This article is from the Health Articles series.
The next steps were the demonstrations that disease was caused by micro-organisms, and that immunity could be provided. In 1835 Bassi showed that a disease of silk worm was due to a fungal infection and in 1839 Schonlein showed that a human skin disease, favus, was due to a fungal infection. The man who revolutionised our understanding of disease by finding bacterial causes was Louis Pasteur (1822-95). Pasteur was a French microbiologist who made his name initially investigating a disease of silkworms.
Pasteur described his great discovery, immunization against rabies.
A dog may be rendered refractory to rabies in a relatively short time in the following way:
Every day morsels of fresh infective spinal cord from a rabbit which has died of rabies developed after an incubation period of seven days, are suspended in a series of flasks, the air in which is kept dry by placing fragments of potash at the bottom of the flask. Every day also a dog is inoculated under the skin with a Pravaz' syringe full of sterilized broth, in which a small fragment of one of the spinal cords has been broken up, commencing with a spinal cord far enough removed in order of time from the day of the operation to render it certain that the cord was not at all virulent. (This date had been ascertained by previous experiments). On the following days the same operation is performed with more recent cords, separated from each other by an interval of two days, until at last a very virulent cord, which has only been in the flask for two days, is used. The dog has now been rendered refractory to rabies.
Joseph Meister, aged 9 years, also bitten on July 4th, at eight o'clock in the morning, by the same dog. This child had been knocked over by the dog and presented numerous bites, on the hands, legs, and thighs, some of them so deep as to render walking difficult. The principal bites had been cauterized at eight o'clock in the evening of July 4th, only twelve hours after the accident, with phenic acid, by Dr. Weber, of Ville.
The third person, who had not been bitten, was the mother of little Joseph Meister.
At the examination of the dog, after its death by the hand of its master, the stomach was found full of hay, straw, and scraps of wood. The dog was certainly rabid. Joseph Meister had been pulled out from under him covered with foam and blood.
The death of this child appearing to be inevitable, I decided, not without lively and sore anxiety, as may well be believed, to try upon Joseph Meister the method which I had found constantly successful with dogs ...
Consequently, on July 6th, at 8 o'clock in the evening, sixty hours after the bites on July 4th, and in the presence of Drs. Vulpian and Grancher, young Meister was inoculated under a fold of skin raised in the right hypochondrium, with half a Pravaz'syringeful of the spinal cord of a rabbit, which had died of rabies on June 21st. It had been preserved since then, that is to say, fifteen days, in a flask of dry air.
In the following days fresh inoculations were made. I thus made thirteen inoculations, and prolonged the treatment to ten days. I shall say later on that a smaller number of inoculations would have been sufficient. But it will be understood how, in the first attempt, I would act with a very special circumspection...
On the last days, therefore, I had inoculated Joseph Meister with the most virulent virus of rabies, that, namely, of the dog, reinforced by passing a great number of times from rabbit to rabbit, a virus which produces rabies after seven days incubation in these animals, after eight or ten days in dogs ...
Joseph Meister, therefore, has escaped, not only the rabies which would have been caused by the bites he received, but also the rabies with which I have inoculated him in order to test the immunity produced by the treatment, a rabies more virulent than ordinary canine rabies.
The ethical implications are evident; the lesson --- medical ethics change.
We owe clean surgery to Joseph Lister (1827-1912) who after training in London and Edinburgh in 1860 became professor of surgery at the Royal Infirmary, Glasgow. Patients then faced danger equal to the battlefield when they went into the operating theatre. Lister had read Pasteur's papers and came to the conclusion that wound sepsis and putrefaction in wine were similar processes. He therefore applied phenol (carbolic acid), a potent antiseptic, directly to wounds and sprayed it into the air. He tried out his new treatment on compound fractures, saving 9 of 11 limbs, losing only one patient. Prior to this time compound fractures necessitated amputation and were often fatal.
In the course of the year 1864 I was much struck with an account of the remarkable effects produced by carbolic acid upon the sewage of the town of Carlisle, the admixture of a very small proportion not only preventing all odour from the lands irrigated with the refuse material, but as it was stated destroying the entozoa which usually infest cattle fed upon such pastures.
James G., aged 11 years, was admitted into the Glasgow Royal Infirmary, on the 12th of August, 1865, with compound fracture of the left leg, caused by the wheel of an empty cart passing over the limb a little below its middle. The wound, which was about an inch and a half long, and three-quarters of an inch broad, was close to, but not over, the line of a fracture of the tibia. A probe, however, could be passed beneath the integument over the seat of fracture and for some inches beyond it. Very little blood had been extravasated into the tissues. My house-surgeon, Dr. Macfee, acting under my instructions, laid a piece of lint dipped in liquid carbolic acid upon the wound, and applied lateral pasteboard splints padded with cotton wool, the limb resting on its outer side, with the knee bent. It was left undisturbed for four days, when, the boy complaining of some uneasiness, I removed the inner splint and examined the wound. It showed no signs of suppuration, but the skin in its immediate vicinity had a slight blush of redness. I now dressed the sore with lint soaked with water having a small proportion of carbolic acid diffused through it; and this was continued for five days, during which the uneasiness and the redness of the skin disappeared, the sore meanwhile furnishing no pus, although some superficial sloughs caused by the acid were separating. But the epidermis being excoriated by this dressing, I substituted for it a solution of one part carbolic acid in from ten to twenty parts of olive oil, which was used for four days, during which a small amount of imperfect pus was produced from the surface of the sore, but not a drop appeared from beneath the skin. It was now clear that there was no longer any danger of deep-seated suppuration, and simple water dressing was employed. Cicatrization proceeded just as in an ordinary granulating sore. At the expiration of six weeks I examined the condition of the bones, and, finding them firmly united, discarded the splints; and two days later the sore was entirely healed, so that the cure could not be said to have been at all retarded by the circumstance of the fracture being compound.
Two of Lister's dressers (assistants) Blanchard and Chown were pioneer Winnipeg surgeons.
By 1870 Pasteur had proven the microbial aetiology of bacterial diseases in silkworms. Pasteur's German rival contributed equally to the development of bacteriology. Robert Koch (1843-1910) was a family physician, who stimulated by clinical experience of an outbreak of anthrax, began to investigate its aetiology.
Koch developed what have become the standard techniques for culture of bacteria, in particular the use of solid agar media. By these he demonstrated that a specific sporing bacillus was the cause of anthrax, and in 1882 demonstrated the cause of tuberculosis. The criteria which he used for proof of bacterial aetiology are now known as Koch's postulates.
To prove that tuberculosis ...is caused by invasion of bacilli and the growth and multiplication of bacilli, it was necessary to isolate the bacilli from the body; to grow them in pure culture...; and, by administering the isolated bacilli to animals, to reproduce the same morbid condition....
In 1885 Koch became Professor of Hygiene in the University of Berlin, from which in 1890, he announced his discovery of tuberculin, at first a secret formula, and later described as a glycerin extract of tubercle bacilli. He believed at first that this would prove effective in the treatment of human tuberculosis; amid much controversy, this proved not to be so.
The treatment of tuberculosis remained unsatisfactory ; patients were isolated for long periods in sanatoria, in conditions which were at once rigorous and non-specifically favourable. In the 1920's a vaccine, BCG came into use in the prevention of childhood tuberculosis; streptomycin was discovered in 1943. The techniques evolved by Pasteur and Koch and elaborated by many others, led to the proof of the bacterial cause of much human disease during the subsequent fifty years.
The idea that there were smaller infective agents than viruses came from work on the mosaic virus of the tobacco plant, which was proved to pass through a fine filter, by Mayer and Ivanovski working separately over the ten years from 1886. Extensive proof of the viral aetiology of human disease depended on the development of satisfactory techniques for tissue culture in the early part of the twentieth century.
by Dr. Ian Carr, Professor Emeritus, Faculty of Medicine, University of Manitoba
 
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