Can science beat the VIRUS DISEASES?
The "miracle" drugs didn't lick all disease. They can’t cope with most viruses. Here’s an up-to-the-minute report on the race to solve such mysteries as POLIO, CANCER, and the COMMON COLD
A new catchword has recently crept into our conversation. Whenever we discuss health, we've found a new whipping boy to blame for every ill from cancer to the common cold. We have a new label for the sniffly, feverish, aching ailments of the 1950s, those baffling sicknesses for which doctors can’t always supply a name. “It’s a virus,” we say when we don’t know what ails us—and we’re probably right.
Virus is a term used to cover a group of microorganisms infinitesimally small but so powerful and pervasive that they prey on humans, animals, birds, fish, frogs, insects, plants and even bacteria. Spread by animals, insects, excrement and respiratory discharge, they cause a multitude of diseases, including poliomyelitis, measles, mumps, influenza and colds in the head. Some scientists even blame viruses for cancer, while others are using them to destroy cancerous growths.
Two great families of germs—viruses and bacteria— are responsible for practically all the contagious disease in Canada. Other agents such as protozoa (minute animals that cause tropical diseases like malaria), rickettsia (insect-borne organisms halfway in size between a bacterium and a virus), parasitic worms and fungi aren’t a serious problem in this country.
Unlike bacterial infections, sickness caused by viruses can seldom be cured with the miracle drugs, sulfa (synthetic chemical compounds) and the antibiotics (penicillin, streptomycin and other natural substances produced by molds). When they first came into use they were so spectacularly successful in combating bacteria that many previously perilous conditions such as syphilis, typhoid, mastoid and peritonitis were brought under control. Though the public glibly predicted the swift conquest of disease, scientists have found that, with a few minor exceptions. virus diseases aren’t susceptible to any wonder drug yet produced. The exceptions include psittacosis, a comparatively rare illness carried by birds; trachoma, an eye infection; and virus pneumonia, which some doctors claim to have curbed with aureomycin. Against other virus diseases our only protection is a vaccine, such as the Salk antipolio vaccine, which keeps us from catching the disease in the first place.
The fact that viruses resist wonder drugs makes them one of our most urgent medical problems. In Ottawa, the Department of National Health and Welfare recently set up a new laboratory devoted to virus study. Dr. A. J. Rhodes, research director of the Hospital for Sick Children in Toronto and a world authority on virology, sa/s, “The discovery of antibiotics has focused our attention on the residue of infectious illnesses, most of which are caused by viruses.”
Some doctors believe that our victory over bacteria has actually given viruses a greater chance to spread because they no longer have to compete with other germs for sources of sustenance. “These virus diseases have been running wild since we've killed off the other diseases,” says Dr. W. S. Aitchison. associate director of the Toronto Department of Public Health.
There's a second reason why the miracle drugs have stimulated virus research. Paradoxically, the antibiotics that won’t cure virus infections are indirectly helping to bring them under control by making them easier to investigate. Scientists study viruses by growing them in live body tissue inside test tubes, and the injection of penicillin into the tube isolates the virus by getting rid of any bacterial interlopers.
While some virologists concentrate on human disease, others study economically important viruses that attack crops and livestock. Animal viruses cause distemper and rabies in dogs, foot-and-mouth disease in cattle and encephalitis in horses. Myxomatosis, recently used to cut down the fast-breeding rabbit population in Australia, is one of the few viruses man has ever harnessed for his own purposes. Horticulturists breed striped tulips by inoculating the flowers with a virus, but most plant viruses cause nothing but trouble for farmers who grow tobacco, tomatoes and potatoes. And Dr. F. d'Herelle, who discovered in 1917 that even bacteria have their own virus diseases, had a magnificent scheme for training viruses to eat bacteria, but his plan didn’t work. Though many scientists spent the next fifteen years trying to control bacterial infections by attacking them with viruses, results were disappointing and the idea was eventually abandoned.
The scientists currently studying bacterial viruses have a long-range purpose—they’re trying to find out exactly how a virus operates. What makes it different from other microbes? First, its size: the world's
smallest living organism is the virus of foot-and-mouth disease whose diameter is only ten millionths of a millimeter. All viruses are so small that no one suspected their existence until 1892, when a Russian botanist named Ivanovski stumbled across the virus of a plant disease called tobacco mosaic. He thought the disease was caused by a bacterium and tried to isolate it by passing tobacco sap through a porcelain filter. To his astonishment he found that the bacteriafree filtrate was still capable of infecting plants. He refused to believe his own evidence, but later researchers confirmed his discovery and named the tiny disease agents “filterable viruses.”
When they found that some viruses such as psittacosis (parrot fever) were large enough to be trapped by filters, scientists dropped the term “filterable” and searched for another characteristic that would distinguish the virus from other germs. They soon learned that unlike a bacterium, which reproduces by simple division and can live indefinitely in earth or water or some other substance, a virus can multiply only inside a living cell in a mysterious manner that isn’t yet fully understood. The fact that a virus has to live inside a cell, like a worm in a rosebud, makes it difficult to study and almost impossible to destroy such a virus
These are some known VIRUS DISEASES
+ Poliomyclitis, which flourishes where the standard of living i~ highest. + Infective hepatitis (jaundice) and virus pneumonia, two diseases apparently growing more common. + Pharyngeal-conjunctival fever, a newly recognized eye disease that reached epidemic proportions in Toronto swim ming pools this time last year. + The common cold, our most trouble some minor complaint and industry's biggest time-waster. + Influenza, the disease that caused the worst pandemic in history after World War 1. + Rabies and psittacosis (parrot fever). bizarre illnesses that strike when man accidentally becomes a link in a chain of infection spread between animals. + Measles, mumps, chicken pox and rubella (commonly called `Geinian measles," but different from measles), childhood diseases with sinister implica tions for adults. + Smallpox and yellow fever, two terrors of the past now almost quenched. + Warts, cold sores, shingles, a tropical fever called dengue, eye infections such as trachoma, and some types of con junctivitis and several kinds of ence phalitis. These are suspected virus diseases + Cancer, the fatal disease twenty-five percent of US will develop. This year the National Cancer Institute of Canada is spending more than $27,000 on virus research grants. + Infectious mononucleosis, the mystery disease that attacks young adults.
without injuring the cell.
The virus is perfectly designed for its job of cell invasion. Viruses differ in shape — bacterial viruses look like tadpoles, plant viruses are round or rodlike. animal viruses are usually spherical or brick-shaped—but each one has a protein coating surrounding a core of nucleic acid. Somewhere on the virus’ rough surface is a set of electrical charges which attach themselves to complementary charges on the surface of a
cell. The cell wall breaks down at this point, allowing the virus to inject its acid contents into the cell while its protein sheath is sloughed off and left outside. Inside the cell, the acid disappears for a time. In some secret way the virus begins to work on the cell, forcing it to manufacture virus material instead of cell material. Soon new viruses begin to form, filling the exhausted cell and finally bursting forth to prey on neighboring cells when the original cell is destroyed or too damaged to sustain its parasites. The virus multiplies with such rapidity that hundreds of new viruses emerge within minutes.
As they trace their path of destruction from cell to cell, the viruses engage in only one activity—reproduction. For this reason scientists compare them to genes,
the basic units of creation that enable every living thing to produce descendants like itself. Like genes, viruses breed true; an influenza virus won’t begin to produce smallpox viruses any more than an elephant will give birth to kittens.
But viruses, again like genes, are capable of mutation within certain limits, and a mild strain of any disease may suddenly change to a more virulent variety. Epidemiologists explain that the disastrous influenza pandemic that killed twenty million people all over the world in 1918-19 was caused by a virus mutation that produced a new strain of the disease, deadly because of its very newness. Since no one had ever been exposed to it before, no one had developed an immunity against it. Only two influenza strains, A and B, are in current circulation, but another mutation could create a dangerous new variant at any time.
Immunity, your defense against infection, is the process that prevents a virus from rampaging endlessly through your body. The entry of the virus stimulates the production of a blood protein called gamma globulin. The gamma globulin particles are called antibodies because each one is an exact fit for each particle of virus; by enveloping and smothering the viruses they fight off the disease. How you fare when a virus attacks you depends to a large extent on how fast your blood can produce antibodies against that particular disease.
After you fight off a virus, you're immune to the disease it causes as long as the antibodies continue to circulate in your blood stream. Some antibodies, like those produced by the common cold, last only a few weeks, while others such as measles usually last a'lifetime. One reason an infant is immune to most in-
fections for the first few months of life is the fact that his blood contains some of his mother’s antibodies.
Even if you haven’t actually had a particular disease, your doctor may have a way of providing an artificial immunity against it. Injections of gamma globulin from the blood of people who have had polio or measles confer temporary immunity. Vaccination with the virus itself protects you longer, even if it’s a killed virus like the one used in Salk vaccine. Vaccination with live virus is the method most effective but also most dangerous; it can be used only against diseases for which laboratory workers have developed a non-virulent strain. For years researchers passed the virus of yellow fever through various animal cells—mouse brains, monkey kidneys, chick embryos—until a series of mutations finally produced a strain of living virus called 17D, w'hich induces you to grow antibodies against yellow fever without suffering symptoms of the disease.
Today, new vaccines against diseases such as polio are hailed as lifesavers, but earlier public reaction to vaccination was anything but favorable. Pioneers like Jenner and Pasteur found patients weren’t entirely happy about having live germs let loose inside them. In Canada
the process was opposed on religious grounds during the great smallpox epidemic that ravaged Montreal in the summer of 1885. One hot September night, enforced vaccination touched off a riot among French-Canadian citizens who regarded artificial immunization as a transgression of God's will. Though twenty thousand people had caught the disease, health officials were besieged on this evening by a howling mob of antivaccinationists who wrecked the city hall, beat up the chief of police, hurled threats at the mayor and aldermen and set fire to the offices of the Montreal Herald. Nowadays only a few' diehards object to vaccination.
Current research is focused on the development of a live antipolio vaccine that will give longer immunity than the Salk vaccine, which uses killed virus. Polio work, probably the most publicized and most accelerated medical project of the last decade, directly owes its spectacular success to four recent developments:
• The discovery that polio virus can be grow'n in live monkey kidney cells inside a test tube, for which Dr...John F. Enders of Harvard won a Nobel Prize in 1954. Scientists had for years been growing viruses in test tubes, as well as in live laboratory animals and hen’s eggs, but no one had previously succeeded in tissue culture of polio virus. Bymaking antipolio vaccine a practical possibility, Enders gave tremendous impetus to virus research in general.
• The perfecting of the electron microscope, a complex instrument that costs upwards of twelve thousand dollars and magnifies up to sixty thousand times. Since most viruses are so small that twenty million of them could perch on the head of a pin, they can’t be seen at all through an ordinary microscope. With an electron microscope, laboratory workers can photograph viruses enlarged to the size of Rice Krispies, which some of them resemble, and view an extraordinary phenomenon: the spread of virus infection across a sheet of living cells. Similar in size, the cells normally present a regular pattern like a honeycomb. But when the tissue is injected with a virus, all regularity of pattern soon vanishes. Some cells are destroyed; others swell to giant size in their attempt to feed the insatiable virus.
• The use of isotopes to trace the course of virus infection inside the cell. First the host cells are grown in a medium that contains radioactive phosphorus, so that the phosphorus is incorporated into the tissue. When the cells are inoculated with a virus, it’s possible to see what use the virus makes of the cell material by watching what happens to the phosphorus.
• The development by Dr. Raymond Parker, and his associates at the Connaught Laboratories in Toronto, of a chemical medium in which to grow cells, which were then used to grow viruses for the production of Salk vaccine. The value of this artificial medium lies in its freedom from the extra germs often carried in the old-fashioned animal-serum medium, which sometimes caused virus infections or hypersensitivity reactions in the people vaccinated.
Last year these delicate new techniques enabled Dr. H. L. Ormsby of the department of ophthalmology at the University of Toronto, and his research group headed by Dr. Ann Fowle, to anticipate last summer’s epidemic of fever caused by a virus belonging to a recently isolated group called the APC (adenoidal - pharyngeal - conjunctival) viruses. Early in 1955 Dr. Ormsby found that several adult patients sent to him by Toronto oculists and public clinics had a peculiar eye infection which he recognized as the product of type 3 APC virus. This infection, pharyngoconjunctival fever, a variety of pinkeye first spotted in Colorado in 1951, is dangerous for adults because it often causes tiny opaque spots to form on the cornea of the eye, temporarily impairing vision. In children it appears as a high fever with sore eyes and throat but does no lasting damage.
Remembering that the disease had caused epidemics in swimming pools in two U. S. cities, Dr. Ormsby set up a research team with Dr. Rhodes and assistant Frances Doanc at the Hospital for Sick Children. At the beginning of August children all over Toronto began catching the fever. Highly contagious, it spread like wildfire through the city’s swimming pools; one pool in North Toronto bred 112 cases within the month. “This disease is so new that we do not know when or where to expect the next epidemic,” Dr. Ormsby says. Frances Doanc adds, “We can’t suggest any treatment for APC diseases until we know more about the viruses themselves.”
Another APC virus, Type 8, causes a form of conjunctivitis that first broke out in shipyards on the U. S. west coast during the war and hit 549 workers at the Ford Motor Company in Windsor, Ont., in 1951. Still another is the source of an influenza-like illness that seems to specialize in attacking new army recruits.
A virus that hasn’t yet been trapped is the one that causes infective hepatitis, a liver disease commonly called jaundice because yellow skin i« usually its most obvious symptom. Since it thrives on poor sanitation, hepatitis has always been a wartime camp follower, but has become a serious peacetime health problem in North America only within the last ten years. Before 1952. the number of cases reported in Canada never rose above a few hundred and the incidence of cases was often less than one in a hundred thousand people. In 1954, with 4,567 reported cases, 104 of them fatal, the incidence jumped to more than thirty cases in each hundred thousand. In the same year, nearly fifty thousand cases were reported in the U. S. Part of this startling increase is undoubtedly due to more accurate diagnosis and reporting, but many doctors believe the disease has really become more common.
Infective hepatitis has a strange stepbrother called serum hepatitis because it's carried only in blood and contracted from transfusion or improperly sterilized needles. Serum hepatitis made its most dramatic appearance in the spring of 1942, just after the U. S. entered the war. Eighty thousand recruits who had been inoculated with certain batches of yellow-fever vaccine came down with jaundice; serum hepatitis had accidentally been transmitted along with the live yellow-fever virus.
Although the two kinds of hepatitis have different incubation periods and modes of transmission, they share the same uncomfortable symptoms—fatigue, loss of appetite, headache, stomach ache, jaundice and sometimes fever. Once you’ve caught either disease, the doctor can’t prescribe anything except plenty of rest and a diet high in proteins, carbohydrates and vitamins. Although you’ll probably recover within three months, hepatitis may permanently damage your liver.
Another self-limiting illness that drugs won’t cure is infectious mononucleosis or glandular fever. Like hepatitis it seems more prevalent, especially among young
adults under thirty-five. After making a five-year study of mononucleosis in the Royal Navy, Surgeon Commander M. A. Rugg-Gunn noticed that the number of cases rose steadily and reported, “One must conclude that the disease is becoming commoner amongst this particular age group.”
Mononucleosis is a chameleon disease with many possible symptoms, including swollen glands, sore throat, exhaustion and jaundice, but its most significant signs are a swollen spleen and a characteristic blood pattern produced by abnormal lymphocytes, diseased blood cells that can circulate almost anywhere in the body. Although no one knows what causes this condition, some doctors suspect a virus transmitted by kissing. Others suggest the disease is a hypersensitive reaction to overdosing with penicillin and prophylactic vaccines. Both groups cite as evidence the high incidence of mononucleosis in the armed services shortly after Christmas, the season with the most social activity—and the most inoculations.
Though the “hypersensitivity” theory of glandular fever isn’t widely held, many health experts warn us that we may be getting too sanitary for our own good. Our high living standard has built-in hazards:
• Overuse of antibiotics is stimulating new strains of drug-resistant bacteria.
• A lower death rate may mean that the world is breeding more people than it can feed. For hundreds of years, infectious disease was the most important agent in preventing overpopulation. Within the last century, science has upset this natural balance of economy.
• Reduced exposure to infection gives us less chance to develop natural immunity. The rise of hepatitis and paralytic polio stems directly from twentiethcentury improvement in sanitation. Polio was considered a rare, non-infectious
disease until about sixty years ago when it first began to appear in epidemic form in areas with a high standard of hygiene —Scandinavia, Australia, New Zealand, the northeastern U. S. and Canada. But authorities agree that countries with primitive hygiene owe their freedom from serious cases of polio to the fact that the disease is circulating perennially in the population, causing subclinical infections so mild that illness is hardly apparent. Investigators have found that half the children in Mexico develop polio immunity before the age of three, while more than half the children in wealthier sections of U. S. cities are still susceptible at fourteen.
Some authorities suggest that children should be exposed to mild forms of the common infections before they’re twelve. Most virus diseases hit adults hard and sometimes tragically. If a woman catches German measles in early pregnancy, she’s likely to lose her baby or give birth to a child with congenital defects of the eyes, ears or heart. Her chance of having a normal child has been estimated as low as fifteen percent.
For many years scientists have suspected viruses as one possible source A>f an illness that doesn’t appear to be infectious at all—cancer. Two months ago. Dr. Wendell M. Stanley of the University of California told doctors attending a National Cancer Conference in Detroit, “The recent findings in the virus field indicate that the virus problem and the cancer problem are one and the same. The time has come when we should assume that viruses are responsible for most, if not all, kinds of cancer, including cancer in man, and design our experiments accordingly. The fact that viruses have not yet been seriously implicated in human cancer does not mean that they are not there.”
On the other hand, most doctors point out that virus research is only a small part of the complicated cancer picture. “Many
authorities would fail to go along with Dr. Stanley’s claim,” comments Dr. Rhodes of the Hospital for Sick Children. “Our new techniques for studying viruses justify a re-examination of the whole question, but until such studies are done it would be better to defer judgment.”
The relationship between viruses and cancer, which no one fully understands, may have something to do with the way a virus stimulates abnormal growth in the cells it attacks. It also involves the fact that viruses behave like genes, our basic reproduction units. Some scientists think cancer may originate when a virus invades a cell and hides among the cell’s own genes. Over the years, as the genes breed, the cell resembles a revolver loaded for Russian roulette. Eventually the virus-gene may cause cancer or induce a cancer-susceptible condition waiting to be touched off by some other agent such as coal tar, radiation or old age.
Although experiments with human cancer aren’t feasible, researchers at the University of Montreal and the Banting Institute in Toronto are working on two types of animal cancer for which virus origin has been proved, leukemia in mice and a malignant tumor that attacks certain fish. A Minnesota virologist, Dr. John J. Bittner, has actually developed a vaccine against a virus that causes breast tumor in mice.
At the Sloan-Kettering Institute in New York City, a group of cancer specialists under Dr. Alice Moore arc using viruses not to grow tumors, but to destroy them. A virus begins its work by accelerating the cell’s growth, but often ends by killing it. Dr. Moore’s team attacks cancer with certain viruses that localize in the tumor and destroy it without damaging surrounding normal tissue.
Some day virus research may provide a cure for cancer, curb the spread of infectious disease and even solve the enigma of the life process itself. We can’t study our reproductive units, the genes, because they’re locked inside body tissue, but we can isolate organisms which are very like genes—viruses. If we learn how viruses multiply, we may eventually understand the operation of genes. Future scientists may actually use this new knowledge to change the heredity of living organisms and perhaps enable people to produce healthier descendants.
What will we do with this new power?' Each year the virologists publish reports whose eagerness can’t be hidden even by the cautious jargon of the medical journals. But here and there some more contemplative observer warns us that we may not be equal to our responsibilities. Some future nation may purposely breed a hyper-virulent virus to unleash on its enemies after immunizing its own citizens.
“In the insane logic of power politics the ultimate weapon is the virus disease which will spread through and destroy those unwilling to accept domination but spare those who have submitted." observes Sir Macfarlane Burnet, Director of the Walter and Eliza Hall Institute for Medical Research in Melbourne, Australia. “I see no reason why with the continuation of current types of research it should not be physically possible to produce such a weapon in twenty or thirty years’ time.”
Like the nuclear physicists, today’s students of virology have their hands on one of the world's most potent powder kegs. Some of us may live long enough to see whether their secret will be used for the service or annihilation of mankind. ★