Virus - History


Louis Pasteur 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 invented a filter (known today as the Chamberland filter or Chamberland-Pasteur filter) with 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 Dmitri Ivanovsky 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. At the time it was thought that all infectious agents could be retained by filters and grown on a nutrient medium – this was part of the germ theory of disease. In 1898, the Dutch microbiologist Martinus Beijerinck 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, but as his experiments did not show that it was made of particles, 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 Wendell Stanley, who proved they were particulate. In the same year Friedrich Loeffler and Frosch passed the first animal virus – agent of foot-and-mouth disease (aphthovirus) – through a similar filter.

In the early 20th century, the English bacteriologist Frederick Twort discovered a group of viruses that infect bacteria, now called bacteriophages (or commonly phages), and the French-Canadian microbiologist Félix d'Herelle described viruses that, when added to bacteria on agar, would produce areas of dead bacteria. 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. Phages were heralded as a potential treatment for diseases such as typhoid and cholera, but their promise was forgotten with the development of penicillin. The study of phages provided insights into the switching on and off of genes, and a useful mechanism for introducing foreign genes into bacteria.

By the end of the 19th century, viruses were defined in terms of their infectivity, their ability to be filtered, and their requirement for living hosts. Viruses had been grown only in plants and animals. In 1906, Ross Granville Harrison invented a method for growing tissue in lymph, and, in 1913, E. Steinhardt, C. Israeli, and R. A. Lambert used this method to grow vaccinia virus in fragments of guinea pig corneal tissue. In 1928, H. B. Maitland and M. C. Maitland grew vaccinia virus in suspensions of minced hens' kidneys. Their method was not widely adopted until the 1950s, when poliovirus was grown on a large scale for vaccine production.

Another breakthrough came in 1931, when the American pathologist Ernest William Goodpasture grew influenza and several other viruses in fertilized chickens' eggs. In 1949, John Franklin Enders, Thomas Weller, and Frederick Robbins grew polio virus in cultured human embryo cells, the first virus to be grown without using solid animal tissue or eggs. This work enabled Jonas Salk to make an effective polio vaccine.

The first images of viruses were obtained upon the invention of electron microscopy in 1931 by the German engineers Ernst Ruska and Max Knoll. In 1935, American biochemist and virologist Wendell Meredith Stanley examined the tobacco mosaic virus and found it was mostly made of protein. A short time later, this virus was separated into protein and RNA parts. The tobacco mosaic virus was the first to be crystallised and its structure could therefore be elucidated 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 DNA structure of the virus in 1955. In the same year, Heinz Fraenkel-Conrat and Robley Williams 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.

The second half of the 20th century was the golden age of virus discovery and most of the over 2,000 recognised species of animal, plant, and bacterial viruses were discovered during these years. In 1957, equine arterivirus and the cause of Bovine virus diarrhea (a pestivirus) were discovered. In 1963, the hepatitis B virus was discovered by Baruch Blumberg, and in 1965, Howard Temin described the first retrovirus. Reverse transcriptase, the key enzyme that retroviruses use to translate their RNA into DNA, was first described in 1970, independently by Howard Martin Temin and David Baltimore. In 1983 Luc Montagnier's team at the Pasteur Institute in France, first isolated the retrovirus now called HIV.

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