Aug 28, 2019
Dr. Hayes interviews Dr. Freireich on his involvement with combination chemotherapy.
Dr. Daniel F. Hayes is the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center. Dr. Hayes’ research interests are in the field of experimental therapeutics and cancer biomarkers, especially in breast cancer. He has served as chair of the SWOG Breast Cancer Translational Medicine Committee, and he was an inaugural member and chaired the American Society of Clinical Oncology (ASCO) Tumor Marker Guidelines Committee. Dr. Hayes served on the ASCO Board of Directors, and served a 3 year term as President of ASCO from 2016-2018.
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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.
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--
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.
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.
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?
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.