By Therese Boyd, ’79
Dr. John Malone, ‘63
Type 1 diabetes—a life-threatening condition—occurs when the pancreas does not produce sufficient amounts of insulin to keep the body functioning. According to the Juvenile Diabetes Research Foundation (JDRF), incidence of Type 1 is on the rise—1.25 million Americans have been diagnosed, and that number is expected to grow to 5 million by 2050. In the first decade of the twenty-first century, the number of people under the age of 20 diagnosed with Type 1 grew 21 percent. While there is presently no cure, there are treatments, but none that are foolproof. Penn State Altoona alumnus Dr. John Malone, ‘63, has spent his entire career in research focused on a solution for this disease.
After medical school at the University of Pennsylvania, Malone began his pediatric residency at Children’s Hospital of Philadelphia (CHOP), where he happened to be in the right place at the right time. “The Juvenile Diabetes Foundation (now the JDRF) was actually started in Philly while I was a fellow,” he says. “I was working in the clinical research center at CHOP one night when they had their first organizational meeting. They became a very aggressive political action group that demanded federal funds for diabetes research, including funding for [what was then called] childhood diabetes. They motivated Congress to establish the National Commission on Diabetes, which launched an international effort termed the ‘Diabetes Control and Complications Trial’ [DCCT].’” That trial has established the standard of care for diabetes management in the world today, Malone says. “It was determined that one could achieve a level of control that will prevent or reduce the complications of diabetes.”
Results from the study were published in the New England Journal of Medicine (329:977–86) in 1993, but research continues. “DCCT has now evolved into an observational study,” known as “Epidemiology of Diabetes Interventions and Complications” (EDIC), and the funding was just renewed for another five years, Malone says. “We evaluate them [study subjects] on an annual basis,” asking, “how are the complications evolving in these individuals that we have been following since 1983?” He notes that “it’s the longest-running clinical trial ever funded by the National Institutes of Health.”
Malone enrolled at Penn State Altoona as a chemistry major in 1959 at a significant point in the campus’s expansion: “The administrative building was brand new when I was there.” Like many college students, Malone knew what he wanted to do and yet didn’t know. “It was my intention to go to medical school even though I had no idea what that meant. I pictured myself as a scientist in a lab curing diseases. I didn’t have any realistic idea of what I was thinking about.”
By the time he had finished his pediatric residency, however, his goals were clearer. Malone knew he wanted to become more involved in diabetes care and management. “There wasn’t a formal training program for that, so I ended up in a program specializing in inborn errors in metabolism, since diabetes was considered a metabolic disease. Today we say diabetes is an endocrine disorder which includes a different set of associated disorders.”
Research to combat this disease comes with many frustrations. “We have tried all kinds of treatment techniques to prevent diabetes,” Malone admits. “Many work in lab animals but none have come close to working in humans. Doctors keep suggesting that if their patients would only try harder they could control the metabolic abnormalities of diabetes, and everything would be better. What you don’t realize is how sophisticated the normally functioning body is. When one part breaks we humans do a terrible job of fixing it. When one component of the body’s regulatory system is missing—insulin—we cannot replace it appropriately, even though we have an abundance of insulin available and sophisticated methods to administer it. Great advances have occurred during the past fifty-nine years of my involvement but our treatment approaches remain relatively primitive.”
One specific project Malone was involved in showed some success for prevention but unfortunately, he says, “no one else has been able to reproduce it.” Money, of course, played a significant role in this process. “We were able to get a grant. We didn’t have a clinical research center so we had to admit newly diagnosed patients into the hospital for two weeks to participate in this research protocol. You could not get away with that prolonged admission today.” Malone used the grant money to purchase the Biostator Glucose Controller, “a closed loop artificial pancreas system which delivers insulin or dextrose to an individual while providing continuous monitoring of the glucose level to achieve absolutely normal blood glucose levels, for two weeks after the onset of diabetes” (S. Shah, J. Malone, and N. Simpson, “A Randomized Trial of Intensive Insulin Therapy in Newly Diagnosed Insulin-Dependent Diabetes Mellitus,” New England Journal of Medicine 320 [1989]: 550–54). Results from that study are still evident today, he notes: “Many of those individuals continue to make some of their own insulin, thirty years later, which makes it easier to control their diabetes.”
That’s great progress. However, the Biostator is not portable and so patients getting treatment are confined to the room where the machine is located. In addition, the device cost was $20,000 in 1983. Malone was part of another group getting funding from NIH that tried to duplicate his first experience but no one could afford a Biostator and therefore no one could duplicate the initial treatment protocol, so that intervention failed. “They’re currently trying again with a less expensive closed-loop insulin pump system that is not as precise as the Biostator,” Malone says. “This effort is in progress and the results are not known to me.”
These days Malone is “basically retired” but still quite busy, as he says, with “a whole hodgepodge of stuff.” The NIH-sponsored clinical research project that started in 1983 and for which he is principal investigator, DCCT/EDIC, is still collecting data. The observations from this study, thus far, have established the Standard of Care recommended by the American Diabetes Association. He is also on the admissions committee for the University of South Florida, Morsani College of Medicine. “I get to talk to a lot of individuals who are in their junior or senior year of college and listen to their plans for the future. They’re always very interesting.” Over the years Malone has published some book chapters and over 100 articles, the most recent being “Diabetic Central Neuropathy: CNS Damage Related to Hyperglycemia”(Diabetes 65, no. 2 [February 2016]: 355–57).
Malone retains his interest in research and the problems associated with finding a cure for Type 1 diabetes. “I just gave a talk the other night to endocrinologists about DCCT/EDIC. That whole story is pretty much a breakdown of the evolution of Type 1 diabetes.” He says, “It’s been exciting, it’s been fun, and we still don’t know anything.” Actually, we know a lot more than we did when he left medical school—and John Malone has played a significant role in that progress.