Historical Commentary

Single-particle cryo-electron microscopy (cryo-EM) has emerged over the last two decades as a technique capable of studying the structure of challenging systems. The author of this Commentary discusses some of the major historical landmarks in cryo-EM that have led to its present success.

The idea of using hybrid proteins containing transcription factor domains to analyze protein-protein interactions was described in 1989. Over the past 25 years, this method has begun to reveal the complex protein networks that underlie cellular behavior.

For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.

Long before mass spectrometry became an important tool for cell biology, it was yielding scientific insights in physics and chemistry. Here is a brief history of how the technology has expanded from a tool for studying atomic structure and characterizing small molecules to its current incarnation as the most powerful technique for analyzing proteomes.

From histology to microcinematography, from cytochemistry to live cell imaging, the history of visualization technology in the life sciences may be understood as a series of cycles of action and reaction between static and dynamic modes of representing life.

Conceptual breakthroughs in science tend to garner accolades and attention. But, as the invention of tissue culture and the development of isotopic tracers show, innovative methods open up new fields and enable the solution of longstanding problems.