Dr. Ernest McCulloch
(This post is one of several addressing a single subject today in a blog carnival to mark the 10th anniversary of the discovery of induced pluripotent stem cells.…
(This post is one of several addressing a single subject today in a blog carnival to mark the 10th anniversary of the discovery of induced pluripotent stem cells. Please click here to read what other bloggers have to say.)
As summer holidays wind down, most parents are now too familiar with the following question: Are we there yet?
Any family trip to a campground, cottage or Nana’s house in Northport starts off with excitement for all concerned, what with getting up early, packing the car and hitting the road. For kids, though, it’s magical. Then, after about an hour of travelling, regardless what onboard entertainment you’ve arranged, boredom sets in. Two hours into the trip, they’re sure you’re never going to get them there.
Waiting for stem cell discoveries to turn into actual treatments is a lot like that, except that instead of hours, it’s decades. Instead of frustration, the feeling is desperation.
Consider the remarkable discovery, by Japan’s Dr. Shinya Yamanaka, that adult cells extracted from skin can be reprogrammed to an embryonic stem-cell-like state to reproduce any cell required for transplant or to repair organs and tissue. We first heard about these induced pluripotent stem cells (iPS cells) on August 25, 2006. A decade later, we’re still waiting for the Nobel Prize-winning work to turn into treatments.
People, especially those suffering from life-threatening diseases, want to know why we’re still waiting. Unlike bored children, they have far more riding on the answer to the Are we there yet? question. For them, it’s life and death.
At the Canadian Stem Cell Foundation hardly a day goes by that someone doesn’t contact us seeking a stem cell treatment for themselves or a loved one. Today, it was a 48-year-old Toronto man whose doctor had told him his ALS will kill him. At least we could point him in the direction of Dr. Eva Feldman at the University of Michigan, who is trying to get a Phase 2 clinical trial going on a stem cell treatment for ALS.
In all areas of medical research, the wheel turns slowly. It can take decades of lab work and clinical trials and hundreds of millions of dollars to bring new treatments to patients. Consider cervical cancer, the second most common cancer among women. In 1972, Germany’s Dr. Harald zur Hausen started working on the notion that the disease is caused by a virus. It took about 35 years — most of his career — for HPV vaccines to make it to market.
It’s even more complicated for stem cells, a relative newcomer to the scene. While their existence was proven in Canada by Drs. James Till and Ernest McCulloch in the early 1960s, the focus afterwards was on bone marrow stem cells for treating leukemia. Embryonic stem cells have only been in play since 1998. Realistically, iPS cells are still the new cells on the block.
Cell-based therapies represent a whole new way of thinking about treating diseases, and regenerative medicine is a disruptive technology. Unlike a vaccine or a drug, the actual therapy isn’t an easy thing to grasp for industry, whose commitment is crucial in moving things from the lab bench to the hospital bed.
What’s needed, then, is an innovative approach. We need to think bigger. That’s why our Foundation is championing the Canadian Stem Cell Strategy, a private/public partnership to deliver up to 10 new curative therapies to the clinic within 10 years. Crafted in consultation with 150 scientists, doctors, leaders from health charities, industry experts and philanthropists, it is backed by an in-depth KPMG study and endorsed by an international panel of experts.
The private sector is already at the table, pledging more than $350 million toward R&D — almost one-quarter of the $1.5-billion Strategy. Other industry partners, health charities and leading Canadian philanthropists are prepared to make major contributions upon demonstration of a federal commitment to the plan. We’re asking the Government of Canada, as part of its Innovation Agenda, to provide one-third, about $50 million annually over 10 years.
Are we there yet? Clearly not. But a coordinated national road map can get us there.
Our Foundation is proud to be a major sponsor of the Till & McCulloch Meetings, Canada’s premier stem cell research event.…
Our Foundation is proud to be a major sponsor of the Till & McCulloch Meetings, Canada’s premier stem cell research event.
Named after Drs. James Till and Ernest McCulloch, the conference brings together Canada’s leading stem cell scientists, clinicians, bioengineers and ethicists, as well as representatives from industry, government, health and NGO sectors from around the world. The 2015 Till & McCulloch Meetings will take place in Toronto from October 26-28, 2015 at the Sheraton Centre Hotel.
For more information about the conference or to register click here.
This year’s session will feature several scientists whose innovative research has been highlighted in this space, including Drs. Jeff Biernaskie, Connie Eaves, Tim Kieffer and Ivar Mendez. As well, Foundation President & CEO James Price and Board Chair Dr. Alan Bernstein will update delegates on the progress being made to secure support for implementing the Canadian Stem Cell Strategy & Action Plan. To show your support for the Strategy, click here.
Dr. Andy Becker, one of the true pioneers of stem cell science, has died in Toronto at age 80.
Dr. Andy Becker, one of the true pioneers of stem cell science, has died in Toronto at age 80.
Dr. Becker was the lead author of the 1963 paper, published in Nature, that definitively demonstrated the existence of stem cells. Using chromosomal markers, he retraced their steps after they had generated the three types of precursor cells needed to make blood.
“It was a key contribution to our early experimental investigations of stem cells,”Dr. Jim Till, who was Dr. Becker’s PhD advisor at the time, wrote via email. “His combination of talent and persistence was what was needed to complete this challenging and innovative research. I’m still amazed at what he accomplished. I doubt if anyone else, at that time, could have succeeded in the way that Andy did.”
Dr. Becker worked closely with Drs. Ernest McCulloch and Till who, in 1961, had successfully shown that single cells drawn from bone marrow could produce colony-forming units containing the precursor cells required to make white blood cells, red blood cells and platelets. That paper laid the foundation for stem cell science.
A third Till & McCulloch paper — also published in 1963 but with Dr. Lou Siminovitch as lead author –proved that stem cells not only differentiate into new cells but also have the capacity to self-renew in order to keep the process going throughout our lifetimes. Combined, the three papers essentially defined stem cells and set the stage for regenerative medicine.
Dr. Becker’s paper proved just how tenacious a researcher he could be. The chromosomal marker method was nothing if not painstakingly frustrating, given the rudimentary technology available at the time. In the University of Toronto Press book Dreams & Due Diligence, Dr. Becker’s wife, Prof. Clelia Ganoza, explains that he had a “killer instinct” for research, which meant that “the goal is the important issue and the obstacles to overcome are just needed lessons towards this end.”
As the Toronto Star obituary explains, Dr. Becker, who was also a medical doctor, not only did seminal work with stem cells but contributed greatly to the development of recombinant DNA technology.
Here at the Canadian Stem Cell Foundation, our hearts go out to Dr. Becker’s family, especially Prof. Ganoza, his wife of 47 years.
The news last week that Dr. Janet Rossant had won the 2015 Gairdner Wightman Award should have come as no big surprise.…
The news last week that Dr. Janet Rossant had won the 2015 Gairdner Wightman Award should have come as no big surprise. The head of research at SickKids Hospital in Toronto, Dr. Rossant perfectly fits the profile of the Wightman winner: a scientist who has demonstrated outstanding national leadership in medicine and medical science.
However, the announcement did give us another reason to celebrate: it brought the Canadian Stem Cell Foundation’s Gairdner Award connections to four — so far.
Dr. Rossant (1) who chairs our Foundation’s Science Leadership Council, has led the way in crafting Canada’s public policy regarding stem cell research and is the immediate Past President of the International Society for Stem Cell Research. She also is an articulate advocate for the Canadian Stem Cell Strategy & Action that sets out how Canada can lead the way to deliver five to 10 new stem cell therapies to the clinic within 10 years. (See the Globe & Mail piece she co-authored here).
With the announcement, Dr. Rossant joins Dr. Alan Bernstein (2), Chair of our Board of Directors, as a fellow Gairdner Wightman winner. Dr. Bernstein, now President & CEO of the Canadian Institute for Advanced Research, won the Wightman in 2008 for his “outstanding contribution to Canadian health research as a scientist, research institute director and as the inaugural President of the Canadian Institutes of Health Research.”
Dr. Bernstein’s stem cell connection goes all the way back to his PhD studies with Dr. Jim Till, co-discoverer of stem cells (with Dr. Ernest McCulloch) in the late 1960s/early 1970s at the Ontario Cancer Institute (OCI). Dr. Till mentored Dr. Bernstein in much the same way that Dr. Bernstein encouraged Dr. Rossant when she came to work at the Samuel Lunenfeld Research Institute (now the Lunenfeld-Tanenbaum Research Institute) at Toronto’s Mount Sinai Hospital in 1985.
Dr. Till (3) is a Gairdner International Award winner, having picked up the prize with Dr. McCulloch back in 1969. His connection to the Foundation? He was original member of the Board of Directors when the Foundation began life in 2006 and has been a trusted advisor ever since. In fact, his “Spleen Team” jersey, from when he led the OCI squad that unveiled the mysteries of hematopoietic stem cells, hangs in a place of honour in the Foundation’s office in Ottawa.
Then there is Dr. Samuel Weiss (4), who won his Canada Gairdner International Award in 2008 in large part for his 1992 discovery of neural stem cells in the brains of adult mammals, which sparked new approaches for brain cell replacement and repair. Dr. Weiss, who leads the Hotchkiss Brain Institute at the University of Calgary, preceded Dr. Rossant as Chair of our Science Leadership Council and was also a member of the Foundation’s Board.
Quite honestly, we’re proud to be associated with these outstanding scientists. That they have chosen to help us as we advocate for the advancement of stem cell research and development to deliver safe, new and effective treatments for an array of diseases is truly inspiring. And we look forward to finding out who will be (5).
Dr. Harry Atkins’ success in treating a rare disease that can turn active, healthy people into living statues is getting the national attention it deserves this week, thanks to the Journal of the American Medical Association’s publication of his paper, Autologous Stem Cell Transplantation for Stiff Person Syndrome.…
Dr. Harry Atkins’ success in treating a rare disease that can turn active, healthy people into living statues is getting the national attention it deserves this week, thanks to the Journal of the American Medical Association’s publication of his paper, Autologous Stem Cell Transplantation for Stiff Person Syndrome.
The JAMA Neurology paper describes two Canadian women who have had all symptoms of their Stiff Person Syndrome (SPF) disappear thanks to a stem cell treatment that Dr. Atkins and his team at the Ottawa Hospital have developed. Readers of this blog will be familiar with one of the women’s stories — we told you all about Tina Ceroni back in December After our post, Canada AM featured Tina and Dr. Atkins.
This week’s reports, including Elizabeth Payne’s excellent news feature (the “living statue” description is hers) that appeared in the Ottawa Citizen and the National Post, explain how SPS, which strikes about one in a million people, triggers episodes in which muscles seize up uncontrollably, leaving a person rigid. Sheryl Ubelacker of the Canadian Press describes it this way in the Toronto Star:
“SPS is characterized by episodes of stiffness in the muscles and painful muscle spasms, which can be brought on by stress, loud noises or emotional distress. Some people with the disorder are so disabled they are unable to walk or move and may isolate themselves at home to avoid triggering an attack.”
Ms Payne’s story also tells of a third woman, a 53-year-old mother of six named Ingrid Steppan who was told she would likely die from her SPS. A recent transplant patient, she has now “put her wheelchair and walker away.”
Success with MS, Crohn’s and other autoimmune conditions
Dr. Atkins has used this technique with other autoimmune diseases, including Multiple Sclerosis (where he led a multi-year clinical trial involving about 30 patients) Crohn’s disease and neuromyelitis optica. The process involves extracting a patient’s bone marrow stem cells, then purifying and fortifying them. After the patient undergoes extreme chemotherapy, in which their immune system is effectively destroyed, the purified and fortified stem cells are put back to build a new disease-free immune system.
A modest and soft-spoken man, Dr. Atkins does not used the word “cured” when he talks about the patients who have had success with this treatment. He refers to his patients as “in remission.” For Jennifer Molson, an MS patient, that remission has lasted more than a decade. And in the case of Jelissa Morgan, the treatment has allowed her to overcome her crippling neuromyelitis optica and will be resuming her nursing career in September.
The success that Dr. Atkins is having is encouraging and offers great hope for the future. But it also harkens back to the past: the procedure he is refining can be traced back to the groundbreaking work the Canadians Jim Till and Ernest McCulloch did in proving the existence of stem cells in the early 1960s. It’s an area of medical science where Canada researchers excel. And people like Tina Ceroni, Jennfer Molson, Jelissa Morgan … and now Ingrid Steppan are living proof.
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.
To mark the Toronto’s 180th birthday this week, the Toronto Star has offered its readers 180 portraits of “the people who helped shape the city” from its Muddy York beginnings to its current status as one the world’s great centres.…
To mark the Toronto’s 180th birthday this week, the Toronto Star has offered its readers 180 portraits of “the people who helped shape the city” from its Muddy York beginnings to its current status as one the world’s great centres.
The list contains most of those you would expect — Father of Confederation George Brown, jazz great Oscar Peterson and business tycoon Kenneth Thomson — and a few you wouldn’t, including “Call In The Army” Mayor Mel Lastman, bank robber Edwin Alonzo Boyd and the Maple Leafs former owner and convicted fraudster Harold Ballard.
But also included are Drs. James Till and Ernest McCulloch, lauded as “the fathers of stem cell research” and as mentors to “generations of scientists in stem cell research, a field that promises to transform medical treatment and health care.”
Despite the enormity of their achievements, Till & McCulloch are virtually unknown across Canada. When CBC ran its Greatest Canadian competition 10 years ago, the two men who discovered stem cells did not even crack the top 100. (No. 1 was Tommy Douglas, while hockey commentator Don Cherry placed seventh.) And there is nothing — no public building, no elementary school, no street, not so much as a plaque — honouring Till & McCulloch in the city where they did their remarkable research.
Also on the Star list under the category of Trailblazers and Innovators is Dr. Tak Mak, the medical scientist who discovered the T-Cell receptor. Dr. Mak is one of those who was mentored by Till and McCulloch and has gone on record as saying McCulloch “was behind me when the rest of the world thought I was crazy.” One of the world’s leading cancer researchers, Dr. Mak has been featured in this space for his recent foray into developing a “sharpshooter” drug to attack tumours.
The Star recognition is a great first step, an indication that the public is finally beginning to appreciate these two medical research giants. Now, if the powers that be could be convinced to rechristen Sherbourne Street, where their original the Ontario Cancer Institute and Princess Margaret Hospital lab was located, as Till & McCulloch Way, that would really be something.
The news broke Monday that three American scientists – Dr. Thomas Südhof of Stanford, Dr. Randy Schekman of University of California at Berkeley and Dr.…
The news broke Monday that three American scientists – Dr. Thomas Südhof of Stanford, Dr. Randy Schekman of University of California at Berkeley and Dr. James Rothman of Yale University have won the 2013 Nobel Prize in Physiology or Medicine.
As the San Jose Mercury explained, the three scientists, working separately, figured out how a cell organizes its internal transportation system, controlling the creation and release of important hormones and enzymes. They showed how this cellular cargo is delivered to the right place at the right time. Breakdowns in this trafficking system lead to neurological diseases, diabetes, immunological disorders and ultimately death.
While the three researchers’ amazing discoveries are to be celebrated as Nobel-worthy, the announcement likely is final proof that the selection committee will never right the grievous wrong of not awarding the most prestigious prize to Canada’s Dr. James Till and Dr. Ernest McCulloch who, in the early 1960s, proved the existence of stem cells – a truly paradigm-shifting moment in medical research.
Every October many Canadian medical scientists hope to see this mistake corrected. Every year they are disappointed.
“Bun” McCulloch’s chance to win is gone: he died two years ago and the Nobel is not awarded posthumously. However, his research partner, Jim Till, is alive and well – no doubt due in large part to the fact he is life-long avid curler – in Toronto.
Many thought that the Till oversight would have been corrected in 2012 when Stockholm decided to award the Nobel to Japan’s Dr. Shinya Yamanaka, who showed how to create induced pluripotent stem (iPS) cells in 2006 (with mice) and 2007 (with humans). However, Dr. Yamanaka’s co-winner last year was the United Kingdom’s Sir John Bertrand Gurdon, for his pioneering work in the late 1950s in nuclear transplantation and cloning. Dr. Till, who could have been the third laureate in a cell-based triple play, was once again left out.
Canada, in fact, has not won a Nobel Prize in Medicine since Sir Frederick Banting captured the prize (with Scotland’s J.J.R. Macleod) in 1923 for discovering insulin. Canadian-born medical researchers who did their work elsewhere have won during that nine-decade Nobel drought, but no native son or daughter who did their groundbreaking work in Canada has made the trip to Sweden for the acceptance ceremony.
We have, of course, won in other categories. For example, the late Dr. Michael Smith, a British-born Canadian, won the Nobel for Chemistry in 1993 for his efforts in developing site-directed mutagenesis. But the Physiology and Medicine prize? Nothing in 90 years.
It is not merely Canadians who, every October, can’t comprehend this oversight. Dr. David Scadden, who co-founded and co-directs the Harvard Stem Cell Institute, has said he can’t fathom why Till and McCulloch were overlooked, noting that, “Till and McCulloch clearly are giants. They clearly paved the way and made this whole field (of stem cells).”
But while it would be enough to give the True North an inferiority complex, the simple truth is many giants in medical research have been overlooked by the Nobel selection committee. A book due for publication later this year or in early 2014 tells the stories of more than a dozen such titans from around the world who got the cold shoulder. Pioneers of Medicine Without a Nobel Prize, to be published by Imperial College Press, includes chapters on Sir Archibald E. Garrod, the founding father of biochemical genetics, Sir William Richard Shaboe Doll, who linked smoking and lung cancer, Dr. Albert Sabin, who developed an oral polio vaccine, and heart transplant pioneers Drs. Christiaan Barnard and Norman Shumway. Also featured are Drs. Inge Edler and Hellmuth Hertz, for their development of ultrasound for clinical use, Drs. Herbert Boyer and Stanley Cohen, who came up with recombinant DNA, and Dr. Akira Endo, who discovered statins.
It will, of course, include a chapter on Till and McCulloch.