History of Virology - Pioneers

Pioneers

Despite his other successes, Louis Pasteur (1822–1895) was unable to find a causative agent for rabies and speculated about a pathogen too small to be detected using a microscope. In 1884, the French microbiologist Charles Chamberland (1851–1931) invented a filter – known today as the Chamberland filter – that had pores smaller than bacteria. Thus, he could pass a solution containing bacteria through the filter and completely remove them from the solution.

In 1892, the Russian biologist Dmitry Ivanovsky (1864–1920) used this filter to study what is now known as the tobacco mosaic virus. His experiments showed that crushed leaf extracts from infected tobacco plants remain infectious after filtration. Ivanovsky suggested the infection might be caused by a toxin produced by bacteria, but did not pursue the idea.

In 1898, the Dutch microbiologist Martinus Beijerinck (1851–1931) repeated the experiments and became convinced that the filtered solution contained a new form of infectious agent. He observed that the agent multiplied only in cells that were dividing and he called it a contagium vivum fluidum (soluble living germ) and re-introduced the word virus. Beijerinck maintained that viruses were liquid in nature, a theory later discredited by the American biochemist and virologist Wendell Meredith Stanley (1904–1971), who proved they were particles. In the same year Friedrich Loeffler (1852–1915) and Paul Frosch (1860–1928) passed the first animal virus through a similar filter and discovered the cause of foot-and-mouth disease.

In 1881, Carlos Finlay (1833–1915), a Cuban physician, first suggested that mosquitoes were carrying the cause of yellow fever, a theory that was proved in 1900 by Walter Reed (1851–1902). During 1901 and 1902, William Crawford Gorgas (1854–1920) organised the destruction of the mosquitoes' breeding habitats in Cuba, which dramatically reduced the prevalence of the disease. Gorgas later organised the elimination of the mosquitoes from Panama, which allowed the Panama Canal to be opened in 1914. The virus was finally isolated by Max Theiler (1899–1972) in 1932 who went on to develop a successful vaccine.

By 1928 enough was known about viruses to enable the publication of Filterable Viruses, a collection of essays covering all known viruses edited by Thomas Milton Rivers (1888–1962). Rivers, who survived typhoid fever at the age of twelve, went on to have a distinguished career in virology. In 1926, he was invited to speak at a meeting organised by the Society of American Bacteriology where he said for the first time, "Viruses appear to be obligate parasites in the sense that their reproduction is dependent on living cells."

That viruses were particles was not considered unnatural and fitted in nicely with the germ theory. It is assumed that Dr. J. Buist of Edinburgh was the first person to see virus particles in 1886, when he reported seeing "micrococci" in vaccine lymph. But he had probably seen clumps of vaccinia virus. In the years that followed, as optical microscopes were improved "inclusion bodies" were seen in many virus-infected cells, but these aggregates of virus particles were still too small to reveal any detailed structure. It was not until the invention of the electron microscope in 1931 by the German engineers Ernst Ruska (1906–1988) and Max Knoll (1887–1969), that virus particles, especially bacteriophages, were shown to have a complex structure. The sizes of viruses determined using this new microscope fitted in well with those estimated by filtration experiments. Viruses were expected to be small, but the range of sizes came as a surprise. Some were only a little smaller than the smallest known bacteria, and the smaller viruses were of similar sizes to complex organic molecules.

In 1935, Wendell Stanley examined the tobacco mosaic virus and found it was mostly made of protein. In 1939, Stanley and Max Lauffer (1914) separated the virus into protein and RNA parts. The discovery of RNA in the particles was important because in 1928, Fred Griffith (c.1879–1941) provided the first evidence that its "cousin", DNA, formed genes.

In Pasteur's day, and for many years after his death the word "virus" was used to describe any cause of infectious disease. Painstaking work, by many bacteriologists, soon discovered the cause of numerous infections. However, some infections remained, many of them horrendous, but for which no bacterial cause could be found. These agents were invisible and could only be grown in living animals. The discovery of viruses was the key that unlocked the door that withheld the secrets of the cause of these mysterious infections. And, although Koch's postulates could not be fulfilled for many of these infections, this did not stop the pioneer virologists from looking for viruses in infections for which no other cause could be found.