Aims
This course aims to:
• provide information that helps improve your understanding of medicine within the context
of society
• enable you to synthesise ideas on the basis of evidence
• highlight the links between us, human evolutionary ancestry and interactions with the environment that potentially impact human health
Content
Who and how are we? Age-old questions asked by generations, likely from our human beginnings when first we were able to ponder such abstractions. The ‘who’ is inherited, most immediately, from our hominin ancestors; their DNA, and DNA’s intra- and intermolecular interactions with the environment within the body and the environment in which we live. The ‘how’ too results from our inheritance and interactions within our body and what we do i.e. how we interact with our environment. These interactions affected our ancestor’s wellness, and indeed survival, and likewise now our health and well-being. We interact, and our ancestors interacted with the biodiversity of organisms of the external environment, the outcomes of the interactions depending on our phylogenetic history, and the phylogenetic histories of the organisms associating with us … viruses, bacteria, and the like. For us, these outcomes today manifest themselves in good health, ill-health and indeed death itself. And by phylogenetic history, I mean the history of the evolution of species with reference to the lineages of descendants, threaded by the phylogeny of DNA to a common ancestor.
In this course Biology of Medicine, we will outline the history of medical thinking, evolutionary thought, our interactions with our internal environment and the environment in which we live and the DNA driven developments of molecular biology as a basis for understanding the basic biology of disease, pathogens, and our medical responses to them.
Thinking about disease within a DNA supported eco-evo-medical context, increases our understanding of the biology of disease, and therefore facilitates medical intervention and the discovery of how best to treat disease and ideally how to prevent it. A brief history of medical thinking helps us to appreciate the different routes from where we’ve come to our present understanding that our health depends upon myriad interactions within us, between us and between us and our environment.
Presentation of the course
The course will be presented through PowerPoints, each for one of the sessions listed below and linked with specific narrative, referenced, and fully illustrated. The PowerPoints and narrative will be the stimulus for discussion and the exchange of ideas - all with the aim of introducing perspectives of environment and evolutionary ancestry to the Biology of Medicine. These PowerPoints will be information rich and a resource for further study for a time limited period after completion of the course. Hard copy written, illustrated, and referenced course materials will support your learning and understanding.
Course sessions
1. DNA: medicine’s molecule – structure and understanding. The City of Cambridge, UK is where, in a pub called The Eagle, the structure of DNA was allegedly first announced on February 28th, 1953, by the American James Watson and Englishman Francis Crick. Nonetheless knowing the molecule’s structure - a ground-breaking event - is only the beginning of our understanding DNA. Progress over the last 70 years or so allows us to glimpse the molecule’s properties, its functions, and the significance of the information carried in its base pair sequences, information that’s beginning to allow our understanding to be applied to health care. But we must be cautious. Rethinking our early hopes of personalised medicine and conquering disease that soon followed discovery of the molecule’s structure, is necessary as work on the function of DNA has/is revealed/revealing the complexity of its intra- and inter molecular reactions, many with unsuspected outcomes for human health and disease. In this presentation we’ll outline the discovery of DNA’s structure and our emerging understanding of the molecule’s function.
2. Human Disease: Plagues, History and Civilisation. The Elder Pieter Bruegel’s painting The Triumph of Death is a frightening work. An army of skeletons advance and devastate the landscape and people, the villagers can offer no resistance. They are defenceless as the massacre unfolds. In the centre foreground of the painting, the church is captured. There is no protecting God here. In Bruegel’s apocalypse, the rage of death plunders the wealth of the kingdom and kills the king. No one is spared. The painting is in an artistic style of the late 15th century and introduces this presentation of Human Disease: Plagues, History and Civilisation. We can imagine skeletons marching out from the image shackling medieval European thinking with chains of the inevitability of the fragility of life and the near certainty of death at an early age. ‘Only God is our salvation’ was the people’s cry. But there is no God – death is triumphant. The presentation’s different themes weave the story together. The tale unfolds the European medieval mind-set about disease and its causes, and then moves historically nearer to our modern world and current medical science. We focus on infectious diseases because they were the greatest cause of disease and death then and are a constant cause and threat of disease today. Case studies illustrate the point and link the occurrence of disease pandemics with the human impact on the global environment.
3. The Immune System: mechanisms, cell recognition and immunotherapy. The presentation draws attention to the immune system’s exquisite and subtle responses to threats to our health. We explore the biology of immunology and its applications to treating different disease morphologies. Immunological recognition of cellular self and non-self is fundamental to the specificity of the white blood cell components of the adaptive immune system. These adaptive responses to pathogenic insults backed up by the more general first-line responses of the innate physical defences keep most of us healthy most of the time. The genetic regulation of some of these responses is discussed. The disruption of the balance between wellness and ill health is highlighted by examining the consequences on the individual of infection by HIV. We look at the way the virus progressively disables the immune system, exposing the HIV positive person to the raft of serious diseases constituting AIDS. The history of the discovery of HIV, the drugs, and the pursuit of a vaccine to treat HIV infection is investigated. The medical potential of immunotherapy in the treatment of diseases with a focus on cancer immunotherapy concludes the story.
4. Parasites and Disease. The presentation looks at parasitism as a category of symbiotic relationship. The focus is on understanding the genetics, ecology, evolution and biology of parasitic diseases. A parasite and its host are interacting associates. Regulation of the interactions between them implies control of the association and carries the notion of equilibrium - a balanced interaction between associates. Parasites and Disease highlights the idea that dis-equilibrium in the interactions between parasite and host results in chronic/acute disease and potentially death. The story also contrasts the medical benefits of balanced symbiotic mutualism, with reference to the gut microbiome, with the medical consequences of parasitism’s dis-equilibrium. All of this has the outcome of biological/medical reality – the idea that ‘we are what we eat’. Perhaps there is a tendency for a doctor to look at a patient entering the doctor’s surgery as an isolated individual without considering the patient’s invisible living associates as the potential cause of medical issues affecting the person as a whole. Increasing understanding of the fundamentals of parasitic disease biology helps to further the notion that wellness and illness result from the myriad of interactions within the individual, as well as the interaction between individuals and their environment. Also, understanding parasitic disease biology will help to inform the way future epidemics and pandemics are dealt with.
5. Evolution: a better understanding of human health and disease. The presentation introduces the idea that many human diseases today are the result of a ‘mismatch’ between our ancestral biology and current environment, including human lifestyles in a so-called developing and developed world. Underlying many of these mismatch diseases is the notion that many of us live with a chronic energy imbalance. Survival depends on avoiding negative energy imbalance. Inactivity and a desire for energy-dense foods are therefore likely adaptive characteristics and were not a problem when anciently and historically food was less abundant and to obtain enough needed a lot of effort.
Evolution: a better understanding… first outlines the growth of the idea of evolution through natural selection and then applies our learning to the notion that obesity (a complex multifactorial disorder combining genetic and environmental factors) can be exacerbated as the result of this positive energy imbalance that post-industrial society allows - eating too much and moving too little. Modern high-sugar and high-fat diets coupled with a sedentary lifestyle are common causes of energy imbalance and often associated with what amounts to a pandemic of different diseases such as type 2 diabetes. Regardless of the genetic background enabling our phenotype, our gastrointestinal biology inherited from our hominin ancestors has not had enough evolutionary time to catch up with modern living.
Learning outcomes
You are expected to gain from this series of classroom sessions a greater understanding of the subject and of the core issues and arguments central to the course.
The learning outcomes for this course are:
• an ability to locate medical science within the context of the biological sciences
• an appreciation of how discovering the structure of and understanding of DNA have contributed to medical science, and an ability to conceptualise medical science within a multidisciplinary framework
• an understanding that the phylogeny of genetic inheritance influences the frequency of pathologies and responses to pathogens in each genetic human population group (haplogroup) as well as the genetic variation of the individuals (haplotypes) within an haplogroup
• an appreciation of the range of evidence for improving our understanding of the causes of disease other than the proximal causes of infection, and an ability to integrate such understanding into medical practice
Required reading
Gluckman, P et al, Principles of Evolutionary Medicine (Oxford University Press, 2016, 2nd edition) ISBN: 9780199663934
Kampourakis, K, Understanding Genes (Cambridge University Press, 2022)
ISBN: 9781108812825
