Jerome Yates became a cancer doctor during a time when medical oncologists were thought to be what he describes as “the garbage collectors of medicine.”
“The attitude among physician colleagues was, why are you wasting your time doing this? Not only are you wasting your time, but you’re making the patients sicker,” said Yates, 85, a retired oncologist who has practiced and administered research at Roswell Park Comprehensive Cancer Center, the University of Vermont, NCI and the American Cancer Society. “Some of them get very sick from the chemotherapy, because there are a lot of side effects with the normal tissues.”
During his internship at San Bernardino County Hospital, Yates, then 29, encountered a metastatic testicular cancer patient around his age. The young man was admitted to the hospital with congestive heart failure.
“They were going to let him die,” Yates said to The Cancer Letter. “I said, ‘If he came in and you didn’t know that he had metastatic cancer, you would treat him for his congestive heart failure.’ I convinced the attending. We treated him, and it bought him another four or five months. I thought it was an important four or five months.”
The prevailing attitude toward cancer treatment was depressing —“That if somebody had metastatic disease, had cancer spread around the body, that they were going to die, and why would you want to prolong their agony?”
In 1965, Yates encountered an optimistic article, “Obstacles to the Control of Acute Leukemia” in the CA: Cancer Journal for Clinicians, written by James Holland, an oncologist at Roswell Park Comprehensive Center.
“He said that they were on the pathway to cure acute leukemia. The way it was structured, and the timing—I was taking care of some chronically ill patients—and it just sounded like it was exciting,” he said.
Yates joined Holland at Roswell Park in 1968 and began conducting clinical trials with members of the cooperative group Acute Leukemia Group B cooperative group, the ALGB. This group, renamed the Cancer and Leukemia Group B in 1976, conducted clinical trials using two, three, or four-drug combinations. This strategy was not received kindly by the mainstream medical community.
“There was a general attitude that we not only didn’t know what we were doing, but what we were doing was potentially harmful to many patients,” Yates said.
Rather than embrace the work of the ALGB, cancer doctors largely adopted the thinking of William Dameshek, an influential hematologist at Harvard who was a mentor to many oncologists.
“His attitude was that we were poison pushers, that we were cowboys, that we were doing things that weren’t in the best interest of the patient,” Yates said. “Because he was extremely influential, we were viewed as outliers.”
Still, Yates remained hopeful—“because, as a physician, taking care of these patients—it made you feel good.”
Members of the ALGB would raise one another’s spirits, too.
“One of the things that we did was pump each other up by talking about the successes,” Yates said. “You see a fusion of basic science information at the cooperative group meetings with the clinical research information, and you see that there is some light at the end of the tunnel for a few of the diseases.”
“We learned from each other and the meetings of the CALGB, because they were relatively small, a few hundred people, at that point in time,” he said. “There were honest to God discussions in the committees and in the hallways.”
With the ALGB, Yates and Holland conducted pilot studies of the combination of cytosine arabinoside and daunorubicin in acute myeloid leukemia—and ultimately developed the 7 + 3 regimen that is still used today.
“Initially, I was treating them with two days of daunorubicin at high doses and five days of cytosine arabinoside by continuous infusion,” Yates said. “We didn’t eradicate the leukemia and the bone marrow with great consistency, so we increased the dose then to seven and three, three days of daunorubicin and seven days of continuous infusion of cytosine arabinocide, and we got good results.”
“In the younger population, we were seeing a high remission rate that we hadn’t seen before,” he said. “We were getting in the range of disease control, probably in about 60% of the patients, at that time.”
This development in AML was one among many successes for the ALGB, and a major boon for cooperative groups. For the first time, the ALGB achieved mainstream approval.
“It was really in the early ‘70s that we started emerging as not being the ‘witch doctors’, or the ‘cowboys,’ or the ‘poison pushers,'” he said. “By the late ‘70s and early ‘80s, it was clear that the protocols, the studies that the cooperative groups were doing, provided new information and better ways of managing patients.
“We started actually getting a little respect. I mean, we were like the Rodney Dangerfields of medicine in the late ‘60s and early ‘70s. We didn’t get any respect. That was real,” he said.
Because of the work of Yates and Holland, many physicians diagnosed with AML sought treatment at Roswell Park.
“They still came to Roswell, because they knew that there was some hope there. A lot of what we did in those days, and a lot of what’s done today is, you provide hope to the patients that maybe you can make a difference,” he said.
Though the 7 + 3 regimen is still considered standard of care, Yates can’t help but think that there’s a better treatment out there. Five-year survival rates are 27% in people older than 20, and 69% in people younger than 20.
“I’d like to be alive one day, a hundred years from now, to see what they’re doing. I’m sure the docs would look and say, ‘Those stupid jerks, what they were doing was so primitive and inappropriate,’” Yates said. “The understanding of the etiology of disease and how it progresses, I’m sure, will be much different a hundred years from now than it is now.”
Yates spoke with Alexandria Carolan, an associate editor with the Cancer History Project and reporter with The Cancer Letter.
Jerome Yates: Well, In high school, I worked in a prescription pharmacy in a physician’s office building. I thought that probably, I would go to pharmacy school, but my parents didn’t have a lot of money. My dad was a farmer and I ended up going in the Army at age 17, primarily to get the GI Bill.
While I was in the army I was with, probably half of the company were college graduates, because it was a medical ambulance company. A couple people said, “You’re smart enough to go to medical school, why don’t you do that?”
One of them, actually, had been a pharmacist at the hospital that later spun off St. Jude’s in Memphis. After I got out of the army, I went to college with the idea I was going to be pre-med and go to medical school. I went to college at Lawrence University.
So, then I went to medical school at the University of Illinois in Chicago. At that time, as I said, my dad had been a farmer and I thought I was going to go into general practice in North Dakota or South Dakota or Montana—someplace in the Plains.
I did a rotating internship at San Bernardino County Hospital in California, because that was one of the last places, as rotating internships were dissolving, that was one of the last places where they trained interns to do surgery. During my internship, I was a little unsettled about what I wanted to do, and I read an article that was written by Jim Holland.
The article, in essence, was saying—and this was 1965. The article, probably I read it in either late ‘65 or early ‘66, midyear in my internship. He said that they were on the pathway to cure acute leukemia. The way it was structured, and the timing—I was taking care of some chronically ill patients—and it just sounded like it was exciting.
I, in fact, looked at the literature a little bit and then I decided that what I would do is go into oncology. There weren’t many training places at that point in time. There was MD Anderson and Fox Chase in Philadelphia, and the NCI in Bethesda, Memorial Sloan Kettering in New York, and Roswell Park. That’s where Jim was—Jim Holland.
I went to Milwaukee, did a couple years of general internal medicine. The head of hematology there was a guy by the name of Anthony Pisciotta, who had trained with [William] Dameshek. Dameshek was at the Peter Bent Brigham [hospital] at Harvard in Boston.
Dr. Pisciotta’s approach to acute leukemia was to give them steroids and send them home, essentially. Send them home to die. Further, his approach to treating these patients was problematic for me.
During the midyear of my internship, I took care of a kid who had metastatic testicular cancer. He was the same age as I was, and they were going to let him die. He was in congestive heart failure.
I said, “If he came in and you didn’t know that he had metastatic cancer, you would treat him for his congestive heart failure.” I convinced the attending. We treated him and it bought him another four or five months. I thought it was an important four or five months.
I saw this with some other patients, because in that era, if you had metastatic cancer, people just sort of wrote you off. I saw a breast cancer patient who had a lot of bone disease, and what they were doing, primarily, was giving her pain medicine and snowing her.
The whole attitude toward cancer was different in those days, different in a couple different ways. One is, there was still a myth that if you told people that they had advanced cancer, that they would give up completely, and it would be the worst thing you could do. There was a certain amount of gamesmanship in talking to the patients with advanced cancer, and talking to the families.
The other thing is that the docs, generally, the surgeons and the other internists, didn’t like to take care of cancer patients. They were happy to transfer them to somebody else’s care at that point in time, because there wasn’t a lot you could do except treat the patients with palliation and supportive care. And frankly, they didn’t do a very good job of it then either.
I went to Milwaukee, and Tony Pisciotta was there, and he was sending the leukemia patients out with, as I said, steroids and forgetting about them. I went and visited Jim Holland at Roswell, and when I went there for a visit, he spent the whole day with me. It was impressive, so I went to Roswell, and that was 1968.
After I had been there a month or so, I started out on one of the services. He asked me if I would take over the laminar air flow rooms, the patient isolators, because at that time we thought that if you gave patients more chemotherapy, obviously, they’d get in more trouble with infection.
We were giving platelets at the time so we could control the bleeding, but the goal was to prevent infections, if you could. We, because the laminar air flow rooms filtered out all of the ambient bacteria, all the bacteria in the air, we thought that we could in fact see less infection in the patients.
We constructed a study and the study really had four arms. One arm was treating patients on the ward in conventional care. Another arm was to treat them on the floor in reverse isolation, but also to give them antibiotics that would suppress the bacteria and the fungi in their gastrointestinal tract. And then the third arm was to treat them in the isolators without the antibiotics to suppress the bacteria and fungi in the isolators. The other arm was to treat them with the antibiotics and the isolators.
What we effectively found after a three year study was that we could, indeed, prevent the patients in the isolators from getting some infections, but the outcomes, in terms of the response to leukemia, didn’t change.
The goal of the isolators was partially accomplished, but it didn’t solve the problem of controlling the leukemia. At the same time, we were transplanting some of the patients, the AML patients. The two places where they were doing a lot of bone marrow transplants for AML was—Don Thomas was at the hospital in Cooperstown, New York, and George Santos was at Johns Hopkins and was doing them. Don Thomas was using radiation to suppress the leukemia, and George Santos was using high-dose cyclophosphamide to induce the patients, and they were having some successes.
We were also trying to transplant some of the patients with advanced solid tumor disease, and we had more success with the leukemia than we did with the solid tumor disease. In parallel to that, with the ALGB, we did pilot studies of the combination of cytosine arabinoside and daunorubicin.
Initially, I was treating them with two days of daunorubicin at high doses and five days of cytosine arabinoside by continuous infusion. We didn’t eradicate the leukemia and the bone marrow with great consistency, so we increased the dose then to seven and three, three days of daunorubicin and seven days of continuous infusion of cytosine arabinocide, and we got good results.
In the younger population, we were seeing a high remission rate that we hadn’t seen before. And we were seeing some of the patients, again this is looking at it retrospectively, who were living for a long period of time. We were getting in the range of disease control, probably in about 60% of the patients, at that time.
We still had problems with infection, and one of the bacteria that caused a lot of infections was Pseudomonas, because it’s a ubiquitous organism that, if you cultured most sinks in the kitchen or in bathrooms, you’d get Pseudomonas out of the sink. I did some of the early studies with both gentamicin and carbenicillin, doing antibiotic studies that were effectively testing whether or not we could successfully treat the infections.
Again, we were controlling the bleeding with platelet transfusions, but the infections were the big problem with these patients and having newer effective antibiotics at the time was important for improving the survival, and thus improving the remission rate for the patients with AML.
This was the late sixties, early seventies, and I published the 7 + 3 data in Cancer Treatment Reports in 1972. Subsequently, the CALGB then mounted a nationwide protocol, because it was the biggest group of hematologists in a cooperative group at that point in time.
They ran 7 + 3 against other regimens that were thought to be effective, and had proved to be the most effective, and also yielded the population with long term survival. We saw people out two and three years, probably about 30% of the patients at that point in time, and we’d never seen anything like that with adult acute leukemia. AML is primarily a disease of adults. There are a few kids that get it, but the median age is probably in the late sixties for getting AML.
We also found, in that original data, that the people over the age of 60 seemed to do worse than the people under the age of 60, that there was an age related phenomenon. This was because they tended to have more serious infections and they didn’t cope with the infections as well.
When older people get infected, because their organs aren’t as resilient as the younger population, they didn’t do as well. That was also before the time that we knew that there were cytogenetic differences. There were differences, molecular differences in the older population, which conferred negative prognosis for the older people.
Clara Bloomfield’s work, and the people at Minnesota at the time, really in subsequent years, demonstrated that the problem with treating the older people aggressively was also probably a sampling problem. There were more older people who had less favorable disease, and that’s why they didn’t do as well.
Clara and I always had a healthy competition over the years, and she would tell me that the reason the older people didn’t do as well was because I didn’t know how to treat the old people and support them as well as she did. Well, subsequently, she showed that, in fact, the sample of the older people had a worse prognosis because of the type of disease that they had, which you could see when you looked at the cytogenetics.
That was probably the early seventies. Then Jim Holland went to Russia in 1973, for a year. That was largely because the state department asked him. They were attempting to soften things in the scientific relationship with the Russians, and he wanted to get out of Roswell Park.
We had looked at a few jobs at the time, and I told him I’d go with him any place, but not New York City. He spent a year in Russia and when he came back, he went to Mount Sinai in New York City, and that’s when I went to Vermont. I went to Vermont and he went to Mt. Sinai in 73, and I went to Vermont in 74.
JY: Because I grew up in the Midwest, and New York City is like Las Vegas for me. About two days is about right, and then I just think there’s too many people squished in such a small place. I wasn’t really interested.
Of course, Jim said, “Well, you can get an apartment in the city, and then you can get a place out in the country so that you can go to the country on weekends.” Well, at the salary I was making at that time—it was not practical for me to even think about an apartment in New York City, almost, let alone have two pieces of property for putting up with the problems in New York City.
JY: Well, you have to be an optimist if you’re a cancer doc, and I was an optimist. I found medicine to be fascinating and fun. What I couldn’t understand is, here’s this kid that’s the same age as me, and he had a reversible disease. He was in congestive heart failure. I couldn’t understand. I didn’t like the idea that they were just going to write him off and send him home, and let him die from congestive heart failure, because that’s what would’ve happened.
I had the attitude that you should be obligated to try to do whatever you can to help the patients, to make the patients better, and that giving up prematurely wasn’t good. Particularly in his case, and in the case of the lady with bony disease, we had pain medicine, but we also—that was the beginning of the era of radiation to try to particularly treat the bony disease.
There were things that we could do to make them both more comfortable and buy a little bit more time. But there was a prevailing attitude in medicine at the time, that if somebody had metastatic disease, had cancer spread around the body, that they were going to die, and why would you want to prolong their agony?
There was a discomfort. It’s funny, because there’s a parallel to that. When the AIDS epidemic occurred in the early ‘80s, there were a lot of physicians who didn’t want to do anything with AIDS patients, because we didn’t have a lot to offer. But the reality is we had something to offer in terms of comfort. It was an opportunity to try to understand the disease better, and figure out if there were some things that we could do better.
Now, I wasn’t operating at that level, in terms of the research level, at that time, because I didn’t know enough about cancer. But I did know about congestive heart failure, and I did know about pain medicine and how you could treat the patients that had these kinds of complications. It was the aversion of most of the physicians, at the time, to manage these patients, that I probably was reacting to, and just couldn’t quite understand.
JY: It was five and two. It was just a smaller schedule of drug treatment. To use an analogy that we used to use. It’s like having a lawn, when you have acute AML, it’s like having a lawn that is infested with weeds and what you do is, you spread weed killer all over the whole lawn. Then you hope that the grass is going to come back as you eradicate the weeds. At that time, when we gave the chemotherapy, in essence, what we were doing, we knew we could wipe out the bone marrows with chemotherapy. Or, we knew from the radiation exposure accidents, that one of the things these people died from was the exposure to the radiation, because it wiped out their bone marrow. Then they got infected or bled to death.
We knew that we could control the disease for a short period of time. Well, the first demonstration of this was actually with acute lymphocytic leukemia. In 1947, Sidney Farber, who was a pathologist at the Peter Bent Brigham in Boston, showed that a drug called Aminopterin, a relative of methotrexate—He found that folic acid was important for the leukemia to have persistent growth, but if you gave these drugs, they would block the folic acid metabolism and you could put the kids in a transient remission.
That was really the first successful treatment for ALL, for acute lymphocytic leukemia, the childhood leukemia. The principle then persisted and people then tried it with combination with single drugs and combinations of drugs, in the late ‘40s and early ‘50s, for treating lymphomas and testicular cancer with some modest success.
The principle was a little different with solid tumors than acute leukemia. The reason the acute leukemia was accessible, and we were able to evaluate it, was because you could put a needle into the middle of the bones and aspirate it and see whether or not the leukemia was present in the bone marrow.
With solid tumors, we largely, in the old days, measured the size of the tumor and then looked at whether or not the tumor shrank when you gave them chemotherapy. Well, the ability to check the bone marrow once a week allowed us to see what the trajectory of the eradication of the leukemia was. It was really the accessibility of the bone marrow that made leukemia a good target for doing clinical research studies in eradication with chemotherapy.
JY: Well, you have to look back at the cooperative groups. The ALGB started with the nidus of Tom Frei, Jim Holland, J Freireich. The three of them were at the NCI, National Cancer Institute, part of NIH. They started the cooperative group because childhood leukemia was relatively uncommon, but also, the kids didn’t live long.
When you look at the prevalence of any disease, if you did a cross section of the population and you looked to see how many people had disease, the prevalence is determined by the duration of the disease and how many new cases occur. Because these kids weren’t living a long time, the prevalence was relatively low. What they did was try to collect incident cases from different institutions and then study these cases. That was the beginning of the ALGB.
It really started at the NCI, and then Jim Holland, when he went to Roswell Park, carried it over to Roswell Park. As your articles in The Cancer Letter have said, that Don Pinkel came to Roswell Park and was the first head of the pediatric services at Roswell Park. He and Jim worked together a good deal in the early ‘60s before he went off to Memphis, Tennessee, and really started the cancer center there.
It was the relative rarity of the tumor, the ability to see that there was a drug, or other drugs allowed you to get the cancer, the leukemia, to respond, that formed the glue to connect the hematologists at different institutions. This included the people at Columbia in New York City, Dartmouth in New Hampshire, in Hanover, NCI, Roswell Park, and Fox Chase. That was the beginning of the ALGB.
The other thing that happened was that biostatisticians were brought into the mix, so that the approaches that they had used to make comparisons between outcomes for diseases based on what the treatment outcomes were, and really facilitated the development and the growth of the cooperative groups.
You ought to do something on the cooperative groups sometime, because, basically it was a combination of the biostatistician educating the hematologist, and the hematologist educating the biostatisticians, that allowed this to happen. One of the founding biostatisticians for the Acute Leukemia Group B, is a guy by the name of Oliver Glidewell, who’s still alive in Canandagua, New York. Oliver and the late Marv Zelen were pioneers in the cooperative group development. It would be worth a conversation with Oliver, and I could give you his phone number if you want to have that.
[sba]JY: Well, Gordon Zubrod was overseeing and facilitated these interactions from the NCI and also drug development program. Gordon Zubrod was instrumental in providing the kind of bureaucratic leadership, in combination with scientific leadership, This allowed the cooperative groups to develop and to prosper.
The other aspect of the cooperative groups that gets overlooked is, the education , of the practicing physicians that were out in the community, They were a sourced of patients because they were taking care of these patients.The cooperative group meetings were a major factor in educating physicians about clinical cancer research because they were taking care of cancer patients and about sharing information.
Jim was the president of ASCO, must have been about 1973 or ‘74. I was on the program committee, and we had our meeting of the program committee in Washington, DC. What we did was we got the abstracts, and there were about 200 abstracts, and because the meetings weren’t so long then, we sorted out the abstracts. The committee reviewed all of the abstracts. There were probably, I don’t know, seven or eight of us involved on the program committee. We took the abstracts and we put them in piles around the periphery of a meeting room in a hotel in Washington, D.C. This is, whatever year it was, whenever he was president.
You go from that, a few hundred abstracts, to literally thousands of abstracts that they deal with now. Complexity increases as you go from a meeting size of 50 to a hundred people, to a meeting of now 37,000 people.
At that time, and my own career reflects this, when I went to Vermont—if you don’t count the guys living in Vermont that were at Dartmouth—I was the only medical oncologist in the state of Vermont. There was a hematologist at the University of Vermont, Stan Burns, but he was very conservative and he didn’t treat the patients the way they needed to be treated, from my perspective.
One of the things I did when I went to Vermont was, I went monthly to tumor boards at Plattsburgh, which is across Lake Champlain in New York state in Rutland, Vermont. We had a shared tumor board with the people at Dartmouth, because there was a radio tower that would transmit linear waves from the mountain top above Stowe.
You could actually transmit visual information back and forth.. This is 1974, and you could see stuff on a TV screen, but it was so primitive compared to what we have now. But it was an opportunity for the people at Dartmouth and for the interested people in Burlington to discuss clinical science.
At that time, the people most interested in treating cancer were the surgeons and the radiotherapists. So, we went around to the tumor boards and they would present the cases, and then we would discuss what we thought was the appropriate management for some of these patients at that time.
That’s essentially the beginning of the cancer center, along with a scientist by the name of Dick Albertini, who was interested in the causes of cancer and carcinogenesis. He was a laboratory-type guy.
We got a planning grant from the NCI to look at the feasibility of developing a cancer center in Vermont in 1974. Then I recruited Irv Krakoff, who had been the chief of medicine at Memorial, to come to Vermont in 1976. Irv was a superb clinical scientist, and a leader in drug development. He identified chemists able to develop new drugs and we shared clinical responsibilities.
JY: No, not really. There had been a medical oncologist there before, by the name of Jim Wallace, who actually came and had trained at Roswell, and then came back to Roswell. He was the one who said, when Jim was looking at a job, at Mount Sinai in New York City, you should look at Vermont.
Jim Wallace said, “Well, why don’t you go to Vermont? You’re single and it would be a good opportunity. You’d have a lot of fun.”
Well, I did go there and I was really lucky because I got a six or $700,000 grant from the NCI to look at cancer rehabilitation in patients with advanced cancer.
Because I was interested in, and again, this comes back to my interest in the kid with the testicular cancer and the other people with metastatic disease—I was able to start a nidus of people who we were looking at whether or not—and I thought what we could do is prolong life with a large group of cancer patients with advanced cancer, if we took care of them better. It turned out that wasn’t the case, but we could improve their quality of life.
We certainly improved pain management and we made some contributions, and that subsequently led to a grant from the Robert Wood Johnson Foundation, and to my participation with the then HCFA [Health Care Finance Administration; now Centers for Medicare & Medicaid Services], in developing the hospice guidelines and the RFP for the evaluation at 23 demonstration sites.
I was a hospice physician. The last couple years of my time in Vermont, I was a hospice physician. So, there were a few common threads in terms of why I went to Vermont, and it was fun. I never realized how small Vermont was. I was a pilot, and I used to fly a lot and-
JY: No, when I went up to Vermont the first time—and I’d never been to Burlington before, I was flying myself and I was flying on instruments, and I broke out of the clouds and I looked down I thought that must be a suburb of Burlington that I’m looking at. I found out I was looking at all of Chittenden County and all of Burlington. At that time, there were only 25,000 people in Burlington and there were about 50 to 75,000 in the county itself, and it was relatively small.
It was funny. I learned a lot of things. When I did go there permanently, I went to a place called Shakey’s Pizza Parlor, and the Vermont Governor came in with a state trooper and sat at the table next to me. It was interesting.
After I started seeing patients, I parked my car downtown. I was going to a restaurant downtown, and one of the patients left a note on my windshield, because this particular patient knew my car. You get a little different feeling in Burlington ccompared with Buffalo.
JY: Well, let me give you a personal example. I had friends who, at the time, and I’m talking about the late ‘60s, early ‘70s, who called me a poison pusher, because that’s what we were doing. We were using chemotherapy at that point in time, selectively poison the cancer cells.
I mentioned to you that I did medicine at Marquette, at Milwaukee County Hospital, and Tony Pisciotta there, who was the head of hematology, would send the leukemia’s home with a little bit of steroids and didn’t bother to ever treat them aggressively.
The attitude among physician colleagues was, why are you wasting your time doing this? Not only are you wasting your time, but you’re making the patients sicker. Some of them get very sick from the chemotherapy, because there are a lot of side effects with the normal tissues.
There was a general attitude that we not only didn’t know what we were doing, but what we were doing was potentially harmful to many patients. Nobody tried to recruit cancer patients with diffuse disease. If the patient had advanced cancer, they would try to transfer them to Roswell, and they were happy to get rid of those patients.
One of the negative influential prominent hematologists, who also trained a lot of hematologists, who subsequently relocated around the country questioned the benefits of chemotherapy for advanced cancer and leukemia. I was trained as a medical oncologist, but also did a lot of hematology. There were not medical oncology boards until 1974. For the first six years of my career, we were viewed with some level of suspicion from our medical colleagues..
When you looked in departments of medicine, and medical schools at the top of the list were the cardiologists. Then you had the pulmonologist, and then the gastroenterologist, and there was sort of, a pecking order for respect as you went down the list of specialties in the departments of medicine.
I can tell you that medical oncologists were treated like we were the “garbage collectors” of medicine. There was Dameshek at the Peter Bent Brigham in Boston, and a guy by the name of Crosby, who I think was at Tufts at the time. I always thought that part of this was because of jealousy toward Sidney Farber, who could be a little pompous. He was a pathologist at the Peter Bent Brigham, who first treated the kids with methotrexate and saw some responses.
Dameshek, as I said, trained many hematologists, and his attitude was that we were “poison pushers” or “cowboys”, and that we were doing things that weren’t in the best interest of the patient. Because he was extremely influential, we were viewed as outliers.
In departments of medicine, when I went to Vermont in the department of medicine, as I think I told you, the head of hematology there didn’t treat lymphomas aggressively. I got some patients that had lymphomas and I treated them the way I would treat them at Roswell Park, and I got some good long term control of disease for these people. The attitude started to change, but it took time for them to change.
At the time, the cooperative groups were evolving, and you have Bernie Fisher and the NSABP, who organized the surgeons to do clinical trials on breast cancer.
One of the surgeons was a guy by the name of Roger Foster, who was in Vermont, who was doing lumpectomies for breast cancer while also participating in the NSABP trials. He legitimized the importance of adjuvant chemotherapy, because he was a surgeon and he was respected.
It was really in the early ‘70s that we started emerging as not being the witch doctors, or the cowboys, or the poison pushers of medicine. Because of the number of successes, and the data by the late ‘70s and early ‘80s, it was clear that the protocols, the studies that the cooperative groups were doing, provided new information and better ways of managing patients. We started actually getting a little respect. I mean, we were like the Rodney Dangerfields of medicine in the late ‘60s and early ‘70s. We didn’t get any respect. That was real.
JY: Because, as a physician, taking care of these patients—it made you feel good. I mean, these people were looking death in the eyes, they were looking having all kinds of problems.
It is wonderful to be a physician. It is wonderful to be able to try to help people, even if you can’t help them. They were so desperate that they were looking for answers that might hold some hope. The biggest group of people that deserve credit were the patient participants in these trials in those years, because they really laid it on the line, personally. We could see progress. One of the things that happened, the CALGB had, at that time, three or four meetings a year. I think it was three meetings a year.
One of the things that we did was pump each other up by talking about the successes, and about where we thought things were going, and in fact, there was progress. There was progress being made, and there was scientific progress that people were understanding better about what needed to be done.
There were two guys at the Southern Institute, Skipper and Schabel, who were studying mice, who really did some of the groundwork in understanding the cell kinetics in acute leukemia. You see a fusion of basic science information at the cooperative group meetings with the clinical research information, and you see that there is some light at the end of the tunnel for a few of the diseases.
Choriocarcinoma was one of them, where, relatively early on, they saw that some responded to chemotherapy. Hodgkin’s disease, combination approaches. At the same time, the cooperative groups also fostered better training for pathologists, for the doctors who look at the cancer under the microscope.
It was a major educational activity that crossed the lines between science and clinical research and laboratory pathology on one side, and radiology as CT scanning emerged. When I went to Vermont, there was one CT scan in the whole state of Vermont. It was in St. Johnsbury, so we sent the patients from Burlington to St. Johnsbury when we thought it was necessary.
Well, it was only about a year, and then they got a CT scan at the University of Vermont, and they got a CT scan at Dartmouth. These were on the job training years, in lots of ways. We learned from each other and the meetings of the CALGB, because they were relatively small, a few hundred people, at that point in time. They were honest to God discussions in the committees and in the hallways.
We shared information and we shared it, obviously, with subsequent publications. Now, the progress was uneven. MD Anderson emerged as a cancer center with a lot of support in Texas, but one of the things they got into was looking at new treatment approaches and then using historical controls.
That set things back a little bit, because whenever you look at medicine outcomes, you have to be careful using historical controls. The outcomes of patients that were treated a decade before will not do as well because there’s enough improvements in antibiotics and other types of supportive care and other medications to blur the results. In fact, when you use historical controls, it almost always looks as if you’re making progress, even if you’re not making progress.
The cooperative groups were doing randomized studies. We did a randomized trial of the isolator studies so that the patients could randomly end up in one of the four groups. That was critically important in terms of showing that we really weren’t doing any better with the treatment of leukemia, but we were doing better in terms of controlling infection.
JY: We did. I can tell you, Jim Holland, because of what we were doing, attracted a lot of physicians who got acute myelocytic leukemia, or some other cancer. They would come. I ended up relatively early in my career, taking care of physicians or other medical scientists who had some of these bad diseases.
They were a funny group, the physicians in particular, because they would either say, “I want to know everything about what you’re doing, everything that’s going on, and I want to understand why and what you’re doing.” Or they would say to me, “You’re the physician, and I’m going to trust you to make decisions that you think are in my best interest.”
And you would talk to them, obviously differently, than you talk to a patient who wasn’t as knowledgeable about medicine. But it was funny how the physicians that I took care of in that era bifurcated. But they still came to Roswell, because they knew that there was some hope there. A lot of what we did in those days, and a lot of what’s done today is, you provide hope to the patients that maybe you can make a difference.
JY: Again, when I was at Roswell, I had a 42 year old lady who had a lymphoma and it had recurred. She had multiple courses of chemotherapy, and she decided she had enough because of the side effects, and it was problematic. She had two teenage kids and a husband, and she said she didn’t want anymore. She didn’t want anymore chemotherapy. She didn’t want to do anything. And she knew she was going to die. Those were the days when we kept people in the hospital, much more than is done now.
I’ll tell you everybody…the nurses, her husband, her two kids, her other relatives, and me, we were all uncomfortable, because she elected this and she had a strong personality and that’s what she wanted to do. One of the hardest things to do as a physician is to sit on your hands sometimes, and not do anything. And certainly it was in that case, but she was an outlier. I’ve only had a few patients like that. Most of the people would like to feel that you’re doing something that may make them more comfortable, or may prolong their life, or both.
JY: We did five and two, but didn’t achieve the result we wanted. Then we went to 7 + 3. The sad thing is that, up until probably the last few years, 7 + 3 is still the standard remission induction. I published a paper in 72. It’s still the standard remission induction in most places around the world.
We haven’t made a lot of progress in terms of long term survival. If you look at the five year survival of adults with AML now, and we arbitrarily use five years—you could use whatever you want, but that’s one of the standards of sorts, it’s 20%. We’re still not doing so well in terms of long term control of the disease. We talk about cures, but we never talked about cures in those days, except for Hodgkin’s disease and some of the lymphomas, and there are cures in childhood leukemia because it is so much more responsive.
When we started out, and I’m sure you came across this statistic, we saw that 80% of the kids would die from induction remission for ALL, and 20% you’d get a remission, but there weren’t cures. Now, the cure rate is probably in the range of 90, 95% of the kids with acute lymphocytic leukemia.
That hasn’t happened with AML, with adults, but we’ve been able to control the disease. If you can buy a year or two, one of the things about if the patients go into remission with AML, they can live a reasonably normal life. They can, in terms of activities and what they can do, but we’re still not curing a large number of people, even with bone marrow transplants and with intensive maintenance therapy. We’ve made some progress. We’re not there yet.
I’d like to be alive one day, a hundred years from now, to see what they’re doing. I’m sure the docs would look and say, “Those stupid jerks, what they were doing was so primitive and inappropriate. Our understanding of the etiology of cancers and how they progress will be much different a hundred years from now than it is now.
