Embryo Project Encyclopedia Articles

First published in 1930 and reprinted in 1972, Edward Stuart Russell's The Interpretation of Development and Heredity is a work of philosophical and theoretical biology. In this book Russell outlines a methodological and philosophical program aimed at reorienting the biological understanding of development and heredity. He argues that the mechanistic perspective on development and heredity ignores aspects of biological phenomena that can only be analyzed if biologists view organisms as whole entities, rather than breaking down developmental and hereditary processes into small causal units. This book is representative of Russell's broad philosophical approach to biology, called "organicism".

During the 1870s and early 1880s, the British morphologist Francis Maitland Balfour contributed in important ways to the budding field of evolutionary embryology, especially through his comparative embryological approach to uncovering ancestral relationships between groups. As developmental biologist and historian Brian Hall has observed, the field of evolutionary embryology in the nineteenth century was the historical ancestor of modern-day evolutionary developmental biology. Balfour's work was notably inspired by Charles Darwin's theory of evolution and Ernst Haeckel's account of the relationships between embryology and evolution. Only a decade after Balfour's program of research began, an alpine climbing accident robbed Britain of its most promising embryologist.

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.'

Edward Stuart Russell was born 23 March 1887 to Helen Cockburn Young and the Reverend John N. Russell in Port Glasgow, Scotland. Friends and co-workers alike knew Russell as a quiet and focused, though always kind and helpful person. Trained in classics and biology, Russell's interests drew him to the study of historical and philosophical issues in the biological sciences, particularly morphology and animal behavior. According to Nils Roll-Hansen, Russell was one of the most influential philosophers of biology in the second third of the twentieth century. It was through history and philosophy, rather than his equally important work as a fisheries biologist, Russell argued that developmental and embryological studies deserve a central role in the biological sciences.

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.