Mark Smith was a microbiology graduate student at the Massachusetts Institute of Technology when, in 2011, a family friend became infected with the notorious superbug clostridium difficile. C. diff can cause severe diarrhea, disability, and malnutrition and is responsible for roughly 14,000 deaths in the United States each year. In 2012, after taking seven rounds of the antibiotic vancomycin and failing to improve, Smith’s friend received a DIY fecal transplant from his roommate—in their apartment, using an over-the-counter enema kit. The friend recovered within days, but “the whole thing was absurd, not at all how it should be done,” Smith said.
Fecal transplantation—transferring the feces of a healthy person into the bowel of someone with an infection—appears in published case reports as early as 1958. But in the past few years, scientists have established with more rigor that it can resolve recurrent C. diff infections around 90 percent of the time. In 2013, a randomized controlled trial published in the New England Journal of Medicine showed that the procedure worked better for this condition than antibiotics—so much better that researchers stopped the study early, saying it was unethical to continue to deny the transplants to the control group.
Within two to three days of the transplant, most patients are “symptom free …They get their lives back,” said Michael Edmond, an infectious disease specialist at Virginia Commonwealth University. It’s about as close to a miracle cure as medicine offers.
Yet access to fecal transplants has proven challenging. As recently as 2013, Amy Barto, a gastroenterologist at the Lahey Clinic in Massachusetts, said her patients had to find their own stool donors, whom the clinic would screen individually. On the day of the procedure, the donor had to provide a fresh stool sample, which Barto said she personally mixed using a blender from Target and transplanted into the patient’s colon. “It was embarrassing and stressful for patients to find their own donors, and expensive to have them screened,” she said. “I did about 100 procedures with the blender, and it was not efficient.”
In 2013, Smith and a college friend, James Burgess, decided to start a not-for-profit stool bank, called OpenBiome, providing pre-screened, frozen samples to doctors and hospitals. Smith’s MIT advisor, Eric Alm, offered guidance as well as a corner of his laboratory, and the team began to recruit donors, mainly among MIT and Harvard researchers. “When OpenBiome was established, my quality of life went through the roof,” Barto said. More importantly, access to the procedure “just blossomed.” More doctors were willing to get involved and patients were able to able to get the procedure more quickly, with fewer barriers and less expense.
One such patient was Natalie Jamil. In April, Jamil, then 25, discovered that a root canal she had had for years was badly infected. Her dentist extracted the tooth, treating her with antibiotics before and after the procedure. A week after she stopped taking the drug, however, she began to vomit and developed severe diarrhea, cramping, and pain in her joints. Jamil had recently taken a job as a secretary in Washington D.C., but “it became impossible to get to work, and I was asked to resign,” she said. “I was left with no job, no health insurance, and no tooth.”
Searching the web in desperation, she found Edmond. “I had lost over 25 pounds in two months,” Jamil said. “I was ready to do anything.”
In June, Jamil received the treatment using frozen stool from OpenBiome. Edmond administered the sample through a tube that threaded in through her nose and down into her small intestine. “It was like the flicker of a light,” she said. “The next day I was back on my feet. My stomach was calm. I wasn’t having diarrhea. It was like magic.”
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OpenBiome is similar in some ways to a blood bank, which also collects, screens, and distributes biological material. Early on, though, it became clear that the group faced different challenges in recruiting donors and testing samples. For one thing, few applicants qualified: Anyone who had had a gastrointestinal disease, recently used antibiotics, or traveled to any country with a risk of waterborne illness was rejected, even before their stool was analyzed for pathogens. It was sometimes awkward turning away MIT colleagues who wanted to contribute stool, Smith said, but “it helped to say, ‘Hey, I’m not eligible either.’”(Smith’s brother lives in Singapore and he visits there each year.) OpenBiome tests stool for an extensive list of pathogens, including HIV, hepatitis, and syphilis, which can be transmitted through bodily fluid. But they also screen for disorders, from obesity to metabolic syndrome to autoimmune diseases, that are not traditionally viewed as contagious but have been at least correlated with disturbances in gut bacteria. At a blood bank, no one worries that transfusions might make patients obese.
Rather than casting its net wide for donors, OpenBiome cultivates a small group of stalwart contributors. That way, the cost of testing, which can be roughly $1500 per donor, is spread over many patients and treatments. Contributors in this model make a major commitment. They are required to bring in samples within an hour of passage, since the bacterial composition of stool changes rapidly with exposure to air. “We have one guy who brings his samples in on [Boston’s T train],” Smith said. But for the most part, donors are students who live or work close by. When the project moved from Alm’s lab at MIT, this spring, to a new location near Tufts University, OpenBiome sought out a new cohort of dedicated graduate students. Their constancy also means the group can reassure doctors that the individual whose stool they are receiving has already cured numerous cases of recurrent C. diff—and has not caused new infections in any recipients.
“Their standards are incredibly high, and the testing they do is much better than what’s done in individual doctors’ offices,” said Edmond, who recently joined OpenBiome’s clinical advisory board. OpenBiome quarantines donors’ samples and retests them for pathogens after 60 days, since new infections, like HIV, can take time to show up on immunological tests. In addition, OpenBiome archives a portion of every sample, in case questions emerge down the road. “If I have a patient 10 years from now” with a virus that’s unknown today, “I can go back and see if it can be traced” to a stool transplant, Edmond said. “We couldn’t possibly have done that before.”
To date, OpenBiome has provided more than 930 samples to doctors and hospitals around the world. “There is nothing else like them in the country or anywhere else, as far as I know,” Rob Knight, a microbiome expert at the University of Colorado, Boulder told me. Not only are they making the procedure more accessible, they also have the potential to collect large-scale data on outcomes. And they can support research by providing standardized, well-characterized samples to scientists.
“That is an absolutely critical piece of the puzzle,” Knight said, since, for all the enthusiasm, researchers have yet to understand how, exactly, the treatment works. Like Jamil, most patients have undergone antibiotic therapy recently for another condition. Those antibiotics “start killing off good bacteria, then C. diff takes over and produces a toxin that causes the diarrhea,” Edmond said. Fecal transplantation reestablishes a healthier community of bugs that seems to drive out the C. diff or hold it in check. The approach is both holistic and rudimentary.