Dr. Ian Carr
Professor Emeritus, Faculty of Medicine, University of Manitoba
The founder of pathology was Giovanni Batista Morgagni (1682-1771), professor of medicine and anatomy at Padua for 56 years. He published at the age of 79 the De Sedibus Causis Morborum containing accounts of aneurysm, acute yellow atrophy of the liver, heart block and valvular disease of the heart, pneumonia and the connection between miliary disease and cerebral abscess. He detailed the case histories and pathological appearances of no less than 700 cases.
A man who had been too much given to the exercise of tennis and the abuse of wine, was, in consequence of both these irregularities, seized with a pain of the right arm, and soon after of the left, joined with a fever. After these there appeared a tumour on the upper part of the sternum, like a large boil. The patient came into the Hospital of Incurables, at Bologna ... in the year 1704. The swelling on ...the chest wall was equal in size to a quince...and began to exsude blood in one place ... very near having broken through the skin ... He (being quite ignorant of the danger which was at hand) began to pull off the bandages, for the sake of showing his disorder. But his circumstance being observed, he was prevented going on, and ordered to keep himself still, and to think seriously and piously of his departure from this mortal life, which was very near at hand, and inevitable. On the day following, he felt the blood gushing forth, and had the presence of mind not only to commend himself to God, but to take up with his own hands a basin that lay at his bed-side; and, as if he had been receiving the blood of another person, put it beneath the gaping tumour, while the attendants immediately ran to him as fast as possible, in whose arms he soon expired.
On examining the body before I dissected it, I saw that there was no longer any tumour, inasmuch as it had subsided after the blood, by which it had been raised up externally, and had been discharged. The skin was there broken through, and the parts that lie beneath it with an aperture, which admitted two fingers at once....In both the cavities of the thorax, also, was a great quantity of water, of a yellowish colour. And there was a large aneurism, into which the anterior part of the curvature of the aorta itself being expanded, had partly consumed the upper part of the sternum, the extremities of the clavicles which lie upon it, and the neighbouring ribs, and partly had made them diseased, by bringing on a caries.
Morgagni had no microscope. Microscopes were needed for further advance in pathology. Marcello Malpighi (1628-1694) of Bologna saw capillaries in the frog's lung and completed Harvey's discovery of the circulation. He also saw the layers of the skin, white pulp of the spleen and renal glomeruli. Athanasius Kircher (1602-1680) studied the blood of plague patients and saw countless masses of small worms - red blood corpuscle. He described striations in muscle fibres, bacteria and protozoa. Rudolph Virchow (1821-92) brought the microscope to pathology and showed that cell changes were the centre of the alterations of the tissues in disease. Omnis cellula e cellula.
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.
Anaesthesia started in North America. Various potions including opiates and alcohol have been used since ancient times to dull pain and lull into sleep. The hypnotic effect of ether, "sweet vitriol," has been known since the sixteenth century, but the first effective anaesthetic dates back only to 1842.
In that year Crawford Long, a physician in the small town of Jefferson, Georgia noticed that when people inhaled ether as a "recreational" drug, they became insensitive to pain. He removed a tumour from a patient's neck under ether anaesthesia, but did not immediately publicize his discovery. Two or three years later others, Wells, Morton and Jackson tried first nitrous oxide then ether for first dental and then other purposes. Over the years Congress voted $100,000 to the inventor of anaesthesia; but there was profound disagreement as to who the inventor was.
Long wrote some time later:
In the month of December, 1841, or January, 1842, the subject of the inhalation of nitrous oxide gas was introduced in a company of young men assembled at night, in the village of Jefferson, Ga., and the party requested me to prepare them some. I (Long) informed them that I had not the requisite apparatus for preparing or using the gas, but that I had an article (sulphuric ether), which would produce equally exhilarating effects and was as safe. The company was anxious to witness its effects: the ether was produced, and all present, in turn, inhaled. They were so much pleased with its effects that they afterwards frequently used it and induced others to use it, and the practice became quite fashionable in the country and some of the contiguous counties. On numerous occasions I inhaled the ether for its exhilarating properties and would frequently at some short time subsequently discover bruises or painful spots on my person which I had no recollection of causing, and which I felt satisfied were received while under the influence of ether. I noticed my friends while etherized, receive falls and blows, which I believed sufficient to cause pain on a person not in a state of anaesthesia, and, on questioning them they uniformly assured me that they did not feel the least pain from these accidents.
Observing these facts I was led to believe that anaesthesia was produced by the inhalation of ether and that its use would be applicable in surgical operations.
The first person to whom I administered ether in a surgical operation was Mr. James M. Venable, who then resided within two miles of Jefferson, and at the present time in Cobb county, Ga. Mr. Venable consulted me on several occasions as to the propriety of removing two small tumors on the back part of his neck, but would postpone from time to time having the operating performed from dread of pain. At length I mentioned to him the fact of my receiving bruises while under the influence of the vapor of ether, without suffering, and, as I knew him to be fond of and accustomed to inhale ether, I suggested to him the probability that the operation might be performed without pain, and suggested to him operating while he was under its influence. He consented to have one tumor removed and the operation was performed the same evening. The ether was given to Mr. Venable on a towel and fully under its influence, I extirpated the tumor. It was encysted and about one-half an inch in diameter. The patient continued to inhale ether during the time of the operation, and seemed incredulous until the tumor was shown to him. He had had no evidence of pain during the operation and assured me after it was over that he did not experience the least degree of pain from its performance ...
The discovery soon crossed the Atlantic and was first used in the University College Hospital, London, 1846. It was followed a year later by chloroform introduced in Edinburgh by James Young Simpson.
Up until 1800, human communities existed with very little control of public health. There were some municipal regulations against the disposal within towns of sewage and garbage and during plagues municipal officials were appointed to seek out cases, but there was little organization or enforcement. Cities of the European Industrial Revolution were overcrowded and had poor water supplies. In the early nineteenth century, over half a million people in London got their water from stand pipes in the street. Excrement was discharged into open sewers. Epidemic cholera and typhoid were frequent and the rates of morbidity and mortality among the general population, and especially among infants were high. These things happened early in England, which was an early country to industrialize. Poor relief cost so much that a number of Royal Commissions were set up to look into various public health matters. These investigations were supported by the leading humanitarians of the day, notably a lawyer named Edwin Chadwick, who led the agitation for control of public health. This started in Britain with the 1848 Public Health Act. There was a major epidemic of cholera in London in 1854; Dr John Snow demonstrated that many cases occurred among people who drank water from a pump in Broad Street; those who obtained water from other pumps did not contract the disease. The pump handle was removed and in that area there were no more cases of cholera. When adequate water supplies and sewage systems were installed and slums were cleared, the epidemics abated. John Snow was also a pioneer in surgical anaesthesia.
Smallpox was the most virulent of the infectious diseases, with a mortality rate well over 50% in previously unexposed populations. Attempts at prevention were made in the early eighteenth century by inoculation with pus from active cases of smallpox. This process, variolation, was often effective, but was lethal in a significant proportion of patients.
Edward Jenner (1749-1823), a Gloucestershire physician, observed that local country people believed that those who had had cow-pox would not contract small-pox. Jenner vaccinated a boy James Phipps with material taken from a cow-pox vesicle on the hands of a dairy maid and then showed that the boy was immune to small-pox.
In this dairy country a great number of cows are kept, and the office of milking is performed indiscriminately by men and maid servants. One of the former having been appointed to apply dressings to the heels of a horse affected with the grease, and not paying due attention to cleanliness, incautiously bears his part in milking the cows, with some particles of the infectious matter adhering to his fingers. When this is the case, it commonly happens that a disease is communicated to the cows, and from the cows to dairy maids, which spreads through the farm until most of the cattle and domestics feel its unpleasant consequences. This disease has obtained the name of cow-pox. It appears on the nipples of the cows in the form of irregular pustules.
Case I. Joseph Merret, now an under gardener to the Earl of Berkeley, lived as a servant with a farmer near this place in the year 1770, and occasionally assisted in milking his master's cows. Several horses belonging to the farm began to have sore heels, which Merret frequently attended. The cows soon became affected with the cow-pox, and soon after several sores appeared on his hands. Swellings and stiffness in each axilla followed, and he was so much indisposed for several days as to be incapable of pursuing his ordinary employment. Previously to the appearance of the distemper among the cows there was no fresh cow brought into the farm, nor any servant employed who was affected with the cow-pox. In April, 1795, a general inoculation taking place here, Merret was inoculated with his family; so that a period of twenty-five years had elapsed from his having the cow-pox to this time. However, though the variolous matter was repeatedly inserted into his arm, I found it impracticable to infect him with it; an efflorescence only, taking on an erysipelatous look about the centre, appearing on the skin near the punctured parts. During the whole time that his family had the smallpox, one of whom had it very full, he remained in the house with them, but received no injury from exposure to the contagion.
Case II. Sarah Portlock of this place, was infected with the cow-pox when a servant at a farmer's in the neighborhood, twenty-seven years ago.
In the year 1792, conceiving herself, from this circumstance, secure from the infection of the smallpox, she nursed one of her own children who had accidentally caught the disease, but no indisposition ensued. During the time she remained in the infected room, variolous matter was inserted into both her arms, but without any further effect than in the preceding case.
Case XVII. The more accurately to observe the progress of the infection I selected a healthy boy, about eight years old, for the purpose of inoculating for the cow-pox. The matter was taken from a sore on the hand of a dairymaid, who was infected by her master's cows, and it was inserted on the 14th day of May, 1796, into the arm of the boy by means of two superficial incisions, barely penetrating the cutis, each about an inch long.
On the seventh day he complained of uneasiness in the axilla and on the ninth he became a little chilly, lost his appetite, and had a slight headache. During the whole of this day he was perceptibly indisposed, and spent the night with some degree of restlessness, but on the day following he was perfectly well.
In order to ascertain whether the boy, after feeling so slight an affection of the system from the cow-pox virus, was secure from the contagion of the smallpox, he was inoculated the 1st of July following with variolous matter, immediately taken from a pustule. Several slight punctures and incisions were made on both his arms, and the matter was carefully inserted, but no disease followed.
The practice spread within two years and by the time of Jenner's death in 1823 was being used in many countries around the world.
Morgagni, G. De sedibus, et causis morborum per anatomen indagatis libri quinque. Dissectiones, et animadversiones, nunc primum editas complectuntur propemodum innumeras, medicis, chirurgis, anatomicis profuturas. Venetiis: Ex Typographia Remondiniana, 1761.