General

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

EGenesis Editing Companygenes, conducting experiments to address the critical shortage of human organs available for transplantation. In 2017, Harvard geneticist George Church predicted that porcine organs with edited genes would be transplanted to people in a couple of years - maybe even in a year.

“I was wrong,” Church now acknowledges.

His startup eGenesis reported on its ambitiousplans to use the CRISPR gene editing technology to modify pigs so that their organs can be safely transplanted to people without rejection. In this way, the critical shortage of human organs available for transplantation could be resolved.

However, in public such trials are not yetwere carried out. Instead, the company is currently testing monkey pig organs in Boston. 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 do is a necessary step,” says Markmann. "It would be difficult for us to place the modified organ in a person without testing it on a large animal."

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

For many decades, doctors have dreamed of usingpigs to solve the problem of lack of organs, transplanting their kidneys, hearts and even lungs to human patients for replacing organs that have stopped working. Now over 100,000 people in the United States are in line for transplants.

Over the past few years, scientists have reached importantturning points in xenotransplantation. Scientists from the National Institutes of Health have been able to maintain the beating of pig hearts in baboons (along with their own monkey hearts) for about two years. Late last year, German surgeons reported that several baboons survived for about six months after their hearts were replaced by pigs.

These experiments were performed usingpigs genetically modified by Rivicor, a subsidiary of United Therapeutics. Animals have genetic changes that should prevent a person from immediately rejecting the organ, stop the formation of blood clots and compensate for other types of immune attacks.

Thanks to such scientific advances, transplant surgeons are now discussing when it will be possible to take a chance and perform an operation on a person.

“We already have a Chevy. Maybe even a BMW. Do we need to wait for Ferrari? The moment will come when you just want to ride, ”says Devin Eckhoff, director of the transplant department at the University of Alabama Medical School in Birmingham.

However, before the organs of pigs can becheck on people, some key problems to be solved. Results with monkeys were not very consistent. Regulators have not publicly stated the conditions under which they will agree to human testing, and there is a debate about how much pigs should be modified.

Church's company - eGenesis - got a badfame, boosting the role of CRISP in making pigs with multiple genetic modifications. In 2015, the company's co-founder and chief scientist Luhan Young demonstrated that she could make 62 changes right away to deactivate the viruses that are naturally hidden in the pig genome.

In addition, Young says that her companycurrently contributed a “two-digit” 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. Young calls his pigs "the most advanced" of genetically modified animals on Earth.

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

But these terms are unrealistic. Yang believes that the greatest obstacle for the entire region will be to achieve consistent results from transplantation from pigs to monkeys. Although some baboons lived for months with pig organs, other animals soon died. Scientists still do not fully understand why. “We feel that there is some kind of biological reason for this,” says Young. "We understand and try to fix it."

This requires a huge amount of porkorgans. Yang says that eGenesis has produced more than 100 pigs in the United States, and his Chinese partner, Qihan Biotech, based in Hangzhou, has grown hundreds, experimenting with various genetic changes. The rules do not allow moving pigs or their bodies between countries.

“I think we will learn much 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. In the interview, Markmann would not say the word "monkey"; he would say "large animal." PETA animal rights advocates oppose the study because "pigs are individuals, not spare parts."

There are also disputes about how much geneticchanges we really need. Muhammad Mohjuddin, director of the cardiac xenotransplantation program at the School of Medicine at the University of Maryland, believes that eliminating viral genes is unnecessary and can harm animals, leading to undesirable consequences. Instead, it would ideally be to edit eight to nine genes and grow a pig with many usable organs - instead of growing one pig for heart transplantation, and the other for kidneys. Other organs should not be thrown away.

Markmann says that previously publishedexperiments on monkeys and his own work inspire optimism in him: 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 unusually good and suggests that this is possible. Everyone understands that we are at a turning point. ”

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