Understanding diverse dimensions and facets of evolutionary medicine will lead to innovative approaches in disease detection and management through genome mapping and genetic engineering
Rapid technological advancements over the past few decades are leading to a deeper understanding of the etiology (causation) and pathophysiology (mechanisms) as well as therapeutics (treatment) of the disease. More we understand the phenomena responsible for the disease more we are led towards the evolutionary changes that have occurred in our genotype (complete set of genetic material of an organism) and phenotype (set of observable traits and characteristics of an organism) over centuries and millennia together. Nobel Laureate in Physiology or Medicine for the year 2022 Svante Paabo while sequencing ancestral human genome reported that the major genetic risk factor for severe COVID-19 has been inherited from our ancestors called Neanderthals and that some other sequences in the same genome also gave modern humans much needed protection against such viruses. Thus, the problem as well as the solution ostensibly lies in our genes. Perhaps all that we need to do is to explore our genome well in order to identify such risks and protective factors among our genes. If we succeed in doing that through modern technological tools like bio-informatics (application of tools of computation and analysis to the capture and interpretation of biological data), chemoinformatics (use of chemical information with computer and information science techniques in a range of descriptive and prescriptive problems), genomics, transcriptomics, proteomics and metabonomics, we shall be in a better position to control and overcome disease. Thereby the focus of disease control shall shift from treatment and curation to protection and prevention leading to an integrated and holistic disease management system.
Cancer is believed to strike obese and elderly people more than the young and small creatures. However, in spite of their large body size and greater life expectancy, elephants defy this logic and exhibit less than five percent mortality due to cancer as against twenty five percent mortality in humans. Well-known secret behind this cancer resistance is that they possess twenty copies of p53 gene alongwith their forty alleles as against only one copy and two alleles in humans. No wonder p53 gene is known as ‘guardian of the genome’ because it plays a crucial role in regulating the inherent repair mechanisms of the DNA and suppresses any unwanted and uncontrolled cell growth as a result of changes or mutations occurring in DNA with each cell division cycle. Cellular senescence is yet another evolutionary adaptation found among naked mole-rats that provides them an effective form of anticancer mechanism, prevents damaged cells from dividing in an uncontrolled and autonomous fashion and developing into cancer. Further they secrete a complex "super sugar" that stops cells from clumping together and forming tumours. Tasmanian devils or Sarcophilus harrisii are also inherently resistant to cancer. If scientists succeed in unravelling these evolutionary protective mechanisms and secrets against dreadful diseases like cancer and decipher the much needed genetic code for its resistance, humanity shall be able to tackle the same with greater ease and confidence.
Similarly, Giraffes have exceptionally high blood pressure or hypertension because a giraffe has to pump blood hard enough towards its head that lies 2 to 3 metres above the level of its heart so as to overcome the huge hydrostatic pressure generated by the tall column of blood in its neck. However, surprisingly this high blood pressure in giraffes does not result in severe vascular lesions, nor does it lead to heart and kidney failure, whereas in humans, the same blood pressure could prove to be catastrophic and cause severe vascular damages. Internal walls of the blood vessels in the legs of giraffes are highly thickened to withstand the increased hydrostatic pressure and are uniquely adapted to overcome the potentially dangerous rise in blood pressure when a giraffe rapidly lowers its head down. It is believed that the adaptation through natural selection has provided it the requisite protective mechanism, because hypertension develops as soon as the giraffe stands up and erects its neck soon after birth. Thus, evolutionary adaptations and selections have been the nature’s way of protection against disease.
Many other animal species too exhibit highly evolved resistance mechanisms and adaptations towards different forms of human pathologies and disease. For instance, Burmese pythons can withstand congestive heart failure; brown bear (Ursus arctos) is immune to type-2 diabetes mellitus, obesity, neurodegenerative diseases, osteoporosis and chronic kidney disease; brown bears, Greenland sharks, jellyfish, rockfish, turquoise killifish, ocean quahog and naked mole rats age very slowly whereas elephant seals are resistant to ischemic heart disease. Scientists from several reputed universities of the world are working on these evolutionary resistant mechanisms using pioneering bioinformatic modelling to investigate the possible molecular interactions between different genes in these animal species and find out the secrets to their intrinsic disease resistance. A deep understanding of evolutionary biology and evolutionary medicine can enhance the biological understanding of disease and lead us to a unique perspective on how evolution can affect human health and disease. Evolutionary medicine applies the principles of evolutionary biology to health and disease and integrates evolution with medicine. It is sometimes referred to as Darwinian Medicine that has significantly contributed to a greater understanding of topics paramount to human health including aging, reproductive health, immune function, infectious disease, cancer, behavioural disorders and mental health, microbiomes, veterinary medicine, inflammation and diet. Thus, a deeper understanding of immunology and molecular biology clubbed with genomics and artificial intelligence can immensely help us unravel the nature’s secrets behind causation as well as curation of disease.
George Christopher Williams, an American evolutionary biologist was the first to apply evolutionary theory to health in the context of senescence. His 1957 paper entitled, “Pleiotropy, Natural Selection, and the Evolution of Senescence” is believed to be one of the most pioneering and influential works in 20th century evolutionary biology. "Evolutionary biology and the treatment of signs and symptoms of infectious disease", the paper published by Paul Ewald in 1980 and the paper of Williams and Nesse published in 1991 entitled, "The Dawn of Darwinian Medicine" were key developments in this field that led to the publication of another book entitled, “Why We Get Sick”. If humanity succeeds in decoding the secrets of risk elevation and protection for various diseases that are deeply embedded inside our genes, day will not be far when modern medicines will become redundant and might be largely replaced by gene editing techniques. Gene editing or genome engineering is a group of techniques that allows the scientists to change a living organism's DNA, thus allowing genetic material to be added, deleted, translocated or altered at specified locations in the genome. As on date, one of the biggest demerits of this technology is that the insertion of DNA into the host genome could lead to impairment or dysfunction of some other gene within that organism. The way we use grafting techniques in plants and grow flowers or fruits of different varieties on the same tree, genetic engineering or gene editing could also be used for adding a gene from one species to another organism from the same or different species to produce a particular desirable characteristic or trait. This technique is already being used in research and industry and applied to the development of cancer therapies, brewing yeasts, genetically modified plants and livestock and much more.
A comprehensive and systematic mapping of genomes across full diversity of life and species is direly required to identify animal cell, tissue, organ and gene model systems for understanding disease vulnerability, resistance, and counter-resistance that could lead to the development of novel and innovative therapeutic approaches for the treatment of disease. Dynamics of the evolutionary medicine could guide us towards novel clinical approaches that target the development of treatment resistance in cancers, lifestyle and degenerative disorders as well as antimicrobial resistance. The insight that many modern human pathologies like obesity result from mismatches between the ecologies in which we have evolved and our modern environments can have significant implications on public health policies, disease identification, prevention and treatment. Additionally evolutionary principles could also be used to understand and address various aspects of human behaviour that create impediments in biomedical innovation and public health like vaccine hesitancy (Ref: Natterson-Horowitz B, et al. The future of evolutionary medicine: sparking innovation in biomedicine and public health. Front Sci 2023;1:997136).
One of the biggest health challenges of contemporary times is antimicrobial resistance that is also believed to be a part of evolution and therefore by applying evolutionary insights to antimicrobial drug resistance we can spark transformational innovations that could be instrumental in saving human lives. An excellent example of such evolutionary approach could be the discovery of evolution-proof treatment regimens for HIV and tuberculosis. It is a well-known fact that antibiotics alter the biodiversity of microbial communities and the presence of many types of antimicrobial resistance genes in soil are affected by agricultural, livestock and other human activities. Detection of antimicrobial resistance genes (resistome) in bacteria isolated from soil and drain samples from distant lands has led to the inference that antimicrobial resistance is a part of evolution and therefore can be tackled through evolutionary biology and medicine alone. Therefore, there is need to explore all dimensions and facets of evolutionary medicine followed by their application in proper understanding of the etiology and pathogenesis of disease as well as their diagnosis, prevention, treatment and management in a proactive manner. With full mapping of human genome, transcriptome, proteome, metabolome as well as microbiome in addition to the advent of new age technologies like artificial intelligence, machine learning, data analytics, robotics, nanotechnology, immunology, molecular biology, stem cell technology, gene therapy, computational biology, bio-informatics, cheminformatics, nuclear and bio-physics, cell culture and in-vitro fertilization, sophistication and modernization of disease and drug therapy management and patient care will become a reality soon.
(Author teaches at the Department of Pharmaceutical Sciences)
