The laboratory of Michael J. Joyner, M.D., is interested in how humans respond to various forms of physical and mental stress during activities such as exercise, hypoxia, standing up and blood loss.
Dr. Joyner and his team study how the nervous system regulates blood pressure, heart rate and metabolism in response to these forms of stress. They are also interested in how blood flow to muscle and skin responds to these stressors. These responses are studied in young healthy subjects, healthy older subjects and people with conditions such as heart failure.
Finally, Dr. Joyner is personally interested in the role of integrative approaches in science as a powerful tool to integrate and critique data from reductionist approaches.
By studying normal physiology and how it is affected by aging, sex and disease, Dr. Joyner and his colleagues gain insight into what body systems are potential therapeutic targets for intervention. Their research also provides insight into the many complex mechanisms that operate together to keep us healthy and able to adapt to the demands of life — or fail in a way that makes us unable to adapt.
J Physiol 592.11 (2014) pp 2381–2388
Ideas about personalized medicine are underpinned in part by evolutionary biology’s Modern Synthesis. In this essay we link personalizedmedicine to the efforts of the early statistical investigatorswho quantified the heritability of human phenotype and then attempted to reconcile their observations with Mendelian genetics. As information about the heritability of common diseases was obtained, similar efforts were directed at understanding the genetic basis of disease phenotypes. These ideas were part of the rationale driving the Human Genome Project and subsequently the personalized medicine movement. In this context, we discuss: (1) the current state of the genotype–phenotype relationship in humans, (2) the common-disease–common-variant hypothesis, (3) the current ability of ‘omic’ information to inform clinical decision making, (4) emerging ideas about the therapeutic insight available from rare genetic variants, and (5) the social and behavioural barriers to the wider potential success of personalized medicine. There are significant gaps in knowledge as well as conceptual, intellectual, and philosophical limitations in each of these five areas. We then provide specific recommendations to mitigate these limitations and close by asking if it is time for the biomedical research community to ‘stop chasingMendel?’
In this essay we want to discuss some ideas and raise questions about how the Modern Synthesis in evolutionary biology has influenced what might loosely be described as biomedical thinking including the current enthusiasm for ‘personalized medicine’ and related ideas (Wilkins,2011; Hood & Auffray, 2014). By ‘Modern Synthesis’ we mean ideas that emerged at the confluence of population inheritance studies, Mendelian genetics and natural selection prior to World War II that have subsequently been applied in an effort to better understand and explain human variation, including the risk of common chronic diseases.
This paper reflects ideas that were presented as part of the 2011 Adolph Lecture at the Experimental Biology meeting that was held in Washington, DC. The goal of the talk was to share a physiologist’s perspective on what reductionism in general and the “omic” revolution in particular has or has not done for biomedical research and associated therapeutic insights or advances. The main ideas highlighted in the lecture were the following.
1) Reductionism via various flavors of molecular biology and “omics” has so far failed to deliver its self-promoted revolution in clinical medicine.
2) Systems biology has a cell-centric focus that is marked by a limited understanding of and application to biology beyond the cell.
3) The failure of systems biology to recognize and use key concepts from physiology about homeostasis, regulation, redundancy, feedback control, and acclimation/adaptation are major limitations to this poorly defined approach.
4) While all the attention has been focused on reductionism and more recently systems biology, physiology continues to provide important biomedical insights that lead to therapeutic advances.
As the title demonstrates, my goal in the Adolph Lecture and in this paper was and is to be intentionally provocative and hopefully generate a dialogue with the reductionists. In this context, and because I am “taking sides”, I have adopted what might be called a conversational approach to this paper.
Evolution evolves: physiology returns to centre stage; J Physiol. 2014 Jun 1;592(Pt 11):2237-44
For a complete list of publications by Michael Joyner, click here.