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For most of human history, when a vital part of the body failed, there was little doctors could do.
Then a series of advances in surgery, immunology, and pharmaceuticals made something once considered impossible increasingly routine.
It required solving problems of compatibility, rejection, preservation, and advanced surgical techniques. Today, tens of thousands of people a year owe their lives to this breakthrough.
Learn more about the history of organ transplants and how they work on this episode of Everything Everywhere Daily.
Organ transplantation is one of medicine’s most remarkable achievements because it required solving several problems that were once considered almost impossible.
Organ transplants are conceptually simple to understand. It is simply replacing a failing organ with a functioning organ taken from another person, or, in experimental cases, another species.
It sounds simple, but solving the problems of organ transplantation required multiple medical breakthroughs, many of which won Nobel Prizes.
One major problem was physical and surgical. Surgeons needed to develop techniques that allowed them to connect blood vessels between the organ and the body.
The second problem, which was arguably larger, was biological. Transplanted organs are foreign tissue, and the body will often reject them as if they were a foreign pathogen.
While organ transplants are relatively recent, the idea is actually quite old.
Ancient myths contain stories of limbs, eyes, hearts, and other body parts being replaced. More practically, ancient Indian physicians developed sophisticated forms of reconstructive surgery. The surgical tradition associated with the Sushruta Samhita, probably compiled during the first millennium BC, described techniques for reconstructing noses using flaps of the patient’s own skin.
It wasn’t an organ transplant per se, but it was transplanting skin from one part of the body to another.
During the Renaissance, the Italian surgeon Gaspare Tagliacozzi developed techniques for reconstructing noses using skin from a patient’s arm. He reportedly recognized that tissue taken from another individual behaved differently and generally failed.
By the nineteenth century, surgeons experimented systematically with skin grafts. Skin taken from the same person often survived. Tissue transferred from another person might initially appear healthy but usually deteriorated and disappeared.
No one yet understood the immune mechanism responsible for rejecting foreign tissue.
A solid organ cannot survive unless its blood supply can be restored quickly. That required surgeons to learn how to sew arteries and veins together without causing catastrophic bleeding, narrowing the vessel, or producing blood clots.
One of the critical pioneers was the French surgeon Alexis Carrel.
At the beginning of the twentieth century, Carrel developed reliable techniques for vascular anastomosis, the surgical joining of blood vessels. He experimented with transplantation in animals and demonstrated that entire organs could be removed and reconnected to another circulatory system.
Carrel received the 1912 Nobel Prize in Physiology or Medicine largely for his work in vascular suturing and transplantation. Modern transplantation would quite literally be impossible without this surgical innovation.
Another important advance came from Karl Landsteiner’s discovery of the ABO blood types in 1901. Blood transfusions had previously been unpredictable. Some worked, while others caused rapid and sometimes fatal reactions.
Landsteiner demonstrated that people possessed different blood types and that antibodies could attack incompatible red blood cells. Although organ rejection is considerably more complicated than blood compatibility, the discovery established an important principle: biological compatibility between people mattered.
Landsteiner was awarded the Nobel Prize for his work in 1930.
Transplant programs eventually learned that blood type was one of the first things to consider when matching donors and recipients.
One form of transplantation succeeded surprisingly early. In 1905, Austrian ophthalmologist Eduard Zirm performed what is generally regarded as the first successful human corneal transplant.
The cornea is unusually favorable for transplantation because it does not normally contain blood vessels, so it’s relatively isolated from much of the immune system.
The kidney became the natural experimental organ for transplantation, for several reasons. Humans have two kidneys and can live normally with one, making living donation possible, and kidneys have comparatively simple vascular connections.
Kidney function can also be easily assessed by monitoring urine output and blood chemistry.
Researchers experimented extensively with kidney transplantation in animals during the early twentieth century.
In 1933, Ukrainian surgeon Yurii Voronoy attempted the first human-to-human kidney transplant.
The donor was deceased, and the recipient suffered from acute renal failure. The kidney never functioned adequately, and the patient died shortly afterward.
The operation was a failure as treatment, but it demonstrated that human organ transplantation was surgically conceivable. The biological problem, however, remained unsolved.
Another major step came in 1950 when Chicago surgeon Richard Lawler transplanted a kidney from a deceased donor into a woman suffering from kidney disease.
The transplanted kidney was eventually removed after about two months. The patient survived because her own kidneys recovered sufficiently.
It wasn’t a permanent cure, but it demonstrated the surgical technique could work.
By this point, surgeons were becoming capable of performing the operation. The problem was that the immune system kept destroying the organ.
The breakthrough came largely from experiments during and after World War II. British biologist Peter Medawar studied skin grafts, partly because severe burns suffered by wartime casualties created an urgent interest in skin transplantation.
Medawar demonstrated that graft rejection was not simply the result of poor surgery. It was an immune response.
The first graft from one individual to another might survive temporarily. A second graft from the same donor would often be destroyed more rapidly. That indicated that the recipient’s immune system had developed a memory of the donor.
The phenomenon became known as acquired immunological tolerance and rejection. Medawar and Australian immunologist Frank Macfarlane Burnet later received the 1960 Nobel Prize for work establishing the concept of acquired immunological tolerance.
That discovery changed the entire problem. Doctors no longer simply had to become better surgeons. They had to manipulate the immune system.
The first unequivocally successful human solid-organ transplant occurred on December 23, 1954, at Peter Bent Brigham Hospital in Boston.
The recipient was Richard Herrick, who was dying of kidney disease, and his donor was his identical twin brother, Ronald Herrick. Because identical twins possess essentially the same genetic makeup, Richard’s immune system did not regard his brother’s kidney as foreign.
Surgeon Joseph Murray headed the recipient operation, while J. Hartwell Harrison performed the donor kidney removal. The kidney began functioning after transplantation, and Richard Herrick lived for about eight more years.
Joseph Murray would share the 1990 Nobel Prize for his work on transplantation.
Transplantation between ordinary people required suppressing the immune system. Early approaches were crude. Researchers experimented with whole-body radiation, attempting to destroy enough of the recipient’s immune cells to prevent rejection.
It sometimes worked, but the treatment could also destroy the bone marrow and leave patients defenseless against infection. In 1959, kidney transplantation between genetically non-identical people achieved some successes using radiation to suppress immunity.
The real future lay in drugs.
One of the first major immunosuppressive drugs was azathioprine. Azathioprine inhibits the proliferation of rapidly dividing immune cells.
By the early 1960s, transplant teams were combining azathioprine with inflammation-reducing corticosteroids such as prednisone.
The combination greatly improved kidney transplant survival. In 1962, Murray’s Boston group performed a landmark successful deceased-donor kidney transplant using drug-based immunosuppression.
That was arguably the moment kidney transplantation began transitioning from experimental surgery into mainstream medicine.
Suppressing the immune system helped, but matching compatible donors improved results further. Scientists discovered that much of transplant rejection revolves around proteins encoded by the human leukocyte antigen system, or HLA.
HLA molecules appear on the surfaces of cells and help the immune system distinguish the body’s own tissue from foreign material. Two unrelated people usually have different HLA profiles.
Transplant centers therefore developed tissue typing to compare donor and recipient HLA markers.
They also developed the crossmatch test.
A crossmatch is a compatibility test performed before a transplant. The recipient’s blood serum is mixed with donor cells to see whether the recipient already has antibodies that attack the donor’s tissue. A positive crossmatch usually means the transplant would carry a high risk of immediate rejection, while a negative crossmatch suggests it is safer to proceed.
Together, blood typing, HLA typing, antibody testing, and crossmatching revolutionized donor selection.
The liver presented a much greater surgical challenge than the kidney.
It is large, richly supplied with blood vessels, and capable of catastrophic bleeding during surgery.
American surgeon Thomas Starzl was central to the development of liver transplantation.
Starzl performed the first human liver transplant attempt in 1963 at the University of Colorado. The early attempts resulted in short survival, and after several failures, the field temporarily halted liver transplantation while surgical techniques and immunosuppression were improved.
In 1967, Starzl’s team achieved the first liver transplant with significant long-term survival. A 19-month-old girl named Julie Rodriguez survived for more than a year before dying from recurrent cancer.
In December 1966, surgeons William Kelly and Richard Lillehei and their colleagues at the University of Minnesota performed the first successful pancreas transplant, together with a kidney transplant, in a patient with severe diabetes and kidney failure.
Heart transplantation captured far more public attention than kidney or liver transplantation, and there were problems that needed to be solved beyond those required for something like a kidney transplant.
Surgeons first needed cardiopulmonary bypass, the heart-lung machine, which allowed surgeons to stop the heart while a machine temporarily oxygenated and circulated the patient’s blood.
Techniques developed during open-heart surgery in the 1950s provided much of the necessary surgical knowledge.
American surgeon Norman Shumway and his colleagues at Stanford carried out crucial experiments in canine heart transplantation and developed many of the surgical techniques ultimately used in humans.
But another surgeon reached the milestone first.
On December 3, 1967, South African surgeon Christiaan Barnard and his team at Groote Schuur Hospital in Cape Town performed the world’s first human-to-human heart transplant.
The recipient was Louis Washkansky, and the donor was Denise Darvall, a young woman who had suffered catastrophic brain injury in a traffic accident.
Washkansky survived the operation and lived for 18 days before dying from pneumonia while heavily immunosuppressed. The short survival might sound disappointing today, but the operation demonstrated that a human heart could be replaced successfully.
Lungs proved particularly difficult to transplant.
They are constantly exposed to the outside environment through the airway, making infection a serious risk. Bronchial connections must heal properly despite a disrupted blood supply, and lung tissue is especially vulnerable to immune injury.
American surgeon James Hardy performed the first human lung transplant in Mississippi in 1963. The patient survived for only 18 days.
A major breakthrough came in 1983, when surgeon Joel Cooper and the Toronto Lung Transplant Group performed a single-lung transplant whose recipient survived for years.
Many of the advancements over the last few decades have involved improved immunosuppressant drugs.
In the 1970s, cyclosporine selectively interfered with T lymphocytes, the immune cells central to transplant rejection. The effect was dramatic.
Instead of broadly destroying a person’s immune function, doctors could target just the pathways involved in rejection much more effectively. Kidney, liver, heart, and eventually lung transplant survival improved sharply.
Another major breakthrough arrived with tacrolimus, which became widely used during the 1990s, especially in liver transplantation.
Work on organ transplants continues, and exciting new developments are on the horizon. The future of transplantation will likely center on making more organs available and reducing rejection.
Major areas include genetically modified pig organs, lab-grown or bioengineered organs from a patient’s own cells, and more precise immune therapies that could eventually reduce or eliminate the need for lifelong immunosuppressive drugs.
Organ transplants have been one of the revolutions of 20th-century medicine. However, it wasn’t a single innovation. It was a series of advancements across multiple disciplines that improved the lives and lifespans of those who were in need of transplants.