Writing the Book on Cancer Care: Holland Reminisces

James F. Holland, MD

James F. Holland, MD, stumbled into the field of oncology by chance. As a captain in the Army Medical Corps during the Korean War, he was preparing to head home from Europe and return to his third year of residency at Columbia University College of Physicians and Surgeons. But when President Harry S. Truman authorized an extension, Holland had to write a letter to Robert F. Loeb, MD, then a professor of medicine at the institution, informing him that he wouldn’t be back to school. Loeb couldn’t hold his spot, but instead offered him a position at Frances Delafield Hospital, then at Columbia University Medical Center in New York. “I’ll call you back when somebody gets tuberculosis or a psychiatric disorder,” his mentor told Holland. “They always do.”

But after being thrown into oncology care when he treated a 4-year-old with acute leukemia named Jennifer—a chapter that Holland calls “a dramatic part” of his life—Holland had a different answer when Loeb called him back to practice general medicine. “I said, ‘Thank you, Dr Loeb, but I think I’ll stay,’” Holland recalled.

Starting in the Trenches

Holland, of course, did more than just stay in the oncology field. In a career that has spanned more than 60 years, Holland has emerged as a groundbreaking and prolific researcher in developing combination chemotherapies for patients with leukemias. Today, the 92-year-old researcher and physician is the Distinguished Professor of Neoplastic Diseases at the Icahn School of Medicine at Mount Sinai in New York City. The choice of specialty was not the only time that Holland’s path could have veered away from oncology. In fact, he could have gone in an entirely different career direction. When he was attending Princeton University in the 1940s, he was also interested in becoming a lawyer. “My father was a lawyer,” said the Morristown, New Jersey, native. “But I had a wonderful biology teacher at Princeton, and I found some of the information that I learned and the way it was taught to be of great interest. Therefore, I chose medicine rather than the law. A good teacher really can inspire.”

Another occurrence that made a significant impact on Holland was his young patient Jennifer, whom he treated as an assistant attending physician at Frances Delafield Hospital. “Unhappily, she died,” he said. “I remember distinctly the great trauma to her mother, father, and to me, when this child relapsed.”

But this hospital also was where he met one of his lifelong mentors, the late Alfred Gellhorn, MD. They bonded after Gellhorn reviewed a thesis that Holland had written on the prostate, which followed the findings of Charles B. Huggins, MD, postulating that castration could be used as a treatment for prostate cancer.

It wasn’t long before Holland was offered a senior attending physician position in 1953 at the National Cancer Institute (NCI) in Bethesda, Maryland, a “terrific experience” that he also credits Gellhorn for granting him. “The National Institutes of Health is a paradise for people who are interested in science and investigation,” said Holland. “It was challenging and tremendous. I learned a great deal there, and I was very happy.”

Setting a New Course

At the NCI, Holland was the first researcher to put 2 drugs together for patients with acute leukemia. “When I went to the NCI, I was lucky to be assigned to help a major league scientist, Dr Lloyd Law. He was the first man to [combine] 2 drugs in treating chemotherapy in mice, and he showed that if you used drug A or drug B together, the outcome was better.”After Holland left the NCI for a position at Roswell Park Cancer Institute in 1954, Emil Frei III, MD, continued his research at NCI. They started a significant collaboration: the first inter-institutional program involving chemotherapy as cancer therapy.

Joseph H. Burchenal, MD, became chairman of Acute Leukemia Group A, while Frei and Holland shared the chairmanship of Acute Leukemia Group B for 33 years. As the group expanded, Holland changed the name to Cancer and Leukemia Group B, which has since morphed into its current name, Alliance for Clinical Trials in Oncology (ACTION).

Also as a result of this collaboration, Holland said he and Frei became “brothers joined at the hip,” so much so that they published a book together, Holland-Frei Cancer Medicine, described as a respected reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat patients with cancer. The ninth edition was issued earlier this year.

“I’m very satisfied with the way things are evolving,” said Holland. “We have changed the concept of cancer from guaranteed death to curing a lot of people. Many oncologists have used this as their educational basis for learning about cancer. That’s been a great satisfaction—having trained a lot of people and treated a lot of patients, many of whom are cured.”

In addition to guiding the field through his writing, Holland has served in leadership roles in the most prominent oncology groups, including as president of the American Association for Cancer Research, president of the American Society of Clinical Oncology, and scientific adviser to the NCI, the World Health Organization, and the African Organization for Research and Training in Cancer. He was a special consultant for a cancer research initiative in the Soviet Union (then the USSR) from 1972 to 1973. He also has served as the scientific director of the T.J. Martell Foundation for Leukemia, Cancer and AIDS Research.

Throughout his career, Holland has been part of many game-changing endeavors, including the development of the POMP chemotherapy combination of mercaptopurine (Purinethol), vincristine (Oncovin), methotrexate, and prednisone for children with acute lymphoblastic leukemia. He has also constructed the 7 + 3 regimen for administering cytarabine and daunorubicin as treatment for adults with acute myeloid leukemia, and he identified cisplatin for the treatment of patients with testicular cancer and doxorubicin for individuals with osteosarcoma.

Today, Holland is at Mount Sinai Medical Center, where he has been since 1973. He started as the director of the cancer center there, prior to the founding of Tisch Cancer Institute. The institution, he adds, is a constellation of people of extremely high caliber. “I have had lots of friends here who are very well specialized in particular areas, such as gynecology, infectious disease, neurology, and cardiology,” he said. “My stay at Mount Sinai has been extremely interesting, provocative, and helpful.”

He still treats patients, albeit on a reduced schedule. “I don’t see as many as I used to see, and I don’t walk as far I used to walk,” said Holland, alluding to his age. “I’m an old man. But I still see patients. I deplore some of the acts and circumstances of what would be called ‘modern computer docs.’ They spend time looking at a computer, not the patient. That’s not the kind of medicine I practice.”

Aside from time spent on applying for grant funding for cancer research, Holland has also been actively studying with a virologist to explore a viral cause of human breast cancer. Thus far, evidence suggests that the human mammary tumor virus may be a causal agent for the disease.

A Key Witness to an Evolving Field

“We found it,” says Holland, adding there is much in oncology still unknown. “Forty percent of American women’s breast cancers contain this virus. It is there before the breast cancer develops; it’s in the milk and probably infects the boys and girls who nurse. Eight percent of American women have it in their milk, and that is enough to account for the viral breast cancer. The overall community does not accept it, but before I die, we will prove that it is the case for 40% of American women’s breast cancers, which would change the entire field. This is because we would have to identify who those 40% are and, potentially, who are the ones who are going to get breast cancer because they got the virus when they were infants and nursing.”In his nearly 70 years of practicing medicine, Holland has seen quite a bit of change. For example, he has seen the demand for his field increase. At Frances Delafield Hospital, his salary was $4000 annually; that figure jumped to $7600 at the NCI and then again to $11,600 at Roswell Park Cancer Institute. “Those were fortunes of dollars in those days,” he said.

Money aside, the explosion of interest in immunology is “wonderful,” he observed. “I have been interested in it for many years, and I worked on [research] that turned out to be partially successful,” he said. “Now, people have recognized more intensely the impact of immunologic defense and the role of the T cell, which now can destroy tumors and which we suspected, but didn’t know.”

With the addition of monoclonal antibodies including the PD-1/PD-L1 checkpoint inhibitors, researchers are learning how to activate the body’s own defenses. “Activating all of the understandable components of the immune system, of which we don’t know a great deal about, is likely to become the future of oncology, and it’s nontoxic because they are T cells that you already have. Can they cause troubles? Sure. Are there side effects? You bet. Nothing is for free.”

Outside of the Clinic

Holland noted that radiation therapy, surgery, and chemotherapy all have downsides that people should take into consideration. “Science is really an extraordinary, romantic, wonderful area in which to work, in which to learn,” Holland reflected. “In medicine, every patient who walks in the door is really an experiment. You shouldn’t [treat anyone] and take it for granted because there are so many potential opportunities to make a wrong diagnosis as well as the satisfaction of making the right diagnosis and proper treatment. It has been very rewarding.” Although he may not have a favorite philosphical maxim, Holland says there is a phrase he does always repeat. “I say ‘I love you’ to my wife. We’ve been married 61 years,” said Holland, whose wife is Jimmie C. Holland, MD, the Wayne E. Chapman Chair in Psychiatric Oncology at Memorial Sloan Kettering Cancer Center. Jimmie Holland is the 2014 OncLive^® Giants of Cancer Care^® winner in the Supportive Care category. The couple, who met while Jimmie Holland was visiting a friend in Buffalo, New York, have 6 children together.

“We have a lot of common interests,” Holland reflected. “The marriage is highly successful not because she is interested in oncology; it is because of who she is. Life has been very good to me.”

Holland, who calls himself a workaholic but spends downtime with his children and grandchildren, remembers one other phase he does keep in mind. “I suppose my one saying is, ‘Nobody’s got a round-trip ticket. It’s a one-way ticket.’ I’m prepared for when the time comes. I don’t want to leave, but I’m not afraid of death. I recognize that I’ve been very lucky in life. I’ve had lots of rewards, satisfactions, and opportunities to do things.”