Monday, 3 November 2025

There be cells: tracing the history of the cell.

The most fundamental thing in biology is the cell. Nothing researched in biology makes complete sense without the cell. Yet this basic unit of life cannot be seen by the human eye and even viewed though the aid of a microscope, nothing about it at first glance gives much indication of how significant it is. So exactly did we find the cell and work out its significance?

Well, it all begins back in the 1600s.

The first time a cell was ever seen was by Robert Hooke.

A painting of a person sitting at a desk

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Robert Hooke, 1680. 

 

Microscopes had been invented in about 1620 and in 1665, Hooke looked though a compound microscope, a simple act that had huge ramifications. 

A compound microscope uses two lens - an eyepiece and objective lens. The objective lens forms a magnified image which is then magnified further by an eyepiece lens. This gives much higher magnification than a simple microscope, using one lens, can give. Compound microscopes are still used in optical microscopes today, although with a much higher magnification than what was possible at the time. Remember, microscopes were not initially designed for cells- they were designed just for magnification.  No one had any idea how important microscopes would ultimately be.

 

 

 

 

A diagram of a lens

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How a compound microscope works. 

 

Hooke initially started with mundane human objects; he discovered tiny pores in thin slices of bottle cork and named them 'cells'. This after the latin word 'cella' which means 'small room' - used to describe the living quarters of monks, and also 'cellulae', meaning the sixth-sided cell of a honeycomb.

 

A close up of a beehive

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Hooke was reminded of honeycombs when looking though his microscope. 

 

 Hooke then looked at microorganisms - specifically the micro-fungus Mucor. His microscope - handcrafted and tooled in leather and gold can still be seen in Maryland.  Whilst beautiful, leather and gold are not practical tools for modern microscopes!

A close-up of a microscope

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Hooke's microscope. 

 

Hooke made drawings of what he saw and had them published in 'Micrographia'. This was the first book to have illustrations of insects and plants seen through microscope. This publication inspired mass interest in the new field of microscopy. Samuel Pepys called the book 'the most ingenious book that ever I read in my life'. It is rather strange to think that cells, one of the most important and essential aspects of biology, were discovered a year before the Great Fire of London. For context, many people in this time could still remember the beheading of Charles I! 

Hooke was not able to see any internal components of the cells- like nuclei and had no clue that these' cells' were alive. The magnification needed for this was not advanced yet and it would take a few more developments in microscopy before that was possible. In fact, being able to include that cells were indeed alive happened in Hooke's lifetime. 

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Robert Hooke's drawing of 'cells' in cork. 

 

Less than 10 years after the publication of Micrographia in 1665, Anton van Leeuwenhoek, was able to take advantage of the improvements in microscopes.  In 1676, Leeuwenhoek became the first to notice that the cells were moving- and therefore must be alive. He described many forms of microorganisms, which he named 'animalcules'. He saw bacteria and protozoa, a type of single-celled organism that feeds on organic matter.  He was also able to accurately describe red blood cells. Crucially though, he was the first to see sperm cells of humans and animals and saw that reproduction would require the sperm cell to enter the egg. This allowed for the prevailing theory of spontaneous generation to be put to rest.  Hooke confirmed his observations.  This was also the first time that cells in animal tissues could be seen- they are much more fragile than plant cells.  

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Antonie van Leeuwenhoek, after 1680

 

Moving onto 1804, Karl Rudolphi and Johann Heinrich Friedrich Link were able to prove that cells had independent walls. This suggested that cells were separate and distinct units; this laid the groundwork for the idea that organisms are composed of separate structural units. 

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Karl Rudolphi

 

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Johann Heinrich Friedrich Link. 

 

 

In 1824, Henri Dutrochet was the first to suggest that the cells were physiological units and that they were a fundamental element to the organisation of an organism. Henri Dutrochet was also the first to come up with the process of Osmosis; how water moves across a membrane. This theory is vital in understanding the physiological processes in cells, giving further information on how cells actually operate. 

 

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Henri Dutrochet 

 

The work of these scientists all came together and allowed Theodor Schwann and Matthias Jakob Schleiden, with contributions from Rudolf Virchow to devise 'cell theory' in 1839. This theory suggested that every structural aspect of a plant and an animal were either made up of cells or resulting from cells. This also allowed them to include that the cell was the most basic unit of life.

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Theodor Schwann

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Matthias Jakob Schleiden 

 

 

In 1855, Rudolf Virchow was able to add to cell theory that all cells arise only from cells already existing. This had first been proposed by Robert Remak in 1852 who also suggested that binary fission was how animal cells reproduced. This marked the completion of classical cell theory. 

 

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Rudolf Virchow

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Robert Remak 

 

 

 

Of course, further discoveries that altered classical cell theory would be made later. However, classical cell theory altered biology for the better. It became clear that to understand life, scientists could no longer look at whole organisms or tissues and instead look deeper- the cell.  Looking closely at the cell gave rise to cellular physiology and also gave rise to modern biochemistry.

For example, in 1877, Wilhelm Pfeffer was able to propose the membrane theory.  This was gradually developed over time, with Ernst Overton suggesting that the cell membrane was made of lipids in 1899. In 1904, David Nathansohn added to this by suggesting the mosaic theory and Wilhelm Ruhland refined the mosaic theory to include pores in the cell membrane. Leonor Michaelis was then able to conclude the role of ions and demonstrated the membrane potential. All of this work was key in understanding how nerves and muscles work, as well as how cells transport vital minerals, vitamins and nutrients. This ultimately led to the first alteration of classical cell theory to modern; biochemical reactions and metabolic reactions occur within cells. It also became possible to add a second alteration; the activity of an organism depends on the total activity of independent cells. 

A diagram of a cell structure

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The mosaic model.

 

The discoveries that altered classical cell theory and turned it to 'modern' cell theory also revolved around DNA. In 1869, Friedrich Miescher first identified what was ultimately DNA. He discovered a microscopic substance that resided in nuclei - he called it nuclein. 

A person in a suit

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Friedrich Miescher 

 

In 1878, Albrecht Kossel isolated nucleic acid from nuclein and isolated its nucleobases- adenine, thymine, cytosine, guanine, and also uracil. In 1909, Phoebus Levene identified the base, sugar and phosphate nucleotide unit of 'yeast nuclei acid' -or as we know it; RNA. 

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Albrecht Kossel

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Phoebus Levene 

 

In 1927, Nikolai Koltsov suggested a 'giant hereditary molecule'. At this stage, he wasn't sure what this hereditary molecule actually was. It was Frederick Griffith in 1928 that came up with the first suggestion that it could be DNA carrying genetic information. 

 

 

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Nikolai Koltsov 

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Frederick Griffith

 

 

In 1929, Levene identified deoxyribose sugar in DNA and suggested it consisted of four nucleotide units linked together through phosphate groups.

In 1933, Jean Brachet suggested that DNA was found in the cell nucleus, with RNA in the cytoplasm. In 1943, Oswald Avery, Colin Macleod and Maclyn McCarthy devised the transforming principle, suggesting how bacteria are capable of transferring genetic information. 

 

A person holding a microscope

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Jean Brachet

 

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Oswald Avery

 

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Colin MacLeod

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Maclyn McCarty

 

By 1951, Alec Todd suggested how the backbone of DNA is structured, which played a crucial role in the work of Franklin, Wilkins, Watson and Crick. In May 1952, photograph 51 was born and in 1957, Crick devised the central dogma describing the flow of genetic information. In simple terms; DNA makes RNA and RNA makes proteins. 

 

A person in a suit and tie

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Alex Todd 

 

In 1958, the Meselson-Stahl experiment was done. In the same year, the discovery of codons allowed for Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenburg to decipher the genetic code. Codons are the triplet DNA bases that give specific amino acids. 

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Har Gobind Khorana

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Robert W. Holley

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Marshall Warren Nirenberg, 2002

 

With this, the molecular age of cell biology had officially began--and this led to some more adjustments to cell theory. The modern theory, still in play, now has seven tenants:

1.All known living things are made up of one or more cells.

2.The cell is the basic unit of organisation and function - all the vital functions of an organism occur within cells; including metabolism, energy, and DNA synthesis 

3.All living cells arise from pre-existing cells; cells have to divide which requires replication of DNA.

4.Cells contain DNA which is found specifically in the chromosome and RNA which is found in the cell nucleus and cytoplasm. 

5.All cells are similar in chemical composition and metabolic processes; including proteins, lipids, carbohydrates and biochemical pathways.

6.Specialised organelles-such as the nucleus, mitochondria, and ribosomes, perform distinct and essential functions with the cell.

7.Energy flow- metabolism and biochemistry occurs within cells. Cells are the site of energy transformation essential for life. 

This modern theory of cells was almost three hundred years in the making, starting with Robert Hooke in 1665, and being altered against in 1958.  Hooke's simple act of looking though a microscope can be said to have changed almost everything about biology - and it may still do so. Discoveries about cells and DNA are still being made on an almost daily basis. In another three hundred years, could more tenants be added and adjustments be made to the modern cell theory?  

 


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