Pore strength

It was early 2010 and Bill Dunbar paced the hallway between his office and his lab in UC Santa Cruz’s Engineering 2 building.

Above: Left to right: Trevor Morin, chief scientific officer, biochemistry; William Dunbar, chief technology officer, nanopores and analytics; and Dan Heller, president and CEO (Photo: C. Lagatutta)A lanky surfer and a drummer with a Ph.D. in feedback control theory, a backbone technology of self-driving cars, Dunbar had come to UC Santa Cruz in 2004 to help bolster the university’s robotics degree program.

But a year after he arrived on the wooded campus, Dunbar met David Deamer and Mark Akeson, two UC Santa Cruz professors who were pioneering a way to sequence DNA strands faster and less expensively by using electronic voltage to pull each molecule through a microscopic hole called a nanopore. They had a problem they thought Dunbar might be able to solve.

The quandary Dunbar faced as he stalked that fluorescent-lit hall was that DNA molecules zipped through the nanometer-scale hole like bullets through a gun barrel, making them hard to read. Was there a way to slow them down and maybe even move them back and forth so you could decipher them with real accuracy?

That’s when an idea hit.

Self-driving cars needed two separate functions to get someone safely from Point A to B. There were the sensors that gathered information like your location, your speed, and the moment the idiot driver in front of you suddenly hit the brakes. Then there were the actuators: the steering, the accelerator, and the braking.

Why not use two nanopores, one as a kind of actuator and the other as a sensor, to slow down and control the molecules in order to read them, Dunbar thought.

It was a great idea, but it needed time to develop. Deamer and Akeson’s team ended up using another method that was licensed by DNA sequencing company Oxford Nanopore Technologies, which created a series of genome sequencing systems. But the two-pore notion stuck with Dunbar.

Fast forward seven years, and Dunbar’s idea became the seed of a company that has created a biosensing device that may revolutionize the way we do medicine and live in our environment.

The device could one day allow a parent to determine if a feverish child has strep throat or the flu with a simple swab of the mouth. It could help doctors diagnose cancer and other diseases, and become a foundation for telemedicine. It could locate E. coli in food, let farmers check for crop-killing disease, help ranchers keep an eye on the health of their cattle, and allow government to monitor water quality with the same ease as using a glucose monitor.

Poring it on

Called Two Pore Guys, the company has captured $25.4 million in venture capital, has grown to 60 employees (more than half of them from UC Santa Cruz), is collaborating with UC San Francisco on a pilot study to detect tumor DNA in the blood and urine of patients with known cancer diagnoses, and already has willing partners waiting in the wings.

At its heart are three men: a successful entrepreneur named Dan Heller, who founded UC Santa Cruz’s Center for Entrepreneurship (C4E) in 2010; a former thoroughbred jockey with a doctorate in biochemistry and molecular pharmacology named Trevor Morin, who worked as a postdoctoral researcher on campus; and Dunbar, who left his professorship at UC Santa Cruz in order to devote himself completely to solving what he sees as a “significant problem” in the modern world.

“There were two reasons we decided to invest in Two Pore Guys,” said Vijit Sabnis, a partner in Khosla Ventures, which was started by billionaire and Sun Microsystems founder Vinod Khosla. “The first reason was that the technology is highly, highly differentiated and revolutionary. No one else in the world is working on this and has made the progress this team has.”

The second reason, he said simply, is “the quality of the people.”

Meeting of the minds

Heller and Dunbar met at UC Santa Cruz in 2010 as Dunbar, now 42, was working on his two-pore idea and Heller, now 54, was teaching courses associated with his Center for Entrepreneurship.

Heller had experience starting technology companies from core inventions like Dunbar’s. And the two men bonded almost immediately over science, a shared sense of humor, and a Right Coast background.

“Sometimes, it’s just easy with certain people,” Dunbar said.

At the time, Heller, who’d earned both a B.A. in computer science (Rachel Carson ’85) and a master’s in digital media (’13), at UC Santa Cruz, thought he was finished with big ventures. He’d already founded and sold a successful email software company, helped steer the nascent digital photo industry, written six books, and circled the globe as a travel photographer. But Dunbar’s two-pore theory, along with the idea of using a nanopore made out of silicon instead of the biological nanopore Deamer and Akeson developed, intrigued him.

“I have a deep enough science background that I can smell something interesting when it comes up,” Heller said.

In 2011, the two men started their company and gave it the tongue-in-cheek name, “Two Pore Guys.”

Like others, Dunbar and Heller also attended engineering seminars on campus. There, they noticed a guy who kept asking questions about possible biological and practical uses for whatever device was being discussed. One day, Heller approached the questioner, learned his name was Trevor Morin, and discovered he was working with UC Santa Cruz Professor Phil Berman, a pioneer in the development of recombinant vaccines for AIDS and other infectious diseases. Heller asked Morin if he would like to join him and Dunbar for breakfast at Kelly’s French Bakery to talk about nanopore technology.

“I was a poor postdoc,” said Morin, a former horse-racing jockey whose riding career ended when he was thrown into a fence, breaking his wrists, back, and neck. He then went on to get a doctorate in biochemistry and molecular pharmacology. Morin said, “If you buy my breakfast, I’ll talk about whatever you want to talk about.”

Morin, who’d worked for a Massachusetts biotech company before following his wife, post-doctoral researcher Tomoko Tabuchi, to UC Santa Cruz, spent the entire night before the meeting reading about nanopore technology.

“I had four pages of notes about what we could do with a solid-state nanopore,” Morin said of that breakfast meeting in 2013. A short time later, Morin officially became the company’s first employee, but he is generally considered the third founder of Two Pore Guys.

“I think we realized early on, by combining our collective expertise, we could be a company that would grow as big as our eyes would allow it,” Morin said.

What those eyes allowed was the development of a palm-sized biosensor device, which uses disposable strips with reagents on them to do the kind of diagnostic tests more expensive machines do now—and to do them more quickly.

Lots of potential applications

Taking a page out of the iPhone playbook, which allowed others to create apps for its iconic device, Two Pore Guys also decided it wouldn’t develop the specific tests for things like bacteria, viruses, and tumor DNA, but rather form partnerships with other diagnostic test makers, according to Heller. Two Pore Guys is currently in contract with five unnamed partners and in negotiations with 15 others.

The first uses are expected to be in agriculture.

Meanwhile, the Two Pore Guys platform is being tested as part of a pilot study led by Dr. Andrew Ko, a professor of clinical medicine in the Division of Hematology and Oncology at UC San Francisco. In this study, patients’ blood and urine samples are being tested for a common mutation in pancreatic, colorectal, and other gastrointestinal cancers called KRAS G12D. If successful, the platform could then possibly be used by patients within their own homes to monitor their response to treatment or discover recurrences early following curative surgery.

“In a grander scheme, this technology even has the potential to become a cost-effective cancer-screening tool on a larger population-wide scale,” Ko said. “There are lots of potential applications.”

Venture capitalist Sabnis, meanwhile, envisions a time that’s very different from how things are now. Instead of a patient visiting his or her doctor and then going to a testing lab, waiting days for results, and freaking out about what the numbers mean before being able to talk to the physician and get treatment, a patient would wait a few minutes while the doctor used the device to test for a suspected disease, explained the results, and got treatment ordered in one visit.

“It saves time and saves anxiety and it saves the system money,” Sabnis said. “That’s a big, big deal.”

Said David Haussler, director of UC Santa Cruz’s Genomics Institute, who is on the advisory board for Two Pore Guys: “This company really breaks through a longstanding technology barrier by creating a modular, portable assay platform for just about everything people care about.”

Scaling up

On a recent morning, Heller stood in Two Pore Guys’ Santa Cruz headquarters dressed in khakis and an untucked collared shirt.

Describing himself as curious by nature, Heller said he is a problem-solver and a guy who likes the journey even more than the destination.

But above all, he considers himself an entrepreneur, he said, as he walked down a hallway and stepped into the heart of Two Pore Guys, a brightly lit room where scientists, programmers, engineers, economists, artists, and fabricators hunched over computers or stood at lab benches.

Right now, the company is refining Dunbar’s original two-pore technology, and has also developed more than 30 tests on behalf of its partners, who will be selling them under their own brand name. Recent funding allows it to scale up the manufacture of its entire system.

​For Dunbar, the leap from tenured professorship into what some might see as a risky venture was a natural decision, he said. He loves discovery, the opportunity to concentrate on and solve a big problem. According to him, Two Pore Guys was that place.

“If I were going to talk to a bunch of young people, I would tell them to find the most significant problem you can think of, or have heard about, and completely devote yourself to it. Otherwise,” Dunbar said, “you’re just kind of wasting your time.”