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Written by Alison Proffitt
Paul Stamets has spent more than four decades in the forests of the Pacific Northwest, carefully excavating tissue samples from the undersides of some of the world’s rarest mushrooms. On the stage of February’s Integrative Health Symposium, that life of fieldwork converged with randomized clinical trials and Department of Defense contracts—a collision of ancient ethnobotany and 21st-century immunology that left the audience energized.
The longest-lived mushroom in the world
At the center of Stamets’ presentation was Agarikon (Fomitopsis officinalis), a conk mushroom that grows on ancient conifers in the Pacific Northwest and has been used medicinally for thousands of years in European and Indigenous cultures. He describes it as the longest-lived mushroom in the world, with individual specimens living 150 years or more. They are also on the brink of extinction, they are legally protected, and can only be harvested in small quantities from mature trees, he soberly noted.
Starting in the early 1980s, Stamets made it a personal mission to collect Agarikon strains before they disappeared. He now owns a genomic library of 118 different strains, a collection he describes as a “national treasure.” The strains are now being genetically sequenced and uploaded to a public database. “If there was a fire coming, this is the only thing I would save,” he said.
His entry into antiviral research came through a chance meeting in 1979 with Dr. Frank Perino, a medical virologist at the University of Wisconsin-Madison Medical School, who asked Stamets for samples of the fungus. Two decades later, in 1999, Peraino published research on a new antiviral compound—RC183—derived from those samples. This work caught Stamets’ attention and shaped the course of his research for years to come.
From financing bioterrorism to clinical trials of the Corona virus
The post-9/11 era proved an unlikely turning point. When bioterrorism came to the top of the US government’s radar, Stamets submitted extracts from agaricone, chaga, turkey tail, oyster mushroom, and other mushrooms to BioShield, a government-funded antiviral screening program supported by the Department of Defense and the National Institute of Allergy and Infectious Diseases. The program performed 2,392 tests on samples.
Of the seven Agarikon strains he introduced, three showed what Stamets described as “remarkable” antiviral activity against smallpox-related poxviruses, herpes viruses, and influenza strains including H1N1, H3N2, and H5N1. Russian virologists have also documented antiviral properties through independent work, he said (DOI: 10.17265/2328-2150/2015.08.001). in In the laboratory In recent tests, Agarikon extracts showed the ability to reduce plaque formation in cells infected with SARS-CoV-2, the virus responsible for the coronavirus (COVID-19).
Despite these findings, transferring research to clinical settings requires funding. The breakthrough came when he and his collaborators at the University of California, San Diego, led by lead researcher Gordon Sacks, designed two randomized, placebo-controlled clinical trials.
Two clinical trials, two surprising results
The first trial enrolled 90 patients receiving mRNA COVID-19 vaccines. Participants were recruited directly from hospital vaccination lines, Stamets said. Half received a combination of Agarikon and turkey tail mycelium (called FoTv); Half of them received a placebo. Participants in the treatment group reported a significant reduction in vaccine side effects — sore throat, headache, and muscle pain — compared to the placebo group.
What’s even more surprising, according to Stamets, is what happened to their antibodies. While antibody levels typically decline after vaccination, the treatment group showed persistent — and in some cases elevated — antibody titers at the six-month mark. The effect was particularly pronounced against the spike protein and its receptor-binding domain, which are the main targets of Covid immunity. The study was published in BMC Immunology (Digital ID: 10.1186/s12865-026-00809-9).
The second trial enrolled 50 patients who arrived at emergency rooms sick enough with COVID-19 to require hospitalization. Some have been vaccinated. Some were not. Everyone received the Agarikon and turkey tail combination for 14 days. Stamets reported a significant reduction in COVID-related symptoms across the group. The Agarikon-plus-turkey-tail group resolved symptoms about 10 to 12 days faster than the control group, he said.
“This is the first study ever to be conducted as a randomized, placebo-controlled clinical study using fungi to enhance the effectiveness of vaccination,” Stamets told the audience.
Türkiye tails, cytokine storms, and the FDA
The turkey tail (Trametes versicolor) has its own clinical lineage. Stamets described a phase 1 trial in breast cancer patients in which mycelium-based turkey tail extracts produced dose-dependent increases in CD8+ T cell counts. He also mentioned his mother, who was diagnosed with end-stage breast cancer in 2011 at age 84 and, by his account, significantly overcame her diagnosis while taking turkey tail mushrooms.
The Covid pandemic has presented a new complication: Some doctors have become wary of recommending immune-stimulating mushrooms to Covid patients, fearing that they may exacerbate the cytokine storms associated with severe disease. Stamets said the concern prompted him and his colleagues to publish research showing that mycelium — specifically the fermentable substrate form, not just the mycelium alone — stimulated the production of anti-inflammatory interleukins while reducing the pro-inflammatory interleukins associated with the cytokine storm. He said this data was enough to satisfy the FDA when his team sought approval to continue clinical trials of the coronavirus.
He noted that a separate randomized, placebo-controlled study found that turkey tail mycelium acted as a prebiotic in patients whose gut microbiota had been disrupted by antibiotics, helping to restore healthy bacterial populations within the microbiome (Digital ID: 10.4161/jmc.29558).
The next pandemic: H5N1 warning
Stamets closed with an urgent warning about H5N1 bird flu. He noted that the virus did something unprecedented in medical history: It jumped an unusually wide range of species, having been detected not just in birds but in pigs, cattle, sea lions, seals, big cats, and, in Washington state, in local wildlife populations. He said that mortality rates in human cases range from 47% to 50%.
“We will face a global pandemic again,” he said frankly. “Too many possible zeros for the patient.” He noted that the initial symptoms of H5N1 closely mirror those of COVID-19 — the main distinguishing feature being the absence of anosmia — suggesting that the two diseases may respond to similar immune modulation strategies.
Broad immune support, of the kind suggested by his research at Agricon, could be valuable precisely because it doesn’t target a single pathogen, he said. “You’re not just using your immune system, you’re going to customize it” to respond to emerging threats, he said. He also pointed to the growing library of strains as a potential resource: with 118 Agarikon strains now catalogued, he hopes to identify a “super strain” with maximum antiviral properties, though he suggested that the pool of strains already used in trials may already be sufficient.
Mycelium sizing
A recurring theme in Stamets’ talk was the practical advantage that mycelium holds over fruiting bodies for large-scale drug production. Unlike the fruiting bodies of mushrooms, which take months or years to form, attract insects and bacteria, and vary greatly in chemical composition, mycelium can be grown quickly, inexpensively, and continuously in controlled fermentation environments. “Scalability, affordability and profitability all fit together,” he said.
He likened the discovery to penicillin, noting that Alexander Fleming’s original mold extract could not be scaled up to commercial production until Mary Hunt, a laboratory technician, found a penicillin-producing mold on a cantaloupe discarded at a farmers’ market, producing a strain potent enough for mass manufacturing. He hinted that the lesson learned was that the correct strain was of great importance and that his library at Agricon might contain the equivalent of that cantaloupe.
Of the estimated 1.5 million species of fungi on Earth, there are approximately 120,000 species, Stamets said, and humans have experimented with cooking and medicinally perhaps 15,000 of them over thousands of years. This trial-and-error process has already done a lot of work, he noted, winnowing the candidates down to about 200 species that have clear health effects, and 10 to 20 species that have particularly compelling immune traits.
“Mycelium is nature’s immune system,” he said, describing how fungal networks produce antibiotics to ward off competitors, prebiotics to invite cooperating organisms, and complex chemical signals that shape entire ecosystems. “The potential of mycelium to aid cross-species immunity is potentially very great. I have spent my whole life getting to this moment.”
