The Discovery of Heterotrophic Carbon Dioxide Fixation by Harland G.Wood
Year: 2005
Type: article
Abstract: Heavy Carbon as a Tracer in Heterotrophic Carbon Dioxide Assimilation(Wood, H. G., Werkman, C. H., Hemingway, A., and Nier, A. O. (1941) J.Biol. Chem. 139,365-376) The Mechanism of Carbon Dioxide Fixation by Cell-free Extracts of PigeonLiver: Distribution of Labeled Carbon Dioxide in the Products (Wood, H. G.,Vennesland, B., and Evans, E. A. (1945) J. Biol. Chem. 159,153-158) The Fixation of Carbon Dioxide in Oxalacetate by Pigeon Liver (Utter, M.F., and Wood H. G. (1946) J. Biol. Chem. 164,455-476) Harland Goff Wood (1907-1991) was born in Delavan, a small village in southcentral Minnesota. He attended Macalester College in Minnesota where hemajored in chemistry. Wood graduated during the Depression, and because jobswere scarce, he decided that he would need a higher degree to meet thecompetition. His biology professor, O. T. Walters, suggested he apply for afellowship in bacteriology at Iowa State College. Wood's application wasreviewed by Chester Werkman, author of a previous Journal of BiologicalChemistry (JBC) Classic(1JBC Classic Utter M.F. Lipmann F. Werkman C.H. J. Biol. Chem. 1945; 158 (http://www.jbc.org/cgi/content/full/280/16/e13): 521-531Abstract Full Text PDF Google Scholar), who was starting toinvestigate the chemistry of bacterial fermentations and was looking for achemistry student. Werkman accepted Wood's application, and in 1931 Wood movedto Ames, Iowa. For his thesis research, Wood was assigned an investigation of fermentationby propionic acid bacteria, a group of bacteria that ferment compounds such asglycerol with the formation of propionic acid. He started by looking intoglucose fermentation and determined that succinate is formed from glucose.Next, he decided to investigate glycerol fermentation in propionic acidbacteria. He determined the products of glycerol fermentation in a bicarbonatebuffer system and calculated the carbon and oxidation-reduction balances toaccount for the carbon of the fermented substrate. Surprisingly, Wood foundthat the products from glycerol fermentation contained more carbon than wassupplied by the fermented glycerol. He subsequently discovered that the extracarbon was derived from CO2 in the buffer and eventually proposedthat CO2 and pyruvate combine to form oxalacetate, which issubsequently reduced to succinate(2Wood H.G. Werkman C.H. The utilizationof CO2 by the propionic acid bacteria in the dissimilation ofglycerol..Biochem. J. 1935; 30 (abstr.): 332Google Scholar,3Wood H.G. Werkman C.H. The utilizationof CO2 in the dissimilation of glycerol by the propionic acidbacteria..Biochem. J. 1936; 30: 48-53Crossref PubMed Google Scholar). This ultimately becameknown as the Wood-Werkman reaction. However, as with many new findings, Wood's discovery of heterotrophicCO2 fixation was extremely controversial. At that timeCO2 fixation was believed to occur only in plants and a few unusualautotrophic bacteria, and the publication of his results was met with muchskepticism. For example, C. B. van Niel stated that, “Wood and Werkmanclaim that carbon dioxide is reduced during the fermentation of glycerol bypropionic acid bacteria. The published results cannot, however, be consideredconclusive, although the data do seem to favor their claim”(4Singleton R. HeterotrophicCO2-fixation, mentors, and students: the Wood-Werkman Reactions.J. Hist. Biol. 1997; 30: 91-120Crossref PubMed Google Scholar). Even Wood thought hisresults might be wrong and didn't include them in his thesis. In 1935 Wood went to the University of Wisconsin where he worked as apostdoctoral fellow with W. H. Petersen for 4 years. At Wisconsin he studiedthe growth factor requirements for propionic acid bacteria with Ed Tatum. Theyshowed, for the first time, that vitamin B1 is required for thegrowth of a microorganism(5Tatum E.L. Wood H.G. Peterson W.H. Growth factors for bacteria. V. Vitamin B12: a growth stimulant forpropionic acid bacteria..Biochem. J. 1936; 30: 1898-1904Crossref PubMed Google Scholar). Werkman then offered Wood a position as an Assistant Research Professor atIowa State, and he returned to Ames in 1936 to continue his work onCO2 fixation. At that time they only had indirect evidence thatCO2 was fixed in succinate. Wood's brother, who was studying forhis Ph.D. and M.D. at the University of Minnesota, mentioned some studiesbeing done with 13C and suggested that he collaborate with a youngphysicist named Alfred Nier who would be able to supply labeled carbon andmeasure it with a mass spectrometer. As reported in the JBC Classic reprintedhere, Wood was able to prove that 13CO2 is fixed insuccinate and that the 13C is located exclusively in the carboxylgroups (6Wood H.G. Werkman C.H. Hemingway A. Nier A.O. The position of carbon dioxide carbon in succinic acidsynthesized by heterotrophic bacteria..J. Biol. Chem. 1941; 139: 377-381Abstract Full Text PDF Google Scholar). Thus, Woodconcluded, “all the carbon dioxide is fixed originally by union of3-carbon and 1-carbon compounds.” Eventually, as shown in a previous JBCClassic (1JBC Classic Utter M.F. Lipmann F. Werkman C.H. J. Biol. Chem. 1945; 158 (http://www.jbc.org/cgi/content/full/280/16/e13): 521-531Abstract Full Text PDF Google Scholar), Werkman and MertonUtter would also prove that a C1 + C2 reaction ispossible. Although the labeling experiments lent credibility to heterotrophicCO2 fixation, Wood was convinced that the full significance ofCO2 utilization would not be fully appreciated until it wasdemonstrated in animals. Unfortunately, Earl Evans and Louis Slotin beat Woodto it and, using 11C, demonstrated CO2 fixation by theliver in 1940 (7Evans E.A. Slotin L. The utilization ofcarbon dioxide in the synthesis of α-ketoglutaric acid..J.Biol. Chem. 1940; 13: 301-302Abstract Full Text PDF Google Scholar). Up until this time, all of Wood's 13C experiments had been donein collaboration with Nier. However, it became increasingly clear that havinga 13C facility at Iowa State would facilitate the studies. Wood andseveral other microbiologists in the department built a mass spectrometer anda thermal diffusion column to concentrate 13C. The thermaldiffusion column extended five stories in an elevator shaft from the basementto the attic of the science building. Shortly after helping to build this newresearch facility, Wood accepted an Associate Professorship in the Departmentof Physiological Chemistry at the University of Minnesota. In 1943 he moved toMinnesota and started studying the conversion of[13C]NaHCO3 to glycogen in animals. These studies arethe subject of the second and third JBC Classics reprinted here. In the second Classic, Wood demonstrates CO2 fixation in pigeonliver extracts by showing that 13CO2 can combine withpyruvate and fumarate to produce products with 13C-labeled carboxylgroups. However, his attempts to investigate the mechanism of fixation wereunsuccessful. Using the liver extracts, he was unable to demonstrate theformation of oxalacetate from pyruvate and CO2. However, Wood wouldeventually discover that the reaction does occur in pigeon liver extracts whenATP is added to the reaction mixture. These results are reported in the finalJBC Classic, along with the finding that ATP also stimulates CO2fixation when fumarate and pyruvate are used as substrates. In 1946 Wood accepted a position as Chairman of the Department ofBiochemistry at the School of Medicine at what was then Western ReserveUniversity in Cleveland (the University merged with Case Institute ofTechnology in 1968 to become Case Western Reserve University). As Chairman,Wood made many changes. He brought in an entire new faculty to focus on usingisotopic tracers to study metabolism, and he reformed the curriculum at themedical school. He also instituted a policy that all faculty honoraria shouldgo onto a student travel fund because he believed that outside activitiesshould have an intrinsic value based on science and not money. Wood retired as chairman in 1965 so that he could have more time forresearch, which for him meant spending time at both the bench and his desk. Inthe 19 years between his 70th birthday and his death in 1991 he published 96papers. The overall direction of Wood's research continued to follow the trailof CO2. His later scientific contributions include establishing thereaction mechanism of transcarboxylase from propionic acid bacteria,discovering a novel pathway for CO fixation in a group of anaerobic bacteria,and studying the role of pyrophosphate and polyphosphate as energysources. Wood was president of the American Society of Biological Chemistry from1959 to 1960 and president of the International Union of Biochemistry from1982 to 1983. He was also a member of the JBC Editorial Board and wasinstrumental in eliminating self-perpetuating appointments when he resignedafter his 5-year appointment was up, saying “Listen, if all you guysdied tomorrow, a good board could be picked the next day to replace you”(8Wood H.G. Then and now..Annu. Rev.Biochem. 1985; 54: 1-41Crossref PubMed Google Scholar). Wood was a member of theNational Academy of Sciences and the American Academy of Arts and Sciences andserved on the President's Science Advisory Committee under Presidents Johnsonand Nixon. 1All biographical information on Harland Goff Wood was taken from Refs.4Singleton R. HeterotrophicCO2-fixation, mentors, and students: the Wood-Werkman Reactions.J. Hist. Biol. 1997; 30: 91-120Crossref PubMed Google Scholar,8Wood H.G. Then and now..Annu. Rev.Biochem. 1985; 54: 1-41Crossref PubMed Google Scholar, and9Goldthwait D.A. Hanson R.W. Biographical Memoir of Harland Goff Wood. 69. NationalAcademy of Sciences, Washington, D. C.1996: 394-428Google Scholar. 1All biographical information on Harland Goff Wood was taken from Refs.4Singleton R. HeterotrophicCO2-fixation, mentors, and students: the Wood-Werkman Reactions.J. Hist. Biol. 1997; 30: 91-120Crossref PubMed Google Scholar,8Wood H.G. Then and now..Annu. Rev.Biochem. 1985; 54: 1-41Crossref PubMed Google Scholar, and9Goldthwait D.A. Hanson R.W. Biographical Memoir of Harland Goff Wood. 69. NationalAcademy of Sciences, Washington, D. C.1996: 394-428Google Scholar.
Source: Journal of Biological Chemistry
Language: English
Subfield: History and Philosophy of Science
Field: Arts and Humanities
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1510747678