OpenBiome – First to Market with Fecal Microbiota

fecal transplant

 It is always seems impossible until it’s done.
Nelson Mandela

 

I recently had the pleasure of interviewing the team at OpenBiome.  I expected to meet a bunch of high wired young entrepreneurs determined to make their first billion from poop before they turned 30. Instead I found a down-to-earth team of post-graduate students with a background in microbiology, medicine, management, public relations and the non-profit sector. While others have been lamenting the difficulty and lack of money in FMT, OpenBiome have been quietly solving the problem. Here is their story.

You mention on your site that one of your family members went through the C diff ordeal. What made you take action – as opposed to just sitting around complaining about it?

A combination of good fortune and outrage. We couldn’t believe how hard it was for our friend to get treatment given the simplicity of the procedure and the strong clinical evidence supporting its efficacy. He suffered for many many months while waiting for a treatment that should have been easy for any gastroenterologist to provide. Tens of thousands are dying and many more are suffering needlessly because this treatment is not yet available for them. This is wrong. So we started off with a feeling that there was a huge problem that needed to be solved. I think everyone who has been involved in FMT has seen that.

In our case we also have had the good fortune of having access to a lot of resources and support at MIT. It’s really an extraordinary place with tremendous resources for biotechnology entrepreneurship. Mark has been deeply involved in microbiome research for many years as a PhD student at MIT. As a result, he was familiar with the technical requirements for implementing our vision and was well positioned to bring together the necessary resources. Many people have been touched by FMT, but not everyone has access to a modern laboratory as we do.

The other piece is that we were all raised with a deep commitment to service. We worked together on service projects during our undergraduate years together at Princeton and although this has been a much more serious time commitment, it seemed like a very exciting and high impact extension of the work that we have all been involved with for years. In college one of our service projects fed a few dozen people – with this project we hope to touch thousands of lives in a much deeper way.

How long have you been working on this?

Two years. We all have full-time day jobs so we have been working on this in our evenings and weekends and funding it out of our own savings and with donations from friends and family.

Have you made a sale yet?

Yes, there are now 11 hospitals using our microbiota preparations and more coming on board every week. We’ve delivered treatments for 73 patients now and look forward to expanding much more in 2014.

What kind of challenges did you encounter in developing OpenBiome?

First, disbelief. Some thought we were crazy, especially early on. One surgeon assigned to advise us through MIT thought he was being punk’d because the idea seemed so crazy! (We later learned he didn’t really have any background in microbiology).

But after people get over the shock factor and become familiar with the evidence supporting FMT the first question everyone asks is how they can help. It has been extraordinary to watch the level of support we’ve had from people with backgrounds ranging from science to law who have been eager to help us achieve our mission.

Lately the biggest challenge has been finding enough time to keep up with all of the exciting progress the organization is making. Thats a big part of why we’re so excited to hire our first employee (we’ve all been working as volunteers for many months now).

How have you dealt with the liability issue?

For an investigational product like this, liability is a major concern. We start by having a CLIA-certified lab do all of our testing. They are responsible for performing all of the tests to evaluate the donors we use. They are regulated to meet standards for accuracy so we can be confident in the results they share.

We also don’t make the final decision to use the material, we leave that up to the medical judgment of doctors using our material. We provide the raw donor screening lab results to our doctors (with personal information removed). The doctor’s are responsible for interpreting the laboratory results themselves to determine whether they feel it is appropriate for use with their patients.

As a further safeguard, we also store a small amount of each sample frozen, in case there are any concerns or adverse events following the administration of our material. In this case, we’re able to revisit each sample and verify that it meets our screening standards. Because of the nature of this material and the difficulties in characterizing it, we cannot provide any absolute assurances that the material is safe, only that it meets our quality standards.

We also have a tracking system in place to immediately quarantine all material in the event of an adverse event. We hope to treat many patients with our material and we have made it a priority to minimize the chance of an adverse event, while being prepared to respond in case one occurs.

How can you be confident there are no infectious agents in the FMT?

Donors must undergo a very thorough screening process before we release their material for clinical use.  First, donors are examined for potential risk factors using this questionnaire.  Once they’ve passed through pre-screening, donors are tested for a variety of pathogens and other health indicators using this protocol which includes 18 different screens. If a donor passes all the tests, we will collect material from them over a two month window at which point they must be re-tested for the same set of pathogens and health indicators.  All samples are quarantined until the donor passes the second set of screens at which point the material is released to hospitals. In future we will also use DNA sequence based assays to further characterize the material that we provide. Our level of screening exceeds the highest standards used in current practice. Furthermore, because our donors have already been used safely in many patients, we feel that the risk of infection is low relative to fresh material from new donors.

Have you considered adding a pre-biotic to the mix?

Although this is an interesting idea, we’re not planning to manipulate stool with pre-biotics, both because it may have consequences for how it is regulated by the FDA and because unmodified material already works extremely well.

How have the FDA been to deal with?

Although they are often painted as boogey-men, the FDA has been great to deal with. They’ve been supportive and communicative, and in return we respect the work they are doing and the guidelines they set. We actually hope that they will provide more regulation, not less, so that we can minimize the risk of an adverse event. My greatest fear is that a serious adverse event will occur due to insufficient donor screening and that besides the immediate harm to the individual patient, this might jeopardize access to this treatment for everyone else.

Your website mentions that although it hasn’t been formally tested, it is likely that microbiota can survive for up to 6 months at -20 degrees Fahrenheit. What compromises are patients making by using poop frozen in home refrigerators?

Freezing causes the formation of ice crystals inside of microbes, destroying their cells and diminishing the viability of the sample.  We are able to avoid this in our lab by putting our material in a cryoprotectant solution that prevents ice crystals from rupturing the cell walls of bacteria. We use a glycerol solution that is common in microbiological work. Without a cryoprotectant, the freezing process will kill many of the bacteria that make FMT effective.

You mention on your website that you will be compiling outcome data across institutions. What kind of data will you be compiling?  Have you started yet? Will the results be published?

Primarily, we will be focusing on collecting efficacy data (did the patient get better or not and how quickly).  However, because we are also deeply connected to the genomics community, we would also like to collect microbiota samples from patients both before and after treatment to sequence and analyze the changes in these microbial communities caused by FMT.

We have not yet begun to collect either of these types of data as we must first get Institutional Review Board (IRB) approvals to collect and analyze data on human subjects.  We aim to have IRB approvals in place in January or February and will begin collecting data thereafter.  The results will be published and publicly available as soon as possible.

What is your view about FMT for conditions other than C diff – is it likely we will see microbiota cocktails produced for specific conditions: Ulcerative Colitis, Crohns, autism, obesity, inflammation, food intolerances, cancer, arthritis, multiple sclerosis, Parkinson’s, body odour, depression, anxiety, autism?

We are really looking forward to supporting research into the use of FMT and other approaches to treat many of those conditions. We see OpenBiome as a platform that doctors can utilize to make research into FMT faster and easier. We hope doctors from a wide array of indications will be interested in collaborating on investigations. Its too early to speculate about which diseases might be effectively treated, but given the proliferation of correlative links between many of these diseases and the microbiome, its not difficult to imagine that some of these links may be causal and amenable to manipulation through FMT or other interventions.

What do you think about the use of antibiotics in animal feed in relation to its effect on the microbiome?

There’s no question that the use of antibiotics both in the agricultural system and in human healthcare has a huge impact on the microbiome. Some of Mark’s earlier work on horizontal gene transfer touched on this topic. However, the extent and nature of the relationship between antibiotic use and the microbiome are still open research questions.

How much consensus is there among the professionals researching FMT? What areas of difference are emerging within the medical-scientific community?

In our experience, all of the medical professionals that we’ve engaged with are aware of and understand the effectiveness of FMT as a treatment for C. diff.  However, this is a dramatic change, even from when we first started working on this project. We have to assume that a lot of this awareness stems from patient-driven organizations like PoP as well as an uptick in scientific interest in the microbiome and its effects on health. There seems to be a strong consensus now that FMT works and should become widely available. The dissent seems to lie mostly in details like how it should be regulated and reimbursed by insurance companies.

Are bacteria labelled as pathogens really being given a bad run? Could we rather call them opportunists? Certain bacteria seem to contribute to a diseased state, but are they necessarily the root cause? eg. C diff  and Candida are present in healthy people, but don’t cause disease. Helminths are increasingly being used by some online patients to stabilize autoimmune conditions. Should we perhaps start changing our language around organisms, removing the term ‘pathogen’ and the word ‘parasite’?

This is a great point. Context absolutely matters when it comes to our microbiome. There are some bacteria that can be beneficial in some contexts and harmful in others. However, some bacteria and parasites are truly nasty and have earned the term pathogen. I think C. difficile falls into this camp. Although even for C. difficile, it is often human behavior (often antibiotic use) that creates the context in which it can thrive.

Why did you decide on non-profit? Is your end goal to commercialize your product?

We will not commercialize fecal microbiota. We are a non-profit because we care about expanding access and improving healthcare much more than seeking profits. We had a conversation about this early on and all felt that the non-profit approach was the right one given our goals. Because many patients pay out of pocket at this point, we wanted to make sure that cost would never be a barrier to care. We charge user fees to cover our costs and enable us to continue to provide care to others, but we evaluate our progress based on patients treated, not dollars earned. Intuitively, it’s poop and it seems like it should be as close to free as possible. Of course we have costs that we need to cover, but we haven’t invented anything new here, we’re just streamlining an existing process. It seems wrong to claim credit for something the medical community discovered a long time ago.

What did your friends and family say about you becoming poop-sellers?

They all laugh, but they are excited about what we are doing!  As we said, after they get over the initial shock and a barrage of jokes they usually ask us how they can help. Ok, they don’t ever really get over the jokes (we don’t either!) but they’re all genuinely supportive and excited about the impact of this work. 

There are those that look at things the way they are, and ask why?

I dream of things that never were, and ask why not?

Robert F. Kennedy

So if you’ve ever had your doubts about Gen Y, think again. What it’s ffinally taken to get fecal microbiota into US hospitals to treat C diff is a group of dedicated young people who saw needless suffering and asked “why not?”

If you’re a patient in the US with C Diff that has not responded to standard treatment, there is now no excuse for your doctor not to organise FMT for you. The FDA permit it, the AGA support it and OpenBiome provide it. If you have C diff but do not want to waste time on anti-biotics, or you have a condition other than C diff and want to try FMT, please see our FAQs and DIY Instructions.

Please do NOT contact OpenBiome asking for microbiota as they cannot provide it to the public. In accordance with US FDA regulations microbiota can only be provided to doctors who are treating patients with C diff. The cost is $250 per 250ml sample and you will need the approval of your gastroenterologist and HMO to access it. 

Microbiota can be purchased in Australia from the Centre for Digestive Diseases and in the UK/Europe from Taymount Clinic, who will ship internationally. The order must be place by a gastroenterologist or hospital.