WEBVTT

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Thank you.

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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,
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 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: 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
1280x800-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 like this.

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It costs about a dollar for each base --
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 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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Then we bring that into software
and reassemble it,

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and tell you what the story is.

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So 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 modern machines:
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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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 of medical literature,

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Moore's law,

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the old way of sequencing,

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and here's all the new stuff.

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Guys, this is a long 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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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, age 37,

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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,

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she comes back with stage 3C
ovarian cancer, unfortunately;

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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,

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in as little as 10 years,
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 took skin cells, healthy skin

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and cancerous bone marrow,

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and sequenced the whole
genomes of both of them

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in a couple of weeks, no big deal.

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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
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 get regular screens
and can catch cancer early,

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and potentially live
a significantly longer life.

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Let me introduce you 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
who didn't believe it;

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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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They had 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 two companies

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that makes these massive
whole-genome sequencing tools.

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And so he got his kids sequenced.

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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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At the time -- this was
a few years ago -- it cost $100,000.

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Today it's $10,000, next year, $1,000,

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the year after, $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;
it's that when he eats,

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his intestine basically opens up
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, please pray for me.

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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
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 5, 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
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 --

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as long as we continue
to increase the population,

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we'll have to continue to grow and eat
genetically modified foods.

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And that's the only position
I'll take today.

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Unless there's anybody in the audience

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who'd 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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Suddenly we had Netscape, we had Yahoo.

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And we had, indeed,
the entire dot-com 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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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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I just recently had to buy life insurance,
and I was required to answer:

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A. I have never had a genetic test;

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B. I've had one, here you go;

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or 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 will flourish.

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Do you want to see
if you're genetically compatible

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with your girlfriend?

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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 that tests
for allele 334 of the AVPR1 gene,

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the so-called cheating gene.

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(Laughter)

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So anybody who's here today
with your significant other,

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just turn over to them,
swab their mouth, send it to the lab

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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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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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Then she challenges all
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
have the last name Resnick, like me?

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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, and all moved
to different parts of the planet.

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So it's likely I'm related
to every Resnick that I ever meet,

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but I don't know.

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So imagine if my genome
were De-identified, 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 the 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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Imagine one more thing,

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that that software is able to ask
both parties for mutual consent:

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"Would you be willing
to meet your third cousin?"

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And if we both say yes -- voilà!

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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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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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OK, 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

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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)