Without eggs, sperm or uterus: the revolution in reproduction arrives

Research into new forms of reproduction has seen many advances in recent times: from Dolly the sheep to mice that have offspring without the need for semen, passing through nanorobots that direct sperm towards the egg. The latest find has made headlines around the world: synthetic mouse embryos created without sperm or eggs, all from a kind of ‘artificial womb’ and stem cells grown in a Petri dish. The experiment, published in the journal ‘Cell’ and carried out by the Weizmann Institute of Sciences, is considered a revolution in its field, although there are already several laboratories investigating this new line of development. The most prudent assure that this method will mark a before and after to study the first moments of life, or to better understand how certain mutations drive various developmental diseases; the most optimistic see it as a way to create ‘photocopies’ of our organs for when the originals don’t work, and even to help combat infertility. In any case, an ethical debate is opened around the possibility of creating life almost from nothing, making its way, as always, but in a unique and synthetic way. The formula that allows reproduction in mammals consists of several ingredients: a sperm fertilizes an egg, which creates a kind of ‘sack’ of shared DNA that needs a uterus to provide it with the necessary nutrients to grow. This is the traditional recipe. Now, however, Weizmann’s Israeli team, led by renowned geneticist Jacob Hanna, has dispensed with all that foundation, creating synthetic embryos that, when viewed under a microscope, are 95% similar to natural embryos and could survive up to 8 years. .5 days out of a womb. To do this, they used a specially designed bioreactor that serves as an artificial matrix for the development of embryos, a kind of ‘artificial womb’ where the embryos float in small boats with a solution full of nutrients. The beakers are enclosed in a rotating cylinder that keeps them in constant motion, simulating how blood and nutrients flow to the placenta. The device also replicates the atmospheric pressure of a mouse’s uterus. Previous science It was not the first time that this device had been used: the researchers carried out another experiment that was published in ‘Nature’ in 2021 in which the team managed to grow natural embryos until the 11th day of gestation (in total, the pregnancy of a female mouse is about 20 days). “With this we demonstrate that mammalian embryos can grow outside the uterus and that this organ functions as a nutritional support,” explains Hanna. This success made them go a step further and think of a new experiment: create embryos from stem cells and make them grow in their ‘mechanical womb’. To do this, they extracted mouse embryonic cells, capable of becoming any type of cell, and induced them to form, on the one hand, organs and tissues; on the other, the placenta; and lastly, the yolk sac. “The last two groups were necessary to create the extra-embryonic tissues that drive the development of the embryo,” explains Hanna in a statement. On the first day, the cells joined together to form compact groups that were introduced into the machine that simulates the uterus. The results surprised the entire team: on day 3 of gestation, the embryos began to lengthen, turning from spheres to cylinders; three days later, the neural tube began to fold at one end, and at the opposite end something that would later become the typical mouse tail could be seen. By day 8, a normally beating heart began to circulate blood through vessels that formed around the embryo’s yolk sac. All in the same way that nature would have made the beginning of a new being blossom, but without the need for an egg, sperm or uterus, only from mouse embryonic cells, for 8.5 days, which would be equivalent to a human pregnancy of about a month and a half. Desktop Code Mobile Image, amp & App Mobile Code AMP Code 4660 APP Code Hanna isn’t the only pioneer. His partner and his ‘rival’, Magdalena Zernicka-Goetz, from the University of Cambridge, has been following the same line in parallel for a decade. Her team will soon publish two studies: one with a similar approach to that of the Israeli group (“although we have managed to get our structures in the embryo to develop a little more,” she explains to ABC); and a second, more budding, in which they use different embryonic cells (trophoblastic stem cells, which are collected from the mouse placenta), with which they achieve a higher success rate and where they observe that the synthetic placenta is much more similar to nature. Geneticist Jacob Hanna I. Weizmann Do they feel even though they are synthetic? For centuries, genetics has always been accused of ‘wanting to play God’: how far can you ‘touch’ the pieces that nature has? The question becomes more evident when life is created from artificial elements, such as a mechanical womb; or by doing away with the ‘building blocks’, such as sperm and eggs. The case of the experiment by Jacob Hanna, from the Weizmann Institute of Sciences, is the clear example. Although its creators defend that it will be a method that will allow us to stop depending on natural embryos, and although all the experts agree that we are not dealing with true embryos, since -for the moment- they do not have the capacity to develop either in the device or within a uterus (they could not be implanted since they lack structures linked to the mother, such as the umbilical cord), “science is always ahead of the law, and always raises new questions to discuss a posteriori”, says Lluis Montoliú, a researcher at the CNB-CSIC. “In experiments like this, questions can arise such as whether the embryo that has a nervous system can feel something, in this case, pain. These are ethical questions that we will have to ask ourselves, just as it happened with the manipulation of stem cells at the time ». “It is necessary to point out that although these structures look like and show the gene expression patterns of embryos, they are not real embryos,” says Zernicka-Goetz. The ‘gold standard’ for these embryos, according to the researcher, would be to be able to implant them in a uterus and develop further. “But they lack the necessary structures for this, such as an umbilical cord that connects them with the mother,” explains the researcher. “These embryos have passed the phase in which these structures that connect them to the uterus are created, so for the time being it is impossible for them to come to term naturally,” adds Lluis Montoliú, a researcher at the National Center for Biotechnology of the CSIC (CNB-CSIC), who is not a member of any of these teams, although he is a world-renowned expert in genetics. “They are groups of cells that have been ‘forced’ to cooperate with each other, and the result is this organization in a synthetic embryo. Even so, it is necessary to take into account that only a small percentage of all these groups have managed to reach term”, points out the Spanish researcher, referring to the fact that only 50 of the 10,000 cell groups (0.5% of the total) that they were created until they formed a viable embryo up to just over eight days of development in the case of Hanna’s experiments, a percentage that rises to 10% in the case of Zernicka-Goetz. “It is a very promising experimental line in the making, but there is still a lot of research ahead,” says Montoliú. Human Applications Hanna has founded his own company, Renewal Bio, to continue his experiments and take them one step further. Based on the idea of ​​the Nobel Prize in Medicine, Shinya Yamanaka, who showed that inserting four genes was enough to transform an adult cell (normally extracted from the bone marrow or skin) into another that behaves as if it were embryonic (called an IPS cell). ), the idea now is to test with their own blood and skin cells to see if it is possible to apply this method to humans. “The embryo is the best 3D bioprinter. The best method to create suitable organs and tissues”, says Hanna, whose company already points to the potential of the system to grow organs from a person’s cells and transplant them to itself if necessary. What’s more, on the company’s website they state that they can “renew human health” and that their goal is “to make humanity younger and healthier by harnessing the power of stem cell technology,” which can be ” apply to a wide variety of human ailments, including infertility, genetic disease and longevity. MORE INFORMATION Engineers manufacture a skin that connects your vital signs to your mobile phone without Bluetooth An ancient and unknown source of oxygen could boost life on primitive Earth Montoliú is critical of these statements: “At the moment there are only these results, which can be very useful and promising. But from there, it’s speculation. There is a long way to go.” For her part, Zernicka-Goetz is also more conservative than Hanna. “It will allow us to study the development of mammals without relying on natural embryos, since currently, to recover them from the uterus, a large number of dissections have to be carried out on females.” Beyond lucubrations, the entire scientific community agrees that the Israeli group’s study has taken a new step towards a new future in reproduction. Now it’s time to wait to see where this new path leads us.