Course code: BIO205

Course Title: Introductory Molecular Biology

1.0 The cell theory

- The cell theory, or cell doctrine, states that all organisms are composed of similar units of

organization, called cells.

- The idea predates other great paradigms of biology including

i. Darwin’s theory of evolution (1859),

ii. Mendel’s laws of inheritance (1865), and

iii. The establishment of comparative biochemistry (1940).

1.1 Pre- 1838/1839 Cell visualization

Before cell theory was formally propounded in 1839,

- 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.

i. 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 century.

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 ii. In 1831, the Scottish botanist Robert Brown (1773-1858) was the first to recognize

the nucleus as an essential constituent of living cells.

1.2 Formulation of the Cell Theory

- In 1838, Matthias Jakob Schleiden (1804-1881; botanist) and Theodor Schwann

(1810–1882; zoologist) had a conversation about their studies on cells during a coffee

break.

- When Schwann heard Schleiden describe plant cells with nuclei, he was struck by the

similarity of these plant cells to cells he had observed in animal tissues.

- Immediately, both scientists went to Schwann’s lab to look at his slides.

- Later in 1838, the botanist M. J. Schleiden suggested that every structural element of

plants is composed of cells or their products.

- In 1839, a similar conclusion was elaborated for animals by the zoologist Schwann

published his book on animal and plant cells (Schwann, 1839) the following year, a

treatise devoid of acknowledgements of anyone else’s contribution, including that of

Schleiden (1838).

- Schwann 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”.

- He summarized his observations into three conclusions about cells:

i. The cell is the unit of structure, physiology, and organization in living things.

ii. The cell retains a dual existence as a distinct entity and a building block in the

construction of organisms.

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 iii. Cells form by free-cell formation, similar to the formation of crystals (spontaneous

generation). This theory of ‘free cell formation’ was reminiscent of the old ‘doctrine of

spontaneous generation.

- 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 DNA.

1.3 Refutation of the theory of ‘free cell formation’

- In the 1850s, Robert Remak (1815-1865), Rudolf Virchow (1821-1902) and Albert

Kölliker (1817-1905) showed that cells are formed through the division of pre-existing

cells.

- However, the correct interpretation of cell formation by division was formally

articulated by Rudolph Virchow’s powerful dictum, Omnis cellula e cellula: “All cells

only arise from pre- existing cells” published in Cellular Pathology (1858).

- This became the basis of the theory of tissue formation, even though the mechanisms of

nuclear division were not understood at the time.

1.4 Protoplasmic constituents

- After Schleiden and Schwann’s formulation of cell theory, the basic constituents of the

cell were considered to be a wall or a simple membrane, a viscous substance called

‘‘protoplasm’’ (a name now replaced by Kölliker’s term ‘‘cytoplasm’’), and the nucleus.

- It soon became evident that the protoplasm was not a homogeneous fluid.

- Some biologists regarded the fine structure of protoplasm as fibrillary, whereas others

described a reticular, alveolar or granular protoplasmic architecture.

staining procedures that caused non-homogeneous precipitation of colloidal complexes.

- However, some staining of real cellular components led to the description of

differentiated elements, which were subsequently identified.

- In 1870, the introduction of the oil immersion lens, the development of the microtome

technique and the use of new fixing methods and dyes greatly improved microscopy.

- Towards the end of the 19th century, the principal organelles that are now

considered to be parts of the cell were identified.

o The term ‘‘ergastoplasm’’ (endoplasmic reticulum) was introduced in 1897;

o In 1898, mitochondria were observed by several authors and named by Carl

Benda (1857–1933),

o Also in 1898, Camillo Golgi (1843-1926) discovered the intracellular apparatus

that bears his name.

- The protoplasm was not the only structure to have a heterogeneous appearance.

o Within the nucleus, the nucleolus and a stainable substance could be seen.

o Moreover, several structures (ribbons, bands and threads) appeared during cell

division.

o As these structures could be heavily stained, they were called ‘‘chromatin’’ by

Walther Flemming (1843-1905)

o In 1882, Walther Flemming also introduced the term ‘‘mitosis’’ and gave a

superb description of its various processes.

o In 1888, Wilhelm Waldeyer (1836-1921) introduced the word chromosomes.

o Flemming observed the longitudinal splitting of salamander chromosomes

during metaphase and established that each half chromosome moves to the

opposite pole of the mitotic nucleus. This process was also observed in plants,

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 providing further evidence of the deep unity of the living world.

1.5 The neuron theory

- The nervous tissue, however, seemed to contradict cell theory.

- Because of its softness and fragility, it was difficult to handle and susceptible to

deterioration.

- But it was its structural complexity that prevented a simple reduction to models derived

from the cell theory.

- Nerve-cell bodies, nervous prolongations and nerve fibres were observed in the first half of

the 19th century.

- However, attempts at reconstructing a three-dimensional structure of the nervous system

were frustrated by the impossibility of determining the exact relationships between body

cells (somas), neuronal protoplasmic processes (dendrites) and nerve fibres.

- A book by Karl Deiters (1834–1863), published posthumously in 1865, contains

beautiful descriptions and drawings of nerve cells studied by using histological methods

and microdissections made with thin needles under the microscope.

- Deiters’s nerve cells were characterized by a soma, dendrites and a nerve

prolongation (axon) which showed no branching.

- Kölliker, in the fifth edition of his important book on histology, published in 1867,

proposed that sensory and motor cells of the right and left halves of the spinal cord were

linked “by anastomoses” (direct fusion).

- In 1872, the German histologist Joseph Gerlach (1820–1896) expanded Kölliker’s

view.

- Joseph Gerlach proposed that, in all the central nervous system, nerve cells

established anastomoses with each other through a network formed by the minute

branching of their dendrites.

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 The black reaction

- In 1873, Golgi developed the ‘black reaction’ considered the most important

breakthrough in Neurocytology and Neuroanatomy.

o He demonstrated the structure of the interstitial stroma of the cerebral cortex by

reacting silver nitrate with pieces of brain hardened in potassium dichromate.

o A precipitate of silver chromate randomly stains black only a few cells (usually

about 1 - 5%), and completely spares the others, allowing individual elements

to emerge from the nervous puzzle.

o For the first time, this reaction provided a full view of a single nerve cell and

its processes.

o Golgi’s network theory was, however, a substantial step forward because it

emphasized, for the first time, the function of branched axons in connecting

nerve cells.

- At the beginning of 1887, similar conclusions were reached by another Swiss scientist,

the psychiatrist August Forel (1848-1931).

- In 1891, Waldeyer introduced the term ‘‘neurons’’ to indicate independent nerve cells.

- Thereafter, cell theory as applied to the nervous system became known as the ‘neuron

theory

1.6 Modern Cell Theory

i. All known living things are made up of cells.

ii. The cell is the structural & functional unit of all living things.

iii. All cells come from pre-existing cells by division. (Spontaneous Generation does not

occur).

iv. Cells contain hereditary information which is passed from cell to cell during cell

division.

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 v. All cells are basically the same in chemical composition.

vi. All energy flow (metabolism & biochemistry) of life occurs within cells.

1.7 Significant Dates in Cell Biology

There have been several significant events throughout history that have led to the development

of the field of cell biology as it exists today. Below are a few of these major events:

- 1655: Robert Hooke gives first description of a cork tree cell.

- 1674: Leeuwenhoek views protozoa.

- 1683: Leeuwenhoek views bacteria.

- 1831: Robert Brown was first to identify the nucleus as an important cell component.

- 1838: Schleiden and Schwann introduce what would become the Cell Theory.

- 1857: Kolliker describes mitochondria.

- 1869: Miescher isolates DNA for the first time.

- 1882: Kock identifies bacteria.

- 1898: Golgi discovers the Golgi apparatus.

- 1931: Ruska builds the first Transmission Electron Microscope.

- 1953: Watson and Crick propose structure of DNA double-helix.

- 1957: Meselson, Stahl and Vinograd developed density gradient centrifugation in

cesium chloride solutions for separating nucleic acids.

- 1965: First commercial Scanning Electron Microscope produced. Ham introduced a

defined serum-free medium.

- 1976: Sato and colleagues published different cell line that required different

mixtures of hormones and growth factors in serum free media.

- 1981: Transgenic mice and fruit flies were produced. Mouse embryonic stem cell line

was established.

- 1995: Tsien identified mutant GFP with enhanced spectral properties

- 1998: Mice cloned from somatic cells

- 1999: Hamilton and Baulcombe discovered siRNA as part of posttranscriptional gene

silencing (PTGS) in plants

- 2003: Human genome DNA sequence draft completed.

- 2006: Adult mouse skin cells reprogrammed into induced pluripotent stem cells (iPS).

- 2010: Neurons, cardiac muscle, and blood cells created directly from reprogrammed

adult cells.

Further reading:

Mazzarello, P. (1999). A unifying concept: the history of cell theory. Nature Cell Biology, 1(1),

E13-E15.