Good News, Bad News: The Mixed Bag of Research Advances

Two news stories last week show that cutting edge medical research is aptly named, since what may be remarkable cures are separated by a thin edge from sometimes great risk.

What's your opinion?

On the same day, the nation's media carried two medical research stories: one discussing a possible breakthrough step in medicine's battle against cancer, and the other reminding us that even in the age of genetic medicine, research carries real risk: in this case, a death in a research trial for gene therapy.

The questions that arise from these very different stories are about both the promise and the pitfalls of medical research as we enter the next century. When should we begin testing unproven therapies in patients? Is it wise to treat diseases while patients are still relatively healthy and have a better chance of success but also more to lose? How can we best foster but not exploit the hope prompted by promising research?

The good news story was about the anxiously awaited first human testing of angiostatin -- what many hope could be a revolution in cancer treatment in the form of new drugs that work to deprive tumors of the blood vessels they need to grow. The first few subjects are being enrolled in a study of the drug, and the fact that demand is great even with strict eligibility criteria speaks to the need for new ways to treat cancer. To be eligible, patients must have specific types of cancer for which treatment has been unsuccessful. This means the patients in the research will be both quite sick and without other treatment options, so that the benefit (if any) offered by the research offsets its risks.

The bad news story was about the death of an 18-year-old man in a study using gene therapy to treat a disorder of ammonia metabolism. Gene therapy has long been considered a promising area of research because rather than treat the symptoms of a disease, it actually repairs or replaces the genetic defect responsible for it. But gene therapy's promise has been marred by a lack of success, and this case will raise even more questions about its future.

The patient in this case was relatively healthy, with the effects of his disorder kept under control by careful diet and medical care. His relatively good health made him an attractive subject for the research. Patients who are symptom-free or whose disease has not yet left permanent damage are more likely to survive the rigors of research and have more to gain from permanent repair at the genetic level. But they also have more to lose. This subject traded life with a treatable disease for a chance at permanent cure, and lost.

As medical research turns its efforts to treating and even curing chronic diseases, the tradeoff presented by gene therapy will become more commonplace. Research is leading to more aggressive treatment approaches, such as bone marrow transplant at early stages of rheumatoid arthritis. How should we measure the tradeoff between a future living with a chronic and potentially debilitating disease, the risks of a potentially toxic and even fatal treatment, and the possibility of a permanent cure? The answer is obvious when we examine a specific case after the fact, such as the recent gene therapy death; the challenge for the future is to find ways to allow us to look forward with similar confidence.

Research advances have been great, and the 21st century will bring even more technical marvels and elegant approaches to treating disease. But all research has and will share some common elements, including that we don't know whether it will work and can't always predict its risks. Remembering these basic facts will keep both researchers and subjects humble in the face of what we don't know and can't control.