MEDICAL MILESTONES By ANNE MULLENS Vancouver Sun VANCOUVER - There is little debate that Canada's most famous contribution to medicine was the discovery of insulin in 1921-22. The historic breakthrough made Frederick Banting and Charles Best household names, earned Banting and advisor J.J.R. Macleod the 1923 Nobel Prize in medicine, and saved the lives of millions of diabetics worldwide. See <20health> for a discussion of research funding crunch See <18health> for a discussion of technician shortage But insulin is far from being the only significant Canadian medical achievement over the years. Other personalities, discoveries and inventions sprinkle the history of Canadian medicine. Although not a definitive list, some notable landmarks follow: - SIR WILLIAM OSLER: Born in Ontario in 1849, Osler rose to become one of the world's most respected and renowned physicians, teaching and practising in Canada, the U.S. and England. ``He was the most brilliant and influential medical teacher of his day,'' says his biographer Harvey Cushing. Although he made many medical observations, he is remembered mostly for his technique of bedside teaching, which was adopted by medical schools around the world, and his text, The Principles and Practices of Medicine (1892), which was translated into four languages and remained a standard western medical text until the late 1950s. - PABLUM: In the late 1920s, three doctors at Toronto's Hospital for Sick Children - Frederick Tisdall, Alan Brown and T.G.H. Drake - came up with the formula for the first vitamin enriched, pre- cooked cereal as a way to combat the scores of malnourished children they saw admitted to hospital. Pablum is now a staple of infant feeding around the world. - HEPARIN: Although discovered in 1916 by a young student researcher at Johns Hopkins University in the U.S., the blood thinner heparin sat unused until it was purified under a team at University of Toronto's Connaught Laboratories, directed by insulin co-discoverer Charles Best. Toronto surgeon Dr. Gordon Murray pioneered the animal and human research of the extract, purified from beef lungs and pork intestines, to establish its safe and effective use to prevent clotting. The use of heparin opened the door to heart surgery, renal dialysis and the treatment of blood clotting disorders. - NORMAN BETHUNE: Born in Gravenhurst, Ont. and trained at the University of Toronto, the hero of Communist China organized the first blood transfusion service in the world in Madrid during the Spanish civil war. He went to China in 1938 to help the guerrilla army, organizing the first mobile hospital unit there and training schools for nurses and medical assistants. He died of blood poisoning contracted during an operation in 1939. - ELECTRON MICROSCOPE: Using the theory and crude model developed by German engineer Ernst Ruska, University of Toronto physicists James Hillier and Albert Prebus built a much-improved electron microscope in 1937 that magnified 7,000 times. Their design became the forerunner of all electron microscopes, which now magnify 200,000 times and make visible the most intimate details of cells, tissues, viruses and micro-organisms. - WILDER PENFIELD: A world-renowned neurosurgeon, the U.S.-born Penfield (1891-1976) was a professor of neurology and neurosurgery at McGill, where he founded the Montreal Neurological Institute. His systematic mapping of the human brain earned him world attention, as did his development of an operation for epilepsy. ``Starting with Penfield and the MNI, a standard of excellence in neurological sciences developed in Canada that continues to this day,'' said Dr. Pierre Bois, president of the Medical Research Council. - BARR BODY: University of Western Ontario researcher Murray Barr was the first to identify the female sex nucleus of a cell, named the Barr body in his honor. Barr and graduate student Ewart Graham found that only the cells from female cats had a mass of chromatin, or genetic material, called sex chromatin. The 1942 discovery helped determine genetic abnormalities and chromosomal disorders. - CURARE: While performing an appendectomy on a young man in 1942, Montreal anesthetist Dr. Harold Griffith became the first doctor to use the South American arrow poison, curare, during an operation. The drug, which causes temporary paralysis by interfering with nerve impulses, enables doctors to work on relaxed muscles, to use less anesthetic and to reduce anesthetic complications. Derivatives of curare are used in operations to this day. - HYPOTHERMIA: In the early 1950s Dr. William Bigelow of the Toronto General Hospital developed the technique in heart surgery of gradually lowering a patient's temperature to slow their metabolism and reduce their need for blood. It enabled blood flow to the heart to be stopped for eight to 10 minutes, allowing a bloodless, clear field of vision to operate on the heart, paving the way for a range of heart repairs. Hypothermia is now combined with heart-lung machines that oxygenate blood outside the body and has enabled surgeons to operate on the heart for hours without damage to the tissue. - VINCA ALKALOIDS: In the 1950s a research team led Dr. Robert Noble, then at the University of Western Ontario, discovered that extracts from the leaves of the Jamaican periwinkle plant, Vinca rosea, stopped the growth of cancerous cells. The compounds, called vinca alkaloids, were the first Canadian contributions to chemotherapy and have dramatically improved the cure rate of Hodgkins and non-Hodgkins lumphoma, and childhood leukemia. - CARDIAC PACEMAKER: Toronto General Hospital scientists, along with researchers at Ottawa's National Research Council, designed and demonstrated the effective human use of the first cardiac pacemaker in the 1950s. Too large to be implanted under the skin, the devices did not become practical until the transistor was refined 10 years later in the U.S. - ENDOCRINE HORMONES: Canadians have isolated a number of important hormones over the years. Biochemist J.B. Collip, who purified insulin for Banting and Best, went on to later isolate a hormone from the parathyroid, called parathormone, which raises blood calcium levels. Collip did extensive work on reproductive hormones secreted from the pituitary and was also the first to isolate the hormone ACTH (adrenocorticotrophic hormone) from the adrenal glands. Montreal endocrinologist Dr. Jacques Genest demonstrated the role of the hormone aldosterone in high blood pressure in the 1950s. In 1962, University of B.C. researcher Harold Copp isolated the hormone calcitonin, produced by the thyroid and parathyroids, which lowers blood calcium. University of Manitoba physiologist Dr. Henry Friesen, while at McGill, isolated and purified human prolactin, which stimulates milk production and can be a major cause of infertility. In 1981, Queen's University biochemist Dr. Aldopho de Bold isolated the heart hormone, atrial natriuretic factor (ANF), which naturally lowers blood pressure. - ``BLUE BABY OPERATION:'' Until a surgeon at the Toronto Sick Children's Hospital developed a technique to repair ``transposition of the great vessels'' of the heart, infants with this malformation, who were blue from the lack of oxygenation of their blood, usually died a few months after birth. Dr. Bill Mustard decided to reroute the blood flow between the chambers inside the heart by taking a piece of tissue from the tough sack around the heart and building a baffle between the left and right atrium of the heart to reverse the blood flow. Said Mustard of the first few minutes after operating on the first patient, Maria, in 1963: ``We could hardly believe it, the blue child turned a beautiful pink right before our eyes.'' Now called the ``Mustard procedure,'' the operation has become the standard correction for the heart defect and is performed around the world. - LUNG TRANSPLANTS: The world's first successful single lung transplant was performed at the Toronto General Hospital in 1983 by Drs. F.G. Pearson and Joel Cooper. The world's first successful double lung transplant was performed at the same hospital in 1986 by Dr. Alex Patterson. The first successful double lung transplant on a patient with cystic fibrosis followed there in 1988. - GENETICS: Canada has developed an international reputation for high-calibre genetics research. In the last five years, genetic researchers at the Hospital for Sick Children and the University of Toronto have made enormous strides in pinpointing genes that cause hereditary diseases. In 1987, Drs. Ronald Worton and Peter Ray identified a portion of the gene for Duchenne muscular dystrophy; in 1988 Drs. Roy Gravel and Don Mahuran identified one of the key enzyme defects that cause Tay Sachs disease; and in 1989 Drs. Lap-Chee Tsui and Jack Riordan, along with Dr. Francis Collins at the University of Michigan, discovered the gene for cystic fibrosis. All the discoveries open the door for greater understanding of the disease, and the potential for drug treatments or prenatal diagnosis.