From the first pig-human heart transplant: what can scientists learn?

Last week in Baltimore, Maryland, the first person to receive a heart transplant from a genetically modified pig is doing well

"It's been a long road to get to this point, and it's a very exciting point, and we're ready to try this," said Megan Sykes, a surgeon and immunologist at Columbia University in New York

For decades, doctors and scientists around the world have pursued the goal of transplanting animal organs into humans, known as xenotransplantation

unusual opportunity

Last week's operation marked the first time a pig's organ has been transplanted into a human with a chance of survival and recovery

Beyond that, most studies so far have been conducted in non-human primates

Pig-to-baboon heart transplant success

"From four patients, we can learn a lot that we can't learn from 40 monkeys," said David Cooper, a transplant surgeon at Massachusetts General Hospital in Boston

In recent years, there have been major advances in xenotransplantation with the advent of CRISPR-Cas9 genome editing technology, which has made it easier to create pig organs that are less likely to be attacked by the human immune system

The researchers had applied to the U.

But David Bennett, 57, gave Muhyiddin's team a chance to go straight to human transplants

The surgery went well and "heart function appears to be fine," Mohyeddin said

If Bennett's procedure proves to be a success, more teams will try similar procedures, said Jeremy Chapman, a retired transplant surgeon at the University of Sydney in Australia, with regulators and ethics Scientists will need to define the conditions under which a person is eligible for pig organs

Chapman likens the process to using experimental cancer drugs, which are too dangerous to test in people with other options
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Regulators and ethicists need to judge that the odds of success outweigh the risk of putting people waiting for an organ transplant, he said
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Exciting and crazy week

Currently, pig transplants are limited by the availability of pigs and regulatory hurdles
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Currently only one company, Revivicor of Blacksburg, Virginia, has the appropriate equipment and clinical-grade pigs
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"It's been a crazy, exciting week," said David Ayares, chief executive of Revivicor
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The company's pigs are raised in a facility near Birmingham, Alabama, but Revivicor is building a larger facility in Virginia that hopes to eventually supply hundreds of organs a year
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Ayaris has been transforming pigs for 20 years, testing how various genetic modifications limit rejection in humans and other primates
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To make pig hearts for transplants, the company removed three pig genes that trigger an attack by the human immune system and added six human genes that help the body receive organs
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The last modification was designed to prevent the heart from responding to growth hormone to ensure that the organs of the 400-kilogram animal remained human-sized
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"Organs-on-chips" go mainstream

While the combination appears to work, it's unclear how many modifications were required
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"More scientific knowledge is needed when evaluating every genetic modification," Sykes said,
adding that "we need this information" because these modifications also have the potential to be harmful to humans
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Because each transplant in baboons costs about $500,000, testing multiple combinations would be prohibitively expensive, Mohiuddin said
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Cooper and others say the future of xenotransplantation could include modifications based on specific organs and recipients
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Cooper's own research, for example, found that in baboons receiving pig kidneys, changes in growth hormone caused problems with urine transport
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But he said his team hopes to get kidney transplants in people as soon as possible, if properly genetically modified pigs are available
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Whatever happens, it may be a while before other organs are ready for clinical use
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Waiting lists for liver transplants have been shortened, making it harder for people receiving pig organ transplants to justify it
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Although people in need of lung transplants often die on waiting lists, Sykes said fragile pig lungs have proven difficult to transplant into primates and are often rejected
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Limitations of animal models

Cooper, Chapman and others say it's important to study transplants in humans, not baboons
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Differences between species "prevent us from using this model to further predict clinical outcomes," Chapman said
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Non-human primates tend to have antibodies that humans don't have, and these antibodies attack proteins on pig organs, so a lot of work is going into making those organs fit for baboons, not humans
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New life in pig-to-human transplantation

In addition, researchers need to be able to study the physiology of pig hearts—for example, whether pig hearts beat at the same rate as human hearts—and whether patients respond to transplants the same as healthy baboons
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Several other companies are also using different genetically modified pigs for solid organ transplants, though none have a medical-grade facility like United Therapeutics
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eGenesis, of Cambridge, Massachusetts, is breeding pigs that cannot transmit the retrovirus, which is present in all pig genomes
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NZeno in Auckland, New Zealand, is breeding miniature pigs whose kidneys are the same size as human kidneys without changes in growth hormone
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Chapman suspects that many more organizations are carrying out genetically modified transplants in pigs, but has yet to disclose commercially sensitive information
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Ayaris and United Therapeutics declined to disclose the cost of production per pig, although they acknowledged that raising the animals was expensive
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But as more companies get involved, Cooper expects costs to drop and the FDA and other regulators to relax some requirements for cleaning facilities
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Infection of pathogens from pig organs does not appear to be a problem yet, although Bennett and any future recipients will need to be monitored
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