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02
Mar 2015
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What’s Sam Weiss excited about?

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Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.

Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s final instalment, we interviewed Dr. Samuel Weiss is a Professor in the Cumming School of Medicine’s Departments of Cell Biology and Anatomy and Physiology and Pharmacology at the University of Calgary and Director of the Hotchkiss Brain Institute. In 1992, he discovered adult neural stem cells. He shared his thoughts on cancer stem cells (cells that can initiate tumours and that cause cancer to return) and advances being made in brain cancer research. 

There is a significant move afoot to apply the knowledge we have gained to understand the stem cell biology of brain tumours. We learned a lot about normal neural stem cells and then there was a big flurry after brain tumour stem cells were identified (in 2004) by Peter Dirks (University of Toronto) and others. Now we’re entering an era of greater sophistication in terms of understanding of the various cell types that make up a brain tumour, because there is still a need to fundamentally understand how a very small number of cells, even a single cell, can end up producing a massive tumour.

That’s part of where I’m going. My lab, working with many others, has also been involved in the development and testing of new compounds. And we have the first compound that we identified in the lab as being very powerful in terms of its ability to block brain tumour initiating cells in cell culture — as well as prolonging survival of xenografted animals – is moving into a clinical trial.

Regardless of the outcome of the trial, what’s exciting is that we published the paper in Clinical Cancer Research in October and simultaneously announced that AstraZeneca had agreed to test it in the clinic — and in Canada first. It will be led out of the Princess Margaret Cancer Centre by Dr. Warren Mason. We are able to collapse the timeframe from publishing our results to testing them in the clinic to less than a year. It shows that we are developing a strategy, based on the science and based on cancer stem cells, to help accelerate testing of new compounds for cancer.

We all know that many compounds need to be tested before a new one is likely to have a big impact, especially in a heterogeneous disease like brain cancer, but at the very least, the approach, which was championed initially by Dr. David Kaplan (The Hospital for Sick Children) through a Stem Cell Network grant and then by the Terry Fox Research Institute, has allowed us to begin bringing compounds to the clinic in a timely fashion.

That’s a predictor of some of the things to come. In fact, we have another (compound) that is very close. We’re working with a biotech company in the States and finalizing the last series of experiments.  We will be meeting with them in Chicago in June at the American Society of Clinical Oncology meetings and there may be a second compound in the clinic before the end of the year.

Five to 10 years ago, you would never have suggested that laboratory-based results would be moving from the lab to clinical testing in months rather than years.

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27
Feb 2015
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What is Denis-Claude Roy excited about?

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Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.

Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s instalment, we interviewed Dr. Denis-Claude Roy, Director of the Centre de recherche de l’Hôpital Maisonneuve-Rosemont and a full professor at the Université de Montréal. Dr. Roy is Chief Executive Officer of CellCAN Regenerative Medicine and Cell Therapy Network. Asked about what he sees developing in the field of stem cells and regenerative medicine he provided the following highlights of his work and others.

In our work with blood-based cancers like leukemia and lymphoma, we have developed a protocol for stem cell transplantation for people who don’t have a matched donor. We are able to do mismatched stem cell transplants, or what’s called haploidentical stem cell transplantation. This means that in place of being fully compatible (with the donor cells), a patient can be 50% compatible and still get a transplant.

Normally (such a transplant) would kill the patient, but we’ve developed a strategy to eliminate the cells that cause Graft Versus Host Disease (GVHD) and attack the patient. GVHD is probably the biggest problem associated with stem cell transplantation. Instead of having the patient develop GVHD or treating the patient with drugs to prevent it from occurring, we treat the cells in the lab and eliminate those that cause GVHD. So, we’re able to do stem cell transplants without immune suppression and the patient won’t have to take immuno-suppressor drugs for the rest of their lives.

We’re very excited about this. Our first study included 19 patients and we have had extremely good results. The patients had few infections and low relapse rates. A second study on another 23 patients, part of an international study, is currently led by our centre. To date, patients are again doing very well.

We’re also starting a clinical trial using a molecule called UM171 that was developed by Dr. Guy Sauvageau (Université de Montréal) to expand umbilical cord blood stem cells while maintaining their properties. Right now, donated umbilical cords have too few cells to treat adults. One donation provides enough cells to treat a child, but not enough for a normal size adult. Currently for an adult, we have to use two donations and that presents immune issues and is very expensive. We want to ramp up the number of stem cells from umbilical cord donations for those patients that have a match but not enough cells. We can grow the cells in the lab to have enough for the transplant.

This will allow us to select from our larger pool of umbilical cord blood donations and therefore improve the match, which should result in decreasing the number of complications associated with transplants and make it possible for more people to get them. This could also accelerate engraftment, shortening the time for the cells to engraft, which would decrease risk associated with the procedure.

The the use of stem cells in cardiac treatments is also starting to gather momentum. Dr. Duncan Stewart (University of Ottawa) has a trial (using genetically modified stems to repair heart damage) that is going very well. I am also working with Dr. Nicolas Noiseux (Université de Montréal) on activating stem cells before they are infused into the heart. He is studying a number of molecules to activate the cells before they are injected. The idea is to repair the hearts of patients who have poor cardiac function.

We will also be starting a trial using cells from the immune system to target leukemia. They are specific, acting like missiles, which will select and kill leukemia cells. Dr Claude Perreault (Université de Montréal) is developing a series of new targets. A new clinical trial is likely to start in the Fall.

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25
Feb 2015
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What is Connie Eaves excited about?

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Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.

Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s instalment, we interviewed Dr. Connie J. Eaves is a Distinguished Scientist at Vancouver’s Terry Fox Laboratory, which she co-founded. A Professor of Medical Genetics at the University of British Columbia, she is world-renowned for her pioneering research in basic blood stem cell biology, which led to new treatments for leukemia. She also isolated breast stem cells and is a leading thinker in the field of breast cancer. Here’s what she’s excited about in 2015.

I was a co-author of a Nature paper in December that was led by Drs. Samuel Aparcio and Sohrab Shah (University of British Columbia) and described the changing genomic composition of breast cancer xenografts — that is fragments of patients’ breast tumours growing in special transplanted mice that have no immune system.  In such mice, many patients’ tumours can grow as if they were still in the patient. You can thus track how the tumour evolves in relation to the original tumour.

This model has significant implications for developing new ways to treat cancer, because you can use the tumours created in the mice to determine which treatments work best and how that compares to the mutations that were present in cells that disappeared and those that may be unique to the cells that proved resistant. Groups all over the world are trying to use this approach, so we’re excited about that.

My lab has another paper in the works that has to do with making human breast tumours starting with normal human breast tissue. We have developed a protocol in which normally discarded breast tissue samples obtained from women undergoing cosmetic surgery are infected with a mutant cancer-causing gene and then produce tumours when transplanted into immunodeficient mice.

The reason this is extraordinarily exciting is because people have been trying to do this this for years with blood cells and it’s been difficult: you can count on one hand the number of different mutant genes (out of many tried) that can produce a leukemia when put into normal human blood-forming cells.  Indeed, this has been very discouraging in the leukemia field.

The idea is, if you could study the early events that cause leukemia or breast cancer, then you would be able to look into the first changes that occur and get a handle on those. You could then look for those changes in a patient’s samples and try to target them specifically.  Since they are the first events, they are likely going to be in every daughter tumour cell in that patient and hence better (more universal) targets.

One of the problems with treating many tumours is their genetic instability, which leads to the genesis of a tremendous diversity of subclones of cells carrying additional new mutations. Thus when you use a treatment strategy that can kill a dominant clone, there may be another 100 subclones that are not eliminated lurking at lower levels that then regrow.  That is why the idea of understanding how a tumour starts to develop from its earliest stages is so captivating.  Being able to do this with human breast tissue was unexpected and opens the door to all sorts of experiments. So we’re very excited about this new line of work.

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24
Feb 2015
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Cystic Fibrosis: the promise of stem cells

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Cystic fibrosis (CF) is the most common fatal genetic disease affecting Canadian children and young adults. One in every 3,600 children born in Canada has CF, which occurs when a child inherits two abnormal genes, one from each parent.…

Cystic fibrosis (CF) is the most common fatal genetic disease affecting Canadian children and young adults. One in every 3,600 children born in Canada has CF, which occurs when a child inherits two abnormal genes, one from each parent. Approximately, one in 25 Canadians carry an abnormal version of the gene responsible for CF. Carriers do not have CF, nor do they exhibit any of the symptoms of the disease.

Over 4,000 Canadians live with CF, which affects their lungs and digestive system, where the linings of these vital organs become clogged with thick mucus. This can lead to chest infections, persistent cough, wheezing and shortness of breath, bowel disturbances, weight loss or failure to gain weight, salty tasting sweat, infertility in men and decreased fertility in women.

The median age of survival for Canadians with CF was 50.9 years in 2013, over 25 years higher than it was in the early 1980s. However, the complications of ongoing infections and inflammation in the lungs, which eventually lead to loss of lung function, cause death in the majority of people with CF. Other frequent complications include difficulty in digesting fats and proteins and vitamin deficiencies due to loss of pancreatic enzymes.

While there is no cure for CF, remarkable progress in CF research has been made since 1989, when Canadian researchers at the Hospital for Sick Children (SickKids) discovered the gene responsible for CF — CFTR.

“Over the past decade there has been tremendous progress with regard to therapy discovery conducted using generic cells induced to possess a particular CF mutant protein,” Dr. Christine Bear, Senior Scientist and Co-Director of the CF Centre at SickKids, said in a press release. “While this approach led to the discovery of a drug called Kalydeco, we believe that a new discovery strategy is needed during the upcoming 10 years to find the next generation of therapies effective in treating all CF patients.”

Dr. Christine Bear

Dr. Christine Bear

Kalydeco is also a very expensive medication, one that is not covered by all provinces in Canada. Also, because of different CFTR mutations and the uniqueness of each patient, Kalydeco is only effective for a small population of those with CF.  “While this is a big step for CF, there is still much work to be done,” added Dr Bear.

Stem cells may provide some of the answers Dr. Bear and others are searching for. Cystic Fibrosis Canada, a national charitable not-for-profit corporation established in 1960 to find a cure or control for CF, recently funded Dr. Bear and her team at SickKids for their project, ‘Individualizing cystic fibrosis therapy.’

Dr. Bear’s lab is developing a resource of induced pluripotent stem cells or iPS cells from a cohort of patients with CF to represent the Canadian patient population. Patient-specific iPS cells will then be differentiated into lung epithelium and used to assess, explain and eventually predict individual specific responses to emerging therapies.

The approach, the first of its kind in Canada, will enable the future implementation of techniques to monitor functional correction of CFTR — techniques that are essential for pre-clinical trials comparing patient-specific responses to CF therapies and the identification of the best treatment for each CF patient.

While the work is in the early stages, it does offer hope that new approaches defeating CF can be made available some day soon.

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20
Feb 2015
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What’s Janet Rossant excited about?

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Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.

Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s premier instalment, we interviewed Dr. Janet Rossant, Chief of Research and a Senior Scientist at The Hospital for Sick Children in Toronto and immediate past president of the International Society for Stem Cell Research. She provided the following highlights.

When I look broadly, I’m seeing a lot of excitement about being able to use stem cells to model human disease. Here in Toronto, we’ve made induced pluripotent stem (iPS) cells from patients with cystic fibrosis, cardiac diseases and autism. We’re beginning to use those cells to differentiate them into different cell types to study the diseases in a Petri dish.  All of that is moving forward. We’re going to see more and more of that.

I think, though, that the area to watch is a little bit more than just taking iPS cells and growing them in a Petri dish in a flat culture but instead growing cells and making little organs or “organoids.” We’ve seen over the last year people making little organoids in a dish: gut organoids, stomach organoids. I’m expecting to see papers on lung organoids.  This means we will be able to study diseases in new ways and use these organoids for doing drug screening.

We’re also seeing the first trials (by Viacyte, a California-based cell-therapy company) going forward with pancreatic progenitor cells for treating type 1 diabetes. We probably won’t get full results, because these are all Phase 1 trials, but we’re going to get some idea of the survival and effectiveness in a relatively short period of time.  Canada will be one of the sites for that trial; Dr. James Shapiro (University of Alberta) is involved.

There have been good Canadian contributions to that. The Viacyte trial is done with pancreatic progenitors that will mature and make the right insulin producing cells. Other people feel you’d be better off starting with the insulin-producing cells and using those directly.  A recent paper from Dr. Tim Kieffer (University of British Columbia) shows really good advances in generating functional beta cells. It gives you a lot of hope that this kind of trial, which is an early one, will be rapidly replaced by better trials and better cells. Dr. Cristina Nostro (University of Toronto) is also moving very fast at getting better and better pancreatic islet cells.

The technology that everybody is jumping on is genome editing.  Now you can think not only about fixing people with stem cells, but you can think about fixing the genetic defects in people’s stem cells before you put them back. Certainly here at SickKids there are a number of people thinking in the very short-term mode about how they might translate that into gene therapy approaches to genetic diseases.

The expanded use of cell-based therapies — whether they are stem cells or other cells — is also having an impact. If we think about immunotherapy for cancer, we’re using either molecules or modified T-cells.  We’re seeing cell-based therapies of all sorts coming forward.

We’re seeing expanded use of bone marrow transplantation for a wider range of autoimmune diseases.The trials that Dr. Harry Atkins (University of Ottawa) and others are doing on MS — those kinds of approaches are going to get more and more refined as we go forward.

Cardiac care is another area where we’re seeing clinical trials with many kinds of cells and molecules to treat heart disease. I think we’re going to see small incremental advances. A big advance has to come if we can actually fix the heart muscle.  I know Dr. Gordon Keller (University of Toronto) and his colleagues are pushing very hard in that direction to try to move from cells in culture to bioengineered matrices of cells that you could think about using to replace damaged parts of the heart.  Also, Dr. Michael Fehlings (University of Toronto) is very active in looking at a number of sources of cells that might be able to remyelenate axons in spinal cord repair.

These are all areas to watch in the future — the whole field is moving rapidly forward.

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24
Oct 2014
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Tricky science made simple, part IV

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Back in June, we announced the release of another StemCellShorts video: “What is a cancer stem cell?” narrated by Dr.

Back in June, we announced the release of another StemCellShorts video: “What is a cancer stem cell?” narrated by Dr. John Dick. Stem Cell Shorts is a series of about-a-minute-long informative videos produced by Ben Paylor, a PhD candidate at the University of British Columbia, and Dr. Mike Long, a post-doctoral fellow at the University of Toronto.

Dr. Dick, senior scientist at Princess Margaret Cancer Centre and the McEwen Centre for Regenerative Medicine, was the first to isolate cancer stem cells — in leukemia in 1994 and in colon cancer in 2007. Recently, he and his team found a way to disarm a gene called BMI-1 that regulates colorectal cancer stem cells.

The new video is co-sponsored by the Canadian Stem Cell Foundation and the Stem Cell Network.

All the videos — including “What is a stem cell?” narrated by Dr. Jim Till, “What are embryonic stem cells?” voiced by Dr. Janet Rossant, “What are induced pluripotent stem cells?” narrated by Dr. Mick Bhatia, and “What is a cancer stem cell?” — are now available on the Foundation’s You Tube channel. Click here to view them.

Another instalment, “What is a retinal stem cell?” narrated by Dr. Derek van der Kooy, will be released soon.

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16
Sep 2014
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Margaret Atwood: the importance of the national cord blood bank

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In Monday’s the Globe and Mail, Margaret Atwood shared her thoughts about the importance of the national public cord blood bank in Canada.…

In Monday’s the Globe and Mail, Margaret Atwood shared her thoughts about the importance of the national public cord blood bank in Canada.

With Canada being an ethnically diverse country, many patients affected by leukemia, lymphoma and other diseases, are unable to find a match among donors to treat their diseases. Umbilical cord blood is rich in stem cells that can be transplanted to patients unable to find a donor.

As featured in several articles here, prior to September 2013, when the first cold blood collection facility opened in Ottawa, Canada was the only G8 country without a national collection program. Private collection banks existed already, but they were not accessible to everyone due to the costs.

Thanks to the initiative of Canadian Blood Services (CBS), there are four public cord blood collection facilities now: in Ottawa, Brampton, Edmonton and Vancouver.

CBS has been leading the $12.5-million fundraising campaign to expand the collection bank and has yet to raise the last quarter of the amount.

“Some may feel that private enterprise can take care of this need. That’s fine for those who can afford it, but what about those who can’t?” writes Ms. Atwood. “Public health services should allow care for all, not just the privileged. And so it should be with cord blood banks. I’m confident that, once they realize the need, Canadians will pitch in and get the bank completed.”

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26
Jun 2014
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stemcelltourism stem cellshorts

Tricky science made simple, Part III

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Back in January, we blogged about the StemCellShorts videos, a series of about-a-minute-long informative videos produced by Ben Paylor, a PhD candidate at the University of British Columbia, and Dr.

Back in January, we blogged about the StemCellShorts videos, a series of about-a-minute-long informative videos produced by Ben Paylor, a PhD candidate at the University of British Columbia, and Dr. Mike Long, a post-doctoral fellow at the University of Toronto.

A brand new video in the excellent series is now available. Narrated by Prof. Timothy Caulfield, a member of our Foundation’s Science Leadership Council, it answers the question “What is stem cell tourism?”

Stem cell tourism is one of the biggest challenges for stem cell community. While great advances have been made in bone marrow stem cell transplants and stem-cell driven skin grafts, most stem cell treatments are still in the research phase. However, the number of clinics offering unproven and unsafe therapies worldwide is growing. (Click here to read our blog entries about stem cell tourism.)

All the videos — including “What is a stem cell?” narrated by Dr. Jim Till, “What are embryonic stem cells?” voiced by Dr. Janet Rossant, and “What are induced pluripotent stem cells?” narrated by Dr. Mick Bathia —  are now available on the Foundation’s You Tube channel. Click here to view them.

Another instalment, covering the topic “What is a cancer stem cell?” and narrated by Dr. John Dick, will be launched later this year. This second set of videos is co-sponsored by the Canadian Stem Cell Foundation and the Stem Cell Network.

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12
May 2014
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CellCAN aims to make regenerative medicine a reality

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CellCAN, a new national Regenerative Medicine and Cell Therapy Network officially began operations today in Montreal.

Based at Maisonneuve-Rosemont Hospital, the new Network will support clinical development of regenerative medicine.…

CellCAN, a new national Regenerative Medicine and Cell Therapy Network officially began operations today in Montreal.

Based at Maisonneuve-Rosemont Hospital, the new Network will support clinical development of regenerative medicine.

“Regenerative cell therapies offer almost unlimited possibilities that will transform the very nature of medicine and will have a significant impact on our health systems,” said Dr. Denis Claude Roy, a member of the Joint Strategy Working Group for the Canadian Stem Cell Strategy and Director of CellCAN, in a press release.

With Canada ranking among the top countries in the world in stem cell research, the goal of CellCAN is “to provide the essential bridge between research and clinical and commercial applications, helping regenerative medicine and cell therapy to successfully meet expectations.”

CellCAN will bring together the main stem cell therapy centres and different stakeholders involved in stem cell research — scientists, governments, researchers, clinicians, funders, industry, charities, patient representatives and the public.

“Specifically, CellCAN will promote exchanges, cooperation, partnership, development and innovation in regenerative medicine and cell therapy,” said Dr. Roy.

Over the next four years, CellCAN will receive $1.6 million through the Networks of Centres of Excellence Program, which provides national funding on behalf of the Natural Sciences and Engineering Research Council, the Canadian Institutes of Health Research, the Social Sciences and Humanities Research Council, along with Industry Canada and Health Canada.

The Canadian Stem Cell Foundation will closely support and partner with CellCAN in its efforts to facilitate and increase access to stem cell therapies for heart diseases, diabetes, cancer and other diseases that affect Canadians.

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23
Apr 2014
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pioneers of medicine without a noble prize

Till & McCulloch in brilliant company with other non-Nobel laureates

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Since the first award was handed out in 1901, the Nobel Prize has become globally regarded as the most prestigious recognition of intellectual achievement.…

Since the first award was handed out in 1901, the Nobel Prize has become globally regarded as the most prestigious recognition of intellectual achievement. What’s amazing, however, is how often the Nobel committee has glaringly overlooked researchers behind outstanding discoveries that changed the practice of medicine.

Pioneers of Medicine Without a Nobel Prize, just published by the United Kingdom’s Imperial College Press, tells the stories of giants in medical science who somehow never won the Nobel Prize for Physiology or Medicine.

Among the 15 featured scientists are:
• heart transplant pioneers Drs. Christiaan Barnard and Norman Shumway;
Dr. Richard Doll, who made the link between smoking and lung cancer;
Drs. Inge Edler and Carl Helmuth Hertz, who developed ultrasound technology; and
Dr. Akira Endo, the discoverer of statins.

One chapter of the book, written by the Foundation’s Joe Sornberger, is dedicated to Drs. James Till and Ernest McCulloch, the “fathers of stem cell research.” The two Canadians proved the existence of stem cells in the early 1960s at the Ontario Cancer Institute, while working on the sensitivity of bone marrow cells to radiation in mice.

Dr. Till still remembers the “Eureka” moment, when his partner Dr. McCulloch showed him a piece of graph paper on which he had illustrated that the more marrow cells were transplanted, the more bumps on the spleens appeared. After two years of work, Till and McCulloch showed that the bumps were formed by individual transplanted cells, which had proliferated and given rise to blood-forming cells.

That Dr. Till & McCulloch were somehow overlooked for the Nobel Prize in Physiology or Medicine is inexplicable to many. As a previous post explained, there was some thought that Dr. Till would be handed his long overdue Nobel Laureate’s wreath two years ago alongside Japan’s Dr. Shinya Yamanaka, who discovered induced pluripotent stem cells. (Dr. McCulloch died in 2011, making him ineligible). Canada has not brought home a Nobel in this category in over 90 years — not since Dr. Frederick Banting, discoverer of insulin, won in 1923.

Then again, when amazing giants such as Drs. Willem Kolff and Belding Scribner, who developed the Renal Haemodialysis, are left off the Nobel list, Drs. Till & McCulloch are in brilliant company.

For those who would like the full story of this amazing Canadian success story, you can purchase a copy of Mr. Sornberger’s book, Dreams & Due Diligence, published by University of Toronto Press, here.

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