Anyone was first a blastocyst, a little ball the size of the dot at the end of this sentence. The blastocyst —an embryo of about five days and about 200 cells— is the structure that is implanted in the wall of the maternal uterus. On day 14 after the union of the ovum and spermatozoon, the enigmatic gastrulation begins, the one-week process in which the ball of cells becomes the first sketch of the individual, with its three axes: left and right, up and down, belly and back. These first days of pregnancy are a mystery, due to the physical and ethical barriers to studying them in humans. A team of Chinese scientists has now succeeded in generating macaque pseudo-embryos in the laboratory and implanting them in the uterus of three female monkeys, initiating three pregnancies. The authors believe this new embryo model will shed light on birth defects and understand why about 25% of human pregnancies end in miscarriage.
The cells of a blastocyst are pluripotent: capable of becoming any cell of an adult person, be it the brain, liver or heart. And they have another amazing ability. Extracted individually and grown in the laboratory, they can divide and create identical copies of themselves indefinitely. They are called embryonic stem cells. French engineer Nicolas Rivron already used these pluripotent cells in 2021 to create models of human blastocysts and simulate implantation at the Institute for Molecular Biotechnology in Vienna. Chinese researchers, led by neuroscientist Zhen Liu, have now achieved the same thing in monkeys and have gone further, taking a step unthinkable in humans: transferring these structures into the uteruses of eight monkeys. In three of them, the false blastocysts, called blastoids, initiated implantation and, therefore, pregnancy.
Gastrulation is probably the most important week in the life of a human being. That day 14 begins a perfect choreography, with which the few cells of the embryo —the old blastocyst— are organized into the three layers that will give rise to everything else. More than three decades ago, the British embryologist Lewis Wolpert coined a mythical phrase in his discipline: “The most important moment in your life is not your birth, nor your marriage, nor your death, but gastrulation.” It is easy to detect that the process has started. That third week of an embryo’s development is when the mother begins to feel her pregnancy for the first time, in the form of nausea and vomiting. There begins the greatest enigma of the formation of a human being.
With current technology, the pregnancy cannot be carried to term
Marta Shahbazi, biologist
July 25, 1978 was a historic day for science: Louise Brown was born, the first “test tube baby”, an English girl who was the result of the fertilization of an egg in the laboratory. With Brown, a question was also born: What moral status did those embryos cultivated for days in a container have? Philosopher Mary Warnock was commissioned to respond in a report for the British Government. Until the 14th, she declared, those embryos were just a bunch of disorganized cells, with no trace of a nervous system. It was even morally justified to investigate with those little balls and then destroy them. Instead, keeping a live embryo in the laboratory for more than 14 days should be a criminal offence. The 14-day rule, proposed in 1984, has been a worldwide red line ever since. That is why it is so important to obtain pseudo-embryos that mimic the development of real embryos without raising insurmountable ethical dilemmas.
Zhen Liu’s team, from the Shanghai Institute of Neurosciences, has achieved the first model of a monkey embryo in the blastocyst stage, according to the Spanish biologist Marta Shahbazi. “The novelty is technical, not conceptual,” explains the researcher, who cultivates human embryos for up to 14 days at the Cambridge Molecular Biology Laboratory (United Kingdom). “They have managed to [los blastoides de macaco] are developed in vitro, showing some important characteristics of the gastrulation stage. In this sense, it seems more advanced than human models”, Shahbazi highlights.
The biologist stresses that the new model is not perfect. “There are cells that do not have a clear identity and the efficiency is low, but I am sure that these limitations will be overcome in the future,” she says. Chinese researchers have used a chemical cocktail to induce self-organization of monkey embryonic stem cells into blastocyst-like structures, with an efficiency of 25%. Three of these blastoids managed to implant in the uterus of the monkeys, but none of them survived for more than a week. Cultivated in a container in the laboratory, the pseudoembryos managed to develop even precursor cells of the blood system, a phase equivalent to day 17: the beginnings of the sought-after gastrulation.
A long-term risk would be allowing a malformed fetus to develop.”
Irene Aksoy, biologist
“The article clearly demonstrates that these embryo models cannot develop in the mother’s womb. That is to say, they are not embryos, they are simply models”, emphasizes Shahbazi. It is a substantial difference. In some countries, such as Australia, human models of blastocysts, such as those made by the Frenchman Nicolas Rivron, are considered embryos and are regulated by the same strict legislation as real human embryos. “This article clearly demonstrates that, with current technology, you cannot carry a pregnancy to term. In future research I do not think it is necessary to go that far. Let’s start by demonstrating that models can gastrulate in vivo. [en el útero de las monas] and begin the process of organ formation,” argues Shahbazi, who has not participated in the Chinese study, published Thursday in the journal Cell Stem Cell.
French biologists Irène Aksoy and Pierre Savatier have created in their Lyon laboratory chimeras of monkey and person: macaque embryos of just 250 cells, of which 10 of them were human. They are another alternative to using fully human embryos in scientific experiments. Aksoy, of the Brain and Stem Cell Research Institute, believes the new monkey blastoids will shed light on the inscrutable implantation of an embryo in the womb.
These blastoids are incapable of giving rise to a viable fetus, thus avoiding legal problems to investigate with them, but Aksoy warns that the situation may change. “If a monkey blastoid is ever shown to have the same developmental potential as a normal monkey embryo, then Catholic conservatives will want to give human blastoids the same moral status as a real embryo, and will say that it is immoral to work with human blastoids”, he predicts. The French biologist also acknowledges the ethical barriers: “A long-term risk would be allowing a malformed, sick and suffering fetus to develop and be born, which is ethically unacceptable.”
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