For over three decades transplantation has been one of London’s pinnacle examples of a world-class translational research program that integrates the work of basic scientists and clinicians in a common goal: saving lives.
Dr. Bill Wall, Professor in the Department of Surgery at Schulich Medicine & Dentistry, vividly remembers the snowy day in 1978 he went to Toronto airport to collect the first vial of cyclosporine to arrive in Canada. It was the “magical white powder” transplant surgeons had been waiting for – a drug that could prevent the immune system from attacking a transplanted organ. Since then the London transplant program has never looked back.
The enormous research enterprise crossing multiple departments at Schulich Medicine & Dentistry, Lawson Health Research Institute and Robarts Research Institute has been the engine driving the clinical success, and continues to push the boundaries of transplantation.
Thanks to the research breakthroughs here, the Multi-Organ Transplant Program at London Health Sciences Centre (LHSC)) has achieved dozens of firsts, including leading the first clinical trial in Canada on cyclosporine, the first liver transplant in Ontario, the first heart-lung transplant in Canada, the world’s first liver-bowel transplant, and the first living donor liver transplants in Canada.
With two new co-directors in place, Dr. Patrick Luke and Dr. Anthony Jevnikar, the program is poised to build a brilliant future, inspired by the legacy of the past.
It all started in 1972 when University Hospital opened and it was determined transplantation would be a focus. At that time the results were dismal. Most died within months and few thought there was a future in transplantation. Dr. Calvin Stiller led the development of the transplant program and was director until 1997.
He also led the groundbreaking Canadian study on cyclosporine in kidney recipients. Cyclosporine proved to be a “quantum leap” in organ transplantation, pushing the success rate of kidney transplants to 80 per cent, and sparking a renewed interest in other transplants such as liver and heart.
“We got the drug before anyone else in Canada because of our connections with the group in Cambridge, England who were the first ones to prove its use both in the laboratory and the clinic,” explains Wall, who trained as a transplant surgeon in Cambridge in 1975 and 1976.
“It was exciting to go from a miserable level of failure to a high level of success within several years. It was a wonderful experience to see these patients who were facing certain death from organ failure have their lives saved.”
Today, dozens of researchers advance transplantation from many angles. From basic molecular studies of the immune system, to microsurgery models of transplantation, to clinical trials on immunosuppressive drugs – the research covers the full spectrum.
“Every member of our current group and every new member as we recruit … has to want to solve the fundamental problem of transplantation,” says Jevnikar, a nephrologist and clinician scientist named to the Canadian Institutes of Health Research (CIHR) Wyeth Chair in Transplantation at Schulich Medicine & Dentistry in 2009.
It’s what transplant surgeon Dr. Luke, a surgeon and clinician scientist, calls a “bench to bedside and bedside to bench” continuum. “Every patient will benefit from the research that we do.”
One quarter of transplant patients at LHSC are in clinical studies (about 160 organs are transplanted annually here). In total, the transplant program has attracted $32.9 million in research grants over the past five years and published 229 publications in peer-reviewed journals. It is the only centre outside the United States to receive National Institutes of Health (NIH) funding to study transplant tolerance. The program also has three endowed research chairs.
Dr. Joaquin Madrenas holds the Canada Research Chair in Transplantation and Immunobiology at Western. His work focuses on T-cells – the ‘generals’ of the immune system’s army that attacks a transplanted organ. His research is essential to improving outcomes and ensuring recipients don’t return for a second or third transplant.
“What we are trying to do is reach a state in which we know what signals can turn off the immune system. As soon as we have those signals, we can reproduce them with certain types of medication. We still don’t know exactly what these signals are, but we are closer than we were a few years ago,” says Madrenas, noting that they use less medication now to achieve transplant survival than 20 years ago.
Another internationally renowned success story in transplant research is microsurgery, an area pioneered by the late Dr. Robert Zhong, professor in the Departments of Professor of Surgery, Pathology and Microbiology & Immunology at Schulich Medicine & Dentistry.
“He developed in the microsurgery laboratory here the technique for transplanting all organs and tissues in rodents and it provided an enormous platform for transplantation models in which we could study rejection, the effectiveness of immunosuppressants or the combination of immunosuppressants,” explains Wall. “Now we have a shelf of the best options for patients.”
More than 150 microsurgeons have been trained in London. The program has also trained hundreds of basic science graduate students, postdoctoral fellows and clinical fellows.
With all of the program’s success, they are still unable to help everyone because of a shortage of donated organs.
Some of the solutions will come from the laboratory. Prevention of chronic disease is key; also designing better medications and finding ways to prevent organ injury.
But there is also the promise of stem cells and regenerative medicine to repair or regenerate organs. Madrenas says “transplantation should be a step to fully regenerative medicine … but this is a global initiative at very, very early stages.”
Not waiting on this futuristic solution, the team is working hard to improve the success rate and health of transplant recipients, and also expanding organ retrieval.
One of the milestones for the program will undoubtedly be the Matthew Mailing Centre for Translational Transplant Studies, a new 10,000 square-foot facility expected to open at LHSC in 2011. The centre will be close to the Multi-Organ Transplant Unit at University Hospital, which Luke says will be a huge advantage. “Five hundred feet from where patients are taken care of, we’ll be doing studies on medications they will receive in five years. It’s amazing.”
“We have a mature program that has been excellent for so many years, sometimes we take that for granted,” says Jevnikar. “If you have a miracle every day, it can just become routine … but they’re still miracles.”
Schulich Medicine & Dentistry is helping to support a new transplant scientist and surgeon through the Schulich Clinician Scientist Program, raising funds to establish an endowed research chair in memory of Dr. Zhong and has announced a unique Centre for Human Immunology which encompasses multi-disciplinary research on transplant immunology.