“Well, I knew that it was Kylie’s wish,” Shirley told me, “and I knew that I wasn’t going to get her back. At that point I wanted her heart to keep going long enough to fulfill her wish. So, I think if her heart would have stopped, and they weren’t able to do the organ donation, it would have been even more sad for me.”
The workup of a brain-dead donor might take twenty-four to thirty-six hours before we would be ready to procure the organs. In addition to placing the organs in hospitals all around the country, sometimes invasive tests are needed (such as a liver biopsy or a cardiac catheterization of the heart). This is usually done before the deployment of a procurement team, which must wait for the results of the blood work indicating donor blood type, organ function, and any infections the donor might have been exposed to, including hepatitis C or HIV. Kylie’s accident took place just after noon. Organ procurement began at around 10:00 p.m. It was that quick.
Kylie’s case was what we call a “drop and run.” Because she was so unstable, before any of the blood work is done, we send a procurement team to get the organs. In these cases, we usually take only the kidneys—we can put them on ice in a cooler or on a pump that flushes solution into them—while we wait for the test results. Then we have the recipients brought in, and perhaps do the transplants twelve to twenty-four hours later.
When our team arrived, Shirley and Bruce went in to say goodbye to Kylie. She was already brain dead, but it would be their last chance to see their beloved, beautiful daughter while she still had a beating heart. It was all very rushed, but Shirley remembers the moment vividly, standing with her husband, gowned up in OR attire, staring at her daughter for the last time. Then they waited until the procurement was done, when Kylie—without her kidneys (which our team took) or eyes (which would be used for a cornea transplant), and with her heart no longer beating—would be returned to the room before being brought down to the morgue.
“I pretty much had guessed that they weren’t going to be able to use her heart for anything,” Shirley said, “since it had stopped so many times. I had kind of assumed that it would be way too damaged, and that, of course, was the case.” Still, she said, “I would have loved for somebody to have gotten Kylie’s heart.”
Shirley and her family still think about Kylie every day. It has been a struggle, and they are just now getting back to living the way Kylie would have wanted them to. I asked Shirley if the donation had helped with her recovery.
She said it had: “I think that it’s a way for Kylie to have lived on and for people to remember.” She added, “And, you know, it has been a good experience, and it helps me. It helps me to know that she wanted to be a donor. She did something fantastic for somebody else and made that person’s life so much better and, you know, I have a connection to this person. And through that connection, it just makes me feel like she’s always still here.”
FOR TRANSPLANTATION TO succeed, implant operations and immunosuppression strategies had to be defined and then revised over many decades. Yet those efforts would have been in vain without a better understanding of death and dying, of what really constitutes death. Transplantation, out of necessity, would serve as a catalyst for further defining society’s feelings on life, death, and the fine line that sometimes separates them.
Louvain, Belgium, June 3, 1963
Guy P. J. Alexandre had just returned to Belgium after spending his third year of residency with Joe Murray in Boston. He came directly after Roy Calne to Murray’s lab, and was the one who prepared the azathioprine solution for the successful human transplants Murray performed in 1962. When he flew back to Belgium to complete his training, Alexandre’s luggage contained vials of azathioprine and other promising immunosuppressive agents. (Yes, it was a simpler time.)
Over the next year, Alexandre completed his surgical training, and then convinced his team that they should move forward with clinical kidney transplantation. “All that remained was to find a suitable patient and to maintain him in a suitable condition until a kidney could be obtained and transplanted.” As he recalls:
On June 3, 1963, a patient was brought in with a head injury and in profound coma. The patient became completely areactive, had a falling blood pressure despite the administration of vasopressive drugs, and presented all the signs of what Mollaret in 1959 had described as a ‘coma depasse ’ (a state beyond spontaneous breathing) . . . Professor Morelle [the chair of the department of surgery], who was quite experienced in neurosurgery, considered the neurological symptoms presented by the patient and took what today could be considered the most important decision of his career: whether to remove a kidney from that patient while the heart was still beating. This procedure was probably the first transplant ever removed from a heart-beating cadaver. Fortunately, this was long before the days of established ethical committees.
Alexandre transplanted the kidney into the recipient, whom he had been operating on in the room next door. The transplanted kidney started making urine right on the table, and the patient had normal creatinine levels a few days later.
This marked a huge turning point in transplant history.
London, March 9, 1966
Transplant pioneer Michael Woodruff, chair of surgery at the University of Edinburgh, had seen fit to organize a conference to discuss ethical and legal issues in transplant. Attendees included Joe Murray, Tom Starzl, and Roy Calne, along with the majority of players in the small but burgeoning field of transplantation. Among the many topics Woodruff wanted to discuss at the conference was the problem of obtaining donors. In the early days of transplantation, meaning the 1950s and early ’60s, so few transplants were being conducted that enough organs could be obtained from living donors, patients having their kidneys removed for other reasons, and patients who had just died (including prisoners). Of course, obtaining organs from these donors was no small task. Surgeons would have to wait until a donor’s heart had stopped and he was declared dead (meaning no heartbeat, no blood pressure, no respiration). At that point, consent would be obtained from the family. Then the patient could be taken to the OR for procurement of the kidneys. A significant amount of time would pass before the kidneys were removed, and all the while they would get no blood flow or oxygen. Everyone knew that wasn’t great for the organ.
In England, Calne was often forbidden from bringing these donors to the OR for procurement:
We knew that kidneys had to be removed from the dead as quickly as possible after the heart had stopped beating, otherwise the organs would be useless. But here we hit a serious snag: the nurse superintendent of the operating theatres would not permit dead bodies to be brought into her operating rooms. So we had to remove the kidneys in the open wards. Looking back on the procedure, it must have resembled a horror film. Other patients in these large wards would see a team of surgeons rush in, go behind a curtain where a patient had died, and operate on the corpse in an ordinary hospital bed. This was very difficult and blood would often trickle onto the floor, where the patients would see it and be further terrified and upset.
At the symposium, after Joe Murray delivered his lecture titled “Organ Transplantation: The Practical Possibilities,” a discussion ensued. At some point, Alexandre got up to make a statement. “To throw some fuel into the discussion, I would like to tell you what we consider as death when we have potential donors who have severe craniocerebral injuries. In nine cases we have used patients with head injuries, whose hearts had not stopped, to do kidney transplantations. ” He went on to describe the very specific conditions these donors needed to meet, including the absence of reflexes, the absence of response to pain, a flat EEG, and the absence of spontaneous respiration five minutes after the ventilator had been withdrawn—in other words, he gave the definition of brain death without using that term. His team simply called it death.
Alexandre’s remarks were a bombshell. Starzl said, “I doubt if any of the members of our transplantation team could accept a person as being dead as long as there was a heartbeat. We h
ave been discussing this practice in relation to renal homografts. Here, a mistake in evaluation of the ‘living cadaver’ might not necessarily lead to an avoidable death since one kidney could be left. But what if the liver or heart were removed? Would any physician be willing to remove an unpaired vital organ before circulation had stopped ?”
Calne went further: “Although Dr. Alexandre’s criteria are medically persuasive, according to traditional definitions of death, he is in fact removing kidneys from live donors. I feel that if a patient has a heartbeat, he cannot be regarded as a cadaver.”
As Alexandre recounted years later, “at the end of the CIBA symposium meeting . . . the president of the meeting asked the participants to let him know those who were prepared to act the way we were doing and to accept our criteria of brain death; I was the only one to raise my hand, all the others did not.” Still, despite his inability to convince anyone in the room that he was right, Alexandre did plant a seed in the mind of Joe Murray, perhaps the most prominent transplant surgeon in the world at the greatest institution for transplantation in that era.
Over the next few years, efforts at transplantation continued to grow, primarily with the kidney but also the liver. Then, in 1967, the first heart transplant was performed. While it remained the standard in the United States that donors had to be declared dead by a physician prior to organ procurement, the notion of what constituted death was slowly shifting. Some surgeons had taken Alexandre’s lead and were removing kidneys from patients with coma dépassé, although they weren’t publicizing it. As Murray recounts in his autobiography, “Across the country, the response to the seemingly simple question ‘When is a person dead?’ varied widely. Most alarming was the position of certain doctors at the kidney conference [not clear which conference] who had stood up and said, ‘I’m not going to wait for the medical examiner to declare the patient dead; I’m just going to take the organ.’ ” This concerned Murray greatly.
Surgeons had recognized by that point that donors with beating hearts were preferable in terms not only of timing and availability but also of outcome. When the donors had beating hearts, the organs continued to receive blood flow and oxygen, and continued to function, until the very moment that they were removed. This made them more likely to work immediately following transplant, and continue to work thereafter. Yet as the successful transplanting of organs (including livers and, ultimately, hearts) was becoming a reality, the importance of finding consensus on this ethical issue became ever more urgent. (It didn’t help that the press had begun accusing the Brigham physicians of playing god in their efforts at organ transplantation.)
Boston, Massachusetts, September 1967–June 1968
Henry Knowles Beecher would play a central role in the definition of brain death. Beecher was a prodigy, a true genius, and his uncommon intelligence was recognized by all who knew him. He became anesthetist in chief at the MGH in 1936, and served in North Africa and Italy during World War II, an experience that affected him greatly. He was one of the first researchers to write about the placebo effect (in 1954), underlining the importance of the double-blind, placebo-controlled trials that are the gold standard today. In 1966, Beecher became both famous and infamous when he published a paper in The New England Journal of Medicine entitled “Ethics and Clinical Research,” which highlighted multiple cases of clinical research that placed the subjects at risk of morbidity and death without true informed consent. Although controversial, this report was one of the first to lay the groundwork for the guidelines on informed consent that we use today.
In September 1967, Beecher wrote to Robert Ebert, dean of Harvard Medical School, asking him to convene a meeting of the school’s Standing Committee on Human Studies to discuss the topic “Ethical Problems Created by the Hopelessly Unconscious Patient.” Beecher wrote, “As I am sure you are aware, the developments in resuscitative and supportive therapy have led to many desperate efforts to save the dying patient. Sometimes all that is rescued is a decerebrated individual. These individuals are increasing in numbers over the land and there are a number of problems which should be faced up to.”
The meeting was held on October 19, 1967. One of the attendees was Joe Murray, who suggested that a new definition of death be codified, and that Harvard was the place to do it. Beecher reached out to Murray in a letter the next day, thanking him for his comments and agreeing that it should be done at Harvard. Murray wrote back a week later: “The subject has been thoroughly worked over in the past several years, and by now areas for action are crystallized into two categories. First is the dying patient, and second, distinct and unrelated, is the need for organs for transplantation.” He went on to identify the necessity for “a medical definition of death” and the need to enlist the “opinions of the neurologists, neurosurgeons, anesthetists, general surgeons and physicians who deal with terminal patients.”
The next paragraph of Murray’s letter highlighted the challenges he was dealing with in transplantation:
The next question posed by your manuscript, namely “Can society afford to lose organs that are now being buried?” is the most important one of all. Patients are stacked up in every hospital in Boston and all over the world waiting for suitable donor kidneys. At the same time patients are being brought in dead to emergency wards and potentially useful kidneys are being discarded. This discrepancy between supply and demand is soluble without any further medical knowledge; it requires merely an educational program aimed at the medical profession, the legal profession, and the general public.
The committee had its first meeting on March 14, 1968, and worked on six drafts, completing its report on June 25, 1968. Murray played a prominent role in the writing, and he and Beecher talked almost every day during those three months. The final document was published on August 5, 1968, in JAMA, under the title “A Definition of Irreversible Coma—Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death.” The first line of the paper states, “Our primary purpose is to define irreversible coma as a new criterion for death.” The authors go on to discuss the importance of this for two reasons: first, to deal with futile care of patients in the ICU, and second, “Obsolete criteria for the definition of death can lead to controversy in obtaining organs for transplantation.”
As David Hamilton writes in his history of organ transplantation, “In normal circumstances, this much-needed new definition of death might have encouraged a slow but orderly change in medical practice. But the times were not normal: Barnard’s transplantation of a human heart, performed just after the Harvard committee had been launched, had changed everything.” Unfortunately, the outcomes of these heart transplants were truly awful in those early years, and the public became frightened by the idea of hungry heart surgeons removing their loved ones’ beating hearts while they were still alive. Public support for heart transplantation, which was at an all-time high when Christiaan Barnard performed the first in December 1967, was at a low by May 1968. Numerous hospitals stopped allowing organ donation, and acceptance of the concept of brain death in the United States was definitely not immediate. It took a little more than a decade for public opinion to align with that of the Harvard committee and accept the definition of brain death.
THE PIONEERS IN transplant were willing to persist even with not only the very clear reality that their colleagues thought they were crazy, and outright killing people, but also the knowledge that they could end up in jail. Why were they willing to risk jail time to make transplant a reality?
The courage and commitment this required are palpable for me when I think of my patient Wayne, whom I first met when he had just been diagnosed with ALS (amyotrophic lateral sclerosis, or Lou Gehrig’s disease). He found himself getting progressively weaker, and eventually ended up in a wheelchair. When he could no longer hold his head up or swallow his own saliva, he knew death was imminent.
I had met Wayne a couple of years before this, when he was considering donating a kidney for trans
plant; he wanted to make his disease mean something for someone. We came up with a plan: we would bring him to the hospital when he got to the point where the quality of his life was so bad that he knew he couldn’t go on. We’d admit him to my service, bring him to the operating room, and remove one of his kidneys (or possibly both) for donation. Then he would be returned to the ICU, and once his anesthesia wore off, we would extubate him and let him die naturally of ALS. This way we wouldn’t be killing him for organ donation, but he would be able to give the gift of donation that was so important to him.
As Wayne deteriorated, we convened an ethics meeting at our hospital to discuss the situation. The meeting was well attended, and support for proceeding was overwhelmingly strong. Then, as we were putting the details in place, I received an analysis by our lawyers of the risks of proceeding. They stated that there was a significant likelihood, if we went ahead with the plan, that we (I) would be charged with murder, or at least acceleration of death, a charge that would be left to the discretion of the district attorney for our state. As I read this report and thought about it, I realized there was no way in hell I would proceed—not that the hospital would have let me anyway, given the legal department’s response. Thoughts of getting charged, going through a trial, and living with that risk were all too much for me to bear. I wasn’t going to jail for this. I had kids to think about!
When I told this story to Tom Starzl, he had a short response: “Well, you just explained exactly how not to go forward . . . We just did it,” he added, referring to the transplant pioneers. “These were sneak attacks that took place. They were done before the naysayers had a chance to say nay.” We all owe a debt of gratitude to Starzl and others like him for their courage.
How Death Becomes Life Page 26
