Scientific milestone: Embryos from the lab – without sperm or egg

Leading stem cell biologists are in a race. It started in mid-June, when Magdalena ?ernicka-Goetz of the University of Cambridge succeeded in growing embryo-like models to a stage resembling 14-day-old embryos. To get there in a petri dish is jaw-dropping.

Now a competing research group led by Israeli researcher Jacob Hanna has also published their results in the journal Nature. They’ve also managed to crack the 14-day stage. Plus, their embryo models are "complete" – meaning they have all the structures that a real embryo would have.  

After two weeks, the cell clusters are about half a milimeter long, the size of a grain of sand. The only difference is that these cell clusters are not a "real" embryo. They were grown from embryonic stem cells, by hand, without a sperm or egg cell. 

An ethical dilemma in embryonic research

"Our goal is not to create life," says Magdalena ?ernicka-Goetz. When her findings were published, various media outlets started throwing around Frankenstein comparisons. But we are getting ever closer to the possibility of artificial life. So where does it end? 

We can put people on the moon and dive to the depths of the ocean, but we know very little about the earliest stages of human life. 

Researchers couldn't get at this early period in our development without endangering a human life, so they are restricted to using animal embryos or human model embryos in their research. These can help researchers understand the causes of miscarriages, genetic conditions and congenital organ defects.

Zernicka-Goetz says she hopes her work will further our understanding of what's known as the "black box" period of human development. But critics are concerned that the way she's going about it is like her playing God.

This is the dilemma in embryonic research: the best research models are the ones that get as close to the real thing as possible.

"For scientific purposes, you want the model to be as like the original as possible. But the closer you get to the original, the closer you get to the ethical problems that drove you away to begin with," says Hank Greely, a law professor at Stanford University and an expert on ethical, legal and social issues in the biosciences. In essence, a model that's too much like a human embryo is too much.

Scientists prefer the term 'embryo-like structures'

The findings of the Israeli research team, led by Jacob Hanna, sent a chill down his spine, says Jesse Veenvliet of Germany's Max Planck Institute of Molecular Cell Biology and Genetics.

As a developmental biologist, Veenvliet can recognize an embryo-like structures straight away and know that it's not real — not so with the ones from the Israeli team. "They look fantastic," says Veenvliet.

Yet like many stem cell researchers, Veenvliet stresses that "these models cannot really be described as embryos." He prefers the term "embryo-like structures" — a distinction also made by the International Society for Stem Cell Research (ISSCR) in late June.

The biologist argues that the duck test —­ that if it looks like a duck, swims like a duck and quacks like a duck, then it probably is a duck —  doesn't apply in the field of embryology.

But Stanford law professor Greely disagrees.

"If it can make a baby, it's an embryo," he says.

Scientists, he says, are determined to tell us it's "no embryo, no embryo, no embryo," which makes sense. In his opinion, they want to keep on doing their research.

Short-lived synthetic embryos

Closer inspection reveals that the models do differ from human embryos, says Veenvliet. For example, he says, they skip implantation in the lining of the womb, which means they are incapable of life — and life was never the intention.

Research with animal embryos is a step further. In early April 2023, researchers in Shanghai succeeded in creating blastoids from the stem cells of macaque monkeys. A blastoid is a stem cell-based model of a pre-implantation embryo.

When researchers put these "synthetic embryos" into the uteruses of adult monkeys, some showed the initial signs of pregnancy. But this pregnancy-like response was short-lived, so they failed to create artificial life.

The 14-day rule in embryonic stem cell research

Legally, embryonic research is one big gray area. Most countries, including China, the United Kingdom and Canada, allow laboratory research on human embryos for up to 14 days.

Such experiments are completely forbidden in other countries, including Germany, Turkey and Russia. Brazil and France don't set a time limit, while in the United States, restrictions vary from one state to another.

The 14-day rule is based on bioethical recommendations contained in what is commonly known as the Warnock Report, the findings of a UK inquiry into human fertilization and embryology that was published in 1984.

Gastrulation, a milestone stage in human development, takes place roughly 14 days after fertilization. During this phase, a single-layered embryo transforms into a multi-layered structure that eventually gives rise to tissues, organs and systems in the body. The 14th day is also important because that's when the embryo is individuated and can no longer become a twin.

In the 1980s, the 14-day rule made sense. It allayed ethical concerns of the day and allowed scientists scope to advance their research. It seemed technically out of reach to culture human embryos beyond about five days, anyway.

Science has come a long way since then, as demonstrated by the research of Magdalena Zernicka-Goetz and Jacob Hanna. But since their embryo-like models do not mature into humans, many scientists believe the 14-day rule is out-of-date.

In 2021, the International Society for Stem Cell Research proposed relaxing the 14-day rule, a move Veenvliet says he would welcome.

The first time researchers were able to grow human embryos outside the uterus and keep them alive was almost exactly 30 years after the 14-day rule was introduced. Even if, for example, the period were extended to 21 days — which is when the heart begins to form — the next breakthrough could take another 30 years.

Double standard: Germany's embryo protection law

In Germany, embryo research is completely banned under the Embryo Protection Act of 1991. But there are thousands upon thousands of unused embryos in the country, leftover from people who have undergone artificial insemination.

It's permissible to discard or preserve the embryos by freezing them, but you're not allowed to use them for research, explains lawyer Jochen Taupitz.

On the other hand, scientists are allowed to import embryonic stem cells from abroad and use them in research. That, says Taupitz, is a clear double standard.

Taupitz says he hopes someone will finally take issue with Germany's ban on embryonic research. But, according to him, that can only happen with a review by the country's Constitutional Court.

The only way for that to happen is if someone breaches the law by doing illegal research. That would give the issue some momentum, he says.

Until now, though, no one has dared risk it.