How ‘Patron Saint of Renegades' Transformed Cancer Care

Medscape

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Chinese American physician researcher Min Chiu Li, MD, liked breaking barriers and busting chops.
Min Chiu Li, MD
At a time when virtually every cancer researcher in the US was White, he landed a job at the National Cancer Institute (NCI) in the 1950s. As colleagues got along to get along, he made enemies galore. Then he went rogue, insisting on treating patients with chemotherapy beyond the point when their tumors had disappeared.
The strategy turned out to be the right approach, even though Li lost his job over his failure to follow the rules. His work helped transform cancer therapy by showing how biomarkers tell the real story of how treatment is working.
Li and his colleague Roy Hertz, MD, 'set the stage for a modern approach to chemotherapy, set the stage for hope,' Alan J. Hunter, MD, an internist at Oregon Health & Science University, Portland, Oregon, who studied Li's life for a 2003 report, told Medscape Medical News .
Pushing Forward and Paying the Price
In the mid-1950s, Li and Hertz were thrilled when antifolate treatment eliminated a young woman's metastatic tumors from choriocarcinoma, a rare type of cancer that develops from placenta cells after pregnancy.
But Li was concerned because levels of a hormone linked to the cancerous cells didn't dwindle back to normal. 'Li became progressively obsessed with the number,' author and cancer physician Siddhartha Mukherjee, MD, DPhil, Columbia University, New York City, wrote in his landmark 2010 book The Emperor of All Maladies: A Biography of Cancer .
Li refused to stop treating the patient despite fears that toxicity would hurt her. 'He kept on doing it' because the therapy worked, recalled Vincent DeVita, Jr, MD, a former director of the NCI and cancer therapy pioneer in his own right, in an interview. 'And he was told to leave at that point.'
The stubborn researcher had been sacked. 'Li was already known to be a renegade, an iconoclast. This time, the NCI felt, he had gone too far,' Mukherjee wrote.
But it turned out that treating cancer beyond the point when tumors are eliminated can be a wise approach. That's because it can kill off a hidden reservoir of tumor cells that are only revealed through biomarkers. The strategy worked in Li's patients. The ultimate result: The obstinance that cost him his job led to the first chemotherapeutic cure of cancer in adults.
From China to Los Angeles, Chicago, and Beyond
As colleague and childhood leukemia treatment pioneer Emil J. Freireich, MD, DSc, wrote in a 2002 remembrance, Li came to the US from China in 1947 for postgraduate studies in bacteriology and immunology at the University of Southern California, Los Angeles.
However, Li couldn't return home due to the 1949 Communist revolution. He went on to jobs at Presbyterian Hospital in Chicago, the Sloan-Kettering Institute in New York City (now an arm of the Memorial Sloan Kettering Cancer Center), and then the NCI in Bethesda, Maryland.
As Hertz recalled in a 1998 NCI oral history interview, he hired Li as a clinical associate after a colleague recommended him. 'Li had become a naturalized American citizen, and as soon as he became American, he was an MD, and as soon as he got his citizenship papers, he got drafted [in the Korean War], and when he got drafted, he wanted to stay out of the draft,' said in a 1998 NCI oral history interview.
Mukherjee picks up the story: 'His current plan was to lie low in Bethesda until the war blew over.'
In the mid-1950s, Li decided to test the antifolate methotrexate — which had recently become a breakthrough new treatment for leukemia — in a 24-year-old woman who'd developed lung metastases from choriocarcinoma. 'There was nothing to lose,' Li wrote in a 1979 report.
'To everyone's surprise,' he wrote, the woman — who was near death — survived the next 20 hours. She ultimately recovered after Li continued to treat her even though her tumors had vanished.
'The response was real: A metastatic, solid cancer had vanished with chemotherapy,' Mukherjee wrote.
But the NCI wasn't impressed. 'They were calling this a spontaneous disappearance, probably an immunologic effect,' DeVita said. 'Everybody was pushing it off as something that was being done mostly by the body.'
As DeVita recalled, Li tried the approach again with a second patient, and it worked again. 'He was told not to do it anymore because it was too dangerous. And he kept on doing it.'
NCI Decides It's Seen Enough
In his 1979 report, Li says he then went to the State University of New York in 1957, but he doesn't explain why he left the NCI. In fact, he'd been fired for failing to follow protocol when he treated patients past the point when their tumors were gone.
But Li had discovered something vitally important about chemotherapy. According to Freireich, who died in 2021, Li realized that patients with metastatic choriocarcinoma 'required intensive systemic 'adjuvant' treatment despite the fact that they had no clinical evidence of disease. This has subsequently proven to be an extraordinarily important new principle in cancer treatment, ie, the treatment of patients who have no [physical] evidence of disease because of either tumor marker or other indirect evidence of a high probability of developing recurrent malignancies.'
But the cautious brass at the NCI concerned itself with rules. 'Li was accused of experimenting on people,' Freireich told Mukherjee in a 2009 interview. 'But of course, all of us were experimenting…To not experiment would mean to follow the old rules — to do absolutely nothing. Li wasn't prepared to sit back and watch and do nothing. So he was fired for acting on his convictions, for doing something.'
'Irascible, Irritable, Pugnacious'
Li, known as 'MC,' had tense relationships with some colleagues. 'He was very irascible, very irritable, pugnacious individual, got into fights with everybody…,' Hertz recalled in the oral history interview. 'He got into fights with a number of people, and I had to intervene a number of times.'
According to Hertz, 'we attributed [this] to his loneliness and his privations' — Li had left his family in China — and 'I was the only one knew how to get along with Li.'
But a lifelong rift apparently developed between the two colleagues. According to Hertz, Li believed he — Hertz — had taken the credit and won a major award for work that Li had done.
'I feel so bad about the whole thing,' Hertz said. 'I've had 40-odd clinical associates. He's the only one who does not honor me. The only one. And that hurts.'
Racism may have played a role in isolating Li from his colleagues. Or perhaps it caused him to be resentful and bitter. Maybe both. DeVita, the former director of the NCI, said casual racism was common in mid-century. 'People would do it and do it casually, not even think they were doing something. That could be part of it,' said DeVita, 90, who once went to Li's home to meet him.
Jonathan P. Yarris, MD, an emergency medicine physician in Oregon City, Oregon, who co-authored the 2003 report that examined the work of Hertz and Li, recalled that he interviewed Hertz and looked at old photos of his lab. 'There's usually one woman in the room, and sometimes, there's someone who's not White. I can only imagine what he heard in the hallways and how he was being slighted at every corner,' Yarris told Medscape Medical News .
As for Li's stubbornness, 'having been a person who didn't always follow the rules, I was sympathetic,' DeVita said. 'Sure, he didn't follow the rules. But what people should have done is look at what happened. Nobody was seriously harmed by what he did, and the patients were actually cured.'
More Medical Advances and a 'Renegade' Legacy
Li conducted more pioneering research after the NCI imbroglio. He pioneered combination drug treatment for testicular cancer, and DeVita considers him to be the first to cure the disease. Patients were cured 'maybe 10% or 20% [of the time] when he tried it, not the 80%, 90% we get now, but it was significant enough to be mentioned in publications, and he usually wasn't,' DeVita said. 'He was generally not given the credit he deserved.'
In 1972, Li won the Albert Lasker Medical Research Award, and colleague Freireich noted in his 2002 report that 'Dr Li remained active both in clinical research, laboratory research, patient care, and perhaps most important, teaching.'
Later, Freireich wrote, 'one of his most important publications appeared…in which he showed that 5-fluorouracil given after colon cancer surgery could result in substantial improvement in long-term survival rate.'
Li died in 1980, decades before several colleagues of his generation, from what Freireich calls 'a tragic illness.'
As for his legacy, Yarris said that Li was 'ultimately vindicated.' And while his name isn't remembered as well as some other cancer researchers, Li's reputation survives at the NCI. There, Mukherjee wrote, he's the 'patron saint of renegades.'