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