t h e P h i ladel phia C h romosome

and the Quest to Cure Cancer at the Genetic Level

1840

Doctors first recognize symptoms of chronic myeloid leukemia (CML), a cancer of the blood that raises white blood cells to deadly levels. Arsenic becomes the prescription of choice for the rest of the 19th centurydoing nothing to prolong life. Researchers Peter Nowell and David Hungerford discover a mutant gene, christened the Philadelphia chromosome, in CML patients, a finding of little significance at the time but that would change the face of cancer research.

J. Michael Bishop and Harold Varmus, studying chicken cancer, show that normal genes in every cell have the potential to cause cancer. It took 31 years of research to verify this connection.

1959

David Baltimore and Howard Temin discover how retroviruses work. Diseases known today to be caused by retroviruses include the common cold, some forms of cancer (including CML), and AIDS.

1976

Scientist Janet Rowley discovers the complete process behind the genetic anomaly linked to CML, showing that pieces of chromosomes 9 and 22 trade places.

1970

1973

1990

1975 1989

First Baltimore and Temin, and then Bishop and Varmus, win the Nobel Prize in Physiology and Medicine for their work.

1971

Scientists develop the banding technique, which reveals the genetic composition of chromosomes in unprecedented detail.

Scientist George Daley proves the Philadelphia chromosome to be the sole cause of CML in mice, the first time a cancer has ever been linked with total certainty to a single genetic mutation.

1996

Phase I trials of a brand new drug, STI-571, tested on monkeys, dogs, rats, and mice, all with CML, show that attacking CML at its genetic source can lower white blood cell counts.

Bud Romine takes 25 milligrams of this new drug, soon to be known as Gleevec, representing the first human use of a drug designed to attack cancer at the genetic level.

1998

Portland, Oregon oncologist Dr. Brian Druker, Gleevecs most ardent champion, reports that 100% of patients receiving high enough doses responded with lower white blood cell counts.

1999
Wa
PneR

In 45% of patients, the Philadelphia chromosome disappeared entirely. Not a single patient in the test reported any serious side effects.
PHotograPHs coUrtesY of Janet roWleY ( toP ), dr. Brian drUker ( Bot tom )

2001

Gleevec so dramatically improves on preexisting treatments that it sets the record for fastest time a drug has ever been approved by the FDA.

The same principles behind Gleevec now lead the charge to defeat the genetic sources of other cancers, including colorectal cancer, kidney cancer, other types of leukemia, lung cancer, and melanoma.

THEEXPERIMENT
theexperimentpublishing.com @experimentbooks

a summary of the story as told in full in The PhilaDelPhia ChROmOsOme: a mutant Gene and the Quest to Cure Cancer at the Genetic level by Jessica Wapner

JessiC

may 10,

additional source: goldman, Jm. 2010. chronic myeloid leukemia: a Historical Perspective. seminars in Hematology 47(4): 30211.

$25.95 | Hardcover | 978-1-61519-067-6

Publishes may 2013