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In 1978, the year the first “test-tube baby” was born, experts in human reproduction agreed on a rule around the world: they prohibited the development of human embryos more than 14 days in the womb.
Its aim was to set an ethical limit for the rapidly expanding field of embryo research, and in some countries the two-week limit was enshrined in law.
This is because, at the end of the second week of pregnancy, a complex process begins, which many consider the most fundamental of our creation: gastric inflammation, during which the foundations are laid, which will form all the organs and tissues of our body. .
It is this stage that defines what we are physically and makes us unique and irreplaceable beings, because when the so-called primitive streak – which marks the beginning of the gastrulation process – the embryo can no longer divide. Twins.
This period between the third and fourth week of pregnancy is not only crucial for our transformation from a group of cells to an individual being, it is also the most delicate period of pregnancy.
This is the most delicate period of pregnancy. Many miscarriages occur during this time, and many birth defects can cause lifelong health problems.
That is why one of the most famous embryologists in history, the British Louis Wolbert, who died in 2021, said, “It is not birth, marriage or death, but diarrhea that is the most important moment of your life.”
Despite its importance, this stage between days 14 and 28 of pregnancy is still considered a black box of human development because scientists are unable to study it in their laboratories.
Advances in technology have made it possible to observe embryos formed in the fetus during the first two weeks of pregnancy.
Experts have been able to reconstruct what happens after 28 days by analyzing tissue from aborted fetuses naturally or automatically and donating them to science.
But as Argentine embryologist Felicidas Aspiros, a researcher at Eugene, a Spanish group specializing in reproductive science, explains, access to embryos less than a month old is almost non-existent.
Therefore, it has not yet been possible to study the mysterious mechanism of the human embryo, the small group of cells that make up the two-week embryo fuse together to form the three germ layers, which contain stem cells. It makes up our body, from our heart and nervous system to our nails and hair.
Scientists are not limited by the 14-day rule, which does not allow them to see what happens to the fetus as it enters the third week of pregnancy.
It is also true that until recently technological capabilities did not allow long-term development of human embryos. But scientific progress, especially in the field of stem cell research, has made this last limit no longer insurmountable.
In May 2021, an international panel of experts decided it was time to postpone this deadline, opening the door to the possibility of studying what happens during the enigmatic gastrulation.
The International Society for Stem Cell Research (ISSCR) recommends that under certain strict conditions, embryo development beyond two weeks may be justified, but that each country should have its own debate on whether such experiments should be allowed.
“It’s not a green light for teams to extend human cultures beyond 14 days,” said Cathy Neagan, a biologist at the University of Cambridge, one of the experts who worked on the study. New guidelines.
“This would be irresponsible and, in many jurisdictions, illegal. Instead, these guidelines call for a proactive dialogue with the public to review the 14-day limit on human embryo culture,” he said.
Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute and head of the ISSCR team of scientists, said that studying the gastrulation process could help understand why one in four pregnancies fail.
“If we can figure out what’s wrong, we can prevent miscarriages and birth defects,” he said.
Until now, scientists have only been able to study gastrulation by analyzing tissue from animal embryos.
In 2019, Spanish scientist Juan Carlos Izpizua conducted a controversial experiment in a Chinese laboratory by injecting human stem cells into 132 monkey embryos.
Three hybrid embryos grew in vitro for 19 days before being destroyed, according to details of the study, published in the scientific journal Cell in 2021.
Izpisúa and his team’s hypothetical goal is to study whether it is possible to grow human organs in animal hosts in the future, but this study shows that the 14-day barrier can be overcome.
The demonstration was finally done in August 2022, when two teams of scientists, one in Israel and the other in the United Kingdom, achieved a goal that had been desired for years and succeeded in creating artificial mouse embryos created from stem cells. .
Jacob Hanna of the Weizmann Institute of Science and Magdalena Zernica-Coetz of the University of Cambridge led the two studies, which are published in Cell and Nature, respectively.
In both cases, the pseudoribbons developed for about eight days, or a third of the mouse’s gestation period, and then formed beating hearts and the base of the brain.
In April this year, Chinese scientists from the Shanghai Institute of Neuroscience published another breakthrough in the journal Cell Stem Cell: they created pseudo-embryos, but from monkeys – whose development is more similar to that of a human than that of a mouse – and were able to create it. Some of these macaque blastoids (when the embryo has more than 200 cells) survive 18 days in vitro by gastrulation.
In the past three years, some have found new ways to study the phenomenon in humans without running into the moral dilemmas of growing viable embryos in the lab.
More advanced methods involve the creation of so-called pseudo-embryos or embryos, which are a collection of human embryonic cells created from stem cells.
Although they are formed without eggs or sperm, they develop like human embryos, following the general rules of development of our species.
In 2020, researchers at the University of Cambridge (United Kingdom), led by Spain’s Alfonso Martínez Arias, succeeded in creating mock embryos that reproduced the essential characteristics of an 18- to 21-day-old embryo from embryonic stem cells.
They called them “gastruloids” because they reproduce the embryo in the gastrulation stage.
These castruloids lacked the brain cells or tissue needed to implant in the uterus, so they lacked the ability to develop into a fully formed embryo, but even though they only developed for a few days, they opened a window to witness a phenomenon. It was hidden until then.
“Our work allows us to study this critical stage of human development in an ethical way,” Martínez Arias said of the research published in the scientific journal Nature.
The expert added that this scientific breakthrough opened for the first time “the possibility of analyzing the moment many pathologies arise.”
A step up
Since then, more advanced methods of creating artificial embryos have been discovered, which may one day be observed in stealth gastric activity.
In 2021, a team from Monash University in Australia, led by Argentinian biochemist Jose Polo, succeeded in creating human pseudo-embryos from embryonic stem cells, but reprogrammed from adult skin stem cells to return to the embryonic state.
However, other scientists went further and raised questions about the boundary between a pseudo-embryo and a real embryo. A team led by French biologist Nicolas Rivron at the Institute of Molecular Biotechnology in Vienna created artificial blastocysts (which they named “blastoids”) from adult stem cells.
By the end of 2021, they had successfully implanted them into endometrial cells grown in vitro.
Although human embryos have not yet completed gastrulation, if the time allocated to their development is extended, Aspiros points out, “in the future they will be one step closer to understanding this complex process.”
Aspiros cautions that in all of these experiments on humans and animals, the fake embryos created lacked the same characteristics and abilities as real embryos and failed to develop beyond a few days. But the potential, he points out, is immense.
“Everything opens the door a little bit more to the possibility that we could do it with humans tomorrow,” he says.
Although we are still a long way off today, if science continues to advance, we may not only be able to create artificial human embryos and saturate their stomachs, but we may finally be able to peer into the black box of development. Unattainable today.
Today we can only reach the limits of what is possible in science fiction.
“Can we clone a human being or create organs? Everything is moving towards that,” he concludes.
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