Félix d'Herelle
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Félix d'Herelle (April 25, 1873 – February 22, 1949) was a French-Canadian microbiologist, one of the discoverers of bacteriophages (small viruses that only attack and kill bacteria), and inventor of phage therapy.
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[edit] Early years
D'Herelle was born in Montreal, Quebec, the son of French emigrants. His father, 30 years older than his wife, died when Félix was 6 years old. Félix, his mother and his younger brother Daniel, moved back to Paris. When sixteen years old, he started to travel through western Europe on bike. When 17, after finishing school, he travelled through South America. Afterwards, he continued his travels through Europe, including Turkey, where he met his wife, Marie Caire.
At age 24, now father of a daughter, he and his family moved back to Canada. He built a home laboratory and studied microbiology from books and his own experiments. He earned money by working for the Canadian government, studying the fermentation and distillation of maple syrup to schnapps. He also worked as a medic for a geological expedition, even though he had no medical degree or real experience. Together with his brother, he invested almost all his money in a chocolate factory, which soon went bankrupt.
[edit] Guatemala and Mexico
With his money almost gone and his second daughter born, he took a contract with the government of Guatemala as a bacteriologist at the hospital in Guatemala City. As a side job, he was asked to find a way to make whiskey from bananas. Life in the rough and dangerous environment of the country was hard on his family, but d'Herelle, always adventurer at heart, rather enjoyed working close to "real life", compared to the sterile environments of a "civilized" clinic. He later stated that his scientific path began on this occasion.
In 1907, he took an offer from the Mexican government to continue his studies on fermentation. He and his family moved to a sisal plantation near Mérida, Yucatán. Disease struck at him and his family, but in 1909, he had successfully established a method to produce sisal schnapps.
[edit] France again
Machines for mass production were ordered in Paris, where he oversaw the machines' construction. Meanwhile, he worked in a laboratory at the Pasteur Institute in his spare time for free. He was offered the job of running the new Mexican plant, but declined, considering it "too boring". He did, however, take the time to attempt stopping a locust plague at the plantation using their own diseases. He extracted bacteria harmful for locusts from their guts.
D'Herelle and his family finally moved to Paris in early 1911, where he worked again as an unpaid assistant in a lab at the Pasteur Institute. He got attention in the scientific community the same year, when the results of his successful attempt to counter the Mexican locust plague with Coccobacillus were published.
[edit] Argentina
At the end of the year, restless d'Herelle was again on the road, this time in Argentina, where he was offered a chance to test these results on a much larger scale. Thus, in 1912 and 1913, he fought the Argentinian locust plagues with coccobacillus experiments. Even though Argentina claimed his success was inconsistent, he himself declared it a full success, and was subsequently invited to other countries to demonstrate the method.
[edit] France and phage
During World War I, d'Herelle and assistants (his wife and daughters among them) produced over 12 million doses of medication for the allied military. At this point in history, medical treatments were primitive, compared to today's standards. The smallpox vaccine, developed by Edward Jenner, was one of the few vaccines available. The primary antibiotic was the arsenic-based salvarsan against syphilis, with severe side effects. Common treatments were based mercury, strychnine, and cocaine. As a result, in 1900, the average life span was 45 years, and WWI did not change that to the better.
In 1915, British bacteriologist Frederick W. Twort discovered a small agent that infects and kills bacteria, but did not pursue the issue further. Independently, the discovery of "an invisible, antagonistic microbe of the dysentery bacillus" by d'Herelle was announced on September 3, 1917. The isolation of phages by d'Herelle works like this:
- Nutritional medium is infected with bacteria; the medium turns opaque.
- The bacteria are infected with phages and die, producing new phages; the medium clears up.
- The medium is filtered through porcelain filter, holding back bacteria and larger objects; only the smaller phages pass through.
In early 1919, d'Herelle isolated phages from chicken feces, successfully treating a plague of chicken typhus with them. After this successful experiment on chicken, he felt ready for the first trial on humans. The first patient was healed of dysentery using phage therapy in August 1919. Many more followed.
At the time, none, not even d'Herelle, knew exactly what a phage is, not until the first phage was observed under an electron microscope by Helmut Ruska in 1939. D'Herelle claimed that it reproduces, somehow feeding off bacteria, which was confirmed much later. Others theorized that phages are inanimate objects, proteins for example, that are already present in bacteria, and only trigger the release of similar proteins, killing the bacteria in the process. Due to this uncertainty, and d'Herelle using phages without much hesitation on humans, his work was under constant attack from many other scientists.
In 1920, d'Herelle travelled to Indochina, pursuing studies of cholera and the plague, from where he returned at the end of the year. D'Herelle, officially still an unpaid assistant, found himself without a lab; d'Herelle later claimed this was a result of a quarrel with the assistant director of the Pasteur Institute, Albert Calmette. The biologist Edouard Pozerski had mercy on d'Herelle and lent him a stool (literally) in his laboratory. In 1921, he managed to publish a book about his works as an official Institute publication, by tricking Calmette. During the following year, doctors and scientists across western Europe took a heightened interest in phage therapy, successfully testing it against a variety of diseases. Since, on rare occasions, bacteria become resistant against a single phage, d'Herelle suggested using "phage cocktails" containing different phage strains.
Phage therapy soon became a boom, and a great hope in medicine. In 1925, d'Herelle received the honorary doctorate of the University of Leiden, as well as the Leeuwenhoek medal, which is only awarded once every ten years. The latter was especially important to him, as his idol Louis Pasteur received the same medal (in 1895). The next year, he was nominated eight times for the Nobel prize, though he was never awarded one.
[edit] Egypt and India
After holding a temporary position at the University of Leiden, d'Herelle got a position with the Conseil Sanitaire, Maritime et Quarantenaire d'Egypte in Alexandria. The Conseil was put in place to prevent plague and cholera spreading to Europe, with special emphasis on the sanitary concerns about muslim pilgrim groups returning from Mecca and Medina. D'Herelle used phages he collected from plague-infected rats during his 1920 visit to Indochina on human plague patients, with success. The British Empire intiated a vast campaign against plague based on his results. 1927, d'Herelle himself changed his focus to new targets: India and cholera.
D'Herelle isolated phages from cholera victims in India. As usual, he did not choose a hospital run by European standards, but rather sought out a medical tent in a slum. According to his theory, one had to leave the sterile hospitals and study and defeat illness in its "natural" environment. His team then dropped phage solution in the wells of villages with cholera patients, reducing the death toll from 60 to 8%. The whole India enterprise took less than seven month.
[edit] United States
D'Herelle refused next year's request by the British government to work in India, as he had been offered a professorship at Yale University. He accepted. Meanwhile, European and US pharma companies had taken up the production of own phage medicine, and were promising impossible effects. To counteract this, d'Herelle agreed to co-found a French phage-producing company, piping the money back into phage research. But all companies suffered from production problems; results from commercial phage medicine were erratic, most likely due to the attempt to mass-produce something that was barely understood, leading to damaged phages in the product, or to insufficient amounts thereof. Also, wrong disagnoses often led to the use of the wrong type of phages, which are specific in the choice of their "victims". Furthermore, many studies on the healing effects of phages were badly conducted. All this led to important parts of the scientific community turning against d'Herelle, who, known for his temper, had made not a few enemies.
[edit] The USSR
But he was already on the move again. In or around 1934, he went to Tbilisi (Georgia, where Joseph Stalin was born). D'Herelle was welcomed to the Soviet Union as a hero, bringing the knowledge of salvation from diseases ravaging the eastern states all the way to Russia. He accepted Stalin's invitation for two reasons: it was said he was enamored of communism, and he was happy to be working with his friend, Prof. George Eliava, founder of the Tbilisi Institute, in 1923. Eliava had become friendly with d'Herelle during a visit to the Pasteur Institute in Paris, where he had learned about phages in 1926.
D'Herelle worked at the Tbilisi Institute off and on for about a year - and even dedicated one of his books, "The Bacteriophage and the Phenomenon of Recovery," written and published in Tbilisi in 1935, to Comrade Stalin. He had planned to take up permanent residence in Tbililsi and had already started to build a cottage on the grounds of the Institute (it would later house the KGB's Georgian headquarters). But just then, his friend Eliava fell in love with the woman with whom the head of the secret police also happened to be in love, and Eliava's fate was sealed. He was executed and denounced as an enemy of the people during one of Stalin's purges. D'Herelle ran for his life and never returned to Tbilisi. His book was banned from distribution. Then, World War II began.
[edit] France for good
Phage therapy boomed, despite all problems, driven by the military on both sides in an effort to keep the troops safe, at least from infections. D'Herelle could not really enjoy this development; he was kept under house arrest by the German "Wehrmacht" in Vichy, France. He used the time to write his book "The Value of Experiment", as well as his memoirs, the latter cointaining 800 pages.
After D-Day, the new antibiotic drug penicillin became public knowledge and found its way into the hospitals in the west. As it was more reliable and easier to use than phage therapy, it soon became the method of choice, despite side effects and problems with resistant bacteria. Phage therapy remained a common treatment in the states of the USSR, though, until its deconstruction.
Félix d'Herelle was striken with pancreatic cancer and died a forgotten man in Paris in 1949. He was buried in Saint-Mards-en-Othe in the department of the Aube in France.
In the 1960s Félix d’Hérelle's name appeared on a list published by the Nobel Foundation of scientists who had been worthy of receiving the Nobel Prize but did not, for one reason or another.
However, France has not completely forgotten Félix d'Herelle. There is an avenue that bears his name in the 16th arrondissement in Paris.
[edit] Literary note
The novel Arrowsmith written by Sinclair Lewis with scientific help from Paul de Kruif was based on the life of d´Herelle.
[edit] References
- Summers, William C. (1999) Félix d'Herelle and the Origins of Molecular Biology, Yale University Press ISBN 0-300-07127-2
- For more information about Félix d'Herelle, including exerpts from his unpublished autobiography, see: Häusler, T. (2006) Viruses vs. Superbugs, Macmillan. [1]
