What happens when two immune systems are interchanged with one another? This was essentially the question being asked in the 1950s by doctors working at the Mary Imogene Basset Hospital in Cooperstown, New York, which was affiliated to Cornell University. They were researching the concept of bone-marrow transplants, which involved the removal of one person’s bone marrow and replacing it by another person’s.
One of the scientists was E. Donnall “Don” Thomas who had recently arrived at the New York hospital and immediately began working on marrow transplantation in human patients and genetically outbred breeds of dog, which were considered a suitable model for humans. The winters were long and cold and the scientists lived near to their place of work, which gave them ample opportunity for long discussions of the problems, Thomas later recalled, when he received the 1990 Nobel Prize in Medicine of Physiology. He remembered this period in his career as being formative in why he later became known as the “father of bone marrow transplantation”.
“Those years had a deep and abiding influence on subsequent work since most of the basic concepts were laid out during that time,” he said.
Bone marrow, the spongy tissue inside the bones, is where the blood cells are made, including many of the cells of the immune system. When the bone marrow malfunctions, it can lead to cancers such as leukaemia, lymphoma and myeloma, or in rare cases an immune deficiency, where babies and children are prone to opportunistic infections they would normally shrug off.
Don Thomas soon realised that transplanting bone marrow risked generating an immune reaction called graft-versus-host disease, when the immune cells of the donated marrow start attacking the “foreign” cells of the recipient’s body. He managed to avoid the problem in the 1950s by transplanting the bone marrow of identical twins, one of whom had leukaemia. In a seminal scientific paper published in the New England Journal of Medicine in September 1957, Thomas and his colleagues laid out the foundations for bone-marrow transplant, even though many respected scientists continued to insist for a decade or more afterwards that the procedure would not work.
In 1968, scientists realised that successful transplants relied on specific HLA tissue matching between donor and patient, which enabled them to perform the first successful bone marrow transplant on non-twin siblings. The first unrelated donor transplant took place in 1973 in New York when a young boy with an immunodeficiency disorder received multiple marrow transplants from a donor identified as a match through a blood bank in Denmark.
Today, bone marrow transplants are a proven method of treating leukaemias and other cancers as well as blood disorders such as aplastic anaemia.