1990 Nobel Prize in Physiology or Medicine: Murray and Thomas, the Moment Organ and Bone Marrow Transplantation Became Standard Treatment
What You Will Learn in This Article
You will understand that the concept of being able to transplant another person's organs into your body was a completely new idea until the mid-20th century. You will learn about Joseph Murray's successful first identical twin kidney transplant in Boston in 1954, and his successful non-related transplant in 1962 using X-rays and immunosuppressants. You will also learn how Donnall Thomas's bone marrow transplant trials, which began in 1955, became the standard for curing leukemia. The trajectories of these two individuals paved the way for what is now 150,000 organ transplants and 20,000 hematopoietic stem cell transplants performed annually worldwide.
A Story Different from Common Sense: Crossing the Boundary Between Self and Non-Self
Our body's immune system is a system that distinguishes between self and non-self. It leaves self-tissues alone and attacks non-self tissues. This system allows us to defend against bacteria and viruses, but it also creates the problem that when we receive an organ from another person, it is attacked and rejected.
Until the mid-20th century, organ transplantation was considered virtually impossible. When skin from another person was transplanted to burn patients, it would gradually be rejected, and eventually, the transplanted tissue would die. This was the problem of whether it is possible to overcome the boundary between self and non-self.
The answer Murray discovered was clear: transplantation is possible between identical twins. Since there was already a report in 1937 that skin transplantation between identical twins was successful, he inferred that the closer the genetic relationship, the higher the success rate of transplantation. After confirming this principle through experiments with dog kidney transplants, he successfully performed the first human kidney transplant between identical twins on December 23, 1954, at Brigham Hospital in Boston. The recipient, Richard Herrick, lived for 8 more yearsβthe beginning of transplant medicine.
To overcome the limitation of identical twins, Murray attempted a combination of X-ray irradiation and immunosuppressants. The idea was that suppressing the recipient's immune system would prevent the rejection of the transplanted organ. Although most of the early attempts failed, he achieved a successful kidney transplant in 1962 between non-identical twins and between people who were not related. The immunosuppressant used was azathioprine (developed by Hitchings and Ellion, who won the Nobel Prize in 1988). This is the moment when the Nobel Prize lineages intertwine.
Meanwhile, Thomas was pushing transplantation forward in a different direction. Beginning in 1955, he began to try bone marrow transplantation in patients with leukemia and hereditary myelodysplastic syndromes. This involved destroying the patient's bone marrow with radiation and then transplanting normal bone marrow. Although most of the early attempts failed, after the 1970s, the standardization of transplantation through HLA matching was established, and it became established as a curative treatment for acute leukemia. This is the origin of today's hematopoietic stem cell transplantation (HSCT).
In CS language, these two transplantations are different types of system interventions. Organ transplantation is a hot swap of service instancesβreplacing a failed service (kidney, liver, heart, lung) with another instance, but maintaining the rest of the system. Bone marrow transplantation is a redistribution of the system kernelβcompletely redeploying the entire hematopoietic system (including the immune system) from scratch. Both interventions have the HLA (human leukocyte antigen) system, which is an authentication system that distinguishes between self and non-self, as a key issue.
The Landscape of the Era: The Final Stage of the End of the Cold War and the Dawn of Globalization
1990 was the year in which the decisive geopolitical restructuring of the late 20th century was completed.
On October 3, the reunification of Germanyβ45 years of division since 1945 came to an end. This was a rapid integration, just 11 months after the fall of the Berlin Wall (November 1989). On February 11, Nelson Mandela was releasedβa crucial milestone in the end of apartheid after 27 years of imprisonment. On August 2, Iraq invaded Kuwaitβleading to the Gulf War (January-February 1991), the first large-scale international war in the post-Cold War era. The Soviet Union approved a 5-year multi-party system reformβthe beginning of the actual collapse of the Soviet system.
In the history of technology, the Hubble Space Telescope was launched on April 24βit became a major player in space observation for the next 30 years. Microsoft Windows 3.0 was released on May 22βa turning point in the popularization of personal computing. Adobe Photoshop 1.0 was released in Februaryβthe beginning of the digital image era. On December 20, Tim Berners-Lee published the world's first webpage at CERNβthe practical opening of the WWW.
In Korean history, on February 15, the Democratic Liberal Party was formed through the merger of three partiesβthe integration of Roh Tae-woo, Kim Young-sam, and Kim Jong-pil established a conservative political landscape that lasted for 30 years. On September 30, South Korea and the Soviet Union established diplomatic relationsβRoh Tae-woo's Northern Policy led to the establishment of formal relations with the Soviet Union. In September, South-North inter-Korean prime minister-level talks beganβthe first regular talks, held alternately in Seoul and Pyongyang.
In this year of world restructuring, the Nobel Committee recognized the two individuals who pioneered transplant medicine. In the year when the boundary between self and non-self was being readjusted in international politics, transplant medicine, which overcomes the boundary between self and non-self within the body to sustain life, was recognized.
Joseph Murray: A Surgeon with Diverse Hobbies, the Implementer of the First Transplant
Joseph E. Murray (1919-2012) was an American physician. He was born in Massachusetts in 1919 to a lawyer father and a teacher mother. As a child, he aspired to become a surgeon, and in high school, he became fascinated with chemistry while looking at the periodic table of elements. At Holy Cross College, a liberal arts college, he was fascinated by Latin, Greek, philosophy, and English, and he received his Ph.D. in Medicine from Harvard University in 1943.
He had many hobbies. While at Harvard, he participated in the choir and met Link (Bobby Link), who majored in music, and they married in 1945 and had six children. He was an avid tennis player, enjoyed family vacations every year, and throughout his life, he traveled to five continents, camping, hiking, and trekking. A well-rounded life that was not just focused on academics.
Murray became interested in transplantation when he transplanted skin from another person to burn patients while working at the Philadelphia General Hospital. Seeing that skin from another person was gradually rejected, he began to explore the problem of self and non-self.
He began working at Brigham Hospital (now Brigham and Women's Hospital) in Boston in 1951 and conducted experiments with dog kidney transplants. On December 23, 1954, he successfully performed the first human kidney transplantβa transplant between identical twins, Richard Herrick and Ronald Herrick. Richard lived for 8 more years, and his twin sister had a child and got married. This was the beginning of transplant medicine.
To overcome the limitation of identical twins, Murray attempted a combination of X-ray irradiation and immunosuppressants. The idea was that suppressing the recipient's immune system would prevent the rejection of the transplanted organ. Although most of the early attempts failed, he achieved a successful kidney transplant in 1962 between non-identical twins and between people who were not related. The immunosuppressant used was azathioprine (developed by Hitchings and Ellion, who won the Nobel Prize in 1988). This is the moment when the Nobel Prize lineages intertwine.
Behind Murray's success, it is a fact that Sir Medawar, who won the Nobel Prize in 1960 for the discovery of immune tolerance, and Hitchings and Ellion, who won the Nobel Prize in 1988 for the development of azathioprine, frequently visited his laboratory to offer advice. This shows that solving the problem of transplantation was the result of collaboration in various fields of study.
E. Donnall Thomas: From Rural Texas to Pioneer of Bone Marrow Transplantation
E. Donnall Thomas (1920-2012) was an American hematologist. He was born in 1920 in a small rural town in Texas as the only son of a 50-year-old doctor. He attended a small rural high school with only 15 students, but his grades were not very good. He entered the University of Texas in 1937, but his first-year GPA was around B, so he was not outstanding. However, as he progressed through his studies, he became interested in chemistry, and he received his Ph.D. in Medicine from Harvard University in 1946.
Thomas served as professor at the University of Washington (Seattle) from 1963 to 1990 and as director of the Fred Hutchinson Cancer Research Center from 1975 to 1990. This became the world center for bone marrow transplantation.
Thomas's pioneering work in bone marrow transplantation was a series of failures. Beginning in 1955, he began to try transplanting normal bone marrow after destroying the bone marrow of patients with leukemia and hereditary myelodysplastic syndromes with radiation. Most of the early attempts failed due to graft-versus-host disease (GVHD) or infection. However, he did not give up and established various conditions for transplantationβHLA matching, conditioning regimen, infection prevention, GVHD preventionβone by one.
Starting in the mid-1970s, it began to be established as a curative treatment for leukemia. After the 1980s, it was established as a standard treatment option for acute myeloid leukemia and acute lymphoblastic leukemia. Today, more than 20,000 hematopoietic stem cell transplants are performed worldwide each year, and this lineage began with Thomas.
Decisive Developments: The 1962 Transplant and Beyond
The successful non-identical twin kidney transplant by Murray in 1962 was the moment when transplant medicine was practically established. Azathioprine and X-ray combination. Subsequently, cyclosporine (introduced clinically in 1983) and tacrolimus (1994) were sequentially developed, refining immunosuppressants. Today, the 1-year survival rate after organ transplantation is 96% for kidneys, 89% for livers, and 87% for hearts.
The discovery of cyclosporine in 1975 revolutionized transplant medicine. Isolated from a Norwegian Scandinavian fungus, this substance specifically blocks the immune response by inhibiting the production of IL-2 by T cells. It is more potent and tissue-specific than azathioprine. With the introduction of cyclosporine, the practical use of liver, heart, and lung transplantation was achieved.
The importance of HLA genotype matching has been clarified, and transplant outcomes have improved dramatically. The discoveries of D'ohnega (Nobel Prize in 1987) and Doussay, Benacerraf, and Snell (Nobel Prize in 1980) completed the perspective of transplant medicine as an authentication system.
CS Frame: Service Hot Swap and Kernel Redeployment
Reconstructing transplant medicine in the language of CS, we have:
Organ transplantation = service instance hot swap: Replacing a failed service (organ) with another instance, but maintaining the rest of the system. Kidney transplantation is replacing the filtering service, liver transplantation is replacing the metabolic processing service, and heart transplantation is replacing the circulatory pump service. Each service must have a standardized interface in order to be replaced.
HLA = authentication system: HLA molecules on the surface of each cell act like self-authentication certificates. Immune surveillance (T cells) verifies this certificate and decides whether to pass or block. The higher the HLA match between the transplanted organ and the recipient, the higher the authentication pass rate.
Immune rejection = authentication failure: If the HLA of the transplanted organ is different from the recipient, T cells recognize it as non-self and attack. This is similar to a system that denies access due to a signature mismatch in a type check.
Immunosuppressants = authentication bypass:
- Azathioprine: Suppresses lymphocyte proliferation (limits parallel processes)
- Cyclosporine and tacrolimus: Inhibit IL-2 production by T cells (turns off specific services)
- Steroids: Broad-spectrum anti-inflammatory (emergency shutdown)
- Monoclonal antibodies (basiliximab, etc.): Inhibit specific targets (pinpoint intercept)
Bone marrow transplantation = system kernel redeployment: Completely replacing the entire hematopoietic system (red blood cells, white blood cells, platelets) that creates the kernel (hematopoietic stem cells). This is a major overhaul that involves reinstalling even the bootloader. If successful, it leads to fundamental healing (curing leukemia), but if it fails, the system itself dies.
Graft-versus-host disease (GVHD) = rebellion of the new kernel: The immune cells of the transplanted bone marrow recognize the recipient's tissues as non-self and attack. This is a situation in which the redeployed kernel misidentifies the original system's data and services as intruders.
This analogy makes it clear why transplantation requires such meticulous management. Service replacement requires standardized interfaces (HLA matching) and continuous authentication management (immunosuppression).
Academic Impact: Standardization and Industrialization of Transplant Medicine
Following this discovery, transplant medicine becomes a standard in advanced clinical medicine.
Expansion of Organ-Specific Transplants: Kidney (1954) β Liver (1963, Starzl) β Heart (1967, Christian Barnard) β Lung (1983) β Small Intestine (1988) β Face (2005, French, Isabelle Dinoire) β Uterus (2013, Sweden). Today, there are approximately 80,000 kidney transplants, 30,000 liver transplants, and 6,000 heart transplants performed worldwide annually.
Establishment of Brain Death and Organ Donation Systems: Along with the advancement of transplant medicine, the concept of brain death was established in the 1968 Harvard Committee report. Subsequently, each country legalized brain death criteria and organ donation/transplantation systems. In Korea, the Act on Organ Transplantation was enacted in 1999.
Expansion of Hematopoietic Stem Cell Transplantation: Expanded from bone marrow to peripheral blood hematopoietic stem cells (PBSC) and umbilical cord blood hematopoietic stem cells. Today, it is the standard treatment for acute leukemia, aplastic anemia, and severe autoimmune diseases.
Expansion to Cell Therapy: The principle of hematopoietic stem cell transplantation has expanded to CAR-T cell therapy (FDA approved in 2017) and induced pluripotent stem cell (iPSC)-derived cell therapy. This represents a new paradigm of using human cells themselves as therapeutic agents.
Attempts at Xenotransplantation: In recent years, attempts have been made in the United States to transplant genetically modified pig kidneys and hearts into humans. In 2024, a genetically modified pig kidney was transplanted into a human at Massachusetts General Hospital. This holds future potential for solving the organ shortage problem.
Korea's Legacy and Today
Transplant medicine in Korea began in 1969 with the first kidney transplant at Seoul National University. Since then, Seoul Asan, Samsung Seoul, Seoul National University, and Yonsei Severance have been at the forefront of transplant medicine.
Seoul Asan Hospital's World-Leading Liver Transplant Outcomes: The living donor partial liver transplantation (living donor liver transplantation) technique developed by Professor Seung-kyu Lee's team has become the world standard. Professor Seung-kyu Lee holds the world record for the most liver transplants performed. Korea's one-year survival rate for liver transplants is among the highest in the world.
Korea's Hematopoietic Stem Cell Transplantation is also very active. Catholic University St. Mary's Hospital (Professor Dong-wook Kim's team) has the highest number of transplants in the world. It is the standard treatment for acute leukemia, multiple myeloma, and childhood aplastic anemia.
Korea's organ donation culture is still developing but is gradually expanding. Since 2000, the number of brain-dead donors has increased, and the KODA (Korea Organ Donation & Transplantation Institute) system has been established.
Why is it Important?
What the two men left behind is the establishment of the idea that "the boundary between self and non-self can be overcome."
It is a prime example of how medicine has expanded the horizons of fundamental healing. Previously, kidney, liver, and heart failure often meant death, but transplantation has transformed this death sentence into a possibility of postponement. Today, patients with chronic renal failure continue their lives with dialysis β kidney transplantation. Patients with end-stage liver failure recover with liver transplantation. Patients with acute leukemia aim for a cure with bone marrow transplantation.
It is a case of combining clinical medicine and basic science. The success of Murray and Thomas was not only due to their surgical and hematological knowledge but also the combination of advances in immunology (Metherow, 1960; Benacerraf-Dausset-Snell, 1980; Dohnawa, 1987; Doherty-Zinkernagel, 1996) and advances in pharmacology (Elion-Hitchings, 1988). It is a point where various academic lineages converge on a single clinical task, transplantation.
The story of two country boys meeting at Harvard and changing the world is also a powerful symbol. Murray was from a small town in Massachusetts, and Thomas was from a rural area of Texas with a high school class of 15. Without any particular academic background, they met at Harvard and, from their respective fields, changed the landscape of medicine in the late 20th century.
Since this award, the trends in transplantation and cell therapy have continued as follows:
- 1996, Doherty and Zinkernagel: MHC-restricted cellular immunity
- 2007, Yamanaka: Discovery of iPSC (2012 Nobel Prize)
- 2017, Kymriah and Yescarta: CAR-T cell therapy FDA approved
- 2024, Xenotransplantation Clinical Trials: Genetically modified pig kidneys transplanted into humans
Clinical and industrial applications of this discovery:
- Standardization of Organ Transplantation: Kidney, liver, heart, lung, pancreas, small intestine, face, uterus
- Hematopoietic Stem Cell Transplantation: Acute leukemia, multiple myeloma, aplastic anemia
- Immunosuppressant Market: Cyclosporine, tacrolimus, mycophenolate, belatacept
- Expansion of Cell Therapy: CAR-T, iPSC, MSC
- Future of Xenotransplantation: Genetically modified pig organs
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