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.

Ovism was one of two models of preformationism, a theory of generation prevalent in the late seventeenth through the end of the eighteenth century. Contrary to the competing theory of epigenesis (gradual emergence of form), preformationism held that the unborn offspring existed fully formed in the eggs or sperm of its parents prior to conception. The ovist model held that the maternal egg was the location of this preformed embryo, while the other preformationism model known as spermism preferred the paternal germ cell, as the name implies.

This embryology image is a pencil sketch by Nicolaas Hartsoeker, published as part of his 1694 French-language paper entitled Essai de Dioptrique, a semi-speculative work describing the sorts of new scientific observations that could be done using magnifying lenses. Dioptrique was published in Paris by the publishing house of Jean Anisson. The image depicts a curled up infant-like human, now referred to as a homunculus, inside the head of a sperm cell. This sketch is important to embryology because it is one of the most illustrative examples of preformationism, a theory of generation stating that each future member of any given species exists, fully formed though miniscule, within the gametic cells (sperm or eggs) of its parents. This theory was popular among naturalists in the eighteenth century.

Nicolaas Hartsoeker, a Dutch astronomer, optics manufacturer, and naturalist, was born 26 March 1656 in Gouda, Netherlands, and died 10 December 1725. His mother was Anna van der Mey and his father was Christiaan Hartsoeker, a prominent evangelical minister. His major contribution to embryology was his observations of human sperm cells, which he claimed to be the first to see under a microscope. His sketch of the homunculus, a tiny preformed human he believed to exist in the head of spermatazoa, is his lasting scientific legacy in the field of embryology. This sketch was only a minor part of his first publication, Essai de Dioptrique (1694), which dealt primarily with the use of optical lenses in science. In subsequent years the sketch became iconic of the theory of embryological development known now as preformationism. Hartsoeker himself was a vocal adherent of spermist preformationism and is often cited as the originator of the idea.

Preformationism was a theory of embryological development used in the late seventeenth through the late eighteenth centuries. This theory held that the generation of offspring occurs as a result of an unfolding and growth of preformed parts. There were two competing models of preformationism: the ovism model, in which the location of these preformed parts prior to gestation was the maternal egg, and the spermism model, in which a preformed individual or homunculus was thought to exist in the head of each sperm. Preformationism was a widely-held theory by Enlightenment-era scientists, but by the early 1800s, most scientists had abandoned it, in part because higher magnification in microscopes enabled them to see the very earliest stages of embryos as small collections of cells. Prior to preformationism, naturalists who studied embryo development favored the theory of spontaneous generation in lower animals, such as flies, which appeared to arise from manure. In higher animals, however, scientists used the theory of epigenesis put forth by Aristotle, who said that maternal and paternal fluids came together in the uterus and solidified during early gestation into a fetus. Preformationism was the first theory of generation and development that applied to all organisms in the plant and animal kingdoms.

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.

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
transplant into eggs after removing their nucleuses (enucleated eggs).
Therefore, in SCNT, scientists replace the nucleus in an egg cell
with the nucleus from a somatic cell.

Marcello Malpighi studied chick embryos with microscopes in Italy during the seventeenth century. Trained as a medical doctor, he was among the first scientists to use the microscope to examine embryos at very early stages. Malpighi described early structures in chick embryos, and later scientists used his descriptions to help develop the theory of preformationism.