Fritz Pregl | Biography

The work of Fritz Pregl is an example of the maxim that every difficulty is an opportunity. It was the problems inherent in analyzing organic matter that motivated Pregl to take microanalysis into new realms of exactitude, developing new instrumentation for the precise measurement of such substances. Such microanalytic tools paved the way for later biochemical research on pigments, hormones, and vitamins. Pregl's innovations in the field earned him the 1923 Nobel Prize in chemistry.

Pregl was born on September 3, 1869, in Laibach, Austria (now Ljubljana, Republic of Slovenia), the only son of Friderike Schlacker and Raimund Pregl, the treasurer of a bank in nearby Krain (now Kranj). Though his father died when he was quite young, Pregl finished Gymnasium or high school in Laibach before he and his mother moved in 1887 to Graz, where he studied medicine at the University of Graz. Early in his academic career, Pregl demonstrated the intelligence and skill that would become more evident in his subsequent work as an analytical chemist. While still a student, his physiology professor, Alexander Rollett, made him an assistant in his laboratory. Upon gaining his medical degree in 1893, Pregl began to practice medicine with a specialty in ophthalmology but also stayed on part-time at Rollett's laboratory.

Becoming an assistant lecturer in physiology and histology at the University of Graz, and working in Rollett's laboratory, Pregl increasingly turned his attention to biological and physiological chemistry, focusing on organic matter. His early research centered on human physiology and, in particular, the properties of bile and urine. His research on the reaction of cholic acid, which is found in bile, and the causality of the high ratio of carbon to nitrogen in human urine, won him a university lectureship at Graz in 1899. In 1904, Pregl went to Germany to study chemistry with Friedrich Wilhelm Ostwald in Leipzig and Emil Fischer in Berlin. Fischer was a 1902 Nobel laureate in organic chemistry for his sugar and purine research, and Ostwald, a physical chemist, would win the Nobel in 1909 for his work in catalysis.

Returning to Graz in 1905, Pregl renewed his bile research and began protein investigations, having been intrigued by Fischer's recent work on the structure of proteins. He also became an assistant at the medical and chemical laboratory of the University of Graz, a position which provided him with valuable research space. In 1907 he was appointed as the forensic chemist for central Styria, the province of which Graz is the capital. In the course of his chemical investigations, Pregl continually came up against one problem: the methods of analysis employed by organic chemistry were much too cumbersome, lengthy, and overly complex for the new discipline of biochemistry in which he was becoming increasingly involved. In particular, Pregl found that he would have to prepare large amounts of test samples if he used traditional analytical methods in his studies on bile acids. Because these acids are complicated proteins, only small quantities can be isolated from liver bile, a process that is both time-consuming and costly: Pregl's research in bile acid alone would require processing several tons of raw bile in order to refine enough of the acid for traditional analysis. It was to overcome such difficulties that he set to improve the methods of microanalysis, thereby altering the direction of his research from biochemistry to analytical chemistry.

By the time Pregl entered the field, microanalysis was already over seventy years old, pioneered by Justus von Liebig, who had developed the combustion method . In Liebig's technique, proportionate amounts of elements in an organic substance could be determined by burning the substance in a glass tube under conditions that would convert the carbon to carbon dioxide (CO2) and all the hydrogen into water. The water and CO2 would in turn be absorbed by other materials such as potassium hydroxide or a lime and soda mixture, and the change of weight in the respective absorbing materials would thus give the relative amounts of carbon and hydrogen in the combusted substance. Additionally, a contemporary of Pregl's, Friedrich Emich , at the Technical University of Graz had shown the reliability of working with small quantities of substances in an inorganic framework. Pregl set out to achieve Emich's measurement techniques with organic material.

It was Pregl's achievement to build upon Liebig and Emich's developments, and to refine and improve them to the point where substantially less of the organic substances were required for analysis. In 1910 he left Graz for Innsbruck, where he took the position of professor of medical chemistry at the University of Innsbruck. With this position, Pregl could devote more time to his research. His first priority was to find or create a balance that would accurately weigh much smaller amounts of substances than those currently available. He turned to W. H. Kuhlman, a German chemist who had recently developed a microbalance accurate to between 0.01 and 0.02 milligrams; Pregl found that with careful adjustments he could accurately utilize Kuhlman's balance to within 0.001 milligrams.

Pregl also took on the combustion analysis of carbon and hydrogen, improving that process by scaling down the size of the analytic equipment and adding a universal filling for the combustion tube that consisted of a mixture of lead chromate and copper oxide set in between two pieces of silver. This adaptation improved the absorption of the carbon dioxide and water. With such refinements, Pregl was able to obtain accurate analyses with between 2-4 milligrams of an organic substance--and fairly accurate readings with only 1 milligram--a significant reduction compared to the .2 to 1 grams needed for Liebig's method. With the new materials employed, Pregl was also able to reduce the time needed for such analysis from three hours to an hour. Pregl and his team also went on to devise new microanalytic techniques for boiling substances to determine their molecular weight by creating apparatus that impeded the substances' contamination with air. This allowed determinations to be made with greatly reduced amounts of such substances. Pregl made these advances known in two public presentations: in 1911 at the German Chemical Society in Berlin, and in 1913 at a scientific congress in Vienna.

Although improved techniques since Pregl's time now allow scientists to work with organic samples of only a few tenths of a milligram, his microanalytic improvements were revolutionary in their day and opened the way to new vistas of biochemical research in both science and industry. World renowned, Pregl returned to the University of Graz in 1913 as a full professor at the Medicochemical Institute, and here he perfected the methods he had pioneered, remaining in Graz--despite other tantalizing offers--until his death. In 1916, in the midst of the First World War, he was made dean of the medical school, and in 1920 became vice chancellor of the university. His major publication on his findings, Die quantitative organische Mikroanalyse, was published in 1917 and has since gone through numerous editions and translations. He subsequently won the Lieben Prize and membership in the Vienna Academy of Sciences. Pregl continued his research into a wide range of organic substances, employing his own methods of microanalysis on bile acids, enzymes, and sera. He also employed microanalysis in forensics, determining poisonous alkaloids from minute amounts of substance.

In 1923 Pregl was awarded the Nobel Prize in chemistry for his advances in microanalysis of organic substances. Though his work was an improvement rather than an invention, it was a well deserved honor for a man who tirelessly devoted his life to the cause of science. A life-long bachelor, Pregl's only pleasures aside from his research were mountain climbing and bicycling. He was also devoted to his students, lending both money and support when needed. In 1929 he endowed an award for chemistry through the Vienna Academy of Sciences, the Fritz Pregl Prize, which continues to provide yearly stipends to promising students. Pregl died following an illness in 1930 at the age of sixty-one.