in my shoes
Sweet science at the Library of Congress For this glycobiology pioneer, there’s no sugarcoating the obligations of science.
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© 2007 American Chemical Societ y
Courtesy of Raymond Dwek
s a Royal Society Fellow up. “It’s a wonder and author of >500 re ful opportunity to search papers, Raymond Dwek interact with people is no stranger to honors and in Washington,” he achievements. But one of the says, “and to reach sweetest, it turns out, was also out to the broader one of the most unusual. It public on issues of came in 1992, Dwek says, when technology and so he received a visit at his Oxford ciety.” The British University (U.K.) office from researcher decided to a woman claiming to represent focus his time in the the letter G. Several years ear American capital on lier, Dwek had been frustrated Raymond Dwek coined three broad subjects: by the lack of attention given the term “glycobiology”. technology and the to the study of sugars and oli In 1992, the Oxford English environment, the gosaccharides in biochemistry, Dictionary decided to list commercialization of so he had come up with a term the term. research, and the ap to describe the emerging field. plication of glycobi His visitor was from the Oxford English ology to the development of new drugs Dictionary (OED), and she had come and vaccines against HIV and other to inform Dwek, over a cup of tea, that viruses. “glycobiology” would be added to the It’s been a long road for Dwek, next edition of the dictionary. The field whose early research career centered already existed, Dwek says, “but having on using NMR for enzyme studies. He a name brought a sense of structure and joined Oxford’s biochemistry depart of identity to it and placed the research ment in 1969, and by the late 1970s, into its biological context in a way it his interest had turned to immunolo hadn’t been before.” Inclusion in the gy and the structure of antibody mol OED, he says, was the ultimate confir ecules. While he was probing the C1q mation that the field was at last gaining receptor site on the immunoglobulin recognition and respectability. G molecule, Dwek had his first taste of A decade and a half later, glyco what would become glycobiology—and biology is more than just respect his life’s work. One surface of the anti able—interest in glycosylated proteins body’s tail region was coated with car as disease markers, vaccine targets, and bohydrate, Dwek noted, so he set out therapeutic agents has made the field to determine its structure. “But instead downright hot. So it may seem like a of one sugar,” he says, “we found 32.” strange moment for one of its found It was an illuminating realization—that ing practitioners to step away from the a single protein could occur as distinct lab, if only for a short while. But that is “glycoforms”, molecules with identi exactly what Dwek is doing—first, to cal amino acid sequences but different serve as Chair of Technology and So surface sugars, which conferred unique ciety at the Library of Congress’s John functional properties on each form. W. Kluge Center in Washington, D.C., and then, later this year, to be a visiting Partnering with industry scholar at the Scripps Research Institute If that insight was the start of Dwek’s in La Jolla, Calif. The initial invitation interest in glycobiology, it also marked from the Library of Congress, Dwek the beginning of his involvement with says, was simply too tempting to pass academic–industrial collaborations.
Sequencing complex biological oligosac charides was technologically daunting, he says, and simply too expensive at the time for public funding. A technology development grant from the biotechnol ogy company Monsanto helped what would become the Oxford Glycobiol ogy Institute to get up and running. “It was Oxford University’s first com mercial grant in its 900-year history,” Dwek notes, “so it stirred up some controversy.” The new center focused initially on technology development, while Dwek’s group pursued basic research, such as studies of tissue plasminogen activator, a drug used to dissolve blood clots after heart attacks and strokes. That research showed that distinct glycoforms of the drug, produced by different cell lines, had different therapeutic characteris tics. “All of a sudden,” Dwek says, “it became quite important to know what sugars are on your protein, and the field developed from there.” A resulting patent, granted in 1985, was also the starting point for Dwek’s long-standing interest in intellectual property (IP) protection for research re sults. “It occurred to me that one could raise the profile of the field by getting patent protection” for significant pro tein glycoforms, Dwek says. “You can patent a gene, but not a protein,” he points out. “But if you can show that your product has a distinct set of glyco forms, you can establish that it is a dif ferent product, and patentable.” Dwek remains a strong advocate of IP protection for academic research, and an exploration of the promises and pitfalls of research commercialization is a central aspect of his work at the Li brary of Congress. “People want to see their ideas applied for the public good,” Dwek says, “but nobody will invest [in an idea] if it’s not protected.” But does commercialization of research inher ently deflect a university from its core
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in my shoe s
Courtesy of Raymond Dwek
mission of research and educa environmental issues and even tion, thrusting professors into peace in the Middle East. As a conflict of interest in the an adviser to Ben-Gurion Uni process? “That can certainly versity of the Negev (Israel) for happen,” Dwek admits, “but it many years, Dwek helped estab doesn’t have to. We’ve thought lish that institution’s National hard at Oxford about how to Institute for Biotechnology in the Negev in 2001. And he do spin-offs in a way that helps the public and does not harm sees a model of results-oriented the university’s mission, based research developing there that on a clear understanding of IP he says could help bring not ownership and of the differ just material comfort but also ences in priorities among the increased understanding and parties.” cooperation to the troubled For examples, Dwek points region. to his own experiences. When “The fact is that science Oxford GlycoSystems (now and technology can help called Oxford GlycoSciences) make a dramatic difference in was spun off from the Gly people’s quality of life,” Dwek cobiology Institute in 1988, says. From water-harvesting the agreement included the techniques and desalination blanket provision that nothing The HIV envelope glycoprotein gp120, the most heavily glycosyl- technology to agricultural should be done “to disgrace ated protein known. biotechnology research into the name of Oxford Univer drought resistance, science and technology have already helped produce sity.” More recently, yet another spin-off to study a lot of other trees first. “In an agricultural boom in the Negev Des has been the oligosaccharide-sequencing theory, there could be billions of dif arm of his glycobiology team. Just last ferent [oligosaccharide] forms,” says ert. Now he’s hoping that sharing that year, under the leadership of Pauline Dwek, “but when you look at what technology—and bringing researchers Rudd, the sequencing operation set up nature actually uses, it turns out to from throughout the region together independent operations in Ireland. The be quite a contained subset.” The se to develop it further—can help to build result is a research group based at Uni quencing team has compiled a database bonds of trust and hope in a way that of >300 known, biologically relevant politics never could. “The goal,” says versity College Dublin and a not-forprofit foundation supported by the Irish oligosaccharide structures. By compar Dwek, “is to try to use technology as government. The foundation has a goal ing HPLC analyses of enzymatically an instrument of peace.” digested, branched carbohydrates to If Israel’s arid desert seems like an of commercializing a high-throughput, transportable, and cheap method for the database, even nonexperts should unlikely spot for an expert in biological glycan analysis. be able to leapfrog their way to 3D se sugars, at least one tenuous link exists. quences. And that, says Rudd, should Cherry tomatoes from the Negev, ir An alphabet with a difference find eager acceptance in the processing rigated with brackish water, are reputed The challenges of oligosaccharide se and quality control of biotech pharma to be the world’s sweetest: the tomato quencing that Dwek faced in the 1980s ceuticals. “A lot of bioprocessing people plants evidently strive to balance the are just now being resolved. The pri know that they should be interested in salty water’s high osmotic pressure by mary problem, he says, is the structural glycosylation,” she says, “but they’re not boosting their production of sugar. complexity that can result from the 3D sure how to be. There’s a real need for a But Dwek’s research attention remains branching structure of complex sugar straightforward, inexpensive method for focused on an even sweeter goal—shep polymers. Just like the amino acid and monitoring glycosylation.” herding glycobiology into a new, ap nucleotide sequences that make up lin plied era, including a big push for gly ear proteins and nucleic acids, glycan Many possible payoffs from coprotein-based antivirals and vaccines. building blocks can be seen as letters biotechnology “When the analytical technology was in an alphabet. “But it’s an alphabet Dwek is also using his time at the Li being developed,” Dwek says, “people with a difference,” Dwek says. “It’s got brary of Congress to focus on other had no idea what the sugars did. Now, branches. You can write down the code we’re seeing the possibility of con long-standing interests, including for a log, but how do you write down speeding the quest for an AIDS vac fronting serious, important problems. the code for a tree?” cine and—somewhat less directly linked There’s an obligation, I think, to try to The approach taken by Rudd and to glycobiology—calling attention to take those on.” a her team, due to be published soon, is the role of biotechnology in addressing —Thomas Hayden 6440
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