TEDxBoston 2011
Richard Resnick: Welcome to the genomic revolution
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Cheap and fast genome sequencing is about to turn health care (and insurance, and politics) upside down. Richard Resnick shows how, in this accessible talk.
Richard Resnick - Entrepreneur
Richard Resnick is on the front lines of the business of genomes, as CEO of GenomeQuest, a maker of genomic software. Full bio
Richard Resnick is on the front lines of the business of genomes, as CEO of GenomeQuest, a maker of genomic software. Full bio
Double-click the English transcript below to play the video.
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Ladies and gentlemen,
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I present to you the human genome.
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(Applause)
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Chromosome one, top left.
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Bottom right are the sex chromosomes.
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Women have two copies of that big X chromosome;
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men have the X
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and, of course, that small copy of the Y.
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Sorry boys, but it's just a tiny little thing that makes you different.
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So if you zoom in on this genome,
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then what you see, of course, is this double helix structure --
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the code of life spelled out with these four biochemical letters,
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or we call them bases, right:
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A, C, G and T.
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How many are there in the human genome? Three billion.
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Is that a big number?
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Well, everybody can throw around big numbers.
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But in fact, if I were to place one base
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on each pixel of this 1280 by 800 resolution screen,
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we would need 3,000 screens to take a look at the genome.
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So it's really quite big.
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And perhaps because of its size,
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a group of people -- all, by the way, with Y chromosomes --
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decided they would want to sequence it.
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(Laughter)
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And so 15 years, actually, and about four billion dollars later,
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the genome was sequenced and published.
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In 2003, the final version was published, and they keep working on it.
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That was all done on a machine that looks like this.
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It costs about a dollar for each base --
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a very slow way of doing it.
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Well folks, I'm here to tell you
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that the world has completely changed
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and none of you know about it.
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So now what we do is we take a genome,
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we make maybe 50 copies of it,
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we cut all those copies up into little 50-base reads,
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and then we sequence them, massively parallel.
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And then we bring that into software,
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and we reassemble it and we tell you what the story is.
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And so just to give you a picture of what this looks like,
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the Human Genome Project: 3 gigabases, right.
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One run on one of these machines:
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200 gigabases in a week.
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And that 200 is going to change to 600 this summer,
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and there's no sign of this pace slowing.
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So the price of a base, to sequence a base,
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has fallen 100 million times.
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That's the equivalent of you filling up your car with gas in 1998,
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waiting until 2011,
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and now you can drive to Jupiter and back twice.
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(Laughter)
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World population,
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PC placements,
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the archive of all the medical literature,
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Moore's law,
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the old way of sequencing, and here's all the new stuff.
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Guys, this is a log scale;
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you don't typically see lines that go up like that.
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So the worldwide capacity to sequence human genomes
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is something like 50,000 to 100,000 human genomes this year.
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And we know this based on the machines that are being placed.
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This is expected to double, triple or maybe quadruple
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year over year for the foreseeable future.
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In fact, there's one lab in particular
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that represents 20 percent of all that capacity.
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It's called the Beijing Genomics Institute.
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The Chinese are absolutely winning this race to the new Moon, by the way.
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What does this mean for medicine?
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So a woman is age 37.
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She presents with stage 2 estrogen receptor-positive breast cancer.
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She is treated with surgery, chemotherapy and radiation.
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She goes home.
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Two years later, she comes back with stage three C ovarian cancer.
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Unfortunately, treated again with surgery and chemotherapy.
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She comes back three years later at age 42
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with more ovarian cancer, more chemotherapy.
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Six months later,
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she comes back with acute myeloid leukemia.
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She goes into respiratory failure and dies eight days later.
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So first, the way in which this woman was treated, in as little as 10 years,
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will look like bloodletting.
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And it's because of people like my colleague, Rick Wilson,
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at the Genome Institute at Washington University,
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who decided to take a look at this woman postmortem.
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And he sequenced, he took skin cells, healthy skin,
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and cancerous bone marrow,
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and he sequenced the whole genomes of both of them
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in a couple of weeks, no big deal.
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And then he compared those two genomes in software,
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and what he found, among other things,
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was a deletion, a 2,000-base deletion
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across three billion bases
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in a particular gene called TP53.
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If you have this deleterious mutation in this gene,
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you're 90 percent likely to get cancer in your life.
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So unfortunately, this doesn't help this woman,
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but it does have severe, profound if you will,
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implications to her family.
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I mean, if they have the same mutation,
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and they get this genetic test, and they understand it,
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then they can go and get regular screens, and they can catch cancer early
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and potentially live a significantly longer life.
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Let me introduce you now to the Beery twins,
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diagnosed with cerebral palsy at the age of two.
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Their mom is a very brave woman
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who didn't believe that the symptoms weren't matching up,
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and through some heroic efforts and a lot of Internet searching,
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she was able to convince the medical community
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that, in fact, they had something else.
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What they had was dopa-responsive dystonia.
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And so they were given L-Dopa,
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and their symptoms did improve,
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but they weren't totally asymptomatic.
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Significant problems remained.
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Turns out the gentleman in this picture is a guy named Joe Beery,
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who was lucky enough to be the CIO
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of a company called Life Technologies.
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They're one of the two companies
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that makes these massive whole genome sequencing tools.
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And so what he did was he got his kids sequenced.
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And what they found was a series of mutations in a gene called SPR,
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which is responsible for producing serotonin, among other things.
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So on top of L-Dopa, they gave these kids a serotonin precursor drug,
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and they're effectively normal now.
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Guys, this would never have happened without whole genome sequencing.
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And at the time -- this was a few years ago -- it cost $100,000.
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Today it's $10,000. Next year it's $1,000.
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The year after it's $100, give or take a year.
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That's how fast this is moving.
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So here's little Nick --
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likes Batman and squirt guns.
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And it turns out Nick shows up at the children's hospital
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with this distended belly like a famine victim.
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And it's not that he's not eating,
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it's that when he eats, his intestine basically opens up
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and feces spill out into his gut.
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So a hundred surgeries later,
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he looks at his mom and says, "Mom,
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please pray for me. I'm in so much pain."
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His pediatrician happens to have a background in clinical genetics
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and he has no idea what's going on,
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but he says, "Let's get this kid's genome sequenced."
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And what they find is a single-point mutation
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in a gene responsible for controlling programmed cell death.
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So the theory is that he's having some immunological reaction
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to what's going on to the food essentially,
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and that's a natural reaction, which causes some programmed cell death.
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But the gene that regulates that down is broken.
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And so this informs, among other things, of course,
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a treatment for bone marrow transplant, which he undertakes.
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And after nine months of grueling recovery,
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he's now eating steak with A1 sauce.
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(Laughter)
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The prospect of using the genome
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as a universal diagnostic
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is upon us today.
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Today, it's here.
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And what it means for all of us
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is that everybody in this room could live an extra five, 10, 20 years
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just because of this one thing.
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Which is a fantastic story,
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unless you think about humanity's footprint on the planet
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and our ability to keep up food production.
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So it turns out
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that the very same technology
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is also being used to grow new lines
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of corn, wheat, soybean and other crops
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that are highly tolerant of drought, of flood,
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of pests and pesticides.
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Now look, as long as we continue to increase the population,
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we're going to have to continue to grow and eat genetically modified foods,
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and that's the only position that I'll take today.
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Unless there's anybody in the audience
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that would like to volunteer to stop eating?
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None, not one.
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This is a typewriter,
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a staple of every desktop for decades.
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And in fact, the typewriter was essentially deleted by this thing.
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And then more general versions of word processors came about.
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But ultimately, it was a disruption on top of a disruption.
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It was Bob Metcalfe inventing the Ethernet
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and the connection of all these computers
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that fundamentally changed everything.
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And suddenly we had Netscape, and we had Yahoo
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and we had, indeed, the entire dotcom bubble.
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(Laughter)
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Not to worry though,
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that was quickly rescued by the iPod, Facebook
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and, indeed, angry birds.
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(Laughter)
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Look, this is where we are today.
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This is the genomic revolution today. This is where we are.
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So what I'd like you to consider is:
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What does it mean
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when these dots don't represent the individual bases of your genome,
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but they connect to genomes all across the planet?
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So I just recently had to buy life insurance.
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And I was required to answer:
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A. I have never had a genetic test, B. I've had one, here you go,
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and C. I've had one and I'm not telling.
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Thankfully, I was able to answer A,
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and I say that honestly in case my life insurance agent is listening.
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But what would have happened if I had said C?
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Consumer applications for genomics, they will flourish.
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Do you want to see whether you're genetically compatible
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with your girlfriend? Sure.
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DNA sequencing on your iPhone? There's an app for that.
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(Laughter)
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Personalized genomic massage anyone?
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There's already a lab today
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that tests for allele 334 of the AVPR1 gene,
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the so-called cheating gene.
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So anybody who's here today with your significant other,
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just turn over to them and swab their mouth,
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send it to the lab and you'll know for sure.
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(Laughter)
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Do you really want to elect a president
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whose genome suggests cardiomyopathy?
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Now think of it, it's 2016
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and the leading candidate releases
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not only her four years of back tax returns,
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but also her personal genome.
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And it looks really good.
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And then she challenges all of her competitors to do the same.
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Do you think that's not going to happen?
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Do you think it would have helped John McCain?
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(Laughter)
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How many people in the audience
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have the last name Resnick like me? Raise your hand.
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Anybody? Nobody.
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Typically, there's one or two.
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So my father's father was one of 10 Resnick brothers.
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They all hated each other.
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And they all moved to different parts of the planet.
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So it's likely
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that I'm related to every Resnick that I ever meet, but I don't know.
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But imagine if my genome were deidentified, sitting in software,
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and a third cousin's genome was also sitting there,
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and there was software that could compare these two
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and make these associations.
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Not hard to imagine. My company has software that does this right now.
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And so imagine one more thing:
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that that software is able to ask both parties for mutual consents,
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"Would you be willing to meet your third cousin?"
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And if we both say yes,
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voila! Welcome to chromosomally LinkedIn.
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(Laughter)
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Now this is probably a good thing, right?
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You have bigger clan gatherings and so on.
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But maybe it's a bad thing as well.
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How many fathers in the room? Raise your hands.
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Okay, so experts think that one to three percent of you
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are not actually the father of your child.
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(Laughter)
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Look --
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(Laughter)
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These genomes, these 23 chromosomes,
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they don't in any way represent the quality of our relationships
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or the nature of our society -- at least not yet.
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And like any new technology,
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it's really in humanity's hands
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to wield it for the betterment of mankind, or not.
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And so I urge you all to wake up and to tune in
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and to influence the genomic revolution that's happening all around you.
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Thank you.
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(Applause)
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ABOUT THE SPEAKER
Richard Resnick - EntrepreneurRichard Resnick is on the front lines of the business of genomes, as CEO of GenomeQuest, a maker of genomic software.
Why you should listen
Richard Resnick is CEO of GenomeQuest , a company that builds software to support genomic medicine -- research and individualized treatments that take advantage of cheap and accessible genome processing. He was previously CEO of Mosaic Bioinformatics; before becoming a bio-entrepreneur, he was a member of the Human Genome Project under Eric Lander at MIT.
Richard Resnick | Speaker | TED.com