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Wednesday, July 26, 2017
Catching up with Baseline
A bit over a decade ago, Andy Conrad and I were lamenting a problem I think of as the “blind men and the elephant” challenge in human research. In essence, because any given technology was capable of assessing only a part of the whole human being, researchers were fundamentally limited in their understanding of health and disease. However, we could clearly see that dramatic advances in measurement, computation and analysis were on the horizon.
Although we weren’t then in a position to take full advantage of these changes, we nevertheless started to lay what we hoped would be the conceptual groundwork for a new approach to research in a North Carolina town called Kannapolis (Greek for “city of looms”) that had been devastated by the offshoring of the textile industry. Thanks to significant investment by philanthropist David Murdock and the joint efforts of Duke University and the University of North Carolina system, with Andy’s guidance we were able to develop a
biotechnology and research campus
on land that once housed a shuttered textile mill. The first major effort initiated through this center, the
MURDOCK Study
, is a large-scale longitudinal population cohort study with the ambitious goal of enrolling the entire population of Kannapolis and surrounding Cabarrus County. Despite challenges created by the 2008 economic downturn, MURDOCK is going strong and, with the help of the people of Kannapolis, we’ve learned a tremendous amount about chronic diseases in real-world settings.
When Andy moved to Google, we and a number of our colleagues started to plan a study that would extend this work by “riding the wave” of coming changes in scientific measurement and analysis. Our idea was to characterize states of health and the transition to states of disease in as many dimensions as possible—something that would move us much closer to seeing the “whole elephant.” With support from Duke, Stanford and Andy’s growing team that evolved into Verily, our team began the tremendous undertaking of developing the construct for what came to be known as the
Project Baseline
study, but in the midst of planning, I departed to serve at the FDA.
Upon returning to Duke and joining the Verily team, I found that an astonishing amount of work had been accomplished, enabling Baseline to “ride the technology wave” by combining Verily’s technological and analytical insight with the scientific and clinical expertise at Duke and Stanford. I was particularly thrilled to learn that the study protocol had been finalized, numerous pilot programs were completed, and participants had been enrolled. Last month, as noted in a
blog post
, both Stanford and Duke, through its Kannapolis site, have enrolled their first participants.
I also met with the Verily Baseline project team to review the study’s progress. The systems in place for biological measurement, laboratory management and information capture, integration, and analysis represent an amazing display of the deep technological, analytical, and organizational expertise available within the Alphabet/Google family. Just as importantly, the respectful engagement with and attention to the needs and preferences of study participants was inspiring, and the team’s good spirits and camaraderie made my day. I wish I could name all the people at Verily, Stanford and Duke who have done the work, but I’ll start by recognizing the leadership of Sam Gambhir at Stanford and Jess Mega and Scarlet Shore at Verily.
Project Baseline is an exciting study for multiple reasons. Because of my involvement with all institutions, I won’t have direct decision-making input in this effort, but I will be its most fervent cheerleader and advocate. The integrative science made possible by combining so many cutting-edge capabilities in a thoughtful way has the potential to enable new understandings of human biology and the subtle interactions of clinical events, individual behavior, and states of health and disease. It will also illuminate new pathways for engaging diverse individuals and communities as active participants in research, and may improve health outcomes, both now and for future generations. In future blogs, I plan to reflect on some of the specifics that make this effort the nidus of a new era of human research.
Posted by Robert Califf, M.D.
Thursday, July 20, 2017
Science Spotlight: Microbiome with Vanessa Ridaura
We sat down with Vanessa Ridaura, a genomics scientist at Verily (center), to learn about her role on Project Baseline. We discussed research on the microbiome, integration of different data types in the study, and the importance of stool samples.
Kasley
: Tell us about your background and what brought you to Verily.
Vanessa
: I completed my PhD at Washington University in St. Louis, School of Medicine. My supervisor was
Jeffrey I. Gordon
, widely regarded as one of the modern fathers of gut microbiome research. My thesis focused on developing techniques to study how the gut microbiome affects metabolism. We did so by raising mice in germ-free environments, giving them either a lean or obese fecal microbiome from human twins, and then evaluating how their microbiomes responded to changes in diet.
We found that mice with the obese microbiome gained more fat than mice with the lean microbiome, even when they ate the same amount of the same healthy diet. However, when we gave mice with the lean microbiome a high fat diet, their microbiome changed to resemble that of a mouse with the obese microbiome.
Then I completed my postdoctoral research at the National Institutes of Health in
Yasmine Belkaid’s
lab, where I started focusing on the skin microbiome. In particular, I was interested in how it can have an effect on inflammatory skin diseases like melanoma and psoriasis.
I’m now part of the Verily research team and am excited to use our breakthrough technology and data science infrastructure to answer challenging questions about how the microbiome influences health and disease.
Kasley
: Where can we read more about your research?
Vanessa
: Here are a few of my publications:
The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
(2009)
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
(2013)
Gut Microbiota: The Link to Your Second Brain
(2015)
Kasley
: Can you explain, for those of us who aren’t scientists, what is a microbiome?
Vanessa
: Sure! The microbiome refers to all the microorganisms (such as fungi or bacteria) that live in close association with a certain environment (such as your gut, your dog’s gut, or even a rock).
When we talk about the human microbiome we usually refer to the beneficial microorganisms that live in close association with different human tissue sites, such as the gut, the skin, the nose, or the mouth. The majority of these microorganisms live in harmony with us and provide useful functions; for example, they can help us metabolize foods or train our immune system to respond to harmful bacteria.
Perhaps it’s helpful to think of your microbiome as all the employees with different roles who work together to achieve a company’s mission. In this analogy, employees are microorganisms, the company is your body, and the mission is your health.
Kasley
: Describe some of the things you’ve been working on thus far.
Vanessa
: My work at Verily aims at achieving three main goals. The first is to measure. I’m interested in developing comprehensive, high-quality ways to measure the microbiomes associated with different human tissue sites.
The second category is to innovate. I’m interested in innovating how we collect samples for microbiome research, the type of data we generate from these samples, and how we store, interpret, analyze, and share the data.
The third is to integrate. With Project Baseline, we have a very exciting opportunity to combine many different types of data with microbiome data. From microbiomes associated with different tissue sites, to laboratory tests, devices, questionnaires, and more, we can do a whole genotypic and phenotypic integration to define and describe human health.
Integration is key because a lot of research has been done on the microbiome in isolation, but we’ve never been able to ask scientific questions in the context of all these other types of data. Creating a holistic view is new and potentially game-changing for healthcare.
Kasley
: We ask study participants to give a stool sample following each site visit. Why?
Vanessa
: I know it can be an awkward experience, but the stool sample is really, really important! It will give so much information about how the gut microbiome and health are related. There has been a lot of research in the last ten years showing that the gut microbiome can affect your whole body, from local gene expression to mood changes. It’s also unique to you, because it’s shaped by your body and your everyday choices like diet, exercise, and sleep—no two microbiomes are the same, even between identical twins.
I’m very excited about the scientific insights we’ll be able to gather with the stool samples collected over time, rather than just once. If you imagine watching a movie of how your microbiome changes over time, it may be that one microorganism is the main character at a certain point in time, but it’s replaced by a new character right before you get sick. We’ll miss these important plotlines unless we watch the whole movie.
Kasley
: What’s the rumor about frozen bananas?
Vanessa
: Here at Verily, we’ve been obsessed with making sure the stool samples arrive at our lab frozen. If they’re not frozen, we’ll miss out on a lot of useful information. So we’ve been testing different kinds of stool kits.
One of the ways we tested shipping logistics and packaging was by putting frozen bananas in kits with temperature sensors to see how long the bananas remained frozen, how much the temperature changed, and how many ice packs we need to keep the sample frozen as long as possible. We’ve even mailed these bananas across the country to test their stability—that’s how much we care about the stool samples!
Kasley
: What most excites you about Project Baseline?
Vanessa
: This study will provide the multidimensional, long-term context we need to better understand health and disease. Using this complex dataset from each of our dedicated participants, we’ll be able to ask questions like what a healthy microbiome looks like, how to design interventions to shift microbiomes to a healthy state, and how changes in the microbiome are related to changes in the rest of the body.
There are so many pieces to the puzzle of health. I’m excited to contribute my piece and see how the microbiome fits into the whole puzzle.
Posted by Kasley Killam, Engagement Manager, Verily
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