Foundations of Yesterday, Successes of Today

jack-hirsh

Research at Hamilton Health Sciences is diverse, innovative and comprehensive. Joint efforts between Hamilton Health Sciences and McMaster University have led to leading-edge, patient-centered research in a number of priority areas including, cardiovascular disease, diabetes, thrombosis and atherosclerosis, cancer, digestive diseases and infectious diseases. Globally, Hamilton-based research consistently earns high rankings, particularly for its impact on world health. Just how did we get to where we are today? Long before international rankings and high-tech, state-of-the-art facilities, a small group of visionaries set the wheels in motion and laid the foundation for what many of us take for granted today – a dynamic environment of multidisciplinary collaboration in medical research.

The inaugural issue of a new regular column features the iconic
Dr. Jack Hirsh. A pioneer in his field and a mentor to many of today’s leading researchers, Dr. Hirsh is one of Canada’s most influential and celebrated researchers. His work has shaped the direction of research at McMaster University and Hamilton Health Sciences and laid the groundwork for some of today’s leading institutes and research teams, both in our city and abroad.

August 2013, telephone interview with Branka Vidovic, Communications and Media, Research Administration

  • What drew you to a career in research?

    Well I’ve been in research since 1965 so I’ve been there for a long, long time. I graduated in Melbourne, Australia, and decided that I wanted to do research. Why did I decide I wanted to do research? Well at that time many of the clinical decisions we were making were not based on good evidence and I became disillusioned with clinical practice in general because my supervisors were making arbitrary decisions based on what their professor had told them twenty years earlier. So, at quite an early stage in my training, probably as early as my second /third year of residency, I decided I wanted to pursue a career in research. I was in Australia, quite isolated, and I wasn’t quite sure how to go about it.

  • It sounds like there were very few opportunities for research training at that time. How did you get your start?

    After completing four postgraduate years in Internal Medicine, I trained in hematology during which time I sought advice and with the help of several mentors, managed to obtain financial support to work overseas. I then spent four years working at various laboratories around the world. First in St. Louis at the Barnes-Jewish Hospital, Washington University with Sol Sherry (1916-1993) whose lab concentrated on fibrinolytic agents [clot busters]; then I went to Hammersmith Hospital, which at that time was the Postgraduate Medical Hospital in London, where I trained with Professor John Dacie (1912-2005). I became interested in the question of why some platelets were more active than others and did research to differentiate active platelets from less active platelets. I reached a wall, could not get the equipment or advice in the UK, and took advantage of a contact that I had made while in St. Louis. While in North America, I visited Fraser Mustard's laboratory in Toronto. I spoke to John Dacie who agreed that Mustard's lab was the place to go and he very kindly introduced me to Sir John McMichael who, among other things, administered the Welcome Fund. He listened to my story and said, "Well that sounds interesting, I think you deserve a traveling fellowship." It was the old boys’ system in operation. No committee, no application; but very generous support for an unknown junior research fellow from Australia. I then contacted Mustard and explained my plan. He was enthusiastic and using his network, secured an award from the Ontario Heart Foundation -- it was their first Visiting Scientist Award. Fraser made up the title on the spot. I was extremely fortunate in having support from shakers and movers.

    So my interest in platelet stickiness took me to Toronto where the most creative platelet lab at that time was run by Fraser Mustard (1927-2011) at the University of Toronto. I then went back to Melbourne for a couple of years where I had a faculty appointment. Around this time the newly established McMaster University Medical School was recruiting and I was invited to visit to see if I was interested in moving back to Canada for at least a brief period of time. I was really impressed with a number of members of the newly formed faculty. David Sackett and his Department of Clinical Epidemiology and Biostatistics, John Evans, Alvin Zipursky and my former mentor Fraser Mustard. For the first time, I realized that clinical decision-making could be investigated scientifically and provide answers to clinically important questions. Before that my research training had been laboratory-based. When I returned to a clinical position in Australia, it was a culture shock because, in contrast to the rigor of laboratory research, clinical practice was based on anecdotal experience and most decisions lacked scientific evidence. I was both excited and attracted by the work of David Sackett and his group. After returning to Australia following my recruitment visit and discussions with my wife, we decided to accept the offer at McMaster. We moved to Canada at the end of 1969 and I started work in 1970.

  • You recognized a fertile environment for new ideas at McMaster, what did you do once you arrived?

    I started work at St. Joseph’s Hospital because the McMaster Medical Centre had not been built yet. I loved the McMaster environment because it encouraged innovation and was so supportive of research. I set up my research program using a two-pronged approach: A basic laboratory at McMaster and a clinical research program in thrombosis. With help of colleagues we developed what was then an unique approach to research whereby our laboratory research was a servant to our clinical research, which in turn was driven by the clinically important questions in thrombosis that we encountered in our daily practice. It was a truly integrated clinical research program; our laboratory research was designed to answer questions that arose from our clinical research program. I received enormous support from Dave Sackett and Michael Gent; without their help and expert advice, the program would not have succeeded. Mike Gent, a mathematician who became a statistician and then a superb methodologist, became a close collaborator and we formed a great team. We began to recruit fellows who are now distinguished biomedical scientists. Their names are familiar within the world of research: Russell Hull, Graham Turpie, Jeff Ginsberg, Jeff Weitz, Mark Levine, John Kelton and many others. We started training research fellows from overseas and then research fellows from Canada. And as a result of our training program, the heads of thrombosis programs in Calgary, Ottawa, British Columbia, Nova Scotia and at Sunnybrook/Women’s Hospital in Toronto, are all our former trainees. In addition, several of the leading thrombosis programs in Europe are headed by our former trainees. In 1981 I became Chairman of the Department of Medicine and, although I maintained my research program with the help of former fellows who now had faculty appointments, I could not give the research my undivided attention. Nevertheless, I enjoyed my time as Chairman and am proud of several accomplishments. With Mark Levine as my assistant we established the half day in education for the residency program in internal medicine, in which we introduced the medical residents to the concept of evidence-based medicine. I considered recruitment one of my important responsibilities and during my tenure, we recruited some of the current leaders at McMaster: Paul O'Byrne, Stuart Connelly, Akbar Panju and Salim Yusuf.

    Then in 1987 an event occurred that was almost as important to me as my recruitment to McMaster. Bill Noonan, the CEO of the Hamilton Civic Hospitals, with great foresight decided to establish a Research Centre at his hospital. It was a bold move and turned out to have a huge impact on Canadian research, on Hamilton and on McMaster University. I was invited to be the foundation Director and with the help of both public and private funds we built the Henderson Research Centre. I resigned my position as Chairman and moved to the Henderson Hospital where initially we worked out of a temporary facility. Michael Gent came with me and Jeff Weitz joined as head of one of the programs after the Centre was built. Michael Gent headed up the Clinical Trials Methodology Group, I headed up Clinical Thrombosis Research, and Jeff Weitz headed up a basic science program in Thrombosis and Atherosclerosis that was the precursor to TaARI. A fourth program was added, Pediatric Thrombosis, headed up by the late Dr. Maureen Andrew [1952-2001]. The research interests of the Centre expanded from thrombosis to other branches of cardiovascular research. I remained director of the Research Centre from 1987-2005 and after I stood down, I stayed on as a researcher as well as maintaining a clinical practice. In 2010 the Programs were moved to the newly built David Brailey Cardiac, Vascular and Stroke Research Institute (DBCVSRI), where the basic program was renamed the Thrombosis and Atherosclerosis Research Institute (TaARI). I moved to the DBCVSRI, but closed my practice so that my primary role was mentoring. The DBCVSRI was conceived by one of our most distinguished scientists, Salim Yusuf [PHRI], and with the enthusiastic support of Murray Martin, our CEO, funds were raised to build an impressive research facility that is world renowned for its innovative research and productivity.

  • And that brings us from 1969 to now. You are semi-retired, what is your involvement in research today?

    I have developed a very close personal and professional relationship with John Eikelboom, who is an outstanding researcher. I help mentor his fellows, discuss research ideas with him almost on a daily basis and through him interact with people like Stuart Connolly, Richard Whitlock, Jeff Weitz and PJ Devereaux. More recently Jeff Ginsberg joined the inner core group, so it is Ginsberg, Eikelboom and myself. We typically have two or three fellows whose research direction is influenced by the results of studies (in which John Eikelboom has been involved ) performed at the PHRI. We meet formally twice weekly to discuss research. I participate as an advisor, mentor, instigator of ideas, and writer and reviewer of research publications and reviewer of grants. I am kept busy, working mainly from my home. It’s exciting work. Since I have no clinical, administrative or formal teaching responsibilities, I am the only person in the group whose only work-related responsibility is research. Once every two months we have a larger meeting of all the fellows, which lasts about half a day.

  • I didn’t realize you were still so involved.

    Well I have not really retired and my association with people like John Eikelboom, Jeff Ginsberg and others has kept me going in research. I feel very fortunate to be involved and love what I am doing.

  • As a young scientist one of your greatest influences was Fraser Mustard. What is the one thing you learned from your mentor that has stayed with you over the years?

    Well I had three mentors as a research fellow and two more as a faculty member at McMaster -- David Sackett and Mike Gent. I have also learned an enormous amount from the people whom I mentored and continue to mentor. I had three great mentors during my fellowship years in the US, England and Canada. They all taught me there are no barriers to research. That you don’t stop and give up because you have a reached a technical barrier that requires expertise that you don’t have. Rather, you master the new technique or look around for a collaborator with the required expertise. A living example of that process is my move from Hammersmith in the UK to work with Mustard in Toronto. We are so fortunate at McMaster and Hamilton Health Sciences because we have so many experts in many diverse fields as well as a culture of collaboration and generosity with our time. In many institutions the culture is much less generous, people work in silos and cooperation is much more difficult to achieve. The spirit of cooperation is one of the strengths of McMaster. It was a feature of the initial culture and has continued, thereby limiting the barriers to cooperative research.

    The second lesson I learned while working with my mentors, was to train with the best. I was extremely fortunate because all three of the people I trained with were giants in their field. You learn what it takes to succeed in research: commitment, hard work, dedication and passion.

    The third important lesson I learned along the way is to avoid the tendency to place too much weight on your own work when other research produces results which are contrary to yours. Keep an open mind. You are not always right. I have been wrong many times; when that happens admit it. It’s important to recognize your errors, acknowledge them and move on .

    We mentioned Fraser Mustard, who were the other two?

    Tony Fletcher, who was the head of the laboratory at Sol Sherry's lab, and Professor John Dacie, who was a distinguished hematologist at Hammersmith Hospital. I learned from all of them. Dacie was a brilliant observer and a prolific writer. He was an old-school researcher, and was not only passionate about work, but also about entomology, his hobby. Both Mustard and Tony Fletcher were young visionaries who didn’t recognize barriers in research, nothing was impossible and they were totally committed to research. Tony moved from the UK to the US because he found the US research environment more conducive to his type of research. Mustard was a maverick in Toronto and stayed clear of the medical establishment. They were both different. They had their personal lives, but research was both their work and their hobby. They were passionate about their research. Others might accuse them -- as they have accused me – of being too narrow in their approach to life, but they share these qualities with other successful researchers who have made important contributions to mankind. We all benefit from their dedication.

    Oh, and there is one other lesson that I learned, and I think it’s an important lesson. Don’t skimp on your research training. I think one of the biggest problems budding researchers have these days is they don’t spend enough time in their research training. Then, after they complete their research training and get a faculty appointment they become consumed with the clinical practice, administration, teaching and so forth, and don’t have sufficient training to keep their research going. So they drop out. Which isn’t to say that people who go on to spend most of their time as clinicians or teachers don’t benefit from one or two years of research, but if you want to be a professional researcher you have to obtain the appropriate training.

  • You recognized something about Hamilton 40 years ago, others are starting to see it now, as one of the pioneers of research in Hamilton, what is it about this city and its healthcare environment that makes it so suitable for research? What does Hamilton offer?

    What I encountered when I first came to McMaster was a group of brilliant mavericks like John Evans, who was the founding Dean of the Medical Faculty; Moran Campbell (1925-2004) the first Chairman of Medicine; Fraser Mustard the first Chairman of Pathology; Dave Sackett, the first Chairman of Clinical Epidemiology and Biostatistics; and Alvin Zipursky the head of pediatrics. These people thought out of the box; they were all very intelligent, very well trained in their area of interest, and very broad in their approach to academia and research. They established a culture of cooperation and mentorship which has persisted .People helped young bright people and were proud to help them. In many institutions this did not happen because the senior person was threatened by the bright young person. We were well placed to take this approach compared to other institutions because we were in a recruitment mode. We were expanding rapidly. We were seeking bright young people to fill positions and we weren’t concerned about them taking our positions. So it wasn’t so much that we were special, but rather it was the situation that we were in that facilitated such a generous approach.

    Hamilton was also innovative in health care delivery. Recognizing that there is strength in numbers, Hamilton introduced regionalization of our specialty health resources. Long before provincial governments promoted rationalization of health resources, the medical leaders in Hamilton decided to regionalize specialty practice so there wasn’t overlap among our hospitals. They established the cardiovascular program at the General Hospital, the renal program at St Joseph's, pediatrics and high-risk pregnancy at McMaster Hospital, and so forth.

    A third development, which in some people’s mind is what McMaster is most famous for, is the innovative education program. It was completely new at the time. A decision was made to completely revamp medical education. Make it problem-based, de-emphasize the importance of annual exams so that students could learn for the pleasure of learning, and allow people to learn at their own pace and to concentrate on areas in which they were particularly interested -- as long as they acquired core knowledge. This approach started with our undergraduate program and slowly became incorporated into our postgraduate program.

    So Hamilton and McMaster were innovative in research, in education, and in health care delivery. The innovation continues. John Kelton, the current Dean and Vice President, among his many outstanding accomplishments has set up off -site campuses in downtown Hamilton, Grimsby, Branford, Burlington, Waterloo, the Niagara peninsula and various other places. Innovation has stimulated more innovation. Creative people are attracted to McMaster and as they become the leaders, they continue the culture of innovation.

  • You mentioned your involvement with John Eikelboom, Jeff Ginsberg, Richard Whitlock and several others, all Hamilton-based, what about the international scene? Is there a scientist or a group whose work you are interested in?

    Basically we maintain interest in all things national and international in our area of research. We have a very close cooperation with the group at the Academic Medical Center (AMC) in Amsterdam where the thrombosis program was set up by Harry Büller who was a fellow of ours over 20 years ago. Through this connection many of our fellows come from the Netherlands. Through John Eikelboom we maintain a strong Australian connection, which provides a stream of outstanding fellows. Over the years I’ve worked with and trained many international scientists, and I continue to work with them today; people from France, Italy, the UK. With modern communications, science, like many other fields, has become internationalized.

  • Now that you are semi-retired do you have a new perspective on research? Do you see research differently now that you are no longer completely immersed in it?

    Yes, I am more convinced than ever that mentors and supervisors should ensure that the research questions they ask and delegate to their students should be important and have the potential to change clinical practice or scientific thinking. Too often, researchers and their students tackle trivial questions. If a person spends time working on a problem, they should try to ensure that it is an important problem.

    My next comment will be unpopular with some and probably label me as an old foggy. Many of my colleagues travel far too much. There are so many inducements to travel; a host of international meetings and a profusion of industrial sponsorships. As a person becomes well known the invitations to speak, consult and attend advisory meetings increase. It’s hard to say no, but if they don’t say no they end up spending far too much time on airplanes and not enough time thinking about their research. They relegate their thinking time and writing time to between 10pm and 2am instead of daytime hours, when they are fresh. If they are really serious about research, they ought to work on it during the day when they are fresh. So two pieces of advice; first, choose research projects that are going to make a difference rather than projects that are easier to complete, but are trivial in their impact; and second, say no to invitations and spend more time on your research. Having said this, there are benefits to travel. Important contacts are made, new ideas are developed. But be selective and don't just go because you receive an invitation.

  • If you were to look 20 years into the future what do you think Hamilton Health Sciences research might look like, and what is the main difference you would like to see?

    That’s a hard question. Well firstly, research at Hamilton Health Sciences is healthy and thriving at present. It’s outstanding by all objective criteria -- national and international.

    Perhaps another way to ask this question is, is there room for improvement moving forward?

    Yes there is always room for improvement, but it’s difficult to plan too far ahead because in choosing research directions you have got to be nimble and be prepared to move if there is an important breakthrough. Suddenly there is a breakthrough in a particular area and you need to be ready. For example, if there was a breakthrough in tissue engineering that has a real potential to bring us closer to the possibility of limb or organ replacement -- this is the stuff of science fiction, but I use it as an example -- then I think it would make sense to transfer resources to develop strong programs, both clinical and research, in this new area of interest. Biomedical research lags behind the IT field where the developments are increasing in leaps and bounds and new gizmos are leap-frogging the old, but advances in biomedical research still move at a pace.

    Your question is important because it is important for an institution to be positioned to move into emerging areas that are likely to become relevant and change medical practice. To do this an institution needs two things: money to recruit, and space to recruit into. It should not only have financial reserves to recruit but also the flexibility to replace established programs. Our academic leaders, John Kelton and Salim Yusuf have been peerless at raising money. Because of their resourcefulness, McMaster and PHRI are well positioned to remain at the forefront of important areas of research. With generous donations from philanthropists like Michael G. DeGroote, David Brailey, Margaret and Charles Juravinski, the Farncombe family and many others, new programs have been established in stem cell research, cancer, infectious diseases, intestinal diseases and many other fields. So to summarize, in 20 years I expect that we will be nimble enough to move into areas that really make a difference.

    Another important lesson that I have learned over the last 40 years is that the strength of research of a department or division is critically dependent on the head. A head who is an accomplished researcher and who makes research an important focus of the department's vision is likely to recruit or develop accomplished and productive researchers. This is achieved both through example and recruitment. In contrast, if a head of a department or division only pays lip service to the importance of research, the research performance of the department of division will be mediocre at best. So the care taken in recruiting department and division heads is critical to the research success of an institution. The foundation chairs appointed by John Evans -- who considered recruitment one of his most important responsibilities -- were superstars in research in their respective fields. His appointments included Peter Cockshott head of Radiology and Steve Garnet head of Nuclear Medicine, along with those I’ve already mentioned Mustard, Campbell, Sackett and Zipursky. Although it is difficult to sustain this quality of recruiting, we are fortunate that this initial illustrious group has been succeeded by a second, third and fourth generation of leaders who are superstars. But it's very important not to rest on our laurels and continue to recruit people who are or have the potential to become outstanding researchers.

    BV: Thank you.