In February 2009, a spike in influenza cases was
detected in hospitals around Mexico City. Mexican government officials sent
samples of throat cultures from patients to the US Centers for Disease Control
(CDC) and the Canadian National Laboratory in Winnipeg, whose scientists found
a new version of the H1N1 influenza virus, named for the type of hemagglutinin
and neuraminidase molecules on its surface that enable it to spread within the
body.
The discovery of what came to be known as “swine flu” - because pigs were the
original source of the virus-aroused enormous concern in public health circles.
The 1918 flu pandemic that killed tens of millions of people globally was also
caused by an apparently new version of H1N1 influenza. Although other H1N1
viruses had been circulating in US populations for more than thirty years, 1
the Mexican virus looked different and at first seemed to be especially
aggressive. Soon the World Health Organization (WHO) began raising the alarm.
Two billion people-one third of the global population-could contract the
disease, the agency warned, and millions might die. World Bank economists
suggested that the total cost of such a pandemic-counting lost business and
increased health spending-could even reach 4.8 percent of global GDP.2
Panic spread throughout the world. In Mexico schools and offices were closed,
flights were canceled, and the country lost $2.2 billion within a few weeks.3
In the UK, the governments swine flu website received 2,600 hits per second and
crashed soon after it opened; in New York so many people panicked over any
flu-like symptom that hospital emergency rooms were swamped with ten times more
patients than normal, worsening care for those who really needed it.4
In China and other countries, border nurses quarantined anyone with a fever
seeking to enter the country. Even though direct pig-to-human influenza
transmission is exceedingly rare, Egypt ordered the slaughter of all the pigs
in Cairo, impoverishing thousands of Christian small-scale farmers. And in
Afghanistan, the nations only pig was quarantined.5
On June 11, 2009, Margaret Chan, the director-general of the WHO, announced
that a “pandemic emergency” -or worldwide epidemic-of H1N1 influenza was officially
underway. Governments around the world placed immediate orders for anti-flu
drugs and vaccines worth hundreds of millions of dollars, as a new stock index,
*RXFLU, tracked company profits. According to J.P. Morgan, up to $10 billion
was spent globally on -influenza preparedness- in 2009, including over $4
billion by the US alone.6
The predicted dire emergency did not occur. In the 2009-2010 “influenza season”
about 18,000 people died from the disease worldwide, fewer than in previous
years, and the vast majority of victims had serious underlying conditions such
as cancer, lung disease, AIDS, or severe obesity, which can impair breathing.7
Since one influenza strain usually dominates all others during a typical flu
season, H1N1 may actually have saved lives by displacing more aggressive
viruses. The WHO maintains that its decisions were based on the best available
evidence, but last year European governments, stuck with hundreds of millions
of euros? worth of unused medicines and vaccines, began asking questions.
In March 2010, a Council of Europe report8 concluded that the H1N1 virus was
known to be mild well before the WHO issued the pandemic “declaration” and
expressed concern about the influence of powerful pharmaceutical companies over
decision-making at the agency. A draft of the WHOs response was released in
March 2011.9 It calls for more “transparency” but concludes that -no critic of
WHO has produced any direct evidence of commercial influence on
decision-making.- Unfortunately, the response does not account for the billions
of dollars lost in the panic or for the lives that may have been put at risk by
the agencys hasty medical recommendations.
Although influenza deaths are relatively rare among those who arent otherwise
ill, since the 1950s experts have periodically warned that a 1918-like pandemic
could recur. They became especially alarmed in 1997, when eighteen people in
Hong Kong contracted a new influenza virus known as H5N1 from chickens, and six
died. This “avian flu” virus didnt spread from person to person, but since it
was a thousand times more lethal than ordinary influenza, some experts feared
that if it mutated into a virus that could spread more easily, it would kill
millions in a very short time.
In 1999, the WHO launched a program to help governments prepare for this
terrifying, if unlikely, possibility. The agency produced a document
urging governments to draw up plans to alert the public and set up mass
vaccination programs in the event that a new “pandemic” virus was found to be
spreading. Because such a virus would have been previously unknown, it would
take around six months for sufficient quantities of vaccine to be produced.
However, the document also contained an annex describing a new class of
anti-influenza drugs known as “neuraminidase inhibitors” that might help
control the pandemic.10
According to the annex, these drugs, by blocking the action of the
neuraminidase protein, prevent the influenza viruses from spreading through the
body, reducing the severity of symptoms. The drugs would also protect people
who had been exposed to the disease, such as health care workers and relatives
of patients, from becoming sick, or so the document suggested. In 1999, the
manufacturers of these new drugs were still seeking approval from government
regulators including the US Food and Drug Administration, but later editions of
the WHOs influenza pandemic guidance documents urged governments to “stockpile”
them, because in an emergency their manufacturers might not have time to produce
enough to meet demand.11
When H5N1 “avian flu” broke out again in Asia in 2003, this “stockpiling”
recommendation led to a surge in influenza “pandemic preparedness” spending. In
2005?2006, the US and European governments stockpiled nearly $3 billion worth
of the most popular neuraminidase inhibitor, known as Tamiflu.12 At $10?$15 a
dose, few developing countries in Africa, Asia, and Latin America would be able
to afford Tamiflu, but Margaret Chan, then assistant director-general of the
WHO in charge of influenza pandemic coordination, joined by representatives
from Hoffman-La Roche, Tamiflus Swiss manufacturer, urged Western governments
to contribute to a Tamiflu stockpile fund for the developing world.13
After the 2009 “pandemic emergency declaration,” another scramble for the drug
was soon underway, and annual Tamiflu sales surged to $2 billion.14 In Korea,
rumors of shortages led HSBC and other powerful banks to compete with hospitals
for stocks of the drug.15 Countries in Asia, Africa, and Latin America placed
urgent Tamiflu orders from WHOs stockpile, and some governments even took out
loans worth tens of millions of dollars from the World Banks Avian and Human
Influenza Facility to purchase it.16
Despite the panic over “avian flu,” ordinary influenza was still seen by most
people as a mild disease, and most of the Tamiflu purchased in the US and
elsewhere was probably “stockpiled” in warehouses and personal medicine
cabinets, and not consumed. But in the early 2000s, Tamiflu was regularly prescribed
in Japan, which accounted for over 60 percent of global consumption.17 It was
there that signs of possible trouble with the drug first began to emerge.
Dr. Rokuro Hama runs the Japan Institute of Pharmacovigilance, an Osaka-based
nonprofit group that monitors pharmaceutical product safety. In 2002, shortly
after Tamiflu was introduced in Japan, he received a number of case reports of
children who had begun behaving strangely within hours of taking it. A
fourteen-year-old boy wandered out of his familys ninth-floor apartment and
jumped over an exterior railing to his death; a seventeen-year-old boy ran out
of his house onto a nearby freeway, where he was killed by a speeding truck; a
thirty-nine-year-old man and two three-year-old boys died suddenly in
their sleep.
Hama wasnt sure that these and the dozens of other similar cases he recorded
were necessarily related to Tamiflu. Influenza itself can cause delirium and
death in severe cases and the vast majority of those who took the drug suffered
no ill effect. But when Hama studied the cases carefully, he realized that the
neurological symptoms differed from those sometimes seen in severe influenza
cases; rather, they more closely resembled symptoms associated with overdoses
of drugs that suppress the central nervous system, such as Valium.18
In response to Hamas case reports, the Japanese Ministry of Health, Labor, and
Welfare commissioned a research team at Yokohama University to study 2,846
pediatric influenza patients, some of whom had taken Tamiflu. The Yokohama
researchers reported that hallucinations and other neuropsychiatric symptoms
were no more common among children who had taken the drug than among those who
had not. When Hama looked closely at this analysis, he concluded there were a
number of errors, most having to do with what epidemiologists call
“misclassification” such as cases in which children with hallucinations were
classified as not having taken Tamiflu when they almost certainly had.19
Hama reanalyzed the Yokohama data and estimated that Tamiflu resulted in a
fourfold increase in the frequency of hallucinations and other neuropsychiatric
side effects in children with influenza.20 A journalist later alerted Hama to
the fact that Chugai, the Roche subsidiary that markets Tamiflu in Japan, had
provided funds for research to two of the scientists who worked on the Yokohama
study. While there is no evidence of wrongdoing, such funding always raises the
possibility of a conflict of interest.21
Shortly after the WHO “pandemic announcement” in June 2009, Keiji Hayashi, a
Japanese pediatrician who was aware of Rokuro Hamas alarming case studies,
decided he wanted more information about the risks and benefits of Tamiflu.
After all, if the drug really saved lives, it would be worth prescribing to his
patients, despite the slight risk of severe side effects. But when Hayashi
turned to the scientific literature, he found very few articles on the
subject-and all of the research had been funded by Roche.
The most important paper, whose main author was Laurent Kaiser, a doctor at the
Swiss Hopital Cantonal de Geneve, appeared in the Archives of Internal Medicine
in 2003.22 This paper, based on a summary of ten studies, concluded that
patients who took Tamiflu were 55 percent less likely to experience severe flu
complications-such as pneumonia-and 50 percent less likely to need
hospitalization than patients who didnt take the drug. Since hospitalization is
expensive, Kaisers finding suggested that the drug not only relieved suffering,
it could also save money-an important consideration for governments considering
the WHOs advice to stockpile the drug.
While Kaisers finding seemed powerful, Hayashi was concerned that the drugs
entire reputation seemed to rest on this one article and a small number of
others. He contacted Tom Jefferson, a British influenza expert with the
Cochrane Collaboration, a British government-funded network of epidemiologists
that conducts independent reviews of medical research. The Cochrane group had
published a favorable review of Tamiflu in 2006, based largely on the same
articles that Hayashi had read.23
When Jefferson and his colleagues read Hayashis letter, they too began to
wonder whether their initial assessment had been correct. They noticed several
ambiguities and errors in Kaisers article that they hadnt recognized before. For
example, the definition of -complications related to influenza- used by the
doctors in the study was imprecise, which made it difficult to tell what the
study was actually measuring; in addition, the high rate of influenza seen in
the clinics where the trials were carried out also seemed odd. Normally, only
about 15 percent of what seem like “flu” cases are actually found upon lab
testing to be caused by the influenza virus-the others are caused by some other
microbe. But in the clinics where the Tamiflu trials were conducted, up to 80
percent of flu-like illnesses were reported to have been caused by influenza
itself, raising the possibility that the patients had been selected for some reason
that wasnt made clear in the article.24
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