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'I Love the Q'

Behind the Science: A conversation with George Q. Daley

George Q. Daley. Image: B.D. Colen

George Q. Daley might have been a philosopher or a psychiatrist if a series of mentors hadn’t enticed him first into science and then into cancer biology and stem cell research.

The world is all the richer for it.

As a graduate student, Daley created the first mouse model of chronic myeloid leukemia, confirming its genetic cause and paving the way for the “magic bullet” drug Gleevec.

Since then, he has discovered new cancer pathways and devised ways to combat chemotherapy resistance, pioneering methods for cellular reprogramming that have produced individualized stem cell models for more than a dozen human diseases.

He has also been a prominent voice in the debate about the ethics of human stem cell research, testifying before Congress and serving as president of the International Society for Stem Cell Research.

Now 53, Daley is the Samuel E. Lux IV Professor of Hematology/Oncology and the director of the Stem Cell Transplantation Program at Boston Children's Hospital, as well as a professor of both pediatrics and biological chemistry and molecular pharmacology at Harvard Medical School. He is as dedicated to being a good mentor to the people in his lab as he is to pushing the frontiers of stem cell biology.

Daley recently sat down to talk about the influence of mentorship and philosophy in his career, how he got his start in science in a Harvard kitchen, his passion for food and wine, and karaoke as the great equalizer of scientists.

HMS: When you were a kid, what did you want to be when you grew up?

DALEY: I always thought I’d be some kind of teacher. My mom was a teacher, and she loved her work. I liked ideas, I liked learning and I liked talking. I love teaching; it has been a significant part of my career.

HMS: Did your mom teach at your school?

DALEY: No, she taught in the next town over because she didn’t want to teach her own kids. She had six, and most of us were hellions.

HMS: So you have five brothers and sisters?

DALEY: Yes. I was born fifth, and my middle name, Quentin, means “fifth-born.”

HMS: I was going to ask why you use the Q.

DALEY: I love the Q. It’s the most distinctive thing about me. Everybody asks, “What’s the Q stand for?”

HMS: What got you interested in science?

DALEY: I came from a very small rural town called Catskill in upstate New York. We were two and a half hours out of the city, so there wasn’t much cultural penumbra there. But I had, quite fortuitously, a spectacular set of high school science teachers. Unusually insightful, intelligent, motivating—inspirational, even. That ignited a lot of interest in physics, biology and chemistry.

HMS: Did that lead you to study science in college?

DALEY: I came to Harvard thinking I would do research and teaching in physics or biology. Then I became disillusioned with the huge introductory science courses so I ran away and hid in philosophy for a couple of years.

HMS: How did you find your way back?

DALEY: I had a work-study job as a dishwasher in the kitchen of Harvard’s Mather House, and I answered an ad to be a dishwasher in a laboratory, thinking that would be a little more interesting. Soon thereafter I was taken under the wing of a really wonderful mentor, a woman named Beth Luna, who was a postdoc working in Dan Branton’s lab. Beth was enormously influential in shaping my desire to pursue biology as a career. I did my senior thesis with her.

HMS: What did she do that drew you in?

DALEY: She just loved research, and she had a very systematic, rigorous approach, which I appreciated. Also, working in the lab made me feel part of a supportive community. It felt like a home to me. That was enormously comforting for a kid from a small town where I’d been the big fish in a tiny puddle. Not even a pond.

HMS: Is that sense of community something you strive to provide for people in your lab now?

DALEY: Yes. Yes. One of my greatest pleasures in being a laboratory PI is having this wonderful second family. Coming up through the system at MIT and Harvard, I felt the pressure to be productive, get grants and write papers. Sometime in the last five years, all of a sudden I stopped worrying about all of that and started realizing that my mission was really about creating a climate of discovery and a community where I could nurture the development of these amazing people who come to train with me.

Look, I’m still excited to publish great papers, but increasingly I’m sustained by coaching one of my trainees to complete a project and get a great paper. That’s so pleasurable.

HMS: You’re an MD/PhD who’s made world-renowned discoveries in both basic and clinical research. What made you decide to go into medicine in addition to bench science?

DALEY: My grandfather was a country doctor, and my brother, who was a graduate student in cell biology when I was in college, was very eager to become a doctor and is now a successful surgeon. I was less driven to study medicine, but late in college I thought I should look into it. The summer between my junior and senior year, I shadowed a physician and fell in love with medicine and the prospect of a career in medical research.

Also, as a senior, I took an inspiring class with a psychiatrist where we read many of Freud’s works. I thought I would go into neuroscience and psychiatry.

HMS: What happened?

DALEY: Well, it was a matter of once again being influenced by profoundly inspirational mentors. In my med school hematology class, my professor Dr. Beck told us about this rare disease called chronic myeloid leukemia that was associated with a distinctive chromosomal aberration called the Philadelphia chromosome. This was the early ’80s when oncogenes were hot. Dr. Beck mentioned papers in which scientists had just mapped the human equivalent of a viral gene that caused leukemia in mice to the breakpoint of the Philadelphia chromosome.

I just thought that was so cool. It suggested that you could get to the deep molecular basis of this leukemia. Right after class I went over to the library to get those papers. You had to physically walk to the library in those days.

Then, as luck would have it, the cancer gene that was implicated was called Abl, and the world’s authority on the Abl gene was [Nobel laureate] David Baltimore, who was at MIT. So I wrote David’s lab and scored an interview. When I met him, I was awestruck and thought, wow, what a great lab environment. So I ended up going to MIT to do my PhD.

So it was this combination of Dr. Beck’s enthusiasm about hematology, my opportunity to work with David and the excitement of understanding this disease, which turned my head away from neuroscience and towards basic cancer biology.

HMS: Are you glad you ended up there?

DALEY: I think I made the right choice for that time. I thought cancer biology was going to yield lots of transformational new insights that would make a difference therapeutically in the course of my career. And it has, it really has. Plus, cancer biology launched me into stem cell biology. The idea that chronic myeloid leukemia is the classic malignancy of hematopoietic [blood-forming] stem cells got me thinking deeply about blood development and the nature of stem cells from different sources.

I think now, if I were looking again at the range of opportunities, I might choose neuroscience. Cancer biology has moved more quickly and more translationally than neuroscience over the last 30 or 40 years, but I would say the next 30 or 40 years is going to be the era of neuroscience, where deep investments in the genetics and signaling biology underlying neural development and function of the brain are going to yield the kinds of insights that will translate into new and meaningful therapeutic paradigms.

HMS: Now that you run your own lab, do you consciously try to implement lessons you’ve learned from the mentors you’ve had?

DALEY: I am really fortunate to have had some fabulous mentors. And none of them was like any of the others, other than that they took a sincere interest in me.

David Baltimore was always about asking the important question. And he was fearless. He asked a question first and then marshaled the scientific and experimental resources required to answer it, whether in his own lab or through collaborations. That’s something that I’ve really tried to practice by doing a lot of our work collaboratively. I reach out to people who are much smarter than I am and have complementary technologies and expertise.

That’s been one of the most rewarding aspects of being at Harvard, the ability to walk down the hall or just across the street to find someone who’s the world’s authority on the very thing you need to exploit at that given time.

HMS: How else would you describe your philosophy of running a lab?

DALEY: Create an environment supportive of curiosity, creativity and collaboration. Then recruit talented individuals who love their work, enjoy and respect their coworkers, and want to immerse themselves in the community. We do a lot of things together, both scientific and social. We do lab happy hours and retreats, and a lot of our social activities involve cooking and enjoying good wine, which are two of my passions.

HMS: Tell me more about that.

DALEY: My wife and I always used to cook together. Then we had two kids, and she took care of them while I evolved to do most of the cooking—and the dishes, which harkens back to my professional dishwashing history. Now she's a professor at Harvard Business School so I still do the dishes. 

The Daley family enjoys an evening of fine dining at La Calcina, Venice

HMS: Do you like it?

DALEY: Oh, I don’t mind washing dishes because I like to keep the kitchen clear for my cooking, which I love. Cooking provides much more immediate pleasure than a scientific project, you know?

HMS: What are your favorite dishes or cuisines?

DALEY: My signature dishes are probably paella in the summer when I go to Maine and we get access to amazing seafood, and risotto, in particular truffled mushroom risottos. Seafood marries very well with Burgundian whites. Especially in the winter I appreciate things like osso buco and braised short ribs, and the kinds of deep, bloody meats that go so well with delicious California cabernet or Barolo.

HMS: It sounds like you also have great opportunities to experience foods from different cultures that pass through your lab.

DALEY: Yeah, that’s really fun. We do a lab picnic each summer as an international potluck. I’ll do the main course and the wine, but I encourage everyone to bring sides. So we’ll get samosas and pakoras from India, kimchi from Korea, sushi from Japan, and always something unexpected for dessert. Great food is one of the perks of having this international melting pot in the lab.

HMS: You’ve traveled extensively as well, for work and with your family. What are your favorite places?

DALEY: Oh, Paris is my favorite city on Earth, but I can never get enough of Kyoto. I’ve been there seven or eight times. I love Italy, especially Venice—it’s so magical. I’ve been to India only once, but it was a remarkable experience to be in Delhi.

And then Shanghai, for me, is the Paris of Asia. It’s different but it’s got similarly spectacular lighting at night. It’s an incredible place.

HMS: You mentioned that you were briefly a philosophy major. Did that spark your interest in joining the public debate about the ethical questions of stem cell research?

DALEY: It was a fortuitous happenstance of my own history that when these questions were raised in the last 12 to 15 years about embryonic stem cells and the manipulation of human embryos and their utility for research, I could return to the foundations I had from studying ethics in my philosophy classes. Even with my primordial undergraduate education I was able to understand the nature of the different arguments made, whether from a utilitarian perspective or a more categorical, so-called deontological, perspective. I had a respect for the importance of diligence at the deepest philosophical level for these issues.

Through my advocacy for stem cell research, I’ve had a fascinating exposure to public policy. The debate has been an amalgam of science, ethics and politics.

HMS: Do you find that your philosophy brain and your science brain work in similar or different ways?

DALEY: I think they’re complementary yet also distinct. Philosophy is all about intellectual rigor and logic, attention to the nuanced meaning of words, and answering questions through pure reason. Science must be equally rigorous, yet adopts an evidence-based approach to answering questions by gathering data about the physical world—because sometimes reasoning alone leads us astray.

HMS: What are some of the most compelling ethical questions in science today?

DALEY: I think that among the most profound challenges to medicine and, indeed, to our social fabric, is the aging of our population, which raises thorny ethical issues about when and when not to intervene to extend life. Moreover, science offers the possibility that we will learn to counteract aging in such a way that 100 years from now you’ll sit across the table from someone and not really know how old they are.

But that has to square with the realities of a constrained “spaceship Earth.” My wife worked for Buckminster Fuller, who coined the term. We’re on a very, very small planet with a very, very thin rind of atmosphere, and we’ve done an awful lot to pollute it. We’ve got to face major issues as a species about climate change and diminishing resources. Stephen Hawking wrote that we as a species might have to take charge of our genetic composition to enable us to adapt to our changing environment. With the extraordinary advances in pluripotent stem cell biology, assisted reproduction, and genome editing, it’s inevitable that we’ll have to confront the ethics of germ line gene modification sooner or later.

I wonder about the future. If you look at the technological advances of the last century and imagine that they’re accelerating, it’s extraordinary to imagine what we will be capable of 100 years from now. At the same time, as a parent, I worry about the world my kids are inheriting.

HMS: What keeps you up at night?

DALEY: Right now, I’ve lost a lot of sleep and felt tremendous angst around funding. I run a large group. A lot of people’s futures depend on my being able to maintain the resources to keep them watered and fed. Budgets are tight and I’ve not been able to be as generous to the lab. That’s deeply upsetting for me.

Daley croons

HMS: Let’s end on a happier note. I hear that you and your lab members sing karaoke. Are you good at it?

DALEY: No, not at all! But that doesn’t matter, that’s not the point. One of the things it does is it equalizes everyone. If your PI can get up and make a fool of himself, it removes the bombast and the kinds of barriers that I think aren’t healthy for science.

You don’t want a hierarchy where people don’t feel comfortable telling you you’re full of crap, because that’s not the best way to get to the deep insights about science or to protect yourself against believing too deeply in your prejudices. I like to think I encourage my trainees to disagree with me, to educate me, to correct my misimpressions so that our science ultimately is as strong as it can be.

 

This interview was edited for length and clarity.