Robert A. Brodsky, MD, is a professor of medicine and the director of the Division of Hematology at Johns Hopkins School of Medicine in Baltimore. He is also the director of the T32 Training Program in Hematology and director of the Physician-Scientist Pathway for the Osler Residency Program. He is the 2022 American Society of Hematology (ASH) president-elect.
When did you become interested in medicine, and what drew you to hematology specifically?
I got interested in medicine kind of late. My dad, Isadore Brodsky, MD, was a well-known hematologist and my first mentor, but when I went to college, I wasn’t sure what I wanted to do. I felt like I had to rule other things out, and it wasn’t until later in my sophomore year that I started to think that maybe medicine was the best choice for me. I still wasn’t sure until I got to medical school.
In medical school, I was drawn to the pathophysiology of hematology, and I liked the idea of looking at blood smears and bone marrows and making diagnoses. It’s one of the things that draws people to hematology; we really love the beauty of it. Many of the advances of medicine come from hematology because the blood is so easy to access. It’s very hard to take a lung or a brain out of someone, put it in a dish, and start growing it and looking at all the individual cells, but you can do that with blood cells. So, a lot of the advances in biochemistry and genetics come from the field of hematology. It’s a stimulating subspecialty.
Dr. Brodsky (right) with his father
on the day of his medical school
graduation.
You are the director of the T32 Research Training Program in Hematology at Johns Hopkins. Tell us a bit about the program and why it’s important to you.
This is an important training grant that’s geared toward training not just MDs, but MD/PhDs and PhDs, in careers in academic hematology. It’s one of the oldest hematology training grants in the U.S., now going into its 39th year. It was started by Jerry Spivak, MD, in the 1980s, and there have been three Nobel laureates associated with this hematology training grant, and a lot of directors and very prominent hematologists have come from this program. It was an important tradition to continue, and it’s geared toward training the next generation of scientists and physician-scientists in academic hematology. We also have a great track record over the past 10 years of more than 25% of our trainees coming from groups that are underrepresented in medicine. Also, about 50% of our trainees on this grant are women. More than 85% of our trainees stay in academic hematology, which is an incredible track record.
There have been a lot of critical developments in sickle cell disease (SCD), including gene therapy. Where do you think the field is going?
It’s a very exciting time in SCD, but I think there’s perhaps a little too much hype on gene therapy and gene editing. The bar has really been raised. When gene therapy and gene editing started to come into play as a curative approach for SCD, we used to say we need this because bone marrow transplant (BMT) – a known cure – isn’t available to most patients. At the time, we thought that for the 80 to 90% of patients who weren’t good candidates for BMT, maybe gene therapy or gene editing would change the game. All you needed to demonstrate was that this could be effective. Now it’s changed because with half-matched BMTs – the haploidentical BMTs that are non-myeloablative – it’s no longer a problem of finding a donor. These transplants are enormously successful. The cure rate is now approaching 90%, and we can find a donor for almost everyone. So now the bar for gene therapy and genome editing is not only to match that, you’ve got to beat it.
It’s exciting, and we need all of these approaches going forward. The technology continues to evolve. I can see the potential for evolution in gene therapy such that it might match or even exceed BMT at some point. But in the next five to 10 years, I think that’s tough because the advances in BMT have been unbelievable.
As excited as we are about curative approaches, these curative approaches are not going to solve the worldwide problem of SCD because it’s a problem in many countries that don’t have the resources to do BMT, let alone gene therapy. We need new, effective drugs. There have been some new drugs that have come out and have activity, but we still have a long way to go. If we’re really going to impact the disease on a global level, we’re going to need better drug therapy.
What do you find most rewarding about your academic work?
The teaching and mentoring and the career development of students, residents, fellows, junior faculty – that’s certainly way up there. Seeing people develop their own careers and go on to experience the joy and passion in hematology that I’ve experienced, that my dad experienced, that my son is getting ready to experience, that is really exciting to me. The other thing is the impact of the translation from our laboratory into patients and seeing the direct impact that has. As a physician-scientist, a lot of times you put stuff out there and we’re pretty sure it’s right. It’s hard to know for sure when you’re working with a cell line, a primary cell, or an animal model. The only way you really know whether your hypothesis was right is if you translate it. Then you’re sure because not only did it work on a cellular level in a dish or an animal model, but it worked in people. When that happens, it’s really exciting. I always tell my post-docs, the most exciting part of being in the lab is when you do that experiment and it gives this amazing insight into a disease process and for that one moment, you’re the only person in the world that knows. You get enormous joy in sharing that information with other people. When you have a new story to tell, it’s exciting.
Who are some of your mentors and how have they helped shape your career?
As I mentioned, my first mentor was my dad, and he and I had an amazing relationship, first as father and son, and then as a mentor, and then as a collaborator. We worked together; we published papers together. He was clearly the first mentor I had, not only in medicine but also in life. Then, when I got to Vanderbilt University, I had two strong mentors there in Sanford Krantz, MD, who was the head of hematology at the time, and John Oates, MD, the head of medicine, who was a true physician-scientist who inspired me. They both encouraged me to go and spend some time in the laboratory. I hadn’t spent any time in the lab and was noticing I had a difficult time reading the hematology literature because the molecular biology and the biochemistry were over my head. They said the only place you’re really going to learn this is in the lab. That was one of the best pieces of advice I got. I ended up spending three years at the National Institutes of Health in the lab of Arthur Nienhuis, MD, who was president of ASH in 1994 and an editor of Blood. Art passed away a few years ago. He was super busy, and it was a big lab, so it was the people in the lab that took me under their wing and were so generous with their time. People like David Bodine, PhD, Steve Jane, MD, and Elio Vanin, PhD. They taught me how to do a Western blot, a Southern blot, and polymerase chain reaction.
When I came to Hopkins, my mentor was Richard Jones, MD, who is the head of the hematologic malignancies program and the BMT program. What Rick taught me was the importance and the power of translational medicine – taking your laboratory findings and putting them in the clinic. It’s a rare thing that you see people do that these days.
What do you see as your biggest professional accomplishment so far?
The first big one was the development of high-dose cyclophosphamide. We started using that as a drug to treat bone marrow failure, aplastic anemia, and other autoimmune diseases, and what we learned from that allowed us to translate this to BMT, and that’s where post-transplant cyclophosphamide came in. That’s when we started doing half-match BMTs for diseases like aplastic anemia and SCD. These diseases now have cure rates that are upwards of 90%. It’s made transplant widely available.
I was also involved in developing a variety of diagnostics that were critical in hematologic diseases. For instance, the development of FLAER (fluorescein-labeled proaerolysin) for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), which is now a laboratory assay that is used around the world. Also, looking at quantitative CD34 counts to distinguish aplastic anemia from myelodysplastic syndromes (MDS) and the development of the modified Ham test for picking up complement-mediated disorders has been super exciting.
I’ve been involved in the clinical development of complement inhibitors for diseases that we had no treatment for, such as PNH. When I started out, patients with PNH would die of thrombosis; they were constantly in the hospital. Now, they have a normal life span and very little in the way of symptoms. It’s the same thing with atypical hemolytic uremic syndrome. Half of these patients used to die or lose their kidney within a year; now, they are often in the hospital for two or three days and then finish treatment on an outpatient basis.
What do you see for the future for these facets of hematologic care?
Going forward, it’s about taking some of these things to the finish line. I think we’re going to see the haploidentical BMTs move up front in aplastic anemia, and we won’t have to do the immunosuppressive therapies. We’re also involved in a national trial using haploidentical BMTs in SCD, and I think we’re not doing enough of these. We’re looking at establishing better diagnostics around these complement-mediated disorders, like HELLP (hemolysis, elevated liver enzymes, low platelets counts) syndrome. My lab is now looking at the connection between complement and blood clots. We’ve known for many, many years that these complement-mediated disorders clot right through anticoagulation, but when you put them on a complement inhibitor, they stop clotting. Recognizing more of these disorders with this modified Ham test that we developed, and also getting them appropriate treatment with complement inhibitors rather than anticoagulants, could have a huge impact.
The Brodsky family, (left to right)
Max, Amy, Robert, Brett, and
their dog Daphne.
Dr. Brodsky kayaks on the
Chesapeake Bay in Maryland.
Tell us a little about your home life and what you do to strike a positive work-life balance.
I have an amazing wife, Amy, who I have been married to for 32 years. I have two unbelievable sons and they have both followed me into medicine. They share a lot of my values and are my two best friends in the world. I am very close with them, and I’m very proud of them. I also have a lot of outside interests that I have developed over the past four to five years. We have a place on the Eastern Shore of Maryland that’s just an hour away, and if I’m not traveling or on call, I’m usually there every weekend. I’ve started doing all sorts of new things. I never played golf, and now I’m playing golf. I’m fishing all the time, crabbing, kayaking, bike riding. I’ve started playing around with photography. I’ve always played the guitar. That really keeps me grounded, and the other thing it’s done is give me a community of close friends down there who are outside of medicine and science. I love my friends in medicine and science, too, but it’s nice to have some people who have different backgrounds and interests. I learn about all sorts of things that they know about that I don’t.
I have nothing but fun outside of work, and I actually have fun inside of work, too. There’s plenty of aggravation and stress, but the key is that I am incredibly grateful for the career I’ve had, the family I have, and the people I work with. All my expectations have been exceeded and I’m grateful every day I come to work with these people. I’m grateful for my family and all the things that we do together. Too often today, people don’t appreciate what they have.
Dr. Brodsky and colleagues at the
2019 ASH annual meeting.
You’re the incoming president of ASH. Why did you want to take on that role and what are your goals for your term?
I remember hearing about ASH almost since I was born. My dad was at the very first ASH meeting in Atlantic City in 1958, and at least one person from my family – often two – has gone since its inception. My dad and I used to room together for many years at the meeting, which was just amazing fun. ASH has always meant something to me. I was an ASH Scholar, and that grant was very helpful. Then I got involved in some of the committees, and it became a way of giving back. It’s been nothing but rewarding. The ASH secretary job was tough, but I learned a lot and I enjoyed it. The ASH staff and volunteers are wonderful.
As the incoming president of ASH, one of the things that I’ve been pushing for are hematology-focused fellowships. Hematology and oncology were linked for good reasons in the early years, and there’s always going to be a link between them, but the fields, to their credit, have become so complex because of the knowledge base and the advances in these disorders that you need to have separate training programs; ASH really took this on.* As president, I also want to be a cheerleader for all the amazing advances in the field and make sure ASH continues to advocate for access to drugs, high quality care, and getting care across the globe. That’s what ASH does.
*Reference to the ASH Hematology-Focused Fellowship Training Program, about which more information can be found at hematology.org/education/educators/resources-for-training-program-directors/hematology-focused-fellowship-training-program and in the ASH Clinical News feature story, “Classical Hematology: A Specialty in Decline?”
