NEUBAUER, OTTO

(b. Karlsbad, Germany, 8 April 1874; d. Oxford, England, 24 November 1957)

biochemistry, metabolic pathology.

The son of Wolfgang Neubauer, a general practitioner in Karlsbad, Neubauer studied medicine at the German University in Prague from 1892 to 1898. He remained there after gradation as an assistant in the Pharmacology Institute and worked with the chemist and physiologist Karl H. Huppert. During this period he acquired (largely on his own) the strong knowledge of chemistry that provided the foundation for much of his later research. In 1901 Neubauer accepted a position as assistant to Friedrich von Müller at the Medical Clinic in Basel; in 1902 he followed Müller to the Second Medical Clinic in Munich. In 1909 he was appointed instructor of internal medicine and in 1917 was promoted to assistant professor. During World War I he was drafted and served in the German army as an internist. In 1918 Neubauer, who was Jewish, was appointed head physician of the Munich Schwabinger Hospital, a position he held until he was forced to resign in 1933 with the rise of the Nazi regime. In 1939 he left Germany and immigrated to England.

Throughout his career, Neubauer worked as a physician and performed his research in the context of his clinical activity. Thus, many of his contributions were directed toward specific pathological conditions or served a clinical function. For example, in 1903 Neubauer developed a test for uribilogen using Paul Ehrlich’s aldehyde reaction. Although he soon realized that this reaction was not a specific test, it became an important clinical-diagnostic tool after Hans Fischer discovered the reaction sequence from bilirubin to uribilogen. In 1914 Neubauer developed a test that used the quantity of creatinine in the blood to evaluate kidney function.

While he was an assistant to Müller, Neubauer made his most significant contributions to basic biochemical science. Müller was much concerned with pathologies of metabolism, and under his influence Neubauer turned his attention to the chemical foundations of metabolic disorders, particularly those concerned with aromatic amino acids. One of these disorders was alkaptonuria, the primary symptom of which is a blackening of the urine upon exposure to air due to the presence of homogentisic acid. It had been established previously that the amino acid tyrosine could give rise to homogentisic acid in alkaptonuria patients, but the effect had been attributed to bacterial action. Two researchers in Müller’s unit, Leo Langstein and Wilhelm Falta, showed that phenylalanine also gave rise to homogentisic acid. With Falta, Neubauer tested a number of aromatic amino acids and showed that all of them were precursors of homogentisic acid. Neubauer interpreted the problem not as due to bacteria but as resulting from the disruption of amino acid metabolism—from the failure to metabolize homogentisate.

Neubauer extended this work into a broader set of liver perfusion studies directed at developing a general schema for amino acid metabolism. In the course of this, he produced evidence that the first step in the catabolism of α-amino acids is not the formation of an α-hydroxy acid, as then thought, but an oxidative deamination to form an α-keto acid. He proposed a schema for the catabolism of phenylaminoacetic acid according to which phenylglyoxylic acid was first produced by an oxidative deamination, and then the hydroxy acid mandelic acid was produced as a side product by a reduction reaction. Neubauer further proposed that phenylglyoxylic acid, but not mandelic acid, was metabolized to yield acetone. He found confirming evidence for this scheme in liver perfusion studies that he conducted with Walter Gross and Hans Fischer.

As a result of further studies on yeast, Neubauer and Konrad Fromherz suggested that pyruvic acid could be formed from the deamination of alanine and that ethanol was produced through a subsequent decarboxylation and reduction. They found that yeast could metabolize pyruvic acid, and therefore proposed that it might be an intermediary not only in amino acid metabolism but also in alcohol fermentation. Until that time pyruvic acid was not thought to figure in fermentation because it was at a higher oxidation level than the end product, ethyl alcohol, but Neubauer used the evidence that it was readily fermented in the process of alanine oxidation to argue for a more general role. Neubauer’s hypothesis may have played a role in the development of Carl Neuberg’s work, for shortly thereafter Neuberg identified an enzyme responsible for the decarboxylation of pyruvic acid. Two years later Neuberg and Johannes Kerb proposed their model of fermentation, which gave a central place to pyruvic acid.

After becoming head physician at Munich Schwabinger Hospital, Neubauer had little time for basic research. He did, however, write two important papers, one on techniques for studying intermediary metabolism and the other on intermediary stages in protein metabolism. In addition, he developed a number of instruments for clinical use. In 1920 he developed an aneroid device for measuring blood pressure. He later devised a slide for counting red and white blood cells. In 1930, with Heinrich Lampert, he invented a blood transfusion device that prevented the coagulation of the blood without adding anticoagulants. A related device allowed for the counting of blood platelets and for easier determination of blood coagulation time.

BIBLIOGRAPHY

I. Original Works. “Über das Schicksal einiger aromatischen Säuren bei der Alkaptonurie,” in Zeitschrift für physiologische Chemie, 42 (1904), 81–101, written with Wilhelm Falta; “Über den Abbau der Aminosiäuren im genunden und kranken Organismus,” in Deutsches Archiv für klinische Medizin, 95 (1909), 211–256; “Zur Kenntnis des Tyrosinabbaus in der künstlich durchbluteten Leber,” in Zeitschrift für physiologische Chemie, 67 (1910), 219–229, written with Walter Gross; “Beitrāge zur Kenntnis der Leberfunktionen,” ibid., 230–240, written with Hans Fischer; “Über den Abbau der Aminosāuren bei der Hefegārung,” ibid., 70 (1910/1911), 326–350, written with Konrad Fromherz; “Verwendung des Kreatinins zur Prüfung der Nierenfunktion,” in Münchener medizinische Wochenschrift, 61 (1914), 857–859; Methoden zur Untersuchung des intermediāren Stofffwechsels: Abderhaldenschen Handbuch der biologischen Arbeitsmethoden, pt.4 sec. 9 (Berlin, 1925); and “Üer den intermediären Eiweissstoffwechsel,” in Albrecht T. Bethe, Gustav von Bergmann, Gustav Embden, and Alexander Ellinger, eds., Handbuch der normalen und pathologischen Physiologie V (Berlin, 1928), 670–989.

II. Secondary Literature. Frederich Valentin,“Nachruf fur Prof. Otto Neubauer,” in Münchener medizinische Wochenschrift, 100 (1958), 354-355

William Bechtel