Traded for a Microscope!

You began your career in immunology – what led you to medicine and urology?

During my postdoctoral fellowship, I worked on Chagas disease and pemphigus, which required some time in South America – my first introduction to the clinical side of things. When I returned, the professor I worked with informed me that I’d be working at a teaching hospital in Buffalo. And there’s a good story as to why. Two urologists were working on the prostate at   that hospital, but they had lost their immunologist to another post; they were left with grant money to continue their work, but no immunology expertise. My professor needed another fluorescent microscope for his lab, but didn’t have the funds. He suggested a deal with the hospital: “If you give me the microscope that I need, I’ll give you Richard J. Ablin.” My professional career in medicine and immunology really occurred as a fortuitous consequence of the resulting move. In short, I was traded for a microscope!

How did the discovery of prostate specific antigen (PSA) change the course of your career?

Before PSA, I discovered that the prostate produced an immunological response when frozen as a consequence of cryosurgery, resulting in the production of an antibody. Freezing the prostates of patients whose cancer had metastasized caused the same response – in our study group, several patients’ cancer went into remission. As the immunologist who discovered this, which I termed “cryoimmunotherapy,” I was invited to many national and international lectures to speak on the topic, and there was a great deal of interest from the scientific community and the press.

Next, I began studying the antigenic components of the prostate to try and understand what was happening. I discovered that the prostate has tissue-specific antigens, one of which was PSA. As I’ve spoken about previously (1), the use of my discovery for PSA screening led to a lot of misery, and to a decreased quality of life for many men because they were overdiagnosed and overtreated. Did it change the course of my career? I’d say yes and no – it certainly affected my subsequent advocacy work to try and undo the damage PSA caused, but I was already establishing myself in the field through my previous work in prostate cancer.

Are you still fighting against the inappropriate use of PSA as a predictive marker?

I have a small cancer foundation in my late father’s name and I’ve tried to educate both the lay public and the medical community on the dangers of PSA screening as, among other things, it is not cancer-specific. I wrote an opinion editorial in the New York Times on PSA in 2010, which really caught a lot of people off guard. I also authored a book, The Great Prostate Hoax, on the subject in 2014. Things are getting better, but it has been an uphill struggle – I felt a bit like Don Quixote fighting windmills.

What about your work outside of PSA?

In addition to my work in cryoimmunotherapy, I became very interested in the immune response in patients with prostate cancer; the immune response we’d seen in patients who had undergone cryotherapy was something of a conundrum, and I set out to understand it. I found that the prostate had its own microenvironment that contains a variety of cells involved in the immune response, such as T cells and macrophages. Why, then, was cancer able to avoid triggering the immune system? I found that the prostate also contained immunosuppressive molecules that could be playing a role in immune evasion, and this has implications beyond the prostate, including in HIV transmission and why the fetus is not rejected by the body during pregnancy. I was able to show that sperm display the same immunosuppressive enzyme, transglutaminase, which also protects the fetus during pregnancy. This aspect of my research just naturally flowed from one topic to another, and it’s something that I still find absolutely fascinating.

What do you consider your career highlights?

It’s hard to sum up a 50-year career – I’ve been fortunate enough to have many highlights. It’s gratifying to see concepts I first described many years ago – such as the importance of performing immune profiling (“immunostaging”) to see if patients are good candidates for immunotherapy – finally recognized and used. Another highlight is that some years before she passed away, I had the privilege of being invited for an audience with Mother Teresa. I was also honored to be considered for the Lasker Award, sometimes called the American Nobel Prize even though I didn’t receive it. Finally, I’ve had countless letters from men and their families thanking me for my advice, and for my book, because it has helped them to better understand the risks and benefits of the treatment options available for prostate cancer. It’s hugely gratifying to know that being outspoken on this topic for many years is helping people.

If you weren’t a scientist, what would you be?

Early on, I was fascinated by the work of well-known architects, such as Frank Lloyd Wright, and I also had a passing interest in becoming an orchestra conductor. I also considered becoming a lawyer – I clearly enjoy a good debate!