Dee-Fense! Dee-Fense!: Preparing for Pandemic Flu; Federal Research, Economic Incentives for Industry, and a More Responsive Regulatory Regime Will All Be Necessary to Produce a Timely and Widely Available Vaccine
Miller, Henry I., Issues in Science and Technology
Vaccination to prevent viral and bacterial diseases is modern medicine's most cost-effective intervention. Were a vaccine to be available quickly after the onset of the widely predicted pandemic from an H5N1 strain of avian influenza, it might save scores of millions of lives worldwide. But that option is not feasible.
Why can't a country that developed the atomic bomb (60 years ago) and the polio vaccine (50 years ago) and put a man on the moon (almost 40 years ago) now produce an appropriate vaccine? The answer is an unfortunate confluence of biology and public policy.
During the past several years, an especially virulent strain of avian flu, designated H5N1, has ravaged flocks of domes ticated poultry in Asia and spread to migratory birds and (rarely) to humans and other mammals. It has been detected in much of Europe, Asia, Africa, and the Middle East, and it continues to spread with each seasonal migration of wild birds. Since 2003, there have been over 200 cases of H5N1 infection in humans, more than half of whom have died--a shockingly high mortality rate for an infectious disease.
Public health experts and virologists are concerned about the potential of this strain because it already possesses two of the three characteristics needed to cause a pandemic: It can jump from birds to humans, and it produces a severe and often fatal illness. If additional genetic evolution makes H5N1 easily and sustainably transmissible among humans--the third characteristic of a pandemic strain--a devastating worldwide outbreak could become a reality. The ease and frequency of worldwide travel could give rise to the first true jet-age flu pandemic.
Although it is not possible to predict the timing of that last evolutionary step, because the genetic changes that would give rise to it are wholly random molecular events, mutations occur each time the virus replicates, so the more H5N1 viruses are produced, the more likely it is that the event will occur. As avian flu spreads and more birds are infected, there are trillions more virus particles in existence every day. Flu can also evolve when both human and animal strains of flu infect a person or animal simultaneously, offering an opportunity for swapping segments of nucleic acid that code for viral proteins. That process, too, is favored by the presence of more viral particles in more locations around the world.
Some background is necessary to understand the threat and the possible public health, economic, and political consequences of a flu pandemic. 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 proteins, enabling the virus to elude detection and neutralization by the human immune system. A minor change is called genetic drift; a major one, genetic shift. The former is the reason why 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 with symptomatic flu that year exceeded 50% in urban populations, and 70,000 people died from it in the United States alone.
Ordinary seasonal flu, which is marked by high fever, muscle aches, malaise, cough, and sore throat, is itself a serious illness that on average kills 36,000 annually in the United States, but the pandemic strains are often both qualitatively and quantitatively worse. The H5N1 strains of bird flu have a predilection for infecting the tissues of humans' lower respiratory tract; that is, deep down in the smaller airways and in the tissues where oxygen exchange takes place, where it elicits hemorrhage and "cytokine storm," an outpouring of hormone-like chemicals that causes huge amounts of fluid to accumulate in the lungs. …