Makers of Modern Medicine

Pasteur's discovery made a profound sensation. The French Academy of Sciences at once proceeded to its investigation. Among the members who were intensely interested, some bore names that now belong to universal science–Arago, Biot, Dumas, De Senarmont. Pasteur told long years afterward of Biot's emotion when the facts were visibly demonstrated to him. Greatly moved, the distinguished old man took the young man's arm and, trembling, said: "My dear child, I have loved science so well that this makes my heart beat." How deeply these men were bound up in their work! How richly they were rewarded for their devotion to science! There were giants in those days.

Pasteur's discovery was much more than a new fact in chemistry and physics. It was the foundation-stone that was to support the new science of stereochemistry–the study of the physiochemical arrangement of atoms within the molecule–that took its rise a few years later. Much more, it was a great landmark in biology. Pasteur pointed out that all mineral substances–that is, all the natural products not due to living energy–have a superposable image and are, therefore, not dissymmetrical. All the products of vegetable and animal life are dissymmetrical. All these latter substances turn the plane of polarization. This is the great fundamental distinction between organic and inorganic substances–the only one that has endured thus far in the advance of science. Dissymmetry probably represents some essential manifestation of vital force. Often there seem to be exceptions to this law; but careful analysis of the conditions of the problem shows that they are not real.

An apparent contradiction, for instance, to this law of demarcation between artificial products and the results of animal and vegetable life is presented by the existence in living creatures of substances like oxalic acid, formic acid, urea, uric acid, creatine, creatinin, and the like. None of these substances, however, has any effect on polarized light or shows any dissymmetry in the form of its crystals. These substances, it must be remembered, are the result of secondary action. Their formation is evidently governed by the laws which determine the composition of the artificial products of our laboratory, or of the mineral kingdom properly so called. In living beings they are the results of excretion rather than substances essential to life. The essential fundamental components of vegetables and animals are always found to possess the power of acting on polarized light. Such substances as cellulose, fecula, albumin, fibrin, and the like, never fail to have this power. This is sufficient to establish their internal dissymmetry, even when, through the absence of characteristic crystallization, they fail to manifest this dissymmetry outwardly.

It would scarcely be possible to indicate a more profound distinction between the respective products of living and of mineral nature than the existence of the dissymmetry among living beings and its absence in all merely dead matter. It is strange that not one of the thousands of artificial products of the laboratory, the number of which is each day growing greater and greater, should manifest either the power of turning the plane of polarization or non-superposable dissymmetry. Natural dissymmetrical substances–gum, sugar, tartaric and malic acids, quinine, strychnine, essence of turpentine, and the like–may be and are employed in forming new compounds which remain dissymmetrical though they are artificially prepared. It is evident, however, that all these new products only inherit the original dissymmetry of the substances from which they are derived. When chemical action becomes more profound–that is, becomes absolutely analytic or loosening of the original bonds imposed by nature–all dissymmetry disappears. It never afterward reappears in any of these successive ulterior products.

"What can be the causes of so great a difference?" We quote from Pasteur's life by his son-in-law: "Pasteur often expressed to me the conviction," says M. Radot, "that it must be attributed to the circumstance that the molecular forces which operate in the mineral kingdom and which are brought into play every day in our laboratory are forces of the symmetrical order; while the forces which are present and active at the moment when the grain sprouts, when the egg develops, and when under the influence of the sun the green matter of the leaves decomposes the carbonic acid of the air and utilizes in diverse ways the carbon of this acid, the hydrogen of the water and the oxygen of these two products are of the dissymmetrical order, probably depending on some of the grand dissymmetrical cosmic phenomena of our universe."

For the first few years after this discovery Pasteur endeavored by every possible means to secure experimental modifications of some of these phenomena of dissymmetry. He hoped thus to learn more fully their true nature. Magnetic influences especially would, he hoped, enable him to pierce, at least to some degree, this fundamental mystery of nature. While acting as professor at Strasburg, he procured powerful magnets with the view of comparing the actions of their poles and, if possible, of introducing by their aid among the forms of crystals a manifestation of dissymmetry. At Lille, where he was for several years dean of the scientific faculty, he contrived a piece of clockwork intended to keep a plant in continual rotary motion, first in one direction and then in the other. "All this was crude," he says himself, "but further than this I had proposed with the view of influencing the vegetation of certain plants to invert, by means of a heliostat and a reflecting mirror, the motion of the solar rays which should strike them from the birth of their earliest shoots. In this direction there was more to be hoped for."

He did not have time, however, to follow out these ingenious experiments. He became involved, as we shall see, in labors more than sufficient to take up all his time and all his energy. These labors were of great practical importance for France. Pasteur always insisted, however, that great discoveries will yet be made in following out this order of ideas, and that there is in this subject magnificent opportunity for young men possessed of the genius of discovery and the power of persistent work.

When, only a few years ago, Professor Duclaux, Pasteur's successor as the head of the Pasteur Institute, and himself one of the greatest living authorities on biological chemistry, wrote the story of the mind of the master,14 he said, of this subject of dissymmetry: "A living cell appears to us, then, as a laboratory of dissymmetrical forces, a bit of dissymmetrical protoplasm acting under the influence of the sun–that is to say, under the influence of exterior dissymmetrical forces. It presides over actions of very different kinds. It can manufacture, in its turn, new dissymmetrical substances which add to or take away from its energy. It can, for instance, utilize one of the elements of a paratartrate without touching another. It can manufacture crystalline sugar at one moment and consume it at another, laying by stores for itself to-day using them up to-morrow. In a word, the living cell presents a marvellous plasticity, which exerts itself without the slightest disturbance by minimal deviations of forces due to dissymmetrical influence. Ah, if spontaneous generation were only possible! If we could only create living matter, raise up in the midst of inactive mineral material a living cell, then it would be easy for us to understand something more of vital manifestations and to comprehend better the mystery of dissymmetry."

But spontaneous generation is as far off as ever. Pasteur's discoveries in dissymmetry have brought us closer than ever before to the mystery of life. Scientists still hope, but it is with ever-waning confidence, that they may pluck out the heart of the mystery. Pasteur's own thoughts with regard to dissymmetry rose above even the lofty heights of mere earthly biology. He saw in it the great force that links the universe together. On one occasion, at the Academy of Sciences, he expressed himself as follows:

"The universe is a dissymmetrical whole. I am inclined to think that life, as manifested to us, must be a function of the dissymmetry of the universe or of the consequences that follow in its train. The universe is dissymmetrical; for, placing before a mirror the group of bodies which compose the solar system with their proper movement, we obtain in the mirror an image not superposable on the reality. Even the motion of solar light is dissymmetrical. A luminous ray never strikes in a straight line. Terrestrial magnetism, the opposition which exists between the north and the south poles of a magnet, the opposition presented to us by positive and negative electricity, are all the resultants of dissymmetrical actions and motions."

This raising of his thoughts far above the sordid realities he is concerned with into the realms of suggestive theory is typical of Pasteur. His was a true creative mind–poetic in its highest sense. The imagination properly controlled is of as great value to the scientist as to the poet. Pasteur's theories were ever pregnant with truth to be. All his life he kept this question of dissymmetry before his mind and hoped to get back to work at it. But opportunity failed. Other and more practical work was destined to occupy the busy half-century of investigation that followed.

Most of Pasteur's work, after this first thrilling discovery and its possible significance, is very well known. His meditations on the distinction between material derived from living and non-living sources led him to investigate certain processes called fermentations–before his time considered merely chemical. It is well known that if a dilute solution of sugar be exposed to the air anywhere in the world it will ferment–that is, certain changes will take place in the liquid, some gas will escape from its surface and alcohol will be formed. There are changes that take place in other organic substances–milk, meat solutions, butter, etc.–that resemble quite closely alcoholic fermentations, though the end-product of the process is not alcohol. Pasteur showed that all these supposed chemical changes are really due to the presence of minute living cells, called ferments. During the growth of these cells they split up the substances contained in the material in which they occur, using parts of them for their nutrition. He proved this very clearly for the lactic acid and butyric acid fermentations. Milk was supposed to become sour and butter rancid because they are unstable organic compounds, liable to change in the presence of the oxygen of the air. These changes were now shown to be due to minute living things that grow in the milk and the butter.

When Pasteur offered the same explanation of the origin of vinegar he found a strenuous opponent in Liebig, the great chemist. Liebig admitted the existence of specific substances, called ferments, but said that they were nitrogenous compounds in unstable equilibrium as regards their composition, and with a marked tendency to undergo alteration when exposed to the air or free oxygen. These alterations, once begun, affect also the liquids in which the ferments are contained–milk, blood, sugar solutions and the like. Theodore Schwann had shown the existence of certain yeast-like bodies in fermenting liquids, but these were considered to be effects, not causes, of the fermentation, and even Schwann, himself, believed that they originated in the liquids in which they were found. It remained for Pasteur to demonstrate, as he did by a brilliant series of ingenious and conclusive experiments, that ferments are living cells, that they never originate except from previous cells of the same species, and that no fermentation takes place unless they are present.

The changes that take place in organic liquids when exposed to the air and the frequent development in such liquids of moving bodies evidently possessed of life constituted, before Pasteur's time, the principal reason for believing that life might originate from some special combination of chemical forces, and without the necessity for preceding life of the same species as its efficient cause. The new explanation of fermentation greatly weakened the position of those who believed in spontaneous generation–that is, the origin of life from dead matter under certain specially favorable circumstances. Pasteur proceeded to show, by rigid demonstration, that if all life were destroyed in organic substances, living beings never originated in them unless living seeds from the air gained access to them. After a meat solution has been thoroughly boiled nothing living develops in it, even though the air is allowed free access, if the air admitted has been previously filtered through cotton, He showed that even the bending of the neck of the tube into the shape of an "S," so as to prevent the entrance of dust particles, suffices to protect the most changeable organic material from the growth of micro-organisms in it. His teaching was not accepted at once. Details of his experiments were impugned. Apparently complete counter-demonstrations were made, but Pasteur knew how, by his marvellous intuition, to detect the fallacy of supposed demonstration, and to invent new crucial tests of the proof of biological succession.

These studies in minute life and in fermentation led him almost naturally to the study of disease. Two centuries before, Robert Boyle, of whom his notorious descendant the great bullster, Sir Boyle Roche, had said that he was the father of chemistry and the brother of the Earl of Cork, made use of an expression wonderfully prophetic in its accurate penetration of the future. "He that thoroughly understands the nature of ferments and fermentations," said Boyle, "shall probably be much better able than he that ignores them to give a fair account of divers phenomena of certain diseases (as well fevers as others) which will perhaps be never properly understood without an insight into the doctrine of fermentations." The marvel is that the very first man who understood the nature of fermentation proved to be the one destined to unlock the mystery of contagious disease and its origin.

Pasteur's first investigations in the field of disease concerned a mysterious malady that affected the silkworm and was ruining the silk industry of France. This disease was first noted seriously about 1850. When a colony of silkworms had been attacked it was useless to try to do anything with them. The only resource for the silk farmers was to get the eggs of an unaffected race of worms from some distant country. These became infected after several generations, and untainted eggs had to be brought from a distance once more. Soon the silkworm plague invaded most of the silk-growing countries of Europe. In 1864, only the races of silkworms in China and Japan were surely not infected. Great suffering had been entailed on many departments of France by the failure of the silk industry. The most careful investigation failed to reveal any method of combating the disease. Acute observers had been at work and some very suggestive observations on the affected worms had been made, but the solution of the problem of the prevention of the disease seemed as far off as ever. In 1863 the French minister of agriculture formally agreed to pay 500,000 francs (about $100,000) to an Italian investigator who claimed to have found a remedy for the disease, if his remedy proved efficient. The offer was to no purpose. In 1865 the weight of cocoons of silk had fallen to 4,000,000 kilos. It had formerly been nearly 30,000,000 kilos. This involved a yearly loss of 100,000,000 francs (about $20,000,000).

Pasteur showed that the failure of the silkworm was not due to one disease, but to two diseases–pebrine and flacherie. These diseases are communicated to the eggs of the worms, so that the young begin life handicapped by the maladies. The crawling of the worms over leaves and stems makes these liable to communicate the diseases. The prevention of the diseases is accomplished by procuring absolutely healthy eggs and then never letting them come in contact with anything that may have been touched by diseased worms. If, at the egg-laying period, worms show any signs of disease their eggs are to be rejected. These simple suggestions were the result of rigid experimental demonstration of the spread of the diseases from worm to worm, including the demonstration of the microbic causes of the two diseases. These precautions proved effective, but their introduction met with opposition. The strain of the work and the worry of controversy brought Pasteur to the brink of the grave by a paralytic stroke. From this he never entirely recovered and was always afterward somewhat lame. After the severest symptoms had passed off he was given the opportunity to make a crucial test of preventing the silkworm diseases at the villa of the French Prince Imperial. The products obtained from the silkworms on the estate had, for years, not sufficed to pay for the fresh supplies of eggs obtained from a distance. Pasteur was given full charge of the silk industry on the estate. The sale of the cocoons at the end of the year gave a net profit of 26,000,000 francs (over $5,000,000). This decisive demonstration effectually ended all opposition.

His attention was next naturally directed to the diseases of animals and human beings. His studies in fermentations and in silkworm diseases had taught him the use of the microscope for such investigations. Splenic fever–known also as anthrax–a disease that attacks most species of domestic animals and may also prove fatal to man, was the first to yield the secret of its origin. The cause proved to be a bacterium–that is, a small, rod-shaped plant. This was but the first of a series of similar discoveries, until now the science of bacteriology has become one of the most important branches of knowledge. Pasteur's investigations included much more, however, than the mere discovery of the germ of the disease. He showed that a series of diseases which passed under different names in different animals were all due to the same cause. Further, he discovered one of the methods of distributing the disease. When the carcasses of animals that have died from the disease are not buried deeply below the surface of the ground, animals grazing above may become infected with the disease. The germs of the disease can be shown to occur in the grass above the graves. It is carried to the surface in the bodies of earth-worms. This important observation was the first hint of the methods of disease distribution by some living intermediary. Modern medicine has come to understand that these biological distributing agents are far more important than the fabled transmission through the air.

Pasteur overturned the notion of spontaneous generation of life. Then his work eradicated the idea of the spontaneous generation of disease. It opened up a new era by showing that the origin of many diseases is not due to changes in the atmosphere nor to some morbid productivity of soil or water under favoring circumstances, but to minute living organisms whose multiplication is encouraged by the conditions that were supposed to produce disease. Finally, came the precious suggestion that living things always convey and distribute disease; man to man, for epidemics travel not with the velocity of the wind but only as fast as the means of communication between distant points; animal to man, as is well known, for many diseases now; and, lastly, insects, worms and the like were also shown to be real carriers of disease.

In investigating chicken cholera Pasteur discovered another great basic principle in the knowledge of disease, especially of its treatment. After considerable difficulty he succeeded in finding the germ of this disease which was causing great losses in the poultry industry of France and other European countries. This germ was cultivated for a number of generations on artificial media and never failed to produce the disease when fowls had been inoculated. During the course of his studies in the malady Pasteur was called away to a distant part of France in connection with his investigation of anthrax. He was away from his laboratory for several months. When he returned he inoculated some fowls with the cultures of chicken cholera which he had left behind. To his surprise and annoyance the inoculations failed to produce the typical symptoms of the disease. The fowls suffered from some slight symptoms and then recovered. When he left his laboratory inoculations had been invariably fatal. It took considerable time and trouble to procure fresh cultures of the chicken-cholera microbe. Meantime, the fowls which had been only slightly affected by the old cultures were carefully preserved. When these birds were inoculated with the fresh virulent cultures they failed to take the disease. Other fowls promptly died, exhibiting all the characteristic symptoms of chicken cholera. Those that had suffered from the mild form of the disease produced by the old cultures were protected from further attacks of the disease.

One of the great mysteries of medicine, the varying virulence of disease, had been thus solved by what seemed an accident. There are no accidents in the lives of great investigators. There are surprises, but genius knows how to reconcile their occurrence with the principles they are working out. Pasteur understood at once the wonderful utility there might be in this discovery for the protection of men and animals from disease. He proceeded to practical applications of the new theory by providing old cultures for the inoculation of fowls in districts where chicken cholera produced serious ravages. Then, working on the same lines as for chicken cholera, he proceeded to elaborate vaccine material for anthrax.

Vaccine was the name deliberately selected for the inoculating substance in order to honor the genius of the English physician Jenner, who had discovered the power of vaccination to protect from smallpox. The weakening of the germs of anthrax, so as to produce only a mild form of the disease, was a much more intricate problem than for chicken cholera, because the anthrax bacillus does not weaken with age, but enters a resting or spore stage, resembling the seed stage in large plants. After a patient series of investigations Pasteur accomplished his object by some ingenious methods that served to show, perhaps better than any other details of his career, how thoroughly practical was his inventive genius.

Unfortunately the absorption in his work proved too much for his health. He was seized by a series of apoplectic attacks which for a time threatened to put an end to his invaluable career. When he did begin to recover his health one of the most serious problems in his regard was to keep him from hindering his convalescence by a return to his old-time absorption in the important problems of the cure and the prevention of disease, at which he had been so happily engaged. The keynote of Pasteur's life was to prevent human suffering as far as possible, and any time not given to this important duty seemed to him to be utterly wasted. With regard to this unfortunate break in Pasteur's work Dr. Christian Herter, in his address on the "Influence of Pasteur in Medical Science," delivered before the Medical Society of Johns Hopkins University,15 has an interesting passage, in which he discusses the significance of the master's work up to this time, and the interest that his illness awakened among all the distinguished medical scientists of Europe at the time:

"It is likely that excessive work and mental stress in some degree contributed to the onset of the series of paralytic seizures which in October, 1868, threatened the life of Louis Pasteur. During the critical period of his illness, many of the most distinguished scientific men of France vied with each other to share with Mme. Pasteur the privilege of nursing the man they loved so well and of rescuing the life that had already placed science and a nation under enduring obligation through discoveries which were either of the greatest practical utility or appeared susceptible of almost unlimited development. Had Pasteur died in 1868, he would have left a name immortal in the annals of science. Others would in some degree have developed his ideas. Already inspired by the researches on fermentation, Lister would have continued to develop those life-saving surgical methods which will forever be associated with his name. But we may well question whether investigations in biology and medicine would not have been for a time at least conducted along less fruitful paths. Who shall say how soon the great principle of experimental immunity to pathogenic bacteria, the central jewel in the diadem of Pasteur's achievements, would have been brought to light?"