By Armaan Singh
Heart transplants have been practiced in medicine since the late 20th century. The first successful human to human heart transplant took place on December 3, 1967 in Cape Town South Africa and was performed by Christiaan Barnard. This operation was performed on Louis Washanky, a 53 year old man who was a diabetic and a smoker and had a severe case of coronary insufficiency. The heart Washanky received was from a young woman Denise Darvall, who had been pronounced brain dead following a fatal car accident, which left her unable to recover. The neurosurgeon assigned to Darvall referred her to an organ donor, and according to South African laws at the time, there was no solid legislation relating to organ donation and brain death, so the surgery was given the green light. The ventilation of Darvall was discontinued, and the chest was opened. Barnard’s team initiated pump oxidation, appropriately cooled the heart, and then removed it. The procedure was successful and Washanky’s body accepted the new heart, with the heart functioning properly. This procedure received widespread coverage overnight, and the theory of heart to heart transplants became a reality. Washanky, however, developed radiographic infiltrates in his lungs. This led Barnard to attempt a transplant on more patients, modifying the operation as time went on, by extending the incision in the right atrium (one of the 4 chambers of the heart, one of two places where deoxygenated blood enters) from the inferior vena cava into the atrial appendage to avoid the sinus node (specialized cells in upper right chamber). While the human to human heart transplant has been a staple medical procedure there are flaws and long wait times for patients.
Heart transplants, while effective, have been increasingly scarce over time. To begin with, the conditions that only heart transplants can treat have been shown to be extremely high maintenance. For example, cardiomyopathy (a condition that occurs when it is more difficult for the heart to pump blood) a condition that worsens over time is often treated by heart transplantation. Coronary artery disease is another condition where patients are eligible to get a heart transplant and is also extremely serious and may worsen without valid treatment. Coronary artery disease occurs when plaque or fatty material builds up in the arteries that provide oxygen rich blood to the heart. Without oxygen rich blood, the heart muscle cannot function properly and has to work harder to pump blood. Left untreated, heart attacks and arrhythmias and death will occur. Now that the severity of these conditions are established, one can reasonably expect treatment to be delivered swiftly. Unfortunately the average wait time for a heart transplant can range up to six months. When patients are suffering from conditions that are proven to worsen over time, such lengthy wait times can be extremely detrimental. This is a direct result of the scarcity of heart donors over time. A study by AHA Journals examines how the number of donors who have been declined for transplants have seen a substantial increase. The number of donors who have also had a history of abusing drugs such as cocaine and other intravenous drugs have also increased. This could pose significant issues since cocaine poses long term effects on the heart such as inflammation. As a result of this scarcity, a bold new solution was proposed: one of abandoning human organ transplants altogether and seeking out animals as an alternative.
The process of trans species organ transplants is not a new concept, but it is a relatively unsuccessful one. Xenotransplantation is the process of transferring animal organs to human organs. While a relatively untested concept, the idea of xenotransplantation dates back to Greek mythology, demonstrating the interest of merging human and animal features (i.e the minotaur). In the 17th century Jean Baptiste practiced animal and human blood transfusions that received varying results, leading to its ban in France. More experiments took place over time involving transplantations of cornea, pancreas cells, and kidneys. The most significant operation took place in 1984, one of the most controversial surgeries in the history of medicine. In this case, Stephanie Fae Beauclair, an infant, had Hypoplastic Left Heart Syndrome at birth. Surgeon Leonard Bailey had an idea to transplant the heart of a baboon into Fae since obtaining human organs from infants at the time was out of the question. Initially, the baboon heart functioned properly. However, after 20 days, as a result of the baboon’s blood type differential, the heart failed as a result of acute rejection. This is extremely symptomatic of transplants in general, but especially in xenotransplantation. Often these operations result in rejection. When a new organ is placed in the body, specialized cells known as CD4+ T cells detect invaders, and B Cells then attack the foreign objects. This has often been the greatest obstacle in xenotransplantation due to this response, causing it to be ruled out as a valid treatment until recently.
On the 14th of January 2022, nearly four decades after baby Fae’s transplant and nearly six decades after Dr. Barnard broke new ground, history was made. A research team spearheaded by Muhammad Mohiuddin was able to perform the world’s first pig to human heart transplant. In this operation, David Bennett, a man in cardiac arrest, could not receive a mechanical heart as a result of his irregular heartbeat. In order to combat the rejection that usually occurs when a foreign organ is transplanted, the team utilized CRISPR–Cas9 gene editing, which reduced the likelihood of rejection. Genetic modification of the pig also occurred weeks in advance. They were able to knock off three genes in the pig that could result in immune rejection and also added three human genes to the pig. The results were ideal with the heart functioning correctly with no rejection. The success of this operation ushers in a plethora of possibilities. Perhaps, if genes can be modified in this fashion, the issues of scarcity may be addressed and rejection will no longer be an issue. While this is only the beginning and there is work to be done, this may lead to xenotransplantation becoming as commonplace as a normal heart transplant that was made by Barnard all those years ago.
What did I learn?
Question 1
What is xenotransplantation?
Answer:
Xenotransplantation is the process of transferring animal organs to human organs.
Question 2:
Why does the human body reject foreign organs?
Answer:
Oftentimes, when a new organ is placed in the body, specialized cells known as CD4+ T cells detect invaders, and then B Cells attack the foreign objects. This has often been the greatest obstacle in xenotransplantation due to this response.
References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200566/#:~:text=Christiaan%20Barnard%20with%20his%20team,operation%20on%203%20December%201967. https://www.ucsfhealth.org/education/faq-heart-transplant#4