Part 31

1. Bacillus of Turned Wine. 2. Ferment of Soured Milk. 3. Butyric Ferment. 4. Ferment of Ropy Wine. 5. Ferment of Vinegar. 6. Amorphous deposit. 7. Sarcinae.

During the next years Pasteur applied himself to a study of ferments and notably of those which involve deterioration of wines and beers. This led him to perceive that there is a great multiplicity and variety of these organisms. Now it was an old and well-known view that fermentation, putrefaction, and the infection of disease had much in common. It was perfectly natural, therefore, for Pasteur to regard the latter in the light of a vital process. A great difficulty was, however, the demand that any such doctrine made on the germ-bearing capacity of the air. Cities were not slow to avail themselves of this weakness, and pointed out that, according to Pasteur, the air must be one solid mass of germs! For the opponents of Pasteur the living organisms found in the process of fermentation or decomposition were the result, not the cause, of the process. These organisms were regarded by them as spontaneously generated in the fermentation process. Thus arose a discussion of the old theme of spontaneous generation.

By 1859--the year of publication of Darwin’s Origin of Species--Pasteur was engaged in controversy as to the ‘Origin of Life’. The discussion specially turned round what were then regarded as the lowest forms of life, the Bacteria. Were they ever spontaneously generated, or were they not? If a flask of broth, supposedly sterilized by boiling, went ‘bad’ and organisms appeared in it, was it certain that they had come from without, or could they have been spontaneously generated by the broth itself? Life must begin somewhere. Then why not here at this lowest stage? If this view be justifiable, Pasteur’s doctrine of the nature of ferments must fall to the ground.

Pasteur had thus before him the task of proving a universal negative--a task impossible in Formal Logic. But Science is not Formal Logic. In the end he clinched the matter by an exquisitely simple experiment which must, at once, carry conviction. A flask with a long S-shaped neck is filled with a putrescible fluid. It is heated to boiling, to kill all organisms, and then left in the still air of a room. Air can enter, but any floating germs that enter naturally fall on the floor of the S-shaped neck of the flask. Months may go by without any change in the liquid, but once the neck is severed, so that organisms can enter freely from the air, fermentation sets in within a few hours, and organisms can be detected in the liquid. Only living organisms from the air can have caused the change.

FIG. 107. PASTEUR’S CRUCIAL EXPERIMENT to prove that fermentation or putrefaction is the result of the action of air-borne organisms. The S-shaped flask contains a putrescible fluid such as meat broth. The flask containing the broth is subjected to prolonged heating to destroy all organisms. It is then left in position with the mouth open. Days, weeks, months, even years, may pass without sign of putrefaction. No organisms reach the broth, since any that enter the open mouth fall on the floor of the neck and remain there. Sever the neck of the flask so that organisms can fall from the air directly on to the surface of the fluid and these multiply. In a few hours putrefaction sets in. This is shown by the formation of a film or scum on the surface just below the severed neck. Microscopically the broth is seen to be teeming with organisms.

The first disease which Pasteur was able to demonstrate as causatively related to a living organism was a condition that was devastating the silk-worm industry of France. In 1866 he proved the contagiousness of the disease, showed that it was due to a living organism, and followed the organism through the life-history of moth, egg, worm, and chrysalis.

In 1870 the Franco-Prussian war broke out. Pasteur now decided to make investigations into the diseases of beer, his object being to improve the French brews and to carry the war into the enemy’s camp by making them equal to the German! He succeeded in isolating special organisms, mostly yeasts, which produced defects in beer (Fig. 106). This work naturally led to an enlargement of his views on the nature and action of micro-organisms.

About this time Pasteur was elected a member of the French Academy of Medicine, a very unusual honor for one not a medical man. Lister had already begun his teaching, based partly on the work of Pasteur, and indeed his first important paper on antiseptic surgery had been published in the very year of the Franco-Prussian war. On entering the Academy Pasteur found himself faced by all kinds of ancient prejudices and misconceptions in connection with his new doctrine, and especially with his denial of spontaneous generation. Among his supporters was the physiologist, Claude Bernard (p. 213). His work proceeded to more and more triumphant issues.

The first disease that affects man on which Pasteur was able to throw light was Anthrax, in relation to which his work interdigitates with that of Robert Koch and some other observers. Anthrax is a deadly and highly contagious condition which commonly affects cattle, but sometimes spreads to man. As early as 1855, a German observer had noted microscopic rod-like objects in the blood of beasts dead of the disease. In 1868 an older French contemporary of Pasteur had shown that a bacillus is not simply the inseparable companion of the disease, but also is its cause and its only constantly acting cause. At this time the losses of cattle from Anthrax in France were enormous. The character of the outbreaks had been studied and seemed wholly unexplained by what was known of the bacillus. Farmers found that they lost cattle in fields from which infected animals had been excluded for months or even years. How was it to be explained?

The explanation was, in fact, advanced in 1876 by the German observer, Robert Koch of Berlin (1843-1910), whose work was now beginning. He showed that the anthrax bacilli under certain conditions formed ‘spores’, that is to say small encysted bodies, exceedingly resistant to heat and to other changes of external conditions (Fig. 108). This discovery opened up a new field which was cultivated by Koch and Pasteur and their followers.

The rod-like organisms are growing typically in chains. Some of the rods have white clear spots in them. These are the highly resistant ‘spores’. ]

While making his studies on ferments in 1863, Pasteur had witnessed the formation of spores in the organisms of butyric fermentation, but had failed to grasp their significance. In 1869 he had again found spores forming in the organisms of silk-worm disease, and had shown that they resisted prolonged drying. On the basis of their resistance he had explained the persistence and latency of the silk-worm disease. Other observers had had similar experiences. The investigations of none of them, however, approached in brilliance and completeness those of Koch.

Koch found that spores always form in the blood and tissues of animals dead of Anthrax, provided that

(1) the temperature is suitable, and (2) there is sufficient oxygen. These two conditions, temperature and oxygen, were found to be necessary. Below 18° Centigrade spores are not formed; at 30° Centigrade they occur at the end of thirty hours; at 35° Centigrade in twenty hours. The rapidity with which spores are formed is, therefore, proportional to the amount of heat. Oxygen was also found to be indispensable. Anthrax blood, if deprived of oxygen, ceases to be virulent in twenty-four hours without putrefaction. When the blood is allowed to putrefy the virulence also disappears if putrefaction exhausts the oxygen quickly enough to prevent the spores having time to form. If the spores have already formed, putrefaction does not kill them, nor does it prevent them from developing later if circumstances become favorable. The persistence of the disease and its return in an infected country was thus explained. It was the spore which was the agent of preservation, which persisted where the conditions of temperature and of aeration had permitted it to form, and which always held itself in readiness to make new victims.

The matter was carried further by Pasteur in 1877. At that time he did not know of all the work of Koch. He succeeded in obtaining pure cultures of Anthrax. The question was then still being debated in France as to whether Anthrax was caused by a ‘virus’, that is to say a non-living poison, or by a microbe. Pasteur had long been a believer in the microbic theory, and it seemed to him probable that the blood of an animal infected with Anthrax, if sown in a suitable medium, would stock it solely with anthrax bacilli which he could then keep pure for an indefinite time in successive cultures, as he had done with yeast and other ferments.

Experiment proved this to be the case, and showed that the anthrax organism multiplied abundantly in urine made neutral or slightly alkaline. From that time the problem was solved. Take a series of cultures of the organism, transferring each time one drop from the preceding culture into 50 c.c. of fresh urine. The first dilution is 1/1000, the second one in a million, the third one in a thousand million. After ten cultures it falls to such a figure that the original drop of blood has been drowned in an ocean. Everything that it carried with it, to which we might attribute the production of Anthrax--red corpuscles, white corpuscles, granules of all sorts--is either destroyed by the change of medium or is widely disseminated in this ocean and is lost. Only the organism can escape the dilution. Why? Because it has multiplied in each of the cultures. A drop from the last culture killed a rabbit or guinea-pig as surely as a drop of anthrax blood. It was, therefore, to the organism that the virulence belonged. A conclusion of the first rank was firmly established.

With a ‘pure culture’ of Anthrax in his possession Pasteur was able to experiment in a way which none had previously attempted. The most interesting stage of his work was now entered upon. He perceived that there are some species of animals which are refractory to Anthrax. Such are the birds. Nevertheless, the blood of a bird, when drawn from the animal, is an excellent culture medium for the bacterium. Why does it resist infection in the animal? Pasteur showed that the anthrax organism will not live in the bird because the living-blood in full circulation is filled with an infinite number of corpuscles which, in order to live and perform their physiological function, need free oxygen. When, therefore, the anthrax organism enters normal blood of living birds, it meets competitors ready to seize the oxygen for their own use. But the blood of other animals besides birds contains corpuscles eager for oxygen. Why can anthrax grow in them and not in birds? This question Pasteur answered by a convincing series of experiments (1878). The normal temperature of birds is higher than that of mammals and is, moreover, higher than that at which the growth of the anthrax organism is most vigorous. Thus the blood corpuscles of the bird have the anthrax bacteria at a disadvantage. But if, by a cold bath, the temperature of a bird be lowered to that of a mammal, and if anthrax organisms be injected into the blood-stream, they will grow and flourish at the expense of the bird.

The experiments with Anthrax on fowls led to experiments on the same creatures with another disease, the virulence of which was known to vary, Chicken Cholera. Thus arose naturally Pasteur’s ideas and observations in the department of Immunity (p. 261).

If Pasteur can be said to have laid the foundations of the knowledge of the nature of infection, it is to Koch that we owe the main basis of the technique by which diseases are now studied. He it was who elevated Bacteriology into the position of a separate science. Soon after his work on Anthrax he published a remarkable research which placed our knowledge of wound infection on a firm footing. He is thus among those who helped to create modern surgical technique. Many other communications came from him. None was of more far-reaching importance than his demonstration of the organism of Tuberculosis in 1882. All subsequent work in connection with Consumption and allied conditions has been rendered possible only by this discovery of Koch. Other investigations associated with his name are on Cholera and on Sleeping Sickness. Koch was unquestionably the greatest bacteriologist that the world has seen. His genius was limited as compared to that of Pasteur, but his exquisite technical skill and acumen have never been excelled.

Since the time of Pasteur and Koch, the study of infectious disease has developed along various special lines. The work of these two men, however, has determined the direction of those lines, and they themselves are the most typical, as well as the greatest, representatives of the most important of all movements in modern Medicine.

§ 7. Anaesthesia.

The aspect of surgical practice was dramatically changed during the course of the nineteenth century by two discoveries, that of Anaesthesia and that of the Antiseptic method. It will be convenient to consider Anaesthesia first.

There were from the earliest times many devices for producing more or less complete unconsciousness during surgical operations. An idea of the extremes to which surgeons at the beginning of the nineteenth century were put in this matter can be gathered from a glance at some of their devices (Fig. 108a).

The new era began in 1846 when the dentist, William Thomas Green Morton (1819-68), demonstrated at the Massachusetts General Hospital the simplicity and safety of Ether anaesthesia. The idea immediately caught on. Before the year was out Ether was being used for surgical purposes in England. In January, 1847, Sir James Young Simpson (1811-70) was using it in Edinburgh for obstetric purposes. A few months later he adopted Chloroform, which had been prepared by Liebig in 1832.

The use of the drugs spread very rapidly and almost as rapidly changed the character of surgical technique. Until the adoption of anaesthesia, speed was of primary importance in surgical procedure. Excessive speed now became a matter of less importance, and operative neatness and completeness took its place as the chief quality of good surgery. Moreover, operations of a more drastic character could be undertaken since the shock to the patient was minimized. Women in labor were found to bear Chloroform peculiarly well and safely, and its use in midwifery steadily spread despite some foolish and fanatical opposition.

Soon after the introduction of anaesthetics efforts were made by various methods to secure a painless state of a part without involving unconsciousness. The first successes were obtained in 1884 at Vienna with applications of solutions of the alkaloid (p. 325) Cocaine, first to the eye, then to the nose and other parts. Cocaine, or some derivative of it, has ever since been much used in Medicine. It was soon being given by injection under the skin for small superficial operations. Next, good results from injecting solutions of it into the nerves were obtained by several American surgeons, earliest of whom was W. S. Halsted (1852-). His work of 1885 was extended in 1898 by Harvey Cushing (1869-). Yet another American surgeon, J. L. Corning (1855-), introduced the method of so-called ‘spinal anaesthesia’. This is secured by injecting a solution of Cocaine or one of its derivatives into the spinal canal and thereby inducing insensibility to pain (‘analgesia’) below the site of injection. In 1908 the American G. W. Crile (1864-) introduced a valuable method of combining local and general anaesthesia, whereby he minimized the effects of ‘shock’ (pp. 310-11) during the progress of the operation.

From first to last almost all the pioneer work upon anaesthetics and analgesics has been of American origin. Even the word anaesthesia is an American invention. It was introduced or at least familiarized by Oliver Wendell Holmes (1809-94), the distinguished and brilliant author of the ‘Breakfast Table’ series. Laughing Gas was first applied to dental purposes a short time before Ether was given its surgical application, and its introduction for this purpose was the work of the American dentist Horace Wells (1815-45), of Hartford, Connecticut.

FIG. 108a. SCREW adapted to the lower limb, as used by surgeons in the eighteenth century and the early nineteenth century, to compress the nerves in order to secure analgesia during amputation. Its application, however, was extremely painful in itself and injurious to the part operated on.