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Profile of J. Woodland Hastings PROFILE Profile of J. Woodland Hastings ippling in the night, wakes ‘‘After its removal, the reintroduction of of ships leave sparkling trails oxygen caused a flash with a peak ap- in the sea, the product of proximately 100 times higher than the innumerable single-celled baseline level prior to oxygen removal, Rdinoflagellates stimulated by the but not requiring the removal of oxygen ocean’s turbulence. This mesmerizing for its decay,’’ he explains. Hastings in- luminescence is present among many terpreted the flash as the result of the species of organisms, ranging from reaction of oxygen with a luciferase- squid and jellyfish to bacteria, glow- bound intermediate accumulated in the worms, and fireflies. Bioluminescence absence of oxygen (3). has evolved a number of different In McElroy’s laboratory, Hastings also times, and the enzymes and substrates started investigating luminous bacteria that cause it, referred to as luciferases and discovered a flavin to be a substrate and luciferins, differ among the major in its luciferase reaction (4). Bacterial organismal groups. luciferases would later become one of J. Woodland Hastings, elected to the the major topics of Hastings’ research. National Academy of Sciences in 2003, reports in his Inaugural Article in this Finding a Circadian Rhythm issue of PNAS on the structure of the In 1953, Hastings accepted a faculty po- luciferase gene in Noctiluca scintillans, sition in the Department of Biological one of the largest and most primitive Sciences at Northwestern University bioluminescent dinoflagellates (1). J. Woodland Hastings (Evanston, IL). He began studies of Hastings’ work shows that Noctiluca’s dinoflagellates after attending the first luciferase possesses domains for both international meeting on biolumines- applied for graduate studies at Princeton catalysis and substrate binding, whereas cence in 1954 at Asilomar, in Pacific University (Princeton, NJ). Still uncer- in some previously described dinoflagel- Grove, CA. There Hastings learned that tain about a career track, he deferred late species, these domains occur as Beatrice Sweeney, at the Scripps Institu- matriculation and left the United States separate proteins. tion of Oceanography (La Jolla, CA), to teach biology at the Colle`ge Cevenol had cultured a bioluminescent marine A Glowing Start in southern France in 1947. dinoflagellate, Gonyaulax polyedra, for Hastings, the Paul C. Mangelsdorf Pro- Returning to Princeton in 1948, Hast- the first time. Interested in elucidating fessor of Natural Sciences at Harvard ings chose to work with E. Newton Har- the biochemistry of its bioluminescence, University (Cambridge, MA), was born vey. ‘‘He was a major figure in the field Hastings began an extended collabora- in 1927 and spent his early years in Sea- of bioluminescence and cell physiology tion with Sweeney. He and Sweeney ford, DE. At age 10, he became a choir- more generally, and a wonderful men- demonstrated that Gonyaulax had a cir- boy at the Cathedral of St. John the tor,’’ Hastings says. ‘‘Already then, prior cadian rhythm of bioluminescence (5, 6) Divine in New York City and attended to the detailed biochemical and molecu- and in ensuing years made several fun- the choir’s in-house boarding school, lar evidence, Harvey had perceived the damental contributions concerning visiting his family only during vacations. evolutionary diversity and independent circadian rhythms. Moving to the Lenox School (Lenox, origins of different bioluminescent sys- In 1957, Hastings joined the Biochem- MA) in 1941 to complete his secondary tems.’’ Under Harvey, Hastings devel- istry Division of the Chemistry Depart- education, Hastings came to love litera- oped techniques to subject organisms to ment at the University of Illinois at ture, mathematics, and physics, as well low oxygen concentrations as a way to Urbana–Champaign (Urbana, IL), as baseball and ice hockey. measure the quantitative requirement where he studied both bacterial and Upon graduation in 1944, Hastings for oxygen in the luminescent reaction dinoflagellate systems. In 1961, he be- enlisted in the Navy V-12 medical offic- of different species (2). came director of the summer physiology ers training program and joined the unit Receiving his doctorate in 1951, Hast- course at the Marine Biological Labora- at Swarthmore College (Swarthmore, ings moved to Johns Hopkins University tory in Woods Hole, MA, where he had PA). Stimulated by research in Swarth- (Baltimore, MD), joining the laboratory spent two summers as a graduate stu- more’s biology department, Hastings of William McElroy, himself a former dent. For Hastings, this experience worked with Per Scholander and Knut student of Harvey. Hastings recalls that launched an enduring association with Schmidt-Nielsen, measuring oxygen- McElroy had excited biochemists with the laboratory and its scientific commu- consumption rates in different small or- his discovery that light emission re- nity. In 1966, Hastings joined the faculty ganisms. ‘‘The program was accelerated quired ATP in firefly extracts. ‘‘My re- of Harvard University as Professor of because of the war,’’ he says, ‘‘and I was search concerned the basic biochemical Biology. Continuing work at Woods scheduled to enter medical school al- mechanism of this luciferase reaction, Hole, he carried out studies with coelen- ready in the fall of 1945. But, although one finding being that coenzyme A terate luminescence systems with graduate the war ended, the draft law required stimulates light emission,’’ Hastings says. student James Morin. In these systems, that I maintain a place in medical ‘‘We had to have a lot of material, so some species emit green light in vivo but school.’’ Hastings did not attend medical we paid a penny per live firefly [to local blue light in the isolated enzyme system. school however, instead completing his residents]. I was in charge and paid the bachelor’s degree in 1947 and resigning children for their catch.’’ This is a Profile of a recently elected member of the National from the Navy, during a period when With purified luciferase, ‘‘I obtained Academy of Sciences to accompany the member’s Inaugural the law had lapsed. Certain that he did evidence that oxygen gating is the mech- Article on page 696. not want to study medicine, Hastings anism for firefly flashing,’’ he says. © 2007 by The National Academy of Sciences of the USA www.pnas.org͞cgi͞doi͞10.1073͞pnas.0610519104 PNAS ͉ January 16, 2007 ͉ vol. 104 ͉ no. 3 ͉ 693–695 Downloaded by guest on September 27, 2021 In Obelia sp., they found that a green flu- It did explain the fact that, whereas in- orescent protein, previously discovered in dividual luminous bacteria in the ocean Aequorea sp. (7), and which they dubbed do not emit light, those cultured as sym- GFP, served as a secondary emitter by bionts in light organs of fish and squid virtue of energy transfer from the lucif- (21), where they are densely packed, do erase-bound excited state (8). bioluminesce. Work on the dinoflagellate Gonyaulax continued apace at Harvard. Graduate Three-Ring Circus student Neil Krieger found luciferase In 1997, Hastings and postdoctoral fellow fractions with different pH dependen- Liming Li found that the Gonyaulax lucif- cies, foreshadowing the discovery of the erase gene contained three homologous regulation of the reaction by pH (9). and contiguous repeated sequences (22). Graduate student Margaret Fogel puri- Hastings, speaking at a lecture Expressed in E. coli, each segment coded fied cellular organelles called scintillons for a peptide catalyzing the same biolumi- and showed that when subjected to a nescent reaction. ‘‘A three-ring circus with pH jump, they emitted a living cell-like communication and the concept of quo- the same act in all three,’’ Hastings quips, flash (10). After readjustment to pH 8.0 rum sensing. He had long noted that, in ‘‘and what is the reason? Maybe because and incubation with fresh luciferin, the newly inoculated cultures, the number of this system is confined in a small organ- scintillons emitted a second flash. Hast- cells doubled every 30 minutes, but lu- elle where protein osmotic pressure is im- ings postulated that an action potential, minescence did not begin to increase portant. So more active sites without leading to the entry of protons via until 2 or more hours later, when it dou- more molecules,’’ he explains. Postdoc- voltage-activated membrane channels, bled every 5 minutes. Hastings and his toral fellow Liyun Liu examined lucif- triggered the pH jump in the scintillons, postdoctoral student Kenneth Nealson erases from seven different dinoflagellate a mechanism now accepted. found an explanation for this lag (18). species and found them all to be like The fact that luciferase activity in- ‘‘The bacteria were producing and re- Gonyaulax: an N-terminal region of un- creased every night and disappeared the leasing into the medium a substance known function followed by three homol- next day remained enigmatic (11). To that turned on transcription of specific ogous luciferase domains (23). Hastings, it seemed possible that the genes that had been repressed,’’ says The regions between tandem copies cycle stemmed from activation and de- Hastings. ‘‘This occurred only when the were strikingly different, with no identi- activation, for example by protein phos- fiable canonical promoter sequences. concentration of this substance, which phorylation. Less likely, he thought, was Individual domains are more similar be- we called autoinducer. reached a criti-
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