The Story Behind a Miracle Cancer Drug [Excerpt]

A new book tells the tale of Gleevec, a breakthrough treatment that targets cancer at the genetic level

By Jessica Wapner

Image: From The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level, by Jessica Wapner. Copyright ? Jessica Wapner, 2013. Available wherever books are sold.

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In The Philadelphia Chromosome journalist Jessica Wapner tells the story of the breakthrough cancer drug Gleevec, which has saved the lives of thousands of patients with chronic myeloid leukemia (CML) and other cancers since the U.S. Food and Drug Administration approved it in 2001. It was the first targeted cancer drug, developed after researchers identified the genetic mutation that gave rise to CML, and it set in motion the race to uncover the genetic roots of a wide range of cancers.

From The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level, by Jessica Wapner. Copyright ? Jessica Wapner, 2013. Available wherever books are sold.

Chapter 1: The First Clue
David Hungerford could not believe what he was seeing. He hovered over a microscope, turning the wheels this way and that to ensure the best view. A small glass slide was illuminated from below. It held a single cell that had been expanded and then stopped in the middle of reproducing, its forty-six chromosomes on full display. He checked and rechecked, and was absolutely certain: One of the chromosomes was too short.

It was 1959, and the field of genetic research was almost nonexistent. The 1956 confirmation of the standard number of chromosomes housed in the human cell?forty-six, in twenty-three pairs, one set inherited from each parent?hinted at something impossible to grasp, a continent on a horizon too distant to see with the tools of the day. Even though James Watson and Francis Crick had made their famous discovery of the helical structure of DNA in 1953 and the genetic root of Down syndrome?an extra copy of one chromosome?had been found the same year, the search for connections between DNA and disease had only just begun. Around the world, laboratories were just starting to toy with the kind of technology needed to explore genetic matter. Genes were units of heredity, a way for traits to be passed on from one generation to the next, including deficiencies. But how disease could possibly be linked to DNA was entirely unknown. Phrases like ?genetic mutation? or ?chromosomal abnormality? were not part of the vernacular yet because there was no need for such language.

And so it was that David Hungerford, a young scientist hovering over a microscope, was stunned by what he was seeing through the lenses. This was a man who knew how chromosomes should look. Camera-equipped microscopes were hot laboratory commodities in the 1950s, and Hungerford, an avid photographer, had gotten a job working with one in a Philadelphia cancer research center. He spent countless hours looking at the starfish-shaped chromosomes of the drosophila fly, training his eyes to see the fine banding patterns within. He was one of a handful of people alive at the time who could have spotted an anomaly among a blurry, inky array of chromosomes.

So it may have been inevitable that he?d ended up working with Peter Nowell, a doctor also in his early thirties doing cancer research across town at the University of Pennsylvania. In 1956, Nowell had accidentally stumbled upon a new method for seeing chromosomes inside cells. He had been studying blood cells from leukemia patients, his work following the usual approach of the day: rinsing the cells and staining them with a bluish-purple dye.

Science had come a long way in its ability to peer inside cells, the basic structural units inside every living thing, since they were first spotted by microscope in 1665. That discovery led to others, which led to the creation of cell theory, the notion that all living things are made of cells, and that new cells are made when old cells divide. But the cutting-edge techniques for seeing the inner clockwork were still rudimentary, calling for the scientist to squash a drop of cells on a covered glass slide with the thumb in order to put pressure on the cells. The 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.

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