Dave Jones has a flat.
He pumps the handbrakes, bringing his bicycle—a sleek, black number—to a stop and hops off. His bike shoes clatter against the asphalt. Above him, the setting sun paints the sky the color of watermelon flesh. But Jones doesn’t seem to notice. He’s removed the front wheel from the bike and laid out a small collection of tools from a bag mounted beneath the seat.
“Cancer research has a lot in common with bicycling,” he says, using a wedge the size of a Swiss Army knife to pry the tire free of the rim. “Both require perseverance. And dedication.” The new chair of OMRF’s Immunobiology and Cancer Research Program fishes the deflated tube from inside the tire. “You also have to be willing to fail.”
Jones runs his fingers along the inside of the rim, searching for anything sharp—a thorn, a shard of glass, a pebble—that might still lurk within. “When there’s a problem, you’re constantly tinkering, trying to figure out what went wrong.” Satisfied that whatever popped the last tube is gone, he whips out a replacement from the bag and threads it into the tire. “And if you don’t have a plan for how to get going again, you’re in trouble.”
He expertly screws a silver cartridge into a tiny, pistol-shaped head, then clamps the head onto the tube’s valve. A sharp hiss escapes as carbon dioxide rushes from the cartridge into the new tube, reinflating the tire. A moment later, Jones has stowed his tools and remounted the tire on his bike. The whole process took less than four minutes.
“A mechanic can do this in half the time it just took me,” he says, clicking his shoes into the pedals. “But I’m getting faster.” He’s planning on a big ride in the hills of eastern Oklahoma in a few days. So tonight will just serve as an easy, get-the-blood-flowing ride.
He pumps his legs rhythmically, and the bike picks up speed. The shores of Oklahoma City’s Lake Hefner fly by at 15, 16 and, finally,18 miles per hour. “You have to believe that by changing one more thing you can improve.” It’s not clear whether Jones is talking about biking. Or cancer research. Or both. “You always have to look for that one thing. The thing that will make the difference.”
Jones didn’t set out to be a cancer researcher. But even before he knew what science was, he felt its pull.
As a five-year-old, he caught crawfish and minnows in buckets at the beach, then spent hours observing the small creatures’ habits. He soon grew old enough to take a rubber canoe to explore the waters of Lake Huron, which laps up against his hometown of Alpena, Mich. But once Jones got out on the water, he would stop paddling and stretch himself out on the bottom of the boat. For hours at a time, the wind and waves would carry the ghost canoe while its lone occupant lay hidden from sight, studying the lake’s aquatic life by pressing his face against a clear plastic window in the vessel’s floor.
He dressed up as a scientist during career day in fourth grade; “I had a friend whose dad was a pharmacist, and he loaned me his lab coat,” recalls Jones. He excelled in chemistry as a high-schooler. But it wasn’t until he turned 20 that he opted to wear a white coat more regularly. As a junior at the University of Michigan, he took a part-time job in a laboratory, “distilling poisons from samples of environmental waters.” He loved the problem-solving, the process of using a set of principles to find answers where others might see only chaos. Although his parents urged him to go to medical school, he decided to pursue a Ph.D.
In the pharmacology program at the University of Colorado, Jones studied blood clotting. In particular, he worked with compounds that caused the blood to coagulate and ones that interfered with the process. When he finished his degree, he decided he’d pursue a post-doctoral fellowship at the University of Utah. That training experience, a rite of passage for young scientists who hope one day to lead their own laboratories, would mark two important milestones for Jones. “It was the first time I thought about my work in the context of cancer,” he says. And it introduced him to a scientist who would have a profound impact on his career: Dr. Stephen Prescott.
Working in Prescott’s lab, Jones developed a method to clone cox-2, an enzyme that had emerged as a potential culprit in arthritis. The work, which Jones and Prescott published in the influential Journal of Biological Chemistry, represented the first time scientists had succeeded in replicating the human form of this enzyme. And it drew significant attention, as both drug companies and academic researchers were focusing their efforts on how blocking the action of cox-2 might lead to new treatments for arthritis and other inflammatory conditions. (This hypothesis would turn out to be correct, leading to the development of cox-2-inhibiting painkillers Vioxx, Bextra and Celebrex.)
“Dave developed an incredibly clever way to tackle this difficult problem,” says Prescott. “It was pretty clear that he was someone special.”
While working with cox-2, Jones became intrigued by the possibility that blocking the enzyme might also represent a potential treatment for colon cancer. Prescott tried to convince the young researcher that he should stay at the University of Utah, where the university offered him his own laboratory to continue his work as an independent scientist. But Jones had other ideas. “He decided that he wanted to go into a commercial environment,” says Prescott. “He really wanted to work on finding new therapies.”
In 1993, Jones took a job at the drug company Upjohn (which later became Pharmacia & Upjohn and, ultimately, Pfizer). Although he rose rapidly through the company’s ranks and was, according to Prescott, “a superstar,” Jones found himself consistently frustrated by the risk-averse corporate culture. “I realized that I did not have the appetite for group decisions,” says Jones. “Groups can make mediocre decisions. They take the safe road. And the safe road is not the innovative one.”
Meanwhile, after Jones had joined Upjohn, Prescott helped engineer the creation of the Huntsman Cancer Institute, a new center at the University of Utah. Prescott, who would become director of the institute, wanted to fill its labs with promising cancer researchers, and Jones fit the bill. At Upjohn, he’d worked on ways to exploit the naturally occurring process of cell death to kill off cancer cells. Unlike many industry researchers, though, Jones had continued to publish his work in peer-reviewed scientific journals. “Dave had become a star scientist,” says Prescott. “And when he’d had enough of working for big pharma, we were lucky enough to recruit him back.”
At Huntsman, Jones focused his efforts on understanding the role that a gene known as APC played in causing colon cancer. Although he spent his days in the laboratory, his regular interaction with people afflicted with the disease served as a constant reminder of what was at stake each time he donned his lab coat.
“Patients came to Huntsman for treatment, and we saw them all the time. They’d pull their oxygen tanks along to lunch in the cafeteria. On the elevator, you’d talk with people who looked like their lives hung in the balance.”
Once, the center’s founding donor, Jon Huntsman Sr., brought Jones to the bedside of a patient facing long odds of survival. “This was an 18-year-old kid,” recalls Jones, “who’d just had a huge sarcoma removed from his femur.” Huntsman told the teen, “Dr. Jones is going to save your life.” But Jones knew that the tumor would almost certainly recur—and that there was nothing he could do to stop it. He felt helpless. “I just shook the young man’s hand and tried to offer some words of encouragement.”
Still, says Jones, the encounter underscored the hope that people invest in scientists who study a disease that claims a half-million lives in the U.S. each year. “When you tell people you’re a cancer researcher, the first thing they say is ‘thank you.’” At an American Cancer Society Relay for Life workshop, Jones was asked to deliver the keynote address. “Before I could even open my mouth, the whole room gave me a standing ovation,” he recalls. “They had no idea who I was. They just knew what I did.” The gesture touched him deeply. “I had tears in my eyes. I choked up. I couldn’t even get the first word out of my mouth.
“As a cancer researcher,” says Jones, “you know that people are depending on you. You feel highly valued.” And that support helps balance out another inescapable truth, one that haunts Jones and his fellow cancer researchers: Despite decades of focused efforts and resources, many cancers remain incurable.
Jones believes that the path to a cure—or at least to more effective ways to treat cancer—leads, improbably, through a tiny, aquatic creature.
Named for the quintet of horizontal stripes that run along its body, a zebrafish grows to no more than an inch or two in length. But what makes the fish special is how it manifests the effects of changes in its genes.
In humans and most other creatures, the process of linking a change in a specific gene to something that later happens in the body is extremely difficult. Take, for example, a baby born with a mutation in a particular gene.
Typically, many years pass before the effects of that mutation show themselves, say, through the growth of a precancerous polyp on the wall of the colon. But even if doctors detect that polyp (through a procedure like a colonoscopy), they can’t say what, exactly, caused the growth. Perhaps it was the mutation in question. Or maybe it was one of the countless other mutations that each of us carries in our genomes. So-called environmental factors, like what a person eats or the chemicals to which he or she is exposed, could also have been responsible. Or perhaps the polyp resulted from a combination of all of these genetic and environmental factors.
In zebrafish, things work much more simply. When a gene is mutated in a fish embryo, any results can reveal themselves in just five days. This makes the fast-growing creature quite a handy tool for a researcher who, like Jones, understands how to alter its genetic makeup. If scientists change a gene and then observe some sort of developmental abnormality, they know that the mutation was responsible for the condition.
Surprisingly, zebrafish share a substantial number of genes with humans. One of these genes is APC, which scientists had implicated as a potential culprit in colon cancer. Jones and his team figured out a way to remove this gene in zebrafish, and when they did, something most peculiar happened: The fish failed to grow jaws.
At first glance, the development didn’t appear particularly promising. After all, what did a missing mandible have to do with colon cancer? But then one of Jones’ graduate students found research showing that zebrafish also failed to grow jaws when they were deprived of vitamin A.
Jones suspected that colon cancer tumors proliferated, at least in part, because they lacked the ability to generate retinoic acid, a derivative of vitamin A. So, he wondered, “What would happen if we gave retinoic acid to the zebrafish who lacked APC genes?”
The answer, Jones and his team soon discovered, was that the fish grew jaws.
When the scientists then treated samples taken from human colon cancer patients with retinoic acid, they found that it inhibited the proliferation of tumor cells.
The work would prove a watershed for Jones. First, it led to the publication of numerous research studies in Cell, the Journal of Biological Chemistry and other influential scientific journals, which in turn helped establish Jones as a national leader in cancer biology. Second, it taught him that using the zebrafish as an experimental model could offer a more efficient way to zero in on complex problems of human biology. Finally, it introduced Jones to a concept that now guides his work: translational research.
You see, once he found that giving retinoic acid to the fish took care of their jaw problems, he could “translate” that work to fixing the linked human problem. Those findings ultimately led to clinical trials of four compounds to treat colon cancer patients. “All thanks to a fish,” he says. For someone who’d spent his boyhood peering into the depths of Lake Huron through the window of his inflatable canoe, it seemed somehow appropriate.
Jones began cycling in earnest a few years ago. But like so many other things he’s taken an interest in—distance running, fly fishing, bird hunting, cooking, raising Weimeraners—this would prove to be no casual hobby. “Dave is a perfectionist,” says Prescott. “And that’s not a switch that just gets flipped off when he leaves the lab.”
Jones scoured training plans on the Internet until he found one to his liking. Ever the scientist gathering data, he used a variety of tools to gauge his daily effort level. Following each workout, he’d upload a torrent of information, things like heartbeats and pedal strokes per minute, distance traveled, average speed, net elevation gain, and power statistics. He made steady progress, so he set a goal: to complete a 100-mile ride in under five hours. To average 20 miles per hour for five hours, though, would be no easy feat.
Jones cranked up his training to a weekly regimen of 150 to 180 miles, incorporating a mix of hard workouts and long efforts. With a busy schedule consisting not only of extensive time in the lab but also responsibilities as a husband (he and his wife, Ann, will celebrate their 24th anniversary in 2015) and father (of Claire, 18, and Ivan, 14), he ended up squeezing in a good deal of his riding in the wee hours before sunrise.
In August, after more than two years of preparation, Jones put his training to the test at the Hotter ‘N Hell Hundred in Wichita Falls, Tex. True to its name, the ride proved to be a sizzler, with temperatures reaching 103 degrees. To make the conditions even more challenging, winds gusted to speeds of nearly 30 miles per hour.
In spite of the weather, Jones held pace for more than 80 miles. “Actually,” he says, “I rode with a group that averaged 23 miles per hour up until the 85-mile mark.” But, unaccustomed to biking in a large, tightly bunched pack of riders, Jones hesitated to drink much during the first four hours of the race for fear of crashing. That left him overheated and dehydrated. When the pack turned into a stiff headwind for the final 15 miles, Jones “bonked,” and the pack left him and his goal of a five-hour finish far behind.
Still, Jones refused to be discouraged. He promptly went out and bought a CamelBak hydration system—“You suck the water out of a tube, so it’s much easier to keep control of your bike”—and resumed training. He also decided to hire a coach. “The first thing he told me after reviewing my workouts,” says Jones, “was that I was training too hard.” Under his coach’s tutelage, Jones dialed back his efforts, balancing hard workouts with easier recovery rides.
He now has his sites set on 2015’s Hotter ‘N Hell. “Last year was an experiment, and I failed,” he says. “But I’m not giving up. No way.”
Around the time Jones got serious about biking, he got an email from his former mentor. Steve Prescott had left Huntsman years before to become president of the Oklahoma Medical Research Foundation. Jones and he had periodically kept in touch over the years, but when Prescott sent a casual “How’s it going?” type of message to Jones in 2012, he got a response from his one-time protégé that he did not expect. Jones, who had then risen to become co-chair of Huntsman’s Department of Oncological Sciences, told Prescott that he was contemplating leaving Huntsman—and Utah.
As it turned out, the timing couldn’t have worked out better for OMRF. For three decades, the foundation had focused its cancer research on the development of the human immune system. Under the leadership of Dr. Paul Kincade, OMRF scientists had made important strides in understanding how errors in this process led to cancers such as leukemias and lymphomas. But Kincade had made the decision to leave the lab to become the foundation’s vice president of research, so Prescott was searching for someone to take the reins of OMRF’s cancer research efforts.
What’s more, OMRF had just entered into a partnership with the University of Oklahoma’s Peggy and Charles Stephenson Cancer Center. With funds provided by the Oklahoma Tobacco Settlement Endowment Trust, Stephenson would help OMRF bring talented new cancer researchers to the state. “The heart and soul of any cancer center is research,” says Stephenson Director Dr. Robert Mannel. “Our goal is to take the knowledge scientists obtain in the lab on cell and animal models and start applying it to human cancer patients.” Jones’ work, which had used fish to identify new strategies for treating human colon cancer patients, fit this vision to a tee. Plus, says Mannel, “Dave also brought an outstanding leadership pedigree.”
In 2013, Jones left Huntsman to join OMRF as the new leader of the foundation’s Immunobiology and Cancer Research Program and the first holder of the Jeannine Tuttle Rainbolt Endowed Chair in Cancer Research. He also agreed to serve as Stephenson’s associate director for translational research. It’s that bridge between two worlds—OMRF’s labs and the clinics at Stephenson—that helped Jones make the decision to leave Utah for Oklahoma. “For the work we do to be meaningful, we need to find physicians who are interested in thinking about clinical trials,” he says. “OMRF’s partnership with Stephenson makes that possible.”
At OMRF, he not only established his own laboratory but created a new resource for use by all foundation scientists: a zebrafish core facility. With a start-of-the-art filtration system and hundreds of tanks full of thousands of fish, Jones will help other scientists at OMRF study problems that reach well beyond cancer.
For example, OMRF’s Dr. Jonathan Wren is working to understand the so-called “third third” of the human genome. “Scientists have characterized about two-thirds of the genes in our genome,” says Jones. “But we still don’t know what those final 8,000 or so genes do.” His plan: Delete a big group of those unknown genes one at a time in the fish and study what happens. Jones also wants to use the fish to investigate other genes that OMRF researchers have identified as candidates for causing various diseases. “If we could give people a clue what the functions of some of those genes are, that would be huge.”
Dr. Linda Thompson, who’s been a researcher in OMRF’s Immunobiology and Cancer Research Program for 25 years and holds the Putnam City Schools Distinguished Chair in Cancer Research, has already been impressed with Jones’ leadership. “He has a grand vision for our department. He believes in personalized medicine for cancer care, in tailoring cancer care to individual patients. And he’s gone out and recruited some very smart people to help execute this vision.”
Indeed, this past summer, with the support of the Stephenson Cancer Center, Jones successfully recruited Drs. Bryan and Alana Welm to OMRF from—you guessed it—the Huntsman Cancer Institute. The Welms’ research focuses on breast cancer, with an emphasis on how researchers can help physicians deliver the optimal care to each individual patient.
Jones says the key to recruiting the couple, whom he calls “superstars,” was trust. “When I recruit people, I tell them that if you come here, I’m going to do everything I can to help you succeed. I told Alana and Bryan that when I recruited them to Huntsman.” So when he told them he’d do the same at OMRF, they decided to make the leap.
“Dave is a fantastic scientist and a fantastic leader,” says Alana Welm. “He’s the reason we’re here.”
Although the OMRF cancer research team now consists of 10 principal researchers. Jones intends to continue expanding the group. “We want to keep adding talented scientists who can complement the skills we have—people with outstanding scientific aptitude who think creatively, work collaboratively and can tackle the hard problems.”
Looking ahead, Jones knows that the OMRF cancer research program will focus on the twin concepts of precision cancer care and transforming discoveries into therapeutic advances that help cancer patients. But as for specifics, those will come in time. Science, after all, is all about serendipity, about discovering the unexpected.
And, Jones says, about making a difference. “The constant vision is to do outstanding science. That work should be impactful, both on the scientific community and on human health.”
For much of his career, he admits, the drive to make meaningful discoveries, “was passionate, but not emotional.” But that changed when his wife, Ann, was found to have a genetic mutation that causes colon cancer. It’s a mutation that both his children may also be carrying.
“Now,” Jones says, “I feel like it’s a personal battle.”
On his bike, at least on this particular night at Lake Hefner, there is no battle to be fought. Just a father, clearing his head and his lungs while his son, a freshman at Bishop McGuinness High School, practices soccer nearby.
Darkness begins to descend, and Jones and his bike head north from Lake Hefner to a quilt of green fields where gaggles of kids chase after black-and-white balls. Jones circles the fields, milking an extra half-mile or so out of the workout. He hops his bike over a final speed bump in a swift, confident motion, then dismounts.
“On the surface, biking and cancer research are both individual sports,” he says, pulling his helmet off to reveal a black bandana wrapped around his head. “But in reality, they’re team sports.” He removes the water bottle from his bike and takes a long drink. “Take the Tour de France. Eight people with different specialties—sprinting, climbing, time trials—ride so that one person can win.”
The last licks of sunlight pour forth from the west, silhouetting Jones as he swallows another mouthful of water. “To be successful in cancer research, it’s exactly the same. You need to assemble a team of specialists to succeed. Then you have to have a plan.”
He wheels his bike around back of his SUV and lifts it onto a carrier that’s secured to the rear of his black Nissan. “But even when you have a plan, it’s not always going to be easy to execute. There will be setbacks. And that’s where perseverance comes in.”
Tomorrow morning will bring another ride. And then another day in the lab. The experiment he’s working on may produce a startling new insight into cancer. Or it may be a dud. “We’re going to fail sometimes.”
But, in the end, he says, solving cancer’s mysteries is a lot like biking. “You have to stick with it in those moments of doubt. And we will.”