The End of Pandemics

Bird flu could be the last super-plague.

President George W. Bush announced his $7.1 billion strategy to fight a bird flu pandemic earlier this month, declaring, "Our country has been given fair warning of this danger to our homeland—and time to prepare." Right now, the H5N1 bird flu virus is spreading across Eurasia via flocks of wild birds; it recently reached Europe. The 124 people who are known to have been infected by the virus—half of whom have died—got it from close contact with poultry. Epidemiologists and virologists worry that the bird flu virus could mutate into a still deadlier form that is easily transmissible between people.

But epidemiology is still an inexact science, and especially so when it comes to trying to predict the course of uncharacterized disease organisms. For some perspective, let's recall another recent disease panic. West Nile Virus somehow entered the United States in 1999. Testifying before a U.S. Senate panel in December 1999, Yale University epidemiologist Durland Fish, warned, "The introduction of a foreign insect-borne virus, never before seen in the Western Hemisphere, is…reminiscent of the introduction of yellow fever and bubonic plague in past centuries." Durland added that the virus was "a public health threat unprecedented in modern times."

West Nile is indeed very nasty. But it is also a far cry from the bubonic plague. Since 1999 it has spread via mosquitoes to 42 states, and in 2005 it infected 2,653 Americans, killing 86 of them. In comparison, about 20 percent of Americans come down with conventional flu each year, and 36,000 of them die of it. Globally, conventional flu infections kill between a quarter and half a million people annually.

So what about avian flu? How likely is it that the virus will soon mutate and cause a pandemic, possibly killing millions? Researchers do not have a good predictive theory about what mutations would necessarily make the bird flu virus both more deadly and more easily transmissible among people. The concern is that, as it spreads to millions of birds, it will have an ever greater chance to mutate. But since viruses thrive by spreading rather than killing their hosts, evolution generally drives flu viruses to become progressively milder infections in birds. So the H5N1 virus could become more easily transmissible but make itself relatively harmless in the process.

"I think many people are crying wolf when it comes to the avian virus," Peter Palese, chairman of microbiology at Mount Sinai School of Medicine in New York, told the Chicago Tribune. Interestingly, Palese also noted in the New York Times that studies of serum collected in 1992 from people in rural China indicated that millions there had antibodies to the H5N1 strain. That means they had been infected with an H5N1 bird virus and recovered, apparently without incident. Nevertheless, Palese adds, "I still think the preparedness is a good idea." And indeed who could be against preparedness?

Is the Bush bird flu plan the right sort of preparedness? After all, there is no proven vaccine against the disease. Instead, the Bush plan would spend $1.2 billion to purchase and stockpile 20 million doses of a close-enough-for-government-work version of bird flu vaccine currently being tested and manufactured. The Bush plan would spend another $1 billion to buy and stockpile antiviral medicines like Tamiflu, which can be used to prevent and treat influenza infections, including bird flu.

A more promising aspect of the Bush bird flu plan proposes allocate $2.8 billion to jumpstart new technologies for rapidly producing new vaccines. But why must the government get involved? Why don't American pharmaceutical companies see the worries over an epidemic as an opportunity to make profits?

Actually, there are few American vaccine makers left. As President Bush observed, "In the past three decades, the number of vaccine manufacturers in America has plummeted, as the industry has been flooded with lawsuits." He added. "Today, there is only one manufacturer in the United States that can produce influenza vaccine." Since 1967 the number of American vaccine manufacturers has dropped from 26 to just 4 today. The problem is that vaccines are low–profit margin products sold for a few bucks per dose, yet potentially they expose manufacturers to hundreds of millions of dollars in liability.

Setting aside the issue of federal financing and liability protections, there are promising biotechnical breakthroughs that could protect hundreds of millions of people against future pandemics. For example, researchers are developing DNA vaccines that can potentially be produced very cheaply in just weeks. Scientists create DNA vaccines by incorporating DNA into a circular loop called a plasmid that contains the construction plans for a protein on the outer surface of the H5N1 virus. If that DNA were injected into muscle cells, it would quickly reproduce the viral coat protein and trigger immunization in much the same way as a conventional vaccine.

There are no DNA vaccines available for human use yet, but DNA vaccines have just been approved for use in horses to prevent West Nile Virus and in salmon to prevent a hemorrhagic disease. Researchers are currently testing human DNA vaccines for AIDS, SARS, Ebola, and West Nile Virus.

The British company PowderMed announced earlier this year that it had developed a DNA vaccine that incorporates the H5 gene from the bird flu into a plasmid. The vaccine is designed to be injected under a patient's skin using tiny gold pellets. "Once we know what strain of flu is causing the pandemic, we think we can have the first vaccines available in 2-3 weeks," said University of London biochemist Peter Dunnill to the Evening Standard. Dunnill, who has been working with PowderMed, added, "A DNA vaccine is not a panacea. However, it could be useful if the situation gets out of hand." And should a bird flu pandemic break out, the usual regulatory requirements for safety testing would have to be set aside in an emergency.

A bird flu pandemic may never happen. And that would be good news. But the development of novel technologies like DNA vaccines point to the really good news: As humanity's biotechnical prowess increa

ses, we may never suffer through another pandemic again.