Welcome to the genomic revolution Richard Resnick
ladies and gentlemen I present to you
the human genome chromosome one top left
bottom right are the sex chromosomes
women have two copies of that big X
chromosome men have the X and of course
that small copy of the Y sorry boys but
it’s just a tiny little thing that makes
you different so if you zoom in on this
genome then what you see of course is
this double helix structure the code
‘life spelled out with these four bio
chemical letters or we call them bases
right AC G and T how many are there in
the human genome 3 billion is that a big
number well everybody can throw around
big numbers but in fact if I were to
place one base on each pixel of this
1280 by 800 resolution screen we would
need 3,000 screens to take a look at the
genome so it’s really quite big and
perhaps because of its size a group of
people all by the way with y chromosomes
decided that they would want to sequence
it
and so 15 years actually in about four
billion dollars later the genome was
sequenced and published in 2003 the
final version was published and they
keep working on it that was all done on
a machine it looks like this costs about
a dollar for each base very slow way of
doing it well folks I’m here to tell you
that the world has completely changed
and none of you know about it so now
what we do is we take a genome we make
maybe 50 copies of it we cut all those
copies up into little 50 base reads and
then we sequence them massively parallel
and then we bring that into software and
we reassemble it and we tell you what
the story is and so just to give you a
picture of what this looks like the
human genome project 3 Giga bases right
one run on one of these modern machines
200 Giga bases in a week and that 200 is
going to change to 600 this summer and
there’s no sign of this pay slowing so
the price of a base to sequence a base
has fallen a hundred million times
that’s the equivalent of you filling up
your car with gas in 1998 waiting until
2011 and now you can drive to Jupiter
and back twice
world population PC placements the
archive of all the medical literature
Moore’s law the old way of sequencing
and here’s all the new stuff guys this
is a log scale you don’t typically see
lines that go up like that right so with
a world wide capacity to sequence human
genomes is something like fifty to a
hundred thousand human genomes this year
and we know this based on the machines
that are being placed this is expected
to double triple or maybe quadruple
year-over-year for the foreseeable
future in fact there’s one lab in
particular that represents twenty
percent of all that capacity it’s called
the Beijing genomics Institute the
Chinese are absolutely winning this race
to the new moon by the way what does it
mean for medicine so woman aged thirty
seven she presents with stage two
estrogen receptor-positive breast cancer
she is treated with surgery chemotherapy
and radiation she goes home two years
later she comes back with stage 3c
ovarian cancer unfortunately treated
again with surgery and chemotherapy
comes back three years later at age 42
with more ovarian cancer more
chemotherapy six months later she comes
back with acute myeloid leukemia she
goes into respiratory failure and dies
eight days later so first the way in
which this woman was treated in as
little as ten years will look like
bloodletting and it’s because of people
like my colleague Rick Wilson at the
genome Institute at Washington
University who decided to take a look at
this woman postmortem any sequenced he
took skin cells healthy skin and
cancerous bone marrow and he sequenced
the whole genomes of both of them right
in a couple weeks no big deal right and
then he compared those two genomes and
software and what he found among other
things was a deletion a 2,000 base
deletion across three billion bases
right in a particular gene called tp53
if you have this deleterious mutation in
this gene you’re 90% likely to get
cancer in your life so unfortunately
this doesn’t help this woman but it does
have severe a profound if you will
implications to her family right I mean
if they have the same mutation and they
get this genetic test and they
understand it then they can go and get
regular screens and they can catch
cancer early and
significantly longer life let me
introduce you now to the beery twins
diagnosed with cerebral palsy at the age
of two their mom is a very brave woman
who didn’t believe it the symptoms
weren’t matching up and through some
heroic efforts and a lot of internet
searching she was able to convince the
medical community that in fact they had
something else what they had was dopa
responsive dystonia and so they were
given l-dopa and their symptoms did
improve but they weren’t totally
asymptomatic significant problems
remained turns out the gentleman in this
picture is a guy named Joe Barry who was
lucky enough to be the CIO of a company
called Life Technologies they’re one of
the two companies that makes these
massive whole genome sequencing tools
and so what he did was he got his kids
sequenced and what they found was a
series of mutations in a gene called SPR
which is responsible for producing
serotonin among other things so on top
of l-dopa that gave these kids a
serotonin precursor drug and they’re
effectively normal now guys this would
never have happened without whole genome
sequencing and at the time this was a
few years ago it cost a hundred thousand
today it’s ten thousand next year at
2000 the year after it’s a hundred give
or take a year that’s how fast this is
moving so here’s little Nick likes
Batman and squirt guns and turns out
Nick shows up at the Children’s Hospital
with this distended belly like a famine
victim and it’s not that he’s not eating
it’s that when he eats his intestine
basically opens up and feces spill out
into his gut so a hundred surgeries
later right he looks at his mom and says
mom please pray for me I’m in so much
pain his pediatrician happens to have a
background in clinical genetics and he
has no idea what’s going on but he says
let’s get this kid’s genome sequence and
what they find is a single point
mutation in a gene responsible for
controlling programmed cell death so the
theory is that he’s having some
immunological reaction to what’s going
on - the food essentially right and
that’s a natural reaction which causes
some programmed cell death but the gene
that regulates that down is broken and
so this informs among other things of
course a treatment for bone marrow
transplant which he undertakes and after
nine months of grueling recovery he’s
now eating steak with a1 sauce the
prospect of using the genome as a
universal diagnostic is upon us today
today it’s here and what it means for
all of us is that everybody in this room
could
live in extra 5 10 20 years just because
of this one thing which is a fantastic
story unless you think about humanity’s
footprint on the planet and our ability
to keep up food production so it turns
out that the very same technology is
also being used to grow new lines of
corn wheat soybean and other crops that
are highly tolerant of drought a flood
of paths and pesticides now look as long
as we continue to increase the
population we’re going to have to
continue to grow and eat genetically
modified foods and that’s the only
position that I’ll take today unless
there’s anybody in the audience that
would like to volunteer to stop eating
none not one this is a typewriter a
staple of every desktop for decades
right and in fact the typewriter was
essentially deleted by this thing and
then more general versions of word
processors came about but ultimately it
was a disruption on top of a disruption
it was Bob Metcalfe inventing the
ethernet and the connection of all these
computers that fundamentally changed
everything right and suddenly we had
Netscape and we had Yahoo and we had
indeed the entire com bubble
not to worry though that was quickly
rescued by the iPod and Facebook and
indeed Angry Birds look this is where we
are today this is the genomic revolution
today this is where we are okay so what
I’d like for you to consider is what
does it mean when these dots don’t
represent the individual basis of your
genome but the connected genomes all
across the planet so I just recently had
to buy life insurance and I was required
to answer a I have never had a genetic
test B I’ve had one here you go and see
I’ve had one and I’m not telling
thankfully I was able to answer a and I
say that honestly in case my life
insurance agent is listening but what
would have happened if I had said C
consumer applications for genomics they
will flourish you want to see whether
your genetically compatible with your
girlfriend
sure DNA sequencing on your iPhone
there’s an app for that
personalized genomic massage anyone
there’s already a lab today that tests
for allele 334 of the AVP r1 gene the so
called cheating gene so anybody who’s
who’s here today with your significant
other just turn over to them and swab
their mouth sent it to the lab and
you’ll know for sure
do you really want to elect a president
whose genome suggests cardiomyopathy now
think of it it’s 2016 and the leading
candidate releases not only her four
years of back tax returns but also her
personal genome and it looks really good
and then she challenges all of her
competitors to do the same do you think
that’s not gonna happen do you think it
would help john mccain how many people
in the audience have the last name
Resnick like me raise your hand
anybody nobody typically there’s one or
two so my father’s father is one of 10
Resnick brothers they all hated each
other right and they all move to
different parts of the planet and so
it’s likely that I’m related to every
Resnick that I ever meet but I don’t
know so imagine if my genome were
de-identified sitting in software right
and a third cousins genome was also
sitting there and there was software
that could compare these two and make
these associations not hard to imagine
my company a software that does this
right now and so imagine one more thing
that that software is able to ask both
parties for mutual consents would you be
willing to meet your third cousin and if
we both say yes voila
welcome to chromosomally LinkedIn right
now this is probably a good thing right
a bigger clan gatherings and so on but
maybe it’s a bad thing as well how many
father’s in the room raise your hands
okay so it just turns experts think that
one to three percent of you are not
actually the father of your child look
these genomes these 23 chromosomes they
don’t in any way represent the quality
of our relationships or the nature of
our society at least not yet and like
any new technology it’s really in
humanity’s hands to wield it for the
betterment of mankind or not and so I
urge you all to wake up and to tune in
and to influence the genomic revolution
that’s happening all around you thank
you