The big question after the first pig heart transplant for humans

Transplanting pig hearts into humans promises to solve the shortage of organs, but it also raises many ethical questions.

For cardiac surgeon Brandon Guenhart from the Stanford University School of Medicine, the most important thing in transplant surgery is timing.

In Mr. P.'s case, the anesthesiologists put him in a deep coma, after the resuscitation team reported the donor heart had arrived. The two surgeons started the operation an hour before the heart was transferred from the airport to the hospital. It's a routine heart transplant procedure.

On January 7, at the University of Maryland Medical Center, patient David Bennett, 57, received a heart transplant from a special donor: a genetically modified pig.

In 2021, 41,354 human-to-human organ transplants were performed, but there are still more than 100,000 Americans waiting for organs to be transplanted. Every day 17 people die because they can't wait another day.

Boundaries between humans and animals

Xenotransplantation (also known as the transplant of cells, tissues and organs from one species to another) promises to address this critical deficiency and reshape the concept of human longevity.

However, the barrier between humans and animals is still limited. The fact that the SARS-CoV-2 virus originated from animals has claimed the lives of more than 6 million people, so violating this boundary could lead to many disasters.

Dr. Muhammad M Mohiuddin placed the genetically modified pig heart in a storage device before transplanting it to Mr. Bennett.

Man is an animal. But animals are not people. However, people have hybrid cultural creations. Egyptian mythology has the god Horus depicted with the head of a falcon, the goddess of war Sekhmet with the head of a lion.

Similarly, the Hindu god Ganesha was beheaded and resurrected with an elephant head transplant. In ancient Greece, fantastical creatures appeared in myths, from the bull-headed Minotaur to the snake-haired Medusa.

The International Society of Transplantation has chosen Lamassu as its mascot. It was the Assyrian god with the body of a bull with the wings of a bird and the head of a man.

Xenotransplantation was initially just cell and tissue transplantation. In France and England in the seventeenth century, blood was transferred from animals to humans to cure diseases.

This improved implant method for bone, cornea and skin grafts. The most famous is the French surgeon Serge Voronoff who grafted slices of the testicles of chimpanzees and baboons into men and the ovaries of baboons into women.

While cell and tissue transplants have been around for a long time, organ transplantation is more difficult to perform. It is very difficult to sew all the blood vessels together. In 1912, French surgeon Alexis Carrel won the Nobel Prize for his work on suturing the vascular system, transplanting blood vessels, solving this problem.

Half a century later in 1964, surgeon James Hardy from the University of Mississippi performed the world's first heart transplant, inserting Bino's chimpanzee's heart into the chest of 68-year-old patient Boyd Rush. Rush only survived for 90 minutes, because the chimp's heart was not enough to support his life.

And Baby Fae is an unbelievable case of xenotransplant method. It was a 12-day-old infant with hypoplastic left heart syndrome. In 1984, surgeons at Loma Linda University, California, transplanted a baboon heart the size of a walnut to Baby Fae.

After the surgery, the situation is positive. However, the girl died after 21 days because her immune system reacted against the transplanted heart tissue. This has sparked outrage from animal rights activists and bioethicists.

Controversy about pigs

Pigs don't have much of a good reputation. Judaism and Islam forbid the consumption of pork. In the epic Odyssey, the witch Circe turns the gluttons of Odysseus into pigs.

However, pigs are actually very intelligent animals that can express emotions. They are considered to be smarter than dogs and chimpanzees, after many IQ tests.

Pigs on the Badersfeld experimental farm in Oberschleissheim, Germany.

After the failure of Baby Fae, primates fell out of favor, and pigs became the new subject of researchers. They suggest that pigs are easy to move around, can be raised in a sterile environment to reduce infection, and can provide the necessary organ size.

That's a good point of view, but Dr. Brad Bolman, a historian at the University of Chicago, argues that sheep, goats or some other animal are also relevant. However. People build scientific arguments to convince that pigs are the right choice.

For Mr. Bolman, pigs were chosen for their economic and social convenience. They reproduce quickly, reaching maturity in just 6 months. Pigs are outside the scope of the Animal Welfare Act and are common farm animals around the world.

The PETA association has deemed pig-to-human transplants 'unethical, dangerous and an enormous waste of resources', insisting that 'animals are not tools for transformation but intelligent beings. '.

Xenotransplantation experts often dismiss ethical concerns with references to the pork industry. After all, if pigs are raised for meat, then raising pigs for science has a higher meaning.

Dr Bolman said: 'Science is consuming animals, or even when they can't be eaten. In short, science is a cannibal."

Pig gene editing

Making xenotransplantation requires selective humanization from a pig. So we can't simply transplant a pig heart into a human body, said Dr. Richard Pierson, director of the Center for Transplant Science at Massachusetts General Hospital.

Doctors are performing a pig heart transplant for David Bennett in Baltimore.

Virginia-based biotech company Revivicor used gene editing technology CRISPR to create a special line of pigs with 10 modifications. Four genes were removed, and six were added. The recipe for "processing pig's heart" for humans is:

Removed 3 sugar genes found only in pigs.

Removed a growth hormone gene to prevent the pig's heart from overgrowing in the new body.
Two more complement inhibitor genes prevent antibodies from destroying the pig's heart and two anticoagulant genes prevent the patient's blood from clotting inside the foreign organ.

Add 2 anti-inflammatory genes to prevent the heart from swelling. One of these genes signals to the immune system that the pig's heart is your friend (belongs to it), not the food (it doesn't belong).

After this "collage" sequence, the next challenge is to keep the pig 'clean'. No one wants to transplant a pig heart filled with viruses, bacteria, and parasites that infect humans. So these pigs will be kept in a sterile environment, not allowed to go out.

With this 'pig in a bubble' method, all exogenous or foreign viruses have been eliminated. Then these pig hearts are safe to transplant into people.

In fact, that's not entirely the case. Mr. Bennet's heart still tested positive for porcine endogenous retrovirus (PERV).

Whether the virus is contagious or not, Mr. Pierson doesn't think that's a big barrier to xenotransplantation. HIV drugs seem to be quite effective against the virus, and the Boston-based biotech company eGenesis even created a 60-gene pig that is PERV-free.

Mr. Bennet had only 60 days to live after the surgery. Maybe he was infected with the swine virus. Dr., thoracic surgeon Bartley Griffith said that the swine virus Mr. Bennet contracted was not PERV, but an external virus called porcine cytomegalovirus (pCMV). It is possible that pCMV was not detected during the examination and evaluation of the pig.

After all, there is no boundary between humans and animals. Pigs have 98% of the same genome as humans. Besides the ethical issue, people can't help but think about the potential of xenotransplantion. If this is possible, we must create a new livestock industry where pigs are produced and slaughtered to give life to humans.

Dr Chris Walzer, executive director of the Wildlife Conservation Society, believes that pig organ transplantation can benefit from OneHealth - a solution that brings together the health, veterinary and environmental sectors to bring about best health for all species.

All are part of a common ecosystem. And it will be very dangerous if this connection is broken.