Notes 2

Viruses in History

The Greek poet Homer characterizes Hector as 'rabid' in 'The Iliad'.

A hieroglyph from Memphis, the capital of ancient Egypt, drawn about 1,400 BC, depicts a temple priest showing typical clinical signs of paralytic poliomyelitis.
Pharaoh Ramses V is believed to have died due to smallpox in 1196 BC. His well-preserved mummified body is now at the Cairo Museum. Evidence of postular lesions on face.
Mesopotamian laws describing the responsibilities of owners of rabid dogs date from before 1,000 B.C.

Smallpox was endemic in China by 1,000 BC.
Variolation was developed (inhalation of dry crusts, inoculation of pus) and practiced for centuries.
Smallpox endemic in the Ganges river basin by the 5^th century B.C., subsequently spread to other parts of the world.

Smallpox patient
Flint et al. 2000. Principles of Virology. ASM Press

An image of Hector from an ancient Greek vase University of Pennsylvania Museum

An Egyptian stele, or stone tablet, from the 18th dynasty (1580-1350 B.C.) depicting a man with a withered leg and "drop foot" syndrome characteristic of polio.

Flint et al. 2000. Principles of Virology. ASM Press

Other viral diseases known in ancient times to humans were mumps and influenza.
Yellow fever has been described since the European colonization of Africa.
Edward Jenner developed vaccination against smallpox in 1796. Technique was almost universally adopted.
Anton van Leewenhoek (1632-1723) constructed the first simple compound light microscope but no viruses were observed.
Louis Pasteur proposed the 'Germ Theory of Disease' (1880's).
Robert Koch proved the germ theory right. He developed the 4 famous postulates still regarded as a proof that an infectious agent is responsible for a specific disease.
Louis Pasteur concluded that rabies was caused by a 'virus' but he did not discriminate between bacteria and other agents of disease. Develops vaccine against rabies.
Dimitri Iwanowski, Russian botanist, showed that extracts from disease tobacco plants could transmit disease to other plants after passage through ceramic filters fine enough to retain the smallest known bacteria -- (1892).
Martinus Beijerinick (1896) was the first to develop the modern idea of the virus which he referred to as "contagium vivum fluidum" (soluble living germ).
Freidrich Loeffler and Paul Frosch (1898) showed that a similar agent caused the 'foot-and mouth') disease in cattle.
Despite discoveries in plants and animals, there was considerable resistance to the idea that viruses might have anything to do with human disease.
Karl Landsteiner and E. Popper (1909) showed that poliomyelitis was caused by a "filterable agent" - the first human disease to be recognized as having a viral cause.
Frederick Twort (1915) & Felix d'Herelle (1917) were the first to recognize viruses which infect bacteria. d' Herelle called them 'bacteriophages'.
Ruska and others developed the TEM and SEM in the 1930's. The first electron micrograph of a virus (TMV) was published in 1939.
In the 1930's and subsequent decades, pioneering virologists such as S.E. Luria, Max Delbruck, and many others used viruses as model systems for many viral investigations.

Koch's Postulates

Dominant paradigm of microbiology.
Outlined an experimental method to be used in all situations.
When these rules broke down and failed to yield a 'causative agent' that the concept of a virus ('filtrable agent') was born.

The Discovery Period

Adolf Mayer (1843-1942) inoculated healthy plants with the juice extracted from diseased plants by grinding up the infected leaves in water.

This was the first experimental transmission of a viral disease of plants.
It established the infectious nature of the disease.
As no bacterial or fungal agent could be cultured or detected so Koch's postulates could not be satisfied.

Mayer concluded that the cause is bacterial, but the infectious forms have not yet been isolated, or are their forms and mode of action.

The Discoverers....

Dimitri Ivanofsky (1864-1920) added an additional step by passing the infected sap through a filter made of unglazed porcelain (Chamberlain filter).
He reported in 1898: "... the sap of leaves infected with tobacco mosaic disease retains its infectious properties even after filtration through Chamberlain filter candles...".
The importance of this experiment is that it provided an operational definition of viruses, an experimental technique by which an agent could qualify as a virus. However, he still believed it was a fault of the filter, perhaps a toxin, or an enzyme.

Pasteur (1885) was working with viruses and developing the rabies vaccine but never investigated the unique nature of that infectious agent.

Martinus Beijerinck in 1898 extended the studies by showing that the filtered sap could be diluted and then regain its "strength" after replication in living, growing plant tissue.

Thus, it could only be grown in the host not in cell-free sap of the plant.
He called it 'contagium vivum fluidum" (contagious living fluid).
A 25-year debate about the nature of the viruses began: were they liquids or particles?
Conflict was laid to rest when d'Herelle developed the plaque assay in 1917 and when the 1^st electron micrographs of TMV were taken in 1939 by H. Ruska and collaborators.

More Discoverers....

Loeffler and Frosch (1898) rapidly described and isolated the first "filtrable agent" from animals ==> the foot-and-mouth disease virus.
Walter Reed and his team in Cuba (1901) recognized the first filtrable virus, the yellow fever virus.
Federick Twort (1915) observed the plaques in plates with bacteria.
Felix d'Herelle developed the use of limiting dilutions with the plaque assay to titer the virus preparation.
Max Schlesinger (1934) showed the viruses were made of protein and DNA. Linear dimension: 0.1 µm and a mass of 4x10^-16 g.
Wendell Stanley crystallized TMV in 1935 and chemists took interest. Studies on structure with X-ray technology started.
From 1929 to 1962, both the structures and the chemical composition of viruses were elucidated.

Earliest Record of Attempts to Control a Disease

Children were inoculated with extracts of smallpox pustules (11^th century China).
Lady Mary Worthy Montage wife of Ambassador from England to Turkey introduced vaccination for smallpox into London in 1721.
Procedures from Greek peasants: smallpox pustules were placed either under the fingernail or on the skin.
Practice widespread in the 1740's when children of the Royal English family were immunized successfully.
After the death of Louis XV from smallpox in 1774, treatment with the smallpox pustules became well accepted in France.
George Washington instituted a program of inoculation of Continental Army soldiers in 1776.
In 1778, Jenner made observations from milkmaids and developed the cowpox vaccine, to control smallpox.

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