Dolly

/dol"ee/, n.

a female given name, form of Doll.

Also, Dollie.

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▪ cloned sheep

 female Finn Dorset sheep that lived from 1996 to 2003, the first successfully cloned mammal, produced by Scottish geneticist Ian Wilmut and colleagues of the Roslin Institute, near Edinburgh. The announcement in February 1997 of the world's first clone of an adult animal was a milestone in science, dispelling decades of presumption that adult mammals could not be cloned and igniting a debate concerning the many possible uses and misuses of mammalian cloning technology.

      The concept of mammalian clones, even humans, was not completely new. Naturally occurring genetic clones, or individuals genetically identical to one another, had long been recognized in the form of monozygotic (identical) twins (twin). Unlike Dolly, however, such clones are derived, as their scientific name indicates, from a single zygote, or fertilized egg. Moreover, clones had been generated previously in the laboratory, but only from embryonic cells (cell) or from the adult cells of plants (plant) and “lower” animals (animal) such as frogs (frog). Decades of attempts to clone mammals from existing adults had met with repeated failure, which led to the presumption that something special and irreversible must happen to the DNA of mammalian cells during the animal's development. Indeed, until 1997 it had been generally accepted dogma that adult mammalian cells are no longer genetically totipotent, or capable of giving rise to all of the different cell and tissue types (e.g., liver, brain, and bone) required for making a complete and viable animal. It was presumed that somatic-cell differentiation, the process by which a single fertilized egg is converted into all of the different cell types found in an adult, involved some irreversible, likely epigenetic (epigenetics) step. That Dolly remained alive and well long after her birth—that she had a functional heart, liver, brain, and other organs, all derived genetically from the nuclear DNA of an adult mammary-gland (mammary gland) cell—proved otherwise. At the very minimum, the specific tissue from which Dolly's nuclear DNA was derived must have been totipotent. By extension, it was reasonable to suggest that the nuclear DNA of other adult tissues also remains totipotent. With the successful creation of Dolly, this speculation became a testable hypothesis.

 Dolly did not spring from the laboratory bench fully formed but developed to term normally in the uterus of a Scottish Blackface Ewe. Although Dolly's nuclear genome was derived from a mammary-gland cell taken from an adult Finn Dorset ewe, that nucleus had to be fused by electrical pulses with an unfertilized egg cell, the nucleus of which had been removed. The “host” egg cytoplasm was taken from a Scottish Blackface ewe, and later another Scottish Blackface ewe served as the surrogate mother. Furthermore, in order for the mammary gland cell nucleus and genomic DNA to be accepted and functional within the context of the host egg, the donor cell first had to be induced to abandon the normal cycle of growth and division and enter a quiescent stage. To do this, researchers deliberately withheld nutrients from the cells. The importance of this step had been determined experimentally, and although a number of hypotheses had been raised to explain its necessity, which, if any, of them was correct remained unclear. Nevertheless, starting with a collection of donor cell nuclei and host egg cytoplasms, a number of fused couplets successfully formed embryos (embryo); these were transferred to surrogate ewes. Of 13 recipient ewes, one became pregnant, and 148 days later, which is essentially normal gestation for a sheep, Dolly was born.

      On Feb. 14, 2003, Dolly was euthanized by veterinarians after being found to suffer from progressive lung disease. Her body was preserved and displayed at the National Museum of Scotland in Edinburgh.

Judith Fridovich-Keil

 

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