Richard Resnick: Welcome to the genomic revolution

Prevoditelj: Senzos Osijek Recezent: Tilen Pigac - EFZG

Dame i gospodo,

Ladies and gentlemen,

I present to you the human genome.

predstavljam vam ljudski genom.

(Applause)

(Pljesak)

Chromosome one -- top left, bottom right -- are the sex chromosomes.

Prvi kromosom u gornjem lijevom kutu.

U donjem desnom kutu su spolni kromosomi .

Women have two copies of that big X chromosome;

Žene imaju dvije kopije velikog X kromosoma,

muškarci imaju X,

men have the X and, of course, that small copy of the Y.

i naravno, jedan mali Y kromosom.

Sorry boys, but it's just a tiny little thing that makes you different.

Žao mi je, dečki, ali od žena vas čini različitim samo sićušna malena stvarčica.

So if you zoom in on this genome,

Dakle, ako povećate prikaz ovog genoma,

then what you see, of course, is this double-helix structure --

primjetit ćete oblik dvostruke zavojnice --

the code of life spelled out with these four biochemical letters,

životni kod sastoji se od ova četiri biokemijska slova,

kojima nazivamo baze.

or we call them bases: A, C, G and T.

To su A, C, G i T.

How many are there in the human genome? Three billion.

Koliko ih ima u ljudskom genomu? Tri milijarde.

Is that a big number?

Je li to velik broj?

Well, everybody can throw around big numbers.

Pa, svatko se može razbacivati velikim brojevima.

But in fact, if I were to place one base

Ali, zapravo, ako bismo mogli zamisliti jednu bazu

on each pixel of this 1280x800-resolution screen,

kao jedan pixel na ovom ekranu rezolucije 1.280x800,

bilo bi nam potrebno 3.000 takvih ekrana da bismo mogli imati pregled cijeloga genoma.

we would need 3,000 screens to take a look at the genome.

Znači, prilično je to velika brojka.

So it's really quite big.

And perhaps because of its size,

Možda je baš u pitanju veličina,

a group of people -- all, by the way, with Y chromosomes --

zbog čega je grupa ljudi -- od kojih svi, kad smo već kod toga, posjeduju Y kromosom --

decided they would want to sequence it.

odlučila sekvencionirati genom.

(Laughter)

(Smijeh)

And so 15 years, actually, and about four billion dollars later,

I tako, 15 godina i četiri milijarde dolara kasnije,

the genome was sequenced and published.

genom je sekvencioniran i objavljen.

In 2003, the final version was published, and they keep working on it.

U 2003.godini objavljena je završna verzija, ali i dalje se nastavlja rad na tom projektu.

Cijeli proces sekvencioniranja učinjen je na uređaju koji izgleda ovako.

That was all done on a machine like this.

Dođe otprilike jedan dolar po bazi --

It costs about a dollar for each base -- a very slow way of doing it.

i to je vrlo spor način sekvencioniranja.

Well, folks, I'm here to tell you

Dakle, ljudi, danas sam ovdje kako bih vam rekao

that the world has completely changed,

kako se svijet potpuno promjenio,

and none of you know about it.

a nitko od vas ne zna za to.

So now what we do is take a genome,

Sada zapravo, uzmemo genom,

we make maybe 50 copies of it,

napravimo 50-ak kopija tog genoma,

we cut all those copies up into little 50-base reads,

isiječemo sve te kopije u male 50-bazne dijelove,

and then we sequence them, massively parallel.

i sekvencioniramo ih većinom paralelno.

Then we bring that into software and reassemble it,

Onda rezultat unesemo u softver,

i ponovno ga sastavimo, i proučimo.

and tell you what the story is.

Samo da vam dam sliku kako to otprilike izgleda.

So to give you a picture of what this looks like,

the Human Genome Project: 3 gigabases, right?

Projekt Ljudski genom: 3 gigabaze.

Pri radu ovog stroja

One run on one of these modern machines: 200 gigabases in a week.

možemo sekvencionirati 200 gigabaza tjedno.

And that 200 is going to change to 600 this summer,

Taj broj od 200 gigabaza, promjenit će se u 600 ovog ljeta,

and there's no sign of this pace slowing.

a nema znakova da će se taj proces napredovanja i ubrzavanja usporiti.

The price of a base, to sequence a base,

Tako je cijena za sekvencioniranje baze

has fallen 100 million times.

pala 100 milijuna puta.

That's the equivalent of you filling up your car with gas in 1998,

To je ekvivalentno punjenju automobila plinom u 1998.godini,

da biste čekali do 2011.

waiting until 2011,

and now you can drive to Jupiter and back twice.

kako biste se odvezli od Jupitera i nazad dva puta.

(Laughter)

(Smijeh)

World population,

Svjetska populacija,

PC prostori,

PC placements,

the archive of all of medical literature,

arhiva cijele medicinske literature,

Moore's law,

Mooreov zakon,

the old way of sequencing,

stari način sekvencioniranja i sve ove novine.

and here's all the new stuff.

Ljudi, ovo je logaritamska skala,

Guys, this is a long scale;

you don't typically see lines that go up like that.

obično se ne viđaju tako strme skale koje idu prema gore.

So the worldwide capacity to sequence human genomes

Dakle, svjetski kapacitet za sekvencioniranje ljudskih genoma

je otprilike od 50.000 do 100.000 genoma godišnje.

is something like 50,000 to 100,000 human genomes this year.

Znamo to na temelju broja strojeva koji postoje.

We know this based on the machines that are being placed.

Očekuje se da će se taj broj povećati dva, tri ili čak četiri puta

This is expected to double, triple or maybe quadruple

year over year for the foreseeable future.

svake godine u doglednoj budućnosti.

In fact, there's one lab in particular

Zapravo, postoji jedan laboratorij

that represents 20 percent of all that capacity:

u kojem se odrađuje 20 posto svih kapaciteta za sekvencioniranje genoma.

It's called the Beijing Genomics Institute.

Zove se Pekinški institut genomike.

The Chinese are absolutely winning this race to the new Moon, by the way.

Kinezi, kad smo već kod toga, apsolutno vode u ovoj utrci do 'novog mjeseca'.

What does this mean for medicine?

Kakvo to značenje ima za medicinu?

So a woman, age 37,

Dakle, žena od 37 godina.

Ona dolazi s drugom fazom raka dojke pozitivnog na estrogenske receptore.

presents with stage 2 estrogen receptor-positive breast cancer.

She is treated with surgery, chemotherapy and radiation.

Liječi se kirurški, kemoterapijom i zračenjem.

She goes home.

Odlazi kući.

Two years later,

Dvije godine kasnije, vraća se s trećom fazom karcinoma jajnika.

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

Nažalost, opet ju se podvrgava kirurškim zahvatima i kemoterapiji.

treated again with surgery and chemotherapy.

She comes back three years later at age 42

Ponovno dolazi tri godine poslije u dobi od 42 godine

s još više raka jajnika, više kemoterapije.

with more ovarian cancer, more chemotherapy.

Six months later,

Šest mjeseci poslije,

she comes back with acute myeloid leukemia.

dolazi s akutnom mijeloidnom leukemijom.

She goes into respiratory failure and dies eight days later.

Dolazi do zatajenja respiratornog sustava i osam dana kasnije umire.

So first: the way in which this woman was treated,

Dakle, ovaj način liječenja žene, za desetak godina

in as little as 10 years, will look like bloodletting.

djelovat će poput puštanja krvi.

And it's because of people like my colleague, Rick Wilson,

I to zato što su ljudi, poput mojega kolege, Ricka Wilsona,

koji radi u Genome Institute-u na sveučilištu u Washingtonu,

at the Genome Institute at Washington University,

who decided to take a look at this woman postmortem.

odlučili pregledati tu ženu poslije smrti.

Uzeo je neke zdrave stanice kože

And he took skin cells, healthy skin

and cancerous bone marrow,

i nekoliko kancerogenih stanica koštane srži,

and sequenced the whole genomes of both of them

te sekvencionirao cijeli genom obiju vrsta stanica

u nekoliko tjedana, što nije velika stvar.

in a couple of weeks, no big deal.

Then he compared those two genomes in software,

Onda je usporedio ta dva genoma u softveru,

and what he found, among other things,

i našao je, izmeđuostalog,

was a deletion -- a 2,000-base deletion across three billion bases

deleciju -- deleciju 2.000 baza

-- u cijelom genomu od tri milijarde baza --

in a particular gene called TP53.

u jednom određenom genu koji se zove TP53.

Ako imate štetnu mutaciju u ovom genu,

If you have this deleterious mutation in this gene,

you're 90 percent likely to get cancer in your life.

90 posto je vjerojatnost da ćete oboljeti od karcinoma tijekom svojega života.

So unfortunately, this doesn't help this woman,

Nažalost, to neće pomoći toj ženi,

but it does have severe -- profound, if you will --

ali imat će ozbiljne implikacije

implications to her family.

za njezinu obitelj.

Mislim, ako članovi njezine obitelji imaju istu tu mutaciju

I mean, if they have the same mutation,

and they get this genetic test and they understand it,

i naprave ovaj genetski test, te razumiju što takav rezultat pretraga za njih znači,

then they can get regular screens and can catch cancer early,

ići će na česte preglede i na taj način mogu rak otkriti u ranoj fazi

and potentially live a significantly longer life.

i uz to imati veće šanse za znatno duži životni vijek.

Let me introduce you to the Beery twins,

Dopustite mi predstaviti vam blizance Beery,

diagnosed with cerebral palsy at the age of two.

kojima je dijagnosticirana cerebralna paraliza kada su imali dvije godine.

Njihova je majka bila vrlo hrabra žena,

Their mom is a very brave woman who didn't believe it;

koja nije vjerovala dijagnozi jer se sistemi nisu poklapali sa simptomima bolesti,

the symptoms weren't matching up.

i uz pomoć herojskih napora i jako puno pretraživanja po internetu,

And through some heroic efforts and a lot of Internet searching,

uspjela je uvjeriti medicinsku zajednicu

she was able to convince the medical community

da boluju od nečega drugoga.

that, in fact, they had something else.

Imali su distoniju koja reagira na dopu.

They had dopa-responsive dystonia.

And so they were given L-Dopa,

Tako da su se primanjem L-Dopa,

and their symptoms did improve,

njihovi simptomi znatno poboljšali,

but they weren't totally asymptomatic.

ali nisu ostali bez simptoma.

Significant problems remained.

Značajan je problem ostao.

Turns out the gentleman in this picture is a guy named Joe Beery,

Gospodin na ovoj slici je čovjek zvan Joe Beery,

sretnik je koji je CIO

who was lucky enough to be the CIO

tvrtke koja se zove Life Technologies.

of a company called Life Technologies.

To je jedna od dvije kompanije

They're one of two companies

that makes these massive whole-genome sequencing tools.

koja se bavi masovnim sekvencioniranjem ljudskih genoma.

And so he got his kids sequenced.

On je sekvencionirao genome svoje djece.

What they found was a series of mutations in a gene called SPR,

Ono što je pronašao su bile serije mutacija u genu SPR,

koji je odgovoran za proizvodnju serotonina, uz neke ostale funkcije.

which is responsible for producing serotonin, among other things.

So on top of L-Dopa, they gave these kids a serotonin precursor drug,

Tako da je uz L-Dopa, terapija pojačana serotonin-prekursorskim lijekovima

and they're effectively normal now.

i sada su potpuno bez simptoma.

Guys, this would never have happened without whole-genome sequencing.

Ovo se nikada ne bi dogodilo bez potpunog sekvencioniranja genoma.

U to vrijeme -- to je bilo prije nekoliko godina -- koštalo je oko 100.000 dolara.

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

Danas se za sekvencioniranje mora izdvojiti 10.000 dolara.

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

Iduće godine će biti 1.000. Godina nakon nje, 100 dolara, godina prije ili poslije.

the year after, $100, give or take a year.

Toliko brzo napreduje taj odsječak medicine.

That's how fast this is moving.

Dakle, ovo je mali Nick --

So here's little Nick --

voli Batmana i oružje.

likes Batman and squirt guns.

And it turns out Nick shows up at the children's hospital

Nick se u dječjoj bolnici pojavio s

with this distended belly, like a famine victim.

proširenim trbuhom, kakvoga imaju inače žrtve gladi.

And it's not that he's not eating; it's that when he eats,

Razlog tome nije glad,

već to što, kada jede -- njegovi se probavni organi jednostavno otvore

his intestine basically opens up and feces spill out into his gut.

i neprobavljena hrana odlazi direktno u crijeva.

I tako, sto operacija poslije,

So a hundred surgeries later,

he looks at his mom and says, "Mom, please pray for me.

on pogleda majku i kaže: ''Mama,

molim te, moli se za mene. Užasno me boli'.'

I'm in so much pain."

His pediatrician happens to have a background in clinical genetics

Njegov pedijatar ima iskustva u kliničkoj genetici,

and he has no idea what's going on,

no ne razumije što se događa,

but he says, "Let's get this kid's genome sequenced."

ali kaže: “Hajdemo sekvencionirati dječakov genom”.

And what they find is a single-point mutation

I ono što su pronašli bila je točkasta mutacija

in a gene responsible for controlling programmed cell death.

u genu odgovornom za kontrolu programirane stanične smrti (apoptoze).

So the theory is that he's having some immunological reaction

Znači, teorija je da on ima nekakvu imunološku reakciju

to what's going on -- to the food, essentially.

na ono što se u organizmu događa s hranom,

And that's a natural reaction, which causes some programmed cell death,

a to je prirodna reakcija koja uzrokuje neke apoptoze.

but the gene that regulates that down is broken.

Ali gen koji regulira tu reakciju je “pokvaren”.

Ovo nas upućuje, između ostalih stvari, naravno,

And so this informs, among other things, of course,

na tretman transplantacije koštane srži, kojem se dječak podvrgava.

a treatment for bone marrow transplant, which he undertakes.

I nakon devet mjeseci napornog oporavka,

And after nine months of grueling recovery,

on sada jede odrezak s “A1 umakom”.

he's now eating steak with A1 sauce.

(Smijeh)

(Laughter)

The prospect of using the genome as a universal diagnostic

Mogućnost korištenja genoma

kao univerzalne dijagnoze

is upon us today.

je pred nama.

Danas je to moguće.

Today. It's here.

I to znači

And what it means for all of us

is that everybody in this room could live an extra 5, 10, 20 years,

da bi svaka osoba u ovoj prostoriji mogla živjeti dodatnih pet, 10 ili 20 godina

just because of this one thing.

samo zbog ove mogućnosti.

Which is a fantastic story,

Ovo je fantastična priča,

unless you think about humanity's footprint on the planet,

ukoliko ne razmišljate o proizvodnji hrane

and our ability to keep up food production.

isključivo „ljudskom rukom“.

Jer se ista tehnologija

So it turns out

that the very same technology is also being used to grow new lines

koristi za uzgoj

novih linija

of corn, wheat, soybean and other crops

kukuruza, pšenice, soje i drugih usjeva

that are highly tolerant of drought, of flood,

koji su visoko tolerantni na sušu, poplave,

of pests and pesticides.

štetnike i pesticide.

Now, look --

Gledajte, dokle god nastavljamo povećavati populaciju,

as long as we continue to increase the population,

morat ćemo nastaviti s uzgojem i konzumiranjem genetski modificirane hrane

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

i to je stajalište za koje se ja danas zauzimam.

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

Unless there's anybody in the audience

Osim ako ne postoji netko u publici

who'd like to volunteer to stop eating?

tko bi volio dobrovoljno prestati jesti?

Ne, nitko.

None, not one.

This is a typewriter,

Ovo je pisaći stroj,

a staple of every desktop for decades.

glavni stroj svake radne površine desetljećima.

And, in fact, the typewriter was essentially deleted by this thing.

U biti, pisaći je stroj prvotno zamjenjen ovim uređajem.

And then more general versions of word processors came about.

Tada dolaze druge verzije procesora.

But ultimately, it was a disruption on top of a disruption.

Ali u konačnici, prijelom nad svime

It was Bob Metcalfe inventing the Ethernet,

bio je Bob Metcalfe koji je izumio „Ethernet“

and the connection of all these computers

i omogućio povezivanje svih ovih kompjutera,

that fundamentally changed everything.

koje je sve iz temelja promijenilo.

Suddenly we had Netscape, we had Yahoo.

I odjednom, imali smo Netscape, imali smo Yahoo,

And we had, indeed, the entire dot-com bubble.

imali smo cijelu dot.com zavrzlamu.

(Laughter)

(Smijeh)

Not to worry though,

Ne brinite,

that was quickly rescued by the iPod, Facebook

i to sve su brzo zamijenili iPod, Facebook

and, indeed, Angry Birds.

i ljute ptice.

(Laughter)

(Smijeh)

Gledajte, ovo je mjesto na kojem smo danas.

Look, this is where we are today.

This is the genomic revolution today. This is where we are.

Ovo je revolucija genoma danas. Ovako danas stojimo.

Volio bih da razmislite o ovome:

What I'd like you to consider is:

Što bi značilo

What does it mean

when these dots don't represent the individual bases of your genome,

kada ove točkice ne bi predstavljale pojedinačne baze vašeg genoma,

but they connect to genomes all across the planet?

već bi bile povezane sa svim genomima diljem planeta?

I just recently had to buy life insurance, and I was required to answer:

Nedavno sam kupovao životno osiguranje.

I morao sam odgovoriti na pitanje s

A. I have never had a genetic test;

A. nikad nisam napravio genetički test, B. testiran sam, izvolite rezultate

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

ili C. testiran sam, ali ne želim podijeliti rezultat.

or C. I've had one and I'm not telling.

Hvala Bogu, mogao sam odabrati odgovor pod A

Thankfully, I was able to answer A,

and I say that honestly, in case my life insurance agent is listening.

i to je istinit odgovor, u slučaju da me moj agent za osiguranje sada sluša.

Ali što bi se dogodilo da sam odgovorio s C?

But what would have happened if I had said C?

Consumer applications for genomics will flourish.

Potrošačke aplikacije vezane za genomiku, one će procvasti.

Želite vidjeti jeste li genetički kompatibilni

Do you want to see if you're genetically compatible

sa svojom djevojkom? Svakako.

with your girlfriend?

DNA sequencing on your iPhone? There's an app for that.

DNK sekvenciranje na vašem iPhoneu? Evo aplikacije.

(Laughter)

(Smijeh)

Personalized genomic massage, anyone?

Personalizirana genomska masaža, možda?

Danas već imamo laboratorij

There's already a lab today that tests for allele 334 of the AVPR1 gene,

koji radi testove na alelu 334 gena AVPR1,

takozvanog „gena za varanje“.

the so-called cheating gene.

Zato se svi vi koji ste danas ovdje sa svojom boljom polovicom

(Laughter)

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

jednostavno okrenite prema njima i uzmite obris iz usta,

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

pošaljite u laboratorij i znat ćete za sigurno.

and you'll know for sure.

(Smijeh)

(Laughter)

Želite li uistinu glasovati za predsjednika

Do you really want to elect a president

čiji genom otkriva kardiomiopatiju?

whose genome suggests cardiomyopathy?

Sad razmislite o ovome, godina je 2016.

Think of it -- it's 2016,

i vodeći kandidat objavljuje

and the leading candidate releases

ne samo svoje četiri godine plaćanja i povrata poreza,

not only her four years of back-tax returns,

već i svoj osobni genom.

but also her personal genome.

I on izgleda jako dobro.

And it looks really good.

Then she challenges all her competitors to do the same.

A tada izaziva sve ostale kandidate da učine isto.

Mislite li da se to neće dogoditi?

Do you think that's not going to happen?

Mislite li da je to moglo pomoći Johnu McCainu?

Do you think it would have helped John McCain?

(Smijeh)

(Laughter)

Koliko se ljudi u publici

How many people in the audience have the last name Resnick, like me?

preziva Resnick poput mene? Podignite ruku.

Raise your hand.

Itko? Nitko.

Anybody? Nobody.

Obično postoji jedan ili dva.

Typically, there's one or two.

So my father's father was one of 10 Resnick brothers.

Moj je djed bio jedan od desetoro braće Resnick.

I svi su se međusobno mrzili.

They all hated each other, and all moved to different parts of the planet.

Svaki se preselio na drugi dio planeta.

Zato je vrlo vjerojatno

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

da sam u rodu sa svakim Resnickom kojeg sam ikad upoznao, samo ja to ne znam.

but I don't know.

So imagine if my genome were De-identified, sitting in software,

Ali zamislite kako bi bilo kad bi moj genom bio identificiran, ubačen u softver,

And a third cousin's genome was also sitting there,

softver u kojemu se nalazi i genom mog bratića u trećem koljenu.

I taj isti softver može usporediti ova dva genoma

and there was software that could compare the two

i otkriti njihovu povezanost.

and make these associations.

Not hard to imagine. My company has software that does this right now.

Nije to tako teško za zamisliti. Moje poduzeće ima softver koji to već radi.

I zamislite još jednu stvar:

Imagine one more thing,

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

zamislite da taj softver može upitati obje strane za međusobnu suglasnost,

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

„ Želite li upoznati svog bratića u trećem koljenu?“

I ako oboje kažemo „DA“

And if we both say yes -- voilà!

Welcome to Chromosomally LinkedIn.

-- voila! Dobrodošli na kromosomski Linkedln.

(Laughter)

(Smijeh)

Now this is probably a good thing, right?

Ovo je vjerojatno dobra stvar, zar ne?

Bigger clan gatherings and so on.

Imat ćete veća obiteljska okupljanja i sve to.

But maybe it's a bad thing as well.

Ali, možda je, ujedno, i loša stvar.

How many fathers in the room? Raise your hands.

Koliko očeva imamo u prostoriji? Podignite ruke.

OK, so experts think that one to three percent of you

Ok, stručnjaci procjenjuju da jedan do tri posto vas

are not actually the father of your child.

nije biološki otac svog djeteta.

(Laughter)

(Smijeh)

Look --

Pogledajte.

(Laughter)

(Smijeh)

These genomes, these 23 chromosomes,

Ovi genomi, ova 23 kromosoma,

they don't in any way represent the quality of our relationships

ni na koji način ne predstavljaju kvalitetu naših odnosa

or the nature of our society -- at least not yet.

ili prirodu našeg društva -- barem ne još.

I kao kod svake nove tehnologije,

And like any new technology,

u ljudskim je rukama

it's really in humanity's hands

to wield it for the betterment of mankind

hoćemo li ju iskoristiti za poboljšanje čovječanstva ili ne.

or not.

I zato vas sve potičem da se probudite, uključite

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.

i utječete na genomsku revoluciju koja se događa svuda oko vas.

Hvala vam.

Thank you.

(Applause)

(Pljesak)