Cyclosporine brought the liver transplants out of dark age: The stories related to Professor Jean Borel, Dr. Thomas Starzl and Dr. Chao-Long Chen (陳肇隆醫師院士)

My interest in history in general evolved from the interest in medicine in particular that began right after my residency training.  Recently I have been reading about the developments of liver transplant and monoclonal antibody.  Speaking of liver transplant, one cannot escape the story of cyclosporine.

In a 7/30/1981 New York Times report showing a stunning success of liver transplant, using cyclosporine (or cyclosporine A) to overcome the rejection of the transplant organ.  This report was based on a New England Journal of Medicine article of the same date.

In the NEJM article as well as NY Times article, Dr. Thomas Starzl reported 10 of the 12 persons survived one year after surgery or 83% (two died on the operating table).  The survival rate was 32% among the 170 liver transplants that he performed over the 17 years period before using cyclosporine.

Dr. Starzl performed the first liver transplant in a 3-year-old boy with biliary atresia in 1963; the boy bled to death on table.  He did five more cases of liver transplants in 1964; all died of hemorrhage or infection within 23 days of transplants.  This was followed by four years of moratorium.  Dr. Starzl began to use cyclosporine at University of Colorado before he moved to University of Pittsburgh January 1981.

The success of cyclosporine lies in the fact that it suppresses the body’s natural immunity so that it will not attack the transplant organ and yet it doesn’t hamper the body’s ability to fight off infections.

Cyclosporine was first used in 22 kidney transplants (survival rate of 85%) before it was used in liver transplant.  Dr. Roy Calne of Cambridge University was the first to use cyclosporine in liver transplant.  The development of cyclosporine was not all rosy and smooth, at one time Sandoz threatened to discontinue the project because of the toxicity to kidney.  Dr. Calne flew to Basel [where Sandoz based] and successfully appealed the decision, allowing an experimental supply to continue.  Dr. Starzl and Dr. Calne shared the 2012 Lasker Award.

Speaking of cyclosporine, it would be remiss of me not to mention Dr. Chao-Long Chen (陳肇隆醫師院士), the father of liver transplant in Asia/Taiwan.  After completing the liver transplant training with Dr. Starzl in 1983, he returned to Taiwan, at which time cyclosporine, not yet approved by FDA, was still an experimental drug.

Realizing there cannot be a success of liver transplant without cyclosporine, Dr. Chen, armed with a recommendation letter from Dr. Starzl, flew to Basel, Switzerland (where Sandoz is based) to apply for the use of the then experimental cyclosporine and was granted for the supply for five patients.

Dr. Chen had a photo taken with Dr. Borel then and again had a photo taken with him in October 2016, 33 years and more than 1,500 liver transplants later, when Dr. Chen was invited to give a talk at the prestigious 15^th Borel-Stӓhelin Lecture, named in honor of Dr. Jean Borel.  Dr. Chen was the first non-European/American doctor to be granted for this honor.

In the late 1960s Sandoz discovered two strains of fungi in soil samples.  The fungi produced substance that they hope can be developed into antibiotic.  It was a fateful twist that Professor Jean Borel of Sandoz who discovered the substance can suppress body’s immune system in 1970-73 and eventually cyclosporine came into being.

Dr. Chen’s lecture at University Hospital Zurich on October 11, 2016 was “Perspectives on Liver Transplantation, Innovation, Education and Beyond”

(I gave a talk of liver transplant to the Taiwanese American community, this is the Power Point)

Dr. Starzl spoke at Dr. Borel’s retirement banquet in 1999; this is how Dr. Starzl began,

“THANK YOU, ladies and gentlemen, and especially Jean Borel. I am honored to be here, and especially by the chance to speak. More than a retirement banquet, we celebrate tonight and tomorrow the descent of a hero from Mt. Olympus. How you, Jean Borel, managed to scale such heights, and returned unscathed is a question to which I will return in a moment. But first, I want to say something about what your journey meant to me personally, and eventually to everyone else in this room, and in the world.”

After talking about the dismal outcome of liver transplants of 17 years prior to the era of cyclosporine came around, Dr. Starzl said,

“At the darkest and most unexpected moment, a mounted torch-bearer appeared in the distance. The torch was cyclosporine; the bearer was Jean Borel, and the horse was the Sandoz Corporation. How the next steps were taken by Roy Caine and his English colleagues is the material of legends. Suffice it to say, both the patients and those who cared for them were liberated from a terrible bondage. There have been improvements in treatment since then, and there will be more. None, in my opinion, will compare in magnitude to those that occurred between 1978 and 1980 as the result of Jean Borel's initiative.”

Professor Borel’s first love was art and that “allowed him to exercise the imagination and creativity of the artist in the pursuit of science. The result was vision.”

Dr. Starzl closed his remark very appropriately at a retirement banquet,

“As for Jean Borel, don't count him out.  There are pictures to be painted, music to be composed, and words to be written.  And there is still plenty of time.”

Cyclosporine brought the  liver transplants out of dark age.  Dr. Thomas Starzl felt he owed his career to Professor Borel’s ingenious and creative work on cyclosporine; this feeling, I think, must be shared by Dr. Chao-Long Chen.