00:00:02 OPRAH WINFREY: "Hattie Mae, this child is gifted," and I heard that enough that I started to believe it.
00:00:08 ROGER BANNISTER: If you have the opportunity, not a perfect opportunity, and you don't take it, you may never have another chance.
00:00:14 LAURYN HILL: It all was so clear. It was just, like, the picture started to form itself.
00:00:19 DESMOND TUTU: There was no way in which a lie could prevail over the truth, darkness over light, death over life.
00:00:27 CAROL BURNETT (quoting CARRIE HAMILTON): “Every day I wake up and decide, today I'm going to love my life. Decide.”
00:00:35 JOHNNY CASH: My advice is, if they're going to break your leg once when you go in that place, stay out of there.
00:00:40 JAMES MICHENER: And then along come these differential experiences that you don't look for, you don't plan for, but boy, you’d better not miss them.
00:00:52 ALICE WINKLER: This is What It Takes, a podcast about passion, vision, and perseverance from the Academy of Achievement. I’m Alice Winkler, and thanks for joining us.
00:01:06 Every episode, we pull an interview out of the Academy’s vault. These are interviews with amazing people, people whose lives and work have stood the test of time and continue to inspire. But on this episode, we’ve got an interview that was done so recently, it hasn’t made it into the vault, so why are we rushing to get this one on? Because it is about a doctor whose research is helping revolutionize the way cancers are going to be treated in the future.
00:01:37 For certain cancers, in fact, the revolution is already well underway. It’s called immunotherapy. So who doesn’t want to hear a story, ASAP, about someone successfully kicking cancer’s butt? Meet Dr. Steve Rosenberg, chief of surgery at the National Cancer Institute. His story, told to Pulitzer Prize-winning journalist Mary Jordan, is riveting.
00:02:03 STEVEN ROSENBERG: When I was a resident in surgery, I was rotating through the West Roxbury VA Hospital. This was as a junior resident.
00:02:10 ALICE WINKLER: It was the mid-1960s.
00:02:12 STEVEN ROSENBERG: And I was working in the emergency ward, taking care of people who were coming in, and this patient came in with right upper quadrant pain. It looked like a typical gallbladder attack. He was a 68-year-old man. And I pulled out his chart because we were going to take him to the operating room to take out his gallbladder, and this remarkable story unfolded. Twelve years earlier he had come to this same VA hospital. He had had a cancer in his stomach, a gastric cancer. He had been operated on. They opened the belly, and they saw the cancer. They saw it had spread to the liver.
00:02:43 They biopsied the tumor in the liver. They could do nothing, and they closed the belly, saying that there was nothing more that could be done for this fellow. Well, they gave him an appointment to come back in three months. They never expected to see him, but sure enough, three months later he showed up.
00:02:57 ALICE WINKLER: And his tumors seemed to be shrinking.
00:02:59 STEVEN ROSENBERG: Six months later, he was gaining weight — and I’m turning the pages — and a year later he was back at work, and here he was 12 years later looking perfectly healthy with some right upper quadrant pain due to a gallbladder stone. So it was one of the first operations I did as a junior resident. We took out his gallbladder. We examined his belly thoroughly, and all of the cancer was gone.
00:03:22 MARY JORDAN: What did you think?
00:03:23 STEVEN ROSENBERG: Somehow his body had figured out how to eliminate his cancer. It’s one of the rarest events in all of medicine, a spontaneous regression of cancer in the absence of any treatment. I’ve only seen that one other time in my entire career of well over 5,000 cancer patients that I’ve treated.
00:03:44 MARY JORDAN: And what did that lead you to do or to think?
00:03:46 STEVEN ROSENBERG: Well, what that told me was that somehow the body, in this particular patient, had the tools to eliminate his own cancer. And the major body function that can protect us against outside influences like viruses, bacteria, and maybe even cancer is the immune system, and I thought that perhaps this patient’s immune system had recognized his cancer as a foreign invader, the way it does the flu virus and so on, and had eliminated it.
00:04:16 And that set me then on the trail of trying to see if I could reproduce that in other patients.
00:04:22 ALICE WINKLER: In other words, could he find a way to fire up the body’s immune system so it would annihilate the invading cancer cells? Dr. Rosenberg didn’t invent the notion, but it had been abandoned decades before in favor of chemotherapy and radiation.
00:04:41 Dr. Rosenberg could not shake what he’d seen in that one patient, and he hasn’t shaken it since, not through the rest of his residency, and not in the 42 years he has served as chief of surgery at the National Cancer Institute, a branch of the National Institutes of Health (NIH), located in Bethesda, Maryland. Rosenberg was appointed chief of surgery in 1974 and began his post the day after finishing his residency. He’s now 76, and it is the only job he has ever had.
00:05:17 Over those 40-plus years, developments in other areas of medicine have been key to helping Dr. Rosenberg and other scientists make leaps forward in immunotherapy. He started doing this work, for example, well before the human genome was mapped and well before there was a way to manipulate immune cells, or lymphocytes, outside of the body.
00:05:39 STEVEN ROSENBERG: And so one of the first things we tried, which in retrospect was very naïve scientifically, is we tried to immunize experimental animals with a patient’s cancer and use their lymphocytes — because the lymphocytes are the immune warriors in the body — use that animal’s lymphocytes to treat the patient. And so we looked for which animal would be most likely to produce cells that would react against the patient’s cancer, and quite unfortunately, it turned out to be mini pigs had immune systems that seemed most relevant, which was a little bit of a problem for my father.
00:06:13 I was brought up as an Orthodox Jew and was quite religious when I was growing up. I’ve wandered. And when I would describe this to my father and tell him that we were going to take pig lymphocytes and put them into a patient, he was horrified. But if it could help people, then, of course, that’s acceptable in any — certainly in the Jewish religion, but it didn’t work.
00:06:35 ALICE WINKLER: Now that Dr. Rosenberg has brought it up, seems like a good time to talk about his personal background. We’ll get back to the research in a minute, but his early life story will give you some insight into what gave this man a determination rare among mortals.
00:06:51 STEVEN ROSENBERG: You know, neither of my parents went past the fifth grade in school. I mean they were caught in the war in Europe and immigrated here in their late teenage years. They were smart. They were smart, and they would help me a lot and give me insights about life. My dad owned a luncheonette in downtown Manhattan, a small store, and I would work behind the counter when I went to high school.
00:07:18 Working at a luncheonette every day after school showed me that that’s not what I wanted to do with my life. And I realized that to break away from that kind of activity, that kind of atmosphere in life, I was going to have to work hard to do something that I thought was a lot more meaningful.
00:07:40 ALICE WINKLER: And he had a pretty clear idea early on what that was going to be.
00:07:44 STEVEN ROSENBERG: I knew from the time I was six or seven that I was going to be a doctor and that I was going to do research, and I had scrapbooks of research that I would pull out of newspapers and magazines. I was lucky enough to go get an education at a place like the Bronx High School of Science, which stimulated young people to think about science. And I was lucky enough to have parents who could help me get to college — I went to Johns Hopkins; I went to medical school at Johns Hopkins — who could give me that opportunity to accomplish and to take advantage of whatever talents I might have.
00:08:21 ALICE WINKLER: It’s a classic story of the American Dream made good: the child of uneducated, hard-working immigrants in the Bronx sets his sights high, and then rises even higher, landing at the frontiers of medicine.
00:08:36 STEVEN ROSENBERG: But again, I want to emphasize the influence that taking care of cancer patients had on me. I mean it’s a holocaust. I mean here are people that for — innocent people who develop cancer that’s widespread through no fault of their own, and their family has to stand by and watch them suffer and die and not be able to do anything about it. It’s an enormous motivating factor to feel as if you have to do something for those people.
00:09:11 And I think that’s part of why I got into this in the first place. I was born in 1940, and so when I was six, seven years old, that was a time when, on a regular basis, we were getting postcards from Europe about this particular relative died in Auschwitz, and this one died in this concentration camp. And at age six or seven, it just seemed inconceivable to me that people could suffer to that degree — to be perfectly innocent, and yet, suffer themselves and have their families watch them suffer.
00:09:49 That’s really what cancer is, and I see that every day when I walk into a patient’s room and I’m taking care of a patient and their family is sitting there. It's — to me, it's — I decided quite early on that I wanted to do something that would help people who are innocent and suffering. And to me, cancer, when I was a resident and saw those patients, it represented that kind of goal.
00:10:14 ALICE WINKLER: And from the beginning, to achieve that goal, Steve Rosenberg did some extraordinary things. In the middle of his residency, for instance, he took off four years to get a Ph.D. in biophysics from Harvard, trying to absorb whatever he could that might help him in his quest.
00:10:33 STEVEN ROSENBERG: Well, of course, there’s no substitute for a wide knowledge base. I wanted to learn. I was studying quantum mechanics. I was studying differential equations. Some of the early papers that I wrote were — would be indecipherable now in terms of the difficulty of their mathematics to me. But I wanted to lose my fear of what I did not know. I wanted to feel as if I had enough base of knowledge in a wide variety of scientific fields such that I could draw on any one of those fields and bring them to bear on a problem. And I had to develop the confidence that if I didn’t understand something and I had a good book, I had the scientific background to actually understand virtually anything I wanted to work on.
00:11:16 ALICE WINKLER: Steve Rosenberg approached his life’s work with a vigor that cannot adequately be described with words as common as “dedicated.” It is as if he saw a train coming toward him on the track and has been trying to outrun it ever since.
00:11:30 STEVEN ROSENBERG: There have probably been 40 days in the last 40 years when I have not been in this hospital when I’ve been in town. So I come in every Saturday to make rounds, Sunday to make rounds, spend a few hours going over data. You have to be willing to immerse your life in a subject if you’re going to take on a really difficult problem — so that when you’re taking a shower, you’re thinking about it. When you’re stopped at a red light, you’re thinking about it. You have to immerse in the problem so that not only are you learning facts when you read about them, but you’re always thinking about modifications.
00:12:03 ALICE WINKLER: And does he ever take time to read for pleasure?
00:12:06 STEVEN ROSENBERG: You know, I love to read, but every time I pick up something to read that doesn’t deal with the science, that doesn’t have something to do with what I think I can use, there’s a guilt associated with taking the time to do that. So once a year, I and my family go down to North Carolina for a week, and for the entire year I save up books that I’m going to read during that one week.
00:12:32 ALICE WINKLER: So how did he manage to raise a family while keeping the kind of laser focus on work that he describes? Take a guess.
00:12:40 STEVEN ROSENBERG: Very early on, my wife, Alice, actually said to me, she said, "Look, what you do is important. You go do it, and I will try to relieve you of many of the normal life burdens so that you can do your work." And she’s done that for the last 48 years of our marriage. So I think that helped me a lot as well when —
00:13:01 MARY JORDAN: What do you do for fun?
00:13:05 STEVEN ROSENBERG: Well, when you say “fun,” there are enormous ups and downs and pleasure in doing scientific research. I mean an exciting result that you worked on for a long period of time can be an ecstatic experience, so that’s fun. Of course, that comes with the agonies of defeat, as well, when things don’t work, but I don’t have hobbies. And in fact, when I get applicants — and I get applicants from all over the world, from fellows who want to work in the lab, and at the end of their resume if they list a long list of hobbies, I toss that into a different pile because I don’t want people with hobbies.
00:13:41 I want people who are going to immerse in the work. Now, I really enjoy watching basketball games, and so sometimes late at night I will have copied a game, and before I go to sleep I’ll watch some of it. But other than that, I get joy from the science and from the work that I do here.
00:14:03 ALICE WINKLER: It’s a joy terribly tempered, though, by those agonies of defeat, as he calls them. Dr. Rosenberg is talking about years of unrelenting heartbreak, watching patient after patient after patient succumb.
00:14:17 STEVEN ROSENBERG: Well, the darkest time was when we were trying to develop immunotherapies when no one had ever gotten it to work. And so we treated a whole series of patients, every one of which was a terrible tragedy. I remember a young woman who had a sarcoma, and she was 23 years old and had four young children. And we had treated her, and it hadn’t worked, and she had a recorder that she was recording messages to her children, who would then hear it when they were older and could understand what she had gone through because she was no longer going to be here.
00:14:54 I mean I was confronting that kind of tragedy every day, never knowing that immunotherapy actually one day would work. But it was that 67th patient that we treated that responded when I knew we were onto something important. Then we knew it was possible, and once we knew it was possible, everything changed because once you know something's possible, you have ways then to begin to work on improving it.
00:15:20 ALICE WINKLER: “The 67th Patient.” That could very well be the name of the movie one day made about Steve Rosenberg’s crusade against cancer, a movie focused on his breakthrough moment in 1984.
00:15:33 MARY JORDAN: Tell us about the 67th patient.
00:15:37 STEVEN ROSENBERG: So we had treated 66 patients in a row, trying to use a particular growth factor that stimulated lymphocytes inside the body and a particular kind of cell that we thought was important. And we treated 66 patients in a row, all of whom had advanced cancer. None of them had responded and all went on to die of their cancer. It was only the 67th patient — she was a young woman who had melanoma that had spread throughout her body.
00:16:08 She had received multiple treatments and was told that there was nothing more that could be done. In fact, she was told to — suggested that she go to Europe and go on a vacation because she didn’t have very much longer to live. Well, she came to us, and we treated her, and she was the first patient ever to respond to immunotherapy.
00:16:29 And I remember her coming back for her first follow-up. We give the treatment. Often, when it’s working, we know within one or two months, and we didn’t see a lot of change in the nodules that were growing in her skin, so we didn’t know whether the treatment was working or not, but we biopsied one of those. We removed them so we could learn to see if anything was happening. We try to learn from patients that don’t respond as well as ones that do. And when we went down to the pathology department and I looked under the microscope, at the pathologist, at this lesion we had removed, all the cells were dead. There was no viable cancer left.
00:17:04 MARY JORDAN: What did you think right then? I mean did your heart start racing?
00:17:07 STEVEN ROSENBERG: Well, it seemed remarkable, but we hadn’t seen a lot of change in the patient at one month. Well, when she came back for the second month of follow-up, all of the tumors were starting to disappear. And I told her about the biopsy result that we had performed, and her tumor went on to go away completely. But she later told me that she went home after that visit and had her family all get together for what they called a “dead tumor party.” It was quite a moment.
00:17:39 MARY JORDAN: Were there moments when you thought about giving up?
00:17:44 STEVEN ROSENBERG: One of the things about treating cancer patients is they present such a desperate problem that when you confront them, it's very hard to think of not trying to do something that will help. We only treat patients that come to us when there's nothing else available to them, and we offer our experimental treatments, and very often they don’t work. And in fact, the most difficult times that I have are having to sit with a patient who has come to us as their last hope and having to sit down with them and tell them that, in fact, it looks like this treatment has not worked.
00:18:26 And I think unless I knew that I was going to go back to the laboratory and try to learn something from that patient and keep working on it, it would be almost impossible to bear.
00:18:39 ALICE WINKLER: The 67th patient, by the way, Linda Taylor, is still in remission more than 30 years after her treatment. These days, Dr. Rosenberg’s success rate with metastatic melanoma and a couple of other cancers is much higher. He now gets to be the bearer of good news about 60% of the time, when a patient's cancer has shrunk significantly, and great news about 25-30% of the time, when a patient's cancer is gone.
00:19:07 STEVEN ROSENBERG: A remarkable patient that I treated quite recently was a young woman, a kindergarten teacher, who had cancer throughout her body again. Nothing had worked. We gave her the latest of our treatments, a cell transfer treatment where we identified cells in her body that could recognize her cancer and give them back, and all of her cancer disappeared. And last Christmas, she sent me a card, and on the card was a photograph with all of her kindergarten students lined up one after the other, each one holding a placard.
00:19:37 One had a T, and the other had an H, and the other had an A, and it spelled out "Thank you," and then she was standing at the end of it. It was quite emotional.
00:19:46 ALICE WINKLER: That patient’s name is Shea Birnie, and she joined Dr. Rosenberg at the end of this interview with journalist Mary Jordan to tell her own side of the story. When she first met Dr. Rosenberg, she had stage 4 melanoma. It was in her lungs and liver, and she had been given no more than ten months to live.
00:20:06 SHEA BIRNIE: He affected my whole family and all of my friends and everyone around me. I mean everybody was crying, and they were scared, but everybody was excited when I was in NIH. And so I can appreciate that life is full of passion and full of miracles, and all you need to do is open your eyes to them because Dr. Rosenberg has made, you know, a tremendous miracle.
00:20:36 I mean there are little miracles in this world, and then there are big ones, and he makes big ones. I mean I'm a preschool teacher, so I was in the middle of teaching preschool, and there's nothing more, like, terrible to think about than you're a preschool teacher — and that was actually one of my worst fears, is that I was going to die and that these little preschoolers were going to have to learn about death, you know, before I feel like any preschooler should have to learn about it.
00:21:05 And I was like — I said, "I don't want that to happen," and —
00:21:10 STEVEN ROSENBERG: Now I'm going to start bawling.
00:21:11 SHEA BIRNIE: So I mean it's like — I think it's just that — you know, it's just that I feel very lucky to be a part of what he has created. And it wasn't my time. And he has given me the opportunity to really try to still continue to make impact on children and, like, to create these little Dr. Rosenbergs.
00:21:36 MARY JORDAN: Do you remember when he told you that you were going to make it?
00:21:40 SHEA BIRNIE: I do. It was kind of different. I had gone — I was, like, a year-and-a-half into the protocol, and I had gone to clinic, and I was waiting in the room. And you kind of know because you go to clinic often. They’re scanning you often, and when I went in at a year-and-a-half, everybody was, like, kind of excited. Everyone’s like, "Shea’s here!" They're like, "Shea’s here!" And I was like, "Why are they all saying, ‘Shea’s here?’"
00:22:08 I’m like, "Hi, I’m here," you know. I was like — the team was — it was the receptionist and the people that were taking my blood work. And I didn’t know why, and then all of a sudden they’re like, "Well, we’d like you to come into the room right away." And usually it takes just a little bit of time for the doctors to come around, and usually — but that day they rushed me back.
00:22:30 And one of the attendings, Dr. Phan, walked in, and shortly after that, the door opened wide and Dr. Rosenberg was there, and he had a big smile on his face, and I was like — he said, "You are cancer free." He said, "You're virtually cancer free," and he said, "Not only that but somebody that is virtually cancer free to the stage that you're at, the cancer almost never comes back." And so —
00:23:02 MARY JORDAN: What was your reaction?
00:23:04 SHEA BIRNIE: I mean I was — actually, at that point, it was — I was almost stunned, and it was then, it was — and then we were all crying.
00:23:15 ALICE WINKLER: Shea Birnie says that she knew she was in good hands the minute she came under Dr. Rosenberg’s care — something about his manner, his brilliance, and his humanity. It’s clear as day, she said, to both the patients and the staff.
00:23:30 SHEA BIRNIE: Everybody on the team loves Dr. Rosenberg. And he brings that energy, I think, that passion and that love of, like, saving people. I mean that takes incredibly special people to create — you know, because you’re dealing with people that could die, and he creates this passion and this, like, this energy — that people get very excited about cancer and really saving people’s lives. And being able to endure the hard, incredible things when you’re, like, brought to death and back again. Because you’re brought to — I was brought to death and to life again, and —
00:24:12 STEVEN ROSENBERG: It’s a tough treatment. It’s tough, and Shea had a lot of courage in dealing with it because we first have to wipe out the patient’s immune system so we can replace it with an immune system that can fight the cancer. And that’s a new kind of approach, and it’s not easy, but Shea was always, "I’m ready."
00:24:30 SHEA BIRNIE: Yeah.
00:24:31 STEVEN ROSENBERG: “I’m ready.” We always tell patients everything that we know. We never keep anything from patients, and sometimes that’s difficult, but we feel it’s very important, especially when you’re using an experimental treatment, something that’s never, ever been done before. It’s important that people know what they’re getting into and what the results have been and what’s going to be involved in the next step, and Shea was always very courageous about it.
00:24:55 So as we tell people what their current situation is and what we’re going to do, we tend to be optimistic. I think cancer patients deserve optimistic doctors.
00:25:07 ALICE WINKLER: Steve Rosenberg doesn’t fake his optimism for the sake of his patients. It’s real, and it’s one of the keys to his perseverance, as Francis Collins will attest. Collins, who once led the Human Genome Project, is the director of the National Institutes of Health, which makes him Steve Rosenberg’s boss.
00:25:25 FRANCIS COLLINS: Steve Rosenberg is a hero in this field. No question about it. He has labored on this issue of how you could get the immune system to be an ally in fighting off cancer for decades. And frankly, it's been a tough go, and many people, as recently as ten years ago, would have said, "This is just not a productive area. We should stop trying because it isn't ever going to work."
00:25:51 Now, here we are, ten years after that skepticism, where everybody would agree that cancer immunotherapy is just about the hottest science going anywhere, and some of that is by identifying pathways where the cancer cells very cleverly send a signal to the immune system, saying, "Go to sleep. It's okay, nothing going on here. Nothing to see." And we can block that signal now, and the immune system wakes up and goes, "Whoa! What's going on over there?" And it goes after it.
00:26:20 And some of it is actually teaching immune cells what to do, taking them to graduate school and teaching them, "Hey, there's a cancer over here. We're going to give you the tools you need to go after it." You know, Steve never wavered. He was determined that “There's something here. We just have to keep trying, and we're going to figure out what it is.” And he's also an incredible, compassionate human being. He never stepped away from his desire to help people and to know who they were.
00:26:49 I mean you watch Steve interact with a patient. This is not just an academic conversation. This is a caring physician trying to help.
00:26:58 STEVEN ROSENBERG: When I lie awake at night, I don’t think of the patients, like Linda, that had good results, whose cancer has disappeared. I think of the people that we have failed, and so I take, obviously, joy and pleasure from seeing people recover, and we can cure patients with widely metastatic cancer now with immunotherapy. But I always have about a dozen patients with advanced cancer in the hospital at any one time. And I’ll walk into one room, and the patient will be doing well, and their cancers are going away, and we’re laughing, and the family is shaking hands, and they’ve heard about all these wonderful results.
00:27:39 But I’ll walk into the next room, and it hasn’t worked, and every patient is despondent, and the family is crying. So it’s the great leveler, what I do. It keeps me focused on what’s important.
00:27:55 ALICE WINKLER: Dr. Rosenberg’s focus, as always, is on continuing to improve the outcomes for his patients with melanoma and kidney cancer and smoking-induced lung cancer. Those have all been proven responsive to immunotherapy, but he says the biggest challenge in the field right now is to figure out how to target the technique at other cancers, of the colon, the ovary, the pancreas, etcetera.
00:28:21 STEVEN ROSENBERG: I'm finally getting the hang of it, after these 42 years, and I think we're going to see enormous progress — enormous progress — in the next five to ten years.
00:28:31 ALICE WINKLER: Optimism. Just what the doctor ordered. I’m Alice Winkler, and this is What It Takes from the Academy of Achievement.
00:28:48 Thanks to the Catherine B. Reynolds Foundation for making What It Takes possible. See you in two weeks.
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