Embryo Project Encyclopedia Articles

Human pluripotent stem cells are valued for their potential to form numerous specialized cells and for their longevity. In the US, where a portion of the population is opposed to destruction of human embryos to obtain stem cells, what avenues are open to scientists for obtaining pluripotent cells that do not offend the moral sensibilities of a significant number of citizens? It is this question that the official position paper, or white paper, "Alternative Sources of Human Pluripotent Stem Cells," published in May 2005 by the President's Council on Bioethics under the chairmanship of Leon Kass, seeks to answer. Three experts external to the council, Andrew Fire from the Stanford University School of Medicine, Markus Grompe of the Oregon Health and Science University, and Janet Rossant from the Samuel Lunenfeld Research Institute in Toronto, also reviewed the white paper prior to publication.

The Human Genome Project (HGP) was an international scientific effort to sequence the entire human genome, that is, to produce a map of the base pairs of DNA in the human chromosomes, most of which do not vary among individuals. The HGP started in the US in 1990 as a public effort and included scientists and laboratories located in France, Germany, Japan, China, and the United Kingdom. Scientists hypothesized that mapping and sequencing the human genome would facilitate better theories of human development, the genetic causes and predispositions for a number of diseases, and individualized medicine. The HGP, alongside the private effort taken up by the company Celera Genomics, released a working draft of the human genome in 2001 and a complete sequence in 2003. The history of the HGP ripples beyond biomedical science and technology into the social, economic, and political.

The Spemann-Mangold organizer, also known as the Spemann organizer, is a cluster of cells in the developing embryo of an amphibian that induces development of the central nervous system. Hilde Mangold was a PhD candidate who conducted the organizer experiment in 1921 under the direction of her graduate advisor, Hans Spemann, at the University of Freiburg in Freiburg, German. The discovery of the Spemann-Mangold organizer introduced the concept of induction in embryonic development. Now integral to the field of developmental biology, induction is the process by which the identity of certain cells influences the developmental fate of surrounding cells. Spemann received the Nobel Prize in Medicine in 1935 for his work in describing the process of induction in amphibians. The Spemann-Mangold organizer drew the attention of embryologists, and it spurred numerous experiments on the nature of induction in many types of developing embryos.

Clomiphene citrate, more commonly known by its brand names Clomid and Serophene, is a medication prescribed to women to stimulate ovulation in order to treat infertility. It stimulates ovulation in women who do not ovulate or ovulate irregularly. This drug was created by Dr. Frank Palopoli in 1956 while he worked for Merrell Company. It first successfully induced ovulation in women in 1961 and was approved by the Federal and Drug Administration (FDA) in 1967. This medication can be used to help women conceive naturally, to time ovulation for intrauterine insemination, or to stimulate the maturation of eggs to be extracted and used in procedures such as in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian transfer (ZIFT).

Assisted reproductive technologies (ART) are a collection of different techniques designed to help those who are infertile achieve a successful pregnancy. The most popular technology currently in use is in vitro fertilization (IVF), but others include gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), intrauterine insemination (IUI), and intracytoplasmic sperm injection (ICSI). Although not encompassed under the umbrella term of ART, there are also various hormonal medications that can induce ovulation such as clomiphene citrate that can either be used alone to help women conceive, or used in conjunction with the above techniques. Infertility is a problem that has affected people throughout history, but it was only in the last half of the twentieth century that medical research developed technologies to help those who are infertile become pregnant.

On 9 August 2001, US President George W. Bush gave an eleven-minute speech from his ranch in Crawford, Texas, on the ethics and fate of federal funding for stem cell research. Bush also announced the creation of a special council to oversee stem cell research. In the speech President Bush acknowledged the importance of issues surrounding stem cell research to many Americans, presented different arguments in favor of and opposing embryonic stem cell research, and explained his decision to limit but not completely eliminate potential federal funding for embryonic stem cell (ESC) research. The speech was important to embryology as a field because it determined the US government's policy on funding human ESC research for the eight years of George W. Bush's administration.

Induced pluripotent stem cells (iPSCs) are studied carefully by scientists not just because they are a potential source of stem cells that circumvents ethical controversy involved with experimentation on human embryos, but also because of their unique potential to advance the field of regenerative medicine. First generated in a lab by Kazutoshi Takahashi and Shinya Yamanaka in 2006, iPSCs have the ability to differentiate into cells of all types. If scientists discover how to induce differentiated cells to return to a pluripotent state using a method that leaves the iPSCs safe for transplantation, then patients could receive stem cell transplants with cells containing their own DNA. This would presumably remove the danger of transplant rejection that comes with foreign cell transplantation.

Shinya Yamanaka gained international prominence after publishing articles detailing the successful generation of induced pluripotent stem (iPS) cells, first in mice, then in humans. Yamanaka induced somatic cells to act like human embryonic stem cells (hESCs), allowing researchers to experiment with non-embryonic stem cells with a similar capacity as hESCs. The research involving iPS cells therefore offered new potential for research and application in medical treatment, without many of the ethical objections that hESC research entailed.

In the July 2007 issue of Nature, Keisuke Okita, Tomoko Ichisaka, and Shinya Yamanaka added to the new work on induced pluripotent stem cells (iPSCs) with their "Generation of Germline-Competent Induced Pluripotent Stem Cells" (henceforth abbreviated "Generation"). The authors begin the paper by noting their desire to find a method for inducing somatic cells of patients to return to a pluripotent state, a state from which the cell can differentiate into any type of tissue but cannot form an entire organism. If this is made possible, the authors claim, the ethical controversy surrounding the use of embryonic stem cells (ES cells) and the dangers of patient rejection of donated ES cells could be bypassed completely.

In November 2007, Masato Nakagawa, along with a number of other researchers including Kazutoshi Takahashi, Keisuke Okita, and Shinya Yamanaka, published "Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts" (abbreviated "Generation") in Nature. In "Generation," the authors point to dedifferentiation of somatic cells as an avenue for generating pluripotent stem cells useful for treating specific patients and diseases. They provide background to their research by observing that previous attempts to reprogram somatic cells to a state of greater differentiability with retroviral factors Oct3/4, Sox2, c-Myc, and Klf4 had succeeded in producing induced pluripotent stem (iPS) cells that contributed to viable adult chimeras and possessed germline competency. However, as they note, the c-Myc retrovirus contributes to tumors in generated chimeras, rendering iPS cells produced with c-Myc useless for clinical applications. The authors attempt to overcome this problem by modifying the standard protocol for producing iPS cells in mice in such a way that the c-Myc retrovirus is removed. They identify problems and benefits associated with this method, but most importantly note that their method generated iPS cells that did not cause tumors in chimeric mice. Nakagawa and colleagues also report that they successfully reprogrammed adult dermal fibroblasts to return to a pluripotent state without c-Myc.