Nose, situated almost at the centre of our face may arguably be the best chemical detector on the planet! It is also the key arbiter of fitness and survival as it determines what animals in general, eat or drink , when to keep away and whom they mate ,and , really humans are no different!
It’s not fishy! We have finally broken the code of nature and understood as to how we appreciate and remember tens of thousands of different odours which have helped us survive through millions of years of evolutionary pressure.
This seminal research into Odorant receptors and complex organisation of the olfactory system, leading to definitive understanding of one of the most enigmatic problems of our sensory nervous system, was awarded the Nobel Prize in Physiology or Medicine in the year 2004 to Dr Richard Axel and Dr Linda B Buck.
This is only the second Nobel Prize related to the nervous system with reference to the olfactory system and that too after almost a hundred years’ interval since Ramon Y. Cajal was awarded in the year 1996 underscoring the difficulties faced by the researchers in the field of nervous system.
The molecular basis of Olfaction, the sense of smell with over thousands of different odours has been a very complex issue. How the brain transforms physical stimuli into perception? , has been one of the most sought after area of research for a very long time!
Dr Axel and Dr Buck together found out thousands of different genes which constitute fairly high - 3% of our total human genes, engaged alone in olfaction. Each gene governs a single olfactory receptor type located mostly in the upper specialised part of the nasal epithelium called olfactory epithelium and possesses the ability to detect even minuscule amounts of inhaled odorant molecules. These olfactory receptors present on the olfactory ciliary membrane , are very specific and definitive for different odours .These chemo- sensory receptors send impulses to nerve fibers to its distinct micro domains known as Glomeruli and then to specialised Mitral cells present in the olfactory bulbs , which is a part of the Fore - Brain . From olfactory bulbs specific nerve fibres reach different parts of the brain called olfactory cortex where information from several olfactory receptors combine to give a specific pattern. Such patterns form conscious appreciation of different shades of smell and eventually become part of our memory. These fibres also reach both hippocampi and Limbic systems to add much needed emotional components into the sense of smell.
Dr Axel and Dr Buck were instrumental in discovery of over thousands of genes largely located on chromosome 17, which code for the different odorant receptors which form the foundation of understanding the phenomena of olfaction.
All living beings depend on odours as a very important tool for survival. Whereas fishes carry only about one hundred odorant receptors ( OR ) , mice have about one thousand ORs - a little more than human beings as we have sadly lost some of them during evolution. Dogs have several times more OR than human beings which is manifested in their much wider range of olfaction and fuller range of related activities.
We all see how newborn pups of mammals use olfaction to locate teats to obtain milk for their early survival and as an adult olfaction comes handy in interpreting the environment around them.
Odorant Receptors are proteins consisting of chains of amino acids anchored into the cell membrane. The amino acid chain makes a pocket where the Odorant molecules get attached and with their attachment the configuration of the receptors change , leading to G protein activation bringing cyclic AMP formation. This messenger molecule - cAMP activates the specific ion channels present in the odorant cells which opens up to generate electrical current which travel upward through the olfactory nerves.
Dr Axel and Dr Buck brought the OR (odorant receptors) into focus and established its relationship with the specific G protein called GPCR. This G protein coupled receptors as mentioned above, are regulated by over thousand genes, each gene coding for one specific receptor. It was possible to show, by documenting the electrical signals emanating from specific odorant receptor cells that each cell does not react to just one odorant substance but to several related molecules in varying intensity making a pattern for specific odour !
Dr Buck could decipher which odorant receptor gene was expressed in which OR and how information are organised in Brain cortex.
Dr Buck used a novel tracing system prepared by her in mice that co - expressed a trans - neuronal tracer with single receptor gene. The tracer travelled from neurones expressing the particular odorant receptor to recipient olfactory glomeruli, and projection neurones present in the olfactory bulb and then to the olfactory cortex. The tracer labelled five to six distinct clusters of neurones projected in the distinctly located olfactory and associated cortex, giving first glimpse of signal organisation in the related cortex and thus advanced the domain knowledge in the field of nervous system and Brain science.
This opened the floodgates of much needed research in the field of neuroscience as aptly put by Nobel laureate and physicist Professor David Gross that “ the most important product of science is ignorance” , re - emphasing the value of more breakthrough researches for scientific progress.
Clinically speaking loss of smell is generally associated with loss of taste also and they together suggest shortened length of life in elderly and calls for intensive exploration for any co existing disease states such as Alzheimer’s ,Parkinson’s disease etc. However, it is strange that Covid 19 patients presenting with loss of smell and taste, have distinctly better outcome stressing for more research in this field!
The author is Former Professor and Head, Dept. of Medicine, RIMS, Ranchi, Jharkhand.