On March 21, it was announced that surgeons at Massachusetts General Hospital (MGH) had successfully transplanted a pig kidney into a living 62-year-old man suffering from severe kidney disease. The surgery, which lasted 4 hours, was performed on March 16.

This procedure in a living recipient represents a milestone in the field of xenotransplantation (the transplantation of organs or tissues from one species to another) as a possible solution to the worldwide organ shortage.

The MGH is recognized for being a center where numerous transplants are performed, both organs and tissues. The doctor who led the operation was Leonardo Riella, who is the Medical Director for Kidney Transplantation at that hospital.

There are two main difficulties that xenotransplants present: on the one hand, the genetic differences that will cause severe immunological rejection responses in the recipient. On the other hand, the possibility of transmitting infectious agents specific to the donor’s species to the recipient, with unpredictable consequences.

To avoid these difficulties, in this case, the pig kidney has been genetically-edited using CRISPR-Cas9 technology to remove harmful pig genes and add certain human genes to improve its compatibility with humans. Additionally, scientists inactivated porcine endogenous retroviruses in the pig donor to eliminate any risk of zoonoses or infection in humans from animal pathogens.

According to the United Network for Organ Sharing (UNOS), more than 100,000 people in the U.S. await an organ for transplant and 17 people die each day waiting for an organ.

Kidney recipient, Richard Slayman is recovering well from surgery and is expected to be discharged soon. In 2018, this same patient already received a kidney transplant from a human deceased donor. That first transplant was performed after he had lived for many years with type 2 diabetes and hypertension and having received dialysis for seven years. That first transplanted kidney showed signs of failure approximately five years later and Mr. Slayman resumed dialysis in May 2023.

Credit: Massachusetts General Hospital;
Photographer: Michelle Rose

The doctors who perform transplants at MGH have nearly 30 years of experience in xenotransplantation research.

Dr Riella stated that “seventy years after the first kidney transplant and six decades following the advent of immunosuppressive medications, we stand on the brink of a monumental breakthrough in transplantation. At MGH alone, there are over 1,400 patients on the waiting list for a kidney transplant. Some of these patients will unfortunately die or get too sick to be transplanted due to the long waiting time on dialysis. I am firmly convinced that xenotransplantation represents a promising solution to the organ shortage crisis”.

Previously, pig organ transplants had been performed on people, but with brain death in the case of the kidneys, and with a serious illness that led to death shortly after the transplant, in the case of the heart.

In the first case of a pig kidney transplant to a brain-dead woman, carried out in September 2021, the kidney functioned correctly and autonomously for 54 hours.

The first transplant of a pig heart, genetically modified to facilitate organ compatibility and reduce the patient’s immune rejection response, was performed in January 2022. The patient, suffering from severe heart failure, survived 2 months.

Bioethical assessment

The use of organs or tissues from animal species for transplantation into humans constitutes an alternative to current organ and tissue transplants, which could alleviate the drama of the shortage of available units, given the long waiting lists of patients who need them.

The bioethical difficulties in this process are situated around its safety and effectiveness. The novelty of the case at hand, which seems promising, lies in the prior process of genetic editing of the organ, which can minimize the immune rejection response.

But the silencing or elimination of numerous genes along with the addition of others of human origin in the porcine organ to be transplanted is a very complex process whose consequences are difficult to predict. The gene editing tools used can introduce unwanted modifications to the genome, which can lead to potentially serious side effects.

Controlling, both in the medium and long term, the consequences of these interventions is an essential requirement to ensure their applicability in humans and to avoid having to take unjustified risks.

Accepting the new therapeutic possibilities related to gene editing requires prudent attitudes, where transparency in research and its complications allows the scientific community to progress towards new, effective and safe clinical tools.

Julio Tudela and Ester Bosch

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

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