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Félix d'Hérelle

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.[2] D'Hérelle has also been credited for his contributions to the larger concept of applied microbiology.[3]

Félix d'Hérelle
Born25 April 1873
Died22 February 1949(1949-02-22) (aged 75)
Paris, France
EducationLycée Condorcet, Lycée Louis-le-Grand, University of Bonn
Known forDiscovery of bacteriophage
SpouseMarie Caire
Parent
  • Hubert Augustin Félix Haerens d'Herelle (father)
AwardsHonorary doctorate, University of Leiden; Leeuwenhoek Medal (1925)
Scientific career
FieldsMicrobiology
InstitutionsGeneral Hospital, Guatemala City; University of Leiden; Pasteur Institute, Paris; Yale University; Tbilisi Institute

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.[4] He realised that he had discovered a new form of virus and later coined the term "bacteriophage".[5][6] Between 1918 and 1921 d'Herelle discovered different types of bacteriophages that could infect several other species of bacteria including Vibrio cholerae.[5] 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.[7]

Biography edit

Early years edit

Félix d'Hérelle's place of birth has been debated, but current research has concluded that he was born in France.[8] Félix d'Hérelle's father, Hubert Augustin Félix Haerens d'Herelle,[9] 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."[citation needed] 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.[10][11] During this period, d'Herelle 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.[12]

Guatemala and Mexico edit

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 edit

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.[3]

Argentina edit

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 edit

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:

  1. Nutritional medium is infected with bacteria; the medium turns opaque.
  2. The bacteria are infected with phages and die, producing new phages; the medium clears.
  3. 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.[13] 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,[14] 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.[15]

Egypt edit

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 edit

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'Herelle 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 Hospial 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.

D'Hérelle and co-workers added phages to wells near camps crowded with many pilgrims. Cases of cholera in the camps were subsequently much lower. The phages were distributed to village head men in Assam and Bengal along with instructions.

However, this was a period when Gandhi's Satyagraha was leading to non-cooperation by Indians. Many of the head men did not collaborate and fewer still reported back on the effectiveness. As a result, the experiment was disbanded in 1937.[16]

United States and commercial failures edit

D'Hérelle refused a request the following year by the British government to work in India, as he had been offered a professorship at Yale University, which he accepted. Meanwhile, European and US pharmaceutical companies had taken up the production of their own phage medicine, and were promising impossible benefits.

To counteract this trend, d'Herelle agreed to co-found a French phage-producing company, piping the money back into phage research. All of the companies suffered from production problems, as results from commercial phage medicine were erratic.

Production problems were most likely due to the attempt to mass-produce phages when they were barely understood. The phages may have been damaged and/or too low in concentration. Another possibility is that incorrect diagnoses led to the use of the irrelevant types of phages that were not adapted to the host bacteria of interest. Many studies on the proposed healing effects of phages were also poorly designed and conducted.

This situation led to many influential members of the scientific community turning against d'Hérelle. The problems may have been compounded by d'Hérelle's reputed bad temper, which was said to have made enemies of several other scientists.

Soviet Union edit

In about 1934, d'Hérelle went to Tbilisi, Georgia. He was welcomed to the Soviet Union as a hero, bringing knowledge of salvation from diseases ravaging the eastern states. He was even awarded with an honorary doctorate from Tbilisi State University in 1934.[17]

D'Hérelle may have accepted Stalin's invitation for two reasons. Firstly, he was said to be enamored with communism. Secondly, d'Hérelle was happy to be working with his friend, Professor George Eliava, founder of the Tbilisi Institute, in 1923.[18] Eliava had become friendly with d'Herelle during a visit to the Pasteur Institute in Paris in 1926, and had used that occasion to learn about phages.

D'Hérelle worked at the Tbilisi Institute off and on for about a year. He even dedicated one of his books to Comrade Stalin: "The Bacteriophage and the Phenomenon of Recovery," written and published in Tbilisi in 1935. Indeed, d'Hérelle may have planned to take up permanent residence in Tbilisi, as he had started to build a cottage on the grounds of the institute. The same building would later house the Georgian headquarters of the NKVD.[19]

Fortunes turned abruptly for d'Hérelle when Eliava fell in love with the same woman as Lavrenty Beria, head of the secret police. Eliava was executed and denounced as an enemy of the people during one of Stalin's purges. As a result, d'Hérelle fled Tbilisi, never to return. His book was banned from distribution.

The Georgian period in d'Hérelle's career has been investigated by author and medical scientist David Shrayer-Petrov.

Final return to France edit

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'Hérelle 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 being 800 pages in length.

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 Soviet Union, though, until its deconstruction.

Félix d'Hérelle was stricken 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.[20]

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. D'Herelle was nominated for the prize ten times.[21]

However, France has not completely forgotten Félix d'Hérelle. There is an avenue that bears his name in the 16th arrondissement in Paris.

Legacy edit

D'Hérelle became widely known for his imaginative approaches to important problems in theoretical, as well as applied, microbiology. At the same time, he was widely reviled for his self-advertisement, his exaggerated claims of success and his sharp financial practices. He also had a talent for making enemies among powerful senior scientists.

D'Hérelle's main legacy lies in the use of phage in the molecular revolution in biology. Max Delbrück and the "phage group" used bacteriophages to make the discoveries that led to the origins of molecular biology. Much of the initial work on the nature of genetic expression and its regulation was performed with bacteriophages by Francois Jacob, Andre Lwoff and Jacques Monod. In fact, immediately before his studies of the structure of DNA, James Watson had earned his Ph.D. by working on a bacteriophage-related project in Salvador Luria's laboratory. A more detailed account of the use of phage in major biological discoveries can be found on the page, bacteriophage.

As one of the earliest applied microbiologists, d'Hérelle's microbe-centered worldview has been noted for its prescience, since microbes are playing increasingly important roles in bioremediation, microbial fuel cells, gene therapy, and other areas with relevance to human well-being.[3]

Namesakes edit

The family Herelleviridae, a group of bacteriophages in order Caudovirales, was named in honor of Félix d'Hérelle.

Literary note edit

The novel Arrowsmith written by Sinclair Lewis with scientific help from Paul de Kruif was based to a certain extent on the life of d'Hérelle. The novel The French Cottage (Russ. Frantsuzskii kottedzh) by David Shrayer-Petrov deals at length with d'Hérelle's experience in Soviet Georgia.

Books edit

  • 1946. L'étude d'une maladie: Le Choléra. French. F. Rouge & Cie S. A., Lausanne. OCLC 11221115
  • 1938. Le Phénomène de la Guérison dans les Maladies Infectieuses. Masson et cie, Paris. OCLC 5784382
    • Russian translation with G. Eliava. 1935. Bakteriofag i fenomen vyzdorovlenija Tiflis Gos. Univ. (Tbilisi National University, Tbilisi, Georgia). OCLC 163085972
    • Georgian translation with G. Eliava. 1935. (cf Summers WC, 1999, page 165)
  • 1933. Le Bactériophage et ses Applications Thérapeutiques. Doin, Paris. OCLC 14749145
    • English translation. with G. H. Smith. 1930. The Bacteriophage and its Clinical Application. p. 165–243. Charles C. Thomas, Publisher, Springfield, Illinois. OCLC 347451
  • 1929. Études sur le Choléra. Impr. A. Serafini, Alexandrie. OCLC 15864352
    • English translation, with R. H. Malone, and M. N. Lahiri. 1930. Studies on Asiatic Cholera. Thacker, Spink & Co., Calcutta. OCLC 25936856
  • 1926. Le Bactériophage et son Comportement. Masson et Cie, Paris. OCLC 11981307
    • English translation, with G. H. Smith. 1926. The Bacteriophage and Its Behavior. The Williams &Wilkins Co., Baltimore. OCLC 2394374
  • with G. H. Smith. 1924. Immunity in Natural Infectious Disease. Williams & Wilkins Co., Baltimore. OCLC 586303
  • 1923. Les Défenses de l'Organisme. Flammarion, Paris. OCLC 11127665
  • 1921. Le bactériophage: Son rôle dans l'immunité. Masson et cie, Paris. OCLC 14794182, Internet Archive
    • German translation, 1922. Der Bakteriophage und seine Bedeutung für die Immunität. F. Vieweg & Sohn, Braunschweig. OCLC 36920828
    • English translation, 1922 The Bacteriophage: Its Role in Immunity. Williams and Wilkins Co./Waverly Press, Baltimore. OCLC 14789160

References edit

  1. ^ Dublanchet A (2017). Autobiographie de Félix d'Hérelle 1873-1949 (in French). Paris: Editions Médicales Internationales. ISBN 978-2-86728-015-3.
  2. ^ Keen EC (2012). "Phage Therapy: Concept to Cure". Frontiers in Microbiology. 3: 238. doi:10.3389/fmicb.2012.00238. PMC 3400130. PMID 22833738.
  3. ^ a b c Keen EC (December 2012). "Felix d'Herelle and our microbial future". Future Microbiology. 7 (12): 1337–9. doi:10.2217/fmb.12.115. PMID 23231482.
  4. ^ D'Herelle F (September 2007). "On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D'Herelle, presented by Mr. Roux☆". Research in Microbiology. 158 (7): 553–4. doi:10.1016/j.resmic.2007.07.005. PMID 17855060.
  5. ^ a b Ackermann H (2009). "History of Virology: Bacteriophages". Desk Encyclopedia of General Virology. Academic Press. p. 3. ISBN 9780123751621.
  6. ^ "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
  7. ^ Shors T (2008). Understanding Viruses. Sudbury, Mass: Jones & Bartlett Publishers. p. 591. ISBN 978-0-7637-2932-5.
  8. ^ Dublanchet A (2017). Autobiographie de Félix d'Hérelle 1873-1949 (in French). Paris: Editions Médicales Internationales. ISBN 978-2-86728-015-3.
  9. ^ Summers WC (10 June 1999). Félix d'Hérelle and the Origins of Molecular Biology. Yale University Press. p. 3. ISBN 978-0-300-17425-0.
  10. ^ Summers WC (2016). "Félix Hubert d'Herelle (1873-1949): History of a scientific mind". Bacteriophage. 6 (4): e1270090. doi:10.1080/21597081.2016.1270090. PMC 5221746. PMID 28090388.
  11. ^ Ireland 2023, p. 36.
  12. ^ Ireland 2023, p. 35.
  13. ^ Dublanchet A, Bourne S (January 2007). "The epic of phage therapy". The Canadian Journal of Infectious Diseases & Medical Microbiology. 18 (1): 15–8. doi:10.1155/2007/365761. PMC 2542892. PMID 18923688.
  14. ^ Jaarboek der Rijksuniversiteit te Leiden 1924 : Promotiën 17 September 1923 tot 12 Juli 1924, Faculteit der Geneeskunde, Doctoraal geneeskunde, p. 134
  15. ^ Ireland 2023, p. 64.
  16. ^ Summers WC (1993). "Cholera and Plague in India: The Bacteriophage Inquiry of 1927–1936" (PDF). Journal of the History of Medicine and Allied Sciences. 48 (3): 275–301. doi:10.1093/jhmas/48.3.275. PMID 8409365.
  17. ^ (PDF). Tbilisi State University. Archived from the original (PDF) on 28 October 2023. Retrieved 28 October 2023.
  18. ^ Parfitt T (2005). "Georgia: An unlikely stronghold for bacteriophage therapy". The Lancet. 365 (9478): 2166–2167. doi:10.1016/S0140-6736(05)66759-1. PMID 15986542. S2CID 28089251.
  19. ^ Kuchment A (2012). The forgotten cure. Springer. pp. 34. ISBN 978-1-4614-0250-3.
  20. ^ Ireland 2023, p. 91.
  21. ^ Nomination Archive. Nobelprize.org. Retrieved on 3 March 2019.

Bibliography edit

Further reading edit

This article incorporates material from the Citizendium article "Félix d'Hérelle", which is licensed under the Creative Commons Attribution-ShareAlike 3.0 Unported License but not under the GFDL.
  • Summers WC (1999). Félix d'Hérelle and the Origins of Molecular Biology. Yale University Press. ISBN 978-0-300-07127-6.
  • Häusler T (2006). Viruses vs. Superbugs. Palgrave Macmillan UK. ISBN 9781403987648. includes excerpts from his unpublished autobiography Macmillan.[citation needed]
  • D'herelle (2007). "On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D'Hérelle, presented by Mr. Roux. 1917". Research in Microbiology. 158 (7): 553–4. doi:10.1016/j.resmic.2007.07.005. PMID 17855060.
  • D'Hérelle (1917). "Sur un microbe invisible antagoniste des bacilles dysentériques". Comptes rendus hebdomadaires des séances de l'Académie des sciences. 165: 373–375.
  • Shrayer David P. (1996). "Felix d'Hérelle in Russia." Bull Inst Pasteur. 94:91–6.
  • Summers (1991). "On the origins of the science in Arrowsmith: Paul de Kruif, Felix d'Herelle, and phage". Journal of the History of Medicine and Allied Sciences. 46 (3): 315–32. doi:10.1093/jhmas/46.3.315. PMID 1918921.
  • Duckworth (1976). "Who discovered bacteriophage?". Bacteriological Reviews. 40 (4): 793–802. doi:10.1128/br.40.4.793-802.1976. PMC 413985. PMID 795414.
  • Peitzman (1969). "Felix d'Herelle and bacteriophage therapy". Transactions & Studies of the College of Physicians of Philadelphia. 37 (2): 115–23. PMID 4900376.
  • Lipska (1950). "In memory of Prof. D'Herelle". Medycyna Doswiadczalna I Mikrobiologia. 2 (2): 254–5. PMID 14815355.
  • William C. Summers, Félix d'Hérelle and the Origins of Molecular Biology, New Haven: Yale University Press, 1999.
  • Shrayer David P. Félix d'Hérelle in Russia. Bull Inst Pasteur. 1996;94:91–6.

félix, hérelle, april, 1873, february, 1949, french, microbiologist, discoverer, bacteriophages, viruses, that, infect, bacteria, experimented, with, possibility, phage, therapy, hérelle, also, been, credited, contributions, larger, concept, applied, microbiol. Felix d Herelle 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 2 D Herelle has also been credited for his contributions to the larger concept of applied microbiology 3 Felix d HerelleBorn25 April 1873Paris France 1 Died22 February 1949 1949 02 22 aged 75 Paris FranceEducationLycee Condorcet Lycee Louis le Grand University of BonnKnown forDiscovery of bacteriophageSpouseMarie CaireParentHubert Augustin Felix Haerens d Herelle father AwardsHonorary doctorate University of Leiden Leeuwenhoek Medal 1925 Scientific careerFieldsMicrobiologyInstitutionsGeneral Hospital Guatemala City University of Leiden Pasteur Institute Paris Yale University Tbilisi Instituted Herelle 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 4 He realised that he had discovered a new form of virus and later coined the term bacteriophage 5 6 Between 1918 and 1921 d Herelle discovered different types of bacteriophages that could infect several other species of bacteria including Vibrio cholerae 5 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 7 Contents 1 Biography 1 1 Early years 1 2 Guatemala and Mexico 1 3 Return to France 1 4 Argentina 1 5 France and phages 1 6 Egypt 1 7 India 1 8 United States and commercial failures 1 9 Soviet Union 1 10 Final return to France 2 Legacy 3 Namesakes 4 Literary note 5 Books 6 References 7 Bibliography 8 Further readingBiography editEarly years edit Felix d Herelle s place of birth has been debated but current research has concluded that he was born in France 8 Felix d Herelle s father Hubert Augustin Felix Haerens d Herelle 9 died at the age of 30 when Felix was six years old From 7 to 17 years of age d Herelle attended school in Paris including the Lycee Condorcet and Lycee Louis le Grand high schools In the fall of 1891 d Herelle traveled to Bonn Germany where he attended lectures at the University of Bonn for several months Between the ages of 16 and 24 d Herelle 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 Herelle 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 citation needed 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 10 11 During this period d Herelle published his first scientific paper De la formation du carbone par les vegetaux in the May 1901 issue of Le Naturaliste Canadien d Herelle contended in the paper that the results of his experiments indicated that carbon was a compound not an element 12 Guatemala and Mexico edit 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 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 Merida Yucatan Disease struck at him and his family but in 1909 he had successfully established a method to produce sisal schnapps Return to France edit 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 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 3 Argentina edit 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 France and phages edit 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 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 Herelle 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 Herelle isolated phages from chicken feces successfully treating a plague of chicken typhoid with them 13 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 was D Herelle 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 Herelle 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 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 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 Herelle received the honorary doctorate of the University of Leiden 14 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 15 Egypt edit 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 India edit D Herelle 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 Herelle 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 Herelle 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 Herelle noting that he was a consummate technician and a most inspiring worker D Herelle 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 Hospial 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 D Herelle and co workers added phages to wells near camps crowded with many pilgrims Cases of cholera in the camps were subsequently much lower The phages were distributed to village head men in Assam and Bengal along with instructions However this was a period when Gandhi s Satyagraha was leading to non cooperation by Indians Many of the head men did not collaborate and fewer still reported back on the effectiveness As a result the experiment was disbanded in 1937 16 United States and commercial failures edit D Herelle refused a request the following year by the British government to work in India as he had been offered a professorship at Yale University which he accepted Meanwhile European and US pharmaceutical companies had taken up the production of their own phage medicine and were promising impossible benefits To counteract this trend d Herelle agreed to co found a French phage producing company piping the money back into phage research All of the companies suffered from production problems as results from commercial phage medicine were erratic Production problems were most likely due to the attempt to mass produce phages when they were barely understood The phages may have been damaged and or too low in concentration Another possibility is that incorrect diagnoses led to the use of the irrelevant types of phages that were not adapted to the host bacteria of interest Many studies on the proposed healing effects of phages were also poorly designed and conducted This situation led to many influential members of the scientific community turning against d Herelle The problems may have been compounded by d Herelle s reputed bad temper which was said to have made enemies of several other scientists Soviet Union edit In about 1934 d Herelle went to Tbilisi Georgia He was welcomed to the Soviet Union as a hero bringing knowledge of salvation from diseases ravaging the eastern states He was even awarded with an honorary doctorate from Tbilisi State University in 1934 17 D Herelle may have accepted Stalin s invitation for two reasons Firstly he was said to be enamored with communism Secondly d Herelle was happy to be working with his friend Professor George Eliava founder of the Tbilisi Institute in 1923 18 Eliava had become friendly with d Herelle during a visit to the Pasteur Institute in Paris in 1926 and had used that occasion to learn about phages D Herelle worked at the Tbilisi Institute off and on for about a year He even dedicated one of his books to Comrade Stalin The Bacteriophage and the Phenomenon of Recovery written and published in Tbilisi in 1935 Indeed d Herelle may have planned to take up permanent residence in Tbilisi as he had started to build a cottage on the grounds of the institute The same building would later house the Georgian headquarters of the NKVD 19 Fortunes turned abruptly for d Herelle when Eliava fell in love with the same woman as Lavrenty Beria head of the secret police Eliava was executed and denounced as an enemy of the people during one of Stalin s purges As a result d Herelle fled Tbilisi never to return His book was banned from distribution The Georgian period in d Herelle s career has been investigated by author and medical scientist David Shrayer Petrov Final return to France edit 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 being 800 pages in length 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 Soviet Union though until its deconstruction Felix d Herelle was stricken 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 20 In the 1960s Felix d Herelle 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 D Herelle was nominated for the prize ten times 21 However France has not completely forgotten Felix d Herelle There is an avenue that bears his name in the 16th arrondissement in Paris Legacy editD Herelle became widely known for his imaginative approaches to important problems in theoretical as well as applied microbiology At the same time he was widely reviled for his self advertisement his exaggerated claims of success and his sharp financial practices He also had a talent for making enemies among powerful senior scientists D Herelle s main legacy lies in the use of phage in the molecular revolution in biology Max Delbruck and the phage group used bacteriophages to make the discoveries that led to the origins of molecular biology Much of the initial work on the nature of genetic expression and its regulation was performed with bacteriophages by Francois Jacob Andre Lwoff and Jacques Monod In fact immediately before his studies of the structure of DNA James Watson had earned his Ph D by working on a bacteriophage related project in Salvador Luria s laboratory A more detailed account of the use of phage in major biological discoveries can be found on the page bacteriophage As one of the earliest applied microbiologists d Herelle s microbe centered worldview has been noted for its prescience since microbes are playing increasingly important roles in bioremediation microbial fuel cells gene therapy and other areas with relevance to human well being 3 Namesakes editThe family Herelleviridae a group of bacteriophages in order Caudovirales was named in honor of Felix d Herelle Literary note editThe novel Arrowsmith written by Sinclair Lewis with scientific help from Paul de Kruif was based to a certain extent on the life of d Herelle The novel The French Cottage Russ Frantsuzskii kottedzh by David Shrayer Petrov deals at length with d Herelle s experience in Soviet Georgia Books edit1946 L etude d une maladie Le Cholera French F Rouge amp Cie S A Lausanne OCLC 11221115 1938 Le Phenomene de la Guerison dans les Maladies Infectieuses Masson et cie Paris OCLC 5784382 Russian translation with G Eliava 1935 Bakteriofag i fenomen vyzdorovlenija Tiflis Gos Univ Tbilisi National University Tbilisi Georgia OCLC 163085972 Georgian translation with G Eliava 1935 cf Summers WC 1999 page 165 1933 Le Bacteriophage et ses Applications Therapeutiques Doin Paris OCLC 14749145 English translation with G H Smith 1930 The Bacteriophage and its Clinical Application p 165 243 Charles C Thomas Publisher Springfield Illinois OCLC 347451 1929 Etudes sur le Cholera Impr A Serafini Alexandrie OCLC 15864352 English translation with R H Malone and M N Lahiri 1930 Studies on Asiatic Cholera Thacker Spink amp Co Calcutta OCLC 25936856 1926 Le Bacteriophage et son Comportement Masson et Cie Paris OCLC 11981307 English translation with G H Smith 1926 The Bacteriophage and Its Behavior The Williams amp Wilkins Co Baltimore OCLC 2394374 with G H Smith 1924 Immunity in Natural Infectious Disease Williams amp Wilkins Co Baltimore OCLC 586303 1923 Les Defenses de l Organisme Flammarion Paris OCLC 11127665 1921 Le bacteriophage Son role dans l immunite Masson et cie Paris OCLC 14794182 Internet Archive German translation 1922 Der Bakteriophage und seine Bedeutung fur die Immunitat F Vieweg amp Sohn Braunschweig OCLC 36920828 English translation 1922 The Bacteriophage Its Role in Immunity Williams and Wilkins Co Waverly Press Baltimore OCLC 14789160References edit Dublanchet A 2017 Autobiographie de Felix d Herelle 1873 1949 in French Paris Editions Medicales Internationales ISBN 978 2 86728 015 3 Keen EC 2012 Phage Therapy Concept to Cure Frontiers in Microbiology 3 238 doi 10 3389 fmicb 2012 00238 PMC 3400130 PMID 22833738 a b c Keen EC December 2012 Felix d Herelle and our microbial future Future Microbiology 7 12 1337 9 doi 10 2217 fmb 12 115 PMID 23231482 D Herelle F September 2007 On an invisible microbe antagonistic toward dysenteric bacilli brief note by Mr F D Herelle presented by Mr Roux Research in Microbiology 158 7 553 4 doi 10 1016 j resmic 2007 07 005 PMID 17855060 a b Ackermann H 2009 History of Virology Bacteriophages Desk Encyclopedia of General Virology Academic Press p 3 ISBN 9780123751621 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 Shors T 2008 Understanding Viruses Sudbury Mass Jones amp Bartlett Publishers p 591 ISBN 978 0 7637 2932 5 Dublanchet A 2017 Autobiographie de Felix d Herelle 1873 1949 in French Paris Editions Medicales Internationales ISBN 978 2 86728 015 3 Summers WC 10 June 1999 Felix d Herelle and the Origins of Molecular Biology Yale University Press p 3 ISBN 978 0 300 17425 0 Summers WC 2016 Felix Hubert d Herelle 1873 1949 History of a scientific mind Bacteriophage 6 4 e1270090 doi 10 1080 21597081 2016 1270090 PMC 5221746 PMID 28090388 Ireland 2023 p 36 Ireland 2023 p 35 Dublanchet A Bourne S January 2007 The epic of phage therapy The Canadian Journal of Infectious Diseases amp Medical Microbiology 18 1 15 8 doi 10 1155 2007 365761 PMC 2542892 PMID 18923688 Jaarboek der Rijksuniversiteit te Leiden 1924 Promotien 17 September 1923 tot 12 Juli 1924 Faculteit der Geneeskunde Doctoraal geneeskunde p 134 Ireland 2023 p 64 Summers WC 1993 Cholera and Plague in India The Bacteriophage Inquiry of 1927 1936 PDF Journal of the History of Medicine and Allied Sciences 48 3 275 301 doi 10 1093 jhmas 48 3 275 PMID 8409365 Honorary Doctorates awarded by Ivane Javakhishvili Tbilisi State University since 1918 PDF Tbilisi State University Archived from the original PDF on 28 October 2023 Retrieved 28 October 2023 Parfitt T 2005 Georgia An unlikely stronghold for bacteriophage therapy The Lancet 365 9478 2166 2167 doi 10 1016 S0140 6736 05 66759 1 PMID 15986542 S2CID 28089251 Kuchment A 2012 The forgotten cure Springer pp 34 ISBN 978 1 4614 0250 3 Ireland 2023 p 91 Nomination Archive Nobelprize org Retrieved on 3 March 2019 Bibliography editIreland T 29 June 2023 The Good Virus Hodder amp Stoughton ISBN 978 1 5293 6524 5 Further reading editThis article incorporates material from the Citizendium article Felix d Herelle which is licensed under the Creative Commons Attribution ShareAlike 3 0 Unported License but not under the GFDL Summers WC 1999 Felix d Herelle and the Origins of Molecular Biology Yale University Press ISBN 978 0 300 07127 6 Hausler T 2006 Viruses vs Superbugs Palgrave Macmillan UK ISBN 9781403987648 includes excerpts from his unpublished autobiography Macmillan citation needed D herelle 2007 On an invisible microbe antagonistic toward dysenteric bacilli brief note by Mr F D Herelle presented by Mr Roux 1917 Research in Microbiology 158 7 553 4 doi 10 1016 j resmic 2007 07 005 PMID 17855060 D Herelle 1917 Sur un microbe invisible antagoniste des bacilles dysenteriques Comptes rendus hebdomadaires des seances de l Academie des sciences 165 373 375 Shrayer David P 1996 Felix d Herelle in Russia Bull Inst Pasteur 94 91 6 Summers 1991 On the origins of the science in Arrowsmith Paul de Kruif Felix d Herelle and phage Journal of the History of Medicine and Allied Sciences 46 3 315 32 doi 10 1093 jhmas 46 3 315 PMID 1918921 Duckworth 1976 Who discovered bacteriophage Bacteriological Reviews 40 4 793 802 doi 10 1128 br 40 4 793 802 1976 PMC 413985 PMID 795414 Peitzman 1969 Felix d Herelle and bacteriophage therapy Transactions amp Studies of the College of Physicians of Philadelphia 37 2 115 23 PMID 4900376 Lipska 1950 In memory of Prof D Herelle Medycyna Doswiadczalna I Mikrobiologia 2 2 254 5 PMID 14815355 William C Summers Felix d Herelle and the Origins of Molecular Biology New Haven Yale University Press 1999 Shrayer David P Felix d Herelle in Russia Bull Inst Pasteur 1996 94 91 6 Retrieved from https en wikipedia org w index php title Felix d 27Herelle amp oldid 1207651923, wikipedia, wiki, book, books, library,

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