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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Finding a likely target, of course, doesn’t guarantee success. Consider colon cancer: scientists believe at least three things have to go wrong for colon cancers to form. They liken the situation to a car accident. One of the genes that tells cells to divide (the accelerator) must get stuck in the “on” position. Another gene that tells cells to slow down (the brake) must be disabled. And the molecules that fix any mistakes in the DNA code (the repair crew) have to go on strike. In half of all colon cancers, the accelerator is a gene called ras, which makes a protein that stimulates cell growth. It was the ideal target for an anticancer drug.

Or so it seemed. “We banged our heads against the wall for 10 years,” says Dr. Alan Oliff, head of cancer research at Merck. “We were on the verge of abandoning the project.” Then Oliff’s team realized something critical: the ras protein can’t do its job until it has been activated by another enzyme called a farnesyl transferase. Maybe that would make a better target? Early word is that it does, but Merck won’t publish the findings from its first human trials until sometime next year.


Whereas traditional drug companies focus on developing chemical compounds, the biotech industry prefers to use biological ones–hormones, proteins and other substances that either already exist in the body or can be created from scratch. Examples include interferon, the clot buster tPA and the new breast-cancer drug Herceptin.

But even among the rarefied biotech elite, there are mavericks who think they have a better idea. They want to move one step closer to the gene by targeting the RNA molecules that transfer information from genes to proteins. And they have the perfect molecular tool with which to do it. By synthesizing strands of DNA that are the mirror image of the RNA they wish to block, researchers can produce a drug that is more specific than anything else on the market. Because it interrupts the “sense” that the cell is trying to make of the RNA molecule, the new technology is called, appropriately enough, anti-sense.

There are still some kinks to work out. For one thing, the body’s own immune system often attacks the anti-sense DNA, mistaking it as a potentially harmful virus. For another, many cells in the body don’t allow the anti-sense molecules to cross their membranes. “Nine years ago, everyone thought, wow, this is dynamite,” says Dr. Art Krieg, editor of the journal Anti-Sense and Nucleic Acid Drug Development. “Then they ran into technical hurdles, and the pendulum swung the other way.” Now, says Krieg, a few anti-sense compounds are starting to show promise. Among them is a drug called Vitravene, which was approved by the Food and Drug Administration in August and is used to prevent blindness in AIDS patients infected with cytomegalovirus.


Genes don’t just tell you how to make drugs. They can also tell you whom to treat.

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