Embryo Project Encyclopedia

In the early 1960s, John W. Saunders Jr., Mary T. Gasseling, and Lilyan C. Saunders in the US investigated how cells die in the developing limbs of chick embryos. They studied when and where in developing limbs many cells die, and they studied the functions of cell death in wing development. At a time when only a few developmental biologists studied cell death, or apoptosis, Saunders and his colleagues showed that researchers could use embryological experiments to uncover the causal mechanisms of apotosis. The researchers published many of their results in the 1962 paper 'Cellular death in morphogenesis of the avian wing.'

Friedrich Tiedemann studied the anatomy of humans and animals in the nineteenth century in Germany. He published on zoological subjects, on the heart of fish, the anatomy of amphibians and echinoderms, and the lymphatic and respiratory system in birds. In addition to his zoological anatomy, Tiedemann, working with the chemist Leopold Gmelin, published about how the digestive system functioned. Towards the end of his career Tiedemann published a comparative anatomy of the brains of white Europeans, black Africans, and Orangutans, in which he argued that there were no appreciable differences between the structure of the brains of blacks, women, and white European men that would suggest they were intellectually different. Tiedemann also researched the embryonic development of the brain and circulatory systems of human fetuses.

Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty times before they cannot divide any further. Researchers later found that the cause of the Hayflick Limit is the shortening of telomeres, or portions of DNA at the ends of chromosomes that slowly degrade as cells replicate. Hayflick used his research on normal embryonic cells to develop a vaccine for polio, and from HayflickÕs published directions, scientists developed vaccines for rubella, rabies, adenovirus, measles, chickenpox and shingles.

Jacques Loeb experimented on embryos in Europe and the United States at the end of the nineteenth and beginning of the twentieth centuries. Among the first to study embryos through experimentation, Loeb helped found the new field of experimental embryology. Notably, Loeb showed scientists how to create artificial parthenogenesis, thus refuting the idea that spermatozoa alone were necessary to develop eggs into embryos and confirming the idea that the chemical constitution of embryos environment affected their development. Furthermore, Loeb' s work showed that scientists could manipulate materials in a laboratory to create, as he called the process, the beginning stages of life.

German embryologist Viktor Hamburger came to the US in 1932 with a fellowship provided by the Rockefeller Foundation. Hamburger started his research in Frank Rattray Lillie's laboratory at the University of Chicago. His two-year work on the development of the central nervous system (CNS) in chick embryos was crystallized in his 1934 paper, "The Effects of Wing Bud Extirpation on the Development of the Central Nervous System in Chick Embryos," published in The Journal of Experimental Zoology. Hamburger was able to use the microsurgical techniques that he had learned from Hans Spemann to show how wing buds influence the development of the CNS in chick embryos. This paper is one of several among Hamburger's important studies on chick embryos and represents the empirical and theoretical cornerstone for his further research on central-peripheral relations in the development of the nervous system.

An important question throughout the history of embryology is whether the formation of a biological structure is predetermined or shaped by its environment. If both intrinsic and environmental controls occur, how exactly do the two processes coordinate in crafting specific forms and functions? When Viktor Hamburger started his PhD study in embryology in the 1920s, few neuroembryologists were investigating how the central neurons innervate peripheral organs. As Hamburger began his research, he had no clue that central-peripheral relations in the development of the central nervous system (CNS) would become one of his major interests for the next seventy-five years. In fact, this research trajectory would lead him to discover programmed cell death as a pivotal mechanism mediating central-peripheral relations, as well as to Nobel-Prize-winning work on nerve growth factors (NGF).

The p53 protein acts as a pivotal suppressor of inappropriate cell proliferation. By initiating suppressive effects through induction of apoptosis, cell senescence, or transient cell-cycle arrest, p53 plays an important role in cancer suppression, developmental regulation, and aging. Its discovery in 1979 was a product of research into viral etiology and the immunology of cancer. The p53 protein was first identified in a study of the role of viruses in cancer through its ability to form a complex with viral tumor antigens. In the same year, an immunological study of cancer also found p53 due to its immunoreactivity with tumor antisera. Although a series of studies found p53 through various routes, and various researchers called it different names, it was eventually confirmed that they had all encountered the same protein, p53.

"Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics" (hereafter abbreviated as "Apoptosis") was published in the British Journal of Cancer in 1972 and co-authored by three pathologists who collaborated at the University of Aberdeen, Scotland. In this paper the authors propose the term apoptosis for regulated cell death that proceeds through active, controlled morphological changes. This is in contrast to necrosis, a passive mode of cell death that results from uncontrolled cellular reactions to injury or stress. The journal article also suggests that apoptosis plays crucial roles in various pathological and physiological conditions including the shaping of digits and the shrinking of vestigial organs in developing embryos.

Richard A. Lockshin's 1963 PhD dissertation on cell death in insect metamorphosis was conducted under the supervision of Harvard insect physiologist Carroll M. Williams. Lockshin and Williams used this doctoral research as the basis for five articles, with the main title "Programmed Cell Death," that were published between 1964 and 1965 in the Journal of Insect Physiology. These articles examine the cytological processes, neuronal and endocrinal controls, and the influence of drugs on the mechanism of cell death observed in pupal muscle structures of the American silkmoth. Those muscle structures disappeared right after the completion of adult development. Several scientists have credited this series of articles as introducing the now standard term "programmed cell death." Among the five articles, "Endocrine Potentiation of the Breakdown of the Intersegmental Muscles of Silkmoths" (abbreviated hereafter as "Endocrine Potentiation") was published first and has been cited the most often. The article suggests that the endocrinal conditions at the beginning of the adult development are necessary, but not sufficient, for precisely scheduling three weeks later the cell death activities in the pupal intersegmental muscles of American silkmoths. The research was among the first to attempt to pinpoint the role of hormones in regulating cell death, a process integral to development.

In the 1910s, Alexis Carrel, a French surgeon and biologist, concluded that cells are intrinsically immortal. His claim was based on chick-heart tissue cultures in his laboratory that seemed to be able to proliferate forever. Carrel's ideas about cellular immortality convinced his many contemporaries that cells could be maintained indefinitely. In the 1960s, however, Carrel's thesis about cell immortality was put into question by the discovery that human diploid cells can only proliferate for a finite period. As it was gradually recognized that chick cells only have a finite proliferative life span in vitro as well, historians and scientists alike attempted to identify experimental errors that could have led to the extremely long life of Carrel's "immortal" chick-heart tissue cultures. Those reassessments not only point out potential experimental mistakes in pioneer tissue culture work in the early twentieth century, but are also relevant to current discussions about the different life spans of germ line cells, embryonic and adult stem cells, normal somatic cells, and cancer cells.