Instruct: Given a question, retrieve documents that can help answer the question.
Query: When were embryonic stem cells first used in research?
1981: Embryonic stem cells (ES cells) were independently first derived from mouse embryos by two groups. Martin Evans and Matthew Kaufman from the Department of Genetics, University of Cambridge published first in July, revealing a new technique for culturing the mouse embryos in the uterus to allow for an increase in cell number, allowing for the derivation of ES cells from these embryos.[43] Gail R. Martin, from the Department of Anatomy, University of California, San Francisco, published her paper in December and coined the term “Embryonic Stem Cell”.[44] She showed that embryos could be cultured in vitro and that ES cells could be derived from these embryos. 1989: Mario R. Cappechi, Martin J. Evans, and Oliver Smithies publish their research which details their isolation and genetic modifications of embryonic stem cells, creating the first "knockout mice".[45] In creating knockout mice, this publication provided scientists with an entirely new way to study disease. 1998: A paper titled "Embryonic Stem Cell Lines Derived From Human Blastocysts" is published by a team from the University of Wisconsin, Madison. The researchers behind this study not only create the first embryonic stem cells, but recognize their pluripotency, as well as their capacity for self-renewal. The abstract of the paper notes the significance of the discovery with regards to the fields of developmental biology and drug discovery.[46] 2001: President George W. Bush allows federal funding to support research on roughly 60—at this time, already existing—lines of embryonic stem cells. Seeing as the limited lines that Bush allowed research on had already been established, this law supported embryonic stem cell research without raising any ethical questions that could arise with the creation of new lines under federal budget.[47] 2006: Japanese scientists Shinya Yamanaka and Kazutoshi Takashi publish a paper describing the induction of pluripotent stem cells from cultures of adult mouse fibroblasts. Induced pluripotent stem cells (iPSCs) are a huge discovery, as they are seemingly identical to embryonic stem cells and could be used without sparking the same moral controversy.[48] January, 2009: The US Food and Drug Administration (FDA) provides approval for Geron Corporation's phase I trial of their human embryonic stem cell-derived treatment for spinal cord injuries. The announcement was met with excitement from the scientific community, but also with wariness from stem cell opposers. The treatment cells were, however, derived from the cell lines approved under George W. Bush's ESC policy.[49] March, 2009: Executive Order 13505 is signed by President Barack Obama, removing the restrictions put in place on federal funding for human stem cells by the previous presidential administration. This would allow the National Institutes of Health (NIH) to provide funding for hESC research. The document also states that the NIH must provide revised federal funding guidelines within 120 days of the order's signing.[50]
In the past, it has been a necessity to research embryonic stem cells and in doing so destroy them for research to progress. As a result of the research done with both embryonic and adult stem cells, new techniques may make the necessity for embryonic cell research obsolete. Because many of the restrictions placed on stem cell research have been based on moral dilemmas surrounding the use of embryonic cells, there will likely be rapid advancement in the field as the techniques that created those issues are becoming less of a necessity. Many funding and research restrictions on embryonic cell research will not impact research on IPSCs (induced pluripotent stem cells) allowing for a promising portion of the field of research to continue relatively unhindered by the ethical issues of embryonic research.
WiCell serves as home to the Wisconsin International Stem Cell Bank. This stem cell repository stores, characterizes and provides access to stem cell lines for use in research and clinical development. The cell bank originally stored the first five human Embryonic stem cell lines derived by Dr. James Thomson of UW–Madison. It currently houses human embryonic stem cell lines, induced pluripotent stem cell lines, clinical grade cell lines developed in accordance with Good Manufacturing Practices (GMP) and differentiated cell lines including neural progenitor cells.
His lab in the Terrence Donnelly Centre for Cellular and Biomolecular Research, carries out various neuroscience and developmental biology research projects. In 1994 his paper on neural stem cells in the adult mammalian forebrain was published in the journal "Neuron". This work first established that adult mammalian neural stem cells were located in the subependyma of the forebrain lateral ventricle, where two types of lineage related precursor cells, progenitor cells and stem cells, were shown to be present. Proliferation of these cell types were characterized in further experiments that were reported in articles in "Development" and the "Journal of Neuroscience". Of note, Derek's lab produced the first report of stem cells in the adult mammalian eye, published in 2000 in "Science". Further work, which was published in the journal, "Neuron", 2001, documented how embryonic stem cells were shown to differentiate directly to neural stem cells through a default mechanism. Derek's lab continues to investigate the nature of stem cells, embryonic and adult, the concept of immortal cells, and the differentiation of embryonic stem cells, capable of forming any tissue in the body, to neural stem cells.
1993 - As per the National Institutes of Health Revitalization Act, Congress and President Bill Clinton give the NIH direct authority to fund human embryo research for the first time.[28] 1995 - The U.S. Congress passes an appropriations bill attached to which is a rider, the Dickey–Wicker Amendment which prohibited federally appropriated funds to be used for research where human embryos would be either created or destroyed. President Clinton signs the bill into law. This predates the creation of the first human embryonic stem cell lines. 1999 - After the creation of the first human embryonic stem cell lines in 1998 by James Thomson of the University of Wisconsin, Harriet Rabb, the top lawyer at the Department of Health and Human Services, releases a legal opinion that would set the course for Clinton Administration policy. Federal funds, obviously, could not be used to derive stem cell lines (because derivation involves embryo destruction). However, she concludes that because human embryonic stem cells "are not a human embryo within the statutory definition," the Dickey-Wicker Amendment does not apply to them. The NIH was therefore free to give federal funding to experiments involving the cells themselves. President Clinton strongly endorses the new guidelines, noting that human embryonic stem cell research promised "potentially staggering benefits." And with the guidelines in place, the NIH begins accepting grant proposals from scientists.[28] 2001–2006 - On August 9, 2001, U.S. President George W. Bush signs an executive order which restricts federally funded stem cell research on embryonic stem cells to the already derived cell lines. He supports federal funding for embryonic stem cell research on the already existing lines of approximately $100 million, $250 million for research on adult and animal stem cells, and creates the President's Council on Bioethics led by Dr. Leon Kass of the University of Chicago to "monitor stem cell research, to recommend appropriate guidelines and regulations, and to consider all of the medical and ethical ramifications of biomedical innovation." 2 November 2004 - California voters approve Proposition 71, which provides $3 billion in state funds over ten years to human embryonic stem cell research. 5 May 2006 - Senator Rick Santorum introduces bill number S. 2754, or the Alternative Pluripotent Stem Cell Therapies Enhancement Act, into the U.S. Senate. 18 July 2006 - The U.S. Senate passes the Stem Cell Research Enhancement Act H.R. 810 and votes down Senator Santorum's S. 2754. 19 July 2006 - President George W. Bush vetoes House Resolution 810 Stem Cell Research Enhancement Act, a bill that would have reversed the Dickey–Wicker Amendment which made it illegal for federal money to be used for research where stem cells are derived from the destruction of an embryo. 7 November 2006 - The people of the U.S. state of Missouri passed Amendment 2, which allows usage of any stem cell research and therapy allowed under federal law, but prohibits human reproductive cloning.[29] 16 February 2007 – The California Institute for Regenerative Medicine became the biggest financial backer of human embryonic stem cell research in the United States when they awarded nearly $45 million in research grants.[30] 4 November 2008 - The people of the U.S. state of Michigan passed Proposal 08-2, allowing Michigan researchers to make embryonic stem cell cultures from excess embryos donated from fertility treatments.[31] 23 January 2009 - The United States Food and Drug Administration approves clinical trials for human embryonic stem cell therapy.[32] 9 March 2009 - President Barack Obama signs an executive order reversing federal opposition to embryonic Stem Cell research.[33] August 2010 - Judge Royce Lamberth of the U.S. District Court for the District of Columbia issued a temporary injunction blocking the federal government from implementing the current NIH guidelines "...ruling that experiments with such cells fall under an "unambiguous" 1996 law by Congress that prohibits federal funding of research that destroys human embryos." This new injunction would not block new funding but it would also interfere with the research allowed under the Bush administration[34] April 2011 - See Dickey-Wicker Amendment, "In the 2-1 opinion of April 29, 2011, the appeals panel said that the Dickey-Wicker Amendment was "ambiguous" and that the National Institutes of Health had "reasonably concluded" that although federal funds could not be used to directly destroy an embryo, the amendment does not prohibit funding a research project using embryonic stem cells. This is an important distinction under the law, because for federal funds to be used directly to support the destruction of embryos."
2008 "GOP" Presidential Candidate John McCain was a member of The Republican Main Street Partnership, and supported embryonic stem cell research,[5] despite his earlier opposition.[21] In July 2008 he said, "At the moment I support stem cell research [because of] the potential it has for curing some of the most terrible diseases that afflict mankind."[22] In 2007, in what he described as "a very agonizing and tough decision," he voted to allow research using human embryos left over from fertility treatments.[23] Former First Lady Nancy Reagan and Senator Orrin Hatch also support stem cell research, after first opposing the issue.[5] Former Senator Frist also supports stem cell research, despite having initially supported past restrictions on embryonic stem cell research. 2008 V.P. candidate Palin opposed embryonic stem cell research, which she said causes the destruction of life, thus this research is inconsistent with her pro-life position and she does not support it.[24] She said, in an interview with Charlie Gibson, that she supports adult stem cell research approaches.[25]
On July 24, 2009, the first publication of a successful breakthrough in Stem cell research was released, where Chinese researchers from the Shanghai Stem Cell Institute, led by Professor Fanyi Zeng, successfully reprogrammed adult stem cells to be able to differentiate into any body cell, as in the case with standard embryonic stem cells, the cells in question known as "induced pluripotent stem cells" (IPS cells). The IPS cells were obtained by genetically reprogramming the skin cells of mice to acts like embryonic stem cells, which then were able to differentiate into all forms of body tissue. The researchers have managed to use the IPS cells to create every type of cell in a mouse, creating entire mouse pups using the technique. This is the first time the technique has been used to make an entire mouse.
The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells.[66] It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.[67]
The discovery of adult stem cells led scientists to develop an interest in the role of embryonic stem cells, and in separate studies in 1981 Gail Martin and Martin Evans derived pluripotent stem cells from the embryos of mice for the first time. This paved the way for Mario Capecchi, Martin Evans, and Oliver Smithies to create the first knockout mouse, ushering in a whole new era of research on human disease. In 1995 adult stem cell research with human use, patented (US PTO with effect from 1995). In fact human use published in World J Surg 1991 & 1999 (B G Matapurkar). Salhan, Sudha (August 2011). Textbook of Gynecology. JP Medical Ltd. pp. 625–. .
Bharadwaj, Aditya; Glasner, Peter E. (2009). Local Cells, Global Science: The Rise of Embryonic Stem Cell Research in India. Taylor & Francis. 
^ "Dr.B.G.Matapurkar gets US patent for surgical procedure for organ regeneration - Patents". www.pharmabiz.com.
^ "Method of organogenesis and tissue regeneration/repair using surgical techniques - US Patent 6227202 Claims". patentstorm.us.
In May 2005, the House of Representatives voted 238–194 to loosen the limitations on federally funded embryonic stem-cell research – by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors – despite Bush's promise to veto the bill if passed. On July 29, 2005, Senate Majority Leader William H. Frist (R-TN), announced that he too favored loosening restrictions on federal funding of embryonic stem cell research. On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill (the Stem Cell Research Enhancement Act) 63–37, which would have made it legal for the federal government to spend federal money on embryonic stem cell research that uses embryos left over from "in vitro" fertilization procedures. On July 19, 2006 President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.
There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009.[20] However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research. On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs.[21] ES cells, being pluripotent cells, require specific signals for correct differentiation—if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[22] Due to ethical considerations, many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.[23]
Terra Incognita: The Perils and Promise of Stem Cell Research, also known as Terra Incognita: Mapping Stem Cell Research, is a documentary film released by Kartemquin Films in 2007. The film follows Dr. Jack Kessler of Northwestern University in his search for a cure for spinal cord injuries using embryonic stem cells. When Kessler was invited to head up the Neurology Department at Northwestern, his focus was on using stem cells to help cure diabetes. However, soon after his move to Chicago, his daughter Allison – then age 15, was injured in a skiing accident and paralyzed from the waist down. In the moments following the accident, Dr. Kessler made the decision to change the focus of his research to begin looking for a cure for spinal cord injuries using embryonic stem cells. 
There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections. There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.
The National Academies called for the establishment of Embryonic Stem Cell Research Oversight (ESCRO) Committees in its 2005 "Guidelines for Human Embryonic Stem Cell Research" to manage the ethical and legal concerns in human embryonic stem cell research. Because of the complexity and novelty of many of the issues involved in that research, the Guidelines committee believes that all research institutions engaged in human embryonic stem cell research should create and maintain these committees at the local level.
In May 2005, the House of Representatives voted 238-194 to loosen the limitations on federally funded embryonic stem-cell research — by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors — despite Bush's promise to veto if passed. On July 29, 2005, Senate Majority Leader William H. Frist (R-TN), announced that he too favored loosening restrictions on federal funding of embryonic stem cell research.[6] On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill, 63-37, which would have made it legal for the Federal government to spend Federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures. On July 19, 2006 President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.
In October 2008, the governing body of the university announced that UCC would be the first institution in Ireland to use embryonic stem cells in research under strict guidelines of the University Research Ethics using imported hESCs from approved jurisdictions. In 2009, Professor of Mathematics at UCC, Des McHale, challenged the University's decision to allow embryonic stem cell research. According to the results of a poll conducted by irishhealth.com, almost two in three people supported the decision made by University College Cork to allow embryonic stem cell research.
The First Presidency of The Church of Jesus Christ of Latter-day Saints "has not taken a position regarding the use of embryonic stem cells for research purposes. The absence of a position should not be interpreted as support for or opposition to any other statement made by Church members, whether they are for or against embryonic stem cell research.”
In 2005, the United States National Academies released its Guidelines for Human Embryonic Stem Cell Research. These Guidelines were prepared to enhance the integrity of human embryonic stem cell research in the public's perception and in actuality by encouraging responsible practices in the conduct of that research. The National Academies has subsequently named the Human Embryonic Stem Cell Research Advisory Committee to keep the Guidelines up-to-date.[26]
Adult stem cells have provided many different therapies for illnesses such as Parkinson's disease, leukemia, multiple sclerosis, lupus, sickle-cell anemia, and heart damage (to date, embryonic stem cells have also been used in treatment), Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors. Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.
Pro-life supporters often claim that the use of adult stem cells from sources such as the umbilical cord blood has consistently produced more promising results than the use of embryonic stem cells. Furthermore, adult stem cell research may be able to make greater advances if less money and resources were channeled into embryonic stem cell research. Stem cell research is highly frowned upon in many ethnic and religious groups.
Stem cell debates have motivated and reinvigorated the pro-life movement, whose members are concerned with the rights and status of the embryo as an early-aged human life. They believe that embryonic stem cell research profits from and violates the sanctity of life and is tantamount to murder. The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell. The view of those in favor is that these embryos would otherwise be discarded, and if used as stem cells, they can survive as a part of a living human being.
Dovery et al. (2010) used HDAC knockout mice to demonstrate whether HDAC1 or HDAC2 was important for the embryonic stem cell differentiation. Examination of global histone acetylation in the absence of HDAC 1 showed an increase in acetylation. Global histone acetylation levels were unchanged by the loss of HDAC2. In order to analyze the process of HDAC knockout mouse in detail, the knockout mice embryonic stem cells were used to generate embryoid bodies. It showed that just before or during gastrulation, embryonic stem cells lacking HDAC1 acquired visible developmental defects. The continued culture of HDAC1 knockout embryonic stem cells showed that the embryoid bodies formed became irregular and reduced in size rather than uniformly spherical as in normal mice. Embryonic stem cell proliferation was unaffected by the loss of either HDAC1 or HDAC2 but the differentiation of embryonic stem cells were affected with that lack of HDAC 1. This shows that HDAC1 is required for cell fate determination during differentiation.
President Bush supported adult stem cell research and umbilical cord blood stem cell research. However, Bush opposed any new embryonic stem cell research, and had limited the federal funding of existing research. Federal funding for embryonic stem cell research was first approved under President Clinton on January 19, 1999, but no money was to be spent until the guidelines were published. The guidelines were released under Clinton on August 23, 2000. They allowed use of unused frozen embryos. On August 9, 2001, before any funding was granted under these guidelines, Bush announced modifications to the guidelines to allow use of only existing stem cell lines. While Bush claimed that more than 60 embryonic stem cell lines already existed from privately funded research, scientists in 2003 said there were only 11 usable lines, and in 2005 that all lines approved for Federal funding are contaminated and unusable. Adult stem cell funding was not restricted and was supported by President Bush as a more viable means of research.
Hescheler has been working with embryonic stem cells ever since the late 1980s. Beginning with studies on cellular signal transduction, and starting with works on signalling pathways in different cells (g-protein phosphorylation, electrophysiology of channels) he focussed on embryonic stem cells and has since defined many important basic aspects of both fundamental research and clinical applications. He was the first scientist worldwide to perform electrophysiological and functional experiments on stem cells and differentiated phenotypes thereof. He achieved a first functional characterization of cardiomyocytes developed from embryonic stem cells which is an important prerequisite for their subsequent use in regenerative medicine. He thus pioneered the establishment of stem cell research for application in transplantation medicine. In 2002, he was among the first scientists in Germany to obtain permission to work with human embryonic stem cells. In his current position, as Chairman and Director to the Institute for Neurophysiology at the University of Cologne, his research areas include work on embryonic and adult stem cells, induced pluripotent stem cells, mesenchymal stem cells and germline pluripotent stem cells. Among progressing the use of stem cells for translational purposes, aiming at tapping the potential of stem cell biology towards clinical application, Hescheler actively promotes the vision of EPAA through innovative alternative testing strategies, applying stem cells towards toxicity testing. Apart from the rationale of promoting 3R principles it is his goal that coordinating a multidisciplinary research effort undertaken by various projects and consortia led by Hescheler will generate pathway- and evidence-based understanding of long-term toxic effects, thus moving toxicology from a rather descriptive science towards a more mechanistic-driven predictive one. 
Hescheler has been appointed coordinator of various European Consortia such as FunGenES, CRYSTAL, and more recently ESNATS and DETECTIVE. He is also coordinator of the BMBF consortium “iPS and adult bone marrow cells for cardiac repair”. In 2004 he founded and since chaired the German Society of Stem Cell Research (GSZ). He is an active member of the Scientific Panel of the AXLR8 Consortium and a member of steering committee of Stem Cell Network North Rhine Westphalia.
Black was an advocate for research using stem cells to repair damage from such conditions as cancer and Alzheimer's disease and his own research showed that the technique could be used to encourage the body's own stem cells to create needed new cells and as a form of gene therapy. Studies he performed in 2000 that were published in the "Journal of Neuroscience Research" showed that when an antioxidant was added to stem cells extracted from bone marrow, the undifferentiated stem cells transformed into cells with the characteristics of neurons within minutes and were successfully transplanted into the brains and spinal cords of rats. The results were called "an incredible achievement" in opening the path to creating treatments for conditions that had been previously untreatable by using stem cells to create needed cells of different forms. Black's approach was to use neurons developed from the individual's own adult stem cells to avoid issues of transplant rejection without requiring modifications to the genome, while avoiding the ethical concerns raised with the use of embryonic stem cells.