Could the clones from Foundation become a reality?

Apple TV+’s television series Foundation may be set in the distant future, but its characters feel all too modern to many viewers of Season One this past fall. In particular, there’s the galactic ruler, Cleon, who has stubbornly refused to relinquish power. While many of Earth’s current leaders would love to rule for as long as Cleon — roughly 400 years — he has one thing that they don’t: the ability to clone himself.

The frightening idea of a “genetic dynasty” of clones has led some viewers to wonder: When might human cloning become a reality?

Biologically speaking, there’s nothing standing in the way of a human clone being produced tomorrow. In fact, human embryos have already been cloned. The bigger challenge is implanting these embryos into a person’s uterus and bringing them to term — a process rife with safety concerns.

One of the forerunning studies to report the successful cloning of human embryos was published in 2013. The research was led by Shoukhrat Mitalipov, a developmental biologist at Oregon Health & Science University. Mitalipov’s team used a method where DNA is obtained from a patient’s skin cell, then inserted into a donor’s egg cell which has had its own DNA removed. These egg cells are then converted into embryos without being fertilized by sperm. That last part is particularly tricky, but the team discovered that a surprising substance — caffeine — can help do the trick.

The resulting embryo is a genetic clone of the patient who offered up their skin cells, Mitalipov explains. If transplanted into a uterus, the embryo can theoretically grow into an adult clone like Cleon in Foundation; this is known as “reproductive cloning.”

Instead, Mitalipov’s team focused on “therapeutic cloning,” where cloned embryos are made for use in patient-specific medical treatments. Specifically, by turning a patient’s skin cell into an embryo, researchers can then harvest “personalized embryonic stem cells,” per Mitalipov’s study. As NPR reports, stem cells have the unique ability to morph into other kinds of cells, meaning they can theoretically be used to treat a variety of ailments from diabetes to Alzheimer’s.

When Mitalipov’s cloning study came out, it had been 17 years since the first sheep embryos were cloned and brought to term, and six years since Mitalipov’s own team figured out how to clone monkey embryos. What made the cloning of human embryos so much more challenging?

“For each species, you have to have its own kind of protocol approach,” says Mitalipov. “And they can be quite different, be it mouse or cattle or monkey or human.” That’s due to the differences in the cells and fertilization processes of various species, he explains.

Plus, embryonic cloning takes a lot of trials to get right. With mouse cloning research, Mitalipov says you may need somewhere around 10,000 egg cells. “When it comes to human cloning, of course, you can’t afford to have 10,000 eggs,” he adds. Instead, Mitalipov’s research had to make do with a few hundred egg cells gathered from willing donors. Waiting for institutional review and legal approval also prolonged his research by several years. But, in the end, the study was a success.

We’ve known how to produce cloned human embryos for almost a decade. So it shouldn’t be long until we see the birth of the first baby Cleon, right?

Well, according to Mitalipov, there are no known instances of a cloned human embryo being brought to term. But in 2018, a group of Chinese scientists successfully cloned our cousin species — macaque monkeys — and brought them to term. Given the genetic similarities between monkeys and humans, this breakthrough study suggests that a cloned human embryo could also be implanted into a uterus and brought to term in the near future.

But there’s one glaring problem: As with the process of cloning embryos, bringing these embryos to term requires a lot of trials to get right. In the macaque study, only six out of 21 surrogate monkeys successfully became pregnant. And, of those six, only two gave birth. (Both babies were healthy.) Those trials were just attempts to clone a macaque fetus. Meanwhile, the team’s attempts to clone an adult macaque were even less successful, producing two unhealthy clones who died within 30 hours.

Human trials would likely be similar. Many of the embryos would have to be discarded, and many fetuses may not make it to term, Mitalipov says. Furthermore, he adds that there would be pain and distress for the adults who volunteer to gestate the embryos in their uteruses as well. All these are risks that researchers are willing to take when it comes to animal testing, but not when it comes to humans.

“My view is that safety is far and away the most important concern,” says Henry Greely, a bioethics expert who directs Stanford University’s Center for Law and the Biosciences. “[Safety] is an order of magnitude more important than any of the other arguments.” 

Regardless of the safety concerns, Greely says that the current legal framework around cloning is vague; there are no clear laws preventing researchers from cloning human embryos and bringing them to term. That’s in the United States, at the federal level, at least. Many countries and some U.S. states have stricter bans on human cloning, Greely says.

Greely also considers the costs and benefits of human cloning trials — suggesting that, in his mind, one side certainly outweighs the other. “It’s hard to come up with many scenarios where there’s a clear benefit to cloning,” he says. “And if there’s no benefit then any risk is too much risk.” Regardless, Greely thinks that there’s a good chance that some researcher will move forward with attempts to bring a cloned baby to term, possibly in an effort to become famous.

But Mitalipov believes that such a rogue effort is unlikely. “It’s not like every scientist, every lab, can do it. In fact, there are probably just a handful of labs that have expertise in this,” Mitalipov says. Those labs, he adds, would be highly unlikely to put their reputations on the line by moving forward with human cloning trials.

Still, given enough time, who knows what could happen. For example, Greely says he can certainly imagine “some rich guy” trying to fund research into how to clone himself. If just one experienced research team is willing to accept the bounty, Greely adds, then we may instantly enter the era of human cloning.

From there, it’s conceivable that humanity might one day find itself under the rule of a line of identical galactic rulers. But let’s hope that idea remains in the realm of fiction.