Biology and Security

An Interview with Dr. Leslie Z. Benet

Dr. Leslie Z. Benet is Professor of Biopharmaceutical Sciences and Pharmaceutical Chemistry at the University of California, San Francisco. He recently chaired a congressionally mandated study entitled "Giving Full Measure to Countermeasures: Addressing Problems in the DoD Program to Develop Medical Countermeasures Against Biological Warfare Agents", which called for a new agency to oversee the Department of Defense's biodefense activities.

Please briefly describe your profession.

I am a professor of biopharmaceutical sciences at the University of California San Francisco. My expertise is what happens to drugs in the body after they are dosed, how those changes affect patients, and how that affects drug development. So I am an expert in metabolism, elimination and toxicology related to drug disposition. I am an expert in drug development.

As chair, I believe you stand by the final decision of the study.

I do. I strongly support them.

Is there anything specific as a scientist that you disagree with, or would otherwise want to emphasize?

There is nothing I disagree with; the committee was in consensus. There were people in the committee--and it is obvious in the report--there were people that were particularly debating whether this research and development should remain in the DoD [Department of Defense] or whether it should be taken out and, for example, put into NIH [National Institutes of Health]. That was the main area of the committee where there was not general agreement. But this is sort of a compromise, as is presented in the report, which says the DoD probably should [conduct this research] now because they have the most interest in it, but if they do not do it successfully, then Congress should really move it someplace else. That is the one area where, within the committee, there were differences of opinion.

In the report, it was mentioned that the reason the DoD should create a new branch instead of moving it to the National Institutes of Health was that the DoD's work was for military personnel.

That is correct. There is a different sense--what you need to do in the military is to protect the warfighters as they go in the zone, as opposed to reacting to it afterwards. So you want to pre-protect, or be ready to pre-protect. That is not the same emphasis you would have in the general population.

Would you feel that the results of the study would apply to some degree, no degree, or a large degree to a civilian defense effort?

There is a lot of overlap- a tremendous overlap. I think another big issue that would be different between [a military effort and a civilian effort] is the licensure aspect. We feel very strongly that these should be licensed by the FDA [Food and Drug Administration] because of the concerns that happened in the Gulf War--because of warfighters' feelings that they were taken advantage of in terms of what they were given . This should be fully licensed. If you were doing this after the fact, as a protective mechanism in biodefense, it is probably not as critical [to seek licensure]. In terms of the science, there is a tremendous overlap, and how you need to develop the drugs.

So you would recommend a larger interaction between government discovery and scientific research on the commercial aspect?

We do. We feel that this cannot be successful without attracting the expertise that is outside the DoD to actually be involved in this. We make recommendations specifically related to that. Congress has the Bioshield legislation directed towards that.

Regarding government/scientist relations: the Thomas Butler case ended with a guilty verdict, but largely on counts that originally were not raised, and that many people in the scientific community were worried about.

I actually was at the DoD when that broke, and it was very interesting. I think it is critical--more a biodefense concern than a biowarfare concern. We have changed our whole procedure on how we monitor and follow those kinds of potential lethal weapons. I think it was very unfortunate what he did, and I do not think he recognized when he did it what the implications would be.

So you feel the government on the judicial/FBI side is acting appropriately to protect citizens from problems such as this?

I think they are trying to. I think it is very difficult. But there will be concerns--there will be privacy concerns related to this too. But this was straight out--he said he did it.

What would you consider the biggest obstacles between government and scientists right now in terms of sharing research and in terms of encouraging scientific development?

In the DoD or in general? If you look at NIH, I do not think there are obstacles--I think there is a strong interactive nature. But I think, in the DoD, the history has been: "We are going to do it our way, we are concerned about confidentiality and not outside interests," and a variety of things that have prevented good interactions from occurring. Now, at the bench level, the scientists at USAMRIID [US Army Medical Research Institute of Infectious Diseases] are excellent scientists--the best in the world. And we are losing them. We are losing them because of this view. There is no appreciation [of interaction]; [the scientists] are not allowed to interact with their outside colleagues--they are facing roadblocks in terms of their ability to work together with outside individuals. I think that is the basis of some of our recommendations.

So you would say that this problem is mostly restricted to the DoD, not government institutions in general?

Yes, I think strong interactions between the NIH and outside scientists exist. Recently, even in the FDA, there has been much more interaction with outside scientists than in the past.

In the study, you mentioned newer, stricter guidelines involving animal testing.

Well, not stricter. New guidelines in the Animal Efficacy Rule. It goes back to the licensure issue. For a drug or any prophylactic to be licensed by the FDA, it has to be proved to be safe and effective in humans. It is possible to show that these vaccines are safe in humans, because you can give them to healthy volunteers. But the only way to prove they are effective is to have an attack, or to have someone be a guinea pig--have someone get the disease, and then treat it. That cannot happen. So the new FDA rule allows effectiveness to be based on animal studies. Safety must still be carried out in humans. This is an advance--it now allows the DoD and other scientists to get products licensed, where in the past this was a problem.

If you had the option to increase or improve the situation regarding the bioterrorism scare in general, what do you think would be the most effective way to aid the situation? What do you think is the most serious problem, and what would you do to solve it?

Part of the bioterrorism problem is fear that is not necessarily founded on a good scientific basis. It gets amplified, and people are concerned about it more than they need to be. I am not saying it is not a real fear--a real danger. I think what we need is good science that goes outside of what are the traditional threats.

Let me expand on that. This was not a specific recommendation in the report, but it is implied. The DoD, in developing countermeasures to biochemical warfare agents, has to have a validated threat. In other words, the intelligence community has to say that this is a real threat, and in fact a weapon has been developed, before they are allowed to spend money on it. And that is really out-of-date. What has happened in terms of science and molecular biology and our ability to modify genes and proteins, is that it is possible for a terrorist to change a particular, relatively harmless virus and make it very infective.

The biggest concern is that we go outside the boundaries of the past--we bring the science and understand that we have to develop what we might call a "multivalent" vaccine - something to protect us against things that we have not anticipated up to the present time. There is a lot of initial work on that, and a lot of that is outside the military, but it was funded in some cases by DARPA [Defense Advanced Research Projects Agency], the agency within the DoD that looks at these far-out approaches. That is why we recommend in the report that DARPA portions related to this kind of science be included in the new agency.

Submitted by: William Yoon, American University, spring/summer 2004 intern