On 20 November 2009 Democrat Barack Obama replaced Republican George W. Bush as president of the United States. Obama soon initiated changes to Bush's 2001 executive order concerning scientific research involving human stem cells. Stem cell research remains a controversial issue in the US. Some individuals consider it immoral to experiment with an embryo because they regard embryos as human beings from the moment of conception, while others believe stem cell research could lead to great scientific advancements. Congress has not passed any legislation on stem cell research, leaving it open to the president to make policy through executive orders. On 9 March 2009, Obama signed Executive Order 13505 to expand experimentation on stem cells. This overturned Executive Order 13435, which was signed by George W. Bush to limit the potential research that could be done on embryonic stem cells.
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.
When James Thomson of the University of Wisconsin announced in 1998 that he had derived and cultured human embryonic stem cells(hESCs), Americans widely believed-and accepted-that stem cells would one day be the basis of a multitude of regenerative medical techniques. Researchers promised that they would soon be able to cure a variety of diseases and injuries such as cancer, diabetes, Parkinson's, spinal cord injuries, severe burns, and many others. But it wasn't until January 2009 that the Food and Drug Administration approved the first human clinical trials using hESCs. The trials were put on hold in August of 2009 before they were ever begun. After more than a decade of being promised curative stem cell therapy, many people have been unwilling to wait for American doctors to provide stem cell treatments. Some people have opted not to wait or rely on other treatments, and have chosen to receive stem cell therapy from international institutions. This phenomenon has been dubbed stem cell tourism, and it has garnered much media attention, both in support and in opposition.
Michael D. West is a biomedical entrepreneur and investigator whose aim has been to extend human longevity with biomedical interventions. His focus has ranged from the development of telomerase-based therapeutics to the application of human embryonic stem cells in regenerative medicine. Throughout his eventful career, West has pursued novel and sometimes provocative ideas in a fervent, self-publicizing manner. As of 2009, West advocated using human somatic cell nuclear transfer techniques to derive human embryonic stem cells for therapeutic practice. Through his testimonies before the US Senate, articles, and even controversies generated by his own research and claims, West has played an important role in shaping the public debate over human cloning and embryonic stem cell research.
James Edgar Till is a biophysicist known for establishing the existence of stem cells along with Ernest McCulloch in 1963. Stem cells are undifferentiated cells that can shift, or differentiate, into specialized types of cells and serve as a repair system in the body by dividing indefinitely to replenish other cells. Till’s work with stem cells in bone marrow, which produces the body’s blood cells, helped form the field of modern hematology, a medical discipline that focuses on diseases related to the blood. He also worked on issues in the medical field including patient inclusion in clinical trials, matters of effective and ineffective clinical communication, and limitations of public access to medical and scientific research. Till’s work with stem cells furthered scientists’ understanding of abnormal blood cell development, which helped set the foundation for regenerative medicine.
John D. Gearhart is a renowned American developmental geneticist best known for leading the Johns Hopkins University research team that first identified and isolated human pluripotent stem cells from human primordial germ cells, the precursors of fully differentiated germ cells. Born in Western Pennsylvania, Gearhart lived on the family farm located in the Allegheny Mountains for the first six years of his life. After his coal-miner father died, Gearhart' s mother and younger brother stayed on the farm while he and his older brother were sent to Girard College, an all-male school for orphans located in inner city Philadelphia, Pennsylvania. Gearhart remained at the college, where he was a mediocre student, for the next ten years-1950 to 1960-while receiving his first through twelfth-grade education. After completing secondary school, he entered Pennsylvania State University, pursuing a Bachelor of Science in Biological Science with dreams of becoming the world's best pomologist.
On 20 January 2001, Republican George W. Bush was sworn in as the forty-third president of the United States, replacing Democrat William J. Clinton. During his eight years in office, Bush issued many executive orders, often altering previous policy. By signing Order 13435 on 22 June 2007, he changed how stem cell research would be performed in America. The Bush administration was influenced by its commitments to conservative ethical values when constructing this executive order; its goal was to expand stem cell research, but only in ways that did not involve the creation of, or damage to, a human embryo or fetus. This order was developed with the belief that pluripotent stem cells could be researched while still being respectful to human dignity and life. The four sections of Order 13435 provided strict guidelines for future stem cell research.
On 2 December 2007, Science published a report on creating human induced pluripotent stem (iPS) cells from human somatic cells: "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells." This report came from a team of Madison, Wisconsin scientists: Junying Yu, Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L. Frane, Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, and James A. Thomson. Earlier that year Shinya Yamanaka at Kyoto University, Japan published a similar paper,"Generation of Germline-Competent Induced Pluripotent Stem Cells," in Nature. Both papers independently identified four genes used to reprogram human somatic cells to pluripotent stem cells, which are cells that have the ability to develop into any specialized cell type making up the body. The reprogrammed somatic cells were referred to as iPS cells and they exhibit fundamental qualities of human embryonic stem (ES) cells.
The discovery of hematopoietic stem cells (HSCs) provided a pioneering step in stem cell research. HSCs are a type of multipotent adult stem cell, characterized by their ability to self-renew and differentiate into erythrocyte (red blood cell) and leukocyte (white blood cell) cell lineages. In terms of function, these cells are responsible for the continual renewal of the erythrocytes, leukocytes, and platelets in the body through a process called hematopoiesis. They also play an important role in the formation of vital organs such as the liver and spleen during fetal development. The early biological knowledge obtained from the studies of HSCs established the base of knowledge for understanding other stem cell systems. In addition, these cells have a vital role in furthering stem cell research for clinical applications. Regenerative medicine is a field of medicine that has applied HSCs to the treatment of blood-borne diseases such as leukemia and lymphoma and of cancer patients undergoing chemotherapy.
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.