Roger Tsien Inducted Into National Inventors Hall of Fame

Shimomura identified the crucial jellyfish protein and revealed that it glowed bright green under ultraviolet light. Chalfie showed how it could be used as a biological marker. Combining his deep skills in chemistry and biology, Tsien found ways to make GFP glow more brightly and consistently; then he created a full palette of fluorescent proteins that scientists could use to track different cellular processes at the same time.

“I’ve always been attracted to colors,” Tsien told The San Diego Union-Tribune in 2008. “Color helps make the work more interesting and endurable. It helps when things aren’t going well. If I had been born color-blind, I probably never would have gone into this.”

The utility of GFP proteins was immediately and broadly recognized, making it possible for biologists to mark and track molecules and functions within living cells in real-time. It became possible, for example, to monitor DNA and which proteins were used to perform different duties; audit gene expression in different kinds of cells and tag molecules as they move in and out of cells.

Emerging GFP tools did not stay locked within laboratories. In 2010, Tsien, Quyen T. Nguyen, MD, PhD, professor of Surgery at UC San Diego School of Medicine and a head-and-neck surgeon at UC San Diego Health and others described using fluorescent probes to light up cancerous tumors. A year later, they published findings about using GFP in surgery, injecting fluorescent peptides into mouse models that caused hard-to-see peripheral nerves to glow, alerting surgeons to their location even before the nerves are encountered.

In 2019, UC San Diego Health opened the Center for Fluorescence-Guided Surgery to leverage the rapidly evolving imaging tool across a spectrum of procedures, from common gallbladder removal and weight loss surgery to complex neurosurgical operations.

Perhaps the greatest potential lies in the drugs that Tsien co-invented using fluorescence to help surgeons ensure safe and complete removal of malignant tissues while preserving critical nerves during surgery.

For example, pegloprastide (licensed from UC San Diego by Avelas Biosciences) is a fluorescent imaging agent currently in clinical trials for patients undergoing breast cancer detection. It received “breakthrough therapy” designation from the U.S. Food and Drug Administration (FDA) in 2020. Bevonescein (licensed from UC San Diego by Alume Biosciences) is another fluorescent marker in clinical trials designed to locate nerves during head and neck surgeries. It recently received FDA fast track designation intended to speed development.
 
“These technologies are legacies of Roger's desire to use fluorescence to make a difference in patient outcomes. Both are in the late stages of development and have received significant FDA recognition for their high clinical impact potential,” said Nguyen. “Roger was a visionary who saw the power and possibilities of fluorescence. His work continues to light the way.”

The smaller picture

Tsien did not rest on his Nobel laurels.

In 2011, he and colleagues created a new type of genetic tag visible under an electron microscope (EM), providing even greater cellular detail.

“The big advantage of EM is that it has always had much higher spatial resolution than light microscopy. You can get up to a hundred-fold higher useful magnification from EM than from light microscopy,” said Tsien at the time.

“Existing EM images of cell structures are analogous to maps or aerial photographs showing major landmarks and populations centers. It was very difficult to see where individual protein types were located, just as most geographical maps do not show the location of individual classes of people, such as everyone with the surname Smith, or all of the orthodontists in an area. Our new technique enables us to put beacons on just about any protein and get a snapshot of its location at the much higher resolution of EM.”

Tsien studiously avoided the spotlight, but scores of awards and accolades found him. 

“Every honor was justly deserved, and always received with humility,” said Pradeep Khosla, chancellor of UC San Diego when Tsien died. “Roger was an extraordinary man: kind, generous, gracious, and always the consummate scientist pushing the limits of his work to expand the possibilities of science. He was a rare talent we cannot replace.”

His achievements, though, shine on.