publication date: Mar. 30, 2018

An Appreciation

James Holland, an oncology pioneer, dies at 92

By Tim Wendel

This article is adapted from “Cancer Crossings: A Brother, His Doctors and the Quest to Cure Childhood Leukemia,” Wendel’s forthcoming book. The book is available for pre-order here.

James Holland became a doctor thanks to what he calls “a series of fortunate mistakes.” The son of a prominent lawyer in Morristown, New Jersey, Holland was raised to go into law, too. But that changed when he took a course in biology at Princeton University and became enthralled with seeing cells under a microscope.

“I was just captivated by what I saw,” he said. “Sometimes life works like that. Things suddenly turn and you’re off and heading in a totally different direction.”

During the Korean War, Holland was in the U.S. Army and had secured an entry position at Columbia-Presbyterian University, only to have President Harry Truman extend the military service time. When Columbia couldn’t hold the position for him, Holland later went to Francis Delafield Hospital, which had opened to care for cancer patients. Holland’s plan was to mark time at Delafield until a new slot became available at Columbia. Yet Holland soon became intrigued with cancer and how best to manage it.

Early on at Delafield, he treated a baby girl named Josephine, who was suffering from leukemia. He used aminopterin, now recognized as the first chemotherapeutic agent for acute leukemia in children, and the four-year-old regained her health. The turnaround was so startling that other doctors wanted to see for themselves, and a viewing was arranged in the semicircular amphitheater at Presbyterian Hospital. On the day of the event, Holland brought in brightly colored balloons and fastened them to the brass railings that cordoned off the area in an effort to reassure his young patient. When the crowd of doctors arrived, Josephine was smiling, captivated by the balloons, and the visit went off without hitch.

Unfortunately, Josephine soon relapsed, and then she again had “the anguish of dealing with nosebleeds, gum bleeding and bruises in the skin; and primitive antibiotics were all we had available then to treat infections,” he later told John Laszlo. “And she was only a child, a crying child.” Holland added, “There was just unbelievable trauma for everybody concerned. I was only a resident at the time, and this was my first case of leukemia after I had come back from the army, and the first cancer patient that I put into remission.”

Soon Columbia called, saying that a position had opened up there. But Holland turned them down. He had found his place in medicine: it was being a cancer doctor.

“Deep down just about everybody likes mysteries and I don’t believe there’s anything better in the world than solving them,” he said. “You look at cancer and realize how much we don’t know and then you realize how much still needs to be done. It’s an opportunity for young, vigorous people—a chance for them to say they want to be a part of that. Something so much bigger than themselves.

“The people I was surrounded by back then, that I’m still surrounded by today, we like to make discoveries. That’s what keeps us going. In a way, I feel sorry for people in other fields. They’re often looking at things that are pretty matter-of-fact. Early in my career, I realized that in dealing with cancer, we were looking at the bigger picture. Issues like what makes one cell stay alive and what makes another cell die? That’s important, challenging work, I think. It’s what has kept me going through the years.”

Holland - GroupShot

Holland, in front row, with members of Acute Leukemia Group B (ALGB).

Photo courtesy of Tim Wendel

Holland was soon called to the National Cancer Institute, where he worked with Lloyd Law, one of the first doctors to use cancer drugs in combinations. With Law’s help, Holland began testing a combination of 6-MP and methotrexate, which proved successful in the early years of leukemia research.

Holland arrived at Roswell Park late in 1954, brought aboard by George Moore, the energetic new director. Moore was determined to hire young, dynamic physicians to head the various departments at his growing hospital complex. Even though Holland wasn’t thirty years old yet, he was appointed as one of three chiefs of medicine for the expanding cancer research facility. With the move, Holland saw his salary jump from $7,600 to $11,300 a year. He soon married Jimmie Holland, who would become a key player in the growing field of psycho-oncology, where psychology and oncology came together for cancer treatment.

Many consider this to be the beginning of a golden era at Roswell Park. Holland’s contemporaries included Donald Pinkel, who was beginning to calculate more effective drug dosages for children with leukemia. Joseph Sokal and his staff developed new protocols for chemotherapy, and Avery Sandberg investigated the role of chromosomes in causing cancer. There were plenty of egos in play, and Holland recalled that he and Moore “used to fight like cats and dogs. But we always respected each other.”

Edwin Mirand, the author of Legacy and History of Roswell Park Cancer Institute, acknowledges that “the interaction between the clinicians and scientists was intense.” Yet he adds that many of the Moore’s hires soon became known far beyond the confines of Roswell Park “for the quality and creativity of their work.”

Back at the NCI, Gordon Zubrod asked Holland if he would continue to be involved in the leukemia program even though he was now in Buffalo. Holland agreed and decided to augment the study of 6-MP and methotrexate at Roswell Park. Emil “Tom” Frei at the NCI took over many of the administrative chores for the collaborative effort and was soon joined by Emil “Jay” Freireich at the NCI and Pinkel in Buffalo. In the beginning, Pinkel said it “was basically us four.”

That was inception of the Acute Leukemia Group B (ALGB), which would later be renamed the Cancer and Leukemia Group B, or CALGB. Members of the cancer research cooperative began to meet every other month, going over initial results and standardizing forms and clinical trial criteria. The Walter Reed Medical Center, the Medical College of Virginia, and the University of Maryland were among the other institutions that soon joined the effort.

Early on, the ALGB struggled to find enough children with leukemia to participate in its new studies. Too many family doctors viewed ALGB with deep suspicion. After all, cancer, especially in kids, was often considered to be incurable. Why put them through the ordeal of combination drug therapy, blood work, and the like?

The ability to motivate people with words soon became one of Holland’s chief assets. In 1965, he published an article entitled “Obstacles to the Control of Acute Leukemia” in the CA: Cancer Journal for Clinicians. Much of it had been originally presented at a symposium sponsored by the American Cancer Society and the National Cancer Institute. The peer-reviewed publication was the most widely circulated oncology journal at the time, going out to more than 100,000 readers and professionals. In the five-page piece, Holland cited the success that the combination of the vincristine and prednisone had had against cancer. Yet what got the medical world buzzing was the confidence, the sheer chutzpah, that Holland exhibited in his belief that childhood leukemia could be conquered in the years ahead—perhaps as early as the next decade. Despite the pessimism in many quarters, Holland insisted “that nearly every obstacle appears to be identifiable and approachable—if not surmountable—at present or in the immediate future.” Holland added that the “data, result and concepts are now such as to allow legitimate informed discussion, planning, and execution of attempts to cure acute leukemia rather than merely palliate it. … It is in times of universal challenge accepted by every man that giant strides are made.”

Jerry Yates was practicing medicine in California when he read Holland’s article. His initial reaction? “I need to talk to this man. I need to find a way to work for him.”

Yates had recently treated a patient who had died of testicular cancer. The man was twenty-seven years old, about the same age as Yates at the time. The young doctor was devastated by his patient’s passing. A few weeks later, Yates came upon Holland’s article.

“And it just rocked me. It just snapped me out of this state I was in,” Yates said. “James Holland was so far ahead of the rest of us. He saw a different world out there—one of real possibility. One in which people could be, did we dare say it, cured? To hear something like that, when you’re working in many of the same areas of care … well, it meant everything to me at the time.”

Holland-Yates

Holland with Jerome Yates, a colleague in leukemia research at Roswell Park.

Photo courtesy of Tim Wendel

Yates landed an interview at Roswell Park and spent much of the day with Holland, going on rounds, talking about the growing possibilities in terms of leukemia care. Their conversation carried on into the late afternoon as Holland drove Yates to the Buffalo airport. When the official job offer arrived from Roswell Park, Yates quickly accepted. He did so even though Holland had warned him about the long hours, the hard winters in western New York, and the often devastating clinical trial results.

“When I look back on those days, it was a good thing that we had to do many of the initial tests ourselves,” Yates said. “There was no sending the patient down the hall to an expert in this field or that. We had to be or become the experts. We had to be the first to learn many of the procedures, setting up the next clinical trial and its parameters. We had to do it because so much of the medicine was that new to everyone involved.”

Audrey Tuttolomondo, who worked for two decades as a nurse at Roswell Park, remembered Holland as a commanding presence. “A lot of it has to do with his voice,” she said. “It turned heads and it demanded respect. It’s this deep baritone-bass voice that could be heard from a long ways down any hallway.”

Holland remained the ALGB chairman for eighteen years, staying on even after a horse he was riding with his four-year-old daughter reared up and fell backward atop him. Holland was able to throw his daughter clear (she was unharmed), but the horse crushed his pelvis. Holland soon made a full recovery.

Holland teamed up with Yates to develop the landmark “7 + 3” regiment that’s now widely used to treat acute myelocytic leukemia. But Holland’s closest collaborator was his wife, Jimmie. She was the founder of psycho-oncology, which explores the psychological, social, behavioral and ethical aspects of cancer. Many of those early conversations took place with members of the ALGB at the Hollands’ home in north Buffalo.

“We ended up meeting so much in our kitchen because back in those days there weren’t a lot of restaurants in Buffalo. Plus, we had had young kids,” Jimmie Holland once told me. (Jimmie died in December 2017). “So it just made more sense for Jim to invite everyone over from Group B, and I’d make something and everyone could relax and talk.”

Growing up, Holland had been taught poetry by his father, and he found motivation and solace in the power of words. I once asked him if he would recite a few lines from a poem, perhaps a favorite of his. “How did you know that about me?” Holland demanded. “That I learned poetry growing up?”

I told him that several of his friends and peers admired this quality about him.

“All right then,” he replied. “How about a few lines from ‘Elegy Written in a Country Churchyard.’ You know it?”

I didn’t.

“Well, you should. It’s one of my favorites. You can look up the particulars about it.” (Indeed, I found that the poem was written by Thomas Gray and was published in 1751. It runs 144 lines, and scholars believe it was inspired by the death of Richard West, Gray’s friend and fellow poet.)

Holland began in a voice that still holds one’s undivided attention.

Full many a gem of purest ray serene,

The dark unfathom’d caves of ocean bear,

Full many a flow’r is born to blush unseen,

And waste its sweetness on the desert air.

“I love the cadence of that, how it rolls off the tongue,” Holland said after reciting those lines. “I learned it when I was young and I’ve never forgotten it. To me, it’s about believing good work can be done. How good work can be accomplished, if you’re willing to push on.”


The author is a writer-in-residence at Johns Hopkins University.

Copyright (c) 2018 The Cancer Letter Inc.