Megan and Morag

Megan and Morag were two sheep produced at the Roslin Institute near Edinburgh, Scotland, in 1995. They are significant in the history of animal cloning because they were the first mammals successfully cloned from differentiated cells. Their creation preceded the better-known birth of Dolly the sheep by approximately one year and demonstrated that cells which had developed beyond an embryonic state could still provide the nuclear genetic material needed to produce a viable animal. The work was undertaken by researchers seeking a more reliable method for altering the genetic constitution of sheep and cattle. At the time, genetic modification by pronuclear microinjection was comparatively inefficient: introduced DNA integrated into the genome only in a small proportion of cases, and the location of integration could produce unpredictable patterns of gene expression. The Roslin team investigated a combined strategy involving cultured sheep cells and nuclear transfer. The researchers initially hoped to use immortalized, undifferentiated embryonic stem-cell lines, but they were unable to establish the required sheep cell lines. They therefore used cultured cells derived from blastocysts. The nucleus from a cultured donor cell was transferred into an unfertilized sheep oocyte whose own nucleus had been removed. Electrical stimulation was used both to fuse the donor cell with the enucleated egg and to initiate embryonic development. The donor cells were placed in a quiescent state to make their cellular condition more compatible with the recipient egg. The experiment involved 244 nuclear-transfer attempts. Thirty-four embryos developed sufficiently to be transferred into surrogate mothers, and five lambs were born in the summer of 1995. Two survived to adulthood: the animals later named Megan and Morag. They were initially identified by laboratory designations 5LL2 and 5LL5 and became healthy, fertile adults. Their survival provided evidence that nuclear transfer from cultured differentiated cells could produce viable and reproductively capable sheep. Megan and Morag were not a conventional consumer or corporate brand. The name refers to the two research animals and, by extension, to a landmark in biotechnology. Their scientific importance lies in establishing a method that helped make subsequent cloning advances possible, including the production of Dolly. They are distinct from Dolly, the first animal cloned from an adult somatic cell, and from Polly, a cloned and transgenic sheep. The achievement initially attracted less public attention than Dolly's later birth, although Megan was reported as still alive in 2005 and was then regarded as the oldest cloned animal.

The Roslin Institute's cloning program was motivated by the limitations of conventional genetic modification in livestock. Pronuclear microinjection could introduce DNA into fertilized eggs, but integration was uncommon and the resulting expression of the inserted material could vary substantially because integration occurred at unpredictable genomic locations. Researchers therefore explored nuclear transfer as a possible route to combine cultured cells with embryo production. The original plan involved creating useful sheep embryonic stem-cell lines. When the team could not establish immortalized, undifferentiated sheep embryonic stem cells, it changed direction and worked with cells cultured from blastocysts. Nuclear transfer involved removing the nucleus from an unfertilized sheep egg and replacing it with the nucleus of a cultured donor cell. Electrical pulses fused the cells and activated development. The donor cells were made quiescent before transfer, a condition intended to improve coordination between the donor nucleus and the recipient egg. In 1995, the team performed 244 nuclear-transfer procedures. Thirty-four resulting embryos reached the stage at which they could be placed in surrogate sheep. Five lambs were born during the summer. Two, identified in the laboratory as 5LL2 and 5LL5 and later named Megan and Morag, survived and matured into healthy fertile adults. Their birth showed that a viable mammal could be produced using nuclear material from cultured differentiated cells rather than only from an early embryonic cell. This result was a technical precursor to the cloning of Dolly, also performed at the Roslin Institute. Megan and Morag were born about a year before Dolly and demonstrated a core principle that underpinned the later experiment. The animals are sometimes confused with Dolly or Polly, but their scientific distinctions are different: Dolly was the first animal cloned from an adult somatic cell, while Polly was a cloned sheep carrying an introduced transgene. Megan and Morag were the first mammals successfully cloned from differentiated cells. The achievement received comparatively limited immediate public attention. Its significance became clearer as the Roslin program produced further cloning and transgenic-animal results. Megan was reported to remain alive in 2005, when she was described as the oldest cloned animal known at that time. Because the subject concerns named research animals rather than a marketed product or operating company, conventional information such as headquarters, ownership, revenue, executives, and commercial markets does not apply.

• 2005

  Megan reported as the oldest cloned animal

  [1]Megan and Moragen.wikipedia.org

  Megan was reported to still be alive and was described at the time as the oldest cloned animal.

• 1996

  Technical foundation for Dolly

  [1]Megan and Moragen.wikipedia.org

  The earlier result helped establish the nuclear-transfer approach later used in the Roslin Institute's production of Dolly.

• 1995

  Megan and Morag are born

  [1]Megan and Moragen.wikipedia.org

  Five lambs were born after nuclear-transfer experiments at the Roslin Institute; two survived to adulthood and were later named Megan and Morag.

• 1995

  First mammals cloned from differentiated cells

  [1]Megan and Moragen.wikipedia.org

  The two sheep demonstrated that cultured differentiated cells could provide nuclear material capable of producing viable, fertile mammals.

Not a commercial brand; Megan and Morag identify two landmark research animals associated with the development of mammalian nuclear-transfer cloning.

1. 1Megan and Moragen.wikipedia.org