Embryo Project Encyclopedia

Leonard Hayflick in the US during the early 1960s showed that normal populations of embryonic cells divide a finite number of times. He published his results as 'The Limited In Vitro Lifetime of Human Diploid Cell Strains' in 1964. Hayflick performed the experiment with WI-38 fetal lung cells, named after the Wistar Institute, in Philadelphia, Pennsylvania, where Hayflick worked. Frank MacFarlane Burnet, later called the limit in capacity for cellular division the Hayflick Limit in 1974. In the experiment, Hayflick refuted Alexis Carrel's hypothesis that cells could be transplanted and multiplied indefinitely from a single parent cell line.

Experiments conducted by Elizabeth Blackburn, Carol Greider, and Jack Szostak from 1982 to 1989 provided theories of how the ends of chromosomes, called telomeres, and the enzyme that repairs telomeres, called telomerase, worked. The experiments took place at the Sidney Farber Cancer Institute and at Harvard Medical School in Boston, Massachusetts, and at the University of California in Berkeley, California. For their research on telomeres and telomerase, Blackburn, Greider, and Szostak received the Nobel Prize in Physiology or Medicine in 2009. Telomeres and telomerase affect the lifespan of mammalian cells and ensure that cells rapidly develop within developing embryos.

In the 1990s, researchers working at the Roslin Institute in Edinburgh, Scotland, performed cloning experiments in collaboration with PPL Therapeutics in Roslin, Scotland, on human coagulation factor IX, a protein. The team of scientists used the methods identified during the Dolly experiments to produce transgenic livestock capable of producing milk containing human blood clotting factor IX, which helps to treat a type of hemophilia. By using a cell's resting state, called quiescence, or G0, and transferring modified nuclear material from one cell to an egg cell that had had its nuclear material removed, the researchers developed a method to produce genetically modified mammals, including humans. Angelika E. Schnieke, Alexander J. Kind, William A. Ritchie, Karen Mycock, Angela R. Scott, Marjorie Ritchie, Ian Wilmut, Alan Colman, and Keith H. S. Campbell published the results of their experiments as Human Factor IX Transgenic Sheep Produced by Transfer of Nuclei from Transfected Fetal Fibroblasts (hereafter called Human Factor IX). The article details the methods that produced the cloned sheep named Polly, as well as other cloned and genetically altered sheep.

In the 1990s, Ian Wilmut, Jim McWhir, and Keith Campbell performed experiments while working at the Roslin Institute in Roslin, Scotland. Wilmut, McWhir, and Campbell collaborated with Angelica Schnieke and Alex J. Kind at PPL Therapeutics in Roslin, a company researching cloning and genetic manipulation for livestock. Their experiments resulted in several sheep being born in July 1996, one of which was a sheep named Dolly born 5 July 1996. Dolly was the first sheep cloned and developed from the nuclei of fully differentiated adult cells, rather than from the nuclei of early embryonic cells. They published their results in Viable Offspring Derived from Fetal and Adult Mammalian Cells (abbreviated Viable Offspring) on 27 February 1997.

In 1995 and 1996, researchers at the Roslin Institute in Edinburgh, Scotland, cloned mammals for the first time. Keith Campbell, Jim McWhir, William Ritchie, and Ian Wilmut cloned two sheep, Megan and Morag, using sheep embryo cells. The experiments indicated how to reprogram nuclei from differentiated cells to produce live offspring, and that a single population of differentiated cells could produce multiple offspring. They reported their results in the article 'Sheep Cloned by Nuclear Transfer from a Cultured Cell Line' in March 1996. This experiment led the Roslin team to later clone mammals from adult body cells and to genetically engineer mammals.

In 2006, Kazutoshi Takahashi and Shinya Yamanaka reprogrammed mice fibroblast cells, which can produce only other fibroblast cells, to become pluripotent stem cells, which have the capacity to produce many different types of cells. Takahashi and Yamanaka also experimented with human cell cultures in 2007. Each worked at Kyoto University in Kyoto, Japan. They called the pluripotent stem cells that they produced induced pluripotent stem cells (iPSCs) because they had induced the adult cells, called differentiated cells, to become pluripotent stem cells through genetic manipulation. Yamanaka received the Nobel Prize in Physiology or Medicine in 2012, along with John Gurdon, as their work showed scientists how to reprogram mature cells to become pluripotent. Takahashi and Yamanaka's 2006 and 2007 experiments showed that scientists can prompt adult body cells to dedifferentiate, or lose specialized characteristics, and behave similarly to embryonic stem cells (ESCs).