The Promise and Glory of Stem Cells

How two Canadian scientists stumbled upon a landmark discovery.

Canada plays in the major league of biomedical research. Our lead funding agency, the Canadian Institutes of Health Research, spends just over a billion dollars annually, supporting the projects of upwards of 9,000 researchers across the country. Various other federal bodies, provincial research institutes, private foundations, hospitals, universities and other organizations spend perhaps another billion. The major medical school and hospital complexes in Toronto, Montreal, Vancouver and Edmonton are internationally recognized research centres. In fact, the border hardly matters as researchers and their ideas circulate freely in not only a continental but a global matrix. Everyone’s goal is discovery, and it surely is more important that breakthroughs happen as quickly as possible rather than in any given lab.

But, of course, it is useful to get recognition. We want to know that the money being spent in Canada is paying off, that our labs and our people really are doing well, that world-class scientists are being trained in Canada, kept in Canada and attracted to Canada. We want our teams to win the health research equivalents of Stanley Cups or most–valuable-player awards.

So it is a matter of frustration in the Canadian research universe that all our domestic efforts in the last hundred years have generated only one Nobel Prize in physiology or medicine, awarded to Frederick Banting and J.J.R. Macleod in 1923 for the discovery of insulin. (We do have Nobel laureates in other areas of science, and we have bred laureates in medicine, such as one of this year’s winners, Ralph Steinman, who have made their contributions while working in the United States.) Why has the Nobel Committee not recognized other “Canadian” discoveries? Are we somehow being discriminated against in awards competitions? Do we not toot our horns loudly enough? Or is it just bad luck?

Such questions are now being asked, particularly in light of the failure of the Nobel system to recognize the Canadians widely called the discoverers of stem cells, James Till and Ernest (“Bun”) McCulloch. In February 1961 they published “A Direct Measurement of the Radiation Sensitivity of Normal Mouse Bone Marrow Cells,” a paper that is widely considered to have been the first confirmation of a very old hypothesis about the existence of the primary building blocks of cells. Particularly in this last decade of excitement about the role of stem cells in cellular biology and the possibility of great breakthroughs in regenerative medicine, expectations of Nobel glory for Till and McCulloch mounted each autumn until the awards were announced. With McCulloch’s death in January 2011 the team can no longer hope for Nobel-induced immortality. The prizes are not given posthumously.

Veteran journalist Joe Sornberger introduces most of the issues involving this matter in his short, once-over-lightly study, Dreams and Due Diligence: Till and McCulloch’s Stem Cell Discovery and Legacy. The book has the merit of showing why the Canadian scientists may have been overlooked even as he argues that they should not have been, and that they should be much more famous in our country today.

We learn, for example, that when they made their discovery half a century ago Till and McCulloch were not looking for stem cells, only found a limited, hematopoietic (blood-forming) class of stem cells, never called them stem cells, published their first article in an obscure journal and never investigated the significance of their discovery of “colony-forming units” in areas beyond hematology. According to Sornberger, their paper went largely unnoticed. Although there were follow-up publications with other collaborators, the Till-McCulloch scientific partnership, something of a Mutt-and-Jeff relationship between a gentle farmer’s son and an outspoken upper-class medical wonk, was not otherwise particularly creative or long-lasting.

Stem cells in general only really became a hot issue after the isolation of embryonic, universal stem cells by James Thomson at the University of Wisconsin in 1998. That was the motherlode; decades earlier the Canadians had stumbled on a venous outcropping. Without quite understanding how insulin had emerged and been honoured in the early 1920s, Sornberger laments that Till and McCulloch are not as famous in Canada as Banting and Best. In fact, Banting and Best had done little more than fumble around incompetently with pancreatic extracts. Without the help of Macleod and the great biochemist J.B. Collip, their work would have led nowhere and they would have disappeared from history. The same would have happened to Alexander Fleming if Howard Florey had not taken up his work on penicillin. On their own, McCulloch and Till were not able to bring home the promise and glory of stem cells.

On the other hand, Sornberger describes how important their work was in the understanding of blood, in the development of bone marrow transplants and in creating a local stem cell–oriented research effort that has made the field somewhat of a Canadian specialty. “If hockey is Canada’s game,” writes former CIHR head Alan Bernstein in the book’s foreword, “stem cell research is Canada’s science. The discovery of neural stem cells, mesenchymal stem cells, and cancer stem cells, as well as important advances in human embryonic stem cell research, are all Canadian discoveries.” Jim Till and Bun McCulloch, an unlikely duo whose contrasting personalities nicely emerge from Dreams and Due Diligence, will always be honoured as the progenitors of this achievement. And, in fact, they did receive major international prizes, both Gairdner and Lasker awards, the next best to Nobels.

On the matter of horn tooting, it is surely a sign of new times how often we are beginning to see advertisements from Canadian universities, hospitals and research institutes celebrating the achievements of their personnel. When I ask if there are not better ways for public institutions to spend their money, my medical friends tell me that it is important for us to do this to keep up with the Americans, who deliberately and systematically trumpet their work and consequently are well rewarded with applause and honours.

I am not so sure we should jump on this bandwagon. First, the noisy advertising may not be as effective as we think. When I visited the Nobel archive to study the award for insulin (it is open to researchers on a 50-year rule), I noticed that lobbying campaigns, which existed even 90 years ago, seemed to have little effect on the committee’s deliberations.

Second, such campaigns may become counterproductive if, as is very possible, they generate a sense that nationalist enthusiasm outweighs sound scientific judgement. This is a fine line, that Sornberger himself zigzags erratically and puzzlingly across. I simply cannot understand the juxtaposition of the author’s very sensible warnings against unproven stem cell therapies with his enthusiasm for the particular work of two Ottawa doctors offering a heroic stem cell treatment for multiple sclerosis. In this respect his book is not even good journalism, let alone the authoritative, judicious study that might actually influence history’s weighing of the work of Canadian scientists.

When will a Canadian writer receive the Nobel Prize in literature? Somehow I do not think that plastering the world with taxpayer-subsidized ads on behalf of Margaret Atwood or Alice Munro would do the trick. Intelligent publicizing can be useful, but when we overhype our writers, as with, say, the Giller Prize, we undermine the credibility of the whole enterprise. In literature, the continued, quiet cultivation of serious reading and criticism is surely the sine qua non. Do your business as well as it can be done, foster a climate that values and nurtures good work and the prizes are bound to flow eventually.

Just so with science. Despite grumbles, weak media coverage (the media are suckers for hype) and perennial funding issues, our national culture of support for science and research seems fairly healthy. We have played in the world league for quite some time now, and in our quiet Canadian way we generally do well. There will be more Nobels.