For decades, five brothers living in rural Kentucky were slowly turned to stone. After just a few minutes of walking, their feet became so painful that even the doctors couldn’t explain their pain.
By the time her eldest sibling, Louise Benge, reached her 50s, she had come to believe that medicine might not be able to explain the causes of her family’s illnesses. After years of medical exams and tests that were inconclusive, her doctor finally referred her to the Undiagnosed Disease Program, a National Institutes of Health program dedicated to solving the most difficult medical mysteries.
What followed was a series of appointments and investigations involving multiple experts from different fields, leading to the discovery of an entirely new disease. The brothers were found to have arterial calcification caused by a deficiency in CD73 (abbreviated to ACDC). When this condition occurs, calcium rapidly builds up in the arteries of the legs, causing them to harden and making walking increasingly painful and difficult.
In 2011, this family became the Undiagnosed Disease Program’s first discoverer of a new disease. Since then, this effort has expanded to the Undiagnosed Disease Network (UDN), a group of clinics at major academic medical centers across the country dedicated to solving the most puzzling diagnoses. Led for many years by longtime NIH physician and scientist William Garr, the network has received more than 8,400 applications, evaluated more than 3,500 patients, and provided diagnoses to more than 1,000 patients with rare or previously unknown diseases.
Its mission is not only to solve individual medical mysteries, but also to use those discoveries to uncover a broader understanding of disease. Given the turmoil of the past year at the NIH, it is fortunate that UDN is still active.
But just surviving is not enough. This should serve as a model to be emulated by many more medical and research centers across the country.
As federal science funding and rare disease research feel increasingly vulnerable to political change, the Undiagnosed Disease Network represents the kind of high-risk, high-return, mission-filled work that NIH should always support. This is an attractive approach with bipartisan support for federally funded research that focuses on diseases that are too rare to attract large-scale pharmaceutical investment, but which can yield insights that will benefit millions of people.
For many Americans, UDN serves as a clinic of last resort. Most people who contact Girl do so after exhausting nearly every other option and cycling through multiple specialists and medical centers. Because rare diseases are inherently unfamiliar to health care providers, patients often endure long periods of misdiagnosis, inaccurate treatments, and extensive testing. “There are a lot of people who go a long time without a diagnosis,” Gahr told me when I was researching a book about diagnosis. “Some people question whether they are really sick.”
People accepted into the network travel to one of its clinical sites (such as NIH in Maryland, Baylor in Texas, or Stanford in California), where their medical records have already been reviewed by a team of experts, including geneticists, neurologists, vascular specialists, and others. They undergo multiple physical and genetic tests, sometimes with family members, while clinicians work together to put the puzzle together. Because this study will be conducted as a research study, patients will have access to advanced diagnostic tools free of charge. Participants’ travel, meals, and lodging expenses are also typically covered.
This model is in stark contrast to what many people experience with the traditional health care system. In traditional healthcare systems, appointments are often short or siled, and treatments are often expensive. “I believe it’s time to sit down and listen because we have something that many other practicing physicians don’t have,” Camilo Toro, an NIH neurologist who collaborates with the program, told me.
Approximately 1 in 10 Americans lives with a rare disease. Although each condition affects a relatively small number of people, rare diseases collectively affect tens of millions of people. Many remain undiagnosed for years, even decades.
Government support is essential as these diseases do not attract much commercial investment in treatments and cures. But the research conducted by UDN may also reveal fundamental biological mechanisms that help scientists understand far more common diseases.
Scientists are using what they learned from Louise Benge and her family to expand our collective understanding of more common vascular diseases, including peripheral artery disease, which affects an estimated 8 million Americans over the age of 40.
The mission of the Undiagnosed Disease Network has historically attracted support across the political spectrum. The network has previously been championed by lawmakers such as former Republican Sen. Roy Blunt of Missouri, who acknowledged its value and opposed the Biden administration’s fiscal 2023 budget proposal that would have cut funding for the network. “I think it’s a problem to get around that,” he said during the subcommittee’s appropriations hearing. Current NIH Director Jay Bhattacharyya said he wants his institution to serve as an innovation catalyzer and to “translate investments in biomedicine to improve the health of Americans.” Few programs embody that goal as clearly as UDN.
Even before the recent debate over federal science funding, network officials had been concerned about its future for some years. The fact that the network continues to operate is an encouraging sign. The Trump administration, which undermined scientific research with its poorly conceived U.S. DOGE service initiative, has at least signaled support for rare disease research, launching a framework to provide personalized treatments to patients with ultra-rare diseases (although patients are frustrated by recent rejections of rare disease drugs).
Still, one of the most important features of UDN is not just access to advanced diagnostic technology. When I interviewed families who participated in NIH programs for my book, I was struck by how often people mentioned the feelings that clinicians and scientists made for them and the tools and tests they used.
This does not mean that empathy is more important than solutions. I believe most people value reassurance more than a doctor’s personality. But the care and empathy that UDN clinicians give to each patient is a critical part of its success. Resolving difficult medical cases is important, but so is the trust that process restores in a health care system that many patients experience as rushed, fragmented, and indifferent.
“They never gave us false hope, but they promised to try everything,” Phil Luken, whose daughter Olivia was diagnosed through the network in 2019 when she was 21, told me. They began searching for answers when Olivia was in kindergarten. “They really cared. Of all the places we went, it was the most personal.”
Olivia was diagnosed with a rare neurological disease called KMT2B-related dystonia (also known as dystonia 28). Before arriving at UDN, her condition had progressed to the point where she could barely move and lost the ability to speak. For years, her parents wondered how much their daughter had lost to the disease.
After receiving her diagnosis through UDN, Olivia underwent deep brain stimulation surgery. The procedure improved her mobility and communication skills. “I realized that Olivia had the same hopes, dreams and thoughts as any other child,” Phil said. “Her mind was intact. Now she can sign her thoughts well enough to share her life with us.”
UDN is not an outlier in healthcare and should be a model for more such clinics in hospitals across the country. Clinics that specialize in solving complex diagnostic cases, including rare genetic diseases and other diseases that have stymied doctors, would give doctors a trusted place to send patients when traditional approaches fail. Not because doctors are abandoning difficult cases, but because not all health care providers (particularly those working in urgent care or emergency rooms) have the time or collaboration necessary to solve them. Ideally, these clinics would be staffed by full-time, multidisciplinary teams, allowing for longer appointments, more intensive treatment, and rapid on-site visits across specialties. This type of investment could also go a long way toward rebuilding trust between patients and health systems.
Of course, all of this may seem impossible given the current health system problems. But just because something is difficult doesn’t mean you shouldn’t try.
More than a decade after their diagnosis, Louise Benge and her siblings still return to the NIH for follow-up visits every year. Researchers continue to track how the disease progresses and look forward to potential treatments. Meanwhile, their participation is already helping to build a body of knowledge that has the potential to shorten diagnosis times for future patients. If someone walks into your doctor’s office one day complaining that their legs hurt and freeze after walking for a few minutes, they probably won’t be fired.
Unfortunately, for many rare diseases, a diagnosis does not necessarily mean there is a cure. But it increases understanding, and with that understanding comes hope that one day the condition will be treatable, other cases will be detected sooner, and new perspectives will unravel the mysteries of other diseases.
Alexandra Sifferlin is the health science editor for the New York Times Opinion Desk. This essay is from her new book, The Elusive Body, published by Viking, an imprint of Penguin Publishing Group, a division of Penguin Random House LLC. Copyright © 2026 by Alexandra Sifferlin.
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