Sir

Your News story 'Long-held theory is in danger of losing its nerve' (Nature 449, 124–125; doi:10.1038/449124b 2007) discussed recent technical criticisms of work by Henri Korn, Don Faber and colleagues that was published in the early 1980s. Korn and his co-authors have replied to this News story in Correspondence ('One-vesicle hypothesis has been extensively discussed' Nature 449, 781; doi:10.1038/449781d 2007).

I would like to add my view, as I find it disturbing not only that you publish suggestions of data fabrication, but also that you revive old allegations against Korn that have already been dismissed in 1989 and 2004.

Classical work by Bernard Katz and colleagues showed that neurotransmitter release is quantized at the neuromuscular junction. These early workers formulated a mathematical approach to investigate the statistics underlying neurotransmitter release, termed quantal analysis. There were two important parameters, the release probability, p, and n, which was interpreted as the number of available vesicles. Because p was small and n was larger, Poisson statistics seemed to be an adequate approximation to neurotransmitter release statistics. When quantal analysis was applied in the central nervous system, n did not seem to be large any more and binomial statistics thus emerged as the model of choice.

This posed a problem regarding the biological interpretation of the parameter n, as it was small in relation to the number of vesicles. Korn, Faber and colleagues, guided by experiment and modelling, proposed that n represents the number of synaptic contacts rather than the number of vesicles. This fundamental insight changed the way in which neuroscientists think about synaptic transmission.

Like every influential theory, this proposal has been extensively scrutinized and refined over the past quarter of a century. It turns out that the model parameters n and p have more complicated biological interpretations and are not stable over time or across synapses. In some systems, even the very concept of quantal transmission seems to be violated.

However, finding exceptions and modifications to scientific theories does not invalidate the theories or make them worthless. Rather, this is the very fabric of the scientific process. To instil a sense of scandal into this process degrades science and misleads the public about the scientific process.