Doctoral Candidate Mark B. Smith was in the middle of cutting a piece of honey-baked ham for Christmas Eve dinner, when he received an urgent phone call. Somebody needed poop.
Dooty. Crap. Dung. There are many words for feces in our society today, but one term is rarely used: cure. For the 500,000 people each year who are infected with the bacteria Clostridium difficile(C. diff), it can be just that. C. diff is the most prevalent hospital-acquired infection in the United States leading to ~14,000 deaths annually.
When one gets a bacterial infection, the first remedy is typically antibiotics. While this treatment often destroys the offending bacteria, it can also clear out the healthy beneficial bacteria in the treated region. Studies have shown that systemic antibiotic treatment can eliminate many strains in the gut microbiota leaving the colon devoid of many of the many indigenous species. This opens the door for opportunistic bacteria like C. diff to colonize and take over the gut. This strain releases toxins that attack the interior lining of the intestine and causes individuals to have debilitating diarrhea and excessive abdominal pain. For most individuals with this infection, an initial course of antibiotics is effective at clearing C. diff. However, for ~20% of those infected, the antibiotics fail to work and they have multiple recurrences of the infection which, in some severe cases, can lead to death.
One such afflicted person was Mark Smith’s friend, Damien Proctor (name changed to protect anonymity). Proctor, a young Harvard biology graduate, came down with C. diff and it completely overturned his life. Smith remarks, “He had a hard time dealing with the disease and balancing his personal and professional life.” In fact, Proctor actually considered leaving his job because the disease was so destructive. He was sick for 18 months and went through 7 rounds of vancomycin without any substantial relief. However, there was one last ditch option Proctor had heard about: Fecal Microbiota Transplant.
Originally developed in 1958 by Dr. Ben Eiseman, Fecal Microbiota Transplant (FMT) proposes that by giving sick individuals fecal matter from healthy donors, their colons can be colonized by beneficial bacteria. The short procedure has been found to be effective in ~90% of all C. diff infections. It begins by screening a potential donor for harmful bacteria and other microorganisms. This blood and stool work and interviews can take multiple days to process. Upon successful completion of the screening, the donor visits the hospital another time and, assuming the donor can “perform,” the stool sample is processed in a blender with saline. This liquefied sample is subsequently administered to the patient through a tube either orally or rectally.
While extremely beneficial to patients, it is difficult for many hospitals to perform this procedure. It takes a lot of effort to go through the long screening process of donors and it is an administrative challenge to make dedicated lab area to process the stool samples. Due to these facts, there are relatively few clinics that do FMTs. Proctor eventually got on the waiting list for one of three doctors in New York City who were performing the transplants. Yet, the idea of waiting even longer for a therapy for such a crippling disease was brutal. Thus, Proctor did what any 20-something armed with a basic knowledge of biology would do: he performed the procedure on himself. Despite Smith’s protests about the potential hazards of using unscreened fecal samples, Proctor was unmoved. He did his “at-home” FMT in his apartment with his roommate’s stool, and gradually recovered over the next few days.
Seeing someone struggle with a potentially curable disease had a profound impact on Smith. “There’s all this literature that says this [procedure] works very well and there aren’t many doctors that are able to provide it yet. What are patients supposed to do?” Therefore, with immeasurable support from his advisor, Professor Eric Alm, Smith and an MIT Sloan MBA candidate, James Burgess, founded the non-profit, OpenBiome. OpenBiome is effectively a “poop bank.” After learning that frozen stool samples are just as effective in FMTs as fresh ones, Smith and Burgess realized that OpenBiome could become a warehouse of screened, processed, frozen stool samples that could be used by doctors on a moment’s notice. Thus, they clear out a majority of the lag time the doctors have to deal with before actually treating their patients. In addition, by spreading out the screening of a donor across many FMTs, they can offer the sample at a heavily discounted price.
Smith has received a bit of resistance from others. Some people believed that OpenBiome should be for-profit. Smith remarks, “A lot of people felt very strongly that we should be making money off of this. We don’t think cost or difficulty should be barriers to treatment.” Some doctors in the beginning did not even know that FMTs were viable therapies. Smith reminisces, “We were on the phone with this doctor and at one point he interrupted us and exclaimed, ‘Is Ashton Kutcher in the room? I feel like MIT’s getting punk’d! You’re going to mail poop to people? This is the craziest thing I’ve heard!’” However, the most major barrier for Smith and his team was with the Food and Drug Administration’s regulations.
Currently, the FDA regulates feces for fecal transplants as a drug. For a doctor to perform a fecal transplant, they would need to submit an investigational new drug application, an extensive document that can take more than 100 hours to produce. This red tape backlog created by the FDA was seen by many as excessive and harmful. Smith recalls a C. diff workshop he attended, “Many people were there to argue for the necessity of FMTs. There were patients that came that wanted access to this treatment saying, ‘I’m dying. What do you want me to do?’…And people from the CDC came and said ‘This is a major epidemic. We need to be treating patients.’” After that meeting, the FDA changed course heavily and was “really flexible and compassionate.” For C. diff, they decided that FMTs would be allowed enforcement discretion. Thus, feces are still seen as a drug, but patients are allowed access to it as long as they have informed consent and they know that it is an experimental procedure.
With this shift in the regulatory environment, OpenBiome was founded last spring and by the fall, they were able to start giving samples to doctors. “We sent an email explaining our service to a mailing list of an FMT working group, and people were really excited. We had a strong response to the initial email.” Yet, no one wanted to be first. There was still a bit of skepticism. Luckily, a doctor in private practice in California was willing to take the first leap. “For our first patient, I was nervous. She was in her 90’s. She had a lot of complications and was very inflamed. But she ended up getting better.” After that, many doctors came out of the woodwork and began using their services.
Today, OpenBiome is booming. They have a 92% success rate with their frozen stool samples and have a goal of being used in 1000 FMTs during 2014. While over 50% of the people who try to donate fail the rigorous screen OpenBiome uses, they still have many productive, anonymous donors. “We have this one donor who has won our ‘lifetime achievement award’ for getting us about four samples a week. We also have an award for ‘the most generous contribution’, for someone who produced a single 322g sample,” – the mass of three chipmunks. They have also been recently profiled in the Chronicle of Higher Education. Even though everything appears copacetic, there are more complications looming.
Some companies are currently still working on getting feces approved as a drug. If they get approved, there is a decent chance that the FDA could rescind the enforcement discretion status and force patients to use these samples. This could easily lead to a monopoly on a tissue as ever flowing as blood. Smith ponders, “I’m worried about the potential of a black market. …. If we regulate [feces] as a drug, we could create a tension between safety and access. If we regulate it as a tissue, FDA can still have oversight, but it’ll be open and widely accessible.” In fact, Smith and Alm are currently writing an opinion piece on this very topic in Nature to attempt to sway the FDA from creating this potentially harmful regulation.
Until regulations change or a new, better product becomes available, Smith and his team will keep on producing poop for the people. “At the end of the day, we’re just trying to make people better.”
For more information on donation to OpenBiome or Fecal Microbiota Transplants, visit OpenBiome atwww.openbiome.com