Serendipity, on Purpose

Caltech surprised chemist and neurobiologist Linda Hsieh-Wilson when she arrived as a new professor in 2000. The unusually interactive campus felt like a community, even a family.

“Here, it is easy to find people with common interests or learn about other people’s research,” says Hsieh-Wilson, who is now Caltech’s Arthur and Marian Hanisch Memorial Professor of Chemistry. “That has helped my students and our research, allowing us to venture into new areas of science.”

For instance, Hsieh-Wilson recently created antibodies that one day could help patients recover from brain or spine injuries—an invention that started with a serendipitous conversation years ago.

About a decade ago, Hsieh-Wilson and her students wanted to see if a sugar molecule they were studying might play a role in the way vision develops in the brain. But as organic chemists, they didn’t have experience with the specialized biological research techniques they needed to follow their hunch.

Then, in a lucky break, one of Hsieh-Wilson’s graduate students struck up a conversation with Caltech biologist Jost Vielmetter, who leads a center in Caltech’s Beckman Institute. That institute’s philanthropic funding and mission give its scientists freedom to assist scholars across campus. So Vielmetter took time to teach Hsieh-Wilson’s group techniques they needed to trace cellular connections between the eyes and brain.

Using those techniques, Hsieh-Wilson and her team discovered that their sugar does help with sensory perception—linking neurons in the eye to those that control vision, deep in the brain. More broadly, they found, it helps wire neurons in the brain during so-called “critical periods” of development, when neural circuits can be sculpted by experience. During critical periods, infants’ and toddlers’ brains are more malleable so that children learn fast during those early years. But later in life, the sugar reverses function to prevent our brains from fully rewiring themselves after they are injured.

The antibodies that Hsieh-Wilson and her students are refining now—with the aim of helping people recover from brain or spine trauma—actually block this sugar so patients can regenerate more neurons. In 2012, researchers at Harvard Medical School used these antibodies to regenerate injured optic nerves in mice.

Hsieh-Wilson has attracted robust philanthropic support, including a Beckman Young Investigator Award, an Alfred P. Sloan Fellowship, and appointments as a Howard Hughes Medical Institute Investigator and as Caltech’s Hanisch Professor.

That generous support has freed her to invent new techniques that open up unexpected possibilities for other scientists in and beyond her areas of research—creating luck for others. Specifically, Hsieh-Wilson’s group invents tools that make studying sugars and their associated proteins easier.

“Carbohydrates are complex molecules,” Hsieh-Wilson says, laughing. “Organic chemistry itself is a conversation stopper, and people roll their eyes at the thought of studying carbohydrates.”

In one case, her group developed a way to tag and visualize certain carbohydrate molecules that are involved in communication inside cells. That technology, now commercially available, is in use by labs around the world.

“People who used to turn away from studying carbohydrates are pursuing investigations now because they have the tools,” she says.

Hsieh-Wilson credits her philanthropic support for helping her make these contributions, which already have changed how science is done and what we know about sensory development.

“The advantage of private support is that it allows you to pursue new ideas, perhaps riskier ideas,” she says. “You can be fearless in your approach. You don’t have to map everything out and know all the answers in advance. That type of intellectual freedom is important to science, because so much of science is serendipitous discovery, and trusting your instinct.”

“I think most faculty would agree that we would get nowhere without the students and postdocs we attract. They’re incredibly bright, independent, and ingenious. You give them a crazy idea and they’ll run with it. It makes a huge difference in the kinds of questions you can tackle.”
- Linda Hsieh-Wilson

A Reflection on Students

Hsieh-Wilson enjoys leading her lab. She relishes helping new graduate students and postdoctoral scholars articulate big challenges, identify what’s already known, and define initial approaches for discovering something new.

Philanthropy helps here, too: Fellowship support increases students’ freedom to choose research projects that depart from the lab’s grant-funded work. As they attack the questions that most fascinate them, young scholars grow by leaps and bounds—advancing the lab’s quest for discovery.

Alumni of Hsieh-Wilson’s group now lead their own labs at universities around the world, practice patent law, and work in pharmaceutical and biotechnology companies.

“I think most faculty would agree that we would get nowhere without the students and postdocs we attract,” she says. “They’re incredibly bright, independent, and ingenious. You give them a crazy idea and they’ll run with it. It makes a huge difference in the kinds of questions you can tackle.”

Giving Priorities