Instruct: Given a question, retrieve relevant passages that can help answer the question.
Query: When were embryonic stem cells first used in 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.
Embryo transfer can be done at day two or day three, or later in the blastocyst stage, which was first performed in 1984.
The first transfer of an embryo from one human to another resulting in pregnancy was reported in July 1983 and subsequently led to the announcement of the first human birth 3 February 1984. This procedure was performed at the Harbor UCLA Medical Center under the direction of Dr. John Buster and the University of California at Los Angeles School of Medicine.
John Edmond Buster (born July 18, 1941) working at the University of California at Los Angeles School of Medicine, directed the research team that performed history's first embryo transfer from one woman to another resulting in a live birth. It was performed at the Harbor-UCLA Medical Center, reported in July 1983, and culminated in the announcement of the first human birth February 3, 1984. In the procedure, an embryo that was just beginning to develop was transferred from the woman in whom it had been conceived by artificial insemination to another woman who gave birth to the infant 38 weeks later. The sperm used in the artificial insemination came from the husband of the woman who bore the baby.
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.
With the cloning of a sheep known as Dolly in 1996 by somatic cell nuclear transfer (SCNT), the idea of human cloning became a hot debate topic. Many nations outlawed it, while a few scientists promised to make a clone within the next few years. The first hybrid human clone was created in November 1998, by Advanced Cell Technology. It was created using SCNT - a nucleus was taken from a man's leg cell and inserted into a cow's egg from which the nucleus had been removed, and the hybrid cell was cultured, and developed into an embryo. The embryo was destroyed after 12 days.
Adult stem cells are found in juvenile or adult tissues. Adult stem cells are multipotent: they can generate a limited number of differentiated cell types (unlike pluripotent embryonic stem cells). Types of adult stem cells include hematopoietic stem cells and mesenchymal stem cells. Hematopoetic stem cells are found in the bone marrow and generate all cells of the immune system all blood cell types. Mesenchymal stem cells are found in umbilical cord blood, amniotic fluid, and adipose tissue and can generate a number of cell types, including osteoblasts, chondrocytes, and adipocytes. In medicine, adult stem cells are mostly commonly used in bone marrow transplants to treat many bone and blood cancers as well as some autoimmune diseases. (See Hematopoietic stem cell transplantation)
The cells were first observed by Karl Wilhelm von Kupffer in 1876. The scientist called them "Sternzellen" (star cells or hepatic stellate cell) but thought, inaccurately, that they were an integral part of the endothelium of the liver blood vessels and that they originated from it. In 1898, after several years of research, Tadeusz Browicz identified them, correctly, as macrophages.
In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see induced pluripotent stem cells)—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.
Discoveries in recent years have suggested that adult stem cells might have the ability to differentiate into cell types from different germ layers. For instance, neural stem cells from the brain, which are derived from ectoderm, can differentiate into ectoderm, mesoderm, and endoderm. Stem cells from the bone marrow, which is derived from mesoderm, can differentiate into liver, lung, GI tract and skin, which are derived from endoderm and mesoderm. This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured "in vitro" or transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity. More recent findings suggest that pluripotent stem cells may reside in blood and adult tissues in a dormant state. These cells are referred to as "Blastomere Like Stem Cells" and "very small embryonic like" – "VSEL" stem cells, and display pluripotency in vitro. As BLSC's and VSEL cells are present in virtually all adult tissues, including lung, brain, kidneys, muscles, and pancreas Co-purification of BLSC's and VSEL cells with other populations of adult stem cells may explain the apparent pluripotency of adult stem cell populations. However, recent studies have shown that both human and murine VSEL cells lack stem cell characteristics and are not pluripotent.
The first ever pregnancy derived from a frozen human embryo was reported by Alan Trounson & Linda Mohr in 1983 (although the fetus aborted spontaneously at ten weeks of gestation); the first term pregnancy derived from a frozen embryo was born in 1984. Since then and up to 2008 it is estimated that between 350,000 and half a million IVF babies have been born from embryos frozen at a controlled rate and then stored in liquid nitrogen; additionally a few hundred births have been born from vitrified oocytes but firm figures are hard to come by. It may be noted that Subash Mukhopadyay from Kolkata, India reported the successful cryopreservation of an eight cell embryo, storing it for 53 days, thawing and replacing it into the mother’s womb, resulting in a successful and live birth as early as 1978- a full five years before Trounson and Mohr had done so. A small publication of Mukherjee in 1978 clearly shows that Mukherjee was on the right line of thinking much before anyone else had demonstrated the successful outcome of a pregnancy following the transfer of a 8-cell frozen-thawed embryo into human subjects transferring 8-cell cryopreserved embryos." (Current Science, Vol .72. No. 7, 10 April 1997)
Later artificial cells have ranged from hundred-micrometer to nanometer dimensions and can carry microorganisms, vaccines, genes, drugs, hormones and peptides. The first clinical use of artificial cells was in hemoperfusion by the encapsulation of activated charcoal.
Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells (from Greek Σωματικóς, meaning "of the body"), they can be found in juvenile as well as adult animals and humans, unlike embryonic stem cells.
The composition of ESCRO committees was specified to include representatives of the public and people with expertise in developmental biology, stem cell research, molecular biology, assisted reproduction, and ethical and legal issues in human embryonic stem cell research.
The earliest study of endocrinology began in China. The Chinese were isolating sex and pituitary hormones from human urine and using them for medicinal purposes by 200 BCE. They used many complex methods, such as sublimation of steroid hormones. Another method specified by Chinese texts—the earliest dating to 1110—specified the use of saponin (from the beans of "Gleditsia sinensis") to extract hormones, but gypsum (containing calcium sulfate) was also known to have been used.
Direct Frozen Embryo Transfer: Embryos can be frozen by SPF in ethylene glycol freeze media and transfer directly to recipients immediately after water thawing without laboratory thawing process. The world's first crossbred bovine embryo transfer calf under tropical conditions was produced by such technique on 23 June 1996 by Dr. Binoy S Vettical of Kerala Livestock Development Board, Mattupatti
Gene therapy is the use of DNA as a pharmaceutical agent to treat disease. Gene therapy was first conceptualized in 1972, with the authors urging caution before commencing gene therapy studies in humans. The first FDA-approved gene therapy experiment in the United States occurred in 1990, on a four-year-old girl named, Ashanti DeSilva, she was treated for ADA-SCID. This is a disease that had left her defenseless against infections spreading throughout her body. Dr. W French Anderson was a major lead on this clinical trial, he worked for the National Heart, Lung, and Blood Institute Since then, over 1,700 clinical trials have been conducted using a number of techniques for gene therapy.
Cell, developmental, and reproductive biology have been a central part of the MBL's programs since the 1890s. Important discoveries in these fields at the MBL reach back to 1899, when Jacques Loeb demonstrated artificial parthenogenesis in sea urchin eggs; to 1905, when Edwin Grant Conklin first identified egg cytoplasmic regions that are programmed to form certain tissues or organs; to 1916, when Frank Rattray Lillie identified circulating hormones that influence sexual differentiation (Lillie, 1944). In the MBL's first two decades, cytologists Edmund Beecher Wilson, Nettie Stevens and others made connections between the chromosomes and Mendelian heredity, while Wilson's colleague at both the MBL and Columbia University, Thomas Hunt Morgan, launched the field of experimental genetics (Pauly, 2000:158). Keith R. Porter, considered by many to be a founder of modern cell biology due to his pioneering work on the fine structure of cells, including the discovery of microtubules, carried out research at the MBL starting in 1937 and directed the laboratory from 1975-77 (Barlow et al., 1993: 95-115).
With the increasing demand of human adult stem cells for both research and clinical purposes (typically 1–5 million cells per kg of body weight are required per treatment) it becomes of utmost importance to bridge the gap between the need to expand the cells in vitro and the capability of harnessing the factors underlying replicative senescence. Adult stem cells are known to have a limited lifespan in vitro and to enter replicative senescence almost undetectably upon starting in vitro culturing.
Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.
Amniotic stem cells are a topic of active research.
Dolly, a Finn-Dorset ewe, was the first mammal to have been successfully cloned from an adult somatic cell. Dolly was formed by taking a cell from the udder of her 6-year old biological mother. Dolly's embryo was created by taking the cell and inserting it into a sheep ovum. It took 434 attempts before an embryo was successful. The embryo was then placed inside a female sheep that went through a normal pregnancy. She was cloned at the Roslin Institute in Scotland by British scientists Sir Ian Wilmut and Keith Campbell and lived there from her birth in 1996 until her death in 2003 when she was six. She was born on 5 July 1996 but not announced to the world until 22 February 1997. Her stuffed remains were placed at Edinburgh's Royal Museum, part of the National Museums of Scotland.
Cell theory led biologists to re-envision individual organisms as interdependent assemblages of individual cells. Scientists in the rising field of cytology, armed with increasingly powerful microscopes and new staining methods, soon found that even single cells were far more complex than the homogeneous fluid-filled chambers described by earlier microscopists. Robert Brown had described the nucleus in 1831, and by the end of the 19th century cytologists identified many of the key cell components: chromosomes, centrosomes mitochondria, chloroplasts, and other structures made visible through staining. Between 1874 and 1884 Walther Flemming described the discrete stages of mitosis, showing that they were not artifacts of staining but occurred in living cells, and moreover, that chromosomes doubled in number just before the cell divided and a daughter cell was produced. Much of the research on cell reproduction came together in August Weismann's theory of heredity: he identified the nucleus (in particular chromosomes) as the hereditary material, proposed the distinction between somatic cells and germ cells (arguing that chromosome number must be halved for germ cells, a precursor to the concept of meiosis), and adopted Hugo de Vries's theory of pangenes. Weismannism was extremely influential, especially in the new field of experimental embryology.
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.
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.
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.
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. 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.