Blood. Virus Diseases

But twentieth-century serology reserved its most spectacular successes for the battle with microorganisms of a type unknown to Pasteur and Koch in their day. Pasteur had failed to find the infective agent of rabies, a clearly infectious disease undoubtedly caused, according to his germ theory, by a microorganism. Pasteur suggested that the microorganism existed but that it was too small to be detected by the techniques of the time. In this, he turned out to be correct.

The fact that an infectious agent might be much smaller than ordinary bacteria was shown to be true in connection with a disease affecting the tobacco plant ("tobacco mosaic disease"). It was known that juice from diseased plants would infect healthy ones and, in 1892, the Russian botanist, Dmitri losifovich Ivanovski (1864-1920), showed that the juice remained infective even after it had been passed through filters fine enough to keep any known bacterium from passing through. In 1895, this was discovered independently, by the Dutch botanist, Martinus Willem Beijerinck (1851-1931). Beijerinck named the infective agent a "filtrable virus" where virus simply means "poison." This marked the beginning of the science of virology.

Other diseases were proved to be caused by such filtrable viruses. The German bacteriologist, Friedrich August Johannes Loffler (1852-1915), was able to demonstrate, in 1898, that hoof-and-mouth disease was caused by a virus; and in 1901, Reed did the same for yellow fever. These were the first animal diseases shown to be virus-induced. Other diseases shown to be caused by viruses include poliomyelitis, typhus, measles, mumps, chicken pox, influenza, and the common cold.

A fine case, in this connection, of the biter bit, arose in 1915, when an English bacteriologist, Frederick William Twort (1877-1950), found that some of his bacterial colonies were turning foggy and then dissolving. He filtered these disappearing colonies and found that the filtrate contained something that caused normal colonies to dissolve. Apparently, bacteria themselves could suffer a virus disease and parasites were thus victimized by smaller parasites still. The Canadian bacteriologist, Felix Hubert d'Herelle (1873-1949), made a similar discovery independently in 1917 and he named the bacteria-infesting viruses "bacteriophages" (bacteria-eaters).

In any listing of virus-caused diseases, cancer must remain a puzzle. Cancer has grown continually more important as a killer over the last century, for as other diseases are conquered, those that remain (cancer among them) claim a larger share of humanity for their own. The slowly inexorable advance of cancerous growths, the often lingering and painful death, have made cancer one of the prime terrors of mankind now.

During the initial successes of the germ theory, it had been thought that cancer might prove to be a bacterial disease, but no bacterium was found. After the existence of viruses was established, a cancer virus was sought for and not found either. This, combined with the fact that cancer was not infectious, caused many to believe that it was not a germ disease at all.

Although this may be so, it also remains true that although no general virus for the general disease has been discovered, particular viruslike agents have been discovered for particular types of cancer. In 1911, an American physician, Francis Peyton Rous (1879- ), was studying a chicken with a kind of tumor called a "sarcoma." Among other things, he decided to test the sarcoma for virus content. He mashed it up and passed it through a filter. The filtrate, he found, would produce tumors in other chickens. He did not himself quite have the courage to call this the discovery of a virus, but others did.

For about a quarter of a century, the "Rous chicken sarcoma virus" was the only clear-cut example of anything like an infectious agent capable of inducing a cancer. In the 1930s and thereafter, however, further examples were discovered. Nevertheless, the matter remains unclear and the study of cancer (oncology) is still a major and frustrating branch of medical science.

While the physical nature of viruses remained unknown for some forty years after their discovery, this did not prevent logical steps being taken to treat virus diseases. In fact, smallpox, the first disease to be conquered by medical science, is a virus disease. Vaccination against smallpox encourages the body to form antibodies which will deal specifically with the smallpox virus and it is thus a kind of serological technique. Presumably, every virus disease could be countered by some serological treatment.

The difficulty, here, is that a strain of virus must be found which will produce no important symptoms and yet will spark the production of the necessary antibodies against the virulent strains (simulating the service per formed by cowpox where smallpox is concerned). This sort of attack had been used by Pasteur in countering bacterial disease, but bacteria can be cultured without much trouble and can be easily treated in ways that will encourage the production of attenuated strains.

A virus, unfortunately, can live only in living cells and this increases the difficulty of the problem. Thus, the South African microbiologist, Max Theiler (1899- ), produced a vaccine against yellow fever in the 1930s only after he had painstakingly transferred the yellow-fever virus first to monkeys and then to mice. In mice, it developed as an encephalitis, or brain inflammation. He passed the virus from mouse to mouse and then, eventually, back to monkeys. By then, it was an attenuated virus, producing only the feeblest yellow-fever attack, but inducing full immunity to the most virulent strains of the virus.

Meanwhile, though, a living analog of Koch's nutrient broths was discovered by the American physician, Ernest William Goodpasture (1886-1960). In 1931, he introduced the use of living chick embryos as a nutrient for viruses. If the top of the shell is removed, the rest of the shell serves as a natural Petri dish. By 1937, a still safer yellow-fever vaccine was produced by Theiler after he had selected a nonvirulent virus strain from among those he had passed along from chick embryo to chick embryo in nearly two hundred transplants.

The most spectacular accomplishment of the new serological techniques was in connection with poliomyelitis. The virus was first isolated in 1908 by Landsteiner who was also the first to transmit the disease to monkeys. Monkeys are expensive and are difficult experimental animals, however, and to find a nonvirulent strain by infecting crowds of monkeys is impractical.

The American microbiologist, John Franklin Enders (1897- ),with twoyoung associates, Thomas Huckle Weller (1915- )andFrederick Chapman Robbins (1916- ),attempted, in 1948, to culture virus in mashed-up chick embryos, bathed in blood. Attempts of this sort had been made earlier by others but always the effort had failed, since whether the virus multiplied or not, the culture was drowned out by the rapidly multiplying bacteria. Enders, however, had the notion of adding the recently developed penicillin to his cultures. This stopped bacterial growth without affecting the virus, and in this way he managed to culture the mumps virus successfully.

He next tried this technique on the poliomyelitis virus and, in 1949, succeeded again. Now it was possible to culture the virus easily and in quantity so that one might search among hundreds of strains for an attenuated one of the proper characteristics. The Polish-American microbiologist, Albert Bruce Sabin (1906- ), had, by 1957, discovered an attenuated strain of poliomyelitis virus for each of the three varieties of the disease, and had produced successful vaccines against the disease.

In similar fashion, Enders and his associate Samuel Lawrence Katz (1927- ) developed an attenuated strain of measles virus in the early 1960s, which may serve as a vaccine to end the threat of that children's disease.