Encounter with J. Lisman

Last Tuesday, I had the opportunity to attend a seminar by Prof. John Lisman, one of the most acknowledged experts in long-term synaptic plasticity and certainly one of the most influential neuroscientists of our times. I was fascinated by the content of his talk but his words went deeper then expected, eliciting a broad range of thoughts that I'd like to share.

As a romantic, Italian scientist, I couldn't avoid recognizing in Prof. Lisman one of the most beautiful stories in Academics. Though his appearance resembles the one of a senior researcher, nothing could arise more evidently than his childlike enthusiasm for every bit and piece of his life-long research. It was like watching my son when at his young age of 2 tries to tell me the story that mum bit the moon and now the moon is not rounded, with a contour of unimaginable surprise. So after flying over the myriad of impressive results that he and his collaborators have collected during the last decades, he finally landed on the Atlantis of his research, or the "Holy Grail" of his life, as he himself called it. The Holy Grail is a picture that shows that using CaMKII inhibitors, CN21 and CN19, it is possible to reverse LTP without destroying synapses (Lisman and Yasuda and Raghavachari, Nature, 2012). Because of this evergreen enthusiastic scientist, we are now able to understand some of the most intricate mechanisms of synaptic potentiation that links single proteins to synaptic plasticity and probably, but most certainly, behavior. We are closer-than-ever to the identification of the fundamental building blocks of memory formation through LTP, though such conclusive evidences on the link between CaMKII and memory are yet to be found. For that, Prof. Lisman hopes that the next experiment is going to be the "cherry on top".

I felt positive after his talk because several times I have experienced the same enthusiasm. I remember running home one day, after a long discussion with a colleague of mine, just for the fact that I couldn't contain the emotion deriving  from our conclusions. However, I am aware of the fact that emotion, passion, enthusiasm, these feelings can't make the whole story. They are the fuel of our life but whether the energy will ever be translated into practical outcomes or not, this is only up to us and our engines. Obviously a good amount of hard work is needed, so engines should work for long time at a good pace, but if one wants to win the race you also need good engines, good engineers to put them together, good maintenance, good practice and so on. For my own race, instead, what if some of the pieces above is missing and I can't do anything about it? What if my engines are just not powerful enough? Do I still have a chance to win the race? To me, winning the race means moving forward human knowledge, inspire new generations of researchers, have a real impact on people's life out of the lab. To be clear, John Lisman won his race. So to stay on the safe side, I will assume that some of the pieces are already missing. I probably don't have the best engine or perhaps there hasn't been perfect maintenance throughout the years. However my conclusion is that, fortunately, it doesn't matter and in fact there probably isn't any race to win in the first place. The race model is probably not a good model for a scientific career. Instead, the advance of human knowledge is determined by a coalesced stack of scientific contributions and our role of scientists, irrespective of the engine, is to keep the stack coalesced and bring it forward.

So, here is my model. As scientists, we are given a certain amount of dominoes, you know the ones with a number on one end and an other on the other end. Some of us is given tons of them, some just a few. While some have various ones, covering all different combinations of numbers, some have a just a bunch of equal pieces. Some can even acquire new ones every now and then during the game, and some don't. Some start with marble dominoes, some with wooden ones, some with shiny handcrafted dominoes made of crystal. Some scientists know the rules of the game, i.e., to stack dominoes if they have the same number on one side. Some misbehave at times and don't follow the rule but others can spot the blunder and can cut parts of the chain if the flaws are found. You know where this is going. Human knowledge is the Domino. Connecting more tiles makes the chain longer but this can be realized only if the right combinations of dominoes can be obtained with the available pieces. The chain cannot proceed any longer if the right combinations can't be satisfied. Though some scientists put tons of crystal tiles on the table, sometimes they need single marble or wooden tiles to stitch the parts together or even to just start their branch in the first place. Hence, irrespective of their nature, all dominoes are in fact fundamental pieces of the chain. Though the chain is mostly made of crystal, at a finer resolution we would notice that fewer marble and even fewer wooden tiles keep the chain all together.

I don't know if the above is a good model of science but is one that for the moment is helping me in defining my future career with more clarity. I like the Domino model because it resembles other interesting models of random growth where the mechanisms that rule the connections between particles are stochastic and their probabilities depend on some changing factors. In fact it is common in Physics to find situations where it is not important what the particles are or how they are built. What's more relevant, instead, is how they interact, just as single proteins bind in the synapse and lead to LTP.

F. Stefanini (Published with the kind permission of Prof. John Lisman.)