Félix d'Herelle
Encyclopedia
Félix d'Herelle was a French-Canadian microbiologist
, the co-discoverer of bacteriophage
s (virus
es that infect bacteria) and experimented with the possibility of phage therapy
.
, Quebec
, the son of French
emigrants. His father, 30 years older than Felix's mother, died when Félix was 6 years old. Following his father's death, Félix, his mother and his younger brother Daniel, moved back to Paris
.
From 7 to 17 years of age, d'Herelle attended school in Paris, including the Lycée Condorcet
and Lycée Louis-le-Grand
high schools. In the fall of 1891, d'Herelle traveled to Bonn
where he attended lectures at the University of Bonn
"for several months." Thus, d'Herelle only obtained a high school education and was self-taught in the sciences. Between 16 and 24, d'Herelle traveled extensively via money given by his mother. When 16 years old, he started to travel through western Europe
by bike. When 17, after finishing school, he traveled through South America
. Afterwards, he continued his travels through Europe, including Turkey
, where he, at 20 years of age, met his wife, Marie Caire.
At age 24, now father of a daughter, d'Herelle and his family moved back 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 shrewdly 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'Herelle published his first scientific paper, "De la formation du Carbone par les vegetaux" in the May 1901 issue of Le Naturaliste Canadien
. The paper is noteworthy for two reasons: it shows an exceptional level of scientific development for a self-taught scientist and reveals a broad level of interest, namely the global balance of carbon
in nature. However, the claims of the paper were in error, as d'Herelle contended that the results of his experiments indicated that carbon was a compound
, not an element
.
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 banana
s. 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.
. 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.
, 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.
, 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:
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 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, 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.
. 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 claimed success. The British Empire
initiated 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; the death toll went down from 60% to 8%. The whole India enterprise took less than seven months.
, which he accepted. Meanwhile, European and US pharmaceutical 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. All of the companies suffered from production problems as results from commercial phage medicine were erratic. This was 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. Another possibility is that wrong diagnoses lead 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.
, Georgia
. 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, Lavrenty Beria 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. The Georgian period in d'Herelle's career has been investigated on site by the author and medical scientist David Shrayer-Petrov
.
, 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. It is believed that d'Herelle was nominated for the prize eight times.
However, France has not completely forgotten Félix d'Herelle. There is an avenue that bears his name in the 16th arrondissement
in Paris.
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
.
Yet d'Herelle himself had scant interest in the field of molecular biology, for he was a life-long Lamarckian, and he clung to his own theory of elementary living "micellae," which would seem hopelessly old-fashioned after proteins were shown to be giant molecules.
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.
Microbiology
Microbiology is the study of microorganisms, which are defined as any microscopic organism that comprises either a single cell , cell clusters or no cell at all . This includes eukaryotes, such as fungi and protists, and prokaryotes...
, the co-discoverer of bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
s (virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es that infect bacteria) and experimented with the possibility of phage therapy
Phage therapy
Phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. Although extensively used and developed mainly in former Soviet Union countries circa 1920, this method of therapy is still being tested for treatment of a variety of bacterial and poly-microbial...
.
Early years
D'Herelle was born in MontrealMontreal
Montreal is a city in Canada. It is the largest city in the province of Quebec, the second-largest city in Canada and the seventh largest in North America...
, Quebec
Quebec
Quebec or is a province in east-central Canada. It is the only Canadian province with a predominantly French-speaking population and the only one whose sole official language is French at the provincial level....
, the son of French
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
emigrants. His father, 30 years older than Felix's mother, died when Félix was 6 years old. Following his father's death, Félix, his mother and his younger brother Daniel, moved back to Paris
Paris
Paris is the capital and largest city in France, situated on the river Seine, in northern France, at the heart of the Île-de-France region...
.
From 7 to 17 years of age, d'Herelle attended school in Paris, including the Lycée Condorcet
Lycée Condorcet
The Lycée Condorcet is a school founded in 1803 in Paris, France, located at 8, rue du Havre, in the city's IXe arrondissement. Since its inception, various political eras have seen it given a number of different names, but its identity today honors the memory of the Marquis de Condorcet. The...
and Lycée Louis-le-Grand
Lycée Louis-le-Grand
The Lycée Louis-le-Grand is a public secondary school located in Paris, widely regarded as one of the most rigorous in France. Formerly known as the Collège de Clermont, it was named in king Louis XIV of France's honor after he visited the school and offered his patronage.It offers both a...
high schools. In the fall of 1891, d'Herelle traveled to Bonn
Bonn
Bonn is the 19th largest city in Germany. Located in the Cologne/Bonn Region, about 25 kilometres south of Cologne on the river Rhine in the State of North Rhine-Westphalia, it was the capital of West Germany from 1949 to 1990 and the official seat of government of united Germany from 1990 to 1999....
where he attended lectures at the University of Bonn
University of Bonn
The University of Bonn is a public research university located in Bonn, Germany. Founded in its present form in 1818, as the linear successor of earlier academic institutions, the University of Bonn is today one of the leading universities in Germany. The University of Bonn offers a large number...
"for several months." Thus, d'Herelle only obtained a high school education and was self-taught in the sciences. Between 16 and 24, d'Herelle traveled extensively via money given by his mother. When 16 years old, he started to travel through western Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
by bike. When 17, after finishing school, he traveled through South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...
. Afterwards, he continued his travels through Europe, including Turkey
Turkey
Turkey , known officially as the Republic of Turkey , is a Eurasian country located in Western Asia and in East Thrace in Southeastern Europe...
, where he, at 20 years of age, met his wife, Marie Caire.
At age 24, now father of a daughter, d'Herelle and his family moved back 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
Fermentation (food)
Fermentation in food processing typically is the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions. Fermentation in simple terms is the chemical conversion of sugars into ethanol...
and distillation
Distillation
Distillation is a method of separating mixtures based on differences in volatilities of components in a boiling liquid mixture. Distillation is a unit operation, or a physical separation process, and not a chemical reaction....
of maple syrup
Maple syrup
Maple syrup is a syrup usually made from the xylem sap of sugar maple, red maple, or black maple trees, although it can also be made from other maple species such as the bigleaf maple. In cold climates, these trees store starch in their trunks and roots before the winter; the starch is then...
to schnapps
Schnapps
Schnapps is a type of distilled alcoholic beverage. The English word schnapps is derived from the German Schnaps , which can refer to any strong alcoholic drink but particularly those containing at least 32% ABV...
. His father's friend shrewdly 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
Geology
Geology is the science comprising the study of solid Earth, the rocks of which it is composed, and the processes by which it evolves. Geology gives insight into the history of the Earth, as it provides the primary evidence for plate tectonics, the evolutionary history of life, and past climates...
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'Herelle published his first scientific paper, "De la formation du Carbone par les vegetaux" in the May 1901 issue of Le Naturaliste Canadien
Le Naturaliste Canadien
Le Naturaliste Canadien is a Canadian French-language peer-reviewed scientific journal published semiannually by the Société Léon-Provancher d'Histoire Naturelle du Canada. The journal publishes articles on all topics of natural sciences with a specific focus on ecology and conservation biology in...
. The paper is noteworthy for two reasons: it shows an exceptional level of scientific development for a self-taught scientist and reveals a broad level of interest, namely the global balance of carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
in nature. However, the claims of the paper were in error, as d'Herelle contended that the results of his experiments indicated that carbon was a compound
Compound
Compound may refer to:* Chemical compounds, combinations of two or more elements* Compound , a cluster of buildings having a shared purpose, usually inside a fence or wall...
, not an element
Element
- Chemistry, electronics, or the geosciences :* Chemical element, a building block in chemistry* Electrical element, an abstract part of a circuit* Heating element, a device that generates heat by electrical resistance...
.
Guatemala and Mexico
With his money almost gone and his second daughter born, he took a contract with the government of GuatemalaGuatemala
Guatemala is a country in Central America bordered by Mexico to the north and west, the Pacific Ocean to the southwest, Belize to the northeast, the Caribbean to the east, and Honduras and El Salvador to the southeast...
as a bacteriologist at the General Hospital in Guatemala City
Guatemala City
Guatemala City , is the capital and largest city of the Republic of Guatemala and Central America...
. Some of his work included organizing defenses against the dread diseases of the time: malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
and yellow fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
. 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 banana
Banana
Banana is the common name for herbaceous plants of the genus Musa and for the fruit they produce. Bananas come in a variety of sizes and colors when ripe, including yellow, purple, and red....
s. 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
Mexico
The United Mexican States , commonly known as Mexico , is a federal constitutional republic in North America. It is bordered on the north by the United States; on the south and west by the Pacific Ocean; on the southeast by Guatemala, Belize, and the Caribbean Sea; and on the east by the Gulf of...
government to continue his studies on fermentation. He and his family moved to a sisal
Sisal
Sisal is an agave that yields a stiff fibre traditionally used in making twine, rope and also dartboards. The term may refer either to the plant or the fibre, depending on context...
plantation near Mérida, Yucatán
Mérida, Yucatán
Mérida is the capital and largest city of the Mexican state of Yucatán and the Yucatán Peninsula. It is located in the northwest part of the state, about from the Gulf of Mexico coast...
. 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 InstitutePasteur Institute
The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax...
. 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
Locust
Locusts are the swarming phase of short-horned grasshoppers of the family Acrididae. These are species that can breed rapidly under suitable conditions and subsequently become gregarious and migratory...
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
Bacillus thuringiensis
Bacillus thuringiensis is a Gram-positive, soil-dwelling bacterium, commonly used as a biological pesticide; alternatively, the Cry toxin may be extracted and used as a pesticide. B...
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
Pasteur Institute
The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax...
. 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
Coccobacillus
A coccobacillus is a type of rod-shaped bacteria. The word coccobacillus reflects an intermediate shape between coccus and bacillus . Coccobacilli rods are so short and wide that they resemble cocci. Haemophilus influenzae and Chlamydia trachomatis are coccobacilli...
were published.
Argentina
At the end of the year, restless d'Herelle was again on the road, this time in ArgentinaArgentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
, 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 IWorld War I
World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...
, 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
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
vaccine, developed by Edward Jenner
Edward Jenner
Edward Anthony Jenner was an English scientist who studied his natural surroundings in Berkeley, Gloucestershire...
, was one of the few vaccines available. The primary antibiotic was the arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
-based salvarsan against syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
, with severe side effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
. Common treatments were based mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
, and cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
. As a result, in 1900, the average life span was 45 years, and WWI did not change that to the better.
In 1915, British
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
bacteriologist Frederick W. Twort
Frederick Twort
Frederick William Twort was an English bacteriologist and was the original discoverer in 1915 of bacteriophages . He studied medicine at St Thomas's Hospital, London, was superintendent of the Brown Institute for Animals , and he was also professor of bacteriology at the University of London...
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 porcelainPorcelainPorcelain is a ceramic material made by heating raw materials, generally including clay in the form of kaolin, in a kiln to temperatures between and...
filter, holding back bacteria and larger objects; only the smaller phages pass through.
In early 1919, d'Herelle isolated phages from chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
feces, successfully treating a plague of chicken typhus
Typhus
Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...
with them. After this successful experiment on chicken, he felt ready for the first trial on humans. The first patient was healed of dysentery
Dysentery
Dysentery is an inflammatory disorder of the intestine, especially of the colon, that results in severe diarrhea containing mucus and/or blood in the faeces with fever and abdominal pain. If left untreated, dysentery can be fatal.There are differences between dysentery and normal bloody diarrhoea...
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
Jules Bordet
Jules Jean Baptiste Vincent Bordet was a Belgian immunologist and microbiologist. The bacterial genus Bordetella is named after him.-Biography:Bordet was born at Soignies, Belgium...
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
Electron microscope
An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...
by Helmut Ruska
Helmut Ruska
Helmut Ruska was a German physician and biologist from Heidelberg. After earning his medical degree, he spent several years working as a physician at hospitals in Heidelberg and Berlin...
in 1939 that its true nature was established.
In 1920, d'Herelle travelled to Indochina
Indochina
The Indochinese peninsula, is a region in Southeast Asia. It lies roughly southwest of China, and east of India. The name has its origins in the French, Indochine, as a combination of the names of "China" and "India", and was adopted when French colonizers in Vietnam began expanding their territory...
, pursuing studies of cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
and the plague
Bubonic plague
Plague is a deadly infectious disease that is caused by the enterobacteria Yersinia pestis, named after the French-Swiss bacteriologist Alexandre Yersin. Primarily carried by rodents and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death...
, 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
Albert Calmette
Léon Charles Albert Calmette ForMemRS was a French physician, bacteriologist and immunologist, and an important officer of the Pasteur Institute. He discovered the Bacillus Calmette-Guérin, an attenuated form of Mycobacterium used in the BCG vaccine against tuberculosis...
. 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, 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
Leeuwenhoek Medal
The Leeuwenhoek Medal, established in 1877 by the Royal Netherlands Academy of Arts and Sciences, , in honor of the 17th- and 18th-century microscopist Antoni van Leeuwenhoek, is granted every ten years to the scientist judged to have made the most significant contribution to microbiology during...
, which is only awarded once every ten years. The latter was especially important to him, as his idol Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
received the same medal in 1895). The next year, he was nominated eight times for the Nobel prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
, though he was never awarded one.
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 AlexandriaAlexandria
Alexandria is the second-largest city of Egypt, with a population of 4.1 million, extending about along the coast of the Mediterranean Sea in the north central part of the country; it is also the largest city lying directly on the Mediterranean coast. It is Egypt's largest seaport, serving...
. The Conseil was put in place to prevent plague and cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
spreading to Europe, with special emphasis on the sanitary concerns about muslim
Muslim
A Muslim, also spelled Moslem, is an adherent of Islam, a monotheistic, Abrahamic religion based on the Quran, which Muslims consider the verbatim word of God as revealed to prophet Muhammad. "Muslim" is the Arabic term for "submitter" .Muslims believe that God is one and incomparable...
pilgrim groups returning from Mecca
Mecca
Mecca is a city in the Hijaz and the capital of Makkah province in Saudi Arabia. The city is located inland from Jeddah in a narrow valley at a height of above sea level...
and Medina
Medina
Medina , or ; also transliterated as Madinah, or madinat al-nabi "the city of the prophet") is a city in the Hejaz region of western Saudi Arabia, and serves as the capital of the Al Madinah Province. It is the second holiest city in Islam, and the burial place of the Islamic Prophet Muhammad, and...
. D'Herelle used phages he collected from plague-infected rats during his 1920 visit to Indochina on human plague patients, with claimed success. The British Empire
British Empire
The British Empire comprised the dominions, colonies, protectorates, mandates and other territories ruled or administered by the United Kingdom. It originated with the overseas colonies and trading posts established by England in the late 16th and early 17th centuries. At its height, it was the...
initiated a vast campaign against plague based on his results. 1927, d'Herelle himself changed his focus to new targets: India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
and cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
.
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
Slum
A slum, as defined by United Nations agency UN-HABITAT, is a run-down area of a city characterized by substandard housing and squalor and lacking in tenure security. According to the United Nations, the percentage of urban dwellers living in slums decreased from 47 percent to 37 percent in the...
. 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; the death toll went down from 60% to 8%. The whole India enterprise took less than seven months.
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 UniversityYale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
, which he accepted. Meanwhile, European and US pharmaceutical 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. All of the companies suffered from production problems as results from commercial phage medicine were erratic. This was 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. Another possibility is that wrong diagnoses lead 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.
USSR
But he was already on the move again. In or around 1934, he went to TbilisiTbilisi
Tbilisi is the capital and the largest city of Georgia, lying on the banks of the Mt'k'vari River. The name is derived from an early Georgian form T'pilisi and it was officially known as Tiflis until 1936...
, Georgia
Georgia (country)
Georgia is a sovereign state in the Caucasus region of Eurasia. Located at the crossroads of Western Asia and Eastern Europe, it is bounded to the west by the Black Sea, to the north by Russia, to the southwest by Turkey, to the south by Armenia, and to the southeast by Azerbaijan. The capital of...
. 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
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
. He accepted Stalin's invitation for two reasons: it was said he was enamored of communism
Communism
Communism is a social, political and economic ideology that aims at the establishment of a classless, moneyless, revolutionary and stateless socialist society structured upon common ownership of the means of production...
, 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, Lavrenty Beria 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
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
began. The Georgian period in d'Herelle's career has been investigated on site by the author and medical scientist David Shrayer-Petrov
David Shrayer-Petrov
David Shrayer-Petrov David Shrayer-Petrov David Shrayer-Petrov (Шраер-Петров, Давид, Russian-American novelist, poet, memoirist, translator, and medical scientist; best known for his novel about refuseniks, "Gerbert i Nelli" (Herbert and Nelly), his poetry and fiction about Russian-Jewish identity,...
.
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 VichyVichy
Vichy is a commune in the department of Allier in Auvergne in central France. It belongs to the historic province of Bourbonnais.It is known as a spa and resort town and was the de facto capital of Vichy France during the World War II Nazi German occupation from 1940 to 1944.The town's inhabitants...
, 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
D-Day
D-Day is a term often used in military parlance to denote the day on which a combat attack or operation is to be initiated. "D-Day" often represents a variable, designating the day upon which some significant event will occur or has occurred; see Military designation of days and hours for similar...
, the new antibiotic drug penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
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
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
bacteria. Phage therapy remained a common treatment in the states of the USSR
Soviet Union
The Soviet Union , officially the Union of Soviet Socialist Republics , was a constitutionally socialist state that existed in Eurasia between 1922 and 1991....
, though, until its deconstruction.
Félix d'Herelle was striken with pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
and died a forgotten man in Paris
Paris
Paris is the capital and largest city in France, situated on the river Seine, in northern France, at the heart of the Île-de-France region...
in 1949. He was buried in Saint-Mards-en-Othe in the department of the Aube
Aube
Aube is a department in the northeastern part of France named after the Aube River. In 1995, its population was 293,100 inhabitants.- History :Aube is one of the original 83 departments created during the French Revolution on 4 March 1790...
in France.
In the 1960s Félix d’Hérelle's name appeared on a list published by the Nobel Foundation
Nobel Foundation
The Nobel Foundation is a private institution founded on 29 June 1900 to manage the finances and administration of the Nobel Prizes. The Foundation is based on the last will of Alfred Nobel, the inventor of dynamite....
of scientists who had been worthy of receiving the Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
but did not, for one reason or another. It is believed that d'Herelle was nominated for the prize eight times.
However, France has not completely forgotten Félix d'Herelle. There is an avenue that bears his name in the 16th arrondissement
Arrondissement
Arrondissement is any of various administrative divisions of France, certain other Francophone countries, and the Netherlands.-France:The 101 French departments are divided into 342 arrondissements, which may be translated into English as districts. The capital of an arrondissement is called a...
in Paris.
Legacy
D'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
Max Delbrück
Max Ludwig Henning Delbrück was a German-American biophysicist and Nobel laureate.-Biography:Delbrück was born in Berlin, German Empire...
and the "phage group
Phage group
The phage group was an informal network of biologists centered around Max Delbrück that contributed heavily to bacterial genetics and the origins of molecular biology in the mid-20th century. The phage group takes its name from bacteriophages, the bacteria-infecting viruses that group used as...
" 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
François Jacob
François Jacob is a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through feedback on transcription. He shared the 1965 Nobel Prize in Medicine with Jacques Monod and André Lwoff.-Childhood and education:François Jacob is...
, Andre Lwoff and Jacques Monod
Jacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
. In fact, immediately before his studies of the structure of DNA, James Watson
James Watson
James Watson is the name of:*James Watson , British film and television actor*James Watson , United States Senator from New York...
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
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
.
Yet d'Herelle himself had scant interest in the field of molecular biology, for he was a life-long Lamarckian, and he clung to his own theory of elementary living "micellae," which would seem hopelessly old-fashioned after proteins were shown to be giant molecules.
Literary note
The novel Arrowsmith written by Sinclair LewisSinclair Lewis
Harry Sinclair Lewis was an American novelist, short-story writer, and playwright. In 1930, he became the first writer from the United States to be awarded the Nobel Prize in Literature, "for his vigorous and graphic art of description and his ability to create, with wit and humor, new types of...
with scientific help from Paul de Kruif
Paul de Kruif
Paul Henry de Kruif was an American microbiologist and author of Dutch descent. Publishing as Paul de Kruif, he is most noted for his 1926 book, Microbe Hunters...
was based to a certain extent on the life of d'Herelle. The novel The French Cottage (Russ. Frantsuzskii kottedzh) by David Shrayer-Petrov
David Shrayer-Petrov
David Shrayer-Petrov David Shrayer-Petrov David Shrayer-Petrov (Шраер-Петров, Давид, Russian-American novelist, poet, memoirist, translator, and medical scientist; best known for his novel about refuseniks, "Gerbert i Nelli" (Herbert and Nelly), his poetry and fiction about Russian-Jewish identity,...
deals at length with d'Herelle's experience in Soviet Georgia.
Published works
This is a list of his published books, not papers and minor publications.- 1946. L’étude d’une maladie: Le Choléra. French. F. Rouge & Cie S. A., Lausanne.
- 1938. Le Phénomène de la Guérison dans les Maladies Infectieuses. Masson et cie, Paris.
- Russian translation with G. Eliava. 1935. Bakteriofag i fenomen vyzdorovlenija Tiflis Gos. Univ. (Tbilisi National University, Tbilisi, Georgia).
- Georgian translation with G. Eliava. 1935. (cf Summers WC, 1999, page 165)
- 1933. Le Bactériophage et ses Applications Thérapeutiques. Doin, Paris.
- English translation. with G. H. Smith. 1930. The Bacteriophage and its Clinical Application. p. 165-243. Charles C. Thomas, Publisher, Springfield, Illinois.
- 1929. Études sur le Choléra. Impr. A. Serafini, Alexandrie.
- English translation, with R. H. Malone, and M. N. Lahiri. 1930. Studies on Asiatic Cholera. Thacker, Spink & Co., Calcutta.
- 1926. Le Bactériophage et son Comportement. Masson et Cie, Paris.
- English translation, with G. H. Smith. 1926. The Bacteriophage and Its Behavior. The Williams &Wilkins Co., Baltimore.
- with G. H. Smith. 1924. Immunity in Natural Infectious Disease. Williams & Wilkins Co., Baltimore.
- 1923. Les Défenses de l'Organisme. Flammarion, Paris.
- 1921. Le Bactériophage: Son Rôle dans l'Immunité. Masson et cie, Paris.
- German translation, 1922. Der Bakteriophage und seine Bedeutung für die Immunität. F. Vieweg & Sohn, Braunschweig.
- English translation, 1922 The Bacteriophage: Its Role in Immunity. Williams and Wilkins Co./Waverly Press, Baltimore.
Further reading
- William C. Summers, Felix d'Herelle and the Origins of Molecular Biology, New Haven: Yale University Press, 1999.
- Shrayer David P. Felix d’Hérelle in Russia. Bull Inst Pasteur. 1996;94:91–6.