Pulling Back the Curtain: Richard Aster, MD, and Jon Aster, MD, PhD

Jon Aster, MD, PhD
Professor of Pathology at Harvard Medical School and Associate Pathologist at Brigham and Women’s Hospital
Richard Aster, MD
Professor of Medicine and Pathology at the Medical College of Wisconsin, a Senior Investigator at Versiti Blood Center of Wisconsin, and the recipient of the ASH 2019 Wallace H. Coulter Award for Lifetime Achievement in Hematology

In this edition, Richard “Dick” Aster, MD, and his son, Jon Aster, MD, PhD, talk about their shared interests in research and golf.

Dick, where did you grow up?

Dick: I was born and grew up in Grand Rapids, Michigan. My father died when I was 6, so I was raised by my mother, a very serious, hard-working school teacher who kept my younger brother and me on a short leash and demanded that we be serious scholars.

After graduating from high school, I went on to the University of Michigan with a scholarship that covered tuition. It wasn’t much because at that time the tuition was $75 per semester. I was able to work on the side and make ends meet on my own throughout my undergraduate education and medical school years.

What brought you to medicine? Did you ever consider another career?

Dick: I was always interested in science, but not necessarily medicine. As a child, I read a lot of library books, and my high school teachers encouraged my interest in science.

When I was about 12 years old, I read a book called Microbe Hunters by Paul de Kruif, PhD. Each chapter focused on someone who had done great things in microbiology, including Louis Pasteur, Robert Koch, and others. It was such a fascinating book that I decided on the spot I wanted to become a scientist. That ambition never left me, although later, in high school, I became interested in math as well. I majored in physics and math at the University of Michigan.

Although I ended up gravitating toward medical school, I have benefited greatly throughout my career from my undergraduate education in hard science. It taught me rigorous thinking.

What led you to focus on hematology?

Dick: I enjoyed hematology in medical school – I loved to look at blood smears and bone marrow slides. In my third year, I worked in a hematology research facility called the Simpson Institute, taking care of mouse colonies for a member of the faculty who was interested in leukemogenesis and its possible viral etiology. During three of my medical school years, I also worked part time with the thyroid group in the Department of Endocrinology with a focus on radioisotopic diagnosis and treatment of thyroid disease.

Richard Aster, MD, and Jon Aster, MD, PhD

At the end of my residency training in internal medicine at Massachusetts General Hospital, I pursued an appointment in endocrinology at the National Institutes of Health (NIH) to focus full-time on research training for a few years. None were available, so I accepted an appointment in hematology. A benefit of an NIH appointment at that time was that it satisfied then-existing military service requirements. After three years at the NIH, I entered a hematology fellowship in the Thorndike Laboratory at Boston City Hospital.

I then served as a full-time member of the Harvard Medical School faculty until 1970, when I relocated to Wisconsin to accept a position as CEO of the Milwaukee Blood Center and Professor of Medicine at Marquette Medical School (now Medical College of Wisconsin). Ultimately, the Blood Center evolved into Versiti, a blood service and research organization that now serves five midwestern states.

I have a total of five sons by two marriages. Jon is the oldest.

Jon, what was your childhood like?

Jon: My father was a bit of a biomedical gypsy. I was born in Ann Arbor, Michigan, when my dad was finishing up medical school. My early memories are of Boston, where he trained. I also remember being in Bethesda, Maryland, when he was at the NIH during the Cuban Missile Crisis. I recall doing duck-and-cover drills in kindergarten.

One weekend when I was about 10 years old and my father was working at the Thorndike Lab in Boston, we went in and did splenectomies on rats. That made a big impression on me – it may have been the moment when I decided I wasn’t going to be a surgeon. I don’t have a “surgical” bone in my body.

Dick: I never had any aspirations for surgery either. The mortality of my surgical work on rats was awful, but enough of them survived to be able to get some data.

Jon: Then my folks divorced when I was about 11. After spending a year in Ann Arbor, I moved back to Boston with my mom, where I went to high school. During the summers, I worked in the lab at the Milwaukee Blood Center, my father’s shop, as a volunteer.

Dick: I think you were paid.

Jon: Well, I don’t remember being paid. I think you kept my paycheck.

Dick: No, no. It was a nominal amount that you were paid, I think.

Jon: I don’t remember cashing any checks, but that could be true.

How did you decide you wanted to go into medicine?

Jon: Growing up, I was exposed to different aspects of biology, research, and medicine and that certainly made a big impression on me. I always wanted to do something involving science and the natural world, and initially was drawn to meteorology. I was fascinated with weather.

“In the past decade, it’s been challenging to convince young people that it’s worth the risk to go into research. I’m interested in using my role to help find solutions to that problem.”

–Jon Aster, MD, PhD

Following in my father’s footsteps, I arrived at the University of Michigan as a freshman and took courses that could have led to a degree in meteorology. My father once told me that while he was working in the physics lab at the University of Michigan, he realized that although he was smart, maybe he wasn’t quite smart enough to be a nuclear physicist. Similarly, I realized I wasn’t a good enough mathematician to pursue an academic career in meteorology.

During my undergraduate studies, I majored in microbiology, but still wasn’t sure what I wanted to do with my life. At that point, my father stepped in and made an important connection for me. He recommended me to George Brewer, MD, from the Department of Human Genetics at the University of Michigan. After graduating, I took a year off to work in his lab. George was a great mentor for physician-scientists and, encouraged by my experience in his lab, I ended up getting into the MD/PhD program at Michigan, earning a PhD in human genetics.

I wasn’t always confident as a kid, and George helped convince me that I could do an MD/PhD and pursue research. George was passionate about training physician-scientists and that relationship was important to me. During my PhD, I studied protein chemistry, including red blood cell physiology, and the membrane skeletal proteins in non-red cells and other kinds of nucleated cells.

During my early days in medical school, I realized I had an aptitude for pathology and interest in fundamental aspects of disease pathogenesis. As a third-year medical student, I remember asking the Chairman of Pathology, Peter Ward, MD, “Where should I try to go for residency?” He recommended Brigham and Women’s Hospital in Boston. So, I came out here, did a visiting rotation, and impressed people enough to get into the residency training program. I started at the Brigham in 1987 and have been here ever since.

How did you become interested in hematopathology?

Jon: During my second year of residency training, I started thinking about hematopathology as a potential area of focus. I liked integrating objective information with what I was seeing under the microscope. Hematopathology was the first area to use immunohistochemistry, cytogenetics, and molecular genetics for diagnostic purposes, which appealed to me. I also liked the fact that the only way to make progress in treatment of these diseases was to understand their pathogenesis, because these were systemic diseases that were not amenable to surgical cure.

After a pathology residency, I did a hematopathology fellowship at the Brigham under the tutelage of Gerry Pinkus, MD, another very important mentor, and then looked to the lab. I felt I needed to develop molecular skills.. I was fortunate to get a postdoctoral fellowship in the lab of Jeff Sklar, MD, PhD, who had just come to the Brigham from Stanford and had trained with Paul Berg, PhD, who won a Nobel Prize for developing recombinant DNA techniques. My training with Jeff taught me the molecular skills that I then took into my faculty position.

In 1993, I accepted a startup package from Ramzi Cotran, MD, Chair of Pathology at the Brigham and another important mentor, while maintaining a clinical role in the department as a diagnostician. Most of my subsequent research has been focused on a signaling pathway called the Notch pathway, which is important in many different kinds of leukemia and lymphoma and, we now know, in solid tumors like breast cancer.

Father and son at a family reunion on the occasion of Dick’s 75th birthday.

In a nutshell, I’ve been fortunate enough to link together key associations that always seemed to occur at just the right time.

Dick: Jon is now the Michael Gimbrone Professor of Pathology at Brigham and Women’s Hospital. Michael Gimbrone, MD, followed Ramzi Cotran as Chairman of Pathology there and I had him as a medical student at Boston City Hospital. He worked with Judah Folkman, MD, and me on projects related to organ perfusion, the possible role of blood platelets, and maintaining endothelial cell viability. We published a couple of papers together. I taught him how to do platelet counts. After Michael retired many years later, Jon was named to his professorship.

Jon: Dr. Gimbrone remains a very active professor emeritus. In fact, he may be sitting in the office exactly one floor above my head at this moment.

Jon, what has been the biggest change over the course of your career?

Jon: Technology has come a long way, particularly with new molecular approaches. There is much more you can learn from patient samples now than ever before. In some ways, it should be the Golden Age of research for physician-scientists working in an academic medical or hospital-based setting.

Of course, there are always challenges. Right now, I would say the principal one is funding. Cancer research has been particularly tough; National Cancer Institute pay lines are really low. In the past decade, it’s been challenging to convince young people that it’s worth the risk to go into research. I’m interested in using my role to help find solutions to that problem.

“There is always a new question to try to answer. If you maintain a childlike curiosity, you will not only be successful in research, but it also won’t feel like a job.”

–Jon Aster, MD, PhD

Dick, did you expect that Jon would follow in your footsteps into a career in hematology and research?

Dick: Not at all. I naturally tried to introduce him to the work I was doing and some of it rubbed off. I never pushed him in any way to go one direction or another, although it was obvious to me that he was talented, intelligent, and capable of doing great things.

Dick, tell us about the mentors you had throughout your career.

Dick: As an undergraduate at Michigan, I established a relationship with one of the professors in the physics department, Bill Parkinson, PhD, who gave me a job working on their cyclotron. The example that he and his associates set was a wonderful learning experience for me. As an undergraduate at the University of Michigan, Bill Beierwaltes, MD, head of the thyroid disease unit, was a valued mentor who steered me toward the East coast for my postgraduate training.

During my residency at Massachusetts General Hospital, I had a fabulous opportunity to work with several senior faculty. One was an endocrinologist named Holly Smith, MD, who later became the Chancellor of the Medical School at the University of California, San Francisco and with whom I had a relationship for about 50 years. Another was Walter Bauer, MD, Chairman of the Department of Medicine and a world leader in rheumatology, who was an early advocate for applying basic science to medical research and an inspiring mentor. At the NIH, I worked with Ray Shulman, MD, a remarkable investigator who introduced me to immunohematology and transfusion medicine. In the Thorndike Laboratory at Boston City Hospital, I had the good fortune to work under world-renowned hematologists William Bosworth Castle, MD, and James Harriman Jandl, MD.

Working with all these amazing individuals was a marvelous learning experience that was absolutely essential to my subsequent professional development.

And Jon, who were your mentors?

Jon: In part because of my father, I had a sense of what biomedical research could be like even before starting medical school, but there’s no substitute for working with people who are successful and set a high bar. When I came to the Brigham in 1987, the chair at the time was Dr. Cotran, who I mentioned earlier. He created a culture in which all residents were curious about how things work, curious about disease, and had an investigatory spirit. It was a wonderful milieu.

Dr. Cotran was an amazing leader and one of the most charismatic people I’d ever met. While he might yell at you if he thought you were doing something that wasn’t good for you, he was constantly telling people, “You can do this.”

On the clinical side, my hematopathology year was done with the remarkable Gerry Pinkus, MD, then the Chief of Hematopathology. I have taken her role as the head of the division, but she’s still working as a clinician in hematopathology, coming in at 6:30 every morning to set up staining runs in the immunohistochemistry lab.

“Most serious scientists work because they love it…We don’t come up with all the answers, but it’s fun trying.”

–Dick Aster, MD

Beyond training at the Brigham, I’ve spent my entire career in this ecosystem at Harvard, where within half a mile of where I’m sitting right now there may be more physician-scientists than anywhere else in the world. The important interactions and collaborations I’ve had here are too numerous to count.

Dick, tell us about your life outside of medicine – do you have time for any hobbies outside of work?

Dick: When I came to Milwaukee in 1970, I was the CEO of the then-Milwaukee Blood Center and Professor of Medicine at the Medical College of Wisconsin. About 23 years ago, I stepped down as CEO. It’s been wonderful to be able to continue with my own research interests and enjoy the fruits of what we were able to develop over those 30 years without having to worry much about administrative responsibilities.

Jon: I think what my father just pointed out is that research is his hobby.

Dick: You could say so. I have one of the longest running NIH grants, active now for 50 years. It’s finally running out in June after many renewals, and I’ve decided that, at my age I don’t need to apply for another renewal. I’ll be phasing out during the rest of this year and plan to pursue other interests.

Do you two share any hobbies?

Jon: We’re both golfers. Years ago, my father joined the Milwaukee Country Club, where we participate in tournaments every year. One year, we won the father-son tournament, which was impressive given how infrequently we golf. We’ve participated in at least one tournament together annually for more than 20 years now.

As I’ve gotten deeper into research, we also discuss our respective projects. I write for pathology textbooks and often canvas my father whenever I’m thinking about red cells, platelets, or other aspects of benign hematology.

It’s always impressed and inspired me that he’s still excited about the ideas he’s pursuing in the lab. One of the great things about research is that there is always a new question to try to answer. It’s a way of staying young. If you maintain a childlike curiosity, you will not only be successful in research, but it also won’t feel like a job.

Dick: Most serious scientists work because they love it. It’s a wonderful position to be in, if you have an environment in which you can do the kind of research you want to do. We don’t come up with all the answers, but it’s fun trying.

Relative to our interest in each other’s research, it works both ways. I have been fascinated to follow Jon’s work with the Notch pathway and related interests. In fact, he has come to visit our institution and give talks several times over the years.

Jon: Usually around the time of a golf tournament, strangely enough.