A Pig at Heart

David Bennett Sr. lay in a hospital bed under the darkness of amnesia on January 7. Tethered to a tube and submerged in a murky solution was the vital organ that would be the key to this man’s life. It wasn’t a human organ, though. It was the heart of a pig.

Bennett was 57 years old, terminally ill, and in end-stage heart failure when he underwent surgery. His uncontrolled arrhythmia (irregular heartbeat) made him a bad candidate for an implantable heart device. Being labeled a “problem patient” was another dilemma that made it challenging to receive a human heart transplant. Bennett missed doctor’s appointments, did not always take medications, and frequently ignored doctor’s orders. Without a transplant, he would surely die. This operation, given emergency authorization by the FDA, was his last chance for survival.

Chief of Cardiothoracic Surgery at the University of Maryland Medical Center Dr. Bartley Griffith was the lead surgeon on the case. Throughout Dr. Griffith’s 40-year career, he has received numerous honors and awards, such as induction into the Royal College of Surgeons. This surgery wasn’t the first time he made history in the field of xenotransplantation, the transplanting or grafting of organs or tissue across organisms of different species. He performed a groundbreaking procedure that used both animal and human donor tissue to reconstruct the top two chambers of a woman’s heart in 2003. Dr. Griffith’s colleague, Dr. Muhammad M. Mohiuddin, with whom he co-runs the University of Maryland’s cardiac xenotransplantation program, also played a central role in the revolutionary surgery. Dr. Mohiuddin was in charge of the lab work that studied the transplantation of pig hearts.

This accomplishment was no spur-of-the-moment surgery. The procedure had been in the works for five years. Bennett had to undergo four psychiatric evaluations to make sure that he was able to consent to the surgery. The pig heart itself was the result of years of work. Pigs are typically used in the practice of xenotransplantation due to their anatomical similarities to humans, ease of breeding, large litters, variety in size, and ability to be genetically modified.

Both Dr. Griffith and Dr. Mohiuddin knew that they needed to make some changes to the pig’s heart in order for it to be compatible with their patient’s body. As a result, the pig, raised by Revivicor, a U.S. firm that spun off from PPL Therapeutics, was genetically modified. This company helped create Dolly the sheep, the first mammal to be cloned from an adult cell. Three genes largely responsible for the production of a sugar molecule called α-gal were knocked out. Normally, this molecule would be on the surface of the pig’s cells, which would trigger an immune response once transplanted. Additionally, six human genes that control the coagulation cycle (the process which creates clotting after an injury), antibody function, and inflammation were added to the pig in order to make the heart more compatible with the human immune system. Lastly, one gene was knocked out to control how fast and large the heart could grow. Specifically, the heart would not be able to grow after transplantation.

Kept active and cold by the constant flow of a fluid consisting mainly of saline and cocaine, the bodiless heart was ready for operation. The rest of the surgery was laborious work, beginning with an eight-inch incision in Bennet’s chest and the sawing of his breastbone. The entire operation was eight hours of painstakingly precise and purely focused stitching, tucking, and connecting. In the end, though, the heart came alive.

To prevent rejection of the foreign heart, he was prescribed a strong, experimental immunosuppressant drug, KPL-404. This drug binds to cell receptor CD40, suppressing B cells and T cells, both responsible for triggering immune system attacks.

Two months after this surgery, Bennet’s health began deteriorating, and he passed away on March 8, with the primary cause not yet identified. Scientists and doctors are still optimistic, which brings up the ethical question of whether humans should raise animals for the express purpose of harvesting their organs. On average, 17 Americans waiting for organ transplants die each day, and xenotransplantation could be the solution. However, campaigners argue that animals are not human resources, but living beings. Furthermore, the genetic modification process may have unknown effects that impact the pigs’ quality of life, not to mention that they would be raised in bio-sealed, controlled environments.

Bennett’s surgery did not end up saving his life, but it did provide valuable insight into this novel field of medicine. Xenotransplantation operations are risky, and most are experimental, as the procedure for entire organs, rather than sections of organs or just tissues, is relatively new. For now, such xenotransplants will only be used as a last resort. Regardless, this development has broken boundaries in the field of medicine, forcing us to confront the future of xenotransplantation in both a practical and moral sense.