Tales of the unexpected

UNDER THE MICROSCOPE
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What endures in science are the discoveries. No records are ever kept of the personal stories, the twists of fate that suddenly enabled an individual to see the world in a slightly different way. But for some of the greatest discoveries, tales occasionally trickle down.

One Camillo Golgi was working away in late 19th century Italy. He was attempting a truly daunting project: to visualise exactly what the brain was made of. Of course any customer at the butcher could see with their naked eye that the brain was composed of some sort of creamy stuff, the consistency of a raw egg. But under a microscope, Golgi saw nothing that could reveal the secrets of the incredible functions of the brain. Then one day, accidently, he knocked a small lump of this brain tissue into a dish of silver nitrate, where it remained for several weeks. When Golgi retrieved the lump, he noticed that it had been transformed: it was now shot through with shining streaks. He earned his place in history by observing, for the first time ever, brain cells, "neurones", stained black against an amber background in exquisite, detailed silhouette. A chance mishap had given birth to modern neuroscience.

A few decades later, in England in 1914, Henry Dale was puzzling over the effects of a particular chemical on the heart. He had already shown that this substance (acetylcholine) could slow heart rate down: but what he could not understand was that its effects were extremely short-lived. Then realisation struck him: the acetylcholine was having such an evanescent effect not because he was doing the experiment badly or "wrongly" - a thought that would be uppermost nowadays in the minds of most graduate students and their supervisors - but because the acetylcholine was itself being destroyed by a special, naturally occurring enzyme (acetylcholinesterase). With this flash of insight Dale identified a critical step for chemical communication by nerves, that was necessary if they were to be clear and unambiguous - the immediate destruction of that chemical once the signal was sent.

The third story is perhaps the least credible scientifically since it involves a dream. Part of the problem in doing good science is designing the experiment that will answer unequivocally the question that you are asking. An Austrian, Otto Loewi, could see no obvious way of demonstrating whether or not a nerve did indeed communicate with an organ such as the heart, by releasing a naturally occurring chemical. But then he dreamed of the ideal experiment. In retrospect, the experiment was simple and obvious. First, stimulate the nerve targeting the heart so that it slows down. This step had already been done. The master stroke, however, that had occurred to Loewi only in the dream, was to transfer the fluid bathing this original heart to a second heart that had not been treated. Amazingly, once bathed in the fluid from the first heart, the second heart also slowed down. The stimulation of the first heart had led to the release of the critical chemical messenger (acetylcholine), present in the transferred fluid. No need to invoke any paranormal happenings here: simply, Loewi finally followed his intuition, an "obvious" solution that occurred to him when he was most relaxed.

All these stories have a common thread: a seemingly "unscientific" way of proceeding. What a shame that the current zeal for caution and predictability among the grandees of the grant-giving bodies means strait-jacketed research applications offering protocols where most of the "proposed" work has effectively already been done, and where there is no room for the insight provided by a mistake, a dream or, heaven forfend, the unexpected.

! Susan Greenfield is a neuroscientist at the University of Oxford, and Gresham Professor of Physic, London

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