"Save the pig's heart", what did the little pig do wrong

Remember David Bennett, the American man who underwent a pig heart transplant earlier this year?

Image source: University of Maryland School of Medicine

Unfortunately, as the world's first pig heart transplant patient, he unfortunately passed away two months after the operation.

Recently, researchers from the University of Maryland in the United States announced that they found that the transplanted pig heart carried porcine cytomegalovirus, but it is not yet certain whether the virus is directly related to the patient's death. But what is certain is that animal organ transplantation still needs further testing and research.

Image source: Global Times

For patients whose organs are severely damaged and whose functions are failing, organ transplantation is their only hope of regaining health.

In my country, hundreds of thousands of patients are waiting for organ transplants every year, and some even die without a suitable donor. In order to solve the problem of organ supply shortage, scientists have been working hard to overcome the difficulties of xenotransplantation.

Organ transplantation has long been a concept

The idea of ​​organ transplantation is not exclusive to modern humans. Thousands of years ago, the ancestors of ancient civilizations had the idea of ​​organ transplantation. In addition to the medical idea, there was also the factor of power worship. The Sphinx with a lion's body and a human's face, the Chimera with a lion's head and a goat's body... Many well-known monster images are spliced ​​from organs from different species.

Chimera on a plate from Puglia, circa 350-340 AD (Louvre), Image source: Wikipedia

The first science fiction novel in literary history, Frankenstein, written by British novelist Mary Wollstonecraft Shelley in 1818, describes a giant human body made up of organs and tissues from different corpses. Various literary and artistic works derived from this classic "monster" image are still meeting audiences today.

The earliest attempt at organ transplantation in medical history can be traced back to the Renaissance, when an Italian surgeon named Gaspare Tagliacozzi tried to save a syphilis patient with a "rotten" nose by using autologous skin transplantation.

Gaspare Tagliacozzi, Image source: Wikipedia

But the results were not satisfactory. The "transplanted" nose was not strong enough to blow the nose down. It was not until 1962 that American doctor Joseph E. Murray achieved long-term survival in a human kidney transplant, and organ transplantation finally became a medical method that could save patients' lives.

Why pigs are the best donors

There are three major technical difficulties from the conception to the final realization of organ transplantation.

First, organ transplantation is a living transplantation. After implantation into the recipient's body, the blood vessels need to be connected immediately to restore blood supply. Secondly, organs separated from the body will quickly inactivate under normal temperature and ischemia, and require appropriate storage and transportation methods to prolong the survival time of the organs outside the body. Thirdly, there is the well-known rejection reaction. Since the human immune system will attack "foreign" organs, if no intervention is made, it may damage the transplanted organs and ultimately lead to transplant failure.

The first two problems have been solved by improving surgical methods and storage technology, but the rejection reaction is much more complicated to solve. Human leukocyte antigen (HLA) matching is performed before transplantation, and transplantation can only be performed after matching. After the transplantation is completed, the recipient needs to take immunosuppressive drugs for a long time to ensure the long-term survival of the transplanted organ.

If this is the case with organ transplantation between humans, how does xenotransplantation solve the problem of rejection?

From the 1920s to the 1990s, people had been trying to use primate kidneys, hearts and livers for transplants, but ultimately failed due to differences in organ size, infectious diseases and other reasons.

Image source: MIT Technology Review

Why do pigs become organ transplant donors?

Pigs have come into people's attention and become the most potential xenogeneic organ donors due to their large production, short maturity period, and organs similar in size to humans.

Image source: pxhere

However, it is not so easy to replace human hearts with pig hearts. The first thing to solve is the headache of rejection. Untreated pig hearts entering the human body will quickly induce super-sexual xenotransplant rejection, directly causing the heart to lose its activity, and there will be a long chronic rejection reaction afterwards.

Before the pig heart transplant, the researchers used gene editing technology to knock out three genes that can cause human immune rejection and added six genes that help the human immune system accept xenogeneic organs. After the operation, the patient also needs to take immunosuppressive drugs to protect the pig heart from losing function under the attack of the human immune system.

Secondly, gene editing technology is also used to knock out growth-related genes to prevent the pig heart from continuing to grow after entering the human body, leading to abnormal myocardial hypertrophy.

In addition, the donor needs to undergo strict infectious disease diagnosis and microbial testing before the transplant to prevent pathogens from entering the human body with the organ transplant and causing disease. The patient also needs to adjust the coagulation function before the operation to prevent blood clots from forming in the pig's heart blood vessels after the transplant.

Is it the beginning or the end?

Although David Bennett's condition stabilized after the operation and there were no obvious abnormalities in the function of the pig's heart, the patient's condition suddenly worsened and he was pronounced dead on March 9.

However, this pioneering initiative bought the patient two months of life, during which time he even watched a televised rugby game accompanied by a physiotherapist.

Bennett's family also expressed their understanding and gratitude for the doctor's work, and hoped that his experience would eventually help those who come after him. "We hope that this story can be the beginning of hope rather than the end."

Pig heart valves were successfully used to treat heart disease decades ago, and pig liver and kidney transplants into humans are also being attempted.

Pig kidney transplant surgery, Image source: BBC News

But Tadpole believes that, like other pioneering medical treatments in human history, this bold attempt at pig heart transplantation must be the prelude to a new stage in medical history, and will surely provide more hope of life for future patients.

END

Review expert: Wang Xin, deputy chief physician of the Department of Cardiology, Jilin City People’s Hospital.

Tadpole Musical Notation original article, please indicate the source when reprinting

Editor/My Neighbor Totoro