Long before human-to-human transplantation was ever imagined by the public, scientists were conducting pioneering medical and surgical research that would eventually lead to today's transplantation successes. From the late 1700s until the early 1900s, the field of immunology was slowly evolving through the works of numerous independent scientists. Among the notable breakthroughs were Ehrlich's discovery of antibodies and antigens, Lansteiner's blood typing, and Metchnikoff's theory of host resistance.
Because of advances in suturing techniques at the end of the 19th century, surgeons began to transplant organs in their lab research. At the start of the 20th century, enough experimentation had taken place to know that xenographic (cross species) transplants invariably failed, allogenic transplants (between individuals of same species) usually failed, while autografts (within the same individual, generally skin grafts) were almost always successful. It was also understood that repeat transplants between same donor and recipient experienced accelerated rejection, and that graft success was more likely when the donor and recipient shared a "blood relationship."
Alexis Carrel was a French surgeon and Nobel laureate whose experiments involved sustaining life in animal organs outside the body. He received the 1912 Nobel Prize in Medicine or Physiology for his technique for suturing blood vessels. In the 1930s, he collaborated with the aviator Charles Lindbergh to invent a mechanical heart that circulated vital fluids through excised organs. Various organs and animal tissues were kept alive for many years in this fashion.
Throughout the 1940s and 50s, small but steady research advances were made. In 1958, Dickinson Richards, MD, chairman of the Columbia University Medical Division, and Andre Cournaud were awarded the same Nobel Prize for their work leading to fuller understanding of the physiology of the human heart using cardiac catheterization.
In that same year, Keith Reemtsma, MD, a member of the faculty of Tulane University who later became chairman of the Department of Surgery at Columbia University Medical Center, showed for the first time that immunosuppressive agents would prolong heart transplant survival in the laboratory setting.
At this time, Norman Shumway, MD, Richard Lower, MD, and their associates at Stanford University Medical Center were embarking on the development of heart-lung machines, solving perfusion issues, and pioneering surgical procedures to correct heart valve defects. Key to their success was experimentation with "topical hypothermia," the localized hyper-cooling of the heart which allowed the interruption of blood flow and gave the surgeons the proper blood-free environment and adequate time to perform the repairs. Next came "autotransplantation," where the heart would be excised and resutured in place.
By the mid-1960s, the Shumway group was convinced that immunologic rejection was the only remaining obstacle to successful clinical heart transplantation. In 1967, Michael DeBakey, MD, implanted a artificial left ventricle device of his design in a patient at Baylor College of Medicine in Houston.
In 1967, a human heart from one person was transplanted into the body of another by a South African surgeon named Dr. Christiaan Barnard in Cape Town. In early December, Dr. Barnard's surgical team removed the heart of a 25-year-old woman who had died following an auto accident and placed it in the chest of Louis Washkansky, a 55-year-old man dying of heart damage. The patient survived for 18 days. Dr. Barnard had learned much of his technique from studying with the Stanford group. This first clinical heart transplantation experience stimulated world-wide notoriety, and many surgeons quickly co-opted the procedure. However, because many patients were dying soon after, the number of heart transplants dropped from 100 in 1968, to just 18 in 1970. It was recognized that the major problem was the body's natural tendency to reject the new tissues.
Over the next 20 years, important advances in tissue typing and immunosuppressant drugs allowed more transplant operations to take place and increased patients' survival rates. The most notable development in this area was Jean Borel's discovery of cyclosporine, an immunosuppressant drug derived from soil fungus, in the mid 1970s.
The cardiac transplant program at Columbia University Medical Center began in 1971 as part of an investigational surgery program initiated by Dr. Keith Reemtsma. At that time, Columbia University Medical Center was one of only a handful of medical centers in the nation actively engaged in cardiac transplant research. Columbia University Medical Center's first cardiac transplant was performed by Dr. Reemtsma in 1977, when survival rates had begun to improve significantly. That patient survived for 14 months. Two additional transplants were performed that year. Initially Columbia University Medical Center accepted patients deemed too risky for transplantation by Stanford and the Medical College of Virginia, the only other medical centers in the country performing heart transplants.
Thanks to the persistence of pioneers in immunosuppression research, transplant patients have dramatically expanded life expectancies. The first immunosuppressant drugs used in organ transplantation were the corticosteroids. In 1983, Columbia University Medical Center became one of a small group of medical centers to initiate clinical trials of cyclosporine, which was approved for commercial use in November of that year, and is still today the most commonly prescribed immunosuppressant used in organ transplantation. General information on the variety of medications that may be prescribed for you is found in the chapter on Medications in the section Care and Concerns after Your Operation.
In 1984, the world's first successful pediatric heart transplant was performed at Columbia on a four-year-old boy. He received a second transplant in 1989 and lived until he succumbed to other health issues in 2006.
Also in 1984, in Loma Linda, California, Leonard Bailey, MD, implanted a baboon heart into a 12-day-old girl who came to be known as "Baby Fae." The infant survived for twenty days as the most famous recipient of xenographic transplantation. Throughout the decade of the 1980s and into the 90s, physicians continue to refine techniques for balancing dosages of immunosuppressant medications to protect the new heart yet allow the patient sufficient immunologic function to stave off infection. In 1994 a new drug, tacrolimus or FK-506, originally discovered in a fungus sample, was approved for immunosuppression in transplant patients. Newer formulations of cyclosporine now enable efficacy (effectiveness) at lower, less toxic dosages.
While research on transplantation issues continues, other techniques for the management and cure of heart disease are also under development. Some future directions include:
Coronary assist devices and mechanical hearts are being developed or perfected to perform the functions of live tissues. Artificial hearts have been under development since the 1950s. In 1966, Dr. DeBakey first successfully implanted a booster pump as a temporary assist device. Columbia's cardiac surgeons have been instrumental in the development of a LVAD (left ventricular assist device) to function as a bridge-to-transplantation for those waiting for a new heart to become available. Columbia University Medical Center's lead role in the REMATCH clinical trial helped to lead to approval for the the LVAD as a permanent, or destination, therapy as well.
In 1969, Dr. Denton Cooley implanted the first completely artificial heart in a human, again on a temporary basis. The first permanent artificial heart, designed by Dr. Robert Jarvik, was implanted in 1982. Numbers of patients have received Jarvik or other artificial hearts since, but surviving recipients have tended to suffer strokes and related problems.
There is a tremendous gap in the number of patients waiting for new hearts and the number of organs that actually become available. In addition to avoiding the immunosuppression and rejection complications of transplantation, success in clinical application of such mechanical devices can help resolve the issue of organ availability and thus, stakes are high to continue research in this arena.
Advances in immunosuppression have most recently involved the development and expanded use of polyclonal and monoclonal antibodies to counteract steroid-resistant rejection. Research continues into the management, reversal and avoidance of accelerated atherosclerosis in the transplanted heart, believed to be caused or aggravated by the required suppression of the body's normal immunology. From the development of more powerful and specific immunosuppressants to new treatments for accelerated graft atherosclerosis, advances in the science of immunology appear to hold the key to expanding the success of heart transplantation in our treatment of end-stage cardiac disease.