Why Integrative Science Remains Indispensable: Revisiting,Reshaping and Restoring the Relevance of Physiology

What is the Need?

The ways in which physiology has influenced or left its mark on science should be remembered, and we should remind ourselves and the rest of society that physiology will continue to contribute its share to the development of science and to improving the health and overall well-being of people, like any other organ in the body that plays its role in the maintenance of homeostasis.

This need for remembering and reminding arose because physiology is experiencing a perceived decline and is no longer seen as valuable and significant in the present scientific arena, especially in areas related to the health of people. Therefore, it is imperative that this impression, which is blatantly false and incorrect, be addressed. However, for that, we need to introspect ourselves, our rich history, legacy, present need for science and society, and last but not least, be ready and make an honest effort to reshape and translate the physiology in alignment with the existing requirements and expectations to maintain its glory and relevance.

Revisiting the Golden Days: Historical Contributions

Since the coining of the term ‘physiology’ by Jean Francois Fernel more than 500 years ago and Claude Bernard’s proposal of a deep link between physiology and medicine to maintain health, physiology has remained a vibrant science and has repeatedly proved its potential. It is at the heart of many discoveries, such as the regulation of gastric secretions (experimentation on the gastric fistula of a post-traumatic patient), circulation, bioelectricity, intercellular communication, electrocardiography, acetylcholine, nitric oxide/endothelial-derived relaxing factor, regulation of electrolyte balance, autophagy, mechanism of oxygen sensing and immune regulation. Moreover, it forms the basis of many tests, such as exercise stress test, gastrointestinal motility, pulmonary function tests and renal clearance. Insights gained from physiology are utilised in many therapeutic interventions, such as drug therapy, hormone replacement therapy, fluid therapy in critical care, medical procedures, as well as preventive and health-promoting strategies, such as diet planning and exercise in many metabolic disorders.^{1, 2} Fundamental themes of physiology are instrumental not only in the conventional treatment of various diseases but have also played a vital role in modifying the approach to their management. Views that seemed counterintuitive initially were later adopted in the successful management of these ailments. For example, congestive heart failure was accompanied by increased sympathetic discharge. It was thought that this was beneficial for the patient to maintain the required cardiac output. However, it was then realised that this could be worsening the condition by compromising the cardiac filling and also affecting the musculature of the heart by increasing the workload. Therefore, beta-blockers were used in the condition, and now they are an accepted treatment modality in the management of congestive cardiac failure. ³ Similarly, in the management of acute respiratory distress, it is now recommended that blood gases should be kept below normal because the maintenance of normal blood gases will require high pressure in ventilator settings and can worsen the condition by causing barotrauma in already compromised airways. ⁴ In both of these conditions, there is application of fundamental physiological principles that the body responds to deterioration by compensatory mechanisms to restore the optimum level for the time being, only until appropriate measures are taken. Second, a few parameters in the body, such as partial pressure of gases, have a reasonable amount of safety factor. Obviously, this is made possible by mutual trust and cooperation between physiologists, clinicians and scientists from diverse fields. Therefore, the relationship of physiology with varied disciplines cannot be undermined, and it has always come forward and contributed in many ways to achieving a common goal, that is, the welfare of science and people.

Reshaping Traditional Physiology: Current Challenges

Change is the only constant thing in this dynamic and ever-interacting world. Every turn of the wheel makes its impact in some way or another. Those who acknowledge it have a high probability of maintaining their relevance in this ever-changing world/continuously changing ecosystem. Physiology is no exception to this rule. The last decade of the 20th century witnessed the emergence of a buzz about gene profiling or editing, which could bring a revolution in medical science and was anticipated to be the solution to the majority of illnesses. It was thought that finding and targeting the genetic variants related to diseases by gene editing would solve the purpose. Physiology also could not afford to fail to adapt to emerging paradigms. It resulted in directing the attention from an integrative or a more holistic approach towards more reductionism. Scientists preferred to rebrand themselves as cell biologists, molecular biologists, network analysts and so on. It also opened new specialised fields such as genomics, proteomics and metabolomics. Though it has greatly reduced the suffering of patients and is beneficial in many diseases, we are still far away from the anticipated solution. Now, the scientific landscape has shifted, and we are starting to realise that integrative physiology and the reductionist approach are both needed to produce a significant impact. For example, while studying the genetic variant of cystic fibrosis, it is also necessary to study the channelopathy involved in it. In fact, drugs are being developed to target the defective proteins involved in channels. ⁵ Similarly, the pathophysiology of Alzheimer’s disease is also complex and needs a more integrative approach. By saying that, it does not mean that physiologists can afford to work in a traditional reductionist framework; they need to broaden their horizons and be receptive and ready to imbibe knowledge gained from diverse fields. They need to further explore the application of their fundamental principles of physiology and thus gear themselves towards translational physiology. The introduction of artificial intelligence in health care is going to be the next leap in this journey and has the potential to completely transform it. Medicine, which was supposed to be more of an art, is gradually losing its ground in favour of technology. Developments once considered speculative are now clinical realities that are hard to ignore. This can be seen as an opportunity rather than a threat by physiologists to expand their methodological scope, venture into novel approaches and utilise current technologies in the application of fundamental principles of physiology. They should not hesitate to collaborate with other disciplines and be ready to assist them in whatever ways are required or feasible. This can lead to futuristic physiological advancement avenues, such as AI-assisted diagnostics using large language models and machine learning to understand physiological parameters (e.g., continuous glucose monitoring + ML); wearable physiology and digital biomarkers, such as Fitbit sleep stages, Apple Watch ECG and continuous blood pressure monitoring; post-COVID physiological insights, such as autonomic dysfunction, respiratory problems, exercise intolerance and immune-physiological interactions, which have all attracted considerable attention since COVID; ex vivo physiological models and organ-on-a-chip, replacing animal research while maintaining a foundation in integrative physiology and digital twins of human physiology being created for personalised treatment using physiological AI twinning. ⁶

Restoring the Relevance of Physiology: Future Directions

As the definition of health includes the physical, mental and social well-being of an individual, true knowledge of body physiology becomes an indispensable aspect of any strategy employed to address health issues. One important thing that emerges from it is that understanding body physiology should not be limited only to health providers or policymakers, but imparting this knowledge to stakeholders can be much more effective in reducing the burden of impaired health. There are many myths or misconceptions widely prevalent in the community that significantly reduce the impact of any health programme aimed at promoting health. Physiologists can share the responsibility of educating the community along with public health providers, and the health literacy gained from it can redefine the role of physiologists in promoting health. Physiology experts can be involved in brainstorming sessions to design the framework of any social outreach programme. This will not only be beneficial for community health, but the involvement of medical students in these activities will rekindle their interest in body physiology. Interaction with laypeople or health-illiterate people will expose them to ground realities and ultimately foster their skills to become good, empathetic doctors. ⁷ Extension of these programmes to school-level education will also develop curiosity in the young budding minds of the community to understand the working of the human body and can pave the way for them to be attracted towards physiology as a career option. In fact, many physiology societies are working in this direction to restore interest in physiology, such as the organisation of ‘Physiology Understanding Week’ by the American Physiological Society (APS). Similarly, Johns Hopkins University is successfully running a multidisciplinary ‘Student Outreach Resource Centre’ (SOURCE), with health literacy as an important goal.^{8, 9} Many countries, such as Brazil, China, Australia and Japan, are making an effort to integrate physiology knowledge with community health. The maintenance of various physiological parameters at an optimum level requires a balanced lifestyle and can be affected by the amount and type of nutrient intake, level of physical activity, stress level, sleep hygiene and circadian misalignment. Addressing unhealthy lifestyles and correct knowledge of body physiology from the very beginning will have more impact and can be more cost-effective for public health. Thus, knowledge of the fundamental principles of physiology can be transferred and translated to ‘physiological epidemiology’ to improve population-level health outcomes. Apart from that, translational physiology can be extended to chronomedicine, which explores the variability of physiological parameters, such as blood pressure, blood glucose and hormones, over a period of time and treats them accordingly through chronotherapeutics. Similarly, chrononutrition involves the optimum timing of food intake in alignment with the circadian rhythm. Sports physiology and sleep physiology principles are already being widely utilised in clinical practice. Immersive physiology is the new avenue that can be valuable in providing a high-fidelity experience of complex biological systems by taking the help of current advances happening in the field of virtual reality. Moreover, translation can occur as per local needs in one way or another, such as high-altitude physiology, which has become a valuable asset in high-terrain regions, and medical physiologists are actively involved not only in providing service and training to prevent high-altitude illness but also in the management of patients.

Physiology will always remain an indispensable part of medical science by contributing its share in all possible ways, and thus, reclaiming the centrality of physiology in modern biomedical science is needed.