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Genetics · the copy of a living thing

Cloning

Making a new organism with the same DNA as an old one. Nature has done it for ever, in identical twins and in every blade of grass that spreads by runners. In 1996 a sheep named Dolly showed we could do it too, from a single adult cell.

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Genetics · First adult-cell clone: Dolly, 1996

Same genome, new individual: copying life rather than editing it.

In Nuclear transfer mode you watch the Dolly method step by step: an egg cell has its own nucleus sucked out, the nucleus from a body cell of the animal being copied is slipped in, a pulse of current fuses the two and wakes the egg, and it divides into an embryo whose every cell carries the donor's DNA. Switch to Embryo splitting and a single early embryo is teased apart into two clumps, each growing into a whole organism, which is how identical twins begin. Drag the slider to step through either one, or press play.

A clone is a living thing that has the same DNA as another living thing. DNA is the set of instructions, written in a long molecule, that tells a body how to build and run itself. Two living things with the same instructions are clones of each other.

Nature makes clones all the time. Identical twins are clones: one fertilised egg split in two, so the twins share one set of instructions. Strawberry plants send out runners that root into whole new plants, each a copy of the parent. Bacteria clone themselves every time they split. Cloning is not strange or unnatural. It is one of the oldest tricks life has.

The famous step was doing it on purpose, from a grown animal. In 1996 scientists made a sheep called Dolly. They took an egg cell and removed its nucleus, the tiny core that holds the DNA. Then they took a single cell from the udder of another sheep, lifted out its nucleus, and put that into the empty egg. A small jolt of electricity made the egg start growing as if it had just been fertilised. It became an embryo, was carried by a surrogate mother, and was born as a copy of the sheep the udder cell came from.

A clone is not a perfect duplicate, though. It shares the DNA, but it grows up in a different womb, eats different food, and has its own experiences, so it ends up its own animal. Even the coat patterns can come out different. A clone is more like an identical twin born years later than a photocopy of a whole creature.

Cloning means producing an organism that is genetically identical to another. The clone shares the same nuclear DNA, the genome packed inside the nucleus of nearly every cell. Some clones happen naturally, and some we make deliberately, but the definition is the same: one genome, more than one body.

The natural kinds. Identical twins form when a single early embryo splits and each half develops into a whole person, so the twins carry one genome between them. Many plants clone themselves through runners, bulbs and cuttings, and a gardener taking a cutting is doing it for them. Bacteria and many single-celled creatures reproduce by simply copying their DNA and dividing. The widget's Embryo splitting mode shows the twin route: tease an early embryo apart and each piece can build a complete individual.

The Dolly method. The headline technique is somatic cell nuclear transfer, or SCNT. A somatic cell is any ordinary body cell, a skin or udder cell, not an egg or sperm. You start with an unfertilised egg and remove its nucleus, leaving a cell full of the machinery of early development but with no DNA of its own. You then take the nucleus from a somatic cell of the animal you want to copy and place it inside that empty egg. A brief electric pulse fuses the two and tricks the egg into behaving as though it has just been fertilised. If it works, it divides into an embryo, which is implanted into a surrogate. Dolly, born in 1996, was the first mammal cloned this way from an adult cell, and the egg's machinery had to wind that adult nucleus all the way back to an embryo's starting state.

Why it is so hard. Cloning from an adult cell is wildly inefficient. Dolly was the single success out of 277 reconstructed eggs. The problem is that a skin cell has spent its life switched into being a skin cell, and the egg has to reset all of that programming back to a blank embryo in a few hours. It usually does the job badly, and most clone embryos fail or develop problems. Since Dolly, the method has been used on many species, including cats, dogs, cattle and horses, and to bring back individuals of endangered animals such as the black-footed ferret. CC, a cloned cat born in 2001, made the point about copies neatly: she had a different coat pattern from the cat she was cloned from, because coat patterns are not set by DNA alone.

Two reasons to clone. Reproductive cloning aims to produce a whole new animal, the Dolly goal. Therapeutic cloning has a different target: it uses nuclear transfer to grow an early embryo only as a source of stem cells that match a patient, cells that could in principle repair tissue without being rejected. Because making and using human embryos this way is ethically fraught, much of that hope has shifted to a newer trick: taking ordinary adult cells and reprogramming them directly into stem cells without any egg or embryo at all.

Nuclear transfer in detail. Somatic cell nuclear transfer takes a metaphase II oocyte, removes the maternal chromosomes (enucleation), and introduces a diploid somatic nucleus, usually by injection or by fusing a whole donor cell to the cytoplast with an electrical pulse that doubles as the activation signal normally supplied by the sperm. The reconstructed egg must then reprogramme the somatic nucleus from a differentiated state back to totipotency, switching off the donor cell's gene-expression programme and re-establishing an embryonic one. Factors in the oocyte cytoplasm drive this, and the fact that it works at all proves a striking point: differentiation removes almost no genetic information, it only changes which genes are read. John Gurdon showed this in frogs in the 1960s, and shared the 2012 Nobel Prize for it.

Why the efficiency is so low. The reprogramming is fast and almost always incomplete. Somatic nuclei carry epigenetic marks, DNA methylation and histone modifications, plus genomic imprinting, that the oocyte cannot fully erase and reset in the time available. The result is widespread aberrant gene expression, a high rate of embryonic and fetal loss, placental defects, and large offspring syndrome in cattle and sheep. Success rates of a few percent are typical even now. Dolly's own early arthritis prompted questions about premature ageing and telomere length, since she was cloned from an adult cell, though later cloned cohorts have shown more reassuring lifespans, leaving the ageing question genuinely open.

A clone is not a perfect copy. SCNT transfers the nuclear genome but not the egg's mitochondria, which carry their own small genome, so a clone is a nuclear copy on the surrogate egg's mitochondrial background, a heteroplasmic mismatch. Add the unerased and stochastic epigenetic differences, random X-inactivation in females (the reason a cloned calico has a different coat), the new uterine and developmental environment, and a lifetime of distinct experience, and the clone is best understood as a delayed identical twin rather than a duplicate. Genotype is shared; phenotype is not guaranteed.

Therapeutic cloning and its successor. Therapeutic, or research, cloning uses SCNT not to make an organism but to derive patient-matched embryonic stem cells from a cloned blastocyst, cells that are pluripotent and immunologically compatible with the nucleus donor. Human SCNT-derived embryonic stem cells were finally produced in 2013, but the approach is constrained by the need for human oocytes and by deep ethical objections to creating embryos for research. Most of that ground has been taken over by induced pluripotent stem cells: Shinya Yamanaka showed in 2006 that a small set of transcription factors can reprogramme an ordinary adult cell into a pluripotent state directly, no egg and no embryo. Yamanaka shared the 2012 Nobel with Gurdon, and iPSCs now deliver much of what therapeutic cloning promised, without the embryo.

Copying versus rewriting, and the line for humans. Cloning copies a genome wholesale; it does not change a single letter of it. That is the clean distinction from CRISPR, which edits specific sequences but does not, by itself, produce a new organism. The two are complementary tools of modern genetics, and they meet in livestock and conservation work where edited cells are cloned into whole animals. Cloning has been used to preserve endangered species, including a Przewalski's horse and the black-footed ferret cloned from decades-old frozen cells, and routinely in agriculture. Reproductive cloning of humans, by contrast, is banned or rejected almost everywhere, on safety grounds given the failure rates and on ethical ones. As with so much of this field, the binding limits are now ethical as much as technical.

Related: CRISPR Gene Editing · next: The Protein Folding Problem · or go back to all topics.