Regenerative Medicine Cluster Initiative in BC
A UBC Research Excellence Cluster

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14
Dec

An interview with Dr. Connie Eaves

Earlier this year, at the meeting of the International Society for Stem Cell Research (ISSCR) in Australia, I had the chance to listen to Dr. Connie Eaves, Professor of Medical Genetics at the University of British Columbia (UBC) and Distinguished Scientist at the Terry Fox Laboratory of the British Columbia Cancer Agency, as she delivered the Tobias Award Lecture, presenting the foundational work her lab has generated in the field of leukemogenesis over the last 40 years. This year alone, on top of ISSCR’s Tobias Award, she was awarded the E. Donnall Thomas Lecture and Prize of the American Society of Hematology, received the BC Life Sciences Don Rix Award (with her husband and co-recipient Dr. Allen Eaves) and was also selected to be inducted into the Canadian Medical Hall of Fame in 2019. What struck me most from her talk was the story of how successive waves of new scientific technologies reshaped and refined the research questions she pursued with her research group, revealing an increasingly detailed picture of the complexity of human biology.

Dr. Connie Eaves’ perspective on the progress of scientific discovery is particularly interesting as she has both helped develop the field of hematopoietic and mammary stem cell biology in Canada and internationally during her career, and watched it evolve. As a young biologist, she trained in Toronto with Drs. James Till and Ernest McCulloch, the Canadian discoverers of stem cells. She currently runs a lab at the Terry Fox Laboratory  (TFL) in Vancouver where the general theme of the research is stem cells in their many different forms, ranging from normal to cancer, in both the mammary and blood systems.

Together with husband Allen, Connie co-founded the Terry Fox Laboratory in 1981. Today, the TFL has become a major research unit under the BC Cancer Agency umbrella, comprising a hub for scientists and clinician-scientists focused on understanding stem cell biology in health and cancer initiation and progression. It has fueled Canadian and global biotechnology by powering STEMCELL Technologies, a growing biotech company with roots that also trace back to the Eaves duo. Today, STEMCELL technology is a world-leading company supporting academic and industrial scientists around the world.

Overall, Connie and Allen’s contribution to BC, and Canadian biology and biotech is remarkable – in the breadth of both the structures they founded, but also, and perhaps most importantly, the dozens of people that they mentored over the years. Naturally, I was particularly enthralled to sit down with Dr. Connie Eaves to discuss her career path, the evolution of her research, the ways in which the BC scientific community has changed over the years, and her philosophy on training new talent. Below is a condensed transcript of our conversation.

What is the story of your becoming a scientist and what were the questions that drove you to do research?
While in high school, I wanted to become a physician and got into pre-med, which was tricky in those years as it was a ten-to-one ratio for girls to get accepted. However, I decided to get directly into research and so finished a BA within three years and then continued with an MSc at Queen’s University. During my Master’s degree I was working with oncogenic viruses, then pursued a PhD in immunology (University of Manchester, England), and got into hematopoiesis as a postdoc in Toronto. I was always interested in how cells make decisions, and how cells change from one type to another based on extrinsic and intrinsic factors.

At that time, the exciting problem was to identify the cell of origin of the hematopoietic system. Doing that in human cells was the big challenge. I started working on red blood cell production, using in vitro colony assays. Back then, we could only study white blood cell production and the idea was that if you study another lineage you might then learn how to identify a cell that has more than one lineage potential.We thought that would be a defining feature of cells close to stem cells – so the goal was to follow that path and then begin to analyze what goes wrong in leukemia.

The scientific questions then and now are actually still very similar.  How can we quantify these cells at the single cell level? How can we isolate them?  How can we characterize them, understand how they become transformed and overcome that? Those are the overriding questions. The systems that we work with are always changing, and we need to take advantage of the methods that each system has at any given time in order to answer those questions. Currently, our lab is focused on trying to make malignant transformation take place de novo in primary isolates of normal human mammary tissue and blood-forming cells.

How has your research changed over the years?
The research questions are still the same, but they are shaping themselves differently with the new technologies that are constantly emerging. A big step forward in the ’60s and ’70s came from the development of the biochemical tools. They provided the reagents that allowed primary cells to grow in vitro and made it possible to obtain purified enzymes that allowed cells to be isolated in a viable state. Then the development of molecular biology yielded pure growth factors and viral vectors that allow defined genes to be transferred and expressed in viable primary cells. Flow cytometry allowed complex suspensions of cells to be subdivided and isolated in a viable state, so their growth properties could be individually measured, and the development of immunodeficient mice allowed the growth of human cells to be analyzed and manipulated experimentally in an in vivo setting. All of these developments would not have been possible if disciplines did not work together. Flow cytometry, for example, was developed by people with a physics background, but it was the immunologists who knew how to work with antibodies and were most interested in understanding different types of cells who first developed the use of this technology.

Most recently, the ability to make organoids in vitro has made it possible to more deeply interrogate mechanisms controlling cell behavior and human development in a multicellular-multi-tissue context. Induced pluripotent stem cells (iPSCs) are not a naturally occurring phenomenon, or at least we do not think they are. When iPSCs first came, people did not believe in them. They were discovered in an era of claimed cell plasticity which was largely based on artifact and wishful thinking or observations of cell fusion. Now iPSCs are bona fide evidence of plasticity and are becoming incorporated into the thinking of how some cells and tissues behave particularly under stress or in the face of a wound response. Our thinking evolves according to what determines cellular behavior. In our field, we have taken the opportunity to analyze the potential of cells using clonal tracking methods. Hematopoiesis has historically led the way in cell and tissue biology in terms of using clonal methods to elucidate what individual cells can do as they grow and differentiate under different circumstances.

After your training in Ontario and England what made you decide to come to Vancouver? How did you become one of the founding members of the Terry Fox Laboratory (TFL)?
My first position as an academic was at UBC and my husband Allen and I chose to come here because Vancouver was still scientifically young as an emerging centre of research in Canada. So, there were a lot of opportunities to do science here as a young person. In Toronto and Montreal, scientific research was already well established. When we came here there was only minimal hematological research. There was only one hematologist who was doing diagnostic work, and no basic research.It was therefore almost intoxicating as scientists starting up in a place where we could pursue almost anything. People were generous in providing us with patient material and were incredibly interested, co-operative and helpful. We were free to work hard in many different areas.
When we came here, the original BC Cancer Research Centre was just beginning to be renovated from its original state as a former bakery. We all felt like pioneers creating labs from nothing as well as doing experiments. Then Terry Fox went on his run, and at the same time we were agitating for more spaces and resources to develop a group. A donation in Terry’s name was made by the government to fund cancer research, and the Chief of Medicine and the Director of the Cancer Agency negotiated with the government to ensure that money should be used to help develop a group under our leadership.

How has the scientific community in Vancouver and British Columbia (BC) changed since then?
This concept of BC being on the frontier and a place where you can develop new things was and remains very attractive to scientists who wanted to explore new areas. So it was possible to attract talented individuals with a lot of skills who sought to develop their dreams in such an environment. This philosophy continues to this day. Scientists who were recruited knew they would have to work hard to achieve their goals, but also realized that, if they collaborated, they could compete with larger centers. This collaborative spirit still prevails, and this is how regenerative medicine here has gained much of its success.

I think Vancouver is now globally competitive on many fronts; there are nuggets of international activity being recognized here, no question about that. It might not be on the same scale as Cambridge, California, or Toronto, as you would expect because there is not the same scale of resources invested here, but that could also change. We also do not face the challenges that centers face when there are such a large number of people working in similar areas that they cannot even know what each other are doing.

Speaking of resources, how do you think the provincial and federal government are doing in terms of funding research?
Canada has fallen behind in terms of investing in science and education. It still relies heavily on natural resources for its income and has a standard of living that, in my opinion, goes above and beyond what people earn through their own creative efforts. Ultimately, provincial and federal decisions about education and science funding priorities come from people who get elected. These people need the support of the voters who are not always people that think of the future in 30 or 40 years. They are thinking about their immediate standard of living. Thus, there is often a problem between what Canada could do and what Canada is doing. In my opinion, if we invest in science and education in the same way we invest in mining and forestry, we can change the entire national standard of living. However, this requires the recognition that this is the only sure way of moving forward, and much of the world is not thinking this way right now. This is a big challenge. I do not think the government invests enough in education and science, which are tightly interwoven. The return on investment is based on the scale of the investment: small investments earn small, but perhaps safer and more immediate returns, whereas large investments get bigger, albeit riskier returns. The latter requires people who have a long-range vision and commitment.

In the last few years, there has been a shift towards translational research. There is a sense that science has done a lot but has not impacted healthcare. This is actually not true as the health that people enjoy today is incredibly better than even just a few years ago, largely because of basic research. But the connections are very diffuse and often hard to trace, perhaps in part because there has also been historically a great gap between the medical translators and the generators of basic science in this country.

What is the most fulfilling part of your job?
I like this question. For someone like myself now, part of it is what can be done in a group where you are training people. It is like training someone in sport, or music, or parenting. You start with people who want something passionately and think they know what it is but are actually pretty naive about the reality of their goals. As they learn the process, they find out how challenging and sometimes painful it can be. Achieving in science is, in fact, quite a masochistic enterprise, so you have to be obsessed with the desire to continue, but then the rewards are also huge.

Because the learning curve is big, students often become quite discouraged after a couple of years. Most of them have done very well in high school and university and they are already “the best”. So, it is very disheartening to experience the feeling of not making expected advances when they transition from being a big fish in a little pond to becoming a little fish in a big ocean. And the recognition usually comes from finally publishing one’s findings which often doesn’t happen until another 2-3 years after the major results are already in hand.

There are often also a lot of ups and downs in research (usually more downs than ups!). But the motivation to be successful, coupled with a solid training plus some luck and intuition about what to capitalize on,can usually be successful. Motivation to strive for the best is a strong element in maintaining a successful career in research. Happiness is also very important, you need to feel fulfilled by what you are doing on a continuing basis.

What would be your advice to graduate students?
You learn best from the people you learn from. Mentors that you admire for the very strong and original science they can pass on can have a huge and lasting impression on your future. They can communicate skills and principles that may be difficult for you to encounter otherwise. And this is most likely to happen only in the early stages of your career development. There is not a huge window of opportunity, and a lot of trainees are not told that when they are starting. Selecting who you train with is probably the most important decision you make as a trainee.

What was it like being a woman in science when you started and how is it now?
It is hard for me to talk about it now because I have had a successful outcome with no direct comparison. When I was a trainee I was very fortunate in working with people, at least initially, where being a woman was not an issue. In Britain, there was already an acceptance of women in science. There were quite a few women already in the cancer institute where I did my PhD, so I did not feel I was in an unusual role. When I came back to Canada, I encountered more skepticism. There were some good examples, but it was also much less common. However, for me, that just felt like more of a challenge. It never occurred to me that I was not going to be successful, but I was also very driven.

Did you feel that you had fewer opportunities than men?
No, I never felt that. But I was always very competitive, so maybe that was just my personality. I like challenges. I like the idea of someone thinking I could not do something and then doing it anyway.

I do think though that it needs to be appreciated that women are the child-bearers in our society, and so in this respect, men and women are not the same. Both need to choose what they want. Being both a mother and having a full-time career is definitely possible, but at a cost to both activities. So every individual needs to decide what is best for themselves.

By Effimia Christidi (PhD Student-Brunham Lab)
This interview has been edited and shortened for clarity.