FIGHTING A HIDDEN ENEMY
Ammo for the War on Germs
We have drugs to fight bioterrorism, if only the FDA will let us use them.
Last Friday, it was unusually busy in my hospital's emergency room as worried but well people came in to be ruled out for anthrax. Doctors created a special "anthrax evaluation room" and set aside a half-dozen respiratory isolation beds. The fear was sparked by news that evening that a case of skin anthrax was diagnosed in Tom Brokaw's assistant at NBC.
Underscoring the risk of this pathogen was news Tuesday that roughly 30 people who work in Senate Majority Leader Tom Daschle's office have tested positive for exposure to anthrax. A letter sent to his office Monday contained weapons-grade anthrax, material that officials say was likely produced by a state-run biowarfare program. Anthrax was also discovered in the office of New York Gov. George Pataki.
But as nasty as this bug is, anthrax is still a one-time agent. It doesn't spread from person to person. To catch it you need to come directly in contact with the spores. And the first thing we do in the hospital is wash down suspected victims. The real test for our nation will come when a communicable disease like smallpox crops up, as some, including former Sen. Sam Nunn in a recent doomsday scenario dubbed Dark Winter, are speculating is highly possible.
Smallpox spreads rapidly from person to person, primarily by aerosols expelled from the throats of those infected and by direct contact. An attack would likely consist of a few suicide bioterrorists self-infecting themselves and walking around New York City. While the infectious dose is unknown, it's believed to be only a few virus particles, compared to thousands of spores in the case of anthrax. Historically, each case of smallpox triggers from 10 to 20 new infections.
The government is starting to take notice. On Wednesday, Health and Human Services Secretary Tommy Thompson asked Congress for $500 million to pay for smallpox vaccine stockpiles, enough for every American, although even a crash program could take at least a year. And President Bush's new director of homeland defense, Tom Ridge, announced the government would consider reinstituting vaccination programs in children. Even a few reported cases could be enough to cripple our economy. In 1972, a single case of smallpox in Yugoslavia touched off an outbreak that required 20 million vaccinations and mass quarantines.
Smallpox can be personally devastating. After a 14-day incubation period, patients experience high fevers, headaches, and sometimes severe abdominal pain. A rash resembling chicken pox appears in the mouth and throat, face, and forearms, and spreads to the trunk and legs. As patients recover, scabs break and pitted scars appear. Mortality is as high as 60%.
We're going to have to prepare for these scenarios. The good news is that our biotechnology industry has come a long way since 1972, and, unencumbered, has scores of agents that could be effective against communicable diseases such as smallpox. The availability of these agents would help quell public fears over smallpox, the same way Cipro has helped mitigate concern over anthrax. The bad news is that regulatory requirements have hobbled the development and marketing of these agents and made it expensive to produce effective vaccines.
In the case of anthrax, Sen. Chuck Schumer's suggestion that the U.S. invoke emergency measures to allow manufacturers to mass produce generic versions of Cipro not only fails to address the current woes but doesn't redress the underlying problems: that every step of the process is so tightly regulated it could take years to bring new production facilities online. Even retrofitting a new facility can take several months to fulfill FDA requirements. A process that should take a week takes a year.
In the case of smallpox, there are at least a half-dozen new antivirals, designed to treat HIV and hepatitis, that work well against models of pox virus. Some can be used as post-exposure prophylaxis. Many of these drugs grew out of research into treatments for AIDS, but are still mired in preclinical and clinical trials aimed at proving they work for their primary indication. Right now, doctors couldn't even try them out by prescribing them off label in the event of an attack. New mechanisms need to be devised when it comes to drugs that might protect against these rare agents that are the weapons of terrorist warfare, for which no clinical trial can reasonably be constructed.
This probably means approving promising drugs for use in bioterrorism after they're tested for safety in healthy college kids in phase I trials, waiving costly and lengthy phase II or phase III trials of infected people. It also means approving drugs that have demonstrated effectiveness in animal and laboratory studies, and theoretical efficacy in human models. After all, there are no human trials demonstrating Cipro works in anthrax. With so few cases, how can there be? In the case of tularemia, smallpox, plague and other likely weapons, we can't wait for clinical trials, since that will mean we've already been attacked.
The Food and Drug Administration streamlined approval processes in the early 1990s to get HIV drugs to the market early, allowing drugs to be approved out of phase II trials, and approving them based on evidence that they benefited certain surrogate markers like blood counts of virus levels, rather than the more difficult-to-prove increases in life expectancy. The FDA needs to do the same thing here.
FDA approval times for vaccines also need to be rapidly compressed. The sole maker of the anthrax vaccine, BioPort Corporation of Lansing, Mich., has been battling the FDA for 20 months to get approval for a new facility that would produce it, reflecting paranoid regulatory requirements for approval of renovated manufacturing facilities, particularly in the vaccine industry. The agency needs to get out of the way.
And if people want to stash away a starter dose of drugs aimed at providing prophylaxis against anthrax or smallpox, doctors and politicians shouldn't stop them. We've been scared from using antibiotics and antivirals out of some kind of weird sense of communal responsibility to keep bugs naive to our powerful weapons. As long as consumers are willing to pay for their own medications and not pass the cost onto their insurers, they should be able to buy peace of mind if it's going to help them go to work in the morning.
This fight is playing out in our cities, with ordinary office workers on the front lines, and panic and fear the real instruments of war. These troops need to know that antibiotics, antivirals and vaccines are available, so that they can confidently carry out their daily missions.
Dr. Gottlieb, a resident in internal medicine at Mount Sinai Hospital in New York, is editor of the Gilder Biotech Report.
