Eamonn Boyle, M.D. says, "Most Things Get Better..."

Having “no grand plan” for his life after high school the young man was idling in front of a bookcase when he spotted a volume on zoology and thought to himself, “That might be interesting.” A few months later, in 1963, he entered the government-sponsored seven-year medical school program at University College, Dublin. Half of the lads (there were very few women) left after the first demanding year.

Eamonn Boyle, M.D., F.A.C.P.

Our protagonist did well and continued his studies. He enjoyed zoology, but also chemistry, biology, physics and, especially, botany.  Dr. John Harman,  “a great pathology professor,” introduced him to the study of inflammation, how the body defends and protects itself, and Dr. Ruy Pérez-Tamayo taught him about tumors. But his interests were still broad and as Dr. Eamonn Boyle (the young man of the story) finished his studies he wondered, “What am I going to do now?”

While preparing to “put in papers” for an internship at the hospital where he trained (as did most of his fellow graduates)  he ran into his alphabetically-arranged classmate Frank Bonner (Bonner, Boyle, etc., you know how it was in the old days when life was simple and orderly). Frank was from Philadelphia, and said, “Why don’t you come to America? I think I can get you in. They’re missing a player!”

So he landed his rotating internship and two-year medicine residency at Bryn Mawr Hospital from 1970 to 1973.  His interest in oncology that was sparked while in medical school became more definite as he closely watched and learned all he could from the “legendary and revered” (according to her 2005 obituary), Dr. Abigail Silvers.  

She let Dr. Boyle know that even if you could not cure their cancers, patients still had general medical needs, and that you could alleviate their symptoms and relieve their suffering, and that they “didn’t all die in one day.” He was deeply affected by her humanity and thought, “This would be a good fit.”  And, he reasoned, treatment for cancer “is only going to get better with the passage of time, since most things get better.”   

Emil Freireich, M.D.

After his time in suburban Philadelphia, he took a fellowship at the M.D. Anderson Cancer Center in Houston, Texas, one of the first comprehensive cancer centers and (according to U.S. News) ranked #1 for 11 of the past 14 years. He spent five intense years in Texas as he worked alongside true cancer treatment pioneers, including Dr. Emil Freireich.

While sleep-deprived (he was on call every third night) but well-fed (they provided “three squares”) at Bryn Mawr he had met a local student-nurse who would later agree to become his wife. When thinking about where to go into practice (academic medicine was not for him) proximity to Philly, where her family lived, was important.   

He interviewed for a position in Lancaster but there was no need for a full-time oncologist at the small Catholic hospital. The radiation therapist there referred him to York Hospital “just down the road” since Dr. Ross Moquin was unexpectedly leaving practice.   On the short drive from Lancaster to York that beautiful cool Mother’s Day weekend the trees and flowers were in bloom and the rolling hills were a welcome break from flat and steamy Houston.  He could be comfortable here, he thought. 

He liked what he saw, particularly when he met several of the general internists at the hospital, including Drs. Leo Samuelson and Jack Kline.  Dr. Moquin queried him and quickly said, “The job is yours.”  Dr. Boyle began to see patients here in 1978, joining Dr. Miodrag Kukrika who had been in York for a few years and, together, they formed “Cancer Care Associates.”  Their practice expanded and evolved over the next 40 years.

The field of oncology, of course, has also changed dramatically in four decades.

Blood Smear of ALL

In the beginning.  Watching children with acute lymphoblastic leukemia (ALL) quickly succumb to their devastating illness Dr. Sidney Farber felt helpless. In 1947 he and his team used the folic acid antagonist aminopterin to block DNA synthesis. Many of the children had their disease go into remission, but they all subsequently developed resistance to the single drug and relapsed and died. 

Treatment was then refined by the aforementioned Dr. Freireich as he gave the kids several agents in combination (similar in concept to the treatment for tuberculosis, it was noted), and the therapy was then continued beyond the acute stage.  

Thus began the era of “multiple-drug induction followed by maintenance chemotherapy.”  By 1971 the cure rate in ALL was 50%.  Dr. Boyle witnessed this, and there was new optimism as he noted that, “Little children could go from inevitably dying, to being cured most of the time.”  The cure rate now at St. Jude is 90+%. 

After the spectacular success with ALL, curative treatment for advanced Hodgkin’s lymphoma followed in 1965, and advanced testicular carcinoma became a very treatable disease in 1975.  For a young optimistic cancer doctor, this was evidence that aggressive chemotherapy might also even halt, for example, metastatic breast, colon, prostate, and lung cancers. As Dr. Boyle said, “That was the proof (we needed).”

In the middle.  The intense and complicated chemotherapy regimens of the 1980s and early 1990s often made patients feel terrible, and as their white blood cell counts dropped precipitously they sometimes developed life-threatening infections.  This “slowed down” but did not really cure many cancers. Colony-stimulating factors helped limit anemia and falling white counts, but that was not enough. Discouraged, Dr. Boyle waited patiently for something better.

(From "Rewire Me")

Along the way, he noted that there were “rough areas” (emotionally) but that he “never thought of doing anything else.” He was a “round peg in a round hole” as a front-line practitioner serving the York community.  As he reflected on this, he noted that the “relationship with people” as he gently guided them along in their cancer travels and helped them cope with the “assault on their personhood and control” was “the biggest thing” for him. As it is for most physicians, he believes.  

But he feels that, ”There could be a little bit more done psychologically for the cancer patient who has trouble keeping the balance," and that "this (struggle) relates to their nature before the cancer, and how much cancer and its treatment is interfering with their life.” 

The current era.  (Here is where things get really complicated, and Dr. Boyle, with patience, and in his gently nudging way, took the time to allow me to get things reasonably straight.) Cancer, he noted, is now recognized "fundamentally" as a gene disorder. Damaged genes (hence called oncogenes) go haywire, causing the affected cells to grow uncontrollably, to spread to other organs, or to block the effects of the body’s usually-protective immune system.  

The damage to the DNA of the genome may be caused by environmental factors including tobacco, chemicals, radiation, and others, still unknown. A number of viruses may alter host genes or introduce new genes that may eventually lead to cancer.

Location of BRCA Genes

There may also be an inherited (i.e., hereditary)  tendency (Dr. Boyle was careful to emphasize this latter point) to develop to certain cancers, such seen in carriers of mutated tumor-suppressor BRCA1 and BRCA2 genes that substantially increase the risk of breast and ovarian cancers. But even here, subsequent gene damage is necessary for the development of a cancer cell.

It was dreamed decades ago that by knowing the exact genome of the cancer cell it might be possible to design agents to attack only those specific altered functions.  It took some time, but this "sequencing" of the gene can now be done relatively easily, and an antibody to the precise target, a so-called monoclonal antibody, can be created in any amounts needed (yes, this is truly amazing science and technology). 

Rituxan, the first monoclonal antibody therapy was introduced in 1997. It attacks the B cells of the immune system that have a unique cell-surface marker called CD20.
  

Structure of Rituximab (Wikipedia)

Other therapeutic antibodies, including what are known as checkpoint inhibitors, have been developed. These include, among others, Herceptin in 1998 for breast cancers, Avastin in 2004 to block the vascular supply to certain tumors, Erbitux, an epidermal growth factor inhibitor, in 2009, for colon, lung and head and neck tumors, and Keytruda, in 2017, that blocks the cancer’s own sneaky self-protective adaptive system to then permit the patient’s immune cells to do their job and attack and destroy the tumor.  

There is already a genetic test to see if the patient will not respond to Erbitux or Keytruda, so, less guessing, making Dr. Boyle's job is a wee-bit easier.

Dr. Boyle notes that in addition to the advanced “biologic” monoclonals (whose tongue-twister generic names all end in -mab, by the way) conventional drugs with simple chemical structures have been designed to attack specific tumor cells.  This may be done by blocking a protein, or enzyme, necessary for the activity of the rogue cells.  Gleevec (released in 2001)  for chronic myelogenous leukemia and certain stomach tumors, and Imbruvica (in 2015), for chronic lymphocytic leukemia, are examples of this.  

More immunology; old and new. Since the 1980s the BCG vaccine used to prevent tuberculosis in countries where TB is endemic has been employed surprisingly effectively to treat minor bladder cancers.  At Duke University a vaccine derived from the patient’s tumor itself is being tested with remarkable success in treating glioblastoma, the highly aggressive and feared primary brain tumor. In fact, it has, on average, tripled survival times. 

Recent experiments in mice showed that when they are vaccinated with their own induced stem cells they eradicated many different types of tumor cells, raising the hope that the same will occur in our species.

Cartoon of CAR-T

The newest immune system therapy, noted Dr. Boyle, is called CAR-T(cell).  This takes the patient’s own T killer-cells and engineers them to have a specific surface marker. It then makes a bunch of these cells to infuse back into the patient.  This has been partially effective in otherwise resistant childhood leukemia and certain stubborn lymphomas. CAR-T is given as a single treatment. Novartis has currently priced its version at $475,000 (while Gilead charges a measly $373,000).  

Multiple Factors in Disease

The future. After a cancer diagnosis or, better yet, after finding a pre-cancer picked up by sophisticated screening, we will calmly sit down with our doctor and be offered perfectly-customized “precision” care uniquely matched to our genetics and epigenetics (the turning-on and turning-off of specific genes), the offending gene mutations of the cancerous cells, the activity (or lack thereof) of our protective immune system, and our personal history of other risk factors and unique biology. There will be less fear, fewer side effects from treatment, less suffering, occasional miraculous cures, and longer survival.

"But, won’t cancer one day be totally eradicated?" I asked. 

Regrettably, but with soft gentle honesty, Dr. Boyle said, "I don’t think so." He noted, instead, that "cancer may be tied up in the way we are.” Implying that this is an integral part of our animal biology, of our evolutionary zoological heritage.

The Pulitzer Prize-winning author of The Emperor of All Maladies, Dr. Siddhartha Mukherjee, agrees:

"The Emperor.."

Cancer, we have discovered, is stitched into our genome. Oncogenes arise from mutations in essential genes that regulate growth. Mutations accumulate in our genes when the DNA is damaged by carcinogens, but also by seemingly random errors in copying genes when cells divide. ..Cancer is a flaw in our growth, but this flaw is deeply entrenched in ourselves. We can rid ourselves of cancer, then, only in as much as we can rid ourselves of the processes in our physiology that depend on growth--aging, regeneration, healing, reproduction...It is possible that we are fatally conjoined to this ancient illness, forced to play its cat-and-mouse game for the foreseeable future of our species...But if cancer deaths can be prevented before old age it will transform the way we imagine this ancient illness...It would be a victory over our own inevitability, (p. 462-3).

I think Dr. Eamonn Boyle would be satisfied with that.

Required Reading: Mukherjee, Siddhartha. "The Emperor of All Maladies; A Biography of Cancer."  New York; Scribner, 2010.