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Genomics and Our Future February 1, 2003

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Juan Enriquez talks about how important the impact of sequencing genomes can be in the course of life now and in the future.


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I'm supposed to scare you, because it's about fear, right? And you should be really afraid, but not for the reasons why you think you should be. You should be really afraid that - if we stick up the first slide on this thing - there we go - that you're missing out. Because if you spend this week thinking about Iraq and thinking about Bush and thinking about the stock market, you're going to miss one of the greatest adventures that we've ever been on. And this is what this adventure's really about. This is crystallized DNA. Every life form on this planet - every insect, every bacteria, every plant, every animal, every human, every politician - (Laughter) is coded in that stuff. And if you want to take a single crystal of DNA, it looks like that. And we're just beginning to understand this stuff. And this is the single most exciting adventure that we have ever been on. It's the single greatest mapping project we've ever been on. If you think that the mapping of America's made a difference, or landing on the moon, or this other stuff, it's the map of ourselves and the map of every plant and every insect and every bacteria that really makes a difference. And it's beginning to tell us a lot about evolution. (Laughter)

It turns out that what this stuff is - and Richard Dawkins has written about this - is, this is really a river out of Eden. So, the 3.2 billion base pairs inside each of your cells is really a history of where you've been for the past billion years. And we could start dating things, and we could start changing medicine and archeology. It turns out that if you take the human species about 700 years ago, white Europeans diverged from black Africans in a very significant way. White Europeans were subject to the plague. And when they were subject to the plague, most people didn't survive, but those who survived had a mutation on the CCR5 receptor. And that mutation was passed on to their kids because they're the ones that survived, so there was a great deal of population pressure. In Africa, because you didn't have these cities, you didn't have that CCR5 population pressure mutation. We can date it to 700 years ago. That is one of the reasons why AIDS is raging across Africa as fast as it is, and not as fast across Europe. And we're beginning to find these little things for malaria, for sickle cell, for cancers. And in the measure that we map ourselves, this is the single greatest adventure that we'll ever be on. And this Friday, I want you to pull out a really good bottle of wine, and I want you to toast these two people. Because this Friday 50 years ago, Watson and Crick found the structure of DNA, and that is almost as important a date as 12 February when we first mapped ourselves, but anyway, we'll get to that.

I thought we'd talk about the new zoo. So, all you guys have heard about DNA, all the stuff that DNA does, but some of the stuff we're discovering is kind of nifty because this turns out to be the single most abundant species on the planet. If you think you're successful or cockroaches are successful, it turns out that there's ten trillion trillion Pleurococcus sitting out there. And we didn't know that Pleurococcus was out there, which is part of the reason why this whole species mapping project is so important. Because we're just beginning to learn where we came from and what we are. And we're finding amoebas like this. This is Amoeba dubia. And Amoeba dubia doesn't look like much, except that each of you has about 3.2 billion letters, which is what makes you you as far as gene code inside each of your cells, and this little amoeba which, you know, sits in water in hundreds and millions and billions, turns out to have 620 billion base pairs of gene code inside. So, this little thingamajig has a genome that's 200 times the size of yours. And if you're thinking of efficient information storage mechanisms, it may not turn out to be chips. It may turn out to be something that looks a little like that amoeba.

And, again, we're learning from life and how life works. This funky little thing: people didn't used to think that it was worth taking samples out of nuclear reactors because it was dangerous and, of course, nothing lived there. And then finally somebody picked up a microscope and looked at the water that was sitting next to the cores. And sitting next to that water in the cores was little Deinococcus radiodurans, doing a backstroke, having its chromosomes blown apart every day, six, seven times, restitching them, living in about 200 times the radiation that would kill you. And by now you should be getting a hint as to how diverse and how important and how interesting this journey into life is, and how many different life forms there are, and how there can be different life forms living in very different places, maybe even outside of this planet. Because if you can live in radiation that looks like this, that brings up a whole series of interesting questions.

This little thingamajig: we didn't know this thingamajig existed. We should have known that this existed because this is the only bacteria that you can see to the naked eye. So, this thing is 0.75 millimeters. It lives in a deep trench off the coast of Namibia. And what you're looking at with this namibiensis is the biggest bacteria we've ever seen. So, it's about the size of a little period on a sentence. Again, we didn't know this thing was there three years ago. We're just beginning this journey of life in the new zoo.

This is a really odd one. This is Ferroplasma. The reason why Ferroplasma is interesting is because it eats iron, lives inside the equivalent of battery acid, and excretes sulfuric acid. So, when you think of odd life forms, when you think of what it takes to live, it turns out this is a very efficient life form, and they call it an archaea. Archaea means the ancient ones. And the reason why they're ancient is because this thing came up when this planet was covered by things like sulfuric acid in batteries, and it was eating iron when the earth was part of a melted core. So, it's not just dogs and cats and whales and dolphins that you should be aware of and interested in in this little journey.

Your fear should be that you are not, that you're paying attention to stuff which is temporal. I mean, George Bush - he's going to be gone, all right? Life isn't. Whether the humans survive or don't survive, these things are going to be living on this planet or other planets. And it's just beginning to understand this code of DNA that's really the most exciting intellectual adventure that we've ever been on.

And you can do strange things with this stuff. This is a baby gar. Conservation group gets together, tries to figure out how to breed an animal that's almost extinct. They can't do it naturally, so what they do with this thing is they take a spoon, take some cells out of an adult gar's mouth, code, take the cells from that and insert it into a fertilized cow's egg, reprogram cow's egg - different gene code. When you do that, the cow gives birth to a gar. We are now experimenting with bongos, pandas, elims*, Sumatran tigers, and the Australians - bless their hearts - are playing with these things.

Now, the last of these things died in September, 1936. These are Tasmanian tigers. The last known one died at the Hobart Zoo. But it turns out that as we learn more about gene code and how to reprogram species, we may be able to close the gene gaps in deteriorate DNA. And when we learn how to close the gene gaps, then we can put a full string of DNA together. And if we do that, and insert this into a fertilized wolf's egg, we may give birth to an animal that hasn't walked the earth since 1936. And then you can start going back further, and you can start thinking about dodos, and you can think about other species. And in other places, like Maryland, they're trying to figure out what the primordial ancestor is. Because each of us contains our entire gene code of where we've been for the past billion years, because we've evolved from that stuff, you can take that tree of life and collapse it back, and in the measure that you learn to reprogram, maybe we'll give birth to something that is very close to the first primordial ooze. And it's all coming out of things that look like this.

These are companies that didn't exist five years ago. Huge gene sequencing facilities the size of football fields. Some are public. Some are private. It takes about 5 billion dollars to sequence a human being the first time. Takes about 3 million dollars the second time. We will have a 1,000 dollar genome within the next five to eight years. That means each of you will contain on a CD your entire gene code. And it will be really boring. It will read like this. (Laughter) The really neat thing about this stuff is that's life. And Laurie's going to talk about this one a little bit. Because if you happen to find this one inside your body, you're in big trouble because that's the source code for Ebola. That's one of the deadliest diseases known to humans. But plants work the same way and insects work the same way, and this apple works the same way. This apple is the same thing as this floppy disk. Because this thing codes ones and zeros, and this thing codes A, T, C, Gs, and it sits up there, absorbing energy on a tree, and one fine day it has enough energy to say, execute, and it goes thump. Right? (Laughter) And when it does that, pushes a .EXE, what it does is, it executes the first line of code, which reads just like that, AATCAGGGACCC, and that means: make a root. Next line of code: make a stem. Next line of code, TACGGGG: make a flower that's white, that blooms in the spring, that smells like this. In the measure that you have the code and the measure that you read it - and, by the way, the first plant was read two years ago; the first human was read two years ago; the first insect was read two years ago.

The first thing that we ever read was in 1995: a little bacteria called Haemophilus influenzae. In the measure that you have the source code, as all of you know, you can change the source code, and you can reprogram life forms so that this little thingy becomes a vaccine, or this little thingy starts producing biomaterials, which is why DuPont is now growing a form of polyester that feels like silk in corn. This changes all rules. This is life, but we're reprogramming it. This is what you look like. This is one of your chromosomes. And what you can do now is, you can outlay exactly what your chromosome is, and what the gene code on that chromosome is right here, and what those genes code for, and what animals they code against, and then you can tie it to the literature. And in the measure that you can do that, you can go home today, and get on the Internet, and access the world's biggest public library, which is a library of life. And you can do some pretty strange things because in the same way as you can reprogram this apple, if you go to Cliff Tabin's lab at the Harvard Medical School, he's reprogramming chicken embryos to grow more wings. Why would Cliff be doing that? He doesn't have a restaurant. (Laughter)

The reason why he's reprogramming that animal to have more wings is because when you used to play with lizards as a little child, and you picked up the lizard, sometimes the tail fell off, but it regrew. Not so in human beings: you cut off an arm, you cut off a leg, it doesn't regrow. But because each of your cells contains your entire gene code, each cell can be reprogrammed, if we don't stop stem cell research and if we don't stop genomic research, to express different body functions. And in the measure that we learn how chickens grow wings, and what the program is for those cells to differentiate, one of the things we're going to be able to do is to stop undifferentiated cells, which you know as cancer, and one of the things we're going to learn how to do is how to reprogram cells like stem cells in such a way that they express bone, stomach, skin, pancreas. And you are likely to be wondering around - and your children - on regrown body parts in a reasonable period of time, in some places in the world where they don't stop the research.

How's this stuff work? If each of you differs from the person next to you by one in a thousand, but only 3 percent codes, which means it's only one in a thousand times 3 percent, very small differences in expression and punctuation can make a significant difference. Take a simple declarative sentence. (Laughter) Right? That's perfectly clear. So, men read that sentence, and they look at that sentence, and they read this. Okay? Now, women look at that sentence and they, uh-uh, wrong. This is the way it should be seen. (Laughter) That's what your genes are doing. That's why you differ from this person over here by one in a thousand. Right? But, you know, he's reasonably good looking, but... I won't go there. You can do this stuff even without changing the punctuation. You can look at this, right? And they look at the world a little differently. They look at the same world and they say... (Laughter) That's how the same gene code - that's why you have 30,000 genes, mice have 30,000 genes, husbands have 30,000 genes. Mice and men are the same. Wives know that, but anyway. You can make very small changes in gene code and get really different outcomes, even with the same string of letters. That's what your genes are doing every day. That's why sometimes a person's genes don't have to change a lot to get cancer.

These little chippies, these things are the size of a credit card. They will test any one of you for 60,000 genetic conditions. That brings up questions of privacy and insurability and all kinds of stuff, but it also allows us to start going after diseases because if you run a person who has leukemia through something like this, it turns out that three diseases with completely similar clinical syndromes are completely different diseases. Because in ALL leukemia, that set of genes over there over-expresses. In MLL, it's the middle set of genes, and in AML, it's the bottom set of genes. And if one of those particular things is expressing in your body, then you take Gleevec and you're cured. If it is not expressing in your body, if you don't have one of those types - a particular one of those types - don't take Gleevec. It won't do anything for you. Same thing with Receptin if you've got breast cancer. Don't have an HER-2 receptor, don't take Receptin. Changes the nature of medicine. Changes the predictions of medicine. Changes the way medicine works.

The greatest repository of knowledge when most of us went to college was this thing, and it turns out that this is not so important any more. The U.S. Library of Congress, in terms of its printed volume of data, contains less data than is coming out of a good genomics company every month on a compound basis. Let me say that again: A single genomics company generates more data in a month, on a compound basis, than is in the printed collections of the Library of Congress. This is what's been powering the U.S. economy. It's Moore's Law. So, all of you know that the price of computers halves every 18 months and the power doubles, right? Except that when you lay that side by side with the speed with which gene data's being deposited in GenBank, Moore's Law is right here: it's the blue line. This is on a log scale, and that's what superexponential growth means. This is going to push computers to have to grow faster than they've been growing because so far, there haven't been applications that have been required that need to go faster than Moore's Law. This stuff does.

And here's an interesting map. This is a map which was finished at the Harvard Business School. One of the really interesting questions is, if all this data's free, who's using it? This is the greatest public library in the world. Well, it turns out that there's about 27 trillion bits moving inside from the United States to the United States; about 4.6 trillion is going over to those European countries; about 5.5's going to Japan; there's almost no communication between Japan, and nobody else is literate in this stuff. It's free. No-one's reading it. They're focusing on the war; they're focusing on Bush; they're not interested in life. So, this is what a new map of the world looks like. That is the genomically literate world. And that is a problem. In fact, it's not a genomically literate world. You can break this out by states. And you can watch states rise and fall depending on their ability to speak a language of life, and you can watch New York fall off a cliff, and you can watch New Jersey fall off a cliff, and you can watch the rise of the new empires of intelligence. And you can break it out by counties because it's specific counties. And if you want to get more specific, it's actually specific zip codes. (Laughter)

So, you want to know where life is happening? Well, in Southern California it's happening in 92121. And that's it. And that's the triangle between Salk, Scripps, UCSD, and it's called Torrey Pines Road. That means you don't need to be a big nation to be successful; it means you don't need a lot of people to be successful; and it means you can move most of the wealth of a country in about three or four carefully picked 747s.

Same thing in Massachusetts. Looks more spread out but - oh, by the way, the ones that are the same color are contiguous. What's the net effect of this? In an agricultural society, the difference between the richest and the poorest, the most productive and the least productive, was five to one. Why? Because in agriculture, if you had 10 kids and you got up a little bit earlier and you work a little bit harder, you could produce about five times more wealth, on average, than your neighbor. In a knowledge society, that number is now 427 to 1. It really matters if you're literate, not just in reading and writing in English and French and German, but in Microsoft and Linux and Apple. And very soon it's going to matter if you're literate in life code. So, if there is something you should fear, it's that you're not keeping your eye on the ball. Because it really matters who speaks life. That's why nations rise and fall.

And it turns out that if you went back to the 1870s, the most productive nation on earth was Australia, per person. And New Zealand was way up there. And then the U.S. came in about 1950, and then Switzerland about 1973, and then the U.S. got back on top - beat up their chocolates and cuckoo clocks. And today, of course, you all know that the most productive nation on earth is Luxembourg, producing about one third more wealth per person per year than America. Tiny landlocked state. No oil. No diamonds. No natural resources. Just smart people moving bits. Different rules.

Here's differential productivity rates. Here's how many people it takes to produce a single U.S. patent. So, about 3,000 Americans, 6,000 Koreans, 14,000 Brits, 790,000 Argentines. You want to know why Argentina's crashing? It's got nothing to do with inflation. It's got nothing to do with privatization. You can take a Harvard-educated Ivy League economist, stick him in charge of Argentina. He still crashes the country because he doesn't understand how the rules have changed. Oh, yeah, and it takes about 5.6 million Indians. Well, watch what happens to India. India and China used to be 40 percent of the global economy just at the Industrial Revolution, and they are now about 4.8 percent. Two billion people. One third of the global population producing 5 percent of the wealth because they didn't get this change, because they kept treating their people like serfs instead of like shareholders of a common project. They didn't keep the people who were educated. They didn't foment the businesses. They didn't do the IPOs. Silicon Valley did. And that's why they say that Silicon Valley has been powered by ICs. Not integrated circuits: Indians and Chinese. (Laughter)

Here's what's happening in the world. It turns out that if you'd gone to the U.N. in 1950, when it was founded, there were 50 countries in this world. It turns out there's now about 192. Country after country is splitting, seceding, succeeding, failing. And it's all getting very fragmented. And this has not stopped. In the 1990s, these are sovereign states that did not exist before 1990. And this doesn't include fusions or name changes or changes in flags. We're generating about 3.12 states per year. People are taking control of their own states, sometimes for the better and sometimes for the worse. And the really interesting thing is, you and your kids are empowered to build great empires, and you don't need a lot to do it. (Music) And, given that the music is over, I was going to talk about how you can use this to generate a lot of wealth, and how code works. (Moderator: Two minutes.) (Laughter) No, I'm going to stop there and we'll do it next year because I don't want to take any of Laurie's time. But thank you very much.

Courtesy of TED

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Source: TED

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- Juan Enriquez
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