Linking human animal biomedical research to benefit both
No one knew what Lyme disease was when Stephen Barthold's daughter was diagnosed with it in 1978. At the time, Barthold and his family were living in Connecticut, the state where the cause of the tickborne disease would be identified four years later.
While a course of antibiotics for an unrelated infection cured his daughter, the father remained intrigued. Today, with 30 years of research and more than 100 papers on Lyme disease under his belt, Barthold, a veterinary pathologist with a joint appointment in the schools of Medicine and Veterinary Medicine, is recognized as one of the leading authorities on how the Lyme bacterium interacts with the hosts it infects.
When he arrived at UC Davis in 1997, Barthold lost no time in creating an ideal home for the kind of interdisciplinary work his research program requires: UC Davis Center for Comparative Medicine.
Housed on the west side of the Davis campus, the unique teaching and research complex draws faculty from the schools of Medicine and Veterinary Medicine to focus on infectious disease and cancer research.
"We take advantage of the concept of ‘one medicine.' That is, since nearly every human disease has an animal counterpart, what we learn from one benefits the other," explains Barthold, who was recruited from Yale School of Medicine to become the center's founding director.
With 23,305 human cases reported to the CDC in 2005, Lyme disease is now the most common vector-borne disease in the United States. Infection is very common among domestic animals, as well. When treated with antibiotics early, it can usually be eradicated.
But, says Barthold, "our work has shown that in the absence of antibiotic treatment, 100 percent of animals infected with Lyme bacteria remain infected even though they have a perfectly functional immune response."
Working with mice, Barthold has found that the bacteria, Borrelia burgdorferi, "literally integrate themselves into collagen tissue. They colonize little spots here and there: one joint, but not another; nervous tissue; the heart. It varies from individual to individual, which explains the disease's highly variable clinical manifestations."
In a study to be published later this year, Barthold outlines his discovery that even after long-term antibiotic treatment, bacteria hidden in collagen tissue are still viable and infectious. "We're trying to be careful in what we claim," he says, "but these findings will be controversial."
Modern foe; old friend
Jay Solnick is one of the 11 faculty members affiliated with the center. An infectious-disease physician with a joint appointment in the medical school's Internal Medicine and Medical Microbiology departments, Solnick works with rhesus macaques to study the unusual interactions between Helicobacter pylori – the bacterium responsible for stomach ulcers and some stomach cancers – and the primates it colonizes.
Infectious-disease researcher Jay Solnick works with bacteria that cause stomach ulcers and stomach cancer.
A century or two ago, virtually everyone was infected for life by H. pylori, "yet clinical problems were a non-issue then," Solnick explains. Stomach ulcer disease was virtually unknown, and few people ever grew old enough to get stomach cancer. "Given that you had almost universal colonization with Helicobacter – both in humans and in a range of mammals – it's reasonable to suspect that the bacteria confer some kind of benefit."
What particularly piques Solnick's interest is how the pathogen and the host adapt to each other during the course of a lifelong infection in the stomach, an exceptionally hostile environment. One of his discoveries is that a certain gene cluster in H. pylori's DNA triggers the stomach's mucous lining to step up production of various antimicrobial molecules.
"It's a little bit paradoxical," Solnick says. "The cluster is inherited and Helicobacter pick it up over generations, so we know it must be advantageous. Yet you'd think that triggering an antimicrobial response would work against it."
His theory? While Helicobacter may be resistant to the host's defenses, other bacteria probably are not. "Helicobacter may be trying to carve out its own niche by modulating the competing flora," he says.
Indeed, recent evidence suggests that H. pylori might protect against various ailments, including intestinal diseases, asthma and possibly even cancer of the esophagus.
Solnick is treading on contentious ground. "The GI community is opposed to the idea that Helicobacter has any benefits at all," he says.
Even if he can show that it does, the fact remains that the bacteria cause stomach cancer in 3 percent of the humans they infect.
In response, Solnick and colleagues from UC Davis and Mexico are looking for biomarkers in stored samples of human serum that might correlate with cases of gastric cancer.
"The Holy Grail of Helicobacter research is to find some way of knowing who will eventually get stomach cancer," he says. "If we can do that, we can eradicate the bacteria in those individuals, and that would have a huge impact on human health."
A decade of teaching, research
It's innovative research like Solnick's that the Center for Comparative Medicine was designed to support, says Barthold. In the 10 years since the center opened its doors, its eclectic mix of projects and expertise has created a rich environment for graduate education and biomedical research – a role that's more important now than ever before, he says.
"With 60 percent of NIH funding involving animal counterparts of human disease, there's a need for what we're doing," he says. "Here we're investigating infectious diseases from the human and veterinary medical perspectives in the same building. The center is truly unique."