Roger Yonchien Tsien

Abstract

Nobel Prize winning biochemist. He was born in New York, NY, USA, on Feb 1, 1952, and died in Eugene, OR, USA, on Aug 24, 2016, aged 64 years. It's not unusual for people outside the relevant science to find themselves bemused by the discoveries for which Nobel Prizes are awarded. This was certainly so with the 2008 Nobel Prize in Chemistry. One of its recipients was Roger Tsien, Professor of Pharmacology, Chemistry and Biochemistry in the School of Medicine of the University of California at San Diego (UCSD). It was awarded for work on a jellyfish protein that emits a green glow when illuminated with blue or ultraviolet light. Arcane though it appears, Tsien's interest in the topic had a practical significance: for researchers this green fluorescent protein offered a real time method of detecting the activity of certain genes or the presence of specific proteins; to clinicians it opened up the prospect of identifying particular tissues inside the body. “Roger's fluorescent proteins are used in virtually every biological laboratory around the world”, says Jack Dixon, Professor of Chemistry and Biochemistry at UCSD. The son of an engineer who emigrated to the USA in the 1940s, Tsien's fascination with science began as a child. A standard chemistry set having proved disappointingly tame he sought out chemical agents with more promise. In the basement of his house he replicated classic chemical experiments: an enterprise in which his ambition ran ahead of his facilities. Writing at the time of his Nobel Prize he recalled trying to synthesise aspirin. This required acetic anhydride, “which had to be made from acetyl chloride, for which I needed phosphorus trichloride, for which I had to burn red phosphorus in a stream of chlorine gas”. No wonder Dixon describes Tsien, admittedly in a different context, as “scientifically fearless”; he'd had much practice. In 1972, with a Harvard degree in physics and chemistry but fascinated by neurobiology, Tsien crossed the Atlantic to do a PhD at the University of Cambridge. On discovering that his putative supervisor was principally interested in muscle he decided to plough his own furrow: to devise a dye that would fluoresce in the presence of extra calcium, an indication that the cell into which it had been introduced had become active. Amazingly he succeeded. After 10 years in Cambridge he returned to the USA, first to the University of California at Berkeley and later to UCSD, where he remained. The roots of research on jellyfish green fluorescent protein go back to 1962 when chemist Osamu Shimomura discovered it during a study of bioluminescence. This earned him a third of the 2008 Nobel Prize. Another third went to biologist Martin Chalfie of Columbia University in New York for showing, in the 1990s, that green fluorescent protein could be exploited as a biological marker. Chalfie and his collaborators first persuaded genes that were active to reveal themselves by making green fluorescent protein. Next they perfected a variant of the technique in which a gene could be modified to specify a hybrid protein carrying a green fluorescent protein component that acted like a lantern. “Wherever the protein went it could be followed”, says Chalfie. It was shortly after this that Tsien too began working on green fluorescent protein. If Chalfie was the architect of fluorescent protein labelling, Tsien was its interior designer. He began to modify it to give different colours. “What Roger did first was change a single aminoacid to make a molecule that emitted blue light”, says Chalfie. Through other interventions he increased the brightness of the fluorescence and did away with the need to use ultraviolet light as a stimulator. The blue fluorescence was soon followed by yellow. Other colours followed—even one that fluoresced in the infrared. A rainbow to brighten the microscopist's life, aesthetically as well as intellectually. “Roger was full of ideas and constantly thinking out of the box”, says Dixon. “He didn't care if it was going to take 5 years to achieve something. He'd put in the time and the effort to make it happen.” Clinical applications of fluorescent labelling are still at an earlier phase of development. But one such is in distinguishing between diseased and healthy tissue, especially in cancer. Tsien was himself investigating this possibility with Quyen Nguyen, a UCSD surgeon. As the pair commented in a recent and optimistic review of the topic, “A glowing new era in cancer surgery may be dawning”. Tsien leaves a wife, Wendy, and two brothers.