To grow human organs in pigs. What can go wrong?

For the ancient Greeks, a Chimera was an ominous creature — partly lion, partly goat and partly a snake. The first Chimera, which Juan Carlos Belmonte Izpisua created in 1992 was significantly less terrible: it consisted of embryonic mouse limbs grafted on the wing of the chick embryo. At that time Belmont was a young scientist working in laboratory in Heidelberg, Germany. He was fascinated by the mysteries of gene expression and biological signals that control the development of the animal — and the pure potential of embryonic cells.

Take any vertebrate: a chicken, pig, human. At maturity, they are completely different organisms, but begin with one and the same. Belmonte began to wonder: if the mouse foot can settle down on a chicken wing, what else might be possible? How scientists can change the signals that determine what will be the creature?

Is it possible to grow from one creature and another?

Interest Belmont to flexibility of embryos was, in a sense, personal. As a child of poor, uneducated parents in rural areas in the South of Spain, he was forced for several years to leave school to support his family, working on the farm. And just as a teenager he returned to the classroom — and from that moment quickly passed from philosophy (favorite was Nietzsche and Schopenhauer) to pharmacology and genetics.

By 2012, Belmont became one of the world’s foremost biologists, working in his own lab at the Salk Institute, La JOLLA, California, and one in its native Spain. Like his colleagues worldwide, he was pondering how to use a powerful new tool in the Arsenal of this discipline — platform editing of genes of CRISPR-Cas9. After the first serious work on CRISPR, Belmonte quickly found a goal. Only in the US, about 100,000 people are in the queue for organ transplants at any given time, and about 8,000 of them die every year because of the lack of donors. According to Belmonte, CRISPR and chimeras could be the solution. He was hoping to use a new technique to edit the genes to transform the bodies of cattle in the chambers of the human heart, kidneys, liver and lungs.

Search Belmonte started with research on mice. Using CRISPR, he and his team removed the genes which enabled the animals to grow multiple organs, including the eyes, heart and pancreas. Instead of allowing these modified mouse embryos to develop on their own, scientists Salk introduced into the mix some stem cells of rats. Then, cells rats had replaced the missing organs and animals lived a normal mouse life. By 2017, Belmonte and his colleagues moved on to larger subjects. They introduced the stem cells of human embryos 1500 regular pigs are then implanted these embryos sows. For about 20 days some of them turned into a Chimera of man-pigs. It was a modest success. Embryos have been much more pork than human: 100 000 pigs was 1 human. But the experiment was successful: it was the first chimeric embryos, created through the merger of two major, distantly related species.

As in the case of mice and rats, Belmonte plans to use CRISPR to turn off the desire of the pig to create their own bodies, and then to fill the gap of human cells. But the second step is to get human cells to take root in pigs with higher speed — was a hell. “The effectiveness of the mouse-rat is very good. The effectiveness of the man-pigs are not particularly high. That’s the problem”. Today in the lab Belmonte is a complex process of trial and error — the scientists check how the various cells of animals and humans interact, in the hope to apply the information obtained to the chimeras pigs and humans. But even this painstaking process, according to scientists, by the standards of previous years is very fast. Using traditional methods they would have had “hundreds of years”. But thanks to NASA we can very quickly collect a lot of genes and modify them.

If CRISPR helped Belmont to his ambitions, he also sent it at one of the most thorny ethical area of science. Ancient people believed chimeras a bad omen, and modern people are similar — especially when the border between man and animal is blurred. In his address 2006, US President George Bush called the creation of such hybrids is one of the “most egregious abuses of medical research.” In 2015, Belmonte found out that claims to be a Pioneer Award, one of the most prestigious and generous grants by the National Institute of health. Then it turned out that the line work was suspended — because of his work with chimeras. In the same year, the nih has suspended Federal funding of any research dedicated to the introduction of human stem cells into animal embryos, citing the need of thinking about ethical problems. A year later, the moratorium promised to cancel, but so far no funding. Bartlesville eventually received the Pioneer Award, however, most of the experiments with pigs in Spain conducted their own expense.

John de Vaux, Director of the Department of cell and tissue engineering, University hospital of Montpellier in France, easily represents the worst-case scenario involving porcine chimeras. For example, if too much human cells get into the brain of a pig, the animal could theoretically develop new types of consciousness and the mind. (In 2013, scientists from Rochester, new York, has introduced the mice cells of the human brain — and mice were smarter than their peers). “It would be terrible to imagine a form of human consciousness, trapped in the body of the animal,” says de Vaulx. What if scientists will accidentally create a pig, is able to comprehend its own suffering, with a sense of moral injustice? Even if you could kill the animal to extract its organs, does not agree with what many activists for the protection of animals, it would surely be monstrous to kill a creature with humanlike intelligence to deprive him of the pancreas.

Bartlesville offers a direct solution to this problem: we need more CRISPR. Using edit the genes according to him, scientists will be able to prevent the colonization of the pig brain human cells. Such interference can interfere with human DNA to penetrate into the germ line of pigs — that it is not passed on to future polosato people. This is another scenario that makes Bielikov to wince. “In the laboratory there are technologies that could help us to avoid these ethical problems,” says Belmonte.

Studies of chimeras — just one of the major areas that are being developed in the laboratory 58-year-old Belmonte using CRISPR. He and his team have also conducted numerous experiments on epigenetic editing — CRISPR variation that modulates the expression of genes, and not break the DNA sequence itself. Because of this, fully address the symptoms of diabetes, kidney disease and muscular dystrophy in mice. You can say scientists are trying to overcome itself aging.

“It pushes the boundaries of what we can do currently,” says Pablo Juan Ross, Professor in the Department of Zoology at the University of California at Davis, which conducts experiments with chimeras in pigs and sheep in his own laboratory. Both scientists are interested in proving the value of the edit genes and create chimeras. Ross relies on the fact that we can’t abandon technologies that will allow us to grow organs in the animals, before another teen dies in a car accident.

But Belmonte is not in a hurry, despite his own impatience. He decided to destroy the first fruits of chimeric embryonic pigs during the first trimester, before they develop into something more ethically complicated — despite the fact that in Spain, where they were grown, the rules would allow Belmont to kill animals at any time. And he’s wary of editing the genes in humans. “We need to learn much more before using CRISPR on people,” he says. “I would not yet dare to make it beyond the lab.”

Progress should not only be in science. Needs to be a thorough debate on the topic of editing genes and the voice must be not only scientists, but doctors, the public and the government. De Vaux agrees: “Einstein made fundamental researches in the field of physics. But at country level it was decided to apply these results to the bombing of Hiroshima — not at the level of scientists.”

Bartlesville firmly believe that today, scientists are on the verge of cure diseases, reverse aging, and save lives with the help of grown organs. It can change our own evolution, our own species.

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