Cell Biology as a science began within the pro­gressive evolution of the Cell Doctrine.

Briefly summarized, this doctrine states that cells are the fundamental units of both structure and function in all living things; that all forms of life (animal, plant, and microbial) are composed of cells and their secretions; and that cells arise only from preexisting cells, each cell haying a life of its own in addition to its integrated role in multi-cellular organisms.

This statement seems both elementary and obvious to any student with some background in the biological sciences.

Nevertheless, it took several centuries for this concept to be developed and accepted. The very existence of cells was not even suspected until the sev­enteenth century, because most cells are too small to be discerned with the naked eye, and because instru­ments for significantly magnifying small objects did not exist.

However, with the introduction of the first crude light microscopes, investigators began to exam­ine small organisms, tissues cut from plants or re­moved from animals, and the “animalcules” in pond water. The invention of the microscope and its gradual improvement went hand-in-hand with the develop­ment of the cell doctrine. It finally became apparent that a fundamental similarity existed in the structural organization of all the living things studied.

What follows is a brief description of a few of the historical highlights i-hat culminated in the cell doc­trine. Although a great many individuals made contri­butions of varying significance to the development of this concept, the works of a certain small number of people stand out as milestones.

Printed in 1558 were the results of Conrad Gesner’s (Swiss, 1516-1565) studies on the structure of a group of protists called foraminifera. What is especially sig­nificant about this work is that Gesner’s sketches in­cluded so much detail that they could only have been made if he had used some form of magnifying lens. This appears to be the earliest recorded use of a mag­nifying instrument in a biological study.

Francis and Zacharias Janssen, who manufactured eyeglasses in Holland, are generally credited with the construction of the first compound microscopes in 1590. Their microscopes had magnifying powers be­tween 10x and 30x and were used primarily to exam­ine small whole organisms such as fleas and other in­sects. The first microscopes were in fact referred to as “flea-glasses.”

Although noted principally for his contributions in the fields of astronomy and physics, Galileo Galilei (Italian, 1564-1642) produced several important bio­logical works. His own microscopes were constructed at about the same time as those of the Janssens (around 1610) and were used for several extensive studies on the arrangements of the facets in the com­pound eyes of insects.

Among the earliest descriptions of the microanat­omy of tissues were those of Marcello Malpighi (Ital­ian, 1628-1694), one of the first great animal and plant anatomists. He was the first to describe the exis­tence of the capillaries, thereby completing the work on the circulation of the blood started by the great English physiologist William Harvey.

Malpighi was among the first to use a microscope to examine and describe thin slices of animal tissues from such organs as the brain, liver, kidney, spleen, lungs, and tongue. His published works also include descriptions of the development of the chick embryo. In his later years, Malpighi turned to investigations of plant tissues and suggested that they were composed of structural units that he called “utricles” (later to be called “cells”).

Antonie van Leeuwenhoek (Dutch, 1632-1723) was one of the most distinguished of all the early microscopists. Although it was only an avocation, Leeuwenhoek became an expert lens grinder and built numerous microscopes, some with magnifications ap­proaching 300 x. Leeuwenhoek was the first to de­scribe microscopic organisms in rainwater collected from tubes inserted into the soil during rainfall. His sketches included numerous bacteria (bacilli, cocci, spirilla, etc.), protozoa, rotifers, and hydra.

Leeuwen­hoek was the first to describe sperm cells (of humans, dogs, rabbits, frogs, fish, and insects) and observe the movement of blood cells in the web capillaries of the frog’s foot and the rabbit’s ear. He described the blood cells of mammals, birds, amphibians, and fish, noting that those of fish and amphibians were oval in shape and contained a central body (i.e., the nucleus), while those of humans and other mammals were round. Leeuwenhoek’s observations were recorded in a series of reports that he sent to the Royal Society of London.

Many of Leeuwenhoek’s observations were con­firmed in experiments conducted by Robert Hooke (English, 1635-1703), an architect and scientist em­ployed by the Royal Society. Hooke popularized the use of microscopes among contemporary biologists in England and built several compound microscopes of his own. On one occasion, Hooke examined a thin slice cut from a piece of dried cork.

In his description, Hooke wrote that he found the sections to be “all per­forated and porous, much like a honeycomb” and re­ferred to the boxlike structures as “cells.” Thus, it is Hooke who introduced the term cell to biology. What he observed, of course, were not cork cells but rather the empty spaces left behind after the living portion of the cells had disintegrated.

Nehemiah Grew (English, 1641-1712), together with Marcello Malpighi, is recognized as one of the founders of plant anatomy. His publications included accounts of the microscopic examination of sections through the flowers, roots, and stems of plants and clearly indicate that he recognized the cellular nature of plant tissue. Grew was also the first to recognize that flowers are the sexual organs of plants.

In 1824, Rene Dutrochet (French, 1776-1847) wrote that all animal and plant tissues were “aggregates of globular cells” and, in 1831, Robert Brown (English, 1773-1858) noted that the cells of plant epidermis, pollen grains, and stigmas contained certain “con­stant structures” that he called nuclei, thereby intro­ducing this term to biology. Brown is also credited with the first description of the physical phenomenon now referred to as “Brownian motion.” Johannes E. Purkinje (Czech, 1787-1869) coined the term protoplasm to describe the contents of cells.

Mathias J. Schleiden (German, 1804-1881) and Theodor Schwann (German, 1810-1882) are often credited, albeit incorrectly, with the first formal state­ment of a general cell theory. Their contributions to the development of the cell doctrine reside in the gen­eralizations that they made based principally on the works of their predecessors. Schleiden and Schwann were particularly influential among their contempo­raries and did, therefore, gain popular acceptance for the developing cell doctrine.

Schleiden, a botanist, ex­tended the studies begun by Robert Brown on the structure and function of the cell nucleus (which Schleiden called a “cytoblast”) and was the first to de­scribe nucleoli. Schleiden’s writings clearly indicate his appreciation of the individual nature of cells. In 1838, he wrote that each cell leads a double life—one independent, pertaining to its own development, and another as an integral part of a plant.

Schwann stud­ied both plant and animal tissues. His work with con­nective tissues such as bone and cartilage led him to modify the evolving cell theory to include the notion that living things are-composed of both cells and the products of cells. Schwann is also credited with intro­duction of the term metabolism to describe the activi­ties of cells.

Rudolf Virchow (German, 1821-1902) was a pathol­ogist and recognized the cellular basis of disease. His writings, often in Latin, also reveal his appreciation of the cellular basis of life’s continuity, as summarized in his now famous expression omnis cellula e cellula, “all cells arise from [preexisting] cells.” In the last part of the 1800s and certainly by the turn of the century, the light microscope approached its limit in terms of magnification and resolving power, and nearly all major cellular structures had at least been described.

In this century, especially during the past 25 years, we have witnessed an unprecedented growth of our knowledge of the cell, its structural organization and diversity, its chemical organization, and the various functions of its component parts. This understanding is founded on the contributions of many thousands of scientists working in laboratories all over the world.

Probably no symbol of recognition of the contri­butions made by scientists in this century has cap­tured the imagination of the public (or for those matter scientists themselves) as has the Nobel Prize, an award recognizing specific contributions in diverse fields of human endeavor. Many such awards in the fields of chemistry, physiology, and medicine have been made for contributions that bear directly on cell biology (see Table 1-1).

Nobel Prizes for cell biology-related contributions

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