Embryo Project Encyclopedia

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.

Frank R. Lillie was born in Toronto, Canada, on 27 June 1870. His mother was Emily Ann Rattray and his father was George Waddell Little, an accountant and co-owner of a wholesale drug company. While in high school Lillie took up interests in entomology and paleontology but went to the University of Toronto with the aim of studying ministry. He slowly became disillusioned with this career choice and decided to major in the natural sciences. It was during his senior year that he developed his lifelong interest in embryology. Graduating with a BA in 1891 Lillie then moved to the Marine Biological Laboratory (MBL) at Woods Hole, Massachusetts, to work and study with Charles Otis Whitman, the founding director of the MBL. Lillie collected and studied cell lineage side-by-side with some of the most prominent embryologists of the time: Edmund B. Wilson, Edwin G. Conklin, and Aaron L. Treadwell. Along with his cell lineage studies, Whitman guided Lillie to work on the question of how blastomeres contributed to the formation of organs in fresh water clams.

Ernest Everett Just was an early twentieth century American experimental embryologist involved in research at the Marine Biological Laboratory (MBL) at Woods Hole, Massachusetts, and the Stazione Zoologica in Naples, Italy. Just was known for simple but elegant experiments that supported the "fertilizing" theory of Frank R. Lillie and served as an antagonist to Jacques Loeb's work with artificial parthenogenesis. Just's many experiments with marine invertebrates showed that the egg surface, or ectoplasm, plays an important role in the fertilization and development of eggs.

Anatomical models have always been a mainstay of descriptive embryology. As the training of embryologists grew in the late 1800s, so too did the need for large-scale teaching models. Embryo wax models, such as those made by Adolf Ziegler and Gustav Born, were popular in the latter part of the nineteenth century and the early twentieth century as a way to visualize, in three dimensions, the fine detail of embryos without the aid of a microscope. While these models were found in many university laboratories, museums of science, and even expositions and world's fairs, they were anything but easy to make or obtain. Wax modeling required skill, patience, and specialized tools. Small laboratories with only one or two embryologists often found the prospect of wax modeling too laborious, too difficult, and too expensive to make the pursuit worthwhile. As an alternative, Susanna Phelps Gage, an embryologist at Cornell University, perfected a technique of using stacks of absorbent blotting paper rather than stacks of wax plates for constructing embryo models. She first demonstrated her blotting paper method to other embryologists at the annual meeting of the Association of American Anatomists in 1905 and later at the International Zoological Congress, held in Boston in August 1907.

Hans Spemann was an experimental embryologist best known for his transplantation studies and as the originator of the "organizer" concept. One of his earliest experiments involved constricting the blastomeres of a fertilized salamander egg with a noose of fine baby hair, resulting in a partially double embryo with two heads and one tail. Spemann continued changing variables such as the amount of time the embryo was constricted and the degree of constriction, all of which added more empirical evidence to Hans Driesch's studies showing that embryonic cells could self-regulate to varying degrees. Spemann's long list of "simple" experiments and significant findings were mainly carried out at his laboratory, the Spemann School at the University of Freiburg, Germany, where numerous graduate students collaborated with Spemann to investigate embryonic induction.

Historically the exact age of human embryo specimens has long perplexed embryologists. With the menstrual history of the mother often unknown or not exact, and the premenstrual and postmenstrual phases varying considerably among women, age sometimes came down to a best guess based on the weight and size of the embryo. Wilhelm His was one of the first to write comparative descriptions of human embryos in the late 1800s. Soon afterward, Franklin P. Mall, the first director of the Carnegie Institution of Washington's (CIW) Department of Embryology, expanded upon His' work. Mall's first efforts were to place embryos into stages based on menstrual ages and body length. This method ran into problems however when it became apparent that obtaining menstrual ages was often impossible or simply too inaccurate even if the information could be obtained from the women who carried the embryos. Mall decided instead to look for patterns among embryos to come up with some type of staging system whereby embryo age could be more accurately determined.

Jacques Loeb is best known for his embryological work investigating parthenogenesis in invertebrates. Artificial Parthenogenesis and Fertilization is a revised and English-translated work from his earlier book, Die chemische Entwicklungserregung des tierischen Eies (1900). Artificial Parthenogenesis describes Loeb's many and varied methodical experiments to initiate egg development without fertilization by sperm. As is true with much of science, some of Loeb's experiments were successful and many were not. Artificial Parthenogenesis presents a sense of what early twentieth century embryology looked like: experimenters' overarching desire for manipulation and control, coupled with their use of chemicals and macromolecules as agents of change. The book also illuminates the historical role of the sea urchin in the study of embryological development.

Leonard Hayflick in the US during the early 1960s showed that normal populations of embryonic cells divide a finite number of times. He published his results as 'The Limited In Vitro Lifetime of Human Diploid Cell Strains' in 1964. Hayflick performed the experiment with WI-38 fetal lung cells, named after the Wistar Institute, in Philadelphia, Pennsylvania, where Hayflick worked. Frank MacFarlane Burnet, later called the limit in capacity for cellular division the Hayflick Limit in 1974. In the experiment, Hayflick refuted Alexis Carrel's hypothesis that cells could be transplanted and multiplied indefinitely from a single parent cell line.

Telomeres are structures at the ends of DNA strands that get longer in the DNA of sperm cells as males age. That phenomenon is different for most other types of cells, for which telomeres get shorter as organisms age. In 1992, scientists showed that telomere length (TL) in sperm increases with age in contrast to most cell of most other types. Telomeres are the protective caps at the end of DNA strands that preserve chromosomal integrity and contribute to DNA length and stability. In most cells, telomeres shorten with each cell division due to incomplete replication, though the enzyme telomerase functions in some cell lines that undergo repetitive divisions to replenish any lost length and to prevent degradation. Cells, and therefore organisms, with short telomeres are more susceptible to mutations and genetic diseases. While TL increases in a subset of sperm cells and longer telomeres may prevent early disintegration of DNA, it may also prevent natural mechanisms of apoptosis, or cell death, from occurring in abnormal sperm.

Apoptosis, or programmed cell death, is a mechanism in embryonic development that occurs naturally in organisms. Apoptosis is a different process from cell necrosis, which is uncontrolled cell death usually after infection or specific trauma. As cells rapidly proliferate during development, some of them undergo apoptosis, which is necessary for many stages in development, including neural development, reduction in egg cells (oocytes) at birth, as well as the shaping of fingers and vestigial organs in humans and other animals. Sydney Brenner, H. Robert Horvitz, and John E. Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their work on the genetic regulation of organ development and programmed cell death. Research on cell lineages before and after embryonic development may lead to new ways to reduce or promote cell death, which can be important in preventing diseases such as Alzheimer's or cancer.