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

by John M. Barry

William Halsted, who introduced rubber gloves into surgery, who insisted upon preparation and thought prior to every step. He took such care that William Mayo once joked that his patients were healed by the time he finished, but the Mayo brothers also stated that they owed him a tremendous

central clearinghouse of scientific medicine. Indeed, he became the central clearinghouse. As founding editor of the Journal of Experimental Medicine, the first and most important American research journal,

He became a national figure, first within the profession, then within science, then in the larger world, serving as president or chairman of nineteen different major scientific organizations, including the American Medical Association, the American Association for the Advancement of Science, and the National Academy of Sciences. Stanford president Ray Wilbur neither flattered nor overstated when in 1911 he wrote him, “Not to turn to you for information in regard to the best men to fill vacancies in our medical school would be to violate all the best precedents of American medical education.” Welch had, said one colleague, “the power to transform men’s lives almost by the flick of a wrist.”

In 1880 Pasteur—who observed, “Chance favors the prepared mind”—was trying to prove he had isolated the cause of chicken cholera. He inoculated healthy chickens with the bacteria. They died. Then chance intervened. He had put aside a virulent culture for several days, then used it to inoculate more chickens. They lived. More significant, those same chickens survived when exposed to other virulent cultures. Crediting Jenner for the idea, he tried to weaken, or “attenuate,” his word, cultures and use them to immunize birds against lethal bacteria. He succeeded.

One of the deadliest of childhood diseases was diphtheria. Usually it killed by choking its victims to death—by generating a membrane that closed

breathing passages. In Spain the disease was called el garrotillo, “the strangler.”

In 1884, German scientist Friedrich Loeffler isolated the diphtheria bacillus from throats of patients, grew it on a special medium (laboratories today still use “Loeffler’s serum slope” to grow the bacteria from suspected cases), and began careful experiments in animals that took several years. His work suggested that the bacteria the...

In the keynote speech at the next meeting of the Association of American Physicians, an association created to foster scientific medicine, Welch said, “The discovery of the healing serum is entirely the result of laboratory work.

eleemosynary

hope to become a science,” Gates explained, “until . . . qualified

Simon Flexner,

Flexner was small and wiry, almost wizened, and no one ever called him charming. He had an edgy insecurity and said, “I have never been educated in any branch of learning. There are great gaps

To fill the gaps, he read. “He read,” his brother Abraham said, “as he ate.” He devoured books, read everything, read omnivorously, from English literature to Huxley and Darwin. He felt he had to learn. His insecurities never fully left him. He talked of “sleepless nights and days of acute fear . . . a maddening nervousness which prevented me from having a quiet moment.”

Welch arranged a fellowship for him in Germany, and four years later he became professor o...

Nobel laureate Peyton Rous later called Flexner’s scientific papers “a museum in print, only they stir with life; for he experimented as well as described.”

place of the comfort and monastic purpose and intimacy that Welch gave the Hopkins, Flexner made Rockefeller sharp, edgy, cold.

Diphtheria antitoxin

Nobel laureates Alexis Carrel and Karl Landsteiner, both of whose work was recognized early,

Peyton Rous, whose undergraduate and medical degrees both came from the Hopkins, would win the Nobel Prize for his discovery that a virus could cause cancer.

Cole had wide interests and late in life wrote a two-volume, 1,294-page study of Oliver Cromwell, the Stuarts, and the English Civil War.

the Carnegie Foundation commissioned Simon Flexner’s brother Abraham to survey medical education. Although not a doctor, Flexner had been an undergraduate at the Hopkins—he said that even among undergraduates

“research was the air we breathed”—and had already demonstrated both a ruthless, unforgiving judgment and a commitment to advancing model educational institutions.

In 1910, the same year the Rockefeller Institute Hospital opened, his report Medical Education in the United States and Canada appeared. It soon came to be known simply as “The Flexner Report.” According to it, few—very, very few—schools met his standards, or any reasonable standard. He dismissed many schools as “without redeeming features of any kind

At North Carolina Medical College Flexner quoted a faculty member saying, “‘It is idle to talk of real laboratory work for students so ignorant and clumsy. Many of them, gotten through advertising, would make better farmers.’”

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

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

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.

The Johns Hopkins School of Hygiene and Public Health was scheduled to open October 1, 1918. Welch had resigned as a professor at the medical school to be its first dean.

Farmers lived in close proximity to hogs and fowl, with

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

Miner had seen influenza often. He diagnosed the disease as influenza. But he had never seen influenza like this.

People suffering from influenza shed virus—expel viruses that can infect others—for

The same week that Homer Moody and a dozen others in Jean, Kansas, fell ill, a young soldier named Dean Nilson came home to Jean on leave from Camp Funston, located three hundred miles away within the vast Fort Riley military reservation.

So army regulations—written for health reasons—detailing how much space each man should have were violated, and men were stacked in bunks with insufficient clothing and bedding and inadequate heating. That forced them to huddle ever more closely together around stoves.

NO ONE WILL EVER KNOW with absolute certainty whether the 1918–19 influenza pandemic actually did originate in Haskell County, Kansas. There are other theories of origin, including France, Vietnam, and China. But Frank Macfarlane Burnet, a Nobel laureate who lived through the pandemic and spent most of his scientific career studying influenza, later concluded that the evidence was “strongly suggestive” that the 1918 influenza pandemic began in the United States, and that its spread was “intimately related to war conditions and especially the arrival of American troops in France.” Numerous other scientists agree with him. And the evidence does strongly suggest that Camp Funston

experienced the first major outbreak of influenza in America; if so, the movement of men from an influenza-infested Haskell to Funston also strongly suggests Haskell as the site of origin.

in biology, especially at the cellular and molecular levels, nearly all activity depends ultimately upon form, upon physical structure—upon what is called “stereochemistry.”

There are three different types of influenza viruses: A, B, and C. Type C rarely causes disease in humans. Type B does cause disease, but not epidemics. Only influenza A viruses cause epidemics or pandemics, an epidemic being a local or national outbreak, a pandemic a worldwide one.

Influenza viruses did not originate in humans. Their natural home is in wild aquatic birds, and many more variants of influenza viruses exist in birds than in humans.

Pandemics often come in waves, and the cumulative “morbidity” rate—the number of people who get sick in all the waves combined—often exceeds 50 percent. One virologist considers influenza so infectious that he calls it “a special instance” among infectious diseases, “transmitted so effectively that it exhausts the supply of susceptible hosts.”

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.

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.

even when outbreaks are not deadly as a whole, influenza strikes so many people that even the mildest viruses almost always kill. Currently in the United States, even without an epidemic or pandemic, the Centers for Disease Control estimates that influenza kills from 3,000 to 56,000 Americans a year, depending chiefly on the virulence of that year’s virus.

The virus itself is nothing more than a membrane—a sort of envelope—that contains the genome, the genes that define what the virus is. It is usually spherical (it can take other shapes), about 1/10,000 of a millimeter in diameter, and it looks something like a dandelion with a forest of two different-shaped protuberances—one roughly like a spike, the other roughly like a tree—jutting out from its surface. These protuberances provide the virus with its actual mechanism of attack.

The protuberances akin to spikes are hemagglutinin. When the virus collides with the cell, the hemagglutinin brushes against molecules of sialic acid that jut out from the surface of cells in the respiratory tract.

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. Inside this vesicle, this bubble, shape and form shift and create new possibilities as the hemagglutinin faces a more acidic environment. This acidity makes it cleave in two and refold itself into an entirely different shape. The refolding process somewhat resembles taking a sock off a foot, turning it inside out, and sticking a fist in it. The cell is now doomed.

From the time an influenza virus first attaches to a cell to the time the cell bursts generally takes about ten hours, although it can take less time or, more rarely, longer. Then a swarm of between 100,000 and 1 million new influenza viruses escapes the exploded cell.

Influenza is an RNA virus. So are HIV and the coronavirus. And of all RNA viruses, influenza and HIV are among those that mutate the fastest. The influenza virus mutates so fast that 99 percent of the 100,000 to 1 million new viruses that burst out of a cell in the reproduction process are too defective to infect another cell and reproduce again. But that still leaves between 1,000 and 10,000 viruses that can infect another cell.

Dendritic cells attack bacteria and viruses indiscriminately, engulf them, then “process” their antigens and “present” those antigens—in effect they chop up an invading microorganism into pieces and display the antigens like a trophy flag.

The dendritic cells then travel to the spleen or the lymph nodes, where large numbers of other white