Four Centuries of Clinical Chemistry (review)

Louis Rosenfeld. Four Centuries of Clinical Chemistry. Amsterdam: Gordon and Breach Science Publishers, 1999. xvi + 562 pp. Ill. $145.00.

In this valuable book, Louis Rosenfeld traces the impact of the development of analytical chemistry and biochemical knowledge on the emergence of clinical chemistry as an important adjunct of medical practice. He recounts the work of the many chemists, physiologists, and physicians whose contributions from the sixteenth century to the recent past have laid the groundwork of the present state of this discipline. He also describes the succession of methods and instruments they developed for the detection and quantitative analysis of a great variety of the chemical constituents of bodily fluids and tissues. During the course of this effort, the pioneer clinical chemists had to overcome the skepticism of leading physicians, and to establish strict standards for the performance and reporting of analytical measurements--a matter also well treated in this book.

After a brief account of the alchemical background, and the resistance of physicians (for example, Sydenham) to the iatrochemistry of the followers of Paracelsus (notably van Helmont and Sylvius), there is a summary of the work of Black, Priestley, and Lavoisier, and the contributions, during the first decades of the nineteenth century, of the remarkable group of medical chemists in London (Prout, Wollaston, Marcet, Bird, Bostock, Rees, Bence Jones). The scene then shifts to the Continent, with attention to Magendie, Liebig, and Bernard, and to the clinical chemical laboratories of Simon (Berlin), Heller (Vienna), and Scherer (Würzburg). By the end of the nineteenth century, there had appeared several manuals for the chemical analysis of urine and blood, with methods of uncertain reliability for the estimation of such constituents as urea, uric acid, glucose, or albumin.

After 1900, clinical chemistry received new impetus from the work of Otto Folin at the McLean Hospital and Harvard Medical School and of Donald Van Slyke at the Hospital of the Rockefeller Institute for Medical Research. Neither man was a physician; both received the Ph.D. degree in organic chemistry (Folin at Chicago, Van Slyke at Michigan). Their association with physicians spurred them to embark on a systematic development of reliable chemical methods for the diagnosis of particular diseases--in Folin's case, of dysfunction in protein metabolism, and in Van Slyke's case, of acidosis and nephrosis. Folin developed a set of new methods for the estimation of creatine, creatinine, uric acid, and several amino acids. Van Slyke invented a manometric apparatus for gas analysis, which he applied to the quantitative determination of various substances (urea, amino acids, lactic acid, etc.) that could undergo chemical reactions with the evolution of a gas. From his data, Folin proposed a theory of protein metabolism that was widely adopted until the 1930s. At Harvard, he had an outstanding group of graduate students, three of whom (Doisy, Hitchings, and Sumner) won Nobel Prizes. With the physician John Peters, Van Slyke wrote a two-volume treatise, Quantitative Clinical Chemistry; for two decades, the volume on methods was the most widely used handbook in its field, and it played a large role in the establishment of clinical chemistry as an institutional discipline. Two other U.S. biochemists, Stanley Benedict (Cornell Medical School) and Victor Myers (Western Reserve), also contributed much to the refinement of clinical chemical methods, as did the Norwegian Ivar Bang (at Lund, Sweden), who specialized in the development of micro methods.

In his account, Rosenfeld also emphasizes the importance of the commercial availability of new instruments, such as the Duboscq colorimeter (used extensively by Folin), the Beckman pH meter, with its glass electrode, and new syringes and Vacutainer tubes for drawing blood. During the 1930s, the Duboscq colorimeter was replaced by photoelectric instruments, and a few years later Beckman produced the DU quartz spectrophotometer, which was widely adopted. For clinical chemistry, the most important advance came in 1957, when Leonard Skeggs (a pupil of Myers) presented his AutoAnalyzer, in which...