Interview with Stanley Falkow

Questions for Stanley Falkow, professor of microbiology and immunology and of medicine at Stanford University, who studies the genetic and molecular mechanisms by which bacteria become pathogenic. The Scientist: The Bush Administration's program calls for spending $1.75 billion annually over the next three years to fund bioterrorism research through the National Institute of Allergies and Infectious Diseases (NIAID) alone. That part of the plan directs the Institute to discover and produce all necessary vaccines, medicines, and diagnostic tests to defeat bioterrorism, and NIAID Director Anthony Fauci has set a goal of 10 years to complete this work. What's your opinion of this strategy? Stanley Falkow: I have been really very upset by the focus on bioterrorism…What I really fear is that the focus on bioterrorism takes away from efforts that could be really done with other, more pressing agents that kill a lot more people, and not on a theoretical basis. If you look at what are the leading causes of disease, we were on track before bioterrorism. People were focusing on tuberculosis, malaria, diarrheal diseases - at least in terms of the infections - and HIV. These are the things that kill more people in the world than anything else. TS: Is Dr. Fauci's goal of creating all necessary anti-bioterrorism vaccines, medicines, booster drugs and diagnostic tests in the next 10 years realistic? SF: What is a reasonable time frame? Ten years? Maybe. I don't know. People I have known for 40 years have been trying to develop a safe and effective vaccine against dysentery. And cholera. And a novel vaccine against typhoid. So what can I say? There's no way of putting a time limit on this. Everyone is talking about the fact that there have not been significantly new, antimicrobial agents that have been developed, in terms of antibiotics, for several decades. And it's not for lack of trying on the part of the pharmaceutical industry. There have been any number of articles written about the feeling of frustration, and to some degree, alarm about our inability to come up with new approaches to make new antimicrobial agents. TS: Fauci also announced in October that President Bush expects him to provide some of those products within just three years. Is that demand realistic? SF: What the President says has no scientific relevance…It has nothing to do with science and shouldn't be mixed up with anything to do with science. Given a four-year window, one could come up with new diagnostic techniques. To make a vaccine that is effective and safe would be difficult, under any circumstances, even using the newest tools. Q: How about 10 years to complete all the needed vaccines? SF: I don't think that 10 years is out of the question. In fact, using a genomic-based paradigm, Rino Rappuoli [of Chiron, working in Italy] was able to design a new meningococcal vaccine in three years and could in principle complete initial human trial in eight years. TS: How did he do that? SF: What they said is, "We have an organism for which it has been very difficult to develop a vaccine against. We have the full genomic sequence. We look at it. We do an analysis and we find out those proteins that are on the surface of the cell. These will be the most likely to be immunogenic and seen by the immune system during an infection." Then you use some logic to say which ones would be novel and which ones where you don't know very much or look worthwhile. You basically express those proteins in e coli. You make antibody against the proteins. You select those that seem to be the best, and you don't use one, you use a combination. And you see whether the combination of those purified proteins, when applied to the vaccine, can protect an animal against disease. So if the goal is to make a protective vaccine, you can do it without necessarily understanding the science. [But] Rappuoli would be the first to say it's better to understand the science…I think it's a model that can be utilized if one is under extraordinary time pressure. It is not what one would like to do. And to give Rino and his colleagues full due credit, there was a lot of decision-making about which components to use or not to use, which was based on a very firm scientific basis. It wasn't quite the randomness that it sounds like.

Interview with Stanley Falkow

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