It’s safe to say that when William Shakespeare wrote these lines at the end of the 16th century, good health was the exception and not the rule. Few people survived much beyond middle age, routinely succumbing to simple infections, injuries and ailments. Surgeons treated gunshot wounds by pouring boiling oil over them; ointments prescribed to cure infections contained ingredients like rabbit hair, puppies’ fat and turpentine; nursing mothers weaned their babies by rubbing bitter-tasting soot on their breasts.

It’s almost dizzying to think how much has changed in the past 400 years. Life expectancy in most Western nations is at an all-time high. Scientists continue to unravel the complexities of the human genome; engineers work to perfect a self-contained artificial heart; doctors perform surgery on the unborn fetus.

Through it all, we struggle to understand the impact that current medical developments will have on our own health and on the health of our children and grandchildren. “The post-genome revolution will transform every aspect of the health-care system: everything from how we treat advanced disease to the use of new designer drugs,” predicts Dr. David Naylor, dean of the Faculty of Medicine. Yet despite the amazing leaps in medical knowledge and practices that have occurred, “the biggest challenge we face is that we still know too little about health and illness,” he says.

To highlight some current issues in health and medicine, we have borrowed a framework from Shakespeare: his famous reflection on the human lifespan as spoken by Jaques in the comedy As You Like It. Our cradle-to-grave tour includes commentary from dozens of scientists, academics, physicians and other health-care professionals in the Faculty of Medicine and the university’s teaching hospitals, and also from alumni and students. And, yes, we forgive Shakespeare the sexist attitudes of his day.

Today, the overwhelming majority of infants in Canada are healthy. Infant mortality rates have dropped significantly over the past century; the rate is currently six per 1,000 births, according to the Canadian Institute of Child Health, compared with the late 1800s, when one in 10 children died in their first year of life. The decrease is due to major strides in medical care, including advances in care for premature babies, sound nutrition, immunization, cleaner water, and improved plumbing and sewage control, says Dr. Hugh O’Brodovich, chair of the department of paediatrics.

Modern public health policies have resulted in thriving infants who would have been miracle babies in Elizabethan times. Similarly, recent developments in maternal-fetal medicine have created what to the modern onlooker may seem like “sci-fi babies.” For example, a small number of fetuses are being operated on inside the uterus for such disorders as heart defects, spina bifida and diaphragm malformations. “These are highly experimental procedures, and they’re not being done in any Toronto hospitals, because of questionable outcomes,” says Dr. Knox Ritchie, chair of the department of obstetrics and gynaecology. Operations that are performed in Toronto include interventions to repair lung and urinary tract malformations.

High-tech interventions are highly dramatic – and extremely expensive. Do the results justify the costs, especially when funds for cancer treatment and home care for the elderly are limited? When it comes to resource allocation, “the more relevant debate is over the resources directed toward very premature babies,” says Dr. Ritchie. For example, he says the leading centre dealing with premature births in the Netherlands has decided to stop the active intensive treatment of babies born before 25 weeks’ gestation. The decision was based on research showing that many infants born at 23 and 24 weeks didn’t survive, and of those who did, half had severe physical or mental handicaps by the age of two.

While fetal screenings may not be as dramatic as fetal surgery, they are imperative tools: Sharon Vanderwerff (BA 1991 New College) was 36 weeks pregnant with her first child when her doctor noticed she had extremely high blood pressure and all the signs of early labour. She immediately sent Vanderwerff to Mount Sinai Hospital’s high-risk pregnancy clinic for an ultrasound. When the technician took a long time examining her, then left to fetch a doctor, Vanderwerff thought, “Something’s wrong.” Her instincts were right. The scan showed that the baby’s brain lacked a corpus callosum – the tissue that connects the brain’s two hemispheres, allowing it to develop and grow.

Later, tests at Mount Sinai and the Hospital for Sick Children revealed that baby Alexis, born in March of 1997, was afflicted with a rare disorder – she had a gene mutation that hampered the production of energy in her cells and prevented her from developing properly.

Given the severity of the baby’s condition, Vanderwerff and her husband, Blake Melnick (BEd 1992), decided against experimental genetic treatments. Instead, they took their baby home, where she died eight months later. “Our decision was to make sure our daughter had a very good quality of life as opposed to a quantity of life,” says Vanderwerff. “It wasn’t life at all costs.”

Dr. David Chitayat, head of Mount Sinai’s prenatal diagnosis and medical genetics program and medical director of U of T’s master’s program in genetic counselling, helped rule out some genetic conditions in Alexis. He explains the challenges of examining a baby prenatally: “We are just peeking from a keyhole into the pregnancy through certain devices, trying to tell the parents if the baby is fine or not.” Some of the tools he uses to peek through that keyhole are nuchal translucency screening, which provides risk figures for Down syndrome and other chromosomal abnormalities; maternal serum screening, which screens for the risk of Down syndrome and spina bifida; and ultrasounds, which, at 19 weeks gestation, can detect about 80 per cent of structural abnormalities.

Chitayat is also trying to track the outcome of different chromosome abnormalities – especially sex-chromosome abnormalities – that are detected prenatally, through long-term follow-up of patients. Ultimately, all of his work aspires to answer a couple’s two biggest questions after the birth of a baby with an abnormality: What lies ahead for our baby? And are we at risk in future of passing along a genetic condition?

There is a second chapter to Vanderwerff and Melnick’s story. Alexis’s skin biopsy results allowed doctors to pinpoint the gene mutation associated with the enzyme deficiency. That meant when Sharon became pregnant just before Alexis died, the fetus could be checked for Alexis’s condition. “If the tools were there to help us to know if we would have another child born with a terminal illness, we were going to use them,” says Vanderwerff. “We would not knowingly go through what we went through again.”
But there was one catch: because Alexis’s condition was so rare, a medical screening test wasn’t available. Instead, a scientist at Sick Kids worked from ground zero, running DNA sequences to determine if the gene mutation was present. The tests came back negative: the fetus had only a three per cent chance of having the syndrome.

In November 1998, Vanderwerff gave birth to a healthy baby girl named Parker Grace. In May, the couple had their third daughter, Rowan Alexis. Each girl carries part of Alexis Parker’s name – a legacy from a sister who helped forecast their own health.

Finding another piece of the cystic fibrosis puzzle
U of T researchers have discovered yet another piece in the puzzle of cystic fibrosis (CF), a chronic inherited disease that typically reveals itself in childhood. The condition causes abnormal secretion of mucus and can lead to severe respiratory problems as well as other health concerns. The newest finding is a defective protein that appears to cause a milder form of the disease (pancreatic-sufficient CF), which affects 10 to 15 per cent of CF patients.

According to lead researcher Dr. Charles Deber, a professor of biochemistry and senior scientist at the Hospital for Sick Children, the protein, called CFTR, regulates the balance of salt (sodium chloride) moving across cell membranes in the lungs and pancreas. In the milder form of CF, segments of this protein stick together, interfering with the flow of chloride in and out of the cell.

The finding, which was published recently in the scientific journal Nature Structural Biology, means scientists can now begin research that could lead to new drug treatments. “We will look for molecules that could possibly break up the abnormal bond that is causing the protein strands to stick together,” says Dr. Deber.

This latest discovery builds on years of cystic fibrosis research by scientists at the Hospital for Sick Children, including the discovery of the CF gene in 1989 by Dr. Lap-Chee Tsui, professor of molecular and medical genetics at U of T.

Understanding pre-term labour
It is estimated that between five and 10 per cent of babies born in Canada come into the world prematurely. These fragile, medically compromised infants account for 70 per cent of neonatal deaths.

Those born before 28 weeks have a 40 times greater chance than full-term babies of having such problems as cerebral palsy, motor or mental disabilities, blindness or lung disease, according to Stephen Lye, co-head of the development and fetal health program at Mount Sinai’s Samuel Lunenfeld Research Institute, and a professor of obstetrics, gynaecology and physiology. There are not only short-term medical costs (keeping a baby alive in a neonatal intensive-care unit can cost $3,000 a day), but also long-term expenses to the health-care system if a baby has a chronic disability, he says.

Why are some babies in such a hurry to be born? One reason for the rise in pre-term labour is the increase in multi-fetal pregnancies. This is due not only to assisted reproduction, but also to advanced maternal age – women are tending to have babies later in life, and older women have a greater chance of ovulating more than one egg at a time, says Lye.

Lye, who also holds a Canada Research Chair in fetal, neonatal and maternal health, is looking into genetic factors that may cause premature births. When a woman goes into labour, the muscle of her uterus moves from a dormant state to a highly active one, and Lye suspects that certain genes must be expressed or “turned on” before this happens. He is trying to identify those genes and understand how they are regulated. “If we know why they’re turned on in labour, then we may be able to turn them off and allow the uterus to stay quiet till full term,” he says.

Obesity levels at all-time high

New research culled from several national surveys shows that Canadian kids have been getting progressively heavier since 1981. Twenty years ago, 15 per cent were considered overweight; by 1996 that number had jumped to 29 per cent of boys and 24 per cent of girls. “While children have become less physically active, they are taking in more and more calories. It’s a recipe for obesity,” says Dr. Khosrow Adeli, a professor in the department of laboratory medicine and pathobiology and head of clinical biochemistry at the Hospital for Sick Children in Toronto.

According to Nielsen Media Research, last year Canadian kids aged two to 17 watched about 15 hours of TV each week. Sitting in front of the TV or computer screen requires almost no expenditure of energy, except when kids walk to the kitchen for a snack. “They’re not just taking in more calories, they’re taking in more calories from fat,” says Adeli.

One alarming consequence of childhood obesity is that doctors now see health problems in schoolchildren that typically didn’t appear until middle age; for example, Type 2 diabetes, hypertension (high blood pressure) and hyperlipidemia (unhealthy levels of cholesterol and other fats in the blood). And overweight children are more likely to be overweight adults and to experience obesity-related problems such as heart disease, diabetes and certain cancers.

The asthma paradox

Another worrisome trend is the rising rate of childhood asthma. Surveys show that between 10 and 15 per cent of school-aged children are affected to some degree by this chronic lung disorder, which involves inflammation of the airways and in turn leads to shortness of breath, wheezing, coughing and chest tightness. The exact cause of asthma isn’t known, but common triggers include animal dander, cigarette smoke, dust mites, pollen, mould spores, exposure to cold air and exercise.

Children suffer more commonly from asthma than adults, mainly because their airways are narrower, explains Dr. Kenneth Chapman, director of the Asthma & Airway Centre at Toronto Western Hospital and University Health Network, and a professor of medicine at U of T. There has been a dramatic rise in asthma in kids under age 14; in just 18 years the rate has increased from 2.5 to 11.2 per cent.

Why the sudden increase? “The layperson assumes that it’s because of pollution,” says Dr. Chapman, “but environmental pollution is less a culprit than we think.” Instead, the real source of the problem lies closer to home: “Children today spend a lot of time indoors instead of playing outside. They also live in better insulated homes, and this has increased their exposure to respiratory irritants such as dust mites, pet dander and secondhand smoke,” he says.

Another problem may be that modern children – who tend to live in isolated, relatively clean environments – aren’t giving their immune systems a regular workout, says Dr. Chapman. “Because their bodies’ defence systems are no longer attending to outside infections, they preoccupy themselves with things that really aren’t hazardous to the body, like cat dander.” This may explain recent research showing that eldest or only children are particularly susceptible to asthma. The theory is that younger kids with older siblings, and those who attend day care at an early age, are exposed to many more germs, which allows their immune responses to develop more vigorously and may decrease their risk for asthma.

If your child has asthma, says Dr. Chapman, you should take the necessary steps to obtain proper treatment, and reduce household triggers such as dust and mould. “Finally, relax,” he adds. “Children often enjoy an improvement in their asthma because, as their bodies grow, their airways become larger. In fact, in about two-thirds of kids, asthma is much improved by adolescence.”

The ADHD explosion

While measles, mumps and chickenpox have largely vanished from childhood, a troubling new disorder has emerged: attention-deficit/hyperactivity disorder, or ADHD, which is believed to affect four to five per cent of school-aged boys and three per cent of school-aged girls. The main symptoms are inattention, hyperactivity and impulsivity, explains Dr. Wendy Roberts, an associate professor of paediatrics and medical director of the Child Development Centre at the Hospital for Sick Children. “The typical picture [of ADHD] is a child who is easily frustrated, can’t pay attention, daydreams too much, is impulsive or disorganized,” she says.

For an ADHD diagnosis, symptoms must have been evident before the child reached age seven, and the problems must have persisted for at least six months in two or more settings; for example, at home and in school. About one-third of children with the disorder also have some other psychological or developmental problem, such as a language or learning disability, says Dr. Roberts.

The common treatment for ADHD is behaviour therapy combined with stimulant drugs such as Ritalin (methylphenidate) or Dexedrine (dextroamphetamine), says Dr. Roberts. These drugs help focus attention and reduce hyperactivity in about 70 to 80 per cent of cases. Studies show that in Canada the number of prescriptions for such drugs has been rising steadily in recent years.

Some child experts and educators wonder if the condition is being overdiagnosed: “It used to be that when you had a kid who was difficult to handle, teachers would say he was challenging,” says Dr. Judith Wiener, a psychologist in the department of human development and applied psychology at the Ontario Institute for Studies in Education (OISE). “Now they call it ADHD and send the parents to the doctor. There are many children labelled ADHD who do not meet the clinical criteria.”

Kids with ADHD seem to benefit from highly structured schedules that include skill-building activities such as art, music, drama, and sports. It’s best to limit their TV or “any electronic hookup” time to one hour a day, advises Dr. Roberts.

Getting kids up off the couch
Here’s something to consider: only two out of every five children aged five to 17 are active enough for optimal growth and development, according to a 1998 survey by the Canadian Fitness and Lifestyle Research Institute in Ottawa. “We know that to maintain health, people need 30 to 60 minutes of moderate to vigorous exercise most days of the week,” says Dr. Roy Shephard, professor emeritus of applied physiology in U of T’s Faculty of Physical Education and Health.

In previous generations, regular participation in gym class and school sports was mandatory. More recently, physical education classes have been cut to a minimum. But people are starting to realize the folly of this approach: according to a recent national poll by the Globe and Mail and CTV, 96 per cent of those surveyed agreed that physical fitness courses should be “an integral part of the curriculum for primary and secondary school students.”

Some research suggests that kids who are more physically active do better academically. One ongoing study, started 25 years ago, has been following children at two elementary schools in Quebec who receive an extra five hours per week of physical education. Not only do these children perform better academically than kids at other local schools who get the standard amount of phys. ed., but they also seem to live healthier lifestyles later on. For example, as adults they are less likely to be smokers.

Maintaining robust good health and vitality throughout these turbulent years can be a challenge. “I don’t do anything I think would jeopardize my health,” says Adam Nayman,20, a second-year English major. But when you’re juggling courses, friends, dating and family, “it’s really easy for health to get lost in the shuffle,” he admits.

Jane LeMoyne (BA 1973, BEd 1975, MEd 1985), a Toronto teacher whose daughters, 18 and 19, are “more interested in health than I was when I was growing up,” believes young people today shoulder greater responsibility for certain health choices (such as managing their diet or stress levels) than kids in the ’50s, for example.

It’s important to establish healthy habits in the teens and 20s, says Dr. Miriam Kaufman, a specialist in adolescent health at the Hospital for Sick Children in Toronto. This can prevent the seeds of later problems, such as heart disease or osteoporosis, from taking root. Here are some health messages that young people – and their parents – should take seriously:

Understand the dangers of smoking. Twenty-five per cent of teens aged 15 to 19 smoke, as do 32 per cent of people aged 20 to 24, according to Health Canada. Smoking damages the lungs and heart, increases the risk of cancer, heart disease and stroke, and ultimately kills 45,000 Canadians each year.

Young people know that cigarettes are harmful, but there’s little motivation to quit since negative health effects take a long time to appear, says Dr. Edward Sellers, a professor in the departments of pharmacology, medicine and psychiatry.

Carolyn Kearns (BA 1972, MSc Pl 1974), says smoking is probably the biggest health concern she has for her two sons, 16 and 21, and her daughter, 19, who are all social smokers. “They do feel they’re invincible. And they all probably feel they will stop at some time,” says Kearns, a management consultant in Toronto.

Pay attention to mental health. Kearns says she’s surprised by her children’s emotional resilience: “They’ve learned to cope much better with pressures around exams [than I did], and they’re very good at multi-tasking.” She attributes these skills to a greater degree of life experience and knowledge than teens possessed even a generation ago.

Unfortunately, this is a time of life when mental health can be at risk: major depression, bipolar disorder, schizophrenia and substance-abuse disorders typically have their onset at this age. “Also, conditions that have been present for years may become clinically diagnosable – anxiety disorders, obsessive-compulsive behaviour, anorexia nervosa,” says psychiatry professor Dr. Anne Bassett, emphasizing that when detected early, many of these illnesses may respond better to treatment.

Dr. Kaufman, who is also the author of Helping Your Teen Overcome Depression: A Guide for Parents (Key Porter, 2000), says up to 20 per cent of teens will experience a diagnosable depression during adolescence.

In addition to the stress of term papers, exams, and the competition for limited spaces in graduate programs and professional faculties, some students must also work part-time to meet financial needs, and foreign students must adapt to a new culture, says Dr. Sara Taman (MD 1972, MBA 2000), physician-in-chief of the university’s Health Service clinic. Proper nutrition, exercise and adequate sleep are the first steps in managing stress and anxiety, she says.

Protect against unwanted pregnancy and sexually transmitted diseases. Last year, a survey of 7,800 students in 16 Canadian universities found that 57 per cent reported engaging in sexual activity in the three or four months after arriving on campus. No surprise, then, that “family planning” was the main reason students visited the university’s Health Service clinic last year.

According to Dr. Kaufman, the most worrisome STDs are HIV infection and HPV (human papilloma virus) infection. Several subtypes of HPV are linked to cervical cancer, so sexually active young women should be sure to have annual Pap smears.

Recognize the addictiveness of drugs. In the survey, 18 per cent of students reported having smoked marijuana since arriving on campus, while four per cent had used heroin, cocaine or other “hard” drugs. The subject of whether marijuana use leads to harder drugs remains controversial, but a recent New Zealand study found that teens who smoked pot at least 50 times in a given year were far more likely than non-smokers to use other illicit drugs. Warning signs of drug dependence include an overpowering desire to take a substance; using increasing amounts; needing it early in the day; having withdrawal symptoms; and having trouble quitting.

Watch unhealthy drinking habits. “The reality is that a lot of university students drink; it’s a major form of socialization,” says Adam Nayman. The survey revealed that 85 per cent of students had consumed alcohol since arriving on campus. Thirty-eight per cent had experienced a hangover, 13 per cent had done something they regretted while under the influence, and 11 per cent had missed classes because of a hangover. (Alcohol is also a known risk factor for unplanned or unwanted sexual activity.)

Eat nutritious food. Plenty of vegetables, fruit and whole-grain foods in the diet will lower the risk of heart disease and cancer later in life, as will cutting back on harmful fats in foods like potato chips, commercial baked goods and deep-fried fast foods. Plenty of calcium-rich foods, such as low-fat dairy products, help growing bones reach maximum density and lower the risk of osteoporosis in later life, a particular concern for women. Vegetarian teens need food combinations that provide complete proteins, such as grains with legumes, or grains with nuts.

Stay active. “I feel better when I move,” says first-year arts student Mariapia Pietropaolo, who likes to walk and bike. Regular physical activity boosts energy and stamina, strengthens the heart, lungs, muscles and bones, helps control weight and results in sounder sleep. According to Health Canada, even 10-minute bouts of activity throughout the day are helpful so long as they add up to between 30 and 60 minutes in total.

Visit your doctor regularly. Even the healthiest young person should visit a family doctor once a year, advises Dr. Kaufman. Regular visits give health professionals a chance to deliver health-promotion messages, and allow young people to raise issues they might not discuss with parents.

Quest for schizophrenia gene narrows

Imagine that the human genome is a map of the world, and the challenge – akin to searching for an individual house – is to find a specific gene for schizophrenia. Dr. Anne Bassett, a University of Toronto psychiatry professor, is zeroing in on that elusive target.

Family, twin and adoption studies suggest that schizophrenia is predominantly genetic. Often arising in the late teens or early 20s, the illness affects one per cent of the population, drastically affecting thinking, perception, mood and behaviour.

“Nobody has found a gene for schizophrenia, but we’re close,” says Dr. Bassett, also a staff psychiatrist at the Centre for Addiction and Mental Health. Last year, she and her colleagues reported finding a link between a region on chromosome 1 and this devastating illness. The discovery arose from a 12-year study of 300 people from 22 Canadian families with a high incidence of schizophrenia. Dr. Bassett speculates that, as in most complex medical conditions, not just one, but several genes may play a role in the development of schizophrenia.

Dr. Bassett was drawn to genetic research when, as an undergraduate, she met Canadian scientist Dr. Michael Smith, who later donated his Nobel Prize winnings to schizophrenia research. By identifying genes susceptible to schizophrenia, Dr. Bassett hopes for a better understanding of the basic brain mechanisms involved, which will lead to improved treatments.

What Mother Nature may know about HIV

HIV infection is rampant among female prostitutes in the east African city of Nairobi – yet some manage to escape infection by the deadly virus that causes AIDS.

Dr. Kelly MacDonald, director of the HIV Research Program in the department of medicine, is trying to unravel this immunological and genetic puzzle: why do some people have higher resistance to HIV infection than others? To that end, she spends three months of the year in Nairobi, Kenya, and the rest of the time directing the research program and working as a microbiologist at Mount Sinai Hospital in Toronto.

Dr. MacDonald’s work involves human leukocyte antigens (HLA), molecules that help the immune system recognize and kill cells infected with a particular virus. Using her findings that people with certain types of HLA are more resistant to HIV infection, she hopes to develop a vaccine that will heighten people’s immunity to HIV. “We’re asking, ‘What is Mother Nature trying to tell us about natural immunity to HIV?’” she says. “And how can we mimic that in a vaccine?”

Vaccines are urgently needed, she says, because behavioural-based strategies to prevent HIV infection – using condoms, selecting partners carefully, avoiding intravenous street drugs – haven’t been completely effective. “In spite of all our efforts, the number of new cases of HIV in Canada in 1999 was exactly the same as in 1996,” says Dr. MacDonald. And the total number of infected persons continues to rise.

Worldwide, AIDS has infected more people than all the military and civilian casualties of the Second World War. Today, 25 million Africans are infected with HIV. “But we think that in the next few years, there will be more cases of HIV in India than in all of sub- Saharan Africa, and the same may be true for China,” says Dr. MacDonald.

Although most 25- to 35-year-olds are likely to be healthier than they will ever be, some now are seeking a sense of community and fulfilment that seems to be missing in society, says Dr. Sid Kennedy, director of the mood and anxiety disorders program at the Centre for Addiction and Mental Health in Toronto. “There’s no doubt that people are much more isolated and stressed, and they feel less in control of their lives than they used to,” says Dr. Kennedy, who is also a professor of psychiatry.

According to last year’s Annual Report Card on Canadians’ Health from the Heart and Stroke Foundation of Canada, 43 per cent of Canadian adults aged 30 and over said they felt overwhelmed by their jobs, families or finances. Such emotions can have both short- and long-term consequences on physical and psychological health, says Dr. Brian Baker, an associate professor of psychiatry with an expertise in cardiovascular disorders. When people are unable to cope with negative stress, they frequently develop unhealthy habits such as overeating, under-exercising, smoking and using alcohol or other drugs, he says. This means that some in their 20s and 30s are literally “priming the pump” for heart attacks or stroke in their 40s and 50s.

Women seem to be particularly vulnerable to the psychological effects of negative stress, says Dr. Donna Stewart, professor and Lillian Love Chair of University Health Network and University of Toronto. “Women’s reproductive years are the highest in anxiety, stress and depression. Because most women now work and are balancing jobs with child-rearing, their main health concern is exhaustion,” she says.

It is well known that the rate of depression among women during childbearing years is double that of men, and that depression is most common among younger women. But even though young working women complain about stress, population studies show that women who go out to work are still generally happier and healthier than those who stay at home, says Dr. Stewart.

While people in their 20s and 30s worry about age-old issues such as unemployment, poverty, family tension and politicial unrest, they are also concerned about things that would probably mystify their parents and grandparents – for example, the current preoccupation with physical appearance that is entrenched in the media. “People today tend to assume that you can judge a person’s character by his or her appearance,” says Carla Rice, clinical programs specialist with the Body Image Project at Regional Women’s Health Centre, Sunnybrook and Women’s College Health Sciences Centre in Toronto. This has led to increasing feelings of dissatisfaction and low self-esteem in the person who is being judged, because they are treated differently, says Rice. “Women think they are too fat, which can perpetuate eating disorders such as yo-yo dieting, anorexia and bulimia. Young men think they need to bulk up, which can lead to their ingesting steroids and working out obsessively.”

Dr. Gary Rodin, head of U of T’s psychiatry, health and disease program and psychiatrist-in-chief at the University Health Network, agrees: “When you look at our culture, you find that between one-third and one-half of normal-sized women feel overweight. The overriding cultural ideal of thinness makes people feel there is something wrong with them.”

In a very small segment of the population – about one per cent – this preoccupation with weight and shape becomes extreme, and people may develop Body Dysmorphic Disorder (BDD). It is most common in young adults, probably because body consciousness and concerns about physical appearance are most prevalent in this age group, says Rodin. People with BDD are preoccupied with some imagined defect in their appearance: either a facial feature, their hair, or some aspect of their body size or shape. The person’s concern is almost always unrealistic and causes significant emotional distress. Some react by withdrawing from social contact, while others may obsessively seek surgery to correct imagined defects.

Dr. Kennedy believes the current focus on the body, including the struggle against growing old, seems to be starting earlier and lasting longer than ever before. “It used to be that you could stop worrying about your appearance after age 35 or 40,” he says. “But not in today’s culture.”

The years between 25 and 35 should be the time of life when people establish healthy habits that will ensure their continuing health in middle age and later, says Dr. Baker. However, certain troubling trends appear to be coming out of recent research in the United States – the country whose lifestyle most closely resembles Canada’s own. For example, a study that appeared in the medical journal Circulation last year found that one in six donor hearts removed from deceased teenagers showed signs of atherosclerosis (a plaque buildup in the arteries). It also found that the number of sudden cardiac deaths among Americans aged 15 to 34 rose about 10 per cent between 1989 and 1996. The overall increase may be caused in part by the increased prevalence of cardiovascular risk factors such as obesity among adolescents, according to Zhi-Jie Zheng, lead author of the study. “What’s happening in the U.S. is likely happening here, too,” says Dr. Baker.

Panic disorder in young adults
About three-and-a-half per cent of Canadians are affected by panic disorder, says Dr. Neil Rector, an assistant professor of psychiatry who heads the Anxiety Disorder Clinic at Toronto’s Centre for Addiction and Mental Health. They experience “out of the blue” panic attacks, which include symptoms such as dizziness, tingling hands and feet, trembling, chest pain, palpitations, shortness of breath, nausea, chills or hot flushes.

Panic attacks occur in people of all ages, but they often start in early adulthood (the mean age is 25). Recurrent incidents constitute a panic disorder that must be treated to prevent life-affecting consequences. “A core feature of panic disorder is intense fear of the next attack,” explains Dr. Rector. “This can lead a person to avoid places where a previous attack has occurred. He or she may not venture beyond a safe zone – a pattern of avoidance known as agoraphobia.”

Panic disorder also appears to affect twice as many women as men, although this may simply reflect that men are less likely to seek help and potentially more likely to medicate their symptoms with alcohol.

Cognitive-behavioural therapy can help the majority of people confront and overcome their fears, while such antidepressant drugs as selective seratonin uptake inhibitors seem to dampen the symptoms of panic.

Certain physical changes normally start to occur in the 40s and 50s: menopausal symptoms in women and sexual changes caused by declining testosterone levels in men. Many suddenly can’t read a phone book without glasses. And as they approach 50, some report being more forgetful.

In most cases, these turn out to be benign signs of fading youth rather than symptoms of serious health problems, says Dr. Baker. More serious cause for concern are mid-life developments such as high blood pressure and high cholesterol, both risk factors for heart disease and stroke. “There’s a whole host of problems that, statistically speaking, people are vulnerable to, even if it’s to a minor degree. In some people, this is when a major disease develops,” says Dr. Baker.

So what is the best way to approach the many changes and challenges of middle age? “It’s important to be aware of what’s going on both physically and emotionally,” says Dr. Baker. “People should see their doctor at least once a year, because some risk factors need treatment, and sometimes illnesses show themselves early. This is the time for PSA [prostate-specific antigen] blood tests that may help detect prostate cancer, for regular colonoscopy [to detect colon cancer] and for breast examinations.”

According to the Heart and Stroke Foundation, the greatest threat to middle age is heart disease and stroke, which kills approximately 79,000 Canadians each year. Classic risk factors, such as high cholesterol, diabetes, high blood pressure, smoking and family history, account for only about 30 to 50 per cent of these diseases, says Dr. Peter Liu, holder of the Heart and Stroke/Polo Chair and director of the Heart and Stroke/Richard Lewar Centre of Excellence. Dr. Liu and his colleagues are working to identify so-called “novel” risk factors – other possible causes of cardiovascular disease such as bacterial or viral infection. One example is chlamydia pneumoniae, a common bacterial infection. “By the time we’re 50, about 80 per cent of us have had exposure to this bacteria,” says Dr. Liu. There’s evidence that chlamydia may infect blood-vessel walls, adding to a build-up of fatty substances (atherosclerosis) that causes blood vessels to narrow dangerously.

Researchers are now working to understand how chlamydia gets into blood vessels, and to what extent this contributes to heart disease. They are also investigating whether antibiotic drugs or even a vaccine against chlamydia might one day protect people from heart attack and stroke.

As we age, most of us also start worrying about cancer. Lung cancer is now the leading cause of cancer deaths among Canadians of both sexes. According to recent statistics, more than 17,000 Canadians died of lung cancer in 1998. “There’s no question that smoking has had a major impact on lung cancer rates, especially in women,” says Dr. Ron Feld, a medical oncologist at Princess Margaret Hospital in Toronto and a professor of medicine at U of T. When he began treating cancer patients 30 years ago, he says lung cancer patients were overwhelmingly male. But as women began to smoke tobacco, their rates of lung cancer began to “catch up.”

If caught early, lung cancers are quite survivable, says Dr. Feld. But until recently, doctors had no really effective tools for early detection. A special type of computed tomography or CT scan, called spiral CT, is now being tested to see if it might help pick up earlier, more curable lung cancers.

Overall, cigarette smoking is the primary cause of lung cancer, accounting for at least 80 per cent of new cases in women and 90 per cent of those in men. Dr. Feld says current smokers can reduce their risk for lung cancer – and also for various head and neck cancers, bladder cancer and heart disease – by doing whatever it takes to give up tobacco.

Among women, the most frequently diagnosed malignancy is breast cancer, which is more common after age 50. Researchers continue to explore early-detection options. A recent study by epidemiologist Dr. Cornelia Baines and colleagues at U of T compared the effectiveness of an annual mammography (breast X-rays) plus a clinical breast exam (CBE) with CBE alone in women aged 50 to 59. CBE involves a specially trained doctor or nurse inspecting the breasts for abnormalities.

“Mammography detected more cancers and picked up smaller cancers than CBE,” says Dr. Baines, a professor in the department of public health sciences and deputy director of the Canadian National Breast Screening Study. “But after 13 years of followup, mammography had not reduced deaths from breast cancer.”

This research establishes that CBE may be an effective choice for women who don’t have regular mammograms, adds Dr. Baines. CBE may be especially useful for women aged 40 to 49, because mammography is less accurate in younger women than in older women.

The major concern for men is prostate cancer. While much research has focused on earlier diagnosis and better treatment, Johanna Rommens, an associate professor of molecular and medical genetics, is working to provide more information about prostate cancer risk.

Dr. Rommens has been part of an international research team that has discovered a new genetic footprint for prostate cancer: earlier this year, scientists reported finding two different mutations – high-risk and moderate-risk – of a gene called ELAC2. Men carrying the high-risk version were five to 10 times more likely to develop prostate cancer than those without this mutation; those with the moderate-risk version were 1.5 to three times more susceptible. Although this finding won’t lead to an immediate genetic test for prostate cancer, Dr. Rommens says, it does provide momentum for further research.

Making choices for menopause
Confused about the alternatives to hormone replacement therapy for relieving menopausal symptoms and reducing the risk of heart disease and osteoporosis? You’re not alone.

U of T researchers are currently studying hormone replacement options known as selective estrogen receptor modulators, or SERMs. “These are compounds that are like hormones, but very specific for various organs,” explains Dr. Angela Cheung, assistant professor in the departments of medicine, public health sciences and health policy, management and evaluation.

Dr. Cheung and Dr. Donna Stewart, professor and chair of women’s health at the University Health Network and University of Toronto, are currently involved in a seven-year international study of the effect of a particular SERM called raloxifene on heart disease. The RUTH (Raloxifene Use for The Heart) trial, involving 10,000 women around the world, is still about five years from completion. Dr. Cheung also took part in a recently published study that found that raloxifene increased bone density only modestly (two to three per cent), but significantly decreased spine fractures (35 to 55 per cent).

SERMs may cause hot flashes, so they may not be the best choice until after menopause, says Dr. Cheung. Menopausal women wanting to protect their heart and bones should first consider exercise, good nutrition and quitting smoking.

Early detection of bone disease
Unless you’ve broken an ankle on the ski slopes, you probably haven’t given much thought to your bones. But bone health becomes important in middle age: according to the Osteoporosis Society of Canada, one in four women and one in eight men over 50 have osteoporosis, a disease in which bones lose mass and become more fragile and prone to fractures.

“Many end up with a fracture, then another fracture, and keep going to a fracture clinic but never seem to get diagnosed and treated for osteoporosis,” says Dr. Rowena Ridout, staff physician at Women’s College Hospital and an assistant professor in medicine, adding that so-called “low-trauma fractures” are often the first sign of osteoporosis. These fractures typically occur after a non-serious injury, or a fall from a standing height or lower, and often affect the wrist, hip or spine. People over 50 who experience such a fracture should investigate the possibility of osteoporosis with their doctor.

Bone density scans can help with diagnosis and treatment, which may include taking a bisphosphonate drug such as Fosamax (alendronate) or Actonel (risedronate). These drugs slow down the resorption or loss of bone that leaves bones fragile, Dr. Ridout explains.

Bombarded with media images of sixtysomethings reaping the rewards of wise investments, we tend to fixate on the monetary aspect of retirement. In reality, living the good life means not only having enough money but also being in good health and being able to spend time with others.

For more than 27 years Jury Kopach (BSc 1969, St. Michael’s) has helped companies prepare retirees-to-be for life after work. Kopach, a senior vice-president at T.E. Financial Consultants Ltd., says that once financial questions are settled, the focus shifts to health: “People become concerned about their longevity; they want to know if they will be around to enjoy their retirement.”

Statistically, a 65-year-old Canadian male can expect to live another 12 years, while a woman the same age can look forward to 16 more years of life. That’s plenty of time to do all those things you’ve been putting off – but also plenty of time for a debilitating illness to set in.

Unfortunately, some older people will face challenges that restrict their activity. Because women tend to live longer, they are more likely to experience the loss of a partner. Others may find themselves caring for extremely elderly parents, even as their own health is starting to deteriorate.

Men are particularly susceptible to loss at this age: the loss of prestige that came from their careers, the loss of physical abilities that can accompany age, the death of a spouse or close friend. These losses put them at high risk for depression, which may explain why suicide rates among older adults are nearly double those of adolescents.
Dr. Marnin Heisel, the Stephen Godfrey Fellow associated with the Arthur Sommer Rotenberg Chair in Suicide Studies in the department of psychiatry, recently developed an assessment measure – the first of its kind – that will help mental-health professionals identify seniors who have suicidal thoughts. The good news is that depression is treatable and should never be accepted as a normal aspect of aging.

Early identification is also vital in diagnosing osteoporosis, which typically begins much earlier in life but usually makes itself known in the sixth age and beyond. Hip and spinal fractures caused by fragile bones are especially common. Research shows that between 25 and 40 per cent of older people who break a hip may never walk unassisted again.

A major cause of disability among older people is osteoarthritis, a chronic condition resulting from years of wear and tear on bones and joints, among other factors. It’s estimated that 85 per cent of Canadians will experience some degree of joint pain and stiffness by age 70. Restorative surgery to replace worn-out hip and knee joints has been widely successful, and researchers have developed many strategies and devices that make it easier to live with osteoarthritis.

Half of all arthritis sufferers say they have pain that limits their activity. But they can improve their quality of life with the help of new medications and arthritis self-management techniques, says Dr. Elizabeth Badley, a professor in the department of public health sciences and director of the Arthritis Community Research Evaluation Unit (ACREU). Most important are proper exercise and healthy weight maintenance.

Recently Health Canada approved the use of COX-2 inhibitors, which may have less gastrointestinal toxicity than some other prescription medications for arthritis. These drugs may provide a useful option for osteoarthritis sufferers who aren’t helped by such traditional pain relievers as acetaminophen or ibuprofen.

One of the greatest fears of people over age 60 is that they will succumb to Alzheimer’s disease (see page 28). It’s true that the percentage of affected people doubles every 10 years after age 65, but occasional memory loss – which some ruefully call “having a senior moment” – is not an early sign of Alzheimer’s, says Dr. Fergus Craik, professor emeritus of psychology and senior scientist at the Rotman Research Institute at Baycrest Centre for Geriatric Care.

Craik explains that without a doubt, memory generally declines with age, but only certain types of memory are affected. Procedural memory – ability to read, drive a car, walk and swim – isn’t usually affected by normal aging. And knowledge of factual information also doesn’t deteriorate much, provided people remain mentally active. Instead, the greatest decline occurs in what’s called episodic memory: the recollection of personal events. As people age, they don’t encode their experiences as richly, says Craik, making it harder to retrieve memories, especially recent ones.

In the past 10 years, substantial advances in the care of the elderly have occurred. But as Dr. Michael Gordon, professor of medicine and head of geriatric and internal medicine at Baycrest Centre for Geriatric Care in Toronto, concludes, “We are getting better at postponing death, but we have not been as successful at eliminating diseases or reversing damage already done.” Gordon believes that the growing demographic of seniors is already setting much of the agenda for health care and research around the world, however, and the breakthroughs and developments along the way will be good news for us all.

Bred in the bone

Imagine one day being able to replace fragile bones with strong, new bone tissue cultured from a person’s own bone marrow cells. In fact, culturing human bone cells and new technologies for bone “scaffolding” are two recent breakthroughs from Dr. John Davies, a professor of biomaterials and biomedical engineering.

One of the major challenges in engineering bone and other tissue is coming up with the massive number of cells required. The use of bioreactor cultures (cell cultures that are prevented from coming into contact with surfaces) has overcome this obstacle. This technique keeps cells in suspension through continual stirring, promoting cell division while inhibiting further development. Vast numbers of precursor cells for human bone tissue can be introduced in this way. To transform these cells into active bone cells, they are extracted from the bioreactor, placed in a medium that encourages self-growth and attached onto a biodegradable scaffold.

This biodegradable scaffolding – a spongelike device – provides a structure to hold the cultured cells when they are placed in the body. As these cells grow and bone is regenerated, the scaffolding breaks down and disappears. While yet to be tried in humans, this bone-engineering process was tested on a laboratory rabbit missing a piece of its femur. After receiving the bioengineered bone tissue, it was up and hopping around within six weeks.

Life expectancy in Canada rose steadily during the 20th century and reached record highs in 1998: 76 years for men and 81 years for women. On average, today’s seniors can expect to live about 20 years longer than their grandparents – the estimated life span for that generation was just 59 years.

The Queen Mum might be the world’s best-known centenarian, but she is by no means alone. Some 3,700 Canadians have already reached age 100, and that number is likely to double over the next 20 years. While life expectancy won’t continue to rise indefinitely, health-policy analysts predict further increases because fewer older people are smoking.

Closer to home, we can take inspiration from the likes of artist Doris McCarthy (BA Woodsworth 1989). McCarthy retired in 1972 after 40 years of teaching art, but continues to paint every summer at a Georgian Bay cottage and is writing her third book. “My passion for my work energizes me,” she says. A living example of lifelong learning, she went back to school and earned a BA in her 70s, and tries to take a course every year at the University of Toronto at Scarborough.

McCarthy, 91, is the perfect rebuttal of Shakespeare’s rather grim characterization of old age. Although her hearing and distance vision are “no great shakes,” she drives, does her own housework and until recently, was able to read without glasses. She still lives in her own longtime home, which she calls “Fool’s Paradise,” overlooking the Scarborough Bluffs. Her landscapes have been exhibited at the McMichael Canadian Art Collection in Kleinburg, Ont., but she calls her home her most precious work of art. “I plan to live there until I’m carried out,” she says.

“The elderly are getting healthier all the time,” observes Dr. Michael Rachlis, health policy analyst and associate professor in the department of health policy, management and evaluation. “Old people today have less disability than their historical peers.”

But will the curtain close on a happy ending for the increasing ranks of the elderly? In just 15 years, seniors will outnumber children in Canada for the first time, and the health-care system and other social programs may become strained to the snapping point. In 25 years, the first baby boomers will turn 80. That’s when some fear the health-care system may finally fall apart, as elderly boomers in their 80s flood the system and overwhelm society’s ability to care for them.

However, we shouldn’t blame old people for rising hospital costs, says Rachlis. “It is illness and dying, not aging itself” that are associated with high medical costs. We need to make better use of our resources, and if we are smart about it, he says, better care for the elderly won’t break the bank. For example, instead of paying physicians to teach diet and preventive care in 10-minute office visits, more nurses, dietitians and social workers should be available to provide patient education for elderly people with diabetes. According to Rachlis, the system also needs more palliative and hospice care for sick, elderly people – particularly cancer patients, who would prefer to die away from expensive hospital settings.

One underserved area that affects many people in the last stage of life is home care. Only a small percentage of Canadian seniors receive some type of health care at home (estimates vary from three to 12 per cent), and that’s a pity, says Dr. Peter Coyte, professor of health economics and co-director of the Home and Community Care Evaluation & Research Centre. He calls our current approach to health care short-sighted. “We have a Cadillac health-care system we can be proud of when it comes to doctors and hospitals,” he says, “but when it comes to services like rehabilitation, physiotherapy, chemotherapy, dialysis, wound care, personal attendants and nursing homes, the system is bankrupt.” If the system doesn’t do a good job of providing health care when people need it at home, it’s going to cost Canadians more: more for emergency and acute care; more for premature institutionalization of the elderly; and more to treat family caregivers dropping from stress-related illnesses, says Dr. Coyte.

Will we have enough health-care providers – family members and professionals – by the year 2025, when the baby boomers become octogenarians? The simple answer is no, according to Dr. Alex Jadad, a professor of health policy, management and evaluation. “We don’t have enough doctors, nurses, medical technologists, physiotherapists and personal attendants now,” he says. But Jadad thinks the natural laws of supply and demand will kick in eventually. Indeed, young people making career choices now who want to ensure they won’t ever be out of work would do well to consider the health-care field.

When it comes to health and well-being, how are older Canadians doing right now? About seven per cent of Canadians over 65 live in a retirement residence, chronic-care hospital or nursing home (we have one of the world’s highest rates of institutionalizing the elderly). But that means that more than 90 per cent of our seniors are still living at home and enjoying relative good health and independence. That’s a good thing, says Pia Kontos, a doctoral candidate in the department of public health sciences, who believes that home “plays a critical role” in maintaining seniors’ sense of personal identity.

McCarthy, for one, doesn’t hesitate when asked how her retirement decades compare with her career era. “Much richer,” she says. “I don’t actually have to do anything,” and “I haven’t lost contact with the young.” What’s her advice? Eat sensibly (at one time she was overweight but gave up desserts), don’t smoke (“I smoked for 20 years and stopped the day I read the first medical report of the relationship between health and smoking, in 1950″) and get exercise (she skates briskly for an hour three mornings a week, except in summer, at her local recreation centre, and every morning, she does 36 leg lifts with eight-pound weights on each leg).

There is no trace of oblivion in her voice.

Alzheimer’s vaccine ready for tests

While most of us who survive to 80 and beyond will do so with our minds intact, there is no doubt that aging is the main risk factor for Alzheimer’s disease. About one-third of those over the age of 85 will show some symptoms – including memory loss, wandering, inappropriate behaviour and hallucinations.

Dr. Paul Fraser, associate professor of medical biophysics at the Centre for Research in Neurodegenerative Diseases, and his colleagues, are ready to test a potential vaccine against Alzheimer’s on humans. The vaccine (developed mainly as a treatment, although it might be used preventively) is based on the theory that an accumulation of beta-amyloid protein in the brain is largely responsible for nerve-cell death, which in turn causes memory loss and the other devastating symptoms of the disease.

Using genetic engineering, Fraser’s team created a strain of mice with brain deposits of beta-amyloid that interfered with their ability to function normally. The researchers developed a vaccine that reduced the protein deposits and also improved the mice’s ability to find a hidden platform in a pool of water. The vaccine-treated mice did almost as well as a healthy group of control mice. “We’re still looking for funding for clinical trials in humans,” says Fraser, who knows how expensive and lengthy such trials are. The therapy appears to be safe and non-toxic, with no adverse side-effects, he says.

Making home a safer place
More than half of those over age 80 already use some kind of mobility aid – a cane, a motorized scooter, a walker – to help them get around their homes and communities more comfortably and safely. Researchers at the Centre for Studies in Aging (CSiA) at Sunnybrook and Women’s College Health Sciences Centre in Toronto are designing new and better devices to keep seniors mobile.

One of the CSiA’s most recent inventions is the “Toilevator” – an easy-to-install, relatively inexpensive device that raises the height of a toilet a few inches at its base, to help people who have trouble using a standard toilet because of arthritis, balance problems and limitations due to wheelchair use. Although the CSiA has designed items that are more high-tech and expensive than this one, CSiA director Geoff Fernie is especially proud of the Toilevator, which won the Canadian Retail Hardware Association’s Best New Canadian Product Award last year. Two other CSiA inventions:


• A safe, easily accessible bathtub with two grab bars and a wide ledge that allows older or disabled persons to sit down, then swing their legs into the tub.

• SturdyLift, the world’s first battery-powered portable overhead lift, which allows caregivers to safely lift someone in or out of a bed, chair or bathtub. Other lifts used in hospitals and homes depend on a ready source of electricity.

The final hours

Most people don’t get to choose what they eventually die from. But if we’re fortunate, we can have a say in how and where our last days will be spent. After her husband, Ian Anderson (Cert. Bus. 1974 Woodsworth), died of cancer in 1990, Margaret Anderson (BA 1981 Woodsworth) decided that quality of life is just as important at the end as in our prime. She donated $1 million to found the Ian Anderson Continuing Education Program in End-of-Life Care in her late husband’s memory. The program will train about 10,000 physicians and specialists across Canada to deal with all aspects of death: everything from breaking bad news to patients and families, to controlling pain and easing the last hours of life.

More than three-quarters of the $100 million in funding is in place, and there’s “a plan for the remainder,” according to James Friesen, chair of the Banting and Best department of medical research and a key player – along with Cecil Yip, vice-dean, research, in the Faculty of Medicine – in the drive to build the new centre.

That’s why, in early summer, a Board of Governors subcommittee okayed the release of $10 million for design work on the building, which will house at least 50 faculty members from departments as disparate as pharmacy and engineering, as well as their grad students and postdoctoral fellows. “It will be a very interesting place,” says Friesen. “No other institution will have the scope it will have. It will be one-stop shopping for collaborations that link the campus and the hospital medical research institutes.”

The centre will have five “platforms,” or areas of research, but the scientists in each will be encouraged to work with collaborators from other specialties. A pharmacist, for instance, might find herself working side by side with an engineer, a molecular biologist and a chemist. “We’ll try to mix them up, so that new ways of interacting can evolve,” says Friesen.

The researchers will be appointed to U of T departments in the conventional manner, he says, “but the research part of their lives will be in this both open and open-ended environment.” The five platforms will be functional genomics, protein structure, bioengineering and molecular engineering, animal models of disease, and functional imaging.
When it’s finished – Friesen hopes that will be within three or four years – the centre’s new home will rise just south of the current Medical Sciences Building.

If you walk into the labs of the Banting and Best department of medical research – possibly ground zero for the explosion of research that some call the New Biology – that comforting scent is the first thing you notice. Researchers in the institute use yeast – yep, the same stuff you make bread or beer with – as a “model organism” to help them probe the origins of life and disease. Not that yeast is the only model organism around. Other U of T scientists study mice, for instance. Still others study raw proteins, stripped of the organisms that produced them. Others are still concentrating on winkling out the secrets of human DNA. And others work in silico – studying via computer the patterns of knowledge that are emerging from the mountains of data thrown up by the sequencing of the human genome.

Earlier this year – as you will know, unless you were on an interplanetary leave of absence – two teams of scientists, one an international consortium and the other an American group, published the sequence of the human genome (the base set of genetic instructions that make us what we are). There were loud huzzahs on both sides of the Atlantic, and we are now officially in the post-genomic age. The future, once again, is upon us; the frontiers of biology and medicine are being pushed forward. Dispatches from the front speak of strange new disciplines: proteomics, functional genomics, bioinformatics, evolutionary genomics, model organism genetics.

Now that the genome sequence is more or less known, “there are a whole lot of ‘ics,’”says James Friesen (PhD 1963), chair of the Banting and Best and a driving force – along with Cecil Yip, vice-dean, research, in the Faculty of Medicine – in U of T’s planned Centre for Cellular and Biomolecular Research. “There are proteomics, functional genomics, phenomics….” He trails off with a wave of his hand. Friesen thinks “functional genomics” is the best catch-all phrase, because it includes the ideas of function and of genes. Essentially, he says, the goal is to go beyond the human genome to understand what exactly it does, now that we know what it is: “What is all that information telling the cell, and how is it put together?”

Regardless of the label you choose, the University of Toronto has been quietly gathering its forces for the new revolution in biology. There is now a host of individual researchers, as well as interlocking partnerships and collaborations that draw their members from the university and the hospital research institutes lining University Avenue, who are on the new knowledge frontier. “That’s where U of T in general and” – another wave of the hand – “the research institutes across the street have a huge amount of strength,” says Friesen.

Up until now, the key player in all of this has been the famous double helix of deoxyribonucleic acid, or DNA. It got the lion’s share of attention, not because of its intrinsic interest, but because it was perceived to be the key to biology. Understand DNA and you would understand How People Work. And not only people, but trees, insects, moulds – everything, in short, that lives on the face of the earth. Genes, the theory went, were all; know the genome and you would know biology.

Unfortunately, that was naive; knowing what one author called the Code of Codes puts you further forward, but you still have to understand the rest of the system. Some of the DNA – the five per cent or so that we call genes – contains the code to make proteins. The proteins do most of the rest of the work: they form the body’s structures, they carry the body’s messages and they are what goes wrong when we get sick. Proteins in bacteria and viruses are the targets for our drugs. Other bits of DNA contain so-called regulatory sequences that tell genes when to turn on and off, and are often guided by message proteins or other molecules in a startlingly complicated feedback loop. And, surprisingly, much of our DNA has no apparent function, which probably means we just don’t know.

Aled Edwards
Knowing every protein on the planet
DNA has occupied the spotlight only because it was an essential first step. “If there was a magic way to study proteins, you wouldn’t have to bother with DNA at all,” says biochemist Aled Edwards of the Banting and Best. “The Human Genome Project has really quantified our ignorance of biology.” Now we have the code, but the surface has only been scratched; almost everything else about how we work still needs to be discovered.

Propping a foot against a nearby wall, a cup of coffee on the table in front of him, Edwards allows that he may have a short attention span. For more than five years, since before he arrived at U of T from McMaster University in 1997, he’s been preaching a gospel in the wilderness: what’s needed, he has been saying, is to characterize all the building blocks of proteins. Be careful what you wish for – he’s now the leader in that endeavour. And, he says, now he’s bored. “To take a dumb idea and make it accepted ? that’s what I got a bang out of,” he says. “Now we’ve just got to sit down and do it.”

The “dumb idea” is this: every protein is composed of a sequence of chemicals called amino acids. But those acids form a finite number of specific substruc-tures, perhaps as many as 50,000, called “domains.” These protein domains are where the action happens, says Edwards. They are where other molecules dock, to bring messages or lock on to form part of a larger structure. The domains are like charms on a bracelet or beads on a string – mixing and matching them is what gives a protein its function. So knowing what each one looks like is a giant step toward knowing how a given protein works. In the long run, says Edwards, knowing how proteins work will mean better and more effective medicine. “Almost every disease is caused by a screw-up in a protein,” he says.

Right now, scientists know the function of less than 20 per cent of the proteins in the body, making it difficult to find and fix “screw-ups.” “You wouldn’t go to a mechanic if he admitted he only knew what 20 per cent of the parts did,” says Edwards. “So we want to determine the three-dimensional structure of every protein on the planet.” With colleague Cheryl Arrowsmith of the Ontario Cancer Institute in Toronto, a professor of medical biophysics, Edwards is leading an international project involving the Argonne National Laboratory in the U.S. to ferret out the domain structures.

Jack Greenblatt
How proteins interact
Jack Greenblatt, a molecular biologist, is taking another approach. For Greenblatt, the new frontier is the way proteins interact. Sure, it may help to know how the protein snaps together, but the interplay between proteins is the central motif of biology. Essentially, much of drug research to date has been the search for molecules that interact with proteins in some useful way. But those searches were retail – one or two proteins at a time – and the value of the human genome sequence, says Greenblatt, is that it allows wholesale study of protein interactions. “We started to think about this five or six years ago,” he says, “and we realized we could get all sorts of information by looking at protein interactions on a whole-genome scale.”

It is not a trivial problem. There are about 4,000 genes in the bacterium E. coli, 6,000-odd in yeast and 35,000 or more in Homo sapiens. Even if you just look at two proteins at a time, you’re talking millions of possible links. And Greenblatt and his colleagues are trying to pull out multiple interactions – perhaps thousands at a time. “It gets to be a fairly demanding project,” he says, “but that’s what we want to do.”

Stephen Scherer
The treasures of chromosome 7
Before you can work on proteins, though, it helps to have the corresponding gene. And there’s a lot more work to be done to get the genes, says molecular geneticist Stephen Scherer, associate professor of molecular and medical genetics, and associate director of The Centre for Applied Genomics (TCAG) at the Hospital for Sick Children. For one thing, neither of the two genome projects has a complete, start-to-finish sequence of human DNA. For another – something that’s often lost sight of – neither project is exactly universal: they studied DNA from a total of a dozen or so individuals. Your mileage, as they say in the car ads, may vary. “There has been a lot of hype,” says Scherer.

“We still have a lot of work to do.”

That’s why he and his colleagues are still beavering away to complete the world’s understanding of the human chromosome 7. Despite the genome projects, actually finding and sequencing the genes on a chromosome is still a time-consuming, difficult and – when you find one – thrilling chore. Chromosome 7 is the home of dozens of genes linked to disease, including some linked to autism, a suite of genes related to a form of epilepsy, and the famous CFTR gene whose mutation causes cystic fibrosis. (CFTR was one of the first disease genes found, and was discovered by TCAG director Lap-Chee Tsui and colleagues.) “There are a lot of really great diseases to study on chromosome 7,” says Scherer.

And, despite the genome projects, the treasures hidden on chromosome 7 (let alone the other chromosomes) are not exhausted. Outside Scherer’s small but tidy office hangs a much-annotated map of 7. It is, he says, the most complete of any of the chromosome maps – thanks largely to the Chromosome 7 Project – but it still has gaps. “Based on our numbers,” he says, the genome projects “missed between 20 and 25 per cent of all the genes on 7 – and we’re missing some genes, too.” Think of the genome as an encyclopedia containing the information on how to make and operate a human being, he says. Some fiend has cut the 23 books into individual words and now – with the two genome projects – “it’s roughly in order, but there are missing pages, rips in pages and some chapters in the wrong order.”

In the long run, though, Scherer sees a day when much of the data we’re now painstakingly sifting through will be used routinely. “In 15 years,” he says, “it will not be unusual for an autopsy to include DNA sequencing.” Drugs will be tailored to match individual DNA sequences. Diseases will be diagnosed by looking at the DNA of pathogens. It may even be possible to cure or prevent DNA-based diseases, such as Alzheimer’s or autism. But, for the near future anyway, it’s more of the same for geneticists: “The next three or four years will be cleaning up the genome, finishing the sequences and finding all the genes,” says Scherer. One major change is that much of the work will be done on the computer screen. “Most of the people in my group now spend at least 50 per cent of their time working on computers,” says Scherer.

Tony Pawson
How the cell behaves
Molecular biologist Tony Pawson, another of the genomic frontiersmen, doesn’t think that “wet science” is going to go the way of the dodo. But more and more work will be done in silico, if only because there’s so much data “you rapidly run out of the ability of the human mind to remember everything, let alone how it’s put together.” Biologists have been slow to join the silicon revolution, in part because there’s just too much complexity and – until now – not enough hard data. But Pawson thinks we’re on the verge of having enough information to be able to create what he calls a “virtual cell.”

“The challenge – now that we have all of the genome – is to figure out in a comprehensive way how the cell is wired together,” says Pawson. That’s what he and others at Mount Sinai Hospital’s Samuel Lunenfeld Research Institute have been working on for years: how the cell’s internal communication system works. “The next challenge is to understand how cell A differs from cell B,” he adds. “And the long-term challenge is to be able to describe these processes in sufficient detail that you can make a mathematical model of how the cell behaves.”

That mathematical model would be Pawson’s “virtual cell,” in which researchers would be able to watch signalling pathways operate, observe the complicated interplay of proteins and DNA, and see what happens when things go wrong. The genome projects have produced a flood of data on DNA; Pawson and colleagues are working on a similar project for protein interactions. The Biomolecular Interactions Network Database (BIND), he says, is intended to help answer his first challenge – understanding the cell’s wiring.

Peter Lewis
Applying computer power to biology
The BIND database will help, but “it’s not the end, it’s a beginning,” says Peter Lewis, head of U of T’s multidisciplinary program in proteomics and bioinformatics. Moving forward is going to take a new breed of specialist: the bioinformatician. These new professionals will keep track of the enormous quantities of data generated by people like Edwards, Greenblatt and Scherer. But they’ll do more than just act as high-tech librarians, says Lewis. They’ll be able to mine the data fields for new relationships and facts. As well, new experimental techniques, such as microarray analysis and mass spectrometry, are throwing up “horrendously complicated” results; bioinformaticians will play an increasing role in analysing experimental data.

Janet Rossant
The roar of the mouse genome
But, of course, there’s more to the study of biology than DNA, proteins or even the living cell. Somehow, all of that is orchestrated to make a living creature: a worm, a mouse or a human being. Janet Rossant, a professor of molecular and medical genetics and co-head of the program in development and fetal health at Mount Sinai Hospital’s Samuel Lunenfeld Research Institute, has spent years studying the development of mice.

“Model organism genetics” – studying one type of creature in the hope of understanding another one entirely – relies on the fact that evolution is thrifty. Once evolved, a gene or a protein, or even a protein complex, is rarely thrown away. So, for instance, scientists studying the fruit fly have found a cascade of protein interactions dubbed the “hedgehog pathway.”

In the fly, the hedgehog pathway governs the formation of body segments. But we humans also have a hedgehog pathway, conserved over millions of years of evolution. If our hedgehog pathway is disrupted, we become susceptible to cancers, such as basal cell carcinoma, as well as several inherited diseases.

So it makes sense to study mice, which are, after all, closer to us than flies. And the deluge of new information, including the sequencing of the mouse genome, has made it possible to do almost industrial-scale functional genomics on mice, says Rossant. She and colleagues are trying to look at the function of not one, not two, but all the genes in the mouse. The idea is to make random mutations in mice and then see if they develop the clinical picture of any human illness, such as hypertension. The mice go through a battery of tests, “essentially like going to the doctor for a checkup” to see if they develop symptoms, says Rossant. When mice show signs of disease, it’s simple, in principle, to track down which genes are mutated and thus possibly responsible for the disease. The power of the technique rests on the ability to study many mice (in the first six months of the pro-ject, Rossant and colleagues screened 2,000) and swiftly to find the genes involved.

Strolling down the bread-scented corridors of the Banting and Best, James Friesen says he has already seen the future. For yeast researchers, the post-genomic age is now five years old; the complete genome of yeast, all 6,000 genes, has been known for that long. In fact, one project now underway at U of T is to create 6,000 varieties of yeast, each with one of the genes knocked out, and then make 36 million pairwise crosses to see how the various genes affect each other. The only problem, says Friesen, is that “the more you know, the more you don’t know.”

This is a good time to be doing post-genomic research, Friesen muses, and Toronto is a good place to be doing it. “We have one of the biggest biomedical research establishments on the continent and, indeed, in the world,” he says. That, combined with good government support for research and the welcoming nature of the city itself, has meant Friesen and his colleagues are able to hire some of the top young guns of the post-genome frontier. Some of them – like Edwards – are already on board, says Friesen, and all told between 25 and 30 new people are coming in over the next few years. “Our science has landed us in the right place,” he says.

The Faculty of Medicine can lay claim to countless research firsts. Take a look at the partial list of breakthroughs over the past 20 years that follows and you will encounter, for example, Robert Salter (MD 1947), an orthopedic surgeon whose innovative work has improved lives everywhere. One of Salter’s numerous surgical procedures carries his name: the Salter innominate osteotomy repairs congenital dislocations of the hip in young children. He also found that bones, cartilage, tendons and ligaments in joints could be stimulated to repair themselves with a gentle movement called continuous passive motion.

Philip Seeman, professor of pharmacology and psychiatry and holder of the Anne and Max Tanenbaum Chair in Neuroscience, was described by the selection committee for the Killam Prize for Health Sciences as one of Canada’s most important neuroscientists. His discoveries regarding dopamine receptors have allowed researchers to begin to unravel the mysteries of schizophrenia and have led to ways to diagnose the disease more precisely.

Michael Sefton (BASc 1971), professor of chemical engineering and applied chemistry and director of 
U of T’s Institute of Biomaterials and Biomedical Engineering (IBBME), discovered a way in 1997 to trigger the growth of new blood vessels, which will help speed the healing of wounds and aid in the growth of artificial organs for transplant. In the field of tissue engineering, he is leading an effort to develop procedures that could enable nerve regeneration, artificial skin and cornea replacement. He also co-ordinates an international group of scientists for the Living Implants from Engineering project that is focusing on organ transplants. John Davies, a professor of biomaterials in the Faculty of Dentistry and head of the bone interface group at IBBME, developed a biodegradable foam that can be used as a scaffolding for bone growth and could lead to new ways to reconstruct bone surgically. In 1998, his experiment to investigate how bone cells interact in space was sent on a space shuttle mission.

Molecular biologist Tony Pawson is recognized worldwide for uncovering some of the mechanisms used by cells to communicate with each other. This work has given researchers the clues they need to find out how cells grow, react with hormones and become cancerous. With more than $300 million a year in research funding, U of T scientists are laying a large part of the groundwork for what will become the advanced technologies of the 21st century.

1981

• Harald Sonnenberg and others discover the atrial natriuretic factor, a hormone secreted by the atrium of the heart that is believed to have an effect on salt balance and blood pressure regulation.
• Griffith Pearson and Joel Cooper perform the world’s first single lung transplant.
• Tak Mak and others identify the T-cell receptor gene, a major advance in understanding the human immune system.
• Ronald Worton and others locate the gene responsible for Duchenne muscular dystrophy.
• Joel Cooper performs the world’s first successful double lung transplant.

1988

• Alan R. Hudson and Susan E. Mackinnon perform the world’s first sciatic nerve transplant on a nine-year-old boy.

1989
• Lap-Chee Tsui, Manuel Buchwald and Jack Riordan isolate the gene that causes cystic fibrosis.
• Menashe B. Waxman and others develop the tilt-table test, which identifies people who lose consciousness as a result of fainting, as opposed to seizures, heart-rhythm disturbances or narrowed heart valves.

1990
• Donald W. Killinger and others discover that the distribution of body fat has an effect on the activity of human sex hormones. Abdominal body fat causesgreater production of androgens, and fat on the lower body is linked to increased levels of estrogen.
• Anthony Pawson discovers that cancer cells will grow without the stimulation of the SH2 domain, an element that allows cell proteins to interact and transmit growth signals.
• Anthony Pawson identifies how cell receptors transmit signals instructing cells to change. This leads to new cancer drugs.

1991

• Philip Seeman identifies two new dopamine receptor proteins, D4 and D5, thus allowing for the development of more effective and safer medicines for treating psychosis, schizophrenia and possibly cocaine addiction.
• Mladen Vranic discovers new mechanisms involved in regulating glucose turnover, a key to understanding the development and treatment of diabetes.

1992
• Mary Hannah and others complete the Canadian post-term pregnancy trial and discover that a policy of inducing labour is best for both mother and baby when pregnancy is overdue by more than one to two weeks.
• Peter St George-Hyslop identifies a defective gene on chromosome 14 that may be responsible for familial Alzheimer’s disease.

1993

• Philip Seeman discovers that the D4 receptor, one of the five known types of brain cell receptors for the chemical dopamine, is six times more abundant in people with schizophrenia than in others.

• Terry Delovitch and others discover that a naturally occurring hormone, interleukin-4, which is produced by white blood cells, halts attacks on insulin-producing pancreatic cells and may protect children from developing insulin-dependent, or juvenile, diabetes.

1994

• Using a powerful atomic-force microscope, Cynthia Goh and others obtain revealing new images of the clusters of protein threads characteristically found in the brain neurons of Alzheimer’s patients.
• David Jenkins discovers that diets high in soluble fibre reduce blood cholesterol levels, even after significant dietary reductions in saturated fat and cholesterol have been achieved.
• Steven Narod and others discover the BRCA1 gene, which is suspectedof causing two to four per cent of breast cancers and five to 10 per cent of ovarian cancers.
• Endel Tulving and others prove that different areas of the brain are activated when different types of memory are engaged.
• Brenda Andrews and others discover a new member of the kinases enzyme family responsible for controlling cell division in yeast. This affords insight into the aging process and diseases like cancer, which are linked to uncontrolled cell division.

1995

• A.Venket Rao and Mi-Kyung Sung discover that saponins, a natural compound found in soybeans, inhibit colon-cancer cell growth in tissue culture.
• Peter Wells and others discover a link between DNA repair and birth defects in mice.
• Colopath, a rapid, non-invasive screening test invented by George Krepinsky and others for the early detection of colorectal cancer, is granted a U.S. patent.
• Steven Narod and others discover a second gene for hereditary breast cancer (BRCA2).
• Peter St George-Hyslop and others identify the defective gene responsible for early onset Alzheimer’s, a rare but extremely aggressive form of the disease. The genes are so dominant that an inheritor is virtually destined to get the disease by age 50, even as early as 25.
• Peter St George-Hyslop and others identify a second gene responsible for the early onset of a less severe form of Alzheimer’s disease.

1996

• Mary Hannah and others complete the International TermPROM Study and discover that inducing labour with intravenous oxytocin is advisable when membranes are ruptured at term but labour has not started spontaneously.
• Luc De Nil and others discover a genetic basis for stuttering, which was previously assumed to result from emotional or psychological difficulties.
• Bibudhendra Sarkar develops an effective treatment of Menkes disease, a fatal genetic neurological disorder caused by defects in copper transport, required by many life-sustaining enzymes.
• Jeff Wrana and others identify a gene implicated in the development of colon cancer.
• Don Low and others develop a method to identify those at greatest risk of developing the severe invasive group A streptococcal (flesh-eating) disease.
• Brenda Gallie and others develop a new therapy for retinoblastoma, a cancer of the eye that leads to blindness. It is the first major new treatment of retinoblastoma in 35 years.
• Using X-ray crystallography, James Rini discovers a critical feature of e-cadherin, a cell membrane protein that suppresses cancer cell invasion.
• Robert Salter discovers a method of regenerating joint cartilage in severely damaged knee joints.
• Michael Moran and others discover that the GRB2 protein acts as a kind of on-off switch for cell growth and cell division. This lays the groundwork for drugs to prevent the growth and division of cancer cells.
• John Dick and others identify a bone marrow cell that produces blood in the human body, a significant step toward new therapies for blood diseases.
• Dan Drucker and others discover that the hormone Glucagon-like Peptide2 (GLP-2) can stimulate the growth of the lining of the small intestine. This could help patients with severely compromised intestinal functions.
• Manuel Buchwald and others identify and clone oneof the genes of Fanconi anemia, a rare but serious genetic disorder.
• Lap-Chee Tsui, Stephen Scherer and Elena Belloni identify a gene that causes cyclopia, a disfiguring disease affecting the fetal development of the forebrain and mid-face.
• Shoukat Dedhar and others discover ILK, a protein kinase. This illuminates new aspects of cell adhesion and demonstrates that an integrin-associated protein may cause tumours.

1997

• Brenda Andrews and others discover a new link between cell regulators that could lead to improved treatments for cancer.
• Ren-Ke Li demonstrates that cell transplantation can improve cardiac function and that transplanted cardiomyocytes survive in myocardial scar tissue and form a cardiac tissue that improves heart function.
• Roderick McInnes and others identify a gene whose mutations cause an inherited degenerative disease called cone-rod dystrophy, which leads to blindness.
• Christopher Feindel develops a new technique of preserving hearts for transplantation.

1998
• Thomas Wolever and others develop a more accurate test for detecting glucose intolerance, which improves diabetes screening.
• Michael Sefton and others initiate the Living Implants from Engineering (LIFE) project, an international research effort to create tissue-engineered organs. The initial effort is directed toward hearts.
• Choy Hew and others identify an antifreeze protein in some Arctic fish that plays a role in preventing damage by cold temperatures and may prove useful in cell and organ preservation.
• John Davies and others create “living bone” by growing human cells in biodegradable polymeric foam.
• John Dick and others discover a new stem cell in human blood that provides insight into the mechanics of the blood system.
• Stephen Scherer and others identify a gene responsible for Lafora disease, one of the most severe forms of epilepsy.

1999

• Lewis Kay receives the Steacie Prize for his work in nuclear magnetic resonance (NMR) spectroscopy, a process allowing for the sophisticated analysis of the interaction of molecules. More than 200 labs around the world currently use the NMR methodology developed by Kay.
•Tak Mak and others discover that Interleukin-13 growth cells facilitate the development of Hodgkin’s disease.
• Josef Penninger and Young-Yun Kong discover how the OPGL gene triggers osteoporosis.
• Josef Penninger identifies a link between heart disease and chlamydia pneumoniae, a bacteria associated with pneumonia and bronchitis.
• Lap-Chee Tsui and others identify a region on chromosome 19 containing a gene that modifies the severity of cystic fibrosis.
• José L. Perez-Velazquez and others unravel one aspect of human seizures. By determining patterns of brain activity, researchers can forecast seizures and manipulate them with electric stimulation.
• Ulrich Krull develops a DNA hybridization detection system that provides on-the-spot screening for fungal and bacterial infections and diseases such as AIDS and hepatitis.

2000

• Emanuela Mundo and others identify a genetic variable in individuals with obsessive-compulsive disorder, which may provide insight into its cause and treatment.
• Roderick McInnes and others identify retinal stem cells in the adult eye, a discovery that opens the door for retinal regeneration as a possible cure for damaged or diseased eyes.
• Josef Penninger and others discover a protein that suppresses colorectal cancer in mice and human cell cultures.
• Geoff Clarke and others demonstrate that mutant genes that lead to inherited neurodegenerative conditions like Parkinson’s disease confer a constant risk of programmed cell death.
• Peter St George-Hyslop and others announce that a new Alzheimer’s vaccine is ready for human testing.
• Janet Rossant is elected to the Royal Society in recognition of her work on the genetic control of normal and abnormal development in the early mouse embryo that provides insight into what can go wrong in early pregnancy.
• Reza Emami develops a software program that can look at a virus or tumour and identify the genes that have an impact on the infected cell.
• Mary Hannah and others complete the International Term Breech Trial and discover that delivery by caesarean section is best for breech babies at term and does not increase the risk for the mother.
• Tony Miller, Cornelia Baines and others report results from the Canadian National Breast Screening Study for women age 50 to 59.

2001

• Josef Penninger and others identify the CD45 protein, a switch that turns off hormones and proteins that control the human immune system.

Josef Penninger

Type in “Josef Penninger” when doing an Internet search and you’ll be bombarded with hundreds of listings. They are all for the U of T associate professor of medical biophysics and immunology, who this year announced that he and his colleagues had discovered a protein, CD45, that acts as an on-off switch for the immune system. The finding may be pivotal in the quest for treatments for diseases in which the immune system is acting too aggressively – such as arthritis, Type 1 diabetes and some kinds of cancer.

In 1999, Penninger and his research team at the Amgen Research Institute in Toronto discovered OPGL, a gene that causes the destruction of bone tissue, leading to severe osteoporosis. The team found that diseases that cause inflammation in the body (for example, arthritis) and activate the immune system initiate an attack against the bones. A natural blocker of OPGL is undergoing human clinical trials in the United States.

That same year, Penninger also found a causal link between chlamydia pneumoniae and heart disease, and last year, he and his lab found a protein that suppresses colorectal cancer in mice.

Lap-Chee Tsui

The Sept. 8, 1989, edition of the journal Science included three scientific papers announcing the discovery of the cystic fibrosis (CF) gene. All three had the name of Lap-Chee Tsui on them. Tsui (pronounced “Choy”), geneticist-in-chief at the Hospital for Sick Children and a professor of molecular and medical genetics, along with an international team of researchers, had just made a huge impact on genetics research.

Since then, genetic tests have been developed for the disease, and researchers are on the path to finding new treatments. In 1999, Tsui and his colleagues found the location of a gene that affects the severity of CF in individuals.

In November 1996, Tsui and his team identified a gene that causes a disfiguring disease in unborn infants known as “cyclops syndrome,” which produces deformations of the forebrain and mid-face. He is also involved in the mapping of the gene responsible for Tourette’s syndrome. Last year he became president of the Human Genome Organization (HUGO), which co-ordinates 1,000 scientists working on the Human Genome Project.

Tak Mak

When Tak Mak, director of the Amgen Institute in Toronto, puts his mind to a problem, great things happen. Indeed, the whole field of immunology was advanced by his discovery of how T-cells work. For years researchers knew that T-cells were the tiny guards in our blood that recognize and attack invaders such as bacteria and viruses, but nobody knew how they did their job. Mak, a professor of immunology who had been working with viruses, turned his attention to T-cells.

On March 8, 1984, two independent papers appeared in the journal Nature announcing the discovery of the T-cell receptor. The lead author of one of them was Tak Mak. Finding the receptor was pivotal to understanding how T-cells recognize what is foreign or native to the body.

In 1999, Mak and colleagues found interleukin-13, a cell that fuels the growth of cancerous cells in Hodgkin’s disease. He continues basic research in cell biology at the Ontario Cancer Institute in Toronto.

Peter St George-Hyslop
As a boy, Peter St George-Hyslop, a neurologist at Toronto Western Hospital and director of U of T’s Centre for Research in Neurodegenerative Diseases, was clearly ahead of his class. Shortly after his family moved to Ottawa from Britain and the young St George-Hyslop started Grade 9, his teachers realized he needed to be advanced to Grade 12. The pattern has continued throughout his adult career. The soft-spoken neurologist has garnered numerous accolades, including the gold medal from the Royal College of Physicians and Surgeons of Canada.

The recognition is well deserved. There are four known genes linked to early-onset Alzheimer’s disease, and St George-Hyslop has found two of them. Both were discovered in 1995 within an astounding two months of each other. The first gene is associated with the most virulent form of early onset Alzheimer’s, while the second is linked to a less severe, inherited form of the disease. He and his team recently developed a vaccine for Alzheimer’s, now ready for human tests.

While it may not be as immediately deadly as certain cancers or AIDS, experts say diabetes deserves to be taken seriously. Without early diagnosis and proper management, people with diabetes are at increased risk for grave health complications, including cardiovascular disease, kidney failure, blindness, nerve damage and lower-limb amputation. Experts estimate that diabetes now accounts for 25,000 deaths each year, making it the seventh leading cause of death in Canada. Besides the human cost, diabetes and its complications account for one out of every seven health-care dollars spent – about $9 billion a year.

But Canadians seem largely unaware of the disturbing facts surrounding diabetes and unconcerned about their own risk for the disease. According to a recent national survey sponsored by the pharmaceutical company Aventis Pharma, only 39 per cent of the 1,500 people questioned said they were “very” or “somewhat” concerned about developing diabetes (compared with 60 per cent who expressed concern about cancer and 57 per cent who worried about heart disease).

Leigh Caplan, now 37, knew more about diabetes than the average person when her Type 2 diabetes was diagnosed after a routine blood test eight years ago. “I’m a nurse, so I already had some basic knowledge,” she says. She had also witnessed the grim reality of uncontrolled diabetes first-hand: her late mother, who had suffered from the disease since adolescence, lost her eyesight as a result of diabetes when Caplan was still a child. Even so, Caplan was unprepared for her own diagnosis. “I was stunned at first,” she recalls. “And scared – especially about the possibility of complications, which I knew all too well because of my mother.”

Caplan assuredly is not alone. It is estimated that 2.25 million cases of diabetes in Canada have already been diagnosed – mainly Type 2. In fact, the World Health Organization forecasts that more than 300 million people worldwide will have the disease by 2025, compared with 135 million in 1995. Until recently, Type 2 diabetes was largely considered an ailment of late middle age or older, but now it’s being routinely diagnosed in 30- and 40-year-olds, and even in children. It’s an all-too-common diagnosis among Canada’s aboriginal population, and also among immigrants from South Asia, China and Japan.

One leading diabetes expert at the University of Toronto likens the rising rate of diabetes to the “perfect storm,” a reference to the raging fronts that converged in the North Atlantic in 1991 to create the greatest storm in recorded history. (The tempest was depicted in the recent movie The Perfect Storm.)

“When it comes to the perfect storm of diabetes, all the conditions are right,” says Dr. Bernard Zinman, a professor of medicine who heads the division of endocrinology and metabolism at Mount Sinai Hospital in Toronto. One contributing factor is that the massive baby boom generation is moving into its 50s, when the risk of diabetes normally increases. Another contributor to the storm is the current climate of what he calls “overnutrition” – the consumption of unhealthy fast foods and super-sized portions, which is driving up the rate of obesity, “a known risk factor for Type 2 diabetes,” he says.

A third factor, says Dr. Zinman, who is also director of the Leadership Sinai Centre for Diabetes at Mount Sinai and the holder of the Sam and Judy Pencer Family Chair in Diabetes at the University of Toronto, is that, in general, “people are exercising less, physical education programs in schools have been downsized or cancelled, and kids spend hours in front of the television or computer screen.”

There could be another explanation for the increased number of recorded diabetes cases: In 1998, the Canadian Diabetes Association (CDA) guidelines that doctors use to diagnose and treat Type 2 diabetes were revised. A major change involved lowering the threshold for “fasting blood glucose” – a person’s glucose level before eating – from 7.8 mmol/L (millimoles per litre) to 7.0 mmol/L. The goal is to catch Type 2 diabetes at an earlier stage so that lifestyle changes and other treatments can begin, and long-term diabetic complications can be prevented, explains Dr. Zinman.

One outcome of the lower threshold is that many more cases of Type 2 diabetes are now being diagnosed. This is important, Dr. Zinman believes, because people with Type 2 diabetes typically have no symptoms, unless their glucose levels are extremely high. In fact, it’s estimated that one-third of adults with diabetes aren’t aware they have it; many live with unhealthy blood-glucose levels for years until the condition is picked up during a routine health check. (The Aventis Pharma survey found that while some people knew some of the signs of uncontrolled diabetes – including unusual thirst, fatigue and frequent urination – 24 per cent couldn’t name a single symptom.)

After the initial shock of her diagnosis wore off, Caplan realized that in some ways, she was fortunate: “My mom had to boil her insulin needles to sterilize them, and test her urine. When it comes to managing my disease, I have so much more at my disposal than she did.”

Today, Caplan takes daily injections of insulin – “to help compensate for my lazy pancreas” – and works to control her glucose levels by monitoring her blood twice daily, eating carefully and walking at least an hour every day. She is especially determined that her two young sons develop healthy eating and exercise habits, which she hopes will reduce their risk for developing diabetes.

Caplan’s own health situation motivated her to become a diabetes nurse educator. As part of a team, she currently works at the Tri-Hospital Diabetes Education Centre (TRIDEC), established in 1971 at Women’s College Hospital and now operated by Sunnybrook and Women’s College Health Sciences Centre. Each year, TRIDEC professionals counsel more than 1,600 people with diabetes, educating them about their disease, teaching self-management skills and supporting them as they deal with their diagnosis.

At some point in these sessions, Caplan usually reveals to her patients that she, too, is “one of them.” They generally seem surprised but pleased to know that their teacher is “walking the walk” and not just “talking the talk.” “I understand how overwhelming it is to learn you have diabetes and to face managing it for the rest of your life,” she says.

Evelyne Michaels is the editor of Health News, published by the Faculty of Medicine.