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- <text id=94TT1234>
- <link 94TO0200>
- <title>
- Sep. 12, 1994: Counterattack:Drugmakers Fight Back
- </title>
- <history>
- TIME--The Weekly Newsmagazine--1994
- Sep. 12, 1994 Revenge of the Killer Microbes
- </history>
- <article>
- <source>Time Magazine</source>
- <hdr>
- COVER/MEDICINE, Page 68
- Counterattack: How Drugmakers Are Fighting Back
- </hdr>
- <body>
- <p>By Leon Jaroff--Reported by Lawrence Mondi/New York
- </p>
- <p> Doctors and the public were not alone in feeling cocky about
- infectious disease a decade ago. The drug companies did too.
- More than 100 antibiotics were on the market, and they had most
- bacterial diseases on the run, if not on the verge of eradication.
- So rosy was the outlook that U.S. government funding for antibiotic
- research was declining, and many pharmaceutical firms were focusing
- on cancer and viral diseases, especially AIDS.
- </p>
- <p> Observes George Miller, a microbiologist at the Schering-Plough
- Research Institute in Kenilworth, New Jersey: "What we in the
- pharmaceutical industry had been doing was to take existing
- classes of antibiotics and modify them to stay one step ahead
- of the bacteria." But that approach seems no longer able to
- stem the spread of drug-resistant bacteria.
- </p>
- <p> Instead, researchers are employing several new strategies that
- they hope will put medicine ahead, at least temporarily, in
- the battle against the bugs. One approach is "rational" drug
- design, based on new understanding of how bacteria function
- at the molecular level. Using the techniques of biochemistry
- and crystallography, scientists are identifying bacterial genes
- and enzymes that confer drug resistance, and are creating antibiotics
- that will act specifically against a targeted microbe.
- </p>
- <p> By discerning the molecular structure of an enzyme used by a
- drug-resistant bacterium to fight off that drug, for example,
- scientists can design a molecule that fits precisely into the
- active site of the enzyme. That neutralizes the enzyme, depriving
- the bacterium of a crucial element of its defense and making
- it susceptible once more to the original drug. "It's like sticking
- a wad of gum into a keyhole and binding it up," says Fred Cohen,
- professor of pharmacology at the University of California, San
- Francisco.
- </p>
- <p> Scientists are pursuing a similar line of attack against viral
- diseases. In their AIDS research, for example, some are concentrating
- on a protein called CD-4, which resides on the surface of immune-system
- T cells where the AIDS virus attacks. Before the virus can enter
- T cells, it must join with a receptor site on the CD-4 protein.
- Here, too, a properly designed molecule might block that site
- and protect the T cell.
- </p>
- <p> Some companies are delving into "combinatorial" chemistry, which
- involves making Lego-like blocks of chemicals that can be joined
- in hundreds of thousands of combinations, one or a few of which
- might create molecular havoc with a particular bacterium.
- </p>
- <p> "Chemists have conceived of ways to build vast libraries of
- these wonderful combinations of building blocks, concepts that
- did not exist five or 10 years ago," says Barry Eisenstein,
- a vice president of the Eli Lilly research labs in Indianapolis,
- Indiana. Roboticized testing has helped make this approach practical
- by enabling researchers to screen hundreds of thousands of compounds
- in just a few months.
- </p>
- <p> Prevention is even better than cure, and scientists are also
- experimenting with new vaccines that will ward off infections
- by alerting and arming the body's immune system against the
- invaders. One such vaccine is already on the market. It is designed
- to prevent the ills brought on by pneumococcus, which include
- sinusitis and ear infections as well as pneumonia.
- </p>
- <p> Scientists are sanguine about regaining the upper hand against
- infectious disease but now realize that no strategy will work
- forever. As long as microbes have the ability to neutralize
- medicine's weapons, the drug companies will have to keep adding
- to the arsenal.
- </p>
- </body>
- </article>
- </text>
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