Matches in SemOpenAlex for { <https://semopenalex.org/work/W2021567165> ?p ?o ?g. }
- W2021567165 endingPage "650" @default.
- W2021567165 startingPage "623" @default.
- W2021567165 abstract "Sickle Cell Anemia: Reexamining the First “Molecular Disease” Simon D. Feldman (bio) and Alfred I. Tauber (bio) Introduction One of the key studies marking the emergence of molecular paradigms in medicine is the 1949 article by Linus Pauling (1901–94), who showed that sickle cell anemia was due to an abnormal hemoglobin molecule. 1 Although Vernon Ingram’s demonstration of the amino acid substitution in the beta-hemoglobin chain defined the molecular basis of sickle cell disease, 2 Pauling’s study elucidated the nature of the disorder. His finding of a physicochemical abnormality in the hemoglobin molecules of sickle cell patients justifies the appellation “molecular disease.” 3 Pauling is celebrated in the historiography of sickle cell anemia research, which presents his work on the relationship between the chemical nature of hemoglobin and the structure of sickled cells as a turning point in the reorientation of research from clinical to molecular. 4 More [End Page 623] broadly, because of his first demonstration of an abnormal protein by physicochemical methods, he is hailed as the key architect of molecular medicine, whose biomedical agenda was to dominate research for the rest of this century. We suggest that the emphasis on the Pauling story reveals a romanticized and unsuccessful attempt to understand the difficult history of sickle cell anemia research. Furthermore, the story (as usually narrated) promotes the promise of a reductionist approach to medicine, serving to illustrate the power and eventual dominance offered by such a strategy. Our orientation reflects a somewhat different attitude; we contend that while the history of sickle cell anemia is indeed illustrative of the respective roles of clinician and chemist, a more subtle and complicated interplay of research traditions and methodologies was at work than simply the final successful application of chemistry to elucidating a complex disease. Setting Pauling’s accomplishment in context, we show how shifting research paradigms influenced successive redefinitions of sickle cell anemia along a broadly reductionist path. The years between 1910 and 1945 were a time of ambiguous characterizations of the basis of the disease. These initial attempts to define the pathophysiology of sickling as well as the genetics of the disorder reflect a complex array of ambiguous factors, not the least of which was the conceptual confusion concerning the nature of proteins during the 1920s, 1930s, and 1940s. The complex nature of Pauling’s revolutionary efforts will be seen more clearly if the story of a chance encounter and a brilliant, novel insight is subjected to critical assessment. This popular narrative relates how William Castle and Pauling shared a train compartment returning from a meeting in Denver in 1945. 5 The two were serving on a committee eventually responsible for the publication of Vannevar Bush’s book Science, the Endless Frontier. According to Castle, while on the train from Denver to Chicago, he happened to mention to Pauling the phenomenon of birefringence of deoxygenated red blood cells, thinking that there might be interesting implications for molecular alignment. This [End Page 624] comment, apparently placing the sickle cell problem in Pauling’s hands, and prompting him to unravel the explicit connection between molecular structure and clinical pathology, is taken as a critical moment in the history of the molecularization of medicine. The human and contingent element of this story is important because it proposes to bridge an apparent disjuncture in the history of sickle cell research by anecdotally representing a well-demarcated boundary between clinical and molecular paradigms. For example, Maxwell Wintrobe emphasizes the function of chance in this incident and its implications for the history of medicine: “As it turned out, it was this incidental observation that, in the course of a chance conversation, was brought to the attention of Linus Pauling. For him the birefringence had some meaning. The resulting series of studies had a momentous impact on biomedical science.” 6 In The Eighth Day of Creation, Horace Judson characterizes Pauling’s contribution in this way: “The nature of the disease was first understood by Linus Pauling, with what was even for him an astounding flash of physical intuition.” 7 Narratives like this have glorified the entire episode, and more specifically, Pauling’s contribution. Pauling himself seems to have revised his own..." @default.
- W2021567165 created "2016-06-24" @default.
- W2021567165 creator A5054748374 @default.
- W2021567165 creator A5085446741 @default.
- W2021567165 date "1997-01-01" @default.
- W2021567165 modified "2023-09-23" @default.
- W2021567165 title "Sickle Cell Anemia: Reexamining the First "Molecular Disease"" @default.
- W2021567165 cites W1484184072 @default.
- W2021567165 cites W1491365494 @default.
- W2021567165 cites W1491604287 @default.
- W2021567165 cites W1529965091 @default.
- W2021567165 cites W1532778603 @default.
- W2021567165 cites W1541479720 @default.
- W2021567165 cites W1605289340 @default.
- W2021567165 cites W1605611176 @default.
- W2021567165 cites W1757735653 @default.
- W2021567165 cites W1973679399 @default.
- W2021567165 cites W1975812679 @default.
- W2021567165 cites W1998842383 @default.
- W2021567165 cites W2000201048 @default.
- W2021567165 cites W2001673977 @default.
- W2021567165 cites W2006330582 @default.
- W2021567165 cites W2013984501 @default.
- W2021567165 cites W2027816595 @default.
- W2021567165 cites W2032886683 @default.
- W2021567165 cites W2033985767 @default.
- W2021567165 cites W2041595751 @default.
- W2021567165 cites W2044789512 @default.
- W2021567165 cites W2055580981 @default.
- W2021567165 cites W2055884604 @default.
- W2021567165 cites W2074294128 @default.
- W2021567165 cites W2076356025 @default.
- W2021567165 cites W2084295229 @default.
- W2021567165 cites W2087003437 @default.
- W2021567165 cites W2089819802 @default.
- W2021567165 cites W2093002151 @default.
- W2021567165 cites W2095791446 @default.
- W2021567165 cites W2124792056 @default.
- W2021567165 cites W2156280661 @default.
- W2021567165 cites W2166255518 @default.
- W2021567165 cites W2316323923 @default.
- W2021567165 cites W2318525553 @default.
- W2021567165 cites W2402564691 @default.
- W2021567165 cites W2405752081 @default.
- W2021567165 cites W2495828235 @default.
- W2021567165 cites W2898870009 @default.
- W2021567165 cites W563562902 @default.
- W2021567165 cites W580343720 @default.
- W2021567165 cites W650295849 @default.
- W2021567165 cites W82328309 @default.
- W2021567165 cites W2081632499 @default.
- W2021567165 cites W2291261177 @default.
- W2021567165 cites W2338867438 @default.
- W2021567165 cites W2413990026 @default.
- W2021567165 doi "https://doi.org/10.1353/bhm.1997.0178" @default.
- W2021567165 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9431738" @default.
- W2021567165 hasPublicationYear "1997" @default.
- W2021567165 type Work @default.
- W2021567165 sameAs 2021567165 @default.
- W2021567165 citedByCount "15" @default.
- W2021567165 countsByYear W20215671652014 @default.
- W2021567165 countsByYear W20215671652015 @default.
- W2021567165 countsByYear W20215671652019 @default.
- W2021567165 crossrefType "journal-article" @default.
- W2021567165 hasAuthorship W2021567165A5054748374 @default.
- W2021567165 hasAuthorship W2021567165A5085446741 @default.
- W2021567165 hasConcept C118552586 @default.
- W2021567165 hasConcept C126322002 @default.
- W2021567165 hasConcept C185592680 @default.
- W2021567165 hasConcept C2778248108 @default.
- W2021567165 hasConcept C2778620579 @default.
- W2021567165 hasConcept C2778917026 @default.
- W2021567165 hasConcept C2779134260 @default.
- W2021567165 hasConcept C71924100 @default.
- W2021567165 hasConceptScore W2021567165C118552586 @default.
- W2021567165 hasConceptScore W2021567165C126322002 @default.
- W2021567165 hasConceptScore W2021567165C185592680 @default.
- W2021567165 hasConceptScore W2021567165C2778248108 @default.
- W2021567165 hasConceptScore W2021567165C2778620579 @default.
- W2021567165 hasConceptScore W2021567165C2778917026 @default.
- W2021567165 hasConceptScore W2021567165C2779134260 @default.
- W2021567165 hasConceptScore W2021567165C71924100 @default.
- W2021567165 hasIssue "4" @default.
- W2021567165 hasLocation W20215671651 @default.
- W2021567165 hasLocation W20215671652 @default.
- W2021567165 hasOpenAccess W2021567165 @default.
- W2021567165 hasPrimaryLocation W20215671651 @default.
- W2021567165 hasRelatedWork W1508664328 @default.
- W2021567165 hasRelatedWork W2310256447 @default.
- W2021567165 hasRelatedWork W2319000399 @default.
- W2021567165 hasRelatedWork W2319862760 @default.
- W2021567165 hasRelatedWork W2471743968 @default.
- W2021567165 hasRelatedWork W2748952813 @default.
- W2021567165 hasRelatedWork W2899084033 @default.
- W2021567165 hasRelatedWork W3196021468 @default.
- W2021567165 hasRelatedWork W4252629617 @default.
- W2021567165 hasRelatedWork W45895407 @default.
- W2021567165 hasVolume "71" @default.