Assassin of warped chromosomes

The emails, from all over the world, indicated the great, global spread of a disease that destroys living cells in myriad ways by using the ultimate weapon—DNA, the genetic fount of human life.

A software engineer from Bangalore sought help for a relative struck by mouth cancer, a son for his father with bone cancer, a man from California for a friend’s wife with lung cancer, a Lebanese dental school instructor for a sister whose breast cancer had spread to the liver. “If you think that you can help my sister with your new medicine, please tell us,” the Lebanese doctor wrote. “Please I am waiting for any answer.”

Across the world people urgently await new medicine and answers, any answers, to a collection of more than 100 diseases that we collectively know as cancer. That urgency dramatically came to life earlier this year for Sathees Chukkurumbal Raghavan, 43, after he announced a preliminary, incremental, and promising, step forward in the long race against cancer. The announcement first came in January in the form of a paper in the prestigious international journal Cell and eventually led to this year’s Bhatnagar award, the national prize for promising Indian scientists under 45.

Raghavan and his team of biochemistry students at the Indian Institute of Science, Bangalore, found a molecule that impedes the repair of DNA broken in the course of radiotherapy and chemotherapy within cancerous cells. The broken DNA accumulates, killing the rogue cells. The molecule, called SCR7 (the SCR stands for Raghavan’s initials, a common method of naming molecules in the course of experimentation), allows a two- to three-fold reduction in radiation and chemotherapy. Tested in mice and on human cell lines, the molecule is a long way from human use, as Raghavan explains to those who hope it somehow might.

“To take this molecule for the treatment of patients (sic), it has to undergo clinical trials, which may take a minimum of five years (it will probably take longer),” writes Raghavan in a standard email reply. A pharmaceutical company—he is talking to one—must undertake the slow, expensive probing of SCR7 for safety and effectiveness. “Although I completely understand the need of the patient,” the email continues, “I am really sorry that I am unable to provide the drug to you at this time.”

Raghavan’s expression of sympathy is genuine. His own father, a Kerala farmer, died of an untreatable cancer. “These emails,” he says, “make you determined to try harder.”

The Cell paper led to a more-welcome kind of interest in Raghavan’s work. Cancer researchers and scientists from the US, Europe and Japan asked for samples of SCR7 or otherwise inquired how they might team up. Raghavan has finalized more than 20 global collaborations to explore SCR7’s properties in various types of cancer cells and its efficacy against other cancers. There is much he does not know about the workings of the warped DNA that triggers cancer.

An elegant double helix first described 60 years ago, DNA—made of sugar and phosphate ladders linked by rungs composed of four chemical letters, or bases—is the genetic blueprint of every living cell. DNA copies itself all the time, at the rough rate of 3,000 letters every minute. In the course of replication, DNA often snaps. “Every day here are several breaks and base modification in almost every cell,” explains Raghavan. “But we have effective DNA repair systems.” When DNA breaks, the chromosomes that it forms are in turn damaged, disurpting normal life in a cell. Broken chromosomes—aggregates of genes where the entire genome, or blueprint, of an individual is stored in the form of DNA—do rejoin but in ways they should not. This jumbled blueprint creates cancerous cells that refuse to die and instead replicate endlessly.

Since he set it up seven years ago, when he returned from a post-doctoral stint at the University of Southern California, Raghavan’s laboratory has focused on the genetics of cancer. They probe the mechanism of oncogenesis, or how cancer cells are created, and hope to formulate therapeutics against it.

An entomologist who went on to a PhD from Banaras Hindu University, Raghavan concentrates on leukemia and lymphoma, cancers that cause the human immune system to turn on the body, the defenders killing what they ordinarily protect. It is ironic—and representative of scientific serendipity—that SCR7, one of many molecules his laboratory was working with, had no effect on these cancers. It works with carcinoma (connected with the skin) and sarcoma (related to connective tissues), groups that together constitute about 90% of all cancers.

“When we started,” says Raghavan, “We didn’t think it would become this big.”

He acknowledges the limitations of SCR7. “It is very good conceptually, but I have my doubts if it can go to clinical trials,” he says. “But, used in conjuction with chemotherapy, the molecule is most interesting.”

With speaking requests proliferating, Raghavan attracts the attention that comes with such molecular fame. But he remains conscious of his modest beginning in rural Kerala and a collegiate scientific education that involved the study of insects and did not include elite institutions. “I put in 100% effort all through,” he says, admitting to no interests others than work. “That was the only strength I had.” In the manner of small-town Indians who try harder than others of metropolitan privilege, Raghavan often works from 8.30am to midnight. “I am,” he confesses, “a bit crazy.”

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