NOTES

PROLOGUE: AUTUMN

Autumn Reddinger was deathly sick: The details of Autumn’s fight with the flu are taken from multiple phone interviews and email correspondence that I had with Autumn, her father, and her physician, Dr. Holt Murray, in December 2017.

kills between 36,000 and 50,000 people each year: “Estimating Seasonal Influenza-Related Deaths in the United States,” Centers for Disease Control and Prevention. Updated January 29, 2018. http://www.cdc.gov/flu/about/disease/us_flu-related_deaths.htm.

more than 2 million people could die: The estimate of the 1918 U.S. death toll was 675,000 out of a population of about 103 million. Today more than 322 million people live in the United States.

“the worst in nearly a decade”: Donald McNeil, “This Flu Season Is the Worst in Nearly a Decade,” New York Times, January 27, 2018: A15.

infected 1,400 people between 2012 and 2015: World Health Organization, “Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Summary of Current Situation, Literature Update and Risk Assessment,” July 7, 2015. Available at http://apps.who.int/iris/bitstream/10665/179184/2/WHO_MERS_RA_15.1_eng.pdf.

originated in animal hosts: SARS seems to have jumped from the Himalayan palm civet population. It’s a real animal, and apparently is eaten in China. Here’s some more free doctor advice: when next in China, avoid the civet dishes. See W. Li et al., “Animal Origins of the Severe Acute Respiratory Syndrome Coronavirus: Insight from ACE2-S-Protein Interactions,” Journal of Virology 80, no. 9 (2006): 4211–19.

only effective in about one-third: B. Flannery et al., “Interim Estimates of 2017–18 Seasonal Influenza Vaccine Effectiveness—United States, February 2018,” Morbidity and Mortality Weekly Report 67 (2018): 180–185.

1. ENEMAS, BLOODLETTING, AND WHISKEY: TREATING THE FLU

The article was published in 1978: K. Saketkhoo, A. Januszkiewicz, and M. A. Sackner, “Effects of Drinking Hot Water, Cold Water, and Chicken Soup on Nasal Mucus Velocity and Nasal Airflow Resistance,” Chest 74, no. 4 (1978): 408–10.

chicken soup is a kind of anti-inflammatory: B. O. Rennard et al., “Chicken Soup Inhibits Neutrophil Chemotaxis In Vitro,” Chest 118 no. 4 (2000): 1150–57.

YouTube video: “Chicken Soup for a Cold.” Accessed December 10, 2017. https://www.unmc.edu/publicrelations/media/press-kits/chicken-soup/.

four rounds of bloodletting: D. M. Morens, “Death of a President,” New England Journal of Medicine 341, no. 24 (1999): 1845–49.

reanimated by a transfusion of lamb’s blood: Mary Thompson, “Death Defied,” George Washington’s Mount Vernon. Accessed November 11, 2017. http://www.mountvernon.org/george-washington/the-man-the-myth/death-defied-dr-thorntons-radical-idea-of-bringing-george-washington-back-to-life/.

described a disease: J. A. B. Hammond, W. Rolland, and T. H. G. Shore, “Purulent Bronchitis: A Study of Cases Occurring amongst the British Troops at a Base in France,” Lancet 190, no. 4898 (1917): 41–45.

they reported that it worked: C. E. Cooper Cole, “Preliminary Report on Influenza Epidemic at Bramshott in September-October, 1918,” British Medical Journal 2, no. 3021 (1918): 566–68. “In some cases venesection relieved the toxemia, especially if combined with (1) saline or (2) glucose and saline interstitially, intravenously, or by the rectum.”

“I am an advocate”: Heinrich Stern, Theory and Practice of Bloodletting (New York: Rebman Company, 1915), iv.

still advocating bloodletting: W. F. Petersen and S. A. Levinson, “The Therapeutic Effect of Venesection with Reference to Lobar Pneumonia,” JAMA 78, no. 4 (1922): 257–58. Petersen and Levinson were real bloodletting groupies. “We believe it but simple justice to many able clinicians of an older period to stress the fact that venesection at times induced striking therapeutic benefits, that a definite and logical basis exists for the therapeutic effects so achieved.”

went out of fashion in the twentieth century: But it took a while. Just how it went out of fashion is discussed in G. B. Risse, “The Renaissance of Bloodletting: A Chapter in Modern Therapeutics,” Journal of the History of Medicine and Allied Sciences 34, no. 1 (1979): 3–22.

a series of bizarre treatments: A. F. Hopkirk, Influenza: Its History, Nature, Cause and Treatment (New York: The Walter Scott Publishing Company, 1914), 155. I am probably being too harsh here, since nearly all physicians would treat illnesses—of practically any variety—in the same way, using laxatives and purges. See David Wootton, Bad Medicine: Doctors Doing Harm since Hippocrates (Oxford: Oxford University Press, 2006).

dying of aspirin overdoses: In February 1917 the aspirin manufacturer Bayer lost its patent on the drug. This allowed other manufacturers to produce it and flood the market, making large doses more available to people desperate for any kind of treatment. In September 1918 the U.S. surgeon general noted that aspirin had been used successfully in foreign countries to relieve a range of symptoms. The very next month there was a peak in the number of deaths from influenza.

“drenched with aspirin”: Richard Collier, The Plague of the Spanish Lady: The Influenza Pandemic of 1918–1919 (London: Macmillan, 1974), 106.

help explain the deaths: See K. M. Starko, “Salicylates and Pandemic Influenza Mortality, 1918–1919 Pharmacology, Pathology, and Historic Evidence,” Clinical Infectious Diseases 49, no. 9 (2009): 1405–10. See also John M. Barry, The Great Influenza: The Epic Story of the Deadliest Plague in History (New York: Penguin, 2005), 353, 358.

“a teaspoonful of Friar’s balsam”: Hopkirk, Influenza, 159.

also prescribed quinine: Ibid., 156.

known as Jesuits’ powder: D. C. Smith, “Quinine and Fever: The Development of the Effective Dosage,” Journal of the History of Medicine and Allied Sciences 31, no. 3 (1976): 343–67.

first-line treatment for malaria: World Health Organization, “Guidelines for the Treatment of Malaria,” Geneva, World Health Organization, 2015.

why not use it to treat all fevers?: Smith, “Quinine and Fever.”

used in England: Cooper Cole, “Preliminary Report on Influenza Epidemic at Bramshott.”

the United States: H. A. Klein, “The Treatment of ‘Spanish Influenza,’ ” JAMA 71, no. 18 (1918): 1510.

the European continent: “. . . il etait logique d’avoir recours aux injections pour traiter cette infection comme on le fait pour le paludisme.” See F. Fabier, “Traitement de la Grippe par les Injections de Quinine,” Journal de Médecine et de Chirurgie Pratiques 90 (1919): 783–84, and more generally M. L. Hildreth, “The Influenza Epidemic of 1918–1919 in France: Contemporary Concepts of Aetiology, Therapy, and Prevention,” Social History of Medicine 4, no. 2 (1991): 277–94.

“ringing in the head”: See, for example, the Muskogee Times-Democrat, December 1, 1919, 6.

in high doses: M. E. Boland, S. M. Roper, and J. A. Henry, “Complications of Quinine Poisoning,” Lancet 1, no. 8425 (1985): 384–85.

small doses of dry champagne: Hopkirk, Influenza, 163, 180.

no finer pick-me-up: Ibid., 167.

could not hide his contempt: “Influenza: Its History, Nature, Cause and Treatment,” book review, JAMA 63, no. 3 (1914): 267. I still cannot be sure for whom the reviewer had more contempt, the British or Dr. Hopkirk. I love that word “nostrum.” It means an ineffective medicine, prepared by an unqualified person.

published seventy years later: R. J. Sherertz and H. J. Sherertz, “Influenza in the Preantibiotic Era,” Infectious Diseases in Clinical Practice 14, no. 3 (2006): 127.

or dicing onions to sterilize a room: Roger Welsch, A Treasury of Nebraska Pioneer Folklore (Lincoln: University of Nebraska Press, 1967), 370.

claimed that he had treated 225 patients: “Influenza Discussions,” American Journal of Public Health 9, no. 2 (1919): 136.

Captain A. Gregor, set off to investigate this claim: A. Gregor, “A Note on the Epidemiology of Influenza among Workers,” British Medical Journal 1, no. 3035 (1919): 242–43.

poison gas workers: F. Shufflebotham, “Influenza among Poison Gas Workers,” British Medical Journal 1, no. 3042 (1919): 478–79. For some reason this immunity did not extend to those who worked with phosgene gas, which had been used to horrible effect in the trenches of World War I.

viruses floating around those gasworks: E. W. Rice et al., “Chlorine Inactivation of Highly Pathogenic Avian Influenza Virus (H5N1),” Emerging Infectious Diseases 13, no. 10 (2007): 1568–70.

a brilliant physician: “James B. Herrick (1861–1954),” JAMA 16, no. 186 (1963): 722–23.

laid the foundations of modern cardiology: See C. S. Roberts, “Herrick and Heart Disease,” in H. Kenneth Walker, W. Dallas Hall, and J. Willis Hurst, eds., Clinical Methods: The History, Physical, and Laboratory Examinations, 3rd ed. (Atlanta: Butterworth Publishers, 1990). Another notable review of Herrick’s work is R. S. Ross, “A Parlous State of Storm and Stress. The Life and Times of James B. Herrick,” Circulation 67, no. 5 (1983): 955–59.

his plea was simple: James B. Herrick, “Treatment of Influenza by Means Other Than Vaccines and Serums,” JAMA 73, no. 7 (1919): 482–87.

“some one has blundered in reaching conclusions”: All the quotations are from Herrick, 483.

squarely in the conservative mainstream: “Proceedings of the Forty-Sixth Annual Meeting of the American Public Health Association,” American Journal of Public Health 9, no. 2 (1919): 130–42.

addressed the use of laxatives: The quote is from Herrick, 483. This focus on the bowel movements of patients with influenza was incredibly widespread and part of the medical establishment’s ingrained wisdom. Here’s part of a physician’s letter published in the Journal of the American Medical Association in November 1918: “I cannot too strongly call attention to the importance of keeping the bowels open by mild cathartics. Often a lingering temperature disappeared after a brisk flushing of the bowels, and this method greatly aided in shortening the course of the disease.” From Klein, “The Treatment of ‘Spanish Influenza,’ ” 1510.

wrote that from the large number of agents: Cooper Cole, “Preliminary Report on Influenza Epidemic at Bramshott.”

what happens more than 31 million times: N. A. Molinari et al., “The Annual Impact of Seasonal Influenza in the U.S.: Measuring Disease Burden and Costs,” Vaccine 25, no. 27 (2007): 5086–96.

the early-morning hours are usually quiet: These observations are based on twenty-five years of my own experience of working in a couple of dozen emergency departments in the U.S. and abroad. Fortunately, my experiences seem to match perfectly with the published data. My former colleague Melissa McCarthy studied emergency department arrivals at a large urban teaching hospital over one year. She found that Mondays and Fridays were the busiest days, and that early-morning hours were the slowest. See M. L. McCarthy et al., “The Challenge of Predicting Demand for Emergency Department Services,” Academic Emergency Medicine 15, no. 4 (2008): 337–46. See also S. J. Welch, S. S. Jones, and T. Allen, “Mapping the 24-Hour Emergency Department Cycle to Improve Patient Flow,” Joint Commission Journal on Quality and Patient Safety 33, no. 5 (2007): 247–55. These patterns are found in emergency departments all over the world. See, for example, Y. Tiwari, S. Goel, and A. Singh, “Arrival Time Pattern and Waiting Time Distribution of Patients in the Emergency Outpatient Department of a Tertiary Level Health Care Institution of North India,” Journal of Emergencies, Trauma, and Shock 7, no. 3 (2014): 160–65.

medical teams are likely to be at their slowest at the end of their shifts: Most emergency departments have three main shifts: 7 a.m. to 3 p.m., 3 p.m. to 11 p.m., and 11 p.m. to 7 a.m. In addition, there are numerous combinations of additional overlapping shifts that vary depending on the peak patient arrival times for a particular ER.

jury awarded the estate: A. Elliott-Engel, “Jury Awards $1.87 Million in Carbon Monoxide Poisoning Case,” Legal Intelligencer, June 1, 2011.

so we treat them: See, for example, M. Glatstein and D. Scolnik, “Fever: To Treat or Not to Treat?,” World Journal of Pediatrics 4, no. 4 (2008): 245–47. A dated but useful review of the subject is Matthew J. Kluger, Fever: Its Biology, Evolution, and Function (Princeton, NJ: Princeton University Press, 1979).

improves the efficacy of another group of blood cells: A review of fever and the thermal regulation of immunity concluded that “febrile temperatures serve as a systemic alert system that broadly promotes immune surveillance during challenge by invading pathogens.” See S. S. Evans, E. A. Repasky, and D. T. Fisher, “Fever and the Thermal Regulation of Immunity: The Immune System Feels the Heat,” National Review of Immunology 15, no. 6 (2015): 335–49.

49,000 people die from the flu each year: These are the CDC estimates. See “Estimating Seasonal Influenza-Related Deaths in the United States.”

plug the McMaster estimates into these flu numbers: D. J. Earn, P. W. Andrews, and B. M. Bolker, “Population-Level Effects of Suppressing Fever,” Proceedings of the Royal Society B: Biological Sciences 281, no. 1778 (2014): 20132570.

they are able to walk out of the ER: Intravenous fluids are a simple intervention, with manufacturers charging about one dollar for a bag. But that doesn’t prevent hospitals from charging the patient an incredible markup. An investigation in the New York Times revealed that some people were charged as much as $787 for “IV therapy.” In one case, a patient was charged $91 for IV fluid that cost the hospital $0.86. And you thought hotel minibars were a rip-off. See Nina Bernstein, “How to Charge $546 for Six Liters of Saltwater,” New York Times, August 27, 2013.

get a completely useless antibiotic: C. G. Grijalva, J. P. Nuorti, and M. R. Griffin, “Antibiotic Prescription Rates for Acute Respiratory Tract Infections in U.S. Ambulatory Settings,” JAMA 302, no. 7 (2009): 758–66.

2. THE JOLLY RANT: A HISTORY OF THE VIRUS

They exist on the edge of life: E. Rybicki, “The Classification of Organisms at the Edge of Life, or Problems with Virus Systematics,” South African Journal of Sciences 86 (1990): 182–98.

incorporated into our own genetic code: M. Emerman and H. S. Malik, “Paleovirology—Modern Consequences of Ancient Viruses,” PLoS Biology 8, no. 2 (2010): e1000301.

a Latin word: Sally Smith Hughes, The Virus: A History of the Concept (London: Heinemann Educational Books, Science History Publications, 1977), 109–14.

Edward Jenner: “. . . what renders the Cow-pox virus so extremely singular, is, that the person who has been thus affected is for ever after secure from the infection of the Small Pox.” Edward Jenner, An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name the Cow Pox (London: Sampson Low, 1798), 6. We will return to Jenner in chapter 9.

“le virus rabique”: Hughes, The Virus, 112.

They contain a core of genetic material: Ibid., 114.

Thucydides described: As cited in A. D. Langmuir et al., “The Thucydides Syndrome. A New Hypothesis for the Cause of the Plague of Athens,” New England Journal of Medicine 313, no. 16 (1985): 1027–30.

wrote Hippocrates: Francis Adams, The Genuine Works of Hippocrates (New York: William Wood, 1886), 298.

a flu epidemic broke out: Charles Creighton, A History of Epidemics in Britain, 2nd ed., vol. 2 (New York: Barnes & Noble, 1965), 328. Creighton records earlier epidemics of coughing, like that which occurred in April 1658. However, influenza is usually a disease of the winter, and it is therefore very unlikely to have been the cause of that April epidemic.

impossible to hear the sermon: Ibid., 328.

Thomas Sydenham suggested: Ibid., 329.

Bloodletting and laxatives: The epidemic in the winter of 1729 seems to have been especially brutal, and affected Britain, Ireland, and, later, Italy. See ibid., 343. Not all of the epidemics mentioned by Creighton were from influenza. For example, there was an epidemic in April 1743 in which “the skin was very frequently inflamed when the fever ran high; and it afterwards peeled off in most parts of the body.” This is not a description of what we now call viral influenza, and was far more likely to have been what was once commonly called scarlet fever, caused by a streptococcal bacterial infection.

a headline in the New York Times: Lawrence Altman, “Is This a Pandemic? Define ‘Pandemic,’ ” New York Times, June 8, 2009, D1. See also D. M. Morens, G. K. Folkers, and A. S. Fauci, “What Is a Pandemic?,” Journal of Infectious Disease 200, no. 7 (2009): 1018–21.

The most useful definition we have: K. D. Patterson, Pandemic Influenza, 1700–1900 (Totowa, NJ: Rowman and Littlefield, 1986), 5.

Some of these outbreaks: Ibid., 83.

Henry Parsons reported on it: Henry Franklin Parsons, Report on the Influenza Epidemic of 1889–90 (London, Eyre and Spottiswoode, 1891).

spread to the United States: Ibid., 24–27.

even a rumor: Ibid., 107. Elsewhere (p. 102) Parsons cites a French professor who believed “that Influenza is a growth of Russian soil, and when not a raging malady is a smoldering one.” Parsons, however, was skeptical of this claim, noting that the conditions that existed in Russia were similar to those in other parts of Europe: “If such conditions may prove a breeding ground for Influenza in Russia, it may be asked why not elsewhere?” It is ironic that I am writing these words during an FBI investigation into Russia’s role in influencing the 2016 U.S. presidential election. Is there nothing for which the Russians don’t get blamed?

caused by the conjunction of Jupiter and Saturn: Creighton, A History of Epidemics in Britain, 397–409.

three possible origins: Parsons, Report on the Influenza Epidemic of 1889–90, 70.

“non-living particulate material”: Ibid., 82.

rates were higher among the clerks: Ibid., 73.

Parsons was convinced: Ibid., 102.

animals were somehow responsible: Ibid., 106.

scientists identified the specific germs: Hughes, The Virus, 6–8.

claimed to have discovered the bacterium: J. K. Taubenberger, J. V. Hultin, and D. M. Morens, “Discovery and Characterization of the 1918 Pandemic Influenza Virus in Historical Context,” Antiviral Therapy 12, no. 4, part B (2007): 581–91.

“an authoritative road sign”: Alfred W. Crosby, America’s Forgotten Pandemic: The Influenza of 1918, 2nd ed. (Cambridge: Cambridge University Press, 2003), 269.

simple virus to depict: J. K. Taubenberger, A. H. Reid, and T. G. Fanning, “Capturing a Killer Flu Virus,” Scientific American 292, no. 1 (January 2005): 62–71.

“A disease of undetermined nature”: “Undetermined Disease—Valencia,” Public Health Reports 33, no. 26 (1918): 1087.

buried among news of the fighting: “Spanish Influenza Is Raging in the German Army,” New York Times, June 27, 1918.

the German Kaiser himself would catch it: In a one-sentence dispatch, the paper reported that “the Kaiser and Kaiserin are suffering from the Spanish influenza in a mild form.” “Kaiser Has Influenza,” New York Times, July 19, 1918.

3. “SOMETHING FIERCE”: THE SPANISH FLU OF 1918

a report to health officials: “Influenza. Kansas—Haskell,” Public Health Reports 33, no. 14 (1918): 502.

first recorded instance: J. M. Barry, “The Site of Origin of the 1918 Influenza Pandemic and Its Public Health Implications,” Journal of Translational Medicine 2, no. 1 (2004): 1–4.

the U.S. Army’s Camp Funston: Ibid.

the virus expanded outward in waves: Ibid. For a general description of the outbreak at Camp Funston, see E. L. Opie et al., “Pneumonia at Camp Funston,” JAMA 72, no. 2 (1919): 108–113.

first at Brest: Barry, “The Site of Origin of the 1918 Influenza Pandemic”; F. M. Burnet and E. Clark, Influenza: A Survey of the Last 50 Years in the Light of Modern Work on the Virus of Epidemic Influenza, monograph from the Walter and Eliza Hall Institute for Research in Pathology and Medicine (Melbourne: Macmillan and Company, 1942), 70–71.

hit between September and November 1918: J. S. Oxford, “The So-Called Great Spanish Influenza Pandemic of 1918 May Have Originated in France in 1916,” Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences 356, no. 1416 (2001): 1857–59.

photographs of French soldiers: Ibid. Oxford specifically addressed the question of whether the virus originated in China. He thought that this possibility, while it could not be excluded, was “unlikely” (p. 1859).

“a curious epidemic resembling influenza is sweeping over North China”: “Queer epidemic sweeps North China,” New York Times, June 1 1918, 1.

predated the general outbreaks: Christopher Langford, “Did the 1918–19 Influenza Pandemic Originate in China?,” Population and Development Review 31, no. 3 (2005): 473–505; K. F. Shortridge, “The 1918 ‘Spanish’ Flu: Pearls from Swine?,” Nature Medicine 5, no. 4 (1999): 384–85.

a precursor to the 1918 flu: Shortridge raises the possibility that “an H1-like virus may have existed in humans, at least in southern China, for some 50 years before the earliest epidemiological evidence of its presence there.”

140,000 Chinese laborers were recruited: Langford, “Did the 1918–19 Influenza Pandemic Originate in China?”

the British Army’s camp at Etaples: Shortridge cites Lynn MacDonald as the source for the claim that there were Chinese workers near Etaples. See Lynn MacDonald, Somme (London: Macmillan, 1984), 189–93. An exhaustively detailed analysis of the Chinese origin theory is found in Langford. He concludes that “the finding that influenza was widespread in China in 1918–19, but at the same time, in many parts of the country, less lethal than elsewhere in the world, despite the generally poor levels of health there at the time, suggests very strongly, Oxford and others notwithstanding, that the 1918–19 influenza virus originated in China” (“The 1918 ‘Spanish’ Flu,” 494). Shortridge is certain of this theory: “I believe that southern China was the source of the virus, in keeping with the hypothesis that the region is a hypothetical influenza epicenter for the emergence of pandemic influenza viruses, and it spread with the economy-driven movement of people out of Guangdong Province” (“Did the 1918–19 Influenza Pandemic Originate in China?,” 385).

did not first erupt in Spain: But the name has stuck. In his excellent history of the 1918 pandemic, Alfred Crosby refers to the influenza as “Spanish” at least forty-seven times, even though the second edition of the book was published in 2003. See Crosby, America’s Forgotten Pandemic. Richard Collier’s 1974 book on the epidemic left no ambiguity; it was titled The Plague of the Spanish Lady (London: Macmillan, 1974).

attacked in two waves: Details come from Carol Byerly, Fever of War: The Influenza Epidemic in the U.S. Army during World War I (New York: New York University Press, 2005) and Barry, The Great Influenza. Some academics have counted four or more waves.

propagated the bacteria: G. D. Shanks et al., “Variable Mortality from the 1918–1919 Influenza Pandemic during Military Training,” Military Medicine 181, no. 8 (2016): 878–82.

around 60 died: There is some disagreement between the numbers in Shanks, and the numbers cited by Barry in The Great Influenza and by Crosby.

His soldiers weren’t able to march: Byerly, Fever of War, 72.

31,000 cases of influenza among British troops: Crosby, America’s Forgotten Pandemic, 26.

troops were unable to report for combat: Barry, The Great Influenza, 174.

3 percent had died: See Crosby, America’s Forgotten Pandemic, 38.

the British Medical Journal reported that influenza was no longer a threat: “The many complications and sequelae by which in times gone by epidemic influenza made itself remembered seem to be happily rare. This circumstance has been held to show that we are not now dealing with an epidemic or a pandemic of influenza at all.” The anonymous author wistfully yearned for earlier days. “How much better it would be for all of us, and how fatal to the spread of influenza,” he wrote, “if we could all go back to our childhood, and learn once more with the thoroughness engendered by the fear of, say, an instant smacking never to cough or sneeze without first covering both mouth and nose with a handkerchief! But this is to ask too much.” See “The Influenza Pandemic,” British Medical Journal 2 (1918): 39.

earliest reports of the second wave: Barry, The Great Influenza, 186.

a letter dated September 29, 1918: The letter was found along with other medical papers in a trunk in Detroit, and eventually wound up in the Department of Epidemiology at the University of Michigan. See N. R. Grist, “Pandemic Influenza 1918,” British Medical Journal 2, no. 6205 (1979): 1632–33.

“demonstrated the inferiority of human interventions”: Victor C. Vaughan, Doctor’s Memories (New York: Bobbs-Merrill Company, 1926), 384.

sickened 14,000 and left 750 dead: Byerly, Fever of War, 75–76.

four times its maximum capacity: Ibid., 84.

life would slowly return to normal: Ibid., 76.

the death toll in the U.S. stood at 675,000: N. P. Johnson and J. Mueller, “Updating the Accounts: Global Mortality of the 1918–1920 ‘Spanish’ Influenza Pandemic,” Bulletin of the History of Medicine 76 (2002): 105–15.

the leap from army camps to civilian neighborhoods: Information is taken from Barry, The Great Influenza, 200–227.

German submarines loaded with germs: Cited in Gina Kolata, Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It (New York: Touchstone, 2005), 3.

masquerading under a new name: Ibid.

an article in the Philadelphia Inquirer: “Big Pageant to Launch Philadelphia’s Fourth Loan Drive,” Philadelphia Inquirer, September 28, 1918, 3.

“a tremendously impressive pageant”: “Representatives of a Great Nation Embattled Take Part in Tremendously Impressive Pageant,” Philadelphia Inquirer, September 29, 1918, 15.

“compelled by the epidemic”: Crosby, America’s Forgotten Pandemic, 75.

Some funeral homes: Ibid., 83.

More than 1,000 people died: Ibid., 99.

imposing a quarantine: Ibid., 239–57.

a fight against germs and Germans: Byerly, Fever of War, 97.

688 were hospitalized and 49 died: Barry, The Great Influenza, 173.

4,000 Parisians died: Ibid., 362.

“It was a grievous business”: Cited in Byerly, Fever of War, 73.

agreed to limit any discussion of the flu: Mark Honigsbaum, “Regulating the 1918–19 Pandemic: Flu, Stoicism and the Northcliffe Press,” Medical History 57, no. 2 (2013): 165–85.

embodied in a letter: J. McOscar, “Influenza in the Lay Press,” British Medical Journal 2, no. 3019 (1918): 534.

a catastrophic outbreak among British and French troops: Influenza Committee of the Advisory Board to the D.G.M.S. France, “The Influenza Epidemic in the British Armies in France, 1918,” British Medical Journal 2, no. 3019 (1918): 505–9.

His advice was limited: Juliet Nicolson, The Great Silence, 1918–1920: Living in the Shadow of the Great War (London: Grove Press, 2010), 93.

“more stoically accepted”: Anon., “6,000,000 Deaths. Influenza World Toll,” Times (London), December 18, 1918, 5.

“cheerfully anticipating”: Anon., “The Spanish Influenza. A Sufferer’s Symptoms,” Times (London), June 25, 1918, 9.

Over 225,000 died: Ben Johnson, “The Spanish Flu Epidemic of 1918,” Historic UK. Accessed April 25, 2018. https://www.historic-uk.com/HistoryUK/HistoryofBritain/The-Spanish-Flu-pandemic-of-1918/.

20 million Indians died: Barry, The Great Influenza, 364.

The first explanation: Taubenberger, Reid, and Fanning, “Capturing a Killer Flu Virus.”

“cytokine storm”: D. M. Morens and A. S. Fauci, “The 1918 Influenza Pandemic: Insights for the 21st Century,” Journal of Infectious Disease 2007, no. 195 (2007): 1019–28.

the biggest unsolved mystery of the pandemic: Ibid.

the death rate was twenty-five times greater: C. J. Murray et al., “Estimation of Potential Global Pandemic Influenza Mortality on the Basis of Vital Registry Data from the 1918–20 Pandemic: A Quantitative Analysis,” Lancet 368, no. 9554 (2006): 2211–18.

that the average life expectancy in 1918: D. W. Smith and B. S. Bradshaw, “Variation in Life Expectancy during the Twentieth Century in the United States,” Demography 43, no. 4 (2006): 647–57. This twelve-year drop should be contrasted with the ongoing opioid epidemic, which also caused a drop in the average life expectancy, but this time by one-tenth of a year. See K. D. Kochanek et al., “Mortality in the United States, 2016,” NCHS Data Brief, no. 293 (2017): 1–8.

It makes for terrifying reading: G. M. Price, “Influenza—Destroyer and Teacher,” Survey 41, no. 12 (1918): 367–69.

“each diseased person in a diver’s suit”: Ibid., 367.

Chicago’s health commissioner: Ibid., 368.

where they could be taught how to stay healthy: Natalie S. Robins, Copeland’s Cure: Homeopathy and the War between Conventional and Alternative Medicine, 1st ed. (New York: Knopf, 2005), 151.

“never again to prate”: As cited in Price, “Influenza—Destroyer and Teacher,” 367.

T. Yamanouchi: T. Yamanouchi, K. Sakakami, and S. Iwashima, “The Infecting Agent in Influenza: An Experimental Research,” Lancet 193, no. 4997 (1919): 971.

when given to live rabbits: P. Olitsky and F. Gates, “Experimental Study of the Nasopharyngeal Secretions from Influenza Patients,” JAMA 74, no. 22 (1920): 1497–99.

Soon there were reports: Taubenberger, Hultin, and Morens, “Discovery and Characterization of the 1918 Pandemic Influenza Virus in Historical Context.” These included a lot of animal diseases: foot-and-mouth disease in cattle, bovine pneumonia, rabbit myxomatosis, and African horse sickness.

eliminated bacteria as a suspect: M. C. Winternitz, I. M. Wason, and F. P. McNamara, The Pathology of Influenza (New Haven, CT: Yale University Press, 1920), 55.

British scientists concluded: W. Smith, C. H. Andrewes, and P. P. Laidlaw, “A Virus Obtained from Influenza Patients,” Lancet 2, no. 5723 (1933): 66–68. The existence of the virus was, at this stage, an assumption. It really meant an infectious particle small enough to pass through the filters that strain out bacteria.

the discovery that the influenza virus could be cultivated: Hughes, The Virus, 93.

4. “AM I GONNA DIE?”: ROUND TWO, AND THREE, AND FOUR . . .

700,000 refugees: “Hong Kong Battling Influenza Epidemic,” New York Times, April 17, 1957, 3.

this outbreak was caused by a different strain: E. D. Kilbourne, “Influenza Pandemics of the 20th Century,” Emerging Infectious Diseases 12, no. 1 (2006): 9–14.

more than 60 percent became clinically ill: D. A. Henderson et al., “Public Health and Medical Responses to the 1957–58 Influenza Pandemic,” Biosecurity and Bioterrorism 7, no. 3 (2009): 265–73.

Hilleman went to work: Lawrence Altman, “Maurice Hilleman, Master in Creating Vaccines, Dies at 85,” New York Times, April 12, 2005.

He recalled later: “1957 Asian Flu Pandemic,” video interview with Maurice Hilleman, The History of Vaccines. Accessed April 25, 2018. https://www.historyofvaccines.org/content/1957-asian-flu-pandemic.

It quickly spread to Southeast Asia: W. C. Cockburn et al., “Origin and progress of the 1968–69 Hong Kong influenza epidemic,” Bulletin of the World Health Organization 41 (1969): 343–48.

provided some immunity against the Hong Kong flu: Kilbourne, “Influenza Pandemics of the 20th Century.”

was still less deadly than the Asian flu: P. R. Saunders-Hastings and D. Krewski, “Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission,” Pathogens 5, no. 4 (2016): 1–19.

Center for Disease Control: The organization was called the Center for Disease Control until 1980, when it was given a plural title, the Centers for Disease Control. In 1992, Congress tweaked its name again. It became the Centers for Disease Control and Prevention.

it was of pivotal importance: Details are from J. C. Gaydos et al., “Swine Influenza A Outbreak, Fort Dix, New Jersey, 1976,” Emerging Infectious Diseases 12, no. 1 (2006): 23–28, and Gina Kolata, Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It (New York: Touchstone, 2005), chapters 5–6.

He also called on the CDC: E. Kilbourne, “Flu to the Starboard! Man the Harpoons!,” New York Times, February 13, 1976, 33.

“Better a vaccine without an epidemic”: Kolata, Flu, 139.

in a letter to the New York Times: Hans Neumann, “After the Flu Shots,” New York Times, September 15, 1976, 44.

Ford said in the White House: Gerald Ford, XXXVIII President of the United States, “Remarks Announcing the National Swine Flu Immunization Program.” Accessed April 25, 2018. http://www.presidency.ucsb.edu/ws/index.php?pid=5752. It is not clear where Ford got the number of 548,000 deaths.

Walter Cronkite appeared on the evening news: D. J. Sencer and J. D. Millar, “Reflections on the 1976 Swine Flu Vaccination Program,” Emerging Infectious Diseases 12, no. 1 (2006): 29–33.

to kill the head of the Gambino crime family: Cited in Kolata, Flu, 165.

A “sorry debacle”: Harry Schwartz, “Swine Flu Fiasco,” New York Times, December 21, 1976, 33.

This was “the swine flu snafu”: Matt Clark, “The Swine Flu Snafu,” Newsweek, July 12, 1976, 73.

CDC’s director, was forced to resign: Bruce Weber. “David J. Sencer Dies at 86; Led Disease-Control Agency,” New York Times, May 4, 2011, A27.

and 23 of those people had died: Douglas Martin, “Edwin Kilbourne, Flu Vaccine Expert, Dies at 90,” New York Times, February 24, 2011, B14.

on its seasonal influenza website: “Guillain-Barré Syndrome and Flu Vaccine,” Centers for Disease Control and Prevention. Accessed May 2, 2018. https://www.cdc.gov/flu/protect/vaccine/guillainbarre.htm. The CDC’s wording has evolved. As recently as 2017, the same website stated that in 1976 there had been “a small increased risk of GBS following vaccination with an influenza vaccine made to protect against a swine flu virus.” See Internet Archive Wayback Machine, “Guillain-Barré Syndrome and Flu Vaccine.” https://web.archive.org/web/20170508051122/https://www.cdc.gov/flu/protect/vaccine/guillainbarre.htm. Accessed April 25, 2018.

Sencer stood by the decision: Sencer and Millar, “Reflections on the 1976 Swine Flu Vaccination Program.”

Kilbourne called for better influenza preparation: All the quotes in this paragraph are from Kilbourne, “Influenza Pandemics of the 20th Century.”

In March 2009: The timeline and data are based on “The 2009 H1N1 Pandemic: Summary Highlights, April 2009–April 2010,” Centers for Disease Control and Prevention. Accessed April 25, 2018. https://www.cdc.gov/h1n1flu/cdcresponse.htm#CDC_Laboratories_Bolster_Nations_Testing.

the strain contained genes from four ancestors: Khan and William Patrick, The Next Pandemic: On the Front Lines against Humankind’s Gravest Dangers, 1st ed. (New York: PublicAffairs, 2016), 24.

director-general of the World Health Organization (WHO) declared it a pandemic: Margaret Chan, “World now at the start of 2009 influenza pandemic,” World Health Organization. Accessed April 25, 2018. http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/.

The FDA received 1,371 requests: A. Sorbello et al., “Emergency Use Authorization for Intravenous Peramivir: Evaluation of Safety in the Treatment of Hospitalized Patients Infected with 2009 H1N1 Influenza A Virus,” Clinical Infectious Diseases 55, no. 1 (2012): 1–7.

“People need to understand that this vaccine is safe”: Jesse Lee, “The President and First Lady Get Vaccinated,” The White House. Accessed April 25, 2019. https://obamawhitehouse.archives.gov/blog/2009/12/21/president-and-first-lady-get-vaccinated.

“If I had the two people that are most important in my life”: Ibid.

an unusually low figure for an influenza outbreak: Peter Doshi, “The 2009 Influenza Pandemic,” Lancet Infectious Diseases 13, no. 3 (2013): 193–94. Final estimates of deaths in the 2009 pandemic are from S. S. Shrestha et al., “Estimating the Burden of 2009 Pandemic Influenza A (H1N1) in the United States (April 2009–April 2010),” Clinical Infectious Diseases 52, suppl. 1 (2011): s75–s82.

“ ‘Am I gonna die?’ ”: Kathryn Tolbert, “Local Teens Describe Their Experiences With Swine Flu,” The Washington Post.com, August 25 2009. Accessed April 25, 2018. http://www.washingtonpost.com/wp-dyn/content/article/2009/08/24/AR2009082402346.html.

there was no cause for alarm: Robert Peer and Gardiner Harris, “Obama Seeks to Ease Fears on Swine Flu,” New York Times, April 27, 2009, A1.

declared the H1N1 outbreak to be a national emergency: “President Obama Signs Emergency Declaration for H1N1 Flu,” The White House. Accessed April 25, 2018. https://obamawhitehouse.archives.gov/blog/2009/10/25/president-obama-signs-emergency-declaration-h1n1-flu.

It now had its own hashtag: Martin Szomszor, Patty Kostkova, and Ed de Quincey, “#Swineflu: Twitter Predicts Swine Flu Outbreak in 2009,” in Electronic Healthcare (New York: Springer, 2011): 18–26.

CNN and Fox News were criticized: John Sutter, “Swine flu creates controversy on Twitter,” CNN. Accessed April 25, 2018. http://www.cnn.com/2009/TECH/04/27/swine.flu.twitter/.

Fiona Godlee, editor of the influential British Medical Journal: Fiona Godlee, “Conflicts of Interest and Pandemic Flu,” British Medical Journal 340 (2010): c2947.

the WHO’s official definition: Cited in Peter Doshi, “The Elusive Definition of Pandemic Influenza,” Bulletin of the World Health Organizaton 89 (2011): 532–38.

“It was a mistake, and we apologize”: Elizabeth Cohen, “When a Pandemic Isn’t a Pandemic,” CNN. Accessed April 25, 2018. http://edition.cnn.com/2009/HEALTH/05/04/swine.flu.pandemic/index.html.

the description of a pandemic did not match its severity: All the examples in this paragraph are taken from Table 2 of Doshi, “The Elusive Definition of Pandemic Influenza.”

John Barry noted: John Barry, “Lessons from the 1918 Flu,” Time, October 17, 2005, 96.

5. RESURRECTING THE FLU

pressure to show Congress: But in the end, the institute was closed. See Christopher Lee, “Pathologists Protest Defense Site’s Closure,” Washington Post, February 4, 2007.

not contain any viral particles: J. K. Taubenberger et al., “Initial Genetic Characterization of the 1918 ‘Spanish’ Influenza Virus,” Science 275, no. 5307 (1997): 1793–96.

later became a division of the AFIP: Byerly, Fever of War, 181.

features in common with bird flu: J. K. Taubenberger, “The Origin and Virulence of the 1918 ‘Spanish’ Influenza Virus,” Proceedings of the American Philosophical Society 150, no. 1 (2006): 86–112.

“It was a gimmick”: Interview with Jeffrey Taubenberger, June 14, 2016. The story of how Taubenberger came to sequence the 1918 flu virus is recalled slightly differently in Kolata, Flu, 193–208.

the sequence of these four letters: Taubenberger et al., “Initial Genetic Characterization of the 1918 ‘Spanish’ Influenza Virus.”

Johan Hultin came to the United States: Many of the details are from Kolata, Flu, chapter 4, and David Brown, “Resurrecting 1918 Flu Virus Took Many Turns,” Washington Post, October 10, 2005.

“try to find a victim of the 1918 flu pandemic”: From an interview with Hultin on Nova: “The 1918 Flu Pandemic That Infected 500 Million People.”

Otto Geist: Kolata, Flu, 95–98.

he was given permission to proceed: Ibid., 108.

they found three other bodies: Hultin, in the Nova documentary.

Hultin’s expedition remained forgotten: Kolata notes that Hultin never published the results of his efforts (Flu, 115). There was a brief newspaper report of the expedition in the Washington Post: N. S. Haseltine, “Scientists Seek 1918 Flu Virus,” September 2, 1951.

“I’m afraid the warranty will run out”: Elizabeth Fernandez, “The Virus Detective / Dr. John Hultin Has Found Evidence of the 1918 Flu Epidemic That Had Eluded Experts for Decades,” SFGate. Accessed May 2, 2018. https://www.sfgate.com/magazine/article/The-Virus-detective-Dr-John-Hultin-has-found-2872017.php.

paper that detailed the findings of Private Roscoe’s flu virus: Taubenberger et al., “Initial Genetic Characterization of the 1918 ‘Spanish’ Influenza Virus.”

Taubenberger offered to analyze: According to Kolata, Taubenberger resigned from the Duncan team after it was alleged that it was charging for media interviews. See also Kirsty Duncan, Hunting the 1918 Flu: One Scientist’s Search for a Killer Virus (Toronto: University of Toronto Press, 2003), 65–85.

buoyed by a federal grant for $150,000: Kolata, Flu, 272.

the lab confirmed the presence of 1918 flu particles: Ibid., 262–65.

now rebuild the entire genetic code of the 1918 virus: Taubenberger, Reid, and Fanning, “Capturing a Killer Flu Virus.”

the New York Times reported: John Noble, “Quest for Frozen Pandemic Virus Yields Mixed Results,” New York Times, September 7, 1998, F3.

she found renown later: Duncan went on to write a book about her experiences and on becoming Canada’s minister of science. She has been referred to as a “badass.” See Maryn McKenna, “Canada’s First (and Female) Science Minister Is a Badass,” National Geographic. Accessed April 26, 2018. http://phenomena.nationalgeographic.com/2015/11/05/canadas-first-and-female-science-minister-is-a-badass/. Her expedition is discussed in detail in Kolata, Flu, chapter 9, and in even greater depth in Duncan, Hunting the 1918 Flu, from where I have drawn the story.

The search widened: There were other attempts to exhume the virus. In September 2008, the British virologist John Oxford led a team that dug up the body of Sir Tatton Benvenuto Mark Sykes. Sykes had risen through the ranks of the British Army to become a colonel, and during World War I, in anticipation of the collapse of the Ottoman Empire, he helped to carve up the Middle East for European powers. In February 1919 Sykes died at the age of thirty-nine, a victim of the tail end of the flu pandemic. He was laid to rest in a lead coffin in St. Mary’s Church in Yorkshire, next to Sledmere House, the ancestral home of the Sykes family. (Sledmere, like so many of Britain’s aristocratic homes, is now making ends meet by providing tours; it is also available for weddings.) Lead coffins seal off the body from the surrounding earth. This slows the natural decay of the body, and so Sykes was a prime candidate for exhumation. John Oxford was hopeful, and became the subject of a documentary about the project. “We’re on the verge of the first influenza pandemic of the twenty-first century,” he told the BBC, “and we think Sir Mark can help us.” Sir Mark’s descendants agreed. “It is rather fascinating that maybe even in his state as a corpse, he might be helping the world in some way,” his grandson said.

Digging up the remains of British aristocracy required some paperwork, which took about two years to complete. Oxford had to obtain permission from the church court covering the Diocese of York, the Department for Constitutional Affairs, and the Health and Safety Executive. A short prayer was offered at the graveside, and then scientists wearing hazmat suits and oxygen masks went to work. They were disappointed and frustrated when, after reaching the coffin, they discovered that its cover was not intact. The body had decayed. After testing seventeen samples of the remains of Sir Mark, Oxford and his team failed to find the virus. The legacy of Sir Mark Sykes would remain tied entirely to his 1916 plan for the Middle East, and not to the 1918 virus that killed him. See James Barr, A Line in the Sand: France and the Struggle for the Mastery of the Middle East (New York: Simon & Schuster, 2011), and “Vital Flu Clue,” BBC. Accessed April 26, 2018. http://www.bbc.co.uk/insideout/yorkslincs/series11/week8_flu.shtml.

died due to a secondary bacterial infection: A. H. Reid et al., “1918 Influenza Pandemic Caused by Highly Conserved Viruses with Two Receptor-Binding Variants,” Emerging Infectious Diseases 9, no. 10 (2003): 1249–53.

the genetic fingerprints across all the samples: Ibid.

a single strain of influenza was in circulation in the early stages: Ibid.

In 2005 the team announced: T. M. Tumpey et al., “Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus,” Science 310, no. 5745 (2005): 77–80.

the 1918 virus appeared to be a bird virus: J. K. Taubenberger et al., “Characterization of the 1918 Influenza Virus Polymerase Genes,” Nature 437, no. 7060 (2005): 889–93.

October 2005 issue of Science: Tumpey et al., “Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus,” Science 310, no. 5745 (2005): 77–80.

Scientists from Stony Brook University: J. Cello, A. V. Paul, and E. Wimmer, “Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template,” Science 297, no. 5583 (2002): 1016–18.

Biotechnology Research in an Age of Terrorism: National Research Council, Biotechnology Research in an Age of Terrorism (Washington, D.C.: The National Academies, 2004).

Kennedy stuck by his decision: D. Kennedy, “Better Never Than Late,” Science 310, no. 5746 (2005): 195. Some scientists were not convinced by reassurances that it was safe to work with the active 1918 virus, and felt that the benefits of what we could learn were outweighed by the risks of bringing the virus back from the dead. Richard Ebright, a microbiologist at Rutgers University, believed that the research was too dangerous to have been performed. “If the virus was to be accidentally or intentionally released,” he said, “it is virtually certain that there would be greater lethality than from seasonal influenza, and quite possible that the threat of pandemic that is in the news daily would become a reality.” But nobody had asked Professor Ebright, who made his comments three months after the announcement that the 1918 virus had been rebuilt. See Jamie Shreeve, “Why Revive a Deadly Virus?,” New York Times Magazine, January 29, 2006, 48.

In 2012 an international group genetically modified: S. Herfst et al., “Airborne Transmission of Influenza A/H5NI Virus between Ferrets,” Science 336, no. 6088 (2012): 1534–41.

more lethal than the original avian virus: T. Watanabe et al., “Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential,” Cell Host & Microbe 15, no. 6 (2014): 692–705.

the White House paused the federal funding: “Doing Diligence to Assess the Risks and Benefits of Life Sciences Gain-of-Function Research,” The White House. Accessed April 26, 2018. https://obamawhitehouse.archives.gov/blog/2014/10/17/doing-diligence-assess-risks-and-benefits-life-sciences-gain-function-research.

to assess the risks and benefits: “U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses,” n.p. n.p October 17, 2014. Available at https://www.phe.gov/s3/dualuse/Documents/gain-of-function.pdf.

“I shall sleep better tonight”: Donald McNeil, “White House to Cut Funding for Risky Biological Study,” New York Times, October 17, 2014.

the White House released new research guidelines: “Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight (P3CO),” n.p, n.p. Available at https://www.phe.gov/s3/dualuse/Documents/P3CO-FinalGuidanceStatement.pdf.

the NIH promptly removed its ban: “NIH Lifts Funding Pause on Gain-of-Function Research,” The NIH Director. Accessed May 2, 2018. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-lifts-funding-pause-gain-function-research.

“I know nothing”: Interview with Jeffrey Taubenberger, June 14, 2016.

6. DATA, INTUITION, AND OTHER WEAPONS OF WAR

in sunny Florida only 43 providers take part: This number appears in the Florida Flu Review, 2015–2016 season, Week 14: April 3–9, 2016.

flu queries spiked on Google Flu Trends: Google.org, “Google Flu Trends Overview,” YouTube video. Accessed November 6, 2017. https://www.youtube.com/watch?v=6111nS66Dpk.

Canada: M. T. Malik et al., “ ‘Google Flu Trends’ and Emergency Department Triage Data Predicted the 2009 Pandemic H1N1 Waves in Manitoba,” Canadian Journal of Public Health 102, no. 4 (2011): 294–97.

Australia: H. Kelly and K. Grant, “Interim Analysis of Pandemic Influenza (H1N1) 2009 in Australia: Surveillance Trends, Age of Infection and Effectiveness of Seasonal Vaccination,” Eurosurveillance 14, no. 31 (2009).

several European countries: A. Valdivia et al., “Monitoring Influenza Activity in Europe with Google Flu Trends: Comparison with the Findings of Sentinel Physician Networks—Results for 2009–10,” Eurosurveillance 15, no. 29 (2010).

the sale of antiviral medications: A. Patwardhan and R. Bilkovski, “Comparison: Flu Prescription Sales Data from a Retail Pharmacy in the U.S. with Google Flu Trends and U.S. ILINet (CDC) Data as Flu Activity Indicator,” PLoS One 7, no. 8 (2012): e43611.

The algorithm was updated: S. Cook et al., “Assessing Google Flu Trends Performance in the United States during the 2009 Influenza Virus A (H1N1) Pandemic,” PLoS One 6, no. 8 (2011): e23610.

it turned out that Google had overestimated: D. Lazer et al., “The Parable of Google Flu: Traps in Big Data Analysis,” Science 343, no. 6176 (2014): 1203–5.

In the influential journal Science: Perhaps, as one group of researchers put it, “the algorithm producing the data (and thus user utilization) has been modified by the service provider in accordance with their business model.” See ibid., 1204.

New York declared a public health emergency: “Governor Cuomo Declares State Public Health Emergency in Response to Severe Flu Season,” New York State. Accessed April 26, 2018. https://www.governor.ny.gov/news/governor-cuomo-declares-state-public-health-emergency-response-severe-flu-season. See also Tim Hartford, “Big Data: Are We Making a Big Mistake?,” Significance, December 2014.

Boston’s Street Bump app: Ibid.

said Alain-Jacques Valleron: Cited in D. Butler, “When Google Got Flu Wrong,” Nature 494, no. 7436 (2013): 155–56.

a goodbye note of sorts: The Flu Trends Team, “The Next Chapter for Flu Trends,” Google Research Blog. Accessed May 2, 2018. https://research.googleblog.com/2015/08/the-next-chapter-for-flu-trends.html.

Nelson started modestly: Telephone interview with Forrest Nelson, November 16, 2017.

It correctly forecast: P. M. Polgreen, F. D. Nelson, and G. R. Neumann, “Use of Prediction Markets to Forecast Infectious Disease Activity,” Clinical Infectious Diseases 44, no. 2 (2007): 272–79.

I spoke with Nelson: Telephone interview with Forrest Nelson, November 16, 2017.

The program started by receiving weekly reports: D. Das et al., “Monitoring Over-the-Counter Medication Sales for Early Detection of Disease Outbreaks—New York City,” MMWR Supplements 54 (2005): 4–46.

Maryland Resident Influenza Tracking Survey: The number of participants is taken from email correspondence with Stephen Stanley of the Maryland Department of Health, April 27, 2018. See also “Maryland Influenza Surveillance Report: 2008–09 Influenza Season Summary,” Division of Communicable Disease Surveillance, Office of Epidemiology and Disease Control Programs, Maryland Department of Health and Mental Hygiene, 2009.

2014–2015 Maryland influenza season: “Influenza in Maryland. 2014–2015 Season Report,” Division of Communicable Disease Surveillance, Office of Epidemiology and Disease Control Programs, Maryland Department of Health and Mental Hygiene, 2014.

Sharon Sanders is the editor in chief: The quotes and information about the history and formation of FluTrackers comes from a phone interview with Sanders, April 24, 2017, and from follow-up email correspondence.

President George W. Bush was reading a history of the flu: Warren Vieth, “Bush Salts His Summer with Eclectic Reading List,” Los Angeles Times, August 16, 2005. Available at http://articles.latimes.com/2005/aug/16/nation/na-bushread16. Accessed May 2, 2018.

In an email: Email dated November 16, 2017.

7. YOUR EVENING FLU FORECAST

the correlation between the phases of the moon and visits to the emergency room: See, for example, S. Kamat et al., “Pediatric Psychiatric Emergency Department Visits during a Full Moon,” Pediatric Emergency Care 30, no. 12 (2014): 875–78.

Other infectious diseases have a seasonality: M. Oshinsky, Polio: An American Story (Oxford: Oxford University Press, 2005), 9–10; N. B. Mantilla-Beniers et al., “Decreasing Stochasticity Through Enhanced Seasonality in Measles Epidemics,” Journal of the Royal Society Interface 7, no. 46 (2009): 727–39.

“It should not cause any greater importance”: “The Epidemic of Influenza,” JAMA 71, no. 13 (1918): 1063–64. While it is true that there were various waves of flu during the pandemic, the overall trends of the disease generally followed the usual pattern: a rise in cases over the fall and winter.

that the way in which air flows: G. W. Hammond, R. L. Raddatz, and D. E. Gelskey, “Impact of Atmospheric Dispersion and Transport of Viral Aerosols on the Epidemiology of Influenza,” Reviews of Infectious Diseases 11, no. 3 (1989): 494–97. The authors hypothesized that “the long-range atmospheric transport of aerosolized influenza . . . and the seasonal changes in atmospheric circulation patterns may lead to the regular annual cycles of influenza activity.” This hypothesis was offered as one model “intended to contribute ideas for discussion.” It’s almost as if the authors didn’t quite manage to convince themselves.

In the tropics: S. Hirve et al., “Influenza Seasonality in the Tropics and Subtropics—When to Vaccinate?,” PLoS One 11, no. 4 (2016): e0153003.

when you dig deeper you find many problems: J. J. Cannell et al., “Epidemic Influenza and Vitamin D,” Epidemiology & Infection 134, no. 6 (2006): 1129–40.

we tend to use public transportation more: Y. Yang, A. V. Diez Roux, and C. R. Bingham, “Variability and Seasonality of Active Transportation in USA: Evidence from the 2001 NHTS,” International Journal of Behavioral Nutrition and Physical Activity 8 (2011): 96. The reasons are not clear, but may have something to do with our use of public transport for vacations.

“London Transport would ensure an all-the-year epidemic”: C. Andrews, The Common Cold (New York: W.W. Norton, 1965), 137.

arrived by comet, as microscopic alien hitchhikers: Fred Hoyle and Chandra Wickramasinghe, Evolution from Space: A Theory of Cosmic Creationism (New York: Simon & Schuster, 1982).

believed instead in a steady-state universe: Simon Mitton, Fred Hoyle: A Life in Science, pbk. ed. (Cambridge: Cambridge University Press, 2011).

letter in the prestigious scientific journal Nature: Fred Hoyle and N. C. Wickramasinghe, “Sunspots and Influenza,” Nature 343, no. 6256 (1990): 304. Hoyle admitted that he was not the first to notice a relationship between solar activity and flu outbreaks. That accolade went to another Brit, by the name of Robert Hope-Simpson. See R. E. Hope-Simpson, “Sunspots and flu: a correlation,” Nature 265, no. 5676 (1978): 86.

in the words of NASA: “Impacts of Strong Solar Flares,” NASA. Accessed April 29, 2018. https://www.nasa.gov/mission_pages/sunearth/news/flare-impacts.html.

it can be manipulated to fit any model: A. von Alvensleben, “Influenza according to Hoyle,” Nature 344 (1990): 374.

rays transform it into vitamin D: For this discovery, the German chemist Adolf Windaus was awarded a Nobel Prize in 1928.

twice as many people die over the dark winter: Cannell et al., “Epidemic Influenza and Vitamin D.”

Britain’s senior citizens: V. Hirani and P. Primatesta, “Vitamin D Concentrations among People Aged 65 Years and Over Living in Private Households and Institutions in England: Population Survey,” Age and Ageing 34 (2006): 485–91.

also much more common in African Americans: A. Zadshir et al., “The Prevalence of Hypovitaminosis D among U.S. Adults: Data from the NHANES III,” Ethnicity & Disease 15, no. 4, suppl. 5 (2005): s5–97–101.

their mortality from pneumonia and influenza: Cannell et al., “Epidemic Influenza and Vitamin D.”

the winter group was eight times more likely to develop a fever: A. S. Shadrin, I. G. Marinich, and L. Y. Taros, “Experimental and Epidemiological Estimation of Seasonal and Climato-geographical Features of Non-specific Resistance of the Organism to Influenza,” Journal of Hygiene, Epidemiology, Microbiology, and Immunology 21, no. 2 (1977): 155–61.

a group of schoolchildren in Japan: M. Urashima et al., “Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza A in Schoolchildren,” American Journal of Clinical Nutrition 91, no. 5 (2010): 1255–60.

healthy adults in New Zealand: D. R. Murdoch et al., “Effect of Vitamin D₃ Supplementation on Upper Respiratory Tract Infections in Healthy Adults: The Vidaris Randomized Controlled Trial,” JAMA 308, no. 13 (2012): 1333–39. An accompanying editorial called for vitamin D to join the list of treatments that were “ineffective for preventing or treating upper respiratory tract infections in healthy adults.” That list includes “echinacea, zinc, steam inhalation, vitamin C, garlic, antihistamines, Chinese medicinal herbs, intranasal corticosteroids, intranasal ipratroprium, Pelargonium sidoides herbal extract, [and] saline nasal irrigation . . .” See J. A. Linder, “Vitamin D and the Cure for the Common Cold,” JAMA 308, no. 13 (2012): 1375–76.

when older adults took extra doses of vitamin D: Abhimanyu and A. K. Coussens, “The Role of UV Radiation and Vitamin D in the Seasonality and Outcomes of Infectious Disease,” Photochemical and Photobiological Sciences 16, no. 3 (2017): 314–38. It is not just Britain’s elderly. A 2010 study from the Institute of Medicine noted that “sun exposure currently contributes meaningful amounts of vitamin D to North Americans and [the data] indicates that a majority of the population is meeting its needs for vitamin D. Nonetheless, some subgroups—particularly those who are older and living in institutions or who have dark skin pigmentation—may be at increased risk for getting too little vitamin D.” See their report brief, “Dietary Reference Intakes for Calcium and Vitamin D,” Institute of Medicine, November 2010. http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdf.

One such analysis pooled the results: P. Bergman et al., “Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-analysis of Randomized Controlled Trials,” PLoS One 8, no. 6 (2013): e65835.

a group from New York’s Mount Sinai School of Medicine: A. C. Lowen et al., “Influenza Virus Transmission Is Dependent on Relative Humidity and Temperature,” PLoS Pathogens 3, no. 10 (2007): 1470–76.

varying both the temperature and the humidity: There are two measures of humidity: relative and absolute. Relative humidity is what you hear about on the weather forecast. It measures how much water is in the atmosphere compared to the amount needed to saturate the particular environment that’s being measured. When the weather forecasters tell you about the outside humidity, this is what they mean. If the amount of water in the atmosphere stays the same, the humidity goes down as the temperature goes up. In winter, the air is colder, so it can hold less water. As a result, the relative humidity is higher in the winter. Shaman and his group at Columbia focused on absolute humidity, which is a measure of the amount of water in a particular atmosphere, period, without regard to another variable. By focusing on the absolute humidity, researchers could eliminate temperature as a variable. It also better reflects the way in which indoor and outdoor humidity are related. Inside our homes, absolute humidity correlates very well with absolute humidity outside, whereas inside and outside relative humidity are poorly correlated. See J. L. Nguyen, J. Schwartz, and D. W. Dockery, “The Relationship between Indoor and Outdoor Temperature, Apparent Temperature, Relative Humidity, and Absolute Humidity,” Indoor Air 24, no. 1 (2014): 103–12. A note of caution, though: the sample size of this study was only sixteen homes.

The uninfected animals remained happy and healthy: Guinea pigs were also victims of the 1918 influenza epidemic. In September 1918 at Camp Cody, a military base in New Mexico, there was an outbreak of influenza that lasted three months. By the time it was over, the base hospital had admitted over 3,000 patients, more than a quarter of all the troops stationed there. Five nurses and almost 250 soldiers had died. In a medical report about the outbreak, the authors described the temperature, blood counts, and urine analysis of the infected soldiers, and then they took an unexpected detour. They noted how, shortly after the 1918 epidemic reached the camp, the guinea pigs in their lab began to die. At first, the physicians thought that they had died from food poisoning, but at postmortem they found “the unmistakable signs of pneumonia.” The animals suffered in the same way that their military cocampers had. “During this time,” they wrote, “the sick animal trembling from chills, with hair ruffled, sat huddled up in a corner of the pen, moving about only to eat. This it would do until shortly before death. The respirations were rapid and wheezing; the characteristic shrill whistle became scarcely audible. The animal was apparently in a stupor which gradually deepened until death supervened. . . . Just before death the animal would fall on one side, rise a time or two, then make a few feeble efforts to do so again. Within fifteen or thirty minutes it would die.” See Frederick Lamb and Edward Brannin, “The Epidemic Respiratory Infection at Camp Cody N.M.,” JAMA 72, no. 15 (1919): 1056–62.

they created a simulated coughing machine: J. D. Noti et al., “High Humidity Leads to Loss of Infectious Influenza Virus from Simulated Coughs,” PLoS One 8, no. 2 (2013): e57485.

“infectious disease dynamics are nonlinear”: J. Shaman and A. Karspeck, “Forecasting Seasonal Outbreaks of Influenza,” Proceedings of the National Academies of Science 109, no. 50 (2012): 20425–30.

ensemble forecasting: Ibid.

their weather model was about 75 percent accurate: J. Shaman et al., “Real-Time Influenza Forecasts during the 2012–2013 Season,” Nature Communications 4 (2013): 2837.

Predict the Influenza Season Challenge: “CDC Announces Winner of the ‘Predict the Influenza Season Challenge,’ ” Centers for Disease Control and Prevention. Accessed April 20, 2017. https://www.cdc.gov/flu/news/predict-flu-challenge-winner.htm.

Almost half of the existing ventilators: This data comes from X. Zhang, M. I. Meltzer, and P. M. Wortley, “FluSurge—a Tool to Estimate Demand for Hospital Services During the Next Pandemic Influenza,” Medical Decision Making 26, no. 6 (2006): 617–23. It assumes a pandemic lasting eight weeks that attacks 25 percent of the population. The numbers are even worse if the pandemic lasts three months and infects a third of the population. In that scenario, 85 percent of the ventilators would be needed for the sickest of the flu patients. The authors were from the CDC in Atlanta, which is probably why they modeled their numbers on that city. The tool they created to produce these estimates is called FluSurge and is openly available. But be warned: the numbers are scary.

hospitals are short of nurses: There are many academic reports about a nursing shortage and they are not consistent. The Bureau of Labor Statistics noted a recent increase in the number of nurses entering the market, which has led to competition for jobs. But only in some places. “Registered Nurses,” United States Department of Labor. Accessed April 29 2017. https://www.bls.gov/ooh/healthcare/registered-nurses.htm#tab–6.

the rate of vaccination in the United States: Tammy A. Santibanez et al., “Flu Vaccination Coverage, United States, 2015–16 Influenza Season,” Centers for Disease Control and Prevention. Accessed April 29, 2018. https://www.cdc.gov/flu/fluvaxview/coverage-1516estimates.htm.

Communities exposed to warnings: Kristin Dow and Susan Cutter, “Crying Wolf: Repeat Responses to Hurricane Evacuation Orders,” Coastal Management 26, no. 4 (1998): 237–52. This paper discussed the reaction to gubernatorial warnings, which, like those from public health offices, are governmental.

8. THE FAULT IN OUR STOCKPILES: TAMIFLU AND THE CURE THAT WASN’T THERE

The bunkers contain our Strategic National Stockpile: I asked to visit one of these bunkers, but was turned down, apparently as a result of “a change in policy.” I blame Nell Greenfieldboyce, a reporter for National Public Radio, who was the first—and apparently last—reporter to visit the stockpile. “Since I had to sign a confidentiality agreement,” she said, “I can’t describe the outside. But the inside is huge.” See “Inside a Secret Government Warehouse Prepped for Health Catastrophes,” National Public Radio, June 27, 2016. http://www.npr.org/sections/health-shots/2016/06/27/483069862/inside-a-secret-government-warehouse-prepped-for-health-catastrophes.

“A cross between Amazon and a local pharmacy”: Interview with Mark Burchess, November 28, 2016.

120 million doses of the H1N1 vaccine were shipped: “2009 H1N1 Flu,” Centers for Disease Control and Prevention. Accessed April 29, 2018. https://www.cdc.gov/h1n1flu/vaccination/vaccinesupply.htm.

baby flu particles could not spread the infection: A. Moscona, “Neuraminidase Inhibitors for Influenza,” New England Journal of Medicine 353, no. 13 (2005): 1363–73.

a group of researchers from Scotland: The authors were a pessimistic bunch, and were less than enthusiastic about their discovery. While noting that it was possible that it could lead to an antiviral drug, they noted the drugs appeared to be “too labile biologically to give any anti-influenza effect in an intact animal.” See J. D. Edmond et al., “The Inhibition of Neuraminidase and Antiviral Action,” British Journal of Pharmacology and Chemotherapy 27, no. 2 (1966): 415–26.

scientists began to test them: Walter Sneader, Drug Discovery: A History (Hoboken, NJ: Wiley & Sons, 2005), 264–65; F. G. Hayden et al., “Safety and Efficacy of the Neuraminidase Inhibitor GG167 in Experimental Human Influenza,” JAMA 275, no. 4 (1996): 295–99.

a TV ad for Tamiflu: “Tamiflu TV Commercial, ‘Small House,’ ” iSpot.tv. Accessed April 29, 2018. https://www.ispot.tv/ad/77Nb/tamiflu-small-house.

targeted mothers whose children had the flu: “Tamiflu TV Commercial, ‘Kids,’ ” iSpot.tv. Accessed April 29, 2018. https://www.ispot.tv/ad/AIqV/tamiflu-kids. This ad aired almost three thousand times.

Two years after the outbreak the WHO published a report: World Health Organization Department of Communicable Disease Surveillance and Response, “Influenza Pandemic Plan. The Role of WHO and Guidelines for National and Regional Planning” (Geneva, 1999). The quotation is on p. 54.

funded by at least seven pharmaceutical companies: This list appears on the ESWI website: “Resources,” European Scientific Working Group on Influenza. Accessed April 29, 2018. http://eswi.org/home/about-eswi/resources/.

These manufacturers joined together: Ibid. According to the British Medical Journal, the ESWI is a group “funded entirely by Roche and other influenza manufacturers.” (See D. Cohen and P. Carter, “WHO and The Pandemic Flu ‘Conspiracies,’ ” British Medical Journal 340 (2010): c2912.) This may have been true in years past, but the ESWI currently lists public funding as well as “unrestricted grants by vaccine and antivirals companies.”

the 1997 avian influenza outbreak: The WHO report mentioned that two other antiviral drugs (amantadine and its derivative rimantadine) had “been shown to be clinically effective in preventing illness” and that they could “reduce the severity and duration of illness when taken early after onset.” These two drugs were not neuraminidase inhibitors, but seemed to work against the flu virus. Since then the clever flu virus has become resistant to them to such a degree that they are no longer given for the treatment of influenza.

In 1999 the Cochrane Collaboration: T. Jefferson et al., “Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults,” Cochrane Database of Systematic Reviews 2 (1999).

Cochrane reviewers pledge to issue reports: Cochrane, “About us.” Accessed April 29, 2018. http://www.cochrane.org/about-us.

a warning letter about its advertising campaign: Department of Health and Human Services, FDA letter MACMIS ID#8675, April 14, 2000. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/UCM166329.pdf.

His speech there: “President Outlines Pandemic Influenza Preparations and Response,” The White House. Accessed April 29, 2018. https://georgewbush-whitehouse.archives.gov/news/releases/2005/11/20051101-1.html.

an effort to detect flu outbreaks earlier: To do this, there would be an international effort to be led by the recently formed International Partnership on Avian and Pandemic Influenza. Within the U.S., the president launched the National Biosurveillance Initiative, which somehow “would provide continual situational awareness.” Ibid.

the president requested $7.1 billion: T. Salaam-Blyther, “U.S. and International Responses to the Global Spread of Avian Flu: Issues for Congress,” in Congressional Research Service Report for Congress (Washington, D.C.: Congressional Research Service, 2006), 7.

five times as much Tamiflu was being prescribed: J. R. Ortiz et al., “Oseltamivir Prescribing in Pharmacy-Benefits Database, United States, 2004–2005,” Emerging Infectious Diseases 14, no. 8 (2008): 1280–83.

healthy people were buying up Tamiflu: A. S. Brett and A. Zuger, “The Run on Tamiflu—Should Physicians Prescribe on Demand?,” New England Journal of Medicine 353, no. 25 (2005): 2636–37.

threats of a shortage: D. Spurgeon, “Roche Canada Stops Distributing Oseltamivir,” British Medical Journal 331, no. 7524 (2005): 1041.

“we will be unable to prevent it reaching the UK”: “Britain Reveals Flu Pandemic Plan,” BBC News, March 1, 2005. Accessed April 29, 2018. http://news.bbc.co.uk/2/hi/health/4305813.stm. The BBC also reported on the government’s decision to stockpile Tamiflu.

only 2.3 million doses were on hand: U.S. Department of Health and Human Services, “HHS Pandemic Influenza Plan” (2005), F-39.

another analysis of antiflu medications: T. Jefferson et al., “Antivirals for Influenza in Healthy Adults: Systematic Review,” Lancet 367, no. 9507 (2006): 303–13.

The World Health Organization declared a pandemic: Margaret Chan, “World Now at the Start of 2009 Influenza Pandemic,” World Health Organization. Accessed April 29, 2018. http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/. This episode is discussed in greater detail in chapter 4.

not as virulent as experts feared: Still, the 2009 pandemic might have caused additional deaths in the U.S. when compared to the seasonal influenza. See Shrestha et al., “Estimating the Burden of 2009 Pandemic Influenza A.”

Ropes & Gray: Liz Kowalczyk, “Firms’ Deals for Flu Drug Draw Fire,” Boston Globe, October 30, 2009.

the Boston Globe admonished Ropes & Gray: “Swine Flu: Firms Shouldn’t Hoard Drugs,” Boston Globe, November 3, 2009.

The CDC issued a curt statement: Kowalczyk, “Firms’ Deals for Flu Drug Draw Fire.”

Dr. Karen Victor: Ibid.

the flu virus was 100 percent resistant to Tamiflu: Centers for Disease Control and Prevention, “Update: Drug Susceptibility of Swine-Origin Influenza A (H1N1) Viruses, April 2009,” Morbidity and Mortality Weekly Report 58, no. 16 (2009): 435–55.

the U.S., Britain, and at least ninety-four other countries: A. Jack, “Flu’s Unexpected Bonus,” British Medical Journal 339 (2009): b3811.

The review by Dr. Kaiser and her colleagues: L. Kaiser et al., “Impact of Oseltamivir Treatment on Influenza-Related Lower Respiratory Tract Complications and Hospitalizations,” Archives of Internal Medicine 163, no. 14 (2003): 1667–72.

In December 2009 Jefferson released an updated review: T. Jefferson, M. Jones, P. Doshi, and C. Del Mar, “Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis,” British Medical Journal 339 (2009): b5106.

Paul Flynn sponsored a motion: “Early day motion 669,” www.parliament.uk. Accessed April 29, 2018. http://www.parliament.uk/edm/2009-10/669. For some odd reason, the motion described the distribution of Tamiflu as a vaccination program. It wasn’t.

salting Britain’s snowy roads: Z. Kmietowicz, “Use Leftover Tamiflu to Grit Icy Roads, MP Suggests,” British Medical Journal 340 (2010): c501.

the way the swine flu pandemic had been handled: “The Handling of the H1N1 Pandemic: More Transparency Needed,” Social, Health and Family Affairs Committee, Council of Europe. Accessed April 29, 2018. http://assembly.coe.int/CommitteeDocs/2010/20100329_MemorandumPandemie_E.pdf.

Fiona Godlee, the editor in chief: F. Godlee, “Conflicts of Interest and Pandemic Flu,” British Medical Journal 340 (2010): c2947. Godlee cited an in-depth review of WHO influenza experts and their ties to industry. See D. Cohen, “WHO and the Pandemic Flu ‘Conspiracies,’ ” British Medical Journal 340 (2010): c2912.

the review showed that Tamiflu reduced some of the complications: M. A. Hernan and M. Lipsitch, “Oseltamivir and Risk of Lower Respiratory Tract Complications in Patients with Flu Symptoms: A Meta-analysis of Eleven Randomized Clinical Trials,” Clinical Infectious Diseases 53, no. 3 (2011): 277–79.

Roche released all the trials requested by the Cochrane group: T. Jefferson and P. Doshi, “Multisystem Failure: The Story of Anti-Influenza Drugs,” British Medical Journal 348 (2014): g2263.

which it released in April 2014: T. Jefferson et al., “Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults and Children,” Cochrane Database of Systematic Reviews 4 (2014): CD008965. In addition, the group reviewed more than 160,000 pages of regulatory documents.

Tamiflu did not reduce the risk of hospitalization: Footnote for the health policy wonks: the Cochrane review wrote on page 2 that “Oseltamivir significantly reduced self reported, investigator-mediated, unverified pneumonia. . . . The effect was not significant in the five trials that used a more detailed diagnostic form for pneumonia. There were no definitions of pneumonia (or other complications) in any trial. No oseltamivir treatment studies reported effects on radiologically confirmed pneumonia. There was no significant effect on unverified pneumonia in children.”

the Lancet released an analysis: J. Dobson et al., “Oseltamivir Treatment for Influenza in Adults: A Meta-analysis of Randomised Controlled Trials,” Lancet 385, no. 9979 (2015): 1729–37.

recommended antiviral drugs only for those high-risk patients: See, for example, “What You Should Know About Influenza (Flu) Antiviral Drugs,” Centers for Disease Control and Prevention. Accessed April 29, 2018. https://www.cdc.gov/flu/pdf/freeresources/updated/antiviral-factsheet-updated.pdf. See also “Influenza Antiviral Medications: Summary for Clinicians,” Centers for Disease Control and Prevention. Accessed April 29, 2018. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm.

At a telephone news briefing: “Transcript for CDC Telebriefing: Update on Flu Season 2014–15,” Centers for Disease Control and Prevention. Accessed April 29, 2018. https://www.cdc.gov/media/releases/2014/t1204-flu-season.html.

earned his doctorate from MIT: P. Doshi, “Influenza: A Study of Contemporary Medical Politics” (Massachusetts Institute of Technology, 2011).

We met there: Interview on June 5, 2017.

the Department of Health and Human Services believed: U.S. Department of Health and Human Services, “HHS Pandemic Influenza Plan,” n.d., Appendix, D20. Much of the information in the following paragraphs is based on a telephone interview with Peter Palese, October 20, 2017.

On the front page was an article: D. Runde, “Still Prescribing Oseltamivir?,” Emergency Medicine News 39, no. 4. (2017): 1, 41.

9. THE HUNT FOR A FLU VACCINE

Vaccination: The terms “vaccination” and “inoculation” are used synonymously.

inoculation was used by the Chinese: C. P. Gross and K. A. Sepkowitz, “The Myth of the Medical Breakthrough: Smallpox, Vaccination, and Jenner Reconsidered,” International Journal of Infectious Disease 3, no. 1 (1998): 54–50.

priests traveled the Indian countryside: Neils Brimnes, “Variolation, Vaccination and Popular Resistance in Early Colonial South India,” Medical History 48, no. 2 (2004): 199–228.

Edward Jenner, a British physician: Biographic information is from S. Riedel, “Edward Jenner and the History of Smallpox and Vaccination,” Proceedings (Baylor University Medical Center) 18, no. 1 (2005): 21–25.

pleaded for his colleagues to stop bickering: E. Rosenow, “Prophylactic Inoculation against Respiratory Infections,” JAMA 72, no. 1 (1919): 31–34.

Leary mixed these samples together: Timothy Leary, “The Use of the Influenza Vaccine in the Present Epidemic,” American Journal of Public Health 8, no. 10 (1918): 754–55.

where at least 18,000 people were inoculated: Crosby, America’s Forgotten Pandemic, 100.

“fluphobia”: Price, “Influenza—Destroyer and Teacher,” 368.

There was no evidence, of course, that any of these vaccines actually worked: J. M. Eyler, “The State of Science, Microbiology, and Vaccines Circa 1918,” Public Health Reports 125, suppl. 3 (2010): 27–36.

Vaccine research didn’t kick into overdrive: Information in the following paragraphs is based on C. Hannoun, “The Evolving History of Influenza Viruses and Influenza Vaccines,” Expert Review of Vaccines 12, no. 9 (2013): 1085–94.

These centers identify the flu strains: C. Gerdil, “The Annual Production Cycle for Influenza Vaccine,” Vaccine 21, no. 16 (2003): 1776–79; “CDC Selecting Viruses for the Flu Season 2016,” Centers for Disease Control and Prevention. Accessed April 30, 2018. https://www.cdc.gov/flu/about/season/vaccine-selection.htm.

In the 2004–2005 flu season, that figure was only 10 percent: Data for the vaccine’s efficacy is from “Seasonal Influenza Vaccine Effectiveness, 2005–2018,” Centers for Disease Control and Prevention. Accessed May 3, 2018. https://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm.

the 2017–2018 influenza season: D. McNeil, “It’s Not Just You. Lots of People Caught the Flu,” New York Times, January 19, 2018, A12; D. M. Skowronski et al., “Early Season Co-circulation of Influenza A(H3N2) and B(Yamagata): Interim Estimates of 2017/18 Vaccine Effectiveness, Canada, January 2018,” Eurosurveillance 23, no. 5 (2018): 18-00035. A more recent paper estimates that overall the vaccine was 36 percent effective, but only 25 percent effective against the H3N2 viruses that were circulating. See B. Flannery et al., “Interim Estimates of 2017–18 Seasonal Influenza Vaccine Effectiveness—United States, February 2018,” Morbidity and Mortality Weekly Report 67 (2018): 180–85.

influenza mortality rate among seniors rose: W. W. Thompson et al., “Mortality Associated with Influenza and Respiratory Syncytial Virus in the United States,” JAMA 289, no. 2 (2003): 176–86.

a natural experiment in Japan: T. A. Reichert et al., “The Japanese Experience with Vaccinating Schoolchildren against Influenza,” New England Journal of Medicine 344, no. 12 (2001): 889–96.

in contrast to the majority of European countries: A. McGuire, M. Drummond, and S. Keeping, “Childhood and Adolescent Influenza Vaccination in Europe: A Review of Current Policies and Recommendations for the Future,” Expert Review of Vaccines 15, no. 5 (2016): 659–70.

Germany provides free vaccines: Ibid.

almost 60 percent in the U.S: “Flu Vaccination Coverage, United States, 2015–16 Influenza Season,” Centers for Disease Control and Prevention. Accessed April 30, 2018. https://www.cdc.gov/flu/fluvaxview/coverage-1516estimates.htm.

One CDC poster: Centers for Disease Control and Prevention. Accessed April 30, 2018. https://www.cdc.gov/flu/pdf/freeresources/general/p_universal_question_officeprint.pdf.

recommended the flu vaccine only for those at high risk: A. E. Fiore et al., “Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010,” MMWR Recommendations and Reports 59, no. RR-8 (2010): 1–62.

It is challenging, therefore, to compare the data: For the U.S., I used K. D. Kochanek et al., “Deaths: Final Data for 2014,” National Vital Statistics Reports 65, no. 4 (2016), Table 11. For England, I used NOMIS, run by the government’s Office of National Statistics. Available at https://www.nomisweb.co.uk/.

the Cochrane Collaborative in 2014: V. Demicheli et al., “Vaccines for Preventing Influenza in Healthy Adults,” Cochrane Database of Systematic Reviews 3 (2014): CD001269.

The CDC describes the flu like this in a poster: Centers for Disease Control and Prevention. Accessed April 30, 2018. https://www.cdc.gov/immigrantrefugeehealth/pdf/seasonal-flu/flu_and_you_english_508.pdf. There are a number of CDC informational posters available for physicians to place in their offices.

on the home page of the CDC’s flu site: “About Flu,” Centers for Disease Control and Prevention. Accessed April 30 2018. https://www.cdc.gov/flu/about/index.html.

advice about the flu from their National Health Service: “Flu,” My Health London. Accessed April 30, 2018. https://www.myhealth.london.nhs.uk/flu.

influenza can be a bit of a nuisance: Ibid.

Pollard is extremely cognizant of the numerous effects of the flu: Much of the information that follows is based on a phone interview with Pollard, July 22, 2017.

In the United States, the cost-effectiveness of the vaccine is less important: “Studies in the U.S. have shown that giving the vaccine to healthy working adults can reduce both the rates of days off work and the number of physician visits. These benefits are seen when the flu vaccine closely matches the circulating virus. In most years, however, the vaccine does not provide an overall economic benefit.” See C. B. Bridges et al., “Effectiveness and Cost-Benefit of Influenza Vaccination of Healthy Working Adults: A Randomized Controlled Trial,” JAMA 284, no. 13 (2000): 1655–63.

it is recommended for those older than seventy: “Shingles vaccine FAQs,” NHS. Accessed April 30, 2018. https://www.nhs.uk/conditions/vaccinations/shingles-vaccine-questions-and-answers.

“We cannot afford to take a chance”: Sencer and Millar, “Reflections on the 1976 Swine Flu Vaccination Program.”

We put more of our patients into the intensive care unit: S. Murthy and H. Wunsch, “Clinical Review: International Comparisons in Critical Care—Lessons Learned,” Critical Care 16, no. 2 (2012): 218. In the UK there are about 5 ICU beds per 100,000 people. In the U.S. there are about five times as many—twenty-five ICU beds per 100,000 people. The UK has a higher life expectancy than the U.S. See M. Prin and H. Wunsch, “International Comparisons of Intensive Care: Informing Outcomes and Improving Standards,” Current Opinion in Critical Care 18, no. 6 (2012): 700–706.

We give more chemotherapy to cancer patients: Ezekiel Emanuel and Justin Bekelman, “Is It Better to Die in America or in England?,” New York Times, January 16, 2016.

10. THE BUSINESS OF FLU

there were an additional 12,000 deaths: N. Hawkes, “Sharp Spike in Deaths in England and Wales Needs Investigating, Says Public Health Expert,” British Medical Journal 352 (2016): 1981.

in those older than sixty-five, there were 217,000 more deaths: L. Hiam et al., “What Caused the Spike in Mortality in England and Wales in January 2015?,” Journal of the Royal Society of Medicine 110, no. 4 (2017): 131–37.

freed up more than £28 billion in pension liabilities: “Slowdown in Life Expectancy Could Ease Pension Deficit by £28 Billion, Says Mercer,” Mercer. Accessed April 30, 2018. https://www.uk.mercer.com/newsroom/continuous-mortality-investigation-pensions-risk.html.

The Metropolitan Life Insurance Company paid out $24 million: Crosby, America’s Forgotten Pandemic, 312.

workers experienced a higher growth in wages: Thomas Garrett, “War and Pestilence as Labor Market Shocks: U.S. Manufacturing Wage Growth 1914–1919,” Economic Inquiry 47, no. 4 (2009): 711–25.

The flu’s positive impact on per capita income growth: Elizabeth Brainerd and Mark V. Siegler, “The Economic Effects of the 1918 Influenza Epidemic,” CEPR Discussion Paper, no. 3791 (2003).

claiming it had overreached: These examples are from Thomas Garrett, “Pandemic Economics: The 1918 Infuenza and Its Modern-Day Implications,” Federal Reserve Bank of St. Louis Review 90, no. 2 (2008): 75–93.

the timetable for banks, theaters, and department stores: F. Aimone, “The 1918 Influenza Epidemic in New York City: A Review of the Public Health Response,” Public Health Reports 125, suppl. 3 (2010): 71–79.

the poor were three times more likely to die: E. Sydenstricker, “The Incidence of Influenza among Persons of Different Economic Status during the Epidemic of 1918,” Public Health Reports 46, no. 4 (1931): 154–70.

Those who lived in a four-bedroom apartment: S. E. Mamelund, “A Socially Neutral Disease? Individual Social Class, Household Wealth and Mortality from Spanish Influenza in Two Socially Contrasting Parishes in Kristiania 1918–19,” Social Science & Medicine 62, no. 4 (2006): 923–40.

Sir Arthur Conan Doyle: Louise Welsh, “Arthur Conan Doyle’s Other Lost World,” Guardian, May 24, 2009.

Trump’s grandfather Frederick: Gwenda Blair, The Trumps: Three Generations That Built an Empire (New York: Touchstone, 2000), 116–17.

Douglas Almond, an economist from Columbia University: Douglas Almond, “Is the 1918 Influenza Pandemic Over? Long-Term Effects of In Utero Influenza Exposure in the Post-1940 U.S. Population,” Journal of Political Economy 114, no. 41 (2006): 672–712.

The Washington Post was outraged: “The Ghoulish Coffin Trust,” Washington Post, October 13, 1918, 4.

took out a full-page ad in the weekly Moving Picture World: Moving Picture World, November 9, 1918, 638.

He died of influenza a week before: Leslie DeBauche, Reel Patriotism: The Movies and World War I (Madison: University of Wisconsin Press, 1997), 149.

Evan Morris was hired by the pharmaceutical giant Roche: Details about Morris are taken from Brody Mullins, “Hidden Influence: The Fall of K Street’s Renegade,” Wall Street Journal, February 14, 2017, A1; and from an interview Mullins gave to C-SPAN, “Q and A with Brody Mullins,” C-SPAN. Accessed April 30, 2018. https://www.c-span.org/video/?424470-1/qa-brody-mullins.

There were 11,000 of them in 2016: This and the other figures cited are from the Center for Responsive Politics. See “Lobbying Database,” OpenSecrets.org. Accessed April 30, 2018. https://www.opensecrets.org/lobby/index.php.

Then he shot himself: Mullins, “Hidden Influence.”

10 percent of the budget of the National Institutes of Health: This 10 percent set aside began in the 1990s and ended in 2015, when it was no longer required by Congress.

less than 1 percent of the U.S. population is infected with the virus: “HIV in the United States: At A Glance,” Centers for Disease Control and Prevention. Accessed April 30, 2018. https://www.cdc.gov/hiv/statistics/overview/ataglance.html.

Nearly $213 million: “HHS FY2016 Budget in Brief,” U.S Department of Health and Human Services. Accessed April 30, 2018. https://www.hhs.gov/about/budget/budget-in-brief/phssef/index.html.

the budget dropped by 60 percent, to $68 million: Ibid.

the news was better in 2017: “HHS FY2017 Budget in Brief,” U.S. Department of Health and Human Services. Accessed April 30, 2018. https://www.hhs.gov/about/budget/fy2017/budget-in-brief/phssef/index.html.

The NIH is heavily invested in influenza research: It is hard to get an exact amount, because reports are generated by looking for any project with a keyword “influenza” or the like, even if the project is really focused on another topic entirely. Even so, it’s the best estimate we have. See “Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC),” NIH Portfolio Online Reporting Tools (RePORT). Accessed April 30, 2018. https://report.nih.gov/categorical_spending.aspx.

The NIH estimates that every one dollar it spends on research: The1:8 ratio is for basic research after eight years. Clinical research yields a more modest 1:2 return on investment after three years. See “Impact of NIH Research,” National Institutes of Health. Accessed April 30, 2018. https://www.nih.gov/about-nih/what-we-do/impact-nih-research/our-society.

in the words of its infomercial: Cue.Me. Accessed April 30, 2018. https://cue.me/#inflammation.

Cue initially received $2 million from angel investors: Douglas Macmillan, “Cue Gets $7.5 Million to Build $199 Home Flu-Testing Device,” Wall Street Journal, November 18, 2014.

“The business is based on the razor-and-blade model”: Ibid.

rapid influenza tests are not very sensitive: C. Chartrand et al., “Accuracy of Rapid Influenza Diagnostic Tests: A Meta-analysis,” Annals of Internal Medicine 156, no. 7 (2012): 500–511.

“Total Economic Consequences of an Influenza Outbreak in the United States”: F. Prager, D. Wei, and A. Rose, “Total Economic Consequences of an Influenza Outbreak in the United States,” Risk Analysis 37, no. 1 (2017): 4–19.

a two-week total electricity blackout in Los Angeles County: A. Rose, G. Oladosu, and S. Liao, “Business Interruption Impacts of a Terrorist Attack on the Electric Power System of Los Angeles: Customer Resilience to a Total Blackout,” Risk Analysis 27, no. 3 (2009): 513–31.

the peak activity of the influenza virus came two weeks later: J. S. Brownstein, C. J. Wolfe, and K. D. Mandl, “Empirical Evidence for the Effect of Airline Travel on Inter-regional Influenza Spread in the United States,” PLoS Medicine 3, no. 10 (2006): e401.

he heard a news report about a shortage of exotic dancers: Details are from a phone interview with Charles Stoecker, October 30, 2017.

“Success Is Something to Sneeze At”: Charles Stoecker, Nicholas Sanders, and Alan Barreca, “Success Is Something to Sneeze At: Influenza Mortality in Regions That Send Teams to the Super Bowl,” Tulane Economics Working Paper Series 2015; working paper 1501.

headline in the New York Times: Austin Frakt, “Your Team Made the Super Bowl? Better Get a Flu Shot,” New York Times, February 1, 2016, A3.

EPILOGUE

Pandemic Influenza Plan: “Pandemic Influenza Plan, 2017 Update,” U.S. Department of Health and Human Services, n.p n.d. Accessed April 30, 2018. https://www.cdc.gov/flu/pandemic-resources/pdf/pan-flu-report-2017v2.pdf.

we still don’t have good enough evidence to drive other policy decisions: T. Jefferson, “Influenza Vaccination: Policy versus Evidence,” British Medical Journal 333, no. 7574: 912–15.

And so do the viruses we are carrying: Many years ago, a plane sat on the runway for three hours while a mechanical problem was fixed. It was carrying one passenger with influenza. Three days later, almost three-quarters of the passengers came down with the very same influenza virus. M. R. Moser et al., “An Outbreak of Influenza aboard a Commercial Airliner,” American Journal of Epidemiology 110, no. 1 (1979): 1–6.

crowded housing is still a fact of life for many: “Charting the Progress of Populations,” United Nations Population Division. Accessed April 30, 2018. http://www.un.org/esa/population/pubsarchive/chart/14.pdf.

the United States is not immune: “Historical Census of Housing Tables,” The United States Census Bureau. Accessed April 30, 2018. https://www.census.gov/hhes/www/housing/census/historic/crowding.html.

In New York, almost 9 percent of households: Office of the City Comptroller, “Hidden Households,” New York City Housing Brief (2015). Accessed April 30, 2018. https://comptroller.nyc.gov/wp-content/uploads/documents/Hidden_Households.pdf.

A virus that is very potent quickly kills its host: D. M. Morens, J. K. Taubenberger, and A. S. Fauci, “The Persistent Legacy of the 1918 Influenza Virus,” New England Journal of Medicine 361, no. 3 (2009): 225–29.