Pulling Back the Curtain: James Bradner, MD

Associate director of the Center for the Science of Therapeutics at the Broad Institute and associate professor of medicine at Harvard Medical School in Boston, Massachusetts

James Bradner

What was your first job?

When I was younger, I worked for many years as a landscaper for the U.S. Army. My mother was an accountant for the U.S. Army, and she informed me about the opportunity to join a landscaping crew at Fort Sheridan Army Base, just north of Chicago. I worked on that team for many years.

As you can imagine, the U.S. Army takes landscaping very seriously, so it was a very precise business. We had to mow the lawns of the offices, weed-whack around the perimeter fence, and perform grave detail, in the graveyards of the Army base – often preparing the cemetery for ceremonies.

Later, I was also a caddy at a golf club in suburban Chicago on the weekends.

Did you ever expect to go into a career other than medicine? 

For sure! When I went to Harvard for undergraduate, I was firmly on the fence between studying an integrated science, like biochemistry, or English literature. Long before I had any clarity on what my career might be, I had always been interested in creative writing, reading American literature, and integrated sciences. Those seem like two opposite ends of the spectrum, but ironically, all I do today is write about science. So, in some respects, it made sense.

I took organic chemistry with Prof. Stuart Schreiber in my second semester of college, and it became clear to me how creative a science chemical biology really is. At that point, I was transfixed by the idea of a career in investigative science.

Were there other teachers or mentors who helped shape your career?

The earliest, and probably most powerful, influence on the path my career would take was Aseem Ansari, a graduate student at Northwestern University (now a professor of biochemistry at the University of Wisconsin-Madison), whom I met while working in Tom O’Halloran’s lab during the summer breaks from college. Aseem worked me ruthlessly, but I was so in awe of him, his devotion to his science, and how passionately and personally he approached his work. The intense curiosity and scholarship of this young man left an indelible impression on me. He was, and still is, a very important and inspiring character in my life in science, and I keep a photo of us in my work office.

What advice did you glean from these mentors, and what advice would you pass on to people just getting started in their medical careers?

Most importantly, I would encourage young scientists to be patient. Many young scientists want to have an immediate impact on medicine or scientific literature – and rightly so. However, they will have their whole career to pursue that lofty goal.

While it took me a long time to train in the disparate disciplines that comprise the allied fields of drug discovery, tomorrow’s scientists will be facile with many different disciplines – biology, computational methods, chemistry, and pharmacology, and, hopefully, the pathophysiology of blood diseases.

I would encourage young scientists to spend time selfishly outfitting their toolbox with every concept and experimental method that could someday be relevant toward a translational impact. And that will take time.

Was patience something you had to learn through experience?

The patience came naturally to me because I was so unsuccessful through science! Looking back, I had so much fun training in the lab with Aseem and Stuart Schreiber, learning about the principles of chemistry, pharmacology, structural determinants of molecular recognition, and the other aspects of drug discovery. I found these things to be so exciting. Perhaps I was lucky because I lacked a clear concept of what my destination would be, so I was completely fascinated in the throes of education and training.

What are the proudest moments of your career? And have you had any major disappointments?

I believe my proudest moments have yet to come. My research is to develop prototype drugs – small molecules in their earliest stage of relevance to patients with disease. I’ve spent the last 10 years designing, optimizing, and biologically characterizing these (hopefully) very special compounds. These molecules have, just in the last two years, entered human clinical testing as cancer drugs.

My greatest hope is that patients will benefit from these substances. It’s a special privilege to deliver an innovative new chemical technology to my clinical colleagues, but it is far too early to celebrate in any way.

My field of research involves a lot of disappointments; for every one successful molecule that we move forward, we might make 900 molecules that don’t because of some unexpected toxicity, inactivity, or misstep. In a way, anticipating, managing, and learning from disappointment are vital parts of drug discovery. But these disappointments are far outweighed by the exhilaration of a new, active chemical entity. My experience in science has outperformed my wildest expectations, and I feel extremely fortunate to have had so many wonderful opportunities and colleagues throughout my career.

In a typical day, what is your rose and what is your thorn?

The best part of any day is when I’m having breakfast with my children. On the work side, the best part of my day is our laboratory’s group meeting. Our laboratory is unique for academia because we have, in one laboratory, synthetic and organic chemists, protein biochemists, cancer biologists, and computer scientists. When we gather around the meeting table, I am always blown away by the scope of their ideas. To have these young, unbiased, fresh, brilliant minds together for three hours dreaming up solutions to longstanding challenges in cancer medicine is an amazing opportunity.

The possibilities for collaboration are incredible and unique in our laboratory. We have tried to exemplify a collaborative model at the next level. For example, we practice open science, where we invite scientists from around the world to work with the molecules that we create, without restriction on their use. Through this open-source work and through discovery, we become closely connected to scientists around the world, from all different disciplines, and have learned about new fields – and also have seen our own field through their vantage points.

How do you spend your time with your family?

Honestly, when I’m not working, I rush home. My wife Jennifer and I have three children: our eight-year-old son and our twin four-year-old daughters. They’re great kids and time with them, at this age, is so wonderful. There aren’t any hobbies or activities that I find more pleasurable, challenging, or rewarding than spending time with them.

My life outside of work is best described as family life. In a prior life, I quite liked to play squash, snowboard, and play and listen to live music; today, life is a bit more organized around our family and close friends. Now, though, I get to share those interests with my kids. My son, for instance, is learning lacrosse, which I used to play, and our little girls learned to swim this summer.

What was your childhood like?

If you’ve seen the movies Ferris Buller’s Day Off or Home Alone, you have a sense of my upbringing. Like most John Hughes movies set in suburban Chicago, I had a fairly typical, but wonderful suburban childhood. We lived in Highland Park, Illinois, 25 miles north of downtown Chicago. I attended a public school that was exceptional in arts and sciences, played youth sports, and terrorized our neighborhood. It was, looking back, exactly the type of childhood we’re trying to provide for our kids.

What is one thing most people don’t know about you that they would be surprised to find out?

I’m a fairly open book, so it’s a challenge to think of something people haven’t figured out already. I’m sure my wife could provide a whole list of things. There’s nothing too edgy about me – I wish there was!

If you could have any superpower, what would you choose?

I would love to be able to see into the future. I am just desperate to understand what the cure for cancer looks like. I’m not even sure that it looks like any of the technologies we have access to today: small molecules, biomolecules, or cell therapy. Beyond that, I’d like to know what year it is when the Chicago Cubs win the World Series. Hopefully, sometime in my lifetime!

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