The history of microscopy and the cell theory – Microscopy (Senior 4 Biology) | Ganzaa

Microscopy

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Senior 4 · Biology

Microscopy

4 lessons

Lesson 1 of 4

The history of microscopy and the cell theory

20 min

A letter the Royal Society did not believe

On 9 October 1676 a cloth merchant from Delft in the Netherlands, Antonie van Leeuwenhoek, sent the Royal Society in London a long letter. In water in which he had soaked peppercorns, he reported, swam living creatures far too small to be seen with the naked eye. He called them "little animals"; we call them microorganisms. Nobody had seen such things before, and the Society's members were doubtful. Only after a group of respected witnesses in Delft had looked through his lenses and confirmed what he described were his observations accepted, in 1677.

Every big step in cell biology has followed a step in the instruments that let people see. This lesson follows that history, from single glass beads to beams of electrons, and shows how it produced the cell theory.

Definition

Simple microscope: a microscope with a single lens, such as a hand lens or Leeuwenhoek's tiny glass-bead lenses.

Compound microscope: a microscope with two lens systems, an objective lens near the specimen and an eyepiece lens near the eye; the total magnification is the product of the two.

Magnification: how many times larger the image is than the real object.

Resolution (resolving power): the smallest distance between two points that can still be seen as two separate points. The smaller this distance, the more detail the microscope shows.

Cell theory: all living organisms are made of one or more cells; the cell is the basic unit of structure and function of life; and all cells arise from pre-existing cells.

From lenses to the cell theory

Figure 1 places the main events on a scale of years. Notice the long gaps: progress waited each time for a better instrument.

Early compound microscopes (1590s onward). Spectacle-makers in the Netherlands put two lenses in a tube. The images were blurred and edged with false colours, because simple glass lenses bend different colours of light by different amounts (chromatic aberration).
Robert Hooke (1665) published Micrographia, with large, careful engravings of a flea, a louse and the honeycomb of tiny boxes in cork, which he called "cells". He was seeing the empty walls of dead plant cells.
Antonie van Leeuwenhoek (letters from 1673) made single-lens microscopes, each little more than a brass plate holding one tiny, high-quality glass lens. A good small lens gave a sharper image than the compound microscopes of his day. He was among the first to describe bacteria, single-celled protoctists and sperm cells.
Matthias Schleiden (1838, plants) and Theodor Schwann (1839, animals) concluded that all plants and animals are made of cells. Rudolf Virchow (1855) added that every cell comes from an existing cell ("omnis cellula e cellula"), so cells do not arise from non-living matter.
Ernst Abbe (1873), working with the lens-maker Carl Zeiss, showed that the wavelength of light sets a limit on resolution, however perfect the lenses. Lenses that correct colour errors, and oil-immersion objectives, brought light microscopes close to that limit by about 1900.
Max Knoll and Ernst Ruska (1931) showed that a magnetic coil focuses a beam of electrons as a glass lens focuses light, and in 1933 Ruska built an electron microscope that resolved more detail than any light microscope. Electrons have a far shorter wavelength than light.
The first commercial scanning electron microscope went on sale in 1965. Ruska shared the 1986 Nobel Prize in Physics, and the 2017 Nobel Prize in Chemistry rewarded cryo-electron microscopy, which shows the shapes of single protein molecules.

Worked example 1: how a tiny lens magnifies

For a single lens held close to the eye, the magnification is about $M \approx \frac{250\,\mathrm{mm}}{f}$ , where $f$ is the focal length of the lens and 250 mm is the closest distance at which most eyes see clearly. (a) Find $M$ for a glass-bead lens with $f = 0.9\,\mathrm{mm}$ . (b) Explain why such small lenses were so hard to use.

(a) $M \approx \frac{250}{0.9} = 278$ , so about ×280.
(b) The smaller the lens, the shorter its focal length, so the specimen and the eye must both be within about a millimetre of the lens. The field of view is tiny and needs bright light, and focusing needs a fine screw, which is what the pin and screws on Leeuwenhoek's plate provided.

Worked example 2: the limit that light sets

Abbe showed that the smallest resolvable distance is about $d = \frac{\lambda}{2\,\mathrm{NA}}$ , where $\lambda$ is the wavelength and NA (numerical aperture) measures how wide a cone of light the objective collects; the best oil-immersion objectives have $\mathrm{NA} = 1.4$ . (a) Calculate $d$ for green light of wavelength 500 nm. (b) Which of these could a light microscope show as separate objects: two mitochondria 1 µm apart; two ribosomes 30 nm apart?

(a) $d = \frac{500\,\mathrm{nm}}{2 \times 1.4} = \frac{500}{2.8} = 179\,\mathrm{nm}$ , about 0.2 µm.
(b) $1\,\mu\mathrm{m} = 1000\,\mathrm{nm}$ , which is larger than 179 nm, so the two mitochondria are resolved. 30 nm is far below 179 nm, so the two ribosomes appear as one blur, or not at all.
Magnifying the image more would not help: it would only make the blur bigger ("empty magnification"). Only a shorter wavelength, such as that of an electron beam, gives better resolution.

HHMI BioInteractive: "Seeing the Invisible: van Leeuwenhoek's first glimpses of the microbial world". Watch how Leeuwenhoek made and used his lenses, and how other scientists checked his claims.

Warning

Common mistakes

Saying Hooke saw living cells. He saw the empty cell walls of dead cork.
Thinking a higher magnification always shows more detail. Detail depends on resolution; beyond the resolution limit, extra magnification shows nothing new.
Stating the cell theory as only "all living things are made of cells". It has three parts, including that all cells come from pre-existing cells.

Tip

Exam technique. When asked how a discovery depended on technology, link three things: the instrument (for example, Leeuwenhoek's high-quality single lens), the property it improved (resolution), and the new observation it allowed (microorganisms). The same chain works for the electron microscope and organelles.

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Practice: history of microscopy

Distinguish between a simple and a compound microscope.
Explain why Hooke's "cells" in cork were empty.
State the three parts of the modern cell theory, and name the scientist linked with the third part.
A lens has a focal length of 1.25 mm. Estimate its magnification, using $M \approx \frac{250\,\mathrm{mm}}{f}$ .
Using $d = \frac{\lambda}{2\,\mathrm{NA}}$ , calculate the limit of resolution for blue light ( $\lambda = 450\,\mathrm{nm}$ ) with an objective of $\mathrm{NA} = 1.25$ .
Explain why the Royal Society did not accept Leeuwenhoek's report at once, and why its caution was good science.
Evaluate the claim: "The cell theory was discovered by one scientist."

Show answersHide answers

A simple microscope has one lens (or lens system); a compound microscope has two, an objective and an eyepiece, and its total magnification is the product of their magnifications.
Cork is bark made of dead cells; their contents had died and gone, leaving only the walls.
All organisms are made of one or more cells; the cell is the basic unit of structure and function; all cells come from pre-existing cells (Virchow, 1855).
$M \approx \frac{250}{1.25} = 200$ , so about ×200.
$d = \frac{450}{2 \times 1.25} = \frac{450}{2.5} = 180\,\mathrm{nm}$ (0.18 µm).
No one else had seen such organisms, and Leeuwenhoek kept his lens-making secret, so others could not repeat the observations. Science accepts a claim when it can be checked independently; the witnesses in Delft provided that check, and the claim was then accepted.
False. It was built over two centuries by many people: Hooke and Leeuwenhoek observed cells; Schleiden and Schwann generalised to all plants and animals; Virchow added that cells come only from cells. Each step depended on better microscopes, made possible by lens-makers and physicists such as Abbe.

Quick check

Put these events in the order in which they happened.

Tap the cards in the right order.

Key points

Hooke named cells (1665); Leeuwenhoek's sharp single lenses revealed microorganisms (1676).
The cell theory (Schleiden, Schwann, Virchow): organisms are made of cells, the cell is the unit of life, and cells come from cells.
Resolution, not magnification, limits what a microscope shows; light limits resolution to about 0.2 µm ( $d = \frac{\lambda}{2\,\mathrm{NA}}$ ).
Electron microscopes (Knoll and Ruska, 1931–33) use the far shorter wavelength of electrons to resolve organelles and molecules.

Sources and credits

2.1.2: Studying Cells, from Biology 2e by OpenStax (Mary Ann Clark, Matthew Douglas, Jung Choi), via LibreTexts Biology, licensed under CC BY 4.0. Used for microscopy, magnification, resolution and the cell theory. Adapted by Ganzaa.
Antonie van Leeuwenhoek, Ernst Ruska and Scanning electron microscope, Wikipedia contributors, licensed under CC BY-SA 4.0. Used for the dates and events of the timeline. Adapted by Ganzaa.
Figure 1, the worked examples, practice and quick check: written by Ganzaa.
Images: Wellcome Collection, CC BY 4.0; Robert Hooke, public domain (National Library of Wales); J Brew, CC BY-SA 2.0; all via Wikimedia Commons.
Video: "Seeing the Invisible: van Leeuwenhoek's first glimpses of the microbial world", HHMI BioInteractive, embedded from YouTube.

This lesson adapts CC BY-SA material and is shared under CC BY-SA 4.0.

1A letter the Royal Society did not believe

2From lenses to the cell theory

A letter the Royal Society did not believe

From lenses to the cell theory