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CRISPR startup transplants pig organs to monkeys to understand how safe it is for humans

Ilya Khel, Hi-News

eGenesis, a gene editing company, is conducting experiments to address the critical shortage of human organs available for transplantation. In 2017, Harvard geneticist George Church predicted that pig organs with edited genes would be transplanted to humans in a couple of years — maybe even a year.

"I was wrong," Church now admits.

His startup eGenesis has announced its ambitious plans to use CRISPR gene editing technology to modify pigs so that their organs can be safely transplanted to humans without rejection. In this way, it would be possible to solve the issue of a critical shortage of human organs available for transplantation.

However, such tests have not yet been conducted on humans. Instead, the company is currently testing pig organs on monkeys in Boston. The experiments are conducted by the chief surgeon of the General Hospital, James Markmann.

Is it possible to transplant pig organs to a person?

"What we are doing is a necessary step," says Markmann. "It would be difficult for us to put an altered organ in a human without testing it on a large animal."

Neither Markmann nor eGenesis describes in detail which organs are being studied or which species of monkeys are involved in the experiments, which are said to include the most high-tech pig organs ever created by surgeons.

For many decades, doctors have dreamed of using pigs to solve the problem of organ shortage by transplanting their kidneys, hearts and even lungs to human patients to replace organs that have stopped working. Now more than 100,000 people in the United States are on the waiting list for a transplant.

Over the past few years, scientists have reached important turning points in "xenotransplantation". Scientists from the National Institutes of Health managed to maintain the beating of pig hearts in baboons (along with the monkey's own heart) for about two years. At the end of last year, German surgeons reported that several baboons survived for about six months after their hearts were replaced with pig hearts.

These experiments were conducted using pigs genetically modified by Rivivicor, a subsidiary of United Therapeutics. Animals have genetic changes that should prevent the immediate rejection of an organ by a person, stop the formation of blood clots and compensate for other types of immune attacks.

Thanks to such scientific achievements, transplant surgeons are now discussing when it will be possible to take a risk and perform surgery on a person.

"We already have a Chevy. Maybe even a BMW. Do we have to wait for a Ferrari? There will come a time when you just want to take a ride," says Devin Eckhoff, director of the Department of transplantation at the University of Alabama Medical School in Birmingham.

However, before pig organs can be tested on humans, some key problems have to be solved. The results with monkeys were not very consistent. Regulators have not publicly stated under what conditions they will agree to human testing, and there is a debate about how much the pigs should be modified.

Church's company, eGenesis, gained notoriety by forcing the role of CRISP in the creation of pigs with multiple genetic modifications. In 2015, the company's co-founder and chief scientist Luhan Yang demonstrated that she could make 62 changes at once to deactivate viruses that naturally hide in the pig genome.

In addition, Yang says her company has now contributed a "double-digit" the number of gene editing (through both excision and addition) to reduce the likelihood of organ rejection by the immune system. These changes are probably similar to the changes created by Revivicor. Yang calls his pigs the "most advanced" of genetically modified animals on Earth.

In 2017, speaking to the Carnegie Institution, Church announced that "we hope to begin transplantation in humans within a year."

But these deadlines are unrealistic. Yang believes that the biggest remaining obstacle for the entire field will be to achieve consistent results of transplantation from pigs to monkeys. Although some baboons lived for months with pig organs, other animals soon died. Scientists don't fully understand why yet. "We feel that there is some biological reason for this," says Yang. "We are looking into it and trying to fix it."

This requires a huge amount of pig organs. Yang says eGenesis has produced more than 100 pigs in the U.S., and its Chinese partner Qihan Biotech, based in Hangzhou, has raised hundreds by experimenting with various genetic changes. The rules do not allow pigs or their organs to be moved between countries.

"I think we will learn a lot more when we transplant several organs with the same modifications and see how they behave," says Markmann.

When it comes to using animals such as pigs and baboons, companies try to be as careful as possible. They don't say where the pigs are kept. In an interview, Markmann would not have said the word "monkey", he would have said "large animal". PETA animal rights advocates oppose the study because "pigs are individuals, not spare parts."

There are also debates about how many genetic changes we actually need. Muhammad Mohyuddin, director of the cardiac xenotransplantation program at the University of Maryland School of Medicine, believes that the elimination of viral genes is unnecessary and can harm animals, will lead to undesirable consequences. Instead, ideally, it would be to edit eight or nine genes and raise a pig with many usable organs - instead of raising one pig for a heart transplant and another for kidneys. The remaining organs should not be discarded.

Markmann says that previously published experiments on monkeys and his own work inspire him with optimism: genetically modified pigs will indeed become a valuable source of organs for humans.

"The fact that pig organs live for six to twelve months or several years is already extraordinarily good and suggests that this is possible. Everyone understands that we are at a turning point."

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