Nowadays we agree that organisms are made up of cells, but reaching this conclusion was a long way. The size of most cells is less than the resolving power of the human eye, which is approximately 200 micrometers (0.2 mm). The resolving power is the ability to distinguish two close points. Therefore, to observe cells it was necessary the invention of devices with higher resolving power than the human eye. This device was the light microscope. Light microscopes use visible light and glass lenses to increase the resolution power. The maximum resolving power of light microscopes is 0.2 microns, a thousand times higher than that of the human eye. But, even with the help of light microscopes, it took a long time to realize that cells were the units that make up all living organisms. This was due to the diversity of cell shapes and sizes, and also to the poor quality of the lenses that were part of the light microscopes crafted at that time. Another issue was the lack of histological techniques to process and study animal and plant tissues.
The ancient Greeks proposed that matter is divided into very small units. Leucippus and Democritus wrote that matter is composed of small parts named atoms (without parts), which can no longer be divided. However, others, such as Aristotle, defended a continuity of the matter, with no empty spaces. Up to the 18th century, when scientists and philosophers discussed about both living and non-living matter, they supported the theory of atoms or the theory of the continuity of matter.
The history of the discovery of the smallest units of which living organisms are made up is the history of the discovery of the cell. It began when glass lenses and the devices to hold them were first crafted; in other words, it began with the invention of light microscopes at the beginning of the 17th century. From the time of the first microscopic observations to the present day, the concept of cell has evolved under the strong influence of the development of microscopes, therefore with the improvement of technology. It is curious, however, that the purpose of the first lenses and microscopes was to verify the quality of fabrics, not to study living organisms.
The following are some of the most important advances and concepts in the history of the discovery of the cell:
2. XVII century
1590-1600. A. H. Lippershey, Z. Janssen and H. Janssen (father and son). They are credited with the invention of the first compound microscope. Two magnifying lenses were placed on each side of a tube. The development of this device and the lens quality improvement would later allow the visualization of cells.
1610. Galileo Galilei described the insect cuticle. He transformed a telescope into a microscope by changing the positions of the lenses. So, he independently invented the compound microscope (he did not know about Janssen's work). 1625. Francesco Stelluti described the surface of the bee body. By that time, only surfaces were observed, but not tissue sections.
1644. J. B. Odierna studied and described the first dissections of animals.
1664. Robert Hooke (physicist, meteorologist, biologist, engineer, and architect) published a book entitled Micrographia, which describes the first evidence for the existence of cells. He studied the cork and observed an arrangement of plant tissue resembling a honeycomb. Each little compartment was given the name of cell, but he was not aware that this cell (from the Latin “cella”: small room) was something like what we know today as a cell. Actually, he believed that these cavities were places where plant nutrients were transported. Although, he did not realize that those cells were the functional units of living things, the word cell was kept to name the little chambers present in every plant, and then it was used to name the little units also found in animals.
1670-1680. N. Grew and M. Malpighi studied many species of plants and described a similar microscopic organization for all of them. In the same way as R. Hooke, N. Grew described plant tissues, but the little chambers were regarded as fermentation bubbles (as in bread). He introduced the name parenchyma for some plant tissues and made many drawings about the organization of plant tissues. M. Malpighi gave names to many plant structures such as trachea (due to its similarity to the trachea of insects). He also worked on animal tissues and studied the capillary network, but these were very rudimentary studies. These authors established the detailed microscopic organization of plants. However, they still did not pay much attention to the cells, which looked like simple air chambers.
As a curiosity, unlike Malpighi, who thought that cells were isolated spaces, Grew proposed that the cavities of the cells were like the spaces left by threads. Thus, Grew compared microscopic organization of plant tissues with that of fabrics. It has been suggested that this misunderstanding led to the incorrect choice of "tissue" as a name to define cells plus extracellular matrix in organisms. A similar misunderstanding kept the name "cell" to define the functional and anatomical unit of living organisms.
By that time, the lenses were of very poor quality, with large chromatic aberrations, and microscopists used to put a lot of imagination in their descriptions. In this way, Gaurtier d'Agoty saw fully formed children in the head of a sperm cell, the homunculus. However, there was steady progress during this period in lens crafting, which resulted in greater definition and higher resolving power of the microscope. J. Huddle (1628-1704) was a very good lenses maker, and he taught A. van Leeuwenhoek and J. Swammerdam how to make high quality lenses.
It is thought that the animal cells were first observed under the light microscope around 1673. They were blood cells. However, it is not known wether it was Malpighi, Swammerdan or Leeuwenhoek.
1670. A. van Leeuwenhoek crafted simple microscopes, with a single lens, but with a perfection that allowed him to reach magnifications higher than 270 times, more than what compound microscopes could offer at that time. He can be regarded as the founder of microbiology because he was the first to report on descriptions of bacteria and unicellular organisms. He wrote many articles about his observations on biological samples, more detailed than anyone before. He observed drops of water, blood, semen, hairs, and many more. He thought that all animals are made up of multiple units, but failed to associate these units with the cells of plants. Leeuwenhoek had described animal cells as "animalcules". Even after detailed microscopic studies of animal tissues, many years passed before animal and plant cells were considered similar structures.
3. XVIII century
1757. Von Haller said that animal tissues are made up of fibers.
1759. The first attempt to put animals and plants at the same level was made by C.F. Wolf, who said that there is a fundamental unit with globular shape in all living organisms. This unit would be globular at first, as in animals, then hollow, and later filled with sap, as in plants. He also said that the growth of the body of living organisms would occur by adding new cells. However, it is possible that what he observed with his microscopes were mostly artifacts, and even so, he made these remarkable statements. In his work Theoria generationis he claimed that living organisms are formed as a result of progressive development and body structures would appear by growth and differentiation of less developed structures. This theory was contrary to another very popular theory at that time: the preformationist theory, which suggested that a complete organism was already present inside the gametes, i.e. a fully developed tiny body was present in each gamete that would accomplish the adult stage only by increasing the size of each part.
1792. L. Galvani discovered the electric nature of muscle contraction.
1827. G. Battista Amici corrected many lens aberrations, allowing much better microscopes.
4. XIX century
1820-1830. The development of the cell theory started in France with H. Milne-Edwards and F.V. Raspail. They observed a large variety of tissues from different animals and reported that the tissues were composed of globular, but unevenly distributed units. Plants were also regarded as having these units and also gave these vesicles a physiological role. R.J.H. Dutrochet, French too, wrote if one compares the extreme simplicity of this striking structure, the cell, with the extreme diversity of its content, it is clear that it is the basic unit of an organized entity. Actually, everything is ultimately derived from the cell. He studied many animals and plants, and came to the conclusion that the cells of plants and the globules of animals were the same thing, but with different morphology. He also proposed some physiological functions for these units and suggested that cells are born inside other cells (not agreeing with the spontaneous generation theory). F.V. Raspail, a French chemist, proposed that each cell is like a laboratory that allows the organization of tissues and organisms. He thought that each cell, like Russian dolls, contained many small vesicles that could grow and be released as independent cells. He even suggested that cells could have sex (mostly hermaphrodite). Finally, he said, and not R. Virchow, "Omnis cellula e cellula", that is, every cell comes from another cell.
1831. R. Brown described the cell nucleus. This is rather controversial because in a letter reported by Leeuwenhoek in 1682, he described a rounded structure inside red blood cells of fish. This structure could not be anything else but the nucleus. However, he did not name it. Furthermore, in 1802, F. Bauer, from the Czech Republic, described a cell structure very similar to the cell nucleus. Much later, M.J. Schleiden proposed that all cells contain a nucleus.
1832. B. Dumortier described binary division in plant cells. He reported the synthesis of new cell wall between the two new cells and proposed that this mechanism was the way cells proliferate. Thus, he refused other theories about cell proliferation such as those saying that cells appear inside other preexisting cells, such as Russian dolls, or those proposing spontaneous generation.
1835. R. Wagner described the nucleolus.
1837. J. Purkinje, from Czech Republic, one of the best histologist at that time, suggested not only that animal tissues were made up of cells but also that animal tissues were analogous to plant tissues.
1838. M. J. Schleiden, a German botanist, wrote the first axiom of the cell theory for plants (he did not study animal tissues). That is, all plants are made up of units named cells. The German physiologist T. Schwann, in his book Mikroscopische Untersuchungen, extended this concept to animals and later to all living organisms. He went beyond by saying that animals and plants follow the same basic mechanisms.
T. Schwann described cells as units surrounded by a membrane. He actually did not observe the "real" membrane of the cells. Two years before, H. Dutrochet had been suggested the presence of a membrane after his studies about osmosis. The membrane described by T Schwann, and M.J. Schleiden, actually was the cell wall plus the cortical cytoplasm of plant cells. That is why they wrongly stated that the nucleus was located inside the cell "membrane". T. Schwann went further and proposed that this "membrane" functions as a barrier to separate the internal from the external environment, which has been proven to be correct, but for the "real" cell membrane.
Although the German school, T. Schwann and M.J. Schleiden, has been recognized for the development of the cell theory statements, there are at least four researchers who wrote similar statements years before: Oken (1805), Dutrochet (1824), Purkinje (1834) and Valentin (1834). Dutrochet stood out among the other researchers. There is a rumor that T. Schwann knew about the Dutrochet's papers and "borrowed" some ideas. T. Schwann and M.J. Schleiden also agreed with cells emerging from the interior of other cells, but this was showon to be incorrect.
1839-1843. F. J. F. Meyen, F. Dujardin and M. Barry connected and unified different branches of biology to show that individual protozoa are nucleated cells similar to those that make up animals and plants, and they also proposed that the continuous cell lineages are the basis for life. Thus, the evolutionary history of living beings could be represented in a single tree of life in which plants, animals, fungi and unicellular organisms were interconnected.
1839-1846.J.E. Purkinge and H. van Mohl independently proposed the name protoplasm for the cell content (excluding the nucleus) of plant cells. Dujardin (1835) previously called it sarcode by for animal cells. It was F Cohn (1850) who realized that protoplasm and sarcode were the same thing. Studying plant and animals at same level was not common at that time. Because plant cells showed a cell "membrane" (remember that this "membrane" was the cell wall plus cortical cytoplasm) but it could not be observed in animal cells, the living matter of cells thought to be the protoplasm. N. Pringsheim (1854) proposed that protoplasm is the living part of plants. At that times, most researchers agreed that living force was contained in the protoplasm so that the cell membrane disappeared as a fundamental component of the cell. This was reasonable because the cell membrane can not be seen with the light microscope.
1856. R. Virchow wrote "The cell, as the simplest form of life-manifestation that nevertheless fully represents the idea of life, is the organic unity, the indivisible living one". By mid-nineteenth century this theory was widely accepted.
1879. W. Flemming described the chromosome segregation and proposed the name mitosis.
1899. C.E. Overton suggested that the interface between the protoplasm and the extracellular space was lipidic. Based on osmosis and lipid diffusion experiments, he proposed the existence of a thin layer of lipids lining the protoplasm.
5. XX century
1932. The electron microscope appeared. It was invented in Germany by M. Knoll and E. Ruska, and developed during the thirties and forties of the XX century. The light microscope uses visible light, but its wavelength cannot discriminate two points that are closer than 0.2 micrometers. Electron microscopy is able to study cell structures that are as small as several nanometers (10-3 micrometers). The existence of the plasma membrane, and other inside the cell, was confirmed. It was the first time that membranes could be observed. With the help of the electron microscope, it was shown the interior of the eukaryotic cell is complex and rich in compartments. By 1960, the cell ultrastructure had already been studied and described.
Cavalier-Smith, T. 2010. Deep phylogeny, ancestral groups and the four ages of life. Philosophical transactions of the Royal Society B. 365: 111-132
Harris, H. 2000. The birth of the cell. Yale University Press. ISBN-10: 0300082959.
Hook, R. Micrographia. 1664. Read it at US National Library of Medicine.
Ling, G. 2007. History of the membrane (pump) theory of the living cell from its beginning in mid-19th century to its disproof 45 years ago - though still taught worldwide today as established truth. Physiological chemistry and physics and medical NMR 39: 1–67.