Experimental Cell Research xxx (xxxx) xxx–xxx

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Experimental Cell Research

journal homepage: www.elsevier.com/locate/yexcr

An historical note on the cell theory

⁎
Domenico Ribattia,b,
a
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy
b
National Cancer Institute “Giovanni Paolo II”, Bari, Italy

A R T I C L E I N F O A B S T R A C T

Keywords: The development of the microscope was a precondition for the discovery of cells. This instrument magnifies
Cell theory objects too small to be seen by the naked eye. In 1673, the Dutch botanist, Anton van Leeuwenhoek, made a
History of medicine more advanced microscope and reported seeing a myriad of microscopic “animalcules” in water. He also made
Nucleus further studies of red blood cells and sperm cells. Most studies that followed were done on the easily studied
Pathology
plant tissues. Plant cells, rigidly encased in their cell walls, were ideal to study in situ. The cell theory proposes
that nucleated cells are the basic structure of plants and animals. This concept was observed and published
separately, first by the botanist, Matthias Schleiden, in 1838, and then by the zoologist, Theodor Schwann, in
1839. Their work demonstrated that cells form the basic unit of life of plants and animals. Rudolf Virchow
concluded that all living organisms are the sum of single cellular units and that cells multiply.

1. Background which he called animalcules (plants and animals), swimming in a drop

In 1665, an English botanist, Robert Hooke (1635–1702), at that
time first secretary of the Royal Society in London, in his book
“Micrographia Or Some Physiological Descriptions of Miniature Bodies
by Magnifying Glass” [1] coined the term ‘cell’ to indicate the micro-
scopic units in cork. With only thirty-times magnification, he saw a
pattern of tiny rectangular holes in a thin slice of cork from the bark of
an oak tree, and then saw a similar pattern in bones and plants. Hooke
examined very thin slices of cork and saw a multitude of tiny pore that
he remarked looked like the walled compartment of a honeycomb.
Because of this association, Hooke called them “cells” or “pores”. Fur-
ther, Hooke had observed that these “little boxes” contained a liquid,
which might possible go from one cell into the other and thus circulate.
However, because Hooke's observations were limited by the magnifying
power of his microscope, it was difficult for him to learn much about
the internal structure and organization of cells.
Anton van Leeuwenhoek (1632–1723) was a Dutch scientist, known
for his work on the development and improvement of the microscope.
Leeuwenhoek used double-convex lenses mounted between brass plates
and held close to the eye. He viewed objects on pinheads, magnifying
them up to 300 times this a lot better than any earlier compound mi-
croscopes. He made a powerful single-lens microscope with which he
observed many types of cells and tissues and even drew bacteria.
From investigating and experimenting with his microscope,
Leeuwenhoek became one of the first scientists to refer to living cells
when he observed an abundant number of single-celled organisms,
of pond water [2]. In 1674, van Leeuwenhoek saw for the first time red
blood cells, and spermatozoa. However, Leeuwenhoek's discoveries of
bacteria and spermatozoa were more or less ignored for many years.
Marcello Malpighi (1628–1694) and Hook's colleague Nehemiah
Grew (1641–1712) made detailed studies of plant cells and established
the presence of cellular structures throughout the plant body. Malpighi
in his paper “Anatome plantarum” published in 1671 [3], called cells
‘utriculi’ and ‘sacculi’. Grew in his book on “The Anatomy of Plants” [4]
used the words “bladders”, “cells” and “pores” indiscriminately, and
provided a number of illustrations of plant material which indicate that
he noticed the cellular structure.
2. The cell theory and their founders
Theodore Schwann (1810–1882) (Fig. 1) and Mattias Jacob
Schleiden (1804–1881) (Fig. 2) are considered the founders of the “cell
theory”. Schleiden, professor of Botany at Jena, formulated the theory
for plant cells, while Schwann generalized it to all living organisms,
animals as well as plants. Schleiden influenced the young Carl Zeiss
(1816–1888) to form his subsequently very important optical firm, the
fruits of which were much improved microscopes.
In 1833, Schleiden joined the laboratory of Johannes Peter Müller
(1801–1858) in Berlin. He sustained that organisms are made up of a
society of cells and focused his attention on their origin, using em-
bryonic plant tissue. He concluded that the cells developed de novo
from a mass of minute granules within the cell which form a nucleus

⁎
Correspondence to: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Policlinico - Piazza G. Cesare, 11, 70124 Bari, Italy.
E-mail address: domenico.ribatti@uniba.it.

https://doi.org/10.1016/j.yexcr.2018.01.038
Received 19 December 2017; Received in revised form 26 January 2018; Accepted 29 January 2018
0014-4827/ © 2018 Published by Elsevier Inc.

Please cite this article as: Ribatti, D., Experimental Cell Research (2018), https://doi.org/10.1016/j.yexcr.2018.01.038
D. Ribatti
Fig. 1. A port trait of Theodore Schwann. (From Wilkipidia).
Fig. 2. A port trait of Mattias Jacob Schleiden. (From Wilkipidia).
called “cytoblast” around the nucleolus, with subsequent progressive
enlargement of such condensed material to become a new cell [5].
Schleiden was wrong in regard to his notions concerning cellular
replication. His main theory in this regard was that new cells were
formed inside old ones from the nucleus. This interpretation which
Schleiden deduced from his preparations is the same as that of the
followers of the “endocytogenesis” theory postulating the formation of
a cell within another.
In 1831, Robert Brown (1773–1858), a Scotch botanist and physi-
cian discovered under a primitive compound microscope the cell nu-
cleus as an essential constituent of living cells. Brown was a naturalist
who visited the "colonies of Australia" from 1801 through 1805, where
he cataloged and described over 1700 new species of plants. Brown
observed that: “a single circular areola, generally somewhat more
opaque 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.” [6]
At that time, also Schwann was in Müller's laboratory as a medical
student. He reported that in October 1837, he was dining with dr.
Schleiden, who pointed out the important role that the nucleus plays in
the development of plant cells. Schwann recalled him to have a similar
organ in the cells of the notochord playing the same role as does the
nucleus of plants in the development of plant cells. Schwann described
nucleated cells of notochord and cartilage, in the larvae of toads, as well
as in the kidney, liver, pancreas, salivary glands, and connective tissue
of pig embryos. He published the results of these observations in three
articles in the January, February, and April 1838 issues of the Neue
Notizen aus dem Gebiete der Natur und Heilkunde [7]. In 1839,
Schwann became professor at the Catholic University of Louvain, and in
1848 at the University of Liege, Belgium.
While studying more closely peripheral nerves, Schwann first de-
scribed the membranous wrapping, produced by a specialized type of
cell, which envelops the prolongation of nerve cell. Schwann's name has
been associated with both the supporting cell and this membranous
sheath. Today, the term Schwann sheath has become obsolete, whereas
2
Experimental Cell Research xxx (xxxx) xxx–xxx
Fig. 3. A port trait of Robert Remak. (From Wilkipidia).
the name of Schwann cell, remains universally used.
Schwann considered that new cells originate in a structure less
substance which he called the Cytoblastema or Cytoblastem. He supposed
that this substance sometimes existed within the pre-existing cells, but
in animals it was usually extracellular. It was often fluid, but might also
be solid: the matrix of cartilage was an example of it. According to
Schwann: “The entire process of the formation of a cell consists of
precipitation, around an initially arising small body (nucleolus), of first
one (nucleus), and then, around it, a second layer (cell substance). The
different layers grow by intake of new molecules among those already
present, by intussusception, and this according to the law that the
precipitation is more pronounced in the outer parts of every layer …
Because of this law, only the outer part of every layer condensates into
a membrane (of the nucleus and of the cell).” [8]
Robert Remak (1815–1865) (Fig. 3) like Schwann and Virchow,
trained in Müller's laboratory at the University in Berlin. In 1852,
Remak summarized his early work on cell generation: “Since the pub-
lication of the cell-theory, it has seemed to me that the extracellular
creation of animal cells is as unlikely as the generation “aequivoca”
(spontaneous generation). These doubts have led to my observations on
the multiplication of blood cells by division in bird and mammalian
embryos (…) and the division of muscle bundles in frog larvae; then
finally in the spring of 1851, I succeeded in finding that all embryonic
cells multiply by division.” [9] He concluded: “These results are just as
closely related to pathology as they are to physiology (…) I venture to
suggest that pathological tissues are, like normal ones, formed not in an
extracellular cytoblastem but are the descendants or products of normal
tissues of the organism.”[9] According to Remak: “The division of the
cleavage cells starts from the nucleus and, when at the end of cleavage,
the nucleolus can be recognized from the latter … At the lower, white
half of the uninjured egg, one can observe by use of a magnifier, in the
last stages of cleavage, how the light spot representing the nucleus di-
vides into two spots, how those spots move away from one another, and
how the cleavage cell divides in a way that each half is furnished with a
light spot (nucleus) … Following cleavage, the cells begin to form an
embryo by separating themselves into three layers (a sensory, a mo-
toric, and a trophic one) and by proliferating within those layers
through division, thus creating the cells that serve as the basis of tis-
sues.” [9].
3. The epigones
Rudolf Virchow (1821–1902) (Fig. 4) received his medical degree in
1843. Although six years Remak's junior, the two were appointed to the
faculty in Berlin in the same year, 1847. In 1849, Virchow was ap-
pointed professor at Würzburg. He returned to Berlin seven years later,
again the victor in a competition with Remak, this time for the coveted
appointment to a new professorship of pathology. Virchow was not only
the most famous pathologist of the nineteenth century but also
throughout his working life a prominent left wing politician. He was at
the barricades in Berlin during the revolution of March 1848.
In 1849, Virchow wrote that: “The cell, as the simplest form of life-
D. Ribatti
Fig. 4. A port trait of Rudolf Virchow. (From Wilkipidia).
manifestation that nevertheless fully represents the idea of life, is the
organic unit, the indivisible living one.” [10]
In 1855, Virchow first published his idea that all cells arise from
other cell other cells: “omnis cellula e cellula” meaning that spontaneous
generation of living things from innominate matter does not occur. This
statement also helped to provide a basis for the idea of evolution as
presented by Charles Darwin a few years later and subsequent advances
in both cytology and medicine have tended to validate Virchow's opi-
nion.
In his text “Cellular Pathology” (Fig. 5), Virchow noted that: “What
Schwann, however, has done for histology, has as yet been but in a very
slight degree built up and developed for pathology, and it may be said
that nothing has penetrated less deeply into the minds of all than the
cell-theory in its intimate connection with pathology. …The chief point
in this application of histology to pathology is to obtain a recognition of
the fact, that the cell is really the ultimate morphological element in
which there is any manifestation of life, and that we must not transfer
the seat of real action to any point beyond the cell.” [11]
After introducing the concept of tissues, Virchow then discussed
epithelium followed by connective tissue, including cartilage and fat,
from this point he went on to enlarge on muscle, nerve, blood vessels
and blood, before entering into the nature of pathological change.
In 1858, Virchow gave the most adequate definition of cellular
pathology as follows: “Each disease originates from the alterations that
affect a smaller or larger number of cellular units within the living
organism; every pathological disturbance, every therapeutic effect can
only then ultimately have interpreted, when it is possible to tell which
particular group of living cellular elements is concerned, and which
kind of alterations each element of such a group has undergone. The
long searched for essence of disease is the altered cell."[11]
Fig. 5. The cover of “Die cellular pathologie” of Rudolf Virchow.
3
Experimental Cell Research xxx (xxxx) xxx–xxx
Fig. 6. A port trait of Oscar Herwtig. (From Wilkipidia).
In 1893, Oscar Hertwig (1849–1922) (Fig. 6), a German embryol-
ogist and cytologist who was the first to recognize that the fusion of the
nuclei of the sperm and ovum was the essential event in fertilization,
confirmed the cell theory in these terms: “Animals and plants, so di-
verse in their external appearance, agree in the fundamental nature of
their anatomical construction; for both are composed of similar ele-
mentary units, which are generally only perceptible under the micro-
scope. Through the influence of an old theory, now discarded, these
units are called cells, and thus the doctrine that animals and plants are
composed in an accordant manner of very small particles of this kind is
called the cell theory (…) the common life-process of a composite or-
ganism appears to be nothing else than the exceedingly complicated
result of its numerous and diversely-functioning cells.” [12] For
Hertwig, embryonic development served as a mechanistic element
capable of explaining the process of evolution, an influence doubtless
inherited from his former instructor.
4. The impact of the cell theory for current and prospective
The collective observations of Schleiden, Schwann, and Virchow
form the cell theory, which states that all organisms are made up of one
or more cells; all the life functions of an organism occur within cells; all
cells come from preexisting cells. The cell theory is one of the main
principles of biology, based on observations that over many years up-
held the basic conclusions of Schwann's 1839 paper. However, one of
Schwann's original conclusions stated that cells formed in a similar way
to crystals. This observation, which refers to spontaneous generation of
life, was discounted when Virchow proposed that all cells arise only
from other cells.
A modern version of cell theory adds a few other tenets to the ori-
ginal postulated by Schleiden and Schwann: the cell has hereditary
information (DNA) that is passed on from cell to cell during re-
production; all cells have virtually the same chemical composition and
metabolic activities; all the cell's basic chemical and physiological
functions are carried out inside the cell itself; and cellular activity is
dependent on the activities of structures within the cell, such as the
organelles, or nucleus.
Almost in all fields of biology, we need some knowledge of cell and
cell theory. It has applications in medicine, evolution, microbiology,
taxonomy. The basic structures of the cells are studied under the cell
theory and in total, it covers the entire courses about cellular structures
as well. In our study of genetic systems, we make use of simpler or-
ganisms which is easier to grow and easily available. Then we use the
results inferred for some higher or more complex organism. This is so
because of a principle in cell theory which says that all cells have same
chemical machinery.
By understanding how cells work in healthy and diseased states, cell
biologists working in animal, plant and medical science will be able to
develop new vaccines, more effective drugs, plants with improved
qualities and through increased knowledge a better understanding of
how all living things live.
D. Ribatti
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