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September '05
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In Pursuit of Pathogens

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Gene Therapy:
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PERSPECTIVES & OPINIONS: In Pursuit of Pathogens

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Over the years, my lab, in collaboration with Barry Bloom, has developed a fairly complete set of genetic tools to do genetics in mycobacteria and complete Koch's corollary. Every time I have had a problem overcoming a genetic obstacle, I went to mycobacteriophages—viruses that infect bacteria—to find solutions. In fact, our first big breakthrough came with the introduction of foreign genes into mycobacteria using chimeric phage vectors that I designed. Using a system based on this original chimeric vector, we can now systematically knock out every gene of M. tuberculosis. Recently, in collaboration with Graham Hatfull, an HHMI professor at the University of Pittsburgh, and David Fidock at Albert Einstein, we have developed an efficient complementation system for Plasmodium falciparum, the parasite that causes malaria, using genes from Bxb1 (alias the Bronx Bomber), a phage I isolated from my backyard in the Bronx.

I have always been interested in problems that affect the developing world. I went to Barry Bloom's lab because he wanted to make a recombinant BCG as a vaccine vector that could maybe protect against TB, malaria, and other diseases affecting the developing world. We have gone back now and remade BCG from virulent M. tuberculosis and M. bovis. Derivatives of these strains have shown promise in mice against M. tuberculosis. To get it into the clinic, we're going to have to prove that they are safe in humans. Toward that goal, we have demonstrated safety in guinea pigs, immunocompromised mice, and recently in monkeys. Further studies are under way.

My life changed the first day I took a plane to Madras, India, on my way to visit a leper colony. I saw masses of humanity like I had never seen before in the U.S. I wish that I could take President Bush and his advisers with me to a leper colony because what we need in the U.S. is to be exposed to the rest of the world's problems. After all, 75 percent of the world's population is threatened by infectious diseases. grey bullet

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HHMI INVESTIGATOR

William R. Jacobs
William R. Jacobs
 
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