STEMCELLNETWORK.CA the Mission of the Stem Cell

Home , Alan Bernstein, Connie Eaves, Ernest McCulloch, James Till, Janet Rossant, Ontario Cancer Institute

SUMMER 2006 VOLUME 5, NUMBER 1

FATHERS OF THE FIELD How two quiet Canadians changed the course of history in biological research.

CRITICAL MASS AHEAD OF THE CURVE A CANADIAN A pioneering past and a culture of Finding the way inside the ‘black box’ COMES HOME collaboration combine to make Toronto of cancer, Dr. John Dick has changed One of America’s leading researchers a world leader in stem cell science. our understanding of how to fight takes up a new challenge in the city the deadly disease. where he began his brilliant career.

WWW.STEMCELLNETWORK.CA The mission of the Stem Cell

Network is to be a catalyst for realizing the full potential of stem cell research for Canadians.

STEM CELL NETWORK

Frank Gleeson, Chair, Board of Directors Dr. Michael Rudnicki, Scientific Director Dr. Janet Rossant, Deputy Scientific Director Drew Lyall, Executive Director Cathy Campbell, SCN Communications Lori Barron, SCN Communications Joe Sornberger, Writer

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TABLE OF CONTENTS

Welcome to Toronto - Dr. Michael Rudnicki ...... 1

Critical Mass ...... 2

The Fathers of the Field ...... 8

A Canadian comes home - Interview with Dr. Gordon Keller ...... 14

The world’s best feel right at home ...... 15 On the Cover: Ahead of the curve - Interview with Dr. John Dick ...... 17 ”Fathers of the Field” Why I work in Canada - Interview with Dr. Mike Bhatia ...... 19 Dr. James Edgar Till and Dr. Ernest Armstrong Business is good...... 20 McCulloch have forever changed the course of Pull-out Map of Toronto...... 23 scientific research in the field of biology

Cover photo credit: Critical Mass Lucas Oleniuk/Toronto Star Toronto is fast becoming the hub Pg.8 of stem cell research. What’s making this metropolis so attractive to the scientific communtiy?

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The world’s best feel right at home Canada’s history of achievement, coupled with attractive programs such as the Canadian Foundation for Innovation and the Canada Research Chairs initiative have made the country a magnet for the world’s best and brightest young stem cell scientists.

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Stem Cell Network two pioneers. Canadians have led advances in the understanding of adult stem cells, of neural, muscle, retinal and pancreatic stem cells. We have probed the cellular beginnings of leukemia and other cancers. We have done groundbreaking work in the root causes of Parkinson’s and degenerative muscular diseases. And we are looking deeply at cardiovascular disease and stroke and applying our stem cell expertise there.

This is remarkable because while Canada is a big country, we do not have a big population. While many of our top stem cell scientists WELCOME TO work closely together in Toronto, many more are spread across the breadth of the country, TORONTO co-operating on outstanding projects in Halifax, Montreal, Ottawa, Hamilton, Calgary, Edmonton, Vancouver and Victoria. This is possible because the culture of collaboration Dr. Michael Rudnicki, Scientific Director, that was initiated by Drs. Till and McCulloch Stem Cell Network and nurtured by those who followed was formalized with the creation of the Stem Cell n behalf of the Stem Cell Network, I am Network. We have succeeded in defeating Odelighted to welcome the members of the geography by bringing together leading thinkers International Society for Stem Cell Research in different locations and different disciplines to Toronto. to find ways to fight diseases that have baffled science for too long. It only seems fitting that the ISSCR’s first conference outside of the United States should But the science of stem cells transcends all be here in Canada. As the pages of this special borders.The ISSCR and this conference stand edition of our newsmagazine show, this is as proof of that. Stem cell science remains, where it all began – thanks to the pioneering in many ways, an emerging field that brings work of Drs. James Till and Ernest McCulloch. together investigators working in many diverse More than 40 years ago, they proved the exis- areas. Consequently, the sharing of knowledge tence of stem cells and launched a whole new and information is critically important towards field of scientific endeavour. advancing our field. We are delighted to have delegates from around the world visit Toronto, We are very proud, too, of the fine work that has and look forward to what promises to be an been carried on by “the descendants” of those unrivalled ISSCR conference. ❧

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By Joe Sornberger

y now, the story is legend. It is also true. On a CRITICAL MASS BSunday afternoon in 1960, Dr. Ernest ‘Bun’ McCulloch dropped in at his old Ontario Cancer There’s something unique about Toronto. Institute (OCI) lab to collect some specimens. He noticed that “bumps” on mice spleens correspond- There’s the history, of course. The ed with the bone marrow cell doses given to the ani- mals.The next day, he showed the results to his bio- pioneering work done at the Ontario physicist partner,Dr.James Edgar Till, and they set Cancer Institute by Drs. James Till and to work, calling call the bumps “spleen colonies.” By 1963, they had published a definitive paper in Ernest McCulloch proved the existence Nature that showed the colonies were created by single cells with “multipotent” properties. Stem of stem cells. But it’s more than that. cell science had begun. The spirit of collaboration they instilled Largely unheralded for years, their remarkable has carried forward, so that four decades achievement was recognized last year with the Lasker Award, North America’s highest honour for later it is stronger than ever.It has made medical science research. Drs. Till and McCulloch, however, did much more than just start the science Toronto – and Canada – one of the best of stem cells.They established an ethos.They created places in the world for stem cell science. a culture of collaboration that, more than 45 years later,has kept Toronto and Canada at the forefront of stem cell research.

“It’s interesting, how an ethos develops in an insti- tution and how that can permeate in the long term,” says Dr. John Dick, a Canada Research Chair and Director of the Stem Cell Biology Program at Toronto General Research Institute, which is part of Toronto’s University Health Network.

“I would argue that it was really the way that science was done, the principles of the scientific process that people like James Till, Ernest McCulloch, Lou Siminovitch and some of the other leaders in Toronto practised at that time.They did science in its purity and with openness. They imbued that in their trainees, so that we’re now living by the principles that they set down 40 years ago in terms of how we operate and how we function.”

Stem Cell Network Page 2 It’s exciting to be part of it.There is so much going on, intellectually. People are now centralized instead Phillips, President and CEO Ontario Cancer of being scattered all over. New Research Network, have recruited and men- tored a brilliant collection of stem cell scien- people are coming in and new money tists. More importantly, they’ve nurtured that is being poured in from donors. It’s original culture of collaboration. great. It’s the classic thing of being “People would rather collaborate than compete,” says Dr. Dick, who counts Drs. Bernstein in the right place at the right time. and Phillips as his mentors. “That creates a very open atmosphere. It means students can Dr. Freda Miller, Senior Scientist, SickKids Hospital easily move from one lab to another.They can get information – nobody’s holding on to information tightly because they’re worried that someone’s going to scoop their latest data. When you can talk about your latest idea before you’ve done any experiments, that creates a legacy that is enormous. Of course, the Stem Cell Network is a part of that. But I think it’s also something unique about Toronto.”

Certainly Toronto has the critical mass for collaboration.Within a five-minute walk of the University of Toronto are four major teaching hospitals (Princess Margaret, Mount Sinai, SickKids and Toronto General), each with affiliated research institutes that are all very large and very active. Dr. Freda Miller Dr. Janet Rossant, Chief of Research at The people who worked with or trained under SickKids and an internationally recognized Drs. Till and McCulloch and Siminovitch, the expert in developmental biology and stem latter a pioneer in the study of genetics in cells, says that ethos of collaboration in Canada, have gone on to do seminal work in Toronto, and across Canada, “really enhances the field of stem cell science. People like Dr. our ability to have an impact. Alan Bernstein, who was supervised by Dr.Till at OCI and who now is President of the “I like to think about the issues around cancer Ottawa-headquartered Canadian Institutes of stem cells,” says Dr.Rossant, who was recruit- Health Research (CIHR), Dr. Ron Worton, ed to come to Toronto by Dr. Bernstein. “John founder and first scientific director of the Dick, of course was the person to really iden- Canada-wide Stem Cell Network, and Dr. Bob tify that leukemias, blood-borne cancers, have

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stem cells that really are the ‘bad guys’ in the cancer. That was built on understanding how hematopoietic stem cells work, built on the generations of work from Till and McCulloch. That whole concept of stem cells fed into the work of Derek van der Kooy, working on neural stem cells.Then along comes Peter Dirks, who’s a neurosurgeon working with devastat- ing childhood brain tumours, and he’s in an environment where he’s thinking… “Hmmm… if I use the techniques that Derek’s using on neural stem cells and apply them to tumours, maybe I’ll find out whether solid tumours like brain tumors also have stem cells.” And the answer is yes. He was able to do that because Dr. Derek van der Kooy he’s in an environment where all those aspects, from the basics to the more clinical, were going on around him.” Stem cells now have a critical high

For a young researcher like Dr. Peter Zandstra profile. Donors want to give to money of the U of T’s Institute of Biomaterials and Biomedical Engineering, a large part of the appeal to this sort of research. And it’s drawing of Toronto is that critical mass of talent: “On the more young researchers – they see it not engineering side of things, we have a very large representation of people working in stem cells, only has basic interest because it’s part perhaps the largest in North America. On top of that there is also the large bio-medical commu- of developmental biology, but it also nity, which is also one of the strongest in North America. So you have this coming together of has a link to clinical therapies that multiple disciplines, all working in the stem cell will come up in the future. area, which is fairly unique.”

Dr. Derek van der Kooy, Director of Regenerative Medicine Program, Dr. Zandstra, who has a new lab on the 11th McLaughlin Centre for Molecular Medicine floor of the new Terrence Donnelly Centre for Cellular and Biomolecular Research, did his post-doc in Boston but was drawn to Toronto. “I’m Canadian and one of the things I feel quite strongly about is the fact that Canada has

Stem Cell Network Page 4 invested quite heavily in my training and Along with bringing the scientists together, success. I decided if there was any possibil- the McLaughlin Centre, which began opera- ity I could carry out my career in Canada, tions in 2003 and is a joint initiative of the I would. The reality of the situation is U of T and four partnering hospital institu- Toronto is a hotbed of stem cell activity. tions, is enabling ground-breaking research, There is nothing that I couldn’t do here such as Dr.Michael Fehlings’ recent advances that could be done elsewhere.” in the use of stem cells to regenerate all- important myelin-forming cells in rats with Just down the hall from Dr. Zandstra is Dr. spinal cord damage. Meanwhile, Dr. Duncan Derek van der Kooy, a leader in neural, reti- Stewart, Director of the McLaughlin Centre, nal and pancreatic stem cell research. Like is working to find ways to use progenitor Dr. Zandstra, Dr. van der Kooy is supported cells to repair blood vessels around hearts in his work by the McLaughlin Centre for damaged by myocardial infarction. Again, Molecular Medicine, which he describes as the critical mass of stem cell talent in a “virtual” centre comprised of about 40 to Toronto is a big help. 50 scholars, with regenerative medicine as one of its key themes of investigation. “I’m not a card-carrying stem cell biologist, “That has allowed us to establish a Toronto I’m a clinician with a major interest in stem cell group that’s been very effective,” molecular medicine,” says Dr. Stewart. says Dr.van der Kooy.“It’s called the McLaughlin “From my perspective (Toronto) is a wonder- Rounds and we have monthly meetings ful place to be because I can draw on a where we get 150 people for beer and pizza tremendous wealth of talent and expertise in and discussions. It has brought the stem terms of trying to understand where the cell community together.” opportunities may lie in how we can best translate all of this great knowledge into something that will be meaningful for treating our patients. The McLaughlin Centre is helping to bring these people together and push these ideas into the clinical arena.”

Then there is the McEwen Centre for Regenerative Medicine, part of the University Health Network. The McEwen Centre this year succeeded in attracting one of the world’s leading stem cell biologists, Dr. Gordon Keller, back to the city where he began his career. Dr. Keller, from the Mount Sinai School of Medicine in New York City, did his post-doc work at the OCI, leaving in 1983. He is returning because he likes “the amount of research, the amount of science

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going on in Toronto. The density of research for Stem Cell and Gene Therapy, under con- on Toronto’s University Avenue is very attrac- struction, will house about a dozen stem cell tive to me. The nearness of one institute to researchers, each with a staff of 10 to 15 another and the outstanding stem cell biolo- people. Top researchers are being recruited gy that’s already going on there is a huge from around the world. attraction.” “It’s a good time to be doing stem cell Toronto is hoping to capitalize on that den- science in Canada,” says Ottawa-based sity of research with the establishment of Dr. Michael Rudnicki, Scientific Director of the Medical and Related Sciences Discovery the Stem Cell Network. “The funding we District (MaRS). Last fall, the gleaming new have here (in Canada) through the CIHR MaRS Centre opened on corner of University and elsewhere has increased five-or six-fold Avenue and College Street to house a vari- from the mid-1990s. We have new funding ety of science and technology research labs through the Canada Foundation for Innovation, alongside technology companies and the Canada Research Chairs. investment capital firms. In April, Ontario Premier Dalton McGuinty, who is also Minister of Research and Innovation, announced an additional $16-million in funding – on top of the $50 the province has already invested – to help with a second phase of construction.

“We are supportive of our stem cell community,” says Stuart McKeen, a senior policy advisor to Mr. McGuinty. “We are coming out with what we call a sector innovation strategy for stem cells but it’s being formu- lated and has yet to be approved. We’re con- sulting on how Ontario could strengthen its stem cell community. Dr. Janet Rossant “We have various areas across Ontario that are strong in stem cells, Ottawa being one of them and McMaster University in Hamilton another. Obviously the biggest concentration is on University Avenue in Toronto, but they all work very well together.”

Ottawa is currently gearing up its stem cell research activity. The $19-million Centre

Stem Cell Network Page 6 Toronto and across Canada allows Canadian stem cell scientists to go further with their work, creating a whole that is greater than the sum of the parts.

“You have two mechanisms,” says Dr.Miller, who collaborates on projects with colleagues in St. John’s, Hamilton, Calgary and Vancouver.“First you have a centre like Dr. Peter Zandstra Toronto where a lot of people are geo- graphically in the same place. Second, while We have an advantage. many of the other stem cell researchers are We have a lot of good history. dispersed, with three of them or four of them in any place, the Stem Cell Network has really worked to bring them together. Dr. Peter Zandstra, Institute of Biomaterials and Biomedical So what you have is a situation in which, Engineering, University of Toronto by either geography or through the Network, all these people are working together, they are willing to work together and there are funding mechanisms to allow The provincial governments are involved. them to work together.” Ontario has the Ontario Research and Development Challenge Fund and Ontario This is important, Dr. Miller says, because Research Fund in supporting the building of what’s needed right now in stem cell biolo- infrastructure and building research criti- gy is co-operation. “At this point in time, cal mass. At a political and public level that’s what you have to do – work together. there is implicit support for science innova- It’s that kind of coherence and co-ordinated tion and technology. There’s an additional effort that makes the difference. In Toronto need for resources, but we’re vastly and across Canada, people aren’t competing improved from where we had been.” with each other.They are, instead, talking to each other to get to the next step.” ❧ Dr. Freda Miller, Senior Scientist at SickKids and a Canada Research Chair in Developmental Neurobiology, says the net- working that goes on among institutions in

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THE FATHERS OF THE FIELD Toiling away in ‘exile’ at the old Ontario Cancer Institute labs on Toronto’s Sherbourne Street, Dr. James Edgar Till, a Yale-trained biophysicist, and Dr. Ernest Armstrong McCulloch, a former family physician, changed the course of scientific research in biology. They proved the existence of stem cells.

The following article originally appeared in the Toronto Star in October of 2005, when Drs. Ernest McCulloch and James Till were awarded the Lasker Prize. The two pioneers of stem cell biology are to be honoured at this year’s ISSCR conference. To mark the occa- sion, the profile of the two great men is reprinted with the permission of the Star. Copyright, the Toronto Star 2005.

Dr. Ernest McCulloch and Dr. James Till By Joe Sornberger

lmost 45 years after their breakthrough After all these decades, however,celebrity may Adiscovery, two septuagenarian Toronto be looking for them. Winning the Lasker – scientists – revered within their field of stem begun in 1946 by philanthropists Albert and cells but largely unknown outside of it – have Mary Woodard Lasker, and known as won North America's most coveted prize in “America’s Nobel” – is often the prelude to medical research: the Lasker Award. capturing the Nobel Prize. Since 1946, 70 Lasker winners have gone on to win the Nobel Dr.James Edgar Till, 74, and Dr.Ernest Armstrong Prize, including 19 in the past 15 years. McCulloch, 79, proved the existence of stem cells while toiling away at the old Ontario Calling Drs .Till and McCulloch the “Fathers Cancer Institute labs on Sherbourne St. Their of Stem Cell Research,” the Lasker Foundation breakthrough 1961 paper on the formation of makes the global impact of their discoveries what were then called colony-forming cells is clear: “Their work laid the foundation for all regarded as the starting point for the science. current work on adult and embryonic stem That paper, and several that followed, also pro- cells and transformed the study of blood-cell vided the scientific underpinning to bone-mar- specialization from a field of observational row transplantation. science to a quantitative experimental discipline.”They also “explained the basis of bone- Public recognition, however,has largely eluded marrow transplantation, a procedure that them. “Both James and I are private people,” prolongs the lives of people with leukemia and the soft-spoken but droll Dr. McCulloch said. other blood-cell cancers.” “We do not seek celebrity.”

Stem Cell Network Page 8 While happy to be so honoured, Dr.McCulloch While Drs. Till and McCulloch stopped doing wished it had happened “10 to 15 years ago” research together decades ago, they have when his health was better and his legs were remained close friends and still have offices a stronger,“so that I could really enjoy it.” few paces apart at Princess Margaret Hospital.

Dr. Till speculated that controversy around They have always been a scientific odd couple. “just about everything to do with stem cells – Dr. McCulloch, a short, stocky man given to stem cell science, stem cell ethics, stem cell wearing academic tweeds and his Order of politics – the whole bit” might have been a fac- Canada pin, is affectionately referred to by tor in the delayed recognition of their work. friends by his childhood nickname, ‘Bun.’ He Stem cells are master cells that provide the comes from Old Toronto Scottish stock but is source material for all organs and tissue.They anything but dour.He reads widely (from Jane are found in the embryo and as “adult” cells Austen to Mordecai Richler), is a keen observ- throughout the body in the blood, skin, muscle er of the world around him (he appreciates and intestines. Because of their regenerative baseball but thinks hockey is “just people run- capabilities, stem cells have the potential to ning around on skates”), and believes the best treat or cure a number of debilitating diseases thing that ever happened to Toronto was the such as muscular dystrophy, blindness, post-war influx of immigrants that brought Alzheimer’s, Parkinson’s, arthritis and diabetes, style and culture – and better restaurants – to as well as spinal cord injures and blood disor- what had been a “nasty, narrow-minded” city. ders.The subject of embryonic stem cells, how- Dr.Till, at least a head taller than his former ever, has been controversial, with religious research partner, is as neat as Dr. McCulloch groups decrying the use of potentially life-cre- is rumpled. The son of Alberta homesteaders, ating organisms for medical science. he went from studying science at the University of Saskatchewan to a doctorate in biophysics at Yale “because they just kept giv- ing me scholarships.” He never worried about Their work in 1961 was a great taking on difficult challenges with his research because,“I knew I could always go back to the inspiration to me and a number of farm.” He prefers curling to golf, retains a future stem cell researchers. I took self-deprecating prairie boy charm, and laughs easily and loudly. their evidence that there had to be blood- The two were brought together by Dr. Harold forming pluripotent or multipotent cells Johns, who ran the physics division at OCI as the stimulus for our isolation when it began operations in 1957. Dr. Johns thought Dr. Till’s hard-headed, check-every- of those cells in mouse and man.” thing-twice, physics-based style of science and his experience with measuring radiation would

Dr. Irving Weissman, Stanford School of Medicine be a good counterweight to Dr. McCulloch’s

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big-picture, what-if conceptual approach.To this day, Dr.Till defers to Dr. McCulloch as the big thinker, saying he “rode Ernest's coattails,” although he will agree to instilling a degree of rigour in their work.

How they discovered stem cells is a research legend. “We were in the salt mines,” said Dr. McCulloch, who recently published a book about the early days at the OCI.“The centre of the world was the Toronto General Hospital, and we had been exiled to Sherbourne Street. It was the best thing that ever happened to us. There was no one looking over our shoulders.” something: colony-forming units originating Back then, in a Cold War world eager for from single cells. information on how to survive nuclear war, they were brash, young men studying the Said Dr. Till: “Of course, being able to find effects of radiation on mice. what were the active cells in that bone marrow – well, you can imagine being able to purify “One has to consider the context of the time,” that and bank those. Whoa! That was the said Dr. Till. “This was the late-1950s, early underlying area of applied rationale.” 1960s.The memories of Hiroshima and Nagasaki were still fresh.There was much concern about Their 1961 paper in the little known journal the threat of nuclear weapons, that we might Radiation Research went largely unnoticed. have to fight an atomic war. So, being able to Their 1963 follow-up in Nature, however – ameliorate the effects of total-body irradiation made possible by the brilliant work of a young by having a bank of marrow was a big deal. researcher named Dr. Andrew Becker – Some of our very early funds came from the showed that the colonies originated from sin- Defence Research Board of Canada.They were gle “multipotent” cells. It changed everything. very interested in this when other agencies Essentially, stem cell science had begun. were less excited. I still feel a debt of gratitude to that agency.” Dr. Irving Weissman, one of the top stem cell scientists in the U.S. and the first person to iso- One Sunday afternoon in 1960, Dr.McCulloch late stem cells, views their work as vital and stopped into the lab to check an experiment deserving of wider recognition. “I’m delighted he was conducting: injecting mice with cells that Till and McCulloch got the Lasker,”he said. from bone marrow. He noticed bumps grow- “I worked hard to make sure they were nomi- ing on the spleens of the mice, and observed nated and appreciated.Their work in 1961 was a “linear” match with the number of marrow a great inspiration to me and a number of future cell doses. Dr.Till agreed they might be on to stem cell researchers. I took their evidence that

Stem Cell Network Page 10 “I didn't want to compete with them for grants and resources,” said Dr. Till. “And Ernest had gone on to much more practical research with leukemia.”

Dr. Bernstein said the fact it took so long for the pair to be recognized is proof of how far ahead of their time they were.

“The public now knows about stem cells,” said Dr.Bernstein, whose early research at OCI was supervised by Dr. Till. “In those days, it was not considered leading edge. It was definitely Drs. Ron Worton, Alan Bernstein and James Till not on the international science radar screen. But, to Jim and Bun's credit, they knew it was They were not interested in fads and important. They were not interested in fads and fashion. They were interested in doing fashion.They were interested in doing beautiful science, important science.” beautiful science, important science. He compares the Till and McCulloch partner- ship to that of American biochemist Dr.James Dr. Alan Bernstein, President of the Watson and British biophysicist Dr. Francis Canadian Institutes of Health Research Crick, the incongruous pair who worked out the double helix structure of DNA in the early 1950s. “Jim basically knew nothing about there had to be blood-forming pluripotent or blood cells. McCulloch knew basically noth- multipotent cells as the stimulus for our isola- ing about colonies and clones and cell division – tion of those cells in mouse and man.” he was a pure and simple clinician interested in blood cancers. It was the two of them com- Drs. Till and McCulloch continued to do ing together as a team that allowed them to ground-breaking work throughout the ’60s make the fundamental insights on stem cells. and ’70s, some of it with Canadian genetics pioneer Dr. Lou Siminovitch, and trained the “The discovery that they made – at the cellu- next generation of cellular scientists in the lar level – is as important as what Watson and process. Their work propelled Canada into the Crick did at the molecular level. And it’s final- front ranks of the new field.The good job they did ly being recognized. It’s terrific for them and encouraging up-and-coming researchers – such terrific for Canada.” as Dr. Alan Bernstein, now the president of the Canadian Institutes of Health Research – eventually led Dr.Till to leave the field in the 1980s.

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Dr. Michael Rudnicki, the Scientific Director professional lives have been less entwined over of Canada’s Stem Cell Network, said Drs.Till the past years, the bond they forged almost 50 and McCulloch are bona fide science heroes. years ago is still strong. “They are absolutely an inspiration. It was minimal technology – they worked it out with “One of the things I’m happiest about,” said their brains.” Dr. McCulloch, “is that even now, all these years later, we're very good friends.” He said that if Drs. Till and McCulloch were working at Harvard or Columbia they would As for the possibility of winning the Nobel likely have won the Nobel Prize by now. Prize, neither Drs.Till nor McCulloch is count- “Absolutely. We don't lobby for these prizes ing on it – or worrying about it. the way Americans do. Canadians are rather understated. We don't blow our horns.” After “I think it’s most unlikely, just because the he left stem cell research, Dr.Till became fas- discovery was so long ago,” Dr. McCulloch cinated with improving the quality of life for said. “Besides, winning the Nobel Prize was cancer survivors. not part of our objective.”

“I wanted to do high-quality, rigorous research on subjective phenomena such as pain. That matters in medical decision-making. I cannot measure your pain with some gauge. I have to ask you questions. Are you in pain? What kind of pain? By being very rigorous, you can quan- tify subjective experience as rigorously as you can measure temperature.”

More recently, Dr.Till has devoted his energies to making the publication of medical journals more widely available online.

As for Dr.McCulloch, he says he “never strayed very far, intellectually or professionally. I’m still an experimental hematologist.”

Both men, who were inducted into the Canadian Medical Hall of Fame in 2004, are semi-retired professors emeriti at the University of Toronto, where they were given honorary degrees recently to commemorate their outstanding careers. While their academic and

Stem Cell Network Page 12 Were it to happen, Dr. Till said he would have similar feelings about the Nobel as he has about the Lasker. “It would be great for science in Canada in general and stem cell science in par- ticular.Because the field has been quite controversial, it hasn't had that much recognition. My hope is that it will get a lot more. I’m hoping we’re the beginning of a trend where this kind of research that has great basic significance is recognized.” But neither he nor Dr. McCulloch cares a whit about glory.

“I actually think those who seek celebrity risk compromising themselves in terms of the quality of the science,” said Dr.Till. “It's very tough to produce creative work on schedule, and that's what you have to do to maintain your celebrity status. That kind of game is not for me. It never was.” ❧

By the turn of the 20th century, scientists were postulating the existence of self-renewing cells that could specialize for a wide variety of purposes. In a series of ingenious and elegant experiments 60 years later, Ernest McCulloch and James Till demonstrated that such a type of cell in the blood-forming—or hematopoietic—system existed. They established the properties of stem cells, which still hold true today.

Furthermore, they lay the foundation for the isolation of stem cells and for the detection of proteins that help these precursor cells develop and mature. Till and McCulloch’s discoveries explained the basis of bone marrow transplantation, which prolongs the lives of patients with leukemia and other cancers of the blood.

Moreover,the team set a new standard of rigour for the field of hematology, trans- forming it from an observational science to a quantitative experimental discipline.

The Lasker Foundation

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A CANADIAN COMES HOME Dr. Gordon Keller is leaving the Mount Sinai School of Medicine in New York City to return to Canada and the city where he began his brilliant career.

Dr. Gordon Keller

Dr. Gordon M. Keller, one of the world’s leading stem cell biologists and researchers in embryonic stem cells, is leaving New York City to return to Toronto to direct the newly established McEwen Centre for Regenerative Medicine. He is coming back to Canada in large part because of the “growth and enthusiasm I sense in Toronto – there’s enormous potential for growth there.” Dr. Keller, who is President of the ISSCR, recently shared his thoughts on his return to his homeland.

Q. You are you from Saskatchewan, are you Q. What will you be doing? a prairie boy? A. I’ll be setting up a new lab as well as a new A. I am. I’m from a small town called Melville, centre for regenerative medicine called the about 100 miles east of Regina. I grew up on a McEwen Centre for Regenerative Medicine. farm outside of Melville. I received my PhD We are developing a plan for the centre at the from the University of Alberta and did my present time. The vision for the centre is to post-doctoral work at the Ontario Cancer promote and support both embryonic and Institute in Toronto. adult stem cell research and translate findings from these programs to a clinical setting. It’s Q. Why are you coming back to Canada? going to be a centre that crosses from basic science to medicine. A. There are several reasons we have decided to move back to Canada. The first is that Q. Who will you be working with? Toronto has an outstanding scientific community that is concentrated along University A. Toronto is a very exciting city from the Avenue.The nearness of various research insti- both the scientific and medical perspectives. tutes including the Ontario Cancer Institute, My immediate neighbours will be Norman the Samuel Lunenfeld Research Institute, the Iscove and John Dick. I’ll be working with SickKids Hospital, the University of Toronto them as well as with other stem cell biologists and the new “MaRS” (Medical and Related and physician scientists in the community. Sciences) Centre to each other together with the outstanding stem cell biology that’s Q. This is certainly not the winding down of already ongoing within the city is a huge your career by any stretch. You are going to attraction. The second is that Toronto is a be at this for some time aren’t you? great place to live. We’ve been thinking about moving back to Canada and when this oppor- A. Setting up a new lab and directing the tunity came up, we decided to take it. McEwen Centre for Regenerative Medicine are exciting challenges that will keep me busy for the foreseeable future.

Stem Cell Network Page 14 Q. When it comes to stem cell science, what international stem cell community. One unique does Canada need to do better? aspect of this meeting is that it’s structured to promote young scientists and to provide an A. It has to sell itself.You have to get the word opportunity for them to speak. Less than half out that this is a great place to do stem cell the speakers are invited. The remainder is research and that there’s a lot of exciting young investigators, selected to participate things happening in the country. When young based on their submitted abstracts. The first researchers are considering a career in stem three ISSCR meetings were held in the United cell research, Toronto and Canada as a whole States and were very successful.This is the first are the first places they should think of.That’s conference to be held outside of the United our challenge, as we want to attract the best States and we are working hard to make it the and the brightest young scientists. biggest and the best. In addition to organizing the yearly meeting, the ISSCR is very active in Q. You are the President of the ISSCR.What public education. We have a great website that is the importance of the organization and contains extensive information on different why is this conference so important? aspects of stem cell biology for the lay public as well as for the scientific community. We are A. The annual ISSCR meeting brings together constantly improving the website as well as stem cell biologists from around the world – thinking of creative ways to inform the public it’s a forum that allows participation from the about the importance of stem cells. ❧

THE WORLD’S BEST FEEL RIGHT AT HOME Canada’s history of achievement, coupled with attractive programs such as the Canadian Foundation for Innovation and the Canada Research Chairs initiative have made the country a magnet for the world’s best and brightest young stem cell scientists.

or Stem Cell Network investigator Dr. things considered, it seemed like the best place. FKelly McNagny, the road to Canada was a The ability to get good students in my lab was long and winding one. Ultimately, though, the higher than at any other place I’d interviewed. trip has been more than worth it. The Canadian Foundation for Innovation (CFI) was a huge draw – I could get equipment that Originally from Massachusetts, he worked on I wouldn’t have gotten because of that organ- his PhD in Birmingham, Alabama, and then ization.There was the potential to make a big moved to Germany for a stint as a post-doc difference, as opposed to being a little fish in a and visiting scientist before taking a job at the big puddle somewhere else. Since then, I’ve University of British Columbia. considered other offers, but every time I look closely at the offers, British Columbia and “I came here in 1998. I remember I had an offer Canada seem like the best place to be. I made in Philadelphia and a couple of other places a smart move.” when this job offer came up in Vancouver. All

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Dr. McNagny remembers worrying that it Rosario Isasi practised law in her native Peru might be difficult to attract strong young for eight years before beginning graduate investigators with whom he could work. But studies at Boston University into the legal and the Canada Research Chairs program and the ethical implications of cloning and stem cell Stem Cell Network’s success in linking labs research.This year she finishes her post-doc and across the country eased that fear. “We got is working as a researcher with Prof. Bartha people like Fabio Rossi (from Stanford) Maria Knoppers at the Université de Montréal’s joining as a Canada Research Chair in Centre de recherche en droit public. “I wanted Regenerative Medicine and it made life a lot to work with the Stem Cell Network,” she says. easier for attracting new people. Now we “They are at the forefront of stem cell research have six investigators in my building who work in Canada and around the world. And for my in immunology or hematopoiesis, including a area – ethical, legal and social issues – Canadian, an Italian, an American, a German, Professor Knoppers was the main reason. She’s a Swiss and an Australian.” a world-renowned expert.” ❧

Canada, he says, is well-positioned to draw the best and brightest young stem cell scientists. “If you look around the world right now, there are probably 10 to 20 new institutes getting set up – specifically based on stem cell biology. It is a real challenge finding good people to fill those positions. I think Canada, because it has the tradition already, has been ahead of the other places.”

One of those bright young scientists is Bernhard Lehnertz who is at UBC working on his PhD. Originally from rural Germany, near the Luxembourg border, he came to Canada for the opportunity to work with Dr. Rossi. Dr. Kelly McNagny

“I had studied molecular biology and bio- I’ve considered other offers, but chemistry in Germany and I wanted to see something new, to move abroad. I contacted every time I look closely at the offers, Fabio Rossi directly. He had just started his lab in Vancouver after leaving Stanford.” British Columbia and Canada seem like the best place to be. I made Funding from the Stem Cell Network and a trainee award helped Mr.Lehnertz get started a smart move. on his PhD studies and the opportunity to attend the Network’s annual general meetings proved worthwhile “to develop an awareness Dr. Kelly McNagny, Stem Cell Network Investigator, of the science going on in Canada.” University of British Columbia

Stem Cell Network Page 16 AHEAD OF THE CURVE Dr.John Dick, Chair of the Program Committee for the ISSCR Conference, has led the way in advancing the understanding of how cancer begins and spreads.A decade after his breakthrough discovery,his findings are gaining worldwide attention.

Colleagues, such as Dr. John Hassell at McMaster University in Hamilton, point to the work as crucial in the campaign against cancer.

“This hypothesis – the cancer stem cell hypothesis – has been around since the Dr. John Dick 1950s,” says Dr. Hassell. “John Dick did an experiment in the 1990s that provided support n many ways, stem cell biology is just for it. His lab physically separated all the Icatching up with Dr. John Dick. tumour cells in leukemia into a tumourigenic (capable of producing tumours) class and a The work he did more than 10 years ago trans- non-tumourigenic class. He discovered that formed our understanding of how the human one in 100,000 of the cells in the leukemia blood system works and how leukemia can be was tumourigenic. So, that’s really hunting for studied. His in vivo (living organism) assays a needle in a haystack. But it’s that one cell in using Severely Combined Immune Deficient the 100,000 that you have to target. If you get (SCID) mice “paved the way inside the ‘black that cell, then you’ll cure the cancer.” box’ of cancer to identify and characterize the leukemic stem cell,” according to the American That Dr. Dick’s seminal studies, published in Society of Hematology, which last year award- Science and Nature in the late 1980s and early ed Dr. Dick its William Dameshek Prize. 1990s, went largely unheralded is not surpris- ing, says Dr. Michael Rudnicki, Scientific To put it Far Side cartoon simple, Dr. Dick Director of the Stem Cell Network. Like many showed what happens when good stem cells go Canadian stem cells scientists, Dr. Dick tends bad: they produce cancer.He did it by success- not to “blow his horn” about his work. fully transplanting normal human stem cells and leukemic human stem cells into SCID “He’s a very understated guy,” says Dr.Rudnicki. mice. The normal stem cells did what they “He’s a head’s down worker who isn’t inter- were supposed to do, rebuilding the blood sup- ested in a lot of the distractions that can ply.The leukemic stem cells produced the same occur to successful scientists. He’s interested kind leukemia that humans suffer. in the science.”

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Also like many Canadian stem cell scientists, colleagues at SickKids, demonstrated that for Dr. Dick, who is part of the stem cell program brain cancer it seemed to be the same way. at the Toronto General Research Institute, can And Mike Clarke in Michigan showed it in trace his work back to Drs. James Till and breast cancer.This finally captivated peoples’ Ernest McCulloch and the Ontario Cancer attention about three years ago. It made every- Institute (OCI). His mentors, Dr.Alan Bernstein, body sit up take notice.” President of the Canadian Institutes of Health Research, and Dr. Bob Phillips, President and Dr. Dick says only time will tell if the work he CEO Ontario Cancer Research Network, spent did will truly change how stem cell biology their salad days in the OCI labs.Their fascina- goes forward. He hopes it sparks the develop- tion with biological mysteries of blood and ment of specific therapies based on the princi- bone marrow rubbed off on him – first when ple of cancer stem cells. And while he’s proud he did his OCI post-doc work and later when he of what has been accomplished so far, there is moved on to set up a lab at SickKids Hospital. much work yet to be done.

“The pioneering work of Till and McCulloch “We’re trying to purify the cells to greater essentially developed a quantitative assay that homogeneity so we can then use molecular detects individual repopulating cells,” says techniques to identify the genetic programs Dr. Dick. “We were faced with a challenge: that are active in those cancer stem cells and how do you study a human stem cell? People then compare them to other stem cells, normal like Connie Eaves (now Deputy Director at the stem cells. That will give us some insight into Terry Fox Laboratory of the B.C. Cancer the cell of origin for cancer. When we know Research Centre) had done a lot of work that, then we can begin to understand how the developing in vitro (petri dish) assays for human genetics, the oncogenes, transform that cell stem cells. But we really wanted to focus on a and make it abnormal.” ❧ repopulating assay, which led us to the whole idea of transplanting human cells into mice and trying to make that work.” We haven’t completed the job yet. Eventually, Dr. Dick and his team showed that leukemic stem cells are the only ones capable We need to go to the next step to of kick-starting the disease and fuelling its growth. It took a while, however, for the find- understand the context within which ings to set off alarm bells around the research these cancer oncogenes are working. world, largely because scientists thought the discovery applied only to blood-borne cancers. Dr. John Dick, Senior Scientist, “It is an idea that languished for some period Toronto General Research Institute of time,” say Dr. Dick. “But it gained some traction when people applied the same princi- ple to solid tumours. Peter Dirks, one of my

Stem Cell Network Page 18 WHY I WORK IN CANADA Dr.Mick Bhatia could have gone outside of Canada to expand his program in human embryonic stem cells, but the ‘intellectual currency’ of Canada’s stem cell science and opportunities at McMaster University kept him from leaving.

Dr. Mick Bhatia hile Toronto is a hotbed of activity, what area of human embryonic stem cells study is W is happening there is only half the story. intellectual depth. In Ontario specifically – Across Ontario and throughout Canada, leading- and certainly in Canada – there are people edge research is under way in labs run by some who have been working intensely on stem cells of the world’s key players in stem cell biology. for more than 20 years. A lot of the systems that they have been working on and approach- For Dr. Mick Bhatia, who until last year es that have been used to successfully move directed the Krembil Centre for Stem Cell the field ahead, now need to be applied to this Biology at the Robarts Research Institute at new area of human embryonic stem cells. the University of Western Ontario in London, The intellectual currency that we have here Canada is the place to be. in Canada, in my view, is difficult to find any- where else. I didn’t feel that there was any rea- When Dr. Bhatia, a Stem Cell Network princi- son to set up elsewhere.” pal investigator, wanted to broaden his work, he considered all the options. He looked at Why Hamilton? At McMaster,with the expan- centres in California and other sites in the sion of the Michael G. DeGroote Medical School United States. Ultimately, he chose to become and focus on biomedical science, there is a Director of the new Cancer and Stem Cell keenness for application, for moving what has Biology Institute at McMaster University in been observed in the lab into cell transplanta- Hamilton, Ontario. tion and tissue regeneration.

“I looked at other places to do my work “McMaster wanted to create a foundation last year. I spent a lot of time in places like with a good, strong stem cell biology group California and had a lot of opportunities to that could then filter into the pipeline of cellu- work with people down there. And other places lar transplants. What they felt they needed in the States, too.There were a lot of opportu- was a highly intensive research institute focus- nities based on the investment and importance ing on human stem cells and their relationship the U.S. has made to human embryonic stem to cancer.What we believe is the novelty of our cell biology and its applications. institute is we have dedicated facilities and investigators to look at the cancer problem “One of the main reasons I stayed here… is using stem cells.We want to better understand that one of the things really needed in the new the basic problems in managing and treating

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cancer in humans. Much of the focus will be on continuing to invest in infrastructure and our work in human embryonic stem cells and building a critical mass in this growing area. how to differentiate them to produce mature “By setting up shop elsewhere, I wasn’t going cells that you can transplant into patients – like to be able to contribute to convincing the pow- those with Parkinson’s and Alzheimer’s, etc.” ers that be that there needs to be more investment in this area. I didn’t want to abandon Dr. Bhatia also wants to be around to make that intellectual depth and dedication to stem sure Canada builds on its stem cell strength by cell research that already exists in Ontario.” ❧

BUSINESS IS GOOD Canada’s strength in research has sparked considerable commercial application of stem cell science.There is a double-barreled benefit to this.Therapies to improve health and fight diseases are coming on-stream more smoothly and research funding – often taxpayer supported – is beginning to translate into positive impacts on the economy. Here are a half-dozen Canadian enterprises, ranging from small shops to large firms, who typify how Canada is turning stem cell promise into stem cell products.

Aggregate Therapeutics Inc. research institutes became founding “sub- While the long-term commercial potential of scribers” in the company.“In essence, they agreed regenerative medicine is immense, early stage to collectively commercialize their intellectual investment has been a challenge to secure. property through Aggregate,” says James Price, Scientists are necessarily focused more on basic Vice-President. “They’ve agreed to disclose any discovery than product development and product unencumbered stem cell technology coming out development expertise is scarce. Beyond that, of their labs to Aggregate so we can have a first creating a single product often involves bundling look and a first opportunity to license those tech- many technologies from several laboratories. nologies and develop them.”

To address these concerns, the Stem Cell Network Aggregate has recruited an experienced team catalyzed the creation of Aggregate Therapeutics with a track record of developing cell-based prod- Inc., a development-stage regenerative medicine ucts and taking them through the regulatory company that integrates technologies from processes. Having reviewed more than 30 tech- Canadian labs and develops them into novel ther- nologies coming out of Canadian labs, Aggregate apeutic products. is in the process of negotiating licences for three. The company has secured almost $5 million in In January, 37 of Canada’s leading stem cell sci- pre-seed funding and is in the process of develop- entists and 16 major university and hospital ing the next round of financing.

Stem Cell Network Page 20 AnorMED Inc. excellent employees here – Vancouver is a real AnorMED Inc. is chemistry-based biopharma- draw in that regard.We’ve had no trouble access- ceutical company located in the Vancouver area ing financing to do the work we need to do. The that focuses on the discovery, development and majority of our clinical trials are being run in the commercialization of new therapeutic products in United States, although we have an active site in the areas of hematology, HIV, and oncology. our Phase III trial in Vancouver.We’ve found that being in Canada is very positive to get to the point The 140-employee company has a number of where we are today.” core products and programs in various stages of development. A key one is MOZOBIL, a stem cell StemCell Technologies Inc. mobilizer currently in a Phase III clinical trials While most of the other firms included here are program for cancer patients undergoing stem cell involved in the commercialization of stem cell transplants. MOZOBIL also has potential appli- research, StemCell Technologies Inc., based in cation in the repair of cardiac tissue. Vancouver,is in the business of enabling that research.

“We are a pharmaceutical company – our prod- StemCell Technologies supports stem cell and uct is a drug, a compound that makes stem cells other life science research worldwide – the compa- more accessible,” says Dr. Michael J. Abrams, ny has customers in over 70 countries – by provid- President and CEO of AnorMED. ing research tools with a wide range of research applications such as cancer,hematology, immunol- A native New Yorker, Dr. Abrams was instrumen- ogy, cell transplantation and gene therapy. tal in setting up AnorMED in British Columbia in 1996, based on the work that he and his col- The quality of research being done in Canada has leagues had done with the drug discovery group at been helpful to StemCell Technologies in develop- Johnson Matthey PLC in the United States. ing innovative products, says Dr. Eric Atkinson, Director of Corporate Development. “For us, Canada is absolutely a great place to do business. We’ve been very fortunate to attract “We have a very close relationship with the researchers at the Terry Fox Laboratory at the B.C. Cancer Agency, particularly with Dr. Connie Eaves, who has been very active in establishing functional assays for a variety of different types of stem cells.Those functional assays are fundamental in helping the field move forward – they are the gold standard for really being able to say a cell is actually a stem cell.”

Stem Cell Therapeutics Corp. Stem Cell Therapeutics Corp. (SCT) is a Calgary- based biotechnology company focused on the development of its technology platform and intel-

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lectual property to selectively induce a patient’s in developing drugs that do that in specific own stem cells to proliferate in the brain. context in the heart and skeletal muscles.”

SCT wants to develop this fundamental technolo- Currently at the discovery stage, StemPath is gy for treatment of stroke and, potentially, engaged in proof-of-concept experiments and Huntington’s disease, Alzheimer’s disease, anticipates entering into preclinical testing by multiple sclerosis and other neurodegenera- early 2007 with a lead candidate for treatment tive disorders. In animal studies, SCT’s lead of heart patients who have experienced acute product, NTx(TM)-265, has been demonstrated myocardial infarction. to increase the number of innate adult stem cells, regenerating damaged brain tissue and improving “We’ve been hitting our milestones,” says Dr. neurological and motor function. Rudnicki.“The experimental results have been very promising and are validating the approach we’ve “We’re moving forward clinically,” says Dr.Joseph been taking.” Tucker,SCT’s President and CEO. He co-founded SCT with Dr.Sam Weiss, the Stem Cell Network Transition Therapeutics Inc investigator who discovered that neural stem cells Transition Therapeutics Inc. is a Toronto-based, can be manipulated to generate all the major cell product-focused biopharmaceutical company types in the central nervous system. that is developing regenerative therapies for the treatment of diabetes, Alzheimer’s disease, multi- “We’ve received approval to do a Phase IIa study ple sclerosis and hepatitis C. in the United States,” says Dr.Tucker.“We want to see if the efficacy we’ve seen in animal models, The company’s Islet Neogenesis Therapy (I.N.T.™) which has now been replicated in several labs, can offers hope for millions of diabetic patients be translated to human stroke patients.We will be dependent on daily insulin injections and strict watching with great eagerness.” diet regimens. It has the potential to free them from regular insulin injections for long periods of StemPath Inc. time by enabling the body to regenerate its own StemPath Inc.,an Ottawa-based biotech firm,aims insulin-producing cells. to become the first pharmaceutical company specializing in therapeutic solutions for skeletal “Any therapy that can reduce or eliminate and cardiac myopathies that modulate the body’s insulin usage by diabetics would have a signifi- natural regenerative capacity. cant impact on the management of the disease” says Dr.Tony Cruz,Chairman and CEO.Transition’s “In most people’s minds, stem cell therapies interim data showing three of four type I dia- involve transplantation of stem cells,” says Dr. betes patients reducing their daytime insulin Michael Rudnicki, Founding Scientist of StemPath. usage by 35 to 75 per cent, while preliminary, “The feeling of many of us is that regenerative are very encouraging and represent an impor- medicine will have arrived when we have drugs tant step in the development of the first diabetes and therapies that will stimulate and harness regenerative therapy. ❧ stem cells present in our bodies. We’re interested

Stem Cell Network Page 22 CRITICAL MASS

A University of Toronto, 27 King’s College Circle The University of Toronto is one of the country’s leading research institutions.The University has gained an international reputation for its research, ranking among the leading providers of innovative research in the world.

Stem Cell Network researchers at the University of Toronto include: Jane Aubin, Julie Audet, Abdullah Daar, Peter Liu, Cindi Morshead, Molly Shoichet, William Stanford, Duncan Stewart, Vince Tropepe, Derek van der Kooy, Peter Zandstra, Juan Carlos Zuniga-Pflucker.

B Princess Margaret Hospital, 610 University Avenue Home of the Ontario Cancer Institute, it was originally located at 500 Sherbourne Street, Princess Margaret Hospital moved to its current location at 610 University Avenue in 1995. Princess Margaret Hospital ranks among the top centres in the world for bone marrow transplantation.The hospital’s bone marrow transplant unit, established in 1971, was the first in Canada to perform allogeneic transplants – transplants between unrelated donors.

Stem Cell Network researchers at Princess Margaret Hospital include: Ernest McCulloch, James Till, Norman Iscove.

C Hospital for Sick Children, 555 University Avenue The Hospital for Sick Children (SickKids) is one of the largest paediatric academic health science centres in the world, with an international reputation for excellence in health care, research, and teaching.

Stem Cell Network researchers at SickKids Hospital include: Janet Rossant, John Dick, Peter Dirks, James Ellis, David Kaplan, Rod McInnes, Freda Miller.

D Toronto General Hospital, 200 Elizabeth Street For more than 165 years, the Toronto General Hospital has provided acute care patient services to the surrounding community. Located in downtown Toronto,Toronto General Hospital has numerous medical and surgical program specialties including heart disease, kidney disease, transplantation, eating disorders clinic, tropical disease, women’s health, nephrology, immunode- ficiency clinic and psychiatry.

Stem Cell Network researchers at Toronto General Hospital include: Andre Schuh

E Mount Sinai, 600 University Avenue Home of The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre, was established in 1985. It is one of the world’s leading centres in biomedical research.

Stem Cell Network researchers at Mount Sinai Hospital include: Andras Nagy

www.ontario.ca/innovation

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ISSCR Meeting Venues

1 MaRS Auditorium, MaRS Centre, 2 Metro Toronto Convention Centre, 3 Fairmont Royal York, 101 College Street Location of 255 Front Street Location of 100 Front Street ISSCR Public Symposium ISSCR Annual Meeting: Headquarters hotel for ISSCR June 28, 6:00 - 8:00 pm June 28 - July 1 *Location of meeting attendees SCN Jr. Investigators Social Event Thursday, June 29, 7:30 - 9:00 pm

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