Being an internist, I rarely wrote about surgery as I am not comfortable
in writing something I am not familiar with.
This is probably why Dr. Thomas Starzl was never mentioned in this blog.
This is to show how great this transplant pioneer is from the
perspective of an internist, not encompassing the breadth and depth of his contribution
to humanity in general and medicine in particular. The transplant surgery stimulates and propels
the advance in almost every field of medicine.
The development of the University of Pittsburgh Medical School can be
safely said to be in two stages: The period before and the period after Dr. Thomas Starzl.
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| Dr. Thomas Starzl and Dr. Chao-Long Chen: The mentor and the protege |
“One of the great biomedical
scientists of the century”
Although Dr. Starzl is often called a great transplant surgeon, the
father of liver transplantation, but Dr. Francis Moore (the former President of
American College of Surgeons, sometime a fierce competitor/rival in the
transplant profession) said of Dr. Starzl, “he is much more than that. He is one of the great biomedical scientists
of the century. He emerged virtually to
stand alone in the breadth of his study, and in the depth of his scientific
penetration.” If one reads some of his
articles in the New England Journal of
Medicines and doesn’t know who he is, one would think he must be an expert
in immunology, and he is, indeed.
Dr. Starzl left Northwestern University Medical School for University of
Colorado Health Science Center in 1962 with a determination to pursue liver
transplant, at which time he began to test the use of Imuran (azathioprine) with
or without Prednisone for rejection on animal transplants.
He made a strategic decision to concentrate on animal kidney transplant
as the liver transplant in dog was technically too difficult then, he wouldn’t
attempt liver transplant in dog without succeeding first with kidney transplant
with immunosuppressive therapy with Imuran and Prednisone.
“Let a genie out
of the bottle”—establishing a standard protocol of immunosuppressive therapy
A group of about 25 transplant experts (among them Dr. Joseph Murray who
performed the first kidney transplant between identical twins in 1954, for
which he was awarded a Nobel Prize in Medicine in 1990; Dr. Murray worked with
Dr. Francis Moore at Peter Bent Brigham Hospital then) gathered in a “National
Research Council” conference in 1963; it turned out to be a watershed event.
It was a very gloomy report, the kidney transplant outcome was terrible;
among about 200 recipients, only 10% lived beyond 3 months and only 6 lived a
year. Even Dr. Murray had only one
patient survived beyond 6 months with Imuran.
The experts felt the kidney transplant was not justified and about to
call it quit. The gloom mood of the
conference was then dispelled by Dr. Starzl’s presentation reporting an 80%
success of his 30 patients, which is more surviving patients than all the world
experts combined, leading to a transplant surgeon from Harvard to say “it is
like letting a genie out of the bottle.”
Many of the conference attendees followed him after the conference to
Denver to learn his method and his Imuran-Prednisone regimen became the
standard immunosuppressive protocol for the next two decades.
I cannot emphasized enough that though a skilled and innovative surgeon
he is, his other non-surgical contribution to this field is enormous and beyond
measure. He is a transplant surgeon with a knife and a mind. It is less well known that “the father of
liver transplant” (a “new kid in the block” then) also single-handedly saved
the fate of kidney transplantation.
Dr. Thomas Starzl: a man of conviction, of courage and of perseverance
The story of Dr. Starzl’s liver transplants in the early days (1963 to
1967) was not rosy. His first patient died on the operating table; the way he
described the case in his autobiography, The
puzzled People: Memoirs of a Transplant Surgeon, was touching. The next four patients all died of either
hemorrhage or infection. He had
self-imposed moratorium of three years, during which he refined the surgical
technique on animal studies. The break
came in 1967 (or 1968) when he had the first successful liver transplant. He had many successes during Imuran era (1967
to 1979), but the success rate was only 50%.
Losing the recipients to death, Dr. Starzl said it is “a tough pill to
keep swallowing.”
Starzl rescued Cyclosporine
and Tacrolimus (Prograf)
When Cyclosporine came along in 1979, about the time he moved to
University of Pittsburgh, it greatly reduced the rejection and improved the
outcome. But Sandoz has made a decision
to take it off the market because of its great toxicity. Dr. Starzl demonstrated that it Cyclosporine
can be safely used at a reduced dosage in combination with Prednisone. The similar story happened in Tacrolimus
(Prograf); he endured all sorts of criticisms and strain.
It is through his assiduous perseverance (and that of Dr. Roy Calne--see below) that led to FDA approval of
Cyclosporine in 1983 and Tacrolimus in 1994.
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| Dr. Starzl and Dr. Calne shaking hands: Lasker Award |
Dr. Thomas Starzl
and Sir. Roy Calne: The trans-Atlantic alliance
Like Dr. Starzl, Dr. Roy Calne of Cambridge University in England is the
father of liver transplant in Europe.
They both began with kidney transplant.
They both pursued and perfected the anti-rejection therapy relentlessly. Dr. Starzl spent his sabbatical in London in
the summer of 1975, during which he went to see Dr. Calne in Cambridge. In his The
Puzzle People, Dr. Starzl wrote, “. . . the fate of liver transplantation
would depend upon an unspoken trans-Atlantic alliance between Cambridge and
Denver without which further efforts would not have continued, much less succeeded,
on either side of the ocean. These
mutually supportive moral and scientific bonds pulled liver transplantation
into the mainstream of medical practice but not until the decade was
finished. By then, Calne had been
knighted.”
It is fitting that Dr. Starzl and Dr. Calne shared the prestigious Lasker
awards (a Nobel precursor or America Nobel) in 2012.
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Dr. Chao-Long Chen
at “Dr. Starzl’s exhibit” in Senator John Heinz History Center
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Quit surgery, but
never retired from research
Dr. Starzl not only established a new field of liver transplantation,
but also trained numerous surgeons from all over the world. After the coronary artery bypass surgery he
stopped doing transplant surgery in 1990 (or 1991) at age of 65, but continued
to very actively pursue and supervise the research.
I recall reading an article of “Graft and Host, Together Forever” in Scientific American (2007), which was
about the concept of what Dr. Starzl called microchimerism that explains why
patients’ bodies were able to accept foreign tissues. He theorized that cells from donated organ
infiltrate tissues and organs throughout the recipient’s body, causing it to
begin accepting the new tissue as its own.
The sacrifice and
peril of a dedicated transplant surgeon
In his The Puzzle People, Dr.
Starzl wrote about his divorce from his first wife, Barbara, “The marriage had
lasted for almost twenty-two years before Barbara’s forbearance ran out. Her rival, Mistress Surgery, had been too strong.”
In his autobiography, In Search of
Memory, Dr. Eric Kandel (the 2000 Nobel laureate in Medicine for his
elucidation of the molecular biology of memory) wrote that in one of the family
gatherings, he apologetically said he probably could only get a grade B as a father due
to the demand and devotion of his research work, his daughter said, “dad, that is grade inflation!”
When the children were out of school in the summer of 1975, Dr. Starzl
brought the whole family to London for his sabbatical. He must have struggled mightily to balance
his family life and the demand of his work.
He wrote “the second priority for the sabbatical was to review with
Porter the reasons for success or failure in each of the first ninety-three
cases of liver transplantation in Colorado.”
He bicycled with his son from London to Cambridge to meet with Dr.
Calne.
In his autobiography, For the Love
of Enzymes, Dr. Arthur Kornberg (The Nobel laureate for his discovery of DNA polymerase) wrote that when he went to NIH, he stopped
by NIH first before going to his new home, just to say hello to his future
colleagues. Once inside NIH he forgot
about his wife and children who ended up waiting outside in the car for the
whole afternoon.
桃李滿天下
What prompted me to write this post is the occasion of the 90th
birthday party for Dr. Starzl, which was held at the UPMC Club Lounge at Heinz
Field in the evening of March 12. I do
not have the details of the party at the time of this writing, but I know there
are more than 200 transplant surgeons from all over the world “coming home” for
the celebration; Dr. Chao-Long Chen (陳肇隆醫師) from Taiwan is one of them. The fellow reunion took place in the evening
of March 11.
In the fellow reunion (March 11) Dr. Starzl expressed his gratification
and pride for the accomplishment of Dr. Chao-Long Chen. Dr. Starzl has followed the work of all the
surgeons he trained over the years.
1926 Chateau Grand Corbin Despagne 謝師酒
Dr. Chen presented a very precious and thoughtful 90th
birthday gift to Dr. Starzl: an extremely rare 1926 Chateau Grand Corbin Despagne.
The accompanied beautifully written greeting card summarizes
what this giant and legend in medicine is all about and why this celebration is
“a special and momentous occasion. There is an air of jubilation and a galaxy
of experts from transplantation field has descended to witness this gala
event.”
Some years ago we gave 100 one-dollar coins for the 100th
birthday gift to our neighbor, Dr. Greenlee, a Mayo Clinic trained surgeon,
with a card, saying “How much do we love thee, Let us count the ways/coins . .
.”
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| Presenting the precious and thoughtful birthday gift: Protege to Mentor |
名師出高徒: Dr. Thomas Starzl
and Dr. Chao-Long Chen 陳肇隆醫師
Dr. Starzl
moved to the University of Pittsburgh in 1981 and the ensuing ten years was his
most active period of doing transplant surgeries in a furious pace; more than a
dozen a week or more than 600 cases a year.
It was at this time that Dr. Chao-Long Chen came to train with Dr.
Starzl. Dr. Goran Klintmalm, head of the Baylor Regional Transplant
Institute in Texas, once said Dr. Starzl “had an extraordinary ability to spot talent, and if you didn't have that talent, you were out.” If one
didn’t have what it took, one couldn’t survive the training. It must be a gratifying and hilarious feeling
to have Dr. Starzl as a mentor.
Dr. Starzl
and Dr. Chen is the best example of 名師出高徒. After graduating from Kaohsiung
Medical University, Dr. Chen had his surgical training at Chang Gung Memorial
Hospital in Taiwan and the Hospital for Sick Children in Toronto, Canada. He then trained in liver transplantation with
Dr. Starzl at the University of Pittsburgh in 1983.
Accomplishments and awards
Dr. Chen
performed the first successful liver transplant in Asia in 1984 and has since
done more than 1,500 cases. He did the first split
liver (one donor liver to two recipients, such as larger right lobe to adult
and smaller left lobe to child) transplantation in Asia in 1997 and performed
the first pediatric living donor liver transplantation in 1994 and the first adult
living donor liver transplantation in 1999 in Taiwan. He has been the foremost in many surgical innovations of
liver transplantation in Asia; he performed the first dual graft (such as two
adult smaller left lobes to one recipient) living donor liver transplantation
in 2002, and the first segment 2 monosegment (I believe this applies to small
infant recipient) living donor liver transplantation in 2013 in Taiwan.
Dr. Chen indeed is the father of liver transplant in Asia; Dr. Starzl of
Taiwan/Asia.
Dr. Chen has published more than
440 SCI-cited scientific articles, has lectured in more than 280 international
congresses, and has received several honorary and visiting professorships. He
is an associate editor of the American
Journal of Transplantation and serves on the editorial board of several
journals, including Annals of Surgery, Transplantation and Liver
Transplantation.
He was appointed as Superintendent
of the Kaohsiung Chang Gung Memorial Hospital in 2003 and became Superintendent
Emeritus in October 2015. The list of
his awards and accomplishments is as long as your arm.
It is no
surprise that Dr. Chen was recently appointed to the prestigious and
influential Advisory Board of Center for Asia Pacific Policy. He is one of the
two from Taiwan to join this USA based institute.
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| Joy Starzl (wife of Dr. Starzl), Dr. Starzl and Dr. Roy Calne (speaker) in Pittsburgh |
Dr. Starzl “had an
extraordinary ability to spot talent,” whether it is a surgical scalpel or a
kitchen knife
Dr. Chen
reminisced an unforgettable event when he was trained with Dr. Starzl in
1983. One day Dr. Starzl asked him to
cook for a birthday party for his wife, Joy, saying several friends will come;
the number increased to “may be 25 people”, and a day before the birthday, Dr.
Starzl announced there will be 100 people more or less. Dr. Chen hurried to Shiow-bih’s (Dr. Chen’s
medical school classmate) home to grab every pot and pan. The party was a great success. Dr. Chen (then not married yet) said his wife
never believed he could cook for more than 100 people.
As I said earlier that Dr. Starzl “had an extraordinary
ability to spot talent,” whether it is a surgical scalpel or a kitchen
knife. It might have become a “folklore” among international transplant
community, as Dr. Barry Kahan, Professor and Director of Immunology and Organ
Transplantation at the University of Texas Medical School at Houston, asked Dr.
Chen when he visited Taipei in 1990 whether he knows who was that famous
“
master cook”.
The
photo below shows Dr. Starzl apparently still had fond memory of the event when he autographed his
Memoirs of A Transplant Surgeon (
The Puzzle People) to Dr. Chen twenty some years ago.
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| Dr. Chao-Long Chen and his medical school classmates |
The pleasant
unexpected side trip
Thanks to Shiow-Bih’s (秀碧) kind and considerate arrangement, Dr. Chen was able to meet with
several of his classmates (林琪雄醫師, 王明仁醫師 and 廖泓淼醫師) coming from New Jersey, Toronto
and Washington D.C., reminiscing good old medical school days. Dr. Chen also met some of the people he made
friends with when he was in Pittsburgh in 1983. He was grateful that 黃呈昌夫婦 were
able to drive him around to Phipps Conservatory and Botanical Gardens, Senator John Heinz History Center and
Thomas E. Starzl Transplant Institute during his spare time before the fellow
reunion.
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| 陳肇隆醫師 黃呈昌夫婦 |
能者多勞 前人種樹,
後人乘涼,
為後人造福
Burdened with the administrative work of the superintendent
of a 2,745-bedded hospital managing the affairs of a very busy liver transplant
program, Dr. Chen has been abroad more than twenty times a year, with the
purpose of giving lectures, surgical demonstrations and help establishing liver
transplant programs across Asia and Central and South America, or receiving
medals, award and honorary doctorate. Despite such a busy schedule he still
managed to plant more than 5,000 of the 9,000 trees around his hospital.
The Chinese idiom of 前人種樹, 後人乘涼 means planting trees is to benefit the generations to come. Being a pioneer of liver transplant in Asia
and training so many surgeons, Dr. Chen is also “planting trees” as a
transplant surgeon, not only benefitting his patients, but also elevates and
advances the level of care in his hospital in years to come.
創造1400個重生奇蹟 : 新肝情願 2
It is very kind of Dr. Chen to give me his autographed book (創造1400個重生奇蹟 : 新肝情願 2),
unfortunately, we’re in a hurry to leave and the book was left behind at
Shiow-Bih’s house, otherwise I would have more story to tell about the father
of liver transplant in Taiwan/Asia. Now I have more incentive
to visit Rong-Chung and Shiow-Bih soon again to get the book,
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| Dr. Tsai Dr. Chen |
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| 陳肇隆醫師 黃呈昌夫婦 陳飛 |
