How the plague bacillus and its transmission through fleas were discovered: reminiscences from my years at the Pasteur Institute in Paris.

At present, there are only occasional cases of human plague reported in the United States. As an example, there were only 14 nonfatal cases of human plague recorded in 1988 and 5 cases in 1990. Each resulted from exposure to wild rodents, carrying the plague bacillus and fleas, in the western United States: Colorado, New Mexico, California, Arizona, and Texas. The affected individuals were treated with antibiotics (usually streptomycin and tetracycline) and recovered. Local, endemic outbreaks of plague have been reported from Uganda, Kenya, and the island of Madagascar. More recently, in outbreaks of plague, bubonic or pneumonic, in limited local epidemics, a total of over 700 patients have been reported from certain areas of India in 1994. This manuscript was prepared in order to describe a few interesting details referring to the initial discovery of the plague bacillus and its mode of transmission from the rat carriers to other rats and to humans. A few centuries ago, plague represented a massive disaster, killing millions of local populations in India, China, IndoChina, Africa, and, particularly, Europe. The cause of this disease was unknown and was attributed to unfavorable constellations of stars, to comets, to the wrath of supernatural powers, and frequently also to poisoning of wells by Jews, or other ethnic groups of people, who paid for this with tortures inflicted on them by the panicked population. The mystery of plague was solved fairly recently. Alexandre Yersin, who discovered the bacillus of plague, died in 1943, during World War II. In June 1940, Yersin was in Paris, attending a Pasteur Institute meeting, and left Lutetia Hotel, where he was staying (and where I was staying also at the same time), barely a few hours before the German armies entered the French capital; in fact, Yersin left Paris for Saigon, by air, only 6 hours before the airport was closed. Paul-Louis Simond, who discovered that plague is transmitted by fleas, was collecting plants, and living quietly in retirement, in Valence (province of Drome, south of Lyon), in France, and he very kindly replied in writing to my letters, which I wrote to him from the Pasteur Institute in 1938, asking him for details of his fundamental discovery. Since my childhood years, I have always been interested in finding out how the great medical discoveries were made and how the epidemics of transmissible diseases were prevented. In my early postdoctoral years, I had the opportunity, shortly before World War II, to spend several years, as a young guest investigator, at the Pasteur Institute in Paris. I was intrigued by an isolated laboratory, located in a separate small building, at 25, rue du Docteur Roux. I was told that the upper floor of this small building has a laboratory dedicated to the problem of plague and that it contains notes and records of Yersin, who recognized that this disease infects predominantly rats, and of Simond. I visited this small laboratory several times and studied the notes of Yersin and Simond. In fact, I was working in the same laboratory where Simond worked, some 40 years earlier. In 1938, when I was tracing the data leading to the clarification of the plague transmission puzzle, Simond lived at that time, as a retired French Army Medical Corps general, in Valence. I was helped and guided in my task by Edmond Dujardin-Beaumetz, a former friend of Yersin, who was working in the plague laboratory. I was impressed by these fundamental discoveries, which provided the means to control and prevent pandemics of this devastating disease. Epidemics of plague have devastated for several centuries not only cities but also entire countries. Millions of people died, populations were decimated, and there were not enough people to bury the dead. People panicked. Medical and church authorities thought that these epidemics were caused by supernatural powers, in retaliation for sins committed by some segments of the population. Innocent groups of people were tortured and killed after being accused of spreading the disease. There did not appear to be any remedy or means to prevent this disaster. The means of a relatively simple solution leading to the prevention of this devastating disease were found just before the turn of this century. These discoveries did not require complicated methods or techniques, except curiosity, common sense, and good observation by a couple of intelligent and persistent investigators, equipped with good will, a microscope, and letters of recommendation signed by Louis Pasteur and his coworker, Emile Roux. These letters facilitated dealing with local authorities in Indo-China and other places where plague epidemics were at that time ravaging the local populations. Both Yersin and Simond were trained at the Pasteur Institute in Paris and were strongly encouraged by Pasteur to follow and to try to solve the problem of plague. The story of this fundamental discovery, very briefly, is as follows. Yersin, born in Switzerland, descendant of French immigrants, studied in France and worked at the Hotel Dieu Hospital in Paris; at that time Pasteur just introduced his vaccine treatment for those infected with rabies. Yersin was performing an autopsy on the spinal cord of a patient who died following a bite by a rabid wild dog; during the dissection of the spinal cord, Yersin cut his finger; he immediately proceeded to Pasteur's laboratory. Pasteur called his assistant, Emile Roux, and asked him to start vaccinating Yersin against rabies. That was the beginning of a long friendship that developed between Yersin, Pasteur, and Roux. Yersin became interested in bacteriology and frequently spent time in Pasteur's and Roux's laboratories. He was also assisted by Roux in preparation of his French medical doctorate thesis. When an epidemic of plague developed in and ravaged Hong Kong, Pasteur suggested that Yersin proceed to Hong Kong to study and attempt to isolate the causative microbe of that devastating disease. Yersin accepted this suggestion enthusiastically. Pasteur requested that the French authorities send Yersin, who was a member of the French medical colonial corps, to Hong Kong. The orders came promptly, by telegram, and Yersin proceeded to Hong Kong.