On Sept. 17, the Lasker Foundation announced that the 2005 Albert Lasker Award for Basic Medical Research was being shared by Ernest McCulloch and James Till, both of the University of Toronto Ontario Cancer Institute in Canada, for "ingenious experiments that first identified a stem cell - the blood-forming stem cell - which set the stage for all current research on adult and embryonic stem cells."
These days, the discovery of a new stem cell type is likely to be the result of much concentrated effort. The same can be said about the blood-forming stem cell, which McCulloch and Till first observed in 1961; the catch, though, is that the effort in that case was directed at something else altogether.
"We weren't looking for it," James Till told BioWorld Today. "We were trying to measure the radiation sensitivity of normal mouse marrow cells." Toward that aim, the scientists were doing quantitative bone marrow transplants of irradiated cells, to test whether and how irradiating cells affected their ability to divide.
"It so happened that [McCulloch] came in on a Sunday to do autopsies on these mice, and he noticed these lumps in their spleen," Till said. In the mouse, unlike in humans, the spleen is a blood-forming organ. When McCulloch graphed his data, he found that the more marrow cells he transplanted, the more lumps he saw. "So when he showed me the data on Monday, we both got excited. Because we both interpreted them the same way.
"He could have easily overlooked them," Till said. "It wasn't like they stood out like a sore thumb, they were just noticeable." In fact, Till and McCulloch were not the first to notice the lumps. "They had been noticed before and described as local areas of regeneration," Till said. But that implied that there might be several different cell types involved, and Till's graduate student, Andrew Becker, showed that the lumps were derived from a single precursor cell that could give rise to different blood cell types, including both red and white blood cells.
Whether adult blood stem cells existed (and if so, whether there were different stem cells for different blood cell types) was a controversial topic at the time. So the fact that their data provided conclusive evidence for a single multipotent blood stem cell "got hematologists a little excited," Till said, with modesty.
Till described the discovery as "part luck, part good judgment." The discovery might have been part luck, but it spawned a stem cell collaboration with McCulloch that lasted more than a decade. After that, McCulloch went on to what Till described as "more practical work in leukemia."
Asking The Right Questions
Like McCulloch, Till found himself interested in doing more applied work; however, because he is not an MD, he was unable to work with patients directly. Instead, Till set out to improve clinical trials so that they were able to more rigorously measure a rather murky concept at the time: quality of life in seriously ill patients, specifically cancer patients.
Many cancer clinical trials, then and now, focus on increased survival as their primary goal. However, Till pointed out that "improving quality of life can be very worthwhile even if survival is not prolonged. So I set out to measure that in a reasonably rigorous fashion."
The problem is that there is no standard tool for measuring pain. "There is no gadget," Till said. "You have to ask questions. And you have to ask the right questions because if you just ask a cancer patient, Are you in pain?' of course the answer is always yes."
Till dedicated himself to finding the questions that would allow clinicians to understand patients' pain in more useful detail, and find effective treatments for it. "I worked on that for quite a while with a very talented group of people," he continued, "and it is something that has made a significant difference to cancer patients."
We've Changed The Culture'
Nancy Brinker, founder of the Susan G. Komen Foundation for breast cancer research and recipient of the 2005 Mary Woodard Lasker Award for Public Service, is another person who understands the importance of quality-of-life issues for cancer patients. The Susan G. Komen Foundation was born out of a promise Brinker made to her dying sister: She would make sure other women would not have to suffer as her sister had suffered.
Like Till, through her foundation Brinker takes what she terms a multifaceted approach to a multifaceted disease. The Komen foundation supports both "soft" quality-of-life approaches and, through its basic and clinical research grants, hard-nosed research. The Lasker Foundation recognized that dual approach; in the words of the jury, Brinker was honored "for creating one of the world's great foundations devoted to curing breast cancer and dramatically increasing public awareness about this devastating disease."
In a commentary on her award, to be published in the October 2005 issue of Nature Medicine, Brinker writes about both aspects of fighting breast cancer. She describes the importance of research efforts to eradicate breast cancer, noting that Komen foundation grants have, to date, funded research on such major topics as key cancer genes, telomerase, and angiogenesis inhibitors.
But Brinker also writes about the importance of addressing quality-of-life issues for breast cancer patients, noting: "We've changed the culture. When [my sister] Suzy was diagnosed, breast cancer was still a silent epidemic. People called it the Big C,' as if you might catch cancer just by saying the word." Today, she said, instead of breast cancer being almost shameful, patients, survivors and their families wear "pink ribbons as a badge of courage."