What Makes a Discovery Successful? The Story of Linda Buck and the Olfactory Receptors.

In 1991, Buck and Axel published a landmark study in Cell for work that was awarded the 2004 Nobel Prize. The identification of the olfactory receptors as the largest family of GPCRs catapulted olfaction into mainstream neurobiology. This BenchMark revisits Buck's experimental innovation and its surprising success at the time.

If Proust had whiskers: Recalling locations with smells.

Recent research suggests that the piriform cortex simultaneously represents spatial and olfactory information. These findings may provide further insight into the non-topographic principles of odor coding.

Odor coding in the mammalian olfactory epithelium.

Noses are extremely sophisticated chemical detectors allowing animals to use scents to interpret and navigate their environments. Odor detection starts with the activation of odorant receptors (ORs), expressed in mature olfactory sensory neurons (OSNs) populating the olfactory mucosa. Different odorants, or different concentrations of the same odorant, activate unique ensembles of ORs. This mechanism of combinatorial receptor coding provided a possible explanation as to why different odorants are perceived as having distinct odors. Aided by new technologies, several recent studies have found that antagonist interactions also play an important role in the formation of the combinatorial receptor code. These findings mark the start of a new era in the study of odorant-receptor interactions and add a new level of complexity to odor coding in mammals.

Imaging the living brain: An argument for ruthless reductionism from olfactory neurobiology.

Should theories of "higher-level" cognitive effects originate in "lower-level" molecular mechanisms? This paper supports reductionist explanations of sensory perception via molecular mechanisms in neurobiology. It shows that molecular and cellular mechanisms must constitute the material foundation to derive better theories and models for neuroscience. In support of "bottom-up theorizing", I explore the recent application of a new real-time molecular imaging technique (SCAPE microscopy) to mixture coding in olfaction. Seemingly emergent "higher-level" psychological effects in odor perception, irreducible to the physical stimulus, are linked back to underlying molecular mechanisms at the receptor level. The SCAPE study has notable theoretical impact. It provides a possible answer to the neurocomputational challenge in olfaction from combinatorial coding at the periphery: how does the brain discriminate different complex mixtures from widespread and overlapping receptor activation? The failure of previous reductionist structure-odor explanations is shown to reside in misconceptualizations of the critical causal elements involved. Causally fundamental features are not of parts independently of a mechanism. Components and their relevant features are units via their causal role within a mechanism. Here, new technologies allow revisiting our understanding of the ontology and levels of organization of a system.

Fashion fades, Chanel No.†5 remains: Epistemology between Style and Technology.

Perfumes embody a chemical record of style and technology. Blurring the boundary between what counts as natural and artificial in both a material and a perceptual sense, perfumery presents us with a domain of multiple disciplinary identities relevant to social studies: art, craft, and techno-science. Despite its profound impact as a cultural practice, perfume has seldom featured in historical scholarship. The reason for this neglect is its inherently qualitative dimension: perfume cannot be understood via codified representation but requires direct acquaintance with its sensory and material basis. The historical study of perfumery thus necessitates an experimental approach that comes not without challenge. This article looks at contemporary recreations of old perfumes to identify the difficulties involved in the experimental recreation of fragrances as sensory and performative artifacts. We highlight the need for a reconceptualization of methodology for inconcrete objects of study as part of the broader interest in experimental approaches to the humanities.

How to be rational about empirical success in ongoing science: The case of the quantum nose and its critics.

Empirical success is a central criterion for scientific decision-making. Yet its understanding in philosophical studies of science deserves renewed attention: Should philosophers think differently about the advancement of science when they deal with the uncertainty of outcome in ongoing research in comparison with historical episodes? This paper argues that normative appeals to empirical success in the evaluation of competing scientific explanations can result in unreliable conclusions, especially when we are looking at the changeability of direction in unsettled investigations. The challenges we encounter arise from the inherent dynamics of disciplinary and experimental objectives in research practice. In this paper we discuss how these dynamics inform the evaluation of empirical success by analyzing three of its requirements: data accommodation, instrumental reliability, and predictive power. We conclude that the assessment of empirical success in developing inquiry is set against the background of a model's interactive success and prospective value in an experimental context. Our argument is exemplified by the analysis of an apparent controversy surrounding the model of a quantum nose in research on olfaction. Notably, the public narrative of this controversy rests on a distorted perspective on measures of empirical success.

What is so special about smell? Olfaction as a model system in neurobiology.

Neurobiology studies mechanisms of cell signalling. A key question is how cells recognise specific signals. In this context, olfaction has become an important experimental system over the past 25 years. The olfactory system responds to an array of structurally diverse stimuli. The discovery of the olfactory receptors (ORs), recognising these stimuli, established the olfactory pathway as part of a greater group of signalling mechanisms mediated by G-protein-coupled receptors (GPCRs). GPCRs are the largest protein family in the mammalian genome and involved in numerous fundamental physiological processes. The OR family exhibits two characteristics that make them an excellent model system to understand GPCRs: its size and the structural diversity of its members. Research on the OR binding site investigates what amino acid sequences determine the receptor-binding capacity. This promises a better understanding of how the basic genetic makeup of GPCRs relates to their diversification in ligand-binding capacities.

The Wire Is Not the Territory: Understanding Representational Drift in Olfaction With Dynamical Systems Theory.

Representational drift is a phenomenon of increasing interest in the cognitive and neural sciences. While investigations are ongoing for other sensory cortices, recent research has demonstrated the pervasiveness in which it occurs in the piriform cortex for olfaction. This gradual weakening and shifting of stimulus-responsive cells has critical implications for sensory stimulus-response models and perceptual decision-making. While representational drift may complicate traditional sensory processing models, it could be seen as an advantage in olfaction, as animals live in environments with constantly changing and unpredictable chemical information. Non-topographical encoding in the olfactory system may aid in contextualizing reactions to promiscuous odor stimuli, facilitating adaptive animal behavior and survival. This article suggests that traditional models of stimulus-(neural) response mapping in olfaction may need to be reevaluated and instead motivates the use of dynamical systems theory as a methodology and conceptual framework.

More than meets the AI: The possibilities and limits of machine learning in olfaction.

Can machine learning crack the code in the nose? Over the past decade, studies tried to solve the relation between chemical structure and sensory quality with Big Data. These studies advanced computational models of the olfactory stimulus, utilizing artificial intelligence to mine for clear correlations between chemistry and psychophysics. Computational perspectives promised to solve the mystery of olfaction with more data and better data processing tools. None of them succeeded, however, and it matters as to why this is the case. This article argues that we should be deeply skeptical about the trend to black-box the sensory system's biology in our theories of perception. Instead, we need to ground both stimulus models and psychophysical data on real causal-mechanistic explanations of the olfactory system. The central question is: Would knowledge of biology lead to a better understanding of the stimulus in odor coding than the one utilized in current machine learning models? That is indeed the case. Recent studies about receptor behavior have revealed that the olfactory system operates by principles not captured in current stimulus-response models. This may require a fundamental revision of computational approaches to olfaction, including its psychological effects. To analyze the different research programs in olfaction, we draw on Lloyd's "Logic of Research Questions," a philosophical framework which assists scientists in explicating the reasoning, conceptual commitments, and problems of a modeling approach in question.

The Value of Failure in Science: The Story of Grandmother Cells in Neuroscience.

The annals of science are filled with successes. Only in footnotes do we hear about the failures, the cul-de-sacs, and the forgotten ideas. Failure is how research advances. Yet it hardly features in theoretical perspectives on science. That is a mistake. Failures, whether clear-cut or ambiguous, are heuristically fruitful in their own right. Thinking about failure questions our measures of success, including the conceptual foundations of current practice, that can only be transient in an experimental context. This article advances the heuristics of failure analysis, meaning the explicit treatment of certain ideas or models as failures. The value of failures qua being a failure is illustrated with the example of grandmother cells; the contested idea of a hypothetical neuron that encodes a highly specific but complex stimulus, such as the image of one's grandmother. Repeatedly evoked in popular science and maintained in textbooks, there is sufficient reason to critically review the theoretical and empirical background of this idea.

A Critique of Olfactory Objects.

Does the sense of smell involve the perception of odor objects? General discussion of perceptual objecthood centers on three criteria: stimulus representation, perceptual constancy, and figure-ground segregation. These criteria, derived from theories of vision, have been applied to olfaction in recent philosophical debates about psychology. An inherent problem with such framing of olfactory objecthood is that philosophers explicitly ignore the constitutive factors of the sensory systems that underpin the implementation of these criteria. The biological basis of odor coding is fundamentally different from the coding principles of the visual system. This article analyzes the three measures of perceptual objecthood against the biological background of the olfactory system. It contrasts the coding principles in olfaction with the visual system to show why these criteria of objecthood fail to be instantiated in odor perception. The argument demonstrates that olfaction affords perceptual categorization without the need to form odor objects.