Watching as Life Begins: The Discovery of the Mammalian Ovum and the Process of Fertilization

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Watching as Life Begins: The Discovery of the Mammalian Ovum and the Process of Fertilization

Overview

The discovery of the mammalian ovum brought the realization that human reproduction occurred in the same way as did that of other animals. In the second half of the nineteenth century, microscopic techniques improved enough to allow scientists to observe the nuclei of cells. Turning this new ability to the study of sexual reproduction, they were able to see that fertilization involved the merging of cell nuclei from the male and female parent. This superseded the previous view of the sperm stimulating the ovum to develop by physical or chemical means, and led the way to the modern understanding of reproduction and genetics.

Background

From ancient times, people have understood that traits may be inherited, and bred animals in order to reproduce desirable attributes. But they had no idea of how heredity actually worked. Aristotle (384-322 B.C.) and other Greek philosophers believed that hereditary traits were passed in the blood, and we still use terms like "blue-blood" and "blood relative" today. While it was clear to the ancients that sexual intercourse resulted in pregnancy, the mechanism by which a new being was conceived and developed was also a mystery. The general view was that the male contributed the "seed" of a new organism, while the female's role was to nourish it as it grew.

In the seventeenth and eighteenth centuries, another school of thought arose, which held that the essence of the new being was concentrated in the egg. These were understood as containing perfect miniature organisms, which needed only the stimulation of the male in order to trigger their growth. Each tiny being carried its own even tinier offspring in miniature, and so on, like a set of nested dolls going all the way back to Creation and forward for all time. Some scientists argued against this theory, called preformation, because it did not explain the inheritance of traits from both parents. Opponents of preformation got a boost in 1651, when the English physician William Harvey (1578-1657) published his studies of deer embryos. In their early stages, the embryos looked nothing at all like fully formed deer.

The invention of the microscope in the mid-1600s by Anton van Leeuwenhoek (1632-1723) allowed scientists to see individual cells for the first time. The term "cell" was coined in 1665 by Robert Hooke (1635-1703), upon observing holes encased by walls in a sample of cork. Leeuwenhoek first described his observations of sperm cells in 1677. This renewed the debate as to whether these tiny "animalcules" contained preformed organisms, or served to awaken those in the egg.

In 1759 Kaspar Friedrich Wolff (1733-1794), a German physiologist, dealt preformation another blow. His experiments with chick embryos showed that specialized organs develop from undifferentiated tissue. This is the same process we can readily observe in the growth of a plant, as a new shoot differentiates into stem, flowers, and leaves. Better microscopic and experimental techniques of the nineteenth century would shed light on the actual mechanisms of reproduction and development.

Impact

It was by no means obvious to early natural historians that eggs had anything to do with the reproduction of humans and other mammals. Many types of animals lay their eggs, but in mammals, fertilization and embryonic development take place internally. The first known claim to have observed the human ovum was made by the Dutch physician Reinier de Graaf (1641-1673) in 1672, but there is some dispute as to what he actually saw. For the next 150 years attention turned to studying the more easily accessed eggs of birds and frogs. The first undisputed observation of the human ovum was made by Karl Ernst von Baer (1792-1876), and reported in a letter in 1827.

Early nineteenth-century scientists watching the first stages of the development of frogs' eggs saw them divide repeatedly, but they did not at first connect this with the concept of cells. The idea that cells are the building blocks of all life was advanced in the 1830s by the German scientists Matthias Schleiden (1804-1881) and Theodor Schwann (1810-1882). It was not until 1858 that Rudolf Virchow (1821-1902) proposed that cells could arise only from other cells. Meanwhile, one of the most important developments in the history of biology was quietly taking place in the garden of an Austrian monk.

Gregor Mendel (1822-1884) discovered the laws of heredity while growing peas, observing red and white flowered plants and how the colors appeared in hybrids. In an 1866 paper he explained that heredity is caused by information-carrying entities we now call genes. The genes exist in pairs, one from each parent. Mendel's ideas appeared before their time, and no one knew what to do with his work. Developments over the next few decades resulted in its rediscovery at the turn of the century. Similarly, DNA, the molecule that codes the genetic information, was discovered in 1869 by Swiss biochemist Friedrich Miescher (1844-1895), but dismissed at the time as unimportant.

In the 1850s the German botanist Nathanael Pringsheim (1823-1894) was among the first to observe the union of egg and sperm, in his experiments with freshwater algae. He watched the sperm force its way through the outer layer of the egg and seem to dissolve within its protoplasm. His studies demonstrated that the sperm cell actually combined with the egg, rather than simply acting upon it.

Microscopy improved in the 1870s and 1880s with the development of immersion lenses, optics corrected for spherical and chromatic aberration, and new specimen fixing and staining techniques. Suddenly the details of cells were revealed. The study of reproduction was revolutionized when scientists could begin to observe the structure of the cell nucleus.

Oskar Hertwig (1849-1922) and Hermann Fol (1845-1892) independently observed the penetration of a sea urchin eggs by sperm cells in the late 1870s. Hertwig was able to discern that fertilization involved the merging of two cell nuclei, one from the egg and one from the sperm cell. This was a major advance in thinking about reproduction. Even after Pringsheim and others had observed the sperm entering the egg, the assumption had been that the "dissolution" of the sperm resulted in some type of chemical stimulation. Hertwig's work showed that the embryo developed from a union of the two cells. He also described how once fertilization has occurred, additional sperm are prevented from entering the egg.

The nucleus was observed to contain a substance called chromatin. During ordinary cell division, or mitosis, the chromatin could be seen to condense into discrete chromosomes. Each cell had a fixed number of chromosomes, depending on the type of organism. Cells divided to form new cells with the same number of chromosomes as those that preceded them. Human cells have 46 chromosomes.

The German biologist August Weismann (1834-1914) realized that if egg and sperm cells were produced by the same mechanism, their merging would result in a doubling of the hereditary information in each generation. The solution to this problem is key to understanding the assortment of hereditary traits we see in sexual reproduction. The gametes, or sex cells, are generated in a process called meiosis, in which the parental gene pairs are split. The gametes are haploid cells, with half the normal complement of chromosomes. Two gametes merge in sexual reproduction, resulting in the embryo's having diploid cells with the normal amount of genetic material, half of which derives from each parent.

In 1892 Weismann wrote that the determinants of hereditary traits were located in the chromosomes, an assertion that was regarded as speculative at the time, and which was not proven until some years later. He called this hereditary information the "germ plasm," a component of the cell nucleus passed along in such a way that it remained isolated from anything that happened to the adult organism. This contradicted the Lamarckian view that traits acquired during an organism's lifetime could be inherited, and provided support to the theory of evolution by natural selection.

SHERRI CHASIN CALVO