TCS Daily

Preparing for the Pandemic

By Henry I. Miller - October 17, 2005 12:00 AM

I have a long and intimate relationship with influenza virus. More than 30 years ago, I was the co-discoverer of one of the viral enzymes that are essential for the virus to duplicate and proliferate. Later, my medical training taught me respect for this pathogen. Real influenza -- as opposed to a garden-variety cold -- is a serious illness. Its victims don't soon forget the fever, headache, muscle aches and profound weakness, and in an average year -- in spite of vaccines that are usually at least moderately effective -- it kills tens of thousands in this country.

Now it appears that the flu virus is poised to repeat its several-times-a-century metamorphosis into something much worse.


First, some background. The exterior of the flu virus consists of a lipid envelope from which project two surface proteins, hemagglutinin (H) and neuraminidase (N). The virus constantly mutates, which may cause significant alterations in either or both of these, enabling the virus to elude detection and neutralization by humans' immune system. A minor change is called genetic drift; a major one, genetic shift. The former is the reason that flu vaccines need to be updated from year to year; an example of the latter was the change in subtype from H1N1 to H2N2 that gave rise to the 1957 pandemic. This new variant was sufficiently distinct that people had little immunity to it: The rate of infection of symptomatic flu that year exceeded 50 percent in urban populations, and 70,000 died from it in the United States alone.


In the 1957 outbreak the mortality rate (the fraction of infected persons who die) was low, but we appear to be on the verge of another, much worse pandemic.


During the past several years, an especially virulent strain of avian flu, designated H5N1, has ravaged flocks of domesticated poultry in Asia and spread to migratory birds and (rarely) to humans. Now found from Russia and Japan to Indonesia, it is moving inexorably toward Europe. Since 2003, more than 60 human deaths have been attributed to H5N1. Public health experts and virologists are concerned about the potential of this strain because it already has two of the three characteristics needed to cause a pandemic: It can jump from birds to human, and can produce a severe and often fatal illness. If additional genetic evolution makes H5N1 highly transmissible among humans -- the third characteristic of a pandemic strain -- a devastating world-wide outbreak could become a reality.


Moreover, this is an extraordinarily deadly variant: The mortality rate for persons infected with the existing H5N1 appears to be around 50 percent, whereas the usual annual flu bug kills fewer than one percent.


We are ill-prepared for a flu pandemic. Reserve capacity is grossly inadequate for vaccines, drugs and hospital beds. The best and most cost-effective intervention -- prevention with a vaccine -- presents many obstacles, technological, economic and logistical.


Anti-flu drugs exist but are not a panacea. Unlike vaccines, which confer long-term immunity after one or two doses, drugs need to be taken for long periods. The only drug that has been shown to prevent the flu is Tamiflu, the prophylactic dose of which is one tablet a day, the effect lasting only as long as one takes the drug. (The other major anti-flu medicine, Relenza, has only been shown to be effective to treat, but not prevent, flu.)


Historically, flu pandemics have come in two or three waves, lasting a total of 13-23 months. In other words, the need to take Tamiflu -- by first responders, health care workers and ordinary citizens -- could go on for months and months, or even years. U.S. public health officials have said they plan to buy 20 million doses of Tamiflu, but that would be enough to treat only 200,000 people (fewer than the number who would attend a seven-game World Series) for 100 days. And the retail price per pill is around $8, so the expense to treat that small number of people for that amount of time would be $160 million.


According to various models, in the absence of sufficient amounts of an effective vaccine -- which is not yet within reach -- to blunt a pandemic we would need to treat perhaps a third to a half of the population with Tamiflu. Do the math: 100 million people for 100 days equals 10 billion doses, at a retail cost of $80 billion, in order to blunt the pandemic's first wave.


Although President Bush and HHS Secretary Leavitt are saying some of the right things about the need to prepare for the pandemic, if they or their staffs have done this sort of calculation, they give no sign of it.


We need push-pull incentives to forming public-private partnerships. Public policy must reward both inputs on R&D (via grants, tax credits and the waiver of regulatory registration fees) and outputs of products (with guaranteed purchases, payments for the regulatory approval of new drugs or vaccines, and indemnification from liability claims). Part of this effort should be R&D on various new technologies and approaches to making flu vaccine, to boosting the immune response to vaccines, and to creating greater reserve capacity for the production of drugs like Tamiflu and Relenza.


Preparation for pandemic flu involves many thorny issues of science, technology and medicine, but also much more. It requires contingency plans for the "social" aspects of a deadly pandemic -- when to shut our borders to travelers from infected regions, close schools, restrict public gatherings, and enforce quarantines, as well as a designated chain of command to implement those decisions.


Like the WWII Manhattan Project to develop the atomic bomb, preparation for a flu pandemic involves scientific uncertainties, strategic decisions that span many specialties and government departments, and prodigious resources. To oversee all this, we'll need a Flu-Pandemic Czar -- someone analogous to Army General Leslie Groves, who headed the Manhattan Project: a plenipotentiary with broad powers and discretion.


There is no time to waste.


Henry I. Miller, a physician and fellow at the Hoover Institution, was the founding director of the Office of Biotechnology at the FDA, 1989-1993. Barron's selected his latest book, "The Frankenfood Myth..." as one of the 25 Best Books of 2004.


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