Chronicling Innovation

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By Kristine Archer

Artificial kidney
Dr. Gordan Murray developed and used North America’s first artificial kidney. In 1955, Murray breaks new ground again, by performing a human heart valve transplant.

Avro C102
The AVRO C102 Jetliner, designed and built in Malton, Ont., became the first-ever jet passenger plane to fly in North America. Reaching speeds in excess of 500 miles per hour early in its test flight program, the Avro C102 is regarded as an engineering milestone.

Cobalt 60 First Used for Cancer Treatment
Dubbed the Cobalt Bomb, the first treatment of a cancer patient using Cobalt 60-based radiation therapy took place in London, Ont. on Oct. 27, 1951. Doctors had been using radiation to kill cancer cells prior to this, but the effectiveness of the treatment was quite limited. In 1940s, the NRC started producing the radioactive isotope cobalt-60, which had roughly 100 times more radioactive power than radium. While two separate Canadian teams — one in Ontario, the other in Saskatchewan — were simultaneously developing a machine to beam the radiation at the cancer source in a controlled, calibrated way, it was the team led by MDS Nordion (Ottawa, ON) founder Roy Errington that crossed the finish line first. The first treatment was administered to a female patient at London, Ont.’s Victoria Hospital. While more modern radiation technologies have replaced the Cobalt 60 method in North America after 1965, the treatment continues to be used in other countries around the world because of its simplicity and effectiveness.

Banting Discovers Insulin
Dr. Frederick G. Banting led a University of Toronto research team — which included Banting’s assistant, then-medical student Dr. Charles Best, and colleague Dr. John MacLeod — to isolate insulin from the pancreas of fetal calves. This groundbreaking discovery allows for the use of insulin to successfully treat diabetes, transforming a diagnosis of the disease from a death sentence into a treatable and controllable problem. Banting earned the 1923 Nobel Prize in Physiology or Medicine, an honour he officially shared with MacLeod. Banting went on to conduct research on silicosis, cancer, and the mechanism of drowning, before becoming interested in flying-related problems during the Second World War.

The World’s First Pacemaker
In 1949, Jack Hopps conducted experiments with medical colleagues Dr. W.G. Bigelow and Dr. J.C. Callaghan at the Banting and Best Institute in Toronto, which ultimately led to the development of the pacemaker. Bigelow and Callaghan had conducted open-heart surgery on a dog, during which the dog’s heart stopped. When Bigelow was able to re-start the heart by poking it with a probe, the idea of the electric pace-making device came into being. The doctors enlisted the help of Hopps, an electrical engineer with the National Research Council of Canada (NRC) (Ottawa, ON) who subsequently designed a pacemaker circuit. The device, the prototype of which was presented at the annual congress of the American College of Surgeons in 1950, provided a gentle electric stimulus duplicating the normal body nerve stimulation with no damage to the heart muscle. Hopps’ device — which measured roughly a foot long and several inches high and wide — served as the model for smaller, implantable versions in later years. The first pacemaker implantation is performed in 1958, in Stockholm, Sweden, by Dr. Ake Senning.

Till & McCulloch Identify Stem Cells
During their collaboration in the late 1950s and early 1960s, the University of Toronto (Toronto, ON) researchers laid the groundwork for several important discoveries by identifying and establishing the properties of stem cells in the blood-forming system. James Till, PhD (above left) and Dr. Ernest McCulloch (above right) demonstrated that colonies were created by single cells with “multipotent” properties — cells that create different types of cells. Their work showed that a single type of bone marrow stem cell could create red cells, white cells and platelets. Their work explained the effect of bone marrow transplantation, used to treat people with leukemia and other blood cancers, and is cited among the most important research in stem cells in the 20th century. The pair received the 2005 Albert and Mary Lasker Foundation prize for basic medical research.

Anik a-1
The ANIK A-1 satellite is launched, giving Canada the world’s first domestic geostationary communications satellite system. As the first satellite in the Telesat program, the ANIK A-1 would go on to provide the nation phone service and television programs.

Canadarm
In its debut in-flight test aboard the U.S. space shuttle Columbia, the Canadarm passes with flying colours. Built mostly in Edmonton-based Spar Aerospace Ltd.’s Toronto facility, the 50-foot mechanical manipulator took seven years to construct, and became a staple of NASA’s space exploration missions.

Lung Transplant
Dr. Joel Cooper performs the world’s first successful single lung transplant in Toronto. Three years later, Cooper makes history once again, performing the world’s first double lung transplant.

Learning How Cells Communicate
Tony Pawson, PhD of the Samuel Lunenfeld Research Institute, who has spent 25 years studying the mechanics of the cell, received international recognition in 1986 for discovering how cells communicate with each other. Pawson’s work confirmed that signal transduction is controlled by the formation of protein complexes, leading to a paradigm shift in understanding the genetics and biochemistry of cell biology and cancer. Pawson uncovered which specific protein interactions control signal transduction, and acknowledged the importance of tyrosine kinases, which transmit commands to hormones, regulating cellular reproduction and metabolism. As a result, new drugs were developed to block the actions of tyrosine kinases, in an effort to stem the development of certain types of cancer cells. Pawson now runs his own lab at Toronto’s Mount Sinai Hospital, where his research team further investigates the mechanisms that underlie intracellular signal transduction.

Tak Mak Discovers T-cell Receptor
A major milestone in understanding the immune system, the discovery of the T-cell receptor by the University of Toronto’s Tak Mak, PhD continues to aid the advancement of cancer and immunology research around the globe. T-cell receptors identify foreign, “intruder” cells and attack them. In autoimmune diseases, these receptors mistakenly identify healthy cells as intruders; conversely, the T-cell receptors of cancer patients are unable to identify intruding cancer cells, allowing the disease to develop unchecked. A better understanding of these cells offered insight into the immune system, while also shedding light on the building blocks of cancer. Since his landmark discovery, Mak has conducted research into leukemia and Hodgkin’s lymphoma. He is perhaps best known for his work with “knock out” mice, which had certain genes removed, allowing investigators to study the role of those genes. This work helped to identify the roles of many of the key regulators of cell growth and differentiation. Mak currently heads the Campbell Family Institute for Breast Cancer Research at the Princess Margaret Hospital in Toronto.

History of Innovation:
Ontario’s academic and research hospitals play a vital role in the development,
introduction and provision of new medical breakthroughs and technologies. Here is a just a small sampling of the many innovations and milestones that have taken place within Ontario’s borders over the years.

•     Milk pasteurization began at Toronto’s Hospital for Sick Children in 1908, 30 years before it became mandatory.
•     Nutritional researchers at the Hospital for Sick Children developed an easy-to-prepare, low-cost cereal for infants, now known around the world as Pablum.
•     Lumpectomies were introduced as a treatment for breast cancer at Toronto’s University Health Network.
•     A surgical procedure for the treatment of basilar aneurysms — located at the base of the brain — was pioneered at London, Ont.’s Victoria Hospital.
•     Toronto-based researchers developed software to control radiation therapy, a technology used worldwide for 20 years.
•     The Ottawa Hospital was the first in the world to use absorbable staples for reconnecting tissue following a hysterectomy.
•     Researchers at the Hospital for Sick Children provided the first proof that second-hand smoke can affect an unborn fetus.
•     Surgeons at the Human Mobility Research Centre, a joint venture of Kingston General Hospital and Queen’s University, performed the first computer-assisted knee replacement surgery.
•     Vision researchers at the Ottawa Hospital developed the artificial cornea.
•     St. Joseph Healthcare Hamilton unveils the world’s largest positron emission tomography (PET) scanner, which provides previously unachievable views of the human body (50 centimetres as opposed to the standard 15 centimetres).

(source: World Class Achievements and Major Medical Breakthroughs From Ontario’s Hospitals, 2003/04, Ontario Hospital Association and The Ontario Council of Teaching Hospitals.)

Ontario has also been on the forefront of genetic research, with the following
discoveries being made in the province:

•     Asthma
•     Breast cancer
•     Alzheimer’s disease (early onset)
•     Neurodegeneration
•     Cystic fibrosis
•     Duchenne’s & myotonic muscular dystrophy
•     Spinal muscular atrophy
•     Malignant hyperthermia
•     Fanconi’s anemia
•     Wilson’s disease
•     Beta-globulin deficiency
•     Severe combined immune deficiency
•     Nerve axon guidance

(source: Canada’s Biomedical Heartland, Market Ontario Publications)

Cystic Fibrosis
Lap-Chee Tsui, PhD, Manuel Buchwald, PhD and Jack Riordan, PhD isolate the defective gene that causes cystic fibrosis.

Imaging Breakthroughs Abound
In 1998, the University of Toronto’s Lewis Kay, PhD was honoured with the Steacie Prize for his work with nuclear magnetic resonance (NMR) spectroscopy, a process that allows for the sophisticated analysis of the molecule interaction. His methodology is used by more than 200 labs worldwide, marking only one of Ontario’s many achievements in the field of medical imaging. In 1991, researchers at Toronto’s Sunnybrook and Women’s College Hospital (SWCH) invented and licensed the world’s first high-frequency ultrasound microimaging scanner, for use in preclinical imaging applications. SWCH also broke ground in 1993, introducing the world’s first international Digital Mammography Development Group. London, Ont.’s Robarts Imaging (affiliated with the Robarts Research Institute) remains at the forefront of medical imaging to this day, most recently receiving $200,000 from RBC Financial Group to further the efforts of Paula Foster, PhD to develop novel cellular imaging methods to detect the early signs of diseases such as cancer and multiple sclerosis, as well as spinal cord injury detection. Ontario is also home to the world’s first 3T MRI for imaging babies at London, Ont.’s St. Joseph’s Healthcare, as well as Canada’s first magnetoencephalography site at Toronto’s Hospital for Sick Children (the first time such a unit has been installed at a pediatric institution).

Living Bone
Living bone, a material created by growing human cells in biodegradable polymeric foam, is developed by researchers at the University of Toronto, led by John Davies, PhD. The invention, which could one day replace conventional bone grafts, is implanted in a bone gap or fracture, where the foam is seeded with the patient’s own bone stem to create living tissue.

Meningitis Vaccines Developed
With the use of a conjugate vaccine developed by a Canadian research team led by NRC’s Harold Jennings, PhD, Britain begins immunize children and adults against group C meningitis infection. Jennings and his team patented a method that chemically combines a protein with complex sugars that cover the group C meningitis bacteria, creating a conjugate vaccine. Based on the technology, 13 patents in the U.S. are also issued for other vaccines, including the first synthetic vaccine against group B meningococcal infection.

Blackberry
Waterloo, Ont.-based Research in Motion launches the BlackBerry® handheld wireless platform, which quickly becomes a must-have for executives around the globe, providing them with constant, secure access to phone service, e-mail and the Internet.

Ontario Researchers Take the Lead Internationally
In April 2003, the Structural Genomics Consortium, an international not-for-profit company led by Aled Edwards, PhD was announced. The consortium currently operates out of the University of Toronto, University of Oxford (Oxford, UK) and Karolinska Institutet (Stockholm, Sweden), and aims to unravel the 3-D structure of more than 400 human proteins over four years and to place this information into the public domain with unrestricted use. This is only one of the major global efforts launched by Ontario-based scientists, with the support of the Ontario government. Steve Scherer, PhD has formed the Structural Genome Variation Project (GENOVA) to catalogue the complete range of large-scale DNA variation in worldwide populations and find the alterations that predispose or cause human disease; Michael Rudnicki, PhD is leading an initiative known as the International Regulome Consortium (IRC), which represents a third-generation genomics project that will address the regulation of genome function at a higher level by mapping the genetic regulatory nodes and networks that control the activity of embryonic stem cells (work in already being conducted in England and France); and Mick Bhatia, PhD is taking the first steps toward leading a large-scale research consortia involving top stem cell researchers in the U.K., Canada and the United States.

World’s First Robotic Surgery
In March 2003, a surgeon at St. Joseph’s Hospital in Hamilton performed a complex stomach operation on a woman 400 kilometres (250 miles) away in North Bay, Ont. constituting the world’s first robot surgical service. The procedure was performed with an array of sensors that monitored the surgeon’s hand movements, which were then transmitted by fibre optic cable to the distant robotic arms. London, Ont. has been home to a variety of robotic surgery breakthroughs, including Dr. Douglas Boyd’s closed-chest, robot-assisted beating-heart bypass operation in 1999, and Dr. Patrick Luke’s urology surgery in 2003, firsts in the world and Canada, respectively. In 2004, London played host to North America’s first robotic cardiac bypass with angioplasty, as well as the first North American renal artery aneurysm repair with CSTAR’s da Vinci® surgical robot system. Last year, the world’s first robot-assisted left atrial appendage ligation — used to reduce change of clot formation and stroke in high-risk atrial fibrillation patients — was performed in London.