Reproductive cloning is a way of making a whole new animal that shares its genetic blueprint with one that already exists, without the usual mix of DNA from two parents. In effect, scientists take an adult’s genetic instructions and persuade an egg to start life over with them. The method still succeeds only rarely, and even a successful clone differs from its original in small but real ways.
Reproductive Cloning Versus Other Kinds of Cloning
Scientists use the word cloning for three different jobs: copying genes, copying whole animals, and making stem cells.1Genome.gov. Cloning Fact Sheet Gene cloning copies a single gene or stretch of DNA by placing it inside a carrier that a host cell, often a bacterium, copies over and over.2Advancements in Genetic Engineering. Brief Note on Reproductive and Therapeutic Cloning Therapeutic cloning creates stem cells matched to a patient, aimed at growing tissue to replace damaged or diseased tissue.3Genome.gov. Cloning Fact Sheet Reproductive cloning is the only kind meant to produce a living, whole organism.4Advancements in Genetic Engineering. Brief Note on Reproductive and Therapeutic Cloning It shares many lab steps with therapeutic cloning, but therapeutic cloning stops at early cells and never makes a pregnancy.5Genome.gov. Cloning Fact Sheet Gene cloning happens daily in labs and is how bacteria are put to work making medicines like insulin.
Nature made clones first. Identical twins form when one early embryo splits in two. For more than 40 years, labs copied that by hand-splitting a two-cell embryo into two separate embryos.6Advancements in Genetic Engineering. Brief Note on Reproductive and Therapeutic Cloning But splitting only copies an embryo that already exists. With an adult you already know its traits, like milk yield or temperament, while an embryo’s future traits are a guess until it grows up. That is why copying adults became the goal of reproductive cloning.
How a Clone Is Made Step by Step
The method used today moves the nucleus, the DNA-holding core, of an ordinary body cell into an egg.7PubMed Central. Somatic cell nuclear transfer: origins, the present position and future opportunities First the egg’s own chromosomes are removed, leaving an empty egg that still holds all its other machinery.8PubMed Central. Somatic cell nuclear transfer: origins, the present position and future opportunities
The egg is essential because its interior contains signals that can reset an adult nucleus. That is why cloning still needs donated eggs, which are often scarce.
Next comes the donor’s DNA. The donor nucleus usually comes from a cell grown in the lab, such as a skin-type cell.9PubMed. Comparison of electro-fusion and intracytoplasmic nuclear injection methods in pig cloning It can be delivered by fusing the whole donor cell to the egg with a brief electric pulse, or by injecting the nucleus with a fine needle.10PubMed. Comparison of electro-fusion and intracytoplasmic nuclear injection methods in pig cloning
A lab-grown donor cell is convenient for several reasons. Cells grown in a dish can be multiplied into many identical copies, so one small tissue sample can be used many times. A small skin sample is enough to start a culture, so the donor does not have to be harmed. And cells can be frozen, so an animal can be cloned years later, even after it has died, as long as living cells were preserved.
Then the egg has to be tricked into starting development. Normally sperm triggers an egg to start dividing, so in cloning the egg must be activated artificially.11PubMed. Activation of bovine somatic cell nuclear transfer embryos by PLCZ cRNA injection Labs use chemicals that raise calcium levels inside the egg, mimicking the signal sperm gives.12PubMed. Activation of bovine somatic cell nuclear transfer embryos by PLCZ cRNA injection In cattle, swapping one standard chemical for strontium raised the share of embryos developing properly from about 14% to about 35%.13Zygote. Use of strontium in the activation of bovine oocytes reconstructed by somatic cell nuclear transfer
After activation, the embryo spends several days in a lab incubator while it divides into a ball of cells. Technicians check which embryos have developed normally and choose those to transfer, because many stall along the way. The chosen embryos are placed in a surrogate mother at a stage her body can accept, and she is monitored to see whether the pregnancy takes hold.
The surrogate is a mother of the same or a related species. If the pregnancy holds, the newborn carries the donor animal’s nuclear DNA, not the surrogate’s. So three animals are involved in one clone: one donates the body cell and its genetic blueprint, a second donates the egg, and a third carries the pregnancy. The clone resembles only the first.
Is a Clone an Exact Copy
Cells also carry a small separate set of DNA inside mitochondria, the cell’s energy units. A cloned embryo gets its main DNA from the donor cell but its mitochondrial DNA from the egg.14Merck Veterinary Manual. Cloning of Domestic Animals – Reproductive System – Merck Veterinary Manual A few donor mitochondria may survive, but they are vastly outnumbered by the egg’s.15Merck Veterinary Manual. Cloning of Domestic Animals – Reproductive System – Merck Veterinary Manual In ten cloned sheep, the mitochondrial DNA came entirely from the eggs, with none detected from the donors.16PubMed Central. Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep Each clone is therefore technically a genetic blend of two animals.17PubMed Central. Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep
That blend is small. Mitochondrial DNA is tiny compared with the main genome and mostly affects energy production, not appearance.
Even so, a clone can look or act differently. Diet, upbringing and experience shape behavior, as with identical twins, and the womb environment of a different surrogate also matters.
Looks are not guaranteed either. Coat patterns such as the spots on a cow or the patches on a cat depend partly on random events as cells migrate and switch genes in the embryo. Tortoiseshell and calico cats are a well-known example, because which color gene is active in each patch of skin is settled by chance. A cloned pet may share the donor’s overall build and coloring genes yet have noticeably different markings.
Why Most Cloning Attempts Fail
Adult DNA carries chemical tags that switch genes on or off for that cell’s job. For a clone to develop, the egg must strip and rebuild those tags as in a fertilized embryo.18PubMed Central. Epigenetic Reprogramming During Somatic Cell Nuclear Transfer: Recent Progress and Future Directions In clones this rebuilding is delayed and incomplete, leaving key development genes wrongly switched.19PubMed Central. Epigenetic Reprogramming During Somatic Cell Nuclear Transfer: Recent Progress and Future Directions Some tags also get added back too much, a barrier that blocks full-term development in mouse clones.20PubMed. Inhibition of Aberrant DNA Re-methylation Improves Post-implantation Development of Somatic Cell Nuclear Transfer Embryos Blocking that excess tagging and adding enzymes that remove other tags greatly improved how many mouse clones survived to birth.21PubMed. Inhibition of Aberrant DNA Re-methylation Improves Post-implantation Development of Somatic Cell Nuclear Transfer Embryos
Pregnancies often fail at the placenta. In cattle, most losses come from early embryo death, failure to implant, or a defective placenta.22UC Davis. Cow Gene Study Shows Why Most Clones Fail Misread genes in the tissue that forms the placenta appear to drive these early losses.23UC Davis. Cow Gene Study Shows Why Most Clones Fail In one cattle study, 82% of cloned fetuses died between days 30 and 90 of pregnancy, while all normal pregnancies survived.24PubMed. Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses
Problems continue at and after birth. Cloned calves and lambs can develop an overgrowth condition.25PubMed. Large offspring syndrome in ruminants: current status and prediction during pregnancy Affected newborns can be oversized with enlarged organs and abdominal wall defects, and struggle to stand and suckle.26PubMed. Large offspring syndrome in ruminants: current status and prediction during pregnancy Births are often hard and frequently need a Caesarean section for the surrogate.27Compassion in World Farming. Farm Animal Cloning Clones also face high illness and death rates in the first days of life.28PubMed Central. Benefits and problems with cloning animals
Some clones show signs of the donor’s age. At age 3, Dolly the sheep had protective chromosome tips much shorter than those of other 3-year-old sheep.29PubMed Central. Extranuclear Inheritance of Mitochondrial Genome and Epigenetic Reprogrammability of Chromosomal Telomeres in Somatic Cell Cloning of Mammals Her length matched her 6-year-old donor, suggesting her cells carried some of the donor’s age.30PubMed Central. Extranuclear Inheritance of Mitochondrial Genome and Epigenetic Reprogrammability of Chromosomal Telomeres in Somatic Cell Cloning of Mammals This led to claims that all clones age early, but it was one finding in one famous animal. It shows cloning can carry over traces of the donor’s age, not a fixed rule.
How Cloning Developed From Frogs to Monkeys
John Gurdon moved nuclei from frog intestine cells into emptied eggs and got normal tadpoles and fertile adult frogs.31PubMed Central. The persistence of potential: The life of Sir John B. Gurdon This proved specialized cells keep all the genetic instructions needed to build a whole animal.32PubMed Central. The persistence of potential: The life of Sir John B. Gurdon
Frogs came first because their eggs are large and develop outside the mother’s body, so researchers could see and handle them with simple tools. Mammal eggs are far smaller and must develop inside a mother, which made the same experiments much harder.
Before Dolly, every cloned mammal came from embryo cells, which was easier but limited what could be copied.33Revive & Restore. What Is Reproductive Cloning and How Does It Work? In 1995 two lambs, Megan and Morag, were cloned from cultured lab-grown cells.34PubMed. Nuclear equivalence, nuclear transfer, and the cell cycle Dolly, born in 1996 and announced in 1997, was the first mammal cloned from an adult body cell.35PubMed. Nuclear equivalence, nuclear transfer, and the cell cycle Monkeys were later cloned the same way, bringing the method to primates.36PubMed. Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer
What Cloning Is Used for Today
Cloning is used commercially in some countries to copy elite breeding animals, mostly cattle.37Compassion in World Farming Report. Farm Animal Cloning An outstanding bull or cow may have excellent traits such as milk yield, but normal breeding shuffles genes so offspring only partly inherit them. A clone carries nearly the same nuclear DNA, so breeders can produce more animals with that genetic makeup. This is useful mainly for an animal whose value is already proven. Breeders also copy prize-winning show cattle.38PubMed. Agro-economic impact of cattle cloning
Clones are mainly breeding stock, not food; their normally bred offspring become the food animals.39U.S. Food and Drug Administration. A Primer on Cloning and Its Use in Livestock Operations So meat or milk usually comes from clones’ offspring, not clones, which are too costly to slaughter.
If cells were saved from a valuable animal, a clone can bring its genetics back even after it has died. The same idea drives the pet cloning business, where owners pay to copy a pet whose cells were preserved.
About a quarter of mammal species are threatened with extinction, so cloning could help preserve some.40PubMed. The perspective of the incompatible of nucleus and mitochondria in interspecies somatic cell nuclear transfer for endangered species Because wild eggs are scarce, scientists can put an endangered animal’s nucleus into an egg from a related species.41PubMed. The perspective of the incompatible of nucleus and mitochondria in interspecies somatic cell nuclear transfer for endangered species A gaur, a wild ox with fewer than 100 animals in breeding programs, was cloned this way using domestic cow eggs and developed normally into late pregnancy.42PubMed. Cloning of an endangered species (Bos gaurus) using interspecies nuclear transfer
Is Human Reproductive Cloning Allowed
International consensus rejects human reproductive cloning.43PubMed Central. Legal, ethical and moral dilemma of human cloning: the conflict between technological progress and human dignity The 2005 UN declaration calling for a ban passed narrowly and is not binding.44PubMed Central. Legal, ethical and moral dilemma of human cloning: the conflict between technological progress and human dignity The narrow vote reflected disagreement over whether to ban therapeutic cloning too. The real rules come from national laws, which differ widely, from criminal bans, as in Germany, to the UK’s approach of allowing regulated therapeutic research while banning reproductive cloning.45PubMed Central. Legal, ethical and moral dilemma of human cloning: the conflict between technological progress and human dignity
Expert panels have called human reproductive cloning dangerous and likely to fail, given the animal failure rates.46American Journal of Law & Medicine. Protecting the Endangered Human: Toward an International Treaty Prohibiting Cloning and Inheritable Alterations In animals, most cloned embryos never become a live birth, so in humans each failed pregnancy would involve a woman, with risks to her health. Animal clones also include sick newborns, which would mean children born with serious problems.