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Many Sleepless Nights
The World of Organ Transplantation
By Lee Gutkind OPEN ROAD INTEGRATED MEDIA
Copyright © 1990 Lee Gutkind
All rights reserved.
ISBN: 978-1-4804-7132-0
CHAPTER 1
THE BIRTH OF A DREAM
It began as a myth, which originally inspired artists—not surgeons.
In the sixth century in Rome, a desperate man, his leg riddled with cancer, is said to have slept for a night in the Church of St. Cosmos and St. Damian, two brothers, both Syrian physicians, who had been made patron saints of medicine. During that night, the dying man saw the brothers emerge from the shadows. One brother surgically removed the diseased leg, while the other went to a nearby cemetery and amputated the leg of a black man—an Ethiopian—who had recently been buried. He brought the leg back to the church, grafted it to the white man's stump. The following morning, the white man opened his eyes, stood up, and walked away on a healthy black leg, while his cancerous leg was found lying beside the black man in his grave. Today, more than 1,500 paintings, drawings and other representations of this story have been counted in churches, galleries, and private collections throughout the world.
Approximately fifteen centuries later, at the turn of the twentieth century, Dr. Alexis Carrel of France solved what had heretofore been considered an impossible surgical mystery by creating a method of joining two blood vessels together. Carrel's technique for the "anastomosis" (from the Greek words ana or "to," and stoma, which means "mouth"; together "joining mouth-to-mouth") was simple and logical: he developed a clamp for the artery to keep blood from leaking out, and a technique whereby three guide sutures or "loops" would hold the arteries in place to be sewn with a specially designed needle and thread. In the future, the transplant surgeon could sever the vessels connecting diseased organs to the body, and then subsequently anastomose them to the bare ends of vessels coming from the donor organ.
But although his anastomosis techniques had basically made transplant surgery a viable possibility, Carrel and other scientists soon recognized that they would nearly always be defeated by the inevitable aftermath of the transplant procedure—the phenomenon known as "rejection." Whether in animal or in man, the body's immune system would not accept—it would automatically reject—the organs implanted into it.
To understand the rejection process, one must first understand how the body defends itself against invasion of foreign substances. Scientists believe that B lymphocytes, which are found in white blood cells, are the first line of defense; they produce proteins called antibodies, which destroy harmful antigens (viruses or bacteria) leaked by foreign invaders. B lymphocytes are usually effective, but if and when they do not work, the body triggers its second line of defense—T lymphocytes, known as "killer" cells, which penetrate the antigens and directly attack the foreign invader.
Under a microscope, you can see the immune system in action soon after the transplant. Immediately, the B lymphocytes approach the antigens of the transplanted organ. Contact occurs—and the immune system must make a decision: Is this an invader, or does this belong? Self or nonself? Us or them? When it is determined that the transplanted organ is a foreign object, the B lymphocytes will joust with and attempt to repel the antigens. T lymphocytes begin to multiply and go into action only after the B cells have failed to do the job ... if and when the transplanted organ has been strong enough to fend off the B cells and establish itself in the body. This is not too dissimilar to a panoramic Pacman game: a beautiful new heart, pink and beefy, but defenseless, appears on a TV screen. Suddenly an army of killer T cells, clad in black, storm onto the screen and swarm all over the heart, causing the heart to swell uncontrollably from infection—and die.
The chief problem is that the immune system lacks the ability to make value judgments, to distinguish between good and evil. Thus, if it perceives foreign tissue, whether it is a friendly foreigner like a transplanted heart, or unfriendly, the B lymphocytes will go after the antigens, and failing that, the killer T cells will attack. Rejection could occur in nine days or nine months, but Carrel and others realized that sooner or later it would always occur. Rejection was part of the transplant process. For transplantation to work, rejection had to be controlled.
During World War II, Dr. Peter Medawar, who in peacetime was a lecturer in zoology at Oxford University, became a member of a surgical group commissioned by the British government to examine and develop methods of skin grafting for soldiers and civilians burned in bombing raids. Medawar, who eventually won the Nobel Prize for thirty years of work in immunology and was knighted by Queen Elizabeth II, discovered that "homografts," transplantation from one species to another member of that same species [of skin in this case] was not a generally successful method of covering burns—except when the grafts were made between identical twins. With these facts established, Medawar and others reasoned that perhaps a kidney could be transplanted into a sick twin from a healthy identical sibling. People have two equally capable kidneys, while the body requires the use of only one kidney for normal functions; the second serves only in an emergency or back-up capacity.
There were other scientists and surgeons who had blazed the transplant trail before and immediately after his vital discovery. In 1936, Dr. U. Voronoy, a Russian surgeon, performed the first kidney transplant on a human; his patient, however, died in two days. In the early 1950s, there were no fewer than eight failed attempts at renal (kidney) transplantation in France. In his book, Transplant, Dr. Francis D. Moore, a respected transplant pioneer from Peter Bent Brigham Hospital in Boston and Harvard University, reports that Dr. Richard Hufnagel, a surgical fellow at "the Brigham" in 1947, was asked to transplant the kidney of a dying patient into a young woman who, while pregnant, had developed an infection in the uterus.
Hufnagel recalls that the patient's condition appeared extremely critical and because of this "there was some administrative objection to bringing the patient to the operating room. In the dark of the night—about midnight—when the kidney had been obtained immediately after the death of the donor, our little group proceeded to one of the end rooms on the second floor, and by the light of two small gooseneck student lamps prepared to do the transplant...." It proceeded perfectly.
The transplanted kidney was only temporary, removed in two or three days, but it had successfully kept the woman alive while she recovered from her infection and until she regained efficient use of her own kidneys. Seven years later, in 1954, Dr. Joseph E. Murray, a young surgeon from "the Brigham," along with a colleague, John P. Merrill, proved that, under the right circumstances, transplantation could work, perhaps indefinitely.
It began with a physician, David Miller, serving at the U.S. Public Health Service in Boston, who was treating a twenty-four-year-old Coast Guardsman, Richard Herrick, for severe end stage renal disease. During the course of treatment, Miller had met Herrick's brother, an identical twin. He knew of Medawar's work during the war, demonstrating the feasibility of skin grafting in identical twins, and he knew that only a few months at most separated the young sailor from death. It could be assumed that with identical twins there would be no biological factor, and thus no rejection. Miller referred Herrick to Murray's surgical group and recommended that he be considered for transplant. David Miller may not have known it then, but he had sparked a climactic event—his idea to help a dying patient was the last link in a series of ideas beginning at the turn of the century with the work of Alexis Carrel.
Before agreeing to attempt the transplant, Murray, trained as a plastic surgeon, employed Medawar's research, when he grafted skin from one brother to another to guarantee that they were indeed identical—not fraternal. It took a number of weeks for the skin graft to take, during which time Herrick was kept alive on Merrill's adaptation of an artificial kidney (dialysis), the prototype of which was developed by an ingenious Dr. Willem J. Kolff under extraordinarily difficult circumstances during World War II in Nazi-occupied Holland. Kolff continued his work after the war at the Cleveland Clinic, where he utilized a tub from a Westinghouse ringer washing machine for the chamber of an improved method of dialysis. Today, Kolff teaches at the University of Utah, where he inspired the work of Robert Jarvik, creator of the world's heretofore most successful version of the artificial heart.
It is impossible to exaggerate the importance of Kolff's artificial kidney in launching the transplant era, for it provided surgeons with a wide range of flexibility in experimentation. Not only did Kolff's creation extend the lives of thousands of people, but it offered the secure knowledge that patients could usually be returned to dialysis if the transplant didn't take. No such "back-up" device existed for the early pioneers working in the extrarenal (other than kidney) transplant field. Once committed, heart and liver transplant surgeons shouldered the full burden of the lives of their patients. There was no second chance, no turning back.
Although twenty-five years ago, scientists were accorded considerably more freedom than today for experimentation, unhindered by government regulation and control, history illustrates that each major step in the evolution of transplantation has stimulated a corresponding legal and/or ethical development or decision that has helped put science into public and social perspective. The legal and ethical evolution began less than two years after the Herrick procedure, when Murray and his team at "the Brigham" were asked to consider a similar procedure for Leon Masden, who was dying from a chronic kidney ailment, and his healthy brother, Leonard. In significant contrast to the twenty-seven-year-old Herrick twins, however, Leon and Leonard were nineteen, which, in the state of Massachusetts, meant that they were minors.
It was a practice in hospitals then, and it is now, that consent be obtained from adult patients prior to surgery. For minors, consent is required from a parent and/or guardian, but in this instance, the hospital questioned the family's ability to be fair and objective. Potentially, the transplant could save Leon's life. At the same time, Leonard would lose one of his two kidneys. What if his remaining kidney was someday jeopardized by accident or illness? With virtually no legal precedent established, hospital attorneys sought a declaratory judgment from the Supreme Court of the Commonwealth of Massachusetts.
At the hearing, Supreme Court Justice Edward A. Counihan, Jr., heard testimony not only from the consenting parent and from Leon, but also from a psychiatrist who had examined the twins and determined that, "if the operation was not performed and the sick twin were to die, it would result in a 'grave emotional impact' on the healthy twin." Thus, the court ruled that the hospital could proceed with surgery. The following year, a similar scenario was followed in two other cases involving twins, one set of which was fourteen, and the other, sixteen. These rulings, the first in particular, which transplant surgeon Thomas Starzl has called "the legal (and probably the moral) basis for living donations," established an important and long-standing precedent for living-related organ donation.
At that time, the only real hope for long-term survival with kidney disease was transplantation involving identical twins, but throughout the next decade, as surgeons became more practiced and sophisticated in transplant techniques, other family members, as well as friends and distant relatives, were included as voluntary kidney donors. Experiments involving the cadaveric, or unrelated "brain-dead" donor, were also becoming increasingly successful—an area of particularly special interest to Starzl, who experienced a change of mind concerning the ethical acceptability of living-related donation midway through his career.
"The most compelling argument against living-donation is that it is not completely safe for the donor," Starzl has explained. The percentage is very small, but he can recall nearly two dozen living-related donor fatalities. "The deaths have been caused by anesthetic complications, postoperative pulmonary emboli [an air bubble or blood clot obstruction in the artery], postoperative hepatic [liver] dysfunction, and technical surgical complications. When deaths have occurred, they have had a devastating effect on everyone even remotely associated with the case. The heartbroken surgeons to whom I have talked, including one whose patient died twenty-three years ago, have told me that the donor deaths represented the most terrible moment in their lifetime, and I suppose it might be fair to say that this kind of suffering pales beside that of family members themselves."
Starzl's objections extend to psychological and moral grounds. "I have seen examples of donor abuse within families. If a prospective donor is deficient in some way, usually intellectually, the family power structure may focus on him or her on the basis of their presumed expendability. I have seen refusal of donation lead to ostracism within a family, or alternatively, donation could be a reluctant sacrifice offered to someone for whom there was little or no affection." Starzl is also concerned about the "donors who may not possess their full civil rights"—children, "who must answer to their parents and are thus captive." He added: "Although I was one of the first to use living donation, and have never had a donor die, the concept remains troubling to me, and I have not operated on a living donor since 1972.
"In my opinion, however, the modern era of renal transplantation could never have developed without living-related donor transplantation. The results with nonrelated donors, for the most part cadaveric, were so poor from 1962 to 1972 that the great effort often was hardly worthwhile. The only real option [for surgeons and scientists] at that time, was the living-related donor."
It was certainly the only conceivable lifesaving option in Boston two days before Christmas, 1954, when Dr. Joseph E. Murray and his surgical team transplanted the kidney of his identical twin, Ronald Herrick, into U.S. Coast Guard Seaman Richard Herrick. After a long and difficult recuperative period, Herrick lived a healthy life for eight years. He died in 1962 of a heart attack, probably never realizing that the courage he and his brother both displayed during a time when transplantation was considered by many to be antireligious and totally impossible has since paved the way for the improvement and preservation of hundreds of thousands of lives.
Murray commented recently: "The longest survivor is Edith Helm, whom we transplanted in 1956. Edith is a mother, the first transplant recipient to complete a pregnancy, and last year Edith became a grandmother. She has normal renal function and leads an active life as wife of a rancher in Oklahoma."
From an historical perspective, Murray's surgery on Richard Herrick was extremely significant in the evolution of organ transplantation. But its impact, especially upon the public's perception and interest in transplantation, is miniscule compared to a sudden and completely unexpected event that occurred nearly fourteen years later and halfway around the globe.
(Continues...)
Excerpted from Many Sleepless Nights by Lee Gutkind. Copyright © 1990 Lee Gutkind. Excerpted by permission of OPEN ROAD INTEGRATED MEDIA.
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