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Gairdner Awards honour seven wonders of the world of medical science

SCIENCE

Seven wonders of science

Here's how the winners of 2017's Gairdner Awards have changed your world with their achievements in medicine and beyond

PROFILES OF THE WINNERS

Lewis KayDavid JuliusHuda ZoghbiRino RappuoliAkira EndoAntoine M. HakimCesar Victora

This year's Gairdner Awards, announced Tuesday, honour pioneering work on vaccines, stroke, pediatric care and a range of fundamental discoveries that have advanced medical research.

The winners come from around the globe but they share a common passion for discovery.


Lewis Kay, winner of the CANADA GAIRDNER INTERNATIONAL AWARD

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One of the world's foremost surveyors of the small

by Ivan Semeniuk


Something about Lewis Kay's laboratory at the University of Toronto makes visitors feel like they were miniaturized while passing through the door.

All around the meandering basement facility are enormous metal cylinders, like giant soda cans, standing apart from benches loaded with electronic equipment.

The "apart" bit is important. Each cylinder can generate a magnetic field many hundreds of thousands of times more powerful than Earth's. Get too close to a machine while it is running, and pocket change and metal tools have a tendency to take flight.

"I've lost a lot of credit cards here," Dr. Kay says.

With these devices, Dr. Kay, 55, has become one of the world's foremost surveyors of the small. His specially is nuclear magnetic resonance – NMR. The field has become indispensable to biomedical researchers trying to understand the intricate behaviour of proteins inside human cells.

Now those efforts have earned him one of this year's five Gairdner International awards – the most prestigious science prize Canada bestows on biomedical researchers from anywhere in the world.

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Given the competition, it is no surprise Canadians seldom win the international award. Too many big discoveries are happening elsewhere. Born in Edmonton and based in Toronto, Dr. Kay is the first homegrown winner of the $100,000 award in nine years.

Explaining what Dr. Kay does can get a bit technical, which tends to keep his type of science out of the limelight. (As he observes in passing during my visit, this is his first media interview in his 25 years of research at U of T.)

But developments in NMR have drawn a bevy of Nobel Prizes since the 1950s. And the Gairdner awards are often good predictors of Nobel glory.

Briefly stated, Dr. Kay uses the magnetic fields in his giant cans to line up atoms the way an ordinary magnet might line up the needle of a compass. In this case, the atoms happen to be the building blocks of a protein, like individual pieces of Lego that are part of a larger, more intricate structure. While the atoms are in his apparatus, Dr. Kay jiggles them with bursts of radio energy, and then measures how they respond. Collectively, the measurements enable him to discern the structure of the larger protein, as though tapping a bunch of Lego blocks might produce a 3D image of what they have been used to build.

"It becomes a game of changing angles, phases, durations and delays so that you can tease out the information from these multitude of particles," Dr. Kay says.

Where Dr. Kay has excelled is by adding a fourth dimension to the equation: time. Not only can he see what proteins look like, he can watch them change. This is a key advance, since many biochemical reactions that are crucial for life involve proteins changing shape. He has also pushed the technology toward visualizing ever-larger and more complex groups of proteins that allow a cell's essential machinery to operate and sometimes fail.

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In one recent project, he collaborated with Aaron Schimmer of Princess Margaret Cancer Centre in Toronto to understand the structure of the proteasome, a barrel-shaped cell component whose working parts are hidden inside. The structure is a target for certain forms of cancer therapy. While waxing poetic about what he calls the molecular "dance of life," Dr. Kay says this patient-oriented research is his true motivator.

"Certainly I like the physics, but the end result has to be a drop-dead application."

Lewis Kay of the University of Toronto is one of the winners of this year’s Gairdner Awards in biomedical science.

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DAVID JULIUS, WINNER OF THE CANADA GAIRDNER INTERNATIONAL AWARD

Physiologist's work sheds light on 'how we interpret the world'

by Ivan Semeniuk


"I've always been fascinated by the interaction between plants and animals," says David Julius, a physiologist at the University of California San Francisco. By that, Dr. Julius means interactions that have evolved at the molecular level and that can reveal much about the human sensory system and its neurochemical underpinnings.

In the 1990s, Dr. Julius began pondering the way the body responds to sensations of heat and cold and their links to the perception of pain. Compared to other sensory systems, such as vision or smell, this important form of "somatosensation" was poorly understood.

His way into the problem was to study molecules that arise naturally in plants, including capsaicin, the ingredient that makes hot peppers taste hot. Dr. Julius worked out the precise way in which capsaicin selectively triggers nerve fibres involved in the perception of heat and found the gene responsible for this capability. Similarly, by employing the molecule menthol, which gives mint its characteristic coolness, his group tracked down the related mechanism involved in sensing cold.

Dr. Julius' discoveries have unlocked key insights into these sensory channels and helped reveal how they are affected by tumour growth, infection and injury. The work has additional relevance as researchers look for ways of mediating pain that do not rely on addictive substances. Ultimately, it sheds light on the complex and invisible system that allows us to have a conscious experience of our surroundings.

"It's really how we interpret the world," Dr. Julius says. "The world is a physical environment, but the way we enjoy it or see it is wholly dependent on all these molecular devices that we have."

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HUDA ZOGHBI, WINNER OF THE CANADA GAIRDNER INTERNATIONAL AWARD

Child neurologist uncovered key gene – and found her calling

by Ivan Semeniuk


The rare childhood disease known as Rett syndrome begins as an unseen presence that slowly but relentlessly emerges to rob those it strikes from the chance to grow up as a fully developed individual. The disorder occurs almost exclusively in girls, and typically does not reveal itself until after a child has reached her first birthday. Then, little by little, cognitive and neurological setbacks mount. In a sad reversal of normal human development, many milestones of the first year of life are lost, including social, language and motor skills.

"When I saw these girls, I was totally intrigued and disheartened by watching their course," says Huda Zoghbi, a child neurologist who became fascinated with Rett syndrome as a young researcher in the 1980s.

Working with few initial clues, including the case of a mother with two Rett syndrome daughters by two different husbands, Dr. Zoghbi became convinced the disorder was caused by a rare mutation on the X-chromosome. In males the mutation is nearly always lethal in utero, but in females, who have two X-chromosomes, probability dictates the mutation will be active in about half of an individual's cells.

An investigator at the Baylor College of Medicine in Houston, Texas, the Lebanese-born physician and researcher spent years tracking down the responsible gene. Resisting criticism that the work would lead to nothing, Dr. Zoghbi and her team eventually found the gene, known as MECP2, in 1999. It is now known to be a key player in nerve cells and a regulator of other genes, leading to a cascade of harmful effects when it is impaired. The finding sheds light on related disorders, including autism.

Since that discovery, Dr. Zoghbi has been working on ways to counteract the mutation. As a doctor, she says, "it was hard to see patients and not be able offer anything meaningful. When I went into research… that's when I found my calling."

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RINO RAPPUOLI, WINNER OF THE CANADA GAIRDNER INTERNATIONAL AWARD

Medical pioneer helped vaccine makers to hit their mark more easily

by André Picard


In 1975, when Rino Rappuoli was studying biology at Siena University in Italy, he attended a lecture by Albert Sabin, the legendary researcher who developed the oral polio vaccine.

"It was obviously very inspirational," he says with a laugh. Dr. Rappuoli, who is now chief scientist and head external R&D at GSK Vaccines, is being honoured for his groundbreaking work on vaccines.

In particular, he pioneered a concept called reverse vaccinology, which has revolutionized vaccine development. For more than three centuries, scientists have tried isolating pathogens, growing them in the lab, then exposing people to a weakened form to generate antibodies and immunity. But this approach is hit-and-miss.

What Dr. Rappuoli did instead was decode the genome of a bacterium, then identify proteins that are good vaccine targets. This approach led to the creation of the first vaccine for meningococcal B, a bacterial infection that tends to spread in young people, and which has a mortality rate of about 25 per cent.

"For the first time in the history of vaccinology, we didn't grow organisms in a lab, we just used information in the computer to design a vaccine," Dr. Rappuoli says. It was then tested and proved effective. (In Canada, the MenB vaccine is sold under the trade name Bexsero.)

Reverse vaccinology is now standard practice, and has been used, for example, to develop a vaccine for Ebola.

"Today, we don't even start to look at vaccines without looking at the genome first," Dr. Rappuoli says.

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AKIRA ENDO, WINNER OF THE CANADA GAIRDNER INTERNATIONAL AWARD

Scientist's discovery gave heart-disease patients a new lease on life

by Carly Weeks


Today, cholesterol-lowering statins are among the most widely used pharmaceutical drugs around the world and are credited with saving countless people from heart disease and stroke.

Akira Endo, a Japanese scientist, discovered the first statin in 1973 after examining about 6,000 fungi culture extracts. Dr. Endo was looking for a specific agent that could inhibit a key enzyme involved in cholesterol synthesis. He discovered ML-236B, also known as compactin or mevastatin, which effectively lowers "bad" low-density lipoprotein (LDL) cholesterol. The discovery would eventually prompt major pharmaceutical companies to produce cholesterol-lowering statins. Some of the most well-known on the market today include atorvastatin, sold under the brand name Lipitor, and rosuvastatin, sold under the Crestor brand name.

"I am deeply moved," Dr. Endo said by telephone about the award. "Millions of people extended their lives through statin therapy. I'm very happy to know that."

He said he became interested in pursuing cholesterol-lowering agents when he was working in New York City in the late 1960s and learned that heart attacks were the No. 1 cause of death in the United States, while stroke was the top killer in Japan.

Joseph Goldstein, chairman of the department of molecular genetics at the University of Texas Southwestern Medical Center, who won a Nobel Prize for his work on cholesterol and statins, said Dr. Endo's work paved the way for the development of a new class of drugs that saves thousands of lives a year.

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ANTOINE HAKIM, winner of the CANADA GAIRDNER WIGHTMAN AWARD

A man on a mission to show that stroke is preventable, treatable and repairable

by André Picard


In the early 1970s, when development of the oil sands was just in its infancy, Antoine Hakim was a chemical engineer working at Syncrude in Fort McMurray, Alta. It was an exciting, lucrative time, "but I didn't feel like I was helping people," he says.

Dr. Hakim, who is now emeritus professor of neurology at the University of Ottawa, decided to leave the oil-and-gas business and try biomedical engineering, and then medicine.

After graduating from Albany Medical College, Dr. Hakim did his residency at the Montreal Neurological Institute and focused his research on strokes. It was an unpopular area, he says, "because the mind was devastated and the person was devastated but, at the time, there was nothing we could do."

There are two types of stroke: An ischemic stroke occurs when a clot impedes blood flow (and oxygen) to the brain; a hemorrhagic stroke occurs when a blood vessel bursts in the brain. In both cases, regions of the brain die and people lose function, such as memory or the ability to speak or use their limbs.

In the early 1980s, Dr. Hakim found that when a person suffered an ischemic stroke (about 80 per cent of all strokes), there is a penumbral region around a stroke's ischemic core – in plain language that means part of the brain affected retained energy and could resume function if blood flow was restored.

"It's as if the region of the brain doesn't die; it just holds its breath waiting for help," he says.

It meant the harm caused by stroke was gradual, not immediate and, if treated quickly, could be limited.

Dr. Hakim, who is receiving the 2017 Gairdner Wightman Award for outstanding leadership in medicine and medical science, has essentially dedicated his career to demonstrating that stroke is preventable, treatable and repairable.

His most difficult task, he says, was changing attitudes and making the system more responsive. After all, if "time is brain" – as the axiom states in stroke care – the system has to be responsive. That means ensuring stroke patients get prompt care, from paramedics through to the ER, and rehabilitation.

Dr. Hakim was instrumental in the creation of the Canadian Stroke Network in the 1990s, a network of centres of excellence designed to improve stroke care. He also championed a stroke strategy that has been adopted by most provinces (and implemented in Europe).

As a result, many hospitals created stroke units, paramedics were trained to treat stroke differently, and prevention programs were launched. (The most notable method of getting people to treatment quickly, from the Heart and Stroke Foundation, stressed key indicators of stroke, such as a crooked face, slurred speech and an inability to hold one's arms up together.)

Dr. Hakim also became an evangelist for tPA (tissue plasminogen activator), a clot-busting drug that, if given promptly, can prevent a lot of the brain damage from stroke.

In 1999, less than 2 per cent of stroke patients were getting tPA; by 2004, it was 42 per cent, which is close to the theoretical maximum. (Only about half of stroke patients benefit from the drug.)

About 50,000 Canadians suffer stroke each year and, as result of improved care, the number with debilitating damage has plummeted.

Dr. Hakim says much of his success is due to applying an engineer's problem-solving approach to medicine. But his greatest achievement, he says, is knowing that some patients who would have been severely disabled by a stroke now walk out of hospital with almost no symptoms.

"If you don't have brain health, you don't have health."

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CESAR VICTORA, winner of the JOHN DIRKS CANADA GAIRDNER GLOBAL HEALTH AWARD

In a Brazilian town, this researcher upended conventional wisdom on breastfeeding

by Stephanie Nolen


There is a joke in the city of Pelotas, in the far south of Brazil: the average family, they say, is comprised of a mother, a father, two children – and a public health researcher. Pelotas' population is often called the world's most examined, because of a study that began in 1982, when researchers set out to track every one of the 6,011 babies born there that year. New cohorts have been enrolled every 11 years – for a total of nearly 30,000 participants – but the first group, now well into their 30s, is still regularly being visited by a field worker toting questionnaires.

The man who dispatches the fieldworkers is Cesar Victora, an epidemiologist whose body of work in Brazil and more than 50 other countries underpins much of what Canadian parents take as received wisdom on their children's health. He defined the growth standards that pediatricians plot on charts, and he did the work that proved breastfeeding has an enormous range of positive effects on children, from higher intelligence to higher incomes and less disease as adults.

It is the breastfeeding work for which Dr. Victora is being recognized with a Gairdner Award (announced on his 65 th birthday) and it is his most (inadvertently) controversial finding. Rather than trying to shame women who do not want to or cannot breastfeed, Dr. Victora says, he wants to demonstrate that breastfeeding is "the responsibility of a society, not an individual woman."

When he began his case-control studies on the impact of breastfeeding, the average Brazilian woman breastfed for just three months – today the median length of breastfeeding is 14 months – and it was Dr. Victora's research that drove much of the policy shift that made this possible. The shift happened, he says, because the Brazilian government established paid maternity leave; banned baby formula advertising; made it mandatory for businesses to have feeding rooms and breaks for nursing mothers; and carried out a vast public education campaign that so thoroughly changed minds that breastfeeding is now nearly universal here.

"For the cohort study, we take every birth – all social classes and conditions," he said. "Brazil is a very unequal country in terms of wealth … and we are documenting the social determinants and how they affect people from cradle to grave. I think that's an important message for global health: it's not just about poor countries and diseases of poverty, it's about humankind and how we can improve health early on regardless of whether a person is rich or poor."

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THE GAIRDNER AWARDS: PAST WINNERS

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