'The Great Influenza' and 'Microbial Threats to Health': Virus Alert

March 14, 2004

By BARRY GEWEN

The numbers astonish and horrify. According to the earliest estimates, 20 million people died during the flu pandemic of 1918. That figure is still used in classrooms and textbooks, but as John M. Barry tells us in ''The Great Influenza,'' it's certainly too low. Modern experts say that 20 million may have died in India alone, and they calculate the total number of victims at somewhere between 50 million and 100 million worldwide. No disease in human history has caused so many fatalities, not even the Black Death. The 1918 influenza pandemic killed more people in 24 weeks than AIDS has in 24 years.

In the United States, about one-quarter of the population, more than 25 million people, took ill, and about 675,000 died (a comparable figure for today's population would be 1,750,000). Undertakers ran out of coffins. Morgues ran out of space. Corpses were placed in spare rooms, in closets, on porches, until they could be collected for mass graves. The odor must have been unbearable.

Most diseases are particularly hard on the very young and the very old, so that a graph of deaths looks like a ''U.'' But one especially insidious feature of the 1918 flu was that it was most severe on those in the prime of life; its mortality graph looks like a cockeyed ''W.'' Life expectancy in the United States for 1918 dropped by 10 years.

The youthful Franklin D. Roosevelt got sick. So did the journalist Walter Lippmann, and Lloyd George in England. In Austria, the artist Egon Schiele perished. The pandemic probably changed the course of history. Erich von Ludendorff, the German Army chief of staff, claimed that the flu caused the failure of his spring offensive, hastening the end of World War I. And during the Paris peace conference, at the height of negotiations, Woodrow Wilson was thrown off course after he fell ill with a 103 temperature; observers report that he was not the same man when he returned to the bargaining table. Little wonder that one leading physician, a former president of the American Medical Association, thought he might be witnessing the end of civilization.

Though influenza, with its associated disease, pneumonia, continues to carry off about 36,000 victims each year in the United States, our notion of the illness is relatively benign: a week in bed and then back to work. Most sufferers in 1918 had the kind of aches and pains we would recognize today, but 10 to 20 percent went through a physical nightmare, even if they did survive it -- high fever, chills, vomiting, incontinence, delirium. Many turned blue because their lungs were too weak to deliver oxygen to the blood. Some coughed so hard they ruptured abdominal muscles, or became so sensitive to any contact that they screamed when touched. Others could not move their eyes without enduring intense pain. Blood spurted from the nose, ears, eyes. Sometimes air pockets formed under the skin, so that when a patient was turned over, his body crackled and popped. Death came instantly to some; they literally keeled over in the street. Others thought they had recovered, only to succumb 10 days or two weeks later.

This historic catastrophe has not received the attention it deserves. The book to consult until now has been ''America's Forgotten Pandemic,'' by Alfred W. Crosby, first published in 1976 and reissued last year with a new preface. ''Flu,'' by Gina Kolata, a science reporter for The New York Times, goes over some of the territory, but she is really concerned with the efforts of present-day scientists to recover the virus that caused the pandemic. ''The Great Influenza'' is easily our fullest, richest, most panoramic history of the subject. Barry, who in the past has written about both cancer and the Mississippi flood of 1927, ranges widely, from the physiology of viruses to the development of the American Red Cross.

He is a good teacher, in part because he assumes that his readers don't know anything. He explains the technical stuff clearly, with nice, homey analogies: the difference between antigen drift and antigen shift, for instance, is presented in terms of football players changing their uniforms. One is treated to mini-lectures in microbiology, immunology, epidemiology. Unfortunately, Barry is a teacher who doesn't know when to stop -- or start. Do we have to begin with Hippocrates, Galen and the history of medicine? The biographies of even his leading figures are too detailed, and Barry feels no compunction about pausing to offer little op-ed digressions on such matters as free speech and the dangers of government repression. Sometimes the narrative doesn't flow so much as trickle. Still, when the book finally arrives at the pandemic, it becomes gripping.

Barry organizes his story as a conflict between medicine and disease. The influenza pandemic, he writes, was ''the first great collision between nature and modern science''; ''for the first time, modern humanity, a humanity practicing the modern scientific method, would confront nature in its fullest rage.'' In this war the genuine heroes were the doctors and nurses on the front lines. Most worked to the point of collapse, risking their lives against an unfathomable killer. Many didn't survive. They tried everything to heal their patients, or at least ease the suffering. If there was no vaccine for the flu, perhaps vaccines against other diseases, like typhoid, could do some good. In Illinois, 18 different ones were used. Because quinine was effective against malaria, it was employed, too. Doctors prescribed codeine, morphine, heroin. They recommended gargling, eating properly and chewing food thoroughly. In a therapeutic throwback, some suggested bleeding the sick. No doubt there were places where leeches were seen again. Nothing worked, and the most effective procedure turned out to be the care provided by the nurses, who kept patients hydrated, rested and warm.

WHERE medicine failed, a panicky public rushed in with its own theories and prescriptions. Laws were hastily passed. In Prescott, Ariz., it became illegal to shake hands. Alfred Crosby writes that San Francisco required its citizens to wear gauze masks -- even though the minute influenza virus could pass easily through the webbing -- and the police raided hotels to arrest the barefaced. Scapegoats could be found everywhere -- Germans, of course, and the Bayer drug company because of its German origins. The health commissioner of Denver pointed his finger at the city's Italian immigrants. Somehow, people in Phoenix decided dogs were the carriers, and the police began killing strays, while owners killed their pets.

The greatest responsibility for halting the pandemic fell on the research scientists in their laboratories, and they performed magnificently, if ineffectually. They were a colorful cast of characters, some among them giants in the history of American medicine, others brilliant oddballs and social misfits, the kind of individuals who were happiest away from people, tediously pipetting liquids from one test tube to another. They were working almost entirely in the dark, and the clues they thought they possessed pointed in the wrong direction. The virus that caused influenza wasn't discovered until the 1930's, long after the last ripple of the pandemic had subsided.

That was then. What about now? Not so long ago, infectious diseases were spoken of largely in the past tense. Science was winning the war against smallpox, tuberculosis, pneumonia, polio and a host of other menaces. Deaths from infectious diseases in the United States were falling dramatically. In 1972, the Nobel laureate Macfarlane Burnet concluded that ''the most likely forecast about the future of infectious disease is that it will be very dull.'' Nobody says such things anymore. The unhappy fact is that we live on a contaminated, disease-ridden planet, full of infectious organisms that constantly evolve and take advantage of any new opportunity. ''Microbial Threats to Health,'' edited by Mark S. Smolinski, Margaret A. Hamburg and Joshua Lederberg, provides an authoritative overview of the current dangers, together with recommendations for improving public health around the world. The book was put together by a committee of scientists, and it reads like a book that was put together by a committee of scientists. It will never make the best-seller lists and was never intended to, yet it contains more horrors per page than any Stephen King novel.

The big three among diseases are AIDS, tuberculosis and malaria. Together, they account for approximately 500 million illnesses and six million deaths each year, with higher numbers on the way, particularly as the AIDS plague makes its way through China and India. About 100 million people contract dengue fever every year. Measles kills some 800,000 victims annually. Then there are the illnesses that require a medical dictionary: lymphatic filariasis (120 million cases), onchocerciasis (18 million), leishmaniasis (10 million), Chagas disease (20 million). It's true that these maladies are mostly confined to the poorer regions -- even AIDS is becoming mainly a third world condition -- but the toll they take cannot be overestimated. One out of every two deaths in developing countries is due to infectious diseases.

Meanwhile, the threat to the United States and other developed countries is growing, partly because of globalization and rapid transportation, which blur the lines between the third and first worlds, partly because of new bacterial strains that resist antibiotics. In just three years West Nile virus, first identified in Uganda, spread to 39 states. Technology has given us homegrown ailments: Legionnaires' disease from air-conditioning, toxic shock syndrome from superabsorbent tampons. Previous generations did not need to worry about SARS, mad cow disease or Lyme disease. And now there is also bioterrorism to lose sleep over.

AS for influenza, both John Barry and the editors of ''Microbial Threats to Health'' say what just about everyone who has studied the disease says: a new pandemic is inevitable. There have been scares in the past, most notably the swine flu fiasco of 1976, when 40 million Americans were vaccinated and several hundred may -- or may not -- have developed a nerve disorder as a result. In 1997, to prevent the spread of a Hong Kong flu virus that killed six people, every chicken in the city was destroyed, 1.2 million birds. Last year, after a new strain emerged on European poultry farms, nearly 30 million animals were wiped out to prevent the virus from adapting to human beings. And as you read this, millions of birds are being eliminated in Asia and elsewhere in an effort to contain avian flu. No one can predict what will happen when the next pandemic erupts, how close it might come to the 1918 experience -- the Centers for Disease Control and Prevention has said that in a worst-case scenario 422,000 Americans would die -- but there is good news and bad news.

The good news is that antiviral vaccines and drugs are available to fight the influenza virus, and that antibiotics can be used against secondary pneumonia infections. The bad news is that the virus mutates so rapidly that the drugs may not be wholly effective and that, as we saw last autumn, shortages of supplies could occur if the virulence of the disease outruns expectations. The good news is that the World Health Organization has an effective influenza monitoring system in place, involving more than 100 laboratories worldwide. The bad news is that because of modern transportation, the virus could spread around the globe within days, and before any symptoms had appeared. The good news is that we have a thorough understanding of the virus's structure -- its spherical shape, its spiky surface and the eight single-stranded RNA segments that make up its core. Indeed, we may soon be able to replicate the 1918 strain in the laboratory. But we still don't understand why it was so lethal. And that may be the worst news of all.

Barry Gewen is an editor at the Book Review.