Drugs By Design

Thanks to genetics, the pharmaceutical industry is exploding with new ideas

By Christine Gorman Monday, Jan. 11, 1999

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So how would you make a gene chip? Let’s say you want to identify which genes get turned on, or “expressed,” by the immune system in the first few weeks after the AIDS virus begins its attack on the body. First you download the sequences of perhaps 10,000 genes–every A, C, G and T of the hereditary alphabet–into a computer. Then, still using the computer, you figure out what the mirror image of each sequence would be. (DNA can mirror itself as well as RNA.) The aim is to transform the mirror-sequence data into actual strands of DNA that are planted like rows of corn on the glass bed of a chip. Each strand is built up, letter by letter, in much the same way the layers in a silicon chip are created.

Once the strands are complete, the gene chip is ready for use. You take a sample of blood from a patient who has just developed a raging HIV infection. Various genes in his immune system are churning out millions of RNA molecules that will assemble the proteins needed to combat the infection. You extract the RNA and break it into pieces, tag each piece with a fluorescent chemical and pour the whole mess over the gene chip. The RNA tightly binds only to its exact DNA complement on the chip. The fluorescent tag tells you where on the chip you have a match. Then you look up the sequence of each matched spot on the chip and read out a precise catalog of which genes are being expressed. By comparing the results from several patients–some of whom are more successful at fighting the virus than others–you may be able to identify targets that could lead to powerful new anti-AIDS drugs.

Such feats of computational biology are still a few years off or, in the worst case, maybe even a few decades away. The point is, we are just beginning to see how dramatically gene-based science can change the ways in which new drugs are discovered and developed. Blind luck will play an increasingly smaller role as scientists tease out the complex interplay between genes, proteins and the environment. There is going to be confusion–some setbacks and disappointments–at least at first. But most in the field agree that pharmaceutical research has finally entered its golden age.

–With reporting by Dan Cray/Los Angeles, Bruce Crumley/Paris and Alice Park/New York

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