For decades, five siblings in rural Kentucky were slowly turning to stone. After walking for just a few minutes, their legs would painfully freeze up, as if turning to rock — an agony no doctor could explain.
By the time the eldest sibling, Louise Benge, reached her 50s, she had come to believe that medicine might never figure out what ailed her family. After years of inconclusive check-ups and exams, her doctor eventually referred her to a program at the National Institutes of Health devoted to cracking the most challenging medical mysteries: the Undiagnosed Diseases Program.
What followed — a series of appointments and investigations involving multiple specialists of different disciplines — led to the discovery of an entirely new disease. The siblings were found to have arterial calcification due to deficiency of CD73, which they call ACDC for short. The condition causes calcium to quickly accumulate in the arteries of the legs, hardening blood vessels and making walking increasingly painful and difficult.
The family became the Undiagnosed Diseases Program’s first novel disease discovery in 2011. Since then, the initiative has expanded into the Undiagnosed Diseases Network (UDN), a constellation of clinics at leading academic medical centers across the country that aim to solve the most baffling diagnoses. Led for years by the longtime NIH physician-scientist William Gahl, the network has received more than 8,400 applications, evaluated over 3,500 patients, and delivered diagnoses to more than 1,000 people with rare or previously unknown conditions.
Its mission is not only to solve individual medical mysteries but also to use those discoveries to illuminate a broader understanding of disease. Considering the turmoil of the past year at the NIH, the UDN is lucky to still be kicking.
But it’s not enough that it should merely survive. It should serve as a model to emulate at even more medical and research centers all over the country.
At a moment when federal science funding and rare disease research feel increasingly vulnerable to political shifts, the Undiagnosed Diseases Network represents the kind of high-risk, high-reward, mission-driven work the NIH should always back. It’s an appealing, bipartisan-supported approach to federally funded research: focusing on diseases that are too rare to attract major pharmaceutical investment, yet capable of yielding insights that benefit millions.
For many Americans, the UDN functions as a clinic of last resort. Most people who reach out to Gahl do so after exhausting nearly every other option and cycling through multiple specialists and medical centers. Rare diseases are by nature less familiar to health care providers, which means patients often endure long periods of misdiagnosis, imprecise treatments, and extensive testing. “Many go a long time without a diagnosis,” Gahl told me when I was reporting for a book on diagnosis. “Some people even experience doubt about whether they’re truly ill.”
People accepted to the network travel to one of its clinical sites (such as the NIH in Maryland, Baylor in Texas, or Stanford in California), where a team of experts, including geneticists, neurologists, vascular specialists, and more, have already reviewed their medical record. They undergo multiple physical exams and genetic testing, sometimes alongside family members, while clinicians collaborate to piece together the puzzle. The work is done as research, meaning patients receive access to advanced diagnostic tools at no cost. Participants’ travel, meals, and lodging expenses are also typically covered.
The model stands in stark contrast to what many people experience in the traditional health care system, where appointments are often brief or siloed and care is expensive. “I believe the commodity that we have that many other physicians in practice don’t is the time to sit and really sink our teeth into the information,” Camilo Toro, a neurologist at the NIH who works with the program told me.
Roughly 1 in 10 Americans lives with a rare disease. While each condition may affect relatively few people, collectively rare diseases impact tens of millions of patients. Many remain undiagnosed for years, sometimes decades.
Government support is essential because these diseases don’t often attract commercial investment for therapies and cures. But the work the UDN has done can also reveal fundamental biological mechanisms that help scientists understand far more common illnesses.
Scientists are using what they’ve learned from Louise Benge and her family to inform the collective understanding of more common vascular conditions, including peripheral artery disease, which affects an estimated 8 million Americans ages 40 and older.
The mission of the Undiagnosed Diseases Network has historically attracted support across the political spectrum. The network has been defended in the past by lawmakers such as former Republican Sen. Roy Blunt of Missouri, who recognized its value and pushed back against the Biden administration’s FY23 budget proposal that would have allowed the network’s funding to wind down. “I think it would be a problem to walk away from that,” he said during a subcommittee appropriations hearing. Current NIH Director Jay Bhattacharya has spoken about wanting his agency to function as an innovation accelerator and to “turn the investments that we make in biomedicine into better health for Americans.” Few programs embody that goal more clearly than the UDN.
Even before recent debates over federal science funding, there have been years when those involved with the network worried about its future. The fact that the network continues to operate is an encouraging sign. The Trump administration, which decimated scientific research through its poorly conceived U.S. DOGE Service initiative, has at least signaled support for rare disease research, including launching frameworks for getting patients of ultra-rare diseases access to individual therapies (though patients have been frustrated by recent rare disease drug rejections).
Still, one of the most important features of the UDN is not just its access to advanced diagnostic technology. In interviewing families that participated in the program at the NIH for my book, I was struck by how often people mentioned the way the clinicians and scientists made them feel versus the tools or tests they used.
This doesn’t mean empathy matters more than resolution — I’m pretty certain most people would value relief over a doctor’s personality. But the attention and empathy clinicians at the UDN devote to each patient are critical parts of its success. Solving difficult medical cases matters, but so does the trust the process restores in a health system many patients experience as rushed, fragmented, and indifferent.
“They never gave us false hope, but they promised to try everything,” Phil Lueken, whose daughter Olivia was diagnosed through the network in 2019 when she was 21 years old, told me. They had begun their search for answers when Olivia was in preschool. “They genuinely cared. Of all the places we went, it was the most personal.”
Olivia was diagnosed with a rare neurological condition called KMT2B-related dystonia, also known as Dystonia 28. Before she arrived at the UDN, her condition had progressed to the point that she could barely move and had lost the ability to speak. For years, her parents wondered how much of their daughter had been lost to the disease.
After receiving a diagnosis through the UDN, Olivia underwent deep brain stimulation surgery. The procedure improved her ability to move and communicate. “It turns out Olivia had the same hopes, dreams, and thoughts as other children,” Phil said. “Her mind was intact. She can now sign enough of her thoughts that she can share her life with us.”
The UDN should not be an outlier in medicine, but a model for more such clinics at hospitals around the country. Clinics dedicated to solving complex diagnostic cases, including rare genetic disorders as well as other conditions that have stumped doctors, would give physicians a reliable place to send patients when traditional approaches fail. Not because doctors are abandoning difficult cases, but because not every medical provider has the time (especially those working in urgent care or the emergency room) or collaborative infrastructure needed to solve them. Ideally, these clinics would be staffed by full-time, multidisciplinary teams, enabling longer appointments, more centralized care, and faster, on-site consultations across specialties. That kind of investment could also go a long way toward rebuilding trust between patients and the health care system.
All of this, of course, might feel impossible given the current health care system’s troubles. But just because something is difficult doesn’t mean we shouldn’t try.
More than a decade after their diagnosis, Louise Benge and her siblings still return to the NIH for yearly follow-up visits. Researchers continue to track how their disease progresses and hope for potential treatments. In the meantime, their participation has already helped build a body of knowledge that may shorten the diagnostic journey for future patients. If someone walks into a doctor’s office one day complaining that their legs painfully freeze after a few minutes of walking, perhaps they will not be dismissed.
Unfortunately, for many rare diseases, getting a diagnosis doesn’t always mean there’s a cure. But it builds understanding, and with that understanding comes hope that one day the condition will be treatable, that other patients will be found faster, that a new perspective will break open the mysteriousness of other diseases.
Alexandra Sifferlin is the health and 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.
