Did “Nobelitis” over-inflate the capabilities of X-ray crystallography as Best Practice?

The reason I summarised Georgina Ferry's biography of Max Perutz in my post of 17 Nov 2021 is that Max Perutz was the main driver in the establishment of x-ray crystallography as Best Practice in all aspects of protein structure. I would say he went too far. Max became an effective promoter of his views about the capabilities of the method. He himself confessed, according to the biography, that winning a Nobel Prize changed his approach. It seems he developed a case of “Nobelitis” that also infected those around him and persists to this day. Because of it's long duration, it may be the most costly case of “Nobelitis” there has ever been. Max was never a scientist of the philosophical kind. He assiduously collected data and, especially after winning a Nobel, would form a view about what it meant and vigorously promote that view. His organisation, the Laboratory for Molecular Biology (LMB), never published any of their own work to validate the method. Under Max's leadership the priority was promotion, not scientific validation. Quite likely some of his more scientifically-minded staff did try experimental validation but, from what we now know, they would have failed. Whatever the case, nothing was ever published. In 1976 Max was under considerable pressure to justify his views, his laboratory having recently been subjected to a Government enquiry in 1974 (the Phillips report) because of the cost and lack of useful results of his work. In 1976 Max made a contribution to a paper by Asakura et al. about a hemoglobin mutant (JMB 104 185-195) in which he claimed that agreement between NMR signal assignments and the crystal structure was evidence that the crystal structure was the same as the solution structure of hemoglobin. This claim ignored the fact that the NMR assignments were derived from the crystal structure. At the same time Max's assistant, Alan Fersht, wrote a textbook entitled “Enzyme Structure and Mechanism” (1977) drawing on the resources of the LMB, in which he addressed the question “Are the crystal and solution structures of an enzyme identical?” on page 15. The discussion can be criticised for dealing with the question as a false dichotomy, for arguing from the particular to the general, and not least for the fact that none of the cited evidence concerning quaternary structure bears scrutiny. With current search engines it is easy to check the claims – perhaps it was not so easy then. Later editions of the book were published in 1985 and 1999 with little change in this section. Statistically, it would take hundreds of well documented examples to reach the sought-after general conclusion. Fersht rightly points out the difficulty of doing the experiments. Nowadays it is widely conceded that crystallised proteins lose most or all of their biological function. There are no known examples of quantitative retention of biological activity. The reason given is that proteins need to breathe. That is, it is claimed the crystal structure is correct but the protein needs some more freedom to move in a way that is beyond knowing. This is a social construct to reconcile current Best Practice with the absence of supporting evidence. Hopefully it is abandoned soon.