Frederick Twort
Encyclopedia
Frederick William Twort was an English
bacteriologist and was the original discoverer in 1915 of bacteriophage
s (virus
es that infect bacteria
). He studied medicine at St Thomas's Hospital, London
, was superintendent of the Brown Institute for Animals (a pathology research centre), and he was also professor of bacteriology at the University of London
. He researched into Johne's disease
, a chronic intestinal infection of cattle, and also discovered that vitamin K
is needed by growing leprosy
bacteria.
, Surrey
on 22 October 1877. Little is known of his youth, except that he studied medicine at St Thomas's Hospital, London. After qualifing in medicine (Membership of the Royal College of Surgeons, Licentiate of the Royal College of Physicians
) in 1900, Twort took the first paid post available, assistant to Dr. Louis Jenner, Superintendent of the Clinical Laboratory of St Thomas' Hospital. There he trained in pathological techniques. In 1902 he became assistant to the Bacteriologist of the London Hospital, Dr. William Bulloch, later F.R.S., and carried out single-handed the whole diagnostic routine of the Hospital. In 1909, Twort became the superintendent of the Brown Institution, a pathology
research centre, and remained there for the duration of his career. In 1919 Twort married Dorothy Nony, daughter of Frederick J. Banister, and together they had three daughters and a son.
, bacteria were often differentiated testing their ability to grow on different media. Twort's first important paper found some shortcomings to this method. He found that the major subgroups identified by sugar
fermentation were not capable of clear-cut subdivision by tests on glucosides, nor even were they strictly separable by sugars. Twort wrote, "It seems, therefore, probable that the separate micro-organisms in the various subgroups are not to be regarded as distinct species, but as varieties or hybrids of one or more species. If this be so, one might expect them to be constantly varying, losing old characters and gaining new ones according to the conditions under which they are grown, and it was with the object of testing this hypothesis that further series of experiments were undertaken." Following prolonged incubation in media that they previously failed to ferment
, several species acquired fermentation powers which originally they did not enjoy. We now know that these mutant
individuals able to ferment novel sugars arose in culture
, and came to dominate the population
. Although ignored at the time (a trend that seemed to plague his career), this work was quite prescient, and anticipated, by decades, the subsequent work on adaptation
and mutation by bacterial chemists and microbiologists.
was still a major concern during the early part of the 20th century. However, work on leprosy was frustrated by the inability to culture the leprosy bacillus
in the laboratory. Twort suspected that the leprosy bacillus had a 'close relationship' with the tubercle
bacillus, a species that was culturable. Twort wrote, "It appeared highly probable that these two organisms would require the same chemical substances for building up their protoplasm
, which could be elaborated from the ordinary media only
by the tubercle bacillus." Twort therefore incorporated dead tubercle bacilli in the growth medium and succeeded in culturing leprosy. The essential substance supplied by the tubercle bacillus that was missing from the media turned out to be vitamin K
. What is important is his demonstration that an organism can grow only when supplied with a substance elaborated by another. This, of course, is the essential feature of all growth factor work and the basis of all studies of bacterial nutrition. However, this work, too, was ignored for several decades.
, a chronic intestinal infection of cattle. Similarly to leprosy, Johne's bacillus could not be cultivated on ordinary media. Incorporation of dead tubercle bacilli in the medium was successful. Johne's
bacillus had been cultivated for the first time. Contrary to previous efforts, Twort's work was recognized immediately.
virus to grow in vitro. At the time, smallpox
vaccines had to be made in the skin of calves and was almost always contaminated with the bacteria Staphylococcus
. Twort speculated that the contaminating bacteria might be the source of the "essential substance" needed by vaccinia to survive. He plated some of the smallpox vaccines on nutrient agar
slants and obtained large bacterial colonies of several colours. Upon closer examination of the colonies with a magnifying glass, he found minute glassy areas that would not grow when subcultured. He quickly realized that these glassy areas were the result of the destruction of the bacterial cells and was able to pick from some of these areas and transmit this from one staph colony to another.
Further experiments showed that the agent could pass through porcelain filters and that it required bacteria for growth. These observations show that Twort had discovered most of the essential features of bacteriophages, although Twort seemed to favor the idea that the principle was not a separate form of life, but an enzyme
which is secreted by the bacteria itself. Twort published these results in The Lancet
in 1915 and called the contagion the bacteriolytic agent. Unfortunately, his discovery was ignored; Felix d'Herelle discovered phage independently, and Twort's work may have been lost to time, but for Jules Bordet
and Andre Gratia's rediscovery of Twort's paper.
and
actually left for Salonika, where he was in charge of the base laboratory, a few weeks after his phage paper was published. Supposedly after that point, Twort was inundated with routine and could no longer pursue his research. To explain why he did not continue his work on bacteriophages, Twort responded, "it was sometime after the end of the war before I was really free again to continue the investigation, but at that time most of the additional details of the phenomenon had been published by other workers under the title of 'the bacteriophage'. So I passed on to other work." This excuse is rather puzzling since, in 1919, bacteriophage research was still in its infancy.
Twort and others wanted to use these bacteriolytic agents to cure bacterial diseases in humans and animals. When this proved to be unsuccessful, Twort went back to expanding his original idea that the bacteriolytic agents themselves needed an addition (essential) factor of a more exceptional nature to satisfy their fundamental needs. He searched for a substance that would allow viruses to grow apart from other forms of life (i.e. a host organism) and when this was unsuccessful, he tried to prove that bacteria evolved from viruses. His prime idea was to devise conditions for the cultivation of viruses from abiotic precursors or hypothetical pre-virus forms which might exist in nature. These experiments, while failures, presaged the famous Miller-Urey experiments of the 1950s. Although he was elected a Fellow of the Royal Society
in May 1929, Twort was never again to publish work of any serious import.
Financial support for his research dwindled, his stipend from the MRC ended in 1936, and his laboratory was destroyed by a bomb in 1944. The University of London took this opportunity to deprive Twort of his post and research facilities. He retired to live in at Camberly and by 1949 his work was largely forgotten, with the term Bacteriolytic Agent being replaced by Bacteriophage, until rediscovered by Jules Bordet
and Andre Gratia. Twort died on 30 March 1950.
England
England is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...
bacteriologist and was the original discoverer in 1915 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
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
). He studied medicine at St Thomas's Hospital, London
London
London is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
, was superintendent of the Brown Institute for Animals (a pathology research centre), and he was also professor of bacteriology at the University of London
University of London
-20th century:Shortly after 6 Burlington Gardens was vacated, the University went through a period of rapid expansion. Bedford College, Royal Holloway and the London School of Economics all joined in 1900, Regent's Park College, which had affiliated in 1841 became an official divinity school of the...
. He researched into Johne's disease
Johne's disease
Paratuberculosis or Johne's disease is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis...
, a chronic intestinal infection of cattle, and also discovered that vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
is needed by growing leprosy
Leprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
bacteria.
Early life and scientific training
The eldest of the eleven children of Dr. William Henry Twort, Frederick Twort was born in CamberleyCamberley
Camberley is a town in Surrey, England, situated 31 miles southwest of central London, in the corridor between the M3 and M4 motorways. The town lies close to the borders of both Hampshire and Berkshire; the boundaries intersect on the western edge of the town where all three counties...
, Surrey
Surrey
Surrey is a county in the South East of England and is one of the Home Counties. The county borders Greater London, Kent, East Sussex, West Sussex, Hampshire and Berkshire. The historic county town is Guildford. Surrey County Council sits at Kingston upon Thames, although this has been part of...
on 22 October 1877. Little is known of his youth, except that he studied medicine at St Thomas's Hospital, London. After qualifing in medicine (Membership of the Royal College of Surgeons, Licentiate of the Royal College of Physicians
Royal College of Physicians
The Royal College of Physicians of London was founded in 1518 as the College of Physicians by royal charter of King Henry VIII in 1518 - the first medical institution in England to receive a royal charter...
) in 1900, Twort took the first paid post available, assistant to Dr. Louis Jenner, Superintendent of the Clinical Laboratory of St Thomas' Hospital. There he trained in pathological techniques. In 1902 he became assistant to the Bacteriologist of the London Hospital, Dr. William Bulloch, later F.R.S., and carried out single-handed the whole diagnostic routine of the Hospital. In 1909, Twort became the superintendent of the Brown Institution, a pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
research centre, and remained there for the duration of his career. In 1919 Twort married Dorothy Nony, daughter of Frederick J. Banister, and together they had three daughters and a son.
Mutation
Early in the history of microbiologyMicrobiology
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...
, bacteria were often differentiated testing their ability to grow on different media. Twort's first important paper found some shortcomings to this method. He found that the major subgroups identified by sugar
Sugar
Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
fermentation were not capable of clear-cut subdivision by tests on glucosides, nor even were they strictly separable by sugars. Twort wrote, "It seems, therefore, probable that the separate micro-organisms in the various subgroups are not to be regarded as distinct species, but as varieties or hybrids of one or more species. If this be so, one might expect them to be constantly varying, losing old characters and gaining new ones according to the conditions under which they are grown, and it was with the object of testing this hypothesis that further series of experiments were undertaken." Following prolonged incubation in media that they previously failed to ferment
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...
, several species acquired fermentation powers which originally they did not enjoy. We now know that these mutant
Mutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
individuals able to ferment novel sugars arose in culture
Culture
Culture is a term that has many different inter-related meanings. For example, in 1952, Alfred Kroeber and Clyde Kluckhohn compiled a list of 164 definitions of "culture" in Culture: A Critical Review of Concepts and Definitions...
, and came to dominate the population
Population
A population is all the organisms that both belong to the same group or species and live in the same geographical area. The area that is used to define a sexual population is such that inter-breeding is possible between any pair within the area and more probable than cross-breeding with individuals...
. Although ignored at the time (a trend that seemed to plague his career), this work was quite prescient, and anticipated, by decades, the subsequent work on adaptation
Adaptation
An adaptation in biology is a trait with a current functional role in the life history of an organism that is maintained and evolved by means of natural selection. An adaptation refers to both the current state of being adapted and to the dynamic evolutionary process that leads to the adaptation....
and mutation by bacterial chemists and microbiologists.
Growth factors
LeprosyLeprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
was still a major concern during the early part of the 20th century. However, work on leprosy was frustrated by the inability to culture the leprosy bacillus
Bacillus
Bacillus is a genus of Gram-positive, rod-shaped bacteria and a member of the division Firmicutes. Bacillus species can be obligate aerobes or facultative anaerobes, and test positive for the enzyme catalase. Ubiquitous in nature, Bacillus includes both free-living and pathogenic species...
in the laboratory. Twort suspected that the leprosy bacillus had a 'close relationship' with the tubercle
Tubercle
A tubercle is generally a wart-like projection, but it has slightly different meaning depending on which family of plants or animals it is used to refer to....
bacillus, a species that was culturable. Twort wrote, "It appeared highly probable that these two organisms would require the same chemical substances for building up their protoplasm
Protoplasm
Protoplasm is the living contents of a cell that is surrounded by a plasma membrane. It is a general term of the Cytoplasm . Protoplasm is composed of a mixture of small molecules such as ions, amino acids, monosaccharides and water, and macromolecules such as nucleic acids, proteins, lipids and...
, which could be elaborated from the ordinary media only
by the tubercle bacillus." Twort therefore incorporated dead tubercle bacilli in the growth medium and succeeded in culturing leprosy. The essential substance supplied by the tubercle bacillus that was missing from the media turned out to be vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
. What is important is his demonstration that an organism can grow only when supplied with a substance elaborated by another. This, of course, is the essential feature of all growth factor work and the basis of all studies of bacterial nutrition. However, this work, too, was ignored for several decades.
Johne's disease
Twort also researched Johne's diseaseJohne's disease
Paratuberculosis or Johne's disease is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis...
, a chronic intestinal infection of cattle. Similarly to leprosy, Johne's bacillus could not be cultivated on ordinary media. Incorporation of dead tubercle bacilli in the medium was successful. Johne's
bacillus had been cultivated for the first time. Contrary to previous efforts, Twort's work was recognized immediately.
Twort-d'Herelle Phenomenon
Twort and his brother, Dr. C. C. Twort, had for some years been trying to grow viruses in artificial media hoping to find a nonpathogenic virus, which might be the wild type of a pathogenic and so more likely to grow. In 1914, Twort set out to identify the elusive (now known to be nonexistent) "essential substance" that would allow vacciniaVaccinia
Vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of...
virus to grow in vitro. At the time, 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"...
vaccines had to be made in the skin of calves and was almost always contaminated with the bacteria Staphylococcus
Staphylococcus
Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....
. Twort speculated that the contaminating bacteria might be the source of the "essential substance" needed by vaccinia to survive. He plated some of the smallpox vaccines on nutrient agar
Nutrient agar
Nutrient agar is a microbiological growth medium commonly used for the routine cultivation of non-fastidious bacteria. It is useful because it remains solid even at relatively high temperatures. Also, bacteria grown in nutrient agar grows on the surface, and is clearly visible as small colonies...
slants and obtained large bacterial colonies of several colours. Upon closer examination of the colonies with a magnifying glass, he found minute glassy areas that would not grow when subcultured. He quickly realized that these glassy areas were the result of the destruction of the bacterial cells and was able to pick from some of these areas and transmit this from one staph colony to another.
Further experiments showed that the agent could pass through porcelain filters and that it required bacteria for growth. These observations show that Twort had discovered most of the essential features of bacteriophages, although Twort seemed to favor the idea that the principle was not a separate form of life, but an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
which is secreted by the bacteria itself. Twort published these results in The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
in 1915 and called the contagion the bacteriolytic agent. Unfortunately, his discovery was ignored; Felix d'Herelle discovered phage independently, and Twort's work may have been lost to time, but for 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...
and Andre Gratia's rediscovery of Twort's paper.
World War I
In the middle of his work, war broke out and a grant from the Local Government Board came to an end. Further, he became interested in the Royal Army Medical CorpsRoyal Army Medical Corps
The Royal Army Medical Corps is a specialist corps in the British Army which provides medical services to all British Army personnel and their families in war and in peace...
and
actually left for Salonika, where he was in charge of the base laboratory, a few weeks after his phage paper was published. Supposedly after that point, Twort was inundated with routine and could no longer pursue his research. To explain why he did not continue his work on bacteriophages, Twort responded, "it was sometime after the end of the war before I was really free again to continue the investigation, but at that time most of the additional details of the phenomenon had been published by other workers under the title of 'the bacteriophage'. So I passed on to other work." This excuse is rather puzzling since, in 1919, bacteriophage research was still in its infancy.
Post-war work
Following the war, the recently formed Medical Research Committee (Council) supplemented his salary as a university professor by an annual grant of very considerable dimensions.Twort and others wanted to use these bacteriolytic agents to cure bacterial diseases in humans and animals. When this proved to be unsuccessful, Twort went back to expanding his original idea that the bacteriolytic agents themselves needed an addition (essential) factor of a more exceptional nature to satisfy their fundamental needs. He searched for a substance that would allow viruses to grow apart from other forms of life (i.e. a host organism) and when this was unsuccessful, he tried to prove that bacteria evolved from viruses. His prime idea was to devise conditions for the cultivation of viruses from abiotic precursors or hypothetical pre-virus forms which might exist in nature. These experiments, while failures, presaged the famous Miller-Urey experiments of the 1950s. Although he was elected a Fellow of the Royal Society
Royal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
in May 1929, Twort was never again to publish work of any serious import.
Financial support for his research dwindled, his stipend from the MRC ended in 1936, and his laboratory was destroyed by a bomb in 1944. The University of London took this opportunity to deprive Twort of his post and research facilities. He retired to live in at Camberly and by 1949 his work was largely forgotten, with the term Bacteriolytic Agent being replaced by Bacteriophage, until rediscovered by 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...
and Andre Gratia. Twort died on 30 March 1950.