Neuroscience tab

2012 Neuroscience Prize

Lily Jan

Although they did not meet until they were university undergraduates, Lily Jan and Yuh Nung Jan had similar childhoods. Both were born in mainland China, but were taken by their families to be raised in Taiwan after the Communists seized control of China in 1949. Although none of their parents were scientists (Lily’s were accountants and Yuh Nung’s were government workers), both families encouraged their children to pursue their own educational interests.

Lily and Yuh Nung each went to a same-sex high school, where they had to choose a career track. Physics was particularly appealing to Taiwanese students in the early 1960s because two Chinese-born scientists, Chen Ning Yang and Tsung-Dao Lee, had won the Nobel Prize for Physics in 1957. “That had a big influence on my decision to pursue physics,” says Lily. “For me,” says Yuh Nung, “it came down to either physics or medicine. So, I flipped a coin.” He pauses and then adds, laughing, “It came out medicine.” But Yuh Nung ignored the coin toss and, like Lily, chose physics.

After high school, both Lily and Yuh Nung pursued their physics studies at National Taiwan University, which is where they met. In 1968, after graduation (and after Yuh Nung had spent a year serving in the Taiwanese air force), they both entered the California Institute of Technology (CalTech) to study theoretical high-energy physics. But two years later, they were persuaded by the late molecular biologist Max Delbrück, who won the 1969 Nobel Prize in Medicine, to switch their majors to biology. “From time to time he would invite biologists to give colloquia in the physics department,” recalls Yuh Nung. “We went to those talks and found them very interesting.” Delbrück was eager to recruit CalTech’s brightest physicists to biology. “He would say that he wanted not just their hands and minds, he wanted their hearts and souls, too,” says Lily.

The Jans were married in 1971, and received their PhDs in biophysics and physics three years later. Delbrück had urged them to work on separate research projects throughout their graduate studies. “I think what he had in mind was that in the student stage we should evolve independently,” says Lily. But during a summer neurobiology course at Cold Spring Harbor Laboratory in 1974, Lily and Yuh Nung decided to team up as partners. They’ve been working together ever since.

The Jans remained at CalTech from 1974 to 1977 to do collaborative postdoctoral work in the laboratory of the renowned molecular biologist and behavioral geneticist Seymour Benzer, where they studied the neurogenetics of the common fruit fly (Drosophila melanogaster) and its effects on the fly’s behavior. Their study of a mutant strain of Drosophila known as “Shaker” (named after the fly’s abnormal limb movements) led them to identify the mutation as having an important impact on the function of potassium channels. At the time, little was known about the molecular properties of these tiny pores on the membranes of nerve cells, which serve as gatekeepers for charged atoms known as potassium ions as they flow in and out of the cells.

To learn to record from nerve cells that are much smaller than the muscle cells they recorded from in their studies of the Shaker mutants, the Jans moved to Boston in 1977 (with their newborn daughter, Emily), where they worked in the Harvard Medical School lab of neurophysiologist Stephen Kuffler for two years. While there, they made their first major discovery: that molecules known as peptides can act as neurotransmitters (chemicals that transfer messages from one neuron to another). In a groundbreaking 1982 paper, they described how a peptide called luteinizing-hormone-releasing hormone (LHRH) acts as a neurotransmitter in clusters of nerve cells (the sympathetic ganglia) that carry messages from the brain throughout the body, by influencing not only those nerve cells near the release sit for this peptide but also other nerve cells within the sympathetic ganglia. Scientists have since discovered dozens of other peptide neurotransmitters, and the study of these peptides and their role in health and disease is now an exciting and important field of neuroscience research.

By the time of publication of those studies, the Jans had returned to the West Coast to teach and set up their own laboratory at the University of California, San Francisco. They continued their research on the Shaker gene. In 1987, they announced another landmark discovery: the cloning of that gene. It was the first successful cloning of a gene for a potassium ion channel. This finding opened up yet another new field of scientific inquiry. During the past twenty-plus years, scientists have successfully cloned dozens of human genes encoding various potassium ion channels, and mutations in these genes have been linked to a variety of diseases, including heart rhythm problems, epilepsy, and hypertension. Many of the advances in this field have come from the Jans’ lab.

In addition to their seminal work on potassium channels, the Jans have made significant discoveries in the field of developmental neuroscience. Their research has helped explain various aspects of embryonic brain development, including how neurons use certain proteins to acquire their identity; how the division of a single neural progenitor cell can generate two dissimilar “daughter” cells, thus ensuring cellular diversity in the mature brain; and how neurons develop dendrites, the branched extension of a neuron that receive and integrate sensory inputs and signals from nearby neurons.

It’s rare for scientists to share both a laboratory and a marriage, but the Jans have pulled off this dual feat with remarkable success. “Scientific collaboration works very well,” says Lily. “Two people can really work well together, and what they end up with is not just the sum of when two people work separately.” Yuh Nung agrees. “It has worked out very well,” he says. “I think we complement each other in our work and in our personality.” She is very patient and focused, he explains, while he tends to be a bit more impulsive, with “wild and crazy ideas.”

Both Lily and Yuh Nung also agree that working together in the lab made it easier to work together at home, raising a family. In addition to Emily, who is currently an artist pursuing her Master of Arts degree in Montreal, they have a son, Max (named after the Jans’ CalTech mentor), who finished his graduate study in cancer biology at Stanford University and is now studying medicine at the University of California, San Francisco. “Being scientists, we have really weird schedules,” explains Lily. “But we were able to work it out so that we each took different shifts on the same experiments early on.” They were also able to take turns traveling to scientific conferences.

With both children now grown, Lily and Yuh Nung are able to travel together more often—and not just to scientific meetings and seminars. They both enjoy hiking, and in recent years have made long treks through New Zealand and visited both the Serengeti National Park and even the base camp of Mount Everest.

Lily and Yuh Nung Jan have received many professional honors and awards during their distinguished careers. They have been investigators for the Howard Hughes Medical Institute since 1984, and became members of the National Academy of Sciences in 1996 and the American Academy of Arts and Sciences in 2007.