Richard T. Silver, MD
Before he helped define criteria for the diagnosis of polycythemia vera (PV) and introduced interferon to treat it; before he chaired the guidelines committee for the treatment of chronic myeloid leukemia (CML) for the American Society of Hematology; and long before his name branded an internationally recognized clinic that specializes in myeloproliferative neoplasms (MPNs); Richard T. Silver, MD, thought his acceptance to medical school was a practical joke by his college fraternity buddies.
While others sat outside in a cold sweat waiting for the admissions interview they feared would live up to their recurring nightmares, Dick Silver was as calm and cool as could be. Why? Because at the time, he honestly wasn’t sure he wanted to be a physician. And more honestly, having just completed his junior year in college, he was so sure he wouldn’t be accepted that he applied to only one program − now his alma mater, Cornell. It was his college advisor who thought that the interview would be a good experience and, according to Dr. Silver, he was right.
Today, proudly still at work in his early 90s, Dr. Silver is globally acclaimed as one of the most influential pioneers in the clinical investigation of MPNs, and the closely related myeloproliferative disease CML.
In 1968, he founded the Cancer Research & Treatment Fund (CR&T), which continues to be the major funder of the Richard T. Silver MD Myeloproliferative Neoplasms Center at Weill Cornell Medicine/NY Presbyterian Hospital. As the center’s director emeritus, and with a world-renowned team of physicians and laboratory scientists, Dr. Silver’s goal remains on course: building the leading translational research and treatment center dedicated to MPNs.
While CR&T’s focus is MPNs, it has awarded more than $16 million in research grants over the past five decades, including breast, lung and prostate cancer investigations.
The center’s importance can be seen in the ripple effects of its existence, according to Dr. Silver. “When an institution brings together world–class physicians and scientists, they draw in equally talented fellows, residents, students, and other physicians, thus providing a center of excellence for patient care.”
From the beginning, it was his belief that investing in blood cancer research would lead to important breakthroughs, including a better understanding of the biology and treatment of all forms of cancer. Although the use of interferon in hematologic disorders began with CML, it has been replaced in this illness by drugs known as tyrosine kinase inhibitors (TKIs), “a spectacular example of precision medicine,” he says. “Now, patients with this once-fatal cancer have a 93 percent 10-year disease-free survival.“
Seeing so many similarities between CML and MPNs, Dr. Silver focused on the use of interferon. Ultimately, he was the first to introduce its use in polycythemia vera.
In the early 2000s, researchers discovered the molecular abnormalities of the MPNs: JAK 2, calreticulin, and MPL genes. At that point, says Dr. Silver, “the entire research field exploded, both in the clinic and in the laboratory. Now we had genetic markers for these diseases!“
Over the next decade, research interest and funding increased significantly from the government, foundations and pharmaceutical industry. “There were mouse models; there were cell culture models . . . There was a tremendous increase in interest because there was a transfer of ideas from bench to bedside,” he explains, “and from an increasing number of very smart, talented and dedicated people around the world.”
Today, we have not only the genetic understanding of these illnesses, but also the use of effective drugs.
“In my earlier days as a physician, I lived through all these illnesses with drugs of limited effectiveness,” Dr. Silver reminds us. “Now, we have three JAK 2 inhibitors approved by the FDA, and another pending, in addition to the approval of ropeginterferon in 2021. The latter, in particular, makes me feel very satisfied. And there are others coming down the line, new drugs that work differently, whole classes of new agents.”
Still active as a consulting specialist, Dr. Silver continues in his lifelong role as a leader in clinical research publications. He lists more than 300 peer-reviewed articles in leading medical journals on his CV, in addition to writing or editing four books, 46 medical chapters, and too many research abstracts to list. He is also credited with developing the bone marrow biopsy technique that is now used throughout the world for the diagnosis of hematologic disorders.
So the question is, what keeps this extraordinary visionary perpetually engaged in an area of rare blood disorders (technically cancers) that have been the center of his professional life for more than 60 years?
“It’s because this is a rapidly expanding arena. It’s like an inverse pyramid,” says Dr. Silver. “Every day there are new discoveries. You can’t keep up with the literature.”
And while MPNs are considered orphan diseases, “they’re really not that rare, particularly when you consider the implication of clonal hematopoiesis (CHIP),” he says. “These genes identify many people over 60 who are at an increased risk of developing not only MPNs, but cardiovascular disease and other types of cancer.“
Then, as anyone who knows Dr. Silver would expect, he adds the perspective that has earned him the highest regard not only among colleagues, but also among his beloved patients: “The MPNs are not as frequent as breast, prostate, colorectal, or lung cancer, which still remain the major issues, public health–wise. But if you’re a patient with a less common disease, you aren’t so worried about the 200,000 other people with breast cancer. You’re worried about yourself.”
And that sums up his commitment not only to the larger research questions and answers, but always to the individual patient, which he says is what sustains him.
“There is a continued sense of exuberance when on the cutting edge of a new clinical finding, or an answer – even a minor one – to a provocative and puzzling aspect of an illness,” he says. “But as a physician, there is nothing better than connecting a new discovery to the treatment of a patient who has sought your help, especially when it leads to improvement, remission, or even cure of a disease. It is a real high.”