Embryo Project Encyclopedia

Mechanism of Notch Signaling: The image depicts a type of cell signaling, in which two animal cells interact and transmit a molecular signal from one to the other. The process results in the production of proteins, which influence the cells as they differentiate, move, and contribute to embryological development. In the membrane of the signaling cell, there is a ligand (represented by a green oval). The ligand functions to activate a change in a receptor molecule. In the receiving cell, there are receptors; in this case, Notch proteins (represented by orange forks). The Notch proteins are embedded in the receiving cell membrane, and they have at least two parts: an intracellular domain (inside the cell) and the receptor (outside the cell). Once the ligand and receptor bind to each other, a protease (represented by the dark red triangle) can sever the intracellular domain from the rest of the Notch receptor. Inside the nucleus of the receiving cell (represented by the gray area) are the cellês DNA (represented by the multi-colored helices) and its transcription factors (blue rectangles). Transcription factors are proteins that bind to DNA to regulate transcription, the first step in gene expression, which eventually yields proteins or other products. Initially, repressor proteins (represented by a red irregular hexagon) prevent transcription factors from allowing transcription. When the severed Notch receptor intracellular domain reaches the nucleus, it displaces the repressor. The transcription factor can then signal for transcription to occur. 1) There is a Notch receptor protein in the membrane of a receiving cell, and a ligand for this receptor (for example, Delta) in the membrane of the signaling cell. When the ligand binds to the receptor, the intracellular domain of the receptor changes shape. 2) Inside the receiving cell, there are proteases. Once the intracellular domain of the receptor changes shape, the protease can bind to it and shear the intracellular domain away from the rest of the receptor molecule. 3) The severed intracellular domain is shuttled to the receiving cell nucleus. Here, the intracellular domain displaces a repressor protein. This allows a transcription factor to initiate DNA transcription. During transcription, DNA is used as a template to create RNA. Following transcription, the process of translation occurs, which uses RNA as a template to create proteins. These proteins influence the behavior, fate, and differentiation of cells, which contribute to normal embryonic development

In 1894, William Stewart Halsted published The Results of Operations for the Cure of Cancer of the Breast Performed at the Johns Hopkins Hospital from June, 1889, to January, 1894, in the medical journal Annals of Surgery. In the article, Halsted describes the results from fifty of his operations on women with breast cancer, performed at Johns Hopkins Hospital in Baltimore, Maryland. Those operations involved a surgical procedure Halsted called radical mastectomy, which consists in removing all of the patient’s breast tissue, chest muscle, and underarm lymph nodes. Halsted’s surgery effectively cured breast cancer in a time period when no other effective treatment options were available. The radical mastectomy remained the standard of care from the 1890s to the 1970s as a means of treating a type of reproductive cancer common to women.

During the twentieth century, Austin Bradford Hill researched diseases and their causes in England and developed the Bradford Hill criteria, which comprise the minimal requirements that must be met for a causal relationship to be established between a factor and a disease. Hill also suggested that researchers should randomize clinical trials to evaluate the effects of a drug or treatment by monitoring large groups of people. In addition, Hill advocated for case-control studies, in which researchers compare a group of people with a medical condition to a group without that condition to investigate the condition's possible causes. Hill's own work with clinical trials and case-control studies helped him prove that smoking caused lung cancer. The Bradford Hill criteria have also been used to establish causal links between factors and cancer, including reproductive cancers such as human papillomavirus that causes cervical cancer.

Percivall Pott was a physician in England during the eighteenth century who identified soot as the cause of chimney sweeps' scrotal cancer, later called testicular cancer. In the 1770s, Pott observed that scrotal cancer commonly afflicted chimney sweeps, the young boys sent up into chimneys to clean away the soot left over from fires, and he hypothesized that the soot inside chimneys might cause that type of cancer. Pott was one of the first doctors to identify some environmental factor as causing cancer. Pott's research helped chimney sweeps to prevent scrotal cancer by using protective clothing, and it also allowed for future research on environmental causes of cancers.

'On the Permanent Life of Tissues outside of the Organism' reports Alexis Carrel's 1912 experiments on the maintenance of tissue in culture media. At the time, Carrel was a French surgeon and biologist working at the Rockefeller Institute in New York City. In his paper, Carrel reported that he had successfully maintained tissue cultures, which derived from connective tissues of developing chicks and other tissue sources, by serially culturing them. Among all the tissue cultures Carrel reported, one was maintained for more than two months, whereas previous efforts had only been able to keep tissues in vitro for three to fifteen days. Carrel’s experiments contributed to the development of long-term tissue culture techniques, which were useful in the study of embryology and eventually became instrumental in stem cell research. Despite later evidence to the contrary, Carrel believed that as long as the tissue culture method was accurately applied, tissues kept outside of the organisms should be able to divide indefinitely and have permanent life.

The 1973 Supreme Court case Roe v. Wade was a significant event in the story of fetal personhood—the story of whether embryos and fetuses are legal persons. Roe legalized abortion care in the United States (US). However, the story of fetal personhood began long before the 1970s. People have been talking about embryos, fetuses, and their status in science, the law, and society for centuries. I studied the history of fetal personhood in the United States, tracing its origins from Ancient Rome and Medieval England to its first appearance in a US courtroom in 1884 and then to the Supreme Court’s decision in 1973.

Christiane Nusslein-Volhard studied how genes control embryonic development in flies and in fish in Europe during the twentieth and twenty-first centuries. In the 1970s, Nusslein-Volhard focused her career on studying the genetic control of development in the fruit fly Drosophila melanogaster. In 1988, Nusslein-Volhard identified the first described morphogen, a protein coded by the gene bicoid in flies. In 1995, along with Eric F. Wieschaus and Edward B. Lewis, she received the Nobel Prize in Physiology or Medicine for the discovery of genes that establish the body plan and segmentation in Drosophila. Nusslein-Volhard also investigated the genetic control of embryonic development to zebrafish, further generalizing her findings and helping establishing zebrafish as a model organism for studies of vertebrate development.

In 1953, Virginia Apgar published the article "A Proposal for a New Method for Evaluation of the Newborn Infant" about her method for scoring newborn infants directly after birth to assess their health and whether medical intervention was necessary. Apgar worked at the Presbyterian Hospital in New York City, New York, as an obstetrical anesthesiologist, a physician who administers pain medication during childbirth. In that capacity, she sought to reestablish clear scoring guidelines for newborn infants so that she could compare which obstetric practices, pain relief methods, and resuscitation methods worked the best during and after childbirth. She published her article in Current Researches in Anesthesia and Analgesia in 1953, and the Apgar scoring system is still used in hospitals around the world as of 2016. In the article, Apgar establishes a scoring system for newborn infants that allows for quick assessment of their health directly after birth and therefore swift intervention by medical personnel to promote healthy development.

William Stewart Halsted was a surgeon at Johns Hopkins Hospital in Baltimore, Maryland, during the late 1800s and early 1900s. In 1894 Halsted described his procedure for treating breast cancer by removing the breast tissue, chest muscles, and lymph nodes in the armpit, a procedure he named radical mastectomy, and that became the standard of care for treating breast cancer until 1970. He also made contributions to other novel medical procedures such as gallbladder surgery, blood transfusions, antiseptic techniques, anesthesia use, and using plates and screws to hold bones in position when setting bone fractures. At Johns Hopkins Hospital, Halsted established a surgical training program in which he allowed medical students and surgical residents to shadow him and perform procedures under his guidance. In the twentieth century, similar training programs spread across the country and informed the standardization of medical training. Halsted devised a surgical treatment for breast cancer and reshaped the way physicians practiced medicine in the twentieth century, which resulted in better health outcomes through more careful surgical methods, especially in women with breast cancer.

In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene expression. Britten worked at the Carnegie Institute of Washington in Washington, D.C., while Davidson worked at the California Institute of Technology in Pasadena, California. Their paper was an early theoretical and mechanistic description of gene regulation in higher organisms.