One of the most difficult things to explain to the public after a pandemic would be why we weren’t prepared, because there have been enough warnings.260
Influenza vaccines are especially disliked by drug companies because they are tricky to produce, become obsolete after one season, and are subject to large fluctuations in demand. Moreover, the basic production process has changed little since the days of Francis and Salk a half century ago, and the industry has failed to invest in the faster and safer cell-culture technology that would eliminate the risk of contamination inherent in using fertile chicken eggs.261 Vaccine manufacturing in general is widely regarded as a broken-down old railroad to be off-loaded at the first opportunity rather than repaired and modernized. Big Pharma, by and large, has spurned the little biotech startups in San Diego, Austin, and Boston that have been searching for capital to develop exciting new recombinant and genetically engineered vaccines. In terms of vaccine development in general, the United States measures poorly even against tiny Cuba which, thanks to the priority given to infectious and “poor people’s” diseases, has become a world leader in creating state-of-the-art vaccines for meningitis B, Haemophilus influenzae, and other important infections ignored by giant drug companies in the United States.262
Meanwhile, aging and poorly maintained vaccine production facilities have been plagued by poor quality control and indifferent management. In September 2000, for example, 12 percent of the influenza vaccine supply was lost when the FDA shut down Parkdale Pharmaceuticals’ contaminated facility, which never reopened; deliveries from Wyeth-Ayerst, which produced one-third of the national supply, were also delayed because of quality problems (the company abandoned vaccine production two years later after a mild flu season left millions of doses unsold).263 By the winter of 2003–4—with the Institute of Medicine sternly warning Washington that the country was still “poorly prepared” for a flu pandemic—only two corporations were still making influenza vaccine for the U.S. market: French-owned Aventis-Pasteur with a manufacturing complex in Swiftwater, Pennsylvania, and Bay Area-based Chiron, with a recently acquired plant near Liverpool.264
This was an extraordinary contrast to the situation in 1976, when thirty-seven companies in the United States produced flu vaccine, or for that matter, to current policy in the UK, where the government retains contracts with six major suppliers.265 Although the GAO had warned HHS in May 2001 about the “fragility of the vaccine supply,” the Department “didn’t display any comprehension of what the problem was and what should be done about it.”266 Even as it hyped the importance of “biosecurity,” the Bush administration in essence mortgaged the lives of tens of thousands of senior citizens, for whom annual influenza is a life-threatening illness, by relying on vaccine production in just two plants—and one of them, it would turn out, had an alarming record of poor quality control.
The 2003–4 flu season brought another vaccine disaster: a virulent strain of annual influenza (H3N2 Fujian), which was not included in the vaccine mixture, proved more dangerous than expected to small children, and the old-fashioned egg-based production system precluded any last-minute reformulation of the vaccine. Even with a component missing, vaccine demand rose steeply; however, the two manufacturers, wary of being stuck with an excess supply as they had been the previous year, had manufactured too little, and some localities had to resort to rationing. While HHS had foreseen the likely shortfall, they had failed to exert enough pressure on the manufacturers to increase production.
As the media headlined stories about children in Texas and Colorado dying from the Fujian strain, the CDC was nervously monitoring the new, extraordinarily widespread outbreak of H5N1 in Asia. Secretary Thompson finally acknowledged—although with less urgency than previous announcements about anthrax and smallpox—that a flu pandemic was an imminent danger, and the administration promised to accelerate vaccine development. Despite widespread criticism of their conduct during the previous flu season, Thompson decided to again make Aventis-Pasteur and Chiron the twin pillars of the U.S. vaccine program. In May both corporations received contracts from the National Institute of Allergy and Infectious Diseases to produce experimental lots of an H5N1 vaccine using a seed strain from Robert Webster’s laboratory at St. Jude; in mid-August, Chiron was also awarded the contract to develop a vaccine against the H9N2 subtype.
In retrospect, it is hard to fathom Thompson’s confidence in Chiron. Under a succession of previous owners, its Liverpool plant had developed a notorious reputation for contamination. “It is an antiquated facility and poorly managed” was the opinion of one business analyst.267 British authorities had once recalled contaminated polio vaccines made in the plant, while the FDA had admonished a previous owner about impurities in its flu vaccine. In the summer of 2003 FDA inspectors discovered significant risk of bacterial contamination in twenty different production activities, especially in the sterilization processes; because the plant was responsible for manufacturing almost half of the U.S. vaccine supply, the inspection team recommended compulsory steps to mitigate the danger. Their superiors, however, insisted upon voluntary, rather than mandatory, compliance. The agency then curiously delayed for nine months before forwarding Chiron its full inspection report, and, instead of sending inspectors back to monitor Chiron’s progress, FDA officials consulted with the company by telephone or email. Lester Crawford, the acting head of the FDA, later assured a skeptical congressional committee that since the 2003–4 vaccine was acceptable, the FDA considered Chiron’s Liverpool problems resolved. (“They had in fact completed what we wanted them to do.”)268
The FDA’s timidity and Crawford’s nonchalance angered U.S. Representative Henry Waxman of California and other members of the House Committee on Government Reform, but they also knew that the agency’s policy of sleeping with the enemy, or rather, “working with the pharmaceutical industry as a trusted partner,” had been promoted by the Clinton administration—supposedly in order to speed production and approval of “breakthrough drugs.” Critics of Big Pharma, on the other hand, saw the FDA’s “partnership” with Chiron as classic evidence that another regulatory agency had been captured by the industry it was supposed to regulate.
In July 2004 Chiron found Serratia marcescens—a bacteria that can cause deadly septic shock—in several batches of vaccine. Instead of immediately alerting the FDA, the company instead issued a press release “boasting that it already had shipped 1 million doses of Fluviron vaccine to the U.S. market and planned to ship 52 million more doses.” Chiron waited more than a month, until 26 August, to notify the FDA of contamination. Once again, Crawford trusted the corporation to rectify the problem. At the end of September, Chiron CEO Howard Pien personally reassured the Senate Committee on Aging that quality control had been restored to the Liverpool plant, which would soon ship 48 million doses of vaccine to the United States; instead, a week later, vigilant British inspectors shut the plant down and revoked Chiron’s license to sell flu vaccine.269 Although the corporation claimed that a portion of the vaccine was uncontaminated, FDA investigators determined that the entire stock was spoiled.
As a result, the United States lost half of its seasonal vaccine and was forced to ration the rest. Although the CDC and local health officials worked miracles in shifting vaccine to areas of greatest need, the crazy quiltwork of the U.S. vaccine distribution system—with literally thousands of independent government and private agents involved—gave a disturbing foretaste of the chaos that a pandemic would create. The Chiron disaster easily risked killing as many Americans through lack of vaccination as the 9/11 attacks, but Thompson, Crawford, and their underlings continued to breezily disclaim any responsibility for errors of oversight. Amazingly they also let Chiron keep its contracts for manufacturing avian flu vaccines.
As public anger grew over the fiasco, which was soon followed by shocking exposes of the FDA’s failure to monitor drug safety in a variety of cases, even the mainstream media was forced to acknowledge structural contradictions in the system. Thus, the New York Times, in a moment of almost Marxist revelation, identified the underlying problem as the “chronic mismatch of public health needs and private control of the production of vaccines and drugs.”270 (In August, the HHS’s draft National Pandemic Influenza Preparedness Plan had made a similar point in more cautious language, noting that the United States’s “primarily private vaccine purchase and delivery system may not be optimal in a pandemic.”)271
The vaccine crisis also prompted closer scrutiny of other major components of the pandemic plan which in its snail’s pace evolution since 1993 had finally arrived at the final comment and discussion phase in fall 2004. The New York Times—the only major newspaper that seemed to take avian flu seriously—published an editorial on 12 October chastising HHS for proposing to add only 2 million courses of oseltamivir (Tamiflu) to the Strategic National Stockpile. The editors pointed out that while Japan had purchased enough Tamiflu for 20 percent of its population, and Australia for 5 percent, the Bush administration’s order would cover less than 1 percent of Americans. “Ten times that amount,” said the Times, “would seem more reasonable. The drug favored in this country is made by a single manufacturer whose capacity is limited, but a contract for massive quantities would presumably energize the industry to ramp up production.”272
In fact, there was gridlock in Switzerland, where Roche had failed to expand capacity to keep pace with its overflowing order book. The manufacturer recommended that governments stockpile enough Tamiflu to cover one-quarter of their populations, the estimated infection rate of an influenza pandemic; this rule of thumb would mandate 1.6 billion courses globally, with 74 million for the United States. Roche’s recommendations might have been self-serving, but they were not far-fetched: Dr. Julie Gerberding, the head of the CDC, told the New York Times that she would like to see a U.S. stockpile closer to 100 million courses than 1 million. But in fall 2004 Roche, although it was trying to add a new production line, was only producing 8 million courses per year. “Some public health experts,” the Times reported, “are strongly critical of Roche for not increasing production of Tamiflu sooner, saying that the company should have expanded production this year, when avian influenza started becoming a problem across much of Asia.”273
The obvious solution to both the Tamiflu shortage and the vaccine fiasco is for the federal government itself to undertake the nonprofit development and manufacture of lifeline medications. But in a political system where almost everyone dances to the tune of the drug industry’s political contributions, the “liberal” alternative to the Bush administration’s negligence was the proposal, supported by presidential candidate John Kerry and other Democrats, to raise market demand with larger government purchases. Meanwhile, for the foreseeable future Americans would be trapped in precisely the dilemma that Robert Webster had warned about: How should the scarce supply of Tamiflu, the only antiviral known to be effective against avian influenza, be rationed? Americans would be faced with a veritable “Sophie’s choice”: who would come first, frontline health workers or their most vulnerable patients? Elderly people or babies? Young mothers or policemen? Or perhaps the imperial legions should be protected first? In late September the Pentagon circulated its own pandemic planning guidelines which emphasized that the Tamiflu “supply is extremely limited world wide, and its use will be prioritized.” The military’s “top priority for use of vaccine or antiviral medications is in forward deployed operational forces. . . . We are currently working with HHS on agreements to share in the HHS/CDC Strategic National Stockpile (SNS).”274 Soldiers first, children last?
Such questions deeply trouble the medical community. At a 2002 meeting of public-health officials from forty-six different states, participants were hopelessly divided when they tried to choose which of five goals (reduce deaths, reduce disease, limit impact, ensure essential services, or “equitable distribution”) should be paramount in allocation of scarce antivirals.275 More recently, in August 2004, the American College of Physicians and the American Society of Internal Medicine jointly expressed concerns about the CDC’s proposal to ration any future avian flu vaccine among vulnerable groups, stating a “strong consensus among our group that limiting vaccine to specific target groups suggested by CDC may be less than optimal.” In October Dr. Andrew Parvia, the chair of the Infectious Diseases Society of America’s pandemic influenza taskforce, reported similar concerns to the society’s annual conference. He emphasized the need for clear, consistent guidelines for “triage,” and he proposed that pneumococcal vaccines that reduce the likelihood of secondary infections be added to the pandemic stockpile. He also criticized the Bush administration’s miserly budget for pandemic influenza: Pavia stated that the proposed $100 million “seriously underestimates the amount of funds realistically needed to effectively respond to the next pandemic.”276
Meanwhile, grim audits of the nation’s real biosecurity situation were piling up at Tommy Thompson’s doorstep. Michael Osterholm, the director of the University of Minnesota’s Center for Infectious Disease Research and Policy, garnered much press attention with a warning that the H5N1 vaccine that the National Institutes of Health had been developing with Aventis-Pasteur had “poor immunogenicity” (ability to trigger an immune response). Osterholm warned: “The earlier versions of this vaccine are not protective against the current [H5N1] strains.” He doubted that the government’s slow-motion vaccine program would provide a safety net in advance of a pandemic. “In the early stages of a pandemic I don’t believe we will have a pandemic influenza vaccine of any substantive nature.”277 (This echoed the offical pandemic plan’s own pessimistic prediction that in the beginning of an outbreak “there will likely be no or very limited amounts of vaccine available. This period could last for up to six months.”)278 Keiji Fukuda, the CDC’s top flu epidemiologist, direly predicted that at the beginning of a pandemic “there would be panic” and that hospitals would be unable to find room for all the acute cases.279
Similarly, in the aftermath of the vaccine fiasco, both the Washington Post and the nonprofit Trust for America’s Health published devastating balance-sheets revealing Project BioShield’s failure to enhance the country’s biological security. The Post reporters, who interviewed former administration officials, found that the “great majority of U.S. hospitals and state and local public health agencies would be completely overwhelmed trying to carry out mass vaccinations.” And indeed, during a May 2003 mock casualty exercise to test Chicago’s capacity to cope with a bioterror attack or a pandemic, the emergency infrastructure collapsed. Richard A. Falkenrath, a former chief advisor on homeland security, told the Post that “the government’s reliance on state and local health agencies to speedily distribute vaccines and drugs is the ‘Achilles heel’ of U.S. biodefenses.” In obvious understatement, the Post characterized as “vast” the task of “redirecting cash-starved hospitals and local health agencies into the unfamiliar field of mass casualty response.”280
The Trust for America’s Health was equally pessimistic. One-third of states had cut back their public-health budgets in 2003–4, and a majority were woefully unprepared to undertake high biosecurity lab work, to distribute vaccines, or to track outbreaks. Although “most public health officials call the emergence of a new lethal strain of the flu ‘an inevitability,’ ” only thirteen states had pandemic plans that met federal guidelines, while twenty states had failed to generate any plan. Earlier in February 2004, the Trust had warned that “pandemic flu could be much more demanding on state and local health resources and much more damaging to the general population than a bioterrorism attack.” It predicted that a pandemic would “cripple the resources of a U.S. public health system already stretched too thin.”281
In short, as Nature pointed out, “Three years of heightened concern about bioterrorism have done nothing to address the fundamental weakness of the U.S. public health system.”282 Except for those lucky few—mainly doctors and soldiers—who might receive prophylactic treatment with Tamiflu, the Bush administration had left most Americans as vulnerable to the onslaught of a new flu pandemic as their grandparents or great-grandparents had been in 1918. Pandemic planners admitted that the bulk of the public, initially at least, would simply have to cower in their homes. In a presidential election season dominated by “national security,” pandemic vulnerability should have been a decisive wedge issue; however, the Kerry campaign scolded Bush for the vaccine debacle and promised to stabilize future production with government purchases of unused stocks, but otherwise offered few substantive ideas for repairing America’s collapsing public-health infrastructure.283 Kerry, in fact, let Bush off the hook, never once mentioning the avian influenza threat in any of the three presidential debates.
The only presidential candidate to pay attention to the monster at the door was Ralph Nader, the candidate whose presence in the campaign was so reviled by “progressive” born-again Democrats. In February 2004 Nader contrasted the administration’s obsession with Iraq’s nonexistent “weapons of mass destruction” with its failure to energetically address avian flu in Asia. “The chain of infections from domesticated Chinese ducks to pigs to humans,” he forewarned in colorful prose, “can explode into a world war of mutant viruses taking millions of casualties before vaccines can be developed and deployed.” Six months later he wrote a public letter to Bush impeaching the administration’s failure to act upon the warnings of top researchers and medical organizations. “Such notice apparently is not enough to move your Presidency to action. These mutating viruses are not like human villains. You need to recognize that their indiscriminate destruction of innocent civilians, however, can be considered a form of viral terrorism.”284 In the WHO’s “worst-case” scenario, 2 million of these “innocent civilians” threatened with death are Americans, most of the remaining 98 million, however, live in the poor cities of the Third World.