Commentary: Gene-Based Therapy: Back To The Couch

Recent setbacks show (again) that biotech needs more patience and less ballyhoo

If the dramatic biological advances of the past two decades had lived up to their original hopes, medicine would have moved beyond the marvels we see today. Diseases would be cured by slipping new genes or cells into people. Knowledge of genes would have made many novel drugs possible. And the scientific descendants of Dolly the sheep -- cloned animals -- would offer nutritionally enhanced foods, new drugs, and organs for human transplant.

That hasn't come to pass. Instead, recent developments are sobering and valuable reminders not to be swept away by the breathless excitement of new discoveries. On Mar. 25, gene-mining pioneer Human Genome Sciences Inc. (HGSI ) announced major layoffs and the retirement of its colorful CEO, William A. Haseltine, in the wake of the failure of several of its drugs. Across the Atlantic, Scotland's PPL Therapeutics PLC, the company that helped create Dolly and other biotech creatures, is liquidating its last assets. Gene therapy, a great buzzword of the past decade, seems little closer to useful treatments than it did when the landmark first human experiment was done in 1990. New drugs are emerging from the biotech industry. But the quest for cures to cancer and other diseases has hit roadblocks. Says Professor John Clark, director of Roslin Institute, where Dolly was born: "The days of the great dream are over."

Why the stumbles? "Medicine is complicated, and we understand only a small fraction of human biology," says Haseltine. Human Genome Sciences was founded in 1992 on an exciting premise: By using a new ability to find thousands of previously unknown genes, researchers could discover scores of natural substances that the body uses to repair damage and tackle diseases. Indeed, HGS scientists thought they'd hit pay dirt early on with a wound-healing chemical. But it failed in clinical trials for skin ulcers. "Curing venous ulcers is difficult, and we did not succeed," says Haseltine.

Haseltine firmly believes that other drugs HGS is developing have a good chance of working. But biotech watchers say that the company rushed to create drugs before fully understanding the underlying biology. That has left its pipeline suspect -- and explains why HGS' stock, now hovering at $12, is worth just a fraction of the March, 2000, high of $112 5/8. In other areas of biotech, the science is moving even more slowly. Seven years after Dolly's birth (and a year after her death), researchers haven't figured out how to consistently make healthy cloned animals -- or define what benefit they bring. PPL's demise began last summer when partner Bayer (BAY ) pulled out of a project to make a protein drug in gene-altered animals. Why? The effort no longer looked economically viable.

Even in the current hot area of stem cells, businesses are running into scientific and regulatory hurdles. Researchers had hoped that such cells, which have the potential to become any cell in the body, could be used to repair or replace organs. But new experiments show that getting stem cells to transform themselves into, say, new heart cells, is harder than first expected -- and injecting such cells into humans might be harmful. Even if the science works, no one yet has a good idea how such cells could be turned into viable products. "There are significant challenges to bringing cell therapy to the market," says T. Rowe Price Group Inc. (TROW ) analyst Dr. Jay S. Markowitz.

The stumbles don't mean we should give up on the new genetic approaches. "The history of biotech is that often the first time around things don't work, then the problems are sorted out," says venture capitalist Alan G. Walton at Oxford Bioscience Partners. Nearly 30 years after scientists first learned how to create designer proteins called monoclonal antibodies -- man-made versions of the chemicals the immune system uses to fight invaders -- it is finally leading to important treatments for cancer and other diseases. Gene-based medicine is indeed on the horizon -- but the distance may be greater than it seems.

By John Carey

    Before it's here, it's on the Bloomberg Terminal.