The Philadelphia chromosome

In 1960, somewhere in the helical wilderness of chromosome 22—one of 23 pairs of chromosomes, stringy storehouses of genes, present in human cells—two US scientists at the privately endowed University of Pennsylvania found a section of DNA missing in most patients with a blood cancer called chronic myeloid leukemia (CML). The flawed gene came to be known as the Philadelphia, or Ph, chromosome.

In 1973, researchers at the University of Chicago, also founded by donors, found the missing bit of DNA on chromosome 9. This phenomenon, called translocation, was later found to be the cause of various cancers. It opened the door to seeking the genetic causes of and cures for cancer, now the world’s leading cause of death.

Real progress came only in the 1980s, when human genes were first mapped. Scientists at the California Institute of Technology, or Caltech, found the Ph chromosome produced a protein (Bcr-Abl) that sabotaged a cell’s genetic blueprint and led to the runaway growth of white-blood cells, causing pain, illness and, often, death.

This was a rare opportunity, a clear genetic target. If a drug could block the action of Bcr-Abl protein, it was possible to conquer CML. In theory.

In 1988, Ciba-Geigy, later Novartis, began that work. Scientists, including Jurg Zimmermann (named as Glivec’s inventor in this week’s Supreme Court judgement), created and tested 400 molecules over two years. It would take another decade before the drug could be tried on patients, with dramatic results. The man responsible was academic oncologist Brian Druker. He identified STI-571, the precursor to Glivec (also known as Gleevec or its chemical name, Imatinib mesylate). In 2009, Druker was one of three scientists awarded the Lasker-DeBakey Clinical Medical Research Award, often termed the “American Nobel", for finding a CML cure.

Druker, whom I contacted for this column, did not earn a penny from the drug (the compound that became the drug was already patented when it came to him), and the price that Novartis fixed for Glivec caused him acute discomfort.

Ranjit Shahani, vice-chairman and managing director of Novartis India, argues that each successful molecule needs to pay for “the thousands of molecules" that fail. You can argue that this isn’t the patient’s problem, but on a global scale, this is only model that really works. “Consider that only one out of 10,000 experimental compounds in development will reach the marketplace," Shahani told me.

Glivec became the first drug to pick molecular targets, attacking specific proteins that cause the spread of cancerous cells. CML has gone from being a death sentence to being a chronic, manageable illness. Druker, now director of the Oregon Health and Science University-Cancer Institute, likens cancer to a light that won’t go off. Chemotherapy is the rod that smashes the light, poisoning other cells in its attempts to kill cancer. Glivec simply switches off the light.

When I ask for Glivec’s development cost, Shahani only offers commonly known averages: 12 years and $1 billion to take a drug to market. Glivec has earned Novartis—the second-most profitable pharma company in the world—in excess of $4 billion since it emerged on the market in 2001. Druker estimates Novartis funded “close to 99%" of Glivec’s development. “But," he said, “that misses 30 years or more of publicly funded science that allowed the target (of Glivec) to be identified."

So, developing blockbuster drugs involves public institutions and private companies, lots of money and, yes, profits. It also requires extraordinary foresight, perseverance and an informed public. In 1996, when Novartis emerged, the new company seemingly lost interest in Glivec. Druker lobbied for clinical trials and when the results went viral in Internet chat rooms, patients pressured the CEO, who then agreed to expand trials.

The profit imperative of drug companies needs to be balanced against the needs of those who need cheap drugs. “But if we too severely restrict the price of medications," said Druker, a consistent opponent of high drug prices, “we may lose the ability to invest in new drugs."

Druker points to Novartis’s patient-assistance programme (in India, the company says 16,000 patients receive Glivec free of charge) and the HIV model of providing access to cheap drugs as worthy of replication. India’s generics industry supplies more than 10 million patients globally with cheap HIV-AIDS medicines, making the country what many call the world’s pharmacy.

The question, Druker said, is this: “When does a country move from needing assistance to make drugs affordable to being able to contribute more to this cycle of drug discovery and innovation?" The court decision is good for patients in the short-term. As for the long-term, it appears India would rather not look that far ahead.

Samar Halarnkar is a Bangalore-based journalist. This is a fortnightly column that explores the cutting edge of science and technology. Comments are welcome at frontiermail@livemint.com. To read Samar Halarnkar’s previous columns, go to www.livemint.com/frontiermail-