Arthur Beyder, M.D., Ph.D., 2014 Donald C. Balfour Award Recipient

Physician-scientist combines love of molecules and patient care

His father was an engineer. His mother was a family physician. He felt drawn to both worlds.

“If you are the firstborn in a physician family in Russia, you are basically donated to clinical medicine – you are going to be a physician,” says Arthur Beyder, M.D., Ph.D. (I ’10, CI ’12, GI ’14), a consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester. “On house calls with my mom, I saw how much personal contact and human touch mean to patients. My dad, on the other hand, was the consummate logical thinker. He taught me brute deconstruction of problems and helped to shape the part of me that loves working on unsolved problems. “I get to exercise both of those interests at Mayo Clinic. No matter how deep you are into the microscope, you still see patients. You never forget that your research needs to link back to the patient.”

Dr. Beyder’s family moved to the United States when he was 13. His mother had died four years earlier. “She was ill for years, and no one could figure out the problem,” he says. “I accompanied her on house calls because she had blackouts. Ultimately, her doctors treated her for what they thought was an arterial thrombus. They gave a strong thrombolytic and inadvertently caused a fatal stroke. It was only much later that we found out she had Takayasu’s arteritis, an inflammatory condition of her vessels, which required a completely different therapy. Without strong diagnostic tools, you’re limited in therapies, and both were lacking in my mother’s case. My childhood experiences drive my quest for better diagnostic tools and therapies for patients.”

Problem-solving pays off in a ‘major achievement’

Recently, Dr. Beyder’s diligent problem-solving revealed a novel way of correcting a patient’s gastrointestinal problem. In the Mayo Clinic laboratory of Gianrico Farrugia, M.D. (I ’91, GI ’94), Dr. Beyder and others were working on a longstanding question – the link between a particular sodium ion channel (NaV1.5) and irritable bowel syndrome (IBS). The group identified several mutations in this gene in patients with IBS, but the mechanisms of disease are not understood and treatments, therefore, cannot be targeted. Dr. Beyder characterized these mutations and found that the majority had a significant loss of function at the molecular level. Focusing on one of the most severe mutations, the group found that the anti-arrhythmic medication mexiletine repaired the underlying defect in vitro. They secured a Clinical and Science Translational Award (CTSA) grant and treated the patient with mexiletine. The patient’s constipation-predominant IBS was completely reversed by treatment. As a result of this research, the group has begun to understand the mechanisms of disease in a well-defined subset of IBS patients which, for the first time, allowed a disease-targeted – instead of symptom-targeted – treatment. “This was a major achievement,” says Dr. Farrugia, director of the Center for Individualized Medicine and consultant in the Division of Gastroenterology and Hepatology. “For the first time, we’ve identified a strong genetic basis for a defined subset of patients with IBS and a defined therapy, and have corrected the problem with a drug that had never been used before with this particular disease.

Dr. Beyder is one of the ever-decreasing breed of physicians who is also a superb basic scientist.” Dr. Beyder’s accomplishments garnered him the 2014 Donald C. Balfour Mayo Clinic Alumni Association Award for Meritorious Research and 2014 Arnold J. Bargen Research Award from the Division of Gastroenterology and Hepatology.

‘We have the perfect storm’ to achieve a lot

Dr. Beyder says this discovery is just the tip of the iceberg in terms of what is needed for the prevalent functional conditions in gastroenterology that may not be fatal but cause significant morbidity and many physician and hospital visits for millions of people. These conditions are difficult to diagnose and treat because they are multi-systemic. “What we are doing requires expertise in disciplines including neurology, cardiology, internal medicine and gastroenterology,” says Dr. Beyer. “I want to solve problems in functional gastroenterology and motility disorders ¾ that’s why I came to Mayo Clinic. Dr. Farrugia and my other mentors have molded my training so that I have the tools to answer these important questions. Research in other fields such as cardiology and neurology will help illuminate our path and allow us to translate findings to patient care. The work we’re doing in GI at Mayo simply hasn’t been done before because it requires collaboration across multiple disciplines. “Twenty years ago, we couldn’t have answered these questions or performed these experiments because the tools didn’t exist,” says Dr. Beyder. “Now, at Mayo Clinic, we have the perfect storm. We know the questions to ask, and we have the tools to answer them. I believe you achieve more as a group. Working together, we’re going to achieve a lot.”