Discovery
Bacteriophages are the viruses that infect and replicate in bacteria. They were discovered in the early 20th century, by the English bacteriologist
Frederick Twort
Frederick William Twort FRS (22 October 1877 – 20 March 1950) was an English bacteriologist and was the original discoverer in 1915 of bacteriophages (viruses that infect bacteria). He studied medicine at St Thomas's Hospital, London, was super ...
(1877–1950).
But before this time, in 1896, the bacteriologist
Ernest Hanbury Hankin (1865–1939) reported that something in the waters of the
River Ganges
The Ganges ( ) (in India: Ganga ( ); in Bangladesh: Padma ( )). "The Ganges Basin, known in India as the Ganga and in Bangladesh as the Padma, is an international river to which India, Bangladesh, Nepal and China are the riparian states." is ...
could kill ''
Vibrio cholerae
''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...
'' – the cause of
cholera. The agent in the water could be passed through filters that remove bacteria but was destroyed by boiling.
Twort discovered the action of bacteriophages on
staphylococci
''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultati ...
bacteria. He noticed that when grown on nutrient agar some colonies of the bacteria became watery. He collected some of these watery colonies and passed them through a Chamberland filter to remove the bacteria and discovered that when the filtrate was added to fresh cultures of bacteria, they in turn became watery.
He proposed that the agent might be "an amoeba, an ultramicroscopic virus, a living protoplasm, or an enzyme with the power of growth".
Félix d'Herelle
Felix may refer to:
* Felix (name), people and fictional characters with the name
Places
* Arabia Felix is the ancient Latin name of Yemen
* Felix, Spain, a municipality of the province Almería, in the autonomous community of Andalusia, ...
(1873–1949) was a mainly self-taught French-Canadian microbiologist. In 1917 he discovered that "an invisible antagonist", when added to bacteria on
agar, would produce areas of dead bacteria.
The antagonist, now known to be a bacteriophage, could pass through a Chamberland filter. He accurately diluted a suspension of these viruses and discovered that the highest dilutions (lowest virus concentrations), rather than killing all the bacteria, formed discrete areas of dead organisms. Counting these areas and multiplying by the dilution factor allowed him to calculate the number of viruses in the original suspension.
He realised that he had discovered a new form of virus and later coined the term "bacteriophage".
Between 1918 and 1921 d'Herelle discovered different types of bacteriophages that could infect several other species of bacteria including ''Vibrio cholerae''. Bacteriophages were heralded as a potential treatment for diseases such as
typhoid
Typhoid fever, also known as typhoid, is a disease caused by ''Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several d ...
and
cholera, but their promise was forgotten with the development of
penicillin.
Since the early 1970s, bacteria have continued to develop resistance to
antibiotics such as
penicillin, and this has led to a renewed interest in the use of
bacteriophages to treat serious infections.
1920-1940: Early research
D'Herelle travelled widely to promote the use of bacteriophages in the treatment of bacterial infections. In 1928, he became professor of biology at
Yale
Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wor ...
and founded several research institutes.
He was convinced that bacteriophages were viruses despite opposition from established bacteriologists such as the Nobel Prize winner
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 for ...
(1870–1961). Bordet argued that bacteriophages were not viruses but just
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s released from
"lysogenic" bacteria. He said "the invisible world of d'Herelle does not exist". But in the 1930s, the proof that bacteriophages were viruses was provided by
Christopher Andrewes
Sir Christopher Howard Andrewes (7 June 1896 – 31 December 1988) was a British virologist who discovered the human influenza A virus in 1933.
Education
Andrewes was educated at Highgate School and later studied medicine at St Bartholome ...
(1896–1988) and others. They showed that these viruses differed in size and in their chemical and
serological
Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
properties.
In 1940, the first
electron micrograph
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a mi ...
of a bacteriophage was published and this silenced sceptics who had argued that bacteriophages were relatively simple enzymes and not viruses.
Numerous other types of bacteriophages were quickly discovered and were shown to infect bacteria wherever they are found. Early research was interrupted by
World War II
World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...
. d'Herelle, despite his Canadian citizenship, was interned by the
Vichy Government
Vichy France (french: Régime de Vichy; 10 July 1940 – 9 August 1944), officially the French State ('), was the fascist French state headed by Marshal Philippe Pétain during World War II. Officially independent, but with half of its terr ...
until the end of the war.
Modern era
Knowledge of bacteriophages increased in the 1940s following the formation of the
Phage Group by scientists throughout the US. Among the members were
Max Delbrück
Max Ludwig Henning Delbrück (; September 4, 1906 – March 9, 1981) was a German–American biophysicist who participated in launching the molecular biology research program in the late 1930s. He stimulated physical scientists' interest int ...
(1906–1981) who founded a course on bacteriophages at
Cold Spring Harbor Laboratory
Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, plant biology, genomics, and quantitative biology.
It is one of 68 institutions supported by the Cancer Centers ...
.
Other key members of the Phage Group included
Salvador Luria
Salvador Edward Luria (August 13, 1912 – February 6, 1991) was an Italian microbiologist, later a Naturalized citizen of the United States#Naturalization, naturalized U.S. citizen. He won the Nobel Prize in Physiology or Medicine in 1969, with ...
(1912–1991) and
Alfred Hershey (1908–1997). During the 1950s,
Hershey and Chase made important discoveries on the replication of DNA during their studies on a bacteriophage called
T2. Together with Delbruck they were jointly awarded the 1969 Nobel Prize in Physiology or Medicine "for their discoveries concerning the replication mechanism and the genetic structure of viruses". Since then, the study of bacteriophages has provided insights into the switching on and off of genes, and a useful mechanism for introducing foreign genes into bacteria and many other fundamental mechanisms of
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
.
Plant viruses
In 1882,
Adolf Mayer (1843–1942) described a condition of tobacco plants, which he called "mosaic disease" ("mozaïkziekte"). The diseased plants had
variegated
Variegation is the appearance of differently coloured zones in the leaves and sometimes the stems and fruit of plants. Species with variegated individuals are sometimes found in the understory of tropical rainforests, and this habitat is the s ...
leaves that were
mottle
Mottle is a pattern of irregular marks, spots, streaks, blotches or patches of different shades or colours. It is commonly used to describe the surface of plants or the skin of animals. In plants, mottling usually consists of yellowish spots o ...
d. He excluded the possibility of a fungal infection and could not detect any bacterium and speculated that a "soluble, enzyme-like infectious principle was involved".
[Quoted in: ] He did not pursue his idea any further, and it was the filtration experiments of Ivanovsky and Beijerinck that suggested the cause was a previously unrecognised infectious agent. After tobacco mosaic was recognized as a virus disease, virus infections of many other plants were discovered.
The importance of tobacco mosaic virus in the history of viruses cannot be overstated. It was the first virus to be discovered, and the first to be
crystal
A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macro ...
lised and its structure shown in detail. The first
X-ray diffraction pictures of the crystallised virus were obtained by
Bernal and
Fankuchen in 1941. On the basis of her pictures,
Rosalind Franklin discovered the full structure of the virus in 1955.
In the same year,
Heinz Fraenkel-Conrat
Heinz Ludwig Fraenkel-Conrat (July 29, 1910 – April 10, 1999) was a biochemist, famous for his research on viruses.
Early life
Fraenkel-Conrat was born in Breslau/Germany.
He was the son of Lili Conrat and Professor Ludwig Fraenkel, direc ...
and
Robley Williams
Robley Cook Williams (October 13, 1908 – January 3, 1995) was an early biophysicist and virologist. He served as the first president of the Biophysical Society.
Career
Williams attended Cornell University on an athletic scholarship, complet ...
showed that purified tobacco mosaic virus RNA and its
coat protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism was probably the means through which viruses were created within their host cells.
By 1935, many plant diseases were thought to be caused by viruses. In 1922,
John Kunkel Small
John Kunkel Small (January 31, 1869 – January 20, 1938) was an American botanist.
Born on January 31, 1869, in Harrisburg Pennsylvania, Kunkel studied botany at Franklin & Marshall College and Columbia University. He was the first Curator of ...
(1869–1938) discovered that insects could act as
vectors and transmit virus to plants. In the following decade many diseases of plants were shown to be caused by viruses that were carried by insects and in 1939,
Francis Holmes, a pioneer in plant virology,
described 129 viruses that caused disease of plants.
Modern, intensive agriculture provides a rich environment for many plant viruses. In 1948, in Kansas, US, 7% of the wheat crop was destroyed by
wheat streak mosaic virus. The virus was spread by mites called ''
Aceria tulipae''.
In 1970, the Russian plant virologist
Joseph Atabekov discovered that many plant viruses only infect a single species of host plant.
The
International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to ap ...
now recognises over 900 plant viruses.
20th century
By the end of the 19th century, viruses were defined in terms of their
infectivity
In epidemiology, infectivity is the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission — that is, how frequently it spreads among hosts that are not in a parent ...
, their ability to be filtered, and their requirement for living hosts. Up until this time, viruses had only been grown in plants and animals, but in 1906,
Ross Granville Harrison
Ross Granville Harrison (January 13, 1870 – September 30, 1959) was an American biologist and anatomist credited for his pioneering work on animal tissue culture. His work also contributed to the understanding of embryonic development. Harrison ...
(1870–1959) invented a method for growing
tissue in
lymph
Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues ...
, and, in 1913, E Steinhardt, C Israeli, and RA Lambert used this method to grow
vaccinia
''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 in fragments of guinea pig corneal tissue. In 1928, HB and MC Maitland grew vaccinia virus in suspensions of minced hens' kidneys.
Their method was not widely adopted until the 1950s, when
poliovirus
A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species '' Enterovirus C'', in the family of ''Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3.
Poliovirus is composed of a ...
was grown on a large scale for vaccine production.
In 1941–42,
George Hirst
George Herbert Hirst (7 September 1871 – 10 May 1954) was a professional English cricketer who played first-class cricket for Yorkshire County Cricket Club between 1891 and 1921, with a further appearance in 1929. One of the best all-r ...
(1909–94) developed assays based on
haemagglutination to quantify a wide range of viruses as well as virus-specific antibodies in serum.
Influenza
Although the
influenza virus
''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ' ...
that caused the
1918–1919 influenza pandemic was not discovered until the 1930s, the descriptions of the disease and subsequent research has proved it was to blame.
The pandemic killed 40–50 million people in less than a year, but the proof that it was caused by a virus was not obtained until 1933.
''
Haemophilus influenzae
''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacter ...
'' is an opportunistic bacterium which commonly follows influenza infections; this led the eminent German bacteriologist
Richard Pfeiffer (1858–1945) to incorrectly conclude that this bacterium was the cause of influenza. A major breakthrough came in 1931, when the American pathologist
Ernest William Goodpasture
Ernest William Goodpasture (October 17, 1886 – September 20, 1960) was an American pathologist and physician. Goodpasture advanced the scientific understanding of the pathogenesis of infectious diseases, parasitism, and a variety of ricketts ...
grew influenza and several other viruses in fertilised chickens' eggs. Hirst identified an enzymic activity associated with the virus particle, later characterised as the
neuraminidase
Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
: Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glyc ...
, the first demonstration that viruses could contain enzymes.
Frank Macfarlane Burnet
Sir Frank Macfarlane Burnet, (3 September 1899 – 31 August 1985), usually known as Macfarlane or Mac Burnet, was an Australian virologist known for his contributions to immunology. He won a Nobel Prize in 1960 for predicting acquired immune ...
showed in the early 1950s that the virus recombines at high frequencies, and Hirst later deduced that it has a segmented genome.
Poliomyelitis
In 1949,
John F. Enders (1897–1985)
Thomas Weller (1915–2008), and
Frederick Robbins
Frederick Chapman Robbins (August 25, 1916 – August 4, 2003) was an American pediatrician and virologist. He was born in Auburn, Alabama, and grew up in Columbia, Missouri, attending David H. Hickman High School.
He received the Nobel Prize in P ...
(1916–2003) grew polio virus for the first time in cultured human embryo cells, the first virus to be grown without using solid animal tissue or eggs. Infections by poliovirus most often cause the mildest of symptoms. This was not known until the virus was isolated in cultured cells and many people were shown to have had mild infections that did not lead to poliomyelitis. But, unlike other viral infections, the incidence of polio – the rarer severe form of the infection – increased in the 20th century and reached a peak around 1952. The invention of a
cell culture system for growing the virus enabled
Jonas Salk
Jonas Edward Salk (; born Jonas Salk; October 28, 1914June 23, 1995) was an American virologist and medical researcher who developed one of the first successful polio vaccines. He was born in New York City and attended the City College of New ...
(1914–1995) to make an effective
polio vaccine
Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chi ...
.
Epstein–Barr virus
Denis Parsons Burkitt (1911–1993) was born in Enniskillen, County Fermanagh, Ireland. He was the first to describe a type of cancer that now bears his name
Burkitt's lymphoma. This type of cancer was endemic in equatorial Africa and was the commonest malignancy of children in the early 1960s.
In an attempt to find a cause for the cancer, Burkitt sent cells from the tumour to
Anthony Epstein
Sir Michael Anthony Epstein (born 18 May 1921) is a British pathologist and academic. He is one of the discoverers of the Epstein–Barr virus, along with Yvonne Barr and Bert Achong.
Personal life
Epstein was born on 18 May 1921, and educ ...
(b. 1921) a British virologist, who along with
Yvonne Barr and
Bert Achong (1928–1996), and after many failures, discovered viruses that resembled herpes virus in the fluid that surrounded the cells. The virus was later shown to be a previously unrecognised herpes virus, which is now called
Epstein–Barr virus
The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus.
It is b ...
. Surprisingly, Epstein–Barr virus is a very common but relatively mild infection of Europeans. Why it can cause such a devastating illness in Africans is not fully understood, but reduced immunity to virus caused by
malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
might be to blame.
Epstein–Barr virus is important in the history of viruses for being the first virus shown to cause cancer in humans.
Late 20th and early 21st century
The second half of the 20th century was the golden age of virus discovery and most of the 2,000 recognised species of animal, plant, and bacterial viruses were discovered during these years.
In 1946,
bovine virus diarrhea
Bovine viral diarrhea (BVD), bovine viral diarrhoea (UK English) or mucosal disease, and previously referred to as bovine virus diarrhea (BVD), is an economically significant disease of cattle that is found in the majority of countries throughout ...
was discovered,
which is still possibly the most common pathogen of cattle throughout the world
and in 1957,
equine arterivirus was discovered.
In the 1950s, improvements in virus isolation and detection methods resulted in the discovery of several important human viruses including
varicella zoster virus
Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...
,
the
paramyxoviruses,
– which include
measles virus,
and
respiratory syncytial virus
Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. ...
– and the
rhinovirus
The rhinovirus (from the grc, ῥίς, rhis "nose", , romanized: "of the nose", and the la, vīrus) is the most common viral infectious agent in humans and is the predominant cause of the common cold. Rhinovirus infection proliferates in tem ...
es that cause the
common cold.
In the 1960s more viruses were discovered. In 1963, the
hepatitis B virus
''Hepatitis B virus'' (HBV) is a partially double-stranded DNA virus, a species of the genus '' Orthohepadnavirus'' and a member of the '' Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B.
Disease
Despite there b ...
was discovered by
Baruch Blumberg
Baruch Samuel Blumberg (July 28, 1925 April 5, 2011), known as Barry Blumberg, was an American physician, geneticist, and co-recipient of the 1976 Nobel Prize in Physiology or Medicine (with Daniel Carleton Gajdusek), for his work on the hepat ...
(b. 1925).
Reverse transcriptase, the key enzyme that retroviruses use to
translate
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transl ...
their RNA into DNA, was first described in 1970, independently by Howard Temin and
David Baltimore
David Baltimore (born March 7, 1938) is an American biologist, university administrator, and 1975 Nobel laureate in Physiology or Medicine. He is President Emeritus and Distinguished Professor of Biology at the California Institute of Technol ...
(b. 1938).
This was important to the development of
antiviral drugs – a key turning-point in the history of viral infections.
In 1983,
Luc Montagnier
Luc Montagnier (; , ; 18 August 1932 – 8 February 2022) was a French virologist and joint recipient, with and , of the 2008 Nobel Prize in Physiology or Medicine for his discovery of the human immunodeficiency virus (HIV). He worked as a res ...
(b. 1932) and his team at the
Pasteur Institute
The Pasteur Institute (french: Institut Pasteur) 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 invented pasteurization and vaccines ...
in France first isolated the retrovirus now called HIV.
In 1989
Michael Houghton's team at
Chiron Corporation
Chiron Corporation ( ) was an American multinational biotechnology firm founded in 1981, based in Emeryville, California, that was acquired by Novartis on April 20, 2006. It had offices and facilities in eighteen countries on five continents. ...
discovered
hepatitis C.
New viruses and strains of viruses were discovered in every decade of the second half of the 20th century. These discoveries have continued in the 21st century as new viral diseases such as
SARS
Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''seve ...
and
nipah virus
Nipah virus, scientific name ''Nipah henipavirus'', is a bat-borne virus that causes Nipah virus infection in humans and other animals, a disease with a high mortality rate. Numerous disease outbreaks caused by Nipah virus have occurred in Sou ...
have emerged. Despite scientists' achievements over the past one hundred years, viruses continue to pose new threats and challenges.
See also
*
List of viruses
References
{{History of medicine