In 1958, Bernie Fisher participated in the first randomized clinical trial in patients with breast cancer. The trial was a disaster, leading most surgeons to abandon chemotherapy. Bernie, however, noticed something different in the data, which leads him on a path that will change the course of cancer treatment forever.

Less Radical is the story of Dr. Bernie Fisher, the surgeon-scientist who not only revolutionized breast cancer treatment, but also fundamentally changed the way we understand all cancers. He was an unlikely hero—a Jewish kid from Pittsburgh who had to make it past antisemitic quotas to get into med school. And the thanks he received for his discoveries? A performative, misguided Congressional hearing that destroyed his reputation and haunted him until his death.

Over six episodes, radiation oncologist Dr. Stacy Wentworth will take you into operating rooms, through the halls of Congress, and into the labs where breakthrough cancer treatments were not only developed, but discovered.

If you or someone you know has had breast cancer, Bernie is a part of your story—and you’re a part of his.

For photos, recommended readings, and show notes, visit Dr. Wentworth’s Substack, Cancer Culture.

Transcript

STACY WENTWORTH: When he was a sickly kid in Pittsburgh, Bernie Fisher read to pass the time. One of his favorite books was Paul de Kruif’s Microbe Hunters.

Like the name suggests, it was about the first doctors to peer into microscopes and discover the origins of disease. It was history that read like science fiction—brave heroes fighting strange, newly discovered beasts in the microscopic realm.

One of the scientists featured in the book is Paul Ehrlich, a Prussian doctor who developed an interest in immunology—digging down into what caused people to be sick and then how to help the body fight illness.

Ehrlich spent his career looking for a treatment that would kill the microbes while sparing healthy cells. The scientific term he coined was chemotherapy. But he used a catchier name in conversation. Ehrlich was looking for a “magic bullet,” a reference to a piece of German folklore, and an opera in Ehrlich’s day, about an enchanted bullet that can’t miss its target.

Ehrlich won the Nobel Prize for his immunology work in 1908. But his biggest breakthrough came the year after. He and his colleague Sahachiro Hata developed what they called Compound 606, later renamed Salvarsan. This was a magic bullet for syphilis. The disease was a scourge in Europe. By some estimates, fifteen percent of the male population was infected with syphilis in the nineteenth century. And this was the cure. 

Ehrlich is an inspiring figure. There was even a movie about him made in the ‘40s starring Edward G. Robinson.

EDWARD G. ROBINSON: Now what we have to do is to keep our operation 100% successful against the microbe, while reducing its poisonous effects on the body to zero. When we have done that, then we shall have been successful in our search for a magic bullet.

STACY WENTWORTH: That movie came out when Bernie Fisher was 23. Maybe he saw it when he was in medical school—one of the characters in his childhood book, now a hero on the big screen.

[MUSIC]

EDWARD G. ROBINSON: I feel it is my duty as a doctor to save the lives of these children. Nothing on earth can prevent me from carrying out my duty.

STACY WENTWORTH: And both men faced similar struggles. Like Bernie, Ehrlich was Jewish, and fought against antisemitism. The Nazi government even took Ehrlich’s name off a street in Frankfurt.

[THEME MUSIC IN] 

STACY WENTWORTH: It’s since been restored, and in addition, Ehrlich’s name appears on a hospital building, a crater on the moon, and a human rights prize given by the Anti-Defamation League.

And Ehrlich, like Bernie, also faced harsh scrutiny from posturing politicians and busybody bureaucrats which would nearly end his career. It’s a storyline we’ve seen play out again and again—I mean, it’s going on now. But we’ll get to that part of the story later. For now, we’re going to focus on the search for a magic bullet for cancer. 

I’m Dr. Stacy Wentworth, and this is Less Radical. 

[SHOW OPEN MONTAGE]

NANCY DAVIDSON: Bernie was changing everything…

BERNIE FISHER: Well, at that time, the treatment was draconian to say the least.

VINCENT DEVITA: The idea that you could cure cancer with drugs was considered insanity.

BERNIE FISHER: A couple of rather liberal thinking surgeons at the time thought that perhaps the reason so many people died following this kind of surgery was because of the surgeons being a klutz. 

BERYL MCCORMICK: I think they really couldn’t change the way they thought. They just…couldn’t do it. (laughs)

EDWARD G. ROBINSON: It’ll take, oh, heaven knows how many….a hundred preparations before we find it, but we shant stop until we do.

VINCENT DEVITA: You could see where they hated him because he wouldn’t give in. 

 

[END SHOW MONTAGE]

[THEME MUSIC OUT]

[MUSIC]

REPORTER: A field of his greatest conquests draws mourning tens of thousands for a final glimpse of America’s best known, best loved sports figure, George Herman “Babe” Ruth, as he lies in state at Yankee Stadium, New York.

STACY WENTWORTH: August 1948. Babe Ruth died of throat cancer, a diagnosis that had been kept secret for two years. Doctors didn’t even tell Ruth himself that he had it. 

When the public read about the diagnosis in press coverage surrounding his death, they also learned about the two-year scramble to save the life of one of the greatest heroes in sports. 

[MUSIC]

STACY WENTWORTH: Doctors threw everything they could at the disease. Radiation kept the cancer at bay for a few months, but when the cancer returned, the head of Mount Sinai’s cancer research department gave Ruth a drug that had only been tested on rats kept in the hospital basement. It was called Teropterin, a derivative of folic acid that seemed to shrink tumors by denying the cancerous cells nutrients. After a series of injections of this experimental treatment, Ruth’s tumor shrank. And scientists even gave a report on the treatment’s success at a conference, with the famous patient’s name omitted.

The success of Teropterin, as well as the discovery of penicillin and the development of the polio vaccine, gave doctors hope that a magic bullet for cancer was just around the corner. In the years after the World Wars, doctors were also interested in how chemical agents could be used to heal instead of to harm. They used the same name for these medicines that Ehrlich coined for his syphilis cure—chemotherapy.

Another new tool in the fight against cancer also made news in 1948. The headlines were smaller than the ones about the Bambino, but it was a huge development. A paper on tuberculosis published in the British Medical Journal detailed a novel technique in medical research—randomized clinical trials.

You’ve probably heard this term used before. It’s something that a lot of news stories gloss over when they describe the exciting results of new research. In a randomized trial, some patients are given a new—usually experimental—treatment, while another group is given the standard treatment. Who gets which is, well, random. The randomized clinical trial is the best tool we have for eliminating all kinds of biases and mistakes that could come up in studies. It gives us the most reliable and objective data possible. Trials had been used before 1948, but not randomized trials.

The paper, which described the trial’s results, put this process on the path to becoming what it is today—the gold standard for medical research.

BERNIE FISHER: And one of the most important accomplishments of the 20th century in my view, has been, relates to the process of therapeutic decision making by use of a scientific process to test scientifically based hypotheses in well designed trials.

STACY WENTWORTH: This is Bernie from 2004, after he had spent nearly half a century working on randomized clinical trials. His introduction to the process came a few years after the study was published, when he went to that meeting with his mentor I.S. Ravdin in 1957. I mentioned in episode two that Ravdin was leading the National Cancer Institute’s search for a magic bullet to cure cancer. Ravdin wanted to use both chemotherapy and clinical trials to develop new treatments for breast cancer. Neither of these ideas was that popular, and both of them together, well…

VINCENT DEVITA: The idea that you could cure cancer with drugs was considered insanity.

STACY WENTWORTH: Dr. Vincent DeVita is the former director of the National Cancer Institute.

VINCENT DEVITA: Everybody knew, I mean, everybody knew, that you couldn’t cure cancer with drugs.

STACY WENTWORTH: In the 1960s and 70s, doctors who advocated for a drug treatment or a randomized trial to test those drugs were considered quacks—at best. In most surgeons’ eyes, the treatment for breast cancer was very well-established and didn’t need any improvements. Women who felt a lump went to the doctor. The doctor did the one-step procedure of a biopsy and then, if needed, an immediate Halsted radical mastectomy. After surgery, the women were sent home and told to come back if they had any further problems. Sometimes the women received radiation after surgery, but not often.

VINCENT DEVITA: The dogma was created by these, these grand surgeons, who were the real gods in the field, the Geheimrat professors. And they show that, you know, that it was a matter of who had the best surgical technique and who got the best results with surgery.

STACY WENTWORTH: Doctors at the time believed cancer spread out from a central tumor, like paint spilling from a bucket. So the important idea was to remove the tumor and as much surrounding tissue as possible while also avoiding touching any of the cancer. At first, the reason for using drugs to treat breast cancer was that the drugs might kill any loose cancer cells that a clumsy surgeon might leave behind. Here’s Bernie again.

BERNIE FISHER: The couple of rather liberal thinking surgeons of the time thought that perhaps the reason so many people died because of, following this kind of surgery was because of the surgeon’s being a klutz. And when he was operating, he was causing tumor cells to be shed, and it was this reason that these people died.

STACY WENTWORTH: And even though the idea that drugs could “clean up” after a doctor was unorthodox, it still adhered to the old belief about how cancer spread. 

And that’s what Ravdin was thinking about. Could they use drugs to basically “clean up” after a surgeon, and could they test this with randomized trials? Bernie, though, still wasn’t convinced this work was right for him. He was in Pittsburgh at the time, studying liver regeneration and organ transplants.

BERNIE FISHER: As I said, I wasn’t really terribly interested in this study until I went home and thought about it. And there were two things that struck me—first, this was about metastases, and there was relatively little work being done on that subject, there was need for more. And the second had to do with clinical trial- conduct of clinical trials. Clinical trials were not very popular in this country. And I really knew little about them, but they in fact, I became fascinated with the idea. So I went home, and I decided, okay, I’ll participate in this trial, but, and at the same time I began to study metastases.

STACY WENTWORTH: So Bernie told Ravdin he was in. They were charter members of what would become the National Surgical Adjuvant Breast and Bowel Project, the NSABP for short.

[MUSIC]

STACY WENTWORTH: In April 1958, these surgeons, including Bernie, began signing up the first cancer patients ever to enter a randomized clinical trial. The women who signed up were placed into two groups. Both groups got radical mastectomies. Then one group got a local injection of chemotherapy around their breast and arm, and the other got a placebo. Doctors gathered the data, and analyzed the results.

Everyone was hoping for amazing results that showed chemotherapy could be a magic bullet, but that wasn’t the case this time. Over half the patients who received chemotherapy required lengthy hospitalizations for weeks with depressed immune systems and horrific wound complications. Eight patients who received one of the drugs died. Surgeons were comfortable with the brutality of the radical mastectomy, but these additional complications were a non-starter. The NSABP had asked them to hand over control of their patients to a randomization process, for an experimental drug that didn’t seem to work and caused way too many headaches. So surgeons weren’t interested. They walked away from clinical trials, and away from chemotherapy. The were confident in their ability to use the knife to get everything out at once, to finish with a patient and move on. 

Without a magic bullet, the findings got little notice. But if you look closely, this first trial wasn’t a total failure.

VINCENT DEVITA: He had done this study in I think 1957 or ‘58 to prevent cells from escaping from the operative site and the study was reported negative. And they published the paper, and I read the paper, and I said, this is not a negative study.

STACY WENTWORTH: Dr. DeVita remembers looking back at that early paper, and being surprised at what he found.

Some younger patients who had cancer in multiple lymph nodes lived longer. Some women saw a delay in their cancer coming back. Despite the complications, Bernie’s study showed for the first time that chemotherapy could work against breast cancer, no matter how much the surgical mainstream wanted to believe otherwise.

VINCENT DEVITA: This is not a negative paper, it’s very important. It was a positive study. And all subsequent studies were positive. You tended to overlook the positive study because your beliefs told you couldn’t do it.

STACY WENTWORTH: This was good news. At the time when these trials began, six out of every one-hundred American women were expected to get breast cancer, and half of them would die of the disease. The knife was not an effective cure, and now this study showed that chemotherapy might be the right path to go down.

This study set in motion a few benefits that would pay off later. By getting surgeons to participate in studies controlled by outside researchers, it helped break down the paternalistic “doctor knows best” mentality and opened the door to more experimental treatments—cures that weren’t the knife. Second, it introduced Bernie Fisher to the clinical trial as a new method of research.

BERNIE FISHER: Well, at this point and forever after I looked upon the conduct of clinical trials as an extension of my laboratory, a mechanism for conducting research, and clinical trials are a mechanism, I can’t emphasize that too thoroughly. Well, they’re like a flow cytometer or like an electron microscope, or like a spaceship to explore outer space. That’s what a clinical trial is.

STACY WENTWORTH: And this embrace of clinical trials would be the way Bernie would eventually undo the old ways of brutal surgery. But it would take time.

[MUSIC]

STACY WENTWORTH: One thing I want to say here about medicine and scientific research, is that it doesn’t all happen in a straight line. Timelines can get confusing. Studies take years to conduct, and can take years to publish, too. A paper in a medical journal might report results that the researchers concluded a year before the paper was published. And while other doctors are reading about it, those original researchers have moved on to their next project.

Bernie was very busy from the mid-1950s until the mid-1990s. He was pretty much always doing several things at once—running studies, researching treatments and drugs, giving lectures, and acting as an administrator for his lab. And while he’s working on different projects, the ideas are cross-pollinating. 

I say all this here because Bernie’s work on the task force was influencing his research back in Pittsburgh. That first NSABP study wasn’t really based on any scientific method.  It was like the old ways—“Hey, here’s something that might work, let’s try it on these patients and see what happens.”  

Working for the task force, Bernie noticed that cancer didn’t seem to behave the way he was taught it should. Doctors thought cancer spiraled out from a tumor and got caught in lymph nodes. But if that was the case, why did cancer come back after doctors removed the tumor and the lymph nodes? And why did it sometimes bypass the hollowed-out chest wall where it began and pop up in other parts of the body? Could this really just be attributed to hamfisted doctors unleashing cancer cells during surgery? Or did cancer spread some other way?

If he could figure out how cancer moved through the body, Bernie thought he might be able to stop it from spreading. Until now, everything was a guess, and only with luck would you ever find the answer. So Bernie wound down his liver research at Pitt and focused for the rest of his life on cancer. He was going to be a microbe hunter, just like the heroes in his favorite childhood book. With the task force, he was working on finding a magic bullet. Now, in his lab, he was figuring out where to aim it.

EDWARD G. ROBINSON: Now what we have to do is to keep our operation 100% successful against the microbe…[FADES UNDER]

STACY WENTWORTH: I want to go back to this movie about Paul Ehrlich from 1940. This is a scene where Ehrlich and his team are testing different treatments on rats, and none seem to be working. He tells them they have to stick with it.

EDWARD G. ROBINSON: It’ll take, oh, heaven knows how many…a hundred preparations before we find it, but we shant stop until we do.

STACY WENTWORTH: Bernie was about to embark on his own research with the same mindset and nothing could stop him. One former colleague of Bernie’s told me he had been a missile without a target before his cancer research—a man who was destined to make a mark but not sure where to focus his efforts. 

[MUSIC]

STACY WENTWORTH: He’d started his career studying the liver, but now he had a different target. And he wouldn’t stop until he hit it. 

To study how cancer cells moved, Bernie set up a test using rats. He put the rats in a small, tube-shaped metal cage. Using extreme precision, he then ran a line into the thoracic duct in their lower bodies to collect the lymphatic fluid that drained out. Then, he injected cancer cells into the rat’s neck veins. With x-rays, Bernie could watch the cells move through the rat’s body. He wanted to see how long it took them to drain out—how long the lymph nodes would act as a filter, as Halsted said they would. Bernie performed this experiment dozens of times. Operate, inject, collect, image. Over and over and over. And what he saw completely upended the long-held beliefs about how cancer spread. 

In 1965, almost ten years after that first meeting on breast cancer, Bernie made his first breakthrough. Unlike what Halsted claimed, the lymph nodes were not trapping cancer cells and holding them for a long time. Most sailed right on through. And when he looked elsewhere in the rats, he saw something even more important. Cancer cells moved through the bloodstream. Halsted hadn’t thought that was possible. For almost one-hundred years, doctors had assumed cancer cells could only travel out from a tumor to adjacent parts of the body, or use the lymphatic system. With these experiments, Bernie proved that wasn’t the case. This was a major discovery. Here he is talking about it, years later, in 1985. 

BERNIE FISHER: Well as a result of about a decade of investigation from clinical and laboratory animal work, we devised an alternative concept of tumor dissemination, which said that tumor cells not only spread by the lymphatics, but they spread by means of the bloodstream.

STACY WENTWORTH: He seems calm in retrospect, but I can’t overstate what a milestone this was. Really, words like “milestone” or “discovery” don’t even do it justice. This is a shout-from-the-rooftops, run down the street yelling “eureka” moment. Not only had Bernie discovered something that overturned years upon years of medical understanding, he had all the data to back it up. And it didn’t just apply to breast cancer. These findings remade our understanding of all cancers. For centuries, women had been shy about discussing breast cancer. Now the study of this little-discussed disease would remake medical science. 

Bernie published these findings in 1967. It was one of dozens of papers he and his younger brother Edwin, a pathologist who worked alongside him, put out in these years. 

[MUSIC]

STACY WENTWORTH: And this model of cancer is sometimes called the Fisher Model, in honor of his discovery. Bernie overturned over a century of surgical dogma. The Halsted model was wrong. Tumors did not spread in an orderly manner. “You may be logical,” Bernie would say, “but cancer is not.”

And if Halsted’s theory was out of date, maybe the surgery that bore his name was, too. This is what Bernie set out to challenge next. 

BERNIE FISHER: Now this hypothesis, of course, needed testing. No hypothesis is any good unless one can test it, and we were very fortunate to be, participate or have available to us the ability to set up large scale clinical trials to test the idea in patients and patients with breast cancer were employed, and we first did a study which showed that the same results existed in terms of survival and distant disease if one just took the breast off, didn’t take out the muscles, didn’t take out the lymph nodes, and so on. 

STACY WENTWORTH: Bernie became chairman of the NSABP in 1967. He moved their operations to Pittsburgh, where he rallied surgeons to begin another major study. He hadn’t yet found a magic bullet, but he knew the old Halsted method for treating breast cancer wasn’t as effective as he and all of his surgical colleagues had been trained to believe. Surgeons were still afraid that they would dislodge cancer cells when removing a tumor, but Bernie knew the cells were already circulating around the body in the bloodstream. 

That meant that removing all of the surrounding tissue wouldn’t make a difference. Bernie’s next study would put the radical mastectomy to the test.

First, he had upended the understanding of cancer. Now, Bernie was about to upend the treatment of breast cancer. But it was more than that. Bernie was a surgeon saying that surgeons didn’t have all the answers. He hadn’t found a magic bullet, but he was certain the knife was no longer the cure.

In the whole country, just a few other surgeons were thinking the same thing, including a doctor named George Crile, Jr. Crile’s father had been a contemporary of Halsted. The younger Crile, who went by Barney, followed in his father’s footsteps, became a surgeon, and led the Cleveland Clinic’s department of general surgery until 1968. And for all his surgical pedigree, Crile did not advocate the knife as a cure. His obituary in The New York Times from 1992, called him “a foe of unneeded surgery.” Here he is in a 1988 NOVA documentary.

BARNEY CRILE: Going to a Catholic Church and standing up next to the bishop and denying that God exists, is very similar to going to a medical meeting at that time and saying that there is no indication for a radical mastectomy.

STACY WENTWORTH: Barney Crile was eleven years older than Bernie. As a Navy SEAL doctor in the Second World War, he argued against the then-standard procedure of doing appendectomies in submarines if a crewman’s appendix burst. Crile argued that trying to operate while in a vessel that was underwater was riskier than treating the patient in other ways and getting them to an operating room on the surface. He questioned the standard surgical remedy for thyroid cancer. 

While Bernie was doing his studies, Crile was learning more about the radical mastectomy. It was a procedure that he, like Bernie, performed in the operating room himself. Crile heard talks given by European surgeons that they were reconsidering the necessity of a radical mastectomy. He looked back over data at the Cleveland Clinic and found that the few women who underwent less-radical surgery saw outcomes similar to those who received radical surgery. When his wife developed breast cancer, Crile recommended she have a smaller procedure. She did. She died of breast cancer, but not because the surgery wasn’t effective. She had metastatic disease, and a Halsted wouldn’t have stopped it. Of course, Crile couldn’t have known that the cancer had metastasized, but that didn’t keep his peers from whispering to each other that his bad advice had killed her. Crile inspired Bernie, who commented on Crile in Congressional testimony in 1992, just after Crile died.

BERNIE FISHER: George Crile was a friend of mine and an inspiration to me as a young man.

STACY WENTWORTH: Crile’s biggest piece of public advocacy was a book he published in 1973. It opened with the line, “You need not have a radical mastectomy. Lesser procedures may be just as effective.”

Here’s Crile in the same NOVA documentary about the history of surgery, describing what happened when his local ethics board took him to task.

BARNEY CRILE: The Cleveland Academy of Medicine didn’t like that, so the academy did what I thought was the most immoral thing that an organized group of medicine had ever done. They criticized me for telling people that they could avoid an operation, and what the academy was trying to do is to suppress the information so more women would have radical mastectomies. And I couldn’t stand it.

 

STACY WENTWORTH: If you listened to the bonus episode on the women fighting for better treatment, you’ll recognize this quote. Crile’s book was called What Women Should Know About the Breast Cancer Controversy.

A year after it was published, journalist Rose Kushner found it in her public library while researching her recent breast cancer diagnosis. It was the only book in the library about breast cancer. Crile’s book, combined with her own experience, inspired Kushner to push to end the one-step procedure and to advocate for all women to have the option of a radical mastectomy or something more conservative. Kushner even called the White House to encourage Betty Ford not to get a radical mastectomy. 

[MUSIC]

STACY WENTWORTH: Now, Barney Crile, Rose Kushner, and Bernie Fisher were all coming to the same conclusion. Kushner as a survivor, Crile as a surgeon, and Bernie as a scientist. Their paths would converge in the early 1970s. As Betty Ford is recovering from surgery, Kushner is pushing for women’s choice, and Bernie and Crile are trying to change medical procedures. They would have to win over women, the public at large, and surgeons. It wasn’t going to be easy. 

That’s where we’ll pick up next time.

VINCENT DEVITA: There was something offensive about the idea you can cure cancer.

NANCY REAGAN: And I had evidently said in the operating room, did you take my breast? And before they could answer me, I’d fall back to sleep again. And finally, after about the fourth time, I stayed awake long enough for them to say yes. And then I didn’t, I didn’t ask anything more.

VINCENT DEVITA: That’s when he said to me, “Vince, I don’t think I can come because I might get some physical harm done to me if I come.” 

Less Radical is produced by me, Stacy Wentworth, and the team at Yellow Armadillo Studios: Melody Rowell, Gabe Bullard, and Sam Gebauer.

Fact checking is by Ryan Alderman. Our artwork is by Arianna Egleston. And we get marketing support from Tink Media. Music is from Epidemic Sound.

Special thanks to Dr. Vincent DeVita, Julie Landford and Cancer Services Incorporated, Wildfire Magazine and Writing Community, Lisa Rainwater Counseling, and Wonder Women Professional Community.

October is Breast Cancer Action Month, which means you’re probably seeing pink everywhere. And that, combined with the stories told in this podcast, it’s a lot. If you want to share your reactions and continue the conversation, join me in the discussion thread for this episode at cancerculture.substack.com. There, you can also see extensive show notes for Less Radical, including photos and links to read more about Bernie Fisher and the history of breast cancer. That’s cancerculture.substack.com. You can follow me on Instagram at drstacywentworth.

And be sure to follow or subscribe to Less Radical in your favorite podcast app so you don’t miss a single chapter of Bernie’s story. While you’re there, please leave us a five star review. 

Thanks for listening.