Breakthrough: World's First Pig Heart Transplant Offers New Medical Insight

Two months after receiving a pig heart transplant, Mr. David Bennett's condition deteriorated and he passed away on March 9, 2022. He was the first patient in the world to receive a pig heart transplant. A spokesperson for the University of Maryland Medical Center said that the cause of death is not yet known and that the hospital's medical staff will publish the results in a medical journal.

In most cases, a heart that stops beating means that a person's life may be coming to an end. But for researchers and for patients who have been waiting for a heart, this seemingly brief 2-month period is the beginning of hope for a historic moment in transplantation.

l Why are heart transplants difficult?

The first successful heart transplant began in 1967 when South African cardiac surgeon Christiaan Barnard obtained a heart from a young woman who had just died in a car accident and transplanted it into a 54-year-old patient. However, due to severe rejection, the patient died 18 days later.

In the more than half century since, organ transplantation has continued to improve with advances in surgery, anesthesia, critical care medicine, and nursing techniques, as well as the introduction of various immunosuppressive agents, and the refinement of organ donation and transplantation protocols.

However, in heart transplantation, not only the surgical technique itself, but also the preoperative and postoperative periods present many difficulties.

Post-operative complications are a major cause of surgical failure and even patient death. However, a bigger difficulty in heart transplantation comes from the pre-operative period, the lack of donors. With approximately 4,000 heart transplants performed each year in the United States, and a waiting list of more than 100,000 patients, the average waiting time for each patient in the United States who needs a heart transplant is six months, and many unfortunately die before they can wait for a heart.

In addition, heart transplants face the same dilemma as other organ transplants: current human medical technology is not yet capable of "creating" a heart with full physiological function.

l Why pig heart?

Faced with a severe shortage of transplant organs, many scientists have begun to turn their donor research to animals, especially pigs. In terms of heart transplantation, pigs have unique advantages: in terms of size and anatomical morphology, the pig heart is very similar to the human heart.

However, the biggest obstacle to achieving a successful transplant comes from immune rejection.

Our immune system is extraordinarily complex, it effectively recognizes various foreign pathogens and actively attacks them, avoiding as much as possible that we get infected or become seriously ill. However, when confronted with a transplanted organ, our immune system also recognizes it as a foreign invader and attacks it. Thanks to the invention of new immunosuppressive agents, the problem of rejection began to be alleviated to a large extent.

Transplanting an organ from a foreign animal into a human is more difficult than transplanting a homologous organ, as the rejection reaction may be greater.

To address this problem, the FDA (United States Food and Drug Administration) has approved the development of a genetically modified pig that has been genetically engineered to reduce rejection by approximately 85% by removing alpha-gal gene from the surface of the pig's cells.

In addition, the pig hearts used for transplantation were genetically engineered with CRISPR-Cas9 technology to modify 10 genes: knocking out three key glycans genes, adding two human genes to prevent blood clotting, modifying four genes to reduce inflammation, and disabling one growth-related gene to prevent the pig hearts from growing too large.

l A historic and innovative research

Although David Bennett died 2 months after the transplant, the pig heart transplant was a huge step forward from today's perspective. David Bennett was doing well in the weeks following his transplant. He was out of ECMO 5 days after surgery and began walking on the floor the next day with no serious rejection noted, and he even watched the Super Bowl live with his doctors.

The exact cause of his death has not been disclosed, but his family remains grateful to the University of Maryland Hospital for the transplant, as his son said in a statement released by the hospital "we are grateful for every innovative moment, every crazy dream, every sleepless night that went into this historic effort. We hope this story can be the beginning of hope and not the end."

"Thomas Starzl, known as the father of transplantation, once said ‘the history of medicine is that what was inconceivable yesterday, and barely achievable today, often becomes routine tomorrow’. We have seen novel technology such as CRISPR for gene editing is changing this world, and are excited to join in the global research to push it further and further," commented by a scientist in gene therapy development at Creative Biolabs.

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