The Vilcek Prize in Biomedical Science
Lily and Yuh-Nung Jan, Ph.D.
In an erudite collection of essays on art that sparkle with his sardonic wit, the English novelist Julian Barnes wisely observes: “An artist’s career...is more likely to be a matter of obsessional overlap, of ferrying back and forth, of process rather than result, journey rather than arrival.” Barnes’ astute observation might just as easily apply to the intertwined careers of Lily and Yuh-Nung Jan, a pair of neuroscientists at the University of California, San Francisco, and co-adventurers on a four-decade quest to unravel the mysteries surrounding nervous system development and function.
In an era when showboating is prescribed as a catalyst for professional advancement, the Jans have shown no more than a spectatorial interest in the spotlight, despite their vast and vital contributions to neuroscience. Their crisscrossing paths and collective efforts have nonetheless led to a clear-eyed understanding of how neurons—the brain’s cellular building blocks—form and function and how ion-conducting channels control the flow of electrical signals through the nervous system.
The story of the Jans’ rise from provincial origins to the pinnacle of neuroscience unfolds as a Stendhalian narrative of love, ambition, struggle, and reward. Raised in nurturing homes in Taiwan, the Jans nursed a love of science from a young age. Whereas Lily’s academic bent surfaced early in her school days, Yuh-Nung’s quicksilver intellect lay buried until he breezed through a competitive college entrance exam, placing among the top 10 of 30,000 high school students.
Before long, the Jans were admitted to the prestigious National Taiwan University, where they enrolled to study theoretical physics in the mid-1960s. Yuh-Nung settled on a major by flipping a coin; Lily defiantly chose a field deemed unsuitable for girls at the time. At university, their separate paths crossed shortly before graduation, during a trip to a nature reserve in central Taiwan. Amid lush forests and sloping mountains swept by damp coastal winds, the Jans fell in love, their bond cemented by a shared penchant for science and an unswerving drive to succeed. Together, they made plans to attend graduate school in the United States, focusing their flame-like intellects, bright and restless, on theoretical physics at California Institute of Technology, then a hotbed of physics research and home to heavyweights like Richard Feynman and Murray Gell-Mann.
In 1968, the Jans arrived in Pasadena, fresh-faced but fearless. But after only two years of studying physics at Caltech, they changed course, inspired by their mentor Max Delbrück and increasingly enamored with biology. Delbrück, a physicist by training, won the 1969 Nobel Prize in Physiology or Medicine for uncovering the genetic structure of viruses. Under his tutelage, the Jans blossomed as biologists. While Yuh-Nung studied sensory transduction in a fungus, Lily set forth to localize the visual pigment rhodopsin in the retina of mouse eyes.
The Jans’ doctoral work did not lead to thunderclap insights, but it jump-started sterling careers in biology. The ensuing years are marked by milestones signaling rigorous apprenticeship that sharpened their minds and manual skills: summer courses at Cold Spring Harbor Laboratory in New York (1974), postdoctoral training with renowned Caltech neurogeneticist Seymour Benzer (1974-77), a second postdoctoral stint with Harvard University neurophysiologist Steve Kuffler (1977-79), and a string of publications in prestigious journals (1974-79), eventually culminating in faculty appointments at the University of California, San Francisco, in 1979. There, they began to assemble their legacy in neuroscience—a treasure chest of fundamental insights into nervous system development and function.
Chief among those insights are the Jans’ discoveries on how neurons arise from their progenitors, acquire distinct identities and shapes, and establish baroque circuits in the brain and peripheral nervous system with seeming ease. Using fruit flies as their favored experimental model, the Jans pulled back the curtain on a graceful symphony of steps guided by a succession of genes that influences the onset and course of neural development and wiring. For example, they found that the genes cut and numb, among others, influence the identity and type of neurons made by their progenitors, and that the fruit fly gene atonal is implicated in vision and hearing. Many of the genes and developmental programs, it turns out, are conserved in mammals, including humans. To wit, years after the Jans’ report on atonal, the role of the gene’s mammalian versions in human sight and hearing came to light.
Surcharged by the success of those efforts, the Jans next uncovered the principles and genes that control the process by which the slender branches of neurons, called dendrites, grow into densely interlacing forests. Dubbed dendritic arborization, the process is crucial to the establishment of neuronal networks in the brain and body’s periphery. The Jans’ genetic studies in this area reach beyond a basic understanding of neural development. Dendrite development, the Jans have shown, may hold a key to unraveling nerve regeneration, touch perception, and human mental disorders such as autism and schizophrenia.
Another gem in the Jans’ trove of findings emerged from their efforts to isolate the gene for proteins that shuttle potassium ions in and out of cells. Known as potassium channels, the proteins, which control the flow of signals in the nervous system, are implicated in a breathtaking array of functions, such as heart rate maintenance, hormone release, and muscle movement. The Jans pinpointed the genes encoding Shaker, the fruit fly counterpart of the human voltage-gated potassium channel Kv1.1. Since the Jans’ initial discovery, potassium channel family members, including Kv1.1, have been fingered in a growing list of conditions, including epilepsy, ataxia, deafness, neonatal diabetes, appetite control, and hypertension.
Building on those findings, the Jans identified the genes for a different family of channels called calcium-activated chloride channels, which shuttle chloride ions to control smooth muscle contraction in the stomach, intestines, and lung airways. The Jans’ work suggests that distinct members of this family of chloride channels might help mediate defense against disease-causing microbes in the fruit fly as well as neuronal signaling. Together, these findings have brought into focus the central role of ion-conducting channels in sustaining normal cellular function and enabled fine-grained analysis of conditions in which the channels go awry.
The Jans say these achievements owe a clear debt to the scientific culture in the United States, where intellectual voracity is often unquestioningly fostered. “The culture here is so open and collaborative, we couldn't possibly do what we did had we not come to the United States,” says Yuh-Nung. Added to these advantages is the relative absence of sclerotic academic hierarchies in the United States. “That makes risk-taking and original work possible,” says Lily. Buoyed by these benefits, the Jans have in turn shepherded a slew of immensely gifted researchers from around the world to successful careers, marked by contributions that have indisputably enriched American neuroscience. “That, you could say, is our way of giving back,” adds Yuh-Nung.
Vilcek Prizes Gala
Browse photos from the Vilcek Foundation Awards Gala, honoring the recipients of the 2017 Vilcek Prizes.