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