The faces of Big Science.

Fifty years ago, academic science was a calling with few regulations or financial rewards. Today, it is a huge enterprise confronted by a plethora of bureaucratic and political controls. This change was not triggered by specific events or decisions but reflects the explosive 'knee' in the exponential growth that science has sustained during the past three-and-a-half centuries. Coming to terms with the demands and benefits of 'Big Science' is a major challenge for today's scientific generation. Since its foundation 50 years ago, the European Molecular Biology Organization (EMBO) has been of invaluable help in meeting this challenge.

Getting mitochondria to center stage.

The question of how eukaryotic cells assemble their mitochondria was long considered to be inaccessible to biochemical investigation. This attitude changed about fifty years ago when the powerful tools of yeast genetics, electron microscopy and molecular biology were brought to bear on this problem. The rising interest in mitochondrial biogenesis thus paralleled and assisted in the birth of modern biology. This brief recollection recounts the days when research on mitochondrial biogenesis was an exotic effort limited to a small group of outsiders.

The fires of life.

This retrospective recounts the hunt for the mechanism of mitochondrial ATP synthesis, the early days of research on mitochondrial formation, and some of the colorful personalities dominating these often dramatic and emotional efforts. The narrative is set against the backdrop of postwar Austria and Germany and the stream of young scientists who had to leave their countries to receive postdoctoral training abroad. Many of them--including the author--chose the laboratory of a scientist their country had expelled a few decades before. The article concludes with some thoughts on the uniqueness of U.S. research universities and a brief account of the struggles to revive science in Europe.

Science in time of crisis.

A crisis usually poses novel challenges that cannot be met with existing knowledge. To confront the unexpected, we need scientific inquisitiveness and long-term basic research. Narrowly focused research programs cater to short-term thinking and are rarely an effective way to spend precious public funds.

The magic garden.

For more than a century after their discovery, mitochondria were viewed almost exclusively as ATP-generating metabolic units. This view changed with the discovery of the mitochondrial genetic system and the central role of mitochondria in programmed cell death. As a result, much of the current research focuses on the complex interplay between mitochondria and the rest of the eukaryotic cell. This interplay is central to mitochondrial biogenesis. The following five reviews published in this volume summarize recent discoveries in this area: DNA Replication and Transcription in Mammalian Mitochondria, Mitochondrial-Nuclear Communications, Translocation of Proteins into Mitochondria, The Machines that Divide and Fuse Mitochondria, and Why Do We Still Have a Maternally Inherited Mitochondrial DNA? Insights from Evolutionary Medicine.