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Photography by: Kathy Stuart

DR. RICHARD KIM

Pioneering Personalized Medicine in London
By Ryan Ford

One of the largest undertakings in the history of medical science involved thirteen years of research to map the human genome.
Completed in 2003 although a working draft was completed in 2000 The Human Genome Project, coordinated by the U.S Department of Energy and the National Institutes of Health, brought together scientists from the United States, the United Kingdom, France, Germany, Japan, and Spain, and ultimately cost $100 million, just to map a single persons genome. Today, a persons genome can be mapped in about a day, at a cost of about $300. The Human Genome Project has proven its worth time and again, and the benefits continue to surprise and inspire hope for millions suffering many, many afflictions. In London, some of the benefits of genetic research are being explored at the Clinical Investigation Unit at the Lindros Legacy Research Building at University Hospital, headed by Dr. Richard Kim. Dr. Kim specializes in personalized medicine targeting drug interactions based on an individuals genetic makeup. Considering that drug costs accounted for sixteen percent of the overall health care expenditure in Canada for $32 billion in 2011, the potential for personalized medicine to save money and reduce deaths and hospitalizations from adverse drug reactions 1FIVE | WINTER is incredible. The personalized medicine clinic opened by Dr. Kim at London Health Sciences Centre in 2008 was the first of its kind in Canada. Although he knew as early as his high school days that he wanted to go into medicine, Dr. Kim couldnt have known he would end up a trailblazer in personalized medicine. However, his undergraduate studies at the University of Saskatchewan got him off to a good start. I was fortunate applying to medical school in Saskatchewan: they allowed for a minimum of one year pre-med before going to medical school, but medical school was five years. So at 18 I went to medical school I got lucky that way, he says. After his internship and studies in internal medicine at Saskatchewan, he went off to Vanderbilt Universitys School of Medicine for his residency and a fellowship in clinical pharmacology. I went to Vanderbilt to do a lot of research and then stayed there after three years of fellowship as a faculty member and then rose through the ranks, he says. We grew a fairly big-sized group doing a lot of translational research in terms of drug effects and the role of genetic differences. We spent a lot of time trying to figure out why people vary in their response to drugs in terms of genetic markers and other things. People can look similar, but most people are surprised to know that, between two people that look similar, their drug levels on the same dose can vary ten to twenty fold. The ability of the body to handle drugs differs so significantly, but you cant tell. Now, with diagnostic technologies we are starting to understand why some people respond worse or better than other patients. In 2006, Dr. Kim and his team moved their research to London from Vanderbilt. Originally from Saskatoon, part of the draw for Dr. Kims move to London was simply returning to Canada as much as he relished the fifteen years he spent at Vanderbilt. Vanderbilts a wonderful place, if you ever have a chance to go to Nashville people dont think of Vanderbilt in Nashville; it sounds like it should be on the East Coast, says Dr. Kim. Its really become a powerhouse both as a medical centre and undergraduate and graduate training in the middle of Music City. I think a lot of times, for those of us who are from Canada, theres a tendency to come back to Canada, so there was this opportunity to bring our program of

research and fellows and some of our folks with us. Its been six years now, and I think Western, London, LHSC, Lawson Health Research Institute, everybody was hoping that we would do something fancy in genomics and personalized medicine and I dont think they quite knew what the state-of-the-art would be in the coming decades. I think whats been really great is that we havent just hyped the field. Weve been one of the groups that really worked with the hospitals, worked with the physicians, worked with the nurses, worked with the pharmacists and other allied health professionals.

some grants to the Ministry of Health and Long-term Cares Drug Innovation Fund. We got that funding to basically tell the Ministry well try to come up with something practical that is genomically based that will help real-world patients, and the hospital and Lawson and everybody was very supportive of starting a clinic geared towards that. With a model in place, the research team could explore other drugs and come up with similar algorithms based on genomic information to provide better care, and to demonstrate that they could provide better care. Soon, the clinic had moved along to the breast cancer drug tamoxifen. We actually still see patients and the clinics going quite well, says Dr. Kim. We see nearly 250 patients on tamoxifen where we do targeted genetic testing as well as measuring drug levels and providing feedback to the referring oncologist, and I think thats been really helpful. Tamoxifen, while critical to the treatment of breast cancer, has some drawbacks. Weve learned a lot about how to better identify a small proportion of patients who may be at risk for suboptimal benefit from a drug, because drugs like tamoxifen are important for breast cancer patients typically for up to five years but is prescribed at a single dose of 20 mg per day, explains Dr. Kim. So everybody gets the same dose. Its hard to know whether its really working or not, but we know from trials that 20 mg a day is very efficacious. But we know from the way the human body differs between patients that some people break down the drug more effectively and others may not benefit as much, and from doing this pharmacogenomic testing, as well as measuring the levels, we actually learned a lot about clinical and genetic predictors of people at risk for low blood level of the active drug, and weve been able to use that to provide care, and of course those findings are very helpful to us to publish to let the rest of the world know that there are other ways of looking at genetic markers to individualize drug therapies like tamoxifen. Dr. Kim and his team have since started looking at statin drugs like Lipitor, drugs used by millions of Canadians to lower their cholesterol. About ten to fifteen percent of statin users will develop muscle aches, and in rare cases, that can lead to muscle damage and even death. Theyre used by millions of people, says Dr. Kim, so understanding, of the people at risk

for aches and pains, which proportion of them are at risk of real muscle damage versus those who may get some aches that may be manageable it means a lot to the patient when we can say We really dont think youre going to get any muscle damage. We can provide reassurance as well as the ability to switch to other statins. Early in 2012, the Canadian Government announced a $67.5 million investment in personalized medicine, recognizing its potential to improve the quality of care for patients across the nation. Ever the pioneer, Dr. Kim will continue to lead the way with his research into tailoring drug treatment approaches to individual patients based on genetic information, with real-world applications. However, Dr. Kim feels the realworld application of research will always be troublesome. Fundamentally, how do you implement what sounds self-evidently helpful? Our genetic makeup in personalized medicine sounds good, but its actually quite difficult to implement because the practice of medicine and introduction of innovative technologies is not as simple as it seems, he says. Its a discipline driven by history, evidence, and caution. I think theres a tendency sometimes to think that researchers should just do research and physicians just look after patients, but a lot of times people do ask, Where are the research dollars going? Why isnt it helping people more? People hear about great discoveries, but then they dont hear about that being translated into better patient care. I think that interface is actually quite difficult. Its not as easy as people think, and I think weve been fortunate to be able to forward momentum in implementation. Better care remains the ultimate goal, however, and is always in focus. Just speaking with Dr. Kim, his passion for his work is immediately evident. His excitement level betrays the amount of promise he sees for personalized medicine, much of which he credits to his team and his working environment. I dont think theres any other group that has this kind of strategy for implementation, with the support of the institutions and physicians and allied health professionals, in part because weve been doing this step-by-step. Although it sounds like were doing big things today, its really a reflection of what we started six years ago. I dont think people know that London is this far ahead. WINTER | FIVE2

Since 2006, Dr. Kim and his team have not regretted the move. I think London, certainly for us, the momentum and the support of institutional leaders and other physicians in the hospital and at Lawson everyone has really supported our long-term vision, he says. We were fortunate, and still are, that weve been able to work with the hospital to implement better care.

Work at the personalized medicine clinic first focused on the drug Warfarin, a blood thinner used to treat conditions like atrial fibrillation. It is a drug that is known to be difficult to manage, says Dr. Kim. Some people need as little as one milligram per day and some need ten or fifteen milligrams a day, so theres a lot of blood testing to get to the right dose and at that time there wasnt really a coordinated way of looking after patients with atrial fibrillation who would benefit from Warfarin. Some of the work his team had done at Vanderbilt and published in the New England Journal of Medicine involved a data set that argued the importance of certain genetic markers that help predict how some people metabolize blood thinners more quickly than others. So we basically said, if you know that information, we could create a clinical decision-making algorithm, and we would come up with that and at that time we actually wrote