Frogs are cloned from specialised cells

Professor Sir John Gurdon, now at The Gurdon Institute at Cambridge University, began his scientific career at the University of Oxford by repeating an experiment that he thought had potential for further analysis. The experiment by Robert Briggs and Thomas King suggested that the development of specialised cells was a one-way process that begins in the early stages of an embryo’s development. Briggs and King were the first to perform cloning by nuclear transfer using eggs and cells from the Northern Leopard Frog, Rana pipiens.

Although these experiments were successful when Briggs and King used unspecialised cells, they found that they could not make cloned frogs when they used more specialised cells. This observation led to the belief that the DNA in specialised cells was ‘fixed’ and could not be used to produce a new organism. In 1958, Gurdon showed otherwise by making clones using specialised cells from the intestines of tadpoles of a different species (Xenopus laevis). Gurdon’s results surprised the scientific community and stirred talk of the possibility of cloning other animals, including humans.

Gurdon used the technique of nuclear transfer to remove the DNA from a tadpole’s intestinal cell and place it into an egg cell. Contrary to Briggs and King’s results, these cells gave rise to adult frogs. To assist with these experiments, he used ultraviolet light to destroy the egg cell’s original DNA and to make the egg cell’s membrane easier to penetrate. Gurdon also developed a specialised pipette fitted with a hypodermic tip to be used for nuclear transfer. The small pipette could safely penetrate the egg and insert the intestinal cell DNA without damaging the delicate egg cell. While his tadpoles matured to fully functioning adult frogs at the time, subsequent experiments trying to clone frogs using fully adult cells only produced tadpoles that did not mature. However, his results and improved methods inspired researchers at The Roslin Institute to use nuclear transfer to clone sheep and produce Dolly the Sheep, the first animal to be cloned from an adult cell.

Together, Gurdon’s and the Dolly team’s successes introduced the concept of reprogramming the DNA of specialized cells to be able to make new organisms or new stem cells. This led to the development of therapeutic cloning as a source for genetically matching replacement cells for patients with degenerative diseases. However, therapeutic cloning depends on the availability of human eggs, which are in very limited supply. As a result, the need to be able to directly reprogram adult cells developed. In 2006, Shinya Yamanaka and Kazutoshi Takahashi successfully reprogrammed specialised cells into induced pluripotent (iPS) cells. In 2012, Professor Gurdon and Shinya Yamanaka were awarded the Nobel Prize in Physiology or Medicine for their work in discovering how cells can be reprogrammed.

Access the paper [Nature – journal subscription may be required]

Professor Gurdon discusses his cloning work [Nature Medicine – journal subscription required]
Written by Paige Atkins