Nobel Winner Ralph Steinman's Quest to Cure Cancer - Including His Own

Three scientists shared the Nobel Prize in medicine Monday for breakthroughs into how the immune system works, just days after the death of one of the researchers, who had adapted his prize-winning insight to treat his own cancer.

Bruce Beutler of the U.S. and Luxembourg-born Jules Hoffmann shared half the prize of 10 million Swedish kronor ($1.46 million). The other half was awarded to Canadian-born Ralph Steinman of Rockefeller University in New York, who died of pancreatic cancer Friday at age 68, three days before the winners of the Nobel Prize in Medicine or Physiology were announced. He died without knowing he was to be honored. The Nobel committee's rules say the prizes can't be awarded posthumously. But the committee decided the decision would stand because Dr. Steinman has been selected in good faith, on the assumption he was alive

His work had been part of an unorthodox experiment to save his life. When Ralph Steinman learned he had pancreatic cancer, the dogged immunologist put his life's work to the test. He launched a life-and-death experiment in the most personal of personalized medicine. By unlucky coincidence, he had been diagnosed with a disease that might benefit from the therapies he had spent his life researching.

Usually, medical research proceeds at a glacial, thorough pace: cell studies lead to studies in small animals which lead to studies in larger animals, which eventually lead to small, highly-selective clinical trials in humans. But Steinman didn't have that kind of time. He did, however, have access to world class facilities, cutting-edge technology, and some of the world's most brilliant medical minds, thanks to his position as a researcher at Rockefeller University.

So Steinman decided to make his own body the ultimate experiment.  He had removed a piece of the tumour that would eventually kill him, and trained his immune cells to track down any hint of the tumour that might have escaped the surgery, like putting hounds on a scent. On Friday, four-and-a-half years after he was diagnosed with a disease that kills the vast majority of its victims in less than one, that experiment came to an end.  Steinman died at the end of a week in which he continued his work in the lab. It was a testament to the undying optimism of the scientific enterprise, to the unrelenting man, and to the limits of both. His experiment was an open secret on campus, registered with the hospital and aided by a long-time friend and staff physician. The sense of hope was palpable, bound up in respect and caring for the man. Could the painstakingly incremental research that seemed to have so much potential on lab animals  grant a reprieve from certain death?

Pancreatic cancer is often known as the "silent killer" because it doesn't often produce truly scary symptoms until it has spread beyond repair. My dad died of pancreatic cancer nearly ten years ago. At that time there was no hope once the cancer was established. I had hopes for this research; it had a lot of promise.
In 1973, along with his mentor, Zanvil Cohn, Steinman published the discovery of a new class of cell in the immune system - the dendritic cell. Like many new discoveries, his faced a deeply sceptical reception. He fought for a decade before immunologists began to broadly recognize the central importance of those cells to their field. In the past 20 years, the study of dendritic cells has spread to hundreds of labs all over the world. Researchers are exploring how they might be harnessed to fight cancer, HIV and transplant rejection, among other major medical problems.

Dendritic cells are the "sentinel cells" of the immune system. Named after the Greek word for tree, they develop distinctive probing branches when activated, sweeping their environment in search of unwelcome things - like bacteria, viruses, tumours. When dendritic cells encounter something they don't like, they take a physical marker of the invader, called an antigen, and present it to B and T cells, the defenders of the body' s immune system. Those cells then adapt weapons to identify and destroy the interlopers. Steinman bet that if he could train his dendritic cells to recognize and tag his cancer, they would be able to convince the T and B cells to do the rest.

There was no good reason to expect that Steinman could fashion a cure for one of the world's most vicious cancers in time to save his own life. But it was easy to think it was at least possible. The made-for-Hollywood story of the renegade scientist who fights the establishment to prove his discovery, and then uses it to cure himself, was powerful enough to compel hope. Unfortunately, the dendritic cell-based treatments didn't work - at least not well enough.

In other words, while there were significant side effects, the therapy seemed to enable him to work much longer than he otherwise would have. Month after month, he remained at the University, continuing his work. He survived much longer than expected, and continued his research until the end.
The research he pioneered continues - and the scientists who continue his work have an extraordinary example to follow