Teeming millions of science students have managed to graduate out of high school with the vague impression that the vesicle?the simplest cellular organelle, a bubble of fluid or gas within a cell?is part-camel?s hump and part-cloaca, micro-storage and micro-excretory organ. A couple of days ago, the allegedly humble vesicle came to the attention of the Nobel committee, which conferred the prize for Physiology or Medicine on James Rothman, Randy Schekman and Thomas S?dhof for their work explaining precisely how vesicles perform mission-critical functions in cells, delivering the right materials to the right organelles at the right time, so that cells can perform not only their own life functions, but also support excretion and the production of substances like insulin and acetylcholine, which are important for the survival of the organism of which they are a part.
While this discovery could come as a surprise to those who were taught in school that the vesicle is a garbage collector, it may not amaze those who stayed with the life sciences a shade longer. They would know, for instance, that vesicular activity is the basis of neurotransmission, by which sensory and motor signals are transmitted across the nervous system. The distance of transmission may be only a couple of inches, as in sensing a bitter taste, which is detected by the back of the tongue, a near neighbour of the sensory cortex, or over a metre, as in the flexor signal sent from a runner?s motor cortex to her toes as she springs off the blocks. Either way, the signal must traverse several neurons and be transmitted to target cells.
It leaps across synapses when, in response to an electrical stimulus transmitted by axons, vesicles in nerve endings filled with neurotransmitters like acetylcholine, epinephrine and dopamine void to the space between the cells, triggering fresh electrical activity in the next cell. This chemical leap?which happens millions of times a day?would be impossible to perform rapidly and repeatedly without vesicles to store the neuro-transmitter and unless the vesicular membrane were almost identical with the cell membrane and could fuse with it to void the chemical. Both consist of a phospholipid bilayer, the general purpose biological barrier between life and the environment. It allows the cell to retain control over its vital signs, such as pH and osmotic pressure, and resist the inimical forces of entropy. The bilayer is key to the victory of death over life.
Nobel awards recognise breakthroughs but their dramatic coverage often suggests that they are breakaways, rather?events which should be celebrated because they are unprecedented. However, scientific advances are never ahistorical. They exist in a timeline which, particularly in the life sciences, may stretch far back, even into the realm of philosophy. Thus, it has long been known that almost all cells produce signalling chemicals that alter the behaviour of other cells. In addition, it has been known that cells actively transport chemicals across their membranes against the osmotic gradient, by means of chemical pumps. In theory, being structurally similar to cell membranes, vesicles can perform the same function within the body of the cell, accumulating and discharging chemicals when necessary. The present research, which has won the Nobel, marks a significant step forward by demonstrating how this works in practice, and how it is genetically controlled.
Now, the medical and pharmacological industries may want to capitalise on it. Since insulin is one of the substances synthesised by vesicular transport, expect an immediate rethink on the politics of diabetes in particular and lifestyle diseases in general. Recently, medicine has reacted to increased disease incidence with heightened wellness fundamentalism. Such as, you deserve to get diabetes because you eat fast food. Switch to raw vegetables and you will be saved. But such quasi-moral extremism and the cultish faddism it encourages (my diet is even smaller than your diet) has failed to reverse the global tide of lifestyle diseases. More interventions are required, perhaps at the level of the membrane and the vesicle. That is the mechanism delivering insulin to the blood from the islets of Langerhans in the pancreas.
Similarly, conditions which are caused by aberrations in neuro-transmission may be easier to understand now. Autism spectrum disorders, bipolarity, panic attacks and serious mood problems, which can trigger behaviour ranging from suicide to homicide, come to mind immediately. Indeed, following further work in the direction set by Rothman, Schekman and S?dhof, many disorders which are caused by the unusual metabolism of hormones, neurotransmitters or any other class of signalling chemicals may become easier to understand and treat. From the point of view of medical practice, their work may become a cornerstone of future therapy. But from the point of view of science, it is just another step in an endless quest.
pratik.kanjilal@expressindia.com