Researchers Qi-Long Ying from USC and Austin Smith from the University of Cambridge have won the 2016 McEwen Award for Innovation, the highest honor bestowed by the International Society for Stem Cell Research (ISSCR). Supported by the McEwen Centre for Regenerative Medicine, the award recognizes groundbreaking stem cell discoveries that open new avenues of exploration toward the understanding or treatment of human disease.
Ying originally joined Smith's laboratory as someone who knew next to nothing about stem cells. The third child of a farmer and a factory worker, he grew up in Yongkang, a small city in China's Zhejiang province, during the Cultural Revolution.
"At that time, as a kid, I was always curious about everything," he said. "So the older generation told me when I was small that I was always asking many different questions, always asking, 'Why, why, why?' "
Despite his natural curiosity, Ying had had little chance of obtaining a higher education. Chinese universities admitted students based on political and family connections, not academics, throughout most of his childhood. This changed with the death of Chairman Mao in 1976, and the subsequent reinstatement of the "Gaokao," China's merit-based college entrance exam. Ying earned a top score.
"At that time, the test was very important and changed your life forever," he said. "That's why many people, when they learned the results, they always cried. My mother [was so happy that she] also cried."
Although he originally dreamed of becoming a detective or a civil engineer, charismatic recruiters from the First Military Medical University persuaded him to choose a different path. What he didn't fully appreciate at the time was that attending one of China's military medical universities carried an obligation of 25 years of army service.
After Ying graduated in 1987, the army decided that he would work at a remote missile base near the Chinese border with North Korea -- a three-day train ride from his hometown, his parents and his three sisters. For a salary of $14 per month, he was charged with treating colds, headaches and minor ailments, and triaging more serious patients to a larger hospital elsewhere.
"We were in the mountains," he said. "It was very, very cold -- minus 30 degrees Celsius in the winter. We were not allowed to contact outside people. It took two hours of driving to go to the nearest town. And there were no women, and there was no hope, and life was very boring. We had no future. Sometimes during the weekends, the young officers drank, and they were crying, because there was no hope."
But Ying was determined to elude his seemingly sealed fate. He spent two years studying for the highly competitive exam to attend graduate school in China and earned admission to Shanghai Medical University, where he pursued his master's and PhD degrees.
During his graduate training in the early 1990s, he and his mentor, a famous Chinese neurosurgeon, injected human embryonic neural tissue into the brains of 18 patients with Parkinson's disease. Some regained the ability to walk, but only temporarily. The procedure also carried a high enough risk of fatal infection that the researchers halted the experiments.
Ying happily pursued these educational and research endeavors for nearly a decade. Then the army noticed his absence and summoned him back to his missile troop -- now relocated to the country's remote central region. He realized that to get out of the army, he had to get out of China.
Ying applied to at least 50 jobs all over the world. It was his unique experience with Parkinson's disease that landed him a two-year postdoctoral position in Smith's laboratory, then at the University of Edinburgh in Scotland. Through six months of dogged persistence and better-than-average luck, Ying secured a passport to embark on his new life.
"Austin Smith asked me to derive neurons from embryonic stem (ES) cells, and then inject these ES cell-derived neurons into a Parkinson's disease rat model," said Ying. "Austin tried very hard to recruit a postdoc to do this and failed, and then I came in. I can do this surgery in a patient. I definitely can do it in a rat."
New to both stem cells and the English language, Ying was determined to make a breakthrough worthy of extending his contract in the Smith Lab.
Ying began trying to "rewind" mouse neural stem cells into ES cells -- and thought he had succeeded. Months later, he realized that that the neural stem cells had spontaneously fused with ES cells in the same petri dish, producing abnormally large ES cells. It was the first proof of spontaneous fusion, and it earned him and Smith a publication in the journal Nature in 2002.
Still under Smith's mentorship, he began exploring new and better ways to induce ES cells to self-renew or differentiate in the laboratory. He found a more efficient way to turn ES cells into neurons, published in Nature Biotechnology in 2003.
Next, he and Smith made the landmark breakthrough that would eventually earn the 2016 McEwen Award for Innovation. They discovered that they could inhibit ES cells from differentiating into specialized cells by exposing them to two proteins -- called leukemia inhibitory factor (LIF) and bone morphogenic protein (BMP) -- and published the results in Cell in 2003. Subsequently, in a 2008 paper in Nature, they used two inhibitory molecules -- dubbed 2i -- to mimic this effect.
"Because of the properties of embryonic stem cells, we can use these cells to generate different cell types," said Ying. "And these cell types can be used for cell replacement therapy, for drug screening and for many other purposes."
Beyond these scientific successes, Ying is keenly aware of how profoundly Smith changed his life.
"Without Austin, I would not have my daughters. In China, I cannot have more than one child, [my eldest son]," he said. "I would still be in the army as a family doctor, and the only diseases I could treat would be colds, headaches and diarrhea. So I said [to Austin], 'Your offer letter changed everything, changed me.' "
After seven productive years, Ying left the Smith Lab to accept a faculty position at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, where he also serves as the director of the Chang Stem Cell Engineering Facility.
Shortly after his arrival at USC, Ying and a team of researchers made one of Science magazine's "Top 10 Breakthroughs of 2010" by using ES cell-based gene targeting to produce the world's first knockout rats, modified to lack one or more genes.
"The rat is not only bigger than the mouse," said Ying. "Physiologically, they are much closer to humans. So many diseases, such as many neurological diseases, can only be mimicked in the rat, but not in the mouse."
In recognition of their accomplishments, Ying and Smith will accept the 2016 McEwen Award for Innovation and shared $100,000 prize at ISSCR's annual meeting this June in San Francisco. Past winners of this prestigious honor include: Irving Weissman and Hans Clevers; Azim Surani; James A. Thomson; Rudolf Jaenisch; and Kazutoshi Takahashi and 2012 Nobel Prize winner Shinya Yamanaka.
ISSCR President Sean Morrison describes Ying and Smith as having "made enormous contributions to our fundamental understanding of pluripotency and how this knowledge can be leveraged to develop new tools that advance our understanding and treatment of human disease."
Ying expressed his deep gratitude for the award along with words of inspiration for young biologists.
"I started my stem cell career maybe 15 years ago," he said. "At that time, I had no experience whatsoever with stem cells, but I believed I could make contribution to this field, and I worked hard. So to be successful in this very competitive scientific career, you have to have confidence that you can achieve something."