By Natalie Castro
In 1959, when a
young pathologist named Peter Nowell accidentally used tap water instead of
distilled water to rinse cultured blood cells taken from patients with chronic myelogenous
leukemia (CML), a type of slow-progressing cancer of the white blood cells, he
noticed a subtle abnormality in one of the chromosomes.
After teaming up with the late David Hungerford, PhD, of the Fox Chase Cancer
Center, who was then a graduate fellow studying human chromosomes at the
Institute for Cancer Research in Philadelphia, the two detected a shortened
chromosome number 22 and named it the Philadelphia chromosome after the city
where it was discovered. In 1960, the Journal of the National Cancer
Institute published Dr. Nowell and Dr.
Hungerford's evidence linking the abnormality with CML, which suggested for the
first time in history that cancer could be caused by genetic mutations.
What was a mistake
is undoubtedly regarded as a scientific breakthrough in cancer research. At the
time, the consensus among scientists was that cancer was caused by a virus or
by extreme exposure to radiation. "It was the first real evidence that a
genetic mutation could cause a cell to grow abnormally," said Dr. Nowell, who
added that viruses can still play a role in cancer diagnosis.
The discovery of
the Philadelphia chromosome prompted researchers to further study the
implications of genetic abnormalities. In 1973, Janet D. Rowley, MD, now a
professor of hematology and oncology at the University of Chicago, discovered
that the shortened chromosome 22 was a result of a translocation, or
rearrangement of chromosomes and exchange of genetic material, with chromosome
9. BCR is a gene found on chromosome 22, but the exchange of information causes
a gene fusion with ABL, a gene found on chromosome 9, creating a new gene
called BCR-ABL. BCR-ABL encodes for a different protein that is responsible for
the growth of abnormal cells. Drug treatments for CML, like imatinib (Gleevec),
which was approved by the FDA in 2001 for the treatment of CML and has
shown high rates of remission in patients living with CML, work by blocking a
certain enzyme called tyrosine kinase which is produced by the BCR-ABL gene.
Dr. Nowell, who is
now a professor of pathology and laboratory medicine at University of
Pennsylvania's School of Medicine and the first director of the school's Abramson
Cancer Center, called the progress in the last 50 years gratifying. "We now
have a treatment that specifically attacks the abnormal production of proteins
caused by the genetic mutation," he said, referring to therapies such as
Gleevec. There are an
estimated 24,800 Americans living with CML, which accounts for 7 to 20
percent of all leukemia cases.
Dr. Nowell
stressed the need for pharmaceutical companies to develop new, additional
specific therapies for different types of cancer and called the lack of support
for basic research on the many different kinds of tumors that can arise from
mutations an "obstacle" in cancer research.
When asked whether he thought the Philadelphia
chromosome discovery was simply an accident or fate, Dr. Nowell quickly
responded with a laugh. "Serendipity, all of the above. I still don't know what
questions I had about those cells or what I expected to find, but it was one of
the two most important observations of my career."
Natalie Castro is an aspiring physician interested in family and community medicine. She hopes to create awareness of health issues through medical journalism.
Published: December 9, 2010
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