Eight Great Canadian Medical Breakthroughs

August 4, 2009 by Sharon Adams
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Canada has good reason to be proud of our medical mavericks and mavens—they are responsible for breakthroughs that have saved lives and affected the health of hundreds of millions of people around the world.

The list of Canadian medical breakthroughs measures in the hundreds, if not thousands, and includes every field of medical endeavour, from developing drugs and vaccines to designing medical equipment, inventing new surgical and treatment techniques, finding causes of diseases, identifying genes whose defects cause disease, pioneering cell-based therapy—and many, many more.

Despite Canada’s small population, our researchers have made many discoveries, many of them world-changing. Canada gets a big bang for its research bucks: although it ranks 14th in research spending among 31 Western industrialized nations, it ranks sixth in producing top research papers.

Some credit international connections. The Canadian Institutes of Health Research notes many Canadian researchers do some training elsewhere, and that Canada hosts and attends international scientific conferences. Several researchers quoted here tell of sudden insights that came while listening to reports of research on completely unrelated topics, or how chatting with a researcher from another country opened up possibilities for moving a discovery ahead through collaboration.

Others cite a Canadian culture of collaboration, reflected in the spirit of generosity found in researchers across the country. They are generous in sharing ideas, sharing credit for work and expressing admiration for other researchers. A number have refused to profit from their discoveries, preferring to share their ideas with anyone who can use them to do good. Some have even used their prize money to fund other researchers.

Perseverance is also a shared characteristic. Many have had difficulty getting groundbreaking work accepted. The prestigious journal Cell turned down as “not of general interest” Dr. Michael Smith’s paper on work that later won a Nobel Prize. Another journal initially dismissed as “irrelevant” a paper on development of a test for screening newborns for congenital hypothyroidism developed by Dr. Jean Dussault of the Centre Hospitalier de l’Université Laval and Dr. Paul Wolfish, now of Mount Sinai Hospital in Toronto. Hundreds of millions of babies have since been screened with this test, which is credited with preventing irreversible mental retardation in more than 100,000 children. And Dr. Wilfred Bigelow’s work on hypothermia was initially given a very cold shoulder by fellow physicians.

Researchers do not live in ivory towers. It’s important, as one said, “to bring it to the bedside.” They are enthusiastic about how their work could be used one day to prevent disease or help save lives or improve the quality of life for suffering people.

The list of groundbreaking Canadian medical advances is too long for one story, but the following Eight Great Canadian breakthroughs shows how researchers are conscious both of the footsteps in which they tread, and the trails they blaze.


1. Development Of Pablum
In 1930, three doctors from The Hospital for Sick Children in Toronto developed Pablum as a way to prevent and treat rickets in children. The popular infant food went on to improve the health of millions of children around the world, and has led to ideas to help hundreds of millions more.

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PHOTOS: HOSPITAL ARCHIVES, THE HOSPITAL FOR SICK CHILDREN, TORONTO

Pediatricians Frederick Tisdall, Theodore Drake and Alan Brown developed a precooked cereal containing minerals and five of the six known vitamins needed by growing children, including vitamin D, which prevents rickets.  “Before the 1920s, the major reason children were admitted to The Hospital for Sick Children was for vitamin D deficiency rickets,” says Dr. Stanley Zlotkin, a pediatrician and senior scientist at the hospital’s Research Institute. “There were thousands of cases per year.” That number was further reduced in the 1960s when Dr. Charles Scriver of Montreal Children’s Hospital linked rickets to vitamin D deficiency and successfully lobbied for fortification of milk. Today there are only about 100 cases of rickets yearly in Canada.Development of Pablum is important for two reasons, says Zlotkin. First, Pablum showed improved nutrition could prevent and cure some diseases, and secondly, it demonstrated fortified food delivered health benefits to large populations. Fortified foods have helped make vitamin deficiency diseases—beriberi, pellagra, rickets, scurvy—that were common in Canada at the turn of the 20th century, a rarity at the turn of the 21st.Today there are hundreds of fortified foods in grocery stores, and more foods are being fortified with individual nutrients to curb specific diseases. Since Canadian grain products began being fortified with folic acid in the late 1990s, neural tube defects have declined by 48 per cent, reports the Public Health Agency of Canada.

Malnutrition is a contributing cause in more than half of children’s deaths in the Third World, and micronutrient supplementation and food fortification are the cheapest solutions to malnutrition, according to the Copenhagen Consensus, a think tank of world economists looking for cheap solutions to the world’s greatest problems.

The World Health Organization estimates more than 250 million preschool children in more than 100 countries are vitamin A deficient; malnutrition will contribute to deaths of more than half within 12 months and up to 500,000 will lose their sight each year. And that’s just one vitamin.

Following in the footsteps of Tindall et al. Zlotkin came up with the idea of home fortification—small envelopes of powdered vitamins and minerals that could be opened and stirred into or sprinkled on babies’ food. “I wanted the intervention to reach millions of children around the world,” says Zlotkin, who dubbed the idea Sprinkles. The technique for making this micronutrient powder was opened to the public domain, and Zlotkin, who is also founder of the Sprinkles Global Health Initiative, began promoting micronutrient programs to relevant United Nations agencies. Result? Initiation of micronutrient powder programs in more than 20 developing countries.


2. Discovery Of The T-cell receptor
“The progress of science, especially medical science, is driven by the way we understand mechanisms and how they work,” says Dr. Tak Wah Mak, co-discoverer in 1984 of the T-cell receptor and the gene that produces it. Understanding how T-cells work has helped in developing new drugs for fighting infection, autoimmune disorders, cancer and post-transplant rejection.

Dr. Tak Wah Mak. [PHOTO: PRINCESS MARGARET HOSPITAL FOUNDATION]

Dr. Tak Wah Mak.
PHOTO: PRINCESS MARGARET HOSPITAL FOUNDATION

Prior to this breakthrough, researchers knew T-cells (named because they are produced in the thymus gland) attacked viruses and bacteria, but nobody knew how they worked. Mak describes T-cells as ‘hit men’ and ‘policemen’ that circulate in the body identifying friend from foe, and ordering battles against pathogens. “How T-cells differentiate between a piece of a virus or a piece of your own cells is absolutely essential for longevity,” says Mak. The surfaces of T-cells are studded with receptors that identify cells containing pathogens like invading bacteria and viruses. There are several types of T-cells, including killer T-cells, which destroy cells containing invaders, and helper T-cells, which marshal the body’s immune response. “If a pathogen comes in and your immune system cannot recognize it as non-self, you’re dead. And if your immune system mistakes a pathogen for a part of the body, you’re dead.”Mak, now director of the Campbell Family Institute for Breast Cancer at Toronto’s Princess Margaret Hospital, has taken two other byways during his long career. The first was to help explore the checks and balances of the immune system—the hundreds, if not thousands of reactions that keep us from cancer and infections, but if overzealous, result in the hundred or so different autoimmune diseases.

In order to understand how this system works, Mak’s team developed mice with one specific immune system gene knocked out. By comparing the working of that mouse’s immune system versus a normal mouse, the function of each gene can be determined. Gene by gene, they built an understanding of how more than 100 different immune system genes worked.

Along the way Mak became interested in programmed cell death.  Each day at least 50 billion cells in our bodies self-destruct as they become diseased or redundant. This programmed cell death is called apoptosis. But some cells don’t die as intended and instead multiply and become tumours.

In 2002, Mak shifted focus to cancer research. Understanding apoptosis of certain T-cells may help understand how to better treat cancer, which has cells that won’t die. Mak hopes if it can be determined how the mechanism has gone awry in cancer cells, drugs can be developed that will reignite the apoptosis process in  tumours. Drugs using this approach are now being used to treat some kinds of leukemia.


3. Development Of The Cobalt Bomb
In 1951, when the first cancer patients were given quick and successive radiation treatment from cobalt-60 therapy units at the Victoria Hospital in London, Ont., and at the Saskatchewan Cancer Commission in Saskatoon, Canada ushered in the age of modern nuclear medicine. It has remained a leader in biophysics research and medical isotope supply ever since.Although ionizing radiation from radium and X-rays had been used for decades in cancer treatment, it was either too weak to penetrate far enough to treat deep tumours, or prohibitively expensive. In 1947, the National Research Experimental Reactor at Chalk River, Ont., began producing radioactive cobalt-60 isotopes about 100 times more radioactive than radium and far cheaper to produce. Dr. Harold Johns of the University of Saskatchewan requested some for a prototype therapy unit that would make deep tissue radiation therapy possible—and relatively affordable.

The Cobalt Bomb. [PHOTO: HAROLD E. JOHNS LIBRARY, SASKATOON CANCER CENTRE]

The Cobalt Bomb.
PHOTO: HAROLD E. JOHNS LIBRARY, SASKATOON CANCER CENTRE

Developed early in the Atomic Age, this new equipment was dubbed the Cobalt Bomb, and was described as an “atomic weapon in the fight against cancer” that cost a fraction of radium of equivalent strength. The equipment resembled a giant science fiction ray gun weighing 31⁄2 tons. Inside, a small cylinder of cobalt-60 weighing mere ounces was surrounded by a lead shield. An aperture in the shield was used to direct rays where needed.For the first time, deep tumours such as those in the bladder, cervix and lungs could be effectively treated with radiation. The cure rate for cervical cancer, for example, increased to 75 per cent from 25 per cent after development of the Cobalt Bomb.

Cobalt-60 and other radioactive therapies emit rays that kill healthy cells as well as cancerous ones, so precision in aim and dosage is vital. Canadian researchers have continued to perfect methods for delivering maximum dosages to tumours, while minimizing damage to healthy tissue.

About 3,000 cobalt-60 therapy units, most of them built in Canada, were distributed around the world and used to treat millions of cancer patients. Nuclear medicine has come a long way; today there are more than 100 applications for treatment and diagnosis. Continuing research has provided positron emission tomography (PET scans), single photon emission computed tomography (SPECT), cardiovascular imaging and bone scanning, among other innovations. Nuclear imaging is now used frequently in diagnosis of heart conditions and neurological disorders as well as cancer.

MDS Nordion technologist in TheraSphere production. [PHOTO: MDS NORDION]

MDS Nordion technologist in TheraSphere production.
PHOTO: MDS NORDION

Higher energy radiation beams make cancer treatment today more effective, improved targeting and precise dosages also make it safer. And radiation treatment delivery has moved inside the body, where radioactive substances are placed near or in a tumour. MDS Nordion of Kanata, Ont., produces a liver cancer treatment called TheraSphere, in which millions of microscopic radioactive glass beads are injected directly into a patient’s liver tumour, thus minimizing impact on healthy tissue and producing fewer side effects. “Canada does command a leadership position in nuclear medicine today in producing isotopes, developing radio pharmaceuticals and turning research into saleable products,” says Peter Covitz, senior vice-president of innovation at MDS Nordion.  “It’s still early days” for discoveries and innovations in diagnosis and therapy, he says. “There’s lots of opportunity for development of new tracers, new radioactive materials, new treatments.”


4. Safer Stem Cells
Researcher Andras Nagy has found a way to safely generate stem cells from adult human skin cells, opening the possibility in the future of using a patient’s own cells to reverse damage caused by disease, injury, aging or genetics and cure diseases whose treatment costs the Canadian health-care system billions of dollars a year. “The idea of curing a broad range of diseases with cells is very new,” says the researcher. “Many diseases are associated with cell loss. If we could replace missing or damaged cells with new ones derived from stem cells, we might be able to cure many devastating diseases that are currently incurable. Alzheimer’s, Parkinson’s, diabetes—we could be not just treating them with drugs, but with cells and curing them. This, I hope is where the field goes.”Stem cells are the master cells of the human body; some are capable of developing into any of about 200 different types of cells. For decades researchers have sought ways to create stem cells and control their development, in hopes they can be used to regenerate defective or damaged tissues and organs, curing or preventing heart disease and stroke, diabetes, degenerative diseases like Parkinson’s, Alzheimer’s and arthritis as well as healing or replacing damaged tissue from spinal cord injuries or burns.

Dr. Andras Nagy. [PHOTO: SID TABAK, MOUNT SINAI HOSPITAL]

Dr. Andras Nagy.
PHOTO: SID TABAK, MOUNT SINAI HOSPITAL

But research has been stymied by the scarcity of usable stem cells. Although stem cells can be derived from human embryos donated by parents, there is moral debate over the use of human embryos. Adult stem cells are less abundant and aren’t able to develop into as many different types of cells, so researchers have been searching for ways to reprogram adult cells to behave like embryonic stem cells.In 2006, Shinya Yamanaka, a Japanese scientist, proved that induced pluripotent stem (iPS) cells (cells as versatile as embryonic stem cells) could be produced from adult cells by adding only four genes. He and other researchers used viruses to insert these four genes into adult cells from skin. However, the technique could destroy healthy genes in the cells or also switch on genes that might cause cancer. The race was on to find a safe means of reprogramming adult cells.

A Canadian and Scottish collaboration crossed the finish line first.

Dr. Keisuke Kaji from the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh was perfecting a method—without using viruses—of inserting into a cell the necessary four genes in a single fragment. But his team had a problem removing all traces of those genes once they’d reprogrammed the target cells. Meanwhile, Nagy’s lab was perfecting a method to safely remove all trace of inserted genes, but was tripped up by having to remove four separate fragments.

Their collaboration resulted in the breakthrough: delivering the genes necessary for reprogramming adult stem cells into iPS cells without using viruses or damaging the cells’ genetic structure.  Not only could the technique overcome some moral objections to using embryonic stem cells, but by using a patient’s own cells, it avoids the possibility of the cells or repaired organ being rejected by the patient’s immune system. And this opens the way for development of personalized cell therapy: using a patient’s own stem cells to rejuvenate cells damaged by aging, disease and injury. It could also be more economical. “The cost to society of diabetes is about $12 billion a year,” says Nagy. “And that is but one disease that could be cured by cell regeneration.”

Now Nagy’s lab at Mount Sinai Hospital’s Samuel Lunenfeld Research Institute is concentrating on “bringing it closer to the bedside,” he said, by further developing the technique to make stem cells safe for future use in humans. “There’s still a lot of hard work that has to be done,” before stem cell therapy is widely used, says Dr. Michael Rudnicki, scientific director of the Canadian Stem Cell Network.

Clinical trials are planned in the U.S. to use stem cells in curing spinal cord injuries. Nagy thinks blindness will be among the first of the degenerative diseases to be treated with cell therapy. This is because eye structure is already well understood, the eye is easily accessible for treatment, and “we do lots of sophisticated operations.”

Canada has a strong history in stem cell research, dating back to 1961 when Canadians Jim Till and Ernest McCulloch proved the existence of blood stem cells in bone marrow. Given the fact there is a pool of researchers in Canada, and there is so much promise in cell therapy, Nagy expects quick progress on research.


5. Safer Heart Surgery
There was a time when heart surgeons were unable to open the heart to correct problems inside, because there was no way to safely stop blood flow to see what they were doing. Enter Canadian surgeon and hypothermia researcher Dr. Wilfred Bigelow.He discovered in the early 1940s that lowering temperature of an arm or leg also reduced its oxygen requirements. In the late 1940s he thought hypothermia might help doctors operating on newborns with heart defects—doctors who were limited to external repairs because interrupting circulation also meant dangerously interrupting oxygen supply to other organs, like the brain. In 1950, he and Toronto General Hospital colleague Dr. John Callaghan presented their work at a medical convention; in 1952, hypothermia allowed the first open-heart operation on a human. After the heart-lung pump came into use, the two techniques were combined. Today cold chemical solutions are injected into coronary arteries to protect the heart during surgery.

Dr. Wilfred Bigelow. [ ]

Dr. Wilfred Bigelow.

Bigelow and Callaghan are also credited with sparking development of the heart pacemaker. In 1949, Bigelow used a probe to prod a dog’s heart which had stopped during an operation. The heart started up again, and Bigelow and Callaghan debated the use of other means of stimulating the heart, including electricity. They enlisted Jack Hopps, an electrical engineer with the National Research Council in Ottawa, who developed the external pacemaker, soon adopted in many hospitals. In 1959, using transistor technology, the first implantable pacemaker was developed in Sweden. Today millions of heart patients benefit from pacemakers. “These two developments have had the widest influence in the field,” says Dr. Ray Chiu, professor and chair emeritus of the division of cardiothoracic surgery at McGill University in Montreal. While the techniques are considered primitive today, “they came up with the concepts,” that have led to continual improvements in techniques and equipment which have improved survival rates for heart patients. “From Day 1,” says Chiu, “Canada has been a big player in this field,” and currently is internationally renowned for cutting-edge research on aortic valve replacement, use of stem cell transplantation to repair muscle damaged during heart attacks and robotics-assisted heart surgery, among many other accomplishments.

Dr. Tirone David. [PHOTO: COURTESY OF UNIVERSITY HEALTH NETWORK]

Dr. Tirone David.
PHOTO: COURTESY OF UNIVERSITY HEALTH NETWORK

Dr. Tirone David, head of cardiovascular surgery at the Toronto General Hospital and on the medical faculty at the University of Toronto, is credited with many innovations in surgery on heart valves. He developed and refined techniques to repair, rather than replace, the mitral valve in the heart, pioneered use of porcine aortic valves and developed the David technique, used by surgeons around the world, to save the aortic valve when repairing aortic root aneurysm.

Dr. Douglas Boyd performed the first robotics-assisted closed-chest bypass surgery in 1999 at the National Centre for Advanced Surgery and Robotics at London Health Sciences Centre in Southwestern Ontario. Instead of cutting open the chest, cleaving the breastbone and forcing the rib cage apart to get at the heart, surgeons can do their job through tiny holes in the patient’s chest. Robotic arms, one holding a small camera and the others holding tiny surgical instruments, respond to the surgeon’s command. Because robotic arms are steadier than human hands, surgeons can work on a beating heart, meaning no heart-lung pump is necessary. Patients have less pain and a shorter recovery period after the procedure.

Dr. Chiu’s own lab at McGill University Health Centre in Montreal reported the first studies on the use of stem cells for repairing damaged hearts in 1992 and 1994. Since then there’s been a flood of research from Chiu’s lab at McGill and that of Dr. Richard Weisel, director and senior scientist at the Toronto General Research Institute, in the transplantation of adult bone marrow stem cells in regeneration of damaged heart muscles. “Our two institutions are internationally recognized centres for cell transplantation for heart failure,” said Chiu. Researchers are very excited about the start of phase two trials on the use of donor stem cells.

Usually when organs or cells from a donor are transplanted into another body they are rapidly rejected and destroyed by the patient’s immune response, unless the patient is given toxic medications to suppress his or her immune system. To avoid this, for years stem cells derived from a patient’s own bone marrow have been used for stem cell therapy, but it isn’t very efficient. In a lengthy and expensive procedure, cells are harvested, sent for purification, returned and then used in the patient from whom the cells were harvested. But a type of bone marrow stem cell that doesn’t cause this immune reaction has been discovered. A new method has been developed using such cells from a healthy donor, which are purified, multiplied, then sent to urgent care centres where they’re stored until needed to treat any heart attack or heart failure patients.

McGill is one centre where recently-approved phase two clinical trials of this approach will take place. The trials will show if the cells repair patients’ damaged hearts without causing further damage. If it’s successful, “this will be a major breakthrough” in the battle against heart disease, which accounts for a third of all deaths in Canada and costs the health-care system more than $18 billion annually in treatment costs and related loss in wages and productivity.

Dr. Wilbert Keon. [PHOTO: MICHELLE VALBERG]

Dr. Wilbert Keon.
PHOTO: MICHELLE VALBERG

Dr. Wilbert Keon was the first Canadian to implant an artificial heart, in 1986, and to do a heart transplant on an infant, in 1989. Dr. Keon founded the University of Ottawa Heart Institute in 1976, and pioneered surgical reperfusion, a technique to reduce tissue damage when blood supply is returned following acute heart attack. The institute continues to achieve heart research ‘firsts,’ including recently unlocking the mechanism that turns on a weight-loss gene in muscle. Obesity increases risk of cardiovascular disease and diabetes.


6. Stress Research
Hans Selye, father of the field of stress research, could not have imagined where his groundbreaking work would lead when the first of his 1,600 scientific papers on stress response was published in 1936. An entire new medical field was born; today there are hundreds of stress researchers around the world, and groundbreaking research continues to this day.At first Selye’s General Adaptation Syndrome theory was controversial. He described three states of reaction to physical or psychological stress. In the alarm state the body prepares for fight or flight. Then the body builds up resistance to the stress. However, if the stress is unrelieved or too acute, the body enters stage three: exhaustion, disease, death. He floated the ideas that there was some general stress response mechanism in the body, and that there was a link between stress and development of disease.

Dr. Hans Selye. [PHOTO: CHRIS LUND/NATIONAL FILM BOARD OF CANADA/LIBRARY AND ARCHIVES CANADA–PA-116671]

Dr. Hans Selye.
PHOTO: CHRIS LUND/NATIONAL FILM BOARD OF CANADA/LIBRARY AND ARCHIVES CANADA–PA-116671

Selye was the first director of the Institute of Experimental Medicine and Surgery at the University of Montreal from 1945-76. After he retired, he was one of the founders of the Canadian Institute of Stress. In 1975, some international colleagues founded the Hans Selye Foundation for stress-related research.As work in the field blossomed, knowledge of the stress response widened to include, among other things, changes in the immune system, hormones, neurotransmitters and now, individual cells. Hans Selye’s work opened up many avenues of research; one is how to use the body’s response to stress to combat neurodegenerative diseases.

Dr. Ian Brown. [PHOTO: IAN BROWN]

Dr. Ian Brown.
PHOTO: IAN BROWN

At about the time of Selye’s death in 1982, researchers were finding evidence that all cells respond to stress in a similar way. “It’s a very ancient response,” says Dr. Ian Brown, Canada Research Chair and director of the Centre for Neurobiology of Stress at the University of Toronto. The cellular stress response is “the way cells in all animals and plants respond to a range of stresses.” Toxic poisons, heat, cold—anything that stresses the cell induces production of stress proteins that play a role in repair and protection against subsequent stress. “So the thing now is, can we make use of that response in new therapeutic approaches to disease?”

Investigation of clumping of proteins may provide the answer. Proteins are part of the body’s toolkit. They fold into unique shapes to do particular jobs. But after a cell is stressed, some of its proteins clump together and don’t work properly. Stress proteins identify and dissolve these clumps and cause the proteins inside to refold and become active.

Although degenerative neurological diseases like Alzheimer’s, Parkinson’s and ALS (amyotrophic lateral sclerosis) have different effects, one feature they have in common is the formation of clumps of proteins in the brain. The clumps lead to the death of brain cells and when that happens, people lose function related to those cells. “The question now,” says Brown, “is if we activate the stress response, can we combat these aggregated proteins that form in those neurodegenerative diseases?” Will proteins in these clumps also refold? And if so, is there a drug that can activate the stress response? Early indications have raised hope: animal research shows breaking up the clumps of proteins in the brain slows down the course of the degenerative disease. It’s not a cure, says Brown, but it does slow progress of the disease.

Researchers are also looking into using stress proteins, also called heat shock proteins because they were initially discovered following heat stress, to protect against brain damage that follows heart attack and stroke.  “We have a robust research community in Canada,” says Brown, who expects many more stress researchers will follow in Selye’s groundbreaking footsteps.


7. Insulin, Treatments And Possible Cures For Diabetes
At the turn of the 20th century it was suspected a substance produced by islet cells in the pancreas regulated sugar in the bloodstream, but it had not been successfully extracted. In 1920, Frederick Banting had an idea how to isolate the substance from the pancreas in dogs.Working in a lab at the University of Toronto, he and Charles Best developed the first pancreatic extract. Enlisting the help of J.J.R. MacLeod and J.B. Collip, on a fellowship from the University of Alberta, the team was able to produce and purify insulin for testing on patients in 1922. Banting and MacLeod were awarded the Nobel Prize in 1923, which they respectively shared with Best and Collip.Prior to insulin, a diagnosis of Type 1 diabetes was a death sentence for children. Today insulin saves and prolongs millions of lives around the world. But insulin is a treatment, not a cure. About 250 million people around the world are estimated to have diabetes; 10 per cent suffer from Type 1, in which the body does not produce enough insulin, and 90 per cent have Type 2, in which the body cannot efficiently use insulin. Canadians face a one-in-four chance of developing the disease at some time in their lives. By 2010, Canada is expected to have three million diabetics. Type 1 diabetes shortens lifespan by as much as 15 years, while people with Type 2 diabetes die up to a decade earlier than non-diabetics. Diabetes causes damage to the eyes, kidneys, nerves and heart. The disease is estimated to cost the Canadian health-care system $15.6 billion a year.

Dr. Charles Best (left) and Dr. Frederick Banting in 1924. [PHOTO: UNIVERSITY OF TORONTO LIBRARIES–B10016]

Dr. Charles Best (left) and Dr. Frederick Banting in 1924.
PHOTO: UNIVERSITY OF TORONTO LIBRARIES–B10016

Since the discovery of insulin, Canada’s first great medical breakthrough, Canadian researchers have been at the forefront of the worldwide effort to find the cause and cure for diabetes and better treatment. Breakthroughs from the last two decades include:

1989: The Islet Transplant group at University of Alberta, founded by Dr. Ray Rajotte in 1982, carried out Canada’s first islet transplant, but only about 10 per cent of patients were freed from  insulin injections.

1999: James Shapiro from the University of Alberta transplants human donor pancreatic islet cells into patients with chronic Type 1 diabetes. This procedure, dubbed The Edmonton Protocol, frees patients from insulin. But due to a shortage of organ donors, only about 450 pancreases become available yearly, compared to about 6,000 annual new diabetic diagnoses.

2005: Rajotte and Dr. Greg Korbutt, in collaboration with researchers from Emory University in Atlanta, Ga., develop a new process to isolate large numbers of islets from pig pancreas, which they used to cure diabetes in monkeys. This process could overcome the critical shortage of pancreas cells for transplantation. Once it’s proved safe for use in humans, the process will proceed to human clinical trials.

2006: A University of Calgary team—led by Leo Behie, a chemical engineer—grow insulin-producing cells in the lab, providing another possible solution to the scarcity of the supply of human pancreatic islet cells for transplantation.

2007: A team led by Rob Sladek of McGill University and Génome Québec Innovation Centre identifies mutations on the four genes that increase risk of developing Type 2 diabetes. Two genes are involved in the function of beta cells in the pancreas, which make insulin. This research could lead to development of a test to identify individuals at risk. As well, one of the mutations might help explain the cause of Type 2 diabetes, potentially leading to new treatments.

2007: Researchers at the Toronto Hospital for Sick Children and the University of Calgary find abnormal nerve endings in the insulin-producing cells of the pancreas trigger a chain reaction that causes Type 1 diabetes in mice. It’s long been thought diabetes is an autoimmune disorder caused by the body attacking its own pancreas cells.
However, the research team, led by Hans Michael Dosch at Sick Kids, discovered destroying the nerve cells prevented mice from developing the disease. Researchers also injected diabetic mice with a neuropeptide whose production is decreased by the abnormal nerve cells. As a result, diabetes disappeared for a time in more than half of Type 1 diabetic mice, and glucose tolerance was improved for those suffering Type 2. This research has opened up the possibility of new treatment.

“Canada has been a leader in diabetes research since the discovery of insulin in 1922,” says Rajotte, “and a leader in the islet field since 1989.”  In 2008, the Alberta Diabetes Institute was established at the University of Alberta, bringing together under one roof 35 scientists and their research teams from all aspects of diabetes research with one mission: to lead the world in finding a cure. “We don’t know what causes diabetes,” says Rajotte. “If we can figure that out, we can develop a vaccine.” While he cannot say when that will happen, he is sure it will.   


8. Controlled Gene Mutation
Before Michael Smith’s groundbreaking discovery, studying gene function could be a chancy—and lengthy—business. The easiest way to see what a gene does is to cause a mutation, then compare function between organisms that had not been changed and those with the mutation. Researchers had to expose organisms to something like radiation or chemicals that cause random genetic mutations, then sift through the organisms to find the ones that mutated, and then observe the difference in function. It could take years.Smith developed a way to cause a mutation at a chosen specific site on DNA, (deoxyribonucleic acid, which contains the genetic instructions used to direct function of all living organisms). This technique, site-directed mutagenesis, allows specific mutations through alteration of the base pairs that make up DNA, the building blocks of life. Altering the base pairs change the genes and proteins encoded by the DNA, resulting in changes in function.

Dr. Michael Smith. [PHOTO: MARTIN DEE, MICHAEL SMITH FOUNDATION FOR HEALTH RESEARCH]

Dr. Michael Smith.
PHOTO: MARTIN DEE, MICHAEL SMITH FOUNDATION FOR HEALTH RESEARCH

Smith’s work opened up the whole field of biotechnology, and was awarded the Nobel Prize in Chemistry in 1993. “There are so many examples of the application of site directed mutagenesis in the areas of basic biological research and biotechnology that it would be difficult to choose a single major breakthrough,” says Dr. Jim Kronstad, director of  The Michael Smith Laboratories at the University of  British Columbia. “The technique is now an integrated approach in fields of molecular biology and molecular genetics.”This technique was used by a biotechnology company to alter the DNA structure of a strain of yeast to form cells that excrete insulin for treatment of diabetes. Site-directed mutagenesis is used by researchers around the world to understand how cancer and viruses work, to develop new drugs and therapies, to make food plants hardier.

Aside from the advances from his laboratory, Smith also played a leading role in establishing The Michael Smith Laboratories and the Michael Smith Genome Sciences Centre which have had many breakthroughs, says Kronstad.  He mentioned work at the Smith lab by Dr. Brett Finlay, which led to development of the vaccine against the E. coli strain associated with the Walkerton outbreak, and discovery of new pain drugs by Dr. Terrance Snutch, as well as sequencing of the SARS virus at the Centre.

Email the writer at: writer@legionmagazine.com

Email a letter to the editor at: letters@legionmagazine.com

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