Roger Yonchien Tsien (Chinese: 錢永健 ; February 1, 1952 – August 24, 2016) was an American scientist who studied living things. He worked as a professor of chemistry and biochemistry at the University of California, San Diego. In 2008, he received the Nobel Prize in Chemistry for developing the green fluorescent protein, which he created with organic chemist Osamu Shimomura and neurobiologist Martin Chalfie. Tsien also helped create a method called calcium imaging.

Early life

Tsien was born in New York in 1952 to a Chinese American family. He grew up in Livingston, New Jersey, and attended Livingston High School. Tsien’s family comes from Hangzhou, China. His father, Hsue-Chu Tsien, graduated from MIT and Shanghai Chiao Tung University. He worked as a mechanical engineer and was among the top students in his university class.

As a child, Tsien had asthma, which meant he spent much time indoors. He conducted chemistry experiments in his basement laboratory. At age 16, he won first prize in the Westinghouse Talent Search for a project studying how metals interact with thiocyanate.

Tsien attended Harvard College with a National Merit Scholarship. He was elected to Phi Beta Kappa as a junior and graduated summa cum laude with a Bachelor of Arts in chemistry and physics in 1972. His freshman-year roommate, Herman Quirmbach, an economist and politician, once said, “It’s probably not an exaggeration to say he’s the smartest person I ever met… [and] I have met a lot of brilliant people.”

After earning his bachelor’s degree, Tsien joined the Physiological Laboratory at the University of Cambridge in England through a Marshall Scholarship. He lived at Churchill College, Cambridge, and received his PhD in physiology in 1977. His research focused on the Design and Use of Organic Chemical Tools in Cellular Physiology. Richard Adrian supervised his work in the physiology department, while Andy Holmes, Gerry Smith, and Jeremy Sanders assisted him in the chemistry department.

Research and career

After earning his Ph.D., Tsien worked as a research fellow at Gonville and Caius College, Cambridge, from 1977 to 1981. He joined the University of California, Berkeley, as a faculty member from 1982 to 1989. Starting in 1989, he worked at the University of California, San Diego, as a professor of pharmacology, chemistry, and biochemistry, and as an investigator for the Howard Hughes Medical Institute.

Tsien helped scientists study cell biology and neurobiology by creating genetically programmable fluorescent tags. These tools allow scientists to observe how molecules behave inside living cells in real time. He also developed fluorescent indicators to measure calcium ions and other ions important for biological processes.

In 2004, Tsien received the Wolf Prize in Medicine for his work designing and applying new fluorescent and photolabile molecules to study cell signaling. In 2008, he shared the Nobel Prize in Chemistry with Osamu Shimomura and Martin Chalfie for their discovery, expression, and development of green fluorescent protein (GFP).

Scientists use multicolored fluorescent proteins developed in Tsien’s lab to track where and when genes are active in cells or whole organisms. A gene of interest is often combined with a fluorescent protein gene, causing the protein to glow when exposed to specific light. This technique has become widely used in molecular biology, cell biology, and biochemistry.

After the discovery of wild-type GFP, Tsien and others created many new versions of GFP through genetic changes. In 1995, Tsien reported a key mutation (S65T) that improved GFP’s brightness and stability. This change made GFP’s excitation peak shift to 488 nm, matching equipment commonly used in labs. These improvements made GFP more practical for research. Tsien’s work helped scientists understand how GFP functions and develop new GFP variants.

Former students of Roger Y. Tsien include Atsushi Miyawaki and Alice Y. Ting.

Key events in GFP development by Tsien:
– 1994: Tsien explained how the GFP chromophore forms through a chemical reaction that requires oxygen but does not need other proteins.
– 1994–1998: Tsien and collaborators created many GFP mutants through genetic changes. These variants glow more brightly and show colors like yellow, cyan, and blue.
– 2000–2002: Tsien developed monomeric variants of DsRED that glow in red, pink, and orange. These tools allow scientists to label complex networks in living organisms using many colors.

Other highlights:
– 2002: Tsien identified a structural difference between GFP and DsRed. A single extra bond in DsRed’s chromophore causes its red color.
– 2002: Monomeric DsRed (mRFP) was first created.
– 2004: New “fruit” fluorescent proteins were developed using directed evolution.

In 2009, Tsien’s group created a new type of infrared fluorescent protein (IFP) from bacterial phytochromes. These proteins can be made fluorescent by removing parts that control signaling. IFPs require an external molecule called biliverdin to glow.

In 2016, Tsien’s team developed a new class of fluorescent protein called smURFP from a cyanobacterial protein. smURFP incorporates biliverdin on its own, without needing an external protein. Unlike jellyfish- or coral-derived proteins, smURFP does not require oxygen or produce harmful hydrogen peroxide. It is as bright as eGFP and twice as bright as most red or far-red fluorescent proteins from coral. Its properties are similar to the dye Cy5.

Tsien helped create the foundation for next-generation DNA sequencing technology. In 1990, he and others patented a method for stepwise DNA sequencing using removable 3' blockers on DNA arrays. Illumina later used this idea in their sequencing technology.

Tsien pioneered calcium imaging and developed dyes that glow in the presence of ions like calcium. Fura-2, indo-1, and fluo-3 are widely used to track calcium levels in cells. He also created indicators for other ions, including magnesium, zinc, copper, and others.

Aequorin is another tool for measuring calcium, but it requires continuous addition of coelenterazine. To solve this, Tsien’s group created Cameleon, a calmodulin-based sensor.

FlAsH-EDT2 is a method for labeling proteins with a tetracysteine motif. It was developed by Tsien and colleagues in 1998.

Tsien’s group tested fluorescent peptides that could guide cancer surgery. These peptides are harmless to tissues and remain in the body for only 4–5 days. Clinical trials are ongoing.

Tsien held or co-held about 100 patents by 2010. In 1996, he cofounded Aurora Biosciences, which became public in 1997. In 2001, Aurora was acquired by Vertex Pharmaceuticals. He also cofounded Senomyx in 1999.

Tsien promoted science education through programs like the San Diego Science Festival Lunch with a Laureate.

Personal life

Tsien is a 34th-generation descendant of King Tsien Liu of Wuyüeh. His father, Hsue-Chu Tsien, was born in Hangzhou, and his mother, Yi-Ying Li, was born in Beijing.

Tsien’s extended family includes many engineers. His father, Hsue-Chu Tsien, was a mechanical engineer who graduated from MIT. His mother’s brothers, Yao-Tzu Li and Shih-Ying Lee, were professors of engineering at MIT. Tsien’s mother, Yi-Ying Li, worked as a nurse. Tsien Hsue-shen, a famous rocket scientist who helped create the Jet Propulsion Laboratory at the California Institute of Technology and later led China’s missile and space programs, was a cousin of Tsien’s father.

Tsien had two brothers: Richard Tsien, a neurobiologist at New York University, and Louis Tsien, a software engineer. Tsien called his own work "molecular engineering" and once said, "I'm doomed by heredity to do this kind of work."

He was married to Wendy Globe.

Tsien died on August 24, 2016. The exact cause of his death was not shared, but reports said he died while riding a bike on a trail in Eugene, Oregon. Before his death, Tsien had survived cancer and had a stroke in 2013.

"He was ahead of us all," said Tsien’s wife, Wendy. "He was ever the adventurer, the pathfinder, the free and soaring spirit. Courage, determination, creativity, and resourcefulness were hallmarks of his character. He accomplished much. He will not be forgotten."