Heritage Snapshot Part 74

The only possibility for babies with hypoplastic left-heart syndrome to live a really normal, active life, Dr. Leonard L. Bailey thought, would be a heart replacement. What about animal hearts? (Fifty thousand valves made of calf- and pig-heart tissues were used to replace faulty human-heart valves every year.) But animal hearts had been tried unsuccessfully in adults on four occasions, the first time by Dr. James Hardy, on January 23, 1964, at the University of Mississippi. He transplanted the heart of a chimpanzee into the chest of a 68-year-old man in a last-ditch effort to save the man’s life. But the patient was too weak and died almost immediately. Controlling rejection is usually the greatest challenge in managing a patient following organ transplantation. Rejection in a cross-species transplant would be even more difficult to control than in most human-to-human transplants. Earlier, Bailey had become aware of the possibility that the immune system in newborns may be somewhat immature. If true, a newborn would be less likely to reject a transplanted organ—even a cross-species transplantation—than would an older patient. Bailey set up a research laboratory with financial support from 40 fellow surgeons who donated monthly for seven years. Results were exciting. His studies documented that newborns (at least in animals) indeed had immature immune systems. Also, since those four failures in human cross-species transplantation in adults years before, scientific research—particularly in immunologic testing, immunosuppression, and pre- and post-surgery management techniques—had taken enormous strides. Tissue typing and cross-matching, sophisticated laboratory analyses of both functional arms (humoral and cellular) of the immune system, development of a more selective agent (cyclosporine) to suppress the immune response to foreign tissue, coupled with laboratory techniques to measure blood levels of this agent (radio-immunoassay and “high performance” liquid chromatography), paved the way for greater expectations in cross-species transplantation. Since 1981 Bailey and his transplant-research team had been gradually applying each of these developments to intense, ongoing research in newborn and infant-heart transplantation. He and his laboratory associates had demonstrated unprecedented positive findings among groups of newborn animals, primarily goats. This research documented that: (1) newborns are generally more tolerant of heart transplants than are adults, (2) transplanted newborns may grow to reach full, healthy maturity without additional surgery, (3) immunosuppressive medications may be well tolerated by newborns and infants (in many ways better than by adults), (4) newborns on experimental drug protocols with unmatched cross-species hearts had survived for up to nearly six months (half-grown), and (5) infection and drug-related tumor growth may be less problematic following heart transplantation during newborn life. In addition, new immunological and biochemical data from the Loma Linda Surgical Research Laboratory strongly suggested that there was good reason for optimism for successful human/subhuman heart transplantation in newborns. After six years of research, Bailey initiated an effort to begin clinical trials. Six to eight babies a year died at Loma Linda University Medical Center from hypoplastic left-heart syndrome. In a university setting, support for such a project is not easily acquired. Approval from the University’s Institutional Review Board (IRB) was mandatory. The IRB, a group of local professionals from a variety of disciplines (some from the community, having no other connection with the institution), would look at the ethics, as well as the scientific merits, of the procedure. Many other people had to be convinced: the Medical Center administration, the Medical Center’s medical ethics committee, the standing transplantation committee, an ad hoc neonatal cardiac transplantation committee, the executive committee of the medical staff, the School of Medicine administration, an advisory committee to the vice president for medical affairs, the department of surgery, the department of pediatrics, the department of anesthesia, the Loma Linda Center for Christian Bioethics, and, ultimately, the University’s board of trustees. These people wrestled with every conceivable objection. They recommended changes in the protocol and on the consent form. They also recommended that respected external scientific consultants be invited to evaluate the project. Through it all, Bailey was gracious and understandingly patient. Scientists from Stanford University, the University of California at Los Angeles, and Albert Einstein College of Medicine in New York were supportive. The results of additional recommended laboratory studies were very encouraging. Dr. Richard Sheldon, chair of the Institutional Review Board, was in close communication with committee representatives and Bailey. Eventually there was consensus. After 14 months of discussion, the groups became convinced that the groundwork had been well laid, that the time had come to move from laboratory to clinical trials, that respected external scientific consultants supported the project, that the procedure emphasized therapeutic intent, and that they should not delay human studies any longer. Confidential Institutional Review Board approval was awarded by majority vote. Approval of the surgery had been an agonizing process.