RACKER, EFRAIM

(b. Neu Sandez, Poland, 28 June 1913; d. Ithaca, New York, 9 September 1991) e

nzymology, energy metabolism, biomembranes.

Racker—Ef to his friends and colleagues—contributed significantly to the study of enzymes and energy in the cell in the mid-twentieth century. He developed methods for reconstituting proteins in biological membranes, fundamental to studying their individual effects. Using these methods, he helped assemble artificial vesicles that demonstrated conclusively the chemiosmotic theory as proposed by Peter Mitchell (who subsequently earned a Nobel Prize for his ideas in 1978).

Racker also earns credit for many important particular discoveries: F_o, a major component of the enzyme that generates adenosine triphosphate (ATP), the basic molecule of energy in the cell; CF₁, the central component of ATP synthase in plant chloroplasts; the mechanism of energy transfer to ATP in glycolysis; the first energy-rich thioester; and transketolase and (in parallel with other labs) the pentose phosphate cycle. These reflect Racker’s remarkable experimental skills in tinkering with and coaxing unfamiliar cellular enzyme systems into relief. Racker was equally important institutionally, mediating debate, writing advanced textbooks, promoting basic research and a strong work ethic, and buoying the high-stakes field of bioenergetics with good humor. He also became involved in two episodes of misconduct by others. One gained wide renown and eventually became a canonical case of fraud in science, although Racker’s role is often misreported. His legacy also includes a series of aphorisms that wittily express experimental know-how.

Pathway to Basic Research Racker was born in a large town in southern Poland to Jewish parents. In his infancy the family moved to Vienna, where the Rackers lived in a poor neighborhood and experienced the anti-Semitism of the era. Young Efraim did not respond well to the formalisms of school. He enjoyed competitive sports and chess. He also liked to draw and paint. Inspired by the work of Viennese native Egon Scheile, and with the encouragement of painter and art educator Victor Löwenfeld, Efraim decided to pursue a career as a painter. At age eighteen he gained admission to the highly selective Akademie der bildenden Künste Wien (Vienna Academy of Art). Again, he became disillusioned with the formal training style, left, and enrolled at the University of Vienna School of Medicine. He passed Sigmund Freud’s home on his daily walk to school and, with his older brother Heinrich, shared a fascination with psychiatry and psychoanalysis. He graduated in 1938 when, as Racker described it, a mass psychosis invaded Vienna. As Nazism advanced, he left via Denmark for England.

After reading a 1936 paper, “Biochemistry and Mental Disorder,” Racker sought work with its author, J. Hirsh Quastel, in Cardiff, Wales. Racker studied the psychotic effects of amines on brain metabolism with him but began to realize that the background knowledge of normal metabolism was then too limited. When Great Britain entered World War II, Racker was classified as an enemy alien. He emigrated to the United States in 1941, ultimately going to the University of Minnesota. Capitalizing on funds available from the March of Dimes, Racker began research (for a salary of 12,000 dimes a year, he noted). on how the polio virus altered metabolism in the brain. Again, he faced problems due to lack of foundational knowledge about glycolysis, the breakdown of sugar in cells. He later called this a turning point, which led him into basic research on carbohydrate and energy metabolism. Later in his career, in 1979, Racker defended the value of basic research against political critics and began by citing this experience.

Glycolysis Following two years as a physician at Harlem Hospital (1942–1944), Racker joined the Microbiology Department at New York University Medical School, where he enjoyed support from Severo Ochoa and Colin MacLeod. Racker continued his research on viral inhibition of glycolysis but soon found that his samples had been contaminated with iron. Undeterred, he traced how the iron inhibited the enzyme glyceraldehyde-3-phosphate (GAP) dehydrogenase and then how glutathione reversed the effect. Glutathione was a known co-factor for another enzyme, glyoxalase, and Racker was led to interpret its role as an intermediate in energy transfer. Although glyoxalase itself was relatively obscure, Racker had identified for the first time how energy could be transferred biologically though an energy-rich (sulfur-containing) thioester bond. His 1951 discovery became an important precedent for interpreting this widely occurring energy-transfer mechanism. Racker would also later instruct his students that “Troubles Are Good for You,” as he put it in his A New Look at Mechanisms in Bioenergetics(1976). He profiled how, as in this case, a skilled investigator can turn ostensibly disastrous results into an advantage.

Continuing his work with his technician, Isidore Krimsky, Racker returned to the glycolysis enzyme that helped break down and capture energy from GAP. There, he found, GAP reacted with an enzyme-bound sulfhydryl group. This, in turn, produced an energy-rich thioester bond (as in the case of glyoxalase), which was handed off, along with its energy, to phosphate. The energy-rich phosphate was transferred again to adenosine triphosphate, or ATP, the basic molecule of energy in the cell. Racker’s findings upset the then widely accepted claims by the renowned biochemist Otto Warburg. More importantly, however, Racker documented the first mechanism for how ATP is generated in cells. This 1952 discovery also set an important precedent, but one that, ironically, misguided biochemists for the next two decades, as described below.

Pentose Phosphate Pathway In 1952 Racker accepted a position at Yale University, where he shifted his metabolic investigations to a reaction pathway that branches off from glycolysis: the hexomonophosphate shunt. Energy is derived from a six-carbon sugar, which is then broken down into a series of five-carbon sugars, or pentose phosphates. Some of these become important components in synthesizing other molecules, such as the units of DNA. Racker’s lab discovered a new enzyme, transketolase, that breaks down the five-carbon sugars further (coincidentally, into GAP as a product). In 1954 Racker returned to New York City, now at the Public Health Research Institute as chief of the Division of Nutrition and Physiology. As he continued work, the successively recrystallized enzyme lost its specific activity. Racker traced the problem to the presence of a second enzyme, an epimerase, that had been extracted along with the first and which partly accounted for the reactions they had been observing. Racker sorted out which enzyme reacted with which pentose, correcting what he and several labs had concluded earlier. Racker found a lasting lesson in his experience, which he later preached to his students: “Don't think, purify first”—and, “Don't waste clean thinking on dirty enzymes” (1979b, p. 572; 1985, p. 26; Hinkle, 1992, p. 517; Miller, 1992, p. 97).

In further work, Racker recognized a chemical analogy that prompted him to test transketolase on another molecule in the pentose phosphate reaction pathway. It worked there as well. The enzyme functioned twice. This helped Racker (aided by students Paul Srere, Dan Couri, and June Fessenden) to reconstruct the whole system. The pathway ultimately recreated the initial hexose; it was a cycle, a conclusion also reached in other labs, notably by Bernard Horecker at the National Institutes of Health. Racker’s transketolase experiment had further significance as well. Melvin Calvin had been working to elucidate the steps of photosynthesis, whereby plants fix carbon dioxide from the air, then synthesize glucose. Many of the enzymes and intermediate compounds were shared with the pentose pathway. While having dinner with Calvin in New York in 1954, Racker mentioned his experiments revealing the second function of transketolase, which transformed a six-carbon molecule into a four-carbon molecule. “I see it all now,” Calvin replied cryptically (Racker, 1979a, p. 572). He then explained to Racker that he had just provided him the clue for linking his own photosynthetic reactions into a cycle—an achievement that earned Calvin the 1961 Nobel Prize in Chemistry.

ATPase Racker’s new institutional surroundings in New York proved exceptionally fruitful. Maynard Pullman arrived shortly after Racker, and they decided to tackle another major metabolic system, oxidative phosphorylation, or ox phos. These reactions in the mitochondria use the oxygen people breathe to transform the energy from the citric acid cycle (breaking down the food they eat) to the energy-rich adenosine triphosphate, or ATP (by adding the final phosphate). Racker believed that to solve complex problems, such as psychoses of the mind or multienzyme systems of the cell, one needed to resolve them into their parts and reassemble them functionally. Racker apparently exhibited his strategy early in life: at age six he took apart a broken clock and tried (unsuccessfully) to fix it. He now applied this strategy to ox phos.

Racker noted later that reconstituting systems successfully required three things. First, one needed cheap labor. Pullman’s skilled new student, Harvey Penefsky, provided that. Second, one needed large quantities of stable material. David Green had pioneered how to prepare mitochondria from beef heart. He invited the team to the University of Wisconsin, where they learned his techniques. Finally, one needed new ideas. Here, that meant a new machine for shaking the cells and proteins apart. Centrifugation then sedimented out submitochondrial particles and the team tested re-adding various soluble fractions to identify functional factors. The first, named F₁, was the main part of the enzyme, ATPase (later called ATP synthase), where ATP was formed. Subsequently, Yasuo Kagawa helped confirm that F₁ units could be seen in electron micrographs as small knobs on the inside of the mitochondrial membrane. Kagawa and Racker then isolated the segment of ATPase, embedded in the membrane, where F₁ attached. It was named F_o for reestablishing a known function: inhibition by oligomycin. Racker tried many other methods of destroying and separating the mitochondria, yielding an array of particle types. More supplemental factors emerged: two factors that held F₁ to F_o (F₆ and part of F₄, later renamed OSCP) and F ₂(also called Factor B), all whose regulatory function was elucidated much later. (F₃, F₄, and F₅ were later reclassified or abandoned as contaminated extracts.)

As progress stalled, Racker looked for a more easily resolvable system, targeting the ATPase in photosynthesis. Switching from beef heart to the more agreeably smelling spinach, he and Vida Vambutas isolated the chloroplast’s analog to F₁: CF₁. Their work helped underscore the strong similarities between ox phos and photophosphorylation (how plants generate ATP from light). Racker summarized his work and the state of the field in a monograph, Mechanisms in Bioenergetics, in 1965. The following year his professional contributions were recognized by his election to the National Academy of Sciences.

Reconstituting Membrane-Bound Enzymes In the mid-1960s, research on ox phos became notoriously frustrating. The system was located in the mitochondrial membrane. Membranes are primarily lipids, chemically more like oil than water, and no one could extract membrane-bound proteins that would still function. Peter Mitchell suggested a possible reason. He contended that energy did not flow through a succession of energy-rich bonds, as modeled in Racker’s 1952 account of glycolysis. Mitchell proposed a chemiosmotic mechanism instead, whereby ox phos generated an electrochemical proton gradient across the membrane. Any system would thus require an intact closed vesicle. The membrane was itself viewed as a functional barrier. Racker met with Mitchell in New York City in 1965, and they discussed his ideas, but Racker did not deem them supported by the available evidence.

Racker accepted an opportunity to lead the new Section of Biochemistry and Molecular Biology at Cornell University and moved to Ithaca, New York, in 1966. His investigative focus also shifted. Whether influenced primarily by Mitchell or by experimental exigencies, he began examining the role of the membrane more fully. He showed first how proteins functioned differently on each side of the membrane and then how they were positioned asymmetrically. Eventually, the membrane became part of his reconstitution strategy. Racker’s lab recombined the isolated proteins with lipids and a detergent, then gradually removed the excess by either dialysis or dilution. In 1971 Yasuo Kagawa, working with Racker, successfully reconstituted ATPase. Racker and his student Anne Kandrach then did the same for a component of the electron transport chain, cytochrome oxidase. Effective reconstitution had finally begun. Racker’s theoretical views changed the following year. Peter Hinkle, a former student then also working at Cornell, was measuring how the reaction rate of reconstituted cytochrome oxidase could be controlled by an electrochemical gradient. Racker, while observing the instrument readings in the lab, seemed to concede that Mitchell was correct, at least about the proton gradient. Soon, Kagawa’s ATPase reconstitutions could also pump protons. These liposome vesicles lost function when the membranes “leaked.” Persuaded that closed compartments were essential, Racker fully switched his allegiance to chemiosmotic principles.

Adopting a new theoretical framework, Racker soon consolidated his laboratory’s findings in a dramatic capstone experiment. In 1973 Dieter Oesterhelt and Walther Stoeckenius isolated a new photosynthetic pigment, bacteriorhodopsin, from halobacteria and showed that when exposed to light, it transported protons across the membrane in accord with chemiosmotic mechanisms. In 1974 Racker collaborated with Stoeckenius to create a thoroughly unnatural vesicle. Introducing sound waves as yet another method of reconstitution, they recombined membrane lipids from soybeans, bacteriorhodopsin from halobacteria, and ATPase from beef mitochondria. Although mixing elements from cells from three kingdoms, the artificial vesicles produced ATP in light. That “unphysiological” chimera epitomized reconstitution for Racker: it integrated the separate parts not just structurally but also functionally. The chimeric vesicles were also an important benchmark in demonstrating chemiosmotic mechanisms for ox phos and photophosphorylation to a wide community of biochemists. By 1975 all the components of ox phos had been isolated and analyzed separately. Racker again summarized the status in the field in a new advanced textbook in 1976, A New Look at Mechanisms in Bioenergetics. Racker shared the Warren Triennial Prize with Mitchell in 1974 and received the National Medal of Science in 1976.

Late Work Racker’s methods of lipsome reconstitution opened wide the investigation of membrane-bound proteins. He helped train a whole new generation in membrane biology, including Günter Hauska, Peter Hinkle, Richard Huganir, Baruch Kanner, Ladislav Kovác, Richard McCarty, Chris Miller, Maurice Montal, Nathan Nelson, Michael Newman, Jan Rydstrøm, Dennis Stone, Bernie Trumpower, and Charles Yocum. Having demonstrated that protons were indeed transferred across membranes, Racker turned to study the mechanisms of transport. He considered many ion pumps for clues. In so doing, he reconstituted the first Ca²⁺-ATPase pump from muscle cells and (with Richard Huganir) the acetylcholine receptor of nerve cells. He showed how the latter functioned through conformational changes, opening a channel for the passage of ions that initiate the nerve impulse. In parallel work, however, he failed with the lactate transporter and with the Na⁺-K⁺-ATPase in tumor cells. Racker once described the erratic behavior of membrane proteins as molecular psychology. In 1985 Racker wrote one last text, Reconstitutions of Transporters, Receptors, and Pathological States, detailing the strategies and methods of reconstitution.

During his career, Racker’s interest in pathological states never waned. Much of his late work, far less fruitful than his earlier achievements, was oriented to cancer. A series of minor contributions, tallied over several decades, was accompanied by many stymied efforts, ironically illustrating his own views about the primacy of basic research. Racker never considered his investigations complete. Even at age seventy-three he was retooling, learning the new techniques of recombinant DNA. He even modified his old adage about proteins, “Don't think, purify first,” to “Don't think, don't purify: clone!” (1985, p. 26).

Professional Leadership Racker’s stature derived in part from his professional leadership. He served on the editorial boards for the Journal of Biological Chemistry in the 1960s and later for the Journal of Membrane Biology and Biochimica et Biophysica Acta. His posture towards resolving disagreement was especially significant, notably during the highly contentious debates over ox phos. For example, after a disagreement about sequence of elements in the electron transport chain with Britton Chance, Racker and his student went to his lab, where additional tests clarified the results. Racker expressed the moral for students: “When you find something that disagrees with a paper or review, … get in touch with the person with whom you disagree. If the issue is indeed important to you, straighten it out by collaborative experiments rather than by polemics” (1976, p. 52).

His early life experience with politics in Europe seemed to shape his later actions. Racker tried to find the middle ground in theoretical debates on chemiosmotic ideas. In a letter to Peter Mitchell in January 1975, Racker offered one conceptual hybrid, he admitted, as “a gentle-man’s political compromise. From my early childhood, I had wanted to live in a peaceful world. Although I have always enjoyed friendly controversy and arguments, I have been most uncomfortable during the bitter polemics in our field in the last decade” (Prebble and Weber, 2003, p. 203). Racker endeavored to quell the ox phos tempest. In March 1974 he circulated a letter to ten leading biochemists, appealing for unity and proposing to publish a joint statement that, he hoped, would help stabilize the field and improve its negative image among other scientists and funding agencies. After two and a half years of correspondence and of alliances severed and mended, with Racker personally coaxing Mitchell to rejoin the project on at least two occasions, six researchers published a multi-authored review that, while hardly free of residual conflicts, was nonetheless widely interpreted as resolving the decades-old controversy. In 1975 Peter Mitchell received the Nobel Prize in Chemistry. Given Racker’s important work on reconstitution and the chimeric vesicles that helped secure the status for chemiosmotic theory, many colleagues were surprised that the honor did not include him as well. He continued to receive recognition, however, with a Gairdner Award in 1980.

Episodes of Research Misconduct Racker became involved in two episodes of scientific misconduct. In one case, he was leading critic; in the other, primary victim. The case in Racker’s own lab gained wide notoriety and remained in the early 2000s an oft-cited example of scientific fraud. Both cases, however, need to be studied to understand fully Racker’s conduct. They are striking complements, yet each illustrates Racker’s professional leadership. His responses were considered exemplary by most colleagues.

The first episode occurred during the heyday of conventional chemical approaches to ox phos. George Webster, working with David Green’s lab, had published a series of papers from 1962 to 1965 proposing a high-energy intermediate in the reaction series: Reduced Cytochrome c Coupling Factor, or RCCF. Racker tried to replicate the findings, hoping to resolve discrepancies with his own findings. At first, he noticed only errors in the methods for measuring ATP. Eventually, Racker went with two colleagues to Green’s lab at the University of Wisconsin, where experiments again failed, using Webster’s methods on samples they had prepared themselves. Racker asked to consult Webster’s laboratory notebooks. Webster acknowledged having fabricated his data. In this episode, Racker was credited for actively pursuing the false claims and for establishing definitive results with his strong experimental skills.

In the second episode, fraudulent data were fabricated in Racker’s own lab. Initially, in 1980, Mark Spector was considered a brilliant PhD student with exceptional technical aptitude and promise. At the time, Racker was shifting his research to cancer cells as he returned to puzzles about rates of glycolysis that he had set aside for several decades. Spector was set the task of purifying the membrane-bound ATPase from tumor cells, where it exhibited increased activity. Spector’s quick success seemed to confirm the strong recommendations that had accompanied his graduate school application. His remarkable work seemed to continue as he reportedly isolated, in turn, a series of enzymes that sequentially triggered inefficient ATP-dependent membrane transport of sodium (leading further to excess glycolysis). Finally, he announced that the first component in the “kinase cascade” was similar to a protein produced by the Rous sarcoma virus. The events that led to viral cancer seemed dramatically solved. The model generated much excitement when first presented to the Tumor Virus Group in May 1981. Racker and Spector published the scheme in Science on 17 July.

Just one week later, one of Spector’s collaborators at Cornell, Volker Vogt, approached Racker. He and his student had earlier encountered problems generating Spec-tor’s results. They had secured some of Spector’s original electrophoretic gels. The radioactive labels on them were not the telltale phosphorus, but an easily applied iodine. The developed images (autoradiograms) used in data analysis would thus have carried no trace of any manipulation. The original gels were the first substantive clue to doctored results. Racker and Vogt confronted Spector. Racker personally supervised the next set of experimental replications. Some of the original results seemed partly confirmed, others not. By September, Racker had dismissed Spector. The coauthors, led by Racker, retracted all the suspect papers. At the first evidence of fraud, Racker acted decisively. He offered to resign from his various committees and editorial boards until the issue was fully resolved, and he even withdrew an important five-year grant renewal. Consequences continued, however. Earlier that spring, U.S. congressional hearings had stirred up public concerns about scientific misconduct. In addition, the case served as grist for Nicholas Wade, a science journalist for Nature, who was actively reporting fraud. Exposure to the Spector episode was thus greatly amplified. Still, colleagues respected Racker for investigating and acknowledging the errors himself, thereby modeling how to manage such problems responsibly. The American Society of Biological Chemists apparently did not find the affair reason against awarding Racker their prestigious Sober Memorial Lectureship the following year, in 1982. Seven years later Racker reflected on his experience, publishing his views on misconduct in science in Nature.

Personality in Professional Context Racker exuded good humor and a dry wit that even enriched his scientific discourse. He made light of the many obstacles that faced chemists working on cell metabolism in the 1960s. For example, “‘Nature may be difficult, but she is never malicious,’” he quoted Einstein as saying. Einstein, he then commented, “obviously had never worked on oxidative phosphorylation” (Rowen, 1986, p. 285). At a 1963 conference, Racker remarked slyly that “anyone who is not thoroughly confused just does not understand the situation.” He reviewed the complex reactions, then concluded: “I shall not show you a scheme of the topography of the various factors in mitochondria because I promised to keep this presentation simple. But I carry a picture of it in my wallet, together with photos of my wife and daughter and I’ll be glad to show all three of them to anyone who cares to see them.” The comment, which appeared in the published paper, was not entirely gratuitous. It conveyed in a light-hearted way, the complexity that so deeply and repeatedly frustrated the “family” of biochemists working on the problem. Such comments helped counterbalance the prevailing mood of debate at the time, characterized by other researchers as contentious and often rancorous, even vitriolic.

In a similar spirit, Racker issued to his entering graduate students at Cornell University “Twelve Rules for Graduate Students in Biochemistry,” styled tongue-in-cheek after the biblical commandments. For example, “When thou usest isotopes, thou shalt remember that ‘not everything that counteth counteth.’” Such pithy lessons also appeared in his advanced textbooks. Examples are “A clean experiment is worth more than a few hundred dirty calculations,” and “It doesn't matter if you fall down as long as you pick up something from the floor while you get up” (1976, pp. 6, 9). Many such witticisms, typically encoding bits of professional wisdom, became stock sayings echoed throughout the field.

Racker was an avid artist. He began painting at age thirteen when he received a box of oil paints for his birthday. Later he likened reconstituting liposomes to drawing a portrait: each was a functional but distorted representation. Colleagues recognized how Racker embodied a fruitful combination of creative thinking and rigorous experimental analysis. Racker’s paintings included landscapes and seascapes in somber hues and an austere, semi-abstracted German expressionist style. For one colleague, they reflected the darker, and also private, side of Racker’s thoughts. He sold many paintings to support scholarships for students. Posthumous sales of others funded an annual lecture in his memory. Racker’s artistic interests also extended to music. He played cello with enthusiasm, although he was also apparently incompetent, according to former students.

Racker also modeled the spirit of investigation. “We need to know more,” he once said, “about ion fluxes, neurotransmitters, mental diseases, love, hate, crime, and mass psychology. I believe they are all related” (1979b, p. 587). He enjoyed “the game of intellectual domination” (Schatz, 1996, p. 326) and “loved argument for its ability to plow up and ventilate the scientific earth” (Miller, 1992, p. 97). He was not afraid to be wrong, however, and extolled the virtues of learning from error. While sometimes “egocentric, insensitive, even overbearing,” Racker was also known to friends and colleagues for his warmth and openness (Schatz, 1996, p. 342). Racker was, above all, a tireless worker. He kept long days in the laboratory, working on Saturdays—and expecting his students and research associates to do likewise. In one of his Twelve Rules, he instructed students: “Every week hath seven days. Six days shalt thou labor for twelve hours of the day. But on the seventh day thou canst stop ONE HOUR EARLIER. And in that hour thou shalt clean thy bench.”

The humor was balanced by Racker’s own dedication to his labors. Indeed, he died at age seventy-eight, two days after a stroke, which had followed a full Saturday of work in the lab.

BIBLIOGRAPHY

WORKS BY RACKER

“Mechanism of Action of Glyoxalase.” Journal of Biological Chemistry 190 (1951): 685–696. Documents the first energy-rich thioester.

With Isidore Krimsky. “Mechanism of Oxidation of Aldehydes by Glyceraldehyde-3-phosphate Dehydrogenase.” Journal of Biological Chemistry 198 (1952): 731–743. First mechanism for transfer of energy to ATP.

With Gabriel de la Haba and I. G. Leder. “Crystalline Transketolase from Baker’s Yeast: Isolation and Properties.” Journal of Biological Chemistry 214 (1955): 409–426. Discovery of enzyme in the pentose phosphate pathway.

With M. E. Pullman, H. S. Penefsky, and A. Datta. “Partial Resolution of the Enzymes Catalyzing Oxidative Phosphorylation. I. Purification and Properties of Soluble Dinitrophenol-stimulated Adenosine Triphosphatase.” Journal of Biological Chemistry 235 (1960): 3322–3329. Discovery of the F₁ part of ATPase.

“A Mitochondrial Factor Conferring Oligomycin Sensitivity on Soluble Mitochondrial ATPase.” Biochemical Biophysical Research Communications 10 (1963): 534–439. Discovery of the F_o part of ATPase.

Mechanisms in Bioenergetics. New York: Academic Press, 1965. First in a series of advanced texts.

With Vida K. Vambutas. “Partial Resolution of the Enzymes Catalyzing Photophosphorylation. I. Stimulation of Photophosphorylation by a Preparation of Latent Ca^++- dependent Adenosine Triphosphate from Chloroplasts.” Journal of Biological Chemistry 240 (1965): 2660–2667. Discovery of the CF₁ part of chloroplast ATPase.

With Yasuo Kagawa. “Partial Resolution of the Enzymes Catalyzing Oxidative Phosphorylation. XXV. Reconstitution of Vesicles Catalyzing³² P_i-adenosine Triphosphate Exchange.” Journal of Biological Chemistry 246 (1971): 5477–5487. First vesicle-based reconstitution of ATPase.

With Anne Kandrach. “Reconstitution of the Third Site of Oxidative Phosphorylation.” Journal of Biological Chemistry 246 (1971): 7069–7071. First reconstitution of component of the electron transport chain.

“Reconstitution of a Calcium Pump with Phospholipids and a Purified Ca⁺⁺ adenosine Triphosphatase from Sarcoplasmic Reticulum.” Journal of Biological Chemistry 247 (1972): 8198–8200.

With Yasuo Kagawa and Anne Kandrach. “Partial Resolution of the Enzymes Catalyzing Oxidative Phosphorylation. XXVI. Specificity of Phospholipids Required for Energy Transfer Reactions.” Journal of Biological Chemistry 248 (1973): 676–684. First reconstitution of ATPase as demonstrated proton pump.

With Walther Stoeckenius. “Reconstitution of Purple Membrane Vesicles Catalyzing Light-driven Proton Uptake and

Adenosine Triphosphate Formation.” Journal of Biological Chemistry 229 (1974): 662–663. Chimeric vesicles as capstone demonstration of chemiosmotic theory.

A New Look at Mechanisms in Bioenergetics. New York: Academic Press, 1976. Racker’s second text.

With Paul D. Boyer, Britton Chance, Lars Ernster, et al. “Mechanisms of Energy Tranformations.” Annual Review of Biochemistry 46 (1977): 955–1026. Benchmark in public resolution of ox phos controversy. Multiple authorship initiated by Racker.

Science and the Cure of Diseases: Letters to Members of Congress. Princeton, NJ: Princeton University Press, 1979a.

“Reconstitutions: Past, Present and Future.” In Membrane Bioenergetics, edited by Chuan-Pu Lee, Gottfried Schatz and Lars Ernster. Reading, MA: Addison-Wesley, 1979b.

With Richard Huganir. “Properties of Proteoliposomes Reconstituted with Acetylcholine Receptor from Torpedo californica.” Journal of Biological Chemistry 257 (1982): 9372–9378.

Reconstitutions of Transporters, Receptors, and Pathological States. Orlando, FL: Academic Press, 1985.

“Twelve Rules for Graduate Students in Biochemistry,” Unpublished, undated, courtesy of William B. Jakoby.

OTHER SOURCES

Lee, C. P., G. Schatz, and L. Ernster, eds. Membrane Bioenergetics: Based on the International Workshop Held at Cranbrook Schools, Bloomfield Hills, Michigan, July 5–7, 1979 in Honor of Efraim Racker. Reading, MA: Addison-Wesley, 1979. Contains autobiographical comments by Racker.

Miller, Chris. “Efraim Racker 1913–1991.” Journal of Membrane Biology 125 (1992): 95–98.

Nelson, Nathan. “Obituary: Efraim Racker (1913–1991).” Photosynthesis Research 31 (1992): 165–166.

Prebble, John, and Bruce Weber. Wandering in the Gardens of the Mind: Peter Mitchell and the Making of Glynn. Oxford, U.K.: Oxford University Press, 2003.

Rowen, Lee. Normative Epistemology and Scientific Research: Reflections on the “Ox-Phos” Controversy, A Case History in Biochemistry. PhD diss., Vanderbilt University, 1986.

Schatz, Gottfried. “Efraim Racker.” In Biographical Memoirs. Vol. 70. Washington, DC: National Academy Press, 1996.

Douglas Allchin