How to read the genome and build a human being | Riccardo Sabatini

Prevoditelj: Sanda L Recezent: Tilen Pigac - EFZG

For the next 16 minutes, I'm going to take you on a journey

U sljedećih 16 minuta povest ću vas na putovanje

that is probably the biggest dream of humanity:

koje je vjerojatno najveći san čovječanstva:

to understand the code of life.

razumijevanje kôda života.

Za mene je sve počelo prije mnogo, mnogo godina,

So for me, everything started many, many years ago

when I met the first 3D printer.

kada sam saznao za prvi 3D printer.

The concept was fascinating.

Sam koncept je bio fascinantan.

A 3D printer needs three elements:

3D printeru su potrebna tri elementa:

a bit of information, some raw material, some energy,

djelić informacije, nešto sirovine, nešto energije

and it can produce any object that was not there before.

i može proizvesti bilo koji predmet koji prethodno nije ni postojao.

I was doing physics, I was coming back home

Bavio sam se fizikom, vraćao sam se kući

and I realized that I actually always knew a 3D printer.

te shvatio da mi je 3D printer oduvijek bio poznat.

Kao i svima ostalima.

And everyone does.

It was my mom.

Bila je to moja mama.

(Laughter)

(Smijeh)

My mom takes three elements:

Moja mama je uzela tri elementa:

djelić informacije, u ovom slučaju između mog oca i moje majke,

a bit of information, which is between my father and my mom in this case,

sirovine i energiju u istom mediju, odnosno hrani,

raw elements and energy in the same media, that is food,

and after several months, produces me.

i nakon nekoliko mjeseci proizvela je mene.

And I was not existent before.

A ja prije toga nisam postojao.

So apart from the shock of my mom discovering that she was a 3D printer,

Pored zapanjenosti moje mame, saznavši da je se smatra 3D printerom,

I immediately got mesmerized by that piece,

istog trena bio sam opčinjen tim dijelom,

the first one, the information.

tim prvim dijelom, informacijom.

What amount of information does it take

Koliko informacija je potrebno

to build and assemble a human?

kako bi se izgradio i sastavio čovjek?

Is it much? Is it little?

Mnogo? Malo?

How many thumb drives can you fill?

Koliko USB diskova biste mogli ispuniti?

Pa, na početku sam studirao fiziku

Well, I was studying physics at the beginning

and I took this approximation of a human as a gigantic Lego piece.

i zamislio tu pretpostavku o čovjeku kao golemoj Lego slagalici.

So, imagine that the building blocks are little atoms

Dakle, zamislite da su kockice sitni atomi

i vodik je ovdje, ugljik ovdje, a dušik ovdje.

and there is a hydrogen here, a carbon here, a nitrogen here.

So in the first approximation,

Prema prvoj pretpostavci,

if I can list the number of atoms that compose a human being,

ako bih mogao navesti broj atoma od kojih se sastoji ljudsko biće,

I can build it.

mogao bih ga sagraditi.

Možete provjeriti brojke

Now, you can run some numbers

and that happens to be quite an astonishing number.

i to izgleda kao prilično zapanjujući broj.

So the number of atoms,

Dakle, broj atoma,

the file that I will save in my thumb drive to assemble a little baby,

dokument koji bih sačuvao na USB-u kako bih sastavio jednu bebu,

zapravo bi ispunio prostor veličine Titanika punog USB-ova,

will actually fill an entire Titanic of thumb drives --

multiplied 2,000 times.

pomnoženo 2.000 puta.

This is the miracle of life.

To je čudo života.

Every time you see from now on a pregnant lady,

Od sada, svaki put kada ugledate trudnicu,

ona u sebi sadrži najveću količinu informacija

she's assembling the biggest amount of information

that you will ever encounter.

koju ćete ikad susresti.

Forget big data, forget anything you heard of.

Zaboravite velike količine podataka, ili bilo što što ste čuli.

This is the biggest amount of information that exists.

To je najveća količina informacija koja postoji.

(Applause)

(Pljesak)

But nature, fortunately, is much smarter than a young physicist,

No, srećom, priroda je daleko pametnija od mladog fizičara

and in four billion years, managed to pack this information

i u četiri milijarde godina uspjela je složiti ove informacije

in a small crystal we call DNA.

u mali kristal koji zovemo DNK.

We met it for the first time in 1950 when Rosalind Franklin,

Prvi put smo saznali za njega 1950. kada je Rosalind Franklin,

an amazing scientist, a woman,

nevjerojatna znanstvenica,

took a picture of it.

napravila sliku kristala.

But it took us more than 40 years to finally poke inside a human cell,

No, trebalo nam je više od 40 godina da konačno prodremo u ljudsku stanicu,

izvadimo taj kristal,

take out this crystal,

unroll it, and read it for the first time.

odmotamo ga i prvi puta pročitamo.

The code comes out to be a fairly simple alphabet,

Ispostavilo se da je kôd prilično jednostavna abeceda,

four letters: A, T, C and G.

četiri slova: A, T, C i G.

And to build a human, you need three billion of them.

A kako biste sagradili čovjeka, potrebno vam je tri milijarde njih.

Three billion.

Tri milijarde.

Koliko je tri milijarde?

How many are three billion?

It doesn't really make any sense as a number, right?

Sam broj zaista nema nikakvog smisla, zar ne?

So I was thinking how I could explain myself better

Stoga sam razmišljao kako bih si bolje objasnio

about how big and enormous this code is.

koliko je velik i ogroman ovaj kôd.

But there is -- I mean, I'm going to have some help,

Ali evo ga, mislim, imat ću malu pomoć,

and the best person to help me introduce the code

a najbolja osoba koja bi mi pomogla predstaviti kôd,

zapravo je prvi čovjek koji ga je sekvencirao, dr. Craig Venter.

is actually the first man to sequence it, Dr. Craig Venter.

So welcome onstage, Dr. Craig Venter.

Stoga, pozdravite dr. Craiga Ventera.

(Applause)

(Pljesak)

Not the man in the flesh,

Ne čovjek glavom i bradom,

but for the first time in history,

već po prvi puta u povijesti,

this is the genome of a specific human,

ovo je genom određenog čovjeka,

printed page-by-page, letter-by-letter:

otisnut stranicu po stranicu, slovo po slovo:

262.000 stranica informacija,

262,000 pages of information,

450 kilograma, isporučenih iz SAD-a u Kanadu,

450 kilograms, shipped from the United States to Canada

thanks to Bruno Bowden, Lulu.com, a start-up, did everything.

zahvaljujući Bruni Bowdenu, dostupno na Lulu.com, sve je odrađeno.

It was an amazing feat.

Bio je to fantastičan podvig.

But this is the visual perception of what is the code of life.

Ali ovo je vizualni doživljaj onoga što je kôd života.

A sada, po prvi puta, mogu učiniti nešto zabavno.

And now, for the first time, I can do something fun.

I can actually poke inside it and read.

Mogu, zapravo, zaviriti unutra i čitati.

So let me take an interesting book ... like this one.

Dozvolite mi da uzmem zanimljivu knjigu... poput ove.

Samo jedna opaska; knjiga je prilično obimna.

I have an annotation; it's a fairly big book.

So just to let you see what is the code of life.

Samo da vidite što je kôd života.

Thousands and thousands and thousands

Na tisuće i tisuće i tisuće

and millions of letters.

i milijune slova.

And they apparently make sense.

I ona očito daju neki smisao.

Pogledajmo jedan specifičan dio.

Let's get to a specific part.

Let me read it to you:

Dozvolite da vam ga pročitam:

(Laughter)

(Smijeh)

"AAG, AAT, ATA."

"AAG, AAT, ATA."

To you it sounds like mute letters,

Vama ovo zvuči kao obična slova bez smisla,

no, ovaj redoslijed određuje Craigovu boju očiju.

but this sequence gives the color of the eyes to Craig.

I'll show you another part of the book.

Pokazat ću vam jedan drugi dio iz knjige.

This is actually a little more complicated.

Ovaj je, zapravo, nešto složeniji.

Chromosome 14, book 132:

Kromosom 14, knjiga 132:

(Laughter)

(Smijeh)

As you might expect.

Kao što biste i očekivali.

(Smijeh)

(Laughter)

"ATT, CTT, GATT."

"ATT, CTT, GATT."

This human is lucky,

Ova osoba ima sreće,

jer ako izostavite samo dva slova u ovom redoslijedu,

because if you miss just two letters in this position --

two letters of our three billion --

dva slova od tri milijarde,

he will be condemned to a terrible disease:

ova osoba bit će osuđena na užasnu bolest:

cystic fibrosis.

cističnu fibrozu.

We have no cure for it, we don't know how to solve it,

Za nju još nemamo lijek, ne znamo kako je izliječiti,

and it's just two letters of difference from what we are.

a samo su dva slova različita od onih koja mi ostali imamo.

A wonderful book, a mighty book,

Predivna knjiga, moćna knjiga,

moćna knjiga koja mi je pomogla razumjeti

a mighty book that helped me understand

i pokazati vam nešto zaista izvanredno.

and show you something quite remarkable.

Every one of you -- what makes me, me and you, you --

Svatko od vas -- ono zbog čega sam ja, ja, a vi ste vi --

is just about five million of these,

samo je oko pet milijuna ovih slova,

half a book.

polovica knjige.

Što se tiče ostalog,

For the rest,

we are all absolutely identical.

posve smo identični.

Pet stotina stranica je čudo života koje predstavljate vi.

Five hundred pages is the miracle of life that you are.

Ostalo svi mi dijelimo.

The rest, we all share it.

So think about that again when we think that we are different.

Zato se sjetite toga kada pomislite kako smo svi različiti.

This is the amount that we share.

Ovo je količina koju svi dijelimo.

So now that I have your attention,

I sada kada imam vašu pažnju,

the next question is:

sledeće pitanje je:

How do I read it?

Kako da to pročitam?

How do I make sense out of it?

Kako da pronađem smisao u tome?

Well, for however good you can be at assembling Swedish furniture,

Pa, koliko god ste dobri u sastavljanju švedskog namještaja,

this instruction manual is nothing you can crack in your life.

ovaj priručnik za upotrebu je nešto što nećete dešifrirati u svom životu.

(Laughter)

(Smijeh)

And so, in 2014, two famous TEDsters,

I tako su 2014. godine, dva čuvena TED-ovca,

Peter Diamandis i Craig Venter osobno,

Peter Diamandis and Craig Venter himself,

decided to assemble a new company.

odlučili osnovati novu tvrtku.

Human Longevity was born,

Rođen je Human Longevity,

with one mission:

sa samo jednom misijom:

trying everything we can try

pokušati sve što možemo

and learning everything we can learn from these books,

i naučiti sve što možemo naučiti iz ovih knjiga,

s jednim ciljem,

with one target --

making real the dream of personalized medicine,

ostvariti san o personaliziranoj medicini,

understanding what things should be done to have better health

razumjeti što se treba učiniti kako bismo bili zdraviji

and what are the secrets in these books.

i koje tajne kriju ove knjige.

An amazing team, 40 data scientists and many, many more people,

Fantastična ekipa, 40 znanstvenika za podatke i još mnogo, mnogo ljudi,

a pleasure to work with.

s kojima je užitak raditi.

The concept is actually very simple.

Koncept je, zapravo, vrlo jednostavan.

We're going to use a technology called machine learning.

Koristit ćemo tehnologiju koja se zove strojno učenje.

On one side, we have genomes -- thousands of them.

S jedne strane imamo genome -- na tisuće njih.

On the other side, we collected the biggest database of human beings:

S druge strane, sakupili smo najveću bazu podataka o ljudskim bićima:

fenotipe, 3D snimke, magnetsku rezonanciju, sve što vam pada na pamet.

phenotypes, 3D scan, NMR -- everything you can think of.

Inside there, on these two opposite sides,

Unutar toga, na ovim suprotnim stranama,

there is the secret of translation.

nalazi se tajna prevođenja.

And in the middle, we build a machine.

A u sredini smo izradili stroj.

We build a machine and we train a machine --

Izradili smo stroj i obučili ga --

well, not exactly one machine, many, many machines --

zapravo, ne baš jedan stroj, već mnogo, mnogo strojeva

to try to understand and translate the genome in a phenotype.

kako bi se pokušao razumjeti i prevesti genom u fenotipu.

What are those letters, and what do they do?

Što su ta slova i čemu ona služe?

It's an approach that can be used for everything,

To je pristup koji se može za sve koristiti,

but using it in genomics is particularly complicated.

ali je njegova upotreba u genetici naročito složena.

Little by little we grew and we wanted to build different challenges.

Malo po malo smo rasli te smo željeli stvoriti drugačije izazove.

We started from the beginning, from common traits.

Počeli smo od početka, od zajedničkih osobina.

Common traits are comfortable because they are common,

Zajedničke osobine su prikladne baš zato što su zajedničke,

everyone has them.

svi ih imamo.

So we started to ask our questions:

Stoga smo počeli postavljati pitanja:

Can we predict height?

Možemo li predvidjeti visinu?

Can we read the books and predict your height?

Možemo li čitanjem ovih knjiga predvidjeti vašu visinu?

Well, we actually can,

Pa, zapravo možemo,

with five centimeters of precision.

preciznošću od pet centimetara.

Indeks tjelesne mase usko je povezan s vašim načinom života,

BMI is fairly connected to your lifestyle,

but we still can, we get in the ballpark, eight kilograms of precision.

ali i dalje možemo pogoditi, preciznošću od osam kilograma.

Možemo li predvidjeti boju očiju?

Can we predict eye color?

Yeah, we can.

Da, možemo.

Eighty percent accuracy.

Preciznošću od 80%.

Can we predict skin color?

Možemo li predvidjeti boju kože?

Yeah we can, 80 percent accuracy.

Možemo, preciznošću od 80%.

Can we predict age?

Možemo li predvidjeti dob?

Možemo, jer izgleda da se kôd mijenja tijekom vašeg života.

We can, because apparently, the code changes during your life.

It gets shorter, you lose pieces, it gets insertions.

Postaje kraći, gubite dijelove, dodaju se umeci.

We read the signals, and we make a model.

Čitamo signale i stvaramo model.

Now, an interesting challenge:

A sada, zanimljiv izazov:

Can we predict a human face?

Možemo li predvidjeti ljudsko lice?

To je malo složenije,

It's a little complicated,

because a human face is scattered among millions of these letters.

jer je ljudsko lice razasuto među milijunima ovih slova.

And a human face is not a very well-defined object.

A ljudsko lice nije precizno definiran objekt.

So, we had to build an entire tier of it

Stoga smo morali napraviti čitav niz njih,

to learn and teach a machine what a face is,

kako bismo naučili i uputili stroj da zna što je lice,

and embed and compress it.

te ga ugradi i sažme.

A ako vam je poznato strojno učenje,

And if you're comfortable with machine learning,

you understand what the challenge is here.

razumjet ćete o kakvom se izazovu ovdje radi.

Sada, nakon 15 godina -- 15 godina nakon što smo pročitali prvu sekvencu,

Now, after 15 years -- 15 years after we read the first sequence --

ovog listopada, počeli smo primjećivati neke signale.

this October, we started to see some signals.

I bio je to izuzetno emotivan trenutak.

And it was a very emotional moment.

What you see here is a subject coming in our lab.

Ovdje vidite ono što je došlo u naš laboratorij.

This is a face for us.

Ovo je za nas lice.

So we take the real face of a subject, we reduce the complexity,

Uzimamo pravo lice ovog subjekta, učinimo ga manje složenim,

because not everything is in your face --

jer nije sve u vašem licu,

lots of features and defects and asymmetries come from your life.

mnoge crte, nedostaci i asimetrija potječu iz vašeg života.

Ujednačavamo simetriju lica i provlačimo ga kroz naš algoritam.

We symmetrize the face, and we run our algorithm.

The results that I show you right now,

Rezultati koje vam upravo pokazujem,

predviđanja su koja dobivamo iz krvi.

this is the prediction we have from the blood.

(Applause)

(Pljesak)

Pričekajte na tren.

Wait a second.

In these seconds, your eyes are watching, left and right, left and right,

U ovim trenucima, vaše oči promatraju lijevo i desno, lijevo i desno,

and your brain wants those pictures to be identical.

a vaš mozak želi da te slike budu jednake.

So I ask you to do another exercise, to be honest.

Zato tražim od vas drugu vježbu, da budete iskreni.

Please search for the differences,

Zamolit ću vas da potražite razlike,

a ima ih mnogo.

which are many.

The biggest amount of signal comes from gender,

Najveća količina signala dolazi od spola,

zatim je tu dob, indeks tjelesne mase te čovjekovo etničko obilježje.

then there is age, BMI, the ethnicity component of a human.

And scaling up over that signal is much more complicated.

Sve dalje preko tog signala postaje daleko složenije.

Ali ono što vidite ovdje, čak i uz razlike,

But what you see here, even in the differences,

lets you understand that we are in the right ballpark,

dozvoljava vam da shvatite kako smo na dobrom putu,

that we are getting closer.

i sve smo bliže.

And it's already giving you some emotions.

Ovo vam već stvara neke dojmove.

This is another subject that comes in place,

Ovo je još jedan primjer koji se posložio,

and this is a prediction.

i ovo je predviđanje.

A little smaller face, we didn't get the complete cranial structure,

Nešto manje lice, ovdje nismo dobili potpunu strukturu lubanje,

but still, it's in the ballpark.

no, ipak, blizu je.

This is a subject that comes in our lab,

Ovo je primjer koji je došao u naš laboratorij,

and this is the prediction.

a ovo je predviđanje.

Dakle, stroj u svojoj obradi nikada nije imao ove ljude.

So these people have never been seen in the training of the machine.

These are the so-called "held-out" set.

Ovo je tzv. "izostavljeni" skup.

But these are people that you will probably never believe.

Ovi ljudi vam vjerojatno nikada neće djelovati uvjerljivo.

We're publishing everything in a scientific publication,

Sve objavljujemo u znanstvenim časopisima

i možete pročitati.

you can read it.

But since we are onstage, Chris challenged me.

Ali budući smo na sceni, Chris me je izazvao.

I probably exposed myself and tried to predict

Vjerojatno sam se otkrio i pokušao predvidjeti

someone that you might recognize.

nekoga koga biste mogli prepoznati.

So, in this vial of blood -- and believe me, you have no idea

Dakle, u ovoj epruveti krvi -- i vjerujte mi, nemate pojma

what we had to do to have this blood now, here --

što smo sve morali učiniti da bismo donijeli krv danas ovdje,

in this vial of blood is the amount of biological information

u ovoj epruveti krvi je količina bioloških informacija

that we need to do a full genome sequence.

koja nam je potrebna za sekvenciranje čitavog genoma.

We just need this amount.

Samo nam je ovoliko potrebno.

We ran this sequence, and I'm going to do it with you.

Izvršili smo sekvenciranje i učinit ću to s vama.

And we start to layer up all the understanding we have.

Počinjemo raslojavati svo znanje koje imamo.

In the vial of blood, we predicted he's a male.

Iz ove epruvete krvi, predvidjeli smo da se radi o muškarcu.

Subjekt i jest muškarac.

And the subject is a male.

We predict that he's a meter and 76 cm.

Predvidjeli smo da je visok 176 cm.

The subject is a meter and 77 cm.

Subjekt je visok 177 cm.

So, we predicted that he's 76; the subject is 82.

Nadalje, predvidjeli smo da ima 76 kg, zapravo ima 82 kg.

We predict his age, 38.

Predvidjeli smo da ima 38 godina.

The subject is 35.

Subjekt ima 35 godina.

We predict his eye color.

Predvidjeli smo njegovu boju očiju.

Too dark.

Pretamna je.

Predvideli smo boju kože.

We predict his skin color.

Skoro da smo pogodili.

We are almost there.

That's his face.

Ovo je njegovo lice.

A sada, trenutak razotkrivanja:

Now, the reveal moment:

the subject is this person.

subjekt je ova osoba.

(Laughter)

(Smijeh)

And I did it intentionally.

Učinio sam to namjerno.

I am a very particular and peculiar ethnicity.

Ja sam vrlo specifičnog, osebujnog porijekla.

Južni Europljani, Talijani -- nikada se ne uklapaju u kalupe.

Southern European, Italians -- they never fit in models.

And it's particular -- that ethnicity is a complex corner case for our model.

A specifično je -- etničko porijeklo je složeni izuzetak za naš model.

Ali, ovdje je još nešto ključno.

But there is another point.

So, one of the things that we use a lot to recognize people

Dakle, nešto što mnogo koristimo kako bismo prepoznali ljude,

nikada neće biti zapisano u genomu.

will never be written in the genome.

It's our free will, it's how I look.

To je naša slobodna volja, naš izgled.

Not my haircut in this case, but my beard cut.

Ne moja frizura, u ovom slučaju, već moja brada.

So I'm going to show you, I'm going to, in this case, transfer it --

Stoga ću vam pokazati, u ovom slučaju ću to prenijeti,

a ovo nije ništa više od Photoshopa, nije modeliranje,

and this is nothing more than Photoshop, no modeling --

the beard on the subject.

brada ovog subjekta.

And immediately, we get much, much better in the feeling.

I odmah imamo mnogo, mnogo bolji dojam.

So, why do we do this?

Dakle, zašto ovo radimo?

We certainly don't do it for predicting height

Sigurno to ne radimo kako bismo predvidjeli visinu,

ili da bismo izradili predivnu sliku iz vaše krvi.

or taking a beautiful picture out of your blood.

We do it because the same technology and the same approach,

Radimo to jer ista ova tehnologija i isti pristup,

the machine learning of this code,

strojno učenje ovog kôda,

is helping us to understand how we work,

pomaže nam razumjeti kako funkcioniramo,

kako vaše tijelo funkcionira,

how your body works,

how your body ages,

kako vaše tijelo stari,

how disease generates in your body,

kako nastaje bolest u vašem tijelu,

kako u vama raste i razvija se rak,

how your cancer grows and develops,

kako djeluju lijekovi

how drugs work

and if they work on your body.

i djeluju li na vaše tijelo.

This is a huge challenge.

To je ogroman izazov.

This is a challenge that we share

To je zajednički izazov nas

with thousands of other researchers around the world.

i tisuće drugih istraživača diljem svijeta.

Zove se personalizirana medicina.

It's called personalized medicine.

To je mogućnost da se odmaknemo od statističkog pristupa,

It's the ability to move from a statistical approach

where you're a dot in the ocean,

u kojem ste samo točkica u oceanu,

to a personalized approach,

prema osobno prilagođenom pristupu,

where we read all these books

gdje čitamo sve ove knjige

and we get an understanding of exactly how you are.

i dobivamo saznanje o tome kako ste baš vi.

But it is a particularly complicated challenge,

Ali ovo je izrazito složen izazov,

because of all these books, as of today,

jer od svih ovih knjiga koje ste danas vidjeli,

we just know probably two percent:

znamo vjerojatno samo 2%.

Četiri knjige od njih preko 175.

four books of more than 175.

A ovo nije tema mog govora,

And this is not the topic of my talk,

jer ćemo saznati i više.

because we will learn more.

There are the best minds in the world on this topic.

Najveći umovi na svijetu bave se ovim pitanjem.

Predviđanje će postati bolje,

The prediction will get better,

the model will get more precise.

model će biti sve precizniji.

And the more we learn,

I što više naučimo,

više ćemo biti suočeni s odlukama,

the more we will be confronted with decisions

that we never had to face before

s kojima se prije nismo susretali,

about life,

o životu,

about death,

o smrti,

o roditeljstvu.

about parenting.

Dakle, dodirujemo samu unutarnju pojedinost onoga kako život funkcionira.

So, we are touching the very inner detail on how life works.

A to je revolucija koja ne može biti ograničena

And it's a revolution that cannot be confined

in the domain of science or technology.

na područje znanosti ili tehnologije.

This must be a global conversation.

To mora biti globalna rasprava.

We must start to think of the future we're building as a humanity.

Moramo početi razmišljati o budućnosti koju gradimo kao o čovječanstvu.

Moramo surađivati s kreativcima, umjetnicima, filozofima,

We need to interact with creatives, with artists, with philosophers,

s političarima.

with politicians.

Everyone is involved,

Svi su uključeni,

because it's the future of our species.

jer se radi o budućnosti naše vrste.

Without fear, but with the understanding

Bez straha, ali uz razumijevanje

that the decisions that we make in the next year

da će odluke koje donesemo u sljedećoj godini

zauvijek promijeniti tijek povijesti.

will change the course of history forever.

Thank you.

Hvala.

(Applause)

(Pljesak)