James Guest, M.D., Ph.D., grew up bouncing between the city, farms, and car repair shops near Toronto, Canada. His mother tended to the home and children and was a strong advocate for his education. His father was a mechanic. As a young boy, Guest spent a lot of time working with his dad, building and fixing cars. “I became very comfortable with tools,” he says, “both fixing and recreating things.”
Uncovering a Career
Neither of Guest’s parents had a university education, and Guest reached the end of high school without a defined goal for university. He took three years off to work with relief organizations in Thailand and Cambodia, the Philippines, and other countries — and that’s where his love of medicine was kindled.
“My first surgical procedure was to repair an abscess on a water buffalo in Cambodia that we were corralling for vaccinations,” Guest says. “I also had an opportunity to do first aid for children who lost limbs from landmines and were suffering from other injuries.” The experiences sparked his desire to work in the medical field. Even though he’d never spoken to a physician or a scientist, when he returned from his travels, he enrolled in medical school at the University of Alberta in Canada. During medical school, he used his elective rotations to work in poorer areas of India, and was involved in his first spinal surgery, a patient with spinal tuberculosis.
When Guest was an intern in Vancouver in the late 1980s, a mentor steered him toward neurosurgery. “I realized from seeing newly injured people in the unit just how devastating spinal cord injury (SCI) was,” he says. “There were patients in casts, when casting was common practice to allow spinal bones to heal, and some were on bedrest for weeks.”
After working as a resident for six months in the SCI unit in Vancouver, Guest discovered a dearth of treatments to repair the damaged spinal cord. To help advance research in this arena, he decided to take a year off from his neurosurgery residency to pursue a research fellowship.
That one-year break evolved into three years when Guest decided to pursue his Ph.D. at the University of Miami, in The Miami Project to Cure Paralysis, one of the nation’s foremost research programs targeting traumatic spinal cord and brain injury, and other neurological disorders.
After Guest completed his Ph.D., he returned to neurosurgery, completing a spine surgery fellowship and ultimately becoming the lead neurosurgeon at the Miami Veterans Administration Hospital, which has a large SCI unit, especially for chronic injury patients.
“I did surgery on people with chronic complications from spinal cord injury, so things like spinal deformity, syringomyelia, and neuropathic pain,” says Guest, who is now a Professor in the Department of Neurological Surgery at the University of Miami. “Some of these patients with neuropathic pain were engaging in suicidal ideation because they were so desperate for relief.”
After his years of service at the Miami VA, Guest was adept at helping people who were suffering from devastating spinal injuries. The University of Miami was involved in international health in Haiti. So, when a 7.0 magnitude earthquake rocked Haiti in 2010, he rushed to Port-au-Prince with colleagues to deliver aid in a series of field hospitals. “Over four or five months, we not only created a hospital in Port-au-Prince, but we also initiated a network of spinal cord rehabilitation hospitals throughout the country,” he says.
From Haiti, Guest turned his focus toward full-time research, advancing scientific discovery for patients with SCI. Their lead preclinical strategy was transplanting Schwann cells, glial cells in the peripheral nervous system that wrap around neuronal axons to form the myelin sheath that allows rapid conduction and protects nerve cells from damage. These unique cells drive axon regeneration and myelination in the peripheral nerves. So, researchers hoped they would perform the same functions in the injured spinal cord.
“At the time, Schwann cell transplantation had been tested all over the world in many preclinical models,” Guest says. “We wanted to create clinical trials to assess their safety and efficacy in people.”
Scientific Discovery in Spinal Cord Injury
Starting in 2011, Guest’s team conducted their first Schwann cell clinical trial on people who were about one month out from their injuries. Then they began by testing the safety and feasibility of cell transplant therapy for people with chronic SCI. Another goal was to understand whether transplanting Schwann cells in patients with SCI from sub-acute to chronic phases could produce functional recovery.
“As part of the chronic trial, participants went through an exercise boot camp to help them achieve a higher level of fitness to help them tolerate the stress of the surgery itself — and to get a meaningful baseline from which we could see whether there was additional recovery after transplant,” Guest says.