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.

John Mathai, M.D., F.A.C.S., F.A.C.C.

The 23-year-old young man arrived at midnight in Pune after a fifteen-hour train ride from Trivandrum.  He slept on a bench on the platform and awoke to someone sticking him in the side. He looked up and the policeman said, “You have a suitcase. Put your feet on top of it so  no one will steal it.”   He left the station and thought, “What have I done now?"  His appointment was in a few days.  He washed up and walked into the main parking area of the busy Indian railway station.

Coastal SW India

With no hotel reservations, he looked around.  He spotted a priest and thought to himself, “He must be an honest guy.”  He went up to him and told him that he was there for an interview and was looking for a place to stay for a few nights. The priest said he had a friend at the university who could give him a room. He was instructed to take a bus and to meet him at a specific stop.  It was very hot, and, after arrival, the young man looked around anxiously for the priest and waited, and was relieved when he finally saw him on his bicycle.  

Lodging at the empty school was arranged (it was summer) and he was told where he could get his suit pressed.  He did what was suggested and he had the interview.  With a “first place” in surgery and “second place” in medicine he was, of course, selected.  He would go to the States for a general internship at Somerset Hospital in Somerville, New Jersey.
.   

John Mathai, M.D.

Dr. John Mathai was that young man with dreams. He finished medical school in lush Kerala on the southwest coast of India in 1962 and decided to go into surgery like his father, a tuberculosis specialist. The hope was to leave India and study and practice in Great Britain where he could learn from the best, and be one of them. He would be a Fellow of the coveted Royal College of Surgeons.  

That would be nice, but he didn’t have the right contacts.  However, he could first get to the U.S. through an Indian foundation and then go to England from there. Thus, the preceding little story.

Yet, arranging the trip to New Jersey was not so simple. India was at war with China and doctors were being denied passports; maybe he would have to stay.  But “someone with money,” noted Dr. Mathai, petitioned the Supreme Court, and it was decided that “it was everyone’s right to get a passport.” He did that and was on his way.

With the help of the then-current “Fly Now; Pay Later” program (this was before credit cards, so we can all “fly now and pay later” ), and a split ticket, he left Bombay.  He flew from there through Cairo to Rome on TWA, and then to New York City on Pan Am.

With the help of his cousin who worked for the Federal Reserve Bank, he had filled out the proper governmental forms so he could take money out of the country for travel. How much did he have with him? Why, the maximum, of course...75 rupees (about fifteen dollars!).  And one flimsy suitcase.

Approaching New York in winter the pilot announced,"Even with snow on the ground we will be landing on schedule."  Dr. Mathai was puzzled at first and didn’t recognize the last word since he was used to the British (and Indian) pronunciation of it as “shedule.”  Was “Skedule” another city? He thought for a moment and then understood.  

More connections…

A sign held up by an airline employee alerted him that the assistant director of the hospital was there to greet him, and he was ready. Walking through the terminal together to get to the car they came upon an escalator.  Having not seen “this animal” before he was baffled as the moving steps appeared and disappeared. Dr.Mathai said, “I watched how these guys got on this thing and I got up my courage and stepped on.”   He was a quick learner.

Mumbai, not N.J.

The director drove through New York City and Dr. Mathai witnessed some of the things he had read about while he was in India, and that was fine. But the most impressive sight by far was the scene when they got to the turnpike.  He was utterly “amazed” by the orderliness of the traffic, with all the cars in a line, and all going in the same direction!  This was not the chaos that he felt in India.
   
After the internship year in Somerville his plan was still to go to England, of course.  So, at a camera shop just off Times Square, he bought a fine Voightlander (he still cherishes it) to preserve his memories of being in America.  Of being in a country where, he noted, “Everything works.”

As it turned out, though, Dr. Mathai didn’t leave after his internship.  There were four years of general surgery at Albert Einstein Hospital in Philadelphia,“York and Tabor,” (where I, the writer, just happened to have been whelped).  He then needed to specialize, and first considered neurosurgery; it was fascinating, but too “depressing.”  But “somehow” he was “attracted to Dryden Morse” a heart surgeon at Hahnemann who had worked with Dr. Charles Bailey (“the father of direct heart surgery” according to Dr. Denton Cooley).   

Pioneer: Dr. Favorolo at Cleveland

Dr. Morse took a special interest in Dr. Mathai and mentored him in the exploding field of open heart surgery in the mid-1960s. The young surgeon considered going to the Cleveland Clinic next, where bypass grafting was being perfected, but was convinced instead to pursue his passion at the university level, and he planned to go to the University of Maryland with the renowned trauma innovator Dr. R Adams Cowley.

Not so fast, buddy boy!  This was the time of the Vietnam Tet Offensive in 1968 and Dr. Mathai was called to serve his new country. He passed his perfunctory physical (”Can you see? Can you walk?”) at the Draft Board in Philadelphia and was ready to go to war, but Dr. Cowley “needed” him in his program.  He pulled strings and used his military contacts and, as a result, Dr. Mathai was able to start his Thoracic Surgery residency.

After completing that grueling program Dr. Cowley steered him to York where he joined the staff in 1970.  He  started work ominously (he felt) on August 6th, “the date of Hiroshima,” and soon realized that he was, in his words, “the only foreigner” on the clinical medical staff, and that “nobody looked like (him).”

Surgical Team in Cleveland

He quickly fit in, however, and was urged by Dr. Jack Gracey (of Cardiology) and Paul Keiser (the CEO of the hospital) to start a full cardiac surgery program.  This had to be approved by the medical staff but they were bitterly divided and needed to be convinced. So Dr. Mathai took a fellowship at the Cleveland Clinic where he met Dr. Joe Hooper.  They became friends and decided to work together to start things in York.  With chutzpah, they brought the Clinic’s Cardiac OR nurse manager, and the capable Physician’s Assistant working with her, to the York Hospital.  The plan was to “duplicate exactly” what was done in Cleveland, and the program here began in 1975.

Two Types of Bypasses

The team was very careful in selecting patients, and the statistics for the first year were excellent.  The service then continued with several other surgeons (including Drs. Peter, Levin, Fried, Haupt., etc.), and Dr. Mathai practiced open heart surgery at York day and night until 2007 when the health system changed.  He then did cardiac procedures for several productive years at  Holy Spirit Hospital in Camp Hill and Pinnacle in Harrisburg with Dr. Brad Levin before unforeseen circumstances forced him in another direction.  After a few months, he started a practice limited to vein surgery, and he enjoys seeing patients even now. 

Dr. Mathai returned to India several times a year for 30 years to work with a Hindu charity, and for the last 20 he went to private hospitals, mostly the Kerala Institute of Medical Sciences.  He has seen many changes over the decades and notes that the facilities in his homeland are now comparable “and sometimes a little better” than hospitals here.

Today, at 79 (that’s correct), Dr. Mathai can look back at his own career and see the history of coronary artery bypass graft surgery.  The first successful CABG was done by Dr. Robert

Goetz (from Frankfurt by way of South Africa) on May 2, 1960, at Albert Einstein in New York.  Unfortunately, his “colleagues were violently against the procedure” and, as a result, he was not permitted to further pursue his exciting technique (the actual artery-to-artery anastomosis itself took...are you ready?...17 seconds!).  

Time passed before Dr. Rene Favorolo (a fiery Argentinian) at the Cleveland Clinic did the first aortocoronary bypass using the patient’s own saphenous vein as the donor vessel in 1967, and by 1970 he and his colleagues had performed more than 1,000 such procedures.  

A Robotic Procedure

Surgeons throughout the United States adopted this technique and have been modifying and perfecting the operation ever since. The number of bypasses performed yearly in the U.S. peaked in 2000 at around 500,000 and has steadily declined since as advances in coronary stenting (by clearing the blocked artery from within rather than going around it)  and preventive therapies (to halt progression or even reverse some of the plaque build-up) have appeared. In fact, coronary artery bypass grafting is now often done robotically, without the need to split the sternum, without the need to open the chest, without the need for the surgeon to touch the patient.  

When It's Over...

Over his nearly 40 years practicing heart surgery, Dr. Mathai has seen and done much as he has been part of and has adapted to changes in medicine.  As stated by the Nobel Laureate cardiologist Dr. Bernard Lown, "No doubt what one does is largely the result of who one is." This is clearly so for the resourceful and resilient Dr. John Mathai who noted that change is woven into the fabric of life, that the trace of the heart’s rhythm changes moment to moment, until one day it doesn’t.

Complex open heart surgery and, specifically, coronary artery bypass, like all significant medical interventions, has been the product of the prodigious talents and sustained efforts of many dedicated individuals. Individuals whose path may not be a straight line, and whose journey may start in a faraway land, on a train platform, in the dark of night.  

We thank them all. 

Dr. Michael Kleinman in the ER

Holocaust Memorial at
the York JCC

Childhood sweethearts Lili and Josef became separated while they were in the concentration camp, the work camp, during the Shoah, the Holocaust.  When the prisoners at Auschwitz were liberated by the Soviets in early 1945 Josef went to find his love again. He walked throughout Germany for six months anxiously asking anyone if they had seen her.  When some claimed that they heard she was dead Josef refused to believe them. He didn’t give up; he kept searching.  And he eventually ran into an old friend who told him that she was recuperating in a nearby hospital.  He found her and nursed her back to health. 

Ready to start a new life, they got married.  The longed-for State of Israel was created on May 14, 1948, and Josef and Lili moved there to help build the nascent country and to start their family.  

Dr. Kleinman

Lili and Josef are the "two dear parents" of Dr. Michael Kleinman, York Hospital ER physician. Dr. Kleinman said of his parents; “They rarely talked about the horror they saw and were not bitter.  Instead, my parents were protective of me and my sister.  (They were) nurturing, but not stifling.”  This awareness of their actions instilled in him a strong desire to be kind and fair to others.  He did not want to see “the other side of humanity” that his parents had witnessed and lived through.  

They often reminded him to “never forget” the Golden Rule.  The traditional Jewish version of this foundation for all ethical conduct is, “That which is hateful to you, do not do to your fellow.” He said that this deeply-felt belief steered him in the direction of providing service to his community. “And so the path of medicine became clear,” he offered.

“How did you decide to become an emergency room doctor?" I asked

He went to the Des Moines University College of Osteopathic Medicine and graduated in 1979, and after his internship, he went into a general medical practice with Dr. Kieren Knapp.  He enjoyed this, and after seeing patients in the office he spent some time “moonlighting”  in the Emergency Department at the York Hospital. 

How could Dr. Kleinman work in an ER without special training?  

Through the early years of the last century (did I really just say that?) and into the 1970’s the ERs were typically staffed by a general surgeon, a general internist, or a general practitioner

Busy Hectic ER Team

who called in specialists when they required help.  Over time, and seeing the need for improved care, and the benefit of specialization, the American College of Emergency Physicians was born on August 16, 1968, by eight maverick physicians in Lansing, Michigan.  The first dedicated ER Residency program was started in 1970 and the American Medical Association quickly recognized emergency medicine as a distinct specialty in 1972.  

Early in his career, Dr. Kleinman experienced this change in approach firsthand; emergency physicians became specialists.  Falling in love with the experience in the ER and the privilege of taking care of a wide variety of patients, Dr. Kleinman realized that if he was “going to do this” he had better get further training.

Dr. Kleinman did his emergency medicine residency training at Memorial Hospital in York, the first such program in the county.  He completed this in 1982 and received his certification in 1984. With a broad smile, he said, “My certificate is number 11.  I treasure this."  Following this, he and several other physicians including Drs. Ron Benenson, Merrill Cohen, Dave Eitel, and Lynn Jensen developed the program at the York Hospital in 1988.  What did he and the others need to know?

An excellent Wikipedia entry (1) notes: "The emergency physician requires a broad field of knowledge and advanced procedural skills...They must have the skills of many specialists--the ability to resuscitate a patient, manage a difficult airway, suture a complex laceration, reduce a fractured bone or dislocated joint, treat a heart attack, manage strokes, work up a pregnant patient with vaginal bleeding, stop a severe nosebleed, place a chest tube, and to interpret (imaging studies).  They also provide episodic primary care to patients during off hours and for those who do not have primary care providers" (whew, that was a mouthful!).

“After all of your years in practice was there, maybe, a single event that especially moved you?" I asked.

"As an intern, all the patients affected me equally,” he said.  Yes, they were all important to him.  But, he went on,“I clearly remember this one patient, a young woman in her early thirties with metastatic ovarian cancer.  She was married with two small children.  She was admitted to the hospital and never left.  She died quickly.  There was nothing we could do. This was in 1981 and there were no tools to help her back then, and I remember feeling so helpless." 

"That was me in 1981, but I lived, I left the hospital," I said, frozen in fear.

I asked Dr. Kleinman to repeat the story, and he did.  Though he was taken off guard by what I had just told him. Yet, I still couldn’t take in what he was saying. When I listened to the recording of the interview later I was jarred by my deafness.  Why did I not hear what he said? I don’t know. (I guess that’s why doctors learn to repeat themselves, repeat themselves, repeat themselves.)

Calvin and Hobbes

Yes, denial.  "Something horrible happens, and our mind plays tricks on us, tells us that it never happened, that it occurred differently than it really did, that it isn't quite what it seems.”  This often works for what has happened in the past. According to Dr. George E. Vaillant, “such trickery can reveal the mind at its most creative and mature, soothing and protecting us in the face of unbearable reality, managing the unmanageable, ordering disorder...putting out in the world what was not there before."  But in the ER the truth must be faced directly; denial is a poor option.

Dr. Kleinman knows this.  In his decades of work, how many thousands of times has he had to give unwelcome news to his patients?  How many times has he imparted unbearably sad information to loved ones?   How many times has he been forced to give up and admit failure?  That Josef will not find Lili.  But how many more thousands of times have things turned out well, much better than expected?   

Maybe, like the Swedish diplomat Raoul Wallenberg or Oskar Schindler, he is just trying to

One of many such plaques

save as many souls as possible.

References:

1.   "Emergency Medicine." https://en.wikipedia.org/wiki/Emergency_medicine

2.  George E. Vaillant. The Wisdom Of The Ego. Harvard University Press, Boston, 1993.

by Anita Cherry 2/17/18

Pediatrician Dr. Nussbaum Says: "Yes, Listen to Your Mother"

Allen Nussbaum, M.D.

"I love kids, and I love watching them grow," said Dr. Allen Nussbaum, recently-retired York pediatrician.  During his 35-plus years of practice he watched carefully as mother and baby formed their unique and critical attachment.  He also observed the mother's overwhelming anxiety about being able to protect her baby, the baby she loves with a new version of loving she had not previously experienced.  He responded by allaying mothers' fears by calm reassurance, frequently saying to them, "You're a good mother, a good mom."  That was nice for us to hear.  

He told me that as a new mother, "It seems that everyone has advice for you."  Because this can be disorienting he said, "So pick one person for advice.  Read one thing on the Internet.  And pick one book on child-rearing.  Because if you don't, you will get confused."

Only one book?  Only one Internet site?  When he said this I was taken aback at first, but as I thought about it later I realized why.  

As I awaited the arrival of our adopted baby I started reading "What to Expect When You Are Expecting" (though I wasn't technically "expecting") and quickly put it down.  My husband was absolutely sure that Burton White's book on the first three years was the best, and we read the first chapter together and gave up (too much).  We knew that Dr. Spock was popular once but sorely out of fashion now.  

Lioness and Cub by Billy Dodson

But later, as I held our daughter in my arms and looked down at her and she looked up at me I realized that if I followed my mammalian biologic evolutionary heritage, and was fully present, and in the moment, and went by instinct everything would go the way it was meant to be.  Dr. Nussbaum was right.  

What is involved in the specialty of pediatric medicine, a specialty that, according to Dr. Nussbaum, must be a true calling?  James Hughes (in his "Synopsis of Pediatrics," 1979, p.1) states that:

"Pediatrics is the knowledge of genetics, for this governs the seed.  It is the knowledge of the events of prenatal life, for this is the soil in which the seed grows.  It is the knowledge of the newborn, the infant and the young child, for this is the early growth period.  And it is the continued scientific supervision of the child until he [or she] achieves maturity."

Gesell and Ilg 1943

Gesell and Ilg write that "in a biological sense the span of human infancy extends from the zero-hour of birth to the middle twenties.  It takes time to grow."   And that, "physical growth is a modeling process which produces changes of form, and at the same time preserves a basic constancy of form.  That is the paradox of all growth--the baby remains himself despite the fact that he is constantly changing.  It might even be said that he is never so much like himself as when he is changing!" ("Infant and Child in the Culture of Today," 1943, p. 15).

So our pediatrician has a unique window on how we become who we are, and who we will be.  

I asked Dr. Nussbaum if he could tell me what led him to want to be a physician?  Without hesitation he said, matter-of-factly, "My mother decided I would become a doctor."   In his nerve-wracking medical school interview he was asked this same question (of course) and he replied the same way, and, as he told me with no irony, "And they took me!"  He then went to Temple and did his Pediatric training at Children's in Cincinnati.

I wondered if he could recall for me some especially high or low moments in his nearly four decades of practice.

"Getting an 18-month-old through an exam without tears was job satisfaction."  Though this sounds like a particularly low bar it is more likely the mark of a caring physician constantly honing his craft.  Dr. Nussbaum paid close attention to seemingly simple things.

Where other physicians might be satisfied by responding to parents' questions in the middle of hectic office hours by texting he needed to hear their voices to gauge their needs, and he always called them on the phone.  If there was a problem at ten o'clock in the evening he told parents to meet him at the office.

"One of the saddest memories was of a baby with acute meningitis.  This was due to Haemophilus influenzae type b (a bacterial illness, not the flu)," he said.  She was diagnosed and treated fairly quickly but the disease progressed rapidly and she died.  Her tragic death and the terrible pain it caused stayed with him.  

The vaccine against Hib was introduced in 1985 and it is 99% effective in preventing disease.  Before it was available there were about 20,000 cases of invasive Hib disease yearly in the U.S. and 1,000 deaths.  In 2006 there were 29 cases.  In 2008 there were seven cases in Pennsylvania.  One child had only a single dose of the vaccine (three or four are needed); the others were not vaccinated at all.  Three of these children died.

Hib cases in England before and after vaccine

In light of his experience Dr. Nussbaum said, "This (vaccine) has been a blessing and I always give that shot first."   The Hib is, of course, one of an ever-lengthening list of recommended childhood immunizations that have saved millions of lives worldwide over the past 50 years including two to three million deaths yearly due to diphtheria, whooping cough, tetanus, and measles, according to the World Health Organization.  Vaccination is one of the great success stories in medicine; prevention is way better than cure.  

But what about people now who fear or mistrust vaccines, saying that such treatments are dangerous and not necessary and refuse to allow vaccination of their children?  He said, "There has always been a group of people that is against vaccinations of any kind."  He and his group wrestled with this dilemma.  He said that while parents have an "absolute right to decide what to do for their child" his practice, as a group, also has the right to follow their conscience and to refuse to treat such patients.  They were, therefore, nicely referred elsewhere. 

Though no longer in practice he remains part of the York community and he is still surprised when parents greet him around town and happily remind him of the pearls of child-rearing wisdom he gave them.  He thought that he was just imparting, in his words, "common sense."  Maybe we all need more of that.  

by Nguyen Thanh Bin

After thirty years the mystery of the long journey of reciprocal love that is parenting has become clearer to me.  A woman is rarely fortunate enough to be at the right time and the right place emotionally, fully prepared, when her baby is placed in her arms.  Parents, like children, are incomplete works and are always becoming who they will be.  The stage may be set, a home, a special room for the baby, a crib, and a box or two of diapers.  But the woman is new to her task and learns on the job.  As children develop they teach their parents that while parenting itself is a fully-natural job it is still maddeningly confounding!

I wonder what would have happened if, when I was developing as a child, I had listened to my mother, like Dr. Nussbaum listened to his?  What if we all listened to our mothers?

References:

1. Hughes, James G. Synopsis of Pediatrics, Fourth Edition. C.V. Mosby, 1975 
2. Gesell, Arnold and Ilg, Frances Infant and Child in the Culture of Today. Harper and Brothers, 1943

Dr. John Manzella's Microbial World

Dr. John Manzella

So, say you are in the seventh grade and the assignment is to write a book report on a famous person. And say this is the late 1950s.  And maybe your favorite uncle was a doctor.  And maybe your uncle miraculously cured your mother’s “quinsy” (a painful abscess next to the tonsil)  a few years ago.  And maybe you were bowled over by that.  Well, you go to the school library and you look for a biography that engages your interest.  If you are John Manzella you read about Louis Pasteur and you think, “This guy is really cool!”  

A Children's Book

The French microbiologist (1822-1895) was the first to blame micro-organisms for spoiling of beer, wine, and milk.  He found that he could prevent this, and the economic losses it was causing, by heating the liquids.  Hence...pasteurization.  

In 1859 (the year of Darwin’s “On the Origin of Species”) he proved the “germ theory” by showing that a heat-sterilized liquid without further exposure to the air remains sterile (that is, life only comes from life).  He created vaccines for prevention of rabies and anthrax.  When he claimed that microbes spread diseases among humans the scientific community was skeptical.

Dr. Manzella didn’t tell me what grade he got on his book report (we will assume it was an A+) but it had a lasting impact.  In high school he liked biology and in medical school he, in his words, “became totally smitten with microbiology."  He attended Canisius College (like his uncle) and went to the SUNY University at Buffalo medical school.  He moved away from snow and went to  the University of North Carolina for residency training in internal medicine (and for basketball).  Two of his most impressive attendings were infectious disease specialists.  The emotional and intellectual connection could not be ignored and he took a fellowship in infectious diseases.  

He joined the York Hospital staff in 1979 and enjoyed his practice as he diagnosed and treated acute infections.  Infection control including rigorous hand-washing was stressed, and all was well.  But then something happened.  

Dr. Manzella faced a frightening situation as young men, men close in age to him, were struck with infections that were not supposed to occur in formerly-healthy individuals. The appearance of AIDS in 1981 forever changed his practice.  Several very intense years ensued as patient after patient suffered and died without explanation.  But in 1984 Dr. Gallo with the NIH and Professor Luc Montagnier from the Pasteur Institute in France (there’s Louis again!) shared in identifying the HIV virus causing AIDS, and there was hope.

However, there was no treatment for the underlying immune deficiency until 1987 when AZT was taken off the shelf and repurposed.  Dr. Manzella was hugely gratified that “something” could now be done.  As he cared for individuals with a chronic viral infection the long-term relationships changed him.  This was, he noted, the most singular experience he had in his life in medicine.  

After highly-active antiretroviral therapy became available in 1995 HIV truly became a “manageable” illness.   But where had this threat to society come from?  

Drop in Deaths after HAART

HIV/AIDS is a zoonosis, an infectious disease caused by an organism that changed and made the leap from a non-human animal host to a human victim.  The HIV virus evolved from a virus infecting chimpanzees in West-Central Africa.   

Zoonotic diseases can be due to viruses, bacteria, fungi, protists, parasites, worms, or misfolded proteins called prions.  They include scary things like rabies, Ebola, Zika, SARS,  MERS, Mad Cow, West Nile, plague, and bird flu, but also common food-borne salmonella and certain E. coli infections.  Zoonoses are fostered by our close connections with the natural world, with other living creatures (as exhaustively reported in David Quammen's "Spillover").

"Spillover" 

Lyme disease is another zoonosis endemic in our area and many of us know someone touched by it (or the fear of it).

One early summer day about fifteen years ago my husband had a circular red rash above his belt-line; he recalled no tick bite but it was itchy.  He had not been in the woods or around deer and he didn’t feel sick, but I said (with absolutely no experience to back it up), "You have Lyme disease!"  

He looked at a photo of the typical bull‘s-eye rash in one of his medical books and thought it dis not quite match.

Bull's eye rash of acute Lyme infection

But by the third day he was not feeling so great and I made an appointment for him to see Dr. Manzella.  He resisted (of course) but he listened and he was immediately put on doxycycline for three weeks.  No blood testing was done since he was seen early, before the diagnostic (IgM) antibodies would appear.   

Within 24 hours the spirochetes responsible for the sickness were being killed off and he developed fever, chills, shaking, and muscle pain of the so-called Jarisch-Herxheimer reaction, confirming Dr. Manzella’s clinical diagnosis.  We were relieved.  But my husband was still achy and tired for about two months.  Adequate treatment, we are told, almost always eradicates the disease, but it took time to feel better.  What if the rash is missed and treatment is delayed?  What then?  

I asked Dr. Manzella.  With early widespread infection, there may be nervous system involvement with headache, stiff neck, and facial paralysis.  There may be a heart arrhythmia, or acute arthritis (usually of the knee).  The neurologic and cardiac problems resolve with the standard treatment of two to four weeks of antibiotics.  But the joint symptoms may remain troublesome for a few years despite therapy, even though bacteria are no longer found in the joint.  Why do people then talk of chronic Lyme?     

Dr. Allen Steere (who was the first to identify Lyme disease in 1976) in a recent review notes that “In about 10% of patients with erythema migrans (the rash), and perhaps a higher percentage of patients with neurologic Lyme, fatigue, cognitive complaints, and musculoskeletal pain can persist for more than six months, or even years, after antibiotic therapy.”  He notes that placebo-controlled, randomized treatment trials of antibiotics (the gold standard) in patients with this syndrome have not demonstrated clinical benefit, and that evidence for the persistence of infection has not (to date) been found (Steere 2017).  

Dr. Manzella said that he is in agreement with these thoughts, conclusions also supported by the Infectious Disease Society of America.  He warns that prolonged antibiotic therapy has substantial risks including the development of resistant organisms, the nasty C. diff diarrheal syndrome, and indwelling catheter-related infections.  As Dr. Steere says, “Additional studies are needed to better understand the pathogenesis of persistent symptoms and to determine the best approaches for symptomatic relief.”  We don’t have all of the answers, and we need to be careful while we are looking for them.

(For example, a pending legal suit against the CDC argues that it suppressed a DNA test for Lyme that is many times more sensitive than the ELISA and Western Blot tests that are

currently used. The scientific community is still grappling with the limits of the technique and we need to be patient as we wait for the answer.)

So how did my husband get his Lyme?  In the garden.  We “knew” of "deer ticks" and the local deer problem, but it turns out that it was the black-legged tick carried by white-footed mice that transmitted the bug.  The busy housing construction in our neighborhood disturbed their natural habitats and they ended up invading our property.  Or did we invade theirs?  

Where will the next zoonosis come from? And will we be able to manage it? And who will be there to help us? 

Maybe somebody who is busily writing and stressing over a middle-school book report.  

By Anita Cherry 1/27/18

Addendum for those of us worried about ticks and acute Lyme disease (having weathered the expected zoonotic pandemic), the Infectious Disease Society of America, the American College of Rheumatology, and the American Academy of Neurology note:

We recommend that prophylactic antibiotic therapy be given only to adults and children within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk (strong recommendation, high-quality evidence). Comment: If a tick bite cannot be classified with a high level of certainty as a high-risk bite, a wait-and-watch approach is recommended. A tick bite is considered to be high-risk only if it meets the following three criteria: the tick bite was from (a) an identified Ixodes spp. vector species, (b) it occurred in a highly endemic area, and (c) the tick was attached for ≥36 hours. 

From: AAN/ACR/IDSA 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clinical Infectious Diseases, Volume 72, Issue 1, 1 January 2021, Pages e1-e48. (A reliable and complete reference,)

AC and SC 4/12/24