Amanda Twinam searched for answers as to why she had low energy levels for years—following suspected illness with mononucleosis in high school and two separate breast cancer diagnoses as an adult—but feels she is closer to a resolution now after she started corresponding with a researcher at the National Institutes of Health (NIH) who subsequently studied her and her family.
Twinam, a lawyer based in Albany, New York, knew something was wrong at a young age, after a bout of mono, she told The Washington Post. In college, she never felt that exercise gave her the boost it did for other people. Instead, after working out, she said she “felt like garbage”.
She was first diagnosed with breast cancer as a 28-year-old, and her treatment plan included chemotherapy and a mastectomy. Her medication triggered seizures and made her ill; for this reason, she sought out a rheumatologist, who eventually discovered a marker that signifies an autoimmune disease in her blood.
Doctors diagnosed Twinam with a genetic cancer disorder called Li-Fraumeni syndrome in 2015, at age 44. Shortly after that, she was diagnosed with breast cancer for the second time and had another mastectomy.
Throughout decades of debilitating symptoms, doctor appointments, and diagnoses, Twinam never felt she had a solid answer as to why she felt the way she did. “Fatigue was my primary complaint, sometimes my only complaint,” she said. “But no one knew what to do.”
She eventually had to quit working full-time, as her symptoms made it too hard to keep up with her legal cases and raise her daughter, Paige, at the same time.
“I was a decreasingly functional human and had no great explanation for it, which made me feel crazy,” Twinam said. “Doctors didn’t know what to do with me.”
Twinam even got another degree in the hopes that it would help her understand what was wrong with her body; she received a master’s in public health in between her two breast cancer diagnoses. “I was genuinely more excited when I got a 100 on a biology midterm than when I passed the bar,” Twinam said.
Then, years after she first started experiencing symptoms, Twinam discovered something interesting while reading new medical research on Li-Fraumeni syndrome published by NIH researcher Dr Paul Hwang. She theorised that the type of Li-Fraumeni syndrome she had could be due to problems with the mitochondria of her cells. Specifically, she wondered if they could be robbing her of adequate energy levels.
She sent Dr Hwang an email that began, “I read with interest your recent article on inhibiting mitochondrial respiration in a mouse model of Li-Fraumeni Syndrome,” but Twinam said she didn’t even know if he would respond. “I had zero expectations,” she said. “Here’s me sending an email to this fancy science researcher who isn’t going to give me the time of day.”
But he did respond and suggested that she might be right. “Yes, I agree with you, it is possible that” you’re correct, Dr Hwang wrote back.
“Amanda showed up and she challenged us,” Dr Hwang told The Washington Post. “So we dug.” As it turned out, their initial hypothesis wasn’t correct. But Dr Hwang and his team continued to study Amanda, and even her brother and father, who had the same gene for Li-Fraumeni syndrome. Dr Hwang used genetically modified mice, dubbed “Amanda mice”, to further his research.
After extensive study, they noticed that Twinam’s body seemed to be producing more than the normal amount of a protein called WASF3. This protein, they discovered, was plugging up the process by which her body was trying to produce energy.
“It’s really striking,” Dr Hwang explained. Mice who were bred to reflect Twinam’s illness—and made too much of the same protein—were found to walk on a treadmill far less than healthy mice.
When Dr Hwang broadened the number of people he was studying, he learned that many with this particular issue had a condition called myalgic encephalomyelitis or ME/CFS. Twinam was subsequently diagnosed with the disorder, and she finally had a name for the condition that was causing her fatigue.
“There’s this difference between cancer and chronic fatigue syndrome,” she said. “Everybody believes you when you have cancer. You joke about having a ‘cancer card’ to get off from doing things.” Twinam didn’t find the same support and sympathy when she was dealing with ME/CFS symptoms, she added. “No one is handing out CFS cards. [But] I can finally say, ‘It’s not psychological. I’m not a malingerer.’ We now have a scientific explanation.”
Dr Hwang’s research on Twinam’s condition was published in the journal PNAS in August, and experts say his findings are important, given that little research on ME/CFS exists. They’re also particularly timely since ME/CFS has been linked to long Covid.
A report published in June in Frontiers in Medicine suggested that research on one is potentially applicable to the other. “The often-similar findings suggest that insights into each disorder will have implications for the other,” the authors of the analysis wrote. “We urge that investigators studying the underlying biology of [long Covid] take note of the robust findings in ME/CFS that have not yet been investigated in [long Covid]...it is likely that pursuing such abnormalities in long Covid will prove instructive.”
Long Covid is a common complication of infection with SARS-CoV-2: A 2022 report from the Centers for Disease Control and Prevention (CDC) found that one-fifth of people aged 18 to 64 who were infected with the virus eventually developed symptoms. As many as one in four people 65 and older developed symptoms, the report found.
Dr Hwang is now focused on curing ME/CFS, and says this goal is what keeps him going. His team of four scientists is planning a clinical trial to determine whether a drug that’s new to the market may help patients with the condition.
Both Dr Hwang and Twinam say they’re grateful for the coincidences that led to Twinam’s diagnosis. “Amazing findings in medicine,” Dr Hwang explained, “are sometimes based on one patient.”