Federally funded research in hepatology

Canada is an enormous landmass with a population no larger than that of California (approximately 30 million). Nearly 50% of citizens in the major cities were born outside of Canada; this raises a wide variety of medical and cultural issues, recently highlighted by the severe acute respiratory syndrome epidemic. The 'silver lining' to this recent crisis was the recognition by the federal government of Canada that formation of a Center for Disease Control North, which would include viral hepatitis—now the most common cause of liver disease worldwide—is appropriate. Medical research in Canada is supported by several federal programs, the largest of which is the Canadian Institutes of Health Research (CIHR) program. There are 13 Institutes; viral hepatitis is a priority for the Institute of Infection and Immunity. Most noninfectious and nonimmunologic liver research falls under the auspices of the Nutrition and Metabolism Institute. Currently funded studies include those on the pathogenesis of hepatic encephalopathy, cirrhotic cardiomyopathy, therapeutic vaccine development for chronic hepatitis B and C, the potential infectious etiology of primary biliary cirrhosis, brain-liver interaction/crosstalk in liver disease (cholestasis-induced fatigue and hepatitis C cognitive dysfunction), pathogenesis of hepatocellular carcinoma, mechanisms of hepatic fibrogenesis, cellular and molecular mechanisms of organ injury, potassium ion channels in hepatocytes, autoimmune molecular mechanisms in a mouse model for autoimmune hepatitis, and molecular mechanisms of iron metabolism. In addition, a request for applications for research on obesity recently has funded studies on lipoproteins, oxidative stress, and lipid peroxidation and its effect on macrophages, as well as another study on fatty acid binding proteins. Following the success of a Health Canada human immunodeficiency virus initiative, a hepatitis C program was introduced in 1999. In collaboration with CIHR, this program provided $18.375 million in research funds over the subsequent 5 years. To date, 128 researchers have received funding and 21 individuals have received salary support. The program has been successful at both luring well seasoned investigators from different fields into the field of viral hepatitis and supporting younger investigators from many different disciplines, all with an interest in hepatitis C. At the time of this writing, a request for renewal of this initiative at a greatly enhanced funding level, with a newly created hepatitis C clinical trials network, is pending approval. A Canadian viral hepatitis network linking three centers has received funding and currently is working on mathematical models for public health policy development and estimation of the cost of therapy. In 2001, CIHR issued a request for applications for research training programs to build research capacity within Canada. Two of the 83 funded programs (each receiving $300,000 per year for 6 years) focus on the liver. One of these, a 'regenerative medicine' program, is led by Gary Levy at the University of Toronto and comprises a multidisciplinary team of mentors in the areas of stem cell therapy, therapeutic cloning, tissue engineering, and gene therapy. The other program focuses on hepatitis C and has recruited mentors with expertise in basic virology, biochemistry (including proteomics), and immunology, as well as the more clinical sciences (nursing, medicine, surgery, biostatistics and health economics, and public health). Students funded by these research training programs choose a specific mentor and are expected to enroll in a postgraduate degree program and participate in an ongoing transdisciplinary education program transmitted across many Canadian universities via webcasting and video conferencing. Other governmental initiatives designed to address issues of recruitment and retention of excellent researchers include the establishment of Canada Research Chairs, which provide both salary support and some operating costs. One such chair has been awarded to Thomas Michalak, of Memorial University in Newfoundland, who studies the natural history and pathogenesis of hepatitis B and hepatocellular carcinoma in the woodchuck and who maintains one of the few such animal colonies in the world. Another federal government initiative, 'Networks of Centers of Excellence', supports the Viral Hepatitis Research Program at the University of Alberta, where Lorne Tyrrell and colleagues have developed a murine model for hepatitis C. Tyrrell and colleagues will use this support predominantly to facilitate their studies on drug development for hepatitis C, performed in collaboration with virologists across Canada. Finally, the Canadian Foundation for Innovation provides lump sums, mainly for equipment (no running costs!), and has provided funds for the Immune Tolerance in Transplantation Program at the University of Toronto. There are 16 Canadian universities that have medical schools, and space permits only a sketch of federally funded research on basic and/or clinical sciences within the field of hepatology, research that is ongoing at almost all 16 of these universities. As is the case worldwide, the electronic age has greatly facilitated collaborative research across this vast country and now is enabling students from all universities to benefit from expertise at specific centers. The future is exciting, with the potential for new initiatives that will further enhance research and its translation, so as to ensure that all Canadians remain well informed and have universal access to the very latest developments in health care.

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