A lifetime of achievement
Bradner: It's interesting when you describe the pre-cure era, because today we all still feel real frustration caring for patients who have refractory tumors [those resistant to treatment]. Thankfully, approaches for relieving suffering have evolved, and we can offer something very meaningful to patients in the way of palliative care. In terms of cures, however, so frequently we can't. Yet we still find ourselves holding out hope for these patients as a group from the treatment strategies you developed and the science that promises to establish more targeted agents with fewer side effects.
Frei: If you go back to when the curative treatment was first developed, there was a lot of concern about whether a cure was possible. Conceptually, it was an enormous stretch in 1955—'60 to think you could eliminate cancer with a specific therapy. In some cases, we found the answer was "yes," but while we do very well for some diseases today, we still don't do so well for others.
Bradner: There have been so many advances and so much progress, but I wish we could get back to that atmosphere where a doctor in the laboratory can find a molecule that works, then bring it more immediately to the patient. That's at the core of translational research, but it seems like obstacles have arisen over the years, increasing the separation of the drug discovery and development process from academic centers.
Frei: When I went into oncology, everything was shrouded in mystery for the patient. I would make rounds and see families, and we were told not to tell them that their brother or mother or son had cancer. It turned out that telling them was the best thing we could do, but it took us a long time to get from Point A to Point B. We had to change the way people thought about cancer. Imparting truth to the patient is not easy, but Dr. Farber felt very strongly about this sort of patient-centered care.
Bradner: My medical education came during the 1990s, a time when patients were becoming incredibly sophisticated about their illnesses, and I think the dynamic of the doctor- patient relationship today is one of the real joys of practicing medicine. Our patients are insightful and sophisticated about their disease, and my eyes are opened all the time by them to new strategies, ideas, and pieces of information. Some of my patients even subscribe to the New England Journal of Medicine and go to medical meetings. At Dana-Farber, patients and family members have advisory councils and their own newsletter.
Frei: The transformation in patient knowledge has been fantastic, but unfortunately it doesn't happen everywhere yet. People worry that these concepts and findings are not making it out to their communities; I worry about that, too. But I have been impressed that when there is something effective like what we discovered for the treatment of Hodgkin's disease, it can spread very fast out to the world.
Bradner: What I still find shocking about the combinations of toxic drugs that you put together early in your career is that you did this without any of the bells and whistles that we have come to rely on so stringently in our clinical trials. You did this with blood counts and a microscope; it's truly remarkable. I hope we don't become too reliant on our tools. I hope we continue to make clinical predictions, scientific hypotheses, and approach problems with the same creativity you did. Technology can be a bit of a crutch.
In the last 10 years, however, we've seen such acceleration in the characterization of new active drugs that I believe we are poised to make the same type of contribution you did 40 years ago. We're equipped with new, targeted—and perhaps better tolerated—cancer therapies. The challenge again is to find the right combination.
Frei: Back in the old days, you needed to be a pioneer in a philosophical sense. You had to persuade yourself that the bricks and mortar of buildings like here and at the National Institutes of Health provided an opportunity to do something of importance. They are a reminder that an essential ingredient for progress, be it in cancer or any field, is faith.
