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The Concepts of Ludwik Fleck and Their Application to the Eukaryotic Cell Cycle

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Science beyond borders Stephen Cooper Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor Michigan (USA) The Center for Cell Cycle Analysis, Longboat Key, Florida (USA) [email protected] http://www-personal.umich.edu/~cooper/ Evidence conforms to conceptions just as often as conceptions conform to evidence. Ludwik Fleck [(1935) 1979, p. 28] The concepts of Ludwik Fleck and their application to the eukaryotic cell cycle Abstract The concepts of Ludwik Fleck (1896–1961), a microbiologist, historian, and philosopher of medicine, can be used to analyze the conservative nature of scientific ideas. This is discussed and applied to ideas dominant in the understanding of the eukary- otic cell cycle. These are (a) the G1-phase restriction point as PUBLICATION e-ISSN 2543-702X INFO ISSN 2451-3202 DIAMOND OPEN ACCESS CITATION Cooper, Stephen 2017: The concepts of Ludwik Fleck and their application to the eukaryotic cell cycle. Studia Historiae Scientiarum 16, pp. 335–364. Available online: https://doi.org/10.4467/2543702XSHS.17.013.7714. ARCHIVE RECEIVED: 19.12.2016 LICENSE POLICY ACCEPTED: 12.07.2017 Green SHERPA / PUBLISHED ONLINE: 18.12.2017 RoMEO Colour WWW http://pau.krakow.pl/Studia-Historiae-Scientiarum/; http://www.ejournals.eu/sj/index.php/SHS/ Stephen Cooper The concepts of Ludwik Fleck and their application to the eukaryotic cell cycle a regulatory element of the mammalian cell cycle, (b) the Rate Change Point proposed to exist in fission yeast, and (c) the pro- posal that a large number of genes are expressed in a cell-cycle- -dependent manner. Fleck proposed that scientific ideas become fixed and dif- ficult to change because criticisms of current and dominant models are either ignored or turned to support of the current model. The idea of a thought-collective leading to the stabili- ty of scientific ideas is a central theme of the theory of Lud- wik Fleck. Keywords: Ludwik Fleck, G0, G1, Restriction Point, Rate-Change Point, Eukary- otic Cell Cycle, Gene Expression in Cell Cycle. Koncepcje Ludwika Flecka i ich zastosowanie do eukariotycznego cyklu komórkowego Abstrakt Koncepcje Ludwika Flecka (1896–1961), mikrobiologa, histo- ryka i filozofa medycyny, mogą być użyte do analizowania zja- wiska skostnienia idei naukowych. Zagadnienie to omówiono i zastosowano do dominujących koncepcji w rozumieniu cyklu podziału komórek eukariotycznych. Są to: (a) punkt kontrolny fazy G1 (tzw. punkt restrykcyjny) jako element regulacyjny cyklu komórkowego u ssaków; (b) punkt zmiany tempa wzrostu ko- mórek mający występować u drożdży rozszczepkowych (Schizo- saccharomyces pombe) oraz (c) postulat, że ekspresja znacznej liczby genów jest zależna od fazy cyklu komórkowego. Fleck zaproponował, że idee naukowe utrwalają się i trudno je zmienić, ponieważ krytyka aktualnych i dominujących modeli jest albo ignorowana, albo przemieniana na poparcie aktualnie obowiązującego modelu. Idea „kolektywu myślowego”, prowa- dząca do stabilizacji idei naukowych, jest centralnym tematem teorii Ludwika Flecka. Słowa kluczowe: Ludwik Fleck, G0, G1, punkt restrukcyjny, punkt zmia- ny tempa wzrostu, eukariotyczny cykl komórkowy, ekspresja genu w cyklu ko- mórkowym. 336 S. Cooper SHS 16 (2017) | DOI: 10.4467/2543702XSHS.17.013.7714 Science beyond borders 1. Introduction The Continuum Model of eukaryotic cell-cycle control is now almost 38 years old.1 This alternative view of the cell cycle2 was actually gene- rated a number of years earlier based on studies of the bacterial cell cy- cle.3 Since its initial proposal, the Continuum Model has not made much headway against what may be called the G1-phase control model of the cell cycle, or better the “Standard Model” of the cell cycle, a model that is current, dominant, and widely-accepted by a broad consensus of re- searchers in the field of eukaryotic cell-cycle studies. It is important to understand how the Standard Model has remained so dominant despite the success of the alternative Continuum Model view of the cell cycle in explaining myriad published experimental results on the cell cycle. No matter how successful the experimental and theoretical work con- firming and supporting the Continuum Model, and no matter how many articles explaining and applying this alternative viewpoint have been published, there appears to be no change in the way people talk about, perceive, or understand, the control of the eukaryotic cell cycle. Why it is so difficult to effect a change in the consensus viewpoint? Why is the currently dominant view of cell-cycle control impervious to the strongest criticisms? Is it because the current model is right? Is it because the alternative analysis has not been clear or strongly present- ed? Is it because not enough allies have been enlisted to study and ex- plain the alternative viewpoint? Recently a friend4 gave me a copy of a small book with a strange title,5 written by a person whose name was unknown to me. The book was by Ludwik Fleck, a deceased microbiologist/immunologist of Polish origin, who thought a lot about why scientific ideas are recalcitrant to change. (See photo of Ludwik Fleck, Fig. 1). This book suddenly illuminated the problem, and explained why it is so difficult to displace a widely held idea, even if that idea may be 1 Cooper 1979; 1981. 2 Cooper, Helmstetter 1968; Helmstetter 1969; Helmstetter, Cooper 1968. 3 Helmstetter et al. 1968; Cooper 1997. 4 Dr. Lawrence Sturman, Head of the Watson Laboratories of the New York State Health Department in Albany, and a friend since Graduate School. 5 Fleck 1979. S. Cooper SHS 16 (2017) | DOI: 10.4467/2543702XSHS.17.013.7714 337 Stephen Cooper The concepts of Ludwik Fleck and their application to the eukaryotic cell cycle Fig. 1. Ludwig Fleck, 1896–1961. Reprinted from: PHILWEB Bibliographical Archive. Theoretical resources off- and on-line; http://philweb.rlwclarke.net/topics/Nature/Fleck/Fleck.jpg incorrect. As will be seen below, Ludwik Fleck codified and described the processes whereby incorrect theories or ideas persist and are ren- dered resistant to change or modification. Some of Fleck’s concepts are presented here in order to explain why dominant ideas are so resistant to change. The ideas of Fleck will be discussed primarily in the context of some widely believed ideas related to the cell cycle that have been strongly criticized but the criticisms have not been widely recognized. 2. Meeting Ludwik Fleck Ludwik Fleck is mostly well known today, if one knows him at all, for his book, Genesis and Development of a Scientific Fact. This book was pub- lished originally in German in 19356 and remained relatively unknown – the original printing was merely 640 printed copies and only 200 of these were sold – until it was republished under the urging and men- torship of Thomas Kuhn, who is famous for his seminal book, Struc- ture of Scientific Revolutions(1962). 7 The English version of Fleck’s book 6 Fleck 1935. 7 However, this thesis does not apply to the German-speaking world – cf. foot- note 19, below. 338 S. Cooper SHS 16 (2017) | DOI: 10.4467/2543702XSHS.17.013.7714 Science beyond borders was published in 19798 with a translation from the original German by Fred Bradley and Thaddeus J. Trenn, with additional editing by Trenn and Robert K. Merton. Fleck died in Israel in 1961, having emigrated there from his native Poland after World War II. One may ask, “What can Ludwik Fleck con- tribute to the study of the mammalian cell cycle, since most of our cur- rent ideas on the cell cycle are of recent vintage and were developed years after Fleck’s book was published as well as years after Fleck’s death?” How can Fleck’s ideas, published in 1935, be applied to the cell cycle as they were written well before there was any understanding or knowledge of even the most basic concepts of the cell cycle, such as the existence of its different phases. The discussion presented below is an answer to this question, illustrating how Fleck’s analysis may be ap- plied to a contemporary scientific debate. To anticipate the conclusion of this presentation of Fleck’s work, the explanations of the difficulty of changing ingrained ideas are not roo- ted in science, or experiments, or even theories, but are related more to the sociology and psychology of science and thought. This concept will be explained using as examples some simple but problematic aspects of cell-cycle control, such as the restriction point, the rate change point in S. pombe, and gene expression at particular times during the division cycle. By concentrating on these simple ideas, I hope to disseminate, and perhaps popularize, some of Fleck’s most relevant ideas. The title of Fleck’s book, Genesis and Development of a Scientific Fact9 (hereafter referred to as GDSF) is somewhat odd. How can a “fact” develop? Aren’t facts solid and immutable? As one commentator is re- ported saying (from Thomas Kuhn’s forward to the translated edition10), “How can such a book be? A fact is a fact. It has neither genesis nor development.” What Fleck presented in his book is a discussion of the way in which scientific facts do “develop” and change over time. The scientific “fact” that Fleck discussed in his book is the development of ideas regarding the nature of syphilis, and in particular how the Was- serman test affected these ideas. The book is a masterful study of the 8 Fleck 1979. 9 Fleck 1935; 1979. 10 Fleck 1979, p. viii. S. Cooper SHS 16 (2017) | DOI: 10.4467/2543702XSHS.17.013.7714 339 Stephen Cooper The concepts of Ludwik Fleck and their application to the eukaryotic cell cycle historical development of ideas regarding what syphilis was, how it could be recognized, and how, during the 1920’s, the Wasserman test, despite numerous problems and confusions, led to an understanding of the nature of syphilis.
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