The Great Influenza: The Epic Story of the Deadliest Plague in History - John M. Barry (2004)

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1. William Henry Welch, the single most powerful individual in the history of American medicine and one of the most knowledgeable. A wary colleague said he could “transform men’s lives almost with the flick of a wrist.” When Welch first observed autopsies of influenza victims, he worried, “This must be some new kind of infection or plague.”

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2. Welch and John D. Rockefeller Jr. (on the right) together created the Rockefeller Institute for Medical Research (now Rockefeller University), arguably the best scientific research institution in the world. Simon Flexner (on the left), a Welch protégé, was the institute’s first head; he once said that no one could run an institution unless he had the capacity to be cruel.

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3. Flexner brought the mortality rate for the most common bacterial meningitis down to 18 percent in 1910 without antibiotics. Today, with antibiotics, the mortality rate is 25 percent.

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4. A dense jungle-like growth of epithelial cells covers a healthy mouse trachea.

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5. Only seventy-two hours after infection the influenza virus transforms the same area into a barren and lifeless desert. White blood cells are patrolling the area, too late.

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6. The virus swept first through military bases, where men were jammed together despite the objections of Welch and Army Surgeon General William Gorgas. This is an army emergency hospital, probably a ward for convalescents.

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7. Army Surgeon General William Gorgas was determined that this would be the first war in which fewer American soldiers died of disease than from combat.

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8. Rupert Blue, the civilian surgeon general and head of the U.S. Public Health Service, was a master bureaucrat but failed to heed warnings of, seek advance information about, or prepare for the epidemic.

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9. Massachusetts was the first state to suffer huge numbers of civilian deaths. This is a hospital in Lawrence.

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10. I n Philadelphia the number of dead quickly overwhelmed the city’s ability to handle bodies. It was forced to bury people, without coffins, in mass graves and soon began using steam shovels to dig the graves.

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Posters and handouts spread warnings and advice. They also spread terror.

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13. The two messages in this photograph—the policeman’s protective mask and patriotism—epitomized a conflict of interest in public officials.

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14. All New York City workers wore masks. Note the absence of traffic on the street and pedestrians on the sidewalk. The same silent streets were seen everywhere. In Philadelphia a doctor said, “The life of the city had almost stopped.”

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15. Oswald T. Avery as a private, when the Rockefeller Institute became Army Auxiliary Laboratory Number One.

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16. A very in later life. Persistent and tenacious, he said, “Disappointment is my daily bread. I thrive on it.” Welch asked him to find the cause of influenza. His work on influenza and pneumonia would ultimately lead him to one of the most important scientific discoveries of the twentieth century.

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17. William Park, who made New York City’s municipal laboratories a premier research institution. His rigorous scientific discipline, when teamed with the more creative temperament of Anna Williams [below], led to dramatic advances, including the development of a diphtheria antitoxin still in use. The National Academy of Sciences hoped they could develop a serum or vaccine for influenza.

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18. Anna Wessel Williams was probably the leading female bacteriologist in the world. A lonely woman who never married, she told herself she would “rather [have] discontent than happiness through lack of knowledge,” and wondered “if it would be worthwhile to make the effort to have friends and if so how I should go about it.” From her earliest memories, she dreamed “about going places. Such wild dreams were seldom conceived by any other child.”

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19. The virus moved inexorably across the country. Here navy nurses and doctors await the onslaught.

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20. Military commanders tried to protect healthy men; at Mare Island in San Francisco sheets were hung in barracks to screen men from each other’s breathing.

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21. In most cities all public meetings were banned, all public gathering places—churches, schools, theaters, and saloons—closed. Most churches simply canceled services but this one in California met outdoors, a technical violation of the closing order but a response to the congregation’s need for prayer.

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22. Rufus Cole, the Rockefeller Institute scientist who had led the successful effort to develop a pneumonia vaccine and treatment just before the outbreak of the epidemic. He also made the Rockefeller Institute Hospital a model for the way clinical research is conducted, including at the National Institutes for Health.

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Seattle, like many other places, became a masked city. Red Cross volunteers made tens of thousands of masks. All police wore them. Soldiers marched through the city’s downtown wearing them.

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26. More than one scientist called Paul A. Lewis “the brightest man I ever met.” As a young investigator in 1908 he proved polio was caused by a virus and devised a vaccine that was 100 percent effective in protecting monkeys. It would be half a century before a polio vaccine could protect man. He too was one of the prime investigators searching for the cause of influenza, and a cure or preventative. Ultimately his ambition to investigate disease would cost him his life.

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27. In the late 1920s Richard Shope, Lewis’s protégé, unearthed a crucial clue in the search for the cause of influenza. While Lewis went to Brazilian jungles to investigate yellow fever, Shope continued his pursuit of influenza. He was the first to prove a virus caused the disease.

*The effort to correlate treatments and results has not yet triumphed. A “new” movement called “evidence-based medicine” has emerged recently, which continues to try to determine the best treatments and communicate them to physicians. No good physician today would discard the value of statistics, of evidence accumulated systematically in careful studies. But individual doctors, convinced either by anecdotal evidence from their own personal experience or by tradition, still criticize the use of statistics and probabilities to determine treatments and accept conclusions only reluctantly. Despite convincing studies, for example, it took years before cancer surgeons stopped doing radical mastectomies for all breast cancers.
      A related issue involves the methodology in “clinical studies”—i.e., studies using people. To stay with cancer as an example, Vince DeVita, former director of the National Cancer Institute; Samuel Hellman, a leading oncologist; and Steven Rosen berg, chief of the Surgery Branch of the National Cancer Institute coauthor a standard reference for physicians on cancer treatments. DeVita and Rosenberg believe that carefully controlled randomized studies—experiments in which random chance determines the treatment given a patient—are necessary to find out what treatment works best. Yet Hellman has argued in the New England Journal of Medicine that randomized trials are unethical. He believes that physicians must always use their best judgment to determine treatment and cannot rely on chance, even when the effectiveness of a treatment is unknown, even to answer a question about what treatment works best, even when the patient has given fully informed consent.

*The critics made some valid points. Clearly the attacking organism does not entirely determine whether someone gets sick. The same organism can attack two people, kill one, and not cause any symptoms in the other. An individual’s genes, immune system, environment, and even such factors as stress all affect susceptibility.
      As late as 1911 the head of the school training French army doctors in public health said that germs alone were “powerless to create an epidemic.” But that particular view was by then an idiosyncratic, not simply minority, opinion.

*Halsted had known Welch well in New York; both of them were trying to apply science to medicine. But Halsted began studying cocaine and became addicted. His life collapsed and he moved to Baltimore to be close to Welch. Once Halsted ended his addiction, Welch gave him a chance at the Hopkins, where he linked surgery to physiological research and became the most influential surgeon in the country and arguably the world. Halsted did marry, but he was eccentric and erratic and became addicted to morphine. It was unclear if Welch knew of this addiction.

*Nonetheless, people today often demand antibiotics from physicians and the physicians too often accommodate them. But antibiotics have no effect whatsoever on viruses. Administering them serves only to increase resistance to antibiotics by bacteria: bacteria that survive exposure to antibiotics become immune to them.

*In 2001 Australian scientist Mark Gibbs advanced a theory that the influenza virus can also “recombine” its genes. Recombination means taking part of one gene and combining it with part of another gene. It is like cutting all the cards of two decks in pieces, taping the pieces together randomly, then assembling the first fifty-two for a new deck. Recombination has been demonstrated in the laboratory, but most virologists are skeptical of Gibbs’s hypothesis.

*During the Vietnam War many physician-scientists joined the Public Health Service to avoid the draft. But their work did go on as usual. They were assigned to the National Institutes of Health, which enjoyed some of its most productive years in history because at the influx of talent.

*It would seem nurses needed their status protected. In the summer of 1918, the Treasury Department informed the secretary of war that army nurses taken captive, unlike soldiers, were not entitled to pay while they were prisoners of war. Outrage later forced a reversal of this policy.

*When antibiotics first appeared in the late 1930s and 1940s, they performed like magic, and much of this research was abandoned; in the early 1960s, public health officials were declaring victory over infectious disease. Now, with dozens of strains of bacteria developing resistance to drugs, with viruses gaining resistance even faster, with such diseases as tuberculosis, once considered conquered, making comebacks, investigators have returned to searching for ways to stimulate the immune system against everything from infections to cancer.

*The same genetic lines of laboratory mice used by Avery are still in use today; the mice have been inbred since at least 1909 to be a useful tool. As one scientist at the National Cancer Institute says, “I can cure cancer in a mouse one hundred percent of the time. If you can’t do that, you may as well hang it up.”

*Rosenau and Flexner had had a running but friendly competition for years. In 1911 Rosenau had shown that Flexner had made an important mistake. Two years later Rosenau won the American Medicine Gold Medal in 1913 for “proving” that stable flies transmitted poliomyelitis. Flexner proved that finding to be in error in 1915. Yet each respected the other, and they got along well. Shortly before the war, with Harvard still underfunding medical research, Flexner wrote him, “I am astonished and pained to learn that you have so small a budget for your lab,” and promptly arranged for a Rockefeller grant to him. Their cooperation was routine, for example when Rosenau asked Flexner earlier in 1918, “Please send Chelsea Naval Hospital at once sufficient antimeningitis serum for 4 patients.”

*Many mechanisms can cause bleeding in mucous membranes, and the precise way the influenza virus does this is unknown. Some viruses also attack platelets—which are necessary for clotting—directly or indirectly, and elements of the immune system may inadvertently attack platelets as well.

*For more about SARS, see Afterword.

*Florence Sabin was the leading female medical scientist in the United States, the first woman to graduate from the Hopkins Medical School, the first woman full professor at any medical school in the country (at the Hopkins), and the first woman elected to the National Academy of Sciences. Sabin was not a bacteriologist or involved in influenza research, and hence is not a part of this story.