Félix d'Hérelle (25 April 1873 – 22 February 1949) was a French microbiologist. He was co-discoverer of bacteriophages (viruses that infect bacteria) and experimented with the possibility of phage therapy. D'Hérelle has also been credited for his contributions to the larger concept of applied microbiology.
d'Hérelle was a self-taught microbiologist. In 1917 he discovered that "an invisible antagonist", when added to bacteria on agar, would produce areas of dead bacteria. The antagonist, now known to be a bacteriophage, could pass through a Chamberland filter. He accurately diluted a suspension of these viruses and discovered that the highest dilutions (lowest virus concentrations), rather than killing all the bacteria, formed discrete areas of dead organisms. Counting these areas and multiplying by the dilution factor allowed him to calculate the number of viruses in the original suspension. He realised that he had discovered a new form of virus and later coined the term "bacteriophage"."The antagonistic microbe can never be cultivated in media in the absence of the dysentery bacillus. It does not attack heat-killed dysentery bacilli, but is cultivated perfectly in a suspension of washed cells in physiological saline. This indicates that the anti dysentery microbe is an obligate bacteriophage". Felix d'Herelle (1917) An invisible microbe that is antagonistic to the dysentery bacillus (1917) Comptes rendus Acad. Sci. Paris Retrieved on 2 December 2010 Between 1918 and 1921 d'Hérelle discovered different types of bacteriophages that could infect several other species of bacteria including Vibrio cholerae. Bacteriophages were heralded as a potential treatment for diseases such as typhoid and cholera, but their promise was forgotten with the development of penicillin. Since the early 1970s, bacteria have continued to develop resistance to antibiotics such as penicillin, and this has led to a renewed interest in the use of bacteriophages to treat serious infections.
Biography
Early years Félix d'Hérelle's place of birth has been debated, but current research has concluded that he was born in France. Félix d'Hérelle's father, Hubert Augustin Félix Haerens d'Herelle, died at the age of 30 when Félix was six years old. From 7 to 17 years of age, d'Hérelle attended school in Paris, including the Lycée Condorcet and Lycée Louis-le-Grand high schools. In the fall of 1891, d'Hérelle traveled to Bonn, Germany where he attended lectures at the University of Bonn for several months. Between the ages of 16 and 24, d'Hérelle traveled extensively via money given by his mother. At 16, he started to travel through western Europe by bike. At 17, after finishing school, he traveled through South America. Afterwards, he continued his travels through Europe, including Turkey, where he, at 20, met his wife, Marie Caire.
At 24, now the father of a daughter, d'Hérelle and his family moved to Canada. He built a home laboratory and studied microbiology from books and his own experiments. Through the influence of a friend of his late father, he earned a commission from the Canadian government to study the fermentation and distillation of maple syrup to schnapps. His father's friend pointed out that Pasteur "made a good beginning by studying fermentations, so it might be interesting to you, too." 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. During this period, d'Hérelle published his first scientific paper, "De la formation du carbone par les végétaux" in the May 1901 issue of Le Naturaliste Canadien. d'Hérelle contended in the paper that the results of his experiments indicated that carbon was a compound, not an element.
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 General Hospital in Guatemala City. Some of his work included organizing defenses against the dread diseases of the time: malaria and yellow fever. He also studied a local fungal infection of coffee plants, and discovered that acidifying the soil could serve as an effective treatment. 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'Hérelle, 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.
Return to France Machines for mass production of sisal schnapps were ordered in Paris, where he oversaw the machines' construction. Meanwhile, in his spare time, he worked for free in a laboratory at the Pasteur Institute. He was soon 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 pathogenic to locusts from their guts. This innovative approach to locust plagues anticipated modern biological pest control using Bacillus thuringiensis also known as Bt.
D'Hérelle 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.
Argentina At the end of the year, restless d'Hérelle 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.
France and phages During World War I, d'Hérelle 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 World War I 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'Hérelle was announced on 3 September 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. The medium is filtered through porcelain filter, holding back bacteria and larger objects; only the smaller phages pass through.
In early 1919, d'Hérelle isolated phages from chicken feces, successfully treating a plague of chicken typhoid 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'Hérelle, knew exactly what a phage was. D'Hérelle claimed that it was a biological organism that reproduces, somehow feeding off bacteria. Others, the Nobelist Jules Bordet chief among them, theorized that phages were inanimate chemicals, enzymes specifically, that were already present in bacteria, and only trigger the release of similar proteins, killing the bacteria in the process. Due to this uncertainty, and d'Hérelle using phages without much hesitation on humans, his work was under constant attack from many other scientists. It was not until the first phage was observed under an electron microscope by Helmut Ruska in 1939 that its true nature was established.
In 1920, d'Hérelle travelled to Indochina, pursuing studies of cholera and the plague, from where he returned at the end of the year. D'Hérelle, officially still an unpaid assistant, found himself without a lab; d'Hérelle 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'Hérelle and lent him a stool (literally) in his laboratory. In 1921, he managed to publish a monograph, The Bacteriophage: Its Role in Immunity 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 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 1924, 25 January, d'Hérelle received the honorary doctorate of the University of Leiden,Jaarboek der Rijksuniversiteit te Leiden 1924 : Promotiën 17 September 1923 tot 12 Juli 1924, Faculteit der Geneeskunde, Doctoraal geneeskunde, p. 134 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.
Egypt After holding a temporary position at the University of Leiden, d'Hérelle 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.
India D'Hérelle then used phages he collected from plague-infected rats during his 1920 visit to Indochina on human plague patients, with claimed success. The British Empire initiated a vast campaign against plague based on his results.
In 1926, the British government in India requested anti-plague phages for trials at the Haffkine Institute. The Institute had trouble maintaining the phages. D'Hérelle took unpaid leave from the Quarantine board of Egypt and went to Bombay at his own expense.
The Haffkine Institute had not used Martin's medium, which included macerated pig stomach and beef muscle that would offend Muslims and Hindus. The institute's medium used a hydrochloric acid digest of goat tissue. D'Hérelle solved the problem by digestion with papaya juice (a source of papain).
Thereafter Lt Col J. Morison, acting director of the Haffkine Institute, became convinced of the effectiveness of phages. Morison wrote to the Government of India to invite d'Hérelle noting that he was "a consummate technician, and a "most inspiring worker."
D'Hérelle returned to India to work on cholera. He collaborated with the assistant director of the Haffkine Institute, Major Reginald Malone and M.N. Lahiri, who conducted experiments at the Campbell Hospital in Calcutta. The Campbell Hospital team also worked with Russian bacteriologist Igor Nicholas Asheshov (1891–1961), who was working in Patna. Experiments were conducted both in hospitals and in the field.