take place in a single stage. This is not the place in which to give an account of a subject regarded as belonging, owing to its applications, to the province of pathology. But Nature is one, however many be the companies into which we divide the explorers of her secrets. We have attempted the merest outline of the observations made up to the present, and have submitted the results for the sake of the light which they throw upon the way in which ferments are prepared as they are wanted to meet the needs of normal every-day digestion and metabolism, rather than for the purpose of showing the methods by which protoplasm combats disease.

Amongst the chemical phenomena of life is respiration. Respiration in this very general sense means oxidation. The force which is exhibited in living is obtained from the union of organic materials with oxygen under the direction of protoplasm. This is true of plants as well as of animals. It is true even of the subdivision of bacteria, termed anaerobic, because they cannot live in air. They secrete ferments which enable them to decompose compounds which contain oxygen, in order that they may use the oxygen for respiration. It might have been supposed that green plants which are receiving radiant energy from the sun would convert this energy into the forces which enable protoplasm to display the phenomena of life. But this is not so. The energy which green plants obtain from the sun is used in constructive metabolism, and not in maintaining life. Life-force, if we may use the expression, is derived from the oxidation of the substances which the sun’s rays enable the plant to make. A plant, equally with an animal, respires. The distinction between the constructive metabolism of a plant and its respiration may be brought out in a striking way by administering to it sufficient anæsthetic to stop the former without stopping the latter. It may be paralyzed without being killed. If a water-weed—potamogeton is the most convenient—enclosed in a bell-glass filled with water and inverted over a dish of water, is placed in sunshine, bubbles of gas rise from the plant. They accumulate at the top of the bell-glass. If the gas be removed and analysed, it is found to be oxygen with a small admixture of carbonic acid. If a second bell-glass containing water-weed be exposed under the same conditions in all respects, save that a small quantity of chloroform is added to the water, the gas that collects at the top of the bell-jar will be much less in amount. It will be found to be carbonic acid without admixture of oxygen. The power which chlorophyll possesses of decomposing carbonic acid with fixation of carbon and liberation of oxygen is suspended by the anæsthetic; whereas respiration is not interfered with.

Lastly, we must attribute to protoplasm a capacity of growing. The activity of protoplasm depends upon constant molecular interchange. It incorporates molecules of food. It excorporates molecules of waste. If food is abundant and “vitality” exuberant, it takes in more than it gives out. It grows.

If we attempt to formulate a definition of protoplasm, we find that our ideas are far from clear, owing to want of knowledge. The questions, What is protoplasm? What is life? are equally unanswerable. Their definition is reciprocal. Protoplasm is the substance, the material, which exhibits life. Life is the complex of phenomena exhibited by protoplasm. All parts of the body are alive, in their degree. The nucleus of a cell lives, as well as its cell-body. Its capsule may be less alive—that is to say, less vibrant—than the soft cell-substance which it encloses; but it lives. So-called intercellular substance, or matrix, is alive. In growing cartilage the matrix does not behave as a dead substance. It does not crack and gape under the pressure of the dividing and multiplying cell-bodies which it contains. If the windows of a house were endowed with the power of spontaneously enlarging, the walls would be crushed. They would bulge, break, tumble. The matrix of cartilage offers as little resistance to the enlargement of the cells which it encloses as the plasma of blood to the multiplication of blood-corpuscles. It grows with the cell-bodies, and must be considered as divisible into areas, each of which is the periphery of a cell. Muscle is alive. So, too, are bone, teeth, hair, nails. But as we proceed outwards we find the quality of aliveness growing less and less apparent, until at last we acknowledge that it is unrecognizable. Vibrations diminish in amplitude and in rapidity, until the material of which the body is made appears to be at rest.

Biologists apply the term “protoplasm” to the most living substance of which plants and animals are composed. It may be that there is an entity, protoplasm. It may be that in certain situations this exists in an unmixed state. It may be that the degree of aliveness of a tissue or constituent part of a tissue varies as the quantity of protoplasm which it contains. The tendency of protoplasm to dispose itself in a reticulum in the meshes of which other substances accumulate favours such a view. The cells of the deeper layers of the skin are rich in it. The superficial layers are composed chiefly of keratin. It is possible that the network opens out, and its strands grow thinner and thinner, as keratin accumulates. But it cannot be demonstrated that this is the case. There is no completely satisfactory reason for concluding that the life of a cell of the skin resides in its protoplasmic network, while its keratin is inert.

Many attempts have been made to prove that living cells contain something which dead cells do not contain; but no evidence which will bear sifting has, as yet, been adduced in support of this thesis.