Cross-species organ transplantation is a marvel of science, but is it ethical?
Words By Maria Margot Kafka, Staff Writer
On January the 7th, David Bennett was given a second chance in life at age 57 by receiving the first successful genetically modified pig heart transplant and is now free of cardiac support.
This scientific breakthrough was conducted by the University of Maryland School of Medicine (UMSOM) and involved three experimental steps: the growing of a gene-edited heart, an experimental immunosuppressant drug, and a novel solution to store bodiless organs. Dr. Muhammad Mohiuddin had to seek a special “compassionate use” authorization from the U.S. Food and Drug Administration (FDA) to complete this surgery which skipped some clinical trials. Bennett was ineligible for a human heart transplant and suffered from terminal heart failure, making him unlikely to leave the hospital alive. Bennett consented to this risky surgery as his only hope and wished that even in the event of his death science would learn something new. UMSOM and Revivicor -the biotech company that produced the heart- have shared their belief that xenotransplantation (the transplantation of cells, tissues, or organs from one species to another) is a viable solution to the organ shortage crisis which kills 17 people daily from the 100,000 individuals on waiting lists.
The human immune system’s response to anything it recognises as foreign is xenotransplantation’s biggest challenge. Pig cells have sugar chains on their surface that act like tags. When the immune system detects them in a graft, it will attack the organ in a similar way that it would attack an organ from a person with a different blood type. The characterisation of an organ as a ‘match’ between donor and recipient is complicated even in human transplants, hence the shortage. Additionally, the patient must be ill enough to qualify for a transplant as a matter of medical urgency, but also healthy enough to receive an organ that would significantly prolong their life. Consequently, finding a match is a rare event; patients wait years (that they may not have) for the life-saving call. So, it comes as no surprise that scientists had to look elsewhere for a solution.
For the creation of the hybrid (biologically called a ‘chimera’) heart, a pig’s embryo underwent 10 precise genetic modifications using CRISPR-Cas9, a tool that can be described as molecular scissors. Revivicor knocked out 3 pig genes that would trigger the human immune system, added 6 human genes to improve functional compatibility, and modified a pig gene that controls organ growth for it to fit in a human chest. However, these 10 gene edits are not enough to prevent organ rejection.
After the surgery, an experimental drug, KPL-404 was used to dampen Bennett’s immune system. KPL-404 targets antibody production and was designed to treat rheumatoid arthritis. KPL-404 successfully passed phase I safety trials on healthy volunteers in May 2021. The post-operative administration of this drug marks an impressive jump in progress.
Lastly, this procedure required special permits by the U.S. Drug Enforcement Administration because one of the ingredients in the novel transport solution (shipped from Sweden) was cocaine – how it works remains unclear but it is evident that it keeps the donor heart healthy. Nevertheless, the regulatory demands of this procedure are not focused on the use of this organ solution. Xenotransplantation is surrounded by a plethora of ethical and philosophical questions that policymakers must tackle before it can materialize as the solution to the organ shortage.
Some religions hold strict laws on using pigs for consumption, and patients who follow Islam or Judaism, for example, might question religious teachings when qualifying for xenotransplants. Religious experts such as Dr. Moshe Freedman, senior London rabbi and member of the UK’s Moral and Ethical Advisory Group, and Dar al-Ifta, Egypt’s central authority for issuing religious rulings, both provided the BBC with statements indicating dispensations that follow the same reasoning. When faced with saving human life, the use of animal material is permitted. Other communities, who hold the rejection of anthropocentric ideology central to their cosmovision may reach different conclusions. If an individual refused xenotransplants for religious beliefs, their choice should not interfere with their eligibility for another treatment.
Transplant priority must be solely determined by medical and logistical factors, regardless of personal or social characteristics even when the distinction is not straightforward. While Bennett’s 1988 knife crime conviction should not affect his right to health, it was his lack of compliance with medical instructions that made him ineligible for a human transplant. “Organs are a precious resource” Dr. Mohiuddin stated, “the main concern was whether to give the heart to a person who may not be able to take care of it”. Bioethicists will need to discuss what would make a patient eligible for a xenotransplant instead of a human one.
On the topic of human rights, the question of treatment accessibility is paramount to the xenotransplantation debate. The main argument for porcine xenotransplants as the solution for the organ shortage crisis is the availability of donor animals. However, the seemingly unlimited supply of pigs for consumption purposes would not be the one used for xenotransplants, and neither would their crowded facilities. Part of the FDA’s reluctance to approve clinical trials was the lack of clinical-grade facilities that tightly control for infections. While Revivicor refused to disclose the cost of producing the heart, they acknowledged that it is expensive. The equipment needed for modification and the raising of chimera animals is unavailable in many countries. Focusing funding on progressing the already morally grey field of medicine can further exacerbate healthcare access inequalities across the globe.
Lastly, news of this surgery has re-sparked animal rights groups that oppose gene modification of animals under any circumstance, under the preface gene-editing may cause unpredictable effects to the animal’s health. The ethics of growing genetically modified animals to study them and harvest their organs from are arguably different from growing animals to eat, however, it is difficult to debate this when the meat industry tramples animal welfare.
In short, this January marks a huge milestone and is a true testament to the discoveries that cross-disciplinary collaboration makes possible. If xenotransplantation becomes the way forward, this future iteration of medicine may require an on-demand organ delivery system with a plethora of jobs being created to support it. A cross between a geneticist and a farmer, to breed chimera animals. Specialized surgeons that bridge veterinary with human medicine. Most importantly, a strong network of regulators that focus on equity and policymaking. Will xenotransplantation turn organ transplants from emergency medicine to planned routine operations; or will geneticists face ethical implications that resemble the plot of Margaret Atwood’s Oryx and Crake novel? Time will tell. David Bennett’s life is an unfolding omen for the future of organ transplants.