Abstract

What is life? There is hardly a more fundamental question raised by aspiring researchers, and one less prone to ever be answered in a scientifically satisfying way. In the long, productive and highly influential period of research following his Nobel-recognised work on relaxation kinetics, Manfred Eigen made seminal contributions towards a quantifiable definition of life, with a strong focus on its evolutionary character. In the last years of his time as an active researcher, however, he devoted himself to another, purely experimental topic: the detection and analysis of single biomolecules in aqueous solution. In this short review, I will give an overview of the groundbreaking contributions to the field of single molecule research made by Eigen and coworkers, and show that both, in its intrinsic motivation, and in its consequences, single molecule research strongly relates to the question of the physical–chemical essence of life. In fact, research on living systems with single molecule sensitivity will always refer the researcher to the question of the simplest possible representation, and thus the origin, of any biological phenomenon.

Highlights

  • In 1994, a review paper appeared that greatly inspired a generation of researchers at the interface of chemistry, physics, and biology

  • “Sorting single molecules: Application to diagnostics and evolutionary biotechnology” (Eigen and Rigler 1994) is a hallmark of scientific communication co-authored by National Academy member Manfred Eigen, a grand scientific authority and Nobel laureate

  • Once being able to detect the presence of single molecules, and their fluctuating number in an open volume element, through random bursts of fluorescence, temporal autocorrelation analysis yields statistically relevant information about all kinds of processes that influence the dynamics of these molecules, from simple three-dimensional diffusion to inter- and intramolecular reactions

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Summary

Introduction

In 1994, a review paper appeared that greatly inspired a generation of researchers at the interface of chemistry, physics, and biology. In this paper, the authors express their excitement about a new technical breakthrough that Rigler and his coworkers had previously accomplished: the direct detection of single fluorescently labeled molecules diffusing freely in aqueous solution.

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