The Nobel Foundation doesn't allow posthumous awards, so when news of Ralph Steinman's death reached Stockholm a few hours later, a minor intrigue ensued over whether the committee would have to rescind the prize. It would not, in fact; but while newspapers stressed the medal mishap ("Nobel jury left red-faced by death of laureate"), they spent less time on the strange story behind the gaffe. That Steinman's eligibility was even in question, that he'd been dead for just three days instead of, say, three years, was itself a minor miracle.
In the spring of 2007, Steinman, a 64-year-old senior physician and research immunologist at Rockefeller University in New York, had come home from a ski trip with a bad case of diarrhea, and a few days later he showed up for work with yellow eyes and yellow skin — symptoms of a cancerous mass the size of a kiwi that was growing on the head of his pancreas. Soon he learned that the disease had made its way into nearby lymph nodes. Among patients with his condition, 80 percent are dead within the first year; another 90 percent die the year after that. When he told his children about the tumor over Skype, he said, "Don't Google it."
But for a man who had spent his life in the laboratory, who brought copies of The New England Journal of Medicine on hiking trips to Vermont and always made sure that family vacations overlapped with scientific symposia, there was only one way to react to such an awful diagnosis — as a scientist. The outlook for pancreatic cancer is so poor, and the established treatments so useless, that any patient who has the disease might as well shoot the moon with new, untested therapies. For Steinman, the prognosis offered the opportunity to run one last experiment.
In the long struggle that was to come, Steinman would try anything and everything that might extend his life, but he placed his greatest hope in a field he helped create, one based on discoveries for which he would earn his Nobel Prize. He hoped to reprogram his immune cells to defeat his cancer — to concoct a set of treatments from his body's own ingredients, which could take over from his chemotherapy and form a customized, dynamic treatment for his disease. These would be as far from off-the-shelf as medicines can get: vaccines designed for the tumor in his gut, made from the products of his plasma, that could only ever work for him.
Steinman would be the only patient in this makeshift trial, but the personalized approach for which he would serve as both visionary and guinea pig has implications for the rest of us. It is known as cancer immunotherapy, and its offshoots have just now begun to make their way into the clinic, and treatments have been approved for tumors of the skin and of the prostate. For his last experiment, conducted with no control group, Steinman would try to make his life into a useful anecdote — a test of how the treatments he assembled might be put to work. "Once he got diagnosed with cancer, he really started talking about changing the paradigm of cancer treatment," his daughter Alexis says. "That's all he knew how to do. He knew how to be a scientist."
First, Steinman needed to see his tumor. Not an M.R.I. or CT scan, but the material itself. The trouble was that most people with his cancer never have surgery. If there's cause to think the tumor has spread — and there usually is — it may not be worth the risk of having it removed, along with the bile duct, the gallbladder, large portions of the stomach and the duodenum. Luckily for Steinman, early scans showed that his tumor was a candidate for resection. On the morning of April 3, 2007, less than two weeks after his diagnosis, he went in for the four-hour procedure at Memorial Sloan-Kettering Cancer Center, just across the avenue from his office at Rockefeller University.
After two hours on the operating table, his surgeon, Dan Coit, lifted the tumor from his abdomen. It was about two and a half inches long. Coit stitched a short thread across its top and a longer one on the side — an embroidered code to help the pathologists get oriented — and sent the specimen upstairs, wrapped in a towel and nestled in a tray of ice.
Claudia and Alexis were waiting in the lobby, along with Sarah Schlesinger, a longtime friend and member of Steinman's lab, who is also a board-certified pathologist. It would be her job to manage the disbursement of the tumor to Steinman's colleagues around the world, so its every nuance could be tested and its fragments incorporated into the drugs that would compose his treatment. When she arrived at the lab upstairs and held the tumor, it was still so warm that she could feel the heat through her latex gloves.
She chopped and sliced the tumor into samples, based on a list that Steinman helped draw up beforehand. A few grams would be placed in screw-top vials filled with a preservative for their RNA. Steinman's administrative assistant would take another piece to Boston on an afternoon train, and some would go to a former student, Kang Liu, so she could sew confetti-sized squares of the tumor into living mice. If there was any left, they would send it to a researcher in Baltimore named Elizabeth Jaffee, who had mastered the art of culturing pancreatic cancer in a dish.
The mass was big enough that Schlesinger could get through all the items on the list. In the days, weeks and months that followed, Steinman's cancer was sent to labs in Boston and Baltimore, Toronto and Tübingen, Germany, Dallas and Durham, N.C. With help from friends and former students, he would squeeze every bit of data from his cancer that he could.
Steinman's last experiment would be, in many ways, the culmination of a new trend in cancer research: designing custom treatments for each patient. When he got sick, Steinman knew that the five-year survival rate for his kind of tumor was, at most, 1 in 10, even at Sloan-Kettering, one of the best oncology centers in the world. Typically, patients live six months. But he also knew that his chances might not be as bad as they looked. The means and medians of his disease were drawn from populations and so did not reflect the fact that every tumor is unique. Even tumors that look the same — cancers starting from a common organ, or a common kind of cell — may behave in different ways: some shrink and some expand; some succumb to chemotherapy. Now doctors can scan each tumor for clues about its DNA and use those clues to determine its strengths and weaknesses. Steinman could have his case described right down to the letters of its genome, in hopes of figuring out which therapies might work best for him.
This "personalized" approach to treating cancer, which subdivides the classic types according to distortions in their genes, has been growing at a rapid pace. In the past few years, laboratories financed by the government have set out to build a comprehensive atlas of the cancer genome — to collect 500 tumors from each of 25 kinds of the disease and then to analyze their DNA and RNA at a cost of more than $100 million a year. The advent of inexpensive genome sequencing has produced a gold rush in the commercial sector, too, with the promise that anyone's tumor can be sliced and processed and analyzed, until its genetic fingerprint is decoded.
