The Hayflick Limit is a concept that helps to explain the
mechanisms behind cellular aging. The concept states that a normal human
cell can only replicate and divide forty to sixty times before it
cannot divide anymore, and will break down by programmed cell death
or apoptosis. The concept of the Hayflick Limit revised Alexis
Carrel's earlier theory, which stated that cells can replicate
themselves infinitely. Leonard Hayflick developed the concept while
at the Wistar Institute in Philadelphia,
Pennsylvania, in 1965. In his 1974 book Intrinsic
Mutagenesis, Frank Macfarlane Burnet named the concept after
Hayflick. The concept of the Hayflick Limit helped scientists study
the effects of cellular aging on human populations from embryonic
development to death, including the discovery of the effects of
shortening repetitive sequences of DNA, called telomeres, on the
ends of chromosomes. Elizabeth Blackburn, Jack Szostak and Carol
Greider received the Nobel Prize in Physiology or Medicine in 2009
for their work on genetic structures related to the Hayflick
Limit.

When cells-but not DNA-from two or more genetically distinct individuals combine to form a new individual, the result is called a chimera. Though chimeras occasionally occur in nature, scientists have produced chimeras in a laboratory setting since the 1960s. During the creation of a chimera, the DNA molecules do not exchange genetic material (recombine), unlike in sexual reproduction or in hybrid organisms, which result from genetic material exchanged between two different species. A chimera instead contains discrete cell populations with two unique sets of parental genes. Chimeras can occur when two independent organisms fuse at a cellular level to form one organism, or when a population of cells is transferred from one organism to another. Chimeras created in laboratories have helped scientists to identify developmental mechanisms and processes across species. Some experiments involving chimeras aim to provide further knowledge of immune reactions against disease or to create animal models to understand human disease.

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 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.

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 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).

Keith Henry Stockman Campbell studied embryo growth and cell differentiation during the twentieth and twenty-first centuries in the UK. In 1995, Campbell and his scientific team used cells grown and differentiated in a laboratory to clone sheep for the first time. They named these two sheep Megan and Morag. Campbell and his team also cloned a sheep from adult cells in 1996, which they named Dolly. Dolly was the first mammal cloned from specialized adult (somatic) cells with the technique of somatic cell nuclear transfer (SCNT). Campbell helped develop cloning techniques that used a common form of connective tissue cells (fibroblasts). Besides working at the Roslin Institute, in Edinburgh, Scotland, for most of his career, Campbell also taught at the University of Nottingham in Nottingham, England.

The Roslin Institute was established in 1993 in the village of Roslin, Scotland, as an independent research center by the Biotechnology and Biological Sciences Research Council (BBSRC), and as of 2014 is part of the University of Edinburgh in Edinburgh, Scotland. Researchers at the Roslin Institute cloned the Dolly the sheep in 1996. According to the Roslin Institute, Dolly was the first mammal to develop into an adult from the transfer of the nucleus of an adult sheep cell into an ovum with the nucleus removed. The Roslin Institute performs genetic and medical based animal studies to help investigate human physiology and medicine and to improve agricultural research. The Roslin Institute studies embryology, cloning, hormones, and genetic alterations in animals and techniques such as Somatic Cell Nuclear Transfer (SCNT).

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.

Researchers in the twentieth and twenty-first centuries identify the study of the intrinsic and external factors that influence human aging as senescence. A commonly held belief in the year 2015 is that at least some kinds of cells can replicate over long periods or even indefinitely, thereby meaning the cell does not undergo senescence (also known as replicative senescence) and is considered immortal. This study aims to provide information to answer the following question: While some scientists claim they can indefinitely culture a stem cell line in vitro, what are the consequences of those culturing practices? An analysis of a cluster of articles from the Embryo Project Encyclopedia provides information to suggest possible solutions to some potential problems in cell culturing, recognition of benefits for existing or historical culturing practices, and identification of gaps in scientific knowledge that warrant further research. Recent research suggests that hESCs, and immortalized cell lines in general, do not escape the effects of senescence. While there exists a constant change in the practices of cell culturing, a large portion of scientists still rely on practices established before modern senescence research: research that seems to suggest that cultured hESCs, among other immortal cell lines, are not truly immortal.