WOOD, HARLAND GOFF

(b. Delavan, Minnesota, 2 September 1907;

d. Cleveland, Ohio, 12 September 1991), biochemistry, enzymology, intermediary metabolism.

Wood was a major force in biochemistry’s twentieth-century disciplinary evolution. His revolutionary work on heterotrophic CO₂-fixation (the ability of nonplants and specialized bacteria to fix CO₂), an investigative pathway that shaped his entire career, challenged existing biological paradigms and was twice nominated for the Nobel Prize. His major biochemical contributions include: demonstrating the biochemical importance of CO₂ (Wood, 1982); using isotopes (especially radioisotopes) as tools to understand metabolic processes (Wood, 1963); elucidating the bacterial propionic acid cycle (Wood, 1976); analyzing the extremely complex structure and mechanism of the enzyme transcarboxylase (Wood, 1979); characterizing the metabolic role of pyrophosphate (PPi) (Wood, 1988); and clarifying the clostridial acetate biosynthesis pathway (Drake, 1993). Completed near his career end, the last project described a totally novel CO₂-fixation mechanism. Wood’s biochemical contributions are historically important because, unlike many of his contemporaries, he focused primarily on bacterial systems that had no medical significance. Wood also contributed to biochemistry’s disciplinary structure as Biochemistry chair at Western Reserve Medical School, where he built the department into one of national distinction. He was also instrumental in organizing and implementing Western Reserve’s unique and innovative medical curriculum that led “the way to experimentation and change in almost every medical school in the nation” (Harvey and Abrams, 1986, p. 253). In all of these activities Harland’s personal and scientific style was characterized by a potent ability to develop close collaborative relationships.

Early Life and Education. Wood was the third son of six children in a middle-class, Midwestern family. His father, William C. Wood, was a real estate businessman and also operated a small family farm in Mankato, Minnesota. His mother, Inez Goff Wood, “operated the family,” no small task considering its size and the economic times. Despite the family’s modest means, all six Wood children completed college degrees; several of Wood’s siblings completed advanced degrees (his younger brother, Earl, was an early recipient of a combined MD/PhD degree).

Wood’s early education was in Mankato’s public schools. A high school yearbook suggests that he was a “school hero”; he lettered in several sports, was Honor Society vice president, class leader, and apparent “heartthrob” of several female classmates. Medicine was his high school career goal, but because of difficulty translating Cicero, a Latin teacher diverted him into chemistry.

In 1927 Wood entered Macalester College in St. Paul, Minnesota, where he completed an undergraduate degree in chemistry. His athletic interests continued in varsity football, track, and swimming. He worked in the college dining hall and as an athletic trainer to help pay college expenses. An unusual aspect of his college education was his marriage to Mildred Davis in September 1929. The marriage, which lasted for more than six decades, began a month before the Great Depression and required the college president’s approval. In his senior year Wood was unsuccessfully applying to chemistry graduate programs, when his biology professor suggested that he apply to the Iowa State College Bacteriology Department in Ames, Iowa. Shortly thereafter he received a $450 fellowship to study bacteriology in Chester Hamlin Werkman’s laboratory.

Iowa State College and Werkman. When Wood joined Werkman’s lab, Werkman apparently provided little direction for his research, beyond handing him a copy of Cornelis Bernardus van Niel’s doctoral thesis on the propionic acid bacteria metabolism (1928) and telling him to find a problem. Wood began to study the organism’s physiology using an analytical technique called a “fermentation balance.”

In 1935, as he was completing his PhD thesis, Wood noticed that when the bacteria were grown on glycerol, not all of the carbon balances totaled 100 percent, nor were the O/R (oxidation and reduction) reactions balanced. However, when he assumed the bacteria fixed CO₂, both experimental components balanced. The difficulty with this assumption was that the existing biological dogma stated that heterotrophic organisms, such as the propionic acid bacteria, could not fix CO₂.

Wood wanted to delay his thesis completion in order to further test the heterotrophic CO₂-fixation hypothesis. However, Werkman—apparently not believing the data— resisted, and Wood finished and defended the dissertation (1934). He spent the next year (1935–1936) at the University of Wisconsin working in William Peterson’s laboratory with Edward Lawrie Tatum on a National Research Council (NRC) postdoctoral fellowship. During the year he wrote the first papers discussing the notion of heterotrophic CO₂-fixation (Wood and Werkman, 1936 a, b). Because of financial considerations and increasing European political instability, Wood abandoned a planned second NRC year in Germany and returned to Ames as a postdoctoral associate with Werkman.

Whatever initial resistance Werkman had to the idea, his laboratory rapidly became devoted to understanding the biochemistry behind heterotrophic CO₂-fixation, a process referred to as “the Wood-Werkman Reaction.” Over the next seven years the lab produced twenty-nine full papers, most of which focused on various aspects of the reaction’s biochemistry.

By the early 1940s Wood had helped establish Werkman’s laboratory as one of the most productive and creative microbial physiology research centers in the country. The laboratory produced several leading American biochemists and microbiologists; three former students (Wood, Merton Utter, and Lester Krampitz), as well as Werkman, were elected to the National Academy of Sciences. Hugo Theorell and Carl and Gerty Cori nominated both Werkman and Wood for the Nobel Prize in Physiology or Medicine in 1948 and 1949.

Breakup with Werkman. Despite its creative and productive nature, Wood’s collaboration with Werkman ended abruptly. In 1942 Wood received the Society of American Bacteriologists’ (subsequently American Society for Microbiology) Eli Lilly Award. The award, one of the society’s most prestigious honors, came with a $1,000 check that the Wood family intended to use for an Ames home purchase. When Werkman heard about the real estate plan, he asked Wood, “Why did you do that, do you think you can stay here forever?” The comment precipitated a major argument; Wood apparently believed that his position was indeed permanent. Within months Wood left Iowa for the University of Minnesota as associate professor of physiological chemistry.

Utter joined Wood in St. Paul, beginning a lifelong friendship and collaboration. Their research focused on using ¹³ C to study metabolism in poliovirus-infected rats and to trace CO₂ incorporation into glycogen. Their Minnesota sojourn was brief; in 1946 Wood was invited to reorganize and chair the Department of Biochemistry at Western Reserve University School of Medicine (WRU, later Case Western Reserve University or CWRU) in Cleveland, Ohio. Although initially perceived as a “farm bacteriologist,” Wood was rapidly recognized as Western Reserve’s leading biomedical faculty member (Williams, 1980, p. 489).

Western Reserve University School of Medicine. Up until the mid-twentieth century, biochemistry at Western Reserve was initially dominated by what Robert Kohler describes as “medical chemists” who were then displaced by practitioners of “physiological or pathological chemistry” (1982). In May 1945, Joseph Treloar Wearn was appointed Medical School dean with a charge to “rehabilitate” both the medical school and its curriculum. To rehabilitate the existing biochemistry program, he transferred its faculty to a newly created Clinical Biochemistry Department. Then, in 1946, he recruited Wood to chair the, now empty, Biochemistry Department and gave him free reign to hire new faculty. Over the next ten to fifteen years the department evolved into one of the top-ranked biochemistry departments in the country.

Early Scientific Research at Western Reserve. Wood’s Western Reserve career, which spanned more than half his life, was extremely diverse, however the papers that he initially published after his arrival at WRU possibly suggest a lack of focus. He and Utter completed projects on poliovirus started at Minnesota. He also extended experiments using ¹³ C as a tracer to study connections between fatty acids and carbohydrate metabolism in rats. When ¹⁴ C became commercially available in the late 1940s Wood immediately shifted to using the isotope and rapidly became a master at tracing metabolic pathways by following isotope labeling patterns. While he explored a variety of different metabolic processes during this time, increasingly his work followed two dominant threads: clarifying metabolic pathways of bacterial propionic acid formation and elucidating the mechanism whereby glucose is fermented to acetic acid.

Trailing the Propionic Acid Bacteria. Although Wood viewed himself as an enzymologist throughout his career, much of his research work prior to the mid-1950s involved whole cells or tissue slices. By 1960, however, this practice changed, and his laboratory began to isolate and characterize pure enzymes in a way that Arthur Kornberg described as “brilliant” (Singleton, 1997b, p. 366).

During the period from 1950 to 1960, Wood returned to the work he had begun at Iowa State. His lab purified all of the major enzymes that cyclically produced propionic acid in the propionic acid bacteria; the research resolved the chemical mechanism for the “Wood-Werkman reaction.” Wood’s research style was critical to this endeavor. The laboratory worked with a sense of unity. Bacteria were grown and harvested, often commercially, in large quantity. Common procedures were used to purify individual enzymes. Enzymatic assays often were performed by coupling reactions with other enzymes under investigation elsewhere in the laboratory. All of these approaches were combined in a single 1964 paper; the Wood lab reported the extensive purification of the major enzymes involved in the cycle, which were combined to achieve a partial reconstitution of the propionate fermentation.

The Role of CO ₂in Acetate Biosynthesis . Shortly after his move to Cleveland, Wood became interested in bacteria that ferment glucose to acetic acid (reaction 1):

In this reaction, one six-carbon compound is converted into three two-carbon compounds, a reaction that posed the following conundrum. When glucose is anaerobically oxidized to pryuvate via glycolysis, reduced nicotinamide adenine dinucleotide (NADH) accumulates; unless NADH is reoxidized to NAD, glucose oxidation ceases. Over evolutionary history, a variety of biochemical processes have evolved to regenerate NAD. The puzzle was that in most of these pathways, pyruvate was converted to either three-carbon entities or two-carbon compounds and CO₂.

Based on Horace Albert Barker and Martin David Kamen’s 1945 work with ¹⁴ CO₂ and his own work with ¹³ CO₂ in 1952, Wood suggested that the fermentation involved two reactions:

Wood then embarked on an investigative trail to clarify the nature of reaction (3), which along with work on transcarboxylase dominated the rest of his career.

Numerous individuals collaborated on the acetate biosynthesis problem; however, Lars Ljungdahl was central to the problem’s resolution. Ljungdahl joined Wood’s lab in the early 1960s, initially as a technician. Wood especially wanted Ljungdahl to be involved in the acetate problem; in a 1962 job offer letter, he stated: “I’d just love to have that problem solved, and I think with more time you could do it. It certainly would be a big feather in your cap if you did and would, I believe, unfold some new things in biochemistry of great importance.” Ljungdahl accepted the job, completed a PhD with Wood in 1964, and became heavily involved in the acetate biosynthesis problem. When he moved to a University of Georgia faculty position in 1967, Wood agreed that Ljungdahl could take part of the problem with him.

After Ljungdahl moved to Athens, Georgia, the two men were clear about which problem component was their individual “territory” and did not hesitate to object when someone appeared to cross the “boundary.” Nevertheless, students might complete a PhD in Athens and move to Cleveland as a postdoctoral, or vice versa. Ljungdahl occasionally went to Cleveland for a crucial experiment; Wood spent a 1969 sabbatical year in Athens. In the days before faxes and e-mail, copies of lab notebook pages were mailed from one lab to the other; long phone conversations involved sometimes heated arguments over the meaning of data. Manuscript drafts were mailed from Cleveland to Athens and back for commentary and revision.

Wood’s 1962 comment to Ljungdahl that the acetate problem might “unfold some new things in biochemistry of great importance” was a significant understatement. Over the next twenty plus years the two labs collaborated to resolve a complete pathway that confirmed Wood’s 1952 proposal outlined in reactions (2) and (3). Part of the pathway [reaction (2)] involved conventional reactions whereby glucose is fermented to acetate and CO₂. The mechanism of CO₂-fixation [reaction (3)], however, was far more complex and novel, involving several newly discovered enzymes and unique cofactors. The research was made more difficult because several key enzymes or intermediates were oxygen or light sensitive, and required anaerobic conditions and absence of light. By 1986 the reaction sequence was referred to in the literature as the “Wood-Ljungdahl pathway” of CO₂ autotrophic fixation (Drake, 1993).

Summary. Arthur Kornberg noted that science is a discipline “that enables ordinary people … to go about doing ordinary things, which, when assembled, reveal the extraordinary intricacies and awesome beauties of nature … [science also] permits them to contribute to grand enterprises” (1987, p. 6891). Wood’s career vividly illustrates these themes. His early life on the Midwestern prairie was certainly ordinary. Yet, within a few years he became a major contributor to the “grand enterprise” of biochemistry’s twentieth-century disciplinary explosion. Furthermore, there is an aesthetic beauty in the intricacy of the two pathways of CO₂-fixation and the complex structure and chemistry of the enzyme transcarboxylase that he described.

Wood’s career is an exemplar of another modern science practice in its illustration of ways that scientific collaboration can alter career patterns. He was, from his earliest days, an accomplished collaborator, who worked with individuals from a variety of disciplines. For example, Wood began as the junior person in his collaboration with Werkman. Within a few years he was virtually running Werkman’s laboratory, so that both men were elected to the National Academy of Sciences and twice nominated for the Nobel Prize. Arguably, Werkman would not have accrued this prestige had he not had Wood as a collaborator; his productivity significantly decreased after Wood’s departure.

Wood’s relationship with Ljungdahl illustrates another aspect of scientific collaboration. Like Wood’s encounter with Werkman, Ljungdahl joined the Wood lab in a junior role as technician/student and rapidly evolved to a coequal stature. However, as the work progressed the two men were able to maintain the collaborative effort for more than thirty years. Both of their careers were enhanced by the interaction, and they remained lifelong friends.

Wood served as a presidential science advisor and was on numerous journal editorial boards. In his life’s last decades he was active in the International Union of Biochemistry and Molecular Biology. However, the laboratory was Wood’s real life passion. Unlike many of his contemporaries, he was active in the lab at the time of his death. Though he had dealt with a form of lymophoma for several years, he died as a result of a fall in a hospital after undergoing chemotherapy. Perhaps much of his life was summarized by his brother Earl, who commented, “Harland and I had three passions in life. Our families were first, science was second, and hunting was third.”

BIBLIOGRAPHY

WORKS BY WOOD

The Physiology of the Propionic Acid Bacteria. PhD diss., Iowa State College, Ames, Iowa, 1934.

With Chester H. Werkman. “Mechanism of Glucose Dissimilation by the Propionic Acid Bacteria.” Biochemical Journal 30 (1936a): 618–623.

———. “The Utilization of CO₂ in the Dissimilation of Glycerol by the Propionic Acid Bacteria.” Biochemical Journal 30 (1936b): 48–53.

“Letter to Lars Ljungdahl, dated Oct. 30, 1962.” Personal communication kindly provided by Professor Ljungdahl.

With Joseph Katz and Bernard Landau. “Estimation of Pathways of Carbohydrate Metabolism.” Biochemische Zeitschrift 338 (1963): 809–847.

“My Life and Carbon Dioxide Fixation.” In The Molecular Basis of Biological Transport: Proceedings of the Miami Winter Symposia, vol. 3, edited by Jacob Frederick Woessner Jr. and F. Huijing. New York: Academic Press, 1972.

“Trailing the Propionic Acid Bacteria.” In Reflections on Biochemistry: In Honour of Severo Ochoa, edited by Arthur Kornberg, Bernard Horecker, L. Cornudella, and Juan Oro. New York: Pergamon, 1976.

“The Anatomy of Transcarboxylase and the Role of Its Subunits.” Critical Reviews of Biochemistry and Molecular Biology 7 (1979): 143–160.

“The Discovery of the Fixation of CO₂ by Heterotrophic Organisms and Metabolism of the Propionic Acid Bacteria.” In Of Oxygen, Fuels, and Living Matter, edited by Giorgio Semenza. New York: Wiley, 1982.

“Then and Now.” Annual Review of Biochemistry 54 (1985): 1–41.

“Squiggle Phosphate of Inorganic Pyrophosphate and Polyphosphates.” In The Roots of Modern Biochemistry: Fritz Lipmann’s Squiggle and Its Consequences, edited by Horst Kleinkauf, Hans von Döhren, and Lothar Jaenicke. Berlin: Walter de Gruyter, 1988.

Interview by J. James Bohning. 19 January 1990 at Case Western Reserve University. Oral History Transcript #0082. Chemical Heritage Foundation. Philadelphia, Pennsylvania.

OTHER SOURCES

Barron, E. S. “Mechanisms of Carbohydrate Metabolism: An Essay on Comparative Biochemistry.” In Advances in Enzymology and Related Subjects of Biochemistry, vol. 3, edited by Friedrich Franz Nord and Chester H. Werkman. New York: Interscience, 1943.

Cartter, Allan Murray. An Assessment of Quality in Graduate Education. Washington, DC: American Council on Education, 1966.

Drake, Harold L. “Co₂, Reductant, and the Autotrophic AcetylCoa Pathway: Alternative Origins and Destinations.” In Microbial Growth On C₁Compounds, edited by J. Colin Murrell and Don P. Kelly. Andover: Intercept Ltd.

Harvey, A. McGehee, and Susan L. Abrams. “For the Welfare of Mankind”: The Commonwealth Fund and American Medicine. Baltimore: Johns Hopkins University Press, 1986.

Kohler, Robert E. From Medical Chemistry to Biochemistry: The Making of a Biomedical Discipline. Cambridge, U.K.: Cambridge University Press, 1982.

Kornberg, Arthur. “The Two Cultures: Chemistry and Biology.” Biochemistry 26 (1987): 6888–6891.

Nier, Alfred O. C. Unpublished interview by Michael A. Grayson and Thomas Krick. 7 and 8 April 1989. Oral History Transcript #0112. Chemical Heritage Foundation, Philadelphia, Pennsylvania.

Ragsdale, Stephen W. “Life with Carbon Monoxide.” Critical Reviews in Biochemistry and Molecular Biology 39 (2004): 165–195.

Singleton, Rivers, Jr. “Heterotrophic CO₂-fixation, Mentors, and Students: The Wood-Werkman Reactions.” Journal of the History of Biology 30 (1997a): 91–120.

———. “Harland Goff Wood: An American Biochemist.” In Selected Topics in the History of Biochemistry: Personal Recollections, vol. 5, edited by Giorgio Semenza and Rainer Jaenicke. Amsterdam: Elsevier Science, 1997b.

———. “From Bacteriology to Biochemistry: Albert Jan Kluyver and Chester Werkman at Iowa State.” Journal of the History of Biology 33 (2000): 141–180.

Van Niel, Cornelis Bernardus. The Propionic Acid Bacteria. Haarlem, The Netherlands: Boisevain, 1928.

Williams, Greer, assisted by Margaret Henning. Western Reserve’s Experiment in Medical Education and Its Outcome. New York: Oxford University Press, 1980.

Wood, Chester W., comp. The Wood-Goff Family Chronicle. Leesburg, FL: privately printed, 1976. Photocopy available from Preservation Department, Iowa State University Library, Ames, Iowa. 2003.

Rivers Singleton Jr .