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"The Rules of Life," an NSF audio documentary

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Can you imagine a world where scientists can predict whether crops will grow in extreme temperatures, just by understanding their genetic makeup, or where doctors can know what cells will become malignant, well before they have the chance to develop into cancerous growths? The "Rules of Life" audio documentary shows how NSF and the research community are working toward building that world, by solving the riddle of predicting phenotype.

Credit: NSF/R L Paul Productions

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Audio Transcript:

This is a partial transcript. Find the full transcript of the Rules of Life at this link.

From the National Science Foundation, this is The Rules of Life.


(dramatic music)

ANNOUNCER: Every year, in January, a small village gets worldwide attention. The world's greatest grandmasters get together with thousands of amateurs to play the ultimate game of minds.


ANNOUNCER: So, you're sitting there and you're watching a game of chess. But you've got a little problem. OK, a big one. You never bothered to learn the rules. Or maybe you only understand one rule: Like maybe all you know is that, except for the king, pieces can't jump over other pieces. But you don't know anything else.


PLAY-BY-PLAY ANNOUNCER 1: F6 is too ugly for contemplation so we have to take and now, knight C -- rook g8 that -- no. Rook g8 hangs the e6.


PLAY-BY-PLAY ANNOUNCER 1: We're not happy about that.


ANNOUNCER: So, there you are and that's the only rule of chess that you know. How on Earth would you possibly be able to predict what a player's next move will be?


PLAY-BY-PLAY ANNOUNCER 2: Maybe you wanna do that. Rook g8, Bishop takes e6 and rook g7 and just say …

PLAY-BY-PLAY ANNOUNCER 1: If that's the defense that the world champion to has to rely upon, guess what? I don't like his game at all.


ANNOUNCER: Now imagine, instead of watching a game of chess, you are observing the game … of life.


TONY GOLDBERG: Hanging out upside-down under this particular leaf is a little mosquito and that's Culex pipiens.

GRAD STUDENT: This is E. coli genomic DNA. So, it contains all the genomic information for bacteria E. coli strain DH10B.

BEASLEY: Looking down at the ground here, I immediately see a mound of dirt that kind of clued me in that we might be getting close to some ants.


ANNOUNCER: In other words, what if you are a scientist, trying to understand exactly how life on Earth works.

ROBB DUNN: There are more individual bacteria in your gut than there are trees in the rainforests

KRISTALA PRATHER: We have Streptomyces coelicolor; we haveClostridium butyricum; we haveLactococcus lactis.

DEANNA BEASLEY: I'm just going to poke a little hole here and, yep, here we have some fire ants


ANNOUNCER: It's almost exactly like knowing only one rule of chess. Science knows a lot about DNA -- what it is, what is does. But despite all our scientific advances, today we still don't know still don't know some of the most basic rules of how the genes within DNA function.

CARROLL: What kinds of things in their DNA determine that a dog is a dog or that a wolfhound is a wolfhound? That's what we've been after.

ANNOUNCER: Doctor Sean Carroll is a professor of molecular biology and genetics at the University of Wisconsin, and author of the book "The Serengeti Rules."

CARROLL: We can stare at the DNA sequence of a creature, running on for hundreds and millions of letters. Now, that does contain the information for making that creature, but at this level, the genetic information is similar enough between, say, something like a sea urchin and a frog or a human and even a fish that you wouldn't be able to just at first glance look at that DNA and say, "Oh, that is gonna make a human."

ANNOUNCER: And even if science had answered that question -- and remember, it hasn't -- we still don't know how those genes behave out in the world. And so just like with chess,


PLAY-BY-PLAY ANNOUNCER 2: Maybe you wanna do that. Rook g8, Bishop takes e6 and rook g7 and just say


ANNOUNCER: How can you begin to predict with any certainty what life's "next move" will be?

JENNIFER ROSS: That is where we are right now with biology, is trying to understand the rules of life. What are the fundamental principles behind how life not only emerged, but how it's functioning now?

ANNOUNCER: The rules of life -- that rule book that governs every aspect of every living thing on Earth -- every plant, every animal, every disease, every person. From the molecular scale…to the entirety of Earth's ecosystems.

CARROLL: Just the pursuit of rules -- thinking that you are not gonna be satisfied until you can sort of constrain the possibilities and winnow things down to a few repeating patterns and make predictions -- that's a very important mindset to have. It's not ubiquitous in science. It's not ubiquitous in biology. Not everybody necessarily thinks that way.

ANNOUNCER: Not everyone. But plenty of biologists -- and other scientists who work in biology -- they do think this way. Dr. Kat Shea is a professor of Biology at Penn State University.

SHEA: When people come to biology, there's a huge amount of variation and a lot of people will look at it and almost throw their hands up and say, "Everything is different and cannot be described according to rules that are used to describe anything else." But I fundamentally believe that that's not true and half the fun is finding out what it actually depends on.

ANNOUNCER: It's half the fun, because -- just like with chess -- if you know the rules, you may be able to figure out life's next move. And that's going to come in pretty handy when you're doing the things biologists do. Things like confidently predicting the future. Dr. Rob Dunn is an Ecologist at North Carolina State University.

DUNN: If the area between Charlotte, North Carolina and Atlanta becomes one giant city, "Charlanta," and it stays that way for 200 years, what can we predict about the ecological and evolutionary trajectories of the species that live there?

ANNOUNCER: Or even tracking a killer.

GOLDBERG: We're in a cemetery and in places like the west suburbs of Chicago. When West Nile virus came into Chicago, we were really not sure why the West Chicago suburbs were a hotspot.

ANNOUNCER: Now, the Rules of Life aren't a total black box. There are a few rules that have been nailed down. At least we think so.

GOLDBERG: The rules of competitive exclusion and competition and evolution.

PRATHER: DNA is going to be transcribed into RNA, and RNA is going to be translated into protein.

CARROLL: Is there an entirely genetic recipe for every different kind of animal, or are there really common ingredients that are just used in different ways? And the answer is the latter.

ANNOUNCER: Largely though, right now we don't know the rules. But imagine if we did: Think of a world where we can predict -- with confidence -- how crops will grow in extreme temperatures, or when cells will turn malignant. By identifying the basic rules of life across scales of time, space, and complexity, we may come to predict how cells, brains, bodies, and biomes will respond to changes around them; how a disease might act in the future; how a disease will respond to a drug, or precisely how much food the nation's farms would turn out next year.


DUNN: Are there central laws -- as we think about the bodies of organisms -- that govern what they would do and that might allow me to predict what happens in some ecosystem I've never seen before?

SHEA: We're looking for general rules that will allow us to address novel outbreaks or novel invasions or novel extinctions so that we don't always have to start from scratch.

CARROLL: All sorts of biologists have been trying to figure out what those rules are. What are the important ingredients that make things the way they are?


SHEA: A fascinating question is, when we look at a community of plants and insects that occur in a native range, and thinking about disturbances -- fires, floods, hurricanes and how very different disturbances are actually fundamentally the same.

GOLDBERG: If it's a directly transmitted pathogen it might follow one set of rules, if it's a vector-borne disease it might follow another set of rules,

DUNN: We're building on the insights from the big general rules to paint a picture of the things we have the most certainty about in what's going to happen in these scenarios. And then to identify the things that are always going to be a little bit muddy.


ANNOUNCER: But the trouble is: Nature seems to do everything it can to make sure humans can't figure out what the rules of life are. In a lot of ways, this makes biology a much more difficult branch of science than others -- like engineering or physics. Ask physicists and engineers. They'll tell you so themselves.

ROSS: We're currently standing in my laboratory which is actually located in the physics department.

ANNOUNCER: Dr. Jennifer Ross is a physicist at U-Mass, Amherst. Her specialty is a critical part of the insides of cells, these tiny things called "microtubules."

ROSS: They're used for the highway system of the cell, and they're also used as the bones of the cell.

She says physics has been about rules from its very beginnings.

ROSS: With Newton and Galileo. And they were just tracking how things fell or how stars went across the sky.

ANNOUNCER: But Jenny Ross is a biophysicist. She works with cells …. which are living things. They change all the time. And because they change ….

ROSS: A lot of these rules are much more difficult to understand than the simple rules of how an apple falls from a tree, or how celestial bodies go across the sky,


PRATHER: We're now in what's called Building E17 and E18 in the Chemical Engineering Department at MIT in Cambridge, Massachusetts


ANNOUNCER: This is Dr. Kris Jones Prather. What her lab does is invent products that can replace petroleum in things like plastics and jet fuel. She's an engineer -- someone who designs and builds things -- like an engine or a bookcase. But Kris is a bio-engineer who builds things out of living organisms. The tough part there is: you can design a bookcase …

PRATHER: And be reasonably confident that the bookcase is not going to spontaneously differentiate into something else.

ANNOUNCER: But a piece of DNA is not a bookcase. It can mutate. It can change. In biology, you're forced to deal with principles like "Diversity," where you have a limited set of rules, but a whole lot of different potential outcomes. You have things like "Emergence," where thousands of individual ants or individual molecules behave individually, but also combine to create some larger system property. Plus, DNA is inside every living thing.


TONY GOLDBERG: American robins, house sparrows, catbirds,

PRATHER: We have Candida albicans, which is a yeast, we've got -- here's a fun one --Archaeoglobus fulgidus.

LAURA RUSSO: We are standing next to carduus acanthoides; it's also known as the plumeless thistle.


ANNOUNCER: There are leaves that are nearly always specific shapes …. Animals that are nearly always the same color or size. All of them are that way because of a complex interaction between DNA and the environment. And the nature of this interaction remains almost completely hidden to scientists.

PRATHER: This comes back to the idea that we don't know all the rules.

ANNOUNCER: Every living thing on Earth -- from birds to bacteria …. All of them interact with the environment on the genetic level. And what happens is: They interact with the environment…which causes changes at their genetic level… which in turn changes how they interact with the environment…which causes more changes at their genetic level. And on and on and on. Here's Tony Goldberg from the University of Wisconsin.

GOLDBERG: I don't think the fact that we can generate millions upon millions of As, Cs, Gs, and Ts is ever going to let us predict what an organism is going to do in a complex world with absolute perfection. There is a big range of possibilities for what an organism can do in an environment, but more than that, if we think about what our genes are, they're not hard and fast decision-making machines.

ANNOUNCER: No. Genes evolved in an uncertain world and so they're prepared to be flexible, depending on the situation they find themselves in. The biggest gap in biological knowledge -- and this is universally recognized -- the biggest gap is our inability to look at the genetics and environment of an organism and predict the impact they'll have on its observable characteristics. So if you see spikey leaves, or green lizards? There are any number of factors that cause them to be spikey or green, and predicting what those are is extremely complex. By the way, scientists have a word for that spikeiness or that greenness -- those observable characteristics. The word they use is phenotype.


JENNY ROSS: Phenotype

GOLDBERG: The phenotype of an organism.

LAURA RUSSO: Phenotype.

ANNOUNCER: Phenotype is the distinctive set of traits that make something "the way it is." Like if maybe that "something" is biologist Sean Carroll.

CARROLL: Here's this Irish Catholic guy with blue eyes and a graying beard and a little bit of a stomach. You know, that's part of my phenotype -- some of that was hard genetics, the blue eyes. The gut definitely is an environmental influence. We want to understand that interplay between genetics and environment that determines the way creatures are or the way some particular human characteristic is.

ANNOUNCER: The scientific search for this elusive ability to predict an organism's phenotype from what we know about its genetics and environment could help in the lab and in practice -- to address diseases or increase the food supply. And understanding the rules is particularly important if you're looking to manipulate them to make life better.

PRATHER: We can take something like sugar and make biofuels. We could also take the molecules that we can make from things like sugar and make pharmaceuticals.

ROSS: We put in the DNA and we engineer it to make the proteins that we want.


ANNOUNCER: We don't know all the rules that lead from beginning to end, but we have hints to what those rules are. Finding those rules is the essence of what biology is doing in the 21st century. You're listening to The Rules of Life, from the National Science Foundation. Coming up, tracking a killer, cracking the cancer code and looking at Alzheimer's from the inside out. Stay with us.

ANNOUNCER: The Rules of Life, from the National Science Foundation.

(Bird call)

ANNOUNCER: You're hearing the call of a drab, little gray bird that lives along streams in western North America. It's called the Western Wood-Pewee. Now there's another bird that looks almost exactly like the Western Wood-Pewee. And it doesn't just look like it. Scientists use to consider it the same species. It's called the Eastern Wood-Pewee. Here's the thing though: Instead of sounding like this

(Bird call)

ANNOUNCER: It sounds like this.

This is a partial transcript. Find the full transcript of the Rules of Life at this link.

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