The Discovery of Viruses

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The Discovery of Viruses

Overview

By the late nineteenth century, the work of Louis Pasteur (1822-1895) and other scientists had established the germ theory of disease and identified the bacteria that caused many ailments.

But they found that some diseases were caused by invisible agents that could not be filtered out, agents that came to be called viruses. The experiments by Martinus Beijerinck (1851-1931) and Dmitri Ivanovsky on the tobacco mosaic virus in the 1890s are generally thought of as the beginning of the science of virology, but it was not until 40 years later that viruses could be isolated with extra-fine filters and imaged using electron microscopes.

Background

Infectious diseases have always been humanity's lot. Throughout history, plagues were not uncommon, and many people died of diseases that would be preventable or easily curable today. Early explanations of disease included possession by evil spirits and imbalance of "humours," or bodily fluids. The name "influenza," coined in the fifteenth century, is Italian for "influence"; the influence, that is, of the heavenly bodies.

During the Renaissance, scholars began to suggest that illnesses could be spread by invisible particles. But until the microscope was invented by Anton van Leeuwenhoek (1632-1723) in the 1600s, scientists had no idea that microorganisms existed. Even then, it was another 200 years before they were proven to be associated with disease.

Meanwhile, contagious illnesses continued to run rampant. In eighteenth-century Europe, about 95 percent of the population contracted smallpox at some point in their lives, and as many as one person in 10 died of it. Carried to the New World by Europeans, it wiped out millions of Native Americans. By 1796 Edward Jenner (1749-1823), an English country doctor, had seen many people die of smallpox. Yet the milkmaids he knew rarely got sick with this dread disease. They did often contract cowpox, an illness with much milder symptoms. Could exposure to cowpox somehow protect against smallpox as well?

It was well known that people who had survived smallpox were thereafter immune. The 1700s had seen widespread adoption of exposure to what was hoped would be a mild dose of smallpox in order to achieve this immunity. But the strategy often backfired, as there was no real way to control the severity of the resulting disease.

Jenner hoped that inoculation with cowpox might be a way to achieve immunity without being exposed to smallpox at all. He tested his theory on a healthy eight-year-old child named James Phipps. He took pus from a milkmaid's cowpox sore and scratched it into the boy's arm, where it caused a small infected spot that soon subsided. Six weeks later, Jenner took the riskier step of inoculating the boy with smallpox in the same way. The child did not get smallpox then, or ever. Jenner had developed the first vaccine for a viral disease, long before anyone knew what a virus actually was.

Impact

The great nineteenth-century French scientist Louis Pasteur was a proponent of the germ theory of disease, the idea that illnesses were caused by living microorganisms, or microbes, that could spread between people and multiply in the body. Pasteur was able to identify and study a number of the microbes called bacteria that were involved in diseases, and also in other processes such as fermentation and the souring of milk. He disproved the then-popular idea that microbes could arise out of nothing by "spontaneous generation," and began to investigate how a human or animal "carrier" could spread a disease without contracting the illness itself.

But there were some diseases, such as rabies, for which Pasteur could not find the germ, although he insisted it must be there. We now know that these diseases are caused by even tinier agents called viruses. Other examples of viral diseases that would have been familiar to Pasteur include the common cold, mumps, measles and polio.

Rabies was of particular concern to Pasteur because it was almost always fatal. In his experiments, he found that rabies-infected tissue transferred from animal to animal gradually became weaker and less likely to cause the dreaded disease. This caused him to hypothesize that a weakened extract of tissue infected with rabies might be protective against the disease, and usable as a vaccine even after a person had been bitten. By 1885 he had prepared such an extract, although he was by no means ready to try it on humans. But when nine-year-old Joseph Meister was brought to Pasteur after having been bitten by a rabid dog, there was no alternative for the boy but a painful death, and Pasteur was persuaded. With great trepidation, he administered the vaccine, and it worked. Joseph Meister did not develop rabies, and lived another 55 years.

Although Pasteur had found a way to defeat rabies, he never did find the germ he was looking for. He assumed that it was simply another type of bacteria, a variety too small to be seen with the microscope. Pasteur was half right; most viruses were much too small to see with nineteenth-century microscopic techniques. The Scottish surgeon John Buist did manage to see the smallpox virus in 1887, but didn't recognize the tiny dots he observed. Even the largest viruses are about one-tenth the size of typical bacteria, and most are much smaller than that. But in fact they are not simply miniature bacteria, but something else altogether.

In 1892 a Russian scientist named Dmitri Ivanovsky was studying tobacco mosaic disease, which destroys the leaves of tobacco plants. The disease was clearly infectious; plants that came into contact with the sap from diseased plants were damaged as well. This ability to reproduce itself eliminated the possibility that the damaging agent might be a simple toxin. Hoping to find the bacteria responsible for the infection, Ivanovsky ran an extract of diseased leaves through a very fine filter, with pores small enough to trap any known type of bacteria. But he found that whatever caused the disease went right through his filter. No matter how many times he tried to strain out the microbe, the liquid still retained the power to infect other plants.

Ivanovsky published his findings, but little attention was paid. He himself thought that there might have simply been a problem with his filters. Six years later, however, not knowing about Ivanovsky's work, the Dutch botanist Martinus Beijerinck performed the same experiments and got the same results. While the infectious agent could not be filtered out, it seemed to be destroyed when the liquid was heated.

Beijerinck concluded that the infectious agent was not a microbe at all, but a "contagious living fluid." Just as Jenner had a century before when writing about his smallpox vaccine, Beijerinck used the term "virus" from the Latin word for poison or pestilence. Other scientists soon showed that hoof-and-mouth disease, yellow fever, and other infectious ailments were also caused by these "filterable viruses."

Late nineteenth-century scientists attempting to study viral diseases were in a sense groping around in the dark. In the 1930s filters could finally be manufactured with pores tiny enough to prove that viruses are particulate after all, rather than being fluid in nature. The earliest electron microscopes also appeared in the 1930s, and viruses could at last be seen. Today we know that viruses are not living cells like bacteria, but rather tiny packets of genetic material that must infect the cells of their unwilling host in order to reproduce. They mutate quickly, and our everincreasing knowledge of them is always under challenge by the appearance of new viral diseases such as AIDS and the Ebola virus.

SHERRI CHASIN CALVO