By Dillon Lim - Medicine Student @ Brasenose College, Oxford
As medical students, particularly at Oxbridge, we study human biology all the way from the macroscopic to the microscopic – from wider physiological and anatomical functions down to intracellular reactions. Molecular biology doesn’t always get a good rap among medical students – it’s sometimes disliked as a subject for being too finicky, mechanistic, or giving a level of detail that simply isn’t required when for medics, instead thought of as being the preserve of the biochemists.
Why bother then? Often, the additional understanding of the molecular mechanisms behind the action of, say, a hormone, help us to make connections that we might otherwise dismiss as coincidental. On the face of it, adrenaline doesn’t appear very similar to glucagon; while adrenaline is derived from a single amino acid and produced in the adrenal glands, glucagon is a polypeptide produced in the pancreas. They both however have very similar effects on adipose tissue, the liver and indeed on most cells when it comes to lipid and carbohydrate metabolism. Although adrenaline and glucagon receptors are very different extracellularly, they are similar intracellularly, and therefore trigger the same kind of intracellular reactions. This reaction pathway characterises responses to both adrenaline and glucagon, and explain why they both have similar effects (at least in metabolic regulation).
Many diseases have molecular explanations. In the age of genetic sequencing, we are identifying more and more mutations that are associated with disease. A mutated ion channel causes cystic fibrosis, while a mutation in a receptor causes the type of dwarfism called achondroplasia. Often, the likelihood of a mutation to significantly affect a protein’s function can be assessed quickly using knowledge of amino acid structures. If the mutation replaces a large negatively-charged amino acid with another large negatively-charged amino acid, for example, it is possible that there is almost no significant effect on the function of the protein in question. If, as in the case of sickle cell anaemia, the negatively-charged amino acid is replaced with a small, nonpolar amino acid (the famous E6V mutation), then it is usually more likely the effect on the protein’s function will be much greater.
Genetic sequencing is also allowing for targeted approaches to diagnostics and treatment; this is perhaps most obvious in cancer, when different tumours are now classed not only on their site but on their molecular identity, and thus their behaviour. Some melanomas have a mutation in the enzyme B-Raf (BRAF-mutant). Drugs which inhibit this enzyme are effective against BRAF-mutant melanomas but not other melanomas, and importantly have now been found to be effective against e.g. BRAF-mutant lung cancers.
Molecular biology is key to understanding many drug mechanisms. Some asthma medications antagonise acetylcholine receptors while others agonise adrenaline receptors, with largely similar effects at the airways. The reasons why acetylcholine receptors and adrenaline receptors have largely opposite effects to each other can be explained molecularly; but more relevant to clinical practice is the understanding that the use of adrenergic agonists in asthma is sometimes not recommended for use in patients with existing cardiac conditions, since the adrenergic agonists can also interact with receptors found in the heart.
So apart from it all just being plain interesting, I would argue molecular biology is of real importance to the medical student. The function of the human body in health and disease makes much more sense viewed through a molecular lens. Our medicine from diagnostics to therapeutics is increasingly reliant on molecular biology, and molecular medicine promises to provide some of the most exciting advances in medicine in the years to come.
About Us: Weatherall Institute of Molecular Medicine. https://www.imm.ox.ac.uk/about/about-us
How molecular biology is making medicine more precise. https://publichealth.wustl.edu/how-molecular-biology-is-making-medicine-more-precise/
Fighting cancer: ushering in a new era of molecular medicine. https://www.nih.gov/sites/default/files/about-nih/impact/fighting-cancer-case-study.pdf