The Great Influenza: The Epic Story of the Deadliest Plague in History

by John M. Barry

Normally influenza chiefly kills the elderly and infants, but in the 1918 pandemic roughly half of those who died were young men and women in the prime of their life, in their twenties and thirties. Harvey Cushing, then a brilliant young surgeon

Although the influenza pandemic stretched over two years, perhaps two-thirds of the deaths occurred in a period of twenty-four weeks, and more than half of those deaths occurred in even less time, from mid-September to early December 1918.

two months later Democrat Samuel Tilden would win the popular vote by a comfortable margin. But he would never take office as president. Instead the Republican secretary of war would threaten to “force a reversal” of the vote, federal troops with fixed bayonets would patrol Washington, and southerners would talk of reigniting the Civil War. That crisis would ultimately be resolved through an extra-constitutional special committee and a political understanding: Republicans would discard the voting returns of three states—Louisiana, Florida, South Carolina—and seize a single disputed electoral vote in Oregon to keep the presidency in the person of Rutherford B. Hayes. But they also would withdraw all federal troops from the South and cease intervening in southern affairs, leaving the Negroes there to fend for themselves.

The war involving the Hopkins was more muted but no less profound. The outcome would help define one element of the character of the nation: the extent to which the nation would accept or reject modern science and, to a lesser degree, how secular it would become, how godly it would remain.

ruthlessness. His dicta included the pronouncement: “The foundation of morality is to have done, once and for all, with lying.”

The two most important questions in science are “What can I know?” and “How can I know it?”

Then in 1798 Edward Jenner, a student of Hunter’s—Hunter had told him “Don’t think. Try.”—published his work. As a young medical student Jenner had heard a milkmaid say, “I cannot take the smallpox because I have had cowpox.” The cowpox virus resembles smallpox so closely that exposure to cowpox gives immunity to smallpox. But cowpox itself only rarely develops into a serious disease. (The virus that causes cowpox is called “vaccinia,” taking its name from vaccination.)

One truth has not changed from the time of Hippocrates until today: when faced with desperate patients, doctors often do not have the heart—or, more accurately, they have too much heart—to do nothing. And so a doctor, as desperate as the patient, may try anything, including things he or she knows will not work as long as they will not harm. At the least, the patient will get some solace. One cancer specialist concedes, “I do virtually the same thing myself. If I’m treating a teary, desperate patient, I will try low-dose alpha interferon, even though I do not believe it has ever cured a single person. It doesn’t have side effects, and it gives the patient hope.”

For the first time in history, a physician was creating a reliable and systematic database. Physicians could have done this earlier. To do so required neither microscopes nor technological prowess; it required only taking careful notes.

Yet the real point at which modern medicine diverged from the classic was in the studies of pathological anatomy by Louis and others. Louis not only correlated treatments with results to reach a conclusion about a treatment’s efficacy (he rejected bleeding patients as a useless therapy), he and others also used autopsies to correlate the condition of organs with symptoms. He and others dissected organs, compared diseased organs to healthy ones, learned their functions in intimate detail.

Disease began to be seen as something that invaded solid parts of the body, as an independent entity, instead of being a derangement of the blood. This was a fundamental first step in what would become a revolution. Louis’s influence and that of what became known as “the numerical system” could not be overstated. These advances—the stethoscope, laryngoscope, ophthalmoscope, the measurements of temperature and blood pressure, the study of parts of the body—all created distance between the doctor and the patient, as well as between patient and disease; they objectified humanity. Even though no less a personage than Michel Foucault condemned this Parisian movement as the first to turn the human body into an object, these steps had to come to make progress in medicine. But the movement was condemned by contemporaries also. Complained one

For if he did no revolutionary science, he lived a revolutionary life. He was personality and theater; he was impresario, creator, builder. Like an actor on a live stage, his life was a performance given once, leaving its impact upon his audience, and only through them echoing in time and place. He led the movement that created the greatest scientific medical enterprise, and possibly the greatest enterprise in any of the sciences, in the world. His legacy was not objectively measurable, but it was nonetheless real. It lay in his ability to stir other men’s souls.

Yet for the rest of Welch’s life he also seemed somehow, in some indefinable way, to generate similar if less intense sentiments in others. He did so without effort. He charmed without effort. He inspired without effort. And he did so without his reciprocating any personal connection, much less attachment. A later age would call this “charisma.”

The greatest challenge of science, its art, lies in asking an important question and framing it in a way that allows it to be broken into manageable pieces, into experiments that can be conducted that ultimately lead to answers. To do this requires a certain kind of genius, one that probes vertically and sees horizontally.

Welch had a vital and wide curiosity, but he did not have this deeper wonder. The large aroused him. But he could not see the large in the small. No question ever aroused a great passion in him, no question ever became a compulsion, no question ever forced him to pursue it until it was either exhausted or led him to new questions. Instead he examined a problem, then moved on.

First, he had not only knowledge but judgment. He had an extraordinary ability to hear someone describe his or her experiments, or read a paper, and immediately define the crucial points still obscure, the crucial series of experiments needed to clarify them. It was as if, although he could not himself conjure, he knew the techniques of conjuring and could teach others conjury.

But his most singular quality was not physical. He seemed so centered and comfortable with himself that he gave comfort to those around him. He exuded confidence without arrogance, smugness, or pomposity. In his disputes—and he had many with those outsiders who resisted changes—he never raised his voice, never seemed to feel, according to a man who watched him for decades, “the exuberant joy of putting an opponent down.”

Science is not democratic. Votes do not matter.

Timid of nature or not, Cole would not yield. Flexner did. As a result, the Rockefeller Institute Hospital applied science directly to patient care, creating the model of clinical research—a model followed today by the greatest medical research facility in the world, the Clinical Center at the National Institutes of Health in Bethesda, Maryland. That model allowed investigators to learn. It also prepared them to act.

Flexner concluded that more than 120 of the 150-plus medical schools in operation should be closed.

By the late 1920s, before the economic pressure of the Depression, nearly one hundred medical schools had closed or merged. The number of medical students, despite a dramatic increase in the country’s population, declined from twenty-eight thousand in 1904 to fewer than fourteen thousand in 1920; in 1930, despite a further increase in the country’s population, the number of medical students was still 25 percent less than in 1904.

Public health was and is where the largest numbers of lives are saved, usually by understanding the epidemiology of a disease—its patterns, where and how it emerges and spreads—and attacking it at its weak points. This usually means prevention. Science had first contained smallpox, then cholera, then typhoid, then plague, then yellow fever, all through large-scale public health measures, everything from filtering water to testing and killing rats to vaccination. Public health measures lack the drama of pulling someone back from the edge of death, but they save lives by the millions.

Epidemiological evidence suggests that a new influenza virus originated in Haskell County, Kansas, early in 1918. Evidence further suggests that this virus traveled east across the state to a huge army base, and from there to Europe. Later it began its sweep through North America, through Europe, through South America, through Asia and Africa, through isolated islands in the Pacific, through all the wide world. In its wake followed a keening sound that rose from the throats of mourners like the wind. The evidence comes from Dr. Loring Miner.

Viruses do not eat or burn oxygen for energy. They do not engage in any process that could be considered metabolic. They do not produce waste. They do not have sex. They make no side products, by accident or design. They do not even reproduce independently. They are less than a fully living organism but more than an inert collection of chemicals.

Whatever the origin, a virus has only one function: to replicate itself. But unlike other life forms (if a virus is considered a life form), a virus does not even do that itself. It invades cells that have energy and then, like some alien puppet master, it subverts them, takes them over, forces them to make thousands, and in some cases hundreds of thousands, of new viruses. The power to do this lies in their genes.

When a virus successfully invades a cell, it inserts its own genes into the cell’s genome, and the viral genes seize control from the cell’s own genes. The cell’s internal machinery then begins producing what the viral genes demand instead of what the cell needs for itself.

Coronaviruses (the cause of the common cold as well as SARS), parainfluenza viruses, and many other viruses all cause symptoms akin to influenza, and all are often confused with it. As a result, sometimes people designate mild respiratory infections as “flu” and dismiss them. But influenza is not simply a bad cold. It is a quite specific disease, with a distinct set of symptoms and epidemiological behavior. In humans the virus directly attacks only the respiratory system, and it becomes increasingly dangerous as it penetrates deeper into the lungs. Indirectly it affects many parts of the body, and even a mild infection can cause pain in muscles and joints, intense headache, and prostration. It may also lead to far more grave complications. The

By entering the cell, as opposed to fusing with the cell on the cell membrane—which many other viruses do—the influenza virus hides from the immune system. The body’s defenses cannot find it and kill it.

When antigen shift occurs, the immune system cannot recognize the antigen at all. Few people in the world will have antibodies that can protect them against this new virus, so the virus can spread through a population at an explosive rate.

Hemagglutinin occurs in eighteen known basic shapes, neuraminidase in nine, and they occur in different combinations with subtypes. Virologists use these antigens to identify what particular virus they are discussing or investigating. “H1N1,” for example, is the name given the 1918 virus, currently found in swine. An “H3N2” virus is circulating among people today.

The war had begun in 1914. Wilson had withstood this pressure. A German submarine had sunk the Lusitania in 1915 and he had not gone to war despite outrage in the press, instead winning a German commitment to limit submarine warfare. He had resisted other justifications for war. He could fairly campaign for reelection in 1916 on the slogan “He Kept Us Out of War.” And he warned, “If you elect my opponent, you elect a war.”

While Welch and his colleagues were revolutionizing American medicine, Jane Delano, Lavinia Dock—both of whom were students in Bellevue’s nursing program while Welch was exposing medical students there to new realities—and others were doing the same to nursing. But they fought not with an entrenched Old Guard in their own profession so much as with physicians. (Sometimes physicians, threatened by intelligent

Influenza causes pneumonia either directly, by a massive viral invasion of the lungs, or indirectly—and more commonly—by destroying certain parts of the body’s defenses and allowing so-called secondary invaders, bacteria, to infest the lungs virtually unopposed.

Spain actually had few cases before May, but the country was neutral during the war. That meant the government did not censor the press, and unlike French, German, and British newspapers—which printed nothing negative, nothing that might hurt morale—Spanish papers were filled with reports of the disease, especially when King Alphonse XIII fell seriously ill. The disease soon became known as “Spanish influenza” or “Spanish flu,” very likely because only Spanish newspapers were publishing accounts of the spread of the disease that were picked up in other countries.

There was Robert Prager, born in Germany but who had tried to enlist in the navy, attacked by a crowd outside St. Louis, beaten, stripped, bound in an American flag, and lynched because he uttered a positive word about his country of origin. And, after that mob’s leaders were acquitted, there was the juror’s shout, “I guess nobody can say we aren’t loyal now!” Meanwhile, a Washington Post editorial commented, “In spite of excesses such as lynching, it is a healthful and wholesome awakening in the interior of the country.”

also areas of hemorrhagic alveoli.” Then he demonstrated for them an innovation he had experimented with: the wearing of gauze masks by patients with respiratory disease. Welch called the mask “a great thing . . . an important contribution in prevention of spray infections.” He encouraged Capps to write an article for the Journal of the American Medical Association and advised Pearce to conduct studies of the masks’ effectiveness. Cole agreed: “This is a very important matter in connection with the prevention of pneumonia.”

Capps did write the JAMA article. He reported finding the masks so successful that after less than three weeks of experimenting he had abandoned testing and simply started using them as “a routine measure.” He also made the more general point that “one of the most vital measures in checking contagion” is eliminating crowding. “Increasing the space between beds in barracks, placing the head of one soldier opposite the feet of his neighbor, stretching tent flags between beds, and suspending a curtain down the center of the mess table, are all of proved value.”

Capps had planned a series of “very carefully controlled” experiments. But now, with nothing else to try, he administered the serum to all as it arrived—it was in short supply. It seemed to work. Two hundred and thirty-four men suffering from pneumonia received the serum; only 16.7 percent died, while more than half of those who did not receive it died. But it was in short supply.

On October 3, only five days after Krusen had let the parade proceed, he banned all public meetings in the city—including, finally, further Liberty Loan gatherings—and closed all churches, schools, theaters. Even public funerals were prohibited. Only one public gathering place was allowed to remain open: the saloon, the key constituency of the Vare machine. The next day the state health commissioner closed them.

In ten days—ten days!—the epidemic had exploded from a few hundred civilian cases and one or two deaths a day to hundreds of thousands ill and hundreds of deaths each day.

Those pockets of air leaking through ruptured lungs made patients crackle when they were rolled onto their sides. One navy nurse later compared the sound to a bowl of Rice Krispies, and the memory of that sound was so vivid to her that for the rest of her life she could not tolerate being around anyone who was eating Rice Krispies.

And it killed enough to depress the average life expectancy in the United States by more than ten years.

Investigators today believe that in the United States the 1918–19 epidemic caused an excess death toll of about 675,000 people. The nation then had a population between 105 and 110 million, while it was approaching 300 million in 2006. So a comparable figure today would be approximately 1,750,000 deaths.

the single greatest number of deaths occurred in men and women aged twenty-five to twenty-nine, the second greatest number in those aged thirty to thirty-four, the third greatest in those aged twenty to twenty-four. And more people died in each of those five-year groups than the total deaths among all those over age sixty.

But 1918 was different. Infants did die then in large numbers, and so did the elderly. But in 1918 the great spike came in the middle. In 1918 an age graph of the dead would look like a W. It is a graph that tells a story of utter tragedy.

And, finally, came the lungs. Physicians had seen lungs in such condition. But those lungs had not come from pneumonia patients. Only one known disease—a particularly virulent form of bubonic plague called pneumonic plague, which kills approximately 90 percent of its victims—ripped the lungs apart in the way this disease did. So did weapons in war. An army physician concluded, “The only comparable findings are those of pneumonic plague and those seen in acute death from toxic gas.” Seventy years after the pandemic, Edwin Kilbourne, a highly respected scientist who has spent much of his life studying influenza, confirmed this observation, stating that the condition of the lungs was “unusual in other viral respiratory infections and is reminiscent of lesions seen following inhalation of poison gas.” But the cause was not poison gas, and it was not pneumonic plague. It was only influenza.

Victims’ lungs were being ripped apart as a result of, in effect, collateral damage from the attack of the immune system on the virus. Since the respiratory tract must allow outside air to pass into the innermost recesses of the body, it is extremely well defended. The lungs became the battleground between the invaders and the immune system. Nothing was left standing on that battleground.

The immune system begins its defense far in advance of the lungs, with enzymes in saliva that destroy some pathogens (including HIV, which makes its home in most bodily fluids, but not in saliva, where enzymes kill it). Then it raises physical obstacles, such as nasal hairs that filter out large particles and sharp turns in the throat that force inhaled air to collide with the sides of breathing passageways. Mucus lines these passageways and traps organisms and irritants. Underneath the layer of mucus lies a blanket of “epithelial cells,” and from their surfaces extend “cilia,” akin to tiny hairs which, like tiny oars, sweep upward continuously at from 1,000 to 1,500 beats a minute. This sweeping motion moves foreign organisms away from places they can lodge and launch an infection, and up to the larynx. If something does gain a foothold in the upper respiratory tract, the body first tries to flush it out with more fluid—hence the typical runny nose—and then expel it with coughs and sneezes. These defenses are as physical as raising an arm to block a punch and do no damage to the lungs. Even if the body overreacts, this usually does no serious harm, although an increased volume of mucus blocks air passages and makes breathing more difficult. (In allergies these same symptoms occur because the immune system does overreact.)

There are more aggressive defenses. Macrophages and “natural killer” cells—two kinds of white blood cells that seek and destroy all foreign invaders, unlike other elements of the immune system that attack only a specific threat—patrol the entire respiratory tract and lungs. Cells in the respiratory tract secrete enzymes that attack bacteria and some viruses (including influenza) or block them from attaching to tissue beneath the mucus, and these secretions also bring more white cells and antibacterial enzymes into a counterattack; if a virus is the invader, white blood cells also secrete interferon, which can block viral infection. All these defenses work so well that the lungs themselves, although directly exposed to outside air, are normally sterile. But when the lungs do become infected, other defenses, lethal and violent defens...

What was killing young adults a few days after the first symptom was not the virus. The killer was the massive immune response itself.