27 May 2021

How to create a chimera?

When will scientists be able to create a mixture of a bulldog and a rhinoceros

Post -science

Why scientists create rats, mice and pigs with human cells, said geneticist Sergey Kiselyov.

The natural way

In Greek mythology, a chimera was an animal whose body parts belonged to different species: the head of a lion, the torso of a goat, the tail of a snake. Already, according to the ancients, the body was formed like this from the very beginning – how else can separate parts of the body and organs be formed? In modern biology, this idea has remained: chimerism, that is, a mixture of cells of two or more different organisms, is formed from the first hours or days of individual development. Imagine a centaur: one part of the body is formed from cells of one type, a human, and the second type of cells forms a part of the horse's body. 

This can really happen in nature when, after the independent fertilization of two eggs, both suddenly unite, after which they develop into one organism. But initially these are two different, independently fertilized eggs (zygotes), thanks to which the embryo from the very beginning has cells and tissues with two different genomes. This is how chimeras differ from hybrids. There are no cells with two different genomes in a hybrid organism. In every cell of a mule there is a genome of a horse and a donkey, so the mule is a hybrid. Now, if some of his cells had only the genome of a horse, and some had only a donkey, then the mule could be called a chimera.

It is known from numerous examples that a chimeric organism can develop into an adult and exist normally, and for some species, for example, small marmoset monkeys, this is almost the norm. A number of cases of chimerism in humans are described, for example, with the American Lydia Fairchild: according to her DNA turned out that she was not the mother of her children born to her in front of witnesses. This is possible if, at the early stages of the formation of a chimeric organism, the cells of one formed ovarian cells, and the cells of the other, with different genetics, blood, which was taken for DNA analysis. I am sure that there can be quite a lot of chimeras among people, but there is no reason and no need to identify it. However, these examples exist within the same kind. How chimeras with genes of distant species will live is completely unclear, because cells of these species can live at different speeds. For example, a mouse lives for two years, and a rat lives for five years. And we don't know yet how long the mouse and rat chimera will live. They have different molecular pathways at the molecular level, different metabolism, different genome work – because of this, chimera embryos can die before they are born.

Laboratory path

The WHO notes that now more than 130,000 organ transplants are carried out worldwide, which is less than 10% of the global need. In the organization, the situation is called acute, and interspecific chimeras are one of the ways to solve the problem of organ shortage. If scientists learn how to grow missing human organs in animals, it will be a big breakthrough in transplantology. 

Professor at Stanford University and Hiromitsu Nakauchi of Tokyo University published the results of his work on the mouse-rat chimera in the journal Nature in January 2017. He injected mouse cells into a rat embryo, and as a result, a pancreas consisting only of mouse cells was formed in the rat embryo. Nakauchi then implanted this gland in a mouse with diabetes, and the pancreas controlled the blood sugar level of the rodent.

Another leader in the creation of interspecific chimeras is the Spanish–American biologist Juan Belmonte. In the same January 2017, he published a study in the journal Cell that he had grown chimera embryos consisting of human and pig cells. By the way, one of the difficulties they faced was that the genes of these species were too far apart, which caused the early death of embryos. Belmonte explained this by a long evolution, during which differences accumulated between species. For example, the development of a pig's fetus is much faster than that of a human: four months versus nine.

Also, Belmonte in 2019 announced an experiment to create a chimera of a man and a monkey. However, the description of the project was then short and published in the newspaper El Pais, and not in a peer-reviewed scientific journal. An article in Cell about these experiments was published only in April 2021.

Sergey Kiselev, Doctor of Biological Sciences, Professor, Head of the Epigenetics Laboratory of the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences:

– I believe that so far we do not know how to create interspecific chimeras at all. So far, only one person on Earth can do this – Professor Hiromitsu Nakauchi, who raised a mouse with a rat liver. There are no other similar examples. When they show us the first centaurs who will also play the lute, that's when we will say: "We know how to create chimeras"!

Political and ethical prohibitions

In order to successfully grow and study interspecific chimeras, appropriate political decisions are needed, and it is not easy with them yet. The leading position is occupied by Japan, which in the summer of 2019 approved the first experiments on the creation of human and animal chimeras, although until the 70th day of development. And, of course, Hiromitsu Nakauchi immediately applied for state support for the creation of chimeras – animals with human cells.

In the unspoken hierarchy, China comes right after Japan, but relevant experiments are not allowed there, rather they exist in the gray zone of law. The Belmonte group, which worked on the chimera of man and monkey, did it in China: there is the necessary infrastructure and scientists are not asked uncomfortable questions. Good and flexible legislation in England: Recently, science has been in good contact with the legislative sphere there. Just recently, in England, it was allowed to grow chimeric organisms for up to 21 days. Previously, the deadline was 14 days, and the new solution is a real step forward.

In the United States, research is allowed up to the stage of a 14-day embryo, but in fact, the National Institutes of Health has had a moratorium on funding them since 2015. However, when in August 2016, the institutes studied the public opinion of the United States about working with chimeras, it turned out that the opinion of Americans has changed significantly in recent years: now a much larger number spoke in favor of allowing such studies. Although the majority still continues to believe that scientists should not "play God" and "pull the strings of development" by creating chimeras of man and animal.

About the author: Sergey Kiselyov – Doctor of Biological Sciences, Professor, Head of the Epigenetics Laboratory of the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences.

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