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How a lab shortcut led to cancer drugs

It was late on a mundane afternoon in 1950 when a young University of Pennsylvania scientist, Peter Nowell, decided to take a shortcut.

It was late on a mundane afternoon in 1950 when a young University of Pennsylvania scientist, Peter Nowell, decided to take a shortcut.

Rather than apply the tedious "squash" method of rinsing cells, Nowell washed a sample of white blood cells in some fresh, Philadelphia tap water.

It was a split-second decision that changed the course of cancer research. Through his microscope, Nowell saw how tap water caused the cells to swell. Suddenly, the chromosomes were magnified.

With the help of Fox Chase Cancer Center's David Hungerford, Nowell perfected this method of observing cells. By 1959, they could see it, "an abnormally small arm of a worm-shaped chromosome" within the cell of a patient with chronic myeloid leukemia (CML). A year later, they published a three-paragraph summary of their findings.

And so the Philadelphia Chromosome - the first gene linked to cancer - came to light.

This find - and the wave of personalized medicine it spawned - is the subject of The Philadelphia Chromosome, published this month by science writer Jessica Wapner. While many have explored the story, this is the first book to focus on it and its vast implications.

In an interview, Wapner, who will speak at the Free Library of Philadelphia on June 4 at 7:30 pm, stressed the significance of Nowell's "mistake." "When we hear about individualized therapy, tumor sequencing, [or] even the whole notion of personalized medicine, [it] can all be traced back to this story and the successful creation of a drug at its root cause."

It took more than a decade for cancer researchers to understand the significance of the shortened chromosome 22. It wasn't until 1990 that researchers identified the mutation as CML's root cause and showed how it affects a specific kind of protein, a tyrosine kinase.

Later, that discovery helped make CML a chronic disease. Oncologist Brian Druker, working on the shoulders of the Philadelphia team, was key in getting FDA approval for Gleevec in 2001. The drug blocks the mutation's disruptive activity.

Hundreds of kinase inhibitor drugs are now in the works, and the $15 billion industry is expected to double in the next 15 years. Wapner stresses how individualized therapies may become the standard in decades to come.

The holdup?

Most cancers are produced by multiple mutations rather than one kind, meaning that drugs must be created that target each mutation.

The rarity of CML, which afflicts about 50,000 people worldwide each year, at first made drug firms reluctant to invest in Gleevec. In the late 1990s, patients had to lobby to get into trials to help drive the approval process.

Then, after pharmaceutical giant Novartis got the drug approved, it came at a stiff price - now $33,000 a year per patient - raising the ire of advocates and doctors. Foreign firms are breaking the patent and selling cheap, generic forms of Gleevec to help the legions of untreated patients.

The scientists continue to reap acclaim. On May 17, Nowell, Druker, and University of Chicago geneticist Janet Rowley shared in the $500,000 Albany Medical Prize.

Wapner's account of all this is heavy going at times, delving more into the nuances of genetics than the personal stories of the scientists. Still, she opens our eyes to a future in which remedies will kill tumors at their root.

And to think it all started with a "mistake."