LLUMC Legacy: Daring to Care
BABY FAE
Her story was beamed by shortwave radio around the world by the powerful Voice of America. It was telecast live, via satellite, into Australia. It was translated into Portuguese and was seen by 20 million people in Brazil. It prevailed over the 1984 United States presidential election. Unknown to her, Baby Fae waged a tug-of-war with our emotions--and she won.
Baby Fae's stretching and sucking, her yawning and blinking, brightened the nightly news for multiple millions of well-wishers. In just three weeks she was known and loved by more people than was any other baby in history. When she was shown listening to her mother's voice over the phone, she reached out and touched everyone. With the transplanted heart of a baboon, she made medical history as the first newborn recipient of a cross-species heart transplant.
Baby Fae raised the consciousness of the world regarding the shortage of organ donors and gave us a new appreciation for our own human worth. Her story stopped a woman from committing suicide and inspired a man to become an organ donor. Within 48 hours of deciding to be an organ donor, that man was killed in an accident, and his heart was used in Connecticut's first heart-transplant surgery.
But Baby Fae's story was clouded with controversy from the beginning. Her compassionate, publicity-shy surgeon was accused of staging a publicity stunt, of practicing grandstand medicine, even of child abuse. Some scientific experts praised him and others condemned him. A conflict developed between the public's right to know and a patient's right to privacy.
Hypoplastic Left-heart Syndrome
Leonard Bailey, M.D., had been studying heart transplantation since he was a junior medical student. In 1968 he entered a four-month surgery-research rotation as part of his medical education. His work in heart-transplant research began shortly after Dr. Christiaan Barnard performed the first successful human heart transplant in South Africa in December, 1967.
Later, after a residency at the Hospital for Sick Children in Toronto (Canada), the largest children's hospital in the world, Bailey specialized in pediatric cardiac surgery. He concentrated his attentions on congenital heart deformities in the very young, an ambitious pursuit that requires precise technical expertise.
The surgeon had dedicated much of his career to finding a solution for a tragic birth defect. Hypoplastic left-heart syndrome (HLHS), a lethal underdevelopment of the left side of the heart, causes otherwise perfectly formed babies to die shortly after birth. HLHS occurs once in 12,000 live births in the United States. In such babies, the left side of the heart is usually unable to pump sufficiently to sustain life for more than a few days.
Early in his career, Bailey got tired of having parents told, "Your baby isn't going to live." The solution seemed simple--just exchange the baby's heart.
By 1984 there were two potentially acceptable alternatives for treating the condition: palliative surgery and human-heart transplantation.
Palliative surgery helps the defect but does not cure it. By its very nature, the birth defect cannot be corrected. Too many vital parts of the heart are missing. At the time of Baby Fae's transplant, multi-stage palliative surgery was reported to have been performed successfully in two hospitals, both on the East Coast. Unfortunately, some writers reported one surgeon's success rate with only the first stage of the surgery, giving the erroneous impression that palliative surgery was 50 percent successful overall.
By a conservative estimate, 2,000 babies with hypoplastic left-heart syndrome were born from the time palliative surgery was successfully begun in the United States (January, 1979) until Baby Fae's transplant. According to Associated Press interviews (published November 25, 1984) at Children's Hospital in Boston and Children's Hospital in Philadelphia (the major institutions reporting any success with this procedure), 130 babies went through the first stage of surgery and 55 survived (42.3 percent). But the story does not end there. Because it was a two-stage surgery, 100 percent of these babies would die without the second-stage major surgery. It is not known how many of them eventually became candidates for the second surgery. But at the time of Baby Fae, only four of the surviving 55 had undergone the second surgery, and only two of them survived (1.54 percent of those undergoing the first surgery). And now it is a three-stage surgery.
But what about human-heart transplantation? The survival record is excellent now. In the Cape Times (November 26, 1984), Dr. Christiaan Barnard, the South African surgeon who pioneered human-heart transplantation, reported the difficulties of performing transplants on infants. "The situation with an infant is much different, death is often only a heartbeat away."
Barnard emphasized the difficulty of finding donor hearts. "Adult donor hearts usually come from brain-injured persons.... Such injuries occur seldom in infants...." To appreciate the problem Bailey faced, one cannot ignore the historical context under which this surgery took place. It has been estimated that approximately 10,000 newborns died from hypoplastic left-heart syndrome in America alone between the first and only newborn-heart transplant (performed in 1967) and Baby Fae's surgery (in 1984). The 1967 operation was performed in New York by Dr. Adrian Kantrowitz, using the heart of an anencephalic (brain-absent) donor, a type of baby that today legally is not considered acceptable as a donor because it usually does not meet brain-death criteria. That patient died within hours of the operation. At the time of Baby Fae's surgery, heart transplantation for a newborn had not been attempted in the United States for almost 17 years.
Could it be that palliative surgery and human-heart transplantation were not realistic options for many of these babies, and that seeking another option was reasonable?
Bailey's associates in neonatology and cardiology had too often experienced the heartache of having to tell young parents that there was no hope for their newborns. The only possibility for these babies to live a really normal, active life, he 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) immunosuppresive 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.
Goats, transplanted with sheep hearts under general anesthesia as newborns, were sometimes exercised by their handlers on the north lawn of the Medical Center. More than 250 animals had been transplanted. They all had names and were treated as pets. Some went to homes in the community.
Institutional Review Board
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, chairman 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.
Countdown Begins
On Sunday, October 14, 1984, a premature baby girl was brought to Loma Linda University Medical Center. She had been born at Barstow Community Hospital on the High Desert of Southern California and was transferred soon after birth. Pediatric cardiologists and neonatologists found upon examination that she had been born with hypoplastic left-heart syndrome. After being presented with options, the mother chose to take the baby home to die. She was told she could bring the baby back at any time. Four days later, a pediatrician called and told her of Bailey's research. Bailey had just returned from a family holiday and would talk to her about the possibility of an animal-heart transplant.
The mother, accompanied by her own mother and a friend, returned to Loma Linda with the infant. The baby was hospitalized, and the three met with Bailey. For several hours he explained his research in detail, including his work with animals. The option of transferring the baby to the East for palliative surgery was discussed, but the mother rejected this option. Bailey told the group it was unlikely that a human heart would become available, because size-matched and tissue-compatible human-infant hearts were, for numerous reasons, extraordinarily rare and, in fact, probably had never before been sought. At the end of the session, the mother gave Bailey permission to begin preliminary testing, and then she left to discuss with the baby's father the possibility of a transplant.
Meanwhile, the baby was beginning to die from her heart malady and required intensive bedside care. Both parents returned the next day, and Bailey repeated the proposal in depth. He also told them he could give no guarantee of success, because this type of surgery had never before been attempted with a newborn human. During the next several days, the family had several opportunities to ask questions. It was the most exhaustive, comprehensive, informed consent ever achieved in the history of the institution.
(Although not well known in the United States, Loma Linda University Medical Center was and still is the educational heart of the world-wide Seventh-day Adventist healthcare service that reaches into 70 countries with 85,000 employees in 725 medical institutions. The Loma Linda University Overseas Heart Surgery Team had performed more heart surgeries in more countries than had any other similar organization. As the only state-designated, level 1, regional trauma center for the four Inland Counties of Southern California, LLUMC was chosen by NASA to be the recovery hospital for space-shuttle astronauts if they should be injured during test-flight landings at Edwards Air Force Base.)
Patient's Rights of Privacy
On Monday, October 22, 1984, the Medical Center's public relations office was told of weekend developments. The baby girl had almost died on her sixth day of life, was hospitalized on the cardio-thoracic surgery intensive-care unit--on life support--and was being tested as a possible candidate for an animal-heart transplant. The historic surgery was tentatively scheduled for the following Friday, October 26.
The public relations office staff explained to the family their rights of privacy. Under California law (Civil Code Section 56.16), only limited, general information can be released about a patient's condition unless the patient or his guardian agrees to release more information. The family decided to allow the Medical Center to release details of the surgery with the understanding that they would remain anonymous. During this meeting, they decided to call the patient by her middle name, Fae--Baby Fae. The name was meaningful. It was also the middle name of the baby's mother, grandmother, and great-grandmother.
In the Medical Center, security was beefed up. Strategic doors were rekeyed. Vacations were cancelled for all security personnel, and they began 16-hour shifts. Electronic surveillance was increased. The institution's police-dog units went on call around the clock. Very few people knew what was happening, but many were curious. Why did employees, even physicians, have to show personal identification to get into certain areas of the Medical Center? Rumors spread that a VIP, or possibly a criminal, was hospitalized. It was a VIP--a five-pound heavyweight named Fae.
Baby Fae Almost Dies
One concern was the difference in blood groups of the potential donors and the recipient: common baboons are virtually all AB, A, or B types. The recipient was type O. Crossing the ABO barrier historically has been shunned. However, scattered reports of human kidney- and heart-transplant survival, despite ABO mismatching, were of some encouragement. The transplant team also felt that crossing the ABO barrier might be less significant than crossing the species barrier and that the baby's immune system might fail to recognize it as being as significant as the species barrier.
Should they proceed? All of the other tests were progressing nicely and showing a significant likeness between Baby Fae and one particular potential baboon donor. The team would be vulnerable to criticism if the risky transplant was not successful. The decision to proceed became a judgment call. This was, after all, a compassionate effort to save a baby's life--and, maybe, eventually, the lives of many other babies.
The Institutional Review Board had been following developments closely and was aware of the surgeon's ongoing discussions with the baby's family and of her condition. Final approval of the IRB was granted on October 24, two days before surgery.
Meanwhile, sophisticated, time-consuming immunological tests were employed to help choose the best tissue-matched donor. Bailey's research had discovered that some baboons are more closely tissue-matched to some humans than are other humans. The longest test, the mixed-lymphocyte culture, took six days, but the transplant team was determined not to rush into surgery without having vital information. At midnight, Thursday, October 25, Baby Fae almost died. She was already on maximum life support and was almost taken to surgery before the tests were completed. Decisions were being made on an hour by hour basis.
At 4 a.m., Friday, October 26, Sandra Nehlsen-Cannarella, Ph.D., the project's chief immunologist, received results from the mixed-lymphocyte culture. Dr. Nehlsen-Cannarella, who at the time was director of transplant immunology at Montefiore Medical Center and the Hospital of Albert Einstein College of Medicine in New York, had been one of the project's external scientific consultants. She had studied in London for three years in the 1970s at England's prestigious National Institute for Medical Research, where she was assistant to 1960 Nobel laureate and world-renowned immunologist Sir Peter B. Medawar. She had been invited to join Loma Linda's transplant team for this surgery.
By this time, Baby Fae had stabilized enough to proceed with surgery on schedule. At 6:30 a.m., she was taken by her support team into the second-floor surgery suite--and into the pages of medical history.
Team Surgery
Heart surgery is a symphony of cooperation and teamwork. At first, the atmosphere is quite casual. The patient is moved under giant lights. All the instruments and supplies that might possibly be needed are set up. The heart/lung machine is primed. The patient is placed under general anesthesia, and the surgery field is prepared. When all is ready, the surgeons scrub and gown. Team members chat informally.
But as time passes, the atmosphere changes. It seems like a countdown. The surgery team works its way through a long series of preoperative procedures.
As the time for surgery approaches, team members move into place. The patient's temperature, blood pressure, respiration, and heart rate are monitored carefully. As this information is announced, it is often accompanied by the word "sir." The team works with precision and technical detail in getting a patient on and off the heart/lung machine. One fact is obvious: these people have been here before.
Baby Fae's anesthesiologist, Robert D. Martin, M.D., administered her anesthesia with extreme caution because of her weak condition. The baby could have died at any moment under the best of conditions. Her body temperature was carefully lowered to 18 degrees centigrade (66 degrees Fahrenheit). This procedure, called deep hypothermia, was done to reduce her metabolic rate and drastically slow her body functions, as in a state of hibernation. This is standard practice in infant heart surgery. It allowed the transplant team to stop Baby Fae's circulation for one hour and 10 minutes.
Implanting the new heart, about the size of a large walnut and weighing about one ounce, took approximately an hour. During the warming procedure, Baby Fae's brand-new, perfectly formed heart started beating on its own at 11:35 a.m. It was a reassuringly strong and regular beat. A feeling of awe prevailed. The heart could have been rejected in minutes, but it wasn't. The only initial problem was a brief tachycardia episode--or rapid heartbeat--and that subsided on its own. Baby Fae's new heart did not require support from stimulating agents.
During surgery, Baby Fae's mother walked slowly through the lobby with Chaplain Bill Hinton. She looked anxious but hopeful. After several hours in the surgery suite, Baby Fae was returned to her intensive-care room for recovery. Her mother hurried with the chaplain to see her little one. The concern was gone from her eyes. Her face was beaming with anticipation and gratitude. Her baby had been pulled from the brink of certain death and given a fighting chance to overcome overwhelming odds.
The new heart was beating 130 times a minute: 7,800 times an hour. Her anesthesiologist later reported that the surgery was the smoothest heart operation he had ever worked on. Baby Fae looked pink and healthy. She never before had looked so well. Her nurses later claimed that she recovered better than many regular pediatric cardiac-surgery patients do.
Questions People Asked
Most people had sincere questions. Would the heart grow with the baby? (Animal research already published and experience with human kidney and liver transplants suggested that it would. The transplanted organ comes under the influence of the growth factors of the recipient.)
Would she live a normal lifespan? (Nobody could say, but animals with transplanted hearts had grown from infancy to adulthood, and had even experienced parenthood.)
Would she need another transplant when she was older? (It was hoped not; however, that could be a possibility. At least human hearts are more readily available in older age groups).
Would it be possible to transplant a baboon heart into an adult? (Probably not. The adult immune system would more readily reject a cross-species transplant, and the heart also would be too small. It would not have the benefit of growing with the patient.
Some, no doubt with good intentions, suggested that such an experimental procedure should be performed on an adult instead of a baby who could not consent for herself. This suggestion not only failed to consider the different immune system of the newborn and the unmatchable sizes of the baboon and human adult hearts, but also could be said to be prejudicial against newborns. If experimental surgery had never been performed on newborns, thousands of children alive today would have died, and would not have the opportunity of becoming adults. Most newborn heart surgery is performed based on the proxie-consent of the baby's parents, who are assumed to be making decisions on behalf of the baby's best interest.
The main question asked by the scientific community was regarding the parents' informed consent: Did they really understand their daughter's condition and did they fully understand the options for her care?
Because the parents had requested anonymity and, therefore, could not be interviewed by the media, suspicions and accusations multiplied. To put the public's mind at ease, Loma Linda University Medical Center invited the National Institutes of Health (NIH) to evaluate the process.
The NIH report concluded that "as a result of the consent process the parents of Baby Fae fully understood the alternatives available as well as the risks and reasonably expected benefits of the transplant.... The site visitors also believe that the explanation was presented in an atmosphere which allowed the parents an opportunity to carefully consider, without coercion or undue influence, whether to give their permission for the transplant."
On April 21, 1985, Arthur Caplan, Ph.D., then associate director of the Hastings Center, a bioethics research institute in Hastings-On-Hudson, New York, interviewed Baby Fae's mother at the close of a biomedical ethics workshop in Loma Linda. In a letter to Bailey, he expressed appreciation for being allowed to chat with her. "I must say the conversation we had was an eye-opening for me. The press had depicted her as being an ill-informed, under-educated individual. I couldn't help but feel, as a result of my conversation, that the press was not only wrong but insulting to her. She seemed to me to be a very bright, articulate and thoughtful woman."
Why not use a human heart? Reports of a two-month-old human heart becoming available on the same day of the surgery led some reporters and ethicists to conclude the baboon heart was used despite the fact that a human heart was available. By coincidence, that heart became available 12 hours after the surgery. But it raised valid questions about the availability of newborn organs. According to the Regional Organ Procurement Agency of Southern California (ROPA), no acceptable newborn hearts were made available through ROPA's network of sources for the 12 months preceding Baby Fae's surgery, probably because no one was performing heart transplants on newborns.
Worldwide, not one newborn was transplanted during the 12 months following Baby Fae's death, even though the opportunity presented itself 40 to 50 times a month in America alone. This fact is eloquent evidence that suitable human donors were indeed rare.
Dr. Stuart W. Jaimeson, who was both director of Stanford University's noted heart/lung transplant team and director of its cardiac surgery experimental laboratory, was the first outside scientific consultant with direct knowledge of the Loma Linda project to comment on it publicly. In a New York Times story, published November 11, 1984, he said he strongly supported the scientific procedures used by the Loma Linda scientists that led the way for the October 26 transplant, and said he was "very impressed by the work the team had done.... It was a legitimate and timely thing to do." His recommendations were few, he said, because Dr. Bailey's research had been so extensive.
Baby Fae Dies
Baby Fae died on November 15, 1984. Her new heart did not show the usual evidence of graft rejection. She died from complications related to antibody production, some of which may be preventable with more compatible donor selection.
At an emotionally charged press conference the day after Baby Fae died, Bailey, in a prepared statement, said, in part, "Baby Fae's experience of a brief month or so has been a uniquely human one. The courageous decisions made for her by her family and all of us who have loved her, have forced us to confront and reexamine our human existence. The discussions and debates should improve all mankind. For her part, I and my colleagues believe Baby Fae has opened new vistas for all, including the as yet unborn infants with similar lethal heart disease."
In response to questioning, he reported the response of Baby Fae's mother: "The last thing her mom said to me was not to let the experience be wasted, but to carry it on. And we plan to honor that request.... I think we can be cautiously optimistic that we'll have an answer for some of these babies in the near future," he said. "In all fairness to the next baby, we should take the time to carefully review what we've learned from this baby we all loved so much."
Epilogue
Baby Fae lived longer than the world's first several adult human-heart transplants. This amazed most scientists. Research has continued on the volumes of data collected during those 20 days. About 20 percent of babies who need a heart transplant have died waiting for donors. One died after being on regional and national organ-procurement lists for more than 18 weeks.
Our society has benefited in several measurable ways from the controversial baboon-heart transplant. Consciousness has been raised to the plight of newborns needing heart transplants and to the possibility of performing those surgeries. This new awareness has led several other institutions to join Loma Linda University Medical Center in attempting the delicate procedure.
Bailey's account of how he cared for the first three newborn human-to-human heart-transplant patients was published in the New England Journal of Medicine, October 9, 1986. Accompanying the article was an editorial congratulating Bailey and his staff for their successes. The editorial was written by scientists from Stanford University School of Medicine.
In November, 1986, the California Legislature approved Resolution No. 481, honoring Bailey and his associates, in recognition of the one-year anniversary of the first successful newborn-heart transplant, on a patient named "Baby Moses." (It is firmly believed that there would not have been a "Baby Moses" had there not been a Baby Fae. Both the donor and recipient were referred to Loma Linda because of the widespread publicity on Baby Fae. The publicity on "Baby Moses" then made the scientific community and the public aware that newborn-heart transplantation was possible.)
Dr. Sandra Nehlsen-Cannarella, Baby Fae's immunologist, accepted an invitation to join the faculty of Loma Linda University School of Medicine. On March 1, 1985, she opened Loma Linda University's Immunology Center, where she directed both clinical and research laboratories involved in the immunology of transplantation and maternal-fetal compatibility.
Baby Fae's daring surgery was a landmark case. It has become a reference point in the public's awareness of hypoplastic left-heart syndrome and the serious efforts being made to save doomed babies. It became the cornerstone of a successful, international, infant-to-infant heart-transplant program begun in Loma Linda about a year later. Baby Fae struck a uniquely human chord in most people: the capacity to hope, and to cheer those who take great risks to help one little person.