Colin, I’m not sure we ever met. We are describing different sides of the coin. The scientific method doesn’t exist without building a model, just as you say.
I first started thinking seriously about what model building means based on the scraps of conversations I had with Sir Aaron Klug in my one year as a post-doc in Cambridge. Aaron was utterly devoted to Rosalind Franklin. I was not in a position then to disagree with him. In time, however, as I meditated on how the structure of DNA emerged, I realized the paramount contribution of Jim Watson and hus relentless pursuit of the answer, and reading more deeply into Franklin’s papers, I began to feel that Franklin never would have tumbled to the double helix. She had all of the data that Watson had, but she was pursuing—in what I came to see as a moral choice—a direction in which the data were more plentiful, but in which the emphasis was inadequate. Memories begin to cloud about those days, but I think I recall a conversation with Strother Arnott in which he acknowledged to me that the A pattern could never have been used to solve the structure, and that all those data could serve only to refine models based on other data. Franklin had the appropriate metaphors—pile of pennies—in her Acta Cryst paper. I am convinced that her scientific rigor prevented her from doing what Watson did, which was to try to make sense of everything known at the time, while Franklin worshipped the data themselves. I have read and re-read Anne Sayre’s wonderful biography of Franklin, because my brief year with Aaron gives me a sense that she a scientific grandparent. I’m sure it is confirmation bias, in part, but I think Sayre also recognized the same distinction I’ve described. Franklin felt it was morally wrong to build models when the X-ray data seemed to be so much more abundant. This is one of the more tragic ironies in the history of science, because I cannot think of any human discovery more transformative in more diverse ways—biology, chemistry, medicine, evolution, epistemology, ethics—than the double helix. Thus, I think there are other scientists out there like Franklin who shrink from building models because they fear over-interpretation, which is where this thread has focused. Charlie On Nov 7, 2022, at 7:34 AM, Nave, Colin (DLSLtd,RAL,LSCI) <colin.n...@diamond.ac.uk<mailto:colin.n...@diamond.ac.uk>> wrote: Charlie What you say is very disturbing. I can’t see how you can do science at all without having a model. It is most likely that the people you refer to have a model but don’t realise it. If this is the case, the model is likely to be a very poor one. A model should be a useful simplification of a complex system in which both the parameters of the model and the values assigned to these parameters are clear. A good model of a 5G mobile phone mast should be able to predict the amount of cancers it is likely to cause. However, politicians who oppose the construction of the phone mast (in order to gain votes) will argue that scientists can’t prove they don’t cause cancer. This happened in the UK (in Bath) and of course the politician was formally correct but their model meant one should not do anything. For those still doubtful about the what a model is see, for example, https://utw10426.utweb.utexas.edu/Topics/Models/Text.html though of course there are many other sources Still all good fun to discuss. Colin From: Carter, Charlie <car...@med.unc.edu<mailto:car...@med.unc.edu>> Sent: 06 November 2022 21:19 To: Nave, Colin (DLSLtd,RAL,LSCI) <colin.n...@diamond.ac.uk<mailto:colin.n...@diamond.ac.uk>> Cc: CCP4BB@jiscmail.ac.uk<mailto:CCP4BB@jiscmail.ac.uk> Subject: Re: [ccp4bb] Another folding AI Colin, A former graduate student of mine alerted me to Box GEP, Hunter WG, Hunter JS. 1978. Statistics for Experimenters. New York: Wiley Interscience in ~1984. I bought a new copy then and have very likely spent more time inside that book than any other over the years since then. So I’m entirely in your court about Box’s contributions. On the other hand, as I diverged from crystallography into mechanistic enzymology and other areas, I began to realize that comments such as those you cited also have had the adverse affect of persuading people not to build models at all and even to induce real skepticism about building and testing models. I find that a shame. Charlie On Nov 6, 2022, at 3:12 PM, Nave, Colin (DLSLtd,RAL,LSCI) <000064fdcfc6624b-dmarc-requ...@jiscmail.ac.uk<mailto:000064fdcfc6624b-dmarc-requ...@jiscmail.ac.uk>> wrote: You don't often get email from 000064fdcfc6624b-dmarc-requ...@jiscmail.ac.uk<mailto:000064fdcfc6624b-dmarc-requ...@jiscmail.ac.uk>. Learn why this is important<https://aka.ms/LearnAboutSenderIdentification> All these quotes are great fun and worth keeping in mind, along with many others. I hadn’t realised that the creationists had adopted James Clark Maxwell as one of their own. However he didn’t go as far as one present day scientist who believes the earth is no more than 10,000 years old. Which discipline? Palaeontology of course. This person is not even some old fossil. I always liked George Box’s comments about models. I remember Eleanor Dodson saying, probably at some CCP4 refinement study weekend, that a structure obtained by protein crystallography was like a curate’s egg. She might have predated George Box with this thought. There should not be any doubt that AF2 models are useful though. The question is how far their usefulness extends. From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK<mailto:CCP4BB@JISCMAIL.AC.UK>> On Behalf Of Bryan Lepore Sent: 05 November 2022 17:03 To: CCP4BB@JISCMAIL.AC.UK<mailto:CCP4BB@JISCMAIL.AC.UK> Subject: Re: [ccp4bb] Another folding AI And of course, "... all models are approximations. Essentially, all models are wrong, but some are useful. However, the approximate nature of the model must always be borne in mind...." Box, G. E. P.; Draper, N. R. (1987) Empirical Model-Building and Response Surfaces John Wiley & Sons "Since all models are wrong the scientist must be alert to what is importantly wrong. It is inappropriate to be concerned about mice when there are tigers abroad." Box, George E. P. (1976) "Science and statistics"<http://www-sop.inria.fr/members/Ian.Jermyn/philosophy/writings/Boxonmaths.pdf> Journal of the American Statistical Association<https://en.m.wikipedia.org/wiki/Journal_of_the_American_Statistical_Association> 71 (356): 791-799 doi<https://en.m.wikipedia.org/wiki/Doi_(identifier)>:10.1080/01621459.1976.10480949<https://doi.org/10.1080%2F01621459.1976.10480949> https://en.m.wikipedia.org/wiki/All_models_are_wrong ________________________________ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 -- This e-mail and any attachments may contain confidential, copyright and or privileged material, and are for the use of the intended addressee only. If you are not the intended addressee or an authorised recipient of the addressee please notify us of receipt by returning the e-mail and do not use, copy, retain, distribute or disclose the information in or attached to the e-mail. 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