The learning-consciousness connection

This is a response to the nine commentaries on our target article “Unlimited Associative Learning: A primer and some predictions”. Our responses are organized by theme rather than by author. We present a minimal functional architecture for Unlimited Associative Learning (UAL) that aims to tie to together the list of capacities presented in the target article. We explain why we discount higher-order thought (HOT) theories of consciousness. We respond to the criticism that we have overplayed the importance of learning and underplayed the importance of spatial modelling. We decline the invitation to add a negative marker to our proposed positive marker so as to rule out consciousness in plants, but we nonetheless maintain that there is no positive evidence of consciousness in plants. We close by discussing how UAL relates to development and to its material substrate

The Transition to Experiencing: II. The Evolution of Associative Learning Based on Feelings

We discuss the evolutionary transition from animals with limited experiencing to animals with unlimited experiencing and basic consciousness. This transition was, we suggest, intimately linked with the evolution of associative learning and with flexible reward systems based on, and modifiable by, learning. During associative learning, new pathways relating stimuli and effects are formed within a highly integrated and continuously active nervous system. We argue that the memory traces left by such new stimulus–effect relations form dynamic, flexible, and varied global sensory states, which we call categorizing sensory states (CSSs). These CSSs acquired a function: they came to act as internal “evaluators ” and led to positive and negative reinforcement of new behavior. They are therefore the simplest, distinct, first-person motivational states that an animal can have. They constitute what we call basic consciousness, and are the hallmark of animals that can experience. Since associative learning has been found in many invertebrate taxa that first appeared during the Cambrian era, we propose that the processes underlying basic consciousness are phylogenetically ancient, and that their emergence may have fueled the Cambrian explosion

Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them

Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network.

PURPOSE: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. METHODS: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation. RESULTS: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression. CONCLUSION: IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers

Living and experiencing: response to commentaries

In our target article, “Learning and the evolution of conscious agents” we outlined an evolutionary approach to consciousness, arguing that the evolution of a form of open-ended, representational, and generative learning (unlimited associative learning, UAL) drove the evolution of consciousness. Our view highlights the dynamics and functions of consciousness, delineates its taxonomic distribution and suggests a framework for exploring its developmental and evolutionary modifications. The approach we offer resonates with biosemioticians’ views, but as the responses to our target article show, our proposal also faces challenges and has led to suggestions that extend, develop and qualify it. Our response to the 14 varied and rich commentaries starts with the recurring and deep question raised by many of them – the relation between life and sentience. We explore this question by introducing and expanding on “vivaciousness”, a term we coined to describe the turbulent, flexible exploration-stabilization processes inherent in the living condition, as well as addressing the related concepts of Umwelt and selfhood. We then consider the question of the adequacy of unlimited associative learning (UAL) as an evolutionary transition marker (ETM) of minimal consciousness (rather than as a marker of a complex form of sentience), and the possible precursors of sentience. The engagement with these broad themes is entangled with a discussion of evolutionary transitions, constitutive emergence and the function/s of consciousness. The suggestions of our commentators, urging us to explore new concepts and new avenues of research within the framework of a richer view of evolution are then discussed. We end by briefly considering what we regard as a conceptual lacuna, which is leading to the indiscriminate use of the term “sentience” and which awaits further investigation

Pain sentience criteria and their grading

On the basis of the target article by Crump and colleagues, we suggest a more parsimonious scheme for evaluating the evidence for sentience. Since some of the criteria used by Crump et al. are not independent and some are uninformative we exclude some criteria and amalgamate others. We propose that evidence of flexible learning and prioritization, in conjunction with relevant data on brain organization, is sufficient for assigning pain-sentience to an animal and we suggest a scoring scheme based on four criteria

Learning and the evolution of conscious agents

The scientific study of consciousness or subjective experiencing is a rapidly expanding research program engaging philosophers of mind, psychologists, cognitive scientists, neurobiologists, evolutionary biologists and biosemioticians. Here we outline an evolutionary approach that we have developed over the last two decades, focusing on the evolutionary transition from non-conscious to minimally conscious, subjectively experiencing organisms. We propose that the evolution of subjective experiencing was driven by the evolution of learning and we identify an open-ended, representational, generative and recursive form of associative learning, which we call Unlimited Associative Learning (UAL), as an evolutionary transition marker of minimal consciousness. This evolutionary marker provides evidence that the evolutionary transition to consciousness has gone to completion and allows reverse-engineering from this learning capacity to the system that enables it – making possible the construction of a toy model of UAL. The model allows us to identify some of the key processes and structures that constitute minimal consciousness, points its taxonomic distribution and the ecological context in which it first emerged, highlights its function and suggests a framework for exploring developmental and evolutionary modifications of consciousness. We point to ways of experimentally testing the relationship between UAL and consciousness in human and in non-human animals and discuss the theoretical and ethical implications of our approach. The framework we offer allows the exploration of the evolutionary changes in agency, value systems, selective processes and goals that were involved in the transition to subjective experiencing from a perspective that resonates with the approaches of bio-semioticians