Part XIII- Dr. Leonard Bailey & Cross-species Transplantation – Standing On Tall Shoulders – The History of Cardiac Surgery by Thomas N Muziani PA-C, CP
“Success is not final, failure is not fatal: it is the courage to continue that counts” – Winston Churchill
In the late 1970’s and early 1980’s, the serendipitous revelation that Leonard Bailey and his team of researchers could resolve their immunosuppression issues for transplants which at first, seemed insurmountable…was cause for elation. The concept of transplanting a baby at birth and have that baby grow up with nothing more than receiving injections of cyclosporin-A was more than a little impactful. This was a sea change. The baby goats would go back to the farm, grow up and become big herd animals…and actually grow old. It became routine to witness, if they did not get into trouble, for the goats to actually die from old age. One of the older goats named Sigmund who was about 3 or 4 years old, managed to find the rubber glove supply. He devoured all of the rubber gloves and then proceeded to die of an intestinal obstruction.
As Dr. Bailey observed: “Well, how are we ever going to transplant baby humans? We don’t have a system for identifying potential donors; if we’re going to transplant them we’re probably going to have to start with cross-species. So we began to transplant lamb hearts into goats, and even pig hearts into goats with nothing more than cyclosporin-A as the lone immunosuppressant.”
With the success and growing confidence in suppressing the immune system of transplanted organs, the Loma Linda team turned their attention to studying potential donors for a human. They collectively agreed almost immediately that chimps, orangutans and gorillas would not be used, primarily because they were all considered endangered species. “We wouldn’t think of using an animal like that” Dr. Bailey continued. “But baboons seemed to have a life all their own; they’re extraordinarily plentiful. There are actually programs to control the populations in South Africa and places like that. They are hardy animals and reproduce easily.”
We all realized; “Now here’s a subject we can study.” The Loma Linda team soon discovered that more than 80 percent of the DNA in a baboon is identical to that of a human. The human leukocyte antigen (HLA) typing method is used to identify your tissue as being you and not your neighbor. Dr. Bailey reflected: “We discovered that we could actually type baboons. And, we discovered we could put baboon cells and human cells together and pretend to do transplants in the laboratory, and find out which baboon might be the most compatible with any one human’s sample.
“There were three or four important immunologic bench studies that we could do to select a baboon donor. The first thing we did was acquire some baboons. We contacted our friends in southwestern Texas at a huge primate center- probably one of the best, if not the best one on the planet. We told them what we wanted. We preferred female baboons. We did not want any male baboons growing up and tearing up the cages.”
“Sure enough, they were able to provide some juvenile female baboons. They would wean the baboons there and then ship them out to us. So, we had about a dozen of these juveniles that we called our donor panel. We did some other bench studies- for instance isolating a baboon heart and then perfusing that heart with human blood in an isolated heart preparation- and did the same thing with the goat and pig hearts. With the barnyard animals, none of the hearts functioned at all; the little baboon hearts functioned beautifully for 12 hours in that experiment.”
Dr. Bailey and his staff applied for Institutional Review Board (IRB) approval. As Dr. Bailey recalled: “It took 14 months from the time we started to when we received approval from the board. As I recall, Dr. Dick Sheldon was the chairman of the board at the time. He was a terrific ally- not that he was all for it, but he just did a really superb, objective job assessing and moving his board through the process.”
Dr. Bailey spoke on the IRB process: “We had to bring in external reviewers. We brought in a number of people to review the protocol and give us their opinions. These were prominent transplant people who were involved, and we had various opinions of course- some were somewhat supportive, some were not supportive at all.”
“One of the opinions was; ‘Why not?’ That opinion came from Dr. Sandra Nehlsen-Cannarella. And, she agreed to serve as our chief corresponding immunologist as we went forward.” “She told us she would be available- if we ever tried this clinically, she would be on the next plane and come out and help us. And sure enough, that happened. Ultimately, Dr. Bruce Branson (the former Chair of Department of Surgery) hired her and she moved from where she was in New York out here, and was here for a number of years as the Chief of Immunology.”
Eventually, the time had arrived when they were very close to starting. The protocol they adopted was to perform five cross-species transplants on newborns with hypoplastic left heart syndrome. As Dr. Bailey recollected: “I was stopped in the hall one day and one of our pediatric cardiologists, Dr. Gene Petry, asked: “You know Bailey, how’s that protocol coming? I happen to have a baby in the nursery now with this problem. Are you interested?” I said: “Well, let me do some checking.” I got back to him and said: “Yes, I think we are.” He said: “Well, I’ve discharged the baby home to die. The baby and her family live up in the high desert (Antelope Valley, CA). I’ll have someone contact them and see if they are interested.”
Dr. Doug Deming, a neonatologist at Loma Linda contacted the mother and said: “We have this protocol that’s never been tried just like this before. Do you have any interest?” They asked to think it over and discuss the issue within their family. When they phoned back they expressed an interest and that they’d like to talk about it more. We invited them to come down- we spent hours actually in discussion. Part of the protocol meant that they had to sign a form saying they were interested and would give us consent to go forward.
After the first meeting, they indicated they wanted to go forward with it. The baby was up in the desert and beginning to die. They brought the baby back down. We did what we needed to do, which, in those days, wasn’t very good, to try and keep the baby alive. The assays comparing the baby with the baboon panel were supposed to take only a week, but on the sixth day or so of this effort, the baby was clearly going to die that day. The tests identified a baboon as most compatible, and that little baboon was set up to become the donor.