Further Developments in Microscopy
January 28, 2009
(Supplement to the History of Medicine Lectures)
Adam Blatner, M.D.
In Lecture 1,
I described the earlier history of the microscope, including pictures
of Hooke's 1660 compound microscope, and describing Anton van
Leeuwenhoek's tiny but powerful simple microscopes, as well as showing
a few microscopes made in the 1700s.
The technology of the microscope advanced: Here are some pictures of 19th century microscopes.
In the next session we'll talk about Joseph Lister, the physician
recognized most commonly for establishing the idea of antisepsis in
surgery. His father was also named Joseph Lister, Senior, was also a
physician, and devised a special combination lens that when put
together countered some of the distortions of light that happen in more
powerful compound microscopes. This happened in 1830, and made further
developments in histology---the just-beginning sub-field of the study
of microscopic anatomy---possible.
In the ensuing decade the nature of cells was then elaborated; and from
this the idea that spontaneous generation was a misleading theory: Only
cells give birth to cells. This was also laying the groundwork for germ
Further developments in microscopy include:
|John J. Lister's 1830 microscope, more stable.
| 1904 microscope with three possible lenses.
Another requirement for the emergence of histology was the capacity to
mount very, very thin sections of tissue so that the overlying elements
don't confuse the picture.T
this requires a machine that can slice thinly, a microtome, below left.
Along with that is the need to develop ways of fixing the tissues so
they don't effectively dissolve or melt---here's where alcohol or
formaldehyde was used, so the tissues hold their structure.
In fact, tissues are rather transparent to light, and are not easily
visible. Another technology was that of figuring out chemicals that
would stain certain parts of a cell and not others, so that their
structures could be seen. Many chemicals were tried and certain
With bacteria, other stains were found. One kind, the "Gram" stain,
colors certain germs such as streptococci and staphylococci blue-black,
while others appear red and are called "Gram-negative." This difference
became interesting when it appeared that drugs like penicillin affected
mainly the former types while other antibiotics sometimes worked with
1830 – Joseph Jackson Lister reduces spherical aberration or the
"chromatic effect" by showing that several weak lenses used together at
certain distances gave good magnification without blurring the image.
This was the prototype for the compound microscope.
1830 – Joseph Jackson Lister (the father of the Joseph Lister mentioned
in Lecture 2 who introduced antisepsis) reduced the problem of
spherical aberration (a distortion of light in strong magnifications)
by showing that several weak lenses used together at certain distances
gave good magnification without blurring the image.
1872 – Ernst Abbe, then research director of the Zeiss Optical Works,
wrote a mathematical formula called the "Abbe Sine Condition". His
formula provided calculations that allowed for the maximum resolution
in microscopes possible.
Other sources: http://en.wikipedia.org/wiki/Timeline_of_microscope_technology; http://www.nationmaster.com/encyclopedia/Timeline-of-microscope-technology
1903 – Richard Zsigmondy developed the ultramicroscope that could study
objects below the wavelength of light. He won the Nobel Prize in
Chemistry in 1925.
1931 – Ernst Ruska co-invented the electron microscope for which he won
the Nobel Prize in Physics in 1986. An electron microscope depends on
electrons rather than light to view an object, electrons are speeded up
in a vacuum until their wavelength is extremely short, only one
hundred-thousandth that of white light. Electron microscopes make it
possible to view objects as small as the diameter of an atom.
|The electron microscope, which
made it possible to see much smaller:
|Here are the smaller fields that modern
microscopy can now see.
The electron microscope allows you to see the insides of cells and
identify sub-cellular structures, even within the much smaller
|This is an electron microscope of a liver cell
|This is a diagram of how packed just the edge of the inside of
an Escheria Coli bacterium can be! (Enlarged 1 million times)
I remember when I studied biology in the 1950s a cell had a more easily
stained nucleus and then a vaguely granular "cytoplasm," and most
science textbooks didn't have anything about the many components we
know know are basic to the cell and operate in that seemingly
featureless gray "cytoplasm" area. Our knowledge of sub-cellular
structure has grown exponentially since the 1940s.
1932 – Frits Zernike invented the phase-contrast microscope that
allowed for the study of colorless and transparent biological materials
for which he won the Nobel Prize in Physics in 1953.
1981 – Gerd Binnig and Heinrich Rohrer invented the scanning tunneling
microscope that gives three-dimensional images of objects down to the
atomic level. Binnig and Rohrer won the Nobel Prize in Physics in 1986.
The powerful scanning tunneling mi
Advances in treatment often awaits the development of the kinds of
tools needed to pursue a goal. For example, the relatively recent field
of echnology makes a difference. For example, in the past, if a finger
or some other part of the body was cut off, efforts at re-implantation
often failed, because what was needed was the re-connection
("re-anastomosis") of blood vessels and nerves that were quite small.
Our needles and equipment was still to large and clumsy for the job.
However, in the mid-20th century, it became technically feasable to
make much smaller sutures and needles. Here's a picture of a needle and
suture used in microsurgery, placed next to a sesame seed (very
enlarged in the picture)! This is the kind of tool needed to put tiny
blood vessels back. This surgery also had to be done under very
powerful magnifying glasses, mixed with binocular vision for estimating
This illustrates the point that until
they figure out how to make certain things it's not easy to figure
out how to use them. In other words, it's not only that necessity is the mother of invention,
but sometimes—not infrequently, in fact—invention, or discovery, ends
up waking people up to possibilities they hadn’t imagined! We’re seeing
that a lot in the computer world, where, given a toy, the game is to
find all the things you can do with that toy.
--- the end for now.