Stiller is from Naicam, Saskatchewan. He was the third of five children born to Reverend Hilmer Stiller, a minister ordained by the Pentecostal Assemblies of Canada, and his wife Mildred (née Parsons). Stiller spent his childhood years in Naicam; later, the family would move to Tisdale, and then finally in 1947 to Saskatoon. Stiller graduated from Bedford Road Collegiate, followed by two years of undergraduate pre-medical studies in Arts and Science at the University of Saskatchewan. In 1961, Stiller entered the medical faculty at the University of Saskatchewan.

Following the completion of his MD degree in 1965, Stiller pursued five years of post-graduate fellowship studies at what was then called the University of Western Ontario in London, Ont., followed by a year spent at the University of Alberta in Edmonton. Stiller developed a specialization in nephrology, as well as in the related areas of transplantation, immunology, and infection. Returning to Western in 1971, and having gained by then his fellowship designation of FRCP(C), he embarked on a long tenure at University Hospital, London. Beginning in 1972, he was appointed Chief of Nephrology and Transplantation, and later, Director of Immunology at the John P. Robarts Institute.

From the early 1970s through to the first decade of the twenty-first century, Stiller would make many contributions to his work, research, advocacy, and medical-based entrepreneurship. Additionally, Stiller had found the time to be an early adopter of computerized patient records, as well as to co-create a telephone-based medical service, which he would make public. This service became the first form of Telemedicine offered by the Government of Ontario. These foundational years of his career were very important at shaping his reputation in the medical community. The eventual widespread success of organ transplantation led to Stiller's establishing the Multi-Organ Transplant Service and the Canadian Centre for Transplantation in London, over which he acted as chief from 1984 until 1996. Organ rejection was (and remains) a major challenge in the field and Stiller was principal investigator in the early 1980s in the clinical trials and market development of the drug Cyclosporine for use as a first-line therapy for transplant rejection. In 1990, he published Lifegifts: The Real Story of Organ Transplantation, in which he, along with his brother, the Reverend Brian Stiller, recounts the history of human organ transplants. Stiller was on a team of researchers that proved in 1984 that human Type I diabetes was an autoimmune disorder and therefore amenable to a regime of immunosuppressant or immunomodulant treatment.

At the same time that Stiller was carrying out his hospital and laboratory work, he was helping also to enlarge steadily the capacity for advanced medical research and development in Canada. Stiller founded the Canadian Medical Discoveries Fund, the largest venture capital fund in Canadian medical history, which, since its inception, has raised and managed over half a billion dollars in assets. Stiller served as founder and chair of the Ontario Institute for Cancer Research, as well as the chair of Genome Canada. Along with Dr. John Evans, a former president of the University of Toronto, and Ken Knox, Stiller catalyzed the founding of the Medical and Related Science (MaRS) Discovery District in downtown Toronto, and then served as its director. It launched in 2000, and was created to bring publicly funded medical and related sciences research to Canadian and global markets. Stiller was invited by the then Premier of Ontario, Mike Harris, to chair the Ontario Research and Development Challenge Fund, which, together with the Ontario Innovation Trust, would provide over $1.2-billion in R&D support during the following decade to Ontario universities in an alliance with research-intensive businesses.

Stiller was named Ontario Entrepreneur of the Year in 1996.^{[citation needed]} In 1999, Western University established the Novartis/Calvin Stiller Chair in Xenotransplantation.^{[citation needed]} The next year, he was named a Member of the Order of Ontario, to go along with having been made a member of the Order of Canada a few years earlier.^{[citation needed]} In 2002, the namesake Stiller Centre for Technology Commercialization was opened in London.^{[citation needed]} He was recognized by his alma mater, the University of Saskatchewan, in its "100 Graduates of Influence", an all-time list celebrated to mark the university's centenary in 2007.^[2]

In 2010, Stiller was inducted into the Canadian Medical Hall of Fame.^[1] Also in 2010, he was made a Distinguished Fellow of the Canadian Academy of Health Sciences,^[3] and won the highly prestigious Canada Gairdner Wightman Award.^[4]

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