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Thesis: Growing Human Organs in Animals: Interspecies Blastocyst Complementation as a Potential Solution for Organ Transplant Limitations

To address the progression of immune-related constraints on organ transplantation, the first part of this thesis contains a historical analysis tracing early transplant motivations and the events that led to the discoveries broadly related to tolerance, rejection, and compatibility. Despite the advancement of those concepts over time, this early history shows that immunosuppression was one of the earliest limiting barriers to successful organ transplantation, and remains one of the most significant technical challenges.

Format: Essays and Theses

Subject: Technologies

Interspecies SCNT-derived Humanesque Blastocysts

Since the 1950s, scientists have developed interspecies blastocysts in laboratory settings, but not until the 1990s did proposals emerge to engineer interspecies blastocysts that contained human genetic or cellular material. Even if these embryos were not permitted to mature to fetal stages, their ethical and political status became debated within nations attempting to use them for research.

Format: Articles

Subject: Theories

Edwin Carlyle (Carl) Wood (1929–2011)

Edwin Carlyle Wood, also known as Carl Wood, was a physician who helped develop in vitro fertilization, or IVF, treatments. From 1964 to 1992, Wood worked as a professor of obstetrics and gynecology at Monash University in Melbourne, Australia, where he was one of the first in the world to lead a team of physicians to establish IVF as a proven treatment for infertility. IVF refers to a medical procedure in which scientists inseminate an egg cell with a sperm cell outside of the body, such as in a glass dish in a clinical setting.

Format: Articles

Subject: People, Technologies, Reproduction

“Transfer of a Human Zygote” (1973), by David De Kretzer, Peter Dennis, Bryan Hudson, John Leeton, Alexander Lopata, Ken Outch, James Talbot, and Carl Wood

On 29 September 1973, researchers David De Kretzer, Peter Dennis, Bryan Hudson, John Leeton, Alexander Lopata, Ken Outch, James Talbot, and Carl Wood published “Transfer of a Human Zygote,” in The Lancet. In the article, the authors describe an experiment that resulted in one of the first pregnancies established via in vitro fertilization, or IVF. Prior to the article’s publication in 1973, there was no published evidence demonstrating whether IVF treatment would work in humans, although evidence existed showing that IVF worked in other mammals for breeding purposes.

Format: Articles

Subject: Publications, Processes

The Process of Implantation of Embryos in Primates

Implantation is a process in which a developing embryo, moving as a blastocyst through a uterus, makes contact with the uterine wall and remains attached to it until birth. The lining of the uterus (endometrium) prepares for the developing blastocyst to attach to it via many internal changes. Without these changes implantation will not occur, and the embryo sloughs off during menstruation. Such implantation is unique to mammals, but not all mammals exhibit it.

Format: Articles

Subject: Processes

Gail Roberta Martin (1944– )

In the twentieth and early twenty-first centuries, Gail Roberta Martin specialized in biochemistry and embryology, more specifically cellular communication and the development of organs. In 1981, she named any cell taken from inside a human embryo at the blastocyst stage an “embryonic stem cell”. During development, an embryo goes through the blastocyst stage just before it implants in the uterus. Embryonic stem cells are useful for experiments because they are self-renewing and able to develop into almost any cell type in the body.

Format: Articles

Subject: People

"Embryonic Stem Cell Lines Derived from Human Blastocytes" (1998), by James Thomson

After becoming chief pathologist at the University of Wisconsin-Madison Wisconsin Regional Primate Center in 1995, James A. Thomson began his pioneering work in deriving embryonic stem cells from isolated embryos. That same year, Thomson published his first paper, "Isolation of a Primate Embryonic Stem Cell Line," in Proceedings of the National Academy of Sciences of the United States of America, detailing the first derivation of primate embryonic stem cells. In the following years, Thomson and his team of scientists - Joseph Itskovitz-Eldor, Sander S. Shapiro, Michelle A.

Format: Articles

Subject: Experiments, Publications

Thesis: The Hwang Woo-Suk Scandal and the Development of Bioethics in South Korea

In 2004, the South Korean geneticist Woo-Suk Hwang published what was widely regarded as the most important research finding in biotechnology that year. In the prestigious American journal Science, he claimed that he had succeeded in cloning a human blastocyst, which is an embryo in its early developmental stages (Hwang et al. 2004). A year later, in a second Science article, he made the earth-shattering announcement that he had derived eleven embryonic stem cell lines using his cloning technique (Hwang et al. 2005). The international scientific community was stunned.

Format: Essays and Theses

Subject: Ethics, People

Fetus in Fetu

Fetus in fetu is a rare variety of parasitic twins , where the developmentally abnormal parasitic twin is completely encapsulated within the torso of the otherwise normally developed host twin. In the late eighteenth century, German anatomist Johann Friedrich Meckel was the first to described fetus in fetu, which translates to “fetus within fetus.” Fetus in fetu is thought to result from the unequal division of the totipotent inner cell mass , the mass of cells that is the ancestral precursor to all cells in the body.

Subject: Theories, Disorders, Reproduction

Human Embryonic Stem Cells

Stem cells are undifferentiated cells that are capable of dividing for long periods of time and can give rise to specialized cells under particular conditions. Embryonic stem cells are a particular type of stem cell derived from embryos. According to US National Institutes of Health (NIH), in humans, the term "embryo" applies to a fertilized egg from the beginning of division up to the end of the eighth week of gestation, when the embryo becomes a fetus. Between fertilization and the eighth week of gestation, the embryo undergoes multiple cell divisions.

Format: Articles

Subject: Processes, Reproduction

"Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells" (1998), by John Gearhart et al.

In November 1998, two independent reports were published concerning the first isolation of pluripotent human stem cells, one of which was "Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells." This paper, authored by John D. Gearhart and his research team - Michael J Shamblott, Joyce Axelman, Shunping Wang, Elizabeith M. Bugg, John W. Littlefield, Peter J. Donovan, Paul D. Blumenthal, and George R. Huggins - was published in Proceedings of the National Academy of Science soon after James A.

Format: Articles

Subject: Publications

"Experimental Chimeras' Removal of Reproductive Barrier Between Sheep and Goat" (1984), by Sabine Meinecke-Tillmann and Burkhard Meinecke

In 1984 Sabine Meinecke-Tillmann and Burkhard Meinecke published their article "Experimental Chimeras - Removal of Reproductive Barrier Between Sheep and Goat" in Nature. Their study conquered the reproductive barrier between sheep and goats through embryo manipulation. Their article appeared in Nature on the same day that a similar experiment, conducted by Carole Fehilly, Steen Willadsen, and Elizabeth Tucker was published regarding reproductive barriers between sheep and goats.

Format: Articles

Subject: Experiments

"Interspecific Chimeras in Mammals: Successful Production of Live Chimeras Between Mus musculus and Mus caroli" (1980), by Janet Rossant and William I. Frels

In 1980 Janet Rossant and William I. Frels published their paper, "Interspecific Chimeras in Mammals: Successful Production of Live Chimeras Between Mus musculus and Mus caroli," in Science. Their experiment involved the first successful creation of interspecific mammalian chimeras. Mammalian chimeras are valuable for studying early embryonic development. However, in earlier studies, clonal analysis was restricted by the lack of a cell marker, present at all times, that makes a distinction between the two parental cell types in situ.

Format: Articles

Subject: Experiments

Shoukhrat Mitalipov and Masahito Tachibana’s Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells (2009)

Shoukhrat Mitalipov, Masahito Tachibana, and their team of researchers replaced the mitochondrial genes of primate embryonic stem cells via spindle transfer. Spindle replacement, also called spindle transfer, is the process of removing the genetic material found in the nucleus of one egg cell, or oocyte, and placing it in another egg that had its nucleus removed. Mitochondria are organelles found in all cells and contain some of the cell’s genetic material. Mutations in the mitochondrial DNA can lead to neurodegenerative and muscle diseases.

Format: Articles

Subject: Experiments

"Sheep Cloned by Nuclear Transfer from a Cultured Cell Line" (1996), by Keith Campbell, Jim McWhir, William Ritchie, and Ian Wilmut

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.

Format: Articles

Subject: Experiments

Somatic Cell Nuclear Transfer in Mammals (1938-2013)

In the second half of the
twentieth century, scientists learned how to clone organisms in some
species of mammals. Scientists have applied somatic cell nuclear transfer to clone human and
mammalian embryos as a means to produce stem cells for laboratory
and medical use. Somatic cell nuclear transfer (SCNT) is a technology applied in cloning, stem cell
research and regenerative medicine. Somatic cells are cells that
have gone through the differentiation process and are not germ
cells. Somatic cells donate their nuclei, which scientists

Format: Articles

Subject: Theories, Technologies, Processes

“Survival of Mouse Embryos Frozen to -196 ° and -269 °C” (1972), by David Whittingham, Stanley Leibo, and Peter Mazur

In 1972, David Whittingham, Stanley Leibo, and Peter Mazur published the paper, “Survival of Mouse Embryos Frozen to -196 ° and -269 °C,” hereafter, “Survival of Mouse Embryos,” in the journal Science. The study marked one of the first times that researchers had successfully cryopreserved, or preserved and stored by freezing, a mammalian embryo and later transferred that embryo to a live mouse who gave birth to viable offspring. Previously, scientists had only been successful cryopreserving single cells, like red blood cells.

Format: Articles

Subject: Experiments, Publications

Matthew Howard Kaufman (1942–2013)

Matthew Kaufman was a professor of anatomy at the University of Edinburgh, in Edinburgh, UK, who specialized in mouse anatomy, development, and embryology during the late twentieth century. According to the The Herald, he was the first, alongside his colleague Martin Evans, to isolate and culture embryonic stem cells. Researchers initially called those cells Evans-Kaufman cells. In 1992, Kaufman published The Atlas of Mouse Development, a book that included photographs of mice development and mice organs over time.

Format: Articles

Subject: People

In the Womb: Identical Twins (2009), by National Geographic

National Geographic's documentary In the Womb: Identical Twins focuses on the prenatal development of human identical twins. Director Lorne Townend uses three-dimensional (3D) and four-dimensional (4D) ultrasound imaging and microscopy to depict twin development , genetic and epigenetic variations in the fetuses, and methods of fetal survival in the confines of the womb. Artist renditions of scientific data fill in areas of development inaccessible to the imaging tools.

Format: Articles

Subject: Outreach, Reproduction

Anne Laura Dorinthea McLaren (1927-2007)

Anne Laura Dorinthea McLaren was a developmental biologist known for her work with embryology in the twentieth century. McLaren was the first researcher to grow mouse embryos outside of the womb. She experimented by culturing mouse eggs and successfully developing them into embryos, leading to advancements with in vitro fertilization.

Format: Articles

Subject: People

"Generation of Germline-Competent Induced Pluripotent Stem Cells" (2007), by Keisuke Okita, Tomoko Ichisaka, and Shinya Yamanaka

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.

Format: Articles

Subject: Publications

Stem Cells

According to the US National Institutes of Health (NIH), the standard American source on stem cell research, three characteristics of stem cells differentiate them from other cell types: (1) they are unspecialized cells that (2) divide for long periods, renewing themselves and (3) can give rise to specialized cells, such as muscle and skin cells, under particular physiological and experimental conditions. When allowed to grow in particular environments, stem cells divide many times. This ability to proliferate can yield millions of stem cells over several months.

Format: Articles

Subject: Processes

The First Successful Cloning of a Gaur (2000), by Advanced Cell Technology

Advanced Cell Technology (ACT), a stem cell biotechnology company in Worcester, Massachusetts, showed the potential for cloning to contribute to conservation efforts. In 2000 ACT researchers in the United States cloned a gaur (Bos gaurus), an Asian ox with a then declining wild population. The researchers used cryopreserved gaur skin cells combined with an embryo of a domestic cow (Bos taurus). A domestic cow also served as the surrogate for the developing gaur clone.

Format: Articles

Subject: Experiments

Karl Oskar Illmensee (1939–)

Karl Oskar Illmensee studied the cloning and reproduction of fruit flies, mice, and humans in the US and Europe during the twentieth and twenty-first centuries. Illmensee used nuclear transfer techniques (cloning) to create early mouse embryos from adult mouse cells, a technique biologists used in later decades to help explain how embryonic cells function during development. In the early 1980s, Illmensee faced accusations of fraud when others were unable to replicate the results of his experiments with cloned mouse embryos.

Format: Articles

Subject: People, People

Developmental Timeline of Alcohol-Induced Birth Defects

Maternal consumption of alcohol (ethanol) during pregnancy can result in a continuum of embryonic developmental abnormalities that vary depending on the severity, duration, and frequency of exposure of ethanol during gestation. Alcohol is a teratogen, an environmental agent that impacts the normal development of an embryo or fetus. In addition to dose-related concerns, factors such as maternal genetics and metabolism and the timing of alcohol exposure during prenatal development also impact alcohol-related birth defects.

Format: Articles

Subject: Disorders, Reproduction

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