The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

Jessica Wapner

Language: English

Pages: 320

ISBN: 1615190678

Format: PDF / Kindle (mobi) / ePub

A Wall Street Journal 10 Best Nonfiction Book of the Year

“Among a small cluster of very good recent books on cancer.” —The New York Times

Philadelphia, 1959: A scientist scrutinizing a single human cell under a microscope detects a missing piece of DNA. That scientist, David Hungerford, had no way of knowing that he had stumbled upon the starting point of modern cancer research— the Philadelphia chromosome. It would take doctors and researchers around the world more than three decades to unravel the implications of this landmark discovery. In 1990, the Philadelphia chromosome was recognized as the sole cause of a deadly blood cancer, chronic myeloid leukemia, or CML. Cancer research would never be the same.

Science journalist Jessica Wapner reconstructs more than forty years of crucial breakthroughs, clearly explains the science behind them, and pays tribute—with extensive original reporting, including more than thirty-five interviews—to the dozens of researchers, doctors, and patients with a direct role in this inspirational story. Their curiosity and determination would ultimately lead to a lifesaving treatment unlike anything before it.

The Philadelphia Chromosome chronicles the remarkable change of fortune for the more than 70,000 people worldwide who are diagnosed with CML each year. It is a celebration of a rare triumph in the battle against cancer and a blueprint for future research, as doctors and scientists race to uncover and treat the genetic roots of a wide range of cancers.

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the captured gene has become an oncogene. RSV was an example of this simple RNA virus. The virus had captured src from a host during replication, and once inside the viral genome, the gene had become an oncogene that caused cancer in chickens. This transport, a hostage from one ship who turns criminal by the time of the next piracy, was the process that Bishop and Varmus would spot with their radioactive DNA flashlight, the src probe that had enabled them to find the normal, proto-oncogene

to see if it might phosphorylate tyrosine. His report that Src was a tyrosine kinase was published in 1980. But the clue eluded Baltimore for the strangest of reasons. Other concurrent work in his lab had uncovered a link between poliovirus and tyrosine. Witte’s kinase work came so close on the heels of that link that Baltimore assumed tyrosine could not be important in both research arenas. What were the odds that two ongoing efforts in his lab could both involve this obscure amino acid? “I put

compound. Starting with substances that had already shown anti-kinase tendencies and sketching out their ideal molecular structures on paper, Zimmermann and the other chemists began introducing other atoms into the mix. Several molecules had already shown some anti-kinase activity (albeit with the coarse profiling tools available at the time). There was the isoquinolinesulfonamide from Hidaka’s work. A group from Japan found that a molecule they named erbstatin inhibited EGFR. A group in Israel,

squash was supposed to burst the cell, spilling out its gene-filled middle. But the approach failed as often as it succeeded, leaving behind broken cell fragments that were useless to researchers. People were frustrated with the technique, which wasted precious time and resources. One day Nowell took a shortcut around the usual scientific procedure. “Pete was in a hurry, as young men tend to be,” Alice Hungerford, David’s wife, would recount years later. Instead of following a more rigorous

would likely be lethal. But they had no explanation for what else could have happened. A piece of genetic material had vanished. Why had it disappeared? Did the change somehow cause leukemia, or did leukemia somehow cause the change? These were questions for another decade. Knowing the standard number of chromosomes had enabled geneticists to create a universal number language. But the view afforded by the technology at the time was so coarse that at first Nowell and Hungerford couldn’t even tell

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