TCGC: Clinical Genome ConferenceTCGC: Clinical Genome ConferenceTCGC: Clinical Genome Conference

Driven by “Why”: Genomic Complexity, Public Engagement and Data Management

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Ann Nguyen:

Welcome, everyone, to another podcast from Cambridge Healthtech Institute for 2015's TCGC: The Clinical Genome Conference, happening June 22-24 in San Francisco, California. I'm Ann Nguyen, the Associate Conference Producer. Today we're chatting with Dr. Nathaniel Pearson, Senior Director of Scientific Engagement & Public Outreach at the New York Genome Center. He's also a keynote presenter at the conference, giving the talk, "Through the Keyhole to Genomic Wonderland: Common Sense, Beyond Uncommon Nonsense."

Nathan, I'm delighted to have you here. Thank you so much for your time.

Nathaniel Pearson:

Likewise. Delighted to join you too.

Ann Nguyen:

Why genomics as your life's work -- your scientific and personal reasons -- and what are your activities now at the New York Genome Center?

Nathaniel Pearson:

Great question. I think many of us, as scientists, when we get to a certain stage, we start to look back and reflect on why we've chosen to do what we do over time. And personally, when I think about how my mind viewed the world as a kid, I think there's some groundwork there that maybe led me to think about and wonder about genomes in particular. When I was a kid, I used to think a lot about biological diversity. I used to love to look at birds, understand how birds varied from each other, etc. I also used to try to make sense of behavior. When you're a kid looking at ants on the sidewalk and trying to understand their society, which is a little bit hidden from yours, maybe the same way that adult human society is mysterious to you in some ways, you start to formulate theories and maybe test them a little bit by blocking the way of the ants, etc., and seeing what happens.

You start to do science at sandbox scale in ways that let you probe the little bit of the world's diversity that's accessible to you as a kid. When I started doing that as a kid, I think I started to get interested in "why" questions a lot. When I look at friends of mine who are engineers, for example, I think that many of them, and some biologists too, depending on the field that they're in, ask questions that are more like "what" questions. They're questions about how things work and about describing in detail the inner mechanisms of particular systems in ways that let you understand them holistically.

For me, the question that drove it was always "Why?" The proximal "why" was never enough. It was always deeper: "But why that? Why that axiom?" Why should we accept that that's the way the world was and how much deeper can we go to understand that "why"? I think that that question lends itself very well to thinking about the way that systems evolve over time. The way that, for example, languages might evolve, the way that our speech patterns evolve, that was something that interested me. As a kid, I used to wonder how one word in Latin became its various descendant words in languages like Italian or Spanish or French.

Likewise, I think, once I started to understand what had been learned from Darwin and others about how life had diversified over time thanks to genomic diversity, that really hooked me. I started to wonder about that in the context of people, how we fit into that broader tree of humanity's diversity and what, in turn, or genomes might today say about not just our history but our health. Other traits, ways that we vary importantly from each other that concern us for practical reasons every day in life.

Those "why" questions eventually led me to see genomes in particular as a framework for much of the "why" inquiry that we can do, despite the fact that they are just a start. They're just part of the reasons why, so genomes are in some ways like musical scores that unfold in different ways in different people, thanks to lifestyle factors and environment and other ways. Eventually, understanding all that complexity really captivated me as a student in college and then afterwards, and led me to specialize in what we could start to say about the genomic framework of all that diversity.

In terms of what we do here at the New York Genome Center now, I think we're a young institution. We have just started about 4 years ago and we've gained some really amazing minds here. Some of the faculty that joined have come together to help think about genomic diversity and what it may mean for gene regulation and transcription, other kinds of ways in which our diverse genomes play out differently. That musical score plays out, so if you look at the work of Tuuli Lappalainen here at the Genome Center or Yaniv Erlich, they're wondering about particular variants that may not affect the protein makeup of a person, in other words, the spelling of individual proteins, but they may affect the mix of proteins, how much of each version gets made over time and under what conditions.

Those questions are going to be increasingly tractable, increasingly informative for the health and other questions that interest us as community. This was a really neat place to be to start working together with colleagues, whom I really admire and love working with already, to do that kind of science. My role here is to help us do good science together with people outside the walls. This is where I think, "What can really distinguish us as a genome center from the other genome centers in the world?" The really accomplished ones, like the Broad Institute, like Sanger, like Wash. U, all of them sequence lots of DNA and RNA.

That's a common given, that they have great machines for doing that, thanks to the boon of technologies today, but they all have specialized, in various ways, in different really tricky facets of that. Broad, for example, has pioneered making software that people want to use and that is very useful for understanding the stream of letters coming off a DNA sequencer, and that software has become widely adopted. Wash. U, likewise, has started to probe the complexities of tumor genomes in very pioneering ways that help with one key, actionable front of genomics today. Baylor, in Texas, has pioneered ways to actually work with the insurance system here in the U.S. and get paid to do clinical sequencing.

All of them have specialized in some way within that framework of being a genome center. I think what distinguishes New York Genome Center is New York itself. It's our front-door access to incredibly diverse people whose ancestors came here from all over the planet; who vary a lot in lifestyle; who, as a civic community, tend to be very engaged in science and in technology and other key facets of the changing world today that genome centers need to leverage. The chance to, perhaps, make the Genome Center a trusted place where people in New York can invest their data as citizens on behalf of science and behalf of a generation-long effort to better understand human health for their own descendants and for their neighbors' descendants. That was a key mission that we could have here that would distinguish us importantly from the other places that are out there, where we could start to excel in some ways, leveraging the minds we've already gathered here scientifically.

Ann Nguyen:

You mentioned the world around the New York Genome Center. What's the scientific value of public engagement? You've worked in a lab as a genome scientist, you've helped build genome interpretation software, and you've generally been in the trenches at well-known schools and companies. How can engaging with non-scientists contribute to the research?

Nathaniel Pearson:

In several ways. First of all, general understanding of science. What humanity knows about the world is ever more important. This has to do with why I took the path that wasn't directly in academic science the whole time. Academic science is a wonderful tradition and a wonderful world unto itself that has evolved over centuries. It's basically the key place where fairly rich societies can contribute some of their riches to better understanding the world on behalf of everyone, and when I sit back and think about why society pays a scientist, it's basically to help discover new things that will help other people, all of us. That's great, and academic science is great at perpetuating that, handing off what is known from one generation to the next, what isn't, the key questions that remain, and then trying to answer those questions.

Nonetheless, the public remains a key stakeholder and a key potential partner in that process. I think, for me, this actually came home starkly in 2001, when I was in graduate school and 9/11 happened, I looked at what had been done to our country from abroad; how people had attacked it. I looked at our response to it, and I felt that both of them, in some ways, reflected people adopting new technology, but not new knowledge. People being perfectly willing to use technology to hurt other people, but not to adapt to the new insights about the world and its causal basis that might challenge ideologies and ways of thinking that actually, maybe, harmed more people than they did good.

That worried me a lot and when I thought about ... I think many of us reflected a lot on our own lives then, wherever we were. I started thinking about my responsibility as a scientist, being entrusted by society to gain new knowledge, but ways to get that knowledge to people faster; to people outside the ivory tower, so that the other people who might need to know about it in the world, be it in our government or abroad, wherever. Alternative career paths became interesting to me and a way to apply my own expertise and convey insights from my field, which was genomics and, in particular, human genomics, to the world at large. In a modest way, maybe help the broader world understand what we had come to know about the world in the way that I could.

That's where I started thinking about companies as a new way of doing that, about other paths besides just becoming a tenure-tracked professor, for example. Here at the Genome Center, I think of this institution as a para-academic one. We are certainly an academic research institution, but we're also a public-facing hub that gathers people from around the city, so scientists, but also lay-folk who are ultimately interested in genomes and what they'll tell us about the world, to make that happen faster.

That's already happening in some key ways in other fields of science. If you look at the way that access to the web, for example, has made citizen science in astronomy possible through the study-at-home project or through projects where people can play games and try folding structures of proteins to find the structure that actually is likely real under given conditions for that protein and actually discover those structures faster than just computers could. People are already contributing as citizens to scientific efforts to understand things, thanks to parallelized technology like the web, in really cool ways.

All that is happening with sort of generic data about the world. Astronomy data being -- trying to find and classify galaxies from great pictures that we can now take of the sky. In the case of genomes, there's the added benefit that the data are actually inside each person who might be a contributor, so your own data can come to the table and you can help understand it in the context of everyone else's. You can learn something as a scientist, and I mean that, as a citizen, you can be a scientist, you can demystify that process. That's a really great possibility for us here at the Genome Center to make that happen within genomics.

Here at the Genome Center, unlike in the astronomy world, the data that we're going to be bringing in over time are from people's own flesh and blood. I think that that is an additional draw to people as potential "participant scientists," is the phrase I like to think of. So I don't think of just science education but participatory science where people are bringing data to the table, and from their own bodies, that are actually scientifically useful. They can be pooled with data from other people to understand ourselves better and they can actually participate as engaged scientists as part of that process.

In the process of doing so, they're helping everybody learn more about the world and they're helping themselves learn more about the world, starting with what interests them most, which is, frankly, the hook of their own curious quirks. What makes me different from people in my own family, from my own siblings, perhaps? What makes me different from people down the block, from people around the world? In various just splendidly myriad ways, how do we differ from each other and what can we understand about those differences from genome data, from RNA sequencing data, from data on lifestyle that don't trace, ultimately, to genomic differences, but we can start to tease apart the causal contributors to our diversity.

Ann Nguyen:

Your keynote presentation on June 22 centers on a critical insight related to long-term healthcare that you deliberately have not revealed. Can you share a little bit more context now?

Nathaniel Pearson:

I meant to be a bit coy there, and I certainly want people to tune in and hear what I think is a really important lesson that we've already learned from other fields about how to manage increasingly big data that are informative about health-relevant stuff. In the talk, I will cast us back to the years between 1850s and '60s. They were really, really scientifically active times, so at this very time, you had people like de Chancourtois and others who were pioneering a lot of what we now know about chemistry, about the diversity of elements in the world. They were working at the same time -- and of course, Mendeleev, so Mendeleev was working around the same time as Mendel, sharing more than just the name.

They were working at this critical time in science where we had actually gathered a fair bit of data about the world. We had started to build a framework for understanding it scientifically and we started to build networks of people to talk about it jointly. There was no Twitter yet, but there were people corresponding with each other in the sciences in really important ways that spurred it forward.

That time is really informative for us because, when we were first -- I think around 1856 or so, there might have been a few dozen elements that were known, so our understanding of chemistry was starting to take form in ways that let us systematize it and de Chancourtois was a key figure in doing so. He came up with a model forerunner of the periodic table called the telluric helix, so there was a helix already involved, and I know how that foreshadows our obsession with helices in genomics.

Without giving away too much, I think that the way that that understanding of chemistry evolved, that we started to first look at elements and then start to tie those elements to their effect on, say, human health in particular ways. It's very informative for us to think about that history and what did and didn't work well in the context of what we've done in clinical genomics, where, likewise, over the past couple of decades, starting with people sequencing a gene or two in several sick people with a given disease, how we've started to look first at just a little slice of human genetic variation and now we're able to look at much broader slices of that. Our early habits for how we classify that knowledge are going to have to adapt to the much bigger data that we have access to now.

I think that the history of chemistry in the 1850s and '60s, that critical time when these chemists were starting to formulate our understanding of chemistry around the same time that Mendel was discovering some of the first key insights into systematically thinking about genetic inheritance and extracting the idea of a gene and of variants, ultimately. The same time that Darwin was systematizing all of the data that had been gathered on his voyages earlier in life and publishing really important works that crystallized insights from that data into a framework of thinking about evolution and its potential causal bases.

That critical time in science is really informative for us now and I want to echo that in the talk. I think that people will get it by the end, that there's some key lessons there. When we go to a drugstore today, a lot of what we see on the back of a mystery bottle at the drugstore reflects the hard-won lessons from how we characterize the chemistry of health, and we're going to need to learn those same lessons in genomics, including a critical one where we're going down the wrong path right now. We can learn from that history in chemistry to figure out what the right path is.

Ann Nguyen:

I guess we'll have to learn more on-site this summer, but, for now, thank you, Nathan, for sharing your past and present experiences and insights.

Nathaniel Pearson:

Absolutely. Looking forward to seeing everyone this summer.

Ann Nguyen:

That was Nathaniel Pearson of the New York Genome Center. He'll be giving his keynote presentation during the opening session at TCGC: The Clinical Genome Conference, again, June 22-24 in San Francisco. To learn more from Dr. Pearson in person, go to www.clinicalgenomeconference.com for registration details and enter the keycode "Podcast”.

This is Ann Nguyen. Thank you for listening.