The world of fecal microbiota transplants

Poop pills or bacteria pills

Not to be confused with these poop pills, FMT requires transplantation directly into the colon

This is the link to my most recent post for uBiome on fecal microbiota transplants (FMT).

A little taste:

Fecal microbiota transplant (FMT) is the therapeutic process of transplanting feces from a healthy individual to an ailing recipient. Despite the obvious “ick” factor of receiving healthy poop from your sister, husband, or friend, people suffering from debilitating Clostridium difficile bacterial infections are overlooking the ick in hopes of a C. difficile cure. Currently the only indication for which FMT is approved by the FDA is C. difficile colitis and there is contention as to the efficacy of FMT for C. difficile treatment.”

Thank you from California Academy of Sciences

Oral swabbing for uBiome by Cal Academy

Angus Chandler, Academy postdoc, and Sean Edgerton, graduate student at SFSU, demonstrate oral swabbing

Check out my blog post on the wonderful thank you letter we received at uBiome from the California Academy of Sciences.  Visit both uBiome and the Cal Academy at Bay Area Discovery Days November 1, 2014.

The real problem of irreproducible data

               

You have to know what is real before you know what is relevant. In science we trust that published means “real”. We may debate the impacts of different conditions and ooze skepticism over significance measurements and choose, sometimes less than tactfully, to object to an author’s conclusions, but overall we trust the data are real for the experimental conditions and that repetition of the experiment under the same conditions would yield the same outcome.

However, in a Catch 22 the data on reproducibility disagree.

In a collection of articles in the open source Nature special issue on data reproducibility, the most optimistic studies show 25 percent reproducibility of academic research. One article from Glenn Begley and Lee Ellis led to the development of Begley’s Six Rule for Reproducibility, which include blinded studies, full disclosure of all results, and reagent validation. Based on these rules, the optimistic 25 percent of reproducible studies are probably coming from far less than 25 percent of total academic labs. I know very few researchers that can honestly read all six rules without a little shame. 

On July 9th, Oxbridge Biotech Roundtable (OBR) hosted a panel discussion on this issue of data reproducibility. The panel included Dr Liz Silva, the MIND Program Manager at UCSF and the former Senior Editor at PLoS ONE; Dr Tim Gardner, founder of Riffyn; Dr William Gunn, Head of Academic Outreach at Mendeley; and Dr Corey Goodman, a partner with venBio.

Goodman opened the conversation with the first question he asks of founders pitching their science to him: “who has reproduced this?” The rest of the discussion focused on the problems, like an increasing rate of article retraction, and potential causes, such as intense pressure to publish, funding shortages, and increased oversight. Somewhat frustratingly, very few solutions were offered.  Gardner made a compelling argument for an incentivized approach to solving the problem. He suggested that two factors hold back scientists from solving the reproducibility issue: our culture and our lack of tools. We operate in “a culture of noise” in biology and accept that irreproducibility is unavoidable. However, if we employed adequate documentation tools similar to other industries it could greatly diminish the issue. Through incentives, like lower costs and timesavings by eliminating unnecessary, faulty repetitions, we can develop and adopt new tools and change the culture. (Gardner discusses this more in the Podcast referenced later.) When asked about automation as another tool in this solution, the panel felt it might be in the future, but currently there are other more pressing issues to address. (This could also be a reflection of the fear of the outdated bench scientist, but that is a topic for another day.)

Another potential, but more dogmatic approach, is a mandated NIH requirement for reproducibility standards. However, this reeks of additional strain on an already stretched system and more delays in publication, which will only compound the stresses that contribute to irreproducibility in the first place.

More adaptable and agile solutions are being developed through the Reproducibility Initiative. This partnership between Science Exchange, Mendeley, PLoS, and Figshare was briefly touched upon, but has the potential to revolutionize the way research is conducted as we incorporate tools, such as those being developed by Riffyn, and commercial replication services become cheaper and more convenient.

Overall this is a discussion that needs to continue and it requires total engagement from the entire scientific community. There is no clear solution but isn’t this the kind of problem we live for?

(To solicit more thoughts on solutions and the topic in general from two of the panelists, Silva and Gardner, I was asked to conduct an impromptu interview for a Podcast. By impromptu, I mean this interview was conducted on about five minutes notice.  I even forget Liz’s last name!  Anyway, it is clear I am not ready for the evening news.  As soon as the Podcast is up I will add the link here, so stay tuned!)

Citizen Science brings humanity and the microbiome to the world

                                               

                                              Badge from Beware Comics

Outsourcing is the reality of modern science. I’ve written posts on contract research organizations (CROs) and the pharmaceutical industry’s move to innovation hubs, but these are dry, corporate initiatives. They are important to our understanding of the business of science today, but where’s the humanity in a CRO? Where’s the joie de vivre in an innovation hub? 

Citizen science is the beating heart of science today. It’s inclusive outsourcing.  

No field of biology has embraced citizen science as enthusiastically as microbiome research, and the reception from the world community has been reciprocally enthusiastic. The success of projects like uBiome and American Gut illustrate the power of community involvement. Both the commercial uBiome and academic American Gut took universal engagement another step to additionally address the research-killing paucity of funding by crowdsourcing.

Give us your fecal samples, your skin swabs, your mouth swabs, yearning to be sequenced

uBiome raised over $300,000 on Indiegogo offering microbiome sequencing services similar to 23andMe in exchange for donations starting at $79. In addition to the monetary donation, they gave participants the option to relinquish ownership of their anonymous sample and results for development of population statistics and future research. After Indiegogo, uBiome continues to offer sequencing commercially with the same option to transfer ownership. They now have control over thousands of samples and a treasure of data that make scientists like me salivate. Unfortunately, we need to swallow and wipe our chins since uBiome is currently keeping their data close.

American Gut is the largest citizen science campaign to date. They have raised over $500,000 in one year on FundRazr and have over 3,000 fully sequenced samples. Working off the same principles as uBiome, they offer contribution levels starting at $99 and going up to thousands. Currently the highest donation has been $3,750 for a Functional Feces characterization.

                

Examples of American Gut donors, part of their “All the cool kids are doing it” approach (from left: author Michael Pollan, ultramarathoner Dean Karnazes, and Mrs. USA 2011 Shannon Ford)

Unlike uBiome, American Gut is making their data publically available through the open-source Earth Microbiome Project and through the European Bioinformatics Institute (EBI). They plan to publish their findings in several papers and hope other researchers apply these data ad libitum

Biased data or no data?

Crowdsourced microbiome initiatives are facing the same criticism of biased data as other crowdsourcing campaigns. Recently Steven Novella reviewed CureCrowd for Science-based Medicine (ultimately concluding it is too biased) and the Institute of Electrical and Electronics Engineers (IEEE) published “From Conservation to Crowdsourcing” in 2011, which touches on the bias issue. It is true, citizen science data are biased to individuals who can afford to contribute financially, are aware of these initiatives, and are motivated to join in citizen science. However, we now have data where we had none before; data that did not rely on tax dollars or single-source private benefactors to generate; both routes that empirically take significantly longer and are lower yield than commercial efforts (e.g. NIH Human Genome Project vs. Celera) or now crowdsourcing (e.g. NIH Human Microbiome Project vs. American Gut). As a side note, according to American Gut’s website, it appears they are closely linked to the Human Microbiome Project.

As long as researchers acknowledge the bias, are committed to addressing the issue, and accept that their findings may require reassessment as less biased cohorts become available, then this is not an end game issue.

The larger issue is the proper application and analysis of all these heaps of data being shared. Elizabeth Beam’s Harvard Science Review article, “DATA: The bigger the better? A survey of analytical traps and tricks,” concisely summarizes this issue.  

Engagement beyond money and samples

The appeal of the microbiome to the general population goes beyond crowdsourcing. Manipulating your microbiota is all the rage and DIY projects abound on the internet. There are recipes for probiotic yogurts and other foods, and plenty of diets to alter and optimize your gut bacteria. However, the most impressive is the DIY fecal transplant on The Power of Poop. I hope never to need to self-administer this procedure, but I’m glad to know there is a step-by-step guide openly available should the need arise.

               

               Fecal transplant shopping list from The Power of Poop

 This DIY prevalence circles back to the humanity of citizen science and the positive implications of investment by the greater community in research. Crowdsourcing is a successful, if not perfect, route to doing valuable science while educating people and removing the image of scientists behind locked doors, hunched secretively over arcane experiments.

Citizen science is the proactive science of today and tomorrow.