key: cord-0944158-et8rms6z
authors: Petersen, Ole H
title: When a Discovery Is a Rediscovery: Do We Know the History of Our Own Subject?
date: 2021-06-08
journal: Function (Oxf)
DOI: 10.1093/function/zqab030
sha: 7d97f0c83c251605382c97e07efaaed68284f16d
doc_id: 944158
cord_uid: et8rms6z

nan

For example, in Xenopus oocytes, where these channels were first described in the early 1980s (1, 2) . . . " The two references in this introductory statement are to papers published in 1982 and 1983, respectively, in which there are no references to earlier descriptions of this channel. Unfortunately, the statement is misleading. As pointed out in my recent review article, 1 this channel was discovered by the late Sir Michael Berridge and his colleagues in the early 1970s and most completely described in their 1975 article in the Journal of Physiology. 3 In this article, there is even a clear diagram illustrating how these Clchannels, activated by a rise in the cytosolic Ca 2+ concentration, are essential for the process of fluid secretion in insect salivary glands. 3 The Ca 2+ -activated Clchannels were extensively characterized in mouse pancreatic acinar cells and described in many papers published several years before their apparent "discovery" in oocytes. 1 It was shown that acetylcholine opens Clchannels in the pancreatic acinar cell membrane and that intracellular Ca 2+ injection can mimic this effect. The anionic selectivity of the Ca 2+ -activated Clchannel in the acinar membrane was established with the following permeability sequence (in descending order of permeability): NO 3 -> I -> Br -> Cl -. 1 This same sequence was (re)established many years later in studies on the Clchannel in Xenopus oocytes and other cells, but again without reference to the original finding. 2 The 2005 review article on Ca 2+ -activated Clchannels 2 has a short section dealing with fluid secretion by exocrine glands, but even in this section there are no references to the original work carried out in the 1970s. Instead, another review article is cited, in which none of the original papers are mentioned, referring-again-to other review articles. This problematic pattern, seen in many review articles in many journals, is the reason that Function insists that discoveries reported in the original research articles are cited in our Evidence Reviews. The misleading information about the discovery of Ca 2+activated Clchannels 2 had consequences, as virtually all subsequent investigators and review writers continued to perpetuate the myth that these channels were discovered in oocytes and neurons in the 1980s, disregarding the reports of the much earlier discovery of these channels in the exocrine glands.

Ca 2+ -activated Clchannels are now known to be TMEM16 proteins, 4 functions, particularly in the nervous system. In 2013, an interesting study reported activation of the TMEM16A channel (also often referred to as ANO1) in nociceptive sensory neurons by local, oscillating, Ca 2+ signals generated by Ca 2+ release via IP 3 receptors. 5 However, this phenomenon was discovered, and described in detail, many years earlier in a study of pancreatic acinar cells. 6 The field of Ca 2+ -activated Clchannels in exocrine glands may be regarded as esoteric by neuroscientists, but may become central in the current COVID era. A very recently published paper shows that the lungs of COVID-19 patients contain pneumocytes with activated SARS-CoV-2 spike protein at the plasma membrane level. These cells have increased cytosolic Ca 2+ oscillations leading to increased TMEM16 activity, potentially causing increased Clsecretion, which could lead to alveolar edema. 7 For most human endeavors, we believe that an accurate knowledge of the past is important, and it is my personal belief that this must also be the case for science and, therefore, of course, also for physiology. If this is so, then we should at least give some priority to getting the history of our many different research fields right. Review writers and referees should therefore not only be concerned about the accuracy of the description of what is currently known in a particular field but also check carefully that the history of the field is correctly described.

As always, rectification of a problem requires in the first instance recognition that there is a problem. The stark example I have given in this editorial is probably not unique and may inspire others to check whether their particular field has an accurate knowledge of its past. I would be interested to hear about other cases where errors, or perhaps even deliberate omissions of key references in a prominent review article, have distorted the general perception of what was shown by whom and when.

The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas

Calcium-activated chloride channels

Membrane permeability changes during stimulation of isolated salivary glands of Calliphora by 5-hydroxytryptamine

Expression cloning of TMEM16A as a calcium-activated chloride channel subunit

Activation of the Cl -channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP 3 receptor

Local and global cytosolic Ca 2+ oscillations in exocrine cells evoked by agonists and inositol trisphosphate

Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia

I thank Nina Burdakova for helpful comments and suggestions.

The author acknowledges support from the European Commission's Horizon 2020, grant agreement 737432.

O.H.P holds the position of Editor-in-Chief for Function.