Daniel Kim’ 19


DK: First of all, a belated congratulations for becoming Dean of the Medical School.


GQD: Yes, thank you… It’s a big job.


DK: Yes, you mentioned in a previous talk that the whole of HMS consists of 11,000 staff?


GQD: Well, fortunately I don’t have to deal with all of them directly… It creates a responsibility around many different issues. Diversity, faculty development, integrity, reproducibility in research – all of those things come back into my office.


DK: Speaking of research, I was wondering if you could give a brief background about your story, and a little about your previous research?


GQD: So I come from a small town. Catskill, NY. There’s only about 20,000 people in the county, but the town itself had around four thousand, forty-five hundred people. It was small-town living. My mom was a schoolteacher. My dad was a travelling salesman. But my mom was well-educated, and came from a family from Connecticut, all of whom had gotten good educations. There was a strong sense of education from both sides of my family. My grandfather, my father’s father, had been a doctor. And I was active in high school. I liked science; I liked everything. But I was also working! I worked in restaurants, in kitchens, doing dishes and busing tables and that was kind of what I did. So when I came to Harvard for my work-study job, I was assigned dishwasher at Mather House. That seemed to make sense to me. I did the dinner shift. It was three nights alternating with four nights every other week. Which was hard, and that’s because dinner’s a time when you’re getting to know your classmates and socializing. But I traipsed down to Mather.


I was interested in so many things when I showed up at Harvard. I got very heavily involved in the Institute of Politics, which was pretty new at that point. I also was interested in government, science, philosophy. By the end of my freshman year, I actually declared my concentration in philosophy, not in science. During sophomore year, I answered an ad for being a dishwasher in a lab. I ended up finishing in biology, finishing all my premed requirements, and did the M.D.-Ph.D. program. And it was in the Ph.D. program where I did work on chronic myeloid leukemia.


What’s interesting is that there are some themes here. When you’re young and you have lots of ideas, they’re not always well-formed, so I made a lot of changes. I came in with broad interests in physics and government, and ended up in philosophy and biology. And when I was applying for medical school, I wrote all of my essays around neuroscience. Then my hematology professor one day started lecturing about this really cool but rare leukemia called chronic myelogenous leukemia, CML. This was 1983, and there had just been a spade of papers in Nature where, as was the trend at the time, lots of scientists were taking the genes that had been found in the context of viruses that caused cancer in animals – chickens, mice, cats – ad they were finding native genes in normal cells related to the genes in the viruses. So one of those viruses was called the Ableson Murine Luekemia virus. It caused leukemia in mice. And its human homolog was found on chromosome 9, which was reorganized, rearranged – so-called “translocated” – in CML. And I thought that was really fascinating! It turned out that the world authority on Ableson virus was David Baltimore at MIT. And that’s how I went to work in his lab. I started working with an Israeli postdoc, a physician-scientist. And there was another postdoc also, Andre Bernards, who’s now on the faculty at Mass General, who was also interested in the Abl gene. So there was a small core of us who came together around studying the human disease.


But my question from the outset was, what was the nature of this altered Abl product? And there were a couple of papers at the time that suggested that the Philadelphia chromosome, which was a translocation, also led to the production of aberrant form of both the Ableson mRNA and the Ableson protein. So it was then later that I was scooped – very, very early in my graduate work I was scooped – by an Israeli lab that actually identified the cDNA for this fusion transcript. That was the Bcr-abl fusion. One of my first challenges was, to assemble a full-length clone of the cDNA so that I could test if this kinase – this altered kinase – was really driving the leukemia. Which now in retrospect, everyone takes it as obvious – but back then, the dominant theme of the day was that the Philadelphia chromosome was actually a second genetic event; that the first genetic event was some undefined clonal abnormality in blood. There was evidence that the Philadelphia chromosome was a secondary thing.


What I did as a graduate student was a lot of characterization of the clone. I was the first person to express the full-length protein in cells to try to test its tumorigenicity. The standard assay of the day was whether your oncogene could transform NIH3T3 cells in culture or not. It turned out that Bcr-abl couldn’t, or at best weakly transformed. That was very different because most of the big oncogenes, like myc and Ras, had really profound effects. I then found a cell line which was a blood cell line that only grew if it was supported by a cytokine, a cytokine called interleukin-3. And it turned out if you introduced Bcr-acl into this interleukin-3-dependent cell line, you could render it highly proliferative in the absence of that cytokine. It was really the first time we could make a leukemia in a mouse. But it wasn’t the same kind of leukemia; it’s a particular kind of leukemia that starts in the blood stem cell. That’s part of what got me first interested in stem cell biology, in that CML was really the classic malignancy of the blood stem cell. So all of these other groups tried to make these transgenic strains of mice, which overexpressed Bcr-abl. And I said, well you know, what you really want is to express it uniquely in the hematopoietic stem cells. Richard Mulligan taught me how to do bone marrow transplants and viral infections to test if we can put a cancer-causing gene into hematopoietic stem cells, which should give it an advantage to grow out, while exposing the target cell of interest of HSCs to the oncogene. So that was four plus years of works in the lab, before it finally worked.


DK: And then you had a really robust model of what occurs in CML in patients.


GQD: Well it’s interesting, when you say robust – the first experiments we did were really inefficient. And I was very convinced of the robustness of the result, that the result was right. But it wasn’t an easy technique to replicate. And even in my own lab, people struggled to make it work. I could make work many times, but it required some refinement before it was able to be really useful to a large number of labs. Just the technique itself was inefficient. And so, a little later, a number of folks in the lab really refined the techniques, and it became a highly efficient standard then for all sorts of leukemia studies.


We knew that if you made a single point mutation in the kinase domain, but knocked out catalytic activity, you had a completely transformation defective mutant. Couldn’t make leukemia. So that said if there was a small molecule that could be made to mimic the knockout, to inactivate the enzyme, it should be a very potent anticancer drug. And that’s what got people thinking: if you make a specific kinase inhibitor, you’d have a good drug. And it was other folks, Nick Lydon working in a drug company on kinase inhibitors and Brian working on very similar cell lines to the ones I had developed, who showed that these inhibitors, which were developed originally against the platelet-derived growth factor receptor, would actually work against Bcr-abl. That became Gleevec, which was hugely exciting.


DK: But you also went to finish clinical training. Were you able to keep up with research during your clinical years?


GQD: Not really. My belief is that when you’re a scientist, be a scientist; when you’re training to be a doctor, train to be a doctor, and learning to be a physician is so all-encompassing, that I just didn’t think I had a lot of time to try to straddle two worlds.


Once I finished medical school, I went to start an internship in medicine at Mass General, and then I did a junior residency – that’s a second year – and then I went to Brigham and Women’s and the Farber and Childen’s Hospital to train in hematology/oncology. And then I came back to the Mass General for a year as chief resident in medicine, which was just a very exciting introduction to all the great cases at Mass General. And then I started my lab again, where I started working on embryonic stem cells, and trying to use them as a model of blood development. Which is what my lab uses today, 20 plus years later.


DK: With all this in mind, what do you think most influenced you in your vision for what HMS could be?


GQD: I would say, there’s equal parts ideas that stimulate vision and people that stimulate vision. During my undergraduate years, it was really people that inspired me. I worked directly for a postdoc named Elizabeth Luna, who’s now faculty at UMass, and Beth was just remarkably generous. She was inspired herself by science. She was wonderfully nerdy, and shared that with me. And that inspired me. She more than anyone really stimulated my interest in getting a Ph.D. and being a scientist. And then getting into graduate school, and having an incredibly brilliant and inspiring mentor in David Baltimore, my Ph.D. supervisor, and other incredible visionaries of science, whether it was Richard Mulligan for gene therapy, Bob Weinberg for oncogenes, Phil Sharp for RNA… And then when I got back to medicine… oh my goodness! I was just surrounded by giants of American medicine! Mort Schwartz at Mass General, John Potts, when I got to Brigham, the Farber, and Children’s, David Nathan, Sam Lux, were just amazing people – each had their own vision around the future of science or medicine or the combination. And then – there are many more. At some point, I started a lab and I started taking on more responsibilities for mentoring younger trainees. But part of my vision to become dean was the natural progression in my interest in mentoring and supporting the careers of others. And so now I see HMS as this remarkably dynamic center of very exciting biomedical ecosystem, which is not just Harvard but MIT, Boston, eastern Massachusetts really. Where I see Harvard is… Harvard has been a leader of new discovery, new treatments, and increasingly becoming the doctors to the globe. And if I think, what’s Harvard Medical School going to be in 2050, it’s going to be an incredibly dynamic place that is overseeing a major revolution in health, not just medicine. I think we have to be imaginative with it. Health is going to be the standard, and disease will be the exception in the future. We’ll conquer problems of aging, we’ll be more or less be doing maintenance on the chassis, dealing with disease but thinking about quality of life and wellness, that’s my hope and that Harvard Medical School be a major leader in that.


We have a long way to go. We got a lot of discovery… there’s a lot of obstacles to realizing that hope. There’s obstacles of delivery, there’s obstacles of resources, we’ve got 7.5 billion going on to 9 plus in that time and we still have incredible poverty and we still have incredibly suffering and diseases that we’ve conquered in the United States are still major challenges in large parts of the world. I’m hopeful that we can recognize global good health, but I’m worried that we’ll never address the health disparities that are so much a part of not just our world but even our local communities.


DK: Even around Boston, there’s some of that disparity. One of the biggest threads through all of your talks is the value of diversity and dynamicness. How do you plan on addressing this disparity?


GQD: The first major initiative I launched is a new task force on diversity and inclusion. And the charge initially is just to understand how we’re doing. If you take a biopsy of our community, we’ve got a vibrant degree of diversity but it still doesn’t reflect the demographics of Boston, of the United States, certainly not of the globe. And so the question then becomes what’s the right strategy for moving forward to try to achieve greater diversity? So we already have a lot of programs in place – we have some incredibly talented and dedicated servants of the community, who lead our Office of Diversity, our student affairs effort, we’ve got really wonderful people working very hard. So in formulating the task force is to not in any way say “well aren’t we doing well.” The people who are working are working tirelessly and doing a wonderful job, but the challenge is momentous, and much bigger than the resources we have to meet it. We have to aspire to listen to disparate viewpoint and learn collectively by integrating those different viewpoints. We need to understand what the bottlenecks are for people getting ahead, the challenges and try to address them. We need to be thoughtful and it may be – I’m perfectly willing to admit perhaps that Harvad Medical School won’t have all the answers and that many of the challenges may arise as early as preschool childhood. And that maybe the best investments are much earlier in life. I don’t know – I know we can do better.


DK: I think your comment really follows with the whole idea of “leading by following” and the importance of listening, and using that in your leadership style.


GQD: I aspire to that. My wife is actually a professor of leadership at HBS. But I’m imperfect, and there’s no one who knows that more than she. But she is always challenging me to think more broadly, to entertain more fully opposing viewpoints. I know that I bring to my work lots of preconceived notions, lots of biases, lots of implicit and explicit biases. And yet I recognize that it’s an important goal, to aspire to be more open-minded, to listen and incorporate opposing views. The evidence is, both historical and sociological, that leaders who integrate opposing views are ultimately more effective. And so one thing my wife always says to me which is a bit of a chastisement but also a great lesson, is “do you want to be right, or do you want to be effective?” And the fact is, you want to be effective. Leaders have a tendency to think they’re right, and to assert that right. But you’ve got to be willing to accept you might be wrong, to listen to others whose opinions might be right, and where together you might formulate what is a more correct pathform. That’s the leadership I aspire to. It’s imperfect, I will fail, no doubt. I’m sure there’s 50% of what I’m initiating right now is going to be a failure. I just don’t know which 50%.


DK: Well, sounds kind of like science, right?


GQD: (laughs) Yeah, yeah. There’s a lot of parallels to running a laboratory. The scientific challenges we face are much more complex than any individual can solve. And therefore a strategy that integrates collaborative efforts of many smarts individuals looking at a common problem and trying to solve it, is the more effective way to get to the right answer. So I think in a science lab, you really try to foster that sense of being able to foster that sense of being able to speak up and identify yourself, being able to question presumptions and work towards more perfect solutions. I think if that works to make good science, it should work to make good policy.


DK: One of the biggest problems that resonated with me and probably with a lot of students is that kids at HMS are in a high-stress environment, and mental health issues are prevalent on campus. How do you deal with having this massive, macro-scale responsibility of overseeing HMS, but also being personable with the students – how do you balance the two with your time, your energy, and your compassion?


GQD: As one person, and as a physician, I’ve always appreciated that I can give tremendous support, both medical and psychological and emotional, in a one-on-one. And part of what has been so satisfying and rewarding as a clinician is to have that one-on-one experience with a patient. I’ve also through my many years at Harvard worked as a counselor. I was a freshman proctor and a house tutor and there were many students who came to me with deep emotional challenges, and in some instances, very acute psychiatric illness. And to be able to give empathy, and to redirect into proper channels of medical support is part of the responsibility of the supervisor but also the deep satisfaction in using your professional skills wisely as a doctor.


I recognize as dean of HMS that I can’t touch everyone individually, but I can create a climate and a culture that is empathetic and supportive. And so when the JAMA article came out that announced that we have startling burden of depression among medical students, the first thing I did was email our Dean of Students and Dean of Medical Education, to inquire about what we were doing. I was encouraged to know that they had also seen the report, and were redoubling their efforts and checking again on our mental health support systems. I also was at a social event over the holidays and I met Stephanie Pinder-Amaker, who runs the college mental health program in McLean. McLean is our flagship psychiatric hospital. It’s got a remarkable history of relieving suffering and believing there’s no more problematic suffering than mental suffering. And she’s now been in touch with our Dean of Students to coordinate efforts around student mental health. I think it’s such a challenge. Medicine is stressful. There’s no doubt about it; medicine is assuming a dramatic responsibility for people’s well-being. I remember in my own training the enormous stress of being on call as an intern, feeling as though the weight of the world was on my shoulders because I had the life or death of 20 or 30 patients hanging on me and my decisions that night. In reality, I probably took on more sense of responsibility than I needed to. Fortunately, I was being watched and the nurses that were caring for my patients were my best allies because most of them were incredibly experienced and they weren’t going to let me screw up. And they were really able to take care of the patients in a way that was really supportive. But medicine – I don’t think we can ever take away all the stress of medicine. I don’t think we can ever take away all the stress of an intense education at a place like Harvard, where people are hard-driving, people are ambitious, people are striving to be the best. With a certain amount of responsibility in medicine comes stress, and stress is a great motivator. But if it becomes pathologic, that’s where we need to intervene. And it’s not going to be perfect. We’re going to make mistakes. But we have to keep striving to be doing better. We have to keep striving to have resources that are readily accessible, that will make it easier for our students to first admit that they have a problem, and then to find help. You know, it takes a village to raise a child; it takes a community to give support.


DK: Another big issue is that with the present political climate, medicine and research and health and health care in general will be touched, in terms of funding and viewpoints. How do you think your approach to mitigating the effects of that will be carried out in HMS?


GQD: I want to draw a distinction between politics and circumstance. For example, I’ve been an advocate for stem cell research for many, many years. And I always try to separate the politics from the policy. When I was spending a fair amount of time in Washington, I had allies who were both Republicans and Democrats. Support for biomedicine has always been a bipartisan issue.


In the current situation, what I think we can advocate for are our core principles on which our work is based, principles that include a deep trust in evidence-based decision making. Evidence has to be applied to whether or not an immigration policy is supportive of the health and vitality of our economy, and our medical ecosystem, or not! And it strikes me that the evidence is that when we take the best and the brightest from all parts of the world, and invite them into Harvard, to be students, to be our trainees and our faculty, we end up with the richest from across the globe. And we only have to look across our remarkable faculty and student body to realize how much we’re being enriched by immigration, including from many of the countries we are currently facing an executive order ban on immigration: Iran, Syria, and the like. And so I can advocate very aggressively and vociferously when I’m advocating for our core principles. I am less comfortable and less likely to advocate based on pure politics. There are others who will do that. And I want to stick to where government policies are opposing our core mission. If that’s the case, I will speak out to try to change those policies. I will equally aggressively advocate for policies that enrich our mission, and that’s why I feel unabashed about advocating for expanded funding for the National Institutes of Health, for more support for our academic medical centers. For rational policies for supporting reimbursements for healthcare so that the broadest swath of our communities can have access. Those are all the issues I’m comfortable fighting for.


DK: Is there anything you’d like to say to the students at the College? Any message concerning your vision in general, or any advice to the students?


GQD: I would love to say this, and I try to say it… I’ve been teaching an undergraduate course for many years, and I lecture in it, I can’t be the director anymore because of my bandwidth…


I still think medicine is a great and noble calling. I think it’s one of the ways you can use your talents, your intellectual and interpersonal talents to make a difference in other people’s lives in a way that is deeply enriching and allows you to derive great satisfaction that you’re using your gifts in the service of others.


I fear that students see medicine or medical research as too taxing, too challenging, too insecure, uncertain; that other fields offer more immediate reward, financial and otherwise, and so the siren song of consulting and banking and investments and even entrepreneurship is drawing some of these students away from the core work of medicine. And I bemoan. I’m sad of that. If I can also have an impact as dean of HMS, it would be to restore the sense that medicine and biomedicine and medical research is a privilege. It’s a privilege, and an exciting calling, and one that I wish that more students would follow.