Nearly $7 million of that grant money is now suspended, a victim of federal cuts targeting Harvard. Other rare-disease patients living without a diagnosis are being left without any answers -- about their disease, but also about whether their case is being researched at all.
"You're always scared as an undiagnosed patient that people won't believe you," Sarah Marshall said. "It's this visceral fear of being dismissed, gaslighted, questioned, like, maybe this is your fault."
Phoebe, now 17, is one of more than 8,000 patients who have applied to the Undiagnosed Diseases Network, a research group coordinated through Harvard Medical School, in a last-ditch effort to find the cause of compounding health issues. The group is made up of clinical and research experts nationwide who collaborate to solve complex cases, often using advanced genetic techniques.
Originally started as a program at the NIH, the network, known as UDN, is considered a massive success. NIH director Dr. Jay Bhattacharya highlighted it in his recent budget justification letter to Congress, advocating for expanding the program.
"We really do think that the UDN should be funded, and we were excited to see that in [Bhattacharya's] letter," said Michele Herndon, program director of the UDN Foundation whose son was a patient of the network. "But the practicalities of, 'How does the network get the money with this Harvard freeze?' That's the unanswered question."
UDN discovered the genetic mutation responsible for her son's never-before-seen neurological disorder, now named after him: Mitchell Syndrome. Mitchell ultimately died from his disease in 2019 at the age of 19.
Only part of the UDN's funding has been stymied, as other grants supporting some of the network's 24 clinical sites haven't been touched. But the UDN's data management coordinating and model organism screening centers, which assure patients are connected with the right scientists and conduct animal-based research, are funded through grants to Harvard.
The consequences of the cuts extend far beyond Massachusetts. Much of the lab work done for the UDN takes place at other universities, the spokes to Harvard's hub. Those schools -- including Baylor College of Medicine in Houston, Washington University in St. Louis, and the University of Oregon -- had their UDN funding withdrawn seemingly overnight. Their research into new cases stopped.
Meanwhile, Harvard and the Trump administration are negotiating a deal that could result in the reinstatement of some NIH funding, although the details are unknown. Even if a deal is reached, it's unclear how quickly the funding spigot would turn back on.
The NIH did not immediately respond to a request for comment.
The UDN doesn't have a list of the patients whose care is getting caught up in the funding freeze. The type of testing required by each patient is individual and can change, so knowing who will be affected by the cuts is difficult.
Those who already received their diagnoses, however, offer a glimpse into what is being lost as other patients' cases gather dust on desks in Houston, St. Louis, or Eugene.
Each day without answers represents more pain, more hospital visits and, for some, less time to race against a disease's clock to find life-saving treatments.
"Even if there isn't a cure immediately, just knowing what's wrong helps the families mentally or emotionally," said John Postlethwait, a scientist who conducts UDN research using zebrafish at the University of Oregon. "It's a huge relief."
The Marshalls understand that better than anyone.
The problems started when Phoebe was an infant.
She was in and out of doctors' offices constantly. She had pneumonia at 6 months, cried about ankle pain as a toddler, and was hospitalized for what her doctor called "the most massive sinus infection he's ever seen in a 2-year-old," Sarah said.
The Marshalls quickly racked up a long list of doctors who took a swing at solving Phoebe's problems: a rheumatologist, an immunologist, an ear, nose and throat doctor, and an infectious disease specialist.
Meanwhile, Phoebe was collecting a long list of diagnoses that defined her symptoms but didn't explain why they were all happening to her.
Black spots clouded Phoebe's vision. The blood vessels in her retina were inflamed, the result of an autoimmune condition. She was diagnosed with low antibody levels in her blood that rendered her more susceptible to infections. And at age 8, she was told she had myasthenia gravis, a disease that causes muscle weakness.
Extra bone built up in her spine, her liver was inflamed, and scar tissue-like adhesions formed between organs in her abdomen. She had kidney stones, sudden hearing loss, and a skin condition triggered by sun exposure. Phoebe suffered through surgeries and hospitalizations multiple times a year.
Almost immediately, Sarah thought that Phoebe's symptoms must be related. How could one person have so many medical problems at such a young age?
"It's only after you see several specialists that don't have answers that you're like, 'Oh, maybe there's not a diagnosis,'" Sarah said.
Then she learned about the UDN from the parent of an undiagnosed child.
With the help of Phoebe's doctors in Minnesota, Sarah applied for her daughter to be a part of the program, crossing "all my fingers and toes." The family flew from their hometown of Eden Prairie to Boston for a week in 2017 to see specialists at Harvard, Boston Children's, and Massachusetts General Hospital.
The doctors confirmed what Sarah already knew: Phoebe had great medical care in Minnesota, but her condition was dumbfounding. They ordered a full sequencing of Phoebe's genome.
"That, to me, is what sets the UDN apart from every place else, even when you live in the best areas with the best resources," Sarah said. "Because if medicine doesn't have an answer for you, the UDN might."
The researchers found a clue -- it was tiny but something to grab onto. She had a "variant of unknown significance" on GDF11, a gene that dictates the production of protein that's important in skeletal and nervous system development.
In order to figure out whether those gene abnormalities explain a patient's symptoms, scientists in partnership with the UDN use a form of testing called model organisms.
They take flies, zebra fish, and nematode worms -- three animals that reproduce quickly and have structures similar to humans -- and alter their genomes to mimic that of a specific patient. If the animals experience similar symptoms following the genetic modification, the scientists have evidence that the gene in question could be responsible for causing those symptoms in humans.
Phoebe's case looked promising.
Researchers at Baylor College of Medicine altered flies to have the same change to GDF11 that Phoebe has. Researchers at the University of Oregon did the same in zebrafish.
The researchers also studied five other patients who had slightly different changes to GDF11. Together, their results showed the gene mutations were likely causing at least some of Phoebe's symptoms.
Knowing the cause of a disease is critical, but it can only do so much for a patient without management options on the other side.
After Phoebe's GDF11 mutation was confirmed, she was still experiencing painful abdominal adhesions.
Every six to eight months, Phoebe underwent surgery to cut away the scar tissue sticking to her organs. What would typically be a same-day procedure resulted in a five- or six-day hospital stay for Phoebe. She became so weak after each operation that she couldn't move or feed herself.
Researchers at the University of Alabama at Birmingham, also affiliated with the UDN, were looking at how the GDF11 gene influenced inflammation in the body. They suggested to Sarah that Humira -- a drug commonly used to treat rheumatoid arthritis and other autoimmune diseases -- could calm down her overactive inflammation.
Since starting the treatment four years ago, Phoebe hasn't required a single surgery to break down the adhesions. She largely lives like a normal teen -- she works at a summer camp, she has her driver's license, and she plans to go to college to study social work.
The medication has been life-changing, said Sarah, who now works for the UDN Foundation as its program development manager.
Not every patient is so lucky. Some come to the UDN after their disease has already progressed too far to be stopped. Others find their disease is the result of a genetic mutation so rare that scientists haven't identified any potential treatments.
Still, each evaluated case adds to the scientific literature that can help other researchers understand how human genes work, with far-reaching implications.
"These are significant opportunities. To me, it's an investment, because you essentially are able to figure out the function of a gene in a real person from these rare mutations," said Hugo Bellen, who leads the fly model organism lab at Baylor.
Bellen, Postlethwait, and the other researchers who make up the UDN's model organisms teams have continued to meet to discuss new cases. Baylor's team managed to find some temporary private funding to continue their work, but the other model organism sites are stalled. They can't begin any experiments without the funding from Harvard's coordinating center.