In 2019, years after developing the myalgic encephalomyelitis (ME/CFS) that had kept her bedridden in a state of chronic pain and exhaustion, Tamara Romanuk experienced something “miraculous”. After taking antibiotics prescribed to treat a separate infection, she experienced a short-term remission in symptoms. “I went from being bedbound to twirling outside,” Romanuk says. “I had no idea that life could be so different from what I’d become adjusted to.”
Sharing her experience online, Romanuk, a former biology professor, discovered that she wasn’t the only person who had had this experience. Both she and Tess Falor, an engineer with a PhD, had developed ME/CFS years before and had picked up a bacterial infection that required antibiotic treatment. Doctors had advised them to take probiotic supplements to help the microbiome recover. Afterwards, both experienced a dramatic remission in ME/CFS symptoms. They called it a “remission event”. Romanuk and Falor have named their project to investigate the experience the RemissionBiome.
Many patients with complex chronic illnesses are dismissed by doctors who don’t believe in their symptoms or disease even when it leaves patients bedridden. Romanuk was initially diagnosed with “conversion disorder” by a doctor who thought the symptoms were psychological.
ME was recognised as a neurological disease by the World Health Organization in 1969. However, in the 1970s some researchers labelled it as hysteria, leading to the US Centers for Disease Control to rename it as chronic fatigue syndrome (CFS). The name was changed to ME in 2015 to help legitimise the symptoms and experiences of patients. Still, the medical stigma persists. Conditions such as ME disproportionately affect women, whose symptoms and concerns are often ignored by doctors.
Many patients with long Covid face similar challenges. Since 2020, an estimated 1.8 million people in the UK have developed long Covid after a Covid-19 infection. The debilitating condition is known to cause more than 200 symptoms. The most common include a loss of smell, brain fog, exhaustion, pain, exercise intolerance and a susceptibility to infection. Coincidentally, long Covid shares many symptoms with ME/CFS, including chronic pain, exhaustion, brain fog and exercise intolerance.
Research into these conditions is moving at a snail’s pace. Between 2007 and 2016, only £10m of UK government funding was doled out for the study of ME/CFS, which affects at least 250,000 people in England and Wales. And just £50m in government funding has gone towards long Covid research. StatNews highlighted the lack of progress in the US, in spite of $1bn in funding. Meanwhile, other funded studies around the world are testing treatments that have already been established as harmful and ineffective for long Covid and ME/CFS: cognitive behavioural therapy and graded exercise.
Linda Tannenbaum, a clinical scientist who founded the nonprofit Open Medicine Foundation to help fund research into diseases such as ME/CFS and long Covid, calls these trials ridiculous. She says that the researchers behind the new studies are “picking up on old research and old information” and that “if they took a look at what is out there and really studied the information in literature, they’d see that that is harmful to patients and not helpful”. These treatments boil down to the idea that the symptoms associated with these complex diseases aren’t real, ignoring the body of evidence that links them with viral infections.
“Unfortunately, a body of folks who review the grant applications are very committed to the idea that postviral illness is largely psychogenic,” says Dr David Putrino, a professor at the Icahn School of Medicine at Mount Sinai in New York and a leading expert in postviral illnesses. Let down by doctors and a lack of funding for their disease, some patients are taking science into their own hands.
***
“The main goal is to see if we could recreate the dramatic remissions and baseline increases [in daily function] that we had both experienced,” says Falor. While the dramatic improvements usually only last a few days, Falor and Romanuk experienced some longer lasting effects. “The RemissionBiome project quickly grew organically, motivated by the dream that we could make these remission events more likely to occur for other people.”
After dozens of interviews with scientific experts, Falor and Romanuk formed a hypothesis. An initial viral infection dysregulated their immune system, leading to some of their symptoms. But modifying the immune system itself is hard. Instead, Falor and Romanuk focused on the gut microbiota – trillions of commensal bacteria, viruses and fungi – shown to regulate aspects of the immune system throughout the body and the brain.
The approach is similar to the more widely reported faecal microbiota (or more colloquially, poo) transplant, which involves delivering healthy microbes to reshape the microbiome. This treatment is already approved for recurrent Clostridioides difficile infection and researchers are testing how well it treats a variety of conditions involving the immune system. For example, scientists are now testing whether the right faecal microbiota transplant could help treatment-resistant melanoma patients respond to drug regimes.
While Falor and Romanuk aren’t able to perform a faecal microbiota transplant themselves, perhaps a mix of antibiotics and gut supplements, they thought, could reset their microbiome. By taking blood and microbiome samples along the way, and partnering with other researchers and biotechnology companies, RemissionBiome hopes to recreate and characterise the “remission event”.
Four people with ME/CFS and one with long Covid who were prescribed antibiotics for infections got in touch with the RemissionBiome team and were able to participate in the experiment. This would be their first attempt at achieving remission. Falor and Romanuk were part of the experiment and attempted to achieve their second “remission event”.
Five people achieved the short-term “euphoric-like” feeling of a full “remission event” for the first time. Falor experienced her second “remission event”. When the symptoms returned a few days later, they were noticeably less severe than before. While Romanuk’s first “remission event” years ago was successful, this time around she only experienced a baseline reduction in symptoms.
Thanks to a grant awarded by the Balvi Filantropic Fund, directed by Ethereum co-founder Vitalik Buterin, the RemissionBiome team is aiming to run a more rigorous trial involving dozens of participants. The team is not publicly releasing the protocol until they’re certain it’s safe. “We do not want people trying to do it themselves,” says Falor.
Intriguingly, research has recently come out supporting the gut-brain connection in ME/CFS. Two studies funded by the National Institutes of Health in the US found a unique microbiome signature in ME/CFS. Certain gut bacteria and their signalling molecules were associated with the disease.
“Many patients are extremely sick and want to feel better now,” Falor says. “They don’t want to wait for researchers to get grants, take years sometimes to run the studies and then months to years to publish the results.” Although she admits there is a risk in undertaking these projects, including the chance that symptoms may worsen, she believes the results can be “life-changing”.
Romanuk explains that the majority of clinical trials for ME/CFS, and other postviral conditions, test a single intervention, compound or drug treatment in a small, defined patient population. This lets researchers tease out potential mechanisms, treatments and side-effects. But the problem is that there isn’t a surefire way to stratify people with ME or long Covid when there are so many different symptoms. Even though the protocol isn’t one specific antibiotic or probiotic, and although the participants in RemissionBiome all had different symptoms to start with, their “remission events” felt similar. The early data collected will help refine the experiment for future participants.
***
Falor and Romanuk have been on the receiving end of an unfair double standard they feel is applied to patients with chronic illnesses. People trying to find the best ways to manage their condition are told that their work is “unethical”, “bad science” or “narcissistic”. Many people don’t have the option to wait for a research breakthrough – postviral conditions such as long Covid and ME may result in substantial disability, leading to job loss, and could strain or even break up families and relationships.
But “biohacking” is socially acceptable for otherwise healthy individuals even when it promotes wrong or pseudoscientific ideas. Podcast hosts such as Andrew Huberman advertise brain-boosting supplements that lack proven clinical benefits. Tech billionaires such as Bryan Johnson glorify pseudoscientific treatments to de-age the body – which researchers point out is nothing more than “tech bro bunk”.
In contrast, patient-researchers, who are often women, face criticism. Lisa McCorkell is the co-founder of the Patient-Led Research Collaborative, which was founded in 2020 and did some of the first research on long Covid and similar conditions. The collaborative consists of researchers from across the sciences who help advise and shape research into postviral conditions. “We deserve more credit when we experiment with treatments,” McCorkell says. While some people might have initial misgivings about others self-experimenting with treatments, when done in a safe manner McCorkell believes it “warrants more acceptance”.
One way people can understand the benefits and side-effects of drugs and supplements is by connecting with patient-researchers on Twitter. One account set up by a pharmacist with long Covid runs large patient surveys online about different supplements patients are taking or trying for their symptoms. This provides people with an idea of how many patients trying to manage their condition have benefited from taking a specific supplement. Putrino points to a recent nattokinase (an enzyme supplement) survey, explaining that this kind of work provides the preliminary evidence that this treatment may be worth a closer look.
Others are participating in exploratory research online. For example, people with long Covid are testing their blood lactate in response to peer-reviewed publications linking high levels with the disease. Some people are trying interventions to lower their lactate levels to see whether it improves their symptoms, sharing their experiences online along the way.
“Anyone who is minimising that sort of work fundamentally doesn’t understand levels of evidence in science,” Putrino says. “Understanding that no data is to be minimised is a fundamental aspect of clinical science. It gives us inspiration for the clinical trials that should be run.”
“When healthcare providers can’t give treatments and when research is going slowly or barely exists, it is not surprising that people who have extremely debilitating symptoms and impacts to every aspect of their life are going to start researching on their own,” McCorkell says. “We become experts not because we necessarily want to but because we have to in order to have a chance at recovery.”
All the advocates and researchers emphasise caution and suggest ways to make self-experimentation a safer experience. “You need to understand the potential risks and benefits of any treatment you try,” says Lauren Stiles, an assistant professor of neurology at Stony Brook University, New York, and the president of another patient-led research advocacy group called Dysautonomia International. “Talking to medical professionals and reading journal articles about the treatment, good and bad, can help you understand the potential risks and benefits.” Dysautonomia International focuses its advocacy on people with autonomic nervous system disorders – such as postural orthostatic tachycardia syndrome, which may cause people to faint when standing up. (Many long Covid patients develop these disorders as well.)
There is a risk that desperate patients could be preyed upon by hucksters with expensive, ineffective and sometimes dangerous treatments. “They claim their treatment works for a long list of complex diseases,” Stiles warns. “They rely on testimonials to prove their product works, rather than rigorous clinical trials.” Many patient-led groups help vet and share problematic treatments.
Working with others as part of a collaborative effort can help patients better understand potential risks and benefits of different treatments, according to Putrino. “Reach out to the community and do things with the community because you can be part of something larger,” he says. Putrino also suggests finding a doctor who is ready to work with and support patients as they try to improve their symptoms, if possible. That way if anything goes wrong, the doctor will be able to take immediate action.
“The reason why patient-led is so key is about the extreme motivation and desire to find solutions today and not tomorrow,” Romanuk says. “It’s not just ME/CFS; I believe that patient-led research will ultimately make the difference for other neglected diseases and rare diseases.”
• This article was amended on 10 July 2023 to add the information that ME was recognised as a neurological disease by the World Health Organization in 1969. Also, a previous version said the UK government provided £10m of funding into ME/CFS research annually; this figure is actually the amount spent between 2007 and 2016.
