The University of Toronto will launch a campaign with the Trillium Gift of Life Network on January 13, 2014, to encourage faculty, staff and students to register as organ donors. Every three days in Ontario, a patient dies waiting for an organ transplant, and the Greater Toronto Area has one of the lowest donor registration rates in Canada.

One organ donor can save up to eight lives. Most Ontarians say that giving consent for organ donation is important, but in the GTA only about 15 per cent are registered. Many people mistakenly believe they are registered because they have signed a paper donor card, but the cards are often not available at the time of need, and the province does not record the information on them.

“For those in the U of T community who want to be donors, this campaign is a great opportunity to ensure they are registered,” said Professor Jill Matus, Vice-Provost Students & First-Entry Divisions at U of T. “We know the University can take a leadership role for the GTA in organ and tissue donation, and really make a difference for those who so desperately need a transplant.”

Potential donors often have concerns that prevent them from registering. These include the belief that their organs are too old or unhealthy, and that they won’t be able to have a funeral with an open casket. But age and health typically aren’t barriers to registration, and most procedures have no impact on funeral arrangements.

Another common misconception is that transplants often don’t work. Transplants save and enhance lives, and include a growing range of organs and tissue: heart, liver, kidneys, pancreas, lungs, small bowel, stomach, corneas, heart valves, bone and skin.

“Transplant medicine has come a long way in a very short time,” said Professor Catharine Whiteside, Dean of the Faculty of Medicine at U of T. “Despite the complexity of the procedures, the biggest challenge we face today is not only how to preserve the function of transplanted organs by controlling a patient’s immune response — equally important is recognizing the shortage of organs for transplantation.”

The University of Toronto has played a central role in the progress of transplant medicine. The University and its affiliated hospitals were home to the first and largest organ transplant program in Canada. Surgeons at the Toronto General Hospital performed the world’s first single and double lung transplants, and today the University Health Network’s Multi-Organ Transplant Program provides surgery to 400 patients and follow-up care for 5,000 patients every year.

The University’s organ and tissue donor registration campaign will run from January 13 to 24, 2014, but members of the U of T community can register any time at https://beadonor.ca/uoft.

It only takes two minutes to register.

Within our Faculty and throughout the health professions, eLearning has been a topic of hot discussion. It offers us a tremendous opportunity to better align our curricula with how our students want to learn, and to reach a broader global audience. Yet, new learning technologies are rapidly developing and their educational efficacy needs to be rigorously evaluated. Many of our peer medical schools and other areas at the University of Toronto are offering new eLearning modules, and we now have the opportunity to organize and plan for the future.

We can take pride in the pockets of eLearning excellence throughout the Faculty, and in the eLearning modules we have created. From eDOT, the Electronic Direct Observation Tool, to EMRaD, the Emergency Medicine Radiology Database, to our very popular online course in basic human physiology, members of our Faculty are deeply invested in eLearning. In order to maintain our Faculty’s position as a leader in eLearning (i.e., teaching, learning and scholarship) across the education continuum, we now need to move forward with a clear strategy for eLearning, so we can leverage the good work we have done and support the work we need to undertake.

To these ends, the Faculty is striking an eLearning Task Force co-chaired by Professors Dimitri Anastakis, Vice Dean of Continuing Professional Development and Jay Rosenfield, Vice Dean of Undergraduate Medical Professions Education. The Task Force will submit a progress report in April and file a formal report in June.

Part of the challenge in harnessing the value of eLearning is understanding what it entails.  eLearning encompasses a large breadth of technologies and applications, and so the Task Force will first define eLearning for our Faculty and learners.  It will then complete an inventory of eLearning efforts and resources across the Faculty. The Task Force will also identify opportunities for partnership with University eLearning initiatives. The Task Force will conduct an environmental scan of other global leaders in this area. With this information in hand, the Task Force will identify the gaps between where we are today, and where we need to be over the next decade and beyond.

Through the recommendations of the Task Force, we will further position the Faculty as a leader in eLearning, and we will lay the foundations to ensure we have the competencies and infrastructure to provide the best education for the learners of today and tomorrow.

Catharine Whiteside
Dean, Faculty of Medicine, and Vice Provost, Relations with Health Care Institutions

In honour of Alzheimer’s Awareness month, Erin Vollick sat down with Sandra Black to discover more about the science behind this devastating disease - and potential ways to combat the disease decades before symptoms appear.

Dr. Black holds the Brill Chair in Neurology in the University of Toronto’s Faculty of Medicine, and is cross-appointed to the Institute of Biomaterials & Biomedical Engineering. She is the executive director of the Toronto Dementia Research Alliance and director of the Brain Sciences Research at the Sunnybrook Research Institute.

What are the differences between Alzheimer’s disease and dementia?

Dementia refers to a state of mental decline, defined by loss of critical abilities such as memory and attention, expressing thoughts in words, planning ahead, organizing and making decisions. To be called dementia, the decline has to be severe enough that the person is no longer able to function completely independently in usual activities of daily living.

There are actually about 80 causes of dementia. One of those is Alzheimer’s disease, which is a key, common contributing factor to dementia but is often combined with stroke and diseases of the small vessels, especially in older people. In fact Alzheimer’s in conjunction with vascular disease of the brain is actually the most common underpinning of dementia in our society.

When was the first case of Alzheimer’s disease detected?

In 1906, [Aloysius] Alois Alzheimer reported a new disease, later named after him, which he called “presenile dementia”; he found “plaques” and “tangles” in the brain in the autopsy of a woman whose memory loss and other symptoms began at age 49. Interestingly, around the turn of the twentieth century, the average life expectancy was 47 years of age.

In the 1960s and 70s, when the electron microscope was invented, researchers noticed that the plaques and tangles seen in the older onset Alzheimer patients had exactly the same microstructure as  pre-senile cases, so they realized the “senile” and “pre-senile” cases were  the same disease, pathologically speaking.

What are the projections for the number of patients expected to suffer from Alzheimers in the future, and its implications for health care?

A study published in The New England Journal of Medicine suggests we are unprepared for the coming surge in the cost and cases of dementia. Worldwide, 38 million people suffer from dementia right now, with the number predicted to more than triple in a generation. By 2040, 9.1 million people in the US and 1.1 million in Canada are expected to have dementia. Dementia care is currently estimated to be $15 billion in Canada and $215 billion in the US. So the economic and social costs are significant.

We know the devastating effects of Alzheimer’s, but what actually causes disease?

There are two classical autopsy findings patients with Alzheimer’s, but we still don’t know what causes this to happen in common variety Alzheimer’s. The first is the amyloid plaque, a sticky deposit of amyloid protein found in between cells in the brain. Amyloid is toxic not only to brain cells but also to brain blood vessels.

The second hallmark of Alzheimer’s disease is the tau protein, which deposits in the microtubular system of the neurons, preventing transport of nutrients and other molecules between the nerve cell body along the axons to the nerve terminations, where nerve cells connect with each other (called synapses). The cells gradually die.

Furthermore, researchers have found a very strong correlation between Alzheimer pathology and silent stroke disease and degree of mental decline. High blood pressure is a key risk factor for brain damage as it can lead to blood vessel injury and stroke as well as speed up Alzheimer’s disease.

How is your lab tackling the study and treatment of Alzheimer’s?

In addition to active involvement in clinical treatment trials, we have been pursuing longitudinal studies in patients with Alzheimer’s and other dementias for some years, using standardized brain imaging and other assessments and developing pipelines to quantify brain tissue loss, small vessel disease burden and stroke lesions. Recently, we have begun to collaborate more actively with memory programs in other U of T academic healthcare centres through a collaborative network, the Toronto Dementia Research Alliance, which I direct, and across Ontario through the Ontario Brain Institute Neurodegeneration project, which is just getting underway. The goal is to gain new insight into mechanisms and genetics and use advanced brain imaging and clinical measures across the different dementias, to predict patterns and rates of decline, and to bring treatments more rapidly to our patients.

Being able to see that a person has amyloid plaques in their brain even before symptoms start opens up new possibilities for preventing decline. For example, we are participating in an international study whereby individuals over 65, who may be at risk for developing Alzheimer’s disease possibly because of family history, will be offered an amyloid PET scan. If they show evidence of amyloid in their brain, they will be invited to participate in a treatment trial with a antibody against amyloid being provided by Eli Lilly, called Solanezumab.

This is very novel as the individuals will still be completely normal and could be as much as 10 years before the onset of the dementia symptoms. The hope is to delay or prevent that onset.

Is Alzheimer’s preventable? What can we do to minimize the risk of developing Alzheimer’s?

We’ve known for about 20 years now about the link between Alzheimer’s and blood vessel disease. The biggest lesson from many observational studies is: take care of your body and you take care of your brain.

Eat heart healthy. Look after your hypertension.

Exercise! Even 30 minutes of aerobic exercise three times a week could improve your brain’s health.

Another really important factor that is emerging is sleep. Poor or insufficient sleep is becoming recognized to also be a risk factor for dementia and we may have a partial explanation. The brain has its own lymphatic system that helps to circulate the cerebrospinal fluid between cells and flushes out the toxins within. This system starts to slow down with aging. But here’s a key finding: most of this flushing happens during sleep!

In August 2009, Elspeth Arbow got the greatest gift anyone could receive: new lungs.

Though her first surgery was successful, Arbow’s donated lungs have worn down, and now function at just 25 per cent of their capacity. Because the body sees transplanted organs as foreign objects, the immune system tries to attack them. Immuno-suppressants help, but the new organs can still lose function over time.

“Some people's bodies reject the organs instantly, and months later they're listed again. For me it happened in four years,” explains the 17-year old Cinema Studies student at the University of Toronto.

Arbow was just 10 weeks old when she was diagnosed with Cystic Fibrosis, a genetic disease that causes thick mucous to build in the lungs and digestive system. The condition leads to severe difficulty with breathing, as well as problems with digestion and nutrient absorption.

Managing the disease meant Arbow had to undergo physiotherapy twice a day to clear her lungs.  She also spent a couple of weeks in hospital every two years for intravenous antibiotics and more rigorous physiotherapy. When she was twelve, she needed more frequent interventions. Her care team referred her to the Hospital for Sick Children for a possible lung transplant, then added her to the wait list.

In March 2009, Arbow and her mother moved from their New Brunswick home to Toronto, to be closer to the hospital for what became a five-month wait for an organ. For the first three months, Arbow and her mother, Judith, kept busy, exploring various parts of the city. But Elspeth’s health declined and she had to be admitted to hospital to continue waiting for an organ donor. 

“We tried not to be depressed by the wait,” says Judith. “It was the last six or eight weeks where she got really sick with her breathing that were the most stressful. And then our miracle happened, the lungs came in when she had a day or two left to live. It was beautiful, and we’ll forever be grateful to the donor family.”

Doctors had just moved Arbow, who was 13 at the time, into the intensive care unit and were preparing to put her on a breathing machine. That night, a set of lungs became available and she received her transplant.

The road to recovery wasn’t easy. There were complications during the operation, and doctors put Arbow on life support before she gradually recovered.

She spent about a month at Sick Kids following her surgery, healing, retraining her muscles and building strength.

“Without the transplant, I definitely wouldn't have made it past middle school, and here I am in my first year of university,” she says.

While she recovered, she developed the passion for movies that led her to U of T.

A group of people, including family, friends, and some hospital staff arranged for her to receive free tickets to a film premiere at the Toronto International Film Festival (TIFF). She attended that screening, as well as several others in following years.

“I'm obsessed with TIFF, and now that I live here, I can go every year, and I want to volunteer next year,” says Arbow. “I guess the whole transplant thing put me in this direction.”

Highly motivated, Arbow is excited about life beyond her next operation. She hopes to become a film festival programmer, and to resume ballet classes — a hobby she began after her first transplant.

“It’s nothing short of a miracle,” says Judith. “With Cystic Fibrosis, she didn’t have the stamina or the lung capacity for any hugely physical activities. She always did as much as she could, but once she got the transplant, she really took off. She started doing some of the things she had been missing out on. And ballet was top of her list.”

Arbow is deeply thankful to her donor for her transplanted lungs, and hopes more will people will be inspired to register themselves as donors.

“If you had told me at the time of my first transplant that I'd need another one in four years, I would have said, 'No, no deal, don't want to do it,'” she says. “But having seen four years of extra life, I wouldn't deny myself because I've had all these experiences that I otherwise wouldn't have had.”

To register as a donor, visit https://beadonor.ca/uoft.

“How many of you have a family member with diabetes?”

David Sadleir puts the question to students from a grade 10 science class, who have just walked half an hour from Banting Memorial High School in Alliston to tour the birthplace of Sir Frederick Banting, co-discover of insulin.

About a third of the students raise their hands. Sadleir nods.

Across Canada, 9 million people have diabetes or prediabetes, Sadleir tells the group. Around the world, 438 million will have diabetes by 2030. “Those numbers are big,” he says, “but what’s really scary is that more and more, they are made up of young people like you.”

Doctors in Canada are seeing kids with type 2 diabetes as early as age eight. In the United States, the number of children with type 2 diabetes is at least 10 times higher than it was just over a decade ago. Childhood rates for this form of the disease — which used to be called “adult-onset” diabetes — are growing around the world.

The good news is that the link between lifestyle and prevention and management of diabetes is stronger than ever. A healthy diet and regular exercise can dramatically lower the risk of getting the disease, and improve outcomes for those who have it.

To get that message out, and to honour the discovery of insulin at the University of Toronto in 1921, the Sir Frederick Banting Legacy Foundation has restored the property on which Banting was born, and turned it into a cultural and educational hub.

The Foundation recently received $249,500 from the Ontario Trillium Foundation to help run the facility for the next three years. The students from Banting Memorial are the first in the Foundation’s school tours program, which Sadleir hopes will bring 700 kids to the property from across Ontario each year.

“Insulin has saved maybe a billion lives. For a discovery with impact, it’s hard to beat that one,” says Sadleir, a former Professor of Mechanical and Industrial Engineering and Vice President at U of T who has been the Foundation’s President since 2010. “As the birthplace of Banting, we knew this property offered a tremendous opportunity to preserve his legacy and fight diabetes through education and research.”

Megan McLaughlin is one of the two-dozen high school students visiting the site. Their tour includes a tutorial by Sadleir on the fifty-year trail of scientific inquiry that led to the discovery of insulin and its mass production, and a “scavenger hunt” among the exhibits for answers to questions about diabetes.

“I didn’t realize the discovery came at the end of such long process,” says McLaughlin, who has several family members living with diabetes. “I learned a lot today.”

The exhibits include a rotating selection from among hundreds of artifacts, manuscripts and paintings, drawn from the Banting Digital Library, the Thomas Fisher Rare Books Library at U of T, the Museum on the Boyne and other sources. Outreach partners from Stevenson Memorial Hospital and Southlake Regional Health Centre recently delivered the Foundation’s first class for diabetes patients, and Sadleir says public access to the site should start in 2014.

Sheila Dickson is McLaughlin’s teacher and the Chair of the Science Department at Banting Memorial. She says the facility is great for the community, and offers her school a chance to build on its curriculum with fascinating science and local history, while emphasizing topics like nutrition that are important to today’s students.

“And I love Banting’s story,” says Dickson. “He came from rural Ontario, like many of our students. Good things can come from small schools.”

Ninety-two years ago this week, Leonard Thompson received the first successful injection of insulin for diabetes. The treatment saved Thompson, then 14 years old, from certain death — he weighed just 65 pounds and had been drifting in and out of a diabetic coma.

Frederick Banting and his colleagues at the University of Toronto discovered insulin, which has saved millions of lives and is essential medicine for many diabetics today. To honour his story, the Sir Frederick Banting Legacy Foundation recently restored the long-neglected site of Banting’s birth in Alliston, Ontario.

David Sadleir is the Foundation’s President. The former Professor in the Department of Mechanical and Industrial Engineering and U of T Vice President has helped turn the historic property into a diabetes management and education facility, and a heritage park that preserves Banting’s legacy.

Sadleir spoke with Faculty of Medicine writer Jim Oldfield about diabetes, the challenges of fixing the Banting homestead and plans for the future.

What do you want people to know about the discovery of insulin?

It’s a classic but extraordinary scientific story. The discovery came at the end of 50-year trail of scientific inquiry. In 14 months, Banting and his team — a group with complementary skills, and that was critical — came up with a very rapid solution to a very horrible problem. That’s not unique in the annals of science, but it sure is special. And, it took a coordinated effort by many folks to bring this discovery to patients. The University of Toronto worked with Connaught Labs to mass-produce insulin, but to help meet the early demand, they brought in Eli Lilly. In 1922, the cost for 100 units of insulin was equivalent to $130 a week. By 1942 it was down to $2.60.

The main purpose of the Banting Legacy Foundation is to fight diabetes. How will you do that?

We decided we could make a difference with a focus on youth, prevention and self-management. Diabetes in children is an epidemic. For those who manage it well, the disease is not a big deal, but many teenagers have trouble doing that — especially as they transition from the paediatric to adult health care system at age 18. So with our outreach team partners at Stevenson Memorial Hospital and Southlake Regional Health Centre, we’re seeking new models of transition care. With the Department of Pediatrics at McMaster University, we’ve launched supporting lectureships, conferences and postdoctoral awards that address this issue and help build capacity in the system. We’re also hosting classes for diabetics on disease prevention and management, and we just launched a tour program for high school students — I’m really happy about that.

What challenges have you faced?

Well, Murphy's law has been hard at work here. The historical society that took over the property from the Banting family about 20 years ago was unable to sustain it. The local community, proud of the Banting legacy, was upset by the visible mess. It took the Town of New Tecumseth years of legal wrangling and political pressure to regain control of the property, before we could get started. Then the renovations for the farmhouse were technically challenging and expensive. We had to provide barrier-free access while preserving the historical features — our solution was the adjacent structure that houses a ground-level lobby, washrooms and wheelchair ramp. Pulling together the artifacts and memorabilia was difficult, but the New Tecumseth Public Library, Museum on the Boyne and, more recently, U of T’s Thomas Fisher Rare Book Library came to our rescue last fall — just in time for the exhibit ribbon-cutting and World Diabetes Day.

What are your next steps?

We want to extend our reach through technology. We plan to build an interactive digital learning wall to remotely access expert care and information. We want a portable kiosk version of the wall, to make the content available to schools. And we plan to install a telemedicine facility to make our diabetes classes more widely available. We really see the park without geographic limitations. Finally, this year, we expect to open the site to the public on weekends. We’ve had tourists stop by — a couple from France, one from Utah. We’ve had buses of Chinese, in part due to our proximity to Bethune Memorial House in Gravenhurst. We knew we had a winner, we just needed to be patient.

The Banting Homestead Heritage Park is now open for school and community group tours. The Foundation accepts donations here.

A team of researchers at the University of Toronto has discovered a method of assembling “building blocks” of gold nanoparticles as the vehicle to deliver cancer medications or cancer-identifying markers directly into cancerous tumors. The study, led by Warren Chan, Professor at the Institute of Biomaterials & Biomedical Engineering (IBBME) and the Donnelly Centre for Cellular & Biomolecular Research (CCBR), appears in an article in Nature Nanotechnology this week.

“To get materials into a tumor they need to be a certain size,” explains Chan. “Tumors are characterized by leaky vessels with holes roughly 50 – 500 nanometers in size, depending on the tumor type and stage. The goal is to deliver particles small enough to get through the holes and ‘hang out’ in the tumor’s space for the particles to treat or image the cancer. If particle is too large, it can’t get in, but if the particle is too small, it leaves the tumor very quickly.”

Chan and his researchers solved this problem by creating modular structures ‘glued’ together with DNA. “We’re using a ‘molecular assembly’ model - taking pieces of materials that we can now fabricate accurately and organizing them into precise architectures, like putting LEGO blocks together,” cites Leo Chou, a 5th year PhD student at IBBME and first author of the paper. Chou was awarded a 2012-13 Canadian Breast Cancer Foundation Ontario Region Fellowship for his work with nanotechnology.

“The major advantage of this design strategy is that it is highly modular, which allows you to ‘swap’ components in and out. This makes it very easy to create systems with multiple functions, or screen a large library of nanostructures for desirable biological behaviors,” he states.

The long-term risk of toxicity from particles that remain in the body, however, has been a serious challenge to nanomedical research.

“Imagine you’re a cancer patient in your 30s,” describes Chan. “And you’ve had multiple injections of these metal particles. By the time you’re in your mid-40s these are likely to be retained in your system and could potentially cause other problems.”

DNA, though, is flexible, and over time, the body’s natural enzymes cause the DNA to degrade, and the assemblage breaks apart. The body then eliminates the smaller particles safely and easily.

But while the researchers are excited about this breakthrough, Chan cautions that a great deal more needs to be known.

“We need to understand how DNA design influences the stability of things, and how a lack of stability might be helpful or not,” he argues.

“The use of assembly to build complex and smart nanotechnology for cancer applications is still in the very primitive stage of development. Still, it is very exciting to be able to see and test the different nano-configurations for cancer applications,” Chan adds.

The project was funded by CIHR, NSERC, CBCF, and CFI.
 

The Canadian Institutes of Health Research (CIHR) is a crucial partner in our research enterprise. We rely on their grants to help support our researchers, who each year receive close to $150 million in CIHR grants.  In 2014 CIHR begins the process of implementing changes in the Open Operating Grant Proposal competitions and simultaneously alters the peer review process. The following briefly outlines the scope of these changes that will have implications for many of our researchers and for our Faculty as a whole.                                                 

The proposed changes were first outlined in March 2012 when the CIHR’s Science Council released its Design Discussion Document - Proposed Changes to CIHR's Open Suite of Programs and Enhancements to the Peer Review Process. The document proposed a number of reforms that have very laudable objectives meant to streamline the application process and ensure more long-term and stable funding. The current 12 funding programs would be condensed into just two:  a Foundation/Programmatic Research Scheme and a Project Scheme. The Foundation Scheme focuses on supporting researchers by providing “long-term support to investigators with a demonstrated track record of success.”  The Project Scheme focuses on ideas and is intended to “encourage researchers who want to explore specific ideas across the spectrum of health and health systems research and knowledge translation.”

Another major series of changes relate to the peer review process. As the report notes, input to the CIHR’s recommended that the peer-review committee structure needed to be overhauled to reduce reviewer burden and to include more individuals with content and research expertise. Part of the solution to this challenge is to establish a College of Reviewers that will increase the number of peer reviewers and utilize online review in the early stages of the review cycle.

Since the release of this report, the CIHR has solicited feedback, which we have actively provided including responses from Town Hall meetings with senior CIHR leaders in 2012 and 2013, the most recent being held in December 2013. While some of our concerns have been addressed, others have not. One of greatest concerns is at the loss of two funding competitions, one we have known about for some time, the September 2014 open competition.  More recently the September 2015 competition has also been removed.  In their place are two new pilot Foundation grant opportunities. While the Foundation grants will fund some of the investigators it is anticipated that a large number will be applying to the March 2014 and 2015 Foundation grant competitions. A significant challenge all Canadian Institutions face is to find a solution to what at best will be a 6 month funding gap and at worst a gap of 18 months.

I appreciate the concern and frustration many have expressed over these changes. Alison Buchan and I are in communication with counterparts in our affiliated hospitals and institutions across Canada with recommended solutions including advocacy for adequate transition revenue for CIHR to support the anticipated gap. Our Vice-President Research and Innovation and other VPRs from the 15 research-intensive major universities in Canada (U15) are also discussing with CIHR possible solutions and mitigation measures for this issue. Your support and patience are appreciated.

I encourage you to stay up-to-date on these important changes. We will be posting new information on the Faculty’s Research and International Relations website as it becomes available and communicating further through MedEmail. You can also find answers to frequently asked questions on the CIHR’s website.

Catharine Whiteside

Dean, Faculty of Medicine

Vice-Provost, Relations with Health Care Institutions

Scientists at the University of Toronto led by Prof. Leah Cowen (Department of Molecular Genetics) have found a molecular mechanism that plays a key role in the transition of Candida albicans yeast into disease-causing fungus—one of the leading causes of hospital-acquired infection. The finding highlights the importance of heat in fungal growth, and provides a new target for drug therapies to counter Candida albicans infection. In an additional study, Prof. Cowen and her colleagues identified 224 new genetic interactors for a central protein in Candida albicans . . . .

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Department of Medicine Professor Emeritus John Dirks, Dr. John Macleod and Dr. Lap-Chee Tsui were entered into the Canadian Medical Hall of Fame yesterday for their extraordinary contributions to health care and research. The CMHF inducted the three along with four other Canadian medical pioneers in a Toronto ceremony hosted by their Honourary Chair, U of T President David Naylor.

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