What's left to explore? - Nathan Wolfe

[Music] [Applause] Recently, I visited Beloit, Wisconsin, and I was there to honor a great 20th-century explorer, Roy Chapman Andrews. During his time at the American Museum of Natural History, Andrews led a range of expeditions to charted regions like here in the Gobi Desert. He was quite a figure; he was later said to be the basis of the Indiana Jones character.

When I was in Beloit, Wisconsin, I gave a public lecture to a group of middle school students, and I'm here to tell you if there's anything more intimidating than talking here at TED, it'll be trying to hold the attention of a group of 12-year-olds for a 45-minute lecture. Uh, don't try that one. At the end of the lecture, they asked a number of questions, but there was one that really stuck with me since then. There was a young girl who stood up and she asked the question: "Where should we explore?"

I think there's a sense that many of us have that the great Age of Exploration on Earth is over, that for the next generation, they're going to have to go to outer space or the deepest oceans in order to find something significant to explore. But is that really the case? Is there really nowhere significant for us to explore left here on Earth? It sort of made me think back to one of my favorite explorers in the history of biology: this is an explorer of the unseen world, Martinus Beijerinck.

So Beijerinck set out to discover the cause of tobacco mosaic disease. What he did is he took the infected juice from tobacco plants, and he would filter it through smaller and smaller filters. He reached the point where he felt that there must be something out there that was smaller than the smallest forms of life that were ever known—uh, bacteria at the time. He came up with a name for his mystery agent; he called it the virus, Latin for poison.

In sort of uncovering viruses, it really opened this entire new world for us. We now know that viruses make up the majority of the genetic information on our planet—more than the genetic information in all other forms of life combined. Obviously, there's been tremendous practical applications associated with this world: things like the eradication of smallpox, the advent of a vaccine against cervical cancer, which we now know is most commonly caused by human papillomavirus.

And Beijerinck's discovery was not something that occurred 500 years ago; a little over a hundred years ago, he discovered viruses. So basically, we had automobiles, but we were unaware of the forms of life that make up most of the genetic information on our planet. We now have these amazing tools to allow us to explore the unseen world—things like deep sequencing—which allow us to do much more than just sort of skim the surface and look at individual genomes from a particular species, but to look at entire metagenomes, the communities of teaming microorganisms in and around us, and to document all of the genetic information in these species.

We can apply these techniques to things from soil to skin and everything in between. Uh, in my organization, we now do this on a regular basis to identify the causes of outbreaks that are sort of unclear, exactly what causes them. Just to give you a sense of how this works—imagine that we took a nasal swab from every single one of you. This is something we commonly do to look for respiratory viruses like influenza.

The first thing that we would see is a tremendous amount of genetic information. If we started looking into that genetic information, we'd see a number of usual suspects out there: of course, a lot of human genetic information, but also bacterial and viral information, mostly from things that are completely harmless within your nose. But we'd also see something very, very surprising.

As we started to look at this information, we would see that about 20% of the genetic information in your nose doesn't match anything that we've ever seen before—no plant, animal, fungus, virus, or bacteria. Basically, we have no clue what this is. For the small group of us who actually study this kind of data, a few of us have actually begun to call this information "biological dark matter."

We know it's not anything that we've seen before; it's sort of the equivalent of an uncharted continent right within our own genetic information. And there's a lot of it—if you think about it, 20% of genetic information in your nose is a lot of biological dark matter. If we looked at your gut, up to 40 or 50% of that information is biological dark matter. Even in the relatively sterile blood, around 1 to 2% of this information is dark matter that can't be classified, can't be typed, or matched with anything that we've seen before.

At first, we thought that perhaps this was an artifact, right? These deep sequencing tools are relatively new, but as they've become more and more accurate, we've determined that this information is a form of life—or at least some of it is a form of life. While the hypotheses for explaining the existence of biological dark matter are really only in their infancy, there's a very, very exciting possibility that exists: that buried in this life, in these genetic information, are signatures of as yet unidentified life that, as we explore these strings of A's, T's, C's, and G's, we may uncover a completely new class of life that, like Beijerinck, will fundamentally change the way that we think about the nature of biology.

Perhaps this will allow us to identify the cause of a cancer that afflicts us or identify the source of an outbreak that we are familiar with, or perhaps create a new tool in molecular biology. I'm pleased to announce that, along with colleagues at Stanford and Caltech and UCSF, we're currently starting an initiative to explore biological dark matter for the existence of new forms of life.

A little over a hundred years ago, people were unaware of viruses, the forms of life that make up most of the genetic information on our planet. One hundred years from now, people may marvel that we were perhaps completely unaware of a new class of life that literally was right under our noses. It's true, we may have charted all the continents on the planet, and we may have discovered all the mammals that are out there, but that doesn't mean that there's nothing left to explore on Earth.

Beijerinck and his kind provide an important lesson for the next generation of explorers—people like that young girl from Beloit, Wisconsin. I think if we phrase that lesson, it's something like this: don't assume that what we currently think is out there is the full story. Go after the dark matter in whatever field you choose to explore. There are unknowns all around us, and they're just waiting to be discovered. Thank you. [Music]