The discovery of insulin 100 years ago transformed type 1 diabetes (T1D) from a death sentence to a chronic illness. Yet T1D is still a relentless disease with no cure. For decades, BRI and Virginia Mason have been working to change that — from testing the first insulin pumps to launching trials of therapies aimed at diabetes prevention. Learn about key research milestones and what’s next for BRI’s quest to predict, prevent, reverse and cure T1D.
1920s: Insulin transforms T1D Into a chronic disease
A T1D diagnosis before the 1920s was a tragedy. People — often kids and teens — would learn they had T1D and die a year or two later.
In late 1921, Canadian scientists Frederick Banting, John Macleod, Charles Best and James Collip purified the extraction of pancreatic secretions to develop insulin. In January 1922, a 14-year-old boy received the first insulin injection. His improved glucose levels signaled a breakthrough for treating T1D.
In 1923, Banting and Macleod won the Nobel Prize, splitting their prize money with Best and Collip. Mass production of insulin began soon after. That year, Virginia Mason’s Lester Palmer, MD, became the first doctor to administer insulin for T1D in the Pacific Northwest.
1930s-1970s: Pioneering tools to manage T1D
Over the next few decades, managing T1D typically meant following a strict diet and administering insulin via glass syringes and needles sharpened on pumice stones. But there was no way to measure glucose levels at home, and people with T1D often experienced dangerous blood sugar levels.
Mary Buse saw this firsthand. She was born in 1916 and would grow up to play a key role in T1D research. By the time she was diagnosed in the 1950s, Mary had seen people with T1D experience complications like kidney failure and blindness. In the 1970s, Robert Mecklenburg, MD — Mary’s physician and a Virginia Mason researcher — had an idea for radically improving how people managed the disease.
Other researchers had demonstrated that short-acting insulin given continuously through a portable pump could stabilize blood sugar for people hospitalized with T1D. Dr. Mecklenburg’s team wanted to adapt this approach to life outside the hospital. Mary was among the first to volunteer to test this experimental approach. Findings from that study paved the way to portable insulin pumps for everyday use — which changed the day-to-day lives and long-term outlook for many.
“People like Mary helped us write the book on living with insulin pumps. We moved from a place where T1D patients relied on doctors to a place where patients everywhere could take charge of their health and stay more active than ever before,” Dr. Mecklenburg says.
Mary wore various iterations of the insulin pump for 25 years. She left one more gift to BRI when she passed away at age 92: $500,000 to advance T1D research.
1980s-2000s: Building BRI, understanding the immune basis of T1D
Jerry Nepom, MD, PhD, moved to Seattle in the early 1980s with a bold goal: Start a laboratory and search for genes that reveal the immune basis of T1D and other autoimmune diseases. By 1983, he reached a major milestone with the discovery of a key immune system gene which helps predict T1D.
“Finding that gene was a portal to decades of advances in understanding what causes T1D and what we can do about it,” Dr. Nepom says.
That discovery caught the eye of Virginia Mason leadership, and they soon recruited Dr. Nepom to build their immunology and diabetes research programs. The research institute had fewer than a dozen scientific staff when he joined in the mid-1980s. The staff grew to over 100 by the time the research institute moved into its current building in the late 1990s.
“Each decade of research built upon the last,” says Dr. Nepom, who went on to serve as BRI’s president for three decades. “The 1980s were about building tools and discovering key genes. The 1990s were about understanding the structure and function of these genes. The 2000s were a time of tremendous growth in T1D research, highlighted by the recruitment of Carla Greenbaum, MD. She has played a pivotal role in building BRI’s clinical research program and leading T1D clinical trial initiatives with an international scope.”
2000s onward: Goal: Predict, prevent and reverse T1D
At the turn of the millennium, BRI set our sights even higher: We launched the Diabetes Clinical Research Program to help translate lab discoveries into innovative patient care.
“We had this incredible startup mentality,” says Dr. Greenbaum, who came to BRI to build and lead the program. “There were challenges but the sky was the limit. We were always saying ‘Is this possible? Maybe, let’s try.’”
They spent the early 2000s building robust databases of patient samples that few institutions had at the time. They focused on key questions: Who will get T1D? And what exactly happens in your body after the disease starts?
“Research from our team and many other scientists pinpointed how to predict T1D,” Dr. Greenbaum says. “We also learned that the age you develop T1D impacts disease course and that the pancreas continues to produce a little bit of insulin after diagnosis.”
Better understanding the disease’s course led to another question: How can we change it? Over the years, BRI, TrialNet and other T1D leaders developed therapies that aim to preserve insulin function. This could help maintain some insulin production for people already diagnosed with T1D and possibly prevent the disease.
“Now there are seven therapies that help preserve insulin production after diagnosis and we’re working to see if they can contribute to prevention,” Dr. Greenbaum says. “In 2019, we made a key breakthrough with a trial of teplizumab, which delayed T1D for a median of two years. This is the first therapy to delay any autoimmune disease, and it’s a vanguard of what we anticipate will be many clinical options.”
Moving forward, BRI’s team aims to expand T1D screening and make T1D care more personalized, so each patient gets the best treatment for their unique biology.
“People with T1D are living longer with fewer complications than ever, which is incredible. But it’s not good enough,” Dr. Greenbaum says. “At BRI, we’ve built a culture of creative thinking and a team who see stopping T1D not just as a job but as a mission. And we use that approach to move close to our goal: Predict, prevent, reverse and cure T1D and all immune system diseases.”
The Next Generation of BRI Researchers: Why Study T1D?
Christine Bender, PhD, Postdoctoral Researcher: “Type 1 runs in my family and seeing how they suffered really impacted me,” says Dr. Bender, whose research focuses on prevention and treatments for T1D. “It’s such an exciting time in T1D research. We have better approaches, better equipment, we’re making progress toward delaying the disease. That’s what motivates me every day.”
Noah Biru, Former Lab Aide, Current PhD candidate at Yale: “Seeing my mom struggle with managing type 1 made me want to help find a cure,” says Noah, who also lives with T1D. “BRI has opened my eyes to how interconnected the immune system is. I’m interested in studying how and why autoimmune diseases develop and persist. And I’ll always have an interest in T1D — we’re going to cure diabetes, that’s the dream.”
Lauren Knabe, Summer Intern: “At the beginning of my internship, they gave me an immunology textbook and I found every chapter to be super interesting,” Lauren says. “This research is fascinating because the immune system is this really complex puzzle that you really have to push yourself towards understanding.”
This story was originally published in the Fall 2021 issue of Powering Possibility.
August 31, 2021
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