Nuclear Transplantation

By Sean Cohmer
Published: 2011-06-14
Keywords: Nuclear transplantation
Nuclear Transplantation

Nuclear transplantation is a method in which the nucleus of a donor cell is relocated to a target cell that has had its nucleus removed (enucleated). Nuclear transplantation has allowed experimental embryologists to manipulate the development of an organism and to study the potential of the nucleus to direct development. Nuclear transplantation, as it was first called, was later referred to as somatic nuclear transfer or cloning.

Yves Delage first wrote about nuclear transplantation in 1895, speculating that if one were to replace an egg nucleus with another egg’s nucleus, full development would occur. Later in 1938, Hans Spemann suggested an experiment whereby, using technologies not yet available to him, one could remove the nucleus of an egg and replace it with a different nucleus extracted from a developed cell. Thomas King and Robert Briggs were the first to perform experimental nuclear transplantation. The technique was soon after used by John Gurdon and eventually led to the first clone of a mammal, “Dolly” the sheep, by Ian Wilmut in 1996.

Nearly fifteen years after Spemann wrote about the possibility of nuclear transplantation, Briggs and King, using northern leopard frogs (Rana pipiens), performed the first nuclear transplantation experiment. They transplanted the nucleus from an early stage embryo to an unfertilized egg that had been enucleated. The egg cell was pricked with a clean glass needle in order to induce a fertilization-like response. The faux activation of fertilization allowed for extraction of the nuclear material inside while also activating the host egg cell. Meanwhile, the nucleus of a donor cell was extracted and then inserted into the newly enucleated and activated egg cell. That process induced development of the host egg according to the instructions of the newly inserted nucleus, resulting in the formation of an organism with the same genetic material as the donor cell, or a clone.

Briggs and King continued to examine the potential of differentiated cells throughout the 1950s. They found that if the donor nucleus was extracted later in development, the potential of directing full development in the activated egg cell was greatly reduced. After the Briggs and King experiments it was generally accepted that the nuclear material in developing cells slowly loses its potential for full development.

That view was challenged in 1958 when Gurdon's experiments with African claws frogs (Xenopus laevis) produced fully developed frogs from the transferred nucleus of cells much later in development. Gurdon allowed the cloned frogs to develop to sexual maturity and was then able to mate two sexually mature clones, suggesting that the donor nuclei were able to fully redirect development. Gurdon’s experiments were widely accepted by the scientific community but questions remained for several decades. Scientists were concerned about whether the nucleus of the host egg cell was truly enucleated. The question of whether remnants of the host egg cell or the inserted nucleus directed development remained unanswered from 1958 to 2002, despite many attempts by Gurdon to prove it was the inserted nucleus.

In 2002, however, Konrad Hochedlinger and Rudolf Jaenisch published an experiment using nuclear transplantation of mature white blood cells to generate mouse clones. Hochedlinger and Jaenisch were able to show that the inserted nucleus induced development in the host egg cell.

Although experimental embryologists continued to use nuclear transplantation to create clones of several species, Ian Wilmut’s cloning experiment in 1996 was a controversial and widely publicized cloning experiment. Dolly was cloned using the nucleus of a mammary gland cell from an adult sheep and transplanting it into an enucleated egg cell from another sheep. The activated egg cell was then transferred into a third surrogate sheep that carried Dolly to term. Dolly died at the age of to six due to lung disease and severe arthritis, and although her death was not attributed to the fact that she was a clone, many believe that the relationship between telomeres and aging was the reason for her demise.

Nuclear transplantation may have begun as a subtle idea in the late 19th and early 20th centuries, but it evolved into a feasible and widely used process by experimental embryologists in the late 1990s. The cloning of Dolly the sheep worried many about the possibility of human cloning and the moral boundaries of modern advances in science. In the context of the embryonic stem cell discourse of the late 1990s and early twenty-first century, somatic nuclear transfer has been contrived into moral arguments about rights of the human embryo. Furthermore, nuclear transplantation has spurred ethical discussion on the value of a human life during all stages of development. Many scientists have abandoned the methods involved in nuclear transplantation and have adopted methods set forth by Shinya Yamanaka in his experiments involving induced pluripotent stem cells.

Sources

  1. Beetschen, Jean-Claude C., and Jean-Louis L. Fischer. "Yves Delage (1854–1920) as a Forerunner of Modern Nuclear Transfer Experiments." International Journal of Developmental Biology 48 (2004): 607–12.
  2. Briggs, Robert, and Thomas J. King. "Transplantation of Living Nuclei from Blastula Cells into Enucleated Frogs Eggs." Proceedings of the National Academy of Sciences of the United States of America 38 (1952): 455–63.
  3. Di Berardino, Maria A., and Robert G. McKinnell. "The Pathway to Animal Cloning and Beyond - Robert Briggs (1911–1983) and Thomas J. King (1921–2000)." Journal of Experimental Zoology Part a-Comparative Experimental Biology 301A (2004): 275–9.
  4. Gilbert, Scott F. Developmental Biology 8th ed. Sunderland, MA: Sinauer, 2006.
  5. Gurdon, John B. "Nuclear Reprogramming in Eggs." Nature Medicine 15 (2009): 1141–44.
  6. Gurdon, John B., Tom R. Elsdale, and Michael Fischberg. "Sexually Mature Individuals of Xenopus-Laevis from the Transplantation of Single Somatic Nuclei." Nature 182 (1958): 64–5.
  7. Hochedlinger, Konrad, and Rudolf Jaenisch. "Monoclonal Mice Generated by Nuclear Transfer from Mature B and T Donor Cells." Nature 415 (2002): 1035–8.
  8. Spemann, Hans, and Hilde Mangold. "The Induction of Embryonic Predispositions by Implantation of Organizers Foreign to the Species." Archiv Fur Mikroskopische Anatomie Und Entwicklungsmechanik 100 (1924): 599–638.
  9. Wilmut, Ian, Angelika E. Schnieke, Jim McWhir, Alex J. Kind, and Keith H. Campbell. "Viable Offspring Derived from Fetal and Adult Mammalian Cells." Nature 385 (1997): 810–3.

How to cite

Cohmer, Sean, "Nuclear Transplantation". Embryo Project Encyclopedia (2011-06-14). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/1758.

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Publisher

Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia.

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© Arizona Board of Regents Licensed as Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported (CC BY-NC-SA 3.0) http://creativecommons.org/licenses/by-nc-sa/3.0/

Last modified

Wednesday, September 25, 2013 - 15:53

Topic

Processes

Subject

Cell nuclei--Transplantation; Concept