When John Laszlo joined the Acute Leukemia Service at NCI in 1956, the field of oncology was nascent—and the cure for childhood leukemia seemed beyond reach.
“It was a time that these children were just not going to do well. You knew that walking in,” Laszlo, 92, professor emeritus at Duke University Medical Center and a retired national vice president for research at the American Cancer Society, said to The Cancer Letter. “It was very challenging to deal with children who were bleeding from the nose, who were bleeding from the rectum, who were vomiting—and parents were hovering about, very concerned about their children.”
Laszlo worked directly with Emil “Tom” Frei, and Emil J Freireich—early researchers and doctors of childhood leukemia at NCI. Their team tried as best they could to help children as young as three. They stopped the bleeding, gave them antibiotics, and packed their noses.
“Most of them you couldn’t help at that stage of the game,” Laszlo said. “It’s very gratifying to think about all the progress that’s been made since those early days of taking care of these tiny children who didn’t know what was wrong, why they were there, why their parents were not with them.”
Laszlo’s book, “The Cure of Childhood Leukemia: Into the Age of Miracles,” is now available for free as a digital download on the Cancer History Project.
Based on taped interviews of doctors and scientists whose work led to the cure of childhood leukemia, Laszlo’s book is an essential primary source for anyone interested in oncology and its history.
Charles Gordon Zubrod, head of the NCI Division of Cancer Treatment (appointed in 1956), who became NCI’s scientific director (1961-1974), described the book as authoritative. “[Laszlo] decided to write up what happened in the cure of leukemia, and I’d suggest you obtain this book from the library,” Zubrod said in an oral history conducted by NCI and made available by the Cancer History Project.
In “Stairway of Surprise,” Zubrod’s previously unpublished memoir made available by the Cancer History Project, he writes:
We chose to try a modified IBM style task force and after obtaining the blessings of Drs. Farber and Ravdin, I began calling together the scientists and physicians whom I thought might give the most help, most were willing to give it a try.
We met every month or two at NCI and the results were spectacular. These are detailed in John Laszlo’s book “The Cure of Childhood Leukemia,” and I refer the reader to his fine history for the details and for the contribution and for the contributions of the individual members.
In brief, my role as chairman was to prepare meaningful agenda, keep the discussions on target, write the minutes, and then use the considerable budget of NCI to carry out the recommendations.
At that time, deaths (almost one hundred percent) of children with acute leukemia, came from hemorrhage and infection, because both the disease and intensive chemotherapy sharply reduced the protective platelets and white cells.
Dr. Freireich from NCI and George Judson of IBM, and later Dr. Seymour Perry, perfected a blood cell separator that harvested from a single donor, enough platelets to stop bleeding.
Meticulous care in stopping hospital bacteria and fungi from causing infections, and massive antibiotics to treat those that occurred, sharply reduced infectious deaths.
These combined improvements permitted the trial of intensive chemotherapy, not previously possible because of early deaths, due to the absence of these protections.
In a conversation with The Cancer Letter, Laszlo also focused on discoveries made by his father, Daniel Laszlo, an oncology pioneer who conducted basic research on folate antagonists.
In 1937, Laszlo’s family fled Vienna as Jewish refugees. His mother, a psychiatrist who trained with Anna Freud, discovered she had breast cancer on the SS Île de France while the family journeyed to America. She died two years later.
His father, Daniel Laszlo, a physician who specialized in cardiovascular physiology, found a job in cancer research at Mount Sinai Hospital.
Daniel Laszlo studied folate antagonists in mice—though folate antagonists hadn’t been characterized yet. One study showed regressions of spontaneous breast cancer in 38 of 89 mice (43%) when treated with folic acid.
“They were working on derivatives of that molecule and were finding some anti-cancer effects in mice,” Laszlo said. “I would go in on weekends and help to change the cages, put the mice in fresh cages, feed them, change the water bottles, and do that kind of thing as a child—in the laboratories at Mount Sinai Hospital.”
The researchers had discovered what seemed to be a vitamin derivative that would inhibit the growth of cancer, “something that they were surprised at,” Laszlo said.
Daniel Laszlo’s team took the information about folates to experts at Memorial Sloan Kettering Cancer Center.
“They were very interested in it, but didn’t quite believe it, so they asked Dr. Sidney Farber from Harvard to comment on it,” Laszlo said.
Farber’s response?
“He pooh-poohed the whole idea,” Laszlo said. “And then took it over himself.”
Daniel Laszlo’s boss, Richard Lewisohn, a surgeon and director of the laboratory, approached Laszlo one day with a proposal.
Babe Ruth had been admitted to Mount Sinai Hospital with symptoms of throat cancer (later determined to be naso-pharyngeal cancer), and Lewisohn was planning to treat Ruth with drugs that had been shown to reduce cancer in mice. Daniel Laszlo worried about the ethical implications of treating someone with drugs that had not been tested in humans.
“My father said he couldn’t do that because it had never been given to patients,” Laszlo said. “They didn’t know what the dose was, how much to give, how long to give it, and so on. However, the hospital director wouldn’t take no for an answer, even though my father thought it was unethical to do that.”
And so, Babe Ruth received the drug teropterin, according to The New York Times—resulting in a brief remission. The drug was closely related to methotrexate, which became standard of care for certain cancers.
“The tumor disappeared, and Ruth had come in miserable shape, when he went home feeling just fine, and he stayed in remission for a time,” Laszlo said.
“My father was very unhappy about being ordered to do something that he felt was unethical, and so he chose to leave Mount Sinai Hospital and was offered an opportunity…to start a new program at Montefiore Hospital in New York, where they had a lot of patients sitting around, taking up hospital beds, and they weren’t doing much for these people,” he said.
In a 1998 news story, a reporter at The New York Times, Lawrence K. Altman, connects the dots in the development of chemotherapy:
[Ruth] joined the often-unaware group of anonymous patients who ushered in the modern era of anti-cancer treatment, which grew out of American research into chemical warfare agents during World War II. In 1942, researchers at Yale University tested one such agent, nitrogen mustard, in a human for the first time. But Government secrecy restrictions prevented publication until 1946, after several hundred patients had been treated.
At the time, a team headed by Dr. Richard Lewisohn, a surgeon at Mount Sinai Hospital in New York City, was experimenting with an anti-cancer drug, teropterin, in mice. There were different teropterins, all extracted from brewers’ yeast, and their effects on mice varied widely with the preparation.
After leaving Mount Sinai, the elder Laszlo started the Neoplastic Disease Division at Montefiore Hospital.
“He took many of these patients and sent them home, because many of them were locals from the Bronx—they could go home and be taken care of at home,” he said. “I occasionally joined my father in making visits to these brownstone houses, and we would walk up two or three or four flights of stairs to see a patient who’d previously occupied a hospital bed, but was now being taken care of at home, and administer what medicine they needed.”
Laszlo spoke with Alexandria Carolan, a reporter with The Cancer Letter, and Paul Goldberg, editor and publisher of The Cancer Letter.
