Researcher clinicians help bridge the gap between scientific discovery and medical care – Part 1

By Charlene N. Rivera-Bonet | Waisman Science Writer

Part 2

Kay Emerson and Harry Waisman
Kay Emerson and Harry Waisman

Research and clinical services go hand in hand. One can’t effectively work without the other. Clinicians are on the front lines, evaluating, diagnosing, and treating patients. Researchers are at the forefront of discovery, unraveling the mysteries of disease mechanisms and then developing potential treatments and interventions. Researcher clinicians (or physician scientists) do both. In the clinics, they make firsthand observations about conditions that can inform their research. Once they have answers, they can take those back to the clinic for better patient care.

Harry A. Waisman, MD, PhD, for whom the Waisman Center was named, exemplified this model and is a role model for the clinicians and researchers who work at the center today.  A bench scientist and practicing pediatrician, he made significant advances in the research and treatment of PKU, a metabolic disorder. The condition is hereditary, caused by the accumulation of the amino acid phenylalanine. Waisman helped develop a dietary approach to preventing the negative effects of the disease. With early detection, PKU can be treated by a low-phenylalanine diet. Left untreated, it can lead to significant intellectual and developmental disabilities.

One of Waisman’s patients, Kay Emerson, was the first successfully treated child with PKU in Wisconsin and one of the first in the United States. She was diagnosed at two weeks old. Her older brother, Keith Emerson, was diagnosed at three years old and had already developed significant intellectual disabilities. Because of the importance of early detection, Waisman advocated for adding PKU testing to the newborn screening panel, which is now routinely done for all children born in the United States.

Being on the frontlines of medical care allows physician scientists like Waisman a vantage point from which they can notice patterns, needs, and gaps in care. Prolonged interaction with patients also gives them a look into their lives, behavior, and family dynamics.

The Waisman Center provides the ideal opportunity for this. With ten specialty clinics and more than 60 research laboratories sharing a building by purposeful design, it creates an incredible interdisciplinary environment for translational research.

Clinicians have a direct day to day connections with patients and families. They hear about their needs and observe how different conditions unfold over time. Based on these observations, they can ask research questions to further improve, not just the care they provide, but the standard of care also provided by other clinicians.

As scientists, they also have to stay up to date with scientific advances made not just in their labs, but in their field, allowing them to bring that evidence-based, up-to-date information to their patients.

Lewis Leavitt, MD
Lewis Leavitt, MD

One of the early researcher clinicians at the Waisman Center was Lewis Leavitt, MD. He began his work at the center in the mid-70s specializing in pediatrics and neonatology. He also researched communication between parents and infants of young children, with a focus on how parents could help their kids – typically developing or with a disability – understand trauma. His work extended beyond the walls of the Waisman Center and the United States. He partnered with Sesame Street on a project to promote positive changes in Palestinian and Israeli children’s attitude toward each other. He also worked with agencies like UNICEF to write guidelines to help children under distress due to difficult situations.

For Leavitt, who was director of the Waisman Center Clinics from 1989 to 2009, the clinics and research spaces at the Waisman Center have changed significantly since their beginnings. “The biggest change has been in the size and importance of the clinical program and the degree to which we’ve been able to attract faculty who are deeply involved in research integrated with a clinical program,” Leavitt says.

Jon Wolff, MD
Jon Wolff, MD with young patient

One of those faculty who was deeply involved in both research and clinics was Jon Wolff, MD, former director of the Biochemical Genetics Program at Waisman. In the clinics, he was an expert in treating metabolic disorders in children. He also served as advisor to the State of Wisconsin’s Newborn Screening Program, helping to establish new programs to detect metabolic disorders and genetic conditions.

As a researcher, Wolff made significant contributions to diagnostic and therapeutic knowledge that helped improve the standard of care for many genetic conditions. His biggest contribution, which allowed for the development of mRNA-based COVID-19 vaccines, was developing a system to introduce DNA to muscle cells. Sadly, Wolff passed away in April of 2020.

Rich Pauli, MD, PhD
Rich Pauli, MD, PhD

An experience similar to Leavitt’s, Wolff’s, and Waisman’s is shared by Rich Pauli, MD, a former pediatric geneticist at the Waisman Center and former director of the Bone Dysplasia Clinic. All of Pauli’s research ideas were generated by clinical observations. Pauli, an expert in bone dysplasia, showed there is an increased risk of death in babies with achondroplasia because of difficulties breathing caused by abnormal spinal cord compression. This discovery led to the nationwide implementation of routine evaluations for kids with achondroplasia for early intervention. “Probably a half dozen kids a year are saved because of the standards that have been established to do evaluations for those kids routinely,” Pauli says.

This began with the sudden passing of one of his patients with achondroplasia. The family’s second child, who also had achondroplasia, was evaluated. In a sleep study, they found that she had central apnea – forgetting to breathe while asleep. Over the span of 15 years, multiple studies pointed to its increased frequency in people with achondroplasia and its cause, which led to the implementation of routine evaluations and interventions. It was because of Pauli’s close relationship with his patients and their families that this was possible.

Upon his retirement, Pauli passed the white coat to Janet Legare, MD.

The current group at Waisman

Janet M. Legare, MD
Janet M. Legare, MD

With a background in genetics, rehab medicine, and working with kids with medical complexities, Legare was a natural fit to take over the Bone Dysplasia Clinic once Pauli retired. “He mentored me for three years, and I had incredible training in this very narrow area of bone dysplasia,” Legare says. Legare is director of the Bone Dysplasia and Neuromotor Clinics, and a pediatrician in the Newborn Follow-up Clinic at the Waisman Center.

In addition to attending to patients in these clinics, Legare also does clinical research ranging from early diagnosis of cerebral palsy, new aspects of various diagnoses of skeletal dysplasia, and onto clinical trials for achondroplasia. The work that she does in research has direct impact in her clinical work, and vice versa. “I can look at what I’m seeing in the clinic and say, what do we not know?” Legare says. She then brings these questions into the research lab.

A study she worked on about hereditary multiple exostosis, a diagnosis of extra bone growth, exemplifies this. They noticed that kids with this diagnosis were at higher risk of fluid filling spaces in their spinal cord. “This was a clinical observation that we then looked through and analyzed. We were able to publish our findings and ultimately take it back and say, ‘this is going to change how we manage these patients when they become adults’,” Legare says. Now they recommend a routine spinal magnetic resonance imaging (MRI) to evaluate patients at risk.

Maria Stanley, MD
Maria Stanley, MD

This hope that research provides, Maria Stanley, MD, developmental behavioral pediatrician and medical director of the Waisman Center Clinics, believes is not only provided at an individual level through the clinic, but also around the country and the world. “Providing contributions to research helps contribute to system level impact,” Stanley says.

Stanley’s research focuses on Down syndrome, with some research also done in the Newborn Follow-up Clinic. One of her studies looks at how children with Down syndrome respond to medications. “Genetic differences may change their response to medication, and it isn’t one size fits all,” Stanley says. “We need to understand what things are the same for all children and what things are really unique and different for these specific populations.” An example of this is looking at kids with Down syndrome that have symptoms of ADHD, and how they respond to medication.

For Stanley, her and other’s research have led her to be more proactive in the clinic about managing specific issues within Down syndrome such as medication management, sleep, and feeding problems.

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