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As South East Queensland awaits Tropcial Cyclone Alfred, here is the latest information from the Bureau of Meterology as of Friday 2pm. Daniel Hayes from the Bureau of Meterology told Gary Hardgrave on 4BC Drive, "The system is still a Category 2 out there moving towards the coast." "The expectation is we'll see it cross over the Moreton Bay Islands, later or early hours of tomorrow morning before making its way across the bay and crossing over the mainland sometime later tomorrow morning," Mr Hayes continued. See omnystudio.com/listener for privacy information.
Denver-based poet/author/musician & spoken word artist Daniel Hayes talks about his latest “Butterfly with Bazookas” featuring “Ecstasy”, “Redemption”, “Wake Up”, “The Witch”, “Eat Fast”, “Bullet Train” and more! Daniel is also the author of the book “Cairns” featured on Amazon about the trail of discovery sharing vulnerable insights into how life cairns, curated by courage & curiosity involved into the unknown with themes over the course of his life, plus releasing 2 albums in '05 & '06 under Significant Effects and campaigns for role-playing games! Check out the amazing Daniel Hays and all streaming/major platforms today! #danielhayes #denvercolorado #poet #author #butterflywithbazookas #cairns #musician #spokenwordartist #ecstasy #redemption #wakeup #thewitch #significanteffects #roleplayinggames #spreaker #iheartradio #spotify #applemusic #youtube #anchorfm #bitchute #rumble #mikewagner #themikewagnershow #mikewagnerdanielhayes #themikewagnershowdanielhayes --- Support this podcast: https://podcasters.spotify.com/pod/show/themikewagnershow/support
Denver-based poet/author/musician & spoken word artist Daniel Hayes talks about his latest “Butterfly with Bazookas” featuring “Ecstasy”, “Redemption”, “Wake Up”, “The Witch”, “Eat Fast”, “Bullet Train” and more! Daniel is also the author of the book “Cairns” featured on Amazon about the trail of discovery sharing vulnerable insights into how life cairns, curated by courage & curiosity involved into the unknown with themes over the course of his life, plus releasing 2 albums in '05 & '06 under Significant Effects and campaigns for role-playing games! Check out the amazing Daniel Hays and all streaming/major platforms today! #danielhayes #denvercolorado #poet #author #butterflywithbazookas #cairns #musician #spokenwordartist #ecstasy #redemption #wakeup #thewitch #significanteffects #roleplayinggames #spreaker #iheartradio #spotify #applemusic #youtube #anchorfm #bitchute #rumble #mikewagner #themikewagnershow #mikewagnerdanielhayes #themikewagnershowdanielhayes --- Support this podcast: https://podcasters.spotify.com/pod/show/themikewagnershow/support
Denver-based poet/author/musician & spoken word artist Daniel Hayes talks about his latest “Butterfly with Bazookas” featuring “Ecstasy”, “Redemption”, “Wake Up”, “The Witch”, “Eat Fast”, “Bullet Train” and more! Daniel is also the author of the book “Cairns” featured on Amazon about the trail of discovery sharing vulnerable insights into how life cairns, curated by courage & curiosity involved into the unknown with themes over the course of his life, plus releasing 2 albums in '05 & '06 under Significant Effects and campaigns for role-playing games! Check out the amazing Daniel Hays and all streaming/major platforms today! #danielhayes #denvercolorado #poet #author #butterflywithbazookas #cairns #musician #spokenwordartist #ecstasy #redemption #wakeup #thewitch #significanteffects #roleplayinggames #spreaker #iheartradio #spotify #applemusic #youtube #anchorfm #bitchute #rumble #mikewagner #themikewagnershow #mikewagnerdanielhayes #themikewagnershowdanielhayes Become a supporter of this podcast: https://www.spreaker.com/podcast/the-mike-wagner-show--3140147/support.
How do you better understand the New Testament? We all want to read the Bible better and hear from God through his Word confidently. In this podcast, Jonathan Morrow talks with Daniel Hayes about helpful ways to engage the New Testament.How should we approach wisdom literature?How should we approach Gospel literature?How should we approach the New Testament letters?How should we approach Revelation?Daniel Hayes discusses answers these and more in his book Journey into God's Word: Your Guide to Understanding and Applying the Bible, Second Edition
How do you better understand the Old Testament? We all want to read the Bible better and hear from God through his Word confidently. In this podcast, Jonathan Morrow talks with Daniel Hayes about helpful ways to engage the Old Testament.What are some best practices when approaching the law?Aren't Christians guilty of picking and choosing?How should we approach the poetic genre?What are some examples of poetic genre?What are some best practices when interpreting the prophets?Daniel Hayes discusses answers these and more in his book Journey into God's Word: Your Guide to Understanding and Applying the Bible, Second Edition
How to better understand and read the Bible. We all want to read the Bible better and hear from God through his Word confidently. In this podcast, Jonathan Morrow talks with Daniel Hayes, we will be talking about how to do that!Why is context so important when interpreting the Bible?What are some of the best practices when it comes to reading biblical narrative?What is an example of a misinterpreted text?Why is context so important when interpreting the Bible?What role doe the Holy Spirit playin interpreting the text?Daniel Hayes discusses answers these and more in his book Journey into God's Word: Your Guide to Understanding and Applying the Bible, Second Edition
It finally happened! After numerous reschedules, we got on Daniel Hayes of Jackson Kayak. We'll talk about all things Jackson including the new Knarr and how Jackson Kayaks continues to innovate and position themselves within the kayaking and fishing community.The One Last Cast Podcast is all about sharing knowledge to help anglers learn about kayaking and fishing on the Texas Coast. It is hosted by two knowledgeable anglers who have years of experience in the industry. Jonathan Hua is an accomplished kayak angler, outdoor writer, and blogger. Merriel Solesky is an accomplished tournament angler and kayak guide.Want to join us live, ask a question, or even win some cool prizes? Join us on our Facebook page where we have our livestream!Shout Outs and Sponsors!4A Custom PrintingDirty South Kayak Anglers (DSKA)Knockin Tail LuresOne of the best soft plastics. It uses swimming on the fall action with a built-in rattle!Want to join us live, ask a question, or even win some cool prizes? Join us on our Facebook page where we have our livestream!Shout Outs and Sponsors!4A Custom PrintingDirty South Kayak Anglers (DSKA)Knockin Tail Lures One of the best soft plastics. It uses swimming on the fall action with a built-in rattle!
Daniel Hayes of Snakebird Stockdogs joined me to discuss the process of learning and succeeding with stock dogs. We talk about the importance of mentors as well as some tips for getting started. Thanks to our Studio Sponsor, Sea-90! You can reach them at www.sea-90.com or (770) 361-6092. Sponsor: Farming Without the Bank Relevant Links:...
Another pivot! We'll eventually catch up with Daniel Hayes and Jackson Kayak. However, we really wanted to talk with Timothy Rodman, a seasoned kayak bass angler here in Houston. That's right! We're moving from the coast and talking about the coveted green fish inland. So sit back, and let's talk bass fishing!The One Last Cast Podcast is all about sharing knowledge to help anglers learn about kayaking and fishing on the Texas Coast. It is hosted by two knowledgeable anglers who have years of experience in the industry. Jonathan Hua is an accomplished kayak angler, outdoor writer, and blogger. Merriel Solesky is an accomplished tournament angler and kayak guide.Want to join us live, ask a question, or even win some cool prizes? Join us on our Facebook page where we have our livestream!Shout Outs and Sponsors!4A Custom PrintingDirty South Kayak Anglers (DSKA)Knockin Tail LuresOne of the best soft plastics. It uses swimming on the fall action with a built-in rattle!
On this episode, host Merriel Solesky talks to Heroes on the Water- Galveston Chapter kayak guys John Stapleton and Daniel Hayes. They discuss how they help veterans through kayaking and fishing. Join us!The One Last Cast Podcast is all about sharing knowledge to help anglers learn about kayaking and fishing on the Texas Coast. It is hosted by two knowledgeable anglers who have years of experience in the industry. Jonathan Hua is an accomplished kayak angler, outdoor writer, and blogger. Merriel Solesky is an accomplished tournament angler and kayak guide.Want to join us live, ask a question, or even win some cool prizes? Join us on our Facebook page where we have our livestream!Shout Outs and Sponsors!4A Custom PrintingDirty South Kayak Anglers (DSKA)Knockin Tail LuresKnockin Tail LuresOne of the best soft plastics. It uses swimming on the fall action with a built-in rattle!Use our exclusive code OLCP2022 for 20% off your Knockin Tail purchase!
Today we take our final WW1 journey through the trenches with the 2019 movie, 1917. The story is based around two British soldiers desperately trying to make it to the front lines in order to save 1,600 men. 1917 is a rare movie masterpiece directed by Sam Mendes, starring Dean-Charles Chapman, George MacKay, and Daniel Hayes. The movie was nominated for 200 awards, won 134, and bagged 3 Oscars. Today we honor Alfred Mendez who enlisted on October 17th 1917, in the first battalion rifle brigade in the British army. He went on to have a successful writing career and worked in his family business until he died in 1991. If you or someone you love have served in the armed forces of any nation, then we would like to honor them on this humble podcast! Just Tweet @NARwaronfilm Not A Robot's War on Film. We discuss all manner of War movies, their historical accuracy, how life is depicted on the screen, the movie itself, all while having some fun. Soldier up and come join us in Not A Robot's War On Film ! Hosted by a US Veteran! NARWarOnFilm@gmail.com NotARobotPodcasts.com --- Send in a voice message: https://podcasters.spotify.com/pod/show/narwaronfilm/message Support this podcast: https://podcasters.spotify.com/pod/show/narwaronfilm/support
Sober October continues on the Ag State of Mind Podcast. Today, we go to South Carolina to speak with my friend Daniel Hayes. Daniel and I first connected over our mutual friend Clay Conry's podcast "Working Cows." We speak to Daniel about his incredible journey through sobriety after a quite tumultuous past. We talk about how both his faith in God and his relationship with his wife helped him become the man who he is today. We then shift the conversation to him transitioning over from cattle to hair sheep on his operation and how that is benefiting his land and his way of life. If you want to reach out to Daniel his email is bootstrapfarmsc@gmail.com
Hayeswinckle managing director Daniel Hayes became a household name this year after starring in the latest season of Big Brother Australia.
This week on Chasin' the Tide, Dustin is joined by Daniel Hayes. Daniel is one of the directors of the Salt Water Survival Series and on the Fishing Tackle Unlimited Pro-staff. Sit back and listen about kayak beginnings, Daniel's take on the growth in the kayak industry, and his choices for "Pick 3" where the guests pick there top 3 setups and baits! Plus...upcoming info on the Flounder Event on November 14th. Yeeewwwww! Patreon-https://www.patreon.com/paddlenfin Podcast & Website- www.paddlenfin.com YouTube- https://www.youtube.com/paddlenfin Email- paddlenfin@gmail.com Social Media- @paddlenfin Anglr- Download the Angler App Rocktown paddlesports - rocktownadventures.com TRC Covers- https://trccovers.com JigMasters Jigs- https://jigmasters.com Ketch Products- https://ketchproducts.com Recycled Plastics Recycling Program - Mail to: 316 Pinewood Dr. Camp Hill,PA 17011
Dr. Hayes interviews Dr. Lawrence Baker on his early involvement with SWOG ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. DANIEL HAYES: Welcome to JCO's Cancer Stories-- The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Today, my guest on the podcast is Dr. Laurence H. "Barry" Baker. Dr. Baker has a long and distinguished career in oncology. It dates back to the early 1970s, when he was intimately involved in new drug development, including doxirubicin or adriamycin, as we know it. He's also led early studies in preoperative chemotherapy in anal cancers. He was instrumental in advances in sarcoma research, and he led the Southwest Oncology Group-- now designated SWOG-- for eight years in the last decade. Dr. Baker was raised in Brooklyn, and since this interview is taking place just a week after the sad loss of Supreme Court Justice Ruth Bader Ginsburg, Dr. Baker informed me that he and his wife Maxine were married in 1964 in the Midwood Jewish Center, Justice Ginsburg's home synagogue. He received his undergraduate degree from the Brooklyn College at the University of New York, and then he graduated from Des Moines University of Osteopathic Medicine in Iowa. He completed a residency in internal medicine at Flint Osteopathic Hospital in Flint, Michigan, and then he has a curious two-year break in his curriculum vitae during which he was on active duty in Vietnam. Upon discharge from the Army, he returned to Michigan, and he served a three year fellowship at Wayne State University, where he stayed on faculty from 1972 to 1994, serving at various times as the chief of the Division of Hematology and Oncology, the chair of the Department of Medicine, and director of the Cancer Center. In 1994, he moved west about 30 miles to Ann Arbor, where he served as the director for the Clinical Research and Translational and Clinical Research Program for the UM Comprehensive Cancer Center, now called the Rogel Cancer Center. And he was also the associate chief of the Division of Hematology and Oncology and currently is the Laurence H. Baker Collegiate Professor in developmental therapeutics. Dr. Baker has authored hundreds of peer-reviewed papers, and like so many of our guests on this program, he has a list of honors that are just, frankly, too long to recite, except two that I want to highlight. He received the ASCO Distinguished Service Award for Scientific Leadership in 2007, and he was named an ASCO Statesman, now designated as a fellow of ASCO in 2010, for his many services to our society. Dr. Baker, welcome to our program. LAURENCE H. BAKER: Thank you. Nice to be here. DANIEL HAYES: Well, it's really great to have you. A lot of questions, but I want to start out, I just can't help but ask you, to be trite, how does a nice boy from Brooklyn end up in the Midwest for the rest of his life? Can you give us some stories about how you got there? LAURENCE H. BAKER: I graduated high school at 15 and went into what some know-- but not everyone knows-- was a very competitive college. Brooklyn College accepted-- was a free school. The grades used in the New York City school system were numerical. They weren't letters. And you had to have a 90 average on high school and certain scores on the state, New York State examinations to get in. And that was it. It didn't matter where your parents went to school. It didn't matter if you had money. And so it was a school largely of relatively low-income families. But that's the one who took me, and I guess they accepted me at 15. To not make this into a long story, but to drag it out a little bit, I was fascinated that I was 15 and I could date 18-year-old girls, and they didn't know it. So that's how I spent the first two years of college. And my grades showed that that was my focus of attention. I did pretty well on the MCAT examination. I would not have gotten into a medical school in this country, and I didn't speak a language that would be sufficient for me to go to Europe, for example, to school. So osteopathy he was where I went. I went to Iowa, but their admitting question to me is, do you have $2,000 a year tuition? To which, of course, I lied. And that's how I ended up being a DO, and that's how I came to the Midwest. And I actually got to like the-- I didn't know anybody from Iowa, as you make reference to my Brooklyn background, but I actually came to really appreciate the Iowa people, and particularly the community people that I came to know. At the time there were-- the really good programs in residency in medicine were in Michigan. That's the direct answer to your question. That's how I came to Michigan. Just about then, just about could have gone to California and gotten an M.D. degree just by taking the licensure examination. And then, that closed. That opportunity closed. So a long story to your question. So I came to Detroit, into Flint, and then returned back to Detroit, and I've been in Michigan ever since. DANIEL HAYES: Now, that raises the second issue I talked about a minute ago. And that is, many of our guests were so-called Yellow Berets at the NIH in the late 1960s and really changed our practice. But you actually ended up in the Evacuation Hospital at Cu Chi in Vietnam. And I've heard horror stories about this. How did that happen? What did you do there? Enlighten me. LAURENCE H. BAKER: Well, there were good and bad things about being an osteopath. The American Osteopathic Association was always in conflict, was always trying to defend itself. And at the time that the Vietnam War was going on, the DOs were not eligible for military service as an officer. You could go in as an enlisted man, but not as an officer. But there was a great need for primary care physicians in Vietnam, and the understanding of the military physicians was that all DOs were primary care physicians. So a deal was struck between the AMA and the Department of Defense that led to the drafting of everyone in my medical school class. Every one of the men-- not women. Every one of the men was drafted. There was a universal draft. I then-- I was given a choice. I could volunteer for the Army or go to jail. Those were the choices. And I had, at the time, two little children with Maxine, and I was not-- you might guess-- not a big fan of the Vietnam War. The alternative was to go to Canada, and I wasn't secure enough to consider that I could actually practice medicine. It was uncertain. So I went in. When I got there, they asked me, did I have any interest in anesthesiology or radiology, because they were really short of those two. And of course, being who I am, I said, if you need a radiologist or an anesthesiologist, why don't you go draft one and let me go home? That didn't work, and so I became-- I was assigned to radiology. DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: They sent me to Fort Jackson, where-- no, that was actually a good experience then, because I learned a lot about imaging, and I still have interest in imaging, but I don't qualify anymore. This is before CAT scans and MRIs. This is IDPs and upper GIs, right? So anyhow, barium lower bowel examinations. So I was trained for six months, and I stayed on for another few months on staff there and then, lo and behold, was sent to Vietnam. I was sent for a year, but I volunteered to stay an extra month so that I could return without any further obligation to the military and begin my fellowship on July 1, which I had actually secured before I went to Vietnam. So that's the gory details of that. I was elevated to Major about, oh, a few months before I was discharged. And then, because they weren't nasty enough to me when I got home, into my fellowship, I then got a letter congratulating me on being in the active reserve. So I had to go two weeks every summer. That was my summer vacation during fellowship and beginning of faculty. And I had to go once a month for a weekend to play soldier with a bunch of guys who were lucky enough that they didn't have to go to Vietnam. And now we're even, I think. So it was an interesting experience, as I've shared some of it with you. It still is a painful experience in some ways. I was out the busy [INAUDIBLE]. DANIEL HAYES: If you don't mind, a quick story you've told me before about the child with leukemia. LAURENCE H. BAKER: Yes. So they made me a radiologist. I'm not a great-- it doesn't matter where you call me. I am who I am, and I'm really interested in patient care. And there were already five internists, and there was only so much gonorrhea that the troops could acquire. So I volunteered to open a pediatric clinic. And the Army thought that was a good thing for publicity. They did stories about it. Anyway, I opened the clinic for pediatrics. I knew nothing about pediatrics. I mean, the truth is, I had a month of rotation. My wife sent me my textbook. It was Nelson's Textbook of Pediatrics. Nothing I ever saw in Vietnam was ever in Nelson's Textbook. But I did what I could of trying to treat the children as best I could. And along came a young girl, eight years old, who had acute lymphacytic leukemia. I had a wonderful pathologist who was my hoochmate. "Hooch" is translated, there were eight guys who lived in a place. That was called a hooch. And he was a pathologist, and he made the diagnosis of ALL. I had my books from my mentor teaching me about chemotherapy. So even though I hadn't started the fellowship, I had some resources about chemotherapy. And now I had to find chemotherapy. Treated her with-- I started with steroids and penicillin, and then I went to find drugs. I was able to-- I won't tell all the details, but I was able to get drugs at an old French hospital in Saigon. And so I would visit that hospital pretending great interest in the pharmacy, but of course, I stole whatever drug I could steal when the pharmacy wasn't looking. And that included some alkylating agents, methotrexate, 6MP. And so I tell Jay [INAUDIBLE]-- to get to where you want to be, perhaps-- that I invented the bicycle therapy, which was every month, you changed the drug to try to avoid resistance. So that's what I did by necessity. [LAUGHS] And I actually-- there was a second child that I also treated. When I left, they were both in complete remission. And I think that that's what you're asking me. I was lucky that I didn't get shot or thrown in jail for many of these escapades. But I look back and think that at least I did somebody some good. So-- DANIEL HAYES: Kind of makes the current generation who complains about work hours look in a different light, I think. LAURENCE H. BAKER: Yeah, we worked every day. We worked seven days a week with-- there was no such thing as time off. This was the busiest American hospital, certainly in Vietnam, and some think the busiest hospital since the Atlanta train station in the Civil War. It was in Cu Chi, which was on the way to Cambodia, which is, of course, where the North Vietnamese troops would enter into South Vietnam. So it was a major, major place. It was about an hour, an hour and a half west of Saigon. DANIEL HAYES: Let's move on to the rest of your career. You come back, then, and trained at Wayne State, and at the time, [INAUDIBLE]-- and I can never pronounce his name. I'll have you do it. Dr. Venutius Vicevicius-- I always heard him Dr. V.-- who was, I think, a real character and really was one of the first chemotherapy pioneers. Can you tell us more about him? Because we've heard a lot about the folks on the East Coast and the folks in Texas, but not so much what was going on in the middle of the country at the time. LAURENCE H. BAKER: Yeah, Dr. V, or Dr. Vicevicius, who was Lithuanian, he has a story of his life that certainly makes me look like a slump. He was a guest of the Nazis, and then he was a guest of the Russians when Auschwitz was freed. So this was as a child. He grew up in a very educated and somewhat affluent family in Vilnius. And when he got out of these camps, he actually got to medical school in Frankfurt, Goethe Medical School in Frankfurt. He had major interest in biochemistry and, without speaking more than three words of English, chose to come to the United States. And he landed-- I don't really know why; I've heard so many different versions-- but he landed in Detroit and showed up at the Detroit Receiving Hospital-- this would be like LA County or Bellevue in New York, that sort of thing, knife and gun club-- not speaking any English but wanting to do training. And somebody was smart enough to accept him. And so he did his training. He also trained-- after medicine, he trained with Mike Brennan-- that's another name from the past who is a past president of ASCO, by the way, the second or third person, perhaps. Mike was present of the Michigan Cancer Foundation and was the card-carrying medical oncologist in the Detroit area. He trained Dr. V., and he trained another man named Bob Tally, who had a great deal of history to contribute to oncology. And then, V was recruited by Wayne to come there and started a program. He was an extraordinary person. English was the eighth language he learned, and he actually taught me how to write. I flunked college English. I had to take it twice. But he taught me how to write and, I think, made me a better writer. He certainly was an inspiration. His devotion to patients was extraordinary. His knowledge was extraordinary. And so he was a great, great teacher. And one of his major early contributions was the recognition that you could make the drug float-- they had four drugs or five drugs at this time-- but one of them was 5-fluorouracil, that was developed by Fred Ansfield in Minnesota. The drug was given for five days and then every other day until their mouth fell out or their white count got to zero. And maybe that's a little of an exaggeration, but not much. At any rate, he figured out if you gave the drug by continuous infusion-- because it had a rather short half-life-- you could avoid a great deal of the toxicity. And that's how infusion of fluorouracil got its start. He then went on to combine it with other drugs and with radiation, and that was the backbone of this anal canal achievement that you mentioned in the introduction. I had very little to do with it, but I was a cheerleader. It was a rectal surgeon who came to us at the time, and those familiar with that disease-- which we now know is a virus disease that could be prevented, but at that time, nobody had any of that-- the treatment was abdominal perineal resection, and it had to be among the most horrible things we did to people. And the surgeon came to us and said, listen, you guys always squirt those drugs in after they relapse, and I'm really tired of this. Maybe you could give those drugs first, OK? And that's how neoadjuvant chemotherapy got started. It wasn't our idea. It was a surgeon's idea. That story gets repeated again in orthopedics, but that's how it began in anal canal tumors. And so we gave 5FU infusion, and mitomycin, and radiation preoperatively. That almost always shrunk the tumor, by the way-- almost always significantly shrunk the tumor. The patient then once they went through that operation but was cured. And so you took a horrible disease and changed its natural history with that development. If it works once, you know, in oncology, then you try it a second and third time. And I had very shortly thereafter the opportunity to work with a wonderful Japanese pediatric oncologist in Houston, Watsu Tao. He was looking for a partner because he was tired of seeing osteosarcoma patients die. Cure rate at the time was around 20%, 30%, and the surgery that was done for osteosarcoma was amputation, usually of the lower extremities. So 2/3 of osteosarcomas occur around the knee, and the orthopedics really dislike the idea of taking a child's leg off. Every teenager and child wants to be exactly like every other teenager and child, so you can imagine how disruptive it is to have a high amputation of your leg. It took about three months to make a prosthesis, and everyone knew that you didn't really have to do an amputation. You could just cut out the bad bone and replace it with a prosthetic device. But it took three months to make it, because they were handmade at the time. And so the idea came to several people-- Jim Holland was involved in this; Tom Frei was involved in this as well. Different cities were approaching it in this way. And we all ended up giving chemotherapy to these young people-- children, teenagers-- and then having the operation. And osteosarcoma went a cure rate of 20% to 30% to 70% or 80%. And they didn't lose their legs. DANIEL HAYES: I have two personal comments on this. One is you mentioned Dr. Brennan and the Michigan Cancer Foundation. Just for our listeners, Michigan Cancer Foundation is MCF. And if you've done any breast cancer work at all, you've worked with MCF-7 cells or MCF-10 cells [INAUDIBLE], which came from that organization. I think people have forgotten what MCF stands for, except for you and me. LAURENCE H. BAKER: That cell line that you talked about, MCF-7, that was developed by a man with, I think, a high school degree who just had a green thumb at that growing cells-- a wonderful man. And that came from a patient of ours. When I say "ours," I mean Dr. V. I was just the flunky, but it was his patient. And she had ascites from breast cancer. And we would tap ascites, in those days, with some frequency. And the cells for MCF-7 came out of that patient. That's its actual origins, and more papers have been written about MCF-7 than even you and I could count. DANIEL HAYES: Including by me. LAURENCE H. BAKER: I understand. No, it was incredibly useful. I mean, we learned about hormone receptors from this [INAUDIBLE]. DANIEL HAYES: Yep, that's [INAUDIBLE]. LAURENCE H. BAKER: It's was incredible. DANIEL HAYES: My other personal story related to your stories is, as a fellow at the then Sidney Farber Cancer Institute, Dr. Frei was my boss. And he, as you mentioned, was starting to work with Holland and others that had already worked with neoadjuvants. And he would cite your data all the time. Now, I didn't know Larry Baker for us from all the tea in China, but we heard a lot about the Wayne State experience when we were fellows. I don't know if that would have [INAUDIBLE] or not, but people definitely-- LAURENCE H. BAKER: No, I came to SWOG-- which is really why you wanted, I think, to talk to me-- in '70 or '71, I can't remember exactly. And Dr. V, it was an incredible experience. He took me with him. You ran into Tom Frei. They knew each other. And he said, Tom, I want you to meet my colleague, Larry Baker. I just had never been introduced like that. DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: And Tom was the friendliest person I think I've ever met in oncology. He had a wonderful smile. He clearly-- I was always paranoid that I'm a osteopath. Maybe I went on too long about that story. But when they tell you in school you're just as good as the MDs, you can quickly figure out if you were just as good, they wouldn't keep saying it, right? So that's socially accepted paranoia, and that's how I was brought up. So here is the wonderful, famous Tom Frei being nice to me! I was just amazed. DANIEL HAYES: He used to come to the lunch room in the Dana Farber two or three times a week and would just sit with us, and was constantly thinking of new stuff. This is not an interview with me, but someday, I'd like to tell the stories he told us. He was really just a fabulous man. I want to segway into your work with adriamycin, which is now, of course, also one of the workhorses of oncology. We've all used it. And I believe you were an author on either the first or one of the first phase II trials of adriamycin in Cancer in 1973. Is that an outgrowth of that introduction you just told us? LAURENCE H. BAKER: Yes. That study-- it's in Cancer, I think, not-- I don't think JCO existed. But that study didn't distinguish what the primary was. So it was a phase II study of cancer. And so there was, I don't know, 800 patients. I worked with Bob or Brian on that study. Bob was at Henry Ford, and there was a student of Bob Tally that I had mentioned, and I was the student of V. And the two of us were basically the schleppers for them. And so it had hundreds of patients in it. And in that study, we recognized that it worked in breast cancer, that it worked in lymphoma, and it worked in sarcoma-- and nothing worked in sarcoma. So that was the study. It's often quoted by Jim Dorshow because he said, we do everything that's disease-specific, but look what came out of one study that, by the way, accrued, as I say, 600 or 700 patients in 18 months. And this is before computers, so you can imagine how much work was done to evaluate the flow sheets. It was an incredible opportunity here to work. But it was an amazing paper, and it changed my life, of course. That's how [INAUDIBLE] and other things. DANIEL HAYES: So at the time, you recognized that this was not just another drug off the shelf, that it really was going to be a game-changer? LAURENCE H. BAKER: Absolutely, absolutely. You saw people getting better. And my experiences were mostly in breast cancer patients getting better, and some lymphoma patients that were refractory. First time I saw solid tumor patients dramatically improve. DANIEL HAYES: So I saw that your name is before another giant in the field who was a young Italian investigator who spent time in the United States named Johnny [INAUDIBLE]. LAURENCE H. BAKER: Yeah, that's how I first met him. I don't know that this story's been told. We were trying to make some level of peace with the Russians, and the Russians, of course, claimed that they discovered adriamycin. I don't know, but if you don't know this, I'll continue. DANIEL HAYES: Please go. LAURENCE H. BAKER: OK, but we all-- everyone knew, and certainly [INAUDIBLE] knew, this was an Italian drug, OK? "Adriamycin" is for the Adriatic Sea. As far as I know, you can't see the Adriatic Sea from Russia. But this was a time when our government wanted to be nice. They cared more about building a relationship with the Soviet Union than they did continuing a friendship with the Italians. Jim Holland was then sent to Moscow to negotiate this. That's where the name doxirubicin came from. In other words, we didn't know generic names, trade names. This didn't exist in the early '70s. So we called it adriamycin, which was not only the generic name, it was the trade name, right? Made by adria-- I think far Pharmitalia is the name of the company, right? And as a result of Jim Holland's diplomacy, it became doxirubicin as the generic name. It's a true story. DANIEL HAYES: Yeah. I know that "adria--" came from the Adriatic Sea, but I've not heard that's where "doxi-" came from. That's a good story. That segways into the next segment of your life that fascinates me, and this is your work in SWOG. When I moved here to the University of Michigan, you were on your way to becoming the chair of SWOG, which you did. And it occurred to me that University of Michigan wasn't even in Southwest Michigan, let alone the Southwest of the United States. Just reminisce a little bit about Dr. Coltman, who ran SWOG, the beginnings of SWOG, even before that, and where you see the [INAUDIBLE] groups now. LAURENCE H. BAKER: So Dr. V brought me to a SWOG meeting in San Antonio, Texas, as you said, in 1970 or '71. At the time, Tom Frei was running the group. J. Freireich was chairman of the Leukemia Committee. Chuck Coltman was chairman of the Lymphoma Committee. V specifically chose to work with this group because of those people. You're right, Michigan is not in the Southwest, obviously, and, there were other groups that wanted-- we had a large population of patients we treated, so there was actually some competition, if you will, for us to join other groups. V was adamant that we would be SWOG and that was it, for reasons that I told you. Tom Frei then was invited to go back to Boston. That's how you came to know him. And there was an election for a replacement. And J. Freireich was somebody that we clearly supported. There was no doubt that J. an absolutely brilliant man-- he still is-- and taught a lot of people, trained a lot of people, and taught us a great deal. But he had one flaw. He could not control his ability to saw inappropriate things. If you knew him, you loved him. If you didn't know him, you were like your reaction to the debate, OK? That's how he ground on people. I grew up with the respect for J., as I told you, as I was introduced to him, and he was always incredibly kind to me. Anyway, so we were actively supporting J. To be the replacement. There were some other people that did not want Freireich. So you had some people who didn't have the same feeling. And that's how Boris Hoogstraten became chairman. Boris Hoogstraten was a hematologist from the University of Kansas. And I remember-- and you'll be very proud of me, Dan-- one of my colleagues from Wayne wanted to do a study of this new drug called tamoxifen-- DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: --for breast cancer, OK? [LAUGHS] And Hoogstraten said, don't you get it, Baker? We're a chemotherapy group. What's with this hormone stuff? I don't have to tell another story, but that one is true. So SWOG didn't study tamoxifen for a long time. Any rate, Boris was an interesting man. I don't want to cut him short. But there came a time when it was clear that SWOG needed to go in a different direction. And we all thought that the right person for that was Chuck Colton. At the time, I have to tell you, there was two things relevant to this. There were lots of regional cooperative groups that don't exist anymore. I led a revolt-- that's what Colton said-- that included the University of Indiana-- Larry Einhorn was in Detroit plotting against Hoogstraten-- along with the University of Michigan. Al Labulio was in Detroit doing that. So you got the idea. So it was a group of institutions, if you want, that were geographically somehow related to the Great Lakes in some way. There were seven or eight of us. And we represented probably 40% of the [INAUDIBLE] of SWOG. And Coltman came to me and said, listen, stay with the group. Don't do this. Stay with the group. And I said, I can't stand this nonsense. I mean, we're not working anymore. We're just-- Anyway, he said, please stay. And he ended up becoming the chairman. And then he turned to me and he said, listen, Larry, I want you to be the deputy. I don't need a title. I don't want a title. He said, no, no, no, I don't care what you need or what you want. I need you right next to me, because if you led a revolt once, I don't want to see it happen again. DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: Absolutely true story. And so we abandoned the idea of a regional group. I still think that may have been a dynamite group, by the way. But we all stayed-- Indiana was not [INAUDIBLE] SWOG, so let me be clear. That was ECOG, I think. I think that's right. Anyway, so that's how I came to know Chuck, and I was his deputy for 25 years. I had the best job as deputy, because I had nothing to do. He just wanted me sitting there, and that's what we wanted. Then there was some push from the NCI that maybe to 25 years of being chair is a long time, and maybe there's a reason to move on. From that team the suggestion from Bob Livingston and John Crowley, that I was the natural person to do that. I really didn't want it, to be honest. I still maintain that. But there was a good deal of pressure exerted, both from within the group and from the NCI, for me to do that. So I became the chairman, I think, for a couple of terms. I made some changes in the group. I think as groups go on, institutions either get better or they get worse. I think that's true. And we made a number of different ways of appointing disease chairs and things like that, that the group did get better and started on a better path. But I really didn't want to continue it, and there was a time when I was not only running SWOG, but I was also running this sarcoma group called SARC. And it became overwhelming to me. I was working literally 80 hours a week there. So I gave up SARC first. That really-- University of Michigan was thrilled that I did that-- and stayed with SWOG another year or two. But I knew that I wasn't going to stay at that. And so after two terms, I thought I would set the precedent that, maybe, group chairs should have two terms and move on. Witshoski had two two terms. [LAUGHS] But anyway, being serious, I really think there should be a limited amount of time. There's so many talented people in our field that it's silly to think that one person has to stay in these jobs. And so that's-- I think I answered your question. I'm not sure my [INAUDIBLE]. DANIEL HAYES: I have to tell just a brief-- Nobel laureate Bruce Beutler was my intern when I was a resident at UT-Southwestern. After he won the prize, he came up here as a visiting professor, and we went to dinner. And I said, Bruce, I kind of lost track. I know you did an internship with us, but I never heard if you finished your clinical training. And he said, no, I went-- I loved the lab and went back into it. I never did go back and finish my training [INAUDIBLE]. And then he looked at me and said, but I think I worked down all right, don't you? LAURENCE H. BAKER: [LAUGHS] DANIEL HAYES: And in a similar manner, I would say, for all your humility that you've laid out, I think it worked out all right. SWOG is a powerhouse and has changed practice in so many ways. And part of that, a lot of that, was your doing. So we've actually run out of time. I had hoped, actually, to-- you've done too much in your lifetime, Larry. I was hoping to get into the sarcoma work, but we've run out of time. I think everybody who's listening to this who knows about the work you've done in sarcoma-- and lord knows there's plenty of work to do in sarcoma, so-- LAURENCE H. BAKER: Can I give you just one more anecdote, and you can cut it, and I'll try to be very [INAUDIBLE]? DANIEL HAYES: No, no. Please do, please do. LAURENCE H. BAKER: Remember I told you I became chair of the Sarcoma Committee of SWOG? The man I replaced was a man named Jeff Gottlieb. Jeff was a pediatric oncologist-- little did people know-- who was a student of J and Tom at the NCI. Jeff died in his mid-30s of cancer, by the way, but he was the most brilliant medical oncologist I ever met. He was the originator of combination chemotherapy that became popular in breast cancer, and he was involved in sarcomas in combinations as well. I was handpicked by Jeff to be his replacement, which was probably the nicest thing that ever happened to me. And during that period when Jeff died, I went to Houston to his funeral. And I can give you one-sentence description of J. Freireich going to speak at Jeff's funeral. He stood up, and he said, Jeff-- and he broke down and cried for minutes. And that was his talk. When anyone says something to me critical of J. Freireich, I remember that love he showed to his colleague. So that's worth [INAUDIBLE]. DANIEL HAYES: No, that's-- LAURENCE H. BAKER: Not many people were at that funeral. DANIEL HAYES: --very touching. He also gave Dr. Frei's eulogy in Boston, and he got through it, but just barely. It was very similar. These are the kinds of stories I'm hoping to capture in this series. Larry, I'd really like to thank you for taking time to be on. I'd also like to thank you for all you've done for the field, for me personally, frankly, with my time here in Michigan the last 20 years, and most importantly, for our patients who have benefited from all your contributions, your training of-- we could go on about all the people you've trained. So anyway, thanks a lot. We appreciate it. LAURENCE H. BAKER: Thank you. DANIEL HAYES: And have a nice day. LAURENCE H. BAKER: Thank you very much. I appreciate your kind words. DANIEL HAYES: Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one ASCO's many podcasts. You can find all the shows at podcast.asco.org
Hello boys and girls,In today's wonderful interview, I get to speak to the future!! Yes, my guest today is 14 hours ahead of me in Australia. As you know, I am a big fan of riders using a motorcycle that is completely inappropriate for the job or task at hand. My guest today, could easily be accused of such fun. His YouTube channel has 55 thousand subscribers where his adventures include everything from selling real estate to riding a Honda Monkey in the desert. It's The Million Dollar Bogan, Danny Hayes. Hey, now is your chance to get your Motorcycle Men shirt!! Yes, that's right, you can now get yourself a Motorcycle Men short sleeve T, Long Sleeve Tee, Sweatshirt, Hoodie or Polo shirt. The fine folks at Great Plains Apparel were kind enough to put together this wonderful package for us and shirts are waiting for you!!Special Thanks to our Sponsors: Tobacco MotorwearShinko TiresScorpion Helmets Wild-Ass SeatsThe Motorcycle Men Support David's Dream and Believe Cancer FoundationThe Gold Star Ride Foundation Don't forget to get over and check out the Ted Shed Video's over on the Motorcycle Men Channel on YouTube. Thanks for listening, we greatly appreciate you support. Ride Safe and remember.... .... We say stupid crap so you don't have to.Support the show (https://www.paypal.com/donate/?token=zPl7v5FjoO6fCov5rwbFo35sxmoOIUqUhcR1q1UVtP34xAVolJzW0aJ6GNSdljsPAT4MC0&fromUL=true&country.x=US&locale.x=en_US)
With the final episode in this series we have several helpful resources to recommend: John Piper, Bloodlines: https://smile.amazon.com/Bloodlines-Cross-Christian-John-Piper/dp/1433528525/ref=sr_1_1?crid=A0KGDPBEVP9R&dchild=1&keywords=john+piper+bloodlines&qid=1593697554&sprefix=john+piper+bloo%2Caps%2C175&sr=8-1 Daniel Hayes, From Every People and Nation: https://smile.amazon.com/Every-People-Nation-Biblical-Theology-ebook/dp/B01D8W4HXC/ref=sr_1_1?dchild=1&keywords=hayes+from+every+people+and+nation&qid=1593697617&sr=8-1 Shai Linn, George Floyd and Me: https://www.thegospelcoalition.org/article/george-floyd-and-me/ Mark Dever and Jamie Dunlop, Compelling Community: https://smile.amazon.com/Compelling-Community-Church-Attractive-9Marks/dp/1433543540/ref=sr_1_1?dchild=1&keywords=compelling+community&qid=1593697641&sr=8-1 Isabel Wilkerson, The Warmth of Other Suns: https://smile.amazon.com/Warmth-Other-Suns-Americas-Migration/dp/0679763880/ref=sr_1_1?crid=CZEQMI19RKEO&dchild=1&keywords=the+warmth+of+other+suns&qid=1593697655&sprefix=the+warmth%2Caps%2C177&sr=8-1 Neil Shenvy, Social Justice, Critical Theory, and Christianity: Are They Compatible? https://youtu.be/E33aunwGQQ4
With the final episode in this series we have several helpful resources to recommend: John Piper, Bloodlines: https://smile.amazon.com/Bloodlines-Cross-Christian-John-Piper/dp/1433528525/ref=sr_1_1?crid=A0KGDPBEVP9R&dchild=1&keywords=john+piper+bloodlines&qid=1593697554&sprefix=john+piper+bloo%2Caps%2C175&sr=8-1 Daniel Hayes, From Every People and Nation: https://smile.amazon.com/Every-People-Nation-Biblical-Theology-ebook/dp/B01D8W4HXC/ref=sr_1_1?dchild=1&keywords=hayes+from+every+people+and+nation&qid=1593697617&sr=8-1 Shai Linn, George Floyd and Me: https://www.thegospelcoalition.org/article/george-floyd-and-me/ Mark Dever and Jamie Dunlop, Compelling Community: https://smile.amazon.com/Compelling-Community-Church-Attractive-9Marks/dp/1433543540/ref=sr_1_1?dchild=1&keywords=compelling+community&qid=1593697641&sr=8-1 Isabel Wilkerson, The Warmth of Other Suns: https://smile.amazon.com/Warmth-Other-Suns-Americas-Migration/dp/0679763880/ref=sr_1_1?crid=CZEQMI19RKEO&dchild=1&keywords=the+warmth+of+other+suns&qid=1593697655&sprefix=the+warmth%2Caps%2C177&sr=8-1 Neil Shenvy, Social Justice, Critical Theory, and Christianity: Are They Compatible? https://youtu.be/E33aunwGQQ4
Dr Hayes interviews Dr. Lawrence Einhorn and patient, John Cleland, on the cure for testicular cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to JCO's "Cancer Stories, The Art of Oncology," brought to you by the ASCO Podcast Network, a collection of nine programs, covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Welcome to the "Cancer Stories." I'm Dr. Daniel Hayes. I'm a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center. And I've also been privileged to be the past president of ASCO. I'll be your host for a series of podcast interviews with the founders of our field, have been, and will continue to be over the next several months. In this series of podcasts, I'm hoping to bring the appreciation of the courage and the vision and the really scientific background among the leaders who founded our field of clinical cancer care over the last 70 years. I hope that by understanding the background of how we got to what we now consider normal in oncology. We can all work together towards a better future for our patients and their families during and after cancer treatment. Today, my guests our Dr. Larry Einhorn, who first demonstrated the cure of testicular cancer with cisplatin. And we have a special guest, Mr. John Cleland, who as far as I know was the first man to be cured of this cancer with cisplatin in the world. Dr. Einhorn is currently the Distinguished Professor of Medicine on the faculty of the section of hematology oncology at Indiana University School of Medicine. Mr. Cleland is now retired after a distinguished career as a high school teacher in track and field coach in Indiana. This interview is really particularly poignant for me. I knew John Cleland socially before I had ever heard of Larry Einhorn because our respective wives worked together while I was in med school as I began my clinical training. I then had the enormous privilege of being assigned to the oncology ward at the University Hospital for one of my rotations in internal medicine during my third year of medical school in 1977. And Dr. Einhorn was the attending. And frankly, for me, the rest is history. I had no chance. I had to become an oncologist. Dr. Einhorn received his undergraduate degree at Indiana University, went to medical school at the University of Iowa. He then returned to Indiana for his residency and fellowship. But he spent an oncology fellowship year at MD Anderson, Houston. After that you then returned back to IU in 1973 and has remained there ever since. He has won nearly every award and honor available in clinical research. And I'm not going to try to name them all, but most importantly, like me, as many people in this podcast series, he has served as president of ASCO, in his case, in the year 2000 and 2001. Dr. Einhorn and John, welcome to our program. Thank you. Thank you. Thank you. Dr. Einhorn, I'll start with you. Obviously, your greatest contribution is the cure for testicular cancer, which is pretty good. Can you kind of walk us through the history? How did you get involved with cisplatin? How did you derive the three drug regimen? What were the early obstacles? Especially with your returning back to Indiana. Can you kind of just walk us through that history? Certainly. So as you mentioned, I did a one-year fellowship in oncology at M.D. Anderson before returning to the faculty in 1973 and Indiana University. And in that time period, which was 46 years ago, the thought was that you might be able to cure adult leukemia like was cured with childhood leukemia from the wonderful studies from St. Jude's and that the studies that were ongoing in lymphomas and other hematological malignancies were very promising. But it was felt that you really don't want to do too much toxicity in a solid tumor, where you're getting a one log kill before you get progressive disease. And there was a clear pervasive atmosphere of pessimism of what can be done with solid tumors in general. So when I joined the faculty in 1973, I was the only oncologist. We had two hematologists that were there in our small faculty, which went from 2 to 3. And I wanted to be involved with both liquid tumors as well as solid tumors. But I wanted to be involved with solid tumors that were chemo sensitive. And even back in the early 1970s, testicular cancer was responsive to older drugs like actin or myosin-D and later with a two-drug combination of vinblastine plus bleomycin. And there were a small number of not just remissions but cures, and that was one of the few solid tumors that actually had a modest cure rate back at that time. And then the platinum story came around. And this is a podcast of itself with the wonderful work of a biophysicist at Michigan State, Dr. Barnett Rosenberg, who first discovered that platinum could be the first heavy metal ever to be looked at as antineoplastic agent. And when platinum entered first in human clinical trials in 1972 and 1973, it was [? selfed ?] at an NCI-sponsored phase I working group that I attended that this drug was producing minimal benefit and tremendous toxicity, especially horrendous nausea and vomiting. And the drug was pretty close to being discarded as a interesting novel mechanism of action, but not a drug that really had much of a future. But what changed the history of platinum and changed the history of testis cancer was the fact that among the phase I patients were treated with platinum, which included melanoma, lung cancer, colon cancer, breast cancer, the usual type of patients that enter phase I studies back in those older days were 11 patients that had testicular cancer who had failed actin or myosin D, failed vinblastine, plus bleomycin, and so they received single agent platinum. And when we, even today-- Actually, where were those studies done? That was done at Roswell Park actually, phase I study. And Roswell Park-- and this was an era, by the way, that there were only four NCI cancer centers in the United States, Roswell Park, M.D. Anderson, Memorial Sloan Kettering, and, of course, the NCI. So Roswell Park did a broad-based phase I study. Jim Holland was there at that time. He has unfortunately subsequently passed away. He was one of the real pioneers and also a past ASCO president. So among the patients in that phase I study were 11 patients with testes cancer. And there were three complete remissions and two partial remissions. And even in 2019, if we saw that with the phase 1 novel agent, there would be a tremendous amount of enthusiasm generated. We also looked at some of the preclinical work with platinum. And it is a drug that can cause testicular atrophy. In my youthful ignorance, I didn't realize that there are many drugs that cause testicular atrophy. So with that as a background, in 1974-- and I was on the faculty for one year at that time-- we wrote a protocol to simply add platinum, a novel experimental drug, and added it to the established two-drug regimen that I learned about when I was at M.D. Anderson, namely vinblastine and bleomycin. And the principles of combination chemotherapy aren't complicated. We want each drug to have single agent activity, different mechanism of cytotoxicity, different toxicity, and platinum as a non-mild suppressive drug, which can be given in full dosage, with vinblastine as a mild suppressive drug, and evidence of synergy. And one of the unique characteristics of platinum is it is synergistic across a panoply of cytolytic agents. So we started to study in the late summer of 1974 as a phase II study. And so we treated 47 patients when we first presented this data at the American Urological Association, later at ASCO. And I would be the first to admit that I was as startled as anyone that we were able to literally have a one logarithmic increase in the cure rate, because most progress in oncology is going from a 5% to a 10% to a 15% long-term survival rate. But all of a sudden with this three-drug combination, 60% of these patients were not only complete remission, but durable complete remission and cures. There was a lot of toxicity with platinum. And over the years, we learned, as science tends to learn, when a drug is active to mitigate the side effects as far as nephrotoxicity and nausea and vomiting. And we made modifications to the treatment regimens as the years went by, as you know, with changing the dosages have vinblastine, lowering the duration of maintenance therapy, and eliminating maintenance therapy, reducing the number of courses of platinum, substituting etoposide for vinblastine to where it's now the standard, bleomycin, etoposide, platinum, or BET. And I will make a final comment, in my long career, that this was a very exciting time in 1974. There were several chemotherapy drugs that were experimental drugs, such as doxorubicin and even a nitrosourea the first drugs to have penetration into the blood brain barrier. But the era of chemotherapy is gone and appropriately so. And science and medicine has moved forward. And now, we look at molecular targeted agents and immune checkpoint inhibitors and immunooncology. And that's what is exciting, so much more exciting about the field in 2019 than it was in 1974. But nevertheless, platinum has had legs. In 2019, it is still first line therapy in 12 different types of malignancies. Of course, testis cancer being the poster child for curable cancer. And I often mention that just as platinum has cured thousands, tens of thousands, hundreds of thousands of young men with cancer, testicular cancer saved platinum, because if it weren't for those early studies showing activity of platinum, I think I can say without fear of contradiction that the drug wouldn't be around right now because of this tremendous toxicity in the early phase I studies. Yeah, Larry, let me ask about that, because in the early 1970s when-- I wasn't around, but you didn't have antiemetics. You didn't have drug fractures. You didn't really understand the renal toxicity. Just briefly, how did you get around those? How do you get people-- I'm going to ask John the same question in a minute. What were you thinking, John? John is the recipient of our ignorance in that era. So taking it one item at a time. Platinum is a heavy metal. And we were somewhat slow in realizing that other heavy metals, like mercury, can cause acute tubular necrosis. And so when patients were getting platinum, as is true in those days, they would often just get IV pushed platinum. And so we learned that in order to prevent acute tubular necrosis, we needed to make sure that patients were well hydrated with IV saline solution before they start chemotherapy. We then give the intravenous platinum and then follow that with intravenous saline hydration, so that the drug doesn't accumulate in the proximal tubules, and we force a diuresis. And we never needed mannitol. And some people back then, in fact, perhaps even now, are doing the silly thing of mannitol diuresis, which is totally unnecessary. And so back in the early days before we had antiemetics, everyone had to be treated as an inpatient because we had to give 24-hour continuous hydration because of the [INAUDIBLE] from severe nausea, vomiting, and dehydration that would happen. Of course, today, it's all done as an outpatient with three or four hours of hydration. As far as nausea and vomiting is concerned, one of our first studies we published in The New Journal of Medicine was a cannabinoid derivative from Eli Lilly, called nabilone. And so nabilone, didn't produce a marijuana-type of high. It didn't cause euphoria. It caused some dysphoria and had a variety of side effects. But it lowered the incidence of nausea and vomiting. But what revolutionized chemotherapy induced nausea and vomiting, and ASCO recognizes this as one of the five leading advances in the past 50 years, was the discovery of the first 5-HT3 receptor antagonists. And this was a rational, selective pharmaceutical development. And this truly changed the face of how we give chemotherapy with drugs like platinum. Instead of having an average of 10 to 12 emetic episodes on day 1 of platinum, today with appropriate anti-emetics, the median number of emetic episodes is zero. People still get nausea. People still get occasional vomiting. But everything is done as an outpatient now. And it's done as an outpatient because of the discovery by others of what is the mechanism with platinum, which is not a gastrointestinal mechanism, but affects the emetic center in the medulla oblongata and the chemo receptor trigger zone and finding that patients get drugs like platinum, they get high level of 5-HT3. And developing a selective 5-HT3 receptor antagonist change the field completely. And, of course, now we also [? weigh ?] a methasone and neurokinin-1 antagonist, aprepitant or fosaprepitant. And we also have olanzapine as far as the nausea issue. And olanzapine is probably the best drug for nausea. So patients today have no concept of what patients like John went through when we had no knowledge about any of this whatsoever. And we were looking at things kind of naively by 2019 standards. I don't think I'm making this up. I recall as a medical student walking down the inpatient at University Hospital and thinking this smells just like my fraternity house. Without the fun involved. Yeah. And I got a kick now out of the so-called medical marijuana. But didn't you talk the administration into looking the other way for a while so that these guys could do that? Sort of. What had happened with nabilone, it had to be under lock and key, as if it were gold at Fort Knox. When we had an audit by the FDA and we had-- I don't know how many, I think 60 or 70 patients on nabilone, you know, we had to make sure we had every consent form and every safety guarded and everything. You know, here, we're using these incredibly toxic chemotherapy drugs and there was no regulation at all. And here we're using a pill to lessen nausea and vomiting, and it was just the hoops you had jump through were tremendous. When did you start realizing you had something big. Was it, you know, after two, three patients, or later-- Well, again, when you're young and dumb, it's easy, because you treat someone like John and you get the first chest X-ray three weeks later and things are gone and with pulmonary metastases. And you naively think, not only this cool, but, gee, that's great, it's not going to come back again. But we know even 40 years later that most epithelial malignancies that we get nice remissions with, the disease does come back again. So we had initial enthusiasm that platinum vinblastine myosin was a very active, but very toxic regimen. And we had the hope that this might be durable remission. And, Dan, I actually first presented data with testes scores, not at ASCO, but with the Annual American Urological Association meeting, and that was 99% urologists there. And so we had 20 patients that we had treated. And then that following year, I submitted an abstract to ASCO. And back then, it wasn't done online. We would send a paper abstract with a self-addressed postcard that they would send back to us whether it was accepted or not. And so when I sent in the abstract, I get the postcard back saying it was accepted as a plenary session paper. And I had no idea what plenary session even meant. It's true. And we get this postcard back in January for this June meeting. And all of a sudden my naivete went away, and I thought what, if I make a fool of myself? And I had this initial abstract with these complete remissions, and by the time June rolls around every one of them would have relapsed, which I was starting to learn happens in other tumors like small cell lung cancer, that are chemo sensitive disease. But fortunately, the time of presentation everyone was still disease free. And, of course, everyone for the most part remain disease free. So we had the first glimpse of activity with the first few patients. But it really wasn't until patients were out at a year that we really had the realization that these were not temporary remissions, but these were durable. And as it turned out, permanent remissions and cures. I wasn't there, but I understand that after you recorded that it looked like you had change the ratio of [? puranoctur ?] from 10%, 90% to 90%, 10%, that people in the audience, you had a standing ovation at the end of your presentation. Yeah, it was very heartwarming. It's literally the walk on the moon type of things is the things that you do once in your career, you know, that you never forget about. I had the opportunity to do that and not one of those four NCI cancer centers, but little Indiana University with our faculty of three. And we had one oncology nurse at that time, Becky Furness. We had no data managers. We had no compliance office or anything else. And we were giving [INAUDIBLE] back in the 1970s. I'd like now to turn briefly to your relationship with John Cleland. John, can you give us a brief history of your cancer treatment before you and Dr. Einhorn decided to go with the cisplatin. I was a student Purdue University, the fall of 1973, when I discovered I had a lump on the my left testicle. And I went to a local urologist. And he examined me on a Tuesday afternoon, in the middle of November, and told me he wanted me at the hospital the following morning. And the following day after that, they performed surgery. And I was diagnosed with testicular cancer. That was November 15, 1973. On the 29th of November then, I had a retroperitoneal node dissection. That was at the UI Cancer Center by Dr. John Donohue. And then on December 3, 1973, on a Monday morning, Larry Einhorn walked into my hospital room. And that was my first introduction to Dr. Einhorn. He talked to me a little bit and said we were going to put me on a 5-day course of a drug called mithramycin. We took mithramycin for five days. And then a couple of days after that, I was released from the hospital. So that was in the 1st of December of 1973. The middle of February of '74, I returned to IU Med Center just for a routine checkup. And I was diagnosed there again with testicular cancer had returned. And Dr. Einhorn began putting me on a three-drug regimen-- adriamycin, bleomycin, and [INAUDIBLE]. And I was on that until about July of '74. Then I was on actin myosin-D for a couple of months. And then we ultimately started in on the cisplatin in early October of '74. You have to tell us the story that you actually had to tell Dr. Einhorn about cisplatin because of a radio show you listened to. Well, by the middle of the summer, I had been pretty beat up, after all the chemotherapy and the nausea and everything. And I didn't really have a job-- or I couldn't do a job or anything. So most of the time, I just lay on the couch in our apartment and listened to the radio or watch TV. And one day-- I really like Paul Harvey-- and he came on the radio every day at noon there in Lafayette, Indiana. And one day he begins talking about researchers at Michigan State University. have maybe come up with the cure for cancer. So I begin listening much closer. And they talked about this chemotherapy called cisplatin. So I just made a mental note to myself, well, the next time I go see Dr. Einhorn, I'm going to ask him about this. Well, a couple of weeks later, I'm down at IU. And he's palpating me and listening to my chest and all this type of thing, you know. And I began asking him about that. And he said, John, just don't get too excited about that. We've heard of these cancer cures before. Probably nothing important has happened here. Don't worry about it, you know. And then two or three months later, I'm taking it. So that was my introduction, Dan, to cisplatin. Well, I can't to you-- Some of those Purdue graduates are pretty smart every now and then. We get lucky, like a blind squirrel. I just say, I can't tell you how many-- probably 100, 200 patients will told me things like this. And I've said exactly what Dr. Einhorn said to them, yeah, yeah, yeah. I wonder how many cures I've missed. OK, and the second story I want you tell us, John, is about your readmission to the hospital after your first cycle of chemotherapy. Yeah, I started this platinum October 7, 1974. I had five doses in the hospital. And then I was released. That was on October 7. October 20 rolls around, which was a Sunday, and I was violently ill. I had a fever of over 104, almost 104 and 1/2. And I was just completely almost derelict. My wife and a couple of friends, we contact Becky first, us my oncology nurse. And I guess she called Dr. Einhorn. And he said, well, come on down and check in through the emergency room at IU. And so that's what we did. We got there late at night, 9:30, 10:00 at night, something like that. And they always-- if I went to the emergency room, they always took a chest X-ray, which they did. And then in the hospital overnight and middle of the next morning, I see Dr. Einhorn and Becky getting off the elevator. My room was kind of in a corner. I could see part of the lobby out there and the elevator and the nurses station. And I could see them kind of go past the nurses station. And I could just tell that something was up. Somebody had good, let's put it that way, just by their body language, and the way they looked at each other and talked and walked. And they kept coming closer and closer and closer to my room. And finally, they walked in. And Dr. Einhorn says, John, your chest X-rays are clear. That's really good news. And, you know, I kind of interpreted that as, hey, I'm cure, you know. And ultimately, I guess I was, because from that chest X-ray the night before, my chest film was-- the weak before, my chest film was just riddled like Swiss cheese. And then the film was totally clear. You probably don't know this, but I've seen your chest x-rays, which is probably illegal now. Probably did a lot of illegal things back then. And, you know, that's when the scales fell from my eyes and I said, I'm going to be an oncologist. This is unbelievable. But, you know, I think to emphasize, it wasn't clear you were going to survive that weekend. To survive, you would be cured. But that goes back to how toxic this drug was at the start. Right. Right. It was not a lot of fun. I know that. Yeah. Well, I want to get back, Larry, to you for a moment, because there were two people in your life who were really essential to this story. One, of course, was Dr. Donohue, with whom you have published the, I think, seminal and classic paper in the annals of internal medicine. You want to say a few words about John. And the other is I'd love you to talk a little bit about Steve Williams. Steve was a fellow when I was a med student that I used to tease-- I mean, he's the only guy I ever knew who went from being a fellow to cancer center director I think in one year. I'm making that but-- he kept saying, you know, I might as well put me on faculty because he doesn't have any other fellows. Sure. So when I joined the faculty in 1973, in July of 1973, as I mentioned, I was the first oncologists. There were two hematologists there. And John Donohue is a true gentleman, one of the world leaders in urological oncology and the urological transplant with kidney transplant and many other fields. His ability to surgically cure patients with extensive retroperitoneal disease was known worldwide. And because of who John was and the fact that there were very few oncologists in the state of Indiana treating solid tumors, when he would see patients who would relapse after a retroperitoneal lymph node dissection, he would give chemotherapy himself, usually with actin myosin-D, which, by the way, causes almost as much nausea and vomiting as platinum did. And when I first got there, I knew John by reputation, but not by his interpersonal relationships with others. And with some fear and trepidation, I walked into his office because I told him I wanted to start looking at clinical trials in testes cancer. And I thought we might have a turf battle because he was treating patients with chemotherapy himself. And he just welcomed me with open arms. And he was so enthusiastic about finally having a partner and someone to collaborate with. And we had a wonderful, 30-plus years of collaboration with many important discoveries that John made equally, as I did. And, unfortunately, after John retired, he subsequently died when he was in Florida. And it's a similar sad story with Steve Williams. So Steve Williams was in my third fellowship class, which means we had one fellow a year. He was great, very humble, from Bedford, Indiana. And father was a newspaper reporter from the small town newspaper. And Steve was the eternal optimist. And to show you what an eternal optimist he was, when the Indianapolis Colts would those 14 games in a row, he always knew they going to win the next game, you know. And that's Steve. And John Cleland talking about Paul Harvey, Steve would have believed that platinum was going to be the cure too, you know. He was just a very positive person. And Steve was very gifted. He has a great relationship with patients. And there's not a person, a doctor, nurse, or patient, who has ever said anything unkind about Steve. He's one of the kindest people that we ever had the privilege of knowing. And Steve was very much involved with our testicular cancer research studies and many other pivotal studies as well. We decided to be a NCI cancer center, which is an enormous amount of work. And by then, we had about 10 faculty members in hematology, oncology. And no one wanted to do it. And so we went up to poor Steve and said, boy, Steve, this would be a great career move for you-- without telling him how much work is involved. We are cancer center today because Steve Williams made us a cancer center and everything that goes along with that. And before leaving, and fortunately, we're talking about John being cured with fourth line therapy with platinum combination chemotherapy, whereas if John had had that disease diagnosed a year earlier, quite honestly, John, you wouldn't be alive right now. And it's sort of the opposite for Steve Williams. He eventually developed metastatic melanoma before any of the marvels with immunotherapy or even the BRAF inhibitors were around. And he eventually died from these diseases that he fought so hard to palliate and prolong survival and cure with metastatic melanoma. And now there's a 30% cure rate-- 30%, 5-year survival and continuous 5-year survival with single agent PD-L1 inhibitors. And I want to make a final comment about John. And if this were 2019, rather than 1974, and you're looking at a patient who has been through mitramycin, which is used by me as adjuvant therapy briefly for adenocarcinoma, which is what John had, and then going through actin myosin-D and all the toxicity with that drug and then gone through a adriamycin combination chemotherapy, and looking at fourth line therapy. So when we started platinum combination chemotherapy, and John his fourth line therapy, yes, his chest X-ray looked like Swiss cheese, as he mentioned, but he was pretty much asymptomatic. And the courage and fortitude that it takes to go through treatment like this, because we knew what the side effects were with platinum. It had been around for about eight months, and we knew about all the horrendous side effects of the drug. We had no idea whether this would produce as fourth line therapy any prolongation of survival or any meaningful quality of life. And to go through this therapy without any idea whether it's going to help you, but to do it with truly altruistic motives and knowing that maybe this will help other patients in the future is really noble and admirable. And this is why John over the decades has been such a role model for clinical trials and for the cancer patient population. And I want to follow up. John, briefly, tell us about your history since then-- your family, your athletics, your career. I think it's inspirational, frankly. Well, I worked for the animal science industry for five years following my cure. And I decided finally I needed to give something back a little more to society than what I was actually doing. So I knew I wasn't smart enough to be a medical doctor. Male nursing wasn't exactly in vogue at that time, which might have been honestly a pretty good job for me. So I thought, well, I could be a teacher. I can teach life sciences. So background is pretty much life sciences in agriculture. So I did. I turned to teaching and teaching biology for 31 years and did a lot of coaching of track and cross country. And my wife and I have three kids. I married my college sweetheart even before I had testicular cancer. And, you know, I owe her just about everything in life. She hung in there with me when times were really dark. And I say we got three kids. And I've had great job and great career and friends. I want to emphasize you've had three children since your treatment. I also want to emphasize I know you've run one or two marathons since your treatment. Actually, Dan, I ran four marathons. So you ran four marathons since your treatment. Four full marathons, yes, sir. And I believe that your baseline creatinine is something like twice normal. And, Larry, you probably know this better than I do. But, again you've been inspirational to all of us. Well, thank you. Thank you, Dan. I'll tell you this. Every day I live is a blessing. I should have probably died 44, 45 years ago. I could drop dead at the end of this telephone conversation and have no regrets in life whatsoever. Well, John, you keep thinking that maybe one day you'll live long enough to see Purdue win the NCAA, but I wouldn't count on it. I was going to make a point, it must pain him truly to thank two guys from Indiana and also be appreciative of Michigan State, you know, for a guy from Purdue that must really be painful. Well, yeah, you know, testicular cure is basically Big 10 centered with Michigan State coming up with this cisplatin and Dr. Einhorn being on the IU you faculty. But it took a Purdue Boilermaker to be tough enough to handle all that to begin with, you know. That's true. OK, we're running out of time. I need to bring this to an end. I want to thank both of you again, both of you're inspirational, John for all the things we've talked about and Dr. Einhorn for so many of us who've gone into the field that we've trained and even the ones we've never touched directly, you touched hundreds of thousands of oncologists around the world indirectly. So thanks for all your contributions and what you've done. And thank you both for being on this podcast. I hope it opens up more inspiration for other young investigators and other young oncologists who don't really realize how we got where we are. So with that, we'll end this. And thanks a lot. And hope you have a nice weekend. OK, thanks, everyone. Have a good rest of the week. Bye, bye. Until next time, thank you for listening to this JCO's "Cancer Stories, The Art of Oncology" podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's "Cancer Stories, The Art of Oncology" podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org
In 2011, Michelle together with her business partner Daniel Hayes opened up their first office in Highton Geelong. They were quickly talk of the town with their bright pink signage & quirky advertising. Their competition even laughed at them until their property management department grew to more than a quarter of a billion dollars worth of investments. Michelle started her journey as a single mum of 2 kids & overcame challenges with anxiety & alcohol addiction. Today, Michelle is a well respected successful business woman & a role model to women. --- Send in a voice message: https://anchor.fm/janelle-johnston/message
Dr. Hayes interviews Dr. Trevor Powles his involvement with translational medicine in the UK and early bisphosphonate. Conflict of Interest: Dr. Powles has not reported any conflicts of interest to ASCO. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to JCO's Cancer Stories-- The Art of Oncology brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all the shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist, and I'm a translational researcher at the University of Michigan Rogel Cancer Center in Ann Arbor. And I'm also the past president of the American Society of Clinical Oncology. Today I am privileged to be your host for a series of podcast interviews with the founders of our field-- today in particular Dr. Trevor Powles. Over the last 40 years, I've been fortunate to have been trained, mentored, and inspired by many of these pioneers. It's my hope that through these conversations all of us can be equally inspired by gaining an appreciation of the courage, the vision, and frankly the scientific understanding that these men and women who established the field of clinical cancer care over the last seven decades. By understanding how we got to the present and what we now consider, quote, "normal," end of quote. I hate using quotes, but in oncology I think we can also imagine our work together towards a better future for our patients and their families during and after cancer treatment. As I've noted today, I'm really honored to have as my guest on this podcast Professor Trevor Powles. He's really generally considered one of the true pioneers in breast oncology. Dr. Powles was raised in London, where he went to medical school. He trained in medicine and surgery at St. Bartholomew's Hospital and associated affiliates, graduating from medical school in 1964. He went on to obtain a PhD at the Institute of Cancer Research. He directed his thesis towards hypoglycemia and bone metastasis. Following his PhD, he then completed specialist training in medical oncology at the Royal Marsden and further pursued training in endocrinology with Professor Philip Bundy, [? who was ?] then Chief of endocrinology at Yale before moving to the UK. Dr. Powles remained at the Royal Marsden hospital during the bulk of his distinguished medical career, first as head of the Marsden breast cancer unit, and ultimately is the founding chairman of the Committee for Clinical Research for the entire Royal Marsden. After he retired-- which again requires [INAUDIBLE]-- at the age of 65, Doctor Powles has served on staff at the Cancer Center at London Parkside. Dr. Powles has authored hundreds of peer reviewed papers. He's mentor of many of the leaders in breast college around the world, which we will discuss in a second. And he's really won too many awards and honors from me to list here, but they include the coveted William McGuire Award presented annually at the San Antonio Breast Cancer Symposium-- and by the way, so have two of his mentees, Professors Mitch Dowsett and Ian Smith. And he's also won the Nancy Brinker Award. Many of you know Miss Brinker founded the Komen for the Cure Foundation. And perhaps what is perplexing to those of us in the colonies, in 2002 he and his twin brother Ray were named Commanders of the Most Excellent Order of the British Empire, or CBE for short-- which of course is one of the highest honors one can obtain in the UK-- for their work in breast in Trevor's case, and haematologic cancers in Ray's case. Trevor, I know that a lot of your work also was done with a variety of other contributors, including Dr. John Kanis, Dr. Eugene McCloskey, and of course Sandy Patterson [? period. ?] You've always been quite generous in pointing out that they had a lot to do with your own contributions, and we appreciate that as well. Dr. Powles, welcome to our program. Thank you very much, and thank you for those kind words. Yeah. Actually, I interviewed someone a few weeks ago, and he said, "Geez, that sounded like my mother wrote that." [LAUGHTER] I have a number of questions for you, and I want to start out-- your research and your background was really in endocrinology of the 1960s. And that was a particularly exciting time for endocrinology with the discovery of the hormones not more than 20 years before that, and then the increasing knowledge of understanding of [? the ?] peptides steroid hormone receptors. What made you veer off from that field into oncology in general and breast cancer specifically? When I was working at the Hammersmith Hospital doing my endocrinology [INAUDIBLE] endocrinology there. And one of the conditions we would be looking at would be hypercalcemia with hyperparathyroidism. And hypercalcemia was occurring very commonly in the breast cancer patients in the oncology and the radiotherapy department. [? And ?] to begin with, we thought this would just be another paraendocrine-type syndrome, and that was the thing that really fired my interest. From there, I then wanted to do my PhD to look more into what was causing the hypercalcemia with breast cancer, and that started the whole path of finding out about bone metastases, what they were doing, how they were causing the hypercalcemia, and the path just continued and continued. Most of your work-- I'm going to get to some of the other things you've done-- has been endocrine therapy, endocrine processes, and the bone metastasis, which is really endocrinology. In the United States about that time, most of the excitement in the 60s was around chemotherapy. Was it difficult for you to stick with the endocrine approach? No, it wasn't really. When I first started, all of in the endocrine treatment was ablative treatment. And I knew that from when I was doing my endocrinology is that the hypophysectomy, adrenalectomy, oophorectomy, those were the early days for chemotherapy at using combination chemotherapy and metastatic disease. [INAUDIBLE] and endocrine therapies were far better treatments from the chemotherapy. And although I was doing chemotherapy because we started with single agents then combination treatments-- and there was a lot of chemotherapy going on at that time at the milestone for haematological cancers, lymphoma, teratomas, et cetera-- I was able to do that, but I really focused on the endocrine side. And coming back to the hypercalcemia, the one thing that really impressed me was when I was originally doing my endocrinology was that rapid response you could get to the hypercalcemia by ablative endocrine therapy for oophorectomy, or adrenalectomy, or hypophysectomy. And that was really the thing that started all of the research I did in bone. It started on my PhD with in vitro work. We set up bone assays, I went to Cambridge to [INAUDIBLE] very famous scientist Cambridge to teach us how to do the bone assays for in vitro bone assays. We also set up the animal model with breast cancer. We were able to show that breast cancers could cause bone breakdown and osteolysis in vitro. We could find that we could block that by using drugs like aspirin, and that got us very interested in cross [? demandings. ?] We could then go into the animal experiments. And when we had a rat model using breast cancer that we knew from our assays caused bone breakdown in vitro, and when we did that in the animals by injecting into the aorta we could get bone metastases [? and ?] soft tissue tumor. When we gave aspirin, we could completely prevent the bone metastases-- quite dramatic experiments. And that was what really fired me into getting into the oncology, getting into the endocrine treatment in oncology because of my background in endocrinology. And that has stayed ever since. So what was the timing there? This is the late 60s? My PhD was 1970 to '73. I was at the Hammersmith from '67 to '69, and then I went to [? Barts ?] to endocrinology, and then I came back and then with Bondy in the Marsden, and then I got on the staff of the Marsden as a senior lecturer in 1975. So what you just described to me sounds like translational science. That word wasn't coined until probably 20 years later. Was it unique where you were to be taking things from the lab straight out to the clinic? And where there obstacles to doing that? No, there weren't. The thing that was good about that was we were doing the laboratory work based on what we'd seen, what I'd seen in the endocrinology with the hypercalcemia and the bone metastases, and responding to endocrine therapy. I then was in the PhD, doing the PhD, and then I was able to translate that into the clinic once I then became a consultant. So the main work I was doing when I was first a consultant, the research work, was actually looking at hypercalcemia bone metastases in patients. We had a surprise because when we took the aspirin into patients, we could see no effect at all even though we'd had very dramatic effects in vitro and in vivo. And it was only when the bisphosphonates came through that we were able to then use those, because at this stage we knew it was working on osteoclasts. And it was only when we started to get the bisphosphonates that we really got into the dimension of first of all, being able to treat the hypercalcemia, then being able to switch off the bone metastases, bone pain, and bone fractures with bisphosphonates. And then take it into the adjuvant, I was then able to take it into the adjuvant scene and set up the first adjuvant bisphosphonate trial. So I'd gone right from in vitro, I continued the path right the way through to clinical work. And then what happened was that if we did the bisphosphonate trial and we got the result of just like that had happened in the rats-- it stopped the development of bone metastases and it stopped the hypercalcemia in the rats, but didn't affect the soft tissue. So in the humans, we had exactly the same result where we were able to reduce bone metastases, not have an impact on soft tissue or other disease, and improve mortality. And so we've gone right the way through. It's a story that's extraordinary from my point of view, because I was able to follow the whole path all the way through. And you're absolutely right. That is a really good example of translational research where you hang in there until you get the answer. What's the history behind transferring the bisphosphonates from prevention of osteoporosis in cancer? Now they're widely used as well as denosumab. In fact, it's malpractice not to use them in a patient with bone metastasis. How did you make that leap where you're standing next to somebody who was treating osteoporosis, and you said, "I wonder if that should work?" And how did you get hold of the drug? There's got to be a history behind it. Well, we were looking. We were looking for [? anti-osteodiscitis ?] agents [INAUDIBLE] the aspirin didn't work but [INAUDIBLE] worked so we knew for no reasons at all that it would prevent, stop hypercalcemia. And so we were going down that path, and two really important people in the way the path was going. One was Herbie Fleisch, and Herbie Fleisch [? had ?] suddenly produced bisphosphonates. It was a terrific story if anybody was interested in bone, because it was an agent that clearly was working on osteoclasts, and that was the target we were after. We knew at that stage that the cancer cells had to activate osteoclasts in order to cause the bone breakdown and develop in bone. And the second person who was key was Craig Mundie, who again I met. And I went over to the Boston Dental Hospital several times, and I met Craig and the others there, and that was linking up with being able to see the story that they were developing where tumor cells were activating osteoclasts that were then causing bone breakdown that was then producing growth factors to activate the cancer. So it became a really preferential site for bone metastases to develop because of the interaction between the cancer cells and the osteoclasts. So then there's Herbie Fleisch in Switzerland. I had a few skis with him. He was a very good skiier. But the spin off was that bisphosphonates were going to be the thing that we really [INAUDIBLE] to be looking at. And then we tried four different bisphosphonates. Five foot was a guy in Amsterdam who had APD that was actually the forerunner for [INAUDIBLE]. And the one that worked best for us was clodronate, which we got originally from Finland. And we set up the bone trials. We had to go through three stages. We had to-- first of all, before we could use adjuvant, we had to show that it worked in metastatic bone disease. And it did. It reduced what's called skeletal related events-- that's fracture, hypercalcemia, pain-- requirements of radiotherapy. We then did a trial for phase 3 trial of using clodronate for patients who had metastatic disease but who didn't have bone metastases. And we could reduce the risk of them getting bone metastases. And then we had the justification for doing the-- So let me interrupt you for a minute. Now you're about 1983 or '4 I think when that was probably? Is that right? It was-- yes, it would be. With the adjuvant trial, we would have started in '86. I think. That's the window of time. And then in that trial, we didn't get the results from that until I think it was 1997 when we did the first analysis, and that we were able to then show in that randomized-- it was placebo controlled as well-- we were able to show a reduction in bone metastases and improved survival. And then we did a subsequent analysis in 2006. So we've got longer term data. Back then where other bisphosphonate trials were going on, adjuvant bisphosphonate trails going on, and then we had the meta analysis in 2015, Oxford meta analysis, which I was involved with Rob Coleman. And we did the analysis there, which confirmed that we could reduce bone metastases and improve survival with adjuvant bisphosphonates. So the story that starts from a test tube, so to speak. Oh, there's one other very interesting experiment we [INAUDIBLE] that's never been repeated. Right at the beginning, we were able to show that doing co-cultures-- you're reminding me of things now-- doing co-cultures of the bone assay with human breast tumors I'd get from the Marsden while I was at the institute. We'd have fresh human tumors, and we would do a co-culture and some of them could cause the complete breakdown of the bone assay, and others would not have osteoporosis. And we did a follow up of those patients-- it was only about 30 patients, I think-- and we did a follow up of those patients, and those who had the most bone breakdown in vitro [? with ?] [? those ?] patients who were then going to get the bone metastases. That was a real incentive to show that link that we were getting. So we knew something was going on there. And that experiment was going on in 1971. And in 2015 with the meta analysis of bone mets and mortality. So that's a long story. That's the story. Let me say that this entire story reiterates the phrase that, "On the shoulders of giants we all stand." You look at the number of people you've laid out who led to this story, which is still ongoing. It's actually fascinating. I want to return just a minute to your work with endocrine therapy of breast cancer and your work with tamoxifen. But first of all, a lot of young people listen to this. 'Cause I came in the field just as surgical ablation of many of the origins of estrogen was going away. Can you talk about what it was like to take care of the patients who were having hypophysectomies and adrenalectomies and oopherectomies? I recall thinking, "I'm an endocrinologist here. I'm not a medical oncologist," as a first year fellow taking care of Addison's disease and other things. There are two things about ablative endocrine therapy. The first was that the responses could be very dramatic, and it was quite a high response rate. There was something [INAUDIBLE]-- don't forget we weren't basing it on ER. ER came later, and then [INAUDIBLE]. Even not based on ER, we were getting 30% to 40% response rates, particularly in bone. The second thing is the management of the patients. The hypophysectomies were relatively easy, because I'd already got experience of patients who got pituitary failure from my endocrinology, and that's much it easier to manage. But the adrenalectomies are much more difficult because you can get very acute glucocorticoid symptoms if you're not getting cortisol, whereas in hypophysectomies it's a relatively slow process. And they were much more difficult to look after. But the thing that was important about it was the fact that although we were doing it, these patients were getting hypercalcemia [INAUDIBLE]. You could have a patient who was hypercalcemia, you do ablative surgery, within 48 hours the calcium is back to normal. In fact, it will go hypoglycemic sometimes on bone hungry [INAUDIBLE] thing. And from a clinical point of view, it was some of the best responses we ever saw even up to this time. Now one of the things that came out of that was that we had one patient-- I can say a name because he's long since dead and [INAUDIBLE] anyway-- her name was Mrs. Pottinger. It's engraved in my mind forever. And she had bone metastases, and she was not particularly well and also had some heart problem. And she was due to have adrenalectomy, and she wasn't well enough for adrenalectomy. And so what I did is I'd used [INAUDIBLE] when I was at the Hammersmith as part of treating Cushing's disease. And so I'd already knew about medical treatment for-- so I then decided that we would do-- and I think it must have been the first patient. I had to get permission from [INAUDIBLE], and I still got the letter I wrote to the medical director of [INAUDIBLE] then saying could we use [INAUDIBLE]. So what we do is the basis was in order to get her well enough to have her adrenalectomy, and she did exactly the same as she would have done if we'd done adrenalectomy. Within 24 to 48 hours, she's getting better, the pain's going, the calcium's down. So she then refused to have an adrenalectomy. There's no way she is going to have it. She said, "No I'll continue with the [INAUDIBLE]." And she continued on [INAUDIBLE] for over a year before she died. And that started a whole new thing. [? Ian ?] [? Smith ?] was my registrar at the time. And so we decided we'd do a phase 2 trial. We did a Phase 2 trial of [INAUDIBLE] on the understanding we were doing a medical adrenalectomy. And that started the whole story that we were doing using [INAUDIBLE], because a [INAUDIBLE] came over, I had various other people come, and what we found was the story was. It wasn't the medical adrenalectomy by blocking postmenopausal estrogen. And then we went down the pathway of doing various, about three or four different aromatase inhibitors with Mitch doing all of endocrinology. It's a wonderful time. We had Adrian Harris, Charlie [INAUDIBLE]-- [COUGHING]. [INAUDIBLE]. [INTERPOSING VOICES] That's a parade of stars. Were you talking across the Atlantic a lot during that time with Dick [? Stanton, ?] and Angela Brody, and the other two who were also-- Yes. Angela Brody was the one who got us a source for [INAUDIBLE]. That was the phase 2. Charlie led on that on the phase 2. That was Angela getting us to do that and linked him with Mitch. And Dick Stanton, yes it was a lot of collaborative work with Donald MacDonald. And a lot of the endocrinologists I knew. So that was how that whole story rolled. That's an amazing library. Let me take you back now to your childhood. I know you and your identical twin, Ray-- by the way for the listeners, if you Google either Trevor or Ray Powles, you'll see pictures of the two of them standing together. And I challenge you to tell who's who. [LAUGHTER] Anyway-- Well I could. I could tell the difference. Yeah I know you can tell the difference. I know that you were both young boys in London during World War II. Tell me about the experience then, and how your mother moved you. Obviously, we were very young. My father was in the Navy abroad, so my mother was alone and was looking after my older brother David, who was four or five years older than us. And I can remember the bombing. I can remember quite a lot about it, surprisingly. We were evacuated up into the north of England 1943, 1944, something like that. And we were there for I think something like six months. And it was an incredible story. I went back to see-- I hadn't been back-- I went back to see-- I was up in the north of England, and I suddenly thought I'll go over. We were at a place called Stockton. And so I was five when we left-- four, four years old when we left. And I had no idea. I knew it was Stockton, and I knew the name of the house was the Priory, and I had a faint recollection of the door. And then I went up to Stockton, and I found the house we were in. And I knocked on the door, and it was a major-- a colonel-- Colonel Brown and his sister who lived there. And the sister was still alive, and she must have been about 90. [INAUDIBLE]. And she looked at me and she said, "You're one of the twins." [LAUGHTER] So we had a chat. [INTERPOSING VOICES] At the time, did you think of this as being frightening, or was it just a great adventure for a young boy? Yeah, I wasn't unaware of danger. My house was bombed down the road flattened and presumably a lot of people died, but I was unaware of danger as such. We had a shelter-- it's something called a [INAUDIBLE] shelter, I think it was called-- that was half buried with corrugated iron as the top thing. And if the siren went, I can remember that we would have to go out and get into the shelter. And we could hear the V-1s very, very-- I can still remember. You can hear the V-1s coming over. It made a hum-- [HUMMING] --like that. And it's gradually getting louder and louder, and then it would stop, and then it would just fall out of the sky at an angle. It would go down at about 45 degrees. So if you could hear the [? stop ?] overhead, you weren't going to be hit. But if you could hear the [? stop ?] coming towards you, there was a chance you were going to get hit. I can remember that. Everybody was sitting listening to where these bombs were cutting out their engine. So that's one of the things I can remember. And I can remember the V-2. It was a huge bang if one went off. I know that you and Ray both also developed tuberculosis as young boys. What was the background behind that, and how were you treated? Yeah, Ray-- we'd just finished school. And we weren't sure what we were going to do, and Ray had developed [INAUDIBLE], which again didn't mean anything to me. He coughed up a couple of times or [INAUDIBLE] of blood. And the next thing he's carted off and he's got tuberculosis, and he's been taken down to a sanatorium down near the Thames out along the marshes sort of thing. And he's there for six months. And during that six months, I can't see him and everything, and I thought, "Well, you know I'd like to do medicine. I think this is rather a good thing." So what I did, I then applied for medical school and got a place. And then Ray gets better, and he then applies to medical school, and he gets a place as well. The dean said to Ray when he saw it, he said, "Haven't we seen you here before?" And Ray said, "No, it's my twin brother." And he then says, "Did we accept him?" And Ray said, "Yes." And then he said, "Pity." [LAUGHTER] And it was the end of the interview. The next thing, he's in as well. [LAUGHTER] And then I get TB, because it's about an 80% chance you get it if an identical twin's had it. And I was in the hospital for three months. So we were both back a year. I would have been a year ahead of Ray, but in fact then suddenly we're both back a year. And it was quite an interesting year for me, because I only had one subject to do. So I was able to do some reading, things like Darwin and that sort of stuff. And then we just carried on. And you were treated with streptomycin in those days? [INAUDIBLE]. You had 50 grams of strep. Yeah, yeah. Sounds like you used that as a springboard to change the practice of medicine. So in every cloud there's a silver lining. The one thing I want to bring up-- I remember several years ago at one of the San Antonio meetings, and you and Dr. [? Bernie ?] Fisher were the bait. And he did all but call for you to be arrested and locked up because your study was negative, and of course the [? PL1 ?] one was positive. And you very graciously responded to that, "You know, Dr. Fisher, I didn't start this trial up to be negative." [LAUGHTER] That was a great response. My goodness did I not admire him. The reason I did the trial is-- again, this is a funny story. I did a lot of horse riding, as you know. And what I did is after the 1985 first meta analysis, Oxford meta analysis, that was the first one to show that chemotherapy worked for the [INAUDIBLE] and other trials that chemotherapies show the reduction. And it showed that tamoxifen worked. That was the first meeting where I was really convinced that both those were positive effects. Up till then, it was one trial and you couldn't be sure if it was going to be reproduced all the like. And that was the 1985 meta analysis meeting in Oxford. And then I came back home, and I got on my horse, and I rode for a week. I took the horse down to the South Downs. The South Downs is a long, expansive country, and it took me five days, I think it was, of riding to get across from one side to the other where I'd stop in a pub. I had to go down the week before and plan out exactly what I was going to do. So I've got five days on a horseback thinking, and that was where I thought, "Well, where do we go from here?" You might say, well, let's do bigger and better chemo or the like, right? And you might say endocrine therapy, let's do more tamoxifen, or different doses, or [INAUDIBLE] down those paths. So I said, "But if you really want to do something different, the two things you could do would be for chemotherapy is why not give it before surgery?" That was the time when I really thought neoadjuvant chemotherapy was where we ought to be going, because then we could see that they're responding or not et cetera. But tamoxifen, if it weren't for adjuvant therapy, then it should work for prevention. We had a clinic at the Marsden that I took over because somebody was leaving-- which was a family history clinic, and they all had very strong family histories three or four relatives, et cetera, et cetera. And I took over this clinic, and I thought to myself we could do a prevention trial here with tamoxifen. We'll do a pilot. What happened at the Marsden they just had a ethics committee set up, one of the first in the world. This is in 1985. And it had never met, it had only passed the trials to be done. And so the first meeting of the ethics committee at the Marsden was to discuss the prevention, because it was such a awful thing to do. Do you know what I mean? And but after two or three goes, I got it through the ethics committee mainly because a colleague of mine who was the head of medicine then was Tim McIlwain. He pushed it through because he said "Look, it makes so much sense." And we did a [INAUDIBLE] and we had an agreement that we could do 250 patients randomized, then go to 500. And then we had a national meeting to discuss setting up the national program. And so it was a feasibility trial actually looking to see what the toxicity was or whether it was acceptable to do it. And we had such a spin off from that, because tamoxifen at that stage was supposed to be a pure anti estrogen. And we were screening all the tissues, we were doing bones that [INAUDIBLE] from the clotting factors. Everything. Cholesterol. We were doing, measuring everything in pre and post menopausal women. And everywhere we looked, tamoxifen wasn't acting as an anti estrogen. It was acting as an estrogen effect, so much so that at the Think Tank-- I presented it at the Think Tank, and I said, "Look these aren't [INAUDIBLE] tamoxifen and anti estrogen at all." And I thought Mark, dear old Mark Lippert, was going to have an epilepsy, which 'cause it's correct because it is an anti estrogen breast cancer effect. But that was the first time. So then in the paper I wrote, I called it a selective anti estrogen. But I didn't coin [INAUDIBLE], but I did coin the expression, the first published thing of a selective anti estrogen. I remember that paper. [INAUDIBLE]. I remember that. So I want to finish up with just-- Let me just finish up one thing. Can I just finish up one thing? [INTERPOSING VOICES] Because it links into [INAUDIBLE]. So after Think Tank presented it possibly as an estrogen. And what was happening is we've got a bell shaped curve that was very narrow. So we were on the estrogen side as opposed to the anti estrogen side, right? And that was what was happening in the normal tissues. So I had a slides that said, "Tamoxifen is not an anti estrogen." You probably remember if you were there. You were there. We go out on the boat, and we get stranded out of the boat in the mist-- the one you've mentioned about where you and I and Mark, et cetera-- when we're approaching the time after about four hours when we're thinking about meeting our maker, Mark says to me, "I've really got to have a word with you about this anti estrogen." Well one other thing-- and this is going to be more my talking than yours. I really just touched on the surface of your contributions to the field, but I think probably the greatest is your mentoring history. And you've already hit on a few of these, but I travel extensively and I'm struck by the number of times I've been in some remote area-- or at least remote to me-- and corner of the world, and somebody-- it's usually my host-- volunteers that he or she trained at the Royal Marsden with Trevor Powles. And I think it's one of the things you should be most proud of all the many things you've done. And I want to know that you set up a system that was opening and inviting and also somehow funded to support people to come from all over the world. What made you do that? How did you do that in the first place? It's hard to do. Certain people came to me, which was very nice. We did have funds. I would be able to get funding even at that stage. There are many more hurdles for getting funding now than there were then. And the other thing about it was the fact that I find that people-- many times we've [INAUDIBLE] [? mentioning ?] things-- but one of the things I really did [? let ?] is let people have the run of doing things as opposed to me doing it maybe with the assistant. And that was very rewarding for me in terms of results and [INAUDIBLE], 'cause people were very motivated to do it, people like you, and Charlie, and the others. So in some senses, I think it was the fact I was looking for the results we wanted to get rather than anything else. That's probably the basis of it, and therefore people came who ere good. And I'm very lucky I had very, very good people come. So just to go through the list briefly-- Ian Smith, Mitch Dowsett, Troy [? Kohns, ?] Adrian Harris, Paul Goss, who am I leaving out? Anyway, it's a who's who of breast cancer, especially endocrinology and breast cancer. And they all came out of your brilliance. So we owe you not just for what you've done, but who you've trained to do even more. Very kind of you to say that, but in fact they get the credit because if you look through my publication lists you can see. Actually, I left out Steven Johnston, of course, who is-- Steve. Yeah, Steve. Yeah. OK, we've run out of time. I very much appreciate the fact that you've taken time to come on and do that for us. I'm sure our listeners will be thrilled by the stories you've told-- at least I always am-- and it's great to hear most of them again. And I hope sometime we can even do this again. So thank you for all you've done, thank you for all the people you've trained, and thank you for taking time to do this today. Well, thank you so much for asking me. Until next time, thank you for listening to this JCO's Cancer Story-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.
Meet the Million Dollar Bogan, Daniel Hayes! This bloke has a rags to riches tale that will have you inspired from the moment we kick off. Tune in to hear about some of his wild adventures with Harley Davidson and his amazing attitude toward life. Another Aussie icon doing some great work for our community and keeping us all well entertained along the way. Enjoy folks :)
Daniel Hayes finds himself among a very hostile crowd deep in the country of Mexico. The south paw is a top rated amateur boxer. Olympic glory is just within his reach. Daniel Hayes has his opponent beaten. He strikes him once again with a very hard left. All of the sudden, he feels something that isn't right. He broke his hand. The Honey Badger will fight through the rest of the match continuously pounding his opponent with his broken hand which will eventually lead him to victory. However, Daniel Hayes 2016 Olympic Dreams are over. This is a must listen episode of overcoming major obstacles, depression, and going through fire to getting your life back on track! Also if you go to www.kuhnbox.com, Kühn - beard balm and beard oil, or hit the qr code in the picture and enter the code "biz beard," kühn Beard Products is going to hook you all up by giving you your first month free when you sign up for kühn box. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/biz-with-beard/message
Dr. Hayes interviews Dr. Lippman discuss on being one of the first translational scientists in solid tumors. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to JCO's Cancer Stories, The Art of Oncology brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all of these shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center. I'm also the past president of ASCO. I'm really privileged to be your host for a series of podcast interviews with the founders of our field. In this series of podcasts, I'm hoping I'll bring appreciation of the courage, the vision, and the scientific background among the leaders who founded our field of cancer clinical care over the last 70 years. I think that by understanding the background of how we got to what we now consider normal in oncology, we can work together towards a better future for our patients and their families during and after cancer treatment. Today, I am privileged to have as my guest on this podcast Dr. Marc Lippman. Dr. Lippman was really instrumental in the early studies of the role of the S receptor in breast cancer. And personally, I consider him with his former colleague Dr. William McGuire the first investigators to perform what we now call, quote, "translational," end of quote, science in solid tumors. Dr. Lippman was raised in Brooklyn. He received his undergraduate degree at Cornell where, by the way, he played on the varsity tennis team. And then he got his medical degree at Yale. He did his residency at Johns Hopkins and returned to Yale for a fellowship in endocrinology. Somewhat surprisingly, to me at least, he served a year from 1970 to '71 as a clinical associate in the leukemia service at the National Cancer Institute while simultaneously working in the laboratory of biochemistry with Brad Thompson, with whom he published extensively. Dr. Lippman has authored nearly 500 peer-reviewed papers. He co-edits Diseases of the Breast, which is considered the Bible of breast cancer with Dr. Jay Harris and Monica Morrow and Kent Osborne. And fundamentally, he has mentored the leaders of breast cancer in the world, in my opinion. Welcome to our program. Hello. I have a number of questions I'd like to ask you. First of all, clearly, you took a really unusual path to being a cancer doctor. To my knowledge, you actually never formally trained in oncology. Can you tell our audience how you went from being an endocrinology Fellow to being an oncologist? I think it's worth it, from my vantage point, to give a little background about me. I came from very, very intellectually rich family. And there was never any question that I was going to do some kind of science. I was certain that that's where I was headed. And when I was in medical school, I think it's important that while everybody was doing research at the school like Yale, a lot of medicine as we now think of it as evidence-based was completely mysterious. In those days, when I was starting medical school, really, I think the only fully scientific field was infectious disease because we had Cox postulates. And we knew what drugs killed what bugs. And we knew what bugs caused what diseases, for the most part. And that was wonderful. But endocrinology, at that time, was completely functional assays. It was completely not scientific. You looked to see if the rabbit ovulated or something like that for a bio assays. And Nobel Prize winning research was done, which developed the radio immuno and the radio receptor assay. And that completely transformed endocrinology over night. And within about one year, virtually every endocrine disease, the pathophysiology of Addison's, thyroid disease, you name it was worked out based on being able to measure minuscule amounts of hormones. And to me, this was fabulous. I was going to be an endocrinologist. I had no doubt about it. This was real science. And I could get into it. When I was in medical school, you had to do a thesis. And for reasons that I'm not even sure of now, I can recall, I got involved with a guy who was a hematologist. But he did work on leukemia. And I enjoyed that work greatly. It was very interesting. And right about then, you may recall, there was a minor episode going on called Vietnam. And many physicians or people who were about to become physicians, myself included, weren't very anxious to go to Vietnam. And one of the main alternative routes was to become an officer in the public health service at the NIH and to do your military service at the NIH. And that seemed like exactly what I wanted to do. It was a very unusual process. People at the NIH picked you for their own personal lab. And because I had been working in this hematology lab, a scientist, an administrator actually at the NCI invited me to join his lab, Saul Perry. And I took him up on that because that seemed like my only alternative. But after I finished my internship and residency and showed up at the NIH, because I was part of Saul Perry's group which was the leukemia service, I had to spend a year on the wards taking care of extremely sick people, most of whom died during that year. But because of my love of endocrinology, I kept studying all kinds of stuff around endocrinology, took the molecular endocrinology courses. And then I met this wonderful mentor, Brad Thompson. And my first project with him actually was an attempt to combine leukemia and endocrinology. And I started measuring glucocorticoid receptors in leukemia. And that's, frankly, some of the best work I ever did. We showed that they existed, that they were receptors, and that they predicted response. I mean, we did in leukemia what people were doing in breast cancer, and I thought that was pretty interesting. And there was always this tension in my mind between the science of endocrinology and the almost complete lack thereof, at that time, in oncology. And I thought that I might try to think about putting them together. But I needed to do formal endocrine training. So after I finished my clinical year at the NIH and my two years in the laboratory with Brad Thompson, I went back to Yale to do endocrinology. And I thought that's where I would complete my career. After I'd been there about a year, Paul Carbone called me up and said, would I like to come back to the NCI and join the breast cancer service? And I have to tell you candidly, I had never treated a case in breast cancer in my life when I went to join the breast cancer program at the NCI. And I completely learned everything I learned about breast cancer absolutely on the fly. So what made Dr. Carbone call you to do breast cancer? Well, I'm not absolutely certain. I had done well at the NCI. I'd been very interested in a lot of things. And I'm not certain I can remember anymore. I don't remember why Paul called me, but he did. And at that time, I had been looking at several endocrine jobs at a variety of institutions, including University of Chicago. And I was thinking I'd just spend my life as an endocrinologist. But I thought this was such a great opportunity to pursue my research that I decided to take my chances. I was extremely full of myself in those days. And I didn't see the problem that I had never treated breast cancer. I know it sounds dumb to say it. But I actually said, well, OK, I'll figure this out. How hard can it be? And I guess I didn't find it all that hard. And at that time, because I had already gotten into what I would refer to as molecular endocrinology, half of which was steroid-hormone action, I was highly familiar with the work of Elwood Jensen, who was the real pioneer at that time, one of two actually. So naturally, it made sense to me to take the work I'd already done in glucocorticoid receptors and try to make models in tissue culture for how breast cancer responded to hormones, the kind of thing you would never suggest that a newly minted faculty member try a completely insane project, which I was extremely fortunate that it succeeded. You refer to Elwood Jensen. Tell us more about Dr. Jensen and what he did that got you where you were. Well, Elwood was a tremendous scientist and basically a chemist. And people don't understand how technology sometimes makes a field possible. And just as I mentioned before, radio immuno and radio receptor assay made the entire field of endocrinology and now so many other subspecialties of medicine possible as you measure pulmonary and GI and cardiac hormones, in the same exact sense, what Elwood succeeded in making was radiolabeled steroids. And you can't do receptor assays unless you have high specific activity compounds. We don't use radio isotopes touch so much anymore, and people don't appreciate that. But there was absolutely no way to measure the binding in picomolar and centimolar ranges without high specific activity steroids. And Elwood was able to manufacture created hexestrol, which is a similar compound to estradiol. And with that, he was able to basically separate bounds from free hormone and prove the existence of receptors. It was extremely important studies that he did at the time. And it opened up the entire field of hormone dependency in breast cancer, which, up until that time, had been based entirely on clinical criteria for response. And furthermore, what occurred almost simultaneously with that was finally the invention of some serious drugs that could interfere with hormone action, most notably tamoxifen but several others that were synthesized at the time. And so rather than just having to oblate organs or use very toxic super pharmacological doses of steroids to treat patients with breast cancer, there was now a readily obtainable and usable oral therapy. And so there was a tremendous need to figure out how and why it worked. And a lot of people got into that field relatively rapidly. Bill McGuire being among them. James [? Whitless ?] being among them, myself for sure. And all of us felt that this was an extremely important aspect. There was the clinical aspect, which became clear in the early '70s that there was, as you would expect, a very, very nice correlation between the presence of receptors and response. And that led up to the entire opening of this field of now that you could measure these receptors of how they worked, where they bound, what they did, what genes they induced. And so that became a lifetime exercise for many. My impression is that before about 1970, endocrine therapy, which dated back the 1890s, was mostly done by the surgeons. Did you have to muscle your way into that field? Or were they openly agreeable that some guy who had never even did oncology would start treating breast cancer patients? Well, I think that what was going on then, in England, there was a much greater delay in medical oncology as a field. And these patients were still treated by surgeons and radiation oncologists. I don't think there was any parallel issue in the United States. There were some very wonderful pioneering surgeons, but they didn't, I think, pretend to fundamentally want to get into molecular endocrinology. I don't recall that as being an area of conflict in terms of doing these kinds of studies. And of course, in this country, we were unbelievably blessed by the extraordinary, absolutely extraordinary pioneering and organizational skills of Bernie Fisher, tremendous scientist, in his own right, a tremendous surgeon, but, even more importantly, the ability to really form the most effective, ragtag, co-operative group the NSABP, which was able, from its very inception, to do some of the most groundbreaking studies not just around hormone therapy, which they certainly did, but obviously as we all know about, differences in surgical care. And so-- You eluded to Dr. Carbone. My impression is the NCI, mostly, in those days, was all about leukemia and lymphoma, the so-called gang of five, MOPP and CHOP and Doctors Frei and [INAUDIBLE]. Who was behind you to move out and start taking care of patients with cancer in a more scientific basis? Was it just Carbone or were there other people at the NCI who [INTERPOSING VOICES] Well, shortly after I got, there Paul left. He went to Wisconsin. And Doug Tormey, who had been nominally head of the breast group, departed. And so I was suddenly given an empty stage and said, well, why don't you do it? So within two years, I was running a program in which, the previous year, I hadn't even treated a patient. It was extraordinary. But right about that-- I was-- that's a very good question and a slightly personal one. About 30. About 30, 31. Yeah. Most 30-year-olds now are just starting their residency or their fellowship. Right. And it is unfortunate that people with the most energy and most intelligence get increasingly pushed downstream. I mean, the age of first RO1s in this country is horrible, as we all know. And that's a major other problem that people need to address. But at that time, as you may recall, several groups were developing the first multi drug combinations for breast cancers. CMF, or as Johnny [INAUDIBLE] used to refer to it as CMF, and of course other variations with the MD Anderson regimens of so-called FAC chemotherapy, F-A-C, and other regimens that included vinca and prednisone. And so for the first time, reasonably active regimens were available for metastatic disease. Where in the past, it had only been a handful of single agents, vinca, methotrexate, 5-FU. And at the same time, I think there were the extraordinary, a little bit later, the extraordinary first data that adjuvant therapy was successful. I mean, the studies done by the NSABP initially was single agents and then the CMF studies from Milan were extraordinary. I mean, breast cancer was and remains the most tractable of the solid tumors with the possible exception of testicular that we've treated in this country or anywhere. Tell us about your lab work and how you established what you did, and then really interested in how you looked at what you were doing in the lab and said, jeez, this relates to my clinical work. Well, thank you. As I said, when I had been working at Yale before I came back to the NCI. And at that point, at Yale, I was trying to develop models of gluconeogenesis in liver cells. It had nothing to do with cancer. And so I arrived at the NCI, recruited by Paul, offered some laboratory space, and said, go to it. And I literally, literally scratched my head and said, well, what am I going to do now? And because I hadn't had a previous thing I was just going to expand on. And because another great miracle that had been growing from very late '50s to the mid '60s was cell culture. I don't think people can now imagine how pioneering the results were to grow cancer cells and to get them to reflect, in any sense, the phenotype of human malignancy. I mean, now we take it for granted. But these were pioneers trying to figure out how to grow cells, Harry Eagle and Hamm and Dulbecco, and all of these other wonderful people. So anyway, it seemed to me, wouldn't it be great, since someone had described a cell line that had estrogen receptor, I said to myself, what would be more straightforward than to figure out how you could manipulate these breast cancer cells with hormone therapies and figure out the mechanisms by using cell culture as a model for steroid hormone action? So I set about doing that. And after about six months, I succeeded. And that was the good news. And ironically, the better news was that nobody else could reproduce it, including Dale McGuire. And lots of people said this was, frankly, garbage, that I was making it up. And so when eventually-- no. It was very upsetting. I don't think many people when they first start off and they have their first big set of papers, and I published this stuff in Nature and serious journals. And all of a sudden, everybody says, it's not true. I remember giving a lecture at Harvard. And somebody at the end at the questions said, we just can't reproduce this data. We don't think you're telling the truth. I mean, how often you want to have that happen in your career? And as I said, what turned out to be very fortuitous was that we were right. And so eventually, that made things even easier for me in terms of my career. There's no question about that. And a lot of people wanted to go to the NIH. I think it's now with so many wonderful-- what are there more than three dozen comprehensive cancer centers? But the United States in those days, there were just a handful. And most of them were doing leukemia and lymphoma, like Stanford, which certainly had almost no breast cancer program at the time. And so people who wanted to work in breast cancer came to work with me. And lots of people wanted to get a BTA degree, Been to America. So I was fortunate to have some very outstanding people from Europe and Asia come to participate in my work. And there was still the tail end of Vietnam. So some of the very best and brightest, if I could misuse that expression, people like Neil Rosen and Ed Gellman and Doug Yee and George Wilding, people who all became cancer center directors were people that I was very fortunate to have work with me. And I was pleasured to deal with them. When did you say you were doing the lab models of cell lines and discovering how ER mediated the effects of estrogen? When did you start saying, let's take this over to the clinic? I mean, what was the first thing you did that you translated into the clinic? Well, the first translational study I did when I was a fellow when I tried to do correlations of response to glucocorticoids in leukemic patients and ALL and AML. So I mean, I was used to going back and forth that kind of way. And we did a series of drug trials in breast cancer patients. I was seeing patients. I haven't spoken much about it. But I don't know how to say that any other way whether it sounds modest or not. I simply love being a physician. I found that the main appeal of oncology was dealing with people at times of enormous obvious stress and disturbance in their lives. And I found that that brought out some of my best skill sets. And so I was anxious. I was always involved with patients like that. One of the main trials that we got involved with involved Allen Lichter because Allen and I were endlessly discussing what was the right therapy for localized breast cancer. You may recall that Sam Hellman, the joint center, refused to be part of clinical trials looking at lumpectomy and radiation, as he was convinced, turns out correctly, that that was equivalent to doing mastectomy. And we felt, Allen and I, I think somewhat maybe arrogantly again, that we could do a single institution trial for lumpectomy versus radiation. And we did. We ran a randomized trial of about 350 women at the NCI, a prospective randomized trial of lumpectomy and radiation versus chemotherapy. And of course, all of these patients became fodder for advanced disease trials and everything else we were doing. And those are some of the happiest days of my life working with Alan side by side in what may have been the first multidisciplinary clinic in breast cancer. If I may, I'm going to interject. Allen Lichter, who started the department of radiation oncology at the University of Michigan, where I'm sitting right now, was my dean when I arrived here, became ASCO president at one point, and then was the ASCO CEO for years. Since this is an ASCO publication, if you will, I'd give him credit for all of that. And well he deserves it. Well he deserves it. Yeah. I can't agree more with that. That's for sure. The other thing I've heard you-- by the way, I've always wondered. How did you get 350 patients onto that trial at the NCI, since you've tended not to see walk in the door kind of breast cancer patients, right? So how did you? Well, the NCI remember, everybody was treated free. So fortunately or unfortunately, given American medical economics, people who had a diagnosis would come to see us because they had no other option. We would pay all their travel and everything else. So we treated patients. And I have to tell you, up until last year when she died, I still had patients from that study who had followed me around the country to be treated. That's a great story. It's true. It's absolutely true. So the other thing I've heard you talk about, and I think people should-- given the proliferation of medical journals now, there's one on every corner, I've heard you talk about the fact that you really have a hard time finding places to present your endocrine results, that the Endocrine Society didn't care about cancer. And AACR didn't care about endocrinology. ASCO didn't really exist almost in those days. Give us some stories about that. Well, that's completely true. It's completely true. There was always a session in the Endocrine Society called cancer and hormones, which was late on Friday afternoon. And everybody had gone home. And AACR had the same thing. Because at that time, there just wasn't an obvious niche for cancer. What began to make it more popular to both societies were when things like, quote, "growth factors," close quote, became more in evidence. And they clearly played a role in cancer. But clinical trials and clinical experience had no role in the Endocrine Society. And basically studies in molecular oncology just didn't seem all that attractive to AACR. It wasn't like you couldn't talk about it. It just wasn't front and center what people were interested in. Everything goes through vogues periods. We're now going through an immunooncology voguish period. And I'm not trying to suggest that that's not extremely important and going to have endless value for people. But now, if you're doing almost anything else, you can't even write a protocol. It's true. It's true in some ways. I was trained. [INAUDIBLE], who's an endocrinologist, was at the Dana Farber and told me that cancer is just endocrinology gone wild. In fact, I believe, in many respects, that's what precision medicine is all about is that we begun to take what you guys did 50 years ago and said, let's do it for all the diseases other than immunology, which is a different issue. I agree with you. I think that that's a good point. I think that one of the fundamental differences between normal and cancer, however, is genomic elasticity. If you had psoriasis, and I put you on methotrexate. Then 10 years later, I doubled the dose, it would kill you. Because you never amplify the target gene, dihydrofolate reductase. And you remain sensitive throughout your entire life. Whereas doing that with a leukemic cell, in a couple of months, you'd be completely resistant. And that is, in my mind, one of the shortcomings of so-called precision medicine in which you're trying to match a pathway, an oncogene, to a specific therapy. In that, oftentimes, these studies are in end stage patients with multiple resistant clones now has become endlessly clear from single cell sequencing studies. And I think that there is, I think, personally, slightly less to most efforts in precision medicine than most people think. And I believe that it's amusing that precision medicine has come to include immunooncology, which has little, in my mind, to do with the initial way in which precision medicine was touted, which is find the oncogene. And we will give you the drug. And I think, by and large, that, except for some incredible successes like Gleevec for CML, hasn't really panned out. Personally, I think what we're going to do is head back to what doctors Hall and Frei and [INAUDIBLE] taught us, which is that resistance is a heterogeneous issue, and we need to combine drugs. We just need to do it more thoughtfully than perhaps we've been doing in the past. Couldn't agree more. I want to change the paths for just a moment. To my knowledge, you are one of the few and maybe you were the first oncologist who's been both a cancer center director at Georgetown's Lombardi Cancer Center but also a chair of medicine. You've been at two major academic centers, here at the University of Michigan and University of Miami. Why do you think there have been so few oncologists who have been chiefs of medicine, chairs of medicine? Well, your personal favorite institution, UT Southwestern, would be an example as well of a chair of medicine who's an oncologist. Right. But no particular reason comes to mind. I think that the skill sets and interests of a chair of medicine, at least as it used to be, up until maybe about 10 years ago, were someone who actually wanted to, A, have somewhat less of a research footprint, which would discourage some people, and something less of the same focus on curing a specific disease, which would certainly describe a cancer center director. And I think that exactly explains some of my clinical interest in becoming a chair of medicine at Michigan. I went there, there are always push and pull reasons. The push reasons were that Georgetown was economically a disaster. And they had sold both the hospital and the clinical practice to a large non-profit community-based hospital. And I thought that would be, more or less, the end of the cancer center as I knew it in. And unfortunately, that prediction turned out to be, in many ways, correct. So there was push issues. I just didn't want to officiate over the deconstruction of the cancer center that I had helped to build. And in addition, I felt clinically, I was raised in the era of great chairs of medicine. I was raised in the era of Don Seldon and Dan Foster and A. Magee Harvey, and people who knew everything and would teach at the bedside and knew everything about disease. And frankly, I felt that breast cancer clinically, not emotionally and not from a research point of view, but clinically is relatively straightforward and not that complicated. And I wouldn't say I was bored. But I was looking for a new challenge. And I thought the notion of really trying to bring other areas to bear in terms of my research would be fun. And so I was thrilled to be chair of medicine. But I don't think that's necessarily the career path that many oncologists or any other subspecialist would want. Which did you enjoy most, being cancer center director or being chair of medicine? Unquestionably, being cancer center director here at Georgetown. It was the thrill of a lifetime. When I came here, there were three people in the division of hematology, oncology. Two of them immediately left. And by the time I moved to Michigan, the Department of Oncology that I had created had more faculty than all of the basic science departments at Georgetown combined and more research money than all of the basic science departments at Georgetown combined. It was tremendously happy, very successful. And I felt we were doing really wonderful things. It was just a fantastic time, just like that, which is one of the reasons why I've come back. And I was going to say, although Georgetown did fall on hard times. My opinion is grown back into a major institution. And I'm sure they're happy to have you back. So we're running out of time. I really just touched the surface of many of your contributions. In addition to your scientific contributions, you really touched on it. You've been one of the most prolific mentors in our field in my opinion. I looked over your CV. I count at least six cancer center directors. I think five, four PIs and probably hundreds of others who are proud to have been under your watchful training eye, by the way, including myself, in our careers. So of all the things you've done, your science, your administration, your mentoring, we've touched on all three of those. How do you want people to remember Mark Lippman when it's all said and done? So there's a wonderful joke about that. These three guys are standing around saying what would they like to hear said around their coffin when they're dead. And one guy was a teacher, and he says, you know, I'd like them to remember what a wonderful teacher I was, how I helped people. And another guy's a physician, and I'd like to hear if I'm lying in my coffin, them say, what a wonderful physician. He did everything for his patients. The third guy says, what I'd like to hear is, look, he's moving. So it's hard to-- right. I am certain that the place that I feel most happy, it's not even a close call, is the ability to have played an important role in helping people's careers succeed. I mean, I'm something of a tough guy. But I have been, I feel, very willing to see people grow up and leave the nest and keep them nurtured and look after them for many additional years in their career and enjoy those relationships. It's incredibly enriching. Well, I also have to say there are hundreds of thousands, if not millions of women who have benefited from the contributions you and your colleagues made 50 years ago at the NCI and since then. I've tried to make it clear through all these podcasts how much we owe all of you for what you've done and where we are now. And the reason we're doing this is so people don't forget about those things as we move into medical economics and some of the other things that I think are less fun. So it's time to conclude here. I want to thank you for taking your time. And again, thank you for all you've done for the field, for those of us who've trained with you, and again, mostly for our patients. And I hope you've enjoyed this conversation as much as I have. Very much, Dan. Thanks for including me in this podcast. Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe, so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.
In this episode, Cole and his guests discuss a transdisciplinary effort at Penn State to advance the printing of living tissues, from skin to bone to organs. Combining the efforts of engineers, nanotechnologists, and surgeons, the team has coined a new term – “intraoperative bioprinting” – to describe their approach.Relevant Links:Bioprinting LabMachine sucks up tiny tissue spheroids and prints them preciselyGuests: Ibrahim Ozbolat is Hartz Family Associate Professor of Engineering Science and Mechanics at Penn State. His major research interest is bioprinting and tissue engineering.Daniel Hayes is an associate professor of Biomedical Engineering at Penn State, with an emphasis on nanomaterials, macromolecules, and composite structures, for applications ranging from regenerative medicine to lab-on-a-chip technologies.Dino Ravnic is an assistant professor in Penn State's Department of Surgery. He directs the Plastic Surgery Research Laboratory at the Milton S. Hershey Medical Center, which focuses on the creation of engineered tissue that is suitable for microsurgical implantation.
Dr. Hayes interviews Dr. DeVita about his role as Director of NCI and his time with CHOP and MOPP. TRANSCRIPT [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Welcome to JCO's Cancer Stories, The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center. And I'm the past president of ASCO. I'm really privileged to be your host for a series of podcast interviews with the founders of our field. In this series of podcasts, I hope to bring appreciation of the courage and the vision and most importantly the scientific background among the leaders who founded our field of clinical cancer care over the last 70 years. I hope by understanding the background of how we got to what we now considered normal in oncology, we can all work together towards a better future for our patients and their families during and after cancer treatment. Today, my guest on this podcast is Dr. Vincent T. DeVita, best known as Vince. Dr. DeVita is generally considered one of the so-called Gang of Five, including Doctors Canellos, Young, Chabner, and Schein, who I've been trying to get on for this podcast in the future, all at the NCI, and who brought many of the concepts we now accept as standard into the clinic in the 1960s and '70s. Dr. DeVita is currently a Professor of Medicine and Epidemiology and Public Health at the Yale School of Medicine. I think it's also fair to say, Dr. DeVita was instrumental in the passage of the 1971 National Cancer Act. And I want to hear more about that as we get into this. He was director of the NCI and the National Cancer Program from 1980 to 1988 and then moved to Memorial Sloan Kettering Cancer Center as Physician in Chief and subsequently became the Director of the Yale Cancer Center in 1993. Among his many honors-- and I don't have time to go through them all-- but he has served as President of the American Cancer Society. And I think most dear to me, he was President of ASCO in 1977 and 1978. Dr. DeVita, welcome to our program. Nice to be here, Dan. I've done a little background. I know you grew up in the Bronx. And I know you went to William and Mary for undergrad and George Washington Medical School. And I also read what I didn't know, which is that you did your internship and residency at the University of Michigan. We're recording this just before the NCAA basketball tourney. And I have to say, go blue. We're all excited here in Ann Arbor about our basketball team. [LAUGHTER] What I'm really interested in is, were your parents physicians? Or what made you choose medicine out of the Bronx? Well, no, my father was a banker. And my mother was an interior decorator. So it was kind of a funny mix. But I think it's kind of peculiar. I was growing up, and my mother-- I tell this story in my book. My mother was kind of frightened by the fact that I really, as a seven- or eight-year-old kid, really thought the guy who delivered the ice-- in those days, we had ice boxes-- was terrific. And I wanted to be like Nunzi the iceman. And she panicked and said, no, no. You're going to be a doctor. And every time someone asked me what I was going to be, I just said I was going to be a doctor. And when I went to school, I decided I'd be a doctor. It was sort of Mama driving me in that direction. So you had a choice of being an iceman or a doctor [LAUGHS]. Right. I like-- I mean, biology was always a favorite subject of mine. So it was a good fit. And tell me about how you ended up going to the NIH and choosing oncology. Was that serendipitous? I talked to Bob Young the other day. And he said, fundamentally, he hadn't planned to be an oncologist and got to the NIH and liked it. Was that your role, or did you know you wanted to do cancer from the start? No, I was going to be a cardiologist. In fact, when I was a first-year resident, I did cardiac catheterizations and was a co-author on a paper that for a long time was well-cited in the field. So I applied to both the Heart and Lung Institute and the Cancer Institute. And those are very competitive positions. And I had an interview with Robert Berliner, which didn't go well [LAUGHS]. So I didn't get invited to the Heart Institute. And I went to the Cancer Institute. And when I walked in, Dr. David Rall was the chief of the pharmacology branch. And I asked him if I could work on the pharmacology of digoxin. And he, wise person that he was, said, sure. Go ahead if that's what you want to do. And I was surrounded by people who were working on anti-cancer drugs. And I actually became fascinated with them. And it was only a few months, because I was also on the wards at the time, that I said, oncology is the way to go. It was an exciting new field. It was kind of a funny field in those days. But I found it exciting, so I switched. So just to give you a plug here, I think many of us know that you wrote a book, The Death of Cancer, published a couple of years ago, co-written with your daughter Elizabeth by the way. But in it, you described a number of things. And one of those that I loved were your stories about Gordon Zubrod. And I trained with Dr. Frei at the Dana-Farber. He always had great things to say about Dr. Zubrod. And I wonder if you could tell the folks listening in who he was-- I think most people don't even know that-- and the impact he had on our field. Yeah, I used to call him the great umbrella. The field was very controversial at the time. And so the people who were doing things like saying, I'm going to try to cure this cancer-- leukemia in Frei's case and Hodgkin's in our case-- were considered just a little bit this side of insane. He was somebody who was distinguished. Now, Frei had-- Zubrod had been at St. Louis as a professor and also at Johns Hopkins. And he was a very distinguished-looking man and a very polite, careful man. And so he used to provide sort of the umbrella for all of us, so that [INAUDIBLE] he'd take the heat. And we could go on and do our work. So he was-- he did enormous number of things. I mean, the whole clinical trial structure was established by Gordon Zubrod. The phase I, II, III trials was all done in a paper by Gordon Zubrod in the late 1950s. So I think he was just a guy who had foresight and was a great leader. I ultimately took his job. He got tired of bucking the bureaucracy and retired and went to Florida as the director of their cancer center there. So I got to know him pretty well. And like Frei, I have great admiration with him. I mean, it's interesting how we take phase I, II, and III for granted. And when he came in, and not too long before you came in, those things weren't-- nobody really knew how to do this stuff. Doctors Frei and Freireich were already at the NCI when you got there, correct? Yes, indeed. Yeah, they were. Yeah. And so they must have been inspirational. They were, and especially Freireich. Freireich was always on the wards. And Tom didn't come over to the wards very much. He was sort of the direct-- he was chief of medicine. And Freireich was the chief of the leukemia service. So we saw Freireich all the time. Tom came over once in a while. And Jay was a super doctor. And it was very hard to stay ahead of him. You'd get an x-ray on a patient. And he'd call you up 20 minutes later and tell you what it was. He was already down looking at it. So you had to stay on your toes with Jay. And of course he was, as everybody knows-- Jay-- he was a bold guy, who-- I mean, he looked like he could walk through a wall. So he frightened a lot of people. But he was an inspiration. So I'm always grateful for what Jay Freireich taught me. There's a great story in your book, that Dr. Frei has told me as well, about the first platelet transfusion at the NCI. Can you elaborate on that? I think most folks don't know about that story. Platelet transfusion was, again, one of those radical departures. But Freireich reasoned that we were losing more people from bleeding than we were from leukemia. So he worked out a way of plasma pheresing people and collecting platelets. And we didn't have a lot of the expertise we have now. And they came in quart bags. I mean, they were plasma bags that were huge. And we were treating little kids. So they were-- throwing them into heart failure was a problem. So it was pretty radical. And he was told to stop doing it by the clinical director at that time. And in fact, he was told that if he didn't stop doing it, he was going to be fired. And he told me-- he said, I went back to my office, sat down, and thought about it. And I decided I didn't want to work at a place where I couldn't do that. So I just kept on doing it. And the person who said he was going to fire him never did. But that was Jay Freireich. [LAUGHS] He believed so strongly in it. And when I went to Yale right after I left the Cancer Institute-- I finished my residency up there. And I told them-- when I saw leukemia patients who were bleeding-- and I said, what you should do is platelet transfusions. And they said, they don't work. And I said, I used them. And I saw them work. So I think we're losing patients unnecessarily. It was just very controversial. So eventually I left the program. I was going to take a residency and then a fellowship in hematology there. And I decided to go back to the Cancer Institute where these adventurous things were going on. Times are different now, of course. Dr. Frei once told me a story that he-- you may have been with him-- that he was making rounds in the clinical center. And in those days, apparently, the adults and the kids were in the same ward. And there was a child with essentially no white cells, who'd been induced for leukemia, and a man next to him with CML. And so-- and actually, when Dr. Frei told me this, I kind of said, I don't think I want to hear this story, because he said, well, you know, the kid didn't have any white cells. And the guy next to him had way too many white cells. So [LAUGHS] I said, tell me you didn't do this. He said, yeah, we took platelets out from the guy and gave them to the kid. And the kid got better for a while. It was really exciting. I thought, boy, you don't see that anymore. Yeah, I mean, it was a very reasonable thing to do, because the white cells in a chronic myelogenous leukemia patient work very well in terms of fighting infection. Yeah. So there was no reason. And the kids, otherwise, wouldn't survive. And so, yeah, I was there when we got these-- we gave these. I mean, they weren't easy to give, because they stuck in the lungs. And we didn't have HLA matching at the time. So they were-- a lot of them were mismatched. But for a while, they were effective. And then we went to collecting white cells from normal people. But the white cells had not worked as well as platelets had worked. Platelets have been a lifesaver. Now it's a couple of hundred million dollar business each year now. So it's routinely done, as many things that Jay started are routinely done now. Of the many things for which you are credited, I think it's the use of combination chemotherapy for Hodgkin's and then subsequently non-Hodgkin's that is one of your lasting legacies. There must have been a lot of drama around doing that. I mean, I think we all just assume you're going to start protocol. You write the protocol. You get funding for it. And you go forward. But can you give us some stories about sitting around at night and thinking about how to do this? Or how did you choose those drugs and why and how to give them and the obstacles that were involved? Yeah, actually, it was a very complicated process. And we didn't have the information we have now. What we had was-- I was doing this with Jack Moxley, who left active medicine and became a dean after he left the Cancer Institute. But we're still in touch. And Jack was working with [? Sy ?] [? Perry ?] using the new isotope, tritiated thymidine, looking at the bone marrow of CML patients and also of mice. And I was doing the same thing with the leukemia 1210, which was a model that we used for chemotherapy all the time. And what we were trying to do was figure out the kinetics of human versus mouse marrow, so we could develop schedules that humans would survive. We quickly found out that you can't use the mouse as a model, because their blood cells went through a kinetic phase about half the length of humans. So you had to schedule in a different way. So we worked that out. And then we looked at very simple-- something that people really ignored is that when you give a chemotherapy agent that is toxic to the marrow, you don't get abnormal blood counts right away. For a week, you'll have a normal white cell. And then on day seven or eight, it begins to fall, because the storage compartment in the marrow works well for about a week. And then there's no replenishment. And the white count falls. So between the two, looking at the marrow and looking at the white cells in the periphery, we came up with a schedule for MOPP. And then the other things were simple. We just decided that you'd have to have three or four drugs that worked by themselves. There had been people doing combination chemotherapy before-- Tom Hall in Boston and [? Alan ?] [INAUDIBLE] at Yale. And their rationale was they're looking at a sequential biochemical blockade. But they ignored whether the drugs actually worked against the tumor, assuming that if you gave them together, that the biochemical blockade would dominate. And it didn't work. In fact, it was very discouraging. But we decided the way to do it was take drugs that had some activity in the disease and use them together and use them in full doses in the schedules that we worked out because of the prior work I was telling you about. So it took a while to put that together. And then Jack Moxley and I used to do this at a bar in Georgetown called the Lehigh Grill, where we used to-- my cardiology desire-- I used to go to Georgetown where there was a wonderful cardiologist Proctor Harvey, who used to hold Thursday night sessions. You had an auditorium that was wired. So you could hear heart sounds. And after that, we'd go to the Lehigh Grill. And we sort of put together the protocol. When we presented it to Tom, he thought it was a good idea. But the other people around him thought it was insane and really tried to stop it. Tom Frei? Yeah. Tom Frei, yeah, yeah. Well, Tom was supportive. Yeah, Emil Frei was his real name. But everybody called him Tom. Yeah, he was supportive. But the people around him and my immediate boss was very much against it, because he thought it would interfere with the protocol that they were doing and so forth. So Tom worked out a solution worthy of Solomon. He said, OK, we could do-- the magic number for phase I trials in those days was 14. If you got nothing in 14 patients, then you didn't go any further. So we could do 14 patients with the first protocol, which was called MOMP-- M-O-M-P. And we had to do the workups ourselves. We couldn't use other colleagues to work up the patients. And we had to go get the patients ourselves. So Jack Moxley and I did all those things. And the results were very encouraging. And then Jack left. And I sat down and decided that we'd put procarbazine. I was working on procarbazine. It was then called [INAUDIBLE]. And I was working on it and doing the pharmacology in the phase I study with it in Hodgkin's disease. It was a promising candidate. So we put it in. And that became MOPP. Also in those days, six weeks of therapy was it. They didn't get more than six weeks. We reasoned that the marrow problems would be acute. But you'd have to give it probably for a long period of time to affect the tumor. So we gave it for at least six months or to a complete remission plus two months. And we assumed that there were cells left after we couldn't see them. So it was a lot of good thinking that went into it that turned out to be correct, because most of the-- since then, a lot of protocols follow the same sort of routine. And it really works for a lot of cancers. But it was controversial. I went to the AACR meeting. This was before ASCO. And I presented it as an abstract. And David Karnofsky, who was sort of a god at that time at Memorial Sloan Kettering, just tore me apart. And what was I doing using the term complete remission for a solid tumor. He said, that was a term that was used in leukemia. Now, I didn't say it. But I'm thinking, the reason you use them is you can get complete remission. So we had complete remissions. And I was kind of shaking with the microphone in my hand at the time. So it was a scary but it was a good experience. I have to say-- So it just gives you an idea that people were not receptive [INAUDIBLE]. Those of us who are junior to you can't imagine that you were intimidated by somebody else [LAUGHS]. Well, I was a youngster, then. I was-- Jack Moxley and I, I would say, thinking back, we were cocky. But the big guys in the field could scare me. And Zubrod was a-- I mean, Karnofsky was a big guy in the field. Yeah. He just had a hard time getting out of the leukemia mind frame. And so of course, we've used complete remission since then in any kind of solid tumor where you can get one. In your book, you have a great quote that you presented somewhere. And Dr. Frei was there. And Wayne Rundles was there. Wayne, of course, has been at Duke for 100 years. And he said, do your patients speak with you after you're done? Well, Wayne Rundles-- when he first saw the MOPP protocol, Wayne Rundles said, that's nonsense. He said, I get the same thing with nitrogen mustard by myself. Well, nobody had ever got that with nitrogen mustard. So we actually had to set up a controlled trial and do it and prove that MOPP was better. So when I presented it when we were first starting it-- at a meeting. Tom had arranged this meeting with all the bigwigs in the field. And when I presented it at that, everybody was sort of quiet. And then Wayne Rundles raised his hand. He looked pale. He raised his hand and said to me, Dr. DeVita, do your patients speak to you after you do this? [LAUGHS] So he-- a few years later when we were obviously getting good results, he invited me to grand rounds. And by then, we were good friends. And I was up on the podium. And after I gave the talk, he was sitting down below smiling at me. And I said, Dr. Rundles, if you remember, you asked me if your patients speak to you when you do this. And I can tell you that they do for a lot longer. So it was fun. But it was fun. He was a good friend by then. And I had great respect for him. Actually, he was a very nice man. He was. When did you start thinking that you had a success? Was it during those first 13 patients or 14 patients that you treated? I mean, was it obvious right away, or did you start [INAUDIBLE]-- Well, it was obvious-- --you were in the wrong place? We put-- no. We thought it pretty early, because we were worried. We put patients in reverse isolation. Nobody knew whether you were going to kill them if you gave them all these drugs together. And it turned out the first surprise was, yeah, they had the usual toxicity. But it really wasn't that bad. So it was doable. And the second was-- we had a small number. But we had-- something like 80% of the patients went into a complete remission. And I think nobody had seen that. Now, the question was, how long were they going to last? So we were optimistic. And when we put patients on it, there was no cure for them at that time. And we said, we're optimistic that this is going to be something that will last. But we don't know. And then by three years, it looked pretty good. And I think I presented the first abstract four years after we started. And by that time, we had relapse-free survival curves. And again, nobody before that time had presented relapse-free survival curves in any of the lymphomas. So by then, by four years, I think we felt we had probably cured some patients with the disease. I asked Bob Young this same question. Did you feel a sense of history at the time, that this was really historical? Or did that come later when you looked backwards? I think what people don't realize about those days is neither Freireich nor ourselves were treating leukemia and Hodgkin's disease. In other words, we weren't out to develop a treatment for those diseases. We were out to prove you could cure cancer with drugs, because nobody believed it. If you said that, they really thought you had gone balmy. So we were out to look-- so we knew if we could do it, it would be historic. So we were excited when we looked like maybe it was going to happen. By that time, when we had first reported it, the VAMP program that Freireich did, which was an historic program-- he only had 17 patients. And they actually never published a paper on VAMP. And I asked Jay why they never did that. And he said because he didn't think they would accept it anywhere. So but by that time, they were getting about a 50% complete remission rate going four or five years. And they were thinking they're curing leukemia. And we were getting 80% complete remission rates. So I think everybody felt that we were going to prove that you could cure cancer with the drugs. And we did. So yes, in a sense, we set out to do something that would be historic. And so when it happened, I think, it is. It was a sort of a door opener for medical oncology in Hodgkin's disease. I'd like to turn now for just a minute to your role in politics. You were pretty instrumental, I think, when the National Cancer Act was signed in 1971. And that also sounds like a TV drama to me. It sounds like-- and I know this anyway, but in reading your book, it was not clear that was going to get through. Can you give us some of the playground behind that and Mary Lasker's role and how that happened? Well, Mary Lasker played a big role. The MOPP program actually played a big role, because Mary Lasker was sort of working in the background. Cancer was always a cause for her. But when we did the MOPP program, there was a guy named Luke Quinn, who she had hired to be a lobbyist, who was sort of hidden in the American Cancer Society so they wouldn't realize it was Mary Laskers' lobbyist. And he was referred to me by Sidney Farber. And I didn't want to take him at first, because he was diagnosed as having gall bladder cancer. And I said to them, you know-- I said to Sidney Farber, I don't really treat patients with gall bladder cancer. And there was silence on the phone. And he said, (SOMBER, COMMANDING VOICE) you will take this patient. [LAUGHS] So I took the patient. And when I examined him, when he came down and I examined him, he had adenopathy in both axillae. And gall bladder cancer just doesn't do that. So I had to do another biopsy. He was not a pleasant guy. So it was not easy to do these things. I had to get another biopsy. And it turned out that my pathologist at the time, Costan Berard, when he compared the biopsy, he said, it's a lymphoma, clearly. It was a diffuse, large cell lymphoma. What they had done is, because Claude Welch did the surgery-- a very famous abdominal surgeon-- and he said it was gall bladder cancer, that the pathologist sort of assumed it was. And it was a compression artifact. Long story short, he went into remission. And Mary Lasker went gaga. Wait a minute. We got something here. And that was what pushed her to get her friend, Senator Ralph Yarborough, to put up a committee on cancer to come up with the Cancer Act. And-- So it must have been quite a day when President Nixon signed that. Yeah, well, it was-- I wasn't at the signing. I wasn't high enough up in the chain to be invited to the signing. But yeah, I have all the photos of him signing it. And later when I met him-- I have a picture in the book of he and I shaking hands and him looking like he's having a roaring laugh. People ask me what I said that was funny. And I have no idea. But when I asked him, I said what is your greatest achievement as a president? He said two-- opening up China and signing the Cancer Act. So he was-- Really? Yeah, so I think he was proud that he did that. That's a great story. Actually, the other story I had not heard, but read in your book-- I'd like you to tell me about your lunch with Mr. Featherstone. [LAUGHS] Featherstone Reid, his name was. Well, this was a very-- this was a regular occurrence. Mary Lasker, when she came to town, would stay with Deeda Blair, Mrs. William McCormick Blair, who was a Washington socialite and had a lovely house on Foxhall Road. And they would have lunches and dinners. And they always arranged it so that people-- the scientists sat next to somebody with influence. And this is how they influenced the Congress to put more money into the cancer program. So one time, I got a call in the morning from Deeda Blair, saying, I'm having a lunch. We'd like to have you there. And I said, gee, I-- it's too short notice. I can't do it. And she said, well, Mary really wants you to be there. Mary was hard to say no to. So I rearranged my schedule, drove down to Deeda's house. And there was a big black limo sitting in the front of the house. I went in, and they introduced me to Featherstone Reid. I had no idea who he was. And every time Mary would say, we want more money for research with leukemias and lymphomas. Vince, tell him about what's going on. And I would tell him about. At the end of the lunch, he left. And Mary and I sat down on the couch to have a cup of coffee. And I said, Mary, who is Featherstone Reid? And she said, he's Warren Magnuson's driver. And when she saw the shock on my face-- Senator Warren Magnuson was the chairman of the appropriations committee of the Senate. When she saw the shock on my face, she said, wait a minute. When Mrs. Maggie-- he takes Mrs. Maggie shopping during the day. And Mrs. Maggie-- he fills her with all this information we're giving him. And then Mrs. Maggie is the last person to put her head down on the pillow next to Warren Magnuson. This is the way she worked. She would take someone like Magnuson, who was a good friend, but she would surround him with extraneous people who would say the same thing. So it was sort of like subliminal stimulation for him. He was always hearing these positive things. And then he supported the program. She was a piece of work. I never got to meet her. But it sounds like she was a force of nature. She was. And of course, the Lasker Award is now named for her and her husband and sort of the American Nobel Prize. She's had such [INAUDIBLE]. Yeah, and our crew won it in 1972-- Frei, Freireich, myself, and other people for other things. So I'm very fond of Mary Lasker, obviously. It's just a wonderful story. And I got to know her pretty well, so. I have one other question. And I'm not sure you'll want-- if you don't want to go off on it, we can edit it out. But in your book, you talked about Howard Skipper and Frank Schabel. And Dr. Frei used to talk about them all the time. And I think it's worthwhile to bring them into the history of what we do. Did you actually work with them or collaborate with them, or just base some of your ideas on what they had in mind? When I was starting at the Cancer Institute, I thought Schabel worked at the Cancer Institute-- I mean, Skipper worked at the Cancer Institute, because I would be working in the lab. I was doing the tritiated thymidine studies on L1210 mice. And he would be looking over my shoulder. He was doing the similar studies, but he was just doing it with cell counts in the abdomen of the mice. And he thought that was good enough. And he was there at a weekly meeting we had, which George Canellos named the Society of Jabbering Idiots. It was a great, great meeting, actually. [LAUGHS] And he was there all the time. And my view and Tom's view differ a little bit on Skipper. I think he was a real driving force, that he did the studies in mice that we were doing in the clinic with people. And he actually-- in 1964, he wrote a paper showing that you could cure L1210 leukemia. It was the first example of curing a mouse with leukemia. And I think-- so it was sort of a feedback mechanism between the Cancer Institute and the Southern Research Institute. So and he did-- he used to do these booklets. And I think he published hundreds of these booklets. Some of them, we convinced him to actually publish as papers. But I have the collection. There may be 100 booklets he wrote. And he would take a concept that we were working on and then work through it in mice. It was very, very important. And he was a wonderful person. His only problem was he smoked like a chimney. But he was-- I liked Frank and Howard. Yeah, Dr. Frei had the entire set of monographs on his bookshelf in his office and would encourage us to come in and borrow them and read them and come back. And frankly, he basically predicted what you've done with combination therapy. He predicted adjuvant therapy working. There were just a number of things he saw in these mice that we've gone on to apply in the clinic. It's pretty remarkable, I think, so. Yeah, I mean, it's not only he predicted it. But he actually showed the concept worked in mice. So as we know, mice and human are very different [INAUDIBLE]. There was a guy in Boston, Stuart Schlossman, a very fine scientist. And he didn't like mouse models. And when asked what he would do when he saw a tumor-bearing mouse, he would say, I would step on it, because he didn't believe mouse models. And but Frank and Howard did experiments and made allowances for the difference between humans and mice. So it was always good to know. I mean, I have the summary he wrote on Hodgkin's disease after he saw the MOPP program. So I think they're very instructive booklets. So I kept them. Like Tom, I think that we sort of live by them. Well, thanks for discussing them. I think our listeners need to remember these two guys. They were great. We're running out of time. I've really just touched the surface of what you've done and contributed to the field. And the people you've trained is sort of a who's who of oncology, frankly. But at the end of the day, what's your-- I'll ask you the same question you asked President Nixon. And that is, what is your legacy? What do you want people to remember that Vince DeVita did? I get asked that question a lot. And I don't have one thing that I can say. I mean, I've been lucky in my career that I've had a chance to do many things. Being the Director of the Cancer Institute was wonderful. You could sit on top of the whole field and just sort of scan it and see what's going on. And it was very important, because you've become the spokesman of practicing physicians at the same time. MOPP, of course, was important. Putting out the first comprehensive textbook in the field and watching it-- we just came out with the 11th edition-- is also very exciting. So there-- we were the first to successfully treat Pneumocystis carinii pneumonia. And we reported it in a paper in the New England Journal. I mean, there were a lot of things. I'm best known, I think, for MOPP, probably, and the principles of MOP, which I'm very proud of. But there's so many that I have a hard time. I like opera. And people ask me, what's my favorite opera? And I usually say, it's the one I just saw. It's very hard for me to pick one opera. There's so many that I like. So I'm not dodging it. But I just never can say, well, it's this. That's very fair. Frankly, I think, without your contributions, I probably wouldn't be sitting here doing what I do. And I think there are thousands of us who would say that. So we're-- Well, that's very flattering. Well, not only are we appreciative, more importantly, there are a lot of people who are alive who wouldn't have been without what you and your colleagues did at the NCI that so many years ago, so-- [INTERPOSING VOICES] I was involved in the training of 93 medical oncologist. At one time, something like 40% of all the [INAUDIBLE] directors were our graduates. So they have gotten around. And that was good for the field. They went out with the same principles we were developing at the Cancer Institute, so that's very gratifying. Have you kept in touch with any of the patients that you're treated back at the NCI? I talked to Saul Rosenberg. And he told me he still sees people that he treated 30 or 40 years ago when he first moved to Stanford. We're writing a paper on the 45-year follow-up of the first 188 patients. Again, nobody has 45-year follow-ups. And we called every one of the survivors. And there's something like 60% or so of the complete remissions are alive. So I talked to some of them. But we had a nurse talk to a lot of them. And I got messages from them after the call. And some of them still contact me, after sort of an anniversary of their treatment. So yeah, I've kept up with them. The gratifying thing is most of them are suffering from the same illness as most people who are getting into their 70s or some of them 80s. They have hip problems and so on and prostate cancer. But there doesn't seem to be any really major increase in anything in these long survivors. Now, mind you, these were patients who got MOPP as their only treatment. And so when you see second tumors in these kinds of patients, it's usually patients who got radiation therapy plus MOPP. So these patients who are 45 years had just got MOPP. And they seem to be perfectly fine. That's remarkable. I love your comment that they are getting the same illness as the rest of us get as they get older. That's great. Yeah, we don't cure bad hips and bad knees and-- Yeah, we can't cure old age. When I was at the Dana-Farber, I had a patient who had been one of Sydney Farbor's original patients from the early '50s. And by this time he was obviously an adult. He was older than I was. And he was fine, as you've said. Although he said Dr. Farber kept treating him and treating him and treating him. And then finally, when Dr. Farber passed away, someone else picked up his chair. And they said, why are you still getting this? And they stopped it. Yeah. So he got a lot of treatment. I had one of Freireich's VAMP patients. She was a girl in her early teens. And she was a wildcat. But she had had something else, and it failed. And she was one of the first patients on VAMP. And she went into remission. And she stayed in remission. And I followed her for many years. She went to college. She got married. She had children. She brought her children in to see me. And last time I had any follow-up with her, she was in her 60s. And she was one of the really first long survivors of that particular program. So it's really neat to see these patients. And it's not rare for me to go to a meeting and have people walk up to me and say they got MOPP 25 years ago. Someone else gave it to them. And they're alive and well. So that's one of the great gifts of having a chance to do this kind of work. What a privilege. Well, I think we need to end. Again, I want to thank you for being on with us today and filling us in with some of these stories. Had really good feedback for my podcast series. And it's because of the people I've had on it. So thank you very much for all you've done. It's really good talking to you. And I look forward to listening to all your podcasts. [MUSIC PLAYING] Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcast or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
Dr. Hayes interviews Dr. Young about his time with CHOP and MOPP TRANSCRIPT Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Hayes: Welcome to JCO's Cancer Stories, The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs, covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist and translational researcher at the University of Michigan, Rogel Cancer Center. And I've also had the pleasure of being past president of the American Society of Clinical Oncology. I'm privileged to be your host for a series of podcast interviews with people I consider the founders of our field. Over the last 40 years, I've really been fortunate to have been trained and mentored and inspired by many of these pioneers. It's my hope that through these conversations we can all be equally inspired by gaining an appreciation of the courage, the vision, and also the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, we can also imagine and we can work together towards a better future for our patients and their families during and after cancer treatment. Today, my guest on this podcast is Dr. Robert Young. Among many designations he has, my favorite I think for Dr. Young is that he was considered one of the, quote, "gang of five," end of quote, I think self-named, who were responsible for developing the first curative chemotherapy regimen for Hodgkin's disease and non-Hodgkin's lymphomas at the National Cancer Institute in the early 1970s. Dr. Young is currently president of RCY Medicine, a private consulting firm based in Philadelphia. He was raised in Columbus, Ohio, where he couldn't get into the University of Michigan. So he went to a second-rate community college in Columbus called Ohio State. My bosses made me say it that way, Bob, here at the University of Michigan. Dr. Young: Not the correct way, The Ohio State University. Dr. Hayes: So he received his MD then at Cornell in 1965, followed by an internship at the New York Hospital. He spent the next two years as a clinical associate in the medicine branch at the National Cancer Institute. And then he completed his residency in medicine at Yale New Haven Medical Center. In 1970, he returned to the NCI, where he stayed for the next 18 years, serving during most of that as the chief of the medicine branch. Dr. Young accepted the role as president of the Fox Chase Cancer Center in Philadelphia and served in that role and then chancellor in 2009. Dr. Young has authored over 400 peer reviewed papers regarding a broad range of both scientific and policy issues in oncology. But in addition to the I consider astonishing and precedent-setting reports of cures in Hodgkin's disease and non-Hodgkin's lymphoma, perhaps most importantly with his longtime colleague and friend Dr. Robert Ozols, he led many of the early and groundbreaking studies in ovarian cancer diagnosis and treatment that I think still guide our care today for patients with this disease. He's won too many awards and honors for me to go through. But of the major ones, he won the prestigious Bristol-Myers Squibb award, which he shared with Dr. Ozols in 2002, the Margaret Foley Award for Leadership and Extraordinary Achievements in Cancer Research from the American Association of Cancer Research, and ASCO's Distinguished Service Award, one of our highest awards, for Scientific Leadership in 2004. Of note and close to my own heart, Bob served as the ASCO president 1989/1990, which I consider a really critical time in the evolution of our society. Dr. Young, welcome to our program. Dr. Young: Thank you. Dr. Hayes: So as I noted, you grew up in Columbus, Ohio, or again, as we say in Ann Arbor, that town down south, but more importantly that your father was a surgeon. And I've heard you tell the stories as a boy you went on rounds with him and that inspired it. Was he academic or was he a really community physician or both? Dr. Young: Well he was a little of both. He was primarily a community physician. But he did, particularly at the time of the Second World War, because he was a very skilled hand surgeon, he got involved with a lot of hand surgery related to a company called North American Aviation that produced a lot of World War II planes. And there were a lot of injuries in that setting. And so he became quite a skilled hand surgeon and actually taught at Ohio State's Medical Center. So he had both an academic and community-based practice. But primarily he was a practicing community surgeon. Dr. Hayes: And did you actually go into the OR with him as a boy? Dr. Young: Oh, yeah. Oh, sure. Dr. Hayes: Wow. Dr. Young: You know, in those days, there weren't any rules and regulations about that. And so I went in and watched surgery and held retractors and participated, you know, when I was a youngster. Dr. Hayes: Wow. What a privilege. You're right, that would not be allowed now. That's a good story. What did you see, bad and good, compared to medicine now then. I mean, if you had to say here are a couple things that we've lost that you regret. Dr. Young: Well, I think that it was more under the control of the physician than it is in this day and age in so many ways. For instance, my father practiced in three different hospitals. And he admitted patients depending upon what kind of surgical support and nursing support they needed. If they were complex, he went to a bigger hospital. If they were very straightforward cases, he put them into a smaller hospital. And so he had a lot more control over how his patients were dealt with and the circumstances under which they were cared for. And, of course, most of his practice was before Medicare and all of the insurance sort of thing, so that people paid what they could pay. And so it was a much simpler and much more physician-driven practice than it is today. Dr. Hayes: Just as an aside, there's a wonderful book called The Brothers Mayo, written by a woman named Clapesattle in the 1930s after both Charlie and Will died. And it's a history of the Mayo Clinic. But in it, she says that Will basically charged people what they could afford to pay. So if you were wealthy, he charged you a lot. And if you were poor, he gave it to you for free and everything in between. And he sort started made up the billing schedule the way he wanted it to happen. And one of his more wealthy patients challenged him on this, and he said, go somewhere else. Dr. Young: Yeah, well, that's exactly the kind of practice my father ran. Dr. Hayes: Yeah. Anyway, I'm intrigued by year two-year stint at the NCI in the late '60s before you then went back and finished at Yale. And hopefully this is not insulting and I know you're considered one of the so-called yellow berets. But tell me, tell us all about your choice to interrupt your residency and go to the NIH. I don't think our young listeners really understand the political climate and the circumstances of the time that led so many of you to go there. Dr. Young: Well, I think that's a great question, because it will lead to some of the other discussions we have later. But essentially, I graduated from medical school in 1965 at the height of the Vietnam War. And in those days, there was not only a general draft, there was a physicians draft. So graduating in medical school in those days, you had one of three choices. You could either take your chances-- and again, the numbers, your priority scores at the time, didn't really have anything to do with it, because they took as many doctors of whatever kind of type they wanted for whatever purpose they wanted. So that you couldn't be sure if you had a low number that you'd not be drafted. But you could take your chance. And in those days, a lot of people did. And a lot of people got drafted. Or you could join the Berry Plan, which was at the time an opportunity to continue your specialty training until you were finished. But then you owed back the military the number of years that you had been in specialty training. Or you could do a much less well-known track and that is with the US Public Health Service. And amongst the opportunities for the US Public Health Service were things like the Indian Health Service and the Coast Guard Service and those sorts of things, or the National Institutes of Health, about which at the time I knew almost nothing except that it existed. And I owe it to some of the folks that I worked with at Cornell, primarily a hematologist oncologist by the name of Dick Silver, Richard Silver, who's still at practice at New York Hospital, who when I was working in the labs there, because I was doing some research when I was at Cornell, and they were telling me about the fact that you could actually apply for a position at the NIH. And you would be in the US Public Health Service. So it took me about 3 milliseconds to figure out that for me that was clearly a track that I wanted to explore. And I had done some research in platelet function and platelet kinetics and so forth. And there was a guy by the Raphael Schulman who is at the NIH at the time. And I said, that would be a miracle if I could get this. So the way it worked was that you applied. And then you actually interviewed with a whole bunch of different people. And as it turned out, I didn't get a position with Dr. Schulman. But I was introduced to the National Cancer Institute and both the leukemia service and the then called the solid tumor service. And I applied to various things like that. And I actually got in on the leukemia service. So I walked in after I signed up and was taking care of little kids with acute leukemia, having never been a pediatrician or knowing anything about leukemia. But it was a baptism of fire and a very exciting place even then. Dr. Hayes: I want to get back to that in a second because that's a critical part of this. But, again, going back to the political climate, my opinion, this entire issue and your personal journey and many others had a profound effect on both the scientific and medical community of this country as a whole. I think it was an unintended effect. But because of the Vietnam War and because the NIH was such a great place to train in those days. Do you agree with me? Dr. Young: You are absolutely correct. I mean, one of the things that needs to be said is that this was a transformational phenomenon for cancer research. But it also took place in every other field. And the NIH at the time was just swarming with people of all medical disciplines who were coming to take advantage of the opportunities that existed within the NIH, but also to serve in this capacity as opposed to some of the alternatives that were around. And I think I heard a figure one time, which I'm sure is true, and that is at one point in time, 30% of the chairmen of medicine in the United States had done training at the NIH before they ended up being chairmen of medicine. So that gives you an idea of the impact of this. And you're absolutely right, it was a totally unintended consequence. Nobody ever designed it that way. Nobody ever planned for it to happen that way. But in retrospect, when looked at it and you can see exactly why what happened happened. Dr. Hayes: Yeah. And I interrupted you, but I did it on purpose, because it didn't sound to me like you really had a plan to go into cancer treatment, but sort of landed there serendipitously. Is that true? I mean how do you end up there? Dr. Young: Oh yeah, oh, yeah, I mean I did get very interested in hematology when I was in medical school. I first went to medical school, of course, thinking I was going to be a surgeon, because my father had a great practice and he had a wonderful experience with surgery and it was really cool. But I just found that I just wasn't designed just the same way. And it was increasingly clear that cancer was not my not my goal-- I mean, surgery was not my goal. And so, you know, I knew I wanted to stay in internal medicine. And I got interested in the research. And I had done some significant research and in platelet function, as I said. I knew that's what I wanted to do, some sort of clinically-related research in medicine. If I'd had my choices, of course, I would have gone into a sort of pure hematology track. And, of course, it's worth saying that it's difficult for oncologists nowadays to understand how big an outlier oncology was. There was no subspecialty in oncology at the time I went to train down there. There was a subspecialty in hematology. And, of course, all of us, the Gang of Five that you mentioned, all of us took hematology boards. And that's because it wasn't clear that there was going to be oncology. When oncology came along we all took the first oncology boards ever given. So that gives you an idea of how early in the history of oncology we were in the late '60s, early 1970s. Dr. Hayes: So we're talking 1970 or so right when you started? Dr. Young: Well, 1967 to '69, I was a clinical associate. Then I was at Yale for a year. And then in 1970, I came back on the senior staff. Dr. Hayes: And who were the characters above you when you came in? I know Doctors Frei and Freireich had been there before. Dr. Young: Yes. Frei and Freireich had just left the year before. One went off to MD Anderson, the other went off to the Memorial. And George and Vince-- George Cannellos, Vince DeVita-- had stayed on, with Vince as the head of the medicine branch. And then when we came back, Vince sort of brought two of us back that he'd had before, Bruce Chabner and I. He'd sort of sent us off to Yale and said they could buff us up a little bit. And he didn't offer us a job coming back. But we went off, and we were training up there. And he called us both up and says, why don't you to come back and join the senior staff. He recruited Phil Schein as well. And so that was the Gang of Five that we started out. Four of us ended up being president of ASCO at one time or another. And I suspect the only one who didn't, Bruce Chabner, probably would have except for the fact that he was the director of the Division of Cancer Treatment of the NCI for a long time. And the NCI and the NIH changed its attitude toward allowing people to participate in major leadership positions nationally, a tragedy as far as I'm concerned, which has I think affected the morale of the NIH and a lot of other things and deprived a lot of good people of opportunities to serve nationally. But that was the way it was, otherwise we would all ended up at some point leading-- Dr. Hayes: So the Gang of Five was you Bruce Chabner, George Cannellos, Phil Schein, and Vince DeVita, right? Dr. Young: Right, exactly. Dr. Hayes: And what were the dynamics among you? I mean, so were you and-- Dr. Young: Well, I mean, it was an incredible time. You know, there was enormous talent that had poured into the NIH, as we talked before. And an enormous amount of talent was present and was recruited in during this period of time. I mean, you know, Paul Carbone was still there. John Minna was recruited. Harman Ayer, who was the longtime chief medical officer of the American Cancer Society. Tom Waldman was a world class hematologist. Max Wicha was a part of this group. Sam Broder, Allen Lichter, an other ASCO president, Steve Rosenberg, Phil Pizzo was the head of the pediatric oncology branch, now dean at Stanford. And it goes on and on and on. And so there's a massive amount of talent and a lot of freedom. And so Vince was clearly the leader, he had a lot of ideas and a lot of creativity. But he let out a lot of people do whatever they wanted at the same time. And it was sort of a situation in which we all participated, because we were all attending at the same time. So Vince and George did a lot of the lymphoma and Hodgkin's disease stuff. We all participated. I got interested in ovarian cancer. And you talked about that. Bruce Chabner and Phil Schein were always very pharmacologically oriented. And so they did a lot of the phase 1 and phase 2 trials and a lot of the laboratory backup associated with the studies we did. And everybody shared. And so there was really not a lot of competition in that sense. Everybody was I think very competitive. Because it was all sort of shared, it worked out so that everybody felt that they were getting a substantial part of the recognition that was going on in the group. Another thing that was unusual about the NIH, but it had unintended, but important consequences is that nobody had anything to do with what they got paid. So that you could go to events and say, well, you know, I deserve to be paid more, but it didn't have anything to do with what you got paid. We had no control over anybody's salary. So that I don't think the whole time I was there, the whole 14 years I was chief of the medicine branch, I don't think I ever had a conversation with anybody about money, because I didn't have anything to do with what people got paid. Let me tell you, that's a big change. It actually has a remarkable, remarkable effect on the way people work. Because if for some reason somebody wanted to make more money, they just had to leave. There wasn't any way to do it. So you either had to accept that this is what everybody got paid and that you were rewarded by the opportunities to do the kinds of research that were done. Or you said, look, I need to go on and go somewhere else. Dr. Hayes: Now, just between you and me, and maybe a few thousand other people who are listening to this, who is the first guy to say let's give combination chemotherapy to Hodgkin's disease? Dr. Young: Well, actually, I don't know the answer to that. I think if I had to guess, I would say Vince, because Vince and George had been around in the Frei and Freireich days. And of course, you know, they'd already had experience with the impact of combination chemotherapy in leukemia. And so the concept was you took drugs that were active in the disease and put them together if they had different kinds of toxicity. And you were then able to utilize the combined impact on the tumor and sort of spread around the toxicity. So it was more tolerable. And that was the concept. And I think that because Vince and George were treating chronic leukemias and treating Hodgkin's disease, the notion of combining it with combinations was pretty straightforward evolution from the experience in leukemia. There are other people who claim that. I think from time to time both Jay Freireich and Tom Frei have claimed it. I think that there was a dust up between Vince and Paul Carbone and George because there was some suggestion by somebody that Paul was the one who originated the idea or Gordon Zubrod. And quite frankly, I don't know. If I knew, I would tell you. But I don't actually know. I can tell you this, that the emotional and passionate driver of the concept of combination chemotherapy as a successful modality in Hodgkin's disease and lymphoma was Vincent. Dr. Hayes: Your answer is very consistent with what other people have said the same thing. It must have been somewhere along the line that all of you began to see that there really were cures. And did you realize, as a group, that you were making history? Or was it just day to day-- Dr. Young: Well, you know, it's interesting. I can tell you one of the most transformational experiences that I had in the early days is, of course, we were following all these patients who had started on MOP. And so to do that you had to sort of go back and pull out the charts and all this kind of stuff. You know, we didn't have electronic systems that had all the stuff recorded. You just had to go down and pull off the charts. And what struck me so tremendously was the attitude of the physicians that had first started some of these patients on this therapy, because the notes made it very clear that they were sort of flabbergasted when these people came back after the first couple of months and they were watching their disease disappear, and that they really didn't anticipate at all, initially, that they were going to see these people after a couple of weeks. And it was very clear in the notes. By the time we had gotten there, of course, there were a significant number of people already on the trial. And it was already clear that we were seeing things that nobody had ever seen before. And I think that's when it first began to dawn on everybody. And as soon as we saw it in Hodgkin's disease based on the experience that we'd seen with non-Hodgkin's lymphoma, we had a suspicion that it would likely be the case as well there. Dr. Hayes: So you already bounced across it, but as I was looking through your CV I knew this anyway, you really mentored a who's who of oncology-- Rich Schilsky, Dan Longo, Max Whishaw, Dan Van Hoff-- and you noted already that oncology training has evolved. I mean BJ Kennedy pushed through boards I think in '74 or '75, something around there. What have you seen in the evolution on oncology training that you think is good or bad? Dr. Young: Oh, I think in general, it's much better. And I think it's much better because, of course, there's a lot of success that's been built into what's been accomplished. And that makes it a lot easier to teach people about how to treat Hodgkin's disease well, than we ever could at the time we were doing it because nobody knew the answer to those things. And I think there's also a lot more of it. You know, I think at the time we were at the NIH, you know, I think credibly you could count on both hands the number of really established academic oncology programs in the United States. And now, there are probably 100. And so the quality of training and the quality of mentoring is dramatically better than it was in those days. In those days, you know, hematologist we're doing most of the treatment of cancers. And they were all sort of in the Sidney Farber mode. You take one drug, and you give it as long as it works. And then you switch to another drug and use that as long as it works. And that was pretty much the way hematologists approached the disease. And by all means, you don't cause any toxicity. Dr. Hayes: I picked up several adults who had been Sidney Farber's patient when I was at the Dana-- Sidney Farber Cancer Institute in those days in the early '80s. So I had his handwritten notes. And sadly, I did not photocopy them. I would have love to have had it. But he had a very different mindset in terms of the way-- Dr. Young: Oh, absolutely, absolutely. And as far as I can tell, this is just my own personal reaction, is that I don't think either George or Vince at the time we got here shared any of that attitude. George is a little more cautious than Vince, as everybody knows. But neither one of them for a minute ever suggested that we were being too aggressive, that it was unfair and immoral to treat people with these kinds of toxicities, not that they desired to make people sick. But they were absolutely convinced that aggressive therapy could make a dramatic difference in the natural history of these diseases. Dr. Hayes: Yeah, certainly, Dr. Frei felt that way too. Dr. Young: Yes. And well, they were his mentors. I mean, you know, all these guys were there at the same time. And they were all influencing one another. Dr. Hayes: You know, it's amazing, I think all of us-- there are 44,000 members of ASCO now-- basically are derived from about 10 people in the 1950s and '60s, most of the DNA, not completely-- Karnofsky and some others around, but-- Dr. Young: Oh, yeah. Dr. Hayes: Well, the other thing is actually, you were talking about the safety, what are the war stories? I mean, how did you give chemotherapy? Were you guys mixing it up and giving it yourself? You know, we got all these bells and whistles. Dr. Young: Well, I mean, for instance, you know this is the first time really protocols were written. And the reason that we wrote protocols was simply because we were working with fellows. And they literally needed the recipe of what it was they were supposed to give and when. And so we wrote up these what were the first of the clinical trial protocols. There was no formal informed consent at the time of these studies. We had, of course, informed consent, the same way you do informed consent now, really. And that is you talk to the patient. You explain to the patient what the treatment is and what your expectations for the treatment are. And the patient understands the disease they face and decide that they can do it or not do it. And it's actually still the same today. The only difference is we now have 14, 17-page informed consent documents that make lawyers happy, but don't really impact, at least in my view, whether patients decide to participate or not. But we didn't have those. So I think that was the other one of the great things about the setting at the NIH, not that I'm anti-informed consent, but it was simpler. It was easier to get something done. You could do unconventional treatment and nobody looked at you and said, "you can't do that, that's never been done before, you're not allowed to do that." We didn't have academic constraints. One of the things that always surprised me is when, you know, we would develop a particular technique, like peritoneoscopy or laparoscopy for ovarian cancer staging, and when guys left the program having been well-trained to do this, they couldn't do it when they went to their new institutions because gastroenterologists did this. That was the sort of thing that the constraint wasn't here. There were also very easy-- I mean, all you had to do was to get an idea and write it up. I took a look at ovarian cancer and said, you know, "It seems to me, here's a disease that's now being managed by gynecologic oncologist. Internists never see these patients. They're all treated with the melphalan. And those that happen to live a long time develop acute leukemia from that treatment. They ought to be something better than what we're doing." And so we just decided that we would begin to take patients with advanced ovarian cancer into the NIH. And the rest sort of is history. But you couldn't do that in another hospital. You know, the biggest treaters of ovarian cancer probably program-wise was MD Anderson. But all his patients were treated by gynecologic oncologists. You couldn't have gone into the MD Anderson and said, "OK, we're going to take over the treatment of advanced ovarian cancer." They would have laughed in your face. Dr. Hayes: Actually, you just segued into my next question. And again, you and Dr. Ozols, in my opinion, completely changed the course of ovarian cancer treatment. Did you get a lot of pushback from the gynecologic community? Dr. Young: Well, no, actually. It's interesting. Now I don't know what we got behind the lines, you know when they were all sitting around the bar after the meetings. We really didn't. First of all, one of the other advantages of being at the NIH is that when you said something, people listened. And the other thing is, of course, when we got really going with ovarian cancer-- this was after the passage of the National Cancer Act-- and there was money at the NIH. So one of the things we did, for instance, was to put on a series of symposia about ovarian cancer treatment, what was going on, what wasn't going on, and brought the movers and shakers of this field together in meetings and talked about what was being done and what should be done and what information we didn't have that we needed. And we actually got funded for a period of time, a group called the Ovarian Cancer Study Group, which eventually evolved into the Gynecologic Oncology Cooperative Group, National Cooperative Group. So we had some other tools that we could bring to bear to drum up an interest in new research in ovarian cancer. And, of course, gynecologic oncologists couldn't prevent us from taking patients that were referred to us. And our surgeons, for instance, none of whom were gynecologic oncologists, were happy to help and to operate on them when they needed to be operated on. And Steve Rosenberg's group has fantastic surgeons. So we didn't have any problem getting state of the art surgery done on these people. And, in fact, they are general surgeons learned some gynecologic oncology at the same time. Dr. Hayes: Yeah, you know, it's been interesting to me that the surgeons, the general surgeons, willingly gave a systemic therapy. But that still in this country, there are very few medical oncologist who do GYN oncology. It's still mostly done by GYN oncologists. Dr. Young: Yes. Dr. Hayes: And there are very few trained medical oncologist in this. And I think it's gotten too complicated for a surgeon to do both. I don't really see why that hasn't happened based on, especially your model and Bob's model, that's my own soapbox. Dr. Young: Yeah, that's an interesting point, because at the NIH, when we were there, Steve Rosenberg and Eli Gladstein in radiation therapy, there were no rules that said that they couldn't do chemotherapy. And, in fact, they did it sometimes. And we didn't say anything about it. Usually, they called on us and said, hey, look, you know, we need you to help us or participate with us or whatever. But there were no rules that said that they couldn't. And sometimes they did. But for the most part they said, "look, this is not the business we're in. We want you guys to do the chemotherapy." And so for the most part we were able to do that. Dr. Hayes: The entire NSABP, those guys were all given their own surgery, their own chemotherapy. And they ultimately handed most of it over to medical oncology through the years. But that's not happened so much in GYN. OK, I want to go into your role in ASCO at the end here. And as I noted, I think you were president during a really critical turning point for the society. And just a few things, you already mentioned that I think you were already at Fox Chase when you ran. So you'd left NCI. And what made you run? But more importantly, tell us about your role in the evolution at that time of the society. Dr. Young: I think actually they recruited me to run just at the time that I was looking to leave. And so I left in December of 1988. And I was president of ASCO 1989 to 1990. At the time, I had moved from the medicine branch and ran the cancer center's program for a year. And I decided that I liked it. I thought, well, maybe I'll just stay here for the rest of my life, the way Steve Rosenberg did and others have done very successfully. But I said, well, you know, it's either sort of now or never. And so I decided that I would make the jump. But when I got into the sort of ladder, if you will, of ASCO through the board and so forth, it became clear that there were a couple of things that were a real challenge for the society. The society had at the time for the most part been essentially run on contract, that there was no organization of ASCO at all. It was it was all run by a contract organization. And it was clear that we had grown to a size such that we really needed to begin to recruit our own leadership staff. And so my year as president was actually the first year we hired a full-time employee. And she was based in a law firm that we used for ASCO legal business. But that was the first employee ever hired by ASCO. And that was in 1990, or 1989, I don't remember which, put in that year anyway. The other thing that was going on, which was critical for the society, is that, of course, there's always been a 'town gown' challenge in all aspects of medicine. And medical oncology was no different. So it had originally been the province of academic oncologists. But the numbers began to change dramatically. And it became clear that there was an enormous number of community-based oncologists, who looked at the challenges that face the organization somewhat differently than the academics. And this is one of the things that I think I benefited from growing up with a father that had both his feet in the community-based practice and the academic practice. And I realized how private practicing physicians view academics and view academic control of organizations. And I realized-- and others did too. I wasn't alone on this-- that we really needed to build up the recognition of community-based oncology as a first class citizen in the society. And so we began to create and bring in all of these state society organizations. And we began to get leadership roles who were based in community oncology, rather than just academics. And Joe Bailes was our first head of the Public Relations Committee of the society and grew this into a national presence and became the first community-based president of ASCO. So I think I think those are the two things that I saw that hopefully I made an impact on. And it always amazes me to realize that the society was really that young. I mean, people can't believe that it's just, what, 30 years ago when we had our first employee. Dr. Hayes: Yeah, that's why I'm doing these podcasts. We make sure we get this history. You know, it's interesting, I often give you credit for the ladder. As president myself, it was made very clear to me that 90% of the patients in this country with cancer are treated by community oncologists, maybe 85% or so. And about 2/3 of our membership are community oncologists. So we now have designated seats on the board of directors. We started a Department of Clinical Affairs that Steve Grubbs is running. That's just a few years old. But, boy, it's been fabulous. We now have a designated chair, the state affiliate council is invited to the board of directors and sits in and presents. And the state affiliate councils meets at ASCO headquarters at least once a year. And we've had a couple presidents who are, besides Joe, Doug Blayney and Skip Burris now coming in in June. So I think we've been reaching out. It always struck me when I sat in the headquarters, the seven founding members were, for the most part, community people. They met just to talk about how do you give chemotherapy. It wasn't, you know, about Tom Frei or Freireich or Jim Holland. It was folks in the community. And then it grew into an academic society. And I think you and then Joe Bailes and others kind of brought us back and grounded us. And to me, that's a really critical evolution in our society. I think it's made us much stronger. So those are most of my questions. You've answered almost everything I had written down that I always wanted to ask you if I got a moment in a cab with you. I want to thank you for taking time to do this. But more importantly, I want to thank you for all the contributions you have made to the field. I mean, I don't think I would be here and I don't think most of us who do oncology would be here if it weren't for you and the Gang of Five and the things you've done, both by the courage to moving forward to giving the kinds of chemotherapy and stuff, establishing science in the field, but also the policy stuff. Your articles in The New England Journal over the years, I think have been classics. You should put this all in a book and send them out to everybody because they have to do with not just giving chemotherapy, but the whys and hows of what we do. So I know I'm being long-winded, but that's because I'm a big fan. Well, thank you very much. Dr. Young: You know one of the things, I got to say is that I've just been a very lucky person. I happened to have had great opportunities. And I think I was able to take advantage of those opportunities. But somebody gave me those opportunities and put me at the right place at the right time. And so I am a very lucky guy. Dr. Hayes: Well, and I want to finish up and say how nice it is to see at least one graduate of Ohio State University do well. You know, it doesn't come very often. So congrat-- Dr. Young: Yeah, yeah, yeah, yeah, yeah The team up north, the team that will not be named, yes. Dr. Hayes: Thank you so much. And appreciate all you've done. Again, appreciate your taking time with us. Dr. Young: Thank you very much, Dan. Dr. Hayes: Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listened. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one ASCO's many podcasts. You can find all the shows at podcast.asco.org.
Dr. Hayes interviews Dr. Muggia about his time at NCI. TRANSCRIPT: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Welcome to JCO's Cancer Stories, the Art of Oncology, brought to you by the ASCO Podcast Network-- a collection of nine programs carrying a range of educational and scientific content, and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. [MUSIC PLAYING] Hi, and welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm the medical oncologist, and I'm also a researcher at the University of Michigan local cancer center. And I'm the past president of the American Society of Clinical Oncology. I am truly privileged to be your host for a series of podcast interviews with the founders of our field. Over the last 40 years, I've really been fortunate. I've been trained, mentored, and I've been inspired by many of these pioneers. It's my hope that through these conversations, we can all be equally inspired and gain an appreciation of the courage and the vision, and frankly, the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. I hope that by understanding how we got to the present and what we now consider normal in oncology, we can also imagine and work together towards a better future for our patients and their families during and after cancer treatment. Today, I'm pleased to have, as my guests on this podcast, Dr. Franco Muggia. He's generally considered one of the pioneers of new drug development oncology going all the way back to the 1960s. Dr. Muggia is currently a professor of medicine and co-chair of the GYN Cancer Working Group at NYU, and a member of their breast cancer program. He was born in Turin, Italy before the war. But when he was about three years old, his family fled to Ecuador to escape Mussolini's fascism. After growing up there at the age of 18, he moved to the United States in Danbury, Connecticut, to finish high school. And then he received his undergraduate degree in biophysics from Yale in 1957. In 1964, he became a US citizen. But he's remained true to his roots and has been very involved with both US/Italian cancer collaborations and mentorship, and also with South America for decades. He went to medical school at Cornell, followed by an internship at Bellevue in New York City, and a residency at Hartford Hospital in Connecticut. He completed a fellowship in medical oncology hospital in 1964-1967. And we're going to talk about that, Franco. And since he's had a number of important academic positions at Einstein, the NCI, University of Southern California, and New York University on two different occasions, and that's where he still practices. He's been involved in the development of clinical trials of hundreds of new drugs through the years, perhaps most notably, cisplatinum. In regards to ASCO, he served on our cancer education committee and on the editorial board of JCO. In fact, I understand you were the first editor of the Spanish edition of JCO. Correct. Correct. And perhaps more importantly, he's been a direct, and an indirect, mentor of hundreds of medical oncologists of the decades at that many institutions he's served, including myself, frankly, in my association with his good friend, George Canellos. Dr. Muggia, welcome to our program. Thank you very much, Dan. And I would just say, just a comment on the citizenship. So once I became a citizen, I actually became eligible for the draft. And that was the main reason why I ended up at the National Cancer Institute. So it had a-- it was a great effect on my career, that I actually volunteered for the Public Health Service in 1969. Because Lyndon Johnson changed the rules for physicians. And if you hadn't served, you had to serve up to age 35. So I decided I should join, not head to Vietnam like the rest of my classmates-- like many of my classmates from Cornell. And it really was a career change for me. Actually, that's a recurring theme in my podcast series. I have interviewed several people at the NCI in the mid to late '60s and early '70s sort of pejoratively, but actually not. You all became known-- as you've put in some of the things you've written-- as the yellow berets. Right. But in fact, it's really, I think, fundamentally changing-- NIH in general, and especially the NCI. We'll talk about that more later. I know your father was a pediatrician. Leaving Europe in the 1930s must have been extraordinarily painful for him and your family. Can you tell us more about that, and getting to Ecuador? Well, he was-- he never joined the fascist party. In fact, he was best friends with the socialists that remained at that time. Mussolini was brutal. He wanted everybody to become a fascist. And anybody who served at the University lost their jobs. He was in a bit of hot water as well. So that, plus the racial laws, which made Jews not be citizens, led to a big decision in the family. It was a phone call, whether we wanted to join an enterprise-- whether he wanted to join an enterprise in Quito, Ecuador in a pharmaceutical company. And my mother said, I don't know where the place is, but let's go. So that's how it happened. So in a matter of a few weeks, we were gone. And I was three years old. So how did you end up getting to Connecticut? Well, that was-- the American School of Quito, which I was a founding member in kindergarten. There was this person who became Ecuadorian, who was actually born in New York because his father was a consult here in the early 1900s, Galo Plaza Lasso. He decided, hey, we need a school-- a private school that-- non-religious, that competes with the German school that's there. We're going to call it the American School of Quito. So I was a founding kindergarten pupil, and ended up going right through to graduation with my class, except that the last year, I was an exchange student in Danbury, Connecticut. Because our principal, who was a champion swimmer-- Ashby Harper-- and John Verdery, who was at the Wooster School principal, they were together in Princeton. And they decided to make this exchange program, which ended when-- I was the last one, actually, of six years. My brother, he was there three years before. But they sent a person, or two people, to be there for their last year. And now I know you went on to Yale to study biophysics. I'm always fascinated by why people end up making decisions. So you were biophysics major. Why did you go into medicine? Was it your father? Well, my father and my two grandfathers were physicians, actually. So my brother was already-- he preceded me at the Wooster School, and then he went to Harvard College. I decided to go with some of the-- it was a small class. We had 16 people. Four of us went to Yale. So I decided to join the group that went to Yale. And my father thought that I should go into the sciences, but not medicine. One doctor was enough. So I started off, and I was actually doing very well in math and physics. And I was friends with a lot of premeds. But I didn't want to take any pre-medical-- the usual biochemical courses that were given at the medical school. So I decided to go with the head of biophysics major, and that suited me fine. So I started with that. And then I decided, well, you know, that's good. But let me head to medical school. So you had no choice. Actually, the really great story, I know you went to Cornell Medical School. Tell us about the lecture by Dr. Karnofsky, which I think has ended up changing oncology. Yeah, so-- yeah, actually, it was the first lectures we had in medical school as freshman. And we had-- in our 30th reunion a few years later, I talked about Karnofsky, how he inspired me to think about the clinical matters in cancer and his performance status evaluation. I remember that very well. Nobody else did. I have to tell you-- I guess it resonated with me, but not with my other mostly surgeons in my medical school. Well, this is, frankly, a recurring theme in these podcasts too, which is many of our pioneers hadn't thought about going into cancer. In fact, in those days, it almost didn't exist. And then one person made a light bulb come on. I have the same issue in my own career with Dr. Einhorn. So I think all of us need to keep in mind, you never know what influence you're going to have on a medical student. Yes, mentorship is extremely important. And going to class, face-to-face meetings are important. I know you've told me some of the stories too, but when you were at Cornell and located through Memorial, that you ran into some of the luminaries-- Joe Burchenal, Irwin Krakoff, Miriam Isaacs-- Well, I took-- well, that's partly mixed with my internship because I did my internship at Bellevue Cornell division. Yeah. And also, my clerkship. So yeah, that's when I took some electives, too, at Memorial as well. What did Miriam Isaac bring into this one? I think a lot of us know about-- Miriam Isaac was head of the metabolism group. Where did you know her from? I've just heard her name, yeah. Yeah, she was part-- Parker Vanamee and Miriam Isaac ran this physiology. It was called physiology elective. And it was ideal for a third year student. I learned everything, because you saw so many derangements that were concomitant with what was happening with the progression of cancer. But they examined all the issues regarding what led to hyperuricemia, hyperkalemia, any electrolyte imbalance. So you really learned a lot. So that almost gets to the birth of translational medicine, in many respects. We think this is new. It's not. It goes way back. Right. It goes way back. I know then you went on and finished your residency. And most importantly, you are an alumnus of the Francis Delafield Hospital. And that spurred me. I've heard this hospital's reputation my entire career. But I never knew who he was, or what it's all about. Tell us about-- Well, so the city of New York, the city of New York, they really had very good outstanding commissioners of health who decided that cancer hospitals were important to take care of New Yorkers with cancer. And they set up one at Cornell, which was called James Ewing Hospital, which was right inside Memorial Hospital. So they were-- I mean, people don't really remember the James Ewing Hospital because it was annexed into Memorial Sloan Kettering. But the one at Columbia was a separate building. And it was Francis Delafield Hospital. And it had real luminaries from the Columbia faculty, including Alfred Gellhorn, who was a professor of medicine and very charismatic. It was an outstanding group of individuals. Gellhorn presided over a group of about 10-12 internists who were dedicated to cancer and also translational research, as you say. And one of my papers that I wrote to my fellows was on hypercalcemia malignancy with Henry Heinemann, who was one of the internists. He devoted all his effort into physiology, so to speak. So it was kind of the same segue to what we I had at Memorial as a student. But the Francis Delafield Hospital had problems. They had staffing problems because the head of medicine would not send their residents to-- stop sending their residents through the oncology services-- I guess that's what it would be, if you're taking care of medical oncology services. They were in all that way. But it was the Department of Medicine at Francis Delafield. And it was kind of a bit of envy, in part, as one interprets, that Gellhorn was so popular with the students. And so there was all this internal discord with these services at Columbia and Francis Delafield, although Francis Delafield was part of Columbia. So at one point, when the residency finally stopped including, the Bellevue first division residents did rotate through. The first division residents were Columbia service at Bellevue. And they rotated through. So when Gellhorn and another name, the president of ASCO later, Jon Altman-- who was a terrific teacher whom I worked with-- he then left and went to the University of Chicago. And Gellhorn left and became dean at the University of Pennsylvania. I was told to get another job. I was there, starting to be an attending physician. And I went to Albert Einstein. So as you see, I've moved around. I've moved around a lot, but I've moved around always twice to the same place, except the University of Southern California. And there, I go every year. I've maintained my ties with the Trojans. I know that Ezra Greenspan came out of there, and Jim Holland. Jim has told several of us this story, that he was in the military. And when it ended, he thought he was going to go back and be an internist with Dr. Loeb at Columbia at the main hospital. Dr. Loeb called him, and told him there was no space. And why don't you go work at Francis Delafield? And apparently, Dr. Loeb said because somebody always gets mental problems or tuberculosis. And we have to replace them anyway. And so Holland went to Francis Delafield and took care of a young girl with leukemia who sadly died. But it changed his life. That's what made him go into oncology. I deeply regret that I won't get the interview Jim Holland. Yeah, Jim Holland was the first alumnus of that program of the Francis Delafield Hospital. And, yeah, 10 years before I went there. And Jim and I remained friends for many years. We had that friendship in common. Jim gave a-- he was an extremely articulate individual. And when Alfred Gellhorn died in 2007, he gave one of the most touching memorials in his honor. We actually interacted recently through various collaborations here in New York, with first, Jim Holland set up this New York gynecology/oncology group. He was kind of the leader in that, even though he was not involved in gynecology. But he loved to host a group-wide effort. And it happened to coalesce first in gynecologic oncology, because everybody-- they all loved Jim Holland, teaching the gynecologists, but chemotherapy in general. And he's a great leader. So he became very active in the Chemotherapy Foundation, which is a New York foundation, and spoke at the meetings. And his wife, Jenny Holland, was on the board of the Chemotherapy Foundation. We gave them-- we gave Jim an award last year in November, of the Chemotherapy Foundation, for scientific excellence. And he gave one the most unbelievable talks there. Everybody who was there, which were fellows from the New York institutions and lay audience that was there at that event, they really learned a lot by Jim's presence. And unfortunately-- unfortunately, two months later, Jimmy Holland passed away-- less than two months. And of course, Jim passed away in March of 2018. We all miss him. And any of us who had been to the Chemotherapy Foundation, especially when Dr. Greenspan was running it, I always loved that meeting. Actually, when you were at Francis Delafield, what was giving chemotherapy like? It can't be as well-organized. Well-- [LAUGHS] Well, it was organized in the lymphoma service, which John Altman ran. And I was-- so my fellowship at Francis Delafield, it was a bit unusual. It was six months of hematology, six months chief resident, six months again hematology/general oncology, then six months chief residency. So we were involved during the fellowship in running some of the-- and orchestrating the work for the medical residents. In our spare time, we did work in the clinics. And in hematology, I worked with Jon Altman. Did you guys mix up your own chemotherapy in those days? Oh, sure. Yes. Well, that went on when-- actually, that went on when I became attending here at New York University. When I came back from the NCI, we mixed the chemotherapy. So yes. Our younger colleagues don't know this. Nowadays, it's all the pharmacists do it. And the nurses hang it up and start the IVs. And in those days, you guys were on the front lines doing the whole thing, right? Yeah. I mean, we gave vinblastine primarily, but the clinic stereo was vinblastine that we gave. Because the other drugs were procarbazine, nitrogen mustard, of course. There is Chuck Martel of Mayo Clinic fame and florouracil fame. He said he used to do morning rounds to give florouracil at the Mayo Clinic. I don't know who mixed the florouracil for him. I mean, it came in already mixed. But he used to deliver the drugs. Life was different then. Actually, I want to change tracks a little bit, and that is because I know you had a lot to do with the development of supplying them when you were at CTEP at the NCI. You and I were fortunate enough to get to attend the 40th anniversary of the approval of cisplatinum by the FDA. It was held in east Lansing. And that's because Professor Barnett Rosenberg discovered it at Michigan State. Can you give me just some history of that, of what your role was, and why Dr. Rosenberg thought that cisplatinum was a good idea in the first place? Well, I mean, it goes of the drug development program, which was one of the major efforts of the chemotherapy program that was the first program that had oncology involved in it. It was mostly the team in lymphoma, with Gordon Zubrod being the head. And he's the one who recruited Fry/Frederick, and then Carbonne/DeVita group. And they were doing the clinical oncology part. Drug development was a very much part of it. And of the drugs that-- they developed drugs for some of the pharmaceutical industries because pharmaceutical industries had no trials. They had their own pipeline. Now their own pipeline had drugs like nitrosoureas, which didn't go anywhere, and dacarbazine. They were not so robust related to the screens that they used for drug development. But they also had drugs from academia and from the Department of Agriculture. And from academia, they got cisplatin, which was isolated by Barnett Rosenberg at Michigan State, as you heard in that great event that they had, the 40th anniversary of its approval. And he was running electrical currents in bacterial cultures and found that the bacteria were developing-- stopped dividing and developing filamentous forms, which were very unusual. And then he thought it was electricity at first, but then only platinum electrodes had that property. And he and his co-workers made the right assumption that it was platinum. They isolated cisdichlorodiamine dichloroplatinum which was known from a century before to be an inorganic platinum salt. That drug, when I was first at the NCI, my first tour duty as a senior investigator, was broadcasted because it had tremendous anti-tumor activity in the screens. And so when there were press releases, like it often happens, lay people call in and they want the drug for their relatives, or for themselves. And I remember answering phones and saying, no. We don't have that drug. It hasn't been given to people. But the story in 1972, the phase I study was-- I attended the ACR, where they presented. Chuck [? Kerlia, ?] from the University of Illinois, he did the first study. And it had activity. But it bumped off some kidneys and some hearing. And I said, well, who needs a drug in head and neck cancer, or Hodgkin's, where you have such terrible toxicities? Well, guess what? I was wrong. First, you deal with the cancer, then you deal with the toxicity. But it was Jim Holland. Actually, Higby, Don Higby, who worked with Jim Holland at the Roswell Park in the Holland service, who identified remarkable activity in testicular cancer. And that's what carried it. And then Larry Einhorn, of course, carried the ball on that on the development of cisplatin in testicular cancer. The group in the [INAUDIBLE] showed tremendous activity. Eve Wilshaw showed tremendous activity in ovarian cancer, but not quite curative, which is an interesting facet. And then, well, the rest is history. The FDA, that was my second time at the NCI. I had the pleasure of sitting with Vince DeVita at the FDA with Bob Kraut, who said, no, this drug is too toxic. You've got to do some randomized studies. And that was 1978 then. Vince pounded the table and said, the best thing that's happened to oncology, you can't recognize it? You know, there's something wrong with your procedures. So that led to some rethinking. And sure enough, it was approved. No need for randomized studies, given that it was curing testis cancer, but a need for educating how to deal with and cope with the toxicities. Actually, I have-- So that's the story of cisplatin. And it was even further detailed by-- when you were there at that meeting-- by Larry Einhorn and his patient. Yeah. Actually, I have three remarks to this. One is that when I was a fellow, Dr. Fry used to teach us that if the drug works and is curing cancer, we'll figure out the toxicities later. That's a little ruthless, but it's always stuck with me. Yeah. Yeah, we don't want to say it too loudly because toxicities are very important in anything you do. But of course, if you are-- you know, if it's the last resort you're looking for, for something to help the patient-- and it is helping-- you kind of have to bite the bullet sometimes. Those were the days where we had many cures anyway. The other thing that struck me at that meeting is cisplatinum is now used in more than half of all cancers-- adult cancers. I didn't realize it was that common. But that's true. The other thing that I didn't realize, that the number of publications continued in research, continued to increase more than imatinib and trastuzumab. Yeah. And that's the other thing I heard. And the final thing, just, if there are any chemists listening, to get lucky from all this-- it turns out, that trans-diaminoplatinum doesn't work, and cisdiamine does-- dichloro, I'm sorry. And the reason why is entry into the cells, is that the trans doesn't get in the cells. And the cis does. And it just goes to show how important that clinical chemistry is in our drug development. I think a lot of us forget that in the pharmacology. Right. There are actually a lot more things to learn in how the platins interact with DNA. Yes. Actually, another layer I want to go into is your importance and the really remarkable growth in the cooperative groups in the late '90s. Can you kind of give us a brief history starting in 1955, when Drs. Fry and Frederick and Holland started? And then what your role was later on in making it really take off? You're talking about the chemotherapy program? Well, weren't you involved with the qualitative groups and-- With our comparative groups, yeah. Oh, yeah, they came together. Yes, no, for sure. I was there first as an intramural person. And I was briefly on loan to the solid tumor service with Vince DeVita and George Canellos. And then I was in their new-- Paul Carbone had put me in the lung cancer study group there, that led on. So I was strictly intramural. When I returned to Einstein after to doing my service, Vince DeVita became the director of the Division of Cancer Treatment, which is the evolution of the chemotherapy program. As director of the division, he gave me a choice of couple of positions. And I actually took the cancer therapy program position as his associate director for CTEP. His predecessor had been-- my predecessor in that position had been Steve Carter. I don't know if you know about Stephen Carter. No, I met Dr. Carter. He was encyclopedic in the knowledge of all the trials that were done in the-- sponsored by the National Cancer Institute and also abroad. So he became a great face of the NCI internationally. And he spurred the development of the EORTC as well. So that was developed initially through a grant of the National Cancer Institute. So he was involved in the EORTC. But the cooperative groups had started during the leukemia program with the acute leukemia group B, which was the counterpart of acute leukemia group A, which was the intramural program. Jim Holland became the chair of the group. He was such an inspiring leader of the cooperative group. His cooperative group was amazing, to go to one of his meetings, which lasted two afternoons. He really commanded-- it was like a plenary session, and doled out all the projects in one afternoon. And then, in the second day, they kind of review whatever had developed. But other groups started. And the Eastern Cooperative Oncology Group became-- I had joined that when I had gone back to Einstein. It developed under founder Paul Carbone. He had assumed chairman-- no, Paul Carbone became the chairman later on. Initially, it was run by-- it'll come to me right now. I have a lapse on who was the group chair. But it was kind of Boston nurtured. And they were primarily devoted in solid tumors. And they started with making inroads into solid tumor beyond the acute leukemia. But in GI, for example, where I was in the GI committee, Chuck Martel did a number of studies. He ran those meetings, floated ideas. A week later-- we didn't have emails, but a week later, he had the protocol on your desk. Let me ask you a final question, to begin to tie it up here. When you were at the Delafield and then at the NCI, was there a sense that you guys were doing historic stuff? Or was it just day-to-day, same old, same old. Then you look back and say, boy, look what we did. Was there a sense that something big was happening in those days? Oh, no. There was always a sense. Well, when senior investigators, there was always a sense there are a lot of things here developing of interest, you know? And there was a full head of steam in part related to the combination chemotherapy. Now in acute leukemia, it was obvious. But the big thing about the solid tumor service since DeVita and Tom Fry, who started the work in lymphomas. Peter Wernick, George Canellos, they found that the combination chemotherapy did something in lymphomas, and also later on with, also, Jim Holland's work. And you've mentioned Ezra Greenspan. They had seen that combinations of drugs did help, to a large degree, breast cancer. Now the same drugs didn't tried to be extended-- the same principles-- to other solid tumors. It didn't work so well. But breast was somewhat sensitive to the drugs, the alkylating agents and the antimetabolites. So those were the first combinations, and the vinca alkaloids. Let me ask you this, my final question. But I've been a breast cancer guy all my life. And Cushman Haagensen, of course, is a giant. That's the name from the past. Yes. So when you were at Delafield, did he try to oppose the chemotherapy because he felt that a chance to cut is a chance to cure? I mean, he was one of the biggest knives of all time. Yes. Actually, no, he opposed it for different reasons. I never understood why. He didn't only oppose chemotherapy, he opposed hormone therapy, which was coming along. Because he thought that any sex hormones were detrimental to the course of disease. But it was also mostly rivalry with a medical service, I think. Because we saw responses. I did my first trial with progestational agents. So I did some clinical trials, actually, when I was a fellow. So we published an observational series of patients treated with medroxyprogesterone acetate, and presented at the American College of Physicians in '67. So you know, he opposed Gellhorn's intervention in breast cancer medical intervention. He liked to give steroids. And we used to see the patients because the patient developed diabetes. So that's how we got involved in some of the disseminate at the patients with metastatic breast cancer. He wouldn't refer them. So I got involved because I saw a lot of diabetes. And then we started our own treatments. We bonded with the patients and started our own treatments. Again, a recurring theme is how much courage it took for you and your predecessors to do what you do. And the confrontation, if not hostility, between the surgeons. I have to say, that what that really does is it brings up Bernie Fisher and Umberto Veronesi, and the courage they had to adopt systemic therapy as opposed to obstruct it. I don't think our younger colleagues are aware of the battle. Oh, yeah, no. Bernie deserves a lot of credit. And I can tell you of arguments he had with Jerry Urban and other surgeons when he came to a meeting in New York. And Sam Hellman was there. He said, Bernie, we agree with you. I think it's taken us some time to process what you just-- the great thing you have done, to rely on other than surgery. Because they came after him, even I'm talking early 1980. Oh, I was at a meeting. I was at a meeting maybe '83 or '4. It was the first time I'd ever met Dr. Fisher. And he and Urban were sharing a podium. I thought there was going to be a fistfight. Yes. I mean, it was really contentious. And that was an eye-opener for me, where I thought, there's a surgeon up there telling us we should do things that will put him out of business. That's a very interesting approach. Well, yes. And the one thing about Bernie Fisher, he understood trials. And I remember, they said-- Jerry Urban said, why do you think that that curve isn't just going to go down and plummet? He said, it's called probability, Doctor. [CHUCKLES] All right. Well, we've run out of time. I hate to say that because these are great stories. But I want to thank you for taking time. Thank you, Dan, for the interview, for sure. And we do share some common background. And we didn't get to talk about all the international things that came out of the National Cancer Institute. As Jim Holland said in that congressional hearing, the National Cancer Institute was the best international weapon we have had. Yeah, I think that's a great point. And I do regret we've run out of time here. Maybe we can do that in another interview. But I want to also thank you for all you've done for the field and the hundreds of people you've trained. I don't go anywhere where I don't bring up your name, and somebody goes, oh, yeah. I worked with that guy. Well, that's a motive a great satisfaction, I have to say, for sure. It takes just the ability to listen to what your fellows are saying and responding to them. Yeah. That's been my secret. And you're very good at that. I've seen you in action. So thanks again. I appreciate this, and look forward to seeing you soon. Thank you, Dan. I appreciate very much all your questions, and your interview, and your friendship. [MUSIC PLAYING] Until next time, thank you for listening to this JCO's Cancer Stories, the Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcast, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, the Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
Dr. Hayes interviews Dr. Freireich on his involvement with combination chemotherapy. TRANSCRIPT: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to JCO's Cancer Stories, the Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center. And I've also had the privilege of being the past president of the American Society of Clinical Oncology. I'm privileged to be your host for a series of podcast interviews with the people who founded our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and also, frankly, inspired by these pioneers. In fact, it's my hope that, through these conversations, we can all be equally inspired by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. In fact, by understanding how we got to the present and what we now consider normal in oncology, we can also imagine, and we can work together towards a better future for our patients and their families during and after cancer treatment. Today, my guest on this podcast is Dr. Emil J. Freireich, who is generally considered one of the pioneers of combination chemotherapy. Dr. Freireich is currently the Ruth Harriet Haynesworth chair and distinguished teaching professor in the Department of Leukemia at the Division of Cancer Medicine at MD Anderson Cancer Center in Houston. He was raised in Chicago during the Great Depression, the son of Hungarian immigrants. Dr. Freireich attended the University of Illinois College of Medicine in Chicago starting, unbelievably, at age 16. And from there, he also received a medical degree in 1949. He completed his internship at Cook County Hospital and his residency at Presbyterian Hospital in Chicago. He then moved to Boston, where he studied hematology with Dr. Joseph Ross at Mass. General. And then he went to the NIH in 1955, where he stayed until he moved to MD Anderson a decade later. And there he still remains. He and his colleagues at the National Cancer Institute, Drs. Jim Holland and Emil "Tom" Frei, were the first to demonstrate that administering concurrent combination chemotherapy, rather than giving it sequentially with each episode of disease progression, resulted in complete responses in childhood acute lymphocytic leukemia. And that paper was first published in the now classic paper in Blood in 1958. In the mid-1960s, they ultimately developed the VAMP regimen. And that was reported in 1965, with really, in my opinion, the first cures that we'd seen with chemotherapy in an advanced cancer of any sort. This work was the groundbreaking basis for the subsequent cures of advanced Hodgkin's disease, non-Hodgkin's lymphomas, adult leukemias, testicular cancer, and, in my opinion, the striking results of adjuvant combination chemotherapy in breast and many other cancers. Dr. Freireich has authored over 500 peer-reviewed papers, numerous reviews and editorials. He's edited 16 different textbooks. And he's won too many awards and honors for me to even begin to list. But in particular in 1972, he received the Lasker Award, America's most highly regarded medical honor. And most importantly to me, frankly, is that he proceeded me as president of ASCO in 1980 to 1981. Dr. Freireich, I'm sorry for the long introduction. But your career is pretty substantial. Welcome to our program. Thank you. I have a number of questions. And to start with, I know, as I said, you grew up in Chicago during the depression and that you entered college at the age of 16. And I think our listeners would love to hear more about those circumstances. That's pretty unusual. And I've actually read about some of your childhood. You want to tell us more about that and how was it you chose medicine in the first place? I was born 1927 of to immigrant Hungarians. I had an older sister three years older. And they had a Hungarian restaurant in Chicago. And 1929, when I was two years old, there was a big event in the United States. They lost their restaurant. My father died suddenly, I believe of suicide, but not proven. And my mother, tough mother, went to work in a sweatshop. She worked 20 hours a day. She had two children. She found an Irish lady who worked for room and board only, no salary. Her name was Mary. So Mary was my ex officio mother. And I grew up, as you pointed out, in a ghetto community. I spent my life stealing things, hubcaps and windshield wipers, and avoiding getting crushed by the roving gangs. When I finished elementary school and when I went to a ghetto high school called Tuley, T-U-L-E-Y. In Tuley High School, I majored in typing and shorthand. My mother thought I could make a living as a secretary. I was prepubescent, short and fat. And I was a frequent victim of my colleagues in school. When I was very young, I can't tell you when, about eight or so, I developed tonsillitis. And we had in our little ghetto community one of these Tree Grows in Brooklyn physicians. His name was Dr. Rosenblum. And he took care of people in the ghetto for favors. My mother made him goulash. Dr. Rosenblum came to your house. He didn't have an office, because we didn't have any transportation. So my mother called him. And I had tonsillitis. He came and looked to me. He was wearing a suit and tie. I'd never seen that. During the depression, all the men wore coveralls and dirty pants. And he looks very elegant. He had a suit and a tie. He looked in my throat, and he said to my mother, the treatment for tonsillitis is ice cream. I always remember Dr. Rosenblum, because my mother had to go out and buy ice scream. And it's not bad treatment. It actually cools off the hot throat. So when I went to high school, taking shorthand and typing and getting beaten up by the bigger guys, a professor appeared like Dr. Rosenblum, suit and tie, young guy, PhD. Came to a ghetto high school to teach physics. Physics fascinated me. So I worked very hard in physics. He had a contest. I did a project on the Bernoulli theorem. And the classic project is a jet of water. You put a ping pong ball in it. And the ping pong ball stays in the jet, amazingly. That was because of Bernoulli. What happens when the ping pong ball goes off to one side, the fluid goes faster on the other side. It reduces the pressure, and that pushes it back in the stream. And that's the principle of airplanes and so on and so forth. So I won first prize. And he called me to his office. He said, Mr. Freireich, you should go to college. I said, what's college? He said, well, there's-- [LAUGHTER] He said there's a place down south of here called the University of Illinois where you can get advanced studies. What do you want to be when you grow up? So I thought a minute, and I said, I want to be like Dr. Rosenblum. I want to be a family doctor. He said, well, you have to go to college first. So I said, what do I need to go to college? He said you need about $25, which in that day was a lot of money. So I went home, and I told if it was my mother, my professor wants me to go to college. And I need $25. My mother, she's hardened in the depression, working in sweatshops. And she said, OK, I'm going to get $25. She asked around in the little Hungarian ghetto community. And we found a lady who had lost her husband and had an insurance policy. And so she had money. And she distributed it to her colleagues in the ghetto community for good causes, wonderful lady. So my mother dressed me up in a borrowed suit. And we went to see Mrs. so-and-so. And she patted my head and gave my mother $25. It's an incredible story. In fact, I'm struck by the fact that one of the founders of our field was a juvenile delinquent stealing hubcaps. Oh, yeah. I did that to hubcaps and windshield wipers and everything you could take off a car. I got a ticket on the Illinois Central Railroad, $6. I got off the Champaign-Urbana. And I said to the guy, where's the university? He said, over there. I went over there. I said, where do you register. They said, over there. So I went over there. And I said, I'm Freireich, and I'm registering for college. The guy said, where's your transcript. I said, well, they told me at the high school that they would send everything they needed. He said, we've never had a student from Tuley High School. I was the first to go. I was the first Tuley student to go to college. And he said, OK, I'll register you. And I'll write the university, and I'll get your transcript. I presume you're qualified. So how much is registration? $6! So I'm down to $13. I'm getting pretty poor. So I registered. And then I said, where do I live? He said, there's a list over there. And I went over there. I found the lady who lost her husband. She rented his bedroom for $6. And then I had to figure out how to eat. And I asked my friend the registrar, where do I eat? He said, go to work in one of these rich sorority houses. You get free meals. So I waited tables in a sorority house. I got good grades. When I had to elect a language, I took German, because at that time, all the science was in the Festschrift. The Germans had invented the chemical industry. And my advisor said, that's good for you if you want to be a doctor. So I took German. My professor in German, he taught stage German. And he read the role the first day. And he came to my name and he said Freireich, [EXAGGERATING "CH" SOUND] because, he said, Americans can't say. [EXAGGERATED "CH" SOUND] Everybody called me "Freireish." But he called me Freireich [EXAGGERATING "CH" SOUND]. And our book was called, Ich lerne Deutsch, I'm learning German. So "ich" was important. Freireich was important. I got an A in German because of my great name. And I did well in physics. And everything was accelerated during the war. So the university had three semesters a year instead of two. There was no summer. And the requirements for medical school were dropped from three years to two years. So two years is four semesters. So at the end of the first year, I was eligible for medical school. And my physics professor said, you better apply, because all the guys coming out of the military want to be doctors. So I said, aw, damn, I'm having such a good time scrubbing floors and smoking and getting along with good looking girls. He said, you better do it. So I applied. And I was accepted. So I had to leave the beautiful campus of Champaign-Urbana and go back to the ghetto of Chicago where my mother and my sister were living. And I couldn't figure out where I was going to get the money to pay for medical school. I had a friend who had had polio. Polio was rampant in those days. And I said to him, how do you get money to go to college? He said he gets money from the state, rehabilitation. And he said my rehab guy is coming to see me tomorrow. Why don't you come and see if you're eligible? So the rehab guy came. He said, what's wrong with you, Freireich? I said, I had a broken leg in college. He said, OK, fill in the forms. And I became a ward of the state of Illinois Department of Rehabilitation. From that point on, they paid all my tuition, all my supplies, all my microscope rentals, and so on. So I went to medical school free thanks to the State of Illinois Department of rehabilitation. So I went to Chicago. And a bunch of us sat in the room for the opening introduction. And the dean of the medical school came in. His name was Andrew C Ivey. I don't know if you know the name, famous GI physiologist. And Dr. Ivey said, you guys are lucky to be in medical school. There were 20 applicants for everyone accepted, 20. Isn't that's amazing? Because all the guys who were medics in the military realized that being a doctor is a soft job. So they all wanted to be doctors. But they didn't have as good an academic career as I did. So anyhow, I went to medical school. I did pretty well. It was complicated, medical school. I had to ride the L in Chicago. It cost a nickel. And I lived at home. And I rode the L in the morning. And I walked to the university campus. I attended classes. I walked to the L. And I went back home. And I did that for four years. And then, as I said, I graduated number six in the class. And I graduated. And I had to decide where to do an intern. I wanted to be a family doctor like Dr. Rosenblum. So I interned at Cook County Hospital. Cook County Hospital was an abattoir, terrible place. In that year, 1949, the two most prominent diseases were tuberculosis and polio. So my first rotation was the TB ward. That was horrible what you had to do to those men. 90% of them died. Then my next rotation was infectious diseases. And that was all children in iron lungs who were doomed to die. So I started off pretty badly. And then I got to the good things like surgery. I delivered a hundred babies. I did the ear, nose and throat. So I did everything. And I felt ready to go into practice. And then I got to internal medicine. Internal medicine was not like OB and all that stuff, not mechanical. It was intellectual. You had the worry about the blood flow to the kidney. And you had to get diuretics and blood and stuff. So internal medicine fascinated me. When I was on-call, I would admit 20 new patients a night, 20. And one guy I admitted was very interesting. He was a learned guy. And he was dying of heart failure. And I had to figure out how to treat him. And I admitted him. And when I got done, exhausted in the morning, I went to make rounds. And I didn't see him. And I said to the nurse, where's Mr. so-and-so. She said, don't worry about him. He's gone. I said, where did he go. She said he goes into the death room. Cook County Hospital, the problem was they had too many patients for the beds. And the head nurse made rounds every day. And the sickest patients went to the death room. And I went in there. And I found my patient. And I said to the nurse, I want my patient on the ward. I'm a young squirt. How old was I? I was 19, I think. So the next day, I get a call from the hospital director. He says, Freireich, I think you better leave County. I said, what do you mean? I'm having a good time. I'm learning everything. He said, you don't know how we operate. The nurses run the ward. And you make trouble. And that means you've got to leave. Uh-oh. So I said, well, the only thing I can do is get a residency in medicine and learn all this complicated stuff. So next door was Presbyterian Hospital, which had the Rush Clinic. Have you heard the rush clinic? They were a bunch of famous guys. I made rounds with Roland Woodyatt, the first physician in the United States to use insulin. I made rounds with-- I forgot the name of the cardiologist who described coronary artery disease. He was the first to recognize the association between chest pain and myocardial infarction. So these guys were great. And Olie Poll, who taught me EKG-- And I was going along fine. But again, the chair of medicine was a Harvard import, S Howard Armstrong. And he had a teaching service. And all the house staff wanted to be on the teaching service where they learned stuff. Private doctors, of course, were offended. So they descended on administration. And they fired the chair of medicine. Armstrong was fired. The house staff teaching service was disbanded. And Armstrong tried to tend to his house. He called me in. He said, Freireich, what do you know about medicine? I said, Dr. Armstrong, you got a wonderful department. I learned EKG. I learned diabetes. I learned heart. I learned everything. The only thing I don't know anything about is hematology, because the guy who teaches hematology is a jerk. Armstrong said, don't worry, Freireich. Go to Boston, that's where the new medicine is coming from Europe. And he gave me letters to the three great hematologists in Boston, Bill Dameshek, Joe Ross, and Dr. Israel, who was a clotter. So I took everything I owned. I put it in my 1946 fastback, broken down Oldsmobile. And I drove to Boston. When I got to Boston, I met Dr. Ross. The guy in the lab who was the chief was so Stuart Finch. I think he just retired. And I collaborated with a young man named Aaron Miller who worked at the VA hospital. And my project funded. Dameshek gave me a job but no money. Israel gave me a job, no money. Ross gave me a job and paid me $5,000 a year, wonderful. So I became a hematologist. I worked on the mechanism of the anemia of inflammation. I studied patients with rheumatoid arthritis. And we had radioisotopes. So I was able to study the iron metabolism and the binding to transferrant. And we did experiments in dogs. And we worked out the mechanism of the anemia. The biggest hematology group in the country, the Wintrobe group, who wrote the textbook, had proven that the anemia of inflammation was due to a failure to incorporate iron into heme. And we found that that was false. When we put the ion on transferrant, it went right into heme. The difficulty was the reutilization of iron from hemoglobin to new heme. And we proved that in dogs. We did experiments with turpentine abcesses in dogs. So I was on a roll. I was doing Nobel laureate stuff. I mean, I gave a paper to the AAP. I gave a paper to the ASCI. I was doing well. And one day I got a letter. You are drafted into the army as a private. If you don't want to be a private, you can become a second lieutenant if you accept the assignment we give you. So I told Ross, I'm leaving. I got to go. I tried to finish up all my experiments. I told my wife we're in trouble. We didn't know what we'd do. We had one baby, one-year-old. She was pregnant with our second child. I didn't tell you the story about my wife. What happened is the head nurse in the clinic, like me, she came for a visit to Boston. They broke into my car and stole her luggage. And so we became attached. And we got married. And we've been married 65 years. But anyhow, she got a job at Mass. General. I had a job at Mass. Memorial. We had enough money to live. And as I say, she got pregnant, and we had babies. And I got this letter that I'm drafted. So I said to my wife, we have to go to the Army. The next morning, I get a call from Chester Scott. Keefer, who you already mentioned-- Dr. Keefer was the physician in charge of the penicillin distribution during the war. He was a very famous infectious disease doctor. He was a brilliant teacher and respected and loved by everybody. When Eisenhower was elected president, as you probably know, like all Republicans, he wanted to decrease the size of the government. So he decided to combine three cabinet departments, Health, Education, and Welfare, into one. That was obviously going to save positions and money. And he appointed Oveta Culp Hobby, who was the publisher of the Houston Post newspaper. She didn't know anything about health. She didn't know anything about education or anything about welfare. So what she did was she hired three people as department heads. And she picked Dr. Keefer to be head of health. Dr. Keefer would not give up the dean of the medical school. So she agreed to have him do both jobs. He was dean of the medical school and Secretary of Health. And he called me to his office. And we all respected Dr. Keefer. You dressed up in a new coat and clicked your heels and said, yes, sir. He said, Freireich, Dr. Ross says you're doing good. Thank you, sir. Have you ever heard of the National Institutes of Health? No, sir. There's a place in Washington where they have a hospital out in the country. And they can't staff it. So we have to send young people who are drafted there. If you go to the public health service, you don't have to go in the army and get shot during the war. Yes, sir. He picked up the phone. Fred, I have a doctor Freireich in my office. He'll be there tomorrow morning. Bye. Thank you. I went home. I told my wife, I have to go to Washington. I got in my car, drove to Washington, 200 miles in a broken down car. I got there. I found the guy at the HEW. He said, Freireich, you have to go to NIH. So go out here and take the bus. It takes you to the clinical center. Before the war, they decided to put a clinical center in the campus of the National Institutes of Health, which were all basic science institutes. There was no medicine. So here was this hospital, and they couldn't staff it. So they took all the draft dodgers. They called us yellow berets. And they staff the NIH with guys right out of their training. So anyhow, I got in my car and drove out there. Where's NIH? There. Who do I talk to? There, you go there. I talked to all the clinical directors. No one needed me. I got to Gordon Zubrod, who had just come from St. Louis University. He was an infectious disease guy. Do you know Gordon Zubrod? Yeah, I actually met him a couple of times with Dr. Frei. Good, yes. Actually, I'd love to hear this story. Dr. Frei has told me the story, your first day at the NCI when you, quote, "found your office." Can you tell us about that one? Yeah. So anyhow, Dr. Zubrod said, what do you do, Freireich? I said, I'm a hematologist. He scratched his head. And he said, I'll tell you what, you have to cure leukemia. I said, yes, sir. You know I'm in the military, so you have to do what you're told. He said, your office is on the 12th floor. I went up to the the 12th floor. I walked along, looked for a name. I came to room that said Emil Frei. I said, isn't that like the damn government? They can't even spell my name. So I walked in. And there was a tall, skinny guy with no hair. I said, sir, you're in my office. He said, your office is next door. I'm Frei. You're Freireich. And we've been friends for a lifetime. He told that story to us many, many times, I'm going to tell you. He thought that was hilarious that this guy walked into his office and said, you're in my office. And he said, no, you're in my office. The other thing I want to talk about then, as you moved on, what made you and Dr. Frei and Dr. Holland decide to go at combination therapy? I think it was based on the infectious disease stuff. Correct, totally. At the time, we had three drugs, 6-MP, methotrexate, prednisone, 48, 53, and about 54, something. Each individually gave some responses. They lasted six to eight weeks. And the children all died. So the world's authority on hematology, Max Wintrobe, wrote a review. And he said, these drugs are simply torturing these children. And they don't do anything. Dameshek wrote editorials in Blood saying they're just killing children. So we were not very popular. But Zubrod came from infectious disease. And Tom Frei was infectious disease. And they had just discovered that in tuberculosis, if you use sequential streptomycin PAS, they became resistant to both drugs. If you gave them simultaneously, their effectiveness was prolonged. So combinations of agents were more effective than the sequences. So Zubrod said, why don't we do the same thing for cancer? We'll do 6-MP and methotrexate in sequence. And we'll do them in combination. To do the combination, we had to work out the doses. Dave Rolle did that in mice. 60% of two immunosuppressive drugs make one. And we gave 6-MP and methotrexate concurrently and in full dose sequentially, that is until they failed, we gave the other one. And the study was called Protocol 1. Jim Holland had gone to Roswell Park. And he agreed to join us. So we became the first acute leukemia cooperative group, Holland at Roswell Park, Frei and Freireich at MD Anderson. Freireich treated the children. And Frei protected Freireich from the rest at NCI and from Zubrod. Zubrod trusted Frei. So if I needed to do anything radical, I'd talk to Frei, and he'd talk to Zubrod. So we were a great team. That was really the start of the cooperative group set, right? That would be CALG, the cancer and leukemia group, is that right? That was the first cooperative group in the country. That's incredible. The cooperative group had to two institutions, Roswell Park and MD Anderson. Who tried to block you on these things? I know it must have taken a lot of courage to put all these drugs together. You mentioned Wintrobe. But were there others who were fundamentally opposed to using combinations? Oh, I'm getting to that. So with the first study, Protocol 1, Russell Park and MD Anderson, children received 6-MP and methotrexate simultaneously and in sequence. And it turned out that Protocol 1 was published. The combination had more frequent remissions and longer duration. So we were onto something. Next we did the prednisone. Prednisone's not myelosuppressive. We could do full-dose prednisone with 6-MP, full dose prednisone with methotrexate, same result. In every instance, the combination was superior to the sequence. So one day I'm sitting in my office. About once a week he'd come around and look. He came in one day. He said, Dr. Freireich, this ward is a mess. Everything is full of blood, the nurse's uniforms, the curtains, the ceiling. Well, anyhow, I was taking care of my bleeding children one day when a guy from Eli Lilly showed up. I think his name was Armstrong. And he said, we've got a new drug that was founded by-- you know who that was. Let me see his name. Mike Black. He discovered it in mice, periwinkle extract. Periwinkle had 80 alkaloids. And they screened them all against mice. And this one was active in one kind of mouse leukemia. But it wasn't active in L1210. So he said, we have this drug. And we offered it to Dr. Farber at Dana Farber. And we're going to offer it to you if you want to do it. I said, wonderful. So I wrote a protocol. And Zubrod said, but this drug is not active in L1210. And we know that the drugs active in L12101 leukemia are active in human leukemia. So this drug cannot be studied. Aha, time for Emil Frei III. I went to Tom. I said, look, Tom, vincristine is not myelosuppressive. As a single agent, it causes 80% complete remissions. I want to vincristine to 6-MP and methotrexate. Zubrod says no. Frei said, leave it to me. He talked to Zubrod. I told Zubrod, these children are dying. I've got to do something. So they approved it. And we did decide the VAMP. We knew prednisone was not myelosuppressive. We could add it to 6-MP and methotrexate, full dose. We knew this dose of 6-MP and methotrexate. Vincristine turned out to be not myelosuppressive, CNS toxicity. So we designed the VAMP drug. Then we said, let's let Holland and the other members of the cooperative group join so we can get this done quick. The cooperative group refused. Jim Holland refused. He wanted to do them one at a time, prednisone, 6-MP, methotrexate, vincristine, prednisone, vincristine, and so on. It would have taken us five years. We went through the same thing with MOPP. They wanted to do it one at a time. So we had to do it alone in the cancer institute. So Frei went to Zubrod and said, why can't we do it? Zubrod said, if you say it's OK, you can do it. Frei was chair of the group. And I'm not going to put my patients on the group. So Frei had to resign. Holland became the chair. And Frei was an advisor. So we started out with VAMP. We had 98% remissions. The remissions lasted about six weeks. We realized that they weren't cured. So we said to the parents, this treatment was toxic. It was full-dose 6-MP and methotrexate. And the parents said they're going to risk their children's life, but we're going to do what we called early intensification. That is, the children in complete remission would get full-dose induction therapy, never done before. And I met with the parents every morning and went over each child to be sure that they were with us. The parents were wonderful. We had solved the bleeding problem with platelet transfusions. We'd had white cell transfusions and so on. And they went along with us. So we did early intensification. We did it in about 12 patients. Two of them almost died, very severe infection on the brain. But we saved them. So we knew this was dangerous. But they all relapsed. Median duration remission was about eight weeks, even though we did early intensification. So MC Li had cured choriocarcinoma. I don't know if you know that story. MC Li and I were residents at Presbyterian at the same time. We were good friends. I was his advisor on this strategy. He measured chorionic gonadotropin in the urine. And he knew that as long as there was gonadotropin in the urine, they weren't cured. So he kept treating them. So we decided to follow the Li model. And what we did was we did early intensification, which they all survived, fortunately. And then we did intermittent reinduction. Every four to six weeks, we'd bring them in and give them another course of treatment. And we did that for a year. And then we stopped. And then we watched them. And that's when we found 20% of the patients were in remission at, I think, 18 months. Never been reported before. And I did report that to AACR. I've seen the AACR abstract. And I would love to know what was the energy in the room when that was presented. Did people stand up and throw rotten tomatoes at you, or did they stand up and applaud, or everything in between? No one applauded. Everybody was incredulous. The people in the group didn't believe it. Most people thought we were lying. If it wasn't for Frei, I'd have never gotten away with it. Let me ask you another question. Dr. Frei told me that the first patient you gave platelets to, you had to sneak out at night and do it. Is that true? He said there were people who did not want you to give platelet transfusions. The platelet transfusions were a bigger fight than the chemotherapy, because everybody knew that platelets were not the cause of it. Dr. Brecher had studied patients in the war from radiation injury. He had dogs that he completely phoresed, zero platelets. And they didn't bleed. So obviously, platelets were not the problem. The problem was a circulating anticoagulant. And I did experiments in the lab and proved that that was false. But anyway, the platelet transfusions are what made all of this possible, because the children all died of hemorrhage. And once we had platelets, we could treat them with the chemotherapy. Is there a story behind the first patients who got platelet transfusions? Again, Dr. Frei told me that-- Oh, boy, that's a wonderful story. I actually published it. This was a young man who was bleeding to death whose father was a minister. And since it was proven that platelets were not important and there was a circulating anticoagulant, I decided that the only way to arrest the hemorrhage was to do an exchange transfusion like you do in eritroblastosis fetalis. So I said to the minister, if you bring me 10 healthy volunteers, I want to do this experiment on your son. And he was desperate. His son was a beautiful 8-year-old boy. His name was Scotty Dinsmore. How do you like that? [LAUGHTER] Scotty Dinsmore was bleeding to death. And he arrived the next morning with 10 volunteers. And I sat down in the treatment room. And I did an exchange transfusion with 50 cc syringes, 50 ccs from Scotty in the trash can, 50 ccs from the donor in Scotty. And we calculated I had exchanged three blood volumes to get to where the concentration was detectable. And when I finished this four-hour procedure, bending over my back with syringes and volunteers, his platelet count was 100,000. And is bleeding completely stopped. So we thought we'd made a breakthrough, but we were smarter than that. We watched him every day and did a platelet count. And we found that the platelet lifespan was four to six days. And when the platelets got below 10,000-- we had done a retrospective study, and we knew what the threshold for bleeding was. And he started bleeding again. So it was obvious that it was not an anticoagulant. I did experiments in my lab. I took the serum and mixed it with the plasma and so forth. So we proved that it was platelets and not an anticoagulant. And then we had to figure out how to get platelets. And Allen Kleiman in the blood bank and I worked together to do platelet phoresis. We took the unit separate platelets, put the blood back, volunteer donors. And we proved that platelets stopped the bleeding. And we published that, a great paper, citation classic. I was going to say for the young folks. And I asked Dr. Frei this too when I was at the Dana Farber. Did you ever doubt yourself? Did you think, we need to quit doing this? This is more than we can handle. I know Dr. Farber was widely criticized in Boston for-- Oh, boy. He studied vincristine at the same time we did. Yeah. So did you ever say, maybe we should set this whole system down and give up? No, I was never intimidated, because Dr. Zubrod gave me orders, cure leukemia. So I was going to do it. Yeah, my impression from talking with Dr. Frei is Gordon Zubrod was the sort of unsung hero in all of this. He is. He is. He had the courage to back a 25-year-old guy and his resident to do things that were potentially insane. We could have gone to jail for what we did. We could have killed all those kids. That's what Dr. Frei-- Dr. Holland has told me the same story. So we owe you a great debt. So let me ask you. When you were the president of ASCO, in those days, what made you decide to run for ASCO? It was still pretty early in the early 1980s. Well, that's a very good story. I'm a pioneer in that regard too. When you became a cancer doctor, you had to join the AACR. AACR was dominant. I joined the AACR. I sent my papers on platelets and chemotherapy to AACR. They accepted all of them. But they put the clinical papers on Saturday morning. When I gave my first paper at AACR, the chairman of the session, my wife and my son were the only ones in the audience. Nobody stayed till Saturday morning. So I got mad. I said, I'm discovering things, and I can't present them at AACR. No one's listening. So we said, let's form a society that is clinical oncology and meets the day before AACR the clinical scientists who want to go AACR don't have to go to two meetings. So we organized a plenary meeting the day before AACR began. In the first session, we had a lecture on CML from-- I forgot who the talker was who is treating CML, Berechenal or someone. Karanovsky? I don't know. So we had lectures, not papers. And we did that for a couple of years. And then AACR knew what we were doing. We were totally cooperating. But we hired a manager. And we started a scientific exhibit. So we had lots of money. And AACR needed money. And we were rich. So I got a call from the president of AACR. And he said, we don't want to continue to meet at the same time, because all of our doctors want to get these free samples. And they go to your meetings, and they don't go to our meetings. So we're separating from ASCO. I said, that's terrible, because the ASCO doctors all want to go AACR. He said, sorry, we can't take you anymore. I forgot who was president at the time. So ASCO had to separate from AACR. They separated from us. Most people think we separated from them. They separated from us. You were there at the very start. So I really appreciate your contributions to the field. And I appreciate your taking time today. And I appreciate all the things you did to help all the patients who've now survived that wouldn't have if you hadn't. Thank you very much. Until next time, thank you for listening to this JCO's Cancer Stories, the Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple podcast or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, the Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist, and I'm a researcher at the University of Michigan Rogel Cancer Center. And I'm also the past president of the American Society of Clinical Oncology. Over the last and now the next several podcasts, I've been really privileged to be your host for a series of interviews with the people I feel are the founders of our field. Over the last 40 years, I personally have been fortunate to have been trained and mentored and I've also been inspired by many of these pioneers. And it's my hope that through these conversations. We'll all be equally inspired by gaining an appreciation of the courage and the vision and the scientific understanding and the anecdotes that let these men and women to establish the field of clinical cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, I think we can also imagine and work together towards a better future for our patients and their families during and after cancer treatment. Today, I'm really pleased to have my guests on this podcast Dr. Norman Wolmark, who was his mentor and longtime colleague, Dr. Bernard or Bernie Fisher, was responsible for the unbelievable success of one of the most influential cancer cooperative groups in the world, the National Surgical Adjuvant Breast and Bowel Project, or the NSABP, which of course, in recent years has now been merged with two other corporate groups to become the NRG. Doctor Wolmark as a professor of surgery at Drexel served as the executive medical officer from 1979 to 1994 during Dr. Fischer's leadership of the NSABP. And then he became the chairman and PI of the group until 2004 when he assumed the same role with the merger into the NRG. The NSABP is generally credited with what is now called de-acceleration of therapy, in particular of local therapy of breast cancer by applying the scientific method to compare a modified radical mastectomy to radical mastectomies and subsequent breast conserving treatment a modified radical mastectomy, as well as testing the concept of sentinel node mapping, which we now use routinely. NSABP was also one of the pioneer groups to test the value of adjuvant systemic therapy. They started with adjuvant chemotherapy, comparing L-phenylalanine mustard, or L-PAM to nothing in the 1970s, and later, tamoxifen versus nil. Other successes of the NSABP include one of the first trials or adjuvant trastuzumab. And further, NSABP was the first to report the prognostic value of the genomic test to guide the use of adjuvant chemotherapy in ER-positive breast cancer. Incidentally, it also conducted the largest and the most definitive set of studies of chemo prevention, first with tamoxifen versus nil, and then later, comparing raloxifene to tamoxifen. Not just breast cancer-- in gastrointestinal malignancies, the NSABP made seminal observations regarding radiation for rectal cancer and adjuvant chemotherapy in colorectal cancers. Dr. Wolmark himself has published over 300 peer reviewed papers, numerous other commentaries and reviews, and frankly, I started to list your honors, Dr. Wolmark, but I ran out of space. You've just had too many to count here. I think it is safe to say that the reduction of both mortality and toxicities related to breast and GI cancers over the last four decades, coupled with improvement on how we treat people, is in large part due to the brilliance and the courage and the hard work of doctors Wolmark and Fisher. Most importantly, I think they showed so many of us the importance of challenging dogma, for example, how study and thinking in breast cancer and applying the scientific method to clinical research and practice. [GASPING] I have to take a deep breath, Norm. Welcome to our program, and thank you for joining us. Well, thank you, Dan. I think after that glowing and complimentary introduction, which was far too generous, probably the most strategically sound decision that I could make is to thank you and to terminate this discussion, because I don't think that I can possibly improve on it. But I don't suppose that that's the purpose of this endeavor here. Yeah, no. People aren't tuning in to hear me. They're tuning in to hear you. And this is hero worship on my part. I want to start out with your background. I know you grew up in Montreal. You graduated from undergraduate, medical school, and later, you did your surgical training at McGill. What were the circumstances that your family was in Canada? And what got you interested in medicine and, specifically, surgery? Well, that's an interesting question. I did not grow up longing to become a physician. As a matter of fact, my interests at McGill, certainly during undergraduate school, included biochemistry. And I was in the honors biochemistry program and was going to pursue a career in nucleic acid research. And at the last moment, I had a change of heart and decided to go into medicine at McGill. And McGill was not an embracing environment for surgeons. I think surgery, certainly in our era, was regarded as a sub-medical species. And it wasn't until my internship and early residency that I embraced the possibility of developing and evolving a career in surgery. Was that attitude out of also having been at McGill-- long before you were there, I know, but most places were dominated by the surgeons. And then medicine came along after that-- Mayo Clinic, for example. Do you know? Was this an outgrowth of Osler's influence? Well, I don't know that it was an outgrowth of Osler's influence, but it was certainly difficult for us to escape Sir William Osler. I think at the graduation after our second year, we were provided with a leather bound copy of Aequanimitas, which of course, nobody read, because medical students are not interested in the history of medicine. It was only years later that I read most of Osler's non-scientific works. That's interesting. So then you went to Pittsburgh to do your surgical residency and then two years at the NCI and a year at Memorial. But then, you returned to Pittsburgh. Why Pittsburgh in those days? Well, what drew me to Pittsburgh in 1973 was my interest in clinical trials. And in 1973, there was a lot of excitement going on in clinical trials and breast cancer directed by Bernie Fisher and the NSABP. So that was something that attracted me, that one could apply the scientific method to evolve therapy. And this was something that I desperately wanted to participate in as a result of my background in basic research and biochemistry. So tell us about the heady days in the early '70s and even further back, if you'll recount sort of Dr. Fisher's history as well, of starting the NSABP. What was his vision? What was his plan? Why did he do that? How did you get involved? The whole evolution of cooperative groups and in particular, the NSABP, was an outgrowth of the initiative of the National Institutes of Health and more specifically, I think, to Bernie Fisher's mentor, IS Ravdin, at Penn. And that led to the creation by the NIH of the Cancer Chemotherapy National Service Center. And this was started by three surgeons and Michael Shimkin at the NIH, who was a medical oncologist, or what was then called a chemotherapist. And from that grew a number of disease-oriented initiatives called the surgical adjuvant chemotherapy projects for specific diseases, breast being one of them. And this was 1957. And by 1958, the NSABP had randomized its first patient. And certainly, Bernie Fisher was amongst the founders of the NSABP and then, of course, became chairman of the group in 1967 and moved it to Pittsburgh in 1970. What did it take to get a bunch of surgeons to believe that more than just surgery was important? The group started in a modest fashion. There were 23 institutions. And I think it's certainly an enormous credit at Bernie Fisher for demonstrating that a cooperative group could indeed be cooperative, with multiple heterogeneous surgeons joining under the rubric of the NSABP to evolve the state of the art breast cancer and challenge existing dogma. One of my first meetings, Dr. Fisher and Dr. Irvin of New York City were in a debate that I thought was going to get into a fistfight, with Dr. Fisher trying to explain the systemic therapy of cancer and that it was more than just surgery, and Dr. Irvin believing if you did super-radical mastectomies, you could cure more. You must have been in the middle of some of those discussions as well. I was, and remember them, and remember the acrimony, the hostility that existed at that time. As a matter of fact, there were societies that were created to counter the influence of the NSABP. The retreat from radical mastectomy was highly contentious. And of course, the debate of the two mutually exclusive hypotheses was certainly extant in Halsted's era. But Bernie Fisher determined instead of debating the issue to test the two mutually exclusive hypotheses using the scientific method, namely the randomized prospective clinical trial, which convinced surgeons that variations on the theme of operative nuance were not going to increase survivorship, that breast cancer was a disease with systemic components at its initiation, and the retreat from a radical mastectomy and the ascent of systemic therapy are inextricably intertwined. And they are so largely because of the efforts of Bernie Fisher and the NSABP. This is an interview with you, except that you know Bernie Fisher better than any of us-- who, incidentally, turned 100 years old in August of this year. What were the driving forces for him to think this way? Do you know? Was there a sudden aha that systemic therapy ought to be as important as the surgery? I know he did some preclinical studies to suggest this. Can you give us more background of what he was thinking and how he got there? Well, when I first joined him in 1973, it was a unique environment. There was a continuum between the laboratory and the clinic. And hypotheses were generated in the lab from murine models and applied to clinical research, which we now call translational research. And certainly, I think he was influenced in many ways by the preclinical work that he did in murine models on metastases and multiple other observations to challenge the sanctity of the radical mastectomy, which was based on the belief that breast cancer was a local, regional disease and spread in a logical, predictable, stepwise manner, again, along fascial planes. This, of course, to scientists, was something that did not stand up to a solid review of the data. Through the years, I've picked up many pithy comments from Dr. Fisher. One of them is that-- what was it? In God we trust. And for everything else, we like data, which I always thought was a great statement, something to that effect. The other was, you may be logical, but breast cancer is not. That really has stuck with me through the years, which is, it doesn't follow a logical string of linear progression. But rather, it becomes systemic, or it doesn't, which I think changed the field. Well, Bernie always challenged existing dogma that was based on empiricism. I think Bernie taught us to challenge the individual who ascends to the professorial pulpit armed with a retrospective case series. And based on personal charisma or the institution that that individual represented, such an individual was able to influence the way a disease was treated for decades and then close to 3/4 of a century. Challenging that dogma, insisting that therapy be evolved based on data rather than retrospective case series, I think, is a lasting contribution. He blazed the trail for the rest of us. Since you were there for a lot of this, how about some of the other luminaries of the time? Dr. Crile had a lot to do with the early thoughts that maybe you didn't need to do mastectomy. Can you enlighten us on some of the other folks that were some of the early pioneers in the field? There were certainly proponents of lesser operative procedures starting with [INAUDIBLE] and in the UK, Vera Peters, in Canada, Barney Crile, or George Crile, Jr. at the Cleveland Clinic. But again, these were based on anecdotalism. There were very few randomized prospective trials challenging the sanctity of the radical mastectomy. There were some-- Sir Hedley Atkins, the Guy's Hospital trial comparing breast-preserving versus mastectomy, a trial that had few patients and was reported, I think, in 1971 was a case in point. And then Umberto Veronesi with the quadrantectomy study, which was reported in 1981, preceded B-06. But certainly, B-06 had an enormous impact in 1985. And I think to Bernie's credit, he was able to convince his colleagues, even his detractors and his coevals of the value of breast preservation. But more importantly, I think he was able to convince surgeons of the biologic behavior of breast cancer with its systemic components. Yeah, I agree. I remember that paper. Actually, I remember most your papers. B-04 for was the predecessor. And of course, if there is a Rosetta Stone for the NSABP, it was comparing radical mastectomy to total mastectomy, which was a heroic trial to have initiated in 1971. If there is a bellwether turning point, it was B-04. This was the trial that truly compared the two mutually exclusive hypotheses to enormous, enormous resistance by the surgical community. And the paradox was that the 23 institutions that participated in the NSABP were run by surgeons. I came into the field in 1982. I have seen maybe three radical mastectomies in my life based on the fact that B-04 was beginning to change that whole field. And the three or four patients I saw had horrendous qualities of life because of that radical mastectomy. So I think our listeners, the younger ones, need to understand how courageous this was. Let me ask another question. I don't think you were part of it then, but as Dr. Fisher began to, then, think about adjuvant chemotherapy, why L-PAM? Most of the people listening to this probably have never heard of L-PAM, let alone used it. Why was that chosen as the chemotherapy to use in the first trial? Well, that's an interesting question. CMF was being developed at the NCI-- Paul Carbone, Vince DeVita, George Canellos. And L-PAM was an oral agent. And we speculated, sotto voce, of course, Bernie and I, that the reason the NSABP got L-PAM was that it was oral and could be given by surgeons, whereas the CMF, which was more difficult to administer, went to Gianni Bonadonna, who reported on the CMF data in the adjuvant setting a year after the L-PAM data were reported in 1975. Ironically-- correct me if I'm wrong-- but I think the relative benefits of both were almost identical. And the reason L-PAM fell out of favor was the secondary leukemias. Is that your perception? Well, L-PAM fell out of favor, certainly. We did L-PAM, then L-PAM 5-FU, then L-PAM 5-FU plus doxorubicin in a stepwise, sequential manner. I think CMF was embraced. Had there been a direct comparison earlier on, perhaps L-PAM would have had a role. But I think it faded away. And it faded away for us largely because when we compared CMF to four cycles of AC, which could be given in a much shorter time, there was no difference. So AC became the standard, certainly for us. Moving on a bit, as I've already-- another of Dr. Fisher's statements that I've lived on is that the hallmark of a good clinical trial is that it raises more questions than it answers. I love that because it means you have to keep thinking. Can you give us examples how you and Dr. Fisher started designing the next trial as the first one was starting to finish, and how that led, one way to the other? I've always been struck by the fact that the NSABP has been more linear in its trial design than most of the other cooperative groups. Well, it was a continuum. The next trial was based on the results from the previous trial or the anticipated results from the previous trial. A case in point, B-04, total mastectomy, where lymph nodes are not fulgurated, left behind completely untreated, compared to radical mastectomy, where they were removed. 40%, it turned out, of the total mastectomy group had histologically positive nodes. And yet, the outcomes were the same, which supported the use of systemic therapy, that patients were failing not because inattention to operative detail, but because they had systemic metastases. Well, you can ask, how did you transpose this data or know about this data to start your next trial? Well, in that era, the results were available to us in real time. We had a magnetic board, for example, for B-04, where every patient that was entered into the study, of course, anonymized, was on that board, and we could see the treatment failures in real time. So we had a pretty good understanding of what the results were when B-06, for example, was started, and certainly when the L-PAM trial was initiated. To us, in that era, alpha-spending meant buying a suit at Bergdorf Goodman. It's only later that these restrictions, appropriately so, were initiated. So we were able to be very nimble in transposing the data from one trial to formulate the hypothesis for the next trial. And that led to, I think, a very elegant, sequential, logical, stepwise series of trials, which I think in this era, could not be conducted. Did you ever get concerned that you were jumping ahead to the next trial with insufficient follow-up with the last one, and you'd get ahead of yourself in terms of unexpected toxicity showing up or, for example, in the deacceleration of therapy, that in fact, you were wrong, and then you had a bunch of patients that you had given less than enough therapy? I can't think of the fact that you have. But was that a concern as you were designing these? Every clinical trial is a concern. And yes, there was a concern. But we believed that we were basing these trials on objective data, data that were generated through clinical trials and the scientific method. So let me ask another question, because I was never in the NSABP, but I was always struck by the fact that your statisticians sat at the table and thought as much about the biology as they did the p-values. Do you want to talk about some of the statisticians you've had the chance to work with? Absolutely. I think that's an accurate description. Carol Redmond was the first statistician with whom I came in contact and was an integral part of clinical trial development, discussing not only sample size, p-values, interim analyses, but also the biology of the disease and what the biologic end points were going to be, and what the ancillary end points ought to be, and calculate appropriate sample sizes to answer these questions. We were very fortunate to have outstanding biostatisticians who were giants. Sam Weiand, who followed Carol Redmond, who was at the University of Pittsburgh, went to the Mayo Clinic, and returned to us around 1994, '95, and John Bryant, who was absolutely instrumental in the joint analysis for the Herceptin trials, B-31 and N9831, who was a driving force, and was certainly a driving force behind the development of the Oncotype DX genomic profiling. These weren't simply numbers people. They were colleagues. They were part of the assault on the hill. I have to jump in for two reasons. One is I never worked directly with John Bryant, but I can't say how many times I called him and said, what do you think of this? because I knew he would understand the biology as well as the statistics. I miss him dearly. He sadly passed away about a decade ago. As do I. The other is, as you know, we lost Jim Holland this year. My first presentation at CALGB, Dr. Holland was sitting in the back of the room and yelled from the back of the room, because he never used a microphone, not unlike my colleague on the line right now, by the way. Dr. Holland yelled from the back of the room, Hayes, if you need a statistician, it's not worth doing. And I said, well with all due respect, Dr. Holland, and there's a lot of respect here, I have to disagree with you. Did Dr. Fisher get along with the statisticians the way you have? Did he feel that this was a two-way street? Or were there times he said, my way or the highway? There's always robust dialogue and discussion. I think that both Bernie and I embraced our statisticians as colleagues. I have to be very careful. This was not unwelcome embracing. But they were always an integral part of developing and analyzing the protocol. And they were colleagues. And certainly, Bernie had that approach and philosophy as well. So let me, perhaps, describe in 1973, when I first arrived, what struck me as extraordinary. There was passion, excitement, drama. We weren't sure where we were going. But we knew we were getting there fast. And we embraced the journey, the quest. And that was an extraordinary time where we knew that the standard of care was going to be changed. We couldn't predict the outcomes, but we knew that what we were doing at the time would have a lasting impact on the field. Actually, that was my question, which was, did you realize what you were doing in the late '60s and early '70s was as exciting as it was? Sometimes, I think we're in the middle of something, and we don't realize how it's going to turn out. And you've just answered my question, which was it must have been years-- It was challenging the basic sanctity of the dogma, the tyranny that existed at the time. And that, in itself, was a courageous and extraordinary thing to do. And I have to say because of that work, and others, but we've seen a remarkable reduction in mortality due to breast cancer over the last 30 years, probably by more than a third, not quite half. And it's because of these kinds of challenges of dogma and courage to move forward. So I think we all owe you and Dr. Fisher and those who were involved in the early days, then also in the other groups, just an enormous debt of gratitude. My final question to you, Norm, and everybody asks this where did you get your style of presentation? I've argued, although I know you're Jewish, you could have been a Baptist minister. Where did this come from? I have no idea. Everybody loves it. Well, that's certainly very gracious of you, Dan. I've certainly, in the era of protocol B-04 and B-06, I have been summarily booed by an audience in unison. So that may not be a uniform perception. Well, I hope that our listeners who are driving to work or having their morning cup of coffee and listening to this have enjoyed it. I certainly have. Thank you for being so gracious and taking the time to do this. Thank you for all your contributions to the field and for mentoring so many, including myself, frankly. And I consider you a great mentor and a great friend. So I appreciate it deeply. Thank you, Dan. It's been my privilege.
Daniel Hayes earned his nickname “The Honey Badger” (an animal known for its fearlessness) in the ring during a pro sparring session. His talent expands beyond the sports realm from Motivational Speaking to Entrepreneurship to being an On-Camera Talent. Hayes started competing in sports from the young age of 8. He competed in Soccer, Basketball, Football, Baseball, to Swimming and Track & Field. By age 16 he was a certified lifeguard and it became obvious that Hayes was born to compete in the sports world with the rising demand for the young athlete.Hayes high school athletic career as a basketball player landed him several scholarship offers from NCAA division I and II schools. Hayes however decided to attend TRU where he and his childhood best friend were offered athletic scholarships. His chosen college major was Kinesiology until he was introduced to his first acting class where he instantly fell in love with acting and changed his major to Theatre. Acting was a natural evolution of talent into a different form of artistic expression for Hayes who has never been camera shy since age 17 he had been a published print model in magazines. His new passion led him to study the art of acting at The Second City and Groundlings, schools that boast alumni like Jim Carrey, Will Ferrell, Seth Rogan and Steve Carell. Hayes continued training at The Ivana Chubbuck Studio a recognized acting academy which has coached Hollywood’s elite such as Halle Berry, Brad Pitt, Terence Howard and many famous actors.In 2016 Hayes joined forces with a lifetime friend and professional basketball player turned filmmaker to produce The Honey Badger, a boxing documentary directed by KB Kutz. The Sport Documentary covers the life of Hayes as an athlete preparing for his professional fight in Mexico. Their project The Honey Badger has won numerous film festival awards in Hollywood, Toronto, New York, San Diego and Los Angeles.On December 3, 2016 Hayes came out of a winning fight with a fractured left hand that required surgery, during his recovery he gained tremendous life wisdom from his successes and losses which he now shares in his work as a Motivational Speaker and Entrepreneur. His message is “I’m using this as an opportunity to be more accountable, I look in the mirror and say, you will be back and you will be better. Remember the times that you had the ability to do something and didn’t. I want to achieve more and I will. I’ll be better in a different way.” He continues his World Championship journey fighting out of the world famous Wild Card Boxing Club, home to superstar world champions Manny Pacquiao and Miguel Cotto. Website - http://www.daniel-hayes.com/Podcast - Life is a Fight PodcastHoneybadger TrailerDave SwansonWebsite - www.goatwrestlingperseverance.comBook - http://bit.ly/TheDotontheLeftDave Swanson Speaks Clothes - www.goat-wrestling.comFree Chapter of my Bestselling Book? - http://bit.ly/DOTLFree1stChapterNeed more information - Text goat to - 737-214-1040Social MediaFacebook TwitterInstagram - https://www.instagram.com/goatwrestlingperseverance/LinkedIn - www.linkedin.com/in/daveswansonspeaksCoaching -
Dr. Daniel Hayes, breast oncologist at the University of Michigan Rogel Cancer Center talks about progress in cancer care and treatment since he started practicing in the late 70s. He also shares his views of what the future holds and needs to help eventually cure all cancers. See acast.com/privacy for privacy and opt-out information.
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to Cancer Stories. I'm Dr. Daniel Hayes, a medical oncologist. And I'm a translational researcher at the University of Michigan Rogel Cancer Center. And I'm also the past president of ASCO. Over the next several podcasts, I am privileged to be your host for a series of interviews with the founders of our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and frankly, inspired by many of these pioneers. It's my hope that through these conversations, we can all be equally inspired by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of cancer clinical care over the last 70 years. By understanding of how we got to the present, and what we now consider normal in oncology, we can also imagine and work together towards a better future, where we offer patients better treatments, and are also able to support them and their families during and after cancer treatment. Today, I am very pleased to have as my guest on this podcast, Dr. John Minna. John is generally considered one of the pioneers of translational research in solid tumors, and he's widely recognized as a leader in lung cancer. Dr. Minna is currently the director of the Hammond Center for Therapeutic Oncology Research, and Professor of Internal Medicine and Pharmacology at the University of Texas Southwestern Medical Center in Dallas, where he also holds the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology, and the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research. Dr. Minna received undergraduate medical degrees from Stanford in the mid-1960s, which were followed by a residency at Harvard's Massachusetts General Hospital in Boston. He then went to the NIH, and the National Heart, Lung, and Blood Institute for his fellowship in biochemical genetics at the NIH with Dr. Marshall Nirenberg. And then he stayed at the NHLBI as the head of the section on somatic cell genetics. In 1975, he became chief of the NCI-VA Medical Oncology branch within the Clinical Oncology program of the Division of Cancer Treatment. And in 1991, he then moved to University of Texas Southwestern in Dallas, where he served as the director of the Sammons Cancer Center and Chief of the Division of Medical Oncology for four years. And since, he has held his current position. Doctor Minna has authored over 700 peer-reviewed papers, and well over 100 other reviews, book chapters, and educationally related manuscripts. He's won too many awards and honors for me to go through in detail. But these include the AACR's Rosenthal award, and ASCO's Scientific Achievement Award, two of the highest in those two organizations. He's also received the ASCO Statesman Award, and he's served on both the AACR and the ASCO boards of directors. He's been PI of the combined UTSW and M.D. Anderson Cancer Center Lung Cancer Specialized Program in Research Excellence. And in 2015, he was named one of the Giants of Oncology by OncLive. Dr. Minna, that's quite a mouthful, though. Welcome to our program. Thank you so much, Dan. And thanks for all your work in ASCO and everything, too. Well, actually, it was, as you can imagine, a great privilege. I just had a fabulous time. Just as an aside, when I got elected, I interviewed about 10 former presidents. And at the end of each of my set of questions, I said, well, fill in the blanks. What do you want to talk about? Almost everyone of them said the saddest day of their career was the day they had to quit being president of ASCO. And I know that now. Anyway, now I know you went to Stanford. Were you always a California boy? Or how did you get to Stanford? Well, yes. I was born in San Francisco, actually at the Presidio, which is now a fancy movie set-- some of the priciest real estate. And then, my dad was in the Army. My mom was a nurse. And then I grew up in San Diego. And my Dad had the largest family practice in San Diego. And my mom was the nurse that ran the office. I never forget, I called them one day when I was an intern at Mass General and complained I had 25 outpatients that I saw that day. And they laughed. They'd seen 80. And I made maybe 500 house calls with my dad, carrying his bag when I was younger. And so, he obviously was in medical school just before and then right after the Depression. And so, he had had an opportunity. He was going to do a fellowship in pediatrics at Harvard, but couldn't do it. He had to support all his parents and everything. And, by the way, he had immigrated from Italy when he was a kid. So this was quite a story. And so they always encouraged me to go into academic medicine. It was interesting, because all his buddies were surgeons that kept telling me to come back and be a general surgeon in San Diego. So anyways, I grew up in San Diego. And then was lucky enough to get into Stanford undergraduate medical school. So I went back and looked at your publication list, which dates back to the mid-1960s. By the way, I was in junior high then. It looks to me from your list of publications that you weren't originally headed to a career in oncology. In fact, it looks like you were doing genetics. So you've done a lot in lung cancer. Tell us what happened at the NIH that you sort of changed gears and went into lung cancer. Well, actually, the cancer decision was actually made back in medical school. And it was those-- two of the people that you mentioned when we were talking before, Henry Kaplan and Saul Rosenberg, that really inspired me at Stanford. And they both took me under their wing. I remember the last six months of medical school I spent full-time on radiation oncology. Actually, I worked up nearly 100 new patients with Hodgkin's, if you can imagine that. It's all because of the clinical trials going on there at Stanford. So there were all these new patients coming in. So both of them absolutely got me committed to a career in cancer way back in medical school, and then helped get me internships, residencies. It was Henry's letter to get me a position with Marshall Nirenberg. But both of them were instrumental. And they took a group of young people-- another person that was a year behind me was Ron Levy, obviously, a very prominent person in oncology. And there was a group of us at Stanford that they took under wing. And so as medical students, we were going to these clinical protocol conferences in cancer, which probably didn't exist anywhere else in the United States at that time. And it was just amazing to see the two of them work together-- totally different personalities, but extremely skilled clinically and in terms of clinical trials. So that was an exciting time. And so the decision for me was made way back there when. And as part of it, at Stanford Medical School, I was fortunate enough to do my research in the Department of Genetics. And the person that took me under his wing there was Leonard Herzenberg, who was the guy that invented the fax machine. Obviously, probably should have won the Nobel Prize for that. And so it was kind of genetics on the one side, and cancer on the other. So you can see how that kind of evolved going forward. What struck me at Mass General was that there were fantastic clinicians and everything. Obviously, a lot of cancer. But nobody wanted to take care of the cancer patients in Mass General. So an intern resident, I kind of volunteered for all of that. And then when I got to the NIH with Marshall, it was more genetics and everything. And we can talk about that. But I realized after five to seven years there I was either going to be a basic researcher, or get back to my clinical love. And that would have been cancer. So those were the ties that brought genetics and cancer together for me. So can I ask you, when you were in Boston, who was the chief of medicine at Mass General? Oh, gosh. [INAUDIBLE]. The real question I'm asking is, had Dr. Farber's work filtered across town to you guys? That was just about the same time he was starting to give chemotherapy to kids over at Children's. Right. No. Obviously, they knew about it. But it really wasn't discussed at all there. And there was obviously a separation between what was going on at Farber and the Brigham and then at Mass General. Now, obviously, things are much more integrated. So what made you go into lung cancer after you got to the NIH? I think it was Vince DeVita. But it happened because I actually-- so I'd been with Marshall and they had given me my own group to work with there that we mentioned. And I'd been working on somatic cell genetics. And so I went to Vince and I said, look it, I have to do an oncology fellowship so I can learn about this stuff now and get ready. Of course, this is-- the boards came in '75, which were later. And so he said, well, John, I'm not going to do that. But I tell you what. There's this branch of the VA hospital that [INAUDIBLE] [? Anson ?] and Frank [INAUDIBLE] and [INAUDIBLE] are running. And I'm trying to decide whether or not to shut it down. So I tell you what. Why don't you go down and run that? And then you'll kind of learn on the job. And, of course, being 35, 36 years old, you think you can do everything. And I said, well, who's the staff there? And he said, well, they're all leaving. And fortunately, one guy [AUDIO OUT]. So I said, well, who are the fellows coming out of the program that are the best fellows? He said, well, that's easy. It's Dan [INAUDIBLE], Paul Bunn, and Jack McDonald. And so I said, well, if I go talk to them, will you at least back me up? And so I did. And fortunately, two of the three agreed to come. I said, you're going from being a fellow to being a senior investigator here in one fell swoop. But this is it. Jack went with Phil [? Stein ?] and did all the work on GI. Phil was leaving the NCI to go down to Georgetown. So they did that. And fortunately, Marty Cohn was down at the VA. He is fantastic clinical trials [INAUDIBLE] and done work with lung cancer. And we did all of that. And so, we went down there. And so, I said, well, OK, got to work on lung cancer. And so we've got to then start working on the genetics of lung cancer. Of course, everybody said that was totally stupid and not possible. And fortunately, I had my collaborator who had been part of the oncogenic virus program, a pathologist, Dr. Adi Gazdar [INAUDIBLE]. So I said, Adi, come on down, and we can do that. So there was people that really gambled on me. Yeah. I wanted to talk about your association with Adi. Before I get to that though, what were you doing for lung cancer in the mid '70s? It must have been pretty crude. Well, we thought it was pretty sophisticated. And, in fact, what we-- obviously, there was the whole series of the first phase of small cell lung cancer clinical trials. There were first reports that occasionally patients respond, have these dramatic responses. And so we set up these whole series of trials. And, of course, at that time, nobody out in the private world wanted to take care. So these patients would come flooding in. And we would do all the staging, get their tissues, and then try to start cell lines from them that nobody had been able to that before. But then they all went on to randomized clinical trials. And Marty Cohn played a big role in that. Obviously, Dan [INAUDIBLE] and Paul Bunn were instrumental. Des Carney came on. And so, these were various combination therapies that [INAUDIBLE] essentially leukemia-like treatment. But Vince always thought the reason we weren't in small cell lung cancer was that we weren't tough enough. And I kept saying, Vince, we're getting-- we're putting them in isolation. We're treating them with more intensive regimens than with leukemia. And so odd responses, but not. And then the other important component of that was Eli Glatstein's recruitment to the NCI as head of the NCI radiation oncology branch. And he really was-- I mean, briefly had known each other at Stanford. And because we were both tied to Henry Kaplan, that made Eli and me instant friends. And basically, we were like brothers. And so he totally threw the support of the radiation oncology branch behind that. And then there were a series of trials with that. Allen Lichter, former president, obviously, and Joel Tepper, he [? added ?] parts to that. So that was fantastic. Anyone from-- So it must have been pretty exciting for you to see some of the first complete responses with chemotherapy in a solid tumor with a small cell. Absolutely. And that's what-- you know, at that time, and particularly then when we started putting this with limited stage, we were really hoping there was going to be a big tail on the survival curve with people who got put into complete remission being able to remain there. And obviously, the therapies would combine modality with chemo and radiotherapy were complex, too. And we were very fortunate to have the various skillful skill set from the radiation oncologists to work with that. And then in '81, by the way-- so we were at the VA from '75 to '81. And then from '81 to '91, it was the NCI-Navy Medical Oncology Branch, when Vince moved us all up to the new National Naval Medical Center. So you and Dr. Gazdar obviously have had a decades-long collaboration. And how did the two of you even hook up? Was it just because you were providing specimens to him in the pathology lab? Or-- No, no. It all actually started five or six years before. We were-- as part of the somatic cell genetics effort is-- I don't know if you remember, there was also a big effort in terms of isolating tumor viruses and the study of retroviruses. And it turned out that the genetics that I was doing with somatic cell genetics could be used to map receptors for retroviruses. And so he and I collaborated on studying the genetics of RNA viruses in human cells and assigning the various linkages to different chromosomes. And so when, again, as I said, when Vince offered me this battlefield promotion, I knew were going to need a laboratory thing. So I said, Adi, come on down. I said that we were going to have to-- we can't study viruses. We're going to need to study something else. And it's going to probably be lung cancer. And so he agreed. And obviously, he has trained as a pathologist, even better part. And he's now, obviously, one of the world's leading lung cancer pathologists. The other person that was at the VA whose name you may not know is Dr. Mary Matthews, who is a pathologist. And she did a lot of the first VA studies, actually determining that small cell lung cancer was highly metastatic, even when it appeared to be localized. So she was-- I've seen her work. Yeah. Actually, so you were there when viruses were going to be the cause of every cancer. Did you get a lot of pushback if you began to say, I don't think that's the case? Well, it's kind of what goes around comes around. We didn't-- no. As it turned out, it was oncogenes that are cause of cancer, which were discovered through Bishop and [INAUDIBLE] thing too. But you do know the other interesting connection with us and viruses and cancer is that we were obviously studying lung cancers and patients and that. But then, Paul Bunn was extremely still interested in lymphomas. But the way the politics, the Onco politics at the NCI intramural program went, that was already the domain of the medicine branch, Bob Young's branch-- Bruce [? Jander ?] and Dan Longo and Bob Young. But there was one lymphoma that they absolutely wanted to have nothing to deal with. And that was Sézary syndrome mycosis fungoides. So Paul said, OK, we're going to study mycosis fungoides. So both at the VA and at the Navy, we had just huge numbers of patients with [? MF ?] come in. And that involved a variety of studies with electron beam and various therapies and staging that Paul was a major figure in. Well, as part of that-- so we started cell lines, tried to start cell lines from those as well. Well, the other thing that was happening was Bob Gallo's discovery of IL-2, T-cell growth factor. And so we got some of that from him, and were able to study, to grow several of these. And it turned out, one of these was from a young patient with highly aggressive HTLV-1 disease. It was a young black guy from the South. He had one of the first-- you know, his bone scan was a super scan with [INAUDIBLE]. Now, we know. So we didn't do that. And it turned out that Bernie Poiesz was a fellow rotating with us. And he went back to work in Gallo's lab and took those cells. And, of course, Gallo was searching everywhere for oncogenic viruses and retroviruses. And the super [? agent ?] from this cell line, H102, blew the roof off. And it turned out to produce HTLV-1. And that was [INAUDIBLE]. Actually, Henry Kaplan submitted for us to PNAS that was with Bernie and Bob Gallo. And that was the first human retrovirus that was discovered. And then it turned out there were other patients that we had, obviously with T-cell lymphomas, that didn't produce virus. But it turned out that those were ones that the virus could replicate in. And that leads off into a whole separate story that you probably need to talk to Adi Gazdar about, because he started this line. And that's the whole Bob Gallo thing. But the point is that Bob knew that if you could get a T-cell line to grow, it could make the retrovirus, and you could identify it. And so, he kept trying to grow T-cells from patients, at that time young, gay guys from New York and San Francisco. Of course, nothing would grow because they were all being killed by HIV. But there were these T-cell lymphoma lines that had that property. So, in any event, this whole thing came back to viruses, that-- it's not my [INAUDIBLE] study. But it was Adi's and Bob Gallo's. You know, you've through this talked a lot about the basic science and the observations. And the term translational medicine really hadn't been invented yet. But you, and I would argue, Marc Lippman and Bill McGuire in breast cancer, were really some of the first to span the gap between [INAUDIBLE] in the clinic in solid tumors. My impression is leukemia and lymphoma had been going on, but it was the solid tumors where you made your big step. Were you thinking about that the whole time? How can I take this and take better care of Mr. Smith or Mr. Jones? Were people trying to stop you from doing that? Who was your role model to give you the courage to move forward? No. I think if you were present back at the NCI-VA and NCI-Navy, it was pretty clear-- and this didn't require any set of smarts-- that the whole idea to start these things was to have models that you could then test to see about new therapies in order to find out what were the underlying causes. And so you remember back there was the [? Amberg ?] and Dan Von Hoff assays for tumor cell sensitivities. So a lot of our first studies were looking at drug response and radiation response phenotypes. And one of the interesting first things was that the small cells, most of them were exquisitely-- they were like lymphocytes, sensitive to radiotherapies, which was what it was like in the clinic. So I think that there was probably kind of obvious some of the things to do. I think the obstacles were-- first of all, the major obstacle was everybody blamed the lung cancer patient for having lung cancer because they smoke. And I'm sure Franco and anybody working in the lung cancer field with Franco Muggia would tell you this. And we're finally over that, I think, and also with the never smoking lung cancer cases. So that was one big obstacle. I think having these models to work with was another. And then just having the genomic techniques to study them. I look at our first publications in Nature with Southern blots and a few samples. And now, you couldn't even-- this wouldn't even qualify as supplementary supplementary data. Actually, I don't know if you were at ASCO. Bruce Johnson's presidential address was an elegant description of the progress made in lung cancer. And he showed pie charts of 10 years ago. And the entire treatment was chemotherapy. And now it's broken up into all the different precision medicine and immunoncology. I've got to think if you were in the audience, and if you weren't, that's fair. But if you were sitting here thinking, boy, shake my head. We've made a lot of progress. Oh, [INAUDIBLE]. Well, I tell you, I get-- some of those slides I know Bruce was-- I was giving those to Bruce. So, you know, clearly, those were the types of obstacles. And everybody thought that-- first of all, everybody thought that lung cancer was not a genetic disease. And in retrospect now, it's obvious. But, you know, so I think there's that-- the technologies. So one brief anecdote about-- and you probably saw this, too, at the Farber. I'll never forget at the NCI-Navy, all of the senior staff rotated. And we had several months worth of attending in there. And we were taking care of patients with all kinds of tumors-- breast, lung, everything. And we had our own ward with 40 beds. And we saw about 70 patients elsewhere in the hospital. And we had 100 patients a day in clinic. So it was a huge service. So I go up, and I'm doing my first day of attending. And I introduce myself. And I'll tell you who my fellows were on that round. So one of them was Nancy Davidson. The other was [INAUDIBLE]. The other was Neal Rosen. And one was George Morstyn, who subsequently became a-- Australian guy became a VP at Amgen. And so they're presenting these cases and everything. And I go back, and I sit down with Paul and [INAUDIBLE] and Dan [INAUDIBLE]. And I say, Jesus. I said, I can't believe it. We have some really good fellows this time. At another time offline when it's not recorded, I'll tell you some of the presentation that Neal Rosen gave that time, which was vintage Neal. And I say this mainly because to our oncology fellows now, I say, look right, look left, and there's going to be some really interesting people that you're meeting right now. Just remember them several years down the line. You know? Nancy was no different in her presentation today than when she gave her presidential address. She had all the [AUDIO OUT] and everything. And so, that was great. Nancy and I are the same age, but she's been my role model for 25 years. [AUDIO OUT] The other thing-- Well, a couple of other questions-- you've been on the board of both the AACR and ASCO. And I'm interested in what you see as both the contrasts and the mutual initiatives going forward and how they've evolved. Do you have any insights into that? Well, I think Saul Rosenberg may have said something about this [INAUDIBLE] to you. He always, from early on, lamented that, quotes, "commercialization" of ASCO, as opposed to its academic thing. I think, number one, ASCO has done a fantastic job in terms of medical education at many different levels. So I think that's a major success. I think also what clearly is needed now is that we get more of the real world experience. So if patients are treated with checkpoint inhibitors with lung cancer, we don't need to know the results of 300, or 400 patients, or 500. We need to know what happens in 10,000 or 20,000 patients. And the only way we're going to get this is to have some kind of interaction with everything that's going on in the real world. And I think ASCO is positioned to do that. And so, I see that type of interaction being very important. Back when I was on the board, there was-- well, how many people from the private sector should be on the board? And we need to have them have a voice, and all of this. And there was kind of the-- then some people in the private sector trying to take control of ASCO for their own group practices. And we won't go into any names or anything here. But I think what's eventually come out is the possibility to really be the best for everything, both educational, translation of findings. So if there's real improvement in discoveries which have happened to be made, we obviously want to get them out as quickly as possible. Patients demand it. But then also, that we can work out some way to get feedback. Actually, this is one of the reasons-- you've hit on a couple of big initiativies over the last 10 years that I've been involved with. One is the development of CancerLinQ. And we hope that CancerLinQ will provide exactly the kind of data you just asked for. The other is the establishment of the Department of Clinical Affairs, and reaching out to the state-affiliated councils. Steve Grubbs is our Vice-President for that. And it's made a big difference. So that instead of being us versus them, academic versus private practice, it's us versus cancer all together. I'm glad you noticed that, actually. One final question, and this is a bit of a trite question. But I'm asking each of my guests on the show, what do you consider your legacy, your greatest accomplishment? In the end, what are people going to remember John Minna has done to change the face of oncology? Is it your science, or your mentoring? Or what's the one thing you would put your finger on? Well, I think Bob Young and I have an agreement about this. It's the mentoring and everything. And I think training the next generation, setting the example, is very important. I would say one other thing that's really important about ASCO that I see going forward is integrating surgery, radiotherapy, other disciplines, too. And I think it's been very successful. It wasn't necessarily all that way at first. But it's been really key. And getting a chance to know some of the giants in surgery and giants in radiation oncology, like Sam Hellman and Eli Glatstein. And I think Vince, in his book, in many ways saw that, too. The DeVita textbook with Hellman and Steve Rosenberg was an important example of that. So I think that's another important legacy from ASCO too. I agree. Well, actually, I think we've run out of time. Dr. Minna, I can't tell you how much I appreciate your taking the time to speak with us today. I'm sure the memberships can be thrilled to listen to the stories you've told. It's interesting, you've referred to several people I've actually already interviewed, or have planned to interview in the near future. You dropped a lot of names. And that's because-- and you sort of alluded to this. I'm not sure any of us recognize where we are in history at the time that history is being made. And then you look back and say, wow, I was there. And that you were fortunate to be at the NIH in those days. I was fortunate to be at the Dana-Farber in a few years after that. And you shed a lot of light. It's been terrific. Any final comments or parting words? Well, no. I think the one thing I would say is I was thinking back to those early ASCO meetings where there would be 5,000, 7,000, 8,000. So you couldn't even walk from one place to another, because you were always stopping and talking. And now you go to 15,000, 17,000 more. And I remember John Niederhuber and I, when he was director of the NCI, on the third day of ASCO walks through and he grabbed me, and he said, John, you're the first person I recognize. And I [INAUDIBLE]. We had roughly 40,000 people at the meeting this year. Yeah. I think that the question-- so going forward is how we need this family, but how do we get it so it could also be on the personal level? Anyway, Dan, it's been good talking to you. And we thank you for your service, Dan. Thank you. It's been great. For more original research, editorials, and review articles, please visit us online at JCO.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening. [MUSIC PLAYING]
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to ASCO's podcast series of cancer stories. I'm Dr. Daniel Hayes, a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center, and I'm also the past president of ASCO. Over the next several podcasts, I'm privileged to be your host for a series of interviews with the founders of our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and inspired by many of these pioneers. It's my hope that through these conversations, we can all be equally inspired by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, we can also imagine and we can work together towards a better future where we offer patients better treatments, and we're also able to support them and their families during and after cancer treatment. Today, I'm fortunate to have my guest on this podcast as Dr. Saul Rosenberg, who is generally considered one of the pioneers of cancer chemotherapy, especially for lymphomas. Dr. Rosenberg is currently a professor emeritus at Stanford University, where he served as the director of the lymphoma program for several decades dating to the early 1960s. Dr. Rosenberg was raised in Cleveland, where he went to medical school at Case Western Reserve and followed that with an internship at University Hospitals in Cleveland. He then did his residency at Harvard's Peter Bent Brigham, now the Brigham and Women's Hospital in Boston, and completed a fellowship at Memorial Sloan Kettering in 1958. He then moved to the west coast, where he joined the radiation oncologist, Dr. Henry Kaplan, to transform the approach towards lymphoma from one that was principally radiation-based to using radiation and combination chemotherapy. Dr. Rosenberg has authored over 150 peer reviewed papers. He has edited several textbooks, in particular one of the classic textbooks on lymphoma. And his teaching and his mentoring skills are legendary among Stanford trainees and frankly as well as the rest of us. Dr. Rosenberg has won more awards than I can count, but most importantly to me is that he also served as president of ASCO in 1982 and 1983. Dr. Rosenberg, welcome to our program. Thank you. I'm glad to be there. One thing you did not mention [INAUDIBLE] was I spent six years in the radiation oncology laboratory while I was in medical school. That helped start me on my career very much. Actually, you beat me to the punch. I didn't mention it, but I was going to ask you if you had trained there. In fact, that segues. I know you grew up in Cleveland. Can you tell us just a bit more about your background? I know that you entered college at a pretty young age during World War II and then had to step out for a while. Can you give us the background and your circumstances and what led to all that? All that's true. I tried to get into medical school when I was 17 in order to not get into World War II. That wasn't successful at the medical school for various reasons. They thought I was too young and they'd [? hit ?] Jewish quota, so I dropped out for a while, went back to night school, and then reapplied when I was 22. They didn't accept me at that time because of my unusual activities, and so they assigned me to a research lab that I did not pick, which was the atomic energy research lab in Cleveland. It had the initial goal to teach radiation oncologists and to use radioisotopes, but that set my whole career toward radiation. And during the two years in the lab and then four years in medical school, I studied radiation oncology, radioisotopes, tumors, and I developed a great interest in the lymphomas at that time. So did you ever actually then do clinical radiation oncology, or this was all when you were in med school before you became faculty? It was all before my faculty, but I've always been a member of the radiotherapy department. I've taken courses in radiation research and physics, and I'm an honorary member of the radiation societies. That's terrific. And so that must have served you well when you worked with Dr. Kaplan. It was necessary because I presented papers at the radiation meetings, and he recognized me, and when I was searching for a job and the one worked out perfectly at Stanford. And that's how we connected. So can we go back for a moment? I'm very interested in these interviews in why, for example, you chose to go into medicine in the first place. What led to that? And more importantly, especially in the 1950s, when there was no real medical oncology, what got you into doing medical oncology? Well, medical oncology was all an accident because I went into this laboratory and studied radiation in tumors. Before I went to medical school, I didn't have any particular interest in that. When I was a youngster-- five, six, 10 years old-- no one in my family had ever gone to college. Nobody was a professional. But the most respected man in our community was our primary care physician. And since I was a good student, my family and my teachers all encouraged me to try to continue to go to college and be a doctor. And that's what I did. You sure did. [LAUGHTER] Actually, the other thing that was fascinating to me when I looked over your background was your days at Memorial. And so that must have overlapped for sure with Dr. Karnofsky. Can you give us some war stories of that time and what he was like? Well, again, there was a great mistake that turned out so well. There was no oncology program when I left the Brigham, and I wanted to study chemotherapy and medical oncology. The only fellowship was called medical neoplasia, which I applied to at Memorial where David Karnofsky was. I received that fellowship, and in July of 1957, I went to Dr. Karnofsky's office. And he said, "You didn't have a fellowship with me. You have one with Lloyd Craver." So in fact I spent that time not with Dr. Karnofsky but with Dr. Lloyd Craver, who turned out to be the leading lymphoma specialist in the world. And I learned more about lymphoma during that year than anyone could possibly teach me. I did, of course, know Dr. Karnofsky and during that fellowship period, I was acquainted with chemotherapy, nitrogen mustard, [INAUDIBLE] antagonists and [INAUDIBLE] antagonists. So it was a combination of some chemotherapy but mostly lymphoma research. And that set my whole career-- that mistake. I didn't have a fellowship with Karnofsky. [LAUGHTER] I actually always worry about someone I interview who knows exactly what they want to do. I usually say, you know, most of what I did was by luck. [LAUGHS] So sounds like you were too. Oh, absolutely. You know, with both of them, how are they putting things together for the treatment of one problem, though? Is it just let's pull stuff off the shelf, or was there actually some direction in terms of the science they understood at the time? What was the atmosphere at the time? Well, it was very minimal. We had only three lymphomas that we knew we diagnosed-- giant follicular lymphoma, small cell lymphoma, and reticulum cell sarcoma, and of course Hodgkin's disease. But the pathology was so crude that there were very little specific therapies or much difference among the approaches to them. We, of course, used radiation therapy for local treatment. And of interest was that with Dr. Craver, I would make rounds, and we would decide where to give the radiotherapy. We'd outline it on the patient with a red crayon, and we'd write a prescription for the radiotherapy and send them down to radiotherapy. Now that's a remarkable story, because nobody nowadays could even believe that internists could do that. It's unbelievable. Actually, I interviewed Dr. [? Hellman ?] for a previous one, and he gave a similar story that there were very few technicians, and you just kind of drew crayons on the patient and sent them down. [LAUGHS] It's a lot different than it is today. Yes, it is. That's amazing. But the interesting thing was there were no computers at that time, and Dr. Craver's experience with lymphoma-- there were 1,269 cases that I reviewed for him and wrote a wonderful paper, I thought. It was published in Medicine in 1961 on 1,269 cases of a lymphosarcoma. And that set my whole career and my experience that was far above most other people of my age and my training. And that's what really made my career was that study. Now, we had no computer, but we had a IBM cell sorter-- card sorter. And I completed 240 questions on each of 1,269 patients according to their charts, and the data I had was terrific. So you did that with shoe boxes full of punch cards? Oh, at least eight box-fuls because we had 1,269 cases-- three cards for each patient. But the card sorter could just spin out anything that I wanted to know and had so much data that there was no computer. And we had that-- was the first of the data systems that made it possible. And-- That's amazing. It is. And you did all the chart reviews yourself? I did all of it myself because I was disappointed I wasn't with Dr. Karnofsky. But I made the best I could. And it was actually a wonderful experience with Lloyd Craver. Now, were most of those patients treated with radiation or was chemotherapy part of the game yet? Well, we didn't have much chemotherapy at that time. We had steroids. We had radiation. We began to have some Leukeran and Cytoxin by the time I left there, but most of it was radiation and medical treatments with steroids. And very few patients had prolonged survivals, except for the follicular lymphomas which have such a good natural history. Yeah. You mentioned that the very few classifications of the lymphomas-- can you give us some insight into when-- I live in Ann Arbor, for example, so the Ann Arbor classification, of course, is near and dear to the hearts here. But how did that all begin? I know you were involved in that early on too. Well, I did very much. And the important work was done by three people-- Henry Rapoport, who at the time was in Chicago, Robert Lukes, who was in USC, and the German group. And they began to separate out the different forms of lymphoma. Henry Rapoport described the difference between follicular and small cell. And Lukes was careful about the Hodgkin's disease. So their classifications began to be used in the 1950s and in the early 1960s. And they make dramatic differences. Ron Dorfman was a student of Rapoport at the time, though he came from South Africa. And fortunately, he came to Stanford, and that gave us a really-- step ahead on good classification. Eventually, there was great debate about which the right classification it was. And we did a study for three years comparing six classifications around the world and which one gave the most data. And I was the principal investigator of that, and that led to a unusual classification called the National-- I can't even remember the name of it now. But it was a very unusual name, and nobody adopted it. Eventually this classification was dropped, and the new classification came out with immune markers and made a great difference. But that classification in pathology was the stimulus that led to the more modern treatments of that time. And that was one of the great advances that led to two important research studies-- one in Paris and one in Rye, New York, which were virtually entitled "The obstacles to the control of Hodgkin's disease." But the pathology classification systems facilitated that along with tremendous advances in radiotherapy. And I would assume almost-- what's called precision medicine now and targeted therapies-- those allowed you to begin to separate out patients who really didn't need systemic therapy and those who were more likely to benefit from the chemotherapy part of it. That must have really been an eye opener for you as you began to realize that. Well, chemotherapy began to become more successful, of course, for leukemias and lymphomas during that period of the 1960s-- the early '60s. But radiotherapy was the only successful treatment that could control disease for long periods of time until good chemotherapy and combination chemotherapy became available. But the radiotherapy advances really advanced the treatment of Hodgkin's disease and some of the lymphomas dramatically. So that actually, in some ways, segues to my next set of questions. How do you get from New York to Stanford? You said Dr. Kaplan had seen you present. Did he see you as joining him as another radiation oncologist, or did he see you as bringing in the therapy to complement what he did? Well, the truth is I was offered a job at Harvard by Farber, and he told me I could treat patients with cancer at the Brigham, but not lymphoma and leukemia. So then I went back to Cleveland, where they did offer me a job in radiotherapy. But the new chairman of medicine did not think that oncology was an appropriate field for medicine. So I had to call Henry Kaplan as a third choice. And he rapidly accepted me and insisted that I had a role in the department of medicine, which they gave me. So I had faculty appointments in both, which I still have today. Why did Farber not allow you to treat lymphoma? Because he thought it was his property. He didn't want it over in the other hospital. Ah ha. That's-- he had passed away before I got to what was then the Sidney Farber Cancer Institute, but I've heard stories like that. So when you got to Stanford then, how did you all start working at chemotherapy? I know that was before the time that the folks at the NCI had really reported the high response rates with combinations. You must have taken that along with you. Well, I knew that, but the treatments with more than one drug wasn't really popular at least until the early '60s. When I got to Stanford, they put me in the hematology department where I was supposed to do hematology, which I only had minimal training in. But I had a lab in radiation oncology, and I was in the clinic with Henry Kaplan, and we decided that we would treat Hodgkin's disease because of the development in radiotherapy. But I insisted that I would treat cancer in the department of medicine, and that was not popular anywhere in the country. And after they found out I couldn't do much red cell medicine, I started a program for cancer patients, and we needed a name for it. And I got together with four people, BJ Kennedy, Paul Carbone, and the fellow at Hopkins-- what's his name? I'll remember it. But with four of us decided that we would have cancer treatments in the departments of medicine, and we would call it oncology. And that's where the name began. And several of them at Hopkins and at Minnesota had separate departments of oncology-- eventually departments of cancer. So it was very unpopular in departments of medicine, and hematologists to try to prevent us from treating cancer in departments of medicine for at least 10 or 15 years. Gradually, we established what we were, and now it's one of the largest divisions of most departments of medicine. Yeah, I think most of our younger colleagues would be surprised by that. I came in in the early '80s and was struck by the fact that most of the major departments of medicine had given oncology away because they felt that the smart folks were working on in red cell stuff, as you pointed out, and the dumb folks could go get 5-FU. What they didn't realize was that there was a tsunami of academic interest and advances just down the pike. And it's interesting that you had to go make your own department just to be able to do that. What were the facilities you had at Stanford to give chemotherapy? Did you just have a nurse that followed you around and gave it, or did you actually have a fusion space or-- Nothing like that. I separated from the hematology clinic, and I would see patients in my own room. There was only one room. I found one fellow who had trained as an [? NCI ?] named Richard Shaw. And we began treating patients with breast cancer and ovarian cancer and children with various childhood malignancies and leukemia. And curiously, when we gave nitrogen mustard, we did it in the hallway of our clinic, and start an IV and mix up the nitrogen mustard and inject it rapidly. There were no infusions facilities whatsoever. It took many months and years to develop what you now think of as a cancer clinic. So you mixed up your own chemotherapy? We did, and I treated any kind of cancer, including children. And we began to see some responses. But the drugs began to come in in which we had a little bit of benefit, but before we could get combination chemotherapy, especially for the lymphomas and leukemias, we didn't have a lot of success. And how did you get Referrals As the department of medicine didn't like what you were doing, did they all come from the surgeons and the radiation oncologist or-- Yes. Where'd they come from? Mostly referrals, but also Stanford began to let it be known that we would see patients with cancer and make a diagnosis and refer them to the proper departments for treatment, and that we had medical treatment. So we attracted patients from the community. Stanford didn't have a big clinical program until it was transferred from San Francisco, but our cancer program became known. I must give great credit to Henry Kaplan, who was a tremendous power and leader of the field. And that attracted a lot of cancer patients to Stanford. And of course, you know that Henry Kaplan and his colleagues invented the linear accelerator, and that made a huge difference in the way we treat patients even today. So he and Ed Gintzon, who is a linear accelerator man, invented the linear accelerator which provided us with super voltage therapy of one million electron volts or more. And that completely revolutionized the treatment of cancer. Yeah, even when I broke in in the early '80s, that was not universally around, but you would see patients who basically were put in front of the machine. They turned it on for a couple seconds-- not at Harvard but outside the Harvard. I know nothing about radiation oncology, except I knew that wasn't right. [LAUGHS] And so we owe Dr. Kaplan for lots of reasons, really-- in great debt, but that probably is one the greatest step forwards. Can I ask another question. I've always been struck that you were one of the early proponents of randomized trials of lymphoma. That must have taken a lot of courage. Well, it was necessary for me because Henry Kaplan wanted to use very broad fields in high doses, and he thought that he was improving the cure and survival of patients. And I admired that and accepted it, but I thought that he was giving too much-- too wide a field and too high a dose for various reasons. So I insisted that if I were to see patients in radiotherapy that we would do trials that would compare two strengths of treatment primarily with radiotherapy-- one with very extended fields and high dose and to just the involved sites. And that's what my program was. And he wanted to extend the fields beyond where the disease was. And we did randomized studies beginning in 1962. They were one of the very first clinical trials that were done in cancer and certainly the first ones in lymphoma. And those clinical trials modified and went on for years. We gradually proved that both of us were correct. Neither of us had an advantage over one or the other, but we learned a great deal about the diseases and their natural history and how to modify the treatments. And of course, eventually chemotherapy came in, and we combined it. But it's a very long story the trials continue to today. We've treated over 3,000 patients with Hodgkin's disease on these trials. And we couldn't have been more successful. Yeah, I think and again that was just about the time that Dr. Fry and others were starting the cooperative groups that could do randomized trials in those days. And you couldn't have had many role models. And again, "courage" is the word I coming up with to get patients to agree to be in a trial where the treatment wasn't assigned until after they signed up. These days we take it for granted, but it was not then true. Well, it's true, but also Dr. Kaplan and I were very good clinicians, and patients trusted us. And they all accepted going on trial as long as both of us agreed that we didn't know the best thing to do. So that was the basis for a randomized trial. And our numbers of our patients were very small-- would never be accepted today as a trial. In fact, we could-- our statistics would not really show the advantage of one treatment over the other. But what our statistics showed was we had patients surviving with a relapse free period-- a plateau-- that went beyond 10 years. And that was unknown in Hodgkin's disease at the time. It became unknown in large cell lymphoma as well as at the time. The late Jim Holland who I loved and helped mentor me in some ways, but when I first joined [? TLGB ?] was sitting in the back of the room when I was presenting the proposal for randomized trials and yelled from the back of the room, "Hayes, if you need a statistician, it's not worth doing." I said, "With all due respect, Dr. Holland, I think it is-- we're doing. But we need a statistician for that." [LAUGHS] All right, so Dan, I had this same argument with J. Fry, right? He said that it was a scandal to have a control group. And I remember in public meetings, I would tell him only you and God know the difference between these two groups. [LAUGHTER] We argued for 50 years until he finally came to Stanford as a visiting professor, and we connected and admired each other's work tremendously. Well, justifiably. I want to ask another question. You've been involved with ASCO almost from the start, I think, and I noted you were present in the early 1980s. What made you run for president of ASCO? In those days, there wasn't much of an organization. It was 3,000 or 4,000 people. What did you see in ASCO that maybe others didn't at the time? Well, I was forced to join by Vince DeVita. He was a member a few years before I was, and he talked about what he thought was right. And I thought that I was right. But the society made a big difference about bringing us together. And then Al Owens, who was at Hopkins, became president, and he invited me to be on the board and then to be his program director. So that's how I got in. Both DeVita and Owens forced me to join them. Then I became a member of the group and committed to it because there was so much value in sharing our information and data. Well, I don't want to put you on the spot. This year we had 43,000 attendees at the meeting, I believe, in Chicago. Do you recall what year and where your first meeting was, and how many people were there? I can't recall. [LAUGHTER] I think when I was president, there were about 8,000 attendees at the meeting. And we all went from one city to the other-- San Diego, New Orleans, St. Louis, San Francisco. But it got out of hand when we got up to $25,000, and the only place we can meet was in Chicago, which was a great loss because Chicago is a great city, but it was great fun to go all over the country. Yeah, I think we'd agree with both of those, but Chicago handles this pretty well. So it's worked pretty well. We're starting to run out of time a little bit, and I want to ask you a big picture question. And you've hit some of these. So what really is your legacy? How would you like the world to remember what Saul Rosenberg has contributed to the field? Is it your science or the administration issues you set up so that people actually accepted our field or the teaching and mentoring? I mean, you've mentored, in my opinion, some of the great oncologists in the world. How do you think this will come out for you? There's only three things that I'm going to leave after me-- my children, my students, and my patients. And my advances for treatment were tremendous but are all now overturned and built upon. But my students, whether it be medical students or postdocs or my colleagues, were my greatest advance. I am so proud that they have succeeded so much. I felt that I have been a trunk of a tree, and every branch that comes off carries twigs and flowers and plants and exaggerate or emphasize-- multiply what I have done just because I started them off. So nothing has been more important to me than to be a good teacher. And my students all know that I'm a wonderful doctor. That's what they tell me. And to be a careful, caring physician, how to talk to patients, how to examine them, how to tell them good news and bad news-- the skill of being a medical oncologist, and actually to be a physician in general is such a joy. I mean, to have these people depend on us and believe in us the moment you walk in the room, if you're gentle and you know how to touch them and to talk to them-- this is such a joy. I can't think of any other word in being a physician but especially being a medical oncologist. It has been a joy. And are you still seeing patients? I saw several this week. I've cut way back. Yeah. I see patients every other Monday. I see mostly my old patients or recent Hodgkin's patients, but gradually fewer and fewer. But there's-- I have 20 patients, perhaps, I won't give up. None of them have lymphoma anymore, but they all have complications of treatment, and they will not let me retire. And 60 years ago, did you think you'd say that you have a bunch of patients who look like they're cured of lymphoma? Never. Yeah, it's something else. Well, Dr. Rosenberg, you've been a great role model for all of us in the field, and we very much appreciate what you've contributed. I have to say your final statement is very similar to what other people have said to me as well-- George Canellos and others-- about their greatest accomplishments are the people they trained, and those of us who you have trained take that very seriously. So thank you. It's a great honor to talk to you. I hope the new therapies-- immunotherapies-- are going to make a big difference. I think they have promised to do so. And sometimes I get to be cynical. I mean, I've been through about six waves of great enthusiasm in treating cancer, chemotherapy, immunotherapy, the old-time advances in radiotherapy, genetics. And gradually there's been improvements but not the great breakthroughs that I want to see. Maybe this new approach will make a difference. I hope so. Yeah, it looks like it. I said to a first year fellow last week that never in my lifetime could I think I'd say it looks like 20% of people with metastatic melanoma may be cured, and that looks like what's happening. That's pretty exciting, I think. How about 90%-- Yeah. --of Hodgkin's patients? Well, actually a lot of that you had already knocked off before I got in the field. [LAUGHTER] Yeah, and I thought this is going to happen again. And it didn't for quite some time. But I agree with you. I think things right now are really, really starting to happen. And we actually have just scratched the surface of the immunotherapy world. I think there are a bunch more checkpoints that are going to be discovered and therapies for them. So the toxicities are considerable, but as Dr. Fry always taught us, "Cure the cancer first, and we'll figure out how to take care of the toxicities later." And I think that's a pretty good strategy, actually. Thank you. I actually-- [INAUDIBLE] Yeah. OK, that's all. Thank you very much. I really enjoyed this. You know, I've told other people it's like if I hop in a cab with Saul Rosenberg, what would I ask him for the next 35 or 40 minutes on the way to the airport? So this is fun for me. All right. Thank you for asking me. For more original research, editorials, and review articles please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.
On this week's episode I bring y'all Heather Morgan's brand new album Borrowed Heart, The Denim Daddies' new EP Thinkin' (plus an interview with Rick and Rodiger), shout outs and a brand new segment: The Dashboard Concert Confessional Heather Morgan: www.heathermorganmusic.com www.facebook.com/heathermorganmusic www.twitter.com/heathereleven https://itunes.apple.com/us/album/borrowed-heart/1432681957 The Denim Daddies: thedenimdaddies.bandcamp.com/ www.facebook.com/thedenimdaddies www.twitter.com/thedenimdaddies https://itunes.apple.com/us/album/thinkin-single/1439273922 Billy Craig: www.billycraigmusic.us www.facebook.com/billycraigmusic www.twitter.com/billycraigmusic https://itunes.apple.com/us/album/sonic-tunesmith/1437085995 Daniel Hayes: www.facebook.com/daniel.hayes.music/ www.twitter.com/ https://itunes.apple.com/us/album/drive/1439833969?i=1439833973 Jim Luke: www.angelthatfell.com www.facebook.com/jimlukesmusic/about/ https://itunes.apple.com/us/album/angel-that-fell-ep/1379960814 Jade Marie Patek: www.jademariemusic.com www.facebook.com/jademariepatek www.twitter.com/jademariepatek https://itunes.apple.com/us/album/fly-bird-ep/1439544800 Will Carter: www.willcarterofficial.com www.facebook.com/willcarterofficial www.twitter.com/willcarterband https://itunes.apple.com/us/album/fiesta-siesta-tequila-repeat/1393159643?i=1393159652 Thanks for listening! Contact: Email: southboundpodcast@gmail.com Twitter: http://www.twitter.com/sbi35 Intro/Outro Music: Down at the Diner by William Naughton via http://www.themusicase.com Podcast Art by Schechter Productions: http://www.pinterest.com/SchechterArts
Today we have the special guest Daniel Hayes, professional boxer and founder of BR Cryotherapy. Daniel and Seth talk about boxing, honey badgers and the successes and failures of starting a business. Video here- https://www.youtube.com/watch?v=mKL5r0b68Wc&t=12s
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnoses or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello. Welcome to "Cancer Stories." I'm Dr. Daniel Hayes, a medical oncologist, and translational researcher at the University of Michigan Rogel Cancer Center, and I've also been the past president of ASCO. I'll be your host for a series of interviews with the founders of our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and inspired by many of these pioneers. It's my hope that through these conversations we can all be equally inspired, by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, we can also imagine and work together towards a better future, where we offer patients better treatments and we're also able to support them and their families during and after cancer treatment. Today, My guest on this broadcast is Dr. Samuel Hellman, who is generally considered one of the fathers of modern radiation oncology in the United States and frankly, worldwide. Dr. Hellman is currently a professor emeritus at the University of Chicago Pritzker Medical School, where he served as the dean from 1988 to 1993. And he's been the A.N. Pritzker Professor of the Division of Biological Sciences. He's also served as the vice president of the University of Chicago Medical Center. Prior to moving to Chicago in the late 1980s, he had previously been physician in chief and the professor of radiation oncology at the Memorial Sloan Kettering Cancer Center. He served there from 1983 to 1988, and he was also chair of the Department of Radiation Therapy at the Harvard Medical School, where he served as the co-founding director of the Joint Center for Radiation Therapy. Dr. Hellman has authored over 250 peer-reviewed papers, and he's been one of the co-editors of one of the leading textbooks on oncology, Cancer, Principles and Practice. Dr. Hellman has won many awards and honors, including being named a fellow of the National Academy of Medicine, formerly the Institute of Medicine, and of the American Association for the Advancement of Science. He is frankly, one of the few individuals to serve as president of both the American Association of Cancer Research and the American Society of Clinical Oncology, for which he was actually, I believe-- correct me if I'm wrong Dr. Hellman-- the first radiation oncologist to hold that position, which he served in 1986 to 1987. Dr. Hellman, welcome to our program. Thank you for having me. I hope I got all that right. Your introduction has taken longer than some of the others. You have been so prominent in the field. I have a series of questions. The whole point of this is sort of like Jerry Seinfeld's Riding in a Cab with Friends. I've always said, if I had an opportunity to right with some of the giants in our field, what would I ask them during a cab ride? So I get to ask the questions, and you get to answer. I know you grew up in the Bronx. Can you tell us a little bit more about your background? I'm particularly intrigued about the fact that a boy from the Bronx ended up at Allegheny College in Pennsylvania. Why'd you go there? What was your interest? Was it always in science and medicine, or did you have something else in mind? OK. Well, start with the Bronx. I was born in 1934 in the Bronx in a nice part of the city, which doesn't often go with descriptions of the Bronx today, but it was at that time. And about well, 1950, which was when I entered my senior year in high school, I had gone to high school at DeWitt Clinton High School. And as I say, my senior year, we moved to Long Island, and I spent my senior year at Lawrence High School. The important part of this is that Clinton had about 4,500 to 5,000 boys, and Lawrence High School was much smaller and most importantly, coeducational, and that made me very much want to go to a smaller school for college and definitely one that was coeducational. And so my mother and I took a little tour of colleges not too far from New York, but Allegheny was the farthest, I think. It's in Western Pennsylvania, very close to the Ohio border. And it was a beautiful day. I had a very nice two people showing me around, and I became enamored of the place. It was a very good fit for me, but I must say, my method was not a very analytic one, but that's how I got to Allegheny College. And was science and medicine in your thoughts then, or did you have other things that you thought you'd do? No, no. I was a middle-class Jewish boy from the Bronx. You're programmed to be interested in medicine. The old comment was, you know what a smart boy who can't stand the sight of blood becomes? The answer is a lawyer. And I was not offended by the sight of blood. So I actually heard about your decision to go to SUNY Upstate Syracuse and the serendipity involved. And I'm always struck by how so many of us have what we plan and what we end up doing. Can you give us that story? I though it was really fascinating. Well, I'm not sure what part of it you want, but I went to Syracuse Upstate because I won a state scholarship, and I hadn't applied to any New York state schools. And fortunately, the medical school advisor and a former Alleghenian, who was at Upstate, arranged an expedited interview, et cetera. So anyway, that's why I ended there. Why I ended up in radiation oncology-- Well, that was my next question is, how did we get lucky that you decided to go into oncology? Well, I interned at Boston at the Beth Israel Hospital, which was essentially very oriented to cardiovascular disease. Our chairman was a renowned cardiologist. He was the first one to use radioactive tracers. He used radium, as it turned out, and there is an award given by the nuclear medicine society. Their big award, their annual award is the Hermann Blumgart Award, and Blumgart was my chairman. And Paul Zoll, the external defibrillator inventor, was there. Louis Wolff of Wolff-Parkinson-White syndrome was there. So it was a cardiac place. And internal medicine was what I wanted to do, but my father was quite hard of hearing and had a lot of trouble making a living, because he was so impaired. And electronic devices, of course, weren't available at that time. And it was widely thought that otosclerosis which is what he had, was a hereditary disease. And so I was discouraged somewhat from entering medicine, not being able to be sure I could use a stethoscope. Parenthetically, I have never had any trouble, and the disease is no longer thought to be hereditary but rather the sequelae of infectious diseases, either diphtheria or influenza. This was the great influenza epidemic. The two, one of those two. But anyway, that's what he had, so I sought to do something else. And I was a little bit put off by taking care of disease which we really could not alter the course of. We could modify it. We could palliate, but probably if I were more dexterous, I would have become a surgeon. But I wasn't, and so I decided I didn't know what to do. I'd take a radiology residency and see where that led. This was late in the year, and there were no radiology residences, literally, in Boston that were available. But a new chief had come to Yale, and he was starting a new program. And one of radiologists in a neighboring institute told me go there. So I did. Well, he turned out to be a radiation oncologist, and he, Morton Kligerman and Henry Kaplan, were the two chairmen of departments of radiology who were radiation oncologists. And Henry had been at the NIH and got them to, with the National Cancer Institute, I guess, to start a fellowship program to encourage radiation oncology. And Kligerman applied for one, got one. I was there. I was captivated by the opportunity to do some curative treatment. I was a chemistry major in college, and physics and chemistry were things I enjoyed. Sounded like a good choice, so that's what happened. So there could not have been very many specific radiation oncology fellowship programs at that time in the United States. Is that true? Yeah, very much true. The ones that stood out was, I say, Henry Kaplan's. There was a very good one at UCSF. And there was one in Penrose Cancer Hospital and one at the MD Anderson, and those were the ones. So your decision to go oncology then, really your decision to go into radiology-- diagnostic radiology originally, sorry-- didn't sound like you were-- Not really. I took a radiology residency, because I thought it would be helpful whatever I decided to do. I really didn't expect to go into diagnostic radiology, but I figured that's something I could do. I didn't have much training or any training in that before. There was a great dynamic radiologist at the Beth Israel Hospital, and he captivated me. And so I figured, there's a lot to learn there, and I'll try it. I think a lot of the younger doctors don't realize that the two were together for a long time. What's your perspective of the split between diagnostic and therapeutic radiology-- I've actually heard you talk about this, so I think I know what you're going to say-- and bringing them back together? Well, I was a great proponent of it. The whole fields are entirely different. But having diagnostic radiology is extremely helpful in radiation oncology, because we depend on images to determine how we treat, where we treat, and so forth, so it was there. But they were interested in entirely different things. And just parenthetically, when I took the Harvard job, I wasn't going to take it unless I had a promise that we could start a Department of Radiation Oncology. Shortly after I came, and the decision was made with just a shake of the hand that, after a year or two, I'd be able to do that, and that's what happened. Actually, that segues into another question I had is I was looking over your background. I met you first when I was a first-year fellow at the medical oncology. That was 1982, by the way, a long time ago, when it was still the Sidney Farber. And I'd heard about your legendary efforts starting the Joint Center and also your teaching methods with your own residencies. But you were rubbing shoulders with Sidney Farber and Francis "Franny" Moore and Tom Frei. That must have been pretty intimidating for a relatively young guy trying to start a whole new department. What was the impetus behind that? It was an interesting experience. Dr. Farber was, of course, the dominant figure in cancer at Harvard, and nationally, he was one of, if not the great leader. I mean, but he was a difficult man, and I don't like to speak disparaging, but we had a rocky relationship. When the Joint Center-- I'm getting ahead of my story, but it's appropriate to this question. When the Joint Center was started, it was started by Harvard Medical School, and the dean for hospital affairs was a man named Sidney Lee. Dr. Lee had formerly been the head of the Beth Israel Hospital, the director, not the chairman of medicine but the director. And he got the idea that all the hospitals in the Harvard area were relatively small, the Mass General was across town and quite large, but that was not true for the Brigham or the BI or the Deaconess or what at that time was the Boston Hospital for Women. And so he got them all together. So there were those, and I think I left out the Children's, but Children's was amongst them, as well as the Sidney Farber, as you say. Or at that time, it wasn't called that. It was called the Jimmy Fund, but that's another story, and one you know better than I, I suspect. But anyway, those six were to get together when I started the Joint Center. Because Dr. Farber and I had so much difficulty with each other-- he wanted really for me to be reporting to him and being part of the Jimmy Fund but that wouldn't have worked with the other hospitals. He was not liked by any of the places, including Children's, which is where he was the pathologist. So those six initial institutions, when we finally came to sign, turned out to be only four because the Children's wouldn't come in, and the Jimmy Fund wouldn't come in. For a number of reasons, two years later, they acquiesced, mostly because we were successful, and they were without supervoltage treatment, and it was just not sensible for them not to join. But that's my relationship with Sidney. Franny Moore is a different story. Franny Moore was an internationally-known surgeon and expected to have his way, but he was very graceful, very nice. I had very few disagreements with him. He expected, and I think, deserved certain deferences. Sydney did, too, but it just made it too difficult to do that but Franny was not that way. Franny and I came to the treatment, conservative treatment of breast cancer from different points of view. He didn't agree with it, but he was entitled to his opinion, and he was fine. Tom is a different story. I got there ahead of Tom, and he came, and if anything, I helped out Tom, although he was much senior. Harvard has its own culture, as you know, and he needed at least an introduction. I mean, he sailed along fine after that. And in fact, at one time, he and I wanted to start a joint residency program. It was to be a four-year program, which would have people take two years together and two years in their respective specialty. But the boards were not in agreement, so it was dropped. But Tom and I always got along fine. Actually, that raises one of my other questions. I spent a lot of time in Europe, and the field of so-called clinical oncology still remains, combining radiation and medical oncology. In fact, they style it as a particular specialty in Great Britain. How did it evolve not that way in the United States? Radiation oncology went off on its own. And I think you had a lot to do with really professionalizing radiation oncology as a specialty in this country. Is that not true? I'd be interested in your perspectives on this, too. Well, I should parenthetically say that I spent a year in the National Health Service in 1965, while I was a fellow at Yale, in clinical oncology at the Royal Marsden Hospital, their major teaching hospital for cancer. And I always believed in the joint efforts of a non-surgical oncology program. You can include the surgeons, mostly because their lives are so different and their technical training is much more extensive, but you can work closely with them, and I've been fortunate to be able to do that. But medical oncology and radiation, in my judgment, would be better off close together. And your comment about me and ASCO, being the first president as a radiation oncologist, and I never call myself a radiation oncologist, at least not initially. I always call myself an oncologist. But I do, I agree and then describe what I do as radiation. But I agree with you, they have the best title-- clinical oncologists. And why it occurred the way it occurred, I'm not sure. I know we started in radiology and medical oncology started in hematology. I mean, the real revolution, and leaving aside Dave Karnofsky and his work, the real changes occurred in acute leukemia. And the real founders of the specialty, Dave was surely one of them, but a great many of them were all hematologists, leukemia doctors, and it grew from there. It grew out of hematology. And a lot of major oncology papers were in Blood, the journal Blood before they were in JCO. So that's the best I can do with it. Our big thing was to separate from diagnostic. Getting closer to medical oncology is much easier, because we have the same book. You said I wrote the textbook with Vince and Steve, and so I did. And that was very easy. We spoke the same languages. We saw the same things, not completely. I saw more head and neck. Vince saw more of the hematologic malignancies, but the rules were similar. It was no-- it was easy. And I've heard Dr. Frei-- I trained with him when he was alive and obviously, Dr. DeVita talked about what it was like to give chemotherapy when they started. And how we really professionalized, in many ways, and split up giving chemotherapy, the different responsibilities. What was it like with radiation oncology back 40 years ago? I mean, how did you-- the safety issues, were you all cognizant of the safety issues related to radiation at the time? How did you do your planning? What was that like? Well, safety was-- Hiroshima made everybody know a lot. In fact, if anything, we were more conservative than we probably needed to be because of radioactivity being an evil and all the things that happened after '45 and at Hiroshima and Nagasaki experience. And so safety wasn't a problem that way. But there were a lot of people in the field who were using the field, who are not radiation oncologists. Some of them were radiologists, diagnostic radiologists and did it part time. They had a cobalt unit, before that, just an orthovoltage, conventional energy, much less effective and more damaging. And also gynecologists, and when I visited Memorial Hospital early on in my training, and the surgeons would send a prescription blank, a regular prescription dying down to the radiation therapist. And that's what they were, technicians, or often were. And they may have differed with the prescription but only by being careful and discussing it with the surgeons and convincing them that some change should be. That's very different. How was the planning done? How was the planning done? The planning was fairly primitive. Well, most places had a physicist, usually a physicist, who did both diagnostic machines and conventional radiation oncology, and they were important in that department and those people subspecialized, too. And in fact, when I came to Boston in 1968, Herb Abrams, who was the new chairman of radiology-- he's the one who chaired the committee that selected me-- but he and I jointly started a physics department. So it was still in diagnosis as well as therapy, but we realized that wasn't a good idea and separated. So physics was evolving, but treatment planning before supervoltage, and even with supervoltage before multileaf collimators and a lot of the newer, what then were newer techniques, was reasonably rudimentary. When I did my residency, we did our own planning, and usually, it got checked by the physicist but not all the time. It's a lot different now. Yes, it is. I want to turn this to an area that's more personal to me and that is your role, out of all the many contributions you've made to the field, your role in the field of breast-preserving therapy. I came in just as you and Jay Harris were really making that institutionalized. Just for our listeners, what were the hurdles there? They must have been both personal and professional and technical. And did you ever doubt that this be successful in the long run? You must have had some second thoughts about getting into this. Well, I have to back up. It was well before Jay, but it was at Yale. And apropos of how many-- going back to our previous question-- how few radiation oncologists there were. There was a club. Before there was a specialty, before there was a society, there was the American Club of Radiation Therapy. And all you had to do to belong to it was do radiation therapy without doing diagnostic radiology. And I was in the low 200ths of the consecutive order of people who belonged to the specialty from its very inception at the turn of the century. So there were very few of us, and we knew each other extremely well and had these little conversing meetings. And a number of people would talk about patients who had medical diseases which wouldn't allow them to have their breasts removed. They still had localized, apparently localized breast cancer, and the radiation therapist took care of them, and I did, too. I had these people. And we also had the Europeans, especially the French, who were treating breast cancer with radiation. In fact, they were doing it with a fundamental difference with what we did from the beginning and they do now. And that is, they did it without removing the breast cancer, because they were doing it primarily for cosmetic reasons. And they felt that taking out the breast cancer might damage the cosmetic effect. So we weren't alone. We weren't first. So I knew that other people had done it. Some people who did, Simon Kramer in Pennsylvania at Jefferson, Thomas Jefferson, did a great deal of it. And we did it, because we had a surgeon at Yale who was interested in sending patients. You mentioned Jay, but really, before Jay, there was Lenny Prosnitz, who you may or may not know of, who was a long-time chairman at Duke. But Len was a medical oncologist at Yale, who was about, I don't know, three or four years behind me in training, and I was either a young assistant professor there at the time or a fellow, I can't remember which. And he came over to me and said, you've got a nice life. You do interesting things. I'm not so crazy with this. Can I get into it? And Lenny, obviously, being trained in medical oncology, being a boarded internist was also interested in breast cancer. Because that's the one disease, even in the beginning that medicine, or one of the few diseases that medicine was interested in for the hormonal aspects of the disease. So Lenny took over when I left with the surgeon Ira Goldenberg, and he kept it up. And when I went to Harvard, I had all those different hospitals, and I had a very good colleague there, who was the only radiation oncologist in those hospital complex, and he also treated some. So we continued to do it. One of the nice things about Harvard at that time was, at least for this purpose, was we had this women's hospital, Boston Hospital for Women. And gynecologists in those days did everything for women and that included breast surgery. And those guys delivered their babies and when they got breast cancer, took care of them. They weren't interventional. They were their private primary care docs, and they were much more sensitive to the cosmetic aspects and the self-image aspects of breast cancer surgery. And so they knew we did it, and they became a big source of suggesting patients and sending them to us. Anyway, Marty, Marty Levine, the fellow I was talking about, and I developed a reasonable number of them. One of my residents, Eric Weber said, why don't you write a paper about this? I said, it's all done. The French have it. The Brits have it. Even the Canadians have it. He said, we don't. So I said all right. We sent out the paper, and the first paper is with Eric and Marty and me, and it was a JAMA paper and that gets to another point. What year was that? I had to bully pulpit. What year was that, the JAMA paper? The JAMA paper? About '75-- '74, '75. And it made a big splash. And then Lenny and Simon Kramer and Luther Brady, two Philadelphia people who had big experience, and us put all of our stuff together. And Lenny brought it all together, and so there was another big paper. I think that one was in JCO, but maybe not. I can't remember. And I think that's how it got started. And my issue with it and my involvement in it is, yes, pioneering the treatment in America. I don't claim to have pioneered it anywhere else. It wouldn't be true. But what I did do is use the bully pulpit of being the Harvard professor, and I went everywhere and talked about it. And I took on the surgeons in a number of places and talked about it. And if I made a contribution to it, it was that. I can remember being in an audience and hearing you talk about the Halstead theory and then the Fisher theory and what became known, in my opinion, as the Hellman theory, which is a combination of the two. That both local and systemic therapies make a difference, and the mortality rate of breast cancer has dropped by almost one-half over the last 30 years, and you should be proud of that. Oh, I'm proud of it. I'm proud of it. But people don't do things in a vacuum. You build on people and on their doings. Well, I want to be respectful of your time, if I can finish up here. I really just touched the surface of many of the contributions you've made. I wanted to talk a little bit about your role in getting radiation oncologists to think about what we now call translational science. But at the end here, what do you think are your greatest accomplishments? What do you think your legacy has been to the field? Do you think it's the science or your administration or your teaching and mentoring or all of those together? I think all of us would like to think about what our legacies would be. Oh, I would say, it's an interesting and not an easy question, because I'm interested in all of those things. But I like to remind people that, and it's been commented on by others, I am one of the few people who maintained a practice of medicine, a real practice, all through being a dean. I always think of myself first as a doctor. And I am an investigator, and I am interested in research, both basic and clinical, and did both of them, but I'm a doctor first, that's number one. Second to that, I was very involved in teaching and believe-- and that's why I became a dean and before that, started a department in Harvard and gave courses in oncology, and my residents are my greatest legacy, if you really want to know. Nobody lives forever, and what you did in the lab and your patients, that passes, but your residents are your history. They continue it, and their residents continue it and so forth. And just to end on a high note that you mention, is that the Karnofsky lecturer this year was one of my residents. Yes, he was. Of course, that's Ralph Weichselbaum. He was. I actually chaired the selection committee, and I can't tell you how proud I was to stand up and introduce him. He did a wonderful job. In addition to your own residents, I'm going to tell you, you're also passing this on to the medical oncology fellows who were hanging around the Farber in those days. And to this day, I tell patients I wear two hats. My first hat is to take care of them as I can with the knowledge I have today, and my second hat is to do research to make it better. But my first hat always wins, because Dr. Hellman said you're a doctor first. So there you go. Well, I haven't changed on it. That's very nice to hear though. OK. I think on that note, we'll end up. I had planned over about half an hour. We're just over that. So thank you very much, both from me, personally, and from those of us in the field and from our patients who have benefited. Dr. Hellman, you are truly a pioneer and a giant in our field. So thank you so much. Well, you're very kind to say so. For more original research, editorials, and review articles, please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.
Daniel Hayes reminds me not to judge a book by it's cover. Before speaking with Daniel, I thought, "Whoa, am I going to like this guy? A boxer, athletic dude? Me, I'm a fat, bald, nerd, will we be able to connect?" Then Daniel was sweet, funny and curious...made me want to work out more. This is one of my favorite shows, so in case you missed him the first time...enjoy. :D Daniel Hayes is a top ranked middleweight boxing prospect and Trinidad & Tobago’s boxing ambassador. Daniel Hayes Growing up Daniel played a variety of sports ranging from Soccer, Basketball, Football, Track and Field, Baseball and Swimming. At just 8 years old, he started playing basketball and continued playing throughout college. At 16, he was already a certified lifeguard and a highly recruited athlete in multiple sports. In his senior year of high school, he was recruited to play basketball for several NCAA Division 1 and 2 schools. Early Veers Hayes however decided to attend Thompson Rivers University where he and his childhood best friend were offered athletic scholarships. College proved to be quite a defining time for Hayes. He started as a Kinesiology major but after just one single acting course, he discovered his love and passion for acting and switched his major to Theatre. Hayes was no stranger to the camera He was a published print model since the age of 17. It wasn't long after his revelation that the acting gigs began pouring in. Hayes landed his first commercial with And1, which was quickly followed by a well-known television ad with Nike. Improv and Acting Eagerly seeking to develop his craft, Hayes began studying at The Second City and Groundlings, schools who boast of alumni including Jim Carrey, Will Ferrell, Seth Rogan and Steve Carell. Hayes added to his training by studying at The Ivana Chubbuck Studio that has trained Hollywood’s elite such as Halle Berry, Brad Pitt, Terence Howard and more. Currently on his Olympic quest, Hayes fights out of the world famous Wild Card Boxing Club, home to superstar world champions Manny Pacquiao and Miguel Cotto. Daniel Hayes Vroom Veer Stories Daniel made the honor roll one semester in High School, the basketball coach was his teacher Learning how to listen to his body after an injury and not push himself too hard Was hyper-focused in high-school on training, didn't have much of a social life Realized he missed out on High School buffoonery when he started college Stories of sibling rivalry, getting bullied & being a bully--yup we are mammals Small regrets of being "so serious" as a freshman in college His college teammates wore him down & he learned to relax & enjoy the moment In sixth grade, Daniel was in the Chess Club - he did 3 tournaments How improv skills help on stage and in life to roll with punches Sleep masks can be tricky if you have to get up in the night for a bathroom trip Daniel Hayes Links Daniel's Web Site is Daniel-Hayes.com
In this episode featuring Daniel Hayes, we talk about his path to becoming a boxer & actor, how to surround yourself with positive people even if you can't find them and the power of setting and reaching your goals.
The Alex Merced Cast - Libertarianism, Blockchain and Economics
Alex Merced discusses the circumstances that lead to the several candidates running for the office of Chair and Vice Chair. Donate at Donate.AlexMerced.com and LibertyDeal.info Check out Alex Merced's campaign at AlexMercedforLNC.comSupport the show (http://www.patreon.com/alexmerced)
Chris Spangle interviews Daniel Hayes, the Libertarian Party Convention Committee Chairman, about the controversy over Ron Paul not being invited to speak. Hayes is also a member of the LNC, so we asked him about Arvin Vohra and Nick Sarwark. Spangle then gives a history of why the LP and the Rothbardians don't get along.
Daniel Hayes earned his nickname “The Honey Badger” (an animal known for its fearlessness) in the ring. Originally from Trinidad and Tobago His talent expands beyond the sports realm from Motivational Speaking to Entrepreneurship to being an On-Camera Talent. In 2016, Hayes worked with filmmaker KB Kutz on The Honey Badger, a boxing documentary that closely follows the life of Hayes as he prepares for his professional bout in Mexico. He continues his World Championship journey fighting out of the world famous Wild Card Boxing Club, home to superstar world champions Manny Pacquiao and Miguel Cotto. "You don't have to be great to get started, but you need to get started to be great"
In this episode, Dr. Ivor Hill discusses the psychological impact of celiac autoimmunity in children, and Dr. Daniel Hayes discusses adjuvant therapy with capecitabine for selected women with breast cancer.
My guest today, on the Join Up Dots free podcast interview is a man who is a top ranked boxing prospect and also Trinidad & Tobago's boxing ambassador. He is also is a sought after model who has been photographed around the world since the age of 17. And when you see the photos ladies (and of course men too) that fact doesn't come as a surprise What does come as a surprise though, is this guy, with a highly tuned competitive streak was so obviously looking for the non-obvious route that could fulfil his dreams. Growing up he was involved in a variety of sports. He loved soccer, basketball, football, baseball and swimming and at just 10 years old started playing basketball and continued playing throughout college. At 16 he was already a certified lifeguard and a highly recruited athlete in multiple sports. In his senior year of high school he was recruited to play basketball for several NCAA Division 1 and 2 schools. Now this is when one of the big twists occured in his life, or as we say he hit one of his big dots. College proved to be quite a defining time for him, he started as a Kinesiology major, but after just one single acting course, he found that he had discovered his love and passion for acting and switched his major to Theatre. It wasn't long after this revelation that the acting gigs began pouring in. He landed his first commercial and this was quickly followed by a well-known television ad with Nike. Now he could have said “This is easy” and coasted a bit, but instead he set out to become the very best that he can be in this new found arena. He started defining his craft, by studying at The Second City and Groundlings, schools who boast of alumni including Jim Carrey, Will Ferrell, Seth Rogan and Steve Carell. He added to his training by studying at The Ivana Chubbuck Studio that has trained Hollywood's elite such as Halle Berry, Brad Pitt, Terence Howard and more. He knew if he was going to be the best he had to surround himself with the best that Hollywood can offer. And now away from the acting he is training for the Olympics, and once again surrounds himself with the best by fighting out of the world famous Wild Card Boxing Club, home to superstar world champions. So what has these diverse uses of his time and talents taught him, as he drives forwards with his ambitions? And is better to become very very good at one thing, or be diverse as he has been up to this point? Well lets find out as we bring onto the show to start joining up dots with the one and only Mr Daniel Hayes. Show Highlights During the show we discussed such weighty topics with Daniel Hayes such as: How “The Revenant”is a truly boring film, no matter how many awards it gains across the film industry…..but why it has an amazing message for all entrepreneurs too! Why Mike Tyson would always get up at [4:00]am in the morning to go running, because all his competitors are asleep, and the reasons behind the decision to do this. Why being in the flow and present in the moment is the state that we must all aim for no matter what arena we put ourselves….it's where the huge wins are found. And lastly…. Who he would choose to be in later years Mickey Rourke or Leo DiCaprio, and the reasons why he believes that both are masters of their art.
Patience, persistence, and perseverance are key factors in pursuing – and being successful – with your passion. In today's podcast, we will be talking to Daniel Hayes, an actor, model, and accomplished athlete who has persevered in his pursuit of his passion for acting and sports. He is a middleweight champion, top-ranking prospect and Olympic boxing ambassador to Trinidad & Tobago. Daniel discovered his love for sports at a very young age. He has played and excelled in a wide variety of sports such as soccer, baseball, football, track and field, basketball, and swimming. At the age of 16, he was already a highly-recruited athlete who was invited to play for several NCAA Division 1 and 2 schools, before deciding on Thompson Rivers University where he had also been offered an athletic scholarship. Daniel's upbringing and story is quite interesting. His self-discipline and focus has paved the way to a successful athletic career and these traits have also helped him overcome the mental strain caused by recovering from a physical injury. In today's podcast, he will share tips on how to improve focus and self-discipline and self-realizations that have allowed him to overcome challenges.
The Winning Youth Coaching Podcast: Youth Sports | Coaching | Parenting | Family Resources
Daniel Hayes is a top ranked middleweight boxing prospect and Trinidad & Tobago's boxing ambassador. Growing up Daniel played a wide variety of sports ranging from Soccer, Basketball, Football, Track and Field, Baseball and Swimming. At just 8 years old he started playing basketball and continued playing throughout college. At 16 he was already a certified lifeguard and a highly recruited athlete in multiple sports. In his senior year of high school he was recruited to play basketball for several NCAA Division 1 and 2 schools. Hayes however decided to attend Thompson Rivers University where he and his childhood best friend were offered athletic scholarships. Currently on his World Championship journey, Hayes fights out of the world famous Wild Card Boxing Club, home to superstar world champions Manny Pacquiao and Miguel Cotto. Website: www.daniel-hayes.com Instagram: @ThisIsDHayes Twitter: @ThisIsDHayes Facebook: @ThisIsDHayes Listen Now: Listen on iTunes: iTunes link Listen on Stitcher: Stitcher link Listen on Google Play Music: Google Play link - Quote 'It's usually what we're hesitant or fearful of doing that leads to our biggest strides and growth' 'The Honey Badger' - the important difference between hard work and talent Honey badgers are fierce, scrappy animals- that is the type of athlete you should aspire to be Motivation, self discipline and nutrition Water is huge! Impactful coach Daniel had a high school basketball coach who benched him because of his attitude - it really changed Daniel's approach to team sports Training and skill development - Keeping it fun Setting goals is fun. There is a positive dopamine effect when you cross something off a list. Track progression and check off milestones along the way. Coach K on the 2008 Redeem Team - Reminded his team that in 20 years they are going to look back and deeply miss those competitive situations, so thrive on it in the present. Developing Self-confidence Visualization is huge Self-mantra and inner monologue - 'I am going to make this shot' Developing culture Constant accountability to one another Setting team goals - and rewarding positive team-first behavior High-fives, huddling as a team before a free-throw, anything that pulls the team together during the game should be a priority Connecting with and impacting kids The Selway Family Foundation - Underprivileged youth scholarships Mentoring - Daniel loves helping younger athletes avoid some of the mistakes he made when growing up The One that got away Daniel got fouled at the end of a basketball game, and his head was full of negative images and thoughts: 'If I miss this...' - and he went on to miss both free throws. He learned the power of positive visualization and staying present and in the moment. Best borrowed or stolen idea 'I don't know if you're going to win this fight, but I know you're going to come out of it a better fighter just because of the experience you have gained' - This was huge for Daniel because it took the pressure off winning and allowed him to just enjoy the competition and do his best. Favorite coaching or leadership quote/book Ray Lewis Ted talk - Persevering through pain Book: Rafa by Rafael Nadal - talks about how he had faulty mental processing before he beat Roger Federer and how he overcame it Daniel Hayes www.daniel-hayes.com - sells shirts - $2 of every shirt sold goes to charitable foundation Parting Advice 'It's usually what we're hesitant or fearful of doing that leads to our biggest strides and growth' - Today's Sponsors I Youth Football helps coaches, organizations, or parents teach football skills to kids ages 3-11. Not only does I Youth Football guarantee your players increase their skills, they will give you individualized pricing based on your situation. So if you are a coach or want your local organization to ...
Click below to listen to this episode on how to effectively start a new civil engineering job… In episode 041 of The Civil Engineering Podcast, I interview Daniel Hayes, PE about how to start out a new civil engineering job on the right foot. Here are some of the points Daniel reviewed in relation to starting […] The post TCEP 041: Strategies for Starting A New Civil Engineering Job on the Right Foot appeared first on Engineering Management Institute.
Daniel Hayes is a Middleweight Champion, top ranked boxing prospect and Trinidad & Tobago’s boxing ambassador. (www.daniel-hayes.com) Growing up Daniel played a wide variety of sports ranging from Soccer, Basketball, Football, Track and Field, Baseball and Swimming. At just 8 years old he started playing basketball and continued playing throughout college. At 16 he was already a certified lifeguard and a highly recruited athlete in multiple sports. In his senior year of high school he was recruited to play basketball for several NCAA Division 1 and 2 schools. Hayes however decided to attend Thompson Rivers University where he and his childhood best friend were offered athletic scholarships. College proved to be quite a defining time for Hayes. He started as a Kinesiology major but after just one single acting course, he discovered his love and passion for acting and switched his major to Theatre. Hayes was no stranger to the camera; he had been a published print model since the age of 17. It wasn't long after his revelation that the acting gigs began pouring in. Hayes landed his first commercial with And1, which was quickly followed by a well-known television ad with Nike.
Daniel Hayes is a top ranked middleweight boxing prospect and Trinidad & Tobago’s boxing ambassador. Daniel Hayes Growing up Daniel played a variety of sports ranging from Soccer, Basketball, Football, Track and Field, Baseball and Swimming. At just 8 years old, he started playing basketball and continued playing throughout college. At 16, he was already a certified lifeguard and a highly recruited athlete in multiple sports. In his senior year of high school, he was recruited to play basketball for several NCAA Division 1 and 2 schools. Early Veers Hayes however decided to attend Thompson Rivers University where he and his childhood best friend were offered athletic scholarships. College proved to be quite a defining time for Hayes. He started as a Kinesiology major but after just one single acting course, he discovered his love and passion for acting and switched his major to Theatre. Hayes was no stranger to the camera He was a published print model since the age of 17. It wasn't long after his revelation that the acting gigs began pouring in. Hayes landed his first commercial with And1, which was quickly followed by a well-known television ad with Nike. Improv and Acting Eagerly seeking to develop his craft, Hayes began studying at The Second City and Groundlings, schools who boast of alumni including Jim Carrey, Will Ferrell, Seth Rogan and Steve Carell. Hayes added to his training by studying at The Ivana Chubbuck Studio that has trained Hollywood’s elite such as Halle Berry, Brad Pitt, Terence Howard and more. Currently on his Olympic quest, Hayes fights out of the world famous Wild Card Boxing Club, home to superstar world champions Manny Pacquiao and Miguel Cotto. Daniel Hayes Vroom Veer Stories Daniel made the honor roll one semester in High School, the basketball coach was his teacher Learning how to listen to his body after an injury and not push himself too hard Was hyper-focused in high-school on training, didn't have much of a social life Realized he missed out on High School buffoonery when he started college Stories of sibling rivalry, getting bullied & being a bully--yup we are mammals Small regrets of being "so serious" as a freshman in college His college teammates wore him down & he learned to relax & enjoy the moment In sixth grade, Daniel was in the Chess Club - he did 3 tournaments How improv skills help on stage and in life to roll with punches Sleep masks can be tricky if you have to get up in the night for a bathroom trip Daniel Hayes Links Daniel's Web Site is Daniel-Hayes.com
A conversation with Trinidad & Tobago's boxing ambassador and middleweight champion, Daniel Hayes, is my next step to getting nicer with the hands! Training as a boxer takes an incredible amount of endurance, agility, and mental strength (among many other skills of course). It's a whole other world, competing individually as opposed to team play. Daniel breaks down the beginning of his athletic career as he played for many team sports, with the reason for switching up his main focus, to become an absolute monster in the ring. Got your gloves handy? Listen up! Some Questions I Ask: Why'd you choose to become a boxing? How does it appeal to you? How did you feel without picking up sports after college? How do you stay motivated for long-term goals? Are you calm/focused before your fights? Do you have any pre-fight routines? What is the key, to remain calm under pressure? What were some specific mistakes of yours? How'd you learn from them? What are your most critical daily habits? How to get in touch with Daniel: Daniel's official website is Daniel-Hayes.com Facebook: Facebook.com/Daniel-Hayes Instagram: @official_dhayes Twitter: @official_dhayes IMDB: Daniel Hayes on IMDB And as always, if you're diggin' the podcast, Please rate and review the show on iTunes! Thanks for listening to another IMNOTYOU Sports Motivation Podcast! Much love!
Daniel Hayes is on a unique and interesting journey; he is pursuing a gold medal in the 2016 Olympics as a boxer representing Trinidad and Tobago. Based in California, he is an authority on fitness, nutrition, and boxing as well as the athletic mindset, perseverance and how that applies to life. Daniel is also an actor. After one semester in college as a Kinesiology major, he switched to Theater. Daniel currently trains at the world famous Wild Card Boxing Club and aspires to motivate and inspire others. Daniel practices mindfulness every single day.Contact InfoWebsite: www.daniel-hayes.com Most Influential PersonGeorge St.PierreKobe BryantEffect on EmotionsOne hundred percent it has because it allows you to be calm and master your emotions because your emotions can result in some of the most erratic actions. It really helps you and for me to really think logical before I react out of emotion.Thoughts on BreathingBreathing is a big part of it just because with anything, with breathing, air, oxygen that's what keeps you centered. That's me when I am practicing yoga but that what keeps you centered and that's what keeps your body centered. So even throughout both physically or mentally our most tedious points or experiences, breathing is always what will keep you centered.Suggested ResourcesBook: Rafa by Rafael Nadal Advice for NewbieThe most important thing is momentum and what I mean by that is breaking it down to very very small steps. I once heard that habit is formed after three weeks. After practicing something for three weeks it becomes a habit so whether it's making sure you just drink two liters of water a day, just something as simple as that. If you are continually building on that and making that a habit and practicing it over and over again you are going to build momentum and then you're going to be able to take on something else. For mindfulness start small and build on it, gain momentum to move forward.Thank You Bonus: As a thank you for listening, download your Calm Your Busy Mind Infographic. It focuses on breathing, exercise and mantras. Please leave your name and email you'll receive your infographic in your inbox right away. Download It here.
Because of his Podcast: He Discovered a Niche Who Needed A Product Got a note from Corey Fineran I just handed my boss my resignation letter! This podcasting journey started 7 1/2 years ago and it's now allowed me to leave my job and start my own business! You've probably heard me talk about Ivy Envy (my podcast on the Chicago Cubs) more than the one I did for my employer. Since 2012, I've been able to call myself a "professional podcast producer" as my employer created a new position for me to do video podcasts for teachers to play in their classrooms to help high school students with disabilities in their transition from high school to life after high school (primarily through work/employment). Well, there is a huge need for this type of curriculum and schools all over the state of Illinois have started using that podcast. I saw a need and last summer, I started working on starting my own business, creating innovative and interactive online transition curriculum and marketing it to schools all over the country. After receiving contracts from school districts and cooperatives, I'm able to leave my job at the end of this school year. Many of the people in this group have influenced me (whether they know it or not) to take this scary jump. +Bob Zerull +Ray Ortega +Daniel Hayes +Nick Seuberling +David Jackson and of course, +Tawny Fineran who has been insanely supportive over the last year as I've worked on building this. If you're curious to check out what I've been working on, you can find it here: http://transitioncurriculum.com Another Problem with Your Show's Title Headline As I now work for Libsyn (where you can get a free month using the coupon code sopfree), and I get to see some mistakes that people are making. Now I'm doing a bit of a repeat, and that is people make horrible headlines. In the past I've talked about starting off a headline with the date. What I am seeing now is people putting the name of their show at the beginning of the headline. Why this makes no sens, is any place you can see the headline (your website, a listing in iTunes) you already see the name of the show. Also here is another thing to keep in mind, on the podcasts app from Apple, you can only see 45 characters of the headline if you're not subscribed to it. Once you subscribe you see the entire headline. However, would you subscribe if every headline was: School of Podcasting - How to Podcast Today w School of Podcasting - How to Podcast Today w School of Podcasting - How to Podcast Today w You're wasting really, really valuable space. Why do we care? I had a client who had a respected media outlet that wanted to put their RSS feed on their site. They tested it and the headlines were horrible, and they wanted the producer to change all of their headlines. Want to make great Headlines, check out my Free Headlines Resources Multiple Websites Question Revisited Paul said, " Heard your comments about updating multiple websites. I have 7 x WordPress sites, have used ManageWP for a couple of years now, love it! VERY easy to update all sites at once, gives you immediate admin access to all sites without login and very simple to add and take new WP installations, with dynamic pricing. Daniel said, " I use iThemes Sync. ]But you should also check out JetPack’s built-in module for plugin updates. Then, you can login to wordpress.com/plugins (I think) and update all your plugins from there. It’s not as thorough as Sync or others. But it’s free with no limit on sites. Is Blab.Im Going Away? The quick answer is no. However, the CEO stated this week "Blab is not doubling down on broadcaster tools.” They want to focus more on equipping people to hang out. We talked about this on the Ask the Podcast Coach show that I do every Saturday at 10:30 AM EST and here are some theories of what this might really mean. They can't make it reliable Podcasters are perfectionists They are working on other projects (an app for teens) This is as good as it gets. For me it means, I'm not leaving the platform until it doesn't work for me. I will be scouting other options. Thanks For the Review "What a fantastic resource this show has been for me. As a 51 year old professional in the entertainment industry, I knew nothing about podcasting when I decided to have my own show. The School of Podcasting has and will continue to be my GPS (great podcasting source). Thanks Dave for doing your homework! Alan Bruess, Tailgate Entertainer" from AlanB-Tractor Guy. This review was sent to me automatically from My Podcast Reviews (have all reviews from all countries, as well as sticher be sent to your email ) Advanced Podcasting Recording Tools in Plain English Today I'm joined by Chris Curran of the podcastengineeringschool.com and http://fractalrecording.com/ who has spent years as an audio engineer in the music business, and is now turning his skills on podcasting. Now keep in mind, you do NOT need these items to get started. Next week I'm doing a podcast with just a microphone and audacity. No effects at all. Today we talk through What is a compressor? What do the knobs do? What does it sound like if I messed up? What is a noise gate? What do the knobs do? What does it sound like if I messed up? What is a De-Esser? What do the knobs do? What does it sound like if I messed up? Thinking of Starting a Podcast? Check out www.podcastingpuzzle.com and www.schoolofpodcasting.com
Hello hello everyone! Glad to be back for another episode of The Inner Changeamaker. If this is your first time checking us out, My name is Jay Wong, I will be your host. This is THE place dedicated to purpose-driven individuals and passionate creators. We are all about learning how to create impact and interviewing people that are choosing legacy over currency. Last week, we had an Olympian by the name of Daniel Hayes giving us the behind the scenes of the Olympic scenes and what goes through his mind as he enters the RIO 2016 games. The mindset of an Olympian. If you missed it, please go check out that episode. As you heard in the teaser, Today, we have THE peter Shankman on the show. But before we get there. This episode is sponsored by Podcast Your Brand Mastermind. Podcast your brand is a 2-month accelerator program meant to help you launch a top-rated podcast, put your personal brand on steroids ( the good kind) and get your message out to the world in a bigger way. If you have been following my journey the last 6-8 months or listened to the last episode, you know that podcasting literally changed my life. I went from no email, no real brand, no business model to speaking internationally on my podcasting story, interviewing my mega-influences such as Yanik Silver, Bob Proctor, and an Olympian haha. I finally created a real online business that allows me to travel and if you follow my vlogs, then you know I am hustling and trying to balance everything in my life. I have been working with a very selective group of messengers and creators the last few months to help them do the same in their lives, create the top-rated show they deserve, get their message out to the world in a bigger way and ultimately change their lives. Right now, I am gearing up for a mega-launch come end of month for a NEW group starting in May, so if you are a messenger, an entrepreneur or creator ready to share your story with the world by launching a top-rated podcast as well as actually figuring out how to make $$$ from this, then I invite you to jump on the waiting list. You can go to www.theinnerchangemaker.com/waitlist You can fill in your name there and be sure to write in the message that you heard this from the podcast. I want to include a bonus for you guys. So once again, its www.theinnerchangemaker.com/waitlist -- Now let's get to today's episode with Peter Shankman. The New York Times has called him "a public relations all-star who knows everything about new media and then some,", while Investor's Business Daily has labeled him "crazy, but effective." I love his twitter, where it list out like 15 things, Including @NASA advisor, Ironman. Skydiver. Dad. Peter Shankman is a spectacular example of what happens when you merge the power of pure creativity with Attention Deficit Hyperactivity Disorder (ADHD) and a dose of adventure, and make it work to your advantage. He is a bestselling author, entrepreneur, speaker, and worldwide connector, Peter is recognized worldwide for radically new ways of thinking about Customer Service, Entrepreneurship, Social Media, PR, marketing and advertising. Peter is best known for founding Help A Reporter Out, (HARO) which in under a year became the de-facto standard for thousands of journalists looking for sources on deadline, offering them more than 200,000 sources around the world looking to be quoted in the media. HARO is currently the largest free source repository in the world, sending out over 1,500 queries from worldwide media each week. HARO's tagline, “Everyone is an Expert at Something”, proves over and over again to be true, as thousands of new members join at helpareporter.com each week. In June of 2010, less than two years after Peter started HARO in his apartment, it was acquired
Daniel Hayes is a Model, Actor, MMA fighter and Olympic boxer who will be representing Trinidad & Tobago in the 2016 Summer Olympics. Throughout his life, Daniel has dominated in a wide range of sports including soccer, football, baseball, swimming and basketball, playing on the collegiate level with an athletic scholarship. He is in MMA Fighter and holds belts in 4 different Martial Arts! He has also found success as a model and actor and has been featured in popular And1 and Nike ads. On his Olympic quest, Hayes fight out of the world famous Wild Card Boxing Club, home to superstar world champions Manny Pacquiao and Miguel Cotto. Go to OctaneAthleticPerformance.com for your Steps to Fitness success.
Podcast your brand is a 2-month accelerator program meant to help you launch a top-rated podcast, put your personal brand on steroids ( the good kind) and get your message out to the world in a bigger way. If you have been following my journey the last 6-8 months or listened to the last episode, you know that podcasting literally changed my life. I went from no email, no real brand, no business model to speaking internationally on my podcasting story, interviewing my mega-influences such as Yanik Silver, Bob Proctor, and an Olympian haha. I finally created a real online business that allows me to travel and if you follow my vlogs, then you know I am hustling and trying to balance everything in my life. I have been working with a very selective group of messengers and creators the last few months to help them do the same in their lives, create the top-rated show they deserve, get their message out to the world in a bigger way and ultimately change their lives. Right now, I am gearing up for a mega-launch come end of month for a NEW group starting in May, so if you are a messenger, an entrepreneur or creator ready to share your story with the world by launching a top-rated podcast as well as actually figuring out how to make $$$ from this, then I invite you to jump on the waiting list. You can go to www.theinnerchangemaker.com/waitlist You can fill in your name there and be sure to write in the message that you heard this from the podcast. I want to include a bonus for you guys. So once again, its www.theinnerchangemaker.com/waitlist -- Now for today's interview, we have Daniel Hayes, an Olympian for the upcoming 2016 games! Daniel Hayes is a top ranked middleweight boxing prospect and Trinidad & Tobago's boxing ambassador. He is going to be representing his country this summer in Rio and in this interview we talk about his story and how everything got started. Currently on his Olympic quest, Hayes fights out of the world famous Wild Card Boxing Club, home to superstar world champions Manny Pacquiao and Miguel Cotto. In this interview, he breaks down for us the Olympic process, how it works. (Sorry, I was really curious.) He also told us what he does differently, what gives him the ultimately edge. His answer will surprise you. It's something we have talked about before on this show and it was really great that he brought that up. www.theinnerchangemaker.com/podcast-shownotes/065 LINKS -- Join the Legacy Driven Entrepreneurs Community (it's FREE): http://www.theinnerchangemaker.com/tribe Are you enjoying the podcast? Listen to the episode here and leave us a review: Apple: http://apple.co/1JUHcG9 Android: http://bit.ly/2nuoGpl TuneIn: http://bit.ly/2BjY0gU Breaker: http://bit.ly/2BRwOCb iHeartRadio: http://bit.ly/2BhMr9L Spotify: http://spoti.fi/2BbuWEg Want to grab my NEW audio training? Grab a FREE copy of "How To Be The Leader You Truly Are": http://www.theinnerchangemaker.com/leadership Launching a podcast? Grab my Podcast Creation Roadmap: http://www.theinnerchangemaker.com/roadmap
LINK TO EPISODE 216 SHOW NOTES
Steve Jobs created the format that our guest entrepreneurs follow on the Join Up Dots free podcast interview, and todays guest is a man who is a top ranked boxing prospect and also Trinidad & Tobago's boxing ambassador. He is also is a sought after model who has been photographed around the world since the age of 17. And when you see the photos ladies (and of course men too) that fact doesn't come as a surprise. He is building multiple careers, and has huge motivation to build a platform more than just a boxing career. What does come as a surprise though, is this guy, with a highly tuned competitive streak was so obviously looking for the non-obvious route that could fulfil his dreams. Growing up he was involved in a variety of sports. He loved soccer, basketball, football, baseball and swimming and at just 10 years old started playing basketball and continued playing throughout college. At 16 he was already a certified lifeguard and a highly recruited athlete in multiple sports. In his senior year of high school he was recruited to play basketball for several NCAA Division 1 and 2 schools. Now this is when one of the big twists occured in his life, or as we say he hit one of his big dots. College proved to be quite a defining time for him, he started as a Kinesiology major, but after just one single acting course, he found that he had discovered his love and passion for acting and switched his major to Theatre. It wasn't long after this revelation that the acting gigs began pouring in. He landed his first commercial and this was quickly followed by a well-known television ad with Nike. Now he could have said “This is easy” and coasted a bit, but instead he set out to become the very best that he can be in this new found arena. He started defining his craft, by studying at The Second City and Groundlings, schools who boast of alumni including Jim Carrey, Will Ferrell, Seth Rogan and Steve Carell. He added to his training by studying at The Ivana Chubbuck Studio that has trained Hollywood's elite such as Halle Berry, Brad Pitt, Terence Howard and more. He knew if he was going to be the best he had to surround himself with the best that Hollywood can offer. And now away from the acting he is training for the Olympics, and once again surrounds himself with the best by fighting out of the world famous Wild Card Boxing Club, home to superstar world champions. So what has these diverse uses of his time and talents taught him, as he drives forwards with his ambitions? And is better to become very very good at one thing, or be diverse as he has been up to this point? Well lets find out as we bring onto the show to start joining up dots with the one and only boxing entrepreneur Mr Daniel Hayes.
Vanessa Hayes, a certified Professional Organizer, and her husband Daniel Hayes come on and share with us how they live a simplified life. They give us tips and tricks on how to organize your life, which plays in to how you organize your home. This episode is full of inspiration and how-to tools.
PM sermon for July 13, 2014
How do find balance when it comes to producing content and then having to promote it via any number of ways (social networks, blogs, forums, etc.)? Have you ever been overwhelmed trying to keep up? Has the need to always be promoting your show in order to grow left you feeling burnt out on podcasting? We'll be discussing podcast promotion and how much is too much? How do you know if what you're doing is actually working and is it really worth your time? The discussion will be focused less on which new social platform is best for podcast promotion and instead will take a deeper look at why or why not to promote, how much and is it necessary to always jump on the next big thing (ex: Pinterest)? Roundtablers for this session will include +Daniel J. Lewis +Rob Walch +Daniel Hayes +Mike Russell, and myself (Ray Ortega). Join us in the chat along with your fellow podcasters to share your experiences with balancing content creation with the challenges of promotion. Links mentioned: Dircetory of podcast directories
14th Feb 2010 pm - 1 Kin. 18 - Daniel Hayes
www.BreastCancerUpdate.com/Surgeons – Conversations with Oncology Investigators. Bridging the Gap between Research and Patient Care. Interviews conducted by Neil Love, MD. Produced by Research To Practice.