Frederick Twort
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Frederick William Twort FRS (22 October 1877 – 20 March 1950) was an English
bacteriologist A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology— a subdivision of microbiology that studies bacteria, typically Pathogenic bacteria, pathogenic ones. Bacteriologists are interested in studying and learnin ...
and was the original discoverer in 1915 of
bacteriophage A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...
s (
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
es that infect
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
). He studied medicine at St Thomas's Hospital,
London London is the Capital city, capital and List of urban areas in the United Kingdom, largest city of both England and the United Kingdom, with a population of in . London metropolitan area, Its wider metropolitan area is the largest in Wester ...
, was superintendent of the Brown Institute for Animals (a pathology research centre), and was a professor of bacteriology at the
University of London The University of London (UoL; abbreviated as Lond or more rarely Londin in Post-nominal letters, post-nominals) is a collegiate university, federal Public university, public research university located in London, England, United Kingdom. The ...
. He researched into Johne's disease, a chronic intestinal infection of cattle, and also discovered that
vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...
is needed by growing
leprosy Leprosy, also known as Hansen's disease (HD), is a Chronic condition, long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the Peripheral nervous system, nerves, respir ...
bacteria.


Early life and scientific training

The eldest of the eleven children of Dr. William Henry Twort, Frederick Twort was born in
Camberley Camberley is a town in north-west Surrey, England, around south-west of central London. It is in the Surrey Heath, Borough of Surrey Heath and is close to the county boundaries with Hampshire and Berkshire. Known originally as "Cambridge Tow ...
,
Surrey Surrey () is a Ceremonial counties of England, ceremonial county in South East England. It is bordered by Greater London to the northeast, Kent to the east, East Sussex, East and West Sussex to the south, and Hampshire and Berkshire to the wes ...
on 22 October 1877. The three eldest sons went to Tomlinson's Modern School in Woking. From 1894 Frederick studied medicine at St Thomas's Hospital, London. After qualifying in medicine (Membership of the
Royal College of Surgeons The Royal College of Surgeons is an ancient college (a form of corporation) established in England to regulate the activity of surgeons. Derivative organisations survive in many present and former members of the Commonwealth. These organisations ...
, Licentiate of the
Royal College of Physicians The Royal College of Physicians of London, commonly referred to simply as the Royal College of Physicians (RCP), is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of ph ...
) 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 Animal Sanatory Institution, a
pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...
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.


Major work


Mutation

Early in the history of
microbiology Microbiology () is the branches of science, scientific study of microorganisms, those being of unicellular organism, unicellular (single-celled), multicellular organism, multicellular (consisting of complex cells), or non-cellular life, acellula ...
, bacteria were often differentiated by testing their ability to grow on different
media Media may refer to: Communication * Means of communication, tools and channels used to deliver information or data ** Advertising media, various media, content, buying and placement for advertising ** Interactive media, media that is inter ...
. Twort's first important paper found some shortcomings to this method. He found that the major subgroups identified by
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecul ...
fermentation were not capable of clear-cut subdivision by tests on
glucosides A glucoside is a glycoside that is chemically derived from glucose. Glucosides are common in plants, but rare in animals. Glucose is produced when a glucoside is Hydrolysis, hydrolysed by purely chemical means, or decomposed by fermentation (bio ...
, 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 is a type of anaerobic metabolism which harnesses the redox potential of the reactants to make adenosine triphosphate (ATP) and organic end products. Organic compound, Organic molecules, such as glucose or other sugars, are Catabo ...
, several species acquired fermentation powers which originally they did not enjoy. We now know that these
mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It i ...
individuals able to ferment novel sugars arose in
culture Culture ( ) is a concept that encompasses the social behavior, institutions, and Social norm, norms found in human societies, as well as the knowledge, beliefs, arts, laws, Social norm, customs, capabilities, Attitude (psychology), attitudes ...
, and came to dominate the
population Population is a set of humans or other organisms in a given region or area. Governments conduct a census to quantify the resident population size within a given jurisdiction. The term is also applied to non-human animals, microorganisms, and pl ...
. 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 In biology, adaptation has three related meanings. Firstly, it is the dynamic evolutionary process of natural selection that fits organisms to their environment, enhancing their evolutionary fitness. Secondly, it is a state reached by the p ...
and mutation by bacterial chemists and microbiologists.


Growth factors

Leprosy Leprosy, also known as Hansen's disease (HD), is a Chronic condition, long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the Peripheral nervous system, nerves, respir ...
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'', from Latin "bacillus", meaning "little staff, wand", is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-sh ...
in the laboratory. Twort suspected that the leprosy bacillus had a 'close relationship' with the
tubercle In anatomy, a tubercle (literally 'small tuber', Latin for 'lump') is any round nodule, small eminence, or warty outgrowth found on external or internal organs of a plant or an animal. In plants A tubercle is generally a wart-like projectio ...
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 (; ) is the part of a cell that is surrounded by a plasma membrane. It is a mixture of small molecules such as ions, monosaccharides, amino acids, and macromolecules such as proteins, polysaccharides, lipids, etc. In some definitions ...
, 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 medium turned out to be
vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...
. Twort's experiment is important as a demonstration of an organism growing only when supplied with a substance elaborated by another. This is the essential feature of all growth factor investigations 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 disease, 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 one, so more likely to grow. In 1914, Twort set out to identify the elusive (now known to be nonexistent) "essential substance" that would allow
vaccinia The vaccinia virus (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...
virus to grow ''in vitro''. At the time,
smallpox Smallpox was an infectious disease caused by Variola virus (often called Smallpox virus), which belongs to the genus '' Orthopoxvirus''. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (W ...
vaccines A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an ag ...
had to be made in the skin of calves and was almost always contaminated with the bacterial genus ''
Staphylococcus ''Staphylococcus'', from Ancient Greek σταφυλή (''staphulḗ''), meaning "bunch of grapes", and (''kókkos''), meaning "kernel" or " Kermes", is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillale ...
''. Twort speculated 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 is a general-purpose solid medium supporting growth of a wide range of non- fastidious organisms. It typically contains ( mass/volume): * 0.5% peptone – this provides organic nitrogen * 0.3% beef extract/yeast extract – the ...
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 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 staphylococci colony to another. Further experiments showed the agent could pass through porcelain filters and it required bacteria for growth. These observations show 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 An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
which is secreted by the bacteria. Twort published these results in ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...
'' in 1915 and called the contagion the bacteriolytic agent. Unfortunately, his discovery was ignored; Félix d'Herelle discovered phages independently, and Twort's work may have been lost to time, but for
Jules Bordet Jules Jean Baptiste Vincent Bordet ( , ; 13 June 1870 – 6 April 1961) was a Belgian immunologist and microbiologist. The bacterial genus ''Bordetella'' is named after him. The Nobel Prize in Physiology or Medicine was awarded to him in 1919 ...
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 Corps The Royal Army Medical Corps (RAMC) was a specialist corps in the British Army which provided medical services to all Army personnel and their families, in war and in peace. On 15 November 2024, the corps was amalgamated with the Royal Army De ...
and actually left for
Salonika Thessaloniki (; ), also known as Thessalonica (), Saloniki, Salonika, or Salonica (), is the second-largest city in Greece (with slightly over one million inhabitants in its Thessaloniki metropolitan area, metropolitan area) and the capital cit ...
, 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.


Postwar work

Following the war, the recently formed Medical Research Committee (Council) supplemented Twort's salary as a university professor by an annual grant but he never was given an assistant to help with the great number of experiments he had in mind. He struggled on under difficult and depressing conditions with singlemindedness and intense interest in his work. 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 In biology and ecology, abiotic components or abiotic factors are non-living chemical and physical parts of the environment that affect living organisms and the functioning of ecosystems. Abiotic factors and the phenomena associated with them und ...
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 The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
in May 1929, Twort was never again to publish work of any serious import. On 19 November 1931 London University's Senate conferred on him the title of Professor of Bacteriology on the following grounds: 1. His distinguished contributions by research to the advancement of his subject. 2. His powers of exposition. 3. His eminence in his subject. 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 was allowed to store the research equipment at his home in Camberley. In 1949, Penguin Books published his chapter on the Discovery of the Bacteriophage alongside a chapter on the Bacteriophage by Felix d'Herelle in the popular series Science News. Twort died on 30 March 1950.


References


Bibliography

*Includes material paraphrased from Molecular Cloning A Laboratory Manual, Third Edition, Sambrook and Russell, Volume I, p. 2.109. Information Panel: Bacteriophages: Historical Perspective. * {{DEFAULTSORT:Twort, Frederick 1877 births 1950 deaths People from Camberley British microbiologists English bacteriologists Fellows of the Royal Society Royal Army Medical Corps officers British Army personnel of World War I Military personnel from Surrey