Harvard University - Department of Molecular & Cellular Biology

IN MEMORIAM: THE GLOWING CAREER OF WOODY HASTINGS

by Cathryn Delude

August 8th, 2014

Woody Hastings (2002)

"Dear friends and colleagues,

It is with great sadness that I write to inform you that Woody Hastings passed away.

Woody's health had been declining over the past few months, and he died peacefully on Wednesday, surrounded by his children and loved ones.

His family is planning a private service, but there will be a memorial service here at Harvard sometime in October. I will share more details with you as they become available.

Woody was a great scientist, an inspiring teacher, and a generous and humble colleague and friend. We will miss him terribly."

Alex Schier, MCB Chair
 

The following tribute is based on a 2010 interview with Woody Hastings.

Bioluminescence delights children catching fireflies, amazes sailors navigating sparkling seas, and intrigues biologists contemplating how bioluminescent bacteria maintain symbiotic relationships with fish, squid, and other organisms. Bioluminescence, the ability of organisms to emit light, also sparked the curiosity of a young Woody Hastings and it continued to hold him in its spell as he wound down his teaching career in the Harvard Department of Molecular and Cellular Biology (MCB).

Studying these beautiful lights led Hastings, the Mangelsdorf Professor of Natural Sciences, from one discovery to another. By studying a single-celled marine bioluminescent dinoflagellate, he detected the inner workings of circadian rhythms that, scientists increasingly realize, affect our lives as well. “Just think of jet lag,” Hastings suggested during an interview in 2010. Along the way, he identified a fluorescent green protein (GFP) in colonial hydroids that is now standard in the biologist’s toolbox. Researchers who applied GFP as a reporter for gene expression won the 2008 Nobel Prize in Chemistry. He also discovered that bacteria can communicate with each other using a mechanism he called autoinduction, later dubbed quorum sensing, which has fundamentally changed the understanding of the microbial world.

All in all, Hastings’s work has relevance to naturalists, basic researchers, medical clinicians, industry, the human sleep lab, the child’s glow stick, and a famous Jules Verne novel (which draws on actual mariners accounts of “milky” seas). His “50 [plus] years of fun” (the title of one of his 400-plus papers) also earned him many awards and honors, including election to the National Academy of Sciences.


Hooked on Bioluminescence

Born in 1927 in Salisbury, Maryland, 10-year-old J. Woodland Hastings became a choirboy at the Cathedral of St. John the Divine in New York, where he attended its boarding school. The United States was in World War II when he graduated from Lenox School in Massachusetts in 1944, so he joined the Navy V12 medical officer-training program, which sent him to Swarthmore College.

Instead of going to medical school when the war ended, Hastings finished his Bachelor’s degree at Swarthmore, resigned from the Navy, taught biology (in French) at a lycée in southern France, and worked on reconstruction in Germany. Returning, he completed a PhD program in biology at Princeton University with E. Newton Harvey, who worked on bioluminescence; Hastings was hooked.

In 1953, Hastings began postdoctoral studies with William McElroy at Johns Hopkins on the biochemistry of firefly luminescence. “Baltimore is the firefly epicenter on the east coast, and they were everywhere on campus,” he recalled. He became the “supervisor of firefly collection,” which involved passing out nets to local children and trying not to be duped into paying them for more than their catch (going rate: a penny apiece).


An Endogenous Biological Clock

Hastings accepted a position at Northwestern University in 1953 and began studying the biochemistry of bioluminescent bacteria and fungi. But he learned that Beatrice Sweeney at Scripps Institution of Oceanography in La Jolla, California had succeeded in culturing a bioluminescent dinoflagellate, Gonyaulax polyedra, which flashes in the ocean at night when mechanically stimulated. Planning to work on the biochemistry of the reaction, Hastings arranged to work with her for the summer of 1955, beginning a long, fruitful collaboration that brought him, unexpectedly, into the field of circadian rhythms and biological clocks.

Sweeney had noted that the dinoflagellate’s bioluminescence followed a diurnal biological rhythm – on at night and off during the day. At the time, some scientists believed that the timing was controlled by the environment. Hastings measured the biochemical rhythm in bioluminescence in laboratory cultures without a light-dark cycle (constant light or dark) and found that the “day-length” of the rhythm was approximately 24 hours and thus was circadian. “So we concluded that the rhythms are endogenous. We now know that all organisms from bacteria to humans exhibit circadian rhythms.”

Hastings continued working on the circadian clock and bioluminescence at his next position at University of Illinois in 1957 and then at Harvard, where he arrived in 1966 and remained until he retired and became Emeritus in June of 2011 – except for sabbaticals, which he took “on every possible occasion,” sometimes to far-flung locations.

At Harvard, Hastings proved that luciferase, the light-emitting enzyme, and luciferin, its substrate, are synthesized and destroyed daily, not just activated or inhibited, and so is the entire cellular organelle called a scintillon that houses these proteins. Carl Johnson, who worked on this project as a postdoc from 1982 to 1987 (“the best five years of my life”), recalled that they had trouble convincing reviewers to publish this work. “It was the first demonstration of any circadian rhythm of protein synthesis. Now it’s commonplace knowledge that many proteins exhibit these rhythms.”

Johnson was one of  “many very bright people who were attracted to Hastings’s manner of directing research – a free exchange of ideas without daily supervision,” said Thérèse Wilson, a Senior Research Associate who joined the lab in 1969, conducted independent research on photochemistry, and also co-authored many papers and later a book with Hastings. “He lets people blossom,” she said. At Vanderbilt University, Johnson said he tries to emulate this style and also Hastings’s willingness to take risks and embrace new technologies.

Hastings’s influence on young people went beyond his lab and classrooms and his own four children. For 20 years, from 1976-1996, he and his late wife of 56 years, Hanna, were much acclaimed “Co-masters of the Universe" at North House (now Pforzheimer), the smallest and some said the most intimate House at Harvard.


Autoinduction and Quorum Sensing in Luminous Bacteria

In the early 1960s, Hastings began working on the biochemistry of the bacterial luciferase reaction and enzyme structure. In growing large quantities of cells to isolate the enzyme, it struck him that, while freshly inoculated luminous cells grew rapidly, they failed to produce any additional light or luciferase for the first several hours. At a density of about 108 cells ml-1, luminescence then rose dramatically.


“People couldn’t make any sense of the data so they invented explanations,” recalled Kenneth Nealson, a former postdoc in Hastings’s lab. Starting in 1968, Nealson took the bull by the horns and demonstrated that a substance accumulating in the growth medium triggered the formation of new messenger RNA and the synthesis of luciferase. He called this substance autoinducer – which he identified as a hormone-like acyl homoserine lactone – because it induced freshly inoculated cells to luminesce without delay.  Then he proved this hypothesis by demonstrating that synthetic autoinducers also caused this effect.

“Nobody in the universe believed our explanation!” said Nealson, a Professor of Geobiology at University of Southern California. “We sent in our papers and got remarks back from the editors like, ‘We don’t see anything wrong with the study, but it can’t be right because bacteria don’t do that.’ But Woody had a fantastic positive attitude and said, ‘If you think you’re right, don’t give up.’ He could have taken all the credit for its discovery, but he always included me. That was a great lesson to me, and we’ve stayed close friends ever since.”

Some colleagues accepted the idea that bacteria could communicate with each other, but thought it functioned only in bioluminescent bacteria. They understood that autoinduction could be functionally important for bacteria living as symbionts, “packed like sardines” in light organs of some fish and squid that use the light to lure prey. Other creatures use it for protective counter-illumination, concealing their silhouettes – “A light to hide by,” as Hastings termed it when studying the pony fish in New Guinea in 1969. In contrast, bacteria living freely in the ocean are too dispersed for their light to be visible, and conserve energy by not synthesizing the luminous system until they sense they are highly concentrated.

But in the 1990s researchers discovered that autoinduction is widespread in bacteria and is used for many different functions. For example, pathogenic bacteria may use quorum sensing to restrict toxin synthesis until their population is large enough to release a potent dose that overwhelms their unsuspecting host’s immune defense. Inhibiting quorum sensing is now an active area of drug research. Hastings believed it also has implications for development. “Autoinduction is a fabulous case of how specific genes are turned on and off in specific circumstances,” which is exactly what happens during embryonic development.


Still Curious After All These Years

Dinoflagellates continued to amaze Hastings throughout his career. His lab showed that the actual biochemistry of the regulation of light emission and flashing is controlled by rapid changes in acidity within the scintillon. At pH 8, luciferase is inactive; at pH 6 it flips to active. “This is a unique mechanism for rapid control of a biochemical reaction on a millisecond time scale,” Hastings observed. Structurally, luciferase has three repeat domains, each of which can function independently as luciferase. Possibly by packaging three of these domains in a single molecule, the cell can increase the number of light-emitting units without increasing protein concentration. Also, all previously known luminous dinoflagellates have separate genes for luciferase and the luciferin binding protein. But Hastings found what might be an ancestral species that has just one gene that encodes sequences for both functions.

Hastings’s interest in circadian rhythms also remained strong, especially in the fact that dinoflagellates employ an unusual mechanism to regulate the circadian synthesis of specific proteins: transcript (RNA) levels remain constant, but protein synthesis oscillates with circadian phase. After he retired from teaching a course with Charles Czeisler from Harvard Medical School on circadian rhythms and sleep, he continued collaborating with Czeisler in designing experiments on circadian rhythm. He also worked with a Massachusetts General Hospital researcher on a substance that may prevent sunburn damage, and he maintained a small lab.

Future generations of students will be educated by professors holding the J. Woodland Hastings Endowed Chair in Biochemistry at University of Illinois in Urbana, endowed in 2008 by George and Tamara Mitchell. "George started as my graduate student at Illinois and transferred with me to Harvard for his PhD. He went with me on the Alpha Helix pony fish expedition to New Guinea in 1969, and his study of fluorescence in my lab was a beginning of work that led to his company SLM," which developed photon-counting instrumentation for measuring fluorescence.

And to tie together the many threads of his research, Hastings wrote a book about bioluminescence with Thérèse Wilson. It is an illuminating volume and much fun to read!

You might like to watch an iBioSeminar video that was shot last summer.


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