The researcher's team Juan Carlos Izpisúa It has managed to create for the first time chimeras of human and monkey in a laboratory in China, an important step towards its final objective of converting animals of other species into factories of organs for transplants, as confirmed by EL PAÍS its collaborator Nunez Star, biologist and vice chancellor of research of the Catholic University of Murcia (UCAM).

The chimeras, according to Greek mythology, were monsters with goats belly and dragon tail, capable of vomiting fire through the jaws of their lion's head. Scientific chimeras are less grotesque. The Izpisúa group, divided between the Salk Institute of the USA and UCAM has genetically modified monkey embryos to inactivate genes essential for the formation of their organs. Next, scientists have injected human cells capable of generating any type of tissue. The fruit is a monkey chimera with human cells that has not been born, since researchers have interrupted pregnancy. The experiment has been conducted in China to circumvent legal obstacles.

"The results are very promising," says Estrella Núñez. The authors do not offer more details because they are pending publication in a prestigious international scientific journal. "From UCAM and the Salk Institute we are trying not only to move forward and continue conducting experiments with human cells and rodents and pigs, but also with nonhuman primates," Izpisúa explains. "Our country is a pioneer and world leader in these investigations," he celebrates.







Juan Carlos Izpisúa, researcher at the Salk Institute.

Izpisúa, born in Hellín (Albacete) in 1960, remembers that his team already carried out in 2017 “the first experiment of the world of chimeras between humans and pigs”, Although with less success. “Human cells did not grab. We saw that they contributed very little (to the development of the embryo): one human cell per 100,000 pigs, ”explains the Argentine veterinarian Pablo Ross, a researcher at the University of California at Davis and co-author of that experiment.

Izpisúa's team has achieved the creation of chimeras among species more closely related to each other, such as the mouse and the rat, five times closer than humans and pigs. Also in 2017, the researchers used the revolutionary CRISPR genetic editing technique to inactivate genes from mouse embryos that are essential for the development of the heart, eyes and pancreas. Then, they introduced rat stem cells, capable of generating those organs. The result was a series of rat and mouse chimera embryos, whose pregnancy was also aborted by researchers following the international consensus on this type of experiments.

The doctor Angel Stripe, director of the Center for Regenerative Medicine in Barcelona, ​​recalls the “ethical barriers” that these experiments with chimeras face. “What happens if the stem cells escape and form human neurons in the animal's brain? Will you have conscience? And what happens if these pluripotent cells differentiate into sperm? ”Says Raya. Estrella Núñez says that Izpisúa's team has "enabled mechanisms so that if human cells migrate to the brain they self-destruct."

Izpisúa already carried out the first chimera experiment in 2017 of the world between humans and pigs

To avoid these ethical obstacles, according to Raya, the scientific community has traditionally set a "14-day red line" of pregnancy, insufficient time for the human central nervous system to develop. Before reaching those 14 days, the chimeric embryos are removed. "Gestation is not carried out in any case," confirms Núñez.

Raya is skeptical about the possibility – in any case far away – of turning animals into organ incubators for humans, but he considers that these investigations will be very useful to obtain models in which to study embryonic development and some diseases of people. "A research path is opened, not an organ factory," he says.

The first scientific team that created rat and mouse chimeras, in 2010, was that of the Japanese biologist Hiromitsu Nakauchi, from Stanford University (USA). In 2017, his team generated mouse pancreas inside rats and showed that these cells reversed diabetes when they were transplanted back to mice with the disease. Nakauchi recalls that the US National Institutes of Health – the main funders of biomedical science in the world – “do not support the research of chimeras human animals, but there are other funding agencies, such as the Department of Defense and the California Institute for Regenerative Medicine, that do support these studies. ”

Chimera experiments have the risk of human neurons forming in animals' brains

Izpisúa's work with monkeys in China has been largely funded by the Catholic University of Murcia. They are very expensive studies. "If we put together the research of human / pig, human / mouse and human / monkey, there are many hundreds of thousands of euros," calculates the Vice Chancellor for Research at UCAM.

In Spain, these types of trials are very restricted and limited only to investigations of fatal diseases. “We are doing the experiments with monkeys in China because, in principle, they cannot be done here,” acknowledges Nunez, who takes away the importance of his university being Catholic. “What we want is to progress for the benefit of people who have a disease. We have asked for our permits and it is within our ethics ”, emphasizes the biologist.

“If nature knows how to do certain things, why do we have to do them on a laboratory plate? It is much harder to reproduce a organoid on a plate that induces nature to manufacture an organ where it is always making it, ”he reflects.

Núñez is aware of the difficulties. As Ángel Raya emphasizes, the mouse pancreas generated within rats still have cells of the rats themselves in structures such as their blood vessels, a possible reason for rejection in case of transplantation. “The ultimate goal would be to get a human organ that can be transplanted, but the path itself is almost the most interesting thing for the scientists who live this moment. These experiments are where you really learn the biology of development of what you are studying. I am practically aware that I will not be able to see it, but to get to that point (the manufacture of human organs in animals) it is necessary to go through this ”, reasons the vice-rector of research of the UCAM.

"What we want is to progress for the benefit of people who have a disease," says biologist Estrella Núñez

“Science is not something you can put doors on. The paths of science then take you to branches that you would never have thought. Although we may not get to get organs for transplants, if we did not pass through here there would be no progress in science, ”he says.

Other scientists, such as the chemist Marc Güell, they are exploring other ways, with a similar objective: to solve the shortage of transplantable organs. Almost all mammals have viruses in their DNA that pass from parents to children. In the case of pigs, these viruses embedded in the genome can infect human cells. Four years ago, when I was at Harvard University, Güell helped inactivate those viruses embedded in the DNA thanks to the genetic editing tool CRISPR. "We humanize the pig through genetic engineering ”, explains the chemist, who remembers that last year a team from the University of Munich managed to make two monkeys survive more than six months with pig hearts transplanted "I do not see why it may not be possible to do engineering to make the development of human tissues in pigs more compatible," argues the researcher, now at the Pompeu Fabra University in Barcelona.

Izpisúa himself invited to open his mind in an interview with this newspaper in 2017: “History shows us again and again that, over time, our ethical and moral scales change and mutate, like our DNA, and what was ethically unacceptable yesterday, if that really means a breakthrough for the progress of the humanity, today is an essential part of our lives ”.