Table of Contents:

Foreword

Introduction

I. Storm Gathering

1. 1918

2. Master of Metamorphosis

3. H5N1

4. Playing Chicken

5. Worse Than 1918?

6. When, Not If

II. When Animal Viruses Attack

1. The Third Age

2. Man Made

3. Livestock Revolution

4. Tracing the Flight Path

5. One Flu Over the Chickenís Nest

6. Coming Home to Roost

7. Guarding the Henhouse

III. Pandemic Preparedness

1. Cooping Up Bird Flu

2. Race Against Time

3. Tamiflu

IV. Surviving the Pandemic

1. Donít Wing It

2. Our Health in Our Hands

3. Be Prepared

V. Preventing Future Pandemics

1. Tinderbox

2. Reining in the Pale Horse

Topics

References 1-3,199

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—Jeffery Taubenberger, molecular pathologist and arche-virologist84
Johan and Mary

Where did this disease come from? Popular explanations at the time included a covert German biological weapon, the foul atmosphere conjured by the war’s rotting corpses and mustard gas, or “spiritual malaise due to the sins of war and materialism.”85 This was before the influenza virus was discovered, we must remember, and is consistent with other familiar etymological examples—malaria was contracted from mal and aria (“bad air”) or such quaintly preserved terms as catching “a cold” and being “under the weather.”86 The committee set up by the American Public Health Association to investigate the 1918 outbreak could only speak of a “disease of extreme communicability.”87 Though the “prevailing disease is generally known as influenza,” they couldn’t even be certain that this was the same disease that had been previously thought of as such.88 As the Journal of the American Medical Association observed in October 1918, “The ‘influence’ in influenza is still veiled in mystery.”89

In the decade following 1918, thousands of books and papers were written on influenza in a frenzied attempt to characterize the pathogen. One of the most famous medical papers of all time, Alexander Fleming’s “On the Antibacterial Actions of Cultures of Penicillium,” reported an attempt to isolate the bug that caused influenza. The full title was “On the Antibacterial Actions of Cultures of Penicillium, with Special Reference to Their Use in the Isolation of B. Influenzae.” Fleming was hoping he could use penicillin to kill off all the contaminant bystander bacteria on the culture plate so he could isolate the bug that caused influenza. The possibility of treating humans with penicillin was mentioned only in passing at the end of the paper.90

The cause of human influenza was not found until 1933, when a British research team finally isolated and identified the viral culprit.91 What they discovered, though, was a virus that caused the typical seasonal flu. Scientists still didn’t understand where the flu virus of 1918 came from or why it was so deadly. It would be more than a half-century before molecular biological techniques would be developed and refined enough to begin to answer these questions; but by then where would researchers find 1918 tissue samples to study the virus?

The U.S. Armed Forces Institute of Pathology originated almost 150 years ago. It came into being during the Civil War, created by an executive order from Abraham Lincoln to the Army Surgeon General to study diseases in the battlefield.92 It houses literally tens of millions of pieces of preserved human tissue, the largest collection of its kind in the world.93 This is where civilian pathologist Jeffery Taubenberger first went to look for tissue samples in the mid ’90s. If he could find enough fragments of the virus he felt he might be able to decipher the genetic code and perhaps even resurrect the 1918 virus for study, the viral equivalent of bringing dinosaurs back to life in Jurassic Park.94

He found remnants of two soldiers who succumbed to the 1918 flu on the same day in September—a 21-year-old private who died in South Carolina and a 30-year-old private who died in upstate New York. Tiny cubes of lung tissue preserved in wax were all that remained. Taubenberger’s team shaved off microscopic sections and started hunting for the virus using the latest advances in modern molecular biology that he himself had helped devise. They found the virus, but only in tiny bits and pieces.95

The influenza virus has eight gene segments, a genetic code less than 14,000 letters long (the human genome, in contrast, has several billion). The longest stands of RNA (the virus’s genetic material) that Taubenberger could find in the soldiers’ tissue were only about 130 letters long. He needed more tissue.96

The 1918 pandemic littered the Earth with millions of corpses. How hard could it be to find more samples? Unfortunately, refrigeration was essentially nonexistent in 1918, and common tissue preservatives like formaldehyde tended to destroy any trace of RNA.97 He needed tissue samples frozen in time. Expeditions were sent north, searching for corpses frozen under the Arctic ice.

Scientists needed to find corpses buried below the permafrost layer, the permanently frozen layer of subsoil beneath the topsoil, which itself may thaw in the summer.98 Many teams over the years tried and failed. U.S. Army researchers excavated a mass grave near Nome, Alaska, for example, only to find skeletons.99 “Lots of those people are buried in permafrost,” explained Professor John Oxford, co-author of two standard virology texts, “but many of them were eaten by the huskies after they died. Or,” he added, “before they died.”100

On a remote Norwegian Island, Kirsty Duncan, a medical geographer from Canada, led the highest profile expedition in 1998, dragging 12 tons of equipment and a blue-ribbon academic team to the gravesite of seven coal miners who had succumbed to the 1918 flu.101 Years of planning and research combined with surveys using ground-penetrating radar had led the team to believe that the bodies of the seven miners had been buried deep in the eternal permafrost.102 Hunched over the unearthed coffins in biosecure space suits, the team soon realized their search was in vain.103 The miners’ naked bodies, wrapped only in newspaper, lay in shallow graves above the permafrost. Subjected to thawing and refreezing over the decades, the tissue was useless.104

Nearly 50 years earlier, scientists from the University of Iowa, including a graduate student recently arrived from Sweden named Johan Hultin, had made a similar trek to Alaska with similarly disappointing results.105 In the fall of 1918, the postal carrier delivered the mail—and the flu—via dogsled to a missionary station in Brevig, Alaska.106 Within five days, 72 of the 80 or so missionaries lay dead.107 With help from a nearby Army base, the remaining eight buried the dead in a mass grave.108 Governor Thomas A. Riggs spent Alaska into bankruptcy caring for the orphaned children at Brevig and across the state. “I could not stand by and see our people dying like flies.”109

Learning of Taubenberger’s need for better tissue samples, Johan Hultin returned to Brevig a few weeks before his 73rd birthday.110 Hultin has been described as “the Indiana Jones of the scientific set.”111 In contrast to Duncan’s team, which spent six months just searching for the most experienced gravediggers, Hultin struck out alone.112 Hultin was “there with a pickaxe,” one colleague relates. “He dug a pit though solid ice in three days. This guy is unbelievable. It was just fantastic.”113

Among the many skeletons lay a young woman whose obesity insulated her internal organs. “She was lying on her back, and on her left and right were skeletons, yet she was amazingly well preserved. I sat on an upside-down pail, amid the icy pond water and the muck and fragrance of the grave,” Hultin told an interviewer, “and I thought, ‘Here’s where the virus will be found and shed light on the flu of 1918.’”114 He named her Lucy. A few days later, Taubenberger received a plain brown box in the mail containing both of Lucy’s lungs.115 As Hultin had predicted, hidden inside was the key to unlock the mystery.

Many had assumed that the 1918 virus came from pigs. Although the human influenza virus wasn’t even discovered until 1933, as early as 1919 an inspector with the U.S. Bureau of Animal Industry was publishing research that suggested a role for farm animals in the pandemic. Inspector J.S. Koen of Fort Dodge, Iowa wrote:
The similarity of the epidemic among people and the epidemic among pigs was so close, the reports so frequent, that an outbreak in the family would be followed immediately by an outbreak among the hogs, and vice versa, as to present a most striking coincidence if not suggesting a close relation between the two conditions. It looked like “flu,” and until proven it was not “flu,” I shall stand by that diagnosis.116
According to the editor of the medical journal Virology, Koen’s views were decidedly unpopular, especially among pig farmers who feared that customers “would be put off from eating pork if such an association was made.”117 It was never clear, though, whether the pigs were the culprits or the victims. Did we infect the pigs or did they infect us?

With the entire genome of the 1918 virus in hand thanks to Hultin’s expedition, Taubenberger was finally able to definitively answer the Holy Grail question posed by virologists the world over throughout the century: Where did the 1918 virus come from? The answer, published in October 2005,118 is that humanity’s greatest killer appeared to come from avian influenza—bird flu.119

Evidence now suggests that all pandemic influenza viruses—in fact all human and mammalian flu viruses in general—owe their origins to avian influenza.120 Back in 1918, schoolchildren jumped rope to a morbid little rhyme:
I had a little bird,
Its name was Enza.
I opened the window,
And in-flu-enza.121