Hsien Wu. Public domain image reproduced from Wikipedia.
Hsien Wu may never have had the chance to become a scientist if not for the Boxer Rebellion and an Englishman’s somewhat controversial book about humans as protoplasm. Born in China, Wu was given one of President Theodore Roosevelt’s first Boxer Indemnity Scholarships, a program designed to improve American–Chinese relations after the Boxer Rebellion. Coming to America in 1911, Wu studied naval architecture at the Massachusetts Institute of Technology. On a break from the university, he read Thomas Huxley’s On the Physical Basis of Life, which unleashed an interest in biochemistry and inspired a career switch after graduation.
Wu subsequently went to Harvard Medical School, where he completed his PhD in the laboratory of Otto Folin. His dissertation, “A System for Blood Analysis,” published in the Journal of Biological Chemistry in 1919, became the essential resource for clinical laboratory analysis and a citation classic (cited >1750 times). His goal was “to combine a number of different analytical procedures into a compact system of blood analysis” (1). Wu’s thesis described the preparation of protein-free blood filtrates, nonprotein nitrogen, urea, creatinine, uric acid, and sugar, creating semi-microchemical scale assays and reducing the volume of blood required to unheard-of small volumes (10 mL vs the typical 100 mL at that time). Wu later took on the challenge of improving the method for glucose, not simply improving it but also allowing analysis on as little as a 0.1-mL sample. The Folin-Wu method for glucose became the standard assay in clinical laboratories for many years, and the Folin-Wu tube is still produced today. In that famous 1919 article from Wu’s graduate work, Folin was listed as first author and Wu the second. Today, graduate students are often given recognition as lead authors and the faculty advisor listed as the last or senior author. If Wu had been a graduate student today, would the methods be known as the Wu-Folin techniques?
Wu went on to establish himself as a pioneer in protein chemistry, publishing dozens of articles in this area. His theories were based on the concept that native proteins were not randomly shaped but had a compact, ordered structures that could be denatured into an open chain but also restored to the original conformation. He was the first to use a labeled antigen for analyzing a protein bound by an antibody (2), something that should sound familiar to clinical chemists.
Although much of Folin and Wu’s work, and others, was done using whole blood, Wu was not convinced that whole blood was the best specimen for clinical diagnosis and prognosis. In a study published in 1921 (3), Wu performed separate analyses of corpuscles (rather than whole blood) and plasma, comparing the distribution of important clinical analytes. Based on the results, Wu was the first to demonstrate the superiority of plasma and recommend that it be substituted for whole-blood analysis.
If Wu is remembered for anything by the clinical laboratory community, it is linked to Folin’s name. To paraphrase John Edsall from a 1995 article in Advances in Protein Chemistry (4), Wu’s contributions are, unfortunately, unknown to many biochemists of today; they should not be forgotten.
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T.M. Annesley, Clinical Chemistry, AACC.
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