Hints at the idea that the cell is the basic component of living organisms emerged well before 1838-39, which was when the cell theory was officially formulated. Cells were not seen as undifferentiated structures. Some cellular components, such as the nucleus, had been visualized, and the occurrence of these structures in cells of different tissues and organisms hinted at the possibility that cells of similar organization might underlie all living matter.
The abbot Felice Fontana (1730-1805) glimpsed the nucleus in epithelial cells in 1781, but this structure had probably been observed in animal and plant cells in the first decades of the eighteenth century7, 10. The Scottish botanist Robert Brown (1773-1858) was the first to recognize the nucleus (a term that he introduced) as an essential constituent of living cells (1831). In the leaves of orchids Brown observed "a single circular areola, generally somewhat more opake than the membrane of the cell... This areola, or nucleus of the cell as perhaps it might be termed, is not confined to the epidermis, being also found not only in the pubescence of the surface... but in many cases in the parenchyma or internal cells of the tissue"11. Brown recognized the general occurrence of the nucleus in these cells and apparently thought of the organization of the plant in terms of cellular constituents.
Meanwhile, technical improvements in microscopy were being made. The principal drawback of microscopes since van Leeuwenhoek's time was what we now call 'chromatic aberration', which diminishes the resolution power of the instrument at high magnifications. Only in the 1830s were achromatic microscopes introduced, allowing more precise histological observations. Improvements were also made in tissue-preservation and -treating techniques.
In 1838, the botanist Matthias Jakob Schleiden (1804-1881) suggested that every structural element of plants is composed of cells or their products12. The following year, a similar conclusion was elaborated for animals by the zoologist Theodor Schwann (1810-1882). He stated that "the elementary parts of all tissues are formed of cells" and that "there is one universal principle of development for the elementary parts of organisms... and this principle is in the formation of cells"13. The conclusions of Schleiden and Schwann are considered to represent the official formulation of 'cell theory' and their names are almost as closely linked to cell theory as are those of Watson and Crick with the structure of DNA4, 14.
According to Schleiden, however, the first phase of the generation of cells was the formation of a nucleus of "crystallization" within the intracellular substance (which he called the "cytoblast"), with subsequent progressive enlargement of such condensed material to become a new cell. This theory of 'free cell formation' was reminiscent of the old 'spontaneous generation' doctrine (although as an intracellular variant), but was refuted in the 1850s by Robert Remak (1815-1865), Rudolf Virchow (1821-1902) and Albert K?lliker (1817-1905) who showed that cells are formed through scission of pre-existing cells7. Virchow's aphorism omnis cellula e cellula (every cell from a pre-existing cell) thus became the basis of the theory of tissue formation, even if the mechanisms of nuclear division were not understood at the time.
Cell theory stimulated a reductionistic approach to biological problems and became the most general structural paradigm in biology. It emphasized the concept of the unity of life and brought about the concept of organisms as "republics of living elementary units"7.
As well as being the fundamental unit of life, the cell was also seen as the basic element of pathological processes. Diseases came to be considered (irrespective of the causative agent) as an alteration of cells in the organism. Virchow's Cellularpathologie was the most important pathogenic concept until, in this century, the theory of molecular pathology was developed.
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