1-11 Viruses are shown to parasitize organisms

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• John Brown Buist was the first to observe a virus, the cowpox virus, although he did not realize it.
• Dmitrii Ivanowski discovered that the cause of tobacco mosaic disease could pass through a porcelain filter, but it was Martinus Beijerinck who correctly deduced that the particle causing the disease was too small to be a bacteria and would later be known as a virus.
• Frederick Twort and Felix d'Herelle each discovered bacteriophage, viruses that infect bacteria.

The ensuing years brought numerous discoveries about the nature of disease. In the latter half of the 19^th century, the causative agents for anthrax, tuberculosis, gonorrhea, diphtheria and many more were discovered. Great strides in understanding maladies caused by bacteria were made at this time, including the solidification of the germ theory of disease. However, some illnesses seemed not to have bacterial origins. Microscopic examination of sera from ill patients revealed no organisms and the causative agents could not be grown on any known medium. Yet if these sera were injected into a susceptible host, disease resulted.

In 1886 John Brown Buist devised a method for staining and fixing liquid from a cowpox vesicle. Observations of this slide showed tiny bodies that he believed were spores. Although he did not realize it, he was the first person to see (and photograph) a virus. It was not until the middle of the twentieth century with the invention of the electron microscope that the true shape and structure of viruses was understood.

In 1884 Charles Chamberland in Pasteur's laboratory created an unglazed porcelain filter that had pores much smaller than bacteria (0.1-1 µm). It was possible to pass a solution containing bacteria through these filters and completely remove them from the solution. This enabled the creation of sterile medium without the use of heat, and also became a standard test for the removal of all bacteria, especially when testing transmission of disease. By removing the microbes, Chamberland clearly demonstrated that an infectious agent, and not the solution, was causing the illness. This concept seemed reasonable until scientists began to investigate a tobacco infection.

Tobacco mosaic disease is characterized by light and dark green areas on plant leaves in a mosaic pattern. The disease stunts the growth of the plant, therefore reducing yields. Europeans recognized the effects of this disease soon after tobacco was introduced from the New World in the 17th century. Adolph Mayer first described transmission of the disease by injecting fluid from a diseased plant into a healthy one. Nine out of ten times the healthy plant would become heavily diseased. In 1892 Dmitrii Ivanowski extended this research by the shocking discovery that the causative agent could pass through Chamberland's porcelain filter. He reported his findings, but the idea that the causative agent could pass through the filter was so troublesome to Ivanowsky he attributed the phenomenon to a cracked filter or to small spores that passed through the pores. It was Martinus Beijerinck in 1898 who realized the true nature of these particles, making the intellectual leap that the causative agent of the disease must be so small as to pass through the filter known to trap all bacteria. He coined the term contagium vivum fluidum a contagious living fluid.

Some scientists thought these agents were toxins in the fluids of the hosts, but further study revealed that tobacco mosaic disease could cause illness through many transfers from plant to plant. A toxin might cause damage on the first plant, but subsequent transfers should make it so dilute that it would no longer have any effect. These filterable entities were different from bacteria and appeared to depend on their host in order to multiply. The term ultrafiltrable viruses and later just viruses (virus means poison in Latin) was coined to describe these tiny pathogens.

Bacteria are also vulnerable to viruses. Bacterial viruses were described by Frederick Twort in 1915 and independently by Felix d'Herelle in 1917. Felix d'Herelle was studying a plague of locusts in Mexico when he noticed that the locusts were being killed by a microorganism. During experiments to characterize this microbe, d'Herelle noticed the appearance of clear, circular spots two or three millimeters in diameter on cultures growing on agar. At this point d'Herelle studied the spots enough to determine that they came from an agent small enough to pass through a porcelain filter. He dropped the investigation, but recalled these observations while studying dysentery in 1915. The illness was affecting soldiers fighting in World War I and he soon determined the cause to be the bacterium Shigella dysentery. In the process of investigating Shigella, similar areas of clearing were observed. d'Herelle realized that something in these areas of clearing was killing the bacterium. He eventually determined these were viruses of bacteria, coining the term bacteriophage (devourer of bacteria). Figure 1-22 lists these and other significant events in the discovery of the cause of disease.

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