Breakthroughs in creating laboratory models of human embryos have raised concerns among scientists

From the moment the sperm fuses with the egg, the development of the human embryo involves a series of complex and poorly understood processes. Much of what is known about embryo development comes from animals such as mice, rabbits, chickens and frogs, but research on human embryos is very tightly controlled and regulated in most countries, CNN says.

But animal studies can only tell researchers so much. What happens during the development of a human embryo, especially in the crucial first month, remains largely unknown.

“The drama happens in the first month, but the remaining eight months of pregnancy are mostly about rapid growth,” says Jacob Hanna, professor of stem cell biology and embryology at the Weizmann Institute of Science in Israel. “But this first month is still very much a black box.”

Being able to peer into this black box could open up a world of biomedical possibilities, allowing scientists to uncover previously obscure aspects of embryonic development, which could ultimately lead to a better understanding of miscarriages, birth defects and the side effects of medications taken during pregnancy. And some researchers believe they have found a way to do this that bypasses the need for eggs or sperm, CNN reports.

Using advances in stem cell technology, laboratories around the world are creating embryonic-like structures – a group of cells that act like an embryo but cannot grow into a fetus.

Recent breakthroughs in the field, the culmination of years of painstaking laboratory work, have raised hope and some concern, raising pressing questions about the ethical status of these models, the extent to which they should be treated like human embryos and whether they are open to misuse.

The embryo-like structures are essentially clumps of lab-grown cells that are smaller than a grain of rice and represent the earliest stages of human development, before any organs have formed. They do not have a beating heart or brain.

The most advanced models, presented in September by an Israeli team of which Professor Hanna was part, show all the cell types that are needed for embryo development – the placenta, yolk sac, chorionic sac (outer membrane) and other tissues the embryo needs to develop.

These structures were left to develop for eight days, reaching a stage of development equivalent to the 14th day of a human embryo in the womb, an important point when natural embryos acquire internal structures that allow them to move on to the next stage: the development of the body’s organ precursors.

Khanna said these were the most accurate models developed so far, and, unlike models created by other teams, no genetic modifications were made to include the genes needed to create different types of cells, only chemical nudges.

Hannah’s team did not use fertilized eggs. They started with human cells known as pluripotent stem cells, which can potentially be programmed into many cell types and are widely used in biomedical research. Some of them were obtained from adult human skin cells.

The team then reprogrammed these cells into what they call a “naïve state,” corresponding to the seventh day of development of a natural human embryo, around the time it implants in the uterus. These “naïve” cells were divided into three groups.

One group, destined to become embryos, was left untouched. The other two groups were nudged using certain chemicals that activate certain genes to develop tissues needed to support the embryo, such as the placenta. According to Hannah, all three groups are getting together in two days.

“In the first three days you don’t see much, you just see a clump of cells growing,” he explained. “But by the fourth day you start to see… it has a structure, you can see where the embryo is going to form.”

At the equivalent stage of the seventh day, the synthetic models of human embryos were clumps of about 120 cells, collectively measuring about 0.01 millimeters across. By day 14, they contained about 2,500 cells and measured 0.5 millimeters in size.

Hanna and his team say the models closely mimic how an early embryo acquires all the structures it needs to begin developing into a fetus. The internal organization matched images in embryology atlases released in the 1960s, and when they applied the secretions from the cells to a commercial pregnancy test, the result was positive.

However, only 1% of the aggregated cells self-organized into an embryo-like structure. For embryo models to become useful tools for scientists, a much higher percentage would be needed, which is possible but would likely take years to perfect, Hannah said.

“I think we can learn a lot from these stem cell-based embryo models. At the moment there are some disadvantages. They are very inefficient to manufacture… so clearly efficiency needs to be improved to really get the most out of what we can get out of these models,” Peter Rugg-Gunn said at a press briefing this week. Rugg-Gunn is a team leader and head of public engagement at the Babraham Institute, which specializes in life sciences research.

To date, no embryo models have been grown beyond 14 days, largely due to the limitations and challenges associated with culturing these structures.

However, 14 days is an important milestone because that is when approved laboratory testing of cultured human embryos typically ends. The line was set by the UK Fertilization and Embryology Act in 1990 in the wake of public concern about test tube babies before in vitro fertilization was widely accepted, and concerns that scientists were ignoring the special moral status of human embryos. The 14-day rule was subsequently adopted by several other countries and eventually became an internationally accepted ethical limit.

This restriction, which some scientists want to expand, does not apply to stem cell-based embryo models, which the International Society for Stem Cell Research says should not be considered embryos. However, the organization recommended that research using models should require ethical oversight.

Perhaps in the future these models could be used to study human development well beyond the 14-day period. Hanna and other groups have grown mouse embryo models to a later equivalent stage. He said that in the future it may be possible to extend lifespan in human embryo models to 40 days.

But grim concerns that model scientists are trying to create an alternative way to produce human life are the stuff of science fiction, Hannah says.

“People immediately think that we’re trying to replace pregnancy or gestation with this embryo model, but that’s actually not the case, not only is that not the goal, but I don’t think it will ever be possible,” he said.

According to current research, embryo models are still in their infancy, with clear scientific differences from the human embryo and lacking the potential to form a fetus.

In addition, the International Society for Stem Cell Research, in its guidelines, prohibits the transfer of any embryo model into the uterus of a person or animal.

“I want to emphasize that these models are not embryos, and every jurisdiction and society… those who have studied this have said that it should be illegal to attempt to transplant any stem cell-based embryo into a woman or a human embryo into the uterus of an animal. It should be banned,” says Robin Lovell-Badge, professor and head of the laboratory of stem cell biology and developmental genetics at the Francis Crick Institute in London.

Many scientists argue that human embryo models, especially if they can be produced in large quantities, offer an ethical alternative to research on rare and valuable human embryos that are typically obtained as a byproduct of IVF.

“With their stem cell base, we can scale everything up. We can conduct experiments on them that we cannot do on precious, rare (human) embryos. And so it just changes the types of experiments we can do and the questions we can answer,” said Naomi Maurice, group leader at the Developmental Models Laboratory at the Francis Crick Institute in London.

One potential application could be drug screening and research. Pregnant women were often excluded from drug trials due to concerns about the safety of the parents and the unborn child.

In her laboratory, Naomi Maurice conducted experiments with embryonic models to see how they responded to drugs such as thalidomide, a drug once marketed as a treatment for morning sickness, which is already known to cause birth defects.

The goal was to find out “if they are sensitive to these drugs that we know will be toxic to the early embryo, and then whether we can use (the embryo model) to screen for drugs that we don’t really know about.” ?”, – she said.

Maurice agreed that the models should not be classified as embryos given their origin from stem cells and because they still lack certain characteristics, but she noted that it was impossible to know for sure.

“We can’t do a golden experiment, which would be to put it in a womb and see if it can continue to grow, and without being able to do that experiment – quite rightly – how can we as researchers decide whether we’ve crossed we this border and have turned into what we would call an embryo? I think this is a big question. And this is not an easy question to answer,” admits Maurice.