Monday, June 27

Spanish scientists create 132 embryos with a mixture of monkey and human in China | Science

The team of Spanish scientist Juan Carlos Izpisua has created 132 embryos with a mixture of monkey and human cells in a laboratory in China, in controversial experiments revealed by EL PAÍS in the summer of 2019 and officially communicated in detail this Thursday. Three of these embryos – simple balls of up to 10,000 cells – grew for 19 days outside the uterus, at which point the researchers interrupted the study, partially funded by the Universidad Católica San Antonio de Murcia. The scientific community refers to these structures as chimeras, referring to the lion-headed, goat-bellied, and dragon-tailed monsters of Greek mythology.

The specialized magazine Cell, what publish the results, has illustrated the advertisement with an allegory of Adan creation, the fresco by Michelangelo in the Sistine Chapel in which the hand of the biblical god gives life to the first man of the Christian tradition. In the new drawing, a monkey hand and a human hand appear to breathe energy into a mixed embryo.

Izpisua, born in Hellín (Albacete) 61 years ago, stresses however that his true objective is the creation of pig and human chimeras, with the ultimate goal of generating human organs in pig cattle. The World Health Organization estimates that about 130,000 transplants a year on the planet, less than 10% of what is needed. The researcher argues that “each year tens of thousands of patients die on the waiting list for an organ.” Those new organs would alleviate the problem.

The Izpisua group – from the Salk Institute, in La Jolla (United States) – already announced in 2017 the creation of rudimentary pig and human chimeras, in which there was barely one human cell for every 100,000 pigs. To understand this failure, attributed to the 90 million years of evolution that separate these animals and people, the Spanish researcher decided to try two much closer species: monkeys and humans.

The researchers have used eggs from a dozen female crab macaque (a type of monkey), fertilized them with sperm of the same species and, after six days of cultivation in the laboratory, they have obtained 132 tiny embryos, with 110 animal cells each. The team has added 25 human cells to those structures, previously reprogrammed with a chemical cocktail to be able to become any cell type: skin, muscle, liver, heart. The result, 19 days after fertilization, is a mixed pellet of 10,000 cells, with a human percentage of 7% maximum. The experiments have been carried out in the Biomedical Research Laboratory with Primates from Yunnan, a facility with thousands of monkeys in the Chinese city of Kunming.

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And they are not safe from criticism. British biologist Christine Mummery, president of the International Society for Research with Stem Cells, warns that the chimeras of humans and animals “are exceeding established ethical and scientific limits.” His organization will issue new guidelines in May to try to ensure the integrity of this type of investigation. Mummery, already from a personal point of view, doubts the arguments offered by Izpisua to defend his essays: “The results of the experiments are interesting, but justify their performance in the context of regenerative medicine to generate human organs in animals for transplantation It seems like a very distant goal to me ”, points out the biologist, from the University of Leiden (Netherlands). In his view, there were “more ethically acceptable” alternatives to the use of monkey embryos, such as the use of animals evolutionarily further removed from humans.

The jurist Federico de Montalvo, President of the Bioethics Committee of Spain, wonders why the experiments have been carried out in China: “Is it because scientifically they are more advanced or is it because ethically they are more relaxed?” De Montalvo is concerned about the possible dual use of these scientific advances. “The current goal is worthy of applause, but perhaps we should also consider whether it can be used for other purposes, such as creating a kind of intermediate subject. The risk is to open a path that other people can travel ”, reflects this expert, at the head of the highest advisory body of the Spanish Government in the field of scientific ethics.

The Chinese scientist Ji Weizhi, co-lead author of the study, and the Spanish Juan Carlos Izpisua.
The Chinese scientist Ji Weizhi, co-lead author of the study, and the Spanish Juan Carlos Izpisua.Instituto Salk

In the mid-twenties of the last century, the Russian zoologist Ilia Ivanov, supported by the Soviet authorities of the time, proposed obtain hybrids of chimpanzees and humans by artificial insemination of females. Ivanov came to travel to West Africa, to what is now Guinea Conakry, with the intention of capturing apes for his experiments, but did not achieve any results in them.

The idea of ​​a half-human, half-animal creature was science fiction a century ago and still is, but it may eventually stop being so. Izpisua insists: “We do not know if monkey-human embryos would be biologically possible, but our goal in chimera research is not to develop new organisms, but to better understand human development to obtain treatments for diseases.”

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The French biologist’s team Pierre Savatier published three months ago an attempt to create chimeric macaque and human embryos in his laboratory at the University of Lyon. The researchers achieved a maximum of 10 human cells in monkey embryonic structures with a total of 250 cells and seven days of development, according to the Spanish biochemist. Manuel Serrano, who participated in the work. Izpisua has used a different chemical cocktail to induce a special state in human cells that he implanted in monkey embryos. Thus it has managed to reach embryos of 19 days with around 7% human. “Their cells work spectacularly well,” says Serrano, from the Institute for Biomedical Research in Barcelona. “The reality is that Izpisua is breaking down barriers. We’re not going to have human organs grown into animals tomorrow, but that’s science. We are learning ”, he adds.

The Polish Biologist Magdalena Zernicka-Goetz he also believes that the new work is “an impressive demonstration” of the ability of human cells to integrate into a macaque embryo, but warns of the difficulty of controlling where those human seeds go, which could end up in an unwanted organ. Izpisua defends that technologies already exist to prevent human neurons from forming in the animal brain. “In the hypothetical case of being able to generate a live pig with human cells, we could prevent these scenarios,” says the Spaniard. Zernicka-Goetz, from the University of Cambridge (UK), calls for society to discuss “the ethical implications” of these experiments.

The Spanish biologist Alfonso Martínez Arias he thinks that “it was unnecessary to open this Pandora’s box”. His group at the University of Cambridge last year produced, from embryonic cells grown in the laboratory, structures similar to a human embryo of about 20 days, without the seed that would give rise to the brain. The researcher believes that these laboratory pseudo-embryos are an alternative to monkey chimeras for studying the development of human organs.

Martínez Arias, recently joined the Pompeu Fabra University in Barcelona, ​​is very critical of Izpisua’s experiments in China, “of dubious ethics” and “low technical quality”. “I think it has not demonstrated the viability of these chimeras,” says the biologist. “This type of experiment can generate unjustified fears in society and endanger the work of other scientists who are trying to create an ethical and legal framework for related research,” adds Martínez Arias.

The lawyer and doctor Carlos RomeoHowever, he sees “no problem” at this stage of the research, as long as the embryos are not implanted in a uterus or cultured in the laboratory for too long. “I have no ethical reproach and there is no basis for these experiments to be legally prosecuted,” clarifies Romeo, the only Spanish member of the scientific ethics committee that advises the president of the European Commission, the German Ursula von der Leyen.

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Romeo, professor of Criminal Law at the University of the Basque Country, recalls that in the 1970s the so-called hamster test, a test to assess male fertility in which human sperm penetrated hamster eggs. “An animal was fertilized and no one was scandalized,” emphasizes the lawyer.

Izpisua, second from the right, with collaborators from the San Antonio de Murcia Catholic University.
Izpisua, second from the right, with collaborators from the San Antonio de Murcia Catholic University.UCAM

Spanish law, drawn up in 2006, prohibits the production of hybrids of different species that include human genetic material, but makes a legally confusing exception: “Except in the cases of currently permitted tests.” Romeo believes that Izpisua’s experiments could be done in the European Union. The pig and human chimeras of 2017, in fact, were largely made in Murcia. Two of the co-authors at the time, the biologist Star Nunez and the vet Llanos MartinezThey have also participated from the San Antonio de Murcia Catholic University in the elaboration of the monkey and human chimeras.

Research with human embryos left over from fertility clinics is subject to a 14-day international red line, the moment in development at which the concept of the individual is supposedly created: thereafter the embryo can no longer divide to give rise to twin brothers. The Spanish biologist Marta Shahbazi and the Polish Magdalena Zernicka-Goetz developed in 2016 a method to cultivating the embryos out of the womb up to that 14 day limit. Izpisua’s team has gone further with chimeric monkey and human embryos, up to 19 days, just before the nervous system begins to develop.

Marta Shahbazi applauds the new research. “This study does show that chimeras are formed. It seems that their system works and is efficient, ”he says. The researcher, from the University of Cambridge, believes that the chimeric structures of monkey and human are “a very useful system” to study embryonic development. “It’s a complementary tool for understanding basic biology,” Shahbazi reflects. Later, that knowledge could be used to return to the pig and have a model of human organ creation in farm animals. That would be ideal. “

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