Part XII- Cross-species Organ Transplantation – Standing On Tall Shoulders The History of Cardiac Surgery Thomas N Muziani PA-C, CP

“Medicine is magical and magical is art- Thinking of The Boy in The Bubble- And the Baby with the Baboon Heart”- “The Boy in the Bubble”- Graceland- Paul Simon-1986

Late in the evening of 23 January 1964, in an operating room of University of Mississippi, Dr. James Hardy, Chair and Professor of Surgery, was confronted with a dilemma on his operating table. His patient, Boyd Rush, was dying before his eyes. The inferior wall of Mr. Rush’s heart was not moving, and no repair was going to save this man. Upon consulting with his colleagues in the operating room, a consensus was reached, and they decided to proceed with the only viable alternative available to them. The implantation of a chimpanzee heart into Mr. Rush. The “new” chimp heart continued to beat for 90 minutes but would not tolerate any workload nor being weaned from the heart-lung machine. The Pathologist at U of M discovered on post-mortem that the chimp, who was old, was also suffering from severe coronary artery disease. In hindsight, the chimp was a poor candidate…to provide life for Mr. Rush… and to make history.

The repercussions for this valiant effort to save a person from certain death by implanting a cross-species organ, the only donor organ available, was swift and in no way kind. The cardiac community, which was rather small at the time, did little to defend Dr. Hardy’s actions.

During the 1960’s and 70’s, the thought of performing pediatric cardiac transplantation was merely academic and solely discussed in the classroom or laboratory. Baby donors were just not available. No registry had yet been implemented as a center for procurement, and the issues of rejection and immunosuppression of the donor’s heart were not fully understood and appeared insurmountable.

Then, an extremely bold and visionary surgeon, Dr. Adrian Kantrowitz of New York City, New York, performed the first human-to-human heart transplant in the United States…on a newborn baby, in 1967. Dr. Kantrowitz along with a young, dynamic surgeon on the West Coast of California, Leonard Bailey, understood there was an urgent need for pediatric transplantation…especially for babies with broken hearts.

The concept of cross-species organ transplantation was certainly neither new nor novel. In literature, it always seemed to embrace a sinister aspect. In medicine, it was usually performed with a quiet routine with the intent of finding a viable alternative for available organs. Dr. Keith Reemtsma, while at Tulane, transplanted chimpanzee kidneys into several humans during the 60’s. His patients actually recovered fairly well. One patient survived for nine months and became somewhat mobile. Please keep in mind, very little was known or understood about how to suppress the immune system and the nuances of treating transplantation patients. What medications that were available at the time, were arcane and rudimentary in formulation.

Dr. Leonard Bailey of Loma Linda University reflected on his dreams and aspirations as a young man; “While I was still in training, I had already made up my mind that someone needed to investigate transplantation in newborns. At that time, babies born with certain kinds of exotic heart disease weren’t even treated-they were set aside to die. And they uniformly did that.”

Dr. Bailey’s fascination with transplantation seemed to gestate after visiting a laboratory at Stanford while still in medical school. As a result, upon returning to the surgery department at Loma Linda, Dr. Bailey was able to convince the department to make funds available to rejuvenate and rebuild their old laboratory. Dr. Lou Smith, who performed the first organ transplant at Loma Linda had become so active clinically that he could not keep their old laboratory active and it had fallen quiet.

So Dr. Bailey hired some very talented technical people who brought the lab up-to-date and they collectively made the decision to start with goats. As Dr. Bailey explained: “We chose goats as recipients because, for one thing, they’re lovely little animals, easy to test, and smarter than most animals- and very hardy, as opposed to lambs, which aren’t nearly as tough. So lambs, at some level, became donors, and goats were always the recipients.”

“We would take a baby goat a few days old and do a heart transplant- orthotopic heart transplant- and that little goat would be jumping around the cage that evening. The next day, we would put it in the pens with other goats, and then in a week it would be back out on the farm with its transplanted heart. What we wanted to learn was how far it would go.”

“One of the greatest stimuli I had when I was studying pediatric heart surgery up in Canada was the awareness that the newborn immune system is indeed fairly special- it has very little of the aggressiveness of the older child or an adult. It has no experience, which helps. And much of the suppressor type behavior is still intact in the newborn.”

“So the possibility that a newborn could receive a graft and actually grow up without any immune suppression was curious enough. We were able to demonstrate close to that. We had a baby goat named Livingston who was transplanted as a newborn and grew to 6 months of age with no immunosuppression at all.”

“On average however, the transplanted goats without immunosuppression survived about two and a half months. Then they began a slow rejection process. So their immune system, we knew from that experience, were intact- they were just much more accommodating as newborns.”

Dr. Bailey continues: “A fellow by the name of John Borel, in Basil, Switzerland, was working for a pharmaceutical house. He had found a fungus-like substance out in the hills. His job was to study it and see if there was anything there that he could make a medicine out of. I think he was originally looking to see if he could find something that would be effective with allergies”

“But he began to study the immune properties of this substance and how it might alter the immune response in a host. It was pretty promising- something called cyclosporin. It was called cyclosporin-A at the time. I suppose they thought there would be a cyclosporin B, C and D.”

“Dr. Bailey reflects: “So this substance was being studied in the laboratories of the Swiss pharmaceutical house and by other laboratory investigators around the world. Here in the West, Stanford had access to it. I contacted John Borel- I’d met him earlier at a presentation I was making one time down in Texas. He agreed to send me some of this material.”

“We performed the transplants and treated them with cyclosporin all along. With that, they lived indefinitely. That was all it took. Cyclosporin-A became the mainstay of our immunosuppression.”