“Replicants are like any other machine - they're either a benefit or a hazard. If they're a benefit, it's not my problem.”
Fans of the movie “Blade Runner” will remember that quote by Rick Deckard (played by Harrison Ford) concerning ‘replicants’ – the bioengineered humanoids "composed entirely of organic substance" to be identical to adult humans but, depending on the model, possessing superior strength, speed, agility, resilience, or intelligence. Because they were created to be slaves, problems ensued (we’ll leave at that for those who haven’t seen the movie). Released in 1982, the film was set in 2019. It is now 2022 and fictional replicants may be on the path to becoming real ones with the news that a team led by researchers from the Weizmann Institute of Science in Israel have developed synthetic mouse embryos from mouse stem cells – no eggs, sperm or fertilization needed. Is this a benefit or a hazard?
“Here we adapt a recently established platform for prolonged ex utero growth of natural embryos, to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extra-embryonic compartments, starting solely from naïve ESCs.”
In a study published in the journal Cell, Weizmann Institute of Science Professor Jacob Hanna explains how he and his team (in scientific terms far beyond this writer’s pay grade) used embryonic stem cells from mice to grow synthetic mouse embryos outside of a mouse uterus and grow them to the point where they had an intestinal tract, the beginnings of a brain, and a beating heart. In this case, ‘synthetic’ means created without fertilized eggs, but make no mistake about it – these were real, albeit very early-stage, organic mouse embryos.
“What's particularly interesting about the newly published model is its very complex structure; not only does it mimic the cell specification and layout of an early-stage body plan—including precursors of heart, blood, brain and other organs—but also the "support" cells like those found in the placenta and other tissues required to establish and maintain a pregnancy.”
In an explanatory article published in The Conversation, Megan Munsie, Professor Emerging Technologies (Stem Cells) at The University of Melbourne (and not part of the study), reveals just how big of a breakthrough this is. Hanna and his team grew the stem cells into embryos without a uterus – so they were shocked when the synthetic embryos developed umbilical cords on their own. While they had no mother to connect it to, the synthetic embryos also created the membrane that surrounds natural embryos in the mother’s abdomen – the liquid-filled ‘yolk’ sac where they develop.
“sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extra-embryonic compartments similar to E8.5 stage mouse embryos.”
The study summary touches on another major breakthrough from this research – the sEmbryos (synthetic whole embryo models) began as a one-dimensional layer of epithelial cells, called a blastula, and then reorganized into a multilayered and multidimensional structure called the gastrula. It was at this point that the sEmbryos began developing a brain, a beating heart and a functioning an intestinal tract … but it is also the point where natural embryos begin to develop problems whose causes are still mysteries to doctors. It is as in the gastrula stage that embryos can be influenced by environmental factors in the womb for example, something blocks cells from receiving the right signals to fully form the spinal cord and they instead develop the birth defect known as spina bifida. The researchers state that being able to study sEmbryos at the gastrula stage will help doctors diagnose or even prevent such birth defects from forming.
“Our findings highlight the plastic potential of naïve pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.”
Of course, the research does not end at gastrulation – the study concludes that these sEmbryos have the potential to become an entire mouse embryo … which implies they could then become entire baby mice with no mouse parents. As expected, this is where the ethical radar system begins blasting alarm signals. Dr. Hanna is ready for them.
“In Israel and many other countries, such as the US and the UK, it is legal and we have ethical approval to do this with human-induced pluripotent stem cells. This is providing an ethical and technical alternative to the use of embryos.”
Hanna is the founder of Renewal Bio, a company whose charter is to grow human synthetic embryos to provide tissues and cells for medical conditions. Of course, that will eventually lead to fulfilling one of medicine’s greatest needs – transplantable organs. Would humans be more open to a heart or liver grown from stem cells than one grown in a pig? Hanna says he has “legal and ethical approval” to use with human-induced pluripotent stem cells for research that undoubtedly now includes plans to create human sEmbryos. Munsie tries to address some of the ethical concerns.
“However, even though these models are a powerful research tool, it is important to understand they are not embryos. They replicate only some aspects of development, but not fully reproduce the cellular architecture and developmental potential of embryos derived after fertilisation of eggs by sperm – so-called natural embryos.”
Not yet. Are we really so naïve to think that this type of research in a country without stringent controls, or a country where profit drives political decisions, would not result in human embryos being created from stem cells and grown into human babies? What next? What is there to stop them?
“The report read "Routine retirement of a replicant." That didn't make me feel any better about shooting a woman in the back.” (Deckard in “The Blade Runner”)
Munsie points out that Hanna and his team made it clear that they were unable to develop the sEmbryos beyond eight days – the normal gestation period for mice is 20 days. That still means that the sEmbryo was 40 percent of the way to becoming a baby mouse – almost halfway there.
“Blade Runner” is based on Philip K. Dick's 1968 novel, “Do Androids Dream of Electric Sheep?”. Dick preferred the term “android” or “andy” but "Blade Runner" director Ridley Scott knew that term connotated ‘robot’ to many people, so he coined “replicant” based on his daughter’s idea that replication is the biological process of a cell making a copy of itself. Isn’t that what an sEmbryo is doing?
How far away are we from replicants?
How far away are we from blade runners?
Does “routine retirement of an sEmbryo” make you feel any better about doing it?