cloning

cloning, the process of generating a genetically identical copy of a cell or an organism. Cloning happens often in nature—for example, when a cell replicates itself asexually without any genetic alteration or recombination. Prokaryotic organisms (organisms lacking a cell nucleus) such as bacteria create genetically identical duplicates of themselves using binary fission or budding. In eukaryotic organisms (organisms possessing a cell nucleus) such as humans, all the cells that undergo mitosis, such as skin cells and cells lining the gastrointestinal tract, are clones; the only exceptions are gametes (eggs and sperm), which undergo meiosis and genetic recombination.

In biomedical research, cloning is broadly defined to mean the duplication of any kind of biological material for scientific study, such as a piece of DNA or an individual cell. For example, segments of DNA are replicated exponentially by a process known as polymerase chain reaction, or PCR, a technique that is used widely in basic biological research. The type of cloning that is the focus of much ethical controversy involves the generation of cloned embryos, particularly those of humans, which are genetically identical to the organisms from which they are derived, and the subsequent use of these embryos for research, therapeutic, or reproductive purposes.

Early cloning experiments

Reproductive cloning was originally carried out by artificial “twinning,” or embryo splitting, which was first performed on a salamander embryo in the early 1900s by German embryologist Hans Spemann. Later, Spemann, who was awarded the Nobel Prize for Physiology or Medicine (1935) for his research on embryonic development, theorized about another cloning procedure known as nuclear transfer. This procedure was performed in 1952 by American scientists Robert W. Briggs and Thomas J. King, who used DNA from embryonic cells of the frog Rana pipiens to generate cloned tadpoles. In 1958 British biologist John Bertrand Gurdon successfully carried out nuclear transfer using DNA from adult intestinal cells of African clawed frogs (Xenopus laevis). Gurdon was awarded a share of the 2012 Nobel Prize in Physiology or Medicine for this breakthrough.

Advancements in the field of molecular biology led to the development of techniques that allowed scientists to manipulate cells and to detect chemical markers that signal changes within cells. With the advent of recombinant DNA technology in the 1970s, it became possible for scientists to create transgenic clones—clones with genomes containing pieces of DNA from other organisms. Beginning in the 1980s mammals such as sheep were cloned from early and partially differentiated embryonic cells. In 1996 British developmental biologist Ian Wilmut generated a cloned sheep, named Dolly, by means of nuclear transfer involving an enucleated embryo and a differentiated cell nucleus. This technique, which was later refined and became known as somatic cell nuclear transfer (SCNT), represented an extraordinary advance in the science of cloning, because it resulted in the creation of a genetically identical clone of an already grown sheep. It also indicated that it was possible for the DNA in differentiated somatic (body) cells to revert to an undifferentiated embryonic stage, thereby reestablishing pluripotency—the potential of an embryonic cell to grow into any one of the numerous different types of mature body cells that make up a complete organism. The realization that the DNA of somatic cells could be reprogrammed to a pluripotent state significantly impacted research into therapeutic cloning and the development of stem cell therapies.

Soon after the generation of Dolly, a number of other animals were cloned by SCNT, including pigs, goats, rats, mice, dogs, horses, and mules. Despite those successes, the birth of a viable SCNT primate clone would not come to fruition until 2018, and scientists used other cloning processes in the meantime. In 2001 a team of scientists cloned a rhesus monkey through a process called embryonic cell nuclear transfer, which is similar to SCNT except that it uses DNA from an undifferentiated embryo. In 2007 macaque monkey embryos were cloned by SCNT, but those clones lived only to the blastocyst stage of embryonic development. It was more than 10 years later, after improvements to SCNT had been made, that scientists announced the live birth of two clones of the crab-eating macaque (Macaca fascicularis), the first primate clones using the SCNT process. (SCNT has been carried out with very limited success in humans, in part because of problems with human egg cells resulting from the mother’s age and environmental factors.)