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So, you know the movie where Batman fights Wolverine and then David Bowie accidentally invents a cloning machine. What was that called? Oh right, The Prestige. Spoiler alert for a movie that came out in 2006, but Hugh Jackman's character basically clones himself over and over again as part of his magic trick. But it's not necessarily, like, cloning himself originally. It's like clones of clones. In the real world, making a copy of, like, a photocopy or something, eventually leads to disaster. But how many times could you actually clone yourself?
How many generations of "you" could you make if you had, the absolute biggest ego known to humankind. Well science is already testing these limits. At least in mice. And in a landmark paper published in 2026, one team set a new record of 58 generations. But as they kept pushing, things started going south. So let's take a look at what happens when you clone a clone. [♪ INTRO] In 1903, a plant physiologist named Herbert Weller argued that…due to advances in horticultural science…we needed a new set of standard terms. He introduced the term clone, which he took from the Greek "klon," meaning "twig" or another plant cutting. At its most general, the word refers to genetically identical
copies of DNA sequences, living cells, or whole organisms created asexually. When someone takes a cutting from their bestie's plant to grow their own at home, they're creating a clone. So humans have been cloning things long before the jargon existed. Meanwhile, animals have been cloning themselves long before humans did it for them. A few species are known to reproduce clonally… from certain flatworms to starfish to lizards. through the regeneration of a body part or so-called virgin birth. Yeah. Sometimes just one body part, like a limb or tail, provides everything an animal needs to build all the tissues and structures in the rest of the animal.
Humans are cool, but we can't grow a whole body from a decapitated head…or like, grow a head back on a body that doesn't have a head anymore. We do know a thing or two about artificial cloning, however. The applications of which range from cultivating organs tailored for transplant recipients, to growing synthetic meat, to species conservation. All of these applications are either already in use, or in various stages of research and development. Each has its own benefits and drawbacks. And yes, the ethics are being passionately debated.
Even before you get into the quagmire that is cloning entire humans. Meanwhile, the methods used to create animal clones have varied widely over the years… including years before Weller coined the term. But generally, the first era of cloning research required embryonic cells. More specifically, an embryo that was just a few cells big. Because at that point, each of those cells has the unique ability to develop into any tissue. Which you kinda need if you want to grow a whole body with lots of specialized parts. If you want to clone an animal from an older, specialized cell, you'd have to find a way
to reprogram it…get it to revert back to its "I can grow up to be whatever I want" stage. It was hard enough getting a clone from an embryo that was too old. Cloning an adult animal was a whole 'nother can of worms. But over time, scientists made more and more tweaks to get their methods to work on more and more highly specialized cells. Which brings us to a baby sheep named after Dolly Parton. In 1996, Dolly became the first fully developed mammal cloned from adult tissue. Specifically, a cell from a mammary gland. Although, technically, she wasn't a full clone.
It's perhaps more accurate to call her a chimera, since scientists later found the mitochondria in her cells came from the enucleated egg cell she grew from. Not the cell from which her DNA was taken. Also, it's worth noting that there were 276 failed attempts at the same experiment before Dolly was born. But Dolly was certainly a success. She lived long enough to naturally conceive through sexual reproduction, and gave birth to six lambs. As far as we know, no one tried to clone Dolly herself. But that doesn't mean scientists haven't done that for other cloned adult animals.
Up until 2004, serial cloning had only been done in mice. But that year, scientists published a paper describing their successful cloning of a bull to the second generation. This was a continuation of a study first published in 2000, in which a group of researchers cultured skin cells from a generation-zero Japanese beef bull, transferred the nuclei into fertilized eggs, and implanted the resulting embryos into surrogate cows' uteri. They ultimately produced six cloned generation-one, or "G1" calves.
The 2004 publication described producing one healthy surviving G2 from one of the G1 calves. This challenged the belief that mammals need sexual reproduction to propagate their genetic lines through multiple generations. That said, when the team attempted G3, only about 20% of the attempted embryo transfers reached the fetus stage. And all of them spontaneously aborted. Still, researchers were tenacious, and the G3 threshold in mammals was soon crossed. And G4. And G5… By 2013, a mouse experiment that began in 2005 had gone on long enough to reach the 25th generation milestone, with almost 600 new mice generated.
One big reason for the researchers' success was they identified chemicals that worked wonders in reprogramming and reverting a specialized cell. If a cell has a certain job in your body, it's going to be physically different in structure and composition than cells that do any other job. It also has modifications to the genetic instructions inside it, including small chemical tags that accumulate on the DNA molecule, and the way that DNA is packaged inside the cell's nucleus. To reprogram a cell back into an immature state, you need a way to both remove those tags and reconfigure how the DNA is packaged.
Only then will it be able to give rise to all the tissues you need for a whole new body. Scientists can use chemicals called small molecules… yes, that is really what they're called… to slip into a cell and mechanically tweak those structural differences back to the embryonic stage. But in addition to some particularly well-chosen small molecules, the team also benefited from using a specific type of cell to make their clones: cumulus cells. Cumulus cells are a specialized adult cell that help eggs mature and ovulate. Just a few years before their study began, other researchers discovered the nuclei are easier to reset than other kinds of specialized cells, like skin cells.
By G25, experiments suggested the clones were fertile and could reproduce sexually. The team also noted the success rate didn't clearly decline from the first to the 25th generation. Instead, it fluctuated. And while there were some genetic errors that popped up, they weren't all harmful, and didn't seem to accumulate in irreversible ways. The scientists cautiously figured if they could just get all of the conditions correct each generation, it could go on forever. But they knew that was a very big "if". With all the tips and techniques they had gleaned over the decades,
the study that started in 2005 continued all the way to 2026, producing a record-breaking 58 generations of mouse clones, and more than 1,200 mice in total. That's when the ultra-complicated hurdles became too high to clear. Basically, from generation 25 onward, the success rates of producing live cloned pups trended downward, and by 58, it dropped to almost zero. The researchers couldn't identify one single point of failure. It was more or less due to the gradual accumulation of various genetic mutations and the resulting problems with cell division.
Scientists use the term mutational load to refer to the number of harmful mutations that accumulate from generation to generation. And generally speaking, that load is far higher in serial clones than sexually reproduced individuals. That's because, in sexual reproduction, as egg and sperm cells are created, each receives a unique, shuffled version of half an animal's genome. It's half because that's part of the nature of being a sex cell. And it's shuffled thanks to a process the chromosomes go through called recombination.
Scientists are pretty sure it's recombination that randomly breaks up harmful mutations. Basically, there's always some chance a given genetic error in an animal's full genome won't end up in the sex cell that then goes on to make a baby. Cloning skips all of this beneficial shuffling. the genetic errors began to affect larger chunks of the genome. These larger errors eventually became deleterious… they made it more likely for the mouse to develop a disease or disorder… to the point that the next generation was no longer viable. Another issue was that the placenta was often abnormal in later generations. And without a healthy placenta, it's harder to bring a healthy pup to term.
But the researchers remain cautiously optimistic that, with a better grasp on all of the factors, serial cloning might continue indefinitely. Which is either miraculous or disastrous, depending on your outlook and preferred subgenre of science fiction. So what does all of this mean? Well, the authors say their results contradict the Red Queen Hypothesis, which holds that sexual reproduction is necessary to increase genetic diversity and propagate. Instead, they found making a copy of a copy can introduce genetic mutations that don't harm the offspring. And that counts as diversity. But they also note their work supports Muller's ratchet theory,
which posits that, without recombination, generation after generation of asexual reproduction will eventually build up so many mutations, the clonal line will go extinct. However, if you look to nature, this isn't necessarily the case. One species of fish in the Amazon has obviously found ways to get around the ratcheting. It has been successfully cloning itself as its only form of reproduction for roughly the past 100,000 years! But those are fish. Not mammals. So as far as we know, Muller's ratchet theory holds for mice, the family dog, Hugh Jackman, and any narcissist billionaire that thinks he can achieve immortality
by transferring his consciousness into clone after clone of himself. Sorry, I should not be giving them ideas. [♪ OUTRO]
