Pandemic? Very, very likely.206
The economic impact of the avian flu epidemic on the Southeast Asian countryside was profound. Thousands of small chicken farmers were bankrupted and forced out of business, thus yielding ground, as Chearavanont had urged, to the corporate operators. Meanwhile, the unprecedented market turbulence unleashed by the H5 epidemic in Asia, followed by the H7 outbreaks in North America, encouraged the big poultry producers to poach one another’s customers. In the United States, giants like Tyson and Pilgrim’s Pride were “already reaping some benefits from the bird flu virus” in late January as they rushed exports to replace the quarantined Thai supply. Jim Summer, president of the Poultry and Egg Export Council, told reporters that the avian flu “is going to have an unbelievable impact on the poultry industry” and boasted of a surge in hiring by U.S. companies. CP, meanwhile, exploited its own disaster by increasing exports from plants in Taiwan and other nonembargoed countries to take advantage of the sharp rise in chicken prices. To offset current and future EU import controls, Chearavanont also announced an ambitious expansion of poultry operations in Romania, Russia, and Ukraine, and he reassured his shareholders that they would soon reap profit from the influenza-driven restructuring of global chicken production.207
All of this cheery news from the giant chicken producers was of little solace to the researchers struggling to understand the spectacular menace of H5N1 GenZ. An extraordinary research consortium combining the resources of Robert Webster’s St. Jude Hospital group, the veteran team from the University of Hong Kong, and local experts from across Asia had been working feverishly to unravel the genealogy and molecular structure of the 2003–4 strain. To achieve a panoramic view of its evolution, they sequenced and compared the genomes of hundreds of viral samples obtained from human victims and poultry. Their findings were disturbing.
In a letter to Nature in July 2004, they warned the virus’s erstwhile conquerors that, in fact, avian flu—now comfortably ensconced among asymptomatic domestic ducks—was almost ineradicable. “H5N1 is now endemic in poultry in Asia and has gained an entrenched ecological niche from which to present a long-term pandemic threat to humans.” Moreover, its sudden retreat in March might have had more to do with influenza’s seasonal cycle than with the mass murder of chickens: “Since 2001, H5N1 viruses have continued to circulate in mainland China with a seasonal pattern, peaking from October to March, when the mean temperature is below 20 centigrade.” They also noted that “the timing and distribution of the H5N1 infection in China from 2001 onwards coincides with the general period of winter bird migration to southern China: however it is not know whether the H5N1 virus has become established in wild bird populations.”208
Although they now possessed a detailed map of the structure of GenZ—each protein had been analysed to the last amino acid group—they were still baffled by its functional organization: they had, so to speak, a splendid view of the wiring, but only a fragmentary concept of its purpose. They knew that GenZ, the sole survivor of a marathon competition between more than a dozen H5N1 genotypes, was a superfit strain, and was evolving rapidly as it passed back and forth between different populations and species. (Other studies would show that GenZ was far more environmentally stable than the 1997 strain and that it was becoming progressively more skillful in infecting mammals.)209 They also knew that natural selection, horrifyingly, seemed to favor increased virulence in humans, but they were unable to nail down the molecular determinants of the human infections in Vietnam and Thailand or, for that matter, explain why H5N1 had not yet acquired pandemic transmissibility. The researchers noted potentially synergistic mutations at strategic sites in the H5 molecule as well as in proteins (PB2 and NSI) involved with replication and immune suppression, but they refrained from speculating how these variations were choreographed in avian or human infections.210
Gen Z, in other words, was not giving away any secrets. Although leading researchers would presumably all concur with evolutionary biologist Simon Levin that “influenza presents a [evolutionary] system that is second to none in terms of complexity,” there had been considerable optimism that a “smoking gun” of some kind would emerge from the high-powered research teams doing parallel work on H5N2 and the resurrected genome of the 1918 virus—science seemed tantalizingly close to unlocking the secret of why some influenzas were such vicious killers. The team working on recovered fragments of the 1918 genome, led by Jeffery Taubenberger, Ann Reid, and Thomas Fanning at the Armed Forces Institute of Pathology in Maryland, had made breathtaking progress in unraveling the molecular structure of H1N1/1918, but they had failed to resolve the central question of the source of its pathogenicity. Indeed, their research to date has only reframed the essential mysteries of the great pandemic, offering “no definite clue to [its] exceptional virulence,” while casting doubt on the traditional hypothesis that it originated either in swine or ordinary waterfowl.211
By the summer of 2004, in other words, the world’s elite influenza researchers had reached the sobering consensus that avian influenza would neither go away nor allow itself to be easily understood. (“It’s troubling to me,” leading CDC researcher Keiji Fukuda confided to the New York Times in fall 2004, “that we still don’t know much more about this virus than we did in 1997.”)212 Many also had begun to worry that the virus might bypass the textbook requirement to reassort with a human influenza and simply evolve on its own to the pandemic stage by the simple accumulation of a few more mutations. “Mutation during human infection,” the WHO had cautioned in April, “is a second mechanism for improving transmissibility; scientists believe that only a small number of mutational changes in the virus may be needed.”213 In August Western scientists were shocked to discover that a team of Chinese virologists from the Harbin Veterinary Research Institute had published a paper in January in which they reported that H5N1 was widespread in swine in southeast China and urged utmost “pandemic preparedness.” That such an important report should have passed unnoticed for months by the WHO and FAO hardly inspired confidence in global influenza surveillance.214
Just as researchers feared, GenZ came creeping back at the end of spring, infecting a mixed flock of chickens and waterfowl at a university research farm in Thailand in late May; by July there were widespread outbreaks in Vietnam, central Thailand, and China’s Anhui province. Thai officials again responded by blaming foreign birds and ordered crews to exterminate open-bill storks and chop down the trees they nested in. (An ornithologist despaired: “I’ve never seen anything like it. Birds had become the enemy.”)215 In mid-August veterinary officers discovered Malaysia’s first case of H5N1 in a pair of fighting cocks returned from a match in Thailand: troubling evidence that the prized sporting birds were now a vector of infection. Vietnam then shattered hopes with a belated announcement that three people, including two young sisters, had died between 30 July and 3 August in Hau Giang province, southwest of Ho Chi Minh City.216
Bad news grew worse in September with human deaths reported in Thailand, the first being a eighteen-year-old game-bird trainer. As they investigated, WHO officials were horrified to find out that it was common practice for the owners of fighting cocks to suck blood and mucous from the beaks of birds injured in a fight. Over the next two weeks an eleven-year-old girl and a thirteen-year-old boy died, while nine other children languished in intensive care. Dr. Shigeru Omi, the WHO’s Regional Director for the Western Pacific Region, warned emphatically in mid-September that “unless intensified efforts are made to halt the spread of the virus, a pandemic is very likely to occur.”217 In an oafish attempt to reassure international opinion that his government was on the job, the Director of the Department of Livestock Development, Yukol Limlamthong, emphasized that avian flu outbreaks had been identified in “only 56 locations across 23 provinces . . . not hundreds of spots as in some news reports.” The exasperated head of the Public Health Ministry, Dr. Charal Trinwuthipong, promptly blasted Limlamthong’s department for its negligence in monitoring and reporting outbreaks: “They’ve not improved! How damned lousy they were last time, that’s how they still are.”218
While the fur was flying between Thai ministries, simultaneous outbreaks of H5N1 and H3N2 in several districts in Thailand again raised the specter of pandemic reassortment. Despite pleas from leading public-health experts, Prime Minister Thaksin refused to import vaccine from Europe to protect the country’s exposed populations. He did, however, robustly defend CP against embarrassing charges by Cambodian farmers that chickens purchased from CP Cambodia Ltd. were the source of a new outbreak in that country.219 He also proposed to aid the big exporters by bartering their contaminated chicken to Moscow. “When we can’t sell in our traditional markets, we need to penetrate new markets by bartering. We can’t leave all this chicken in Thailand.” He ordered his ambassador in Moscow to offer a mountain of chicken in exchange for Sukol SU-30 fighters for the Thai air force. Vladimir Putin, unsurprisingly, declined to accept the bargain.220
All this, however, was just a bizarre prelude to the devastating news revealed to the world by the WHO on 28 September: Pranee Thongchan in Kamphaeng Phet was the first victim of a probable human-to-human transmission of the virus, which she contracted from her mortally ill daughter (see Preface). Although Klaus Stohr, the former East German veterinarian who was now head of the WHO Global Influenza Program, reassured the public that the case was epidemiologically a “nonsustained, inefficient, dead-end street,” CDC scientists were, in fact, frantically sequencing viral samples from the dead mother and daughter to see if GenZ had “mutated significantly—or worse, reassorted with a human flu”—a possible consequence of the government’s failure to vaccinate hot-spot populations. In a joint statement, the WHO and FAO warned that avian influenza was now “a crisis of global importance.”221
Although no human flu genes were found in the viral samples, Pranee’s death was an earthquake that thoroughly shook international confidence in Thailand. More than chicken exports were now endangered: tourism, the source of 6 percent of the nation’s GDP, was under threat. Prime Minister Thaksin responded with a tantrum in which he blamed the “ignorance” of villagers for the persistence of the outbreak and—music to the ears of corporate poultry producers—threatened to ban farm families from raising fowl in their yards. He melodramatically ordered his ministers to eradicate the flu in a month or lose their heads. And facing charges that livestock authorities were bungling the monitoring of poultry, he called for a million volunteers to search the country for sick chickens. “I want to X-ray every single inch of the country,” he told provincial governors. “If we see dead birds during the inspection, we will assume that it’s bird flu and start culling in the region. The government will spend any amount of money on the project.”222
Thaksin’s crusade against small farmers and wild birds, however, did not prevent further deaths. Neighbors of nine-year-old Kanda Siluangon, who died in early October, “blamed district and provincial livestock officials, saying they did nothing for one month after being notified of the chicken deaths.”223 A female worker at a chicken-processing plant died a few days later, followed in mid-October by a fourteen-year-old farm girl. The most unexpected victims in October, however, were cats, big and small. As their horrified keepers stood helpless, more than eighty Bengal tigers at the famed Sriracha Tiger Zoo near Bangkok perished in spasms of viral pneumonia. They had been fed raw chicken. Similarly, GenZ was identified in house cats, presumably as a result of their feeding on infected poultry or wild birds. Influenza experts were dismayed because cats had long been considered resistant to all varieties of influenza A. They also discovered that cats could pass the virus to each other, making felines suddenly suspect as significant flu vectors and possible incubators.224
Then, on 26 October, Europe was provided with a firsthand demonstration of how comprehensively GenZ was spreading through Southeast Asian fauna after a Thai smuggler was stopped at the Brussels airport; he had two tiny rare eagles hidden in a PVC pipe in his hand luggage. The man was eventually let go, and the birds were put into quarantine. A few days later they tested positive for H5N1, setting off a frantic hunt to identify passengers who might have had inadvertent contact with the smuggler. The veterinarian who was called in to euthanize the little eagles (as well as the four hundred other birds in quarantine at the airport) developed a mild but nonetheless alarming case of conjunctivitis. Belgium’s leading influenza expert, Rene Snacken, at the Scientific Institute of Public Health, warned New Scientist: “We were very, very lucky. It could have been a bomb for Europe.”225
A few weeks later, Ken Shortridge, the senior member of the famed Hong Kong team that had battled H5N1 in 1997 and SARS in 2003, told a scientific conference that the increasing interspecies transmission of avian influenza risked something even more profound than a new human pandemic. “If this virus gets into bird life beyond poultry,” he warned, “we could wreck the global ecosystem.” Eight years of research on H5N1 had convinced him that this cunning little Darwinian demon was capable of ecocide—the wiping out of entire species.226
There was no shortage of dismaying visions in the late fall of 2004. When Newsweek asked a leading microbiologist whether a pandemic was possible, he replied, “I don’t think we completely understand why it hasn’t happened already.”227 Indeed, there was broad agreement among researchers that an H5 pandemic was not simply imminent, it was “late.” Getting this urgent message across to news media, the nonspecialist medical community, NGOs, and ultimately, to presidents, prime ministers, and kings the world over was the urgent task entrusted to the WHO (in theory, the medical conscience of humanity). It was an uneven and divided effort compromised by undue deference to the interests of powerful states, including China and the United States, which generated some lurid headlines and rhetorical promises but none of the truly decisive action urged by experts on the ground.
In late October, a conference at Cold Spring Harbor on Long Island, sponsored by the Sabin Vaccine Institute, brought WHO authorities, U.S. health officials, and drug manufacturers together to discuss a global vaccine strategy in face of the pandemic threat. This dialogue was resumed in Geneva in mid-November under WHO auspices. A parade of experts complained that “very little action” had been taken to avert pandemic “devastation,” and the WHO’s Klaus Stohr told delegates, “If we continue as we are now, there will be no vaccine available, let alone antivirals, when the next pandemic starts.” He also played to the U.S. obsession with terrorism by urging counties “to raise the profile of pandemic preparedness as a matter of national security.”228 An Aventis-Pasteur executive, however, warned public-health officials that manufacturers were prepared to develop new vaccines only if governments were willing to underwrite the costs of research and guarantee sales. The position of the drug industry, in other words, was “no vaccine” unless broad profit margins were guaranteed. This excluded participation by most poor countries. Apart from South Africa and Brazil, which already produce small quantities of annual flu vaccine, the prospects for a truly “global” vaccine that would be available in the Third World were bleak at best. A third WHO-sponsored meeting in Bangkok at the end of November elicited new pledges from ASEAN health ministers, who promised regional coordination in an intensified fight against the poultry plague; however, no concrete commitments emerged dealing with live-animal markets, vaccine development, or the stockpiling of antivirals.229
Many researchers and activists wondered if the WHO was not being too meek in sounding the tocsin. In particular, they worried that WHO’s influenza czar, Klaus Stohr, had been deliberately underselling the menace of H5N1 in order to safeguard the organization’s credibility in the face of skeptical governments. When asked about possible mortality, Stohr routinely referred to a U.S. CDC study that projected 2 to 7.4 million deaths globally, but CDC health economist Martin Meltzer had derived these figures by extrapolating from the mild 1968 pandemic; most influenza experts actually feared that H5N1 could become as deadly as the 1918 virus. Michael Osterholm, the respected director of the Center for Infectious Disease Research and Policy at the University of Minnesota, characterized Stohr’s cautious estimates as “rather ridiculous.”230
Table 9.1.
How Many Might Die?
1957 mortality | 2 million |
1968 mortality | 0.7 million |
1968 extrapolated (Stohr) | 2 to 7.4 million |
1918 mortality | 40 to 100 million |
Omi’s estimate | 7 to 100 million |
1918 extrapolated | 325 million (maximum) |
H5N1 mortality extrapolated | 1 billion |
Most of the scientific community, therefore, was heartened when the WHO’s Shigeru Omi evoked the 1918 precedent when he warned the press on 29 November: “We are talking at least seven million [deaths], but maybe more—10 million, 20 million and the worst case, 100 million.” (Omi was still being conservative: an direct extrapolation of maximum 1918 mortality to today’s world population would be 325 million dead.) The cat was out of the bag, and top experts, like Malik Peiris at the University of Hong Kong, rushed to defend Omi’s figures as “consistent with current research.” Scotland’s Sunday Herald, moreover, in mid-December printed frightening excerpts from a leaked UK government study that projected a near-breakdown of British society during a pandemic. “A minimum of 25 percent of the population will become ill over each six- to eight-week period. . . . Mortality is likely to be high—estimated at 1 percent of the total population.”
The WHO ultimately bowed to majority opinion and, over Stohr’s objections, revised his previous estimates as “a best-case scenario”; 50 million dead was now officially the “worst case.” Yet a few epidemiologists think even 50 million dead is wishful thinking. Extrapolating from the current lethality of GenZ rather than from 1918 mortality (i.e., 72 percent versus 2.5 percent), they reminded officials that the true worst-case scenario, in fact, was more in the range of 1 billion deaths.231