The System Never Sleeps
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Eric Klee, Ph.D., applied to medical school and subsequently pulled his application.
What made all the sense in the world for young Eric to do with his life made none in his own mind. His father was a Mayo Clinic pathologist and his mother a nurse. His siblings were all in the process of becoming clinicians themselves.
For an institution built more than 160 years ago by a family of medical practitioners, the Klees were as close to a modern story of the Mayo family as one could get.
"I was born and raised in Rochester, Minnesota,” Dr. Klee says. “I was surrounded by medicine.”
Dr. Klee was very interested in healing patients, but he didn’t want to study biology as an undergraduate followed by years of medical school.
"I knew once I got into medical school, I’d be doing residency and locked into a long-term career,” Dr. Klee says. “That’s why I pulled my application.”
His quest to find a career led him in the late 1990s to the office of Franklyn Prendergast, M.D., Ph.D., a friend of his father, searching like so many others did for some advice from the visionary clinician.
The conversation with Dr. Prendergast, who passed away in 2023, would chart Dr. Klee’s direction and set the stage for the future.
“I was interested in engineering and technology. I was interested in medicine. I wanted to figure out how it all came together,” Dr. Klee recalls. “Dr. Prendergast said, ‘Eric, there’s an emerging field called bioinformatics. It doesn’t actually exist yet, but I promise you it will in five years, and it’ll be important for at least 30 years to come.’”
Today, Dr. Klee, who first graduated with a degree in electrical engineering, has found his answer to what it means to practice medicine as an engineer. And it’s transforming how Mayo Clinic cares for patients with the rarest diseases.
BUILDING BEHIND THE SCENES
Dr. Klee, who is recognized as the Everett J. and Jane M. Hauck Midwest Associate Director, Research and Innovation, Center for Individualized Medicine, has spent his career building systems that aid doctors in new ways. As a leader in Mayo Clinic’s rare disease research and digital innovation efforts, he and his teams have created platforms that keep diagnosing patients years after their genetic sequencing tests. These platforms automatically watch for new scientific discoveries while families sleep, multiplying the impact of the organization’s expertise far beyond exam rooms.
His work represents a distinctive Mayo Clinic approach. It’s focused on cross-disciplinary collaboration where mindsets like his in engineering meet clinical needs. Infrastructure investments from a decade ago enable today’s artificial intelligence (AI) breakthroughs, and through it all, the institution’s commitment to patients extends even when they’re not physically present.
I was interested in engineering and technology. I was interested in medicine. I wanted to figure out how it all came together.
— ERIC KLEE, PH.D.
From increasing diagnostic success rates for rare diseases to being at the forefront of AI initiatives in the Mayo Clinic Comprehensive Cancer Center, Dr. Klee has found his own path to honoring the family calling — one that feeds his soul in ways a traditional practice would not have.
Choosing to study engineering led to an opportunity with the medical device maker Medtronic before going back to graduate school. After obtaining his doctorate degree, the pull of Mayo Clinic brought him back to Rochester, where he would practice medicine in a different way through systems and infrastructure.
None of this was more apparent than in the rare disease space, where finding answers requires something far beyond traditional clinical care — even at a place steeped in subspecialty expertise.
THE RARE DISEASE PARADOX
There are more than 6,800 identified rare diseases, generally considered to be diseases that affect fewer than 200,000 people in the United States at any time. Altogether, rare diseases affect an estimated 25 million to 30 million Americans, according to the National Human Genome Research Institute. These conditions span so many specialties that even the most skilled clinicians around the world can struggle to see the complete picture.
“A patient might have cardiac symptoms, neurological issues, immune system concerns and physical differences — but when these signs are scattered across different body systems, it creates what we call the ‘elephant problem,’” Dr. Klee explains. “Each specialist sees their part clearly, but few clinicians can observe the whole elephant at once.”
Even further, what happens if the latest breakthrough occurs after an episode of clinical care? What then?
“Our understanding of what genes and what variants cause disease is growing,” Dr. Klee says. “So what we know today is different than what we knew six years ago, six months ago or even six days ago. When you have a static report, you miss out on what we’ve learned since that test.”
To address this challenge, in 2022 Dr. Klee’s teams launched an automated system called RENEW. The tool is built to literally renew clinical test results by looking at what’s been learned since the last time the test was run or the patient’s data was accessed.
The system works with elegant simplicity.
RENEW automatically pulls in newly published discoveries of disease-causing genetic variants from research labs around the world. It compares these findings against Mayo Clinic’s database of unsolved patient cases — nearly 2,000 and growing.
Special filters whittle down the flood of new genetic information to focus only on what’s meaningful and could explain a patient’s symptoms.
When it flags a match, a team of genomic researchers digs deeper by reviewing medical records and clinical histories and correlating DNA alterations with new findings. The question they ask: Could this newly described variant be the answer someone’s been waiting years to hear?
So far, RENEW has delivered dozens of definitive diagnoses for Mayo Clinic patients with rare and previously unexplained diseases. And it takes less than a minute per patient to run the analysis.
“Every time we get a diagnosis, it makes me feel proud of what we’ve been able to accomplish at Mayo,” Dr. Klee says. “It’s this concept that the patients put trust in — not my team, not a single clinician — they put their trust in Mayo Clinic, and Mayo Clinic as an organization has supported this type of really challenging work.
“The parents and families, they believe that someday we will call them with an answer. And it’s incredibly gratifying for everyone when we do.”
VISIONARY LEADERSHIP, VISIONARY BENEFACTORS
A bigger question is why does this happen seemingly so often at Mayo Clinic? While Dr. Klee’s engineering background might seem like an unconventional foundation for rare disease research, at Mayo Clinic, cross-collaboration and diverse skill sets aren’t just accepted — they are championed.
But even the best collaborative culture needs infrastructure to reach its potential. Mayo Clinic leadership invested in this space a decade ago, and it’s paying dividends today.
“One thing that has set Mayo Clinic apart from a lot of other academic medical centers was the foresight of our institution, and now President and CEO Gianrico Farrugia, M.D., to think about data organization,” Dr. Klee says. “While other health systems were still figuring out electronic health records, Mayo Clinic was organizing all its clinical data in the cloud, creating Mayo Clinic Platform, de-identifying patient information and making it available for research.”
It was a massive investment bolstered by visionary benefactors despite an uncertain future, and the foresight it unlocked has set the stage for something much bigger.
“It opened the door for the transformative power of what we’re starting to realize in artificial intelligence, agentic AI and other emerging capabilities,” Dr. Klee says. “That realization is you’re only as successful as the data you have organized and readily available.”
In other words, Mayo Clinic didn’t just build strong and secure data systems. It built the foundation for the AI tools and future breakthroughs that didn’t even exist when the foundation was laid.
This work extends through Mayo Clinic Research enterprise priorities, including the Research Data Atlas, an initiative led by Dr. Klee to unify and mobilize research data at scale. It brings diverse research datasets into a secure, cloud-based environment where they become discoverable, interoperable and ready for advanced analysis. By increasing access to high-quality, harmonized data, the Research Data Atlas strengthens collaboration across the institution and accelerates Mayo Clinic’s ability to advance artificial intelligence-enabled discovery and translational research.
That infrastructure has allowed Dr. Klee to expand his impact beyond rare diseases. When Cheryl Willman, M.D., the Stephen and Barbara Slaggie Executive Director of Mayo Clinic Cancer Programs and Director of the Mayo Clinic Comprehensive Cancer Center1, approached Dr. Klee about leading data and AI initiatives in oncology, he identified a chance to scale what he’d learned.
“I saw the opportunity in the Cancer Center to take a lot of what we had done in the Center for Individualized Medicine with regard to how we think about our genomic data and other omics data and organizing it to have an impact by breaking down barriers and opening doors to new discoveries.”
The same engineering mindset now applied to a different problem — making the data frictionless, accessible and useful across the entire enterprise to create systems that multiply the impact of every researcher, clinician and discovery.
RETURNING TO HIS ROOTS
Back to that conversation nearly 30 years ago in Dr. Prendergast’s office about the field that didn’t exist.
Bioinformatics employs hundreds of researchers at Mayo Clinic alone. And Dr. Prendergast’s prediction it would be important for at least 30 years has turned out to be conservative.
While Dr. Klee doesn’t have the same deep physician-patient relationships others in his family do, he keeps working on hope and healing in the way only an engineer could — leading teams who are building systems that never stop looking and leveraging infrastructure built with the forethought of what might be to come.
Because of that, in a cloud server room tonight, the system Dr. Klee championed runs. New databases of discovery are being checked against organized data files of patients. Algorithms are filtering results for meaningful changes.
And when tomorrow comes, a multidisciplinary team may get a notice to review results that could contain an answer someone has been waiting years to hear.
What kind of medicine can an engineer build? The kind that practices medicine even when patients aren’t there — because at Mayo Clinic, the needs of the patient come first, whenever and wherever they are.
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