The Philadelphia Chromosome is a poster-child for chromosome translocation. This is the example most students will give when asked about chromosomal translocation. I was taught this in my M.Sc. and I teach it to my students in Human Genetics when I talk about diseases caused by chromosome translocation. The importance of this translocation is underscored by the type of cancer it causes- Chronic Myeloid Leukemia (CML).
The DNA in our cells are present in the form of 24 chromosomes. Each chromosome has a specific set of DNA sequence. It is same in every individual. Occasionally, two chromosomes can exchanges pieces in a process known as Chromosomal Translocation. This is bad because it can result in loss of information. In case of Philadelphia Chromosome, it results in the formation of a rogue gene that results in cancer.
Jessica Wapner has traced the discovery of this chromosome and the cure for the cancer it causes- Gleevec. The story begins in 1959 when David Hungerford discovered that one of the chromosomes was too short in the blood samples of patients suffering from CML. At that time the concept of chromosome translocation was unknown. The minute chromosome was named Philadelphia Chromosome in honor of the city of its discovery.
From there, the story traverses across continents and laboratories wherein it was firmly established that the Philadelphia chromosome is due to exchange of DNA between chromosome 9 and 14 and this exchange results in the synthesis of an abnormal protein known as Bcr-abl that causes cells to divide indefinitely. This abnormal protein is a kinase- it transfers a phosphate group from ATP to proteins causing them to become active.
The discovery that an abnormal protein kinase causes cancer spurred researchers and doctors- in particular Brian Druker- to push for an inhibitor that would specially block the function of this abnormal kinase. Today we call this strategy Rational Drug Design and it really begins with knowing the structure of the protein. However, for Bcr-abl, the structure was unknown and the scientists working in Ciba-Geigy synthesized chemicals and screened them for inhibition activity. Gleevec was discovered in this screen.
Ciba-Geigy was purchased by Novartis. Not many people were convinced that the inhibitor would be a good drug. Further, there was the cost factor- CML affected too few people to make it an attractive market. However, Druker persists and finally, Gleevec was approved for drug trials. And of course finally for medical use.
Gleevec is that rare chemotherapeutic medicine that a patient can take at home with very few side effects. It is effect also against c-kit, which causes GIST cancer. The only caveat is that Gleevec has to be taken for life- at least till now that is the story.
Jessica Wapner traces this 40 year old story and I enjoyed it tremendously.
As an aside: There was a dispute over the drug in India which Novartis lost. Jessica barely mentions it though it was landmark decision where the Supreme Court of India ruled that Novartis cannot patent Gleevec in India allowing for the generic drug to be manufactured.
Finally: Nothing to do with Gleevec. Winter did arrive in Delhi albeit late.
The DNA in our cells are present in the form of 24 chromosomes. Each chromosome has a specific set of DNA sequence. It is same in every individual. Occasionally, two chromosomes can exchanges pieces in a process known as Chromosomal Translocation. This is bad because it can result in loss of information. In case of Philadelphia Chromosome, it results in the formation of a rogue gene that results in cancer.
Jessica Wapner has traced the discovery of this chromosome and the cure for the cancer it causes- Gleevec. The story begins in 1959 when David Hungerford discovered that one of the chromosomes was too short in the blood samples of patients suffering from CML. At that time the concept of chromosome translocation was unknown. The minute chromosome was named Philadelphia Chromosome in honor of the city of its discovery.
From there, the story traverses across continents and laboratories wherein it was firmly established that the Philadelphia chromosome is due to exchange of DNA between chromosome 9 and 14 and this exchange results in the synthesis of an abnormal protein known as Bcr-abl that causes cells to divide indefinitely. This abnormal protein is a kinase- it transfers a phosphate group from ATP to proteins causing them to become active.
The discovery that an abnormal protein kinase causes cancer spurred researchers and doctors- in particular Brian Druker- to push for an inhibitor that would specially block the function of this abnormal kinase. Today we call this strategy Rational Drug Design and it really begins with knowing the structure of the protein. However, for Bcr-abl, the structure was unknown and the scientists working in Ciba-Geigy synthesized chemicals and screened them for inhibition activity. Gleevec was discovered in this screen.
Ciba-Geigy was purchased by Novartis. Not many people were convinced that the inhibitor would be a good drug. Further, there was the cost factor- CML affected too few people to make it an attractive market. However, Druker persists and finally, Gleevec was approved for drug trials. And of course finally for medical use.
Gleevec is that rare chemotherapeutic medicine that a patient can take at home with very few side effects. It is effect also against c-kit, which causes GIST cancer. The only caveat is that Gleevec has to be taken for life- at least till now that is the story.
Jessica Wapner traces this 40 year old story and I enjoyed it tremendously.
As an aside: There was a dispute over the drug in India which Novartis lost. Jessica barely mentions it though it was landmark decision where the Supreme Court of India ruled that Novartis cannot patent Gleevec in India allowing for the generic drug to be manufactured.
Finally: Nothing to do with Gleevec. Winter did arrive in Delhi albeit late.
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