Spring 2002 Newsletter: Why Do Basic Scientific Research?

The story of the development of an important anti-cancer drug

In 1960, two Philadelphia physicians had observed that patients withchronic myeloid leukemia (CML) usually had one abnormally small chromosome. Chromosome 21 maybe; chromosome 22 maybe.

In 1972, at the University of Chicago, Dr. Janet Rowley discovered that white blood cells of patients with CML not only had a short chromosome in pair 22, but they also had a longer than usual chromosome in pair 9. Parts of chromosomes 9 and 22 had traded places, she surmised. This is called translocation. And maybe this was the cause of CML.

Dr. Rowley said that there was little interest in this outside the community of chromosome-studiers. This was a discovery with no immediate use. Little did she realize that this observation would lead to a drug heralded as the first big breakthrough in cancer treatment since Nixon declared war on the disease in 1971.

In the 1980s, investigators discovered that the 9;22 translocation placed genes ( parts of chromosomes9 and 22) side-by-side, and that parts of these two genes formed an altered gene. The altered gene produced a new protein. This gene had been identified in 1969 by Dr. Herbert T. Abelson, now Chairman of the Department of Pediatrics at the University of Chicago.

Researchers recognized this altered gene was the gene that breaks off and migrates from chromosome 9 to chromosome 22.

Dr. Albelson said that his discovery had nothing to do with anything clinical at the time. It was a discovery with no immediate use.

In the mid-1980s, the new protein was found to regulate cell division by initiating a chain of reactions leading to nonstop cell replication. Cancer.

A pharmaceutical company was developing molecules that might block this protein while leaving normal cells unharmed.

Clinical trials in patients with CML began, and in about half of the patients taking this pill, cells with the mutant 9;22 chromosome could not be detected. The new drug worked.

The Federal Drug Administration approved this new drug, Gleevac, manufactured by Novartis Pharmaceuticals,for treating CML. Since its introduction in 1998, Gleevac has brought more than 90 percent of newly diagnised CML patients into remission, with few side effects. Clinical trials are being conducted using Gleevac for gastrointestinal stromal tumors, and there will betrials for leukemia and other cancers.

Dr. Janet Rowley said that basic research may take years or decades to bear fruit. “You have to believe in yourself, that what you are doing is important and really it’s only a matter of time before its importance is recognized - and that people will then try to proceed to translate the observations you and others make into effective treatments for patients.”

Source of information: Credits to author Candy Shufro who wrote the article published in University of Chicago Magazine, October 2001.