When Carolyn Edelstein’s friends and family gathered for Thanksgiving in 2012, the conversation kept turning to feces.
Ms. Edelstein, a graduate student at Princeton University’s Woodrow Wilson School of Public and International Affairs, had recently seen a close friend suffer through an infection with Clostridium difficile, a bacterium that can cause severe and sometimes fatal diarrhea. After several rounds of antibiotics failed, her friend finally turned to an experimental treatment: a stool transplant.
The procedure is just what it sounds like. Fecal material from a healthy donor is placed into the patient’s intestines via colonoscope, enema, or a tube routed through the patient’s nose.
That line of talk would bring most Thanksgiving meals to an end. Not in this case. One of the guests was Mark B. Smith, a graduate student in microbiology at the Massachusetts Institute of Technology whom Ms. Edelstein had met in 2007, when they were both undergraduates at Princeton. Mr. Smith performs computational analyses of the genetic material in gut bacteria, and he had long been fascinated by the basic science behind stool transplants.
He was alarmed to learn that day about the severe logistical barriers that Ms. Edelstein’s friend and his doctors had faced in getting a transplant done. The Food and Drug Administration requires masses of paperwork. Few laboratories are equipped to screen would-be donors’ stool for the vast array of viruses, parasites, and other conditions that might make their feces too dangerous to transplant. And most hospitals simply don’t have protocols in place for stool transplants. The gears in Mr. Smith’s mind started turning.
By the end of the weekend, the two graduate students and James Burgess—another friend from their Princeton days—had hatched a plan. They would open the world’s first public stool bank, offering prescreened, frozen fecal specimens to hospitals around the country. What the Red Cross has done for blood, their project—known as OpenBiome—would do for feces.
“I have a picture in my mind from that dinner,” Ms. Edelstein says. “Mark was talking to my grandfather, who’s a lawyer, about how to make this happen. My grandfather was very skeptical at first, but then he started to get excited. He was hammering Mark on the regulatory and liability issues, trying to see if we were serious.”
They were. Mr. Smith spent the first half of 2013 negotiating permissions with the FDA and securing lab space at MIT.
Ms. Edelstein, meanwhile, drew on her past experience as a program assistant at the U.S. Agency for International Development to help write proposals for funding. Once those elements were in place, Mr. Burgess took a leave from his studies at MIT’s Sloan School of Management to serve as OpenBiome’s full-time director. They also brought in a fourth principal, Emir Sandhu, an elementary-school friend of Mr. Smith’s who is now a medical student at Harvard University, where he has worked with C. diff. patients.
The bank started to collect stool in September and shipped its first specimens a month later. As of late January, OpenBiome had sent a total of 109 fecal specimens to 12 hospitals and clinics. “When we sent our first shipment, I was nervously emailing the clinician every day, asking how the patient was doing,” Mr. Smith says. “We haven’t heard of any failures or adverse outcomes so far.”
“If you’d told me a year earlier that I’d be leaving school to run a nonprofit stool bank, I wouldn’t have believed you,” Mr. Burgess says. “But I think this is an opportunity to make a real dent in the C. diff. epidemic, and also to move forward with the science of the human microbiome.”
Logistical Hiccups
To understand why a stranger’s feces might cure C. diff. illness when antibiotics have failed, you must first understand how the disease arises. Roughly 3 percent of the population (and perhaps as much as 15 percent of the elderly population) carries the C. diff. bacterium. The organism usually lives benignly in the gut; it makes trouble only after the carrier undergoes chemotherapy, antibiotic therapy, or some other disruption to the gut’s normal ecology. When that happens, C. diff. can run wild, causing long days of watery, green-tinged diarrhea. (Roughly 14,000 Americans, most of them elderly, are estimated to die from the illness each year.)
Fecal transplantation resolves C. diff. illness by restoring a healthier ecosystem to the patient’s gut, undoing whatever insults were done by chemotherapy or antibiotics. The idea is not new—as early as 1958, a team of doctors in Denver reported a successful treatment—but it has gained much more attention during the last decade, as C. diff. infections have become less susceptible to vancomycin and other typically used antibiotics.
“Ten years ago, eight years ago, we didn’t have this enormous number of people with recurrent infections,” says Colleen Kelly, a clinical assistant professor of medicine at Brown University, who is one of the country’s best-known practitioners of stool transplant. “Now you’re seeing patients who go through vanco after vanco after vanco, and they still aren’t cured.”
When Dr. Kelly performed her first transplant, in 2008, the idea seemed slightly outlandish to her. (She was talked into it by a patient who’d read about the procedure in medical journals.) But when she saw how powerfully it worked, she got hooked. She is now overseeing an NIH-financed randomized double-blind trial in which some patients receive actual stool transplants and some receive “sham” transplants in which their own stool is reinstilled.
So far, Dr. Kelly has not used any of OpenBiome’s specimens. But she says that such a service has been badly needed because many physicians who want to perform transplants have found the hurdles overwhelming. In addition to the paperwork and shortage of qualified labs, there are plain old logistical hiccups.
“A patient dropped out of my current study because the day of her procedure, the donor wasn’t able to poop,” Dr. Kelly says. “If you have a study patient who’s there, prepped, on the colonoscopy table, and you don’t have the study treatment to administer to them because the donor can’t poop—I mean, it’s not as predictable as urinating in a cup.” For that reason, she says, a service that can reliably provide frozen specimens is deeply appealing.
Unanswered Questions
That is the heart of OpenBiome’s pitch. “All of those petty logistical issues are what we deal with at the end of the day,” Mr. Burgess says. “We want to allow doctors to do what they do best, which is focus on treatment.”
So far, OpenBiome’s infrastructure is modest. Mr. Burgess is the project’s only full-time employee. It operates on a not-for-profit basis—the $3,000-per-donor stool-screening costs are covered by a gift, and OpenBiome charges only a processing-and-shipping fee for its specimens. The 109 specimens it has shipped have been produced by just three donors. (Another handful of potential donors applied, but failed the initial stool screen for one reason or another.)
Specimens are kept at minus-80 Celsius in a freezer in the laboratory of Eric J. Alm, an associate professor of biological engineering at MIT. “I’m deeply grateful that the Alm lab has been so supportive,” Mr. Smith says. “It sounds like a crazy project, so it took a certain amount of courage on his part.”
Daniel Murphy, a gastroenterologist in Winston-Salem, N.C., has treated nine patients since September with specimens provided by OpenBiome. Unlike some others in the field, Dr. Murphy believes that the FDA has been wise to treat stool transplants cautiously. “There are a huge number of unanswered long-term questions about this therapy,” he says.
For one thing, variations in the gut microbiome have recently been associated with obesity and other chronic conditions. The cause-and-effect relationships behind those variations are still unclear, but Dr. Murphy and others believe there is a risk that stool transplants might permanently alter the recipient’s metabolism. “We have to be very candid with our patients about the fact that this is an investigational technique.”
But whatever cautions are in order, Ms. Edelstein is surprised and gratified that her 2012 Thanksgiving dinner has had such a long afterlife. “I think we’ve managed to answer a real need from clinical practitioners,” she says. “I’m glad that we had the resolve to actually make this happen.”
