An unstoppable spirit

Anne H. Cross, M.D., believes anything in life that’s worthwhile is hard. “Like Winston Churchill said, ‘Never give up; never, never, never,'” she says.

Cross not only embraces challenges, but she’s also inspired by them. When three of her classmates during medical training developed the debilitating and then-untreatable neurological disease multiple sclerosis (MS), Cross decided to focus her studies on finding a cure.

And when her mentor, John L. Trotter, M.D., passed away suddenly in 2001, she took on the bittersweet challenge of continuing his legacy as director of what was later named the John L. Trotter MS Center in the School of Medicine.

Her spirit of determination has been passed on, not only to her son and daughter, but also to the many colleagues and trainees she’s worked with, including Sheng-Kwei “Victor” Song, Ph.D., who was inspired to focus his radiology research on studying MS thanks to Cross’ guidance and mentorship.

“You often get discouraged in research, and it’s easy to become bitter about the process,” he says. “But Anne is always persistent, and she continuously reminds me that whether you’re frustrated or whether you’re very successful, you always have to be nice.”

Cross also is professor of neurology and head of the neuroimmunology section. Maintaining an active clinical practice is what helps her persevere through the often-challenging rigors of research.

“I like taking care of patients who have the disease that I study in the laboratory,” she says. “And they like it, too. It gives them hope, and it helps keep me motivated.”

While three classmates developing MS may be unusual, Cross’ friends are not alone. About 200 people are diagnosed with the disease every week, and most are between 20-50 years old, according to the National Multiple Sclrosis Society. Worldwide, MS affects an estimated 2.5 million people.

When Cross was in medical school, little was known about the disease and even less was known about how to treat it. Now, thanks in part to her own scientific contributions, it is more fully understood.

Although there still is no cure, there now are multiple drugs that can slow progression of the disease in some patients, particularly those whose conditions are diagnosed early.

Most experts now believe MS involves a dysfunction of the immune system. The body’s natural defense mechanisms somehow go awry and begin to destroy the fatty tissue that insulates nerves in the brain and spinal cord.

The fatty tissue, called myelin, normally helps nerve cells communicate quickly and efficiently. Messages between nerve cells are thwarted if their surrounding sheet of myelin becomes damaged and scarred.

Because myelin is present in almost every part of the central nervous system, the disease can affect a variety of brain and spinal cord areas, which can lead to a wide range of symptoms.

Because MS combines immunology and neurology, it provides a uniquely intriguing opportunity for someone like Cross, who was always fascinated by both fields. Her training also makes her distinctly qualified to combine the two.

A curative combination

Early in her career, Cross was able to learn about the diverse aspects of MS from an equally diverse range of opportunities and mentors.

She had fallen in love with and married her classmate at the University of Alabama School of Medicine, DeWitte T. Cross III, M.D., now an associate professor of radiology and of neurological surgery and director of interventional neuroradiology at Washington University.

He was indentured to the Navy for several years after medical school, so the newlyweds moved around, with naval obligations and a love for medicine as their guide.

Anne Cross’ interest in MS never wavered. After completing her clinical training — first as an intern at Mercy Hospital and Medical Center in San Diego and then as a neurology resident at George Washington University — she realized the importance of laboratory research and, in particular, the basic science of immunology underlying MS.

She then joined the National Institutes of Health as a fellow in neuroimmunology, and subsequently became a fellow in virology and molecular biology at St. Jude Children’s Research Hospital in Memphis.

After rounding out her research training with three years as a fellow in pathology at Albert Einstein College of Medicine, Cross felt equipped to become an independent investigator and set up her own laboratory.

“I love working in the lab because I think that’s where one can have the biggest impact,” she says. “My research focus has evolved as the field and the science of immunology have evolved, but my goal has remained the same: to figure out what causes MS and how to cure it.

“I think you can have an impact on many more patients in the long run by doing research in the lab, and the idea of discovering things no one else knows is really exciting and fun.”

Putting patients first

In 1991, having established herself as an independent researcher at Einstein, Cross and her husband, then free from his naval obligations, finally settled down. They chose St. Louis for one reason: Washington University.

“We both thought we’d enjoy working at the University because of its reputation as a good research center and because of the caliber of the faculty,” she says. “It’s the best institution I’ve ever been associated with, and I’m really happy to be here.”

During her tenure here, Cross has continued her pivotal contributions to the field, and she’s had the rare thrill of seeing some of her own early laboratory discoveries make their way into clinical studies.

For example, she was instrumental in showing that the immune system’s B cells play an important role in animal models of MS. Her team is launching the first controlled human trial to examine whether the drug rituximab (commercially known as Rituxan), which is used to treat a type of cancer called B cell lymphoma, may help MS patients who are not responding well to standard therapies. The trial is sponsored by the National Multiple Sclerosis Society.

Whether it’s human brain-imaging studies or test-tube experiments, Cross never loses sight of her true motivation: her patients. In fact, she makes a point of periodically bringing her Ph.D. students into the clinic to ensure they always appreciate the greater context.

“Anne speaks with the affirmation of a person who actually sees and treats MS patients, which most of us in the field don’t do,” says longtime mentor and collaborator Cedric Raine, Ph.D., D.Sc., professor of neuropathology, neurology and neuroscience at the Albert Einstein College of Medicine. “She’s a rare bird in as much as she has the skills and acumen to both treat MS and to take her clinical knowledge in to the lab and apply it to research.”

Cross’ dedication to her patients is part of why she’s so touched to hold the Manny and Rosalyn Rosenthal and Dr. John L. Trotter MS Center Chair in Neuroimmunology at BJH.

In addition to its recognition of Cross’ own contributions to the University and to the field of MS research, the professorship recognizes her beloved mentor and friend.

For Cross, the opportunity to work with Trotter was part of the allure of the University. The two shared a passion for science and a drive to find a cure for MS.

Cross still has an overflowing stack of their scrawled notes about scientific ideas, ranging from the bizarre to the truly inspired — the product of years of lunchtime brainstorming sessions.

Perhaps the most important thing they shared, though, is their love for their patients, who helped fund the professorship Cross now holds.

Cross not only hopes to continue the tradition of personal and academically driven clinical care that Trotter established, but she also hopes to pass on the energy and inspiration she owes to Trotter and all her other mentors. She recently received a mentoring award from the National Institutes of Health to do just that.

“I’m at a point in my career where I think I have things to teach new clinicians and scientists, and I want to try to pass that on,” she says. “I’ve had such good mentors that I feel like I now know what it means to be a good mentor myself.”