Microbiome-focused companies have many different areas of interest—but what they have in common is a drive to learn more about the conditions and activities of bacteria and other microorganisms.
Martha Carlin, CEO and co-founder of The BioCollective, has thought extensively about how to facilitate this knowledge as it relates to human health. A vision of rapid and continual microbiome innovation is what prompted her to start the company, along with co-founders Jack Gilbert, PhD, of University of Chicago, and Suzanne Vernon, PhD, formerly of the Centers for Disease Control.
The company has built—and continues to build—a ‘microbiome bank’ of viable human samples that allows continued innovation and testing of new hypotheses. They and their collaborators can ‘bioprospect’ using these samples—isolating and culturing different strains of bacteria for a variety of uses. Carlin and her team aim to support discoveries across the entire industry with their uniquely collaborative and data-driven approach to microbiome discovery.
We spoke with Martha Carlin for an exclusive interview on how the company’s approach could facilitate innovation across the microbiome industry.
MT: What led you to start The BioCollective?
My background and work history was in operations… I was trained in a process called ‘transaction flow review’, a method of looking at a business and following everything that flows through the business, looking for weak points in the system to identify risk.
I applied that approach throughout my career, and then in 2002 when my husband was diagnosed with Parkinson’s I looked at the way science and medicine were approaching neurological disease with point solutions.
And I understood Parkinson’s as a systemic problem; these are systemic conditions and require that same systems approach from my business career to fully understand what’s going on. So I started applying my systems thinking to the problem. When I read Martin Blaser’s “Missing Microbes” in 2014, I quickly realized the microbiome was of critical importance in the human health system including Parkinson’s.
When we founded the BioCollective, we decided to take a different approach by building samples and data that were not just focused on one disease, because many diseases are functionally similar in the human body. The microbiome helps us do this. That’s the whole idea of the BioCollective.
MT: Why did you take such a broad approach, rather than focusing on a single disease and a single treatment?
We could see common elements across diseases. We didn’t know where the field of the microbiome was going to go, but we saw it as the future of medicine, drug development, nutraceuticals, testing of consumer products—all of these things. That’s the potential broad canvas for the microbiome. We knew that in order to be opportunistic in this emerging field, we needed quality samples and expanded data sets to understand.
MT: How did you build your bank of microbiome samples?
We designed and patented a user friendly, collection kit for whole stool that preserved the quality end-to-end with temperature stability. We developed a process for homogenization and aliquoting multiple samples, so we would have multiple aliquots of a viable sample for use in genomics, metabolomics and culturing.
We filed an IRB that allowed us to ask health-related questions to people, re-contact and follow up and additional sampling. We wanted broad IRB, in the event that we wanted to go back and get more information or get another sample.
We recruited a broad age group in order to better understand population changes. We have samples from one-year-olds, all the way up to one-hundred-and-two-year-olds. This allows us to see how the microbiome is changing as we age.
As we had capital, we did metagenomic sequencing on the samples to build our data set. In 2018, we began isolating and culturing unique strains from our samples.
MT: Why is it so important that your samples are viable?
We wanted to enable the broadest possible data sets from a sample. In order to accomplish that, some portion of the sample must be preserved neat and with cryopreservative for culturing. We can go through our data and identify a strain of interest in a sample or samples, and isolate and culture the strain from those samples.
Most of the research to date has been done with DNA tubes or swabs where the DNA is lysed so you can’t isolate and culture or do repeat sample analysis from the same sample.
MT: What is your approach to product development—like the new probiotic formulation your company recently developed?
We can look at data across age groups, across health states, compare multiple diseases and see common elements across those diseases at a functional level. We looked at the problem from a different perspective and thought about restoring function to the gut across the population, and not about treating a disease. We have taken a nutraceutical approach to putting function back.
Our Director of Bioinformatics, Naseer Sangwan, developed our BioFlux™ Metabolic Model, an in silicoapproach to community metabolic output. We can model a formula and see how it would interact and grow together. We can also overlay the formula with microbiome sample data. At some point we see this being used for personalized product development. We used BioFlux™ when we were making our first probiotic formulation, SugarBuster Biotica™. We tested our hypothesis of functional restoration in the system, and could later see in our n-of-1 testing that it did shift the system the way the model predicted that it would.
BioFlux™ can be used to test any chemical, food ingredients, foods, probiotics, prebiotics and mixed formulas.
MT: What are you doing to support standardization and comparison of research results across the industry?
For our own purposes we need to develop standard methods. In 2017, we developed our method of standardization of homogenization of human stool to make a reference sample for one of the MOSAIC challenges that is currently underway and sponsored by Janssen and DNA Nexus.
We made 5 different cohorts, 1000 aliquots each of identical samples, for this challenge—to develop standards of comparability between different extraction methods, pipelines and sequencing approaches. One of the biggest issues now is there are no standards. Comparability of the current research is pretty difficult.
We are working to expand on this project to OEM a more scalable reference fecal sample that the industry could start to use to better standardize their research.
MT: In general, there seems to be a growing concern with preserving microbiomes for posterity. Why do you think this is?
From my first reading of Dr. Blaser’s book I connected with his concerns about what the pervasive use of antibiotics in our ecosystem is doing, and how that could be driving the extinction of many species of bacteria. I believe it is important to have a bank, just like the plant seed banks we have around the globe to preserve this diversity that we are rapidly losing.
MT: The BioCollective is partnering with Microbiota Vault, an organization that’s building a global repository of human microbes. How did you get involved?
We believed in what Gloria, Martin, Rob and Jack were looking to build. We became involved because we had developed these methods for aliquoting and storing samples. Our CSO Raul Cano has a long and storied history in reviving ancient bacteria, and developing methods and media for storage and revival of strains of bacteria and fungi. We wanted to lend our expertise to the project because it is such an important project for the future.
There are so many great discoveries ahead in this field—and we are laying the groundwork for the innovation that’s to come.