Biologist Researches Built Environments

If a cyclist zips toward you on a moonless night and the beacon on his helmet temporarily blinds you, it’s probably Willem Griffiths heading home from campus after an evening spent spying on the secret lives of drug-resistant superbugs.

The 23-year-old biologist strives to see as much as he can, while he still can, in his race against the relentless progression of a disease that is stealing his sight.

Willem Griffiths zips through campus on his bike.
Griffiths zips through campus on his bike.

Without artificial light, he’s already blind by dusk.

Griffiths was four when his parents realized something was wrong. At an ice rink, their enthusiastic boy could not find his gray skates, which were on the floor near his feet.

They later learned he had retinitis pigmentosa, a rare genetic eye disease that destroys peripheral vision and the ability to see in low light. The skates had been just outside Griffiths’ field of vision, and the lack of color contrast with the carpet rendered them nearly invisible to him in the dimly lit locker room.

“This was before the genetic revolution, so no one knew the specific cause or what to expect as the disease progresses,” says Griffiths, whose younger sister also has the condition. “I grew up hoping genetic research would clarify our prognosis.”

Griffiths, who earned his biology degree from the UO in 2018, would get his answer during his junior year at the UO—but the devastating news that he will go blind in midlife nearly imploded his dream of becoming a scientist.

Neither Griffiths nor his family would let his eye condition affect his active and energetic boyhood. His love of the outdoors led him to Oregon and the UO, where his innate curiosity tugged him along a nuanced and nonlinear path through three of the UO’s kingpin research labs.

Full Immersion in Biomedical Research

The humble zebrafish, denizen of starter aquariums everywhere, is a superhero in the quest to improve human health. More than 8,000 labs now rely on the small striped swimmers in their pursuit of new treatments, drugs, and therapies—but biology professor Monte Westerfield remembers when his lab was one of only eight in the entire world.

A protégé of the late George Streisinger, the UO biologist credited with introducing zebrafish as an ideal research model, Westerfield is renowned for identifying genetic factors that cause rare diseases affecting hearing and vision, including retinitis pigmentosa.

He is also a founder and codirector of two cherished research treasure houses. The first, the UO-based Zebrafish International Resource Center (ZIRC), is the National Institutes of Health’s flagship zebrafish repository. Its companion, the Zebrafish Information Network (ZFIN), is a digital goldmine allowing scientists everywhere to better understand gene function by providing a searchable database that integrates findings from zebrafish studies with data from other model organisms and humans.

Griffiths knew none of this when he looked up part-time jobs for student workers shortly after arriving as a freshman. He landed one in husbandry at ZIRC.

Scrubbing thousands of freshwater tanks and feeding legions of fish representing more than 40,000 genetic strains precious to researchers all over the planet, he had no inkling his first research opportunity would involve creating a new strain of zebrafish in the storied Westerfield Lab. He doubts that he would know it exists now, if not for the Summer Program for Undergraduate Research (SPUR).

In applying to SPUR, Griffiths noted that his “intrinsic motivation” for neuroscience research stems from having a genetic eye condition. Three options came back, including the Westerfield Lab.

“I interviewed with Monte and his research associate, Jennifer Phillips,” he says. “They sent an email inviting me to join their lab later the same day.”

Griffiths arrived just as Phillips was developing strains of zebrafish with Usher syndrome type 1F, a mutation that causes congenital deafness and retinitis pigmentosa in about 2 percent of people of Ashkenazi Jewish descent. Introducing a genetic change in fish to mimic the human condition is the necessary and difficult first step for testing hundreds of potential treatments.

Griffiths’ mentor, Jennifer Phillips, showed him how CRISPR gene-editing technology allows scientists to explore possible treatments for rare inherited diseases.
Griffiths’ mentor, Jennifer Phillips, showed him how CRISPR gene-editing technology allows scientists to explore possible treatments for rare inherited diseases.

To test the feasibility of potential therapies, Phillips showed Griffiths how to use “CRISPR” gene editing to modify the zebrafish DNA further, creating targeted mutations that would help them understand more about the best treatment options for individuals with Usher 1F.

Griffiths continued to work with Phillips as a research assistant for two years, helping to characterize symptoms in the mutant fish and contributing to new understanding of the molecular nature of Usher 1F. They were also able to use the fish models to rule out one potential therapy that looked good on paper but did not improve hearing and vision symptoms when introduced to the Usher 1F fish. This achievement saved time and money for Usher 1F research teams around the world.

From Despair to Acceptance

Halfway through their project, Griffiths received hopeful news. A lab in Massachusetts called to say the culprit in his case is the gene PDE6B—the most common of 50 genes known to cause retinitis pigmentosa.

“Willem came to the lab to tell me the day he found out,” says Phillips, an expert on hereditary retinal disease. “If you think of a rod photoreceptor as having a recycling plant, the PDE6B gene codes the protein that breaks waste into parts and sends them out of the cell for reuse or disposal. When PDE6B is absent due to mutation, the spent products build up. The recycling center becomes more like a landfill, and the rod is polluted to death.”

As he read up on PDE6B, Griffiths took heart from learning the gene only affects rods, which provide peripheral and night vision.

“Good,” he thought. “At least I still have cones for fine focal vision.”

He looked forward to getting a definitive prognosis from Dr. Mark Pennesi, an assistant professor at Oregon Health and Science University’s Casey Eye Institute who specializes in degenerative eye diseases.

“The outlook seemed okay at first,” Griffiths says of his appointment with Pennesi. However, as they studied scans of his retinas, they noticed some of his cones—the photoreceptors responsible for color and fine focal vision—also were beginning to die due to “the bad neighbor effect” of his polluted rods.

Realizing this meant he would certainly go blind, Griffiths, a self-described “happy optimist,” fell headlong into a black pool of anxiety.

“I didn’t deal with it well for the first three or four months,” he says. “It was a heavy hit, especially in the middle of college when I was figuring out that I wanted a career in research. How could I do that without vision?”

His psychological lifeguard turned out to be Hank Shipman, a childhood friend. Willem remembers every word he said. “Look, this disease is not going away. It’s outside your control, so don’t let it control you.”

Serendipity by Design

Architects designed the Allan Price Science Commons and Research Library to increase the probability of serendipitous encounters among members of the UO’s science community.

The next fall, when Griffiths dropped in for a cup of green tea, he bumped into biology professor emerita Bitty Roy, an expert on the influence of factors such as climate change and fire on plant pests. “Do you know of any ecology labs with an opening for an undergrad research assistant?” he asked.

“Willem was a terrific student, one of four who always sat in the front row with their eyes and brains wide open,” says Roy, a member of the Institute of Ecology and Evolution. “I knew he was a curious mind.”

She referred him to Roo Vandegrift in the UO’s Biology and the Built Environment Center (BioBE), a national research center uniting architects and biologists in the mission to understand indoor microbiomes, the complex bacterial ecosystems found inside buildings.

Physics department head Richard Taylor
Physics department head Richard Taylor

Griffiths landed a rare paid student research position with BioBE shortly before classes started in the fall of 2017. Just as in the Westerfield Lab, he arrived at the launch of a new study.

Vandegrift quickly made use of skills Griffiths had developed over the summer. Back home in Utah, Griffiths helped his stepfather build a colossal hay barn.

In the lab, Vandegrift and Griffiths wanted to see how bacterial communities—especially drug-resistant pathogens that infect an estimated one in 20 patients in US hospitals every day—evolve on different types of building materials.

“We needed to make a ventilation system connecting to individual microcosms that house samples of concrete, drywall, cobb (earthen plaster over straw bale), and cross-laminated timber,” says Griffiths, who built the entire setup.

Unexpected Hope in the Form of a Bionic Eye

In the science building next door to BioBE, physics department head Richard Taylor contemplates the potential for geometric shapes called fractals to revolutionize electronics. A professor of physics, art, and psychology, he enlists fellow scientists in ambitious projects to test his ideas. He also makes time every year to teach the introductory physics course for nonmajors.

“Out of everything I do, teaching is the most exciting,” he says. On the first day of class during fall term of 2017, Taylor told the students about his all-star team working on a bionic eye.

A tall, dark-haired young man near the front snapped to attention.

“I must have a word with that guy,” Griffiths remembers thinking. “For the first time, I caught a glimpse of hope. ‘Cure’ is a big word, and a lot of work has to happen, but this bionic eye project might rescue my little sister and me from the ominous fate we’re faced with.”

A few months later, his path crossed Taylor’s again at a meeting for recipients of joint grants to research teams involving scientists from both the UO and Oregon Health and Science University. Griffiths was there with the BioBE team tackling the dreaded Clostridium difficile, which can cause life-threatening diarrhea in patients on antibiotics.

As he watched Taylor’s colleagues lay out the roadmap for their bionic eye project, he felt buoyed by their determination.

Sharing the Wealth

For Griffiths, one of the most astonishing advantages of being at the UO—even as an undergrad—is how the faculty shares the world’s most powerful instruments in nine research core facilities rather than hoarding them in individual labs.

“It’s an amazing catalyst for discovery,” he says.

Curious to explore the microtopography of the building materials, he asked for training on the environmental scanning electron microscope in the UO’s Center for Advanced Materials Characterization in Oregon.

He marvels at how it revealed the “infinite porosity” of a one-inch piece of concrete, visible when magnified to 4,500 times its actual size. He wonders if communities of microbes dwell deep within—or even pass through—concrete walls. He also uses powerful new tools in the Genomics and Cell Characterization Core Facility to analyze DNA and identify microbes living on his sample materials.

Like most UO scientists, Griffiths’ research involves working with colleagues at other universities. He collaborated with Portland State University’s Elliott Gail to study airborne chemicals released by the microbes on his material samples and the materials themselves. Their findings will help architects and engineers design healthier indoor environments.

Griffiths examines surfaces, like this one-inch piece of timber, under high magnification to reveal material microtopography and detect bacterial colonies.
Griffiths examines surfaces, like this one-inch piece of timber, under high magnification to reveal material microtopography and detect bacterial colonies.

As he explores the frontiers of his hybrid field, Griffiths looks forward to earning a master of science degree—in architecture—from the UO. His goal is not to become an architect, but to apply biology to the design of buildings.

When he recently accompanied his girlfriend to an ER filled with sick students, he looked around the waiting room and pondered the resiliency of biofilms, thick matrixes of pathogenic bacteria that cling to indoor surfaces.

“Biofilms are very resistant to removal because the bacteria excrete proteins and structural carbohydrates to build themselves war bunkers,” he explains. “You can spray surfaces and wipe them down, but the biofilms persist.”

Full Speed Ahead

When Griffiths was first diagnosed, his father reacted by making sure that limited eyesight would have zero impact on his ability to lead an active life, from wilderness backpacking to working as a whitewater rafting guide and competing in aerial skiing. As he neared the end of high school in his native Salt Lake City, Oregon’s wealth of outdoor wonders helped attract him to the UO.

Last winter, as he punctuated a freestyle run down Mount Bachelor with a joyful flip, no one would have guessed Griffiths has tunnel vision.

“Most of his acquaintances have no idea,” says Schuyler Hamilton, a biology major who met Griffiths in avalanche safety class.

If a companion does catch him being inexplicably clumsy, such as knocking over a “wet floor” sign while grocery shopping, Griffiths makes light of it.

“Happens every time,” he says good-humoredly. “Those signs are my arch-nemeses because they sit just outside my field of vision.”

And while he hopes efforts like UO’s ambitious bionic eye project will succeed, Griffiths now views becoming blind as more blessing than curse.

“Time seems more valuable than it would if I had the prospect of vision for the rest of my life,” he explains. “It has put me on a trajectory to make the most of every day. In that sense, I’m thankful for it.”

* Editor's note: a previous version of the video mistakenly contained images from the lab of Benjamín Alemán, an assistant professor in the physics department. Oregon Quarterly regrets the error. 

—By Melody Ward Leslie, BA ’79 (humanities), University Communications
Photos by Chris Larsen and Dustin Whitaker, University Communications