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Biomedicine

Finding an Antidote to Bioterror

Virologist C.J. Peters on bioterrorism preparedness.

C.J. Peters

Position: Director, Center for Biodefense, University of Texas Medical Branch at

Galveston, TX
Issue: Bioterrorism preparedness. We need to ramp up development of life-saving vaccines and drugs to protect ourselves from attacks with anthrax, smallpox, and other life-threatening bioweapons.
Personal Point of Impact: Former chief, Special Pathogens Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention

Technology Review: What are the worst bioweapon threats? How prepared are we?

C.J. Peters:  Inhalation anthrax is one of the highest threats. Manufacturing stable material for a weapon is easier with anthrax than with other bioweapons. Plus, we have both the threat of antibiotic-sensitive anthrax, which is huge, and also the threat of antibiotic-resistant anthrax, which would be even worse. We know that antibiotic-resistant anthrax is easy to make. It’s been done. It’s in the literature. The Soviets claimed they made anthrax resistant to six different classes of antibiotics. Anthrax properly prepared and introduced into the ventilation system of a large building that might have thousands of inhabitants could kill virtually all of them. And you could repeat this building by building, or in a subway, or in a closed arena.

But other agents, if they’re in a state-sponsored program, are also a huge threat. First of all, the viruses can be grown in animals, so you don’t need a bunch of high tech cell cultures. We need to understand these agents better, particularly the agents that are natural disease problems. With hemorrhagic fevers like Ebola, you’ve got lethal agents for which there’s very little, if any, therapy. Our preparedness on these fronts is still in the fantasy stage. We need to be moving forward: we have a couple of vaccines that could be developed further, and we have one antiviral drug that could be useful but has not been produced in large quantities or blessed by the FDA [Food and Drug Administration].

TR: What’s wrong with our current efforts to protect ourselves against anthrax and other bioweapons? And what do we need to do?

Peters: We need to improve how we develop drugs to treat the effects of bioweapons. Our pharmaceutical industry and national health research systems aren’t set up to do this. In the past, if we had a disease, the CDC went out and defined the threat. They would tell you, Here’s polio, or, Here’s measles, and so on. Then the NIAID [National Institute of Allergy and Infectious Diseases] would develop the science to make a vaccine or other remedy possible. And then industry picked it up and manufactured it because it was profitable, and it was the thing to do. With bioweapons, the CDC doesn’t know what the threat is any more than anybody else. We have the intelligence community telling us, and we’re not used to that. The National Institutes of Health is sponsoring a lot of research, but industry is not going to pick these things up. It’s just not going to. But let’s don’t beat up on the pharmaceutical industry. The industry was set up to make profits; it will spend a lot more effort making Viagra than thinking about anthrax. So we need a model where NIAID can contract directly or indirectly with industry or somehow find a way to motivate industry to pick these items up and actually develop them.

Inhalation anthrax is a great example of this; it’s a very rare disease naturally, so there haven’t been any drugs made specifically to treat it. Anthrax can be treated in early stages with antibiotics developed for more common infections. But anthrax toxins go on acting after we treat the bugs themselves. We don’t have any approved treatments for those toxins. Research at Harvard and several other places has indicated some of the ways to go: striking at the toxins, binding them up, neutralizing them. We should sort through those approaches and get some of them out on the shelf where physicians can use them.

TR: What changes would help us better develop drugs against bioweapons?
Peters: The good news is NIH is getting a huge boost in funding for biological-defense-related work. And [NIAID director Anthony] Fauci has made a very important statement: there will be an effort to have financing that provides a stable and adequate financial motivation for industry. I think this is the right path, although it may need either more bucks than we are ready to ante up or even some sort of stick, saying, You do it, or we will go outside the paradigm. Meaning that the federal government would manufacture the remedies itself, spawn new companies, or otherwise influence the big drug companies to undertake the mission.

TR: These are long-term solutions that will obviously take years. What can we do more immediately to prepare the nation?

Peters: We need to get diagnostics out to the emergency room level for all the biowarfare agents, so we can diagnose people directly-not at CDC headquarters in Atlanta a week later when someone thinks about it and mails a sample to Atlanta. That way we can test anybody who looks sick with something that is hard to explain. Right now we don’t have that capability. The technology exists. In many cases it could be done, but we don’t have the actual machine that can do it for us. We need to develop that platform and get it out into the emergency rooms.

TR: What about smallpox vaccinations? Do you think parents should vaccinate their children against smallpox?
Peters: No, I would not suggest they do that. The vaccine is overall a good vaccine. But as with all vaccines, some people will be hurt. So we should not vaccinate the general population until the threat is higher.

We’re actually getting close to being ready on smallpox. We’ve got enough vaccine. We have some plans as to how to give it. We now have a decision to go ahead and vaccinate medical staff most likely to see the first cases. And we could respond to an outbreak right now. Maybe not as well as we’d like to. We’re a year away from being in as good a position as the currently perceived threat suggests we should be. But today, we’re still in a pretty good position.

We’re not ready for every scenario, of course. The old Soviet plan was to use tons of smallpox delivered by missiles and cluster bombs and literally saturate urban areas with smallpox. So you’d have lots of direct infections followed by the contagion. We’re not ready for a massive attack of that nature. But I don’t think we’re concerned about the former Soviet states mounting it. And I don’t think other state actors have that kind of capability.

TR: Are we ready for a genetically engineered superstrain of a bioweapon such as vaccine-resistant smallpox?
Peters: I don’t think engineered smallpox is a real consideration right now. Genetically modifying viruses and knowing what’s really going to happen when they’re modified-whether it’s really going to work-that’s a lot harder than making antibiotic-resistant bacteria.

But I don’t think it will always be that way. The future will be more dangerous if current trends continue. We’re going to have to be thinking that people will be trying different things, looking for ways to get around vaccines or drugs. And we have to be thinking about how they might do it; how we can counter it. Above all, we have to have the intelligence out there to find out about it.

Online Extra: Peters on vaccine development and what scares him the most.

TR: In terms of developing vaccines against biowarfare agents in general, isn’t vaccine development even more problematic than drug development?

Peters: We are not undertaking the production of new vaccines because it is so complicated, so expensive, and so tied to liability issues. We need exemptions from liability for unpredictable results that are a natural possibility. It’s possible to have a  vaccine perfectly manufactured to every standard that anyone would imagine, and you can give it to somebody and they can still get hurt. We should hold vaccine makers safe from unanticipated consequences, while still helping any injured people.

TR: What about that experiment in Australia, where a gene was inserted into mousepox virus and made the virus lethal even to the vaccine-resistant mice.  Could such a trick have the same effect with smallpox and render human vaccines useless?
Peters: That’s entirely speculation. All the pox viruses have a complicated set of regulatory molecules that can turn down host immune responses and get around host immune responses. And just because one gene in one particular system in mice will tip the balance, doesn’t mean that it will or won’t tip the balance with human smallpox and vaccine. I think there’s not enough data and frankly, I hope I never see the data.

TR: Now, you’ve been all over the world. What’s the scariest thing you’ve seen and what lesson might you draw from it?
Peters: The scaredest I’ve been-when you get that lump in your stomach and you think, “Oh, my God,” was when we started looking at the hantavirus pulmonary syndrome cases in the Southwestern U.S.  Why was it scary? Well, here was a disease that we’d sat down and discussed as a group of experienced, infectious diseases virologists-and nobody knew what it was. I mean, it was a new disease, and it wasn’t way the hell and gone somewhere, it was right in the middle of the U.S, and that was really scary. I think when things start happening at home, that’s when you start puckering up. Inhalation anthrax is just as bad -invisible and lethal. I mean, you just think about it-it’s not supposed to happen here in River City. 

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