The manipulability of what? The history of G-protein coupled receptors

  title={The manipulability of what? The history of G-protein coupled receptors},
  author={Ann-Sophie Barwich and Karim Bschir},
  journal={Biology \& Philosophy},
This paper tells the story of G-protein coupled receptors (GPCRs), one of the most important scientific objects in contemporary biochemistry and molecular biology. By looking at how cell membrane receptors turned from a speculative concept into a central element in modern biochemistry over the past 40 years, we revisit the role of manipulability as a criterion for entity realism in wet-lab research. The central argument is that manipulability as a condition for reality becomes meaningful only… 
5 Citations
Laser Lights and Designer Drugs: New Techniques for Descending Levels of Mechanisms "in a Single Bound"?
  • J. Bickle
  • Computer Science, Medicine
    Top. Cogn. Sci.
  • 2020
Optogenetics and DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) are important research tools in recent neurobiology. These tools allow unprecedented control over activity in
The Value of Failure in Science: The Story of Grandmother Cells in Neuroscience
This article advances the heuristics of failure analysis, meaning the explicit treatment of certain ideas or models as failures, and is illustrated with the contested idea of a hypothetical neuron that encodes a highly specific but complex stimulus, such as the image of one’s grandmother.
Fishing for Genes: How the Largest Gene Family in the Mammalian Genome was Found (and Why Idiosyncrasy in Exploration Matters)
Abstract In 1991, Linda Buck and Richard Axel identified the multigene family expressing odor receptors. Their discovery transformed research on olfaction overnight, and Buck and Axel were awarded
How to be rational about empirical success in ongoing science: The case of the quantum nose and its critics.
  • A. Barwich
  • Medicine
    Studies in history and philosophy of science
  • 2018
It is argued that normative appeals to empirical success in the evaluation of competing scientific explanations can result in unreliable conclusions, especially when the authors are looking at the changeability of direction in unsettled investigations.


Seven transmembrane receptors: something old, something new
A very personal retrospective of research over the past 35 years which ultimately led to the identification, purification, reconstitution and cloning of the adrenergic receptors is provided.
“Receptive Substances”: John Newport Langley (1852–1925) and his Path to a Receptor Theory of Drug Action
  • A. Maehle
  • Computer Science, Medicine
    Medical History
  • 2004
During the last twenty years the modern techniques of molecular biology have helped to determine the genetic basis of receptor proteins, to identify their amino acid sequences, and to further elucidate their remarkable structural diversity as well as their similarities and evolutionary relationships.
The structural basis of G-protein-coupled receptor signaling (Nobel Lecture).
  • B. Kobilka
  • Chemistry, Medicine
    Angewandte Chemie
  • 2013
Given the central role played by GPCRs in nearly all physiologic processes, they represent the largest group of targets for drug discovery for a broad spectrum of diseases.
What is so special about smell? Olfaction as a model system in neurobiology
  • A. Barwich
  • Biology, Medicine
    Postgraduate Medical Journal
  • 2015
Research on the OR binding site investigates what amino acid sequences determine the receptor-binding capacity, and promises a better understanding of how the basic genetic makeup of GPCRs relates to their diversification in ligand-binding capacities.
The structure and function of G-protein-coupled receptors
G-protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a
G protein-coupled receptor rhodopsin.
Evidence is provided of the propensity of rhodopsin and, most likely, other GPCRs to dimerize, a property that may be pertinent to their function.
Seven transmembrane receptors: a brief personal retrospective.
  • R. Lefkowitz
  • Biology, Medicine
    Biochimica et biophysica acta
  • 2007
Biographies of scientific objects
Why does an object or phenomenon become the subject of scientific inquiry? Why do some of these objects remain provocative, while others fade from centre stage? And why do objects sometimes return as
Crystal structure of the human β2 adrenergic G-protein-coupled receptor
Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in
The quantitative analysis of drug-receptor interactions: a short history.
  • D. Colquhoun
  • Biology, Medicine
    Trends in pharmacological sciences
  • 2006