AURORA, Colo. (May 27, 2009) – Before he could rock the medical world by discovering how childhood diabetes develops, George Eisenbarth had to discover a way to go to college. Eisenbarth, whose life’s work just won him the American Diabetes Association’s most prestigious prize, the Banting Award, took a distinctly different route to scientific genius than most of his peers.
Eisenbarth, now Executive Director of the Barbara Davis Center for Childhood Diabetes and Professor of Pediatrics, Medicine, and Immunology at the University of Colorado Denver School of Medicine, grew up in a working class neighborhood in Brooklyn. His father, John, had a sixth-grade education. His mother, Esther, also not a high school graduate, worked in an electronics factory. Grover Cleveland High, the public school from which Eisenbarth graduated in 1965, produced about 1,000 graduates a year in those days. Only about 50 went to college.
Still, the young man who would eventually prove that type 1 diabetes was a chronic immune disease that could be predicted by genes specific to the immune system and the presence of certain antibodies knew he would find a way to realize his mother’s dream.
“My mother always assumed I would be a doctor,” said Eisenbarth, who earned his medical degree and a PhD at Duke University. “I remember rowing a boat with my mother on a lake in the Catskills, and she would read to me from a science encyclopedia. My father worked as a cook at the Natural History Museum in New York City. My parents sort of signed me up to visit.”
It took very little convincing. Science “was fun” for Eisenbarth. So when one of his high school English teachers suggested that he apply for a Pulitzer Scholarship to Columbia University, he did. Each year, the university gave one full ride Pulitzer to a single student at ten New York City’s high schools, Eisenbarth recalled. The fact that so few of his classmates planned to attend college cast the odds in his favor.
His dad remained suspicious even after Columbia named him a Pulitzer scholar. “My father,” said Eisenbarth, “made me check to make sure it wasn’t a scam.”
It was not scam. It was the hand up that a smart kid from humble, hardworking roots needed.
In nominating Eisenbarth for the ADA’s Banting Award, a series of physicians and researchers from across the country called Eisenbarth’s body of research transformative in a field that affects millions of children and adults.
The fact that Supreme Court nominee Sonia Sotomayor has type 1 diabetes has called public attention to the disease in the past few days. George Eisenbarth has been paying attention for nearly 40 years.
“Every 20 years in the Western world, the rate of type 1 diabetes doubles,” Eisenbarth said. “In poor countries, that doesn’t happen.” The reasons for the spiraling rate of type 1 diabetes remain unclear, Eisenbarth continued. It could be diet. But it could be that developed countries have actually become “too clean,” not getting exposed to enough microorganisms that stimulate the immune systems. Ironically, we may not be dirty enough.
Wednesday (May 27) the leading British medical journal, Lancet, reported on a large study in Europe, which showed the rate of diabetes doubling in some European countries even faster than previously predicted. Between 2005 and 2020, new cases of type 1 diabetes in European children younger than 5 years are expected to double. The prevalence of diabetes cases in those younger than 15 years will increase by 70 percent, Lancet reported. In a comment accompanying the Lancet article, Dana Dabelea, MD, PhD, an epidemiologist at UC Denver’s Colorado School of Public Health, explained that younger age at onset of type 1 diabetes typically means patients arrive with more serious symptoms, including an increased risk of potentially deadly diabetic ketoacidosis and the need for hospitalization.
All of this adds to the importance of Eisenbarth’s work. His Banting Award nominators praised the 61-year-old physician researcher for his willingness to collaborate as well as innovate over the course of his career.
In announcing Eisenbarth as the Banting Award winner, the American Diabetes Association noted that “the major tenets developed as a consequence of his discoveries guide basic research, clinical diagnosis, and disease therapy to this day.”
Not only did Eisenbarth find specific kinds of insulin antibodies in the blood of non-diabetic twins whose brothers or sisters already had diabetes, he found ways to link those antibodies back to certain amino acids produced by certain genes in the immune system. This opened the way for genetic testing of hundreds of thousands of newborns to assess their vulnerability to a life-altering disease.
But none of it would have happened without the opportunity for Eisenbarth to realize his potential.
His mom’s reading from that science encyclopedia and his dad’s insistence that he visit the natural history museum begat an honor student who a high school teacher wanted to help rise above the limits of a neighborhood or a family history. The scholarship from Columbia begat a Bachelor’s degree in biology, that, in turn, begat admission to Duke’s medical school, where Eisenbarth met and adopted as his mentor a famous research physician, an endocrinologist named Harold Lebovitz.
Lebovitz opened the door for Eisenbarth to study autoimmune diseases and then packed his young protégé off to the National Institutes of Health in Washington, D.C., to learn more from Nobel Laureate Marshall Nirenberg, the biochemist who discovered how the genetic code transforms its chemical information into proteins.
From NIH, Eisenbarth went back to Duke and honed in on the cause of type 1 diabetes at a time when the scientific world believed that viral infections caused 90 percent of cases and that immune system problems caused just 10 percent.
In 1982, Eisenbarth left Duke for the Joslin Diabetes Center at Harvard Medical School, where he studied twins who had identical genetic profiles but only one in the pair had diabetes. In 1992, Eisenbarth left Harvard to join the faculty at the UC Denver School of Medicine and to run the Barbara Davis Center.
Now, primarily because of Eisenbarth’s work, the world understands a different model for diagnosis and treatment of type 1 diabetes – genetic predisposition, a triggering event that causes the genes to begin a process that results in an attack on insulin, the loss of irreplaceable insulin cells in the pancreas over months in infants or years in children, and, finally, full blown type 1 diabetes.
“Diabetes is caused when the body’s own white blood cells make a mistake and kill the body’s insulin cells,” Eisenbarth explained. Once destroyed, insulin cells in the human pancreas don’t grow back. When that happens, the body can’t absorb sugar. An inability to absorb sugar turns debilitating and sometimes deadly.
“If the body can’t use sugar, the body makes ketones to try to burn fat,” Eisenbarth said.
It’s called ketoacidosis, and it’s like starving. Unabsorbed sugar pulls water out of the system, causing dehydration through frequent urination. If type 1 diabetes treatment begins at such an advanced stage of the disease, the brain may swell and kill the patient.
Even at this point in the sophistication of research, Eisenbarth said, “about one child every other year dies at the onset of diabetes.”
The toll would be much greater were it not for the early identification of risk factors that Eisenbarth fathered. In addition to his study of diabetic and non-diabetic twins, Eisenbarth helped isolate the gene that causes diabetes in animals. He did it in a way that defied the natural course of things as surely as being read science encyclopedias while rowing a boat. He did it with internationally transplanted mice.
In 1986 at Harvard, Eisenbarth hired a researcher named Masakazu Hattori, who lived in Japan. Japan was the one country in the world that was known to have an accident of nature called the “non-obese diabetic mouse” or NOD mouse. When Hattori arrived at Eisenbarth’s American lab, he brought some NOD mice with him, beginning the worldwide study of this very important model.
The hitchhiking mice proved monumental for millions of people. Eisenbarth, Hattori and others eventually identified a gene that caused diabetes in these mice when bred with normal mice.
These days, the newly anointed Banting Award winner works in Colorado in concert with an international league of scientists to find a way to change the diabetes-linked gene so it won’t go through the process that causes it to form the antibodies that destroy insulin cells.
Physicians and PhD’s around the world, including several at the Barbara Davis Center at UC Denver, work to test newborns for genetic vulnerability to type 1 diabetes and to track them through childhood. Researchers now conduct human trials on medicines to treat or stop the progression to diabetes, including oral insulin and a drug that stops the insulin destruction process for up to a year. On tap is a cocktail of medications that may permanently stop the destruction of insulin producing cells. Hope also exists for development of a vaccine to intervene even earlier in those at risk.
Meanwhile, the guy who facilitated much of this progress sits in his office on Anschutz Medical Campus in Aurora and ponders a way not to treat type 1 diabetes, but to prevent it.
“The body produces billions of T cells, but only a small percentage have a receptor that will attack insulin,” Eisenbarth said. “These T cells start to activate with some kind of trigger. We want to ‘reeducate’ the T cells so that they won’t attach to the targeted amino acid in the insulin peptide and attack the beta cells that produce insulin. I think we’re getting to the real molecular core.”
Though his mom and dad didn’t live to see him graduate from medical school, much less change the world of diabetes research, there is no doubt of one thing:
George Eisenbarth’s parents got what they wanted.
The School of Medicine faculty work to advance science and improve care as the physicians, educators and scientists at University of Colorado Hospital, The Children’s Hospital, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. Degrees offered by the UC Denver School of Medicine include doctor of medicine, doctor of physical therapy, and masters of physician assistant studies. The School is part of the University of Colorado Denver, one of three campuses in the University of Colorado system. For additional news and information, please visit the UC Denver newsroom online.
Contact: Jim Spencer 303.724.5377; 720.346.4242 [email protected]