IN THE FALL OF 1914, ELIE METCHNIKOFF, NOBEL PRIZE WINNER,
father of immunology, and optimistic philosopher, was alone in his laboratory at the Pasteur Institute. It was not a good time for philosophers of optimism. He could not yet hear the sound of the artillery on the Marne, but he was, he tells us, waiting for it. Unable to work, he decided to occupy his time by writing a book for students called “Three Founders of Modern Medicine: Pasteur, Lister, Koch.” Metchnikoff, then over 70, had known all of the protagonists in the battle for the germ theory of infectious disease. Pasteur was his mentor and Joseph Lister, the father of antiseptic surgery, was his friend. Robert Koch, the great German bacteriologist, was an opponent who did not believe in immunity or in the ability of certain immune cells, phagocytes, to consume bacteria. Metchnikoff was the father of cellular immunology and phagocytosis was his great discovery.
|An operation in the 1880s, showing the surgeons wearing street clothes.
By the late 1880s sterile gowns had appeared and, in the 1890s, gloves. In the foreground on a stool is a vaporizer that sprays 2 percent carbolic acid over the operating field. This device was later abandoned when it was determined that most infecting bacteria came from instruments, hands, and clothing, rather than the air. From “Medicine-An Illustrated History” by A.S. Lyons and R.J. Petrucelli, published by Harry N. Abrams NY 1978.
The manuscript was not published and Metchnikoff died of heart disease in 1916. In 1933, a group of his friends published it as a memorial. Columbia has copies in French and in Russian, but not English. We know from library records that someone checked out the French version in 1937. A 1991 biography of Metchnikoff never mentions this small masterpiece. This is Metchnikoff’s introduction:
These pages have been written in special circumstances. If we do not yet hear
the growling of cannons, it is in waiting for them that I have had to spend several weeks in Paris, in my laboratory, which has been put in a state of war. The state of war has been accompanied by a near complete cessation of all scientific activity at the Pasteur Institute. From fear of a lack of food for the experimental animals, we have had to kill them, which keeps us from doing our research. The stables of the Institute have been emptied of cows, whose milk was destined for hospitals and orphanages. The majority of young collaborators, assistants, and technicians have been mobilized and we now have only women and old men.
Myself, as an old man, find myself unable to experiment and in possession of much free time. I have employed it to write this book, in the hope that it will be useful. It is not for doctors, but for young people looking for an orientation in their research.
We can be sure that this senseless war, which burst upon us as a result of a lack of understanding and will from those who should have valued peace, will be followed by a long period of calm. We must hope that this slaughter without precedent will suppress for a long time the desire to fight and that people will feel the need for more reasonable activities. Let those with a combative spirit be directed to the fight not against humans but against the innumerable microbes, visible and invisible, which menace us from everywhere and keep us from achieving the normal and complete cycle of our existence.
Who would not keep reading such a writer? Consider what Metchnikoff then tells us of surgery and medicine during the Crimean war from 1854-1856. The French army dispatched to the Crimean peninsula consisted of more than 300,000 men. About 10,000 were killed in combat, but 85,000 men, more than a quarter of the army, were lost from illness and as a result of wounds. According to the official army medical report by a General Chénu, published in 1865, 10,000 men died of wounds — many bled to death en route to hospitals but a large number died of erysipelas, general septicemia, or the ghastly disease called hospital gangrene. Of 1,681 wounded men whose legs were amputated above the knee only 136 survived, a mortality rate of 92 percent. Amputations below the knee had a death rate of 71 percent. Dr. Chénu noted that the “lack of success of surgery was depressing.” The results of surgery were similar during the American Civil War. But surgery was not the worst of it. Surgeons operated only on those who had been wounded. Infectious disease had no prerequisites.
|Lister greets Pasteur on his 70th birthday in December, 1892. Pasteur, by
then infirm, is being assisted by Sadi Carnot, President of France. Lister
and Pasteur were cordial colleagues and exchanged letters and scientific materials. Lister repeated Pasteur’s experiments on spontaneous generation for his students. Painting by Jean André Rixens, The painting is at The Sorbonne. Photo courtesy of Duke University Photo Archives.
At the beginning of 1854, cholera attacked the French army and caused it to retreat. In July, within a corps of 55,000 men, more than 8,000 had cholera. In August, the situation became worse and many of the army’s physicians and surgeons died. In September, the commander, Maréchal Saint-Arnaud, died. Cholera came back in 1855. When cholera diminished during the winter of 1854-1855, typhus appeared, killing 30 percent of its 1,523 victims, again taking many of the medical corps. The British armies, also engaged in the Crimea, were no better off, although the dramatic intervention of Florence Nightingale did help. In October of 1854, Richard James MacKenzie, surgeon to the infirmary and lecturer on surgery at the Edinburgh Extramural School, volunteering with the 79th Highlanders, died of cholera. Joseph Jackson Lister filled Mackenzie’s position in Edinburgh.
Metchnikoff tells us how Lister changed this helpless state of surgery. How he did it, how much the surgeons and physicians of his time opposed him, and how the new ideas came to Presbyterian Hospital are the subjects that concern us here and in the next issue of P&S.
|Lister’s realization of the relevance of Pasteur’s ideas to disease was a critical moment in the history of medicine.
By 1860, Lister was professor of surgery in Glasgow. He could not understand why compound fractures had a terrible prognosis, while simple fractures, where the skin was not broken, healed without suppuration or putrefaction. Lister wrote:
Lister’s patients were consumed with gangrene and erysipelas. The ward, later to become famous as the Lister Ward, stank from the smell of putrefaction.
These and many other considerations had long impressed me with the greatness of the evil of putrefaction in surgery. I had done my best to mitigate it by scrupulous ordinary cleanliness and the use of various deodorant lotions. But to prevent it altogether appeared hopeless while we believed with Liebig that its primary cause was the atmospheric oxygen, which in accordance with the researches of Graham, could not fail to be perpetually diffused through the porous dressings? But when Pasteur had shown that putrefaction was a fermentation caused by the growth of microbes, and that these could not arise de novo, in the decomposable substance, the problem assumed a more hopeful aspect. [Leibig, the greatest organic chemist of the period, initially opposed the idea of a biological agent of fermentation and putrefaction, thinking it was vitalism
and smacked of mystery.]
In late 1864, Lister talked to his friend Dr. Thomas Anderson, a chemist at the University of Glasgow. Professor Anderson, an expert in shale products and petroleum, suggested that Lister read the papers of Louis Pasteur. Pasteur had proved that fermentation was accomplished by living bacteria and that, furthermore, putrefaction was similar to fermentation but of albuminoid (protein) substances. He showed through now famous experimentation that bacteria did not arise from inanimate matter but came from the air or other sources of contamination. Lister, who spoke French, read the papers.
Lister’s realization of the relevance of Pasteur’s ideas to disease was a critical moment in the history of medicine. Pasteur, across the channel, was consumed with efforts to debunk spontaneous generation theories and industrial problems in the beer, wine, and silk industries. He was not a physician and, although he surely realized the relevance of his ideas to medicine, he was not ready to take on the medical establishment. That would come later and meet bitter resistance. But Metchnikoff tells us that for Lister there was no waiting. As Lister recalled in 1891:
But when Pasteur had shown that putrefaction and other fermentative changes were caused by the growth of micro-organisms, and
had at the same time demolished the idea of spontaneous generation, the problem
of the prevention of putrefaction in wounds seemed no longer hopeless. The fermentative microbes could not arise de novo in the
blood or tissues, and the experience of the absence of all danger in simple fracture seemed to indicate that they could not
gain access by any other channel than an open wound. It therefore seemed possible that putrefaction might be entirely prevented in wounds by treating them with some substance which might destroy the life of the microbes, though not excluding the atmospheric gases.
|Ken Forde, Rich Kessin, and Steve Novak in Archives & Special Collections, photographed with a collection of original notes from the Presbyterian Hospital surgical service in 1876.
Professor Anderson, whose role is not appreciated, suggested and then supplied a compound that would kill bacteria — carbolic acid (phenol), which had been used to remove the smell from sewage in the town of Carlisle. Lister prepared for an appropriate patient to test the compound and his new procedures: He repeated some of Pasteur’s experiments on spontaneous generation, showing that no bacteria formed de novo in sterilized media. He worked out that a 5 percent solution of phenol kills bacteria and he developed ways to sterilize catgut for ligatures. He prepared lotions of dilute phenol to sterilize the patient’s skin and special sterile dressings of exact thickness imbedded with dilute phenol or other antibacterial substances. Eventually, he made a machine to spray dilute phenol over the operating field. In March of 1865, he had a patient with a compound fracture of the femur. At that time amputation was the only treatment for compound fractures and, as the survival rates show, was not very effective. Lister sterilized the wound with carbolic acid and the wound remained uninfected. The leg and the patient were saved. In 1867 Lister reported the results of a number of cases in The Lancet.
|Lister repeated some of Pasteur’s experiments on spontaneous generation, showing that no bacteria formed de novo in sterilized media.
Despite Lister’s success, opposition to antiseptic surgery throughout the 1870s and 80s was widespread. Surgeons (and obstetricians) of the day could not believe that anything as small as a bacterium could cause such disaster. Acceptance would mean that surgeons, with their contaminated hands and instruments, had been the cause of endless suffering and death. Opponents argued that antiseptic surgery did not always prevent infection and that traditional techniques often worked, with no infection. The antiseptic techniques of Lister were a developing art; failures, especially by the careless or unqualified, discredited the techniques. Some surgeons rejected the methods because phenol was hard on the hands. (It was not until the 1890s that William Halsted, an 1876 P&S graduate, solved this problem by introducing gloves). Some surgeons, especially in France, carped about Pasteur’s lack of medical qualifications. Surgeons in England sniffed at a fancy French invention. Late in the 1880s, after Lister had moved to London, two schools of surgery — antiseptic and classical — defined the discipline. Sir William Watson Cheyne, one of Lister’s house officers, who wrote an excellent biography of Lister in 1925, said examiners of one school would fail students of the other during exams.
But what of America? In New York, John Call Dalton, eminent physiologist and later president of the College of Physicians and Surgeons, wrote a long, even masterful, monograph in which he summarized the history of the idea of spontaneous generation. He concluded that by 1872 everyone agreed that animals or complex beings could not form by spontaneous generation and that they came from eggs. He leaned toward the conclusion that bacteria could not form spontaneously from inanimate matter but was not ready to conclude that they could not. This was in 1872, a decade after Pasteur had laid the matter to rest and five years after Lister’s first reports. In that same year, Presbyterian Hospital opened. Its surgical wards had patients dying of the same causes as the wounded soldiers of the Crimean and Civil wars.
During this period, a young New Yorker, a veteran of the Civil War, had quit the family investment house, moved his wife and children to Europe, and started to attend lectures in medicine at the University of Paris. His name was Lewis Atterbury Stimson (his son, Henry Stimson, later served as Secretary of State under Hoover and Secretary of War during World War II). He made many important contributions to surgery and medical education. His letters from Paris to his brother, the Rev. Henry Stimson in New York, explain how he came to join the antiseptic school of surgery. Here is one:
Stimson was primed with ideas on antisepsis by the time he returned to New York later in 1875 to receive his M.D. degree from Bellevue Medical College. By January of 1876, he was an attending surgeon at the still-new Presbyterian Hospital. He was soon to perform the first operation in America under complete antiseptic conditions — an amputation at the thigh, for which the survival, as we have seen, was typically low.
Paris, February, 28, 1875: My dear Henry: I went to the Academy of Medicine the other day and was lucky enough to see and hear Pasteur. The subject under discussion was bacteria and brought to their feet several men with whose names and work I became familiar while studying the subject last summer so that it was doubly interesting to me. Pasteur is a man 50-55 years old, with black hair and beard, medium height, rather squarely built, spectacles, and as aggressive a pug nose as one often sees. He speaks slowly and not fluently, is quiet in manner but merciless, utterly without levity, toward his wretched opponents, and has a little streak of humor which is very effective.
The audience was evidently much interested in him, all bent forward and eagerly greeting every point, but his colleagues seemed rather cool towards him. Still, when he got through there was nothing to be said, he had completely cleared the ground, and the discussion ended almost immediately. It had been provoked by a paper presented by a young man who had examined the pus of 18 or 20 abscesses and found bacteria in most of them. He allowed himself to intimate that he had found spontaneous generation. It would have been easy for anyone to overthrow the argument, but Pasteur gave only a word or two to its weak points and then said, “I have read the young man’s paper carefully and will quote only one thing to show how utterly unreliable it all is. He says he carefully cleaned all his instruments, glasses, knives etc., with the hyposulphite of lime which instantly destroys all germs. Now the hyposulphite of lime is
a slightly alkaline liquid (all this in the quietest most professorial tone) in which bacteria live and thrive most readily.” As
you see, there was nothing more to be said. I felt sorry for the young man whom I happened to know, but he deserved it,
for I had seen several of his examinations, and they were not conducted carefully.
The authors have found the original case notes from the historical operation, the recollections of Stimson’s assistant, Dr. David Bryson Delavan, and Stimson’s own descriptions of the case. This dramatic event — and the difficulties faced by a new generation of New York surgeons — will be recounted in the next issue of P&S.
The authors thank Stephen Novak, head of
Archives and Special Collections, for his knowledge