
Celebrating 50 Years of Electron Microscopy and Modern Cell Biology
Journey Into the Cell

"The key to every biological problem must finally be sought in the cell," wrote
the great classical cell biologist, E.B. Wilson, in 1925. Yet at the time
Wilson wrote, the world inside the cell was largely inaccessible. The primary
instrument
of investigation for classical cell biologists--the
light microscope--was physically incapable
of resolving a cell's fine interior details. Albert Claude compared the
situation encountered
by Wilson and his contemporaries to that faced by astronomers, "who were
permitted to see
the objects of their interest, but not to touch them; the cell was as distant
from us as the
stars and galaxies...."
Indeed, before the advent of modern cell biology, pioneered by Claude at The
Rockefeller University (then Institute) in the 1940s, many biologists viewed
the cell as a mere "bag of enzymes," a "biochemical bog" filled with formless
protoplasm and devoid of inner structure.

This famous first electron micrograph of an intact cell
was published in The Journal of Experimental Medicine in
March 1945, in "A Study of Tissue Culture Cells by Electron Microscopy," by
Keith R. Porter, Albert Claude, and Ernest F. Fullam. The cell is a cultured
fibroblast originating from a chick embryo, which was grown by Porter on
polyvinyl film, then peeled off and transferred to a wire specimen grid.
The cell was fixed with osmium tetroxide, washed and then dried in order to
prevent evaporation in the electron microscopeUs vacuum chamber.
Magnified 1600 times, this first electron micrograph of a cell reveals
mitochondria, the Golgi apparatus and a "lace-like reticulum" which
Porter later named the "endoplasmic reticulum".
The electron microsope used for this historic image was an
RCA EMB model, operated by Fullam at the Interchemical Corporation in
New York City.
Entrance to the Inner - World of the Cell
All this changed 50 years ago, when
Claude, Keith Porter and Ernest Fullam
published the first picture of an intact
cell taken with an electron microscope.
With technical advances in preparing thin
slices of tissue for the electron microscope, this instrument would eventually
provide one hundred times the resolving power of the best light microscopes. A
new biological world, teeming with mysterious subcellular structures, was made
visible. Claude, Porter and other pioneering
cell biologists at Rockefeller--George Palade, Christian de Duve, Philip
Siekevitz and their colleagues--combined electron microscopy with
biochemistry and cell fractionation techniques
to isolate and study these subcellular structures, or organelles. A cellular
city was entered and explored, a domain of subcellular power stations
(mitochondria), waste disposal stations (lysosomes), protein factories
(ribosomes), and protein packaging and export facilities (the endoplasmic
reticulum and Golgi apparatus).

Pictured in an early electron micrograph, these fragments of the endoplasmic reticulum
are studded with ribosomes, cellular factories for protein synthesis.
A Unified Science of Life
Today cell biology has merged with molecular biology and genetics to create a
unified science
of life. Modern cell biology, born 50 years
ago, now lies at the foundation of all biology
and medicine. As Albert Claude, who died in 1983, said upon receiving the
Nobel Prize for Medicine in 1974 with de Duve and Palade: "Looking back...the
facts have been far better than the dreams. In the long course of cell life
on this earth it remained for our age, for our
generation, to receive the full ownership of our inheritance. We have entered
the cell, the mansion of our birth, and started the inventory of
our acquired wealth."
The Rockefeller University celebrates
the 50th anniversary of the beginning of the
modern era of cell biology with a three-day
symposium on the past, present and future of
this central science.

Today RU biologist Seth Darst uses the electron microscope to image single-layer crystals of the
DNA transcription enzyme, RNA polymerase II, whose molecular structure is then modeled on a computer.
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Updated: 3/21/1995 amp