Danny Hillis: Understanding cancer through proteomics

57,414 views ・ 2011-03-16

TED


Please double-click on the English subtitles below to play the video.

Prevodilac: Jelena Nedjic Lektor: Ivana Korom
00:15
I admit that I'm a little bit nervous here
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Moram priznati da sam malo nervozan s obzirom
00:18
because I'm going to say some radical things,
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da planiram da predstavim večeras veoma radikalne ideje
00:21
about how we should think about cancer differently,
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koje imaju za cilj da promene naš generalni pogled na rak
00:24
to an audience that contains a lot of people
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ispred veoma mnogo ljudi
00:26
who know a lot more about cancer than I do.
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koji znaju znatno više o raku u poređenju sa mnom.
00:30
But I will also contest that I'm not as nervous as I should be
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Ali moram priznati da nisam onoliko nervozan koliko bi se to očekivalo
00:33
because I'm pretty sure I'm right about this.
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jer sam poprilično siguran da sam u pravu.
00:35
(Laughter)
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(Smeh)
00:37
And that this, in fact, will be
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Tvrdim da će ovo zaista biti
00:39
the way that we treat cancer in the future.
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način lečenja raka u budućnosti.
00:43
In order to talk about cancer,
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Kako bih mogao da pričam sa vama o raku,
00:45
I'm going to actually have to --
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moraću da vam pokažem
00:48
let me get the big slide here.
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ovaj ogroman slajd.
00:53
First, I'm going to try to give you a different perspective of genomics.
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Pre svega, želim da vam predstavim drugačiji pogled na genomiku.
00:56
I want to put it in perspective of the bigger picture
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Želim da posmatramo genomiku iz šire perspektive,
00:58
of all the other things that are going on --
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koja uključuje različita znanja do kojih dolazimo
01:01
and then talk about something you haven't heard so much about, which is proteomics.
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a potom želim da govorim o metodologiji o kojoj niste mnogo čuli, a to je proteomika.
01:04
Having explained those,
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Mislim da ćemo, nakon objašnjenja koja će uslediti,
01:06
that will set up for what I think will be a different idea
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biti spremni da govorimo o novoj i drugačijoj ideji
01:09
about how to go about treating cancer.
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o lečenju raka.
01:11
So let me start with genomics.
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Pa, hajde da počnemo sa objašnjenjem genomike.
01:13
It is the hot topic.
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Danas je to poprilično popularna tema.
01:15
It is the place where we're learning the most.
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To je oblast u kojoj najviše učimo.
01:17
This is the great frontier.
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To je tehnologija koja ima velike potencijale,
01:19
But it has its limitations.
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ali isto tako ima i svoja ograničenja.
01:22
And in particular, you've probably all heard the analogy
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Naročito bih naglasio da ste svi vi čuli analogiju
01:25
that the genome is like the blueprint of your body,
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koja govori da je vaš genom zapravo slika vašeg tela.
01:28
and if that were only true, it would be great,
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I kada bi to bilo tačno, to bi bilo odlično,
01:30
but it's not.
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ali nije. To je nešto
01:32
It's like the parts list of your body.
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kao lista sastavnih delova vašeg tela.
01:34
It doesn't say how things are connected,
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Ne govori ništa o tome kako su komponente vašeg organizma
01:36
what causes what and so on.
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povezane, šta uzrokuje koji proces i tako dalje.
01:39
So if I can make an analogy,
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Tako da bih ja želeo da napravim ovde jednu analogiju,
01:41
let's say that you were trying to tell the difference
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recimo da vi želite da objasnite razliku
01:43
between a good restaurant, a healthy restaurant
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između dobrog restorana, restorana zdrave hrane,
01:46
and a sick restaurant,
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i restorana brze hrane,
01:48
and all you had was the list of ingredients
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i sve što imate na raspolaganju jeste lista sastojaka
01:50
that they had in their larder.
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koji pomenuti restorani imaju u svojoj ostavi.
01:53
So it might be that, if you went to a French restaurant
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Tako možemo zamisliti, da ukoliko ste analizirali listu
01:56
and you looked through it and you found
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sastojaka koju koristi francuski restoran i pri tome pronašli
01:58
they only had margarine and they didn't have butter,
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da oni koriste samo margarin i da nemaju puter u ostavi,
02:00
you could say, "Ah, I see what's wrong with them.
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mogli biste da kažete : "Ah, pa vidim zašto je ovde hrana loša.
02:02
I can make them healthy."
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Mogu da im pomognem da pređu na zdrav način."
02:04
And there probably are special cases of that.
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I verovatno postoje izdvojeni slučajevi kao ovaj.
02:06
You could certainly tell the difference
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Mogli biste da uočite razliku
02:08
between a Chinese restaurant and a French restaurant
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između kineskog i francuskog restorana
02:10
by what they had in a larder.
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na osnovu liste sastojaka koje možete naći u njihovoj ostavi.
02:12
So the list of ingredients does tell you something,
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Tako da vam definitivno lista sastojaka nešto govori,
02:15
and sometimes it tells you something that's wrong.
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i ponekada možete na osnovu iste zaključiti šta je loše.
02:19
If they have tons of salt,
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Ukoliko ste pronašli velike količine soli,
02:21
you might guess they're using too much salt, or something like that.
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možete pretpostaviti da oni koriste previše soli ili nešto slično.
02:24
But it's limited,
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Ali te informacije imaju limitirani kapacitet,
02:26
because really to know if it's a healthy restaurant,
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jer da biste znali da li je to restoran zdrave hrane,
02:28
you need to taste the food, you need to know what goes on in the kitchen,
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morate probati hranu, morate znati šta se dešava u kuhinji,
02:31
you need the product of all of those ingredients.
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neophodan vam je kranji produkt koji nastaje sjedinjavanjem tih sastojaka.
02:34
So if I look at a person
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Tako da ukoliko ja pogledam jednu osobu
02:36
and I look at a person's genome, it's the same thing.
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i analiziram genom te osobe, to je apsolutno ista stvar.
02:39
The part of the genome that we can read
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Deo genoma koji mi možemo dešifrovati
02:41
is the list of ingredients.
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je ništa drugo do lista sastojaka.
02:43
And so indeed,
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I naravno,
02:45
there are times when we can find ingredients
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ponekada možemo naći sastojke
02:47
that [are] bad.
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koji su loši.
02:49
Cystic fibrosis is an example of a disease
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Cistična fibroza jeste odličan primer bolesti tog tipa
02:51
where you just have a bad ingredient and you have a disease,
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gde imate loš sastojak i imate bolest
02:54
and we can actually make a direct correspondence
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i mi u ovom slučaju možemo napraviti direktnu vezu
02:57
between the ingredient and the disease.
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između "sastojka" i bolesti.
03:00
But most things, you really have to know what's going on in the kitchen,
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Ali u većini slučajeva, vi morate znati šta se dešava u kuhinji,
03:03
because, mostly, sick people used to be healthy people --
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s obzirom da su bolesni ljudi najčešće bili pre toga zdravi -
03:05
they have the same genome.
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što znači da imaju isti genom.
03:07
So the genome really tells you much more
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Tako da vam genom moze reći mnogo više
03:09
about predisposition.
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o određenim predispozicijama.
03:11
So what you can tell
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Ono sto vi možete prepoznati
03:13
is you can tell the difference between an Asian person and a European person
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jeste razlika između Azijata i Evropljana
03:15
by looking at their ingredients list.
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na osnovu analize njihove liste sastojaka.
03:17
But you really for the most part can't tell the difference
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Ali u realnosti vi najčešće ne možete uočiti razliku
03:20
between a healthy person and a sick person --
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između zdrave i bolesne osobe
03:23
except in some of these special cases.
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sem u specifičnim slučajevima.
03:25
So why all the big deal
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Usled čega se pravi onda velika pompa
03:27
about genetics?
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oko genetike?
03:29
Well first of all,
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Pa, pre svega,
03:31
it's because we can read it, which is fantastic.
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mi genom možemo da "pročitamo", što je fantastično.
03:34
It is very useful in certain circumstances.
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U određenim situacijama to je veoma korisno.
03:37
It's also the great theoretical triumph
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Takođe, predstavlja neverovatan teoretski uspeh
03:40
of biology.
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biologije.
03:42
It's the one theory
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To je jedina teorija
03:44
that the biologists ever really got right.
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oko koje su biolozi ikada bili u pravi.
03:46
It's fundamental to Darwin
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To je fundamentalna osnova Darvinove teorije
03:48
and Mendel and so on.
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kao i Mendelove teorije nasleđivanja.
03:50
And so it's the one thing where they predicted a theoretical construct.
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To je otkriće kojim su biolozi u mogućnosti da predivide teorijski konstrukt.
03:54
So Mendel had this idea of a gene
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Mendel je imao ideju o genima
03:56
as an abstract thing,
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u apstraktnom smislu.
03:59
and Darwin built a whole theory
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I Darvin je uspostavio čitavu teoriju
04:01
that depended on them existing,
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koja u potpunosti zavisi od postojanja gena.
04:03
and then Watson and Crick
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I kada su Vatson i Krik proučavali
04:05
actually looked and found one.
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nasledne jedinice, napokon su ih i pronašli.
04:07
So this happens in physics all the time.
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Ovo se dešava u fizici sve vreme.
04:09
You predict a black hole,
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Vi predvidite postojanje crne rupe,
04:11
and you look out the telescope and there it is, just like you said.
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pogledate kroz teleskop i pronađete je, baš kao što ste i rekli.
04:14
But it rarely happens in biology.
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Ali to se retko dešava u biologiji.
04:16
So this great triumph -- it's so good,
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Tako da je ovaj fantastičan trijumf - toliko fascinirajući -
04:19
there's almost a religious experience
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da je to skoro religiozno iskustvo
04:21
in biology.
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u biologiji.
04:23
And Darwinian evolution
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I Darvinova teorije evolucije
04:25
is really the core theory.
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jeste zaista centralna teorija.
04:30
So the other reason it's been very popular
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I drugi razlog popularnosti genetike
04:32
is because we can measure it, it's digital.
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jeste činjenica da je digitalna, genom možete da izmerite.
04:35
And in fact,
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I u stvari,
04:37
thanks to Kary Mullis,
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zahvaljujući Kariju Malisu,
04:39
you can basically measure your genome in your kitchen
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vi možete izmeriti svoj genom u kuhinji
04:43
with a few extra ingredients.
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uz pomoć nekoliko ekstra sastojaka.
04:46
So for instance, by measuring the genome,
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Na primer, odgonetajući genom,
04:49
we've learned a lot about how we're related to other kinds of animals
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naučili smo koliko smo srodni sa ostalim životinjskim vrstama
04:53
by the closeness of our genome,
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na osnovu sličnosti naših genoma,
04:56
or how we're related to each other -- the family tree,
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ili kako smo međusobno povezani - porodično stablo,
04:59
or the tree of life.
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ili stablo života.
05:01
There's a huge amount of information about the genetics
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Možemo doći do mnogo informacija o genetici
05:04
just by comparing the genetic similarity.
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na osnovu jednostavnog poređenja genetičkih sličnosti.
05:07
Now of course, in medical application,
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Naravno i primena ovih znanja u medicini,
05:09
that is very useful
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je jako korisna
05:11
because it's the same kind of information
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s obzirom da je to isti tip informacije
05:14
that the doctor gets from your family medical history --
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koji doktor dobija analizirajući istoriju bolesti vaše famlije,
05:17
except probably,
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sa tom razlikom da najverovatnije
05:19
your genome knows much more about your medical history than you do.
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vaš genom zna mnogo više o vašoj istoriji bolesti od vas samih.
05:22
And so by reading the genome,
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Tako da dešifrujući genom, možemo
05:24
we can find out much more about your family than you probably know.
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da saznamo mnogo više o vašoj porodici nego što vi sami znate.
05:27
And so we can discover things
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Tako da možemo da otkrijemo činjenice
05:29
that probably you could have found
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do kojih biste i vi sami mogli doći
05:31
by looking at enough of your relatives,
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ukoliko biste ispitali dovoljno vaših rođaka,
05:33
but they may be surprising.
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ali te činjenice mogu da budu iznenađujuće.
05:36
I did the 23andMe thing
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Ja sam uradio "23 i ja" test i
05:38
and was very surprised to discover that I am fat and bald.
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bio sam veoma iznenađen kad sam otkrio da sam debeo i ćelav.
05:41
(Laughter)
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(Smeh)
05:48
But sometimes you can learn much more useful things about that.
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Ali ponekada možete saznati mnogo korisnije informacije o tome.
05:51
But mostly
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Ali najčešće ono što je
05:54
what you need to know, to find out if you're sick,
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vama potrebno da znate da li ste bolesni
05:56
is not your predispositions,
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nisu vaše predispozicije, nego
05:58
but it's actually what's going on in your body right now.
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ono što se zaista događa u datom trenutku u vašem telu.
06:01
So to do that, what you really need to do,
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A da biste to uradili, ono što je zaista neophodno
06:03
you need to look at the things
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da uradite jeste da sagledate
06:05
that the genes are producing
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produkte kodirane vašim genima
06:07
and what's happening after the genetics,
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i šta se dešava nizvodno od nivoa genetike.
06:09
and that's what proteomics is about.
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To je ono što definiše proteomiku.
06:11
Just like genome mixes the study of all the genes,
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Baš kao što genomika ispituje sve gene,
06:14
proteomics is the study of all the proteins.
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proteomika se bavi izučavanjem svih proteina jednog organizma.
06:17
And the proteins are all of the little things in your body
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A proteini su "radilice" vašeg organizma
06:19
that are signaling between the cells --
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koje prenose informacije između ćelija
06:22
actually, the machines that are operating --
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u principu mašine koje odrađuju sve funkcije organizma.
06:24
that's where the action is.
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Proteini su nosioci radnih delatnosti.
06:26
Basically, a human body
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U principu, ljudsko telo
06:29
is a conversation going on,
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jeste komunikacija, razgovor na globalnom nivou,
06:32
both within the cells and between the cells,
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i to na oba nivoa, i u ćeliji i između ćelija,
06:35
and they're telling each other to grow and to die,
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i oni saopštavaju jedni drugima da rastu i da umiru.
06:38
and when you're sick,
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A kada ste bolesni, to znači
06:40
something's gone wrong with that conversation.
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da je došlo do greške u tom razgovoru.
06:42
And so the trick is --
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Tako da je trik u tome da -
06:44
unfortunately, we don't have an easy way to measure these
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na nesreću, nemamo odgovarajući način da izučavamo proteine
06:47
like we can measure the genome.
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kao što možemo da izučavamo genom.
06:49
So the problem is that measuring --
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Dakle, problem je u tom merenju - ukoliko
06:52
if you try to measure all the proteins, it's a very elaborate process.
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probate da izmerite sve proteine, to je veoma zahtevna procedura.
06:55
It requires hundreds of steps,
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To zahteva stotine pojedinačnih koraka,
06:57
and it takes a long, long time.
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i zahteva mnogo, mnogo vremena.
06:59
And it matters how much of the protein it is.
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I važno je koliko je proteina prisutno.
07:01
It could be very significant that a protein changed by 10 percent,
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Može biti veoma značajno da je 10% proteina promenjeno,
07:04
so it's not a nice digital thing like DNA.
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tako da ovde ne pričamo o finom, digitalnom fenomenu kao što je DNK.
07:07
And basically our problem is somebody's in the middle
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Naš je problem da neko u samoj sredini
07:09
of this very long stage,
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ovog veoma dugog procesa,
07:11
they pause for just a moment,
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pauzira za samo jedan trenutak,
07:13
and they leave something in an enzyme for a second,
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i ostavi nešto u enzimu na samo sekund,
07:15
and all of a sudden all the measurements from then on
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i odjednom, od tog momenta sva merenja koja
07:17
don't work.
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slede ne funkcionišu.
07:19
And so then people get very inconsistent results
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I usled toga ljudi dobijaju veoma nekonzistentne rezultate
07:21
when they do it this way.
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kada pokušaju da rade na opisani način.
07:23
People have tried very hard to do this.
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Ljudi su uložili puno truda kako bi uspeli da urade ovo.
07:25
I tried this a couple of times
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Ja sam probao nekoliko puta
07:27
and looked at this problem and gave up on it.
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skoncentrisao se na problem i odustao od istog.
07:29
I kept getting this call from this oncologist
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Ali me je jedan onkolog zvao telefonom non-stop
07:31
named David Agus.
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po imenu Dejvid Agus.
07:33
And Applied Minds gets a lot of calls
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I mnogi ljudi zovu "Primenjene Umove",
07:36
from people who want help with their problems,
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ljudi koji žele pomoć u rešavanju svojih problema,
07:38
and I didn't think this was a very likely one to call back,
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i nisam mislio da ima mogućnosti de će ovaj zvati ponovo,
07:41
so I kept on giving him to the delay list.
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i tako je razgovor sa njim bio non-stop na listi čekanja.
07:44
And then one day,
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I potom jednog dana,
07:46
I get a call from John Doerr, Bill Berkman
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pozvaše mene Džon Doer, Bil Berkman
07:48
and Al Gore on the same day
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i Al Gor istoga dana
07:50
saying return David Agus's phone call.
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da mi kažu da pozovem Dejvid Agusa.
07:52
(Laughter)
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(Smeh)
07:54
So I was like, "Okay. This guy's at least resourceful."
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I ja pomislih: "Okej, ovaj tip barem ima puno kontakata."
07:56
(Laughter)
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(smeh)
08:00
So we started talking,
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Tako mi počesmo da razgovaramo,
08:02
and he said, "I really need a better way to measure proteins."
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i on mi reče: "Zaista mi je neophodan bolji način da analiziram proteine."
08:05
I'm like, "Looked at that. Been there.
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Ja rekoh, "Već sam razmišljao o tome. Išao sam tim stopama.
08:07
Not going to be easy."
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Ovo neće biti lako."
08:09
He's like, "No, no. I really need it.
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On reče: "Ali ne, ne. Meni je to zaista neophodno.
08:11
I mean, I see patients dying every day
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Ja gledam pacijente kako umiru svakoga dana
08:15
because we don't know what's going on inside of them.
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samo zato što mi ne razumemo šta se dešava u njihovim telima.
08:18
We have to have a window into this."
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Moramo napraviti prozor koji će omogućiti da to sagledamo."
08:20
And he took me through
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Onda mi je izneo specifične primere
08:22
specific examples of when he really needed it.
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situacija u kojima su mu te nove metode apsolutno neophodne.
08:25
And I realized, wow, this would really make a big difference,
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I ja shvatih da ovo zaista može da napravi ogromnu razliku,
08:27
if we could do it,
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ukoliko bismo mogli to da odradimo.
08:29
and so I said, "Well, let's look at it."
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rekao sam, "Pa, hajde da pokušamo."
08:31
Applied Minds has enough play money
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"Primenjeni Umovi" imaju zaista dovoljno para u igri
08:33
that we can go and just work on something
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da možemo jednostavno da radimo na problemu
08:35
without getting anybody's funding or permission or anything.
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bez traženja novih sredstava i specijalnih dozvola ili bilo čega.
08:38
So we started playing around with this.
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Tako da smo počeli da se zanimamo ovim.
08:40
And as we did it, we realized this was the basic problem --
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I dok smo se bavili time, shvatili smo da je to osnovni problem -
08:43
that taking the sip of coffee --
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upravo taj srk kafe
08:45
that there were humans doing this complicated process
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činjenica da su ljudi izvršavali ovu komplikovanu proceduru
08:47
and that what really needed to be done
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i da je zaista bilo neophodno
08:49
was to automate this process like an assembly line
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automatizovati proces kao pokretnu traku
08:52
and build robots
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i napraviti robote
08:54
that would measure proteomics.
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koji bi analizirali proteomiku.
08:56
And so we did that,
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I tako smo to i uradili.
08:58
and working with David,
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Dok sam radio sa Dejvidom, osnovali
09:00
we made a little company called Applied Proteomics eventually,
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smo malu kompaniju koju smo nazvali "Primenjena Proteomika",
09:03
which makes this robotic assembly line,
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koja prozivodi robotizovanu pokretnu traku,
09:06
which, in a very consistent way, measures the protein.
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koja, na veoma konzsistentan način, analizira proteine.
09:09
And I'll show you what that protein measurement looks like.
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I sada ću vam pokazati kako to merenje proteina izgleda.
09:13
Basically, what we do
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U principu, ono što mi radimo je
09:15
is we take a drop of blood
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da uzmemo kap krvi
09:17
out of a patient,
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iz pacijenta
09:19
and we sort out the proteins
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i izolujemo proteine
09:21
in the drop of blood
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u toj kapi krvi
09:23
according to how much they weigh,
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na osnovu onoga koliko su ti proteini teški
09:25
how slippery they are,
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i koliko su pokretljivi,
09:27
and we arrange them in an image.
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i poređamo ih u sveobuhvatnu sliku.
09:30
And so we can look at literally
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Tako da nam to omogućava da bukvalno
09:32
hundreds of thousands of features at once
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analiziramo stotine hiljada karaktersitika u jednom datom
09:34
out of that drop of blood.
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momentu iz samo jedne kapi krvi.
09:36
And we can take a different one tomorrow,
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Sledećeg dana možemo uzeti novu kap
09:38
and you will see your proteins tomorrow will be different --
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i videćete da će vaši proteini sledećeg dana biti drugačiji -
09:40
they'll be different after you eat or after you sleep.
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drugačiji u zavisnosti od toga da li ste upravo jeli ili se probudili.
09:43
They really tell us what's going on there.
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Govore nam o procesima koji se dešavaju u telu čoveka.
09:46
And so this picture,
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Tako da ovde prikazana slika,
09:48
which looks like a big smudge to you,
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koja vama izgleda kao ogromna mrlja,
09:50
is actually the thing that got me really thrilled about this
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je u principu otkriće koje je mene jako uzbudilo
09:54
and made me feel like we were on the right track.
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i zbog kojeg sam pomislio da smo na pravom putu.
09:56
So if I zoom into that picture,
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Ukoliko ja uveličam ovu sliku,
09:58
I can just show you what it means.
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mogu vam pokazati šta to zaista znači.
10:00
We sort out the proteins -- from left to right
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Mi grupišemo proteine: s leva na desno
10:03
is the weight of the fragments that we're getting,
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na osnovu težine fragmenata koje analiziramo.
10:06
and from top to bottom is how slippery they are.
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A od vrha na dole, na osnovu njihove pokretljivosti.
10:09
So we're zooming in here just to show you a little bit of it.
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Sad ćemo uveličati kako bih vam pokazao mali deo.
10:12
And so each of these lines
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Svaka od ovih linija predstavlja
10:14
represents some signal that we're getting out of a piece of a protein.
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u principu neku vrstu signala koju mi dobijamo od dela proteina.
10:17
And you can see how the lines occur
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I isto tako možete primetiti patern linija
10:19
in these little groups of bump, bump, bump, bump, bump.
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- to su male grupe sastavljene od blagih krivina, krivina, krivina, krivina.
10:23
And that's because we're measuring the weight so precisely that --
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To se dešava zato što merimo težinu toliko precizno da -
10:26
carbon comes in different isotopes,
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s obzriom da ugljenik ima različite izotope,
10:28
so if it has an extra neutron on it,
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ukoliko ima jedan dodatni neutron,
10:31
we actually measure it as a different chemical.
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mi u principu učitavamo to kao drugačiju supstancu.
10:35
So we're actually measuring each isotope as a different one.
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Tako da mi beležimo svaki izotop kao drugačiji.
10:38
And so that gives you an idea
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Na osnovu ovoga možete razumeti
10:41
of how exquisitely sensitive this is.
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koliko je fantastično osetljiv opisani sistem.
10:43
So seeing this picture
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Gledanje ove slike
10:45
is sort of like getting to be Galileo
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je slično kao kada bismo bili Galilej
10:47
and looking at the stars
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i gledali u zvezde kroz
10:49
and looking through the telescope for the first time,
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teleskop po prvi put i iznenada
10:51
and suddenly you say, "Wow, it's way more complicated than we thought it was."
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rekli, "Opa, mnogo je komplikovanije nego što smo mislili."
10:54
But we can see that stuff out there
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Ali mi sada možemo da sagledamo taj mali univerzum
10:56
and actually see features of it.
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i uočimo njegove karakteristike.
10:58
So this is the signature out of which we're trying to get patterns.
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Ovo je skup podataka iz kojih pokušavamo da izvučemo obrasce.
11:01
So what we do with this
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Ono što mi radimo sa informacijama ovog tipa
11:03
is, for example, we can look at two patients,
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je da, na primer možemo analizirati dva pacijenta,
11:05
one that responded to a drug and one that didn't respond to a drug,
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jednog koji je reagovao na lek i drugog koji nije,
11:08
and ask, "What's going on differently
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i postaviti pitanje, "Koji je proces koji je drugačiji
11:10
inside of them?"
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u organizmima ovih ljudi?"
11:12
And so we can make these measurements precisely enough
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Takođe možemo da odradimo ta merenja dovoljno precizno
11:15
that we can overlay two patients and look at the differences.
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da možemo da uporedimo dva pacijenta i uočimo razlike.
11:18
So here we have Alice in green
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Ovde možete videti Alis u zelenom kodu
11:20
and Bob in red.
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i Boba predstavljenog crvenim kodom.
11:22
We overlay them. This is actual data.
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Poredimo njihove podatke. Ovo su pravi rezulati.
11:25
And you can see, mostly it overlaps and it's yellow,
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Postoji puno sličnosti i obeležene su žutom bojom
11:28
but there's some things that just Alice has
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ali postoje određeni proteini koje ima samo Alis
11:30
and some things that just Bob has.
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i određeni proteini koje ima samo Bob.
11:32
And if we find a pattern of things
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I ukoliko pronađemo šablon koji opisuje
11:35
of the responders to the drug,
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grupu ljudi na koje postojeći lek ispoljava željeni
11:38
we see that in the blood,
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efekat, mi vidimo to u krvi,
11:40
they have the condition
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oni imaju uslove koji im
11:42
that allows them to respond to this drug.
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omogućuju da uspešno odreaguju na tretman.
11:44
We might not even know what this protein is,
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Mi možda čak ni ne znamo koji je to protein,
11:46
but we can see it's a marker
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ali znamo da taj protein jeste marker,
11:48
for the response to the disease.
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koji govori da će određeni tretman biti uspešan.
11:53
So this already, I think,
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Već ovo saznanje, po mom mišljenju,
11:55
is tremendously useful in all kinds of medicine.
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jeste od neopisive koristi za različite grane medicine.
11:58
But I think this is actually
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Ali ja isto tako mislim da je ovo
12:00
just the beginning
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tek početak razvijanja procedura
12:02
of how we're going to treat cancer.
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kojima ćemo se boriti protiv raka.
12:04
So let me move to cancer.
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A sada bih da pričam malo više o raku.
12:06
The thing about cancer --
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Zanimljiva činjenica o kanceru je ta
12:08
when I got into this,
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da kada sam ja počeo da se bavim ovim
12:10
I really knew nothing about it,
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zaista nisam znao ništa o raku,
12:12
but working with David Agus,
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ali radeći rame uz rame sa Dejvidom Agusom
12:14
I started watching how cancer was actually being treated
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počeo sam da razumevam kako mi danas lečimo rak
12:17
and went to operations where it was being cut out.
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i odlazio sam na operacije koje su imale za cilj otklanjanje raka.
12:20
And as I looked at it,
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I kada sam sagledao tu proceduru,
12:22
to me it didn't make sense
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to meni i nije baš imalo puno smisla,
12:24
how we were approaching cancer,
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takav pristup lečenju raka.
12:26
and in order to make sense of it,
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I kako bih razumeo proces lečenja,
12:29
I had to learn where did this come from.
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morao sam naučiti kako smo došli do današnjih tretmana.
12:32
We're treating cancer almost like it's an infectious disease.
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Borimo se protiv raka na način na koji se borimo protiv infektivnih bolesti.
12:36
We're treating it as something that got inside of you
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Tretiramo ih kao nešto što vas je inficiralo
12:38
that we have to kill.
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i što moramo da ubijemo.
12:40
So this is the great paradigm.
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To je velika paradigma.
12:42
This is another case
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Ovo je drugi primer u biologiji gde se
12:44
where a theoretical paradigm in biology really worked --
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teorijskom paradigmom zaista došlo do rezultata,
12:46
was the germ theory of disease.
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a to je "patogen - teorija bolesti".
12:49
So what doctors are mostly trained to do
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Doktori su u najvećem broju slučajeva obučeni da
12:51
is diagnose --
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uspostave dijagnozu -
12:53
that is, put you into a category
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- što znači da vas oni svrstavaju u određenu kategoriju
12:55
and apply a scientifically proven treatment
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i onda primene naučno odobreni tretman protiv bolesti
12:57
for that diagnosis --
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za koju su postavili dijagnozu.
12:59
and that works great for infectious diseases.
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To je odličan pristup u lečenju infektivnih bolesti.
13:02
So if we put you in the category
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Tako da ukoliko je ustanovljeno
13:04
of you've got syphilis, we can give you penicillin.
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da bolujete od sifilisa, možemo vas lečiti penicilinom.
13:07
We know that that works.
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Mi znamo da je to uspešan način.
13:09
If you've got malaria, we give you quinine
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Ukoliko bolujete od malarije, prepisaćemo vam kinin
13:11
or some derivative of it.
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ili neki od derivata kinina.
13:13
And so that's the basic thing doctors are trained to do,
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To je u principu osnovna stvar za koju su doktori obučeni.
13:16
and it's miraculous
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Tako da je zapravo čudesno
13:18
in the case of infectious disease --
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kako u slučajevima infektivnih bolesti -
13:21
how well it works.
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ovi tretmani ekeftivno rešavaju probleme.
13:23
And many people in this audience probably wouldn't be alive
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Mnogi ljudi u ovoj publici najverovatnije ne bi bili živi
13:26
if doctors didn't do this.
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da lekari ne rade ovo.
13:28
But now let's apply that
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Hajde da pokušamo da primenimo ovaj princip
13:30
to systems diseases like cancer.
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na sistemski tip bolesti kao što je rak.
13:32
The problem is that, in cancer,
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Problem je što u slučaju raka
13:34
there isn't something else
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ne postoji strano telo koje treba ubiti,
13:36
that's inside of you.
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koje je ušlo u vaš organizam.
13:38
It's you; you're broken.
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To ste vi, vaše ćelije su nefunkcionalne.
13:40
That conversation inside of you
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Komunikacija koja postoji na sistemskom nivou u vašem telu
13:44
got mixed up in some way.
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je postala pometena na neki način.
13:46
So how do we diagnose that conversation?
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Kako možemo da dijagnostikujemo problem u komunikaciji?
13:48
Well, right now what we do is we divide it by part of the body --
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U ovom trenutku grupišemo rak prema različitm delovima tela -
13:51
you know, where did it appear? --
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znate, gde se pojavio -
13:54
and we put you in different categories
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i stavimo vas u različite kategorije
13:56
according to the part of the body.
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na osnovu dela vašeg tela.
13:58
And then we do a clinical trial
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I onda sprovedemo klinička istraživanja
14:00
for a drug for lung cancer
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za lek koji pokazuje efekat na rak pluća
14:02
and one for prostate cancer and one for breast cancer,
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i za lek koji deluje na rak prostate, rak dojke,
14:05
and we treat these as if they're separate diseases
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i lečimo ove slučajeve kao da su različite bolesti
14:08
and that this way of dividing them
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kao da ovaj način na koji grupišemo pod-tipove raka
14:10
had something to do with what actually went wrong.
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ima ikakve veze sa onim što nije u redu.
14:12
And of course, it really doesn't have that much to do
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I naravno, to nema baš puno veze sa tim
14:14
with what went wrong
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šta je pošlo naopako.
14:16
because cancer is a failure of the system.
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Jer rak je malfunkcionisanje sistema.
14:19
And in fact, I think we're even wrong
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U principu, ja mislim da je potpuno pogrešno
14:21
when we talk about cancer as a thing.
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pričati o raku kao o predmetu, stvari.
14:24
I think this is the big mistake.
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Ja mislim da je to velika greška.
14:26
I think cancer should not be a noun.
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Ja mislim da rak ne bi trebalo da bude imenica.
14:30
We should talk about cancering
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Mi treba da pričamo o ovoj bolesti kao o "rakovanju"
14:32
as something we do, not something we have.
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nečemu što mi sami radimo, a ne nečemu što imamo.
14:35
And so those tumors,
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Različiti tumori
14:37
those are symptoms of cancer.
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su simptomi raka.
14:39
And so your body is probably cancering all the time,
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Tako da vaše telo verovatno "rakuje" sve vreme.
14:42
but there are lots of systems in your body
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Ali postoji puno sistema u vašem telu
14:45
that keep it under control.
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koji taj proces drže pod kontrolom.
14:47
And so to give you an idea
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Da bih vam dao ideju
14:49
of an analogy of what I mean
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analogije na koju konkretno mislim
14:51
by thinking of cancering as a verb,
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kada govorim "rakovati" u vidu glagola,
14:54
imagine we didn't know anything about plumbing,
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zamislite da ne znamo ništa o vodoinstalaterstvu,
14:57
and the way that we talked about it,
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tako da bismo pričali o tome na sledeći način,
14:59
we'd come home and we'd find a leak in our kitchen
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došli bismo kući i uočili da je u kuhinji procurela voda
15:02
and we'd say, "Oh, my house has water."
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i rekli bismo, "Oh, u mojoj kući ima vode."
15:06
We might divide it -- the plumber would say, "Well, where's the water?"
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Vodoinstalater bi rekao, "Pa, gde je ta voda u kući?"
15:09
"Well, it's in the kitchen." "Oh, you must have kitchen water."
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"Pa, u kuhinji." "Oh, pa vi onda imate kuhinjsku vodu."
15:12
That's kind of the level at which it is.
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To je plastični primer nivoa našeg sagledavanja stvari.
15:15
"Kitchen water,
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"Kuhinjska voda?
15:17
well, first of all, we'll go in there and we'll mop out a lot of it.
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Pa, pre svega, mi ćemo obrisati dosta vode.
15:19
And then we know that if we sprinkle Drano around the kitchen,
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Isto tako znamo da ukoliko koristimo "Mr. Musculo"
15:22
that helps.
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u kuhinji, to će sigurno pomoći.
15:25
Whereas living room water,
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Dok u slučaju vode u dnevnoj sobi
15:27
it's better to do tar on the roof."
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bolje rešenje je da popravimo krov."
15:29
And it sounds silly,
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Znam da zvuči ludo,
15:31
but that's basically what we do.
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ali u principu to je ono što danas radimo.
15:33
And I'm not saying you shouldn't mop up your water if you have cancer,
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Ne kažem da ne treba da izbacite vodu ukoliko imate rak.
15:36
but I'm saying that's not really the problem;
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Ali želim da poručim da to nije uzrok problema;
15:39
that's the symptom of the problem.
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to je samo simptom problema.
15:41
What we really need to get at
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Mi zaista treba da tretiramo
15:43
is the process that's going on,
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proces koji se dešava,
15:45
and that's happening at the level
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a taj proces se dešava na nivou
15:47
of the proteonomic actions,
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proteina i njihove komunikacije,
15:49
happening at the level of why is your body not healing itself
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pitanje je zašto vaše telo ne štiti sebe
15:52
in the way that it normally does?
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na način na koji se to normalno dešava?
15:54
Because normally, your body is dealing with this problem all the time.
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Vaše telo se suočava sa problemima ovog tipa svakog dana.
15:57
So your house is dealing with leaks all the time,
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Vaša kuća se bori protiv prokišnjavanja sve vreme.
16:00
but it's fixing them. It's draining them out and so on.
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Ali se i odupire prokišnjavanju. Isušuje vodu.
16:04
So what we need
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Tako da je nama neophodan sada
16:07
is to have a causative model
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uzročni model
16:11
of what's actually going on,
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onoga što se zaista dešava.
16:13
and proteomics actually gives us
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Proteomika nam pruža
16:16
the ability to build a model like that.
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mogućnost da napokon izgradimo takav model.
16:19
David got me invited
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Dejvid me je pozvao da održim
16:21
to give a talk at National Cancer Institute
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govor na Nacionalnom Institutu Izučavanja Raka
16:23
and Anna Barker was there.
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i Ana Barker je bila tamo.
16:27
And so I gave this talk
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Tako sam održao taj govor
16:29
and said, "Why don't you guys do this?"
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i rekao, "Zašto vi ne biste uradili ovo?"
16:32
And Anna said,
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I Ana reče,
16:34
"Because nobody within cancer
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"Zato što niko ko se bavi problemom raka
16:37
would look at it this way.
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ne bi gledao na problem raka na ovaj način.
16:39
But what we're going to do, is we're going to create a program
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Ali mi ćemo svakako uspostaviti program
16:42
for people outside the field of cancer
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koji će okupiti ljude koji se ne bave rakom
16:44
to get together with doctors
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i povezaćemo te stručanjake sa medicinarima
16:46
who really know about cancer
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koji znaju puno o raku
16:49
and work out different programs of research."
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i na taj način ćemo smisliti drugačiji program istraživanja."
16:53
So David and I applied to this program
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Tako smo Dejvid i ja konkurisali za pomenuti program
16:55
and created a consortium
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i stvorili konzorcijum
16:57
at USC
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na Univerzitetu Južne Kalifornije
16:59
where we've got some of the best oncologists in the world
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gde smo okupili neke od najboljih onkologa sveta
17:02
and some of the best biologists in the world,
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i neke od najboljih biologa sveta
17:05
from Cold Spring Harbor,
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iz Kold Spring Harbora
17:07
Stanford, Austin --
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Stanforda, Ostina...
17:09
I won't even go through and name all the places --
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Ne mogu sada navesti imena svih instituticija -
17:12
to have a research project
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kako bismo odradili naučno-istraživački projekat
17:15
that will last for five years
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koji će trajati pet godina sa krajnjim
17:17
where we're really going to try to build a model of cancer like this.
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ciljem postavljanja modela kancera po opisanim principima.
17:20
We're doing it in mice first,
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Radićemo ova istraživanja prvo na miševima.
17:22
and we will kill a lot of mice
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Puno ce miševa stradati
17:24
in the process of doing this,
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u toku razvijanja ovih eksperimenata
17:26
but they will die for a good cause.
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ali će oni umreti za opšte dobro.
17:28
And we will actually try to get to the point
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Mi ćemo u principu pokušati da dođemo do momenta
17:31
where we have a predictive model
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kada imamo uspostavljeni uzročni model
17:33
where we can understand,
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na osnovu kog možemo da razumemo,
17:35
when cancer happens,
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kada se rak desi,
17:37
what's actually happening in there
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šta se u osnovi dešava u organizmu
17:39
and which treatment will treat that cancer.
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i koji specifičan tretman će biti efektan u lečenju.
17:42
So let me just end with giving you a little picture
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I za sam kraj bih vam pokazao mali shematski prikaz
17:45
of what I think cancer treatment will be like in the future.
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kako ja zamišljam da tretman protiv raka izgleda u budućnosti.
17:48
So I think eventually,
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Ja mislim da na kraju,
17:50
once we have one of these models for people,
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kada budemo imali ovakav model za ljude,
17:52
which we'll get eventually --
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koji ćemo svakako na kraju imati -
17:54
I mean, our group won't get all the way there --
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naša istraživačka grupa neće sama doći do cilja
17:56
but eventually we'll have a very good computer model --
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ali ćemo na kraju imati veoma dobar kompjuterski model -
17:59
sort of like a global climate model for weather.
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nešto kao globalni model vremenske prognoze.
18:02
It has lots of different information
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Model će imati puno različitih informacija o
18:05
about what's the process going on in this proteomic conversation
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procesima koji se dešavaju u toku komunikacije u
18:08
on many different scales.
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proteomu na različitim nivoima.
18:10
And so we will simulate
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Na taj način mi ćemo simulirati
18:12
in that model
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tim modelom specifičan rak
18:14
for your particular cancer --
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od kojeg osoba boluje i taj model
18:17
and this also will be for ALS,
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će imati primenu i za amiotrofičnu lateralnu sklerozu (ALS)
18:19
or any kind of system neurodegenerative diseases,
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ili bilo koju sistemsku neurodegenerativnu bolest,
18:22
things like that --
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bolesti kao te
18:24
we will simulate
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mi ćemo simulirati
18:26
specifically you,
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Vas posebno, ne neku
18:28
not just a generic person,
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generičku osobu, nego baš
18:30
but what's actually going on inside you.
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same procese koji se odvijaju unutar vašeg tela.
18:32
And in that simulation, what we could do
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I ono što možemo da uradimo u takvoj simulaciji
18:34
is design for you specifically
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jeste da specifično dizajniramo
18:36
a sequence of treatments,
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za Vas kombinaciju tretmana,
18:38
and it might be very gentle treatments, very small amounts of drugs.
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koji mogu biti veoma blagi, veoma male doze lekova.
18:41
It might be things like, don't eat that day,
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To mogu biti saveti tipa: nemojte jesti ovog dana,
18:44
or give them a little chemotherapy,
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ili primenićemo malu dozu hemoterapije,
18:46
maybe a little radiation.
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možda malo zračenja.
18:48
Of course, we'll do surgery sometimes and so on.
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Naravno, ponekad ćemo odraditi operativni zahvat.
18:51
But design a program of treatments specifically for you
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Ali ćemo dizajnirati poseban program tretmana samo za vas
18:54
and help your body
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i pomoći vašem telu
18:57
guide back to health --
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da se oporavi - tako ćemo
19:00
guide your body back to health.
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usmeravati vaše telo ka zdravom stanju.
19:02
Because your body will do most of the work of fixing it
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Jer će vaše telo odraditi najveći deo posla da reši problem
19:06
if we just sort of prop it up in the ways that are wrong.
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ukoliko mu mi samo pomognemo u tome.
19:09
We put it in the equivalent of splints.
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To bi bio ekvivalent metalnim udlagama.
19:11
And so your body basically has lots and lots of mechanisms
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Vaš organizam ima veoma puno mehanizama
19:13
for fixing cancer,
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koji se mogu uspešno boriti protiv raka
19:15
and we just have to prop those up in the right way
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i mi samo treba da stimulišemo te mehanizme na pravi način
19:18
and get them to do the job.
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i pokrenemo ih da ponovo počnu da rade svoj posao.
19:20
And so I believe that this will be the way
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Ja sam duboko ubeđen da će ovo biti način
19:22
that cancer will be treated in the future.
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na koji ćemo lečiti rak u budućnosti.
19:24
It's going to require a lot of work,
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To će zahtevati mnogo, mnogo rada,
19:26
a lot of research.
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mnogo istraživanja.
19:28
There will be many teams like our team
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Biće mnogo timova koji kao i naš tim
19:31
that work on this.
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pokušavaju da razumeju pomenuti fenomen.
19:33
But I think eventually,
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Ali ja mislim da ćemo u budućnosti
19:35
we will design for everybody
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biti u mogućnosti da dizajniramo
19:37
a custom treatment for cancer.
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specifičan tretman protiv raka za svaki pojedinačni slučaj.
19:41
So thank you very much.
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Na kraju, mnogo vam hvala.
19:43
(Applause)
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(Aplauz)
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