The flat fluorescent glare shines late into the night at the nexus of University and College streets. Illuminated offices dot the evening sky, static above the hum and wail of the city's heart.
In nearby emergency rooms, lives are won and lost. But under those quiet lights, away from emergency's frantic pace and panic, scores of researchers perch over microscopes and sift through reams of data, devoting days and nights to the unknowns of human function.
This is Toronto's research district, a maze of concrete and glass where the finest minds collaborate, turning the city into a global centre of biomedical discovery.
Nine research institutes employing 5,000 university faculty members, 2,000 graduate students and 1,100 postdoctoral and clinical fellows lie within a 20-minute walk of each other. This biomedical cluster at the heart of Toronto is one of the largest on the continent, and is one of the 10 largest in the world.
In the past two years, the city has scored some major coups, luring world-leading cancer scientist Tom Hudson from Montreal; cell biologist Ben Neel from Boston; and stem-cell biologist Gordon Keller, who came to Toronto in 2006, just months after New York magazine named him one of the scientists that city could not afford to lose.
Toronto is also home to Tak Mak, who discovered the "key to the immune system" T-cell receptor, and John Dick, who discovered the first cancer stem cell in 1994 and last year grew a human cancer in a lab mouse for the first time.
But one just has to look at 12 of Toronto's leading researchers (seen at right and profiled inside) to see a cross-section of our medical community's great achievements - from reversing the damage caused by heart attacks and spinal injury to better understanding our immune system through the study of sea urchins.
Each of these researchers is set to break new ground in 2008, and their stories represent just a fraction of the exceptional work being pursued in Toronto.
"There's an enthusiasm in the research community that's very exciting to be part of," says Dr. Keller, who now heads the McEwan Centre for Regenerative Medicine.
Dr. Hudson, who left Quebec to head the Ontario Institute for Cancer Research, says the city's "tremendous power" is built on a strong history: Stem-cell research began here.
"It's innovative," he says of Toronto. "I've never felt closer in my research career to thinking we will have an impact. I feel my goals are going to happen here."
But the sector's size is also its greatest challenge. While government funding changes in the mid-1990s helped to create the current fertile environment, Peter Lewis, vice-dean of research for the University of Toronto's faculty of medicine, says co-ordinating and running the research is expensive. "What we really need is the full cost of research [to be]funded," he says.
For every dollar given to research, U of T must source 83 cents for related, indirect costs. U.S. colleges generally only have to source 50 cents per grant dollar, he says. "That's what's really limiting us," he says. "We [in Canada]do need a little bit more."
That bid could be difficult. A survey of the nation's federal politicians last year showed that most policy-makers do not realize that grants don't cover indirect costs of research, and were largely unaware that hospitals have become the driving force of health research.
Still, John Evans, board chairman of the non-profit MaRS Centre, which helps to turn research into viable businesses, envisages a day when research is seen as a social and economic driver, and the city shines as brightly as better-known centres such as Boston and Palo Alto.
And the physical concentration of Toronto's research in a strong, shining core gives it an advantage no other city shares, he says.
"When you develop a concentration of people with a shared objective and bring different skills, that's when most rapid advances will occur," he says. "Toronto has a chance to do that, to develop areas of tremendous strength. It's a very exciting time. There's tremendous vitality."
MEDICAL MINDS
PRABHAT JHA: THE NUMBERS GUY
Saving lives by charting millions of them
Dr. Jha is the director of the Centre for Global Health Research at St. Michael's Hospital
Prabhat Jha likes to joke that he's professionally obsessed with sex and death. As lead researcher on the Million Death Study - the largest health study in the world - he's only partly kidding.
The Indian-born researcher, who was raised in Winnipeg, did his PhD at Oxford and was then lured to Toronto from the World Health Organization in Geneva, has already had a massive impact on worldwide health. His essays showing the impact of tobacco control around the world spurred the Bill & Melinda Gates Foundation and the Bloomberg Family Foundation to pour hundreds of millions of dollars into global tobacco control and formed the basis of the WHO treaty against tobacco in 2005.
Since 1997, he has been recording and analyzing deaths in southern India. So far, 350,000 have been recorded, with 650,000 more to be done by 2014. Field researchers speak to families about both how the deceased lived and how they died, in a bid to find out more about "the world's big killers."
"I have a nerdy love of numbers that most people can't understand," he admits jovially in his downtown Toronto office. But at the start of the 21st century, with health surging into the public spotlight, he says these numbers are proving essential. "There's some serious money that's being put on the table," he says. "We could have a rapid transformation of the lives of a billion poor."
The Million Death Study covers 14 million people in two million households over about 14 years, and is creating a wealth of information. Dr. Jha's plans to store a drop of blood from each interview subject could one day turn the database into the world's largest bio-bank as well.
Not even halfway through the project, the impacts are already being felt. The earliest data showed there are up to 10 million girls missing from the Indian population. Two decades of selective abortion was shown to be the likely cause, a finding that spurred debate and government action in 2006 to improve support for girl children and help change the public perception that girls were less worthy.
This year, their calculation of HIV numbers in India turned up a startling result, one the researchers did not believe at first: The spread of HIV has declined in that country, a drop chiefly attributed to improved education for sex workers in the south. That finding was a major factor in the United Nations' decision to reassess its global HIV numbers. In November, the global estimate of people living with HIV was reduced to 32.7 million from 39.5 million, and the education program in India's south is now being extended across the country.
While his data-analysis work is viewed as a curiosity to some, it has real-world impact. Dr. Jha's tobacco studies have helped persuade Caribbean nations to take tobacco control seriously.
"You can come up with all these gee-whiz-fantastic essays and new molecular discoveries and the like, but they ultimately have to be tested in the human population for their relevance," Dr. Jha says.
"I think both are really beautiful sciences. Toronto's really good at that basic, elegant science work, but just understanding how disease unfolds in a population is also beautiful."
Q&A
Most influential role model:
Sir Richard Peto, University of Oxford, and Sir Mick Jagger.
Most satisfying point of your career so far:
Designing, in 1999, the national AIDS program in India, which has turned around the HIV epidemic in South India. And writing the reports that became the basis for a worldwide treaty on tobacco control.
Best-kept secret in the research district:
B Espresso Bar on Queen Street East.
Your favourite thing/place/activity in Toronto:
Sherwood Park with my daughters on a sunny day.
What you do to forget about work:
Ask my wife why the heck she married me.
Toughest part of your job:
Dealing with management consultants who think they know public health.
Average duration of New Year's resolution:
I keep the resolution, but just switch to Chinese, Indian or Ethiopian New Year dates as needed.
STEVE SCHERER: GENOME TRACKER
Racing to solve the puzzle of autism
Dr. Scherer is a senior scientist in the field of genetics at the Hospital for Sick Children. He is also a professor of medicine at the University of Toronto.
At right: Dr. Scherer jogs in High Park.As Steve Scherer celebrates his 44th birthday today, he won't have to look far to count his blessings. There are his wife and two young children, the million-dollar research grant he will receive this month from the Wellcome Trust, and the satisfaction of seeing Science Magazine name the genetic studies he worked on Story of the Year for 2007.
But one thing remains out of reach, although he is getting closer to an answer each year: understanding the genetics of autism.
Every human genome is 99.5 per cent identical. The few changes are what make everyone unique. Some mutations make us better; others have no noticeable impact. Sometimes a change hits a critical gene, leading to disorders or disease.
"Everybody carries these changes. It's just a roll of the dice. Some lead to medical outcomes. Some don't," Dr. Scherer says.
The Hospital for Sick Children has been cataloguing genetic variations for a decade, creating a massive information bank called the Database of Genomic Variants, now known worldwide as the Toronto database. When American scientist Craig Venter became the first human to have his entire DNA sequenced this year, he came to Dr. Scherer to analyze it.
By cataloguing the differences between humans, or the "copy number variations," Dr. Scherer hopes to find what mutations predispose people to certain diseases. "It's arguably the hottest topic in science," he says. "We have no idea what we're going to find. Every time we look closer and closer, we find interesting things."
But his main focus is the spectrum of disorders known as autism. In a paper to be published this year, he shows that 7 per cent of autism cases share a certain variation in genetic copy numbers, involving specific regions of the chromosome. That means a couple of genes are definitely involved in autism, he says.
That knowledge can help develop faster genetic testing and better therapeutics, but he stresses that it does not solve the entire puzzle.
"Autism is a complex condition. It's a group of many different conditions. Some are single gene changes, some probably very complex," he says.
By using what's known as "discovery science" - a brute-force approach that basically throws a lot of ideas on the wall to see what sticks, as opposed to exhausting one idea before moving onto the next - he says entirely new avenues are opening up very quickly. "Things go so fast now," he says. "No one has a five-year plan any more. Things change almost on a monthly basis."
Q&A
Most influential role model:
My PhD supervisor, Dr. Lap-Chee Tsui, who discovered the cystic fibrosis gene and is now president of the University of Hong Kong.
What you always forget about your specialty area:
Meiosis (how chromosomes pair and exchange DNA).
What you expect to achieve or discover in 2008:
Sequence the genome of the most famous person in history, find more autism susceptibility genes and then pick up the pace in the second and third quarter of the year.
Best-kept secret in the research district:
How to win a Nobel Prize in Medicine (tongue in cheek since nobody in Toronto has one).
Toughest part of your job:
Keeping on top of the 200 e-mails I receive each day.
Favourite quote:
"Life is what happens to you when you're busy making other plans." - John Lennon.
DARCY FEHLINGS: REHAB GAMER
Turning fun into cutting-edge therapy
Dr. Fehlings is a developmental pediatrician at Bloorview Kids Rehab, and also does research in the area of cerebral palsy. At right: Dr. Fehlings skating at Rennie Park with her son, Nick.
Botox and video games aren't often lauded as gifts to humanity, but for developmental pediatrician Darcy Fehlings, they are secret weapons to help children with cerebral palsy.
Through her work at Bloorview Kids Rehab and the University of Toronto, Dr. Fehlings is pioneering the use of botulinum toxin to relax the stiff muscles of children with the disease, which affects two to three people in every 1,000.
The botulinum toxin - which is also the basis for Botox - is injected into muscles to ease the spasms and stiffness that can cause stunted growth and twisted limbs. While the muscle is temporarily relaxed, rehab workers can move the affected muscles and limbs to relieve pain and promote normal growth. In some cases, Dr. Fehlings hopes the treatment may even help children avoid altogether the orthopedic surgery that is often used to cut muscles and release tightness.
Meanwhile, her team has linked up with rehabilitation engineer Tom Chau to create virtual-reality games for children who have a weakened side, one of the most common symptoms of cerebral palsy. Using virtual-reality games, children unwittingly use the weak arm or hand that usually may be ignored.
"It is a mainstream activity so that kids with disabilities aren't singled out when they are doing their therapy," Dr. Fehlings said. "It is also something that they can do with friends and siblings in the home rather than coming to the rehab institute."
And for children with the condition, being given a prescription for half an hour of play time isn't too hard to swallow.
This year will be important for Dr. Fehlings's research: Her team will evaluate the games' effectiveness, while a long-term study of the botulinum treatment - which was used for 416 children in 2006 - will begin this year.
On top of that, Dr. Fehlings, who is married to neurosurgeon and researcher Michael Fehlings (see page M4), was named the first chair in development pediatrics for the Bloorview Children's Hospital Foundation in November. She will also head Bloorview's Centre for International Leadership in Child Development, which she hopes will be launched this year.
"It's always difficult to gauge the impact of your work," Dr. Fehlings said. "A banner year would be a positive outcome, but we have to wait to see what the research shows."
Q&A
What you forget about your specialty area:
How much time it takes to do things well!
What you do to forget about work:
I'm learning how to play the guitar.
Best part of your job:
Because of my dual role as a doctor and scientist, I can bring together clinicians, scientists, graduate students and families to create cutting-edge treatments for children with disabilities.
Most demanding aspect of working in medical research:
Figuring out the important research questions to ask in order to improve the lives of children with disabilities and their families.
Favourite quote:
"Seize the day, put not trust in the morrow!" (Carpe diem, quam minimum credula postero) - Horace.
Average length of New Year's resolution:
I avoid New Year's lists. I prefer a daily "to do" list.
KELLY MACDONALD: VIRUS FIGHTER
Getting Creative With The Hiv Vaccine
Dr. MacDonald is a physician and a microbiologist at Mount Sinai Hospital. She is also the director of the HIV research program and holder of the Ontario HIV Treatment Network endowed chair of HIV research at U of T
At right: Dr. MacDonald drawing in her home studio.
When the news emerged in the mid-1990s that a group of sex workers in Nairobi were naturally resistant to HIV, Kelly MacDonald was already thinking beyond the headlines. The new clue to resistance was stunning, but as part of the University of Manitoba's research team in Kenya, she realized they were still a long way from beating such a rapidly mutating virus.
Recruited to the University of Toronto in 1994 and now heading its HIV research program, Dr. MacDonald hopes that she is about to unlock another piece of the puzzle that is HIV/AIDS.
In the rapid-fire delivery of a woman with too many ideas and too little time, Dr. MacDonald says her light-bulb moment came during a lecture she was giving about chicken pox. HIV vaccines are expensive and must be regularly boosted, so she had been searching for a way to get those vaccines into the body in a simple, targeted, long-lived way. Suddenly, she realized: Why not attach the HIV medicine to a chicken-pox vaccine?
The chicken-pox vaccine used in Canada is a live virus that has been crippled to make it virtually harmless. Injecting it into the body gets the natural immune system to fend off the illness with minor risk and means the body can recognize the full virus if it's contracted. "Why couldn't we use this vaccine as a vector, or carrier?" she wondered. A child could receive an HIV/chicken-pox vaccination, with a booster late in life. Dr. MacDonald believes this approach could work well in Africa, where chicken pox is uncommon and adults wouldn't yet have been made resistant.
So far, her research team has built an HIV vaccine into the human chicken-pox vaccine, but to test it, they have to use animal models.
It's not known if Rhesus macaques used in testing can handle the human chicken-pox virus (without the HIV vaccine). The team should find that out this month. If it works, the study could move on to the HIV/chicken-pox combination almost immediately. If not, the researchers will have to build the HIV vaccine onto a monkey virus, setting the project back about nine months.
Through clinical work in Kenya and research work based in Toronto, Dr. MacDonald says she can retain her confidence while facing the challenge of HIV/AIDS.
"Before I came here, we didn't really have any HIV lab research. Now we have probably one of the best known immuno-biology labs of HIV," she says.
That collaboration between Toronto, Manitoba and Nairobi is seen as one of the most important projects in HIV worldwide, she notes, and her team has collaborations all around the world.
According to Dr. MacDonald, if they choose the wrong carrier virus, the entire project could fail. "Vaccine research almost always fails. I almost don't dare to dream too big," she says. She also admits a vaccine alone will not beat HIV: Public education and behavioural change is needed too. "There's not going to be a magic bullet."
Nonetheless, the gains brought about by a vaccination would be significant. "Every day that we have a delay, we're paying a huge price as a society," Dr. MacDonald says. "This is a very novel strategy, a prototype that could offer us a big jump ahead."
Q&A
Your one-line response to "So, what do you do?"
Mostly I change the topic because it always generates more questions if I admit the truth. If I confess, I usually limit it to "I am a scientist." That way I get to hear about them instead of listening to the same old stuff from me.
What you always forget about your specialty area:
My pager number! It keeps getting changed, or maybe it's a subliminal wish to receive fewer midnight calls.
Best part of your job:
Struggling along with my graduate students to get them through their PhDs, then watching them defend their theses and go on to surpass all of my achievements.
Most demanding aspect of medical research:
The requirement to be "on your game" constantly, over a whole career. In science, you are really only worth what you have produced in the last three years.
RANDY MCINTOSH: BRAIN CARTOLOGIST
Cooking up a map of the mind
Dr. McIntosh is a neuroscientist at the Rotman Research Institute's Baycrest Centre.
At right: Dr. McIntosh prepares a gourmet meal for himself and his wife, a Friday-night tradition
The knife slices into juicy flesh, liquid spilling over Randy McIntosh's hand. He flings another ingredient into the pan. When this researcher isn't using his brain to find ways to see into yours, he's in the kitchen, cooking up another original feast.
"The nice thing about cooking is you start with a way from going from this mess of ingredients to a meal, but along the way you might change things," he explains. "Despite what people think, that's how the brain works."
According to Dr. McIntosh, if one brain area is disrupted, others cover the gap, with varying degrees of success. Slurred speech after a stroke may not be due to the injury: It could be the brain's flawed effort to recover from injury. The brain reorganizes itself, but never in exactly the same way. "That's how cooking is. You don't put exactly the same amount of salt in each time, but the final meal is much the same," Dr. McIntosh says.
The brain is not like a computer, he adds, describing it rather as an orchestra in which each section acts in relation to every other section.
For his work at the Rotman Research Institute, which is part of the Baycrest Centre, volunteers are hooked up to machines that record brain activity. They then do a variety of tasks to gauge reaction time, memory, attention and other functions, and the results are turned into a map of the brain's function (its "dynamic range"). Some brains exhibit more localized activity, while others have a larger dynamic range. Under current theory, the more widespread the brain's function, the better a person's ability to recover from injury.
"It has pretty profound implications about how mental function comes about, but also how to deal with disease," Dr. McIntosh says.
Toronto is one of three or four centres in the world pursuing this idea, and Baycrest hopes to open a Centre for Brain Fitness by the end of this year. In the meantime, Dr. McIntosh is wading through dynamic-range maps in a bid to create standard maps that could be used to predict treatment outcomes.
Dr. McIntosh hopes to create a five-minute diagnostic test one day that would gauge the health of a person's brain and pick up any changes or early problems, with referral for a full test if necessary. Plus, dynamic-range mapping during rehabilitation could show in real time whether it's working, he notes.
"I think we're at the point now in understanding how the brain works that we need a new perspective on the whole enterprise," he says.
Q&A
What you always forget about your specialty area:
High-pass vs. low-pass filters. We use them for data processing and the terms are backwards from what you would think intuitively. Wikipedia is great for straightening this out.
Your exercise regime:
Running and yoga, primarily to compensate for my love of food.
Who/what shares your home:
My wife, who is also a scientist, and a neighbourhood cat, who has taken a liking to us and probably three or four other homes.
Average length of New Year's resolution:
There were two that I can remember. The first was in grad school when I resolved to quit smoking. I haven't smoked since. The second was to cut out junk food. I had Cheezies and a beer when I got home last night. So I guess the average is somewhere between forever and never.
HELEN MCNEILL: PATHWAY EXPLORER
Uncovering the true nature of cancer
Dr. McNeill is the director of the collaborative program in developmental biology at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital
At right: Dr. McNeill in the Cedarvale Ravine, one of her favourite spots in the city.
There are many holy grails in cancer research, and Helen McNeill hopes 2008 will take her a step closer to finally holding one aloft. Her groundbreaking work, which she began at Cancer Research UK in London and brought to Toronto in 2005, looks at how cells organize into tissues. At heart is the question of why one cell stops growing while others surge out of control through the body.
Experimenting mostly on fruit flies - whose two-week lifespan she says both promotes quick results and alleviates some measure of guilt - Dr. McNeill has been unlocking the secrets of a gene named Ft (scientists commonly call it "fat"). Ft is an adhesion molecule that not only binds proteins together, but also tells cells how they should interact with other cells, and how large to grow. When an organism has a problem with Ft, the cells overgrow and can turn into tumours. Without the gene, you couldn't exist, she says. With one hitch, you could be prone to a disease or illness.
In something of a global watershed last year, a number of labs simultaneously realized Ft's role in cell change, finding that Ft regulates both cell size and pre-programmed cell death called apoptosis (which occurs if a cell is damaged). Dr. McNeill's lab is the only one thus far to apply that research to vertebrates. Its studies found that mice without that binding-and-communication molecule develop "a bunch of human diseases" involving kidney function, hearing and other things, Dr. McNeill said.
Ft is also involved in a pathway called Hpo (known as "Hippo"). A pathway is a group of cells that perform a certain function, and Hpo is emerging as a major new player in cell control. It is implicated in a large number of human cancers, including breast cancer, sarcomas and liver cancer. The pathway is the same in fruit flies and humans, and Dr. McNeill is hoping to uncover what specific role Ft plays in Hpo's function.
By fully knowing Ft's part, Dr. McNeill hopes that pharmacists could create something that inhibits the growth of disease. "It helps understand disease more and might help find therapy," she says. "We could have drugs to treat this regulation. That's certainly the hope, but it's a long, tough thing."
Mutations of the Ft gene could also become a biomarker to help identify women at most risk of breast cancer and cancer recurrence. "It's going to be very important for a bunch of human cancers and a bunch of diseases," she says.
Q&A
What you do to forget about work:
Be with my family - ski, hike, read books.
Your favourite activity in Toronto:
Biking with family through ravines.
Best part of your job:
When you get a totally surprising result you hadn't expected, then trying to fit it in with all we know.
Toughest part of your job:
Knowing when to stop an area of investigation.
Favourite quote:
"Science has great beauty. A scientist in his laboratory is not only a technician: He is also a child placed before natural phenomena which impress him like a fairy tale." - Marie Curie.
Your exercise regime:
Sporadic at best. First thing to be dropped when faced with home or work demands.
Who/what shares your home:
Connor (son), Geoff (husband) and Keiko (kitten).
Anne-Claude Gingras is an investigator of systems biology at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital.
ANNE-CLAUDE GINGRAS: PROTEIN DETECTIVE
Studying the secret of disease's off-switch
At right: Dr. Gingras at the Dark Horse Espresso bar, one of her haunts
As a young leader in protein studies working in Seattle in 2005, Anne-Claude Gingras was flooded with job offers from around the world: Switzerland, the United States and her home province of Quebec all wanted the talented researcher. But when Toronto came calling, she couldn't say no. "It's definitely the place to be in Canada, and I'd say top five in the world," she says.
Now, as the youngest principal investigator at Mount Sinai Hospital's Samuel Lunenfeld Research Institute, Dr. Gingras is studying a family of proteins that could play a role in the development of cancer, drug resistance, and even in innate immunity.
The group she is focusing on, a complex called protein phosphatase 4, controls cells by adding or removing phosphates to activate certain actions, in essence turning a cell on or off. By themselves, they don't do much, she says, but together, the proteins affect cell growth, division and other activity. "When this protein [group]gets deregulated," she says, "the cell doesn't stop when it's supposed to, and bad things happen." Bad things like cancer.
But it may not be the proteins themselves determining what changes occur: Dr. Gingras says the binding partners that hold the structure together could be the key.
"My dream would be to be able to really validate the link with DNA imaging," she says, referring to a process she is going to explore using leading-edge mass spectrometry equipment at the Lunenfeld Institute. If that is validated, the research could one day be used for human treatment. "I hope that would be feasible. We want to cure people. We want to help people," she says.
Dr. Gingras has already found a link between this protein complex and human resistance to the cancer drug cisplatin, used to treat many forms of cancer. It's one of the most potent anti-tumour agents known, but many patients become resistant to the therapy. "By working out why and how, we can understand how to get a better therapy for people who've had cancer and are resistant to those drugs," she explains.
This year, Dr. Gingras will be pushing the boundaries of knowledge again, investigating PP4 and another very large protein complex she believes is related to innate immunity. While she is hush-hush about details - an article on the subject is pending publication in a leading journal - she says it appears the new protein complex could be an on-off switch for genes that helps to create an immediate defence system against infection.
While she foresees a "really, really nice year" ahead for her lab, she admits that few people outside the science realm will probably be interested. Even for researchers, the big picture can be intimidating.
"It's amazing," Dr. Gingras says. "The human system is so complex. Every cell type behaves in a slightly different manner. It's a bit daunting if you sit down and think about it."
Q&A
What you forget about your specialty area:
I always forget that cells in culture don't know it is the weekend.
High point of your career:
Probably finally getting a "real" job, so that my uncle stops asking me why it is taking me so long to get done with school.
What you do to forget about work:
I cook - same principle as doing experiments, but sometimes it tastes better.
Most demanding aspect of medical research:
It really is a balancing act where you must design experiments, bring in money, train students and fellows, administer the funds and communicate scientific results. You frequently end up working long hours.
Your exercise regime:
Flexing my thumb muscles by pipetting, running to catch the streetcar and pretending I am doing yoga.
Who shares your home:
Another scientist! Hours of exciting conversations at breakfast.
MICHAEL FEHLINGS: NERVY INVESTIGATOR
Shaping solutions to spinal cord injury
Dr. Fehlings is the Krembil Chair in Neural Repair and Regeneration, the medical director of the Krembil Neuroscience Centre at Toronto Western Hospital, and a professor of neurosurgery at University of Toronto
At right: Dr. Fehlings works on the Christmas tree he cut down from his family farm.
Medical success is relative. One paraplegic person learns to walk again; another learns to hold a glass. For neurosurgeon Michael Fehlings, both events are equally momentous. When the nervous system is involved, every gain can be a life-changer.
As a young surgeon in the early 1990s, Dr. Fehlings saw many people with spinal-cord injuries whose lives weren't being made much better in the hospital. It seemed medicine wasn't doing enough, he says, so he dived into research.
Now, as a dominant force in neural medicine, Dr. Fehlings believes that spinal-cord research and regenerative medicine are about to enter a golden era, one where theory will turn into viable treatments. "The old rules don't apply any more," he says.
In a major trial led by Dr. Fehlings last year, doctors operated on damaged spinal cords within hours of the injury. Some results were striking: One man paralyzed from the neck down after a skiing accident near Barrie, Ont., recovered near-normal function.
While that result was exceptional, Dr. Fehlings said it was a promising example of what early intervention can achieve. This year, national protocols to adopt early surgery will be developed, and Dr. Fehlings hopes that it will be standard practice within five years.
He is also leading other trials that use drugs and stem cells to reduce damage in the spinal cord, and possibly promote regrowth. One drug, riluzole, protects neurons from an influx of sodium. Sodium is a trigger that kills off cells that are damaged, such as those hurt by spinal-cord injuries.
Early studies in mice produced "astounding" results when the drug was applied after spinal-cord injury, Dr. Fehlings said. "It reduces the extent of the injury by about 50 per cent," he said.
Another drug, Cethrin, blocks a molecule that also kills off injured cells. The first phase of drug trials produced a 30-per-cent improvement in neurological recovery, well above the norm of 5 to 10 per cent. A year after treatment, one paralyzed man was able to move his hand, regain some bowel and bladder control and reposition himself in a wheelchair. The drug will enter randomized clinical trials this year.
"This is not a home run," Dr. Fehlings says. "It's a step in the right direction, but for somebody who can't even move their hands or has no bowel or bladder function, restoring some of this allows major improvement."
While Dr. Fehlings doubts there will ever be a true "cure" for the neural damage sustained in spinal-cord injuries, trying to attain that goal can create great benefits. "Even a relatively small amount [of recovery]can have a huge impact."
Q&A
Most influential role model:
My mentor in neurosurgery and spinal-cord injury, Dr. Charles Tator.
Best-kept secret in the research district:
Toronto is becoming the "Medici Court" of biomedical research of the 21st century - an incredible talent pool.
Your favourite place in Toronto:
I love High Park and the proximity to the waterfront of Lake Ontario.
Toughest part of your job:
Realizing that despite my best efforts, I can't always save people's lives or impact on their disability.
Favourite quote:
"I am a lucky man and the harder I work, the luckier I get."
Who shares your home:
My wife, Darcy, who is an academic developmental pediatrician at Bloorview and our son Nick, age 16. Our daughters Tara, 21, and Lauren, 19, are at university.
DAVID JAFFRAY: IMAGE MAKER
Rocking the radiology world
Dr. Jaffray is the head of radiation physics at Princess Margaret Hospital
At right: Dr. Jaffray strums a tin-and-wood guitar he made with his son, Alexander.'Too little," David Jaffray says, referring to what humans know about cancer tumours. "Way too little, considering how big a problem it is."
And yet, when sick people seek treatment, doctors have to act. "You have to treat them without the complete picture," Dr. Jaffray says.
As a physicist with the University Health Network, Dr. Jaffray is finding ways to fill in that picture. At the turn of the century, he developed an imaging system that allowed doctors to watch how a patient responded to treatment. That revolutionary targeting system is now used in 80 per cent of imaging systems.
"The human body doesn't take the same shape in two seconds apart, let alone two years apart," Dr. Jaffray says. This new system can essentially change the radiotherapy target field as a person breathes.
One theory says this tailored radiation treatment will produce better results. But Dr. Jaffray thinks that it will also help reveal when the radiation treatment isn't working, allowing patients to stop that treatment and pursue other options.
But for him, this advance prompted a question: Should doctors change their methods to match the technology?
The technology for "adaptive radiation therapy" - altering treatment as the situation changes - is being refined, but Dr. Jaffray says traditionalists will be hard to win over. Interventions like radiation are extremely serious and are rarely ceased early.
Yet the possible impact of adaptive techniques - which could require changing treatments on the fly - makes him believe doctors should embrace the technology and consider trying more fluid approaches to treatments.
"Unless we start to explore the use of them, I don't think new innovations in biology will be able to impact patients," he says. "... I think we'd all love to hear a magic bullet, and I guess I'm not willing to wait for one."
A number of Dr. Jaffray's projects in 2008 will push that bid further. His research team will try to improve imaging so cancers can be more accurately targeted, and continue using computer simulations to see if patient treatments should be redesigned.
Plus, he is exploring how nanotechnology can be used to make cancers more sensitive to radiation, with a paper expected to be published in spring.
"What's cool about Toronto right now, there are a number of hot areas that just taste like they're all connected somehow," Dr. Jaffray says. "Cancer, imaging, stem cells. You get the feeling that something's going to come out [of it]"
Q&A
Your one-line response to "So, what do you do?"
I use physics to help treat cancer patients.
Most influential role model:
My dad.
What you always forget about your specialty area:
To say "nuclear" not "nucular."
Best-kept secret in the research district:
It wouldn't be a secret then, would it?
What you do to forget about work:
Go north.
Your exercise regime:
Walk fast.
Average time you maintain a New Year's resolution:
Never made one.
MOLLY SHOICHET: THE REGENERATOR
Spinning ideas to save spines
Dr. Shoichet is a professor at the University of Toronto, much of her work dedicated to cellular and biomolecular research.
At right: Dr. Shoichet with her two boys, Sebastian, right, and Emerson.
Adamaged spine is like a no man's land, the injury forming a core impact zone that widens into a region of pain and loss. Or it's like a bombed-out highway, the control centre - the brain - cut off from the rest of the body.
No matter how Molly Shoichet explains it, her deft hands drawing stick figures on the paper before her, the optimism in her voice doesn't waver: There could be a way to repair it.
Dr. Shoichet holds the Canadian research chair in tissue engineering, and according to Peter Lewis, vice-dean of research in the faculty of medicine at University of Toronto, she is a world leader in the field of regenerative medicine.
Her team is currently developing a gel that can be pumped full of drugs or stem cells, and then injected into the spinal cord. Unlike drugs delivered with a liquid, these gel drugs aren't spirited away via spinal fluid, and the gel prevents spinal fluid from escaping into the body. Early tests in rats show that the gel performs much better than a liquid drug.
"If we get [the drug]right where it needs to be, you don't get all that related toxicity," Dr. Shoichet says, referring to the damage that can be wrought when spinal fluid escapes into the body.
Then there is her work building a hydrogel to act as scaffolding for damaged spinal cords. This cylinder of special plastic could coax damaged nerve-cell lines called axons to grow along their original paths, to reconnect, to regenerate, while protecting them from the body's growth-inhibiting chemicals. "That concept was out there, but what we've done, which is new, is the engineering," Dr. Shoichet explains. "We're trying to use materials that make sense. When it was first done, they were using chemicals used in carpets."
When she was working with polymers at a leading stem-cell lab in the United States, Dr. Shoichet had no concept of the intricacies of spinal-cord research.
Now, she says, her dream is to have a direct impact on patients, although she quickly points out that these treatments probably won't work for everyone.
"If they can't walk out, at least we can give them better quality of life," she says. "Walking is a big step. ... It's more realistic to think about one thing at a time."
As if all that isn't enough, Dr. Shoichet is also finding ways to beat breast cancer. In her work with cancer drugs, she is creating nanoparticles that are the right size and chemistry to circulate in the body long enough to track down metastasized breast cancer, get through the cancer's walls and deliver drugs such as Herceptin right to the tumour.
"It works beautifully in the lab," she says. "Now, we have to demonstrate it works beautifully with animal models." That work involving mice will begin this year, with results emerging later in 2008.
Q&A
Most influential role model:
I have several for various aspects of my life, but my most influential role model is definitely my mom, Dorothy Shoichet.
Your favourite thing/place/activity in Toronto:
I love going to the zoo. With two kids (and being a kid at heart), I love taking advantage of the many kid-friendly places. We love going to the ROM as well.
How you forget about work: I love to spend time with my children and get involved in their lives, such as coaching their soccer teams or taking them skiing.
Your exercise regime:
Not good enough! I do try to stay active, but balancing family and work commitments seems to take away from consistent exercise (I should put this on my New Year's resolution list - again).
Who shares your home:
My supportive husband, Kevin Bartus, and my two beautiful boys, Sebastian and Emerson.
TERRENCE M. YAU: PUMP MAN
Looking for the heart of cell matters
Dr. Terry Yau is a cardiovascular surgeon, the director of research, division of cardiovascular surgery at the University Health Network and associate professor in the department of surgery at U of T.
At right: Dr. Yau by the Harbourfront, where he and his family like to take walks.
Few patients are truly glad to see Terry Yau. He may be kind and thoughtful, but this heart surgeon is also many people's last hope. And all too often, he has to explain there's nothing he can do. A lack of donors means 99 per cent of potential transplant recipients don't receive an organ. Others can't have surgery because of complications. "It's a miserable life," Dr. Yau said. "Instead of living, they're just waiting to die. That's the thing that I hate the most."
So Dr. Yau is finding new ways to help. At the Peter Munk Cardiac Centre, he is researching turning bone-marrow stem cells into preliminary heart cells. If successful, these "supercells" could be injected into a damaged heart area, where they would make the full conversion from heart-like stem cell to a regular heart cell. "Ultimately, the idea would be to rebuild a completely normal heart," Dr. Yau says.
Toronto researchers have long been interested in stem cells, even though other researchers often regarded their early work as crazy. In 1996, researchers at the Toronto General Research Institute and University of Toronto were the first to show a heart's pumping function could be improved by transplanting cells instead of a whole heart. Then in 2001, a separate finding showed that modified cells could boost blood flow. Now, the method that was once thought of as crazy is an accepted fact.
Late last year, Dr. Yau announced a new advance: The genetically modified supercells work in rats. This year, his team will test them in pigs. If that works, testing will progress to humans.
In the meantime, Dr. Yau is hoping to combine two current therapies to gain better recovery rates for patients. First, a laser would punch holes in the heart muscle - a system used in the United States to improve blood flow through blocked muscle - and then unmodified stem cells would be transplanted into the prepared zone. If the therapy is approved by Health Canada, Dr. Yau is aiming to start trials involving the genetically modified supercells later this year.
Through his work, Dr. Yau hopes to change the current reality of heart failure, which strikes 500,000 North Americans each year. "You can't reverse [a heart attack]no matter how many bypasses you put into them," he says. "Heart attacks are always a permanent thing."
But with these new approaches, Dr. Yau is hoping to change that reality, make hearts repairable and have some good news the next time someone knocks on his door.
"[A patient]may not feel like she's 20 years old again, but she'll be able to go walking with her family, go shopping and live better," Dr. Yau says. "You or I don't need a super heart. All we need is a normal heart that doesn't get worse."
Q&A
Most influential role mode l:
Two of them - Dr. Richard Weisel, who knows every aspect of cardiac surgical research inside out, and Dr. Tirone David, who can perform any operation ever devised in cardiac surgery.
Best-kept secret in the research district:
Even researchers working on new treatments for heart disease will (occasionally) eat pizza.
How you forget about work:
Come home, open the door, and say, "Daddy's home!" A hug and kiss from our five-year-old will instantly wipe the day's little aggravations from my mind.
Favourite quote:
"Imagination is more important than knowledge." - Albert Einstein.
Exercise regime:
Walking. I speed-walk through the hospital corridors and like long walks with my wife and daughter on weekends when the weather co-operates.
Average duration of New Year's resolutions:
I made one resolution not to make any more New Year's resolutions and have kept that for decades.
JONATHAN RAST: CURIOUS URCHIN
Seeking answers down the evolutionary ladder
Dr. Rast is a scientist at Sunnybrook Health Sciences Centre, where he researches developmental biology and immunology.
At right: Dr. Rast looks for fish to add to his home aquarium.
Nature can be deceptively simple. Take the humble sea urchin, for example. Existing on Earth for hundreds of millions of years, these spiny sea creatures were left behind in the evolution of immune systems, but they are far from simple, immunologist Jonathan Rast says.
"The sea urchin has an amazingly complex immune system," says Dr. Rast, who specializes in studying sea-urchin larvae. "They have their own separate solution to dealing with immunity problems. It's a gold mine of new ideas."
Every multiple-celled organism needs an immune system to recognize and block disease-causing micro-organisms called pathogens. By studying different systems, scientists can find novel solutions to immunity problems.
The hot topic at the moment, Dr. Rast says, is a type of receptor known as the gatekeeper of innate immunity. Called a "toll-like" receptor because of its close relation to toll receptors first found in fruit flies, these developmental genes recognize and bind to pathogens. Most animals have about 10 of them. Humans have nine. The sea urchin has about 200.
Researchers were surprised to see so many in the sea urchin and are hoping to now figure out how these receptors work, both in the animals and in humans.
Because sea urchins are a sister group to vertebrates, some information will be directly transferable, while major differences may offer up ideas for new antibiotics. Long-term results could help understand how immune systems go awry, as happens with leukemia, and find ways the human immune system can better attack intruder cells.
"Somehow our immune system evolved out of this system," Dr. Rast notes. "... If you study it closely enough, [you]ll find things you would never think of on [your]own."
In 2006, Dr. Rast co-wrote a paper that showed the genome of the sea urchin was more closely related to humans than suspected: The urchin shares 7,077 of its 23,300 genes with people, which is a much greater proportion than occurs with the more commonly studied fruit fly. Yet, even in an eminent immunology hub such as Toronto, life as a sea-urchin specialist can be tough.
"People are interested in it, but often have a hard time seeing what you're doing because you're not working on a particular disease," Dr. Rast says.
"Even though I'm in some ways the oddball, in the end I'm studying the same genes. ... Sometimes just looking at something very different will lead somewhere you can't predict. If everybody was looking at the same thing, we wouldn't get anywhere."
Q&A
What you always forget about your specialty area:
Nothing in particular about my specialty, but I constantly forget my glasses by the microscope.
Your favourite activity in Toronto:
Looking through aquarium stores for interesting marine invertebrates.
What you do to forget about work:
Play guitar and build robots with my son.
Toughest part of your job:
Maintaining confidence in your chosen research direction in the face of criticism from both self and colleagues.
Favourite quote:
"Nothing in biology makes sense except in the light of evolution." - Theodosius Dobzhansky.
Your exercise regime:
Chasing my children around the house to get them ready for school.
Who/what shares your home:
Another immunologist, two kids, two cats, three fish and a bunch of invertebrates, including a pet sea urchin.