The Riddle of the Centuries

Improvement Era Vol. XXVIII MAY, 1925 No. 7 THE RIDDLE OF THE CENTURIES By Dr. J. E. Greaves There are probably few individuals who have lived to the age of understanding without asking, at least themselves, the questions: What is life? From whence does it come, and how does the living dif- fer from the lifeless? These have been the riddles of the centuries. The philosophers have pondered over them. The scientists have taken their laboratories in an endeavor to wring from Nature an answer. From the very dawn of history we find that all mankind have concerned themselves with these momentous questions, and today some will say that they are no nearer being solved than when primitive man strolled from his cave, club in hand, to slay the living that by so doing he might live. Be this as it may, contrary to the belief of many the search has yielded a harvest rich in very deed. It is the history of this harvest and some of its fruits which we wish to briefly examine. The race is like the child in that during the early stages of development the imagination is the predominating instinct. Hence, we find the first descriptions of the origin of life highly imaginative. The Greeks looked on the Goddess of Gea as the mother of mankind. In their glorious mythology they picture men and wo- men as springing into life from the stones cast on her. The Celts have pictured the soil as peopled with gnomes and pixies, friends or enemies of mankind. Many ancient writers fancifully portrayed the transforming of dead into living matter. The Greek philosophers taught it, Aristotle wrote, "Animals sometimes arise, in soil, in plants, or in other animals. Three centuries later Ovid, in his dissertation on the Pytha- gorean philosophy, defends the doctrine of spontaneous generation, while Virgil in the Georgics gives directions for the artifical production of bees. Entered at the Post Office, Salt Lake City, Utah, as second class matter. Acceptance for mailing at special rate of postage provided for in Section 1103, Act of October i, 1917, authorized on July 2. 1918, $2 per annum. Address Room 406. Church Office Building, Salt Lake City, Utah.

622 IMPROVEMENT ERA Paracelsus (1493-1541), the Swiss medical philosopher who greatly confused fact and fancy, gives instructions for the making of homunculi. Certain substances are to be placed in a bottle; the bottle is well stoppered and buried in a manure heap. Everyday certain incantations must be pronounced over the bottle. In time, so Paracelsus declares, a small living human being (homunculus) will appear in the bottle. However, he naively admits that he has never succeeded in keeping the homunculus alive after it is taken from the bottle. Kircher even goes a step further and describes and even pictures certain animals which he claims were spontaneously produced before his eyes through the influence of water on fragments of plants. Cardano (1501-71) taught that water gave rise to fish and animals and that it was the cause of fermentation. As late as the sixteenth century a famous chemist and physicist, Van Helmont, stated that mice can be generated spontaneously by placing some dirty rags together with a few grains of wheat or a piece of cheese in a dark place. Today the same philosopher's method of producing scorpions is amusing. "Scoop out a hole in a brick, put into it some sweet basil. Lay a second brick upon the first so that the hole may be imperfectly covered. Expose the two bricks to the sun and at the end of a few days the smell of the sweet basil, acting as ferment, will change the herb into a real scorpion." An Italian, Bononani, tells of a wonderful transformation which he claims to have witnessed. Rotten timber which he rescued from the sea produced worms; these gave rise to butterflies; and, strangest of all, the butterflies became birds and flew away. Gradually these gortesque, fanciful opinions concerning spontaneous generation were abandoned and it was believed that only lower plants and animals, seaweeds, algae, lichens, lice, mites, and maggots, could develop with- out parents. Even today we can find fairly intelligent individuals who believe that mites and lice can develop without parents and that the hair from the tail or mane of a horse will change into a worm or snake if placed in water, and exposed to light and warmth. Everyone took it as a self-evident fact that maggots originated spontaneously from decomposing meat, or cheese, until an Italian poet and physician, Redi (1626-98), took the simple precaution of screening the mouth of jars containing meat so that flies could not enter. They were attracted by the odor and deposited their eggs on the gauze, and it was from these that the so-called "worms" arose. By the middle of the sixteenth century the theory of the spontaneous generation of mice, scorpions, and maggots had been proven untenable. But at this time Leuwenhoek discovered various living moving animalcules in raindrops, saliva, and many putrefying substances. Then all were sure there had been discovered the origin of life. For anyone provided with this new instrument, the microscope, could easily demonstrate for himself the spontaneous generation of

THE RIDDLE OF THE CENTURIES 623 microscopic eels in vinegar or produce myriads of different and in- teresting living creatures in simple infusions of hay or other organic material. Needham, a Catholic priest, in 1745, placed decaying organic matter in a closed vessel. This he placed on hot ashes to destroy any existing life. On examining the contents of the vessel after a time, he found micro-organisms which were not there in the beginning. From this he evolved his theory that a force called "productive" or "vegetative" existed which was responsible for the formation of organized beings. The great naturalist, Buffon, elaborated the theory that there were certain unchangeable parts common to all living creatures. After death these ultimate constituents were supposed to be set free and become very active until with one another and still other particles they gave rise to swarms of microscopic living creatures. In 1769 Spallanzani repeated the work of Needham. He boiled the material for one hour and kept it in hermetically sealed flasks. He wrote, "I used hermetically sealed vessels. I kept them for one hour in boiling water, and after opening and examining their con- tents, after a reasonable interval, I found not the slightest trace of animalcules, though I had examined the infusion from nineteen different vessels." But the believers in the theory of spontaneous generation were not convinced, as they claimed that boiling had altered the character of the infusion so it became unfit for the production of life. Voltaire, with his characteristic satire, took up the fight at this point and ridiculed the operations of the English clergy "who had engendered eels in the gravy of boiled mutton" and wittily remarked: "It is strange that men should deny a creator and yet attribute to them- selves the power of creating eels." This, however, was a controversy to be settled not by ridicule but by experimental evidence. Spallanzani answered their objections by cracking one of the flasks Air entered and decay immediately set in. Even this was not sufficient to overthrow an age-long belief. The abiogenist argued "the sealing of the flask excludes air, and the oxygen or air is essential for the generation of life." This objection was answered by the work of many an ingenious investigator. Schulze, in 1836, passed air through strong acids and then into boiled infusions and failed to find life even after the infusion had stood some time. Schwann passed the air through highly heated tubes with the same results. To this the argument of the opponents was, heat and chemicals so alter the physical and chemical composition of the air that it is unable to engender life. The work of Shroeder and Dusch (1853) was more convincing, for they found that it is suf- ficient to use cotton stoppers in bottles containing heated milk, meat, and other perishable substances and they will keep indefinitely. Since the dawn of history man has been interested in the wonder- ful process of fermentation, and although many an ingenious theory

624 IMPROVEMENT ERA has been evolved to explain it, little more than theory existed until the classic works of Pasteur on fermentation appeared about 183 7. He taught that all forms of fermentation are due to the action of organized microscopic cells. Helmholtz and Liebig opposed this idea. The latter even scoffed at such an idea, writing: "Those who pretend that the putrefaction of animal substances is due to the presence of micro-organisms reason very much like a child who would explain the rapidity of the Rhine by attributing it to the violent motions imparted to it in the direction of Burgen by the numerous wheels of the mills of Venice." However, the carefully planned experiments of Pasteur soon demonstrated that without micro-organisms there would be no fermentation, no putrefaction, no decay of any kind, except by the slow process of oxidation. If there were any doubts left in the minds of the scientists as to the fallacy of the theory of spontaneous generation after the work of Pasteur, they were dispelled by the work of Tyndall. He demon- strated that in an atmosphere devoid of dust, as on the tops of moun- tains and ingeniously constructed boxes used by him, perishable sub- stances, if sterile, when placed in such an atmosphere, will keep for an indefinite period. Thus was established the principle that life springs only from life. From the viewpoint of the welfare of the human race the most momentous discovery made by man, for on it is reared those three sciences which have done so much to prevent, alleviate, and cure human ills — bacteriology, pathology, and surgery. Having received from Nature the dictum that life springs only from life, the scientist has come to divide objects on the surface of the earth into two great classes — the living and the lifeless. The former possess certain characteristics which are not possessed by the latter. These properties are movement, growth, reproduction, respiration, and irritability. It is to a study of these that the scientist has turned his attention during the last quarter of a century. Lifeless matter often manifests movement. A rock, cut from the side of a mountain, rolls into the valley below. Movement is due to position. The migration of the ameba may be closely imitated with a drop of cloroform placed in water on a superficially hardened shellac surface. A marked surface tension develops between the chloroform, the water, and the moist shellac layer; soon the chloroform and shellac commence to be moistened at some point, and at this point the surface tension of the chloroform is lowered and it seeks to spread itself out. By various modifications of this method one can imitate the chasing of small ameba by larger ones, the taking up of food and very many interesting life phenomena. In all these imitations, however, it is to be noted that the impelling factor comes from without; whereas, in the living cell it comes from within. This may manifest itself as the change

THE RIDDLE OF THE CENTURIES 625 of position on the earth's surface as in the case of the animal or the internal protoplasmatic movements of the plant cells. While much of this may be due to osmotic changes of the protoplasm yet the energy comes from the food and in this the law of the conservation of energy has been found to rigidly hold. From it we are learning that the efficient engines for the transformation of energy are not man- made but the natural living cells. And although in this respect the body of man is wonderful, yet the little firefly we observe darting about on a dark summer evening is probably the most wonderful dynamo in existence. Growth, yes lifeless material grows, as even the young boy understands as he rolls his snow man. A lump of copper sulphate thrown into a dilute solution of potassium ferrocyanide soon develops a brown envelope which throws out upward-growing runners, and in half an hour's time the fluid is filled with figures which vividly recall both the shapes and color of the seaweed. The weight of the resulting arti- ficial plants may be 150 times that of the original copper sulphate. We all know that a crystal placed in the mother liquid grows. This has been likened unto the growth of the living organism, but only a moment's thought is necessary to show that the likeness is only super- ficial. Crystals grow by the addition of a like material, whereas the living cell takes dissimilar substances and transforms them into another material — living tissue. Inasmuch as growth viewed from the physiological viewpoint consists of the transforming of unorganized food stuffs into new chemical entities which constitute the organized protoplasm of the animal, it is evident that the living organism must have food. It is but a short time since the rule was that the food of man should contain carbohydrates, fats, proteins, and water. Ash was looked upon more as an impurity which was tolerated but not essential until it was found that an animal on such a diet died sooner than another receiving only water. Ash then was found essential not alone as building ma- terial but as a regulator of body processes, and some even claim that life phenomena function even more through the mineral elements than through the organic. Today we know that a diet consisting of carbo- hydrates, fats, proteins, ash, and water will not maintain growth unless the growth promotion Vitamin 5 is present, and even then for only a short time unless the regulatory Vitamins A and C are also included in the diet. Nor is the kind of protein without significance. The growth-promoting lysine and the regulatory trypto- phane must be contained within their molecule. The diet may meet all these requirements and still there be no growth even in the young animal, or when there is growth it may be abnormal as in the case of rickets where there is a defective parathyroid or a lack of Vitamin D and thus is the myxoedemic con- dition which results when there is under-activity of the thyroid.

626 . IMPROVEMENT ERA The results which have been obtained in transforming the cretin into a normal individual is a metamorphosis as wonderful as the trans- forming of the tadpole into the frog. Gudermatsch made the re- markable discovery that even this metamorphosis, which in our climate usually occurs during the third or fourth month of life of the tadpole, can be brought about at will even in the youngest tadpoles by feeding them thyroid gland — no matter from what animal. By feeding very young tadpoles with this substance frogs no larger than a fly can be produced. Allen added the observation that if a young tadpole is deprived of its thyroid gland it is unable ever to become a frog, and it remains a tadpole which, however, can reach a long life and continue to grow beyond the usual size of the tadpole. However, when such abnormal tadpoles are fed with thyroid they promptly undergo metamorphosis. Similarly the thyroxin governs the form and rate of growth in man. The size which the individual reaches is not alone determined by inheritance and the food received, but also by the activity of the pituitary gland. For today in animal experiments there is produced at will the giant or the pygmy by the use of tethelin which not only increases the size but also lengthens the life of the animal. These discoveries have placed in the hands of the dietitian and physician weapons against abnormalities of growth in stature and in mind which in the age of mythology were attributed only to the gods. In man there are periods of rapid growth followed by quiescent periods. These are three in number, each beginning with a period of relatively slow growth followed by a period of very rapid growth and culminating with the termination of the cycle in a period of slackening growth again. In the case of the first two cycles this slackening of growth is followed by a fresh spurt of acceleration due to the succeeding cycle. The first cycle closes toward the end of the first year the second about the sixth year, and the third at maturity.. It has been recently shown by Robertson that these cycles of growth obey the equation of an autocatalyzed mono-molecular reaction. The third characteristic of the living, and the only property it is certain that some of the simpler organisms possess — organisms too small to be seen with even the most powerful microscope — is that of reproduction. Although the morphological changes occurring in multiplication have long been studied, it is only recently that successful attempts have been made to study the first stage in reproduction — fertilization. The work of Loeb on the egg of the sea urchin or frog has demon- strated that they may be successfully fertilized by treating first with a dilute solution of butyric acid and then with hypertonic sea water. When thus treated the unfertilized egg develops into the adult possess- ing maternal characteristics. This called forth from the laity the statement that life had been created, but the answer from the scientist

THE RIDDLE OF THE CENTURIES 627 came, "No; life has not been created. There has only been arrested a chemical process which has its origin with the origin of the cell and which ultimately ends in the death of the organism." To test this proposition the unfertilized cell was treated with anticeptics strong enough to retard enzymic action but not strong enough to kill the cell, and then even the unfertilized cell developed for some time. Moreover, Loeb found that the duration of life, barring accidents and bacteria in the metazoa, is inversely proportional to the temperature at which the animal is living. Decrease the temperature ten degrees and one doubles or trebles the length of life. If certain salt-water fish be placed in a solution of common salt having the same osmotic pressure as has sea water the fish soon die. Death in this case is not due to a lack of food, as a similar fish placed in distilled water lives for some time. Now, if a small quantity of calcium chloride had been added to the first solution the fish would have lived. Moreover, if the heart be removed from the body of an animal and placed in a salt solution it soon dies, but if small quantities of calcium salts be present the heart beats normally. Now, the tissues of the animal are all bathed during health in a solution having a balanced composition, but in diseases this con- centration is changed. Hence, we have abnormal function, or even death. This plays a part in many nervous disorders. Probably it is often the prime factor in corea, or even some tumorous growths may have their origin in some such fashion. Moreover, this dis- covery explains the action of many of the common cathartics on the human organism. Inasmuch as they are calcium precipitant, they leave an unbalanced condition in the protoplasm — hence, the in- creased muscular contractions. The same laws hold in the unicellular and multicellular plants, that is, there must be not only sufficient mineral food but it must be in the right proportion. Hence, when viewed by themselves the ex- periments on the fertilization of the egg appear trivial, but from them has been developed this fundamental law: "Normal life is possible only when necessary salts combine with the colloids of living sub- stances in a definite ratio." Finally, we have the two other properties of living matter — respiration and irritability — which often require special apparatus for their detection, but which are just as fundamental as the others. All living things respire and consume oxygen, liberate energy, and give off carbon dioxide. This is obvious in the case of man but not in the case of the potato; but allow water to find its ways into the potato pit, and the potatoes are drowned. Two kernels of wheat side by side appear the same — one is alive and will grow if placed in suitable soil, the other is dead and will not grow. The two seeds placed in the chamber of a biometer show unmistakable differences in the quantity of carbon dioxide produced.

628 IMPROVEMENT ERA Both the living and the dead seed gives off certain dioxide, the difference being only in quantity. The living cell, however, markedly differs from the dead in that it is irritable. Prick a man with a pin and he jumps and says "Ouch," or he may even use stronger language. Prick the living seed with a pin and it also jumps and says, "Ouch" but in language which it requires the biometer to detect and interpret. It gives off more carbon dioxide. This is true of all cells even the nerves which some individuals think obtain their energy from some other source than the metabolized food. This property of increased carbon dioxide output and irritability is so general that it has come to be spoken of as "a chemical sign of life." By following this gaseous exchange in the higher animals it is possible to determine whether carbohydrates, fats, or proteins are being burned, or whether one is being transformed into one of the others. For years all these transformations were explained by the state- ment that they were "cell activities." But refined chemical and bio- logical methods have made it possible to push aside the mantle sur- rounding the cell and to gather some of the engines with which life acts. And today many scientists are busy studying these engines — the enzymes. At first, attempts were made to obtain the purified product, but inasmuch as we have no criterion by which purity can be judged, and further because of the extreme unstability of the product the work is extremely difficult. Efforts therefore are being made to synthesize the enzymes and to learn the laws governing their activity. Advances have already been made. Euler has produced an artificial oxidase, Falk an artificial lipase. The synthesis and con- trol of artificial enzymes will revolutionize the science and art of organic synthesis. It may make it possible to control or combat pathological condition in the human organism. All the vital steps in digestion are due to enzymes. When they fail, due to disease, will it be possible to replace them by the laboratory product? The diabetic has lost his power to oxidize sugar. Is it due to the absence of an enzyme or an activator? If either, will it be possible to replace it by a synthetic product and thus save from a living death these un- fortunate individuals? The sugar-beet by means of its leaves gathers carbon dioxide and kinetic energy. Through its roots it drinks in water. In the cell they are transformed into sucrose. Sometime in the future will the sugar factory be a place in which carbon dioxide of limestone through the intervention of catalysts be made to combine with water, thus producing formaldehyde which on condensation will yield sugar? Having synthesized the carbohydrates, why not the fats, and finally the proteins, and thus the laboratory in place of the field become the source of the food of man? This I grant is imaginary and today sounds like a dream. But we must remember that synthetic alazarine red and indigo blue have replaced the natural products from

THE RIDDLE OF THE CENTURIES 629 the madder and indigo plants. Camphor no longer comes only from the camphor tree. The synthetic perfumes are destroying the flower industries of Italy and France. Cocaine has been replaced by the synthetic product, procaine, which possesses all of the anaesthetic properties of the natural product and is devoid of its toxicity. A synthetic modification of quinine bids fair to accomplish in the case of pneumonia what salvarsan and quinine are doing in the case of syphilis and malaria. Today it appears as if a synthetic drug is to conquer that horrible plague, leprosy. Hence, it requires a vivid imagination to even portray the possibilities of the future. We have seen how rich has been the harvest from a functional study of the living cell. No less interesting and remunerative has been the structural study. You all recognize that there are no two men exactly alike. The cattle man tells us that he has no two cattle alike, the sheep herder that there are no two sheep alike, the botanist that no two leaves or blades of grass are alike, and now the biologist tells us that the proteins composing our tissues are different from those composing the tissues of other individuals. Our indi- viduality goes back to each individual cell. True, they are composed of the same amino acids, but these are arranged in different combina- tions. Now, from the nineteen amino acids could there be produced enough different proteins for all? Calculating the theoretical number of permutations and combinations we find there to be no less than two million billion different proteins possible. These, while the stream of life is coursing through the living cell, are held in a certain liable position. When death comes they swing back to the stable. Throughout the study of the living cell one is impressed with the order, the correlation, the smoothe and compact way in which the reaction goes on in the living cell in opposition to the many imitative methods of man. One example will make this clear. Man fixes nitrogen by means of a gigantic arc light in a chimney through which a current of hot air is blown. The flaming disk has a diameter of seven feet and reaches a temperature in the neighborhood of 6,300° F. The product dissolved in water gives us nitric acid. In another method air is cooled to -194° C, the nitrogen boiled off, mixed with hydrogen in the proportion of 1 to 3, heated to a temperature of 1,300° O, and then passed over finely divided uranium. There results ammonia. Thus, in synthetic processes great variations in temperatures and huge, complicated, expensive apparatus are used. When the bacterial cell fixes nitrogen there is also a real con- flagration in which plant residues act as the fuel and the bacterial body the furnace. But how different are the two! The living cell is 90 per cent water, and weighs only one hundredth million of a milligram. It works in the dark, damp, warm soil and generates little

630 IMPROVEMENT ERA heat and no light. It produces not simple nitric acid and ammonia but the highly complex proteins. This living cell is an engine which not only does its work, but it repairs its own worn out parts. It works by means of enzymes. The reactions of each is accurately timed to meet the reactions of all the others and to meet the requirements of the living cell. Old protoplasm is torn out, new is made to take its place. The carbohydrates and fats are systamated, fragmented so the energy is nicely liberated to meet the needs of the living organism. However, when the master of ceremonies, life, departs each works independent of the others. They pull and they tear until they destroy their very home. It is as if they are vying with each to see which can do the most damage. A study of the reactions which go on in the living cell begets in the mind of a man a reverence akin to worship, and we can readily understand how Dr. Hodges of Princeton could have said in all solemnity, just before the performing of an experiment, "Boys, remove your hats. I am going to ask God a question." Utah Agricultural College, Logan Seasons Four Birds sing, trees put forth tender leaves, flower buds swell. Little children gather dandelion gold from the green sward. Love searches Love's eyes — Life is full of promise, It is Spring. Birds twitter from leafy trees, flowers hang their heads, the air is hot, Little children stretch in the shade of vine-covered bowers. Love laughs in Love's eyes — Life is doubly sweet, It is Summer. Birds seek the south, leaves turn to crimson, flower petals scatter. Little children run in the nippy frost of the morning. Love smiles into Love's eyes — Life is fleeting. It is Autumn. Birds have flown, boughs are bare, the world is clothed in white. Little children gather round the blazing hearth. Love drinks deeply from Love's eyes — Life's memories are sweet, It is Winter. San Diego, California. DOROTHY C. RETSLOFF.