The Fraser Mustard Institute for Human Development

Two babies are born in the same neighbourhood, both with genetic predispositions to develop depression in their 20s, obesity in their 30s and diabetes in their 50s.

One child will grow up to have all these conditions, while the other will develop none of them.

It’s the same story with other non-communicable conditions, including learning disabilities, anxiety disorders, high blood pressure and cardiovascular disease. Why does this happen, what environmental influences may be interacting with those genes, and how can we intervene to help more children—in fact, all children—stay on the path toward optimal health and lifelong well-being?

As researchers around the world pursue these questions, the University of Toronto is creating a unique new research and outreach institute that could revolutionize our understanding of these issues. The Fraser Mustard Institute for Human Development is an academic umbrella that links researchers across multiple disciplines.

A virtual construct whose scope is not restricted by the size of a building, the Fraser Mustard Institute immediately attracted interest from 75 researchers and expects to keep growing.

“It’s bigger, wider and more comprehensive than anything we’ve ever done,” says Executive Director Stephen Lye, a U of T Professor in the Departments of Obstetrics and Gynaecology and Physiology, and the Associate Director of the Samuel Lunenfeld Research Institute (SLRI) at Mount Sinai Hospital.

While many conditions don’t manifest themselves until adulthood, researchers at the Fraser Mustard Institute will be examining what occurs years or even decades earlier.

“Rather than trying to treat the symptoms, we’re better off trying to prevent them in the first place, and we have a very real prospect of doing that in the first 2,000 days of life,” says Lye.

He emphasizes that what happens during that crucial time—from conception to around age five—can set a child on trajectories that will impact his or her entire life.

Those far-reaching effects encompass not only physical and mental health but also the ability to learn and the capacity to form positive social interactions. Traditionally, research has been divided into discrete “silos” of health, education and social sciences. But the Fraser Mustard Institute removes those barriers.

“Our belief is that a developing individual doesn’t separate his or her health, learning part or social functions,” says Lye, who holds the Canada Research Chair in Improvement in Health and Function. “Studying these aspects together will allow innovations to emerge rapidly.”

While attracting researchers from various areas of human development, the initiative has also recently attracted the attention of an international superstar whose field isn’t science at all, but professional sport.

National Hockey League legend Mats Sundin (centre, below) former captain of the Toronto Maple Leafs, feels so passionately about the issues that he has established fellowships for an elite exchange program for two scientists in developmental biology between U of T and Karolinska Institutet in his home country of Sweden. Beginning in September, one candidate from each university will be chosen to do a year of postdoctoral research at the other’s institution.

“I’m really excited about being able to get involved and give back to two of the best research centres in the world,” says Sundin.

The early years have long been an area of interest for Sundin, son of a pediatric nurse.

“Over my years in Toronto I had a big involvement in different charities, but what kept me coming back was children,” he says.

He often visited young patients in hospital, and he started Captain’s Corner, where kids dealing with life challenges had special box seats to watch hockey games in Toronto’s Air Canada Centre.

“When I was part of a seminar on sports and health at Karolinska, I started thinking about ways I could support research that could help children in the early stages of lif," says Sundin, who now lives in Sweden. "It was important for me to give back in Sweden, but maybe even more important in Toronto, where I spent most of my career.

"Toronto really feels like my home.”

He was encouraged to learn that U of T and Karolinska already had academic partnerships, so his involvement was an easy fit.

There are surprising parallels between elite scientists and elite athletes, says Sundin, who will be inducted into the Hockey Hall of Fame in November, and had his number 13 jersey honoured in a Toronto ceremony in February.

He says, “When you’re a professional athlete you’re always trying to be on the edge, at the forefront, collaborating with your teammates but having that competitive drive to be the best.”

Sundin now has a new reason for his interest in the well-being of children: his wife Josephine gave birth to their first child, a baby girl, in August.

Sundin has personally donated more than $300,000 for the fellowships, matched by U of T and Karolinska, with another $50,000 from Maple Leaf Sports and Entertainment. But Sundin’s involvement goes far beyond money, says Lye, who will oversee the fellowships from the U of T side. Sundin has made several personal appearances (when he announced the fellowships earlier this year he proudly brought his entire family to U of T, including his parents and siblings), he is helping to fundraise, and he inspires young people to think about careers in science and research.

“Professional hockey is all about excellence and attracting the best talent from around the world, and so is our institute," says Lye. "Having Mats Sundin involved offers us a great opportunity to get our message out.”

Indeed, Sundin’s announcement generated widespread media attention, which is shining a spotlight on various research initiatives in U of T Medicine that are having an international impact.

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Much of the research focuses on the interplay between genes and the environment. Whereas the genes that we inherit were once thought to be our destiny, it’s now believed that they interact with the environment in ways that can alter their expression. Those environmental influences, both positive and negative, may include nutrients, contaminants, medicines, stress, stimulation and potentially thousands of other factors.

Lye’s own research, in an international collaboration with colleagues in Perth, Australia, involves a huge dataset of 3,000 children who have been genotyped and followed from age 18 weeks to age 21 years. The researchers, led by Dr. Craig Pennell, found that those children born with a specific genetic variant that predisposes them to obesity had a higher than normal body mass index as early as age seven.

“But the really interesting bit,” Lye says, “is that if the mother exclusively breast-fed for the first three to six months, the children with the adverse variant had a normal BMI by age seven.”

That finding, by SLRI investigator and U of T Dalla Lana School of Public Health Professor Laurent Briollais, shows that in the right environment, adverse effects can be mitigated, says Lye. A large part of the research is determining exactly what the “right” environment is in every instance to produce optimal outcomes. To that end, the Fraser Mustard Institute is spearheading another initiative called the Ontario Birth Study. It is recruiting women to take part in an observational study that will follow them through their pregnancies, then follow their children through early childhood and beyond.

“It will be a living laboratory, and I think it’s going to be a remarkable resource,” Lye says.

Obesity, which carries higher risks for diabetes, heart disease, stroke and some cancers, is a major cause of disability around the world. But another leading cause of disability is depression. Physician-researcher Valerie Taylor is investigating how these two disorders—obesity and depression—are connected.

“I’m interested in what comes first,” says Taylor, Head of U of T’s Division of Women’s Mental Health and Psychiatrist-in-Chief at Women’s College Hospital. “And I keep going back further and further, to early fetal programming and what’s happening in utero.”

Taylor emphasizes that not everyone with depression has a weight problem, and not everyone who is overweight has a mental illness. But she says several links have been found. For example, fat tissue, which is biologically active, contains the stress hormone cortisol. Elevated cortisol levels are common in people with depression. And, in what may be a vicious circle, excess cortisol leads to an accumulation of abdominal fat. Likewise, many antidepressants and antipsychotics lead to weight gain, and yet people with depression may lack the energy or motivation to plan healthy meals or pursue physical activity.

To complicate the issue further, these drugs cross the placenta to the fetus, and the effects aren’t fully understood. What is known is that significantly overweight children are at much higher risk of developing a mental illness as they get older, and children with a mental illness are at much higher risk of becoming obese.

This connection has major implications not only in Canada, where almost two-thirds of Canadian adults are overweight and one in four will experience depression, but also worldwide, where these two conditions are increasingly spoken of as a “double epidemic.” Early interventions may potentially include specific antioxidants or behaviour modifications for the pregnant woman that could have protective effects for the fetus, says Taylor.

More research is needed, but Taylor, a member of the Fraser Mustard Institute, believes the answers lie in studying the early years. “For me, looking at the first 2,000 days is essential for understanding the next 90 years.”

One of the driving forces in genetics research is better, cheaper technology. Stephen Scherer (below) is professor of Molecular Genetics, director of U of T’s McLaughlin Centre and one of the world’s top autism researchers.

 “Technology is moving at a breakneck pace,” Scherer says.

Eighteen months ago, as part of the international Autism Genome Project to analyze the genes of 10,000 families with autism diagnoses, Scherer’s lab was able to sequence only 1.5 per cent of all DNA in a genome. This past summer, they could sequence the entire human genome within a couple of weeks at a cost of $5,000. This fall, with new technology they will complete the same process within a couple of hours for $1,000.

 Some of the results have been stunning.

“The new story is that genes we’re finding in our autism studies are also being found in schizophrenia, attention deficit hyperactivity disorder and bipolar disorder,” says Scherer, who holds the Glaxo-Smith-Kline Chair in Genetics and Genomics and is also the director of the Centre for Applied Genomics at The Hospital for Sick Children.

Several studies are looking at why the same genes lead to one condition over another. Since many of the genes are involved in the same genetic pathways, there’s a very real possibility that drugs that work for one condition may be useful in another. But since Scherer’s work suggests that people with autism—and perhaps schizophrenia too—each have their own individual genetic form of the condition, it’s important to translate the data for families in order to personalize treatment.

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While studying common conditions of childhood can yield significant data, conversely so can studying rare disorders.

Department of Paediatrics Professor Berge Minassian, who holds the Michael Bahen Chair in Epilepsy Research and is also a Scientist at SickKids, studies a rare, neurodegenerative form of epilepsy called Lafora disease. Affecting one in 200,000 people, it’s a fatal seizure disorder that progresses rapidly to constant seizuring and dementia, and leads to death about 10 years after onset.

Although symptoms don’t show until age 13 or 14, the roots of the disease begin much earlier. Minassian’s lab discovered the two gene defects that cause the disease by producing an accumulation of glycogen in the brain.

“We’re actually very close now to having an almost complete understanding of all the steps of the disease,” Minassian says. But one of the barriers to progress is the difficulty of getting funding to research a disease like Lafora.

“People think these diseases are too rare to fund," he says. "But these rare diseases are gems for research. They give us precise views of what happens when one specific piece is affected.”

Minassian says the study of Lafora will increase the understanding of other, more common forms of epilepsy. Moreover, since the brain is continually changing and developing in the early years, animal studies are helping to determine the optimal time for drug intervention to prevent or mitigate the disease. Minassian’s lab is also studying a rare form of infant-onset Parkinson’s disease, which may have implications for the much more common adult-onset form.

At U of T Medicine, it’s not just about research; it’s about outcomes, says the Fraser Mustard Institute’s Lye.

“We don’t just want to do research,” he stresses. “We want to take our research and the information that’s already out there and apply it to improve the health, learning and social function of children.”

With its interdisciplinary approach and global reach, Lye says U of T has the potential to be the world leader in looking for best practices around the globe and applying them to significantly improve the lives of children, and the adults they will become.

“The biology that takes a single fertilized egg to a child who can learn in school in a few short years is nothing short of a miracle,” Lye says. “We’re committed to finding how to make that development optimal so that children will be set on trajectories that are optimal for life.”

The Fraser Mustard Institute involves U of T’s Faculty of Medicine, U of T Mississauga and Scarborough, the Faculty of Arts & Science and the Ontario Institute for Studies in Education, and links into several of U of T’s partner hospitals. It is named for Dr. Fraser Mustard, the internationally renowned physician and scientist who passionately campaigned to bring the world’s attention to the importance of the earliest years of life.

To mark its official opening, the Fraser Mustard Institute is hosting the Connaught Global Challenge International Symposium from September 27 to 29, where national and international scientists will speak on “Investing in Mothers and Children: Developmental Trajectories, Health, Learning and Society.”