For over 100 years the Nobel Foundation has recognized outstanding individuals for contributions to their respective fields. The rules, however, stipulate that prizes cannot be awarded posthumously. But in October 2011, an exception was made for an exceptional individual: Dr. Ralph Steinman was awarded the joint Nobel Prize in Physiology or Medicine three days after he died of pancreatic cancer. At the time of the announcement, the news of his death had not yet reached the Nobel committee. So they decided that his wife and children would be able to accept his prize on his behalf. But the story doesn’t end there; Steinman had been battling pancreatic cancer for over 4 years and was treating himself using exactly what the Nobel committee was awarding him for – his 40-year career in researching a previously unknown immune system component he called ‘dendritic cells’.
Steinman, a Montreal native and McGill alumnus, was jointly credited with the discovery of dendritic cells in 1973 and spent the rest of his career researching how these special cells might be used to fight difficult diseases like HIV and cancer. Dendritic cells, so named because of their tree-like shape, mediate communication between harmful antigens (molecules which stimulate the immune system) and lymphatic T-cells (white blood cells which activate molecules to fight off these antigens). Steinman showed that these dendritic cells are able to capture invaders, like the common cold, and signal specific lymphocytes to in turn to destroy them.
However, cancer is not like the common cold. Tumor antigens released from cancer cells evade the immune system by either eliminating or hiding from our defensive T-cells. A common way they do this is by activating checkpoint pathways, which tell the body to “turn off” active white blood cells, preventing them from destroying the invading cancer cells. Our greatest weapon against them, chemotherapy, works like a large bomb: it blasts through the entire body directly destroying cancerous cells, but is not very selective and many benevolent cells are destroyed as well.
But thanks to research like Steinman’s, cancer immunotherapy treatments can harness the selective abilities of our natural immune system, and fight back with extreme precision. Immunotherapy vaccinations would manipulate dendritic cells to capture tumor antigens and present them to cancer-specific lymphocytes. Thus improving the ability of the body to find and destroy tricky cancer cells with much better accuracy than chemotherapy. However, unlike chemotherapy which works relatively quickly, immunotherapy builds the body’s immune system over time, time that patients often do not have especially if the treatment should fail. Furthermore, it appears that not all patients respond in the same way. It has been estimated that currently about 10% of cancer patients can benefit from immunotherapy treatments. But this number is expected to grow as more research unveils how these mechanisms work.
Thus in 2007 when Steinman received his cancer diagnosis with an estimated 6 months to live, he set to work right away, sending samples of his golf-ball sized tumor across the globe to several colleagues in immunotherapy labs. Even at the time Steinman knew he was maybe a decade or two too early for this kind of treatment; we now know there are dozens of kinds of dendritic cells which target different antigens, whereas back then they were essentially taking shots in the dark. Even so he put his faith behind his research and in his last experiment he became his own patient. In total he was treated with 8 different FDA-approved cancer vaccines in addition to several rounds of chemotherapy. He managed to prolong his life three and a half years longer than they had predicted and maintained good physical health for most of it. But without another patient to compare to, and with the hasty time taken in between treatments, it’s very difficult to tell what exactly was keeping Ralph Steinman alive. Eventually the cancer stopped responding to the vaccines he was on and the disease spread throughout his whole body. He passed away on September 30, 2011, just three days shy of knowing that he had been awarded the most prestigious mark of scientific achievement. Now he stands as the only deceased recipient of a Nobel prize who actually became a patient of his own research. I’d say that’s well worth the exception.