Michael Levin: The electrical blueprints that orchestrate life | TED

507,144 views ・ 2021-03-31

TED


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Prevodilac: Milenka Okuka Lektor: Ivana Korom
Kris Anderson: Majk, dobro došao.
Dobro je videti te. Uzbuđen sam zbog ovog razgovora.
Majkl Levin: Mnogo ti hvala. Srećan sam što sam tu.
KA: Većina nas ima sledeći biološki mentalni model
00:12
Chris Anderson: Mike, welcome.
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00:14
It's good to see you. I'm excited for this conversation.
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da je DNK svojstvo svih živih bića,
00:16
Michael Levin: Thank you so much. I'm so happy to be here.
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da se radi o nekakvom softveru koji gradi hardver našeg tela.
00:19
CA: So, most of us have this mental model in biology
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00:22
that DNA is a property of every living thing,
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Tako mnogi od nas razmišljaju o ovome.
Taj model ostavlja suviše suštinskih tajni.
00:27
that it is kind of the software that builds the hardware of our body.
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Možeš li da podeliš sa nama neke od tih tajni,
00:32
That's how a lot of us think about this.
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kao i kakve veze punoglavci imaju s tim?
00:34
That model leaves too many deep mysteries.
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ML: Svakako. Da.
00:37
Can you share with us some of those mysteries
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Želeo bih da vam pružim drugi pogled na ovaj problem.
DNK, između ostalog, specifikuje hardver svake ćelije.
00:40
and also what tadpoles have to do with it?
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00:44
ML: Sure. Yeah.
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Dakle, DNK saopštava svakoj ćeliji koje bi proteine trebalo da ima.
00:45
I'd like to give you another perspective on this problem.
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00:48
One of the things that DNA does is specify the hardware of each cell.
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Stoga, kada imate punoglavce, na primer,
vidite baš ono
00:52
So the DNA tells every cell what proteins it's supposed to have.
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što većina ljudi smatra nekakvim progresivnim odmotavanjem genoma.
00:57
And so when you have tadpoles, for example,
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Naročiti geni se uključuju i isključuju,
01:00
you see the kind of thing
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i punoglavac, kako postaje žaba, mora nanovo da sklopi lice.
01:02
that most people think is sort of a progressive unrolling of the genome.
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Oči, nozdrve, vilica - sve mora da se pomeri.
01:07
Specific genes turn on and off,
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A način da se o tome misli je bio, pa dobro,
01:09
and a tadpole, as it becomes a frog,
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imate nekakav urođen skup pokreta
01:11
has to rearrange its face.
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01:12
So the eyes, the nostrils, the jaws -- everything has to move.
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gde se sve ove stvari kreću okolo i daju vam žabu.
01:15
And one way to think about it used to be that, well,
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Zapravo, pre nekoliko godina, otkrili smo prilično neverovatnu pojavu,
01:18
you have a sort of hardwired set of movements
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a to je, ako napravite takozvane Pikaso žabe -
01:20
where all of these things move around and then you get your frog.
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radi se o punoglavcima kod kojih vilica može da bude skroz s profila,
01:24
But actually, a few years ago, we found a pretty amazing phenomenon,
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oči su ovde gore, nozdrve su pomerene,
01:27
which is that if you make so-called "Picasso frogs" --
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dakle, sve je izmešteno -
ovi punoglavci izrastu u uglavnom normalna žablja lica.
01:30
these are tadpoles where the jaws might be off to the side,
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Sad, ovo je neverovatno
01:33
the eyes are up here, the nostrils are moved,
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jer svi organi započinju na abnormalnim mestima,
01:35
so everything is shifted --
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01:37
these tadpoles make largely normal frog faces.
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ipak, i dalje na kraju daju prilično dobra žablja lica.
01:40
Now, this is amazing,
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Ispostavlja se da ovaj sistem,
01:42
because all of the organs start off in abnormal positions,
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poput mnogih živih sistema,
nema urođen skup pokreta,
01:45
and yet they still end up making a pretty good frog face.
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već zapravo radi na umanjivanju greške između onoga što se dešava sada
01:48
And so what it turns out is that this system,
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01:50
like many living systems,
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i onoga za šta zna da je ispravna konfiguracija žabljeg lica.
01:52
is not a hardwired set of movements,
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Ovaj vid donošenja odluke,
01:54
but actually works to reduce the error between what's going on now
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koji podrazumeva fleksibilne odgovore na nove okolnosti,
01:58
and what it knows is a correct frog face configuration.
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u drugim kontekstima nazivali bismo inteligencijom.
Trenutno ne treba samo da razumemo mehanizme
02:02
This kind of decision-making
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02:03
that involves flexible responses to new circumstances,
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po kojima ove ćelije izvode svoje pokrete
02:07
in other contexts, we would call this intelligence.
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i ispoljavanje gena itd,
već zaista moramo da razumemo tok informacija:
02:10
And so what we need to understand now is not only the mechanisms
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kako ove ćelije međusobno sarađuju
02:14
by which these cells execute their movements
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kako bi izgradile nešto veliko i kako bi prestale da grade
02:16
and gene expression and so on,
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02:18
but we really have to understand the information flow:
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kada je ta naročita struktura gotova?
02:21
How do these cells cooperate with each other
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A ovi vidovi proračuna, ne samo mehanizmi,
02:23
to build something large and to stop building
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već proračuni anatomske kontrole,
02:26
when that specific structure is created?
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budućnost su biologije.
KA: Pretpostavljam da je tradicionalni model
02:29
And these kinds of computations, not just the mechanisms,
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da ćelije nekako šalju biohemijske signale jedna drugoj
02:32
but the computations of anatomical control,
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02:35
are the future of biology.
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koji omogućavaju da se taj razvoj desi na pametan način.
02:37
CA: And so I guess the traditional model
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02:39
is that somehow cells are sending biochemical signals to each other
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Ti, ipak, smatraš da je još nešto na delu.
O čemu se radi?
02:43
that allow that development to happen the smart way.
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ML: Ćelije svakako komuniciraju biohemijski i putem fizičkih sila,
ali još nešto se dešava što je veoma interesantno,
02:48
But you think there is something else at work.
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02:50
What is that?
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a to se u suštini naziva bioelektricitetom,
02:51
ML: Well, cells certainly do communicate biochemically and via physical forces,
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ne-neuronskim bioelektricitetom.
02:55
but there's something else going on that's extremely interesting,
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Ispostavlja se da sve ćelije -
ne samo nervi, već sve ćelije u vašem telu -
02:58
and it's basically called bioelectricity,
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međusobno komuniciraju upotrebom električnih signala.
A ono što vidite ovde je tajm-laps snimak.
03:02
non-neural bioelectricity.
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03:04
So it turns out that all cells --
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Prvi put,
03:05
not just nerves, but all cells in your body --
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trenutno smo u mogućnosti da prisluškujemo sve električne razgovore
03:07
communicate with each other using electrical signals.
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koje ćelije međusobno vode.
03:10
And what you're seeing here is a time-lapse video.
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Razmišljajte o ovome.
03:12
For the first time,
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Upravo gledamo -
Ovo je embrion žabe u začetku.
03:14
we are now able to eavesdrop on all of the electrical conversations
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Ovo je nakon oko osam do 10 sati razvoja.
03:17
that the cells are having with each other.
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A boje vam pokazuju stvarna električna stanja
03:19
So think about this.
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03:20
We're now watching --
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koja vam omogućuju da vidite sav električni softver
03:22
This is an early frog embryo.
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03:23
This is about eight hours to 10 hours of development.
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koji radi na ćelijskom hardveru definisanom genomom.
03:26
And the colors are showing you actual electrical states
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Dakle, ove ćelije u suštini razgovaraju jedna s drugom
03:30
that allow you to see all of the electrical software
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ko će da bude glava, ko će da bude rep,
03:33
that's running on the genome-defined cellular hardware.
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ko će da bude levo i desno i sačinjava oči i mozak, itd.
03:36
And so these cells are basically communicating with each other
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Dakle, ovaj softver
omogućava ovim živim sistemima da ostvare specifične ciljeve,
03:40
who is going to be head, who is going to be tail,
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03:43
who is going to be left and right and make eyes and brain and so on.
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poput izgradnje embriona
ili regeneracije uda kod životinja koje to mogu,
03:46
And so it is this software
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that allows these living systems to achieve specific goals,
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a sposobnost da vidimo ove električne razgovore
03:51
goals such as building an embryo
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03:53
or regenerating a limb for animals that do this,
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nam pruža neke prilično izvanredne mogućnosti
03:56
and the ability to see these electrical conversations
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da ciljamo i nanovo ispisujemo ciljeve prema kojima
se ovi sistemi upravljaju.
KA: U redu. To je prilično radikalno.
04:02
gives us some really remarkable opportunities
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Sačekaj da vidim da li sam razumeo.
04:05
to target or to rewrite the goals towards which
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Kažeš da kada organizam počne da se razvija,
04:08
these living systems are operating.
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čim se ćelija podeli,
04:10
CA: OK, so this is pretty radical.
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električni signali se razmenjuju između njih.
04:12
Let me see if I understand this.
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04:14
What you're saying is that when an organism starts to develop,
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Međutim, kad stignemo do stotinu, nekoliko stotina ćelija,
04:18
as soon as a cell divides,
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04:19
electrical signals are shared between them.
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nekako ovi signali na kraju tvore nešto u suštini nalik kompjuterskom programu,
04:23
But as you get to, what, a hundred, a few hundred cells,
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programu koji nekako uključuje sve potrebne informacije
04:27
that somehow these signals end up forming essentially like a computer program,
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kako bi saopštio organizmu
njegovu sudbinu?
04:34
a program that somehow includes all the information needed
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Je li ovo razmišljanje ispravno?
ML: Da, poprilično.
U suštini, dešava se da ove ćelije,
04:39
to tell that organism
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obrazujući električne mreže nalik mrežama u mozgu,
04:41
what its destiny is?
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04:43
Is that the right way to think about it?
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one obrazuju električne mreže,
04:45
ML: Yes, quite.
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04:46
Basically, what happens is that these cells,
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a ove mreže obrađuju informacije uključujući šablonsku memoriju.
04:48
by forming electrical networks much like networks in the brain,
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One uključuju prikaz anatomskih struktura velikih razmera
04:52
they form electrical networks,
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04:54
and these networks process information including pattern memories.
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za smeštanje različitih organa,
koje ćemo različite ose kod životinje - napred i nazad, glava i rep -
04:58
They include representation of large-scale anatomical structures
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da imamo,
a ovo je bukvalno sadržano u električnim kolima
05:03
where various organs will go,
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duž velikih tkiva
05:05
what the different axes of the animal -- front and back, head and tail --
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na isti način na koji mozgovi pohranjuju druge vidove pamćenja i učenja.
05:08
are going to be,
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05:10
and these are literally held in the electrical circuits
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KA: Da li razmišljam ispravno?
05:12
across large tissues
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05:14
in the same way that brains hold other kinds of memories and learning.
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Jer se ovo čini ogromnim preokretom.
Mislim, kad sam prvi put nabavio kompjuter,
bio sam očaran ljudima koji su znali tzv. mašinsko programiranje,
05:20
CA: So is this the right way to think about it?
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05:22
Because this seems to be such a big shift.
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poput direktnog programiranja pojedinačnih bitova kompjutera.
05:24
I mean, when I first got a computer,
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05:27
I was in awe of the people who could do so-called "machine code,"
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To je bilo nemoguće većini smrtnika.
Da bismo mogli da kontrolišemo kompjuter,
morali smo da programiramo nekim jezikom,
05:32
like the direct programming of individual bits in the computer.
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a to je bio daleko jednostavniji način da se dese opštije stvari.
05:36
That was impossible for most mortals.
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05:38
To have a chance of controlling that computer,
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05:40
you'd have to program in a language,
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I ako te dobro razumem,
05:42
which was a vastly simpler way of making big-picture things happen.
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ti kažeš da se trenutno biologija uglavnom odvija
pokušavajući ekvivalent programiranja mašinskim jezikom,
razumevajući biohemijske signale između pojedinačnih ćelija,
05:49
And if I understand you right,
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05:51
what you're saying is that most of biology today has sort of taken place
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kad, čekaj malo, sveca mu, imamo ovaj jezik,
05:54
trying to do the equivalent of machine code programming,
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ovaj električni jezik, koji, ako bismo ga razumeli,
05:57
of understanding the biochemical signals between individual cells,
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06:00
when, wait a sec, holy crap, there's this language going on,
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pružio bi nam skroz drugačiji skup razumevanja
06:03
this electrical language, which, if you could understand that,
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o tome kako se organizmi razvijaju.
Da li je ova metafora u suštini tačna?
ML: Da, baš tako.
06:08
that would give us a completely different set of insights
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Ako se setimo kako je programiranje rađeno tokom ’40-ih,
06:11
into how organisms are developing.
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da biste naveli kompjuter da uradi nešto drugačije,
06:13
Is that metaphor basically right?
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morali ste fizički da ispomerate žice.
06:15
ML: Yeah, this is exactly right.
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06:17
So if you think about the way programming was done in the '40s,
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Pa ste morali da uđete i nanovo povežete hardver.
Morali ste direktno da interagujete sa hardverom,
06:20
in order to get your computer to do something different,
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a sve vaše strategije manipulacije tom mašinom
06:23
you would physically have to shift the wires around.
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bi bile na nivou hardvera.
06:25
So you'd have to go in there and rewire the hardware.
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A razlog što trenutno imamo ovu izvanrednu tehnološku revoluciju,
06:28
You'd have to interact with the hardware directly,
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informacijske nauke itd,
06:30
and all of your strategies for manipulating that machine
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je što je nauka o kompjuterima preusmerila pažnju sa hardvera
06:33
would be at the level of the hardware.
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06:35
And the reason we have this now amazing technology revolution,
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na razumevanje da, ako vam je hardver dovoljno dobar -
06:38
information sciences and so on,
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a ja vam kažem da je biološki hardver apsolutno dovoljno dobar -
06:40
is because computer science moved from a focus on the hardware
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onda možete da interagujete sa sistemom, ne lupkajući i menjajući hardver,
06:43
on to understanding that if your hardware is good enough --
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06:46
and I'm going to tell you that biological hardware is absolutely good enough --
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već zapravo, možete se povući nazad i dati mu stimulans ili unos
06:50
then you can interact with your system not by tweaking or rewiring the hardware,
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na način kako biste to uradili sa rekonfigurišućim kompjuterom
navodeći ćelijsku mrežu da uradi nešto sasvim suprotno
06:56
but actually, you can take a step back and give it stimuli or inputs
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06:59
the way that you would give to a reprogrammable computer
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onome što bi inače uradila.
Stoga nam vidljivost ovih biohemijskih signala
07:02
and cause the cellular network to do something completely different
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pruža direktnu ulaznu tačku u softver
07:07
than it would otherwise have done.
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koji upravlja anatomijom velikih razmera,
07:09
So the ability to see these bioelectrical signals
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a to je potpuno različit pristup medicini
07:12
is giving us an entry point directly into the software
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od ponovnog povezivanja specifičnih prolaza unutar svake ćelije.
07:15
that guides large-scale anatomy,
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KA: Dakle, na razne načine, tvoj rad je neverovatan
07:17
which is a very different approach to medicine
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jer ti počinješ da dešifruješ kôd ovih električnih signala,
07:21
than to rewiring specific pathways inside of every cell.
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i imaš sjajnu demonstraciju ovoga
07:25
CA: And so in many ways, this is the amazingness of your work
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kod ovih pljosnatih crva.
Kaži nam šta se ovde dešava.
07:27
is that you're starting to crack the code of these electrical signals,
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ML: Ovo je biće poznato kao planarija.
07:31
and you've got an amazing demonstration of this
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Radi se o pljosnatim crvima.
07:33
in these flatworms.
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Oni su zapravo prilično složena bića.
07:35
Tell us what's going on here.
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Imaju pravi mozak, mnoštvo različitih organa, itd.
07:37
ML: So this is a creature known as a planarian.
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A neverovatna stvar kod ovih planarija
07:40
They're flatworms.
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je da su veoma, veoma regenerativne.
07:41
They're actually quite a complex creature.
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Pa, ako je isečeta na komadiće - zapravo, na preko 200 komadića -
07:43
They have a true brain, lots of different organs and so on.
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07:46
And the amazing thing about these planaria
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svaki delić će dograditi tačno šta je neophodno
07:48
is that they are highly, highly regenerative.
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07:50
So if you cut it into pieces -- in fact, over 200 pieces --
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da se sačini savršen crvić.
Razmislite o tome.
Radi se o sistemu gde svaki delić
07:54
every piece will rebuild exactly what's needed
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tačno zna kako prava planarija izgleda
i gradi odgovarajuće organe na odgovrajućim mestima i potom staje.
07:58
to make a perfect little worm.
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08:00
So think about that.
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08:01
This is a system where every single piece
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A to je nešto najneverovatnije kod regeneracije.
08:03
knows exactly what a correct planarian looks like
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Mi smo otkrili da ako je isečemo na tri dela
08:06
and builds the right organs in the right places and then stops.
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i amputiramo glavu i rep, i samo uzmemo ovaj središnji fragment,
08:09
And that's one of the most amazing things about regeneration.
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a to vidite ovde,
08:12
So what we discovered is that if you cut it into three pieces
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iznenađujuće, imamo električni gradijent, od glave do repa, koji nastaje
08:15
and amputate the head and the tail and you just take this middle fragment,
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i koji kaže tom delu gde idu glava i rep,
08:19
which is what you see here,
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i, zapravo, koliko glava ili repova bi trebalo da ima.
08:20
amazingly, there is an electrical gradient, head to tail, that's generated
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Mi smo naučili da manipulišemo ovim električnim gradijentom,
08:24
that tells the piece where the heads and the tails go
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a važna stvar je da ne upotrebljavamo elektricitet.
08:27
and in fact, how many heads or tails you're supposed to have.
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Umesto toga, uključujemo i isključujemo malene tranzistore -
08:30
So what we learned to do is to manipulate this electrical gradient,
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u stvari to je kanal jonskih proteina -
08:34
and the important thing is that we don't apply electricity.
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koji svaka ćelija izvorno koristi da bi podesila ovo električno stanje.
08:37
What we do instead was we turned on and off the little transistors --
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Sada imamo načine da ih uključimo i isključimo,
08:41
they're actual ion channel proteins --
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a kada to radite, nešto što možete
je da promenite strujno kolo u stanje koje kaže, ne, gradi dve glave,
08:44
that every cell natively uses to set up this electrical state.
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08:47
So now we have ways to turn them on and off,
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ili, zapravo, gradi bez glave.
08:49
and when you do this, one of the things you can do
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A ovde vidite stvarne crve koji imaju dve glave ili nijednu
08:52
is you can shift that circuit to a state that says no, build two heads,
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koji su rezultat ovoga
jer je električna mapa ono što ćelije koriste
08:56
or in fact, build no heads.
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da bi odlučile šta da rade.
08:58
And what you're seeing here are real worms that have either two or no heads
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A ovde vidite žive dvoglave crve.
09:02
that result from this,
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Kada smo stvorili sve ovo, obavili smo skroz blesav eksperiment.
09:03
because that electrical map is what the cells are using
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09:06
to decide what to do.
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Uzmete jedan od ovih dvoglavih crva i otkinete obe glave,
09:08
And so what you're seeing here are live two-headed worms.
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i ostavite samo normalni središnji fragment.
09:11
And, having generated these, we did a completely crazy experiment.
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Sad, imajte na umu, ove životinje nisu genomski modifikovane.
09:15
You take one of these two-headed worms, and you chop off both heads,
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Apsolutno ništa u vezi s njihovim genomima nije drugačije.
09:19
and you leave just the normal middle fragment.
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Njihov genomski niz je potpuno prirodan.
09:21
Now keep in mind, these animals have not been genomically edited.
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Dakle, amputirate glave, imate fin, normalan fragment,
09:24
There's absolutely nothing different about their genomes.
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a onda pitate: u običnoj vodi, šta će da se desi?
09:27
Their genome sequence is completely wild type.
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I, naravno, standardna paradigma bi glasila:
09:30
So you amputate the heads, you've got a nice normal fragment,
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ako ste se rešili suvišnog ektopičnog tkiva,
genom nije redigovan, dakle, trebalo bi da dobijemo skroz normalnog crva.
09:34
and then you ask: In plain water, what is it going to do?
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09:37
And, of course, the standard paradigm would say,
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A neverovatno je da se to ne dešava.
09:39
well, if you've gotten rid of this ectopic extra tissue,
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Ovi crvi, kada se ponovo i ponovo iseku, u budućnosti, u običnoj vodi,
09:42
the genome is not edited so it should make a perfectly normal worm.
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09:46
And the amazing thing is that it is not what happens.
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nastavljaju da se regenerišu kao dvoglavi.
09:49
These worms, when cut again and again, in the future, in plain water,
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Razmišljajte o ovome.
Šablonska memorija po kojoj se ove životinje regenerišu nakon oštećenja
09:55
they continue to regenerate as two-headed.
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je trajno izmenjena.
09:57
Think about this.
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I zapravo, sada možemo da je vratimo na staro i da ih vratimo na jednoglave
09:58
The pattern memory to which these animals will regenerate after damage
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bez bilo kakve izmene genoma.
Ovo ovde vam govori da informaciona struktura
10:04
has been permanently rewritten.
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10:06
And in fact, we can now write it back and send them back to being one-headed
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koja saopštava ovim crvima koliko glava bi trebalo da imaju
10:09
without any genomic editing.
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nije direktno u genomu.
Već je u dodatnom bioelektričnom sloju.
10:11
So this right here is telling you that the information structure
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Verovatno je i štošta drugo.
10:14
that tells these worms how many heads they're supposed to have
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I mi sada imamo sposobnost da to menjamo.
10:17
is not directly in the genome.
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A to je, naravno, osnovna definicija memorije.
10:19
It is in this additional bioelectric layer.
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Mora da bude stabilna, dugoročno stabilna i mora da bude podložna redigovanju.
10:21
Probably many other things are as well.
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10:23
And we now have the ability to rewrite it.
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A mi trenutno počinjemo da dešifrujemo ovaj morfogenetički kôd
10:25
And that, of course, is the key definition of memory.
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kako bismo ispitali kako ova tkiva skladište uputstva za rad
10:29
It has to be stable, long-term stable, and it has to be rewritable.
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10:33
And we are now beginning to crack this morphogenetic code
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i kako mi možemo da uđemo i da izmenimo uputstva radi novih ishoda.
10:36
to ask how is it that these tissues store a map of what to do
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KA: Mislim, to se čini kao neverovatno ubedljiv dokaz
10:41
and how we can go in and rewrite that map to new outcomes.
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da DNK nije jedina koja kontroliše stvarni krajnji oblik
10:46
CA: I mean, that seems incredibly compelling evidence
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ovih organizama,
10:50
that DNA is just not controlling the actual final shape
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da imamo nešto potpuno drugo što se dešava
i, čoveče, dešifrovanje tog koda
do čega bi još dovelo.
10:57
of these organisms,
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Usput, samo posmatrajući ove.
10:59
that there's this whole other thing going on,
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Kako izgleda život dvoglavog pljosnatog crva?
11:02
and, boy, if you could crack that code,
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Mislim, čini se kao nagodba.
11:04
what else could that lead to.
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Dobre vesti su da imaju neverovatan trodimenzionalan pogled na svet,
11:06
By the way, just looking at these ones.
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11:08
What is life like for a two-headed flatworm?
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ali loše vesti su da moraju da kake kroz oba svoja usta?
11:11
I mean, it seems like it's kind of a trade-off.
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11:13
The good news is you have this amazing three-dimensional view of the world,
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ML: Crvi imaju malene tube koje se nazivaju ždrelom,
11:17
but the bad news is you have to poop through both of your mouths?
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a tube su otprilike na sredini tela,
i kroz njih izbacuju izmet.
11:22
ML: So, the worms have these little tubes called pharynxes,
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Ove životninje su skroz održive.
U potpunosti su srećne, verujem.
11:26
and the tubes are sort of in the middle of the body,
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Problem je, međutim,
što dve glave ne sarađuju tako dobro,
11:29
and they excrete through that.
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11:30
These animals are perfectly viable.
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pa oni ne jedu tako dobro.
11:32
They're completely happy, I think.
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Ako, pak, možete rukom da ih hranite,
živeće zauvek,
11:35
The problem, however,
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i, zapravo, trebalo bi da znate da su ovi crvi praktično besmrtni.
11:36
is that the two heads don't cooperate all that well,
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Ovi crvi jer su tako izrazito regenrativni,
11:39
and so they don't really eat very well.
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11:41
But if you manage to feed them by hand,
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nemaju starosno ograničenje,
11:43
they will go on forever,
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i saopštavaju nam da ako dešifrujemo njihovu tajnu regeneracije,
11:44
and in fact, you should know these worms are basically immortal.
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11:47
So these worms, because they are so highly regenerative,
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koja nije samo razvoj novih ćelija, već i znanje kada se zaustaviti -
11:50
they have no age limit,
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vidite, ovo je apsolutno ključno -
11:52
and they're telling us that if we crack this secret of regeneration,
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ako u kontinuitetu možete da ispoljavate ovu suštinsku kontrolu
11:55
which is not only growing new cells but knowing when to stop --
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nad trodimenzionalnim strukturama koje ćelije pokušavaju da postignu,
11:58
you see, this is absolutely crucial --
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mogli biste da pobedite starost kao i traumatske povrede
12:00
if you can continue to exert this really profound control
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i slične stvari.
Jedna stvar koju treba imati na umu je da mogućnost izmene
12:04
over the three-dimensional structures that the cells are working towards,
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telesnih anatomskih struktura velikih razmera
12:08
you could defeat aging as well as traumatic injury
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nije tek uvrnuti trik planarija.
12:11
and things like this.
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Nije nešto što samo deluje kod pljosnatih crva.
12:12
So one thing to keep in mind is that this ability to rewrite
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12:15
the large-scale anatomical structure of the body
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Ovde vidite punoglavca s okom i crevom,
12:18
is not just a weird planarian trick.
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a mi smo uključili veoma specifičan jonski kanal.
12:20
It's not just something that works in flatworms.
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U suštini smo prosto manipulisali ovim malenim električnim tranzistorima
12:23
What you're seeing here is a tadpole with an eye and a gut,
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12:26
and what we've done is turned on a very specific ion channel.
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koji su untar ćelija,
i nametnuli smo stanje nekim od ovih crevnih ćelija
12:31
So we basically just manipulated these little electrical transistors
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koje je obično povezano sa izgradnjom oka.
12:34
that are inside of cells,
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I kao rezultat, ćelije će sagraditi oko.
12:36
and we've imposed a state on some of these gut cells
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Ove oči su potpune.
Imaju optički nerv, sočivo, mrežnjaču,
12:39
that's normally associated with building an eye.
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sve ono što bi oko trebalo da ima.
12:42
And as a result, what the cells do is they build an eye.
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Usput, mogu da vide na ove oči.
12:45
These eyes are complete.
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12:46
They have optic nerve, lens, retina,
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A ovde vidite
da pokrećući subrutine za izgradnju oka
12:50
all the same stuff that an eye is supposed to have.
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u fiziološkom softveru tela,
12:52
They can see, by the way, out of these eyes.
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lako mu možete saopštiti da izgradi složen organ.
12:54
And what you're seeing here
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12:55
is that by triggering eye-building subroutines
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A ovo je važno za našu biomedicinu
12:58
in the physiological software of the body,
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jer ne znamo kako da do sitnih detalja upravljamo izgradnjom oka.
13:01
you can very easily tell it to build a complex organ.
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Smatram da će poprilično potrajati
pre nego što budemo u stanju da od nule sagradimo oči, ruke itd.
13:04
And this is important for our biomedicine,
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13:06
because we don't know how to micromanage the construction of an eye.
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Međutim, ne moramo jer telo već zna kako da to uradi
13:10
I think it's going to be a really long time
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i imamo ove subrutine koje mogu da se aktiviraju
13:12
before we can really bottom-up build things like eyes or hands and so on.
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putem specifičnih električnih nacrta koje možemo da otkrijemo.
13:17
But we don't need to, because the body already knows how to do it,
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A to nazivamo „dešifrovanjem biolektričnog koda”.
13:20
and there are these subroutines that can be triggered
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Možemo da pravimo oči, dodatne udove.
13:23
by specific electrical patterns that we can find.
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Ovo je jedan od naših punoglavaca s pet nogu.
Možemo da dodamo još jedno srce.
13:26
And this is what we call "cracking the bioelectric code."
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Počinjemo da dešifrujemo kôd kako bismo razumeli gde su subrutine
13:29
We can make eyes. We can make extra limbs.
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u ovom softveru
13:31
Here's one of our five-legged tadpoles.
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koje možemo da aktiviramo i gradimo ove složene organe
13:33
We can make extra hearts.
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mnogo pre nego što zapravo naučimo da detaljno upravljamo procesom
13:35
We're starting to crack the code to understand where are the subroutines
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na ćelijskom nivou.
13:39
in this software
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KA: Kada si počeo da izučavaš ovaj električni sloj
13:40
that we can trigger and build these complex organs
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13:43
long before we actually know how to micromanage the process
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i šta on sve može,
uspeo si da stvoriš -
13:46
at the cellular level.
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13:47
CA: So as you've started to get to learn this electrical layer
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je li u redu reći skoro nov, novi oblik života
nazvan ksenobot?
13:52
and what it can do,
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Pričaj mi o ksenobotima.
13:53
you've been able to create --
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ML: Tako je.
Ako razmišljaš o ovome, ovo vodi do zaista čudnog predviđanja.
13:56
is it fair to say it's almost like a new, a novel life-form,
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14:00
called a xenobot?
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Ako su ćelije uistinu voljne da grade na osnovu specifične mape,
14:01
Talk to me about xenobots.
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14:03
ML: Right.
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14:04
So if you think about this, this leads to a really strange prediction.
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mogli bismo uzeti genetski neizmenjene ćelije,
a ovde vidite ćelije uzete iz tela žabe.
14:08
If the cells are really willing to build towards a specific map,
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Spojile su se tako da to od njih zahteva da ponovo zamisle svoju multicelularnost.
14:12
we could take genetically unaltered cells,
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14:16
and what you're seeing here is cells taken out of a frog body.
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A ovde vidite
da kada se oslobode od ostatka tela životinje,
14:19
They've coalesced in a way that asks them to re-envision their multicellularity.
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grade ova sićušna nova tela koja, u smislu ponašanja,
14:24
And what you see here
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vidite da mogu da se kreću, da jure po lavirintu.
14:25
is that when liberated from the rest of the body of the animal,
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Potpuno su različita od žaba ili punoglavaca.
14:28
they make these tiny little novel bodies that are, in terms of behavior,
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Kada upitamo žablje ćelije da osmisle kakvo telo žele da naprave,
14:32
you can see they can move, they can run a maze.
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14:35
They are completely different from frogs or tadpoles.
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one urade nešto krajnje interesantno.
14:38
Frog cells, when asked to re-envision what kind of body they want to make,
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Koriste hardver koji im obezbeđuje njihova genetika,
na primer, ove malene dlakice, ove malene cilije
14:44
do something incredibly interesting.
302
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koje se obično koriste za preraspodelu sluzi na spoljašnjosti žabe,
14:46
They use the hardware that their genetics gives them,
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one su genetski određene.
14:51
for example, these little hairs, these little cilia
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Međutim, ova bića,
jer su im ćelije u stanju da formiraju nove vrste tela,
14:54
that are normally used to redistribute mucus on the outside of a frog,
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14:58
those are genetically specified.
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su otkrila kako da koriste ove malene cilije
14:59
But what these creatures did,
307
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da umesto toga veslaju uzvodno i ona su sad pokretna.
15:02
because the cells are able to form novel kinds of bodies,
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4649
Dakle, ne samo da mogu da se kreću, već mogu, a ovde vidite
15:06
they have figured out how to use these little cilia
309
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15:09
to instead row against the water, and now have locomotion.
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da se ove ćelije spajaju.
Sada započinju razgovore o tome šta će da urade.
15:13
So not only can they move around, but they can, and here what you're seeing,
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Ovde vidite svetlucanje, tj. razmenu informacija.
15:18
is that these cells are coalescing together.
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Imajte na umu, ovo je samo koža.
15:21
Now they're starting to have conversations about what they are going to do.
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Nema nervnog sistema. Nema mozga. Ovo je samo koža.
15:24
You can see here the flashes are these exchanges of information.
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Ovo je koža koja je naučila da pravi novo telo,
15:28
Keep in mind, this is just skin.
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da istražuje okolinu i da se kreće naokolo.
15:30
There is no nervous system. There is no brain. This is just skin.
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I imaju spontana ponašanja.
15:34
This is skin that has learned to make a new body
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Ovde vidite kako pliva niz lavirint.
U ovoj tački, odlučuje da se okrene i vrati odakle je krenula.
15:37
and to explore its environment and move around.
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15:40
And they have spontaneous behaviors.
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Dakle, ima sopstveno ponašanje, i radi se o izvanrednom modelu sistema
15:42
You can see here where it's swimming down this maze.
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iz više razloga.
15:45
At this point, it decides to turn around and go back where it came from.
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Pre svega, pokazuje nam neverovatnu plastičnost ćelija
15:48
So it has its own behavior, and this is a remarkable model system
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koje su genetski neizmenjene.
Ovde nema genetske redakcije.
15:52
for several reasons.
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Ovo su ćelije koje su zaista sklone gradnji nekakvog funkcionalnog tela.
15:53
First of all, it shows us the amazing plasticity of cells
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15:57
that are genetically wild type.
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Druga stvar,
15:58
There is no genetic editing here.
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a ovo smo radili u saradnji sa Džoš Bongardovom laboratorijom na UVM,
16:00
These are cells that are really prone to making some sort of functional body.
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radili su modele struktura ovih stvari i evoluirali ih u virtuelnom svetu.
16:05
The second thing,
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16:06
and this was done in collaboration with Josh Bongard's lab at UVM,
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Ovo je bukvlano - na kompjuteru, modelirali su ga na kompjuteru.
16:10
they modeled the structure of these things and evolved it in a virtual world.
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Ovo je bukvalno jedini organizam koji mi je poznat na našoj planeti
čija evolucija se nije desila u biosferi zemlje,
16:16
So this is literally -- on a computer, they modeled it on a computer.
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već unutar kompjutera.
16:19
So this is literally the only organism that I know of on the face of this planet
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Pojedinačne ćelije imaju evolutivnu istoriju,
16:23
whose evolution took place not in the biosphere of the earth
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ali ovaj organizam nikad pre nije postojao.
Evoluirao je u ovom virtuelnom svetu,
16:27
but inside a computer.
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a mi smo se onda zaputili i napravili ga u laboratoriji,
16:29
So the individual cells have an evolutionary history,
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i vidite ovu izvanrednu plastičnost.
16:31
but this organism has never existed before.
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Ovo nije samo za izgradnju korisnih mašina.
16:34
It was evolved in this virtual world,
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16:36
and then we went ahead and made it in the lab,
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Možete da zamislite kako ih programiramo da izađu u spoljni svet
16:39
and you can see this amazing plasticity.
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i čiste toksine i prečišćavaju,
16:41
This is not only for making useful machines.
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ili možete da ih zamislite napravljene od ljudskih ćelija
koje bi se kretale kroz vaše telo i sakupljale ćelije raka
16:45
You can imagine now programming these to go out into the environment
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ili bi lečile artritične zglobove,
16:49
and collect toxins and cleanup,
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16:50
or you could imagine ones made out of human cells
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dostavljale proregenerativna jedinjenja,
razne stvari.
16:53
that would go through your body and collect cancer cells
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Ne radi se samo o korisnim primenama - ovo je izvanredno igralište
16:56
or reshape arthritic joints,
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za učenje komunikacije morfogenetičkih signala sa ćelijskim kolektivom.
16:58
deliver pro-regenerative compounds,
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17:01
all kinds of things.
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17:02
But not only these useful applications -- this is an amazing sandbox
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Čim ovo dešifrujemo, čim razumemo kako ove ćelije odlučuju šta da rade,
17:05
for learning to communicate morphogenetic signals to cell collectives.
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onda ćemo, naravno, naučiti da menjamo tu informaciju,
17:10
So once we crack this, once we understand how these cells decide what to do,
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sledeći korak su velika unapređenja u regenerativnoj medicini
17:15
and then we're going to, of course, learn to rewrite that information,
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jer ćemo tada biti u stanju da saopštimo ćelijama da grade zdrave organe.
17:18
the next steps are great improvements in regenerative medicine,
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Pa je ovo trenutno uistinu ključna šansa
da naučimo da komuniciramo sa grupama ćelija,
17:23
because we will then be able to tell cells to build healthy organs.
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ne da do detalja upravljamo njima, ne da forsiramo hardver,
17:27
And so this is now a really critical opportunity
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već da komuniciramo i menjamo ciljeve koje ove ćelije pokušavaju da ostvare.
17:30
to learn to communicate with cell groups,
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KA: Radi se o stvarima koje raspamećuju.
17:32
not to micromanage them, not to force the hardware,
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Za kraj, Majk, reci nam samo još jednu priču
17:35
to communicate and rewrite the goals that these cells are trying to accomplish.
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o medicini koja bi mogla da nastane
dok ti razvijaš razumevanje
17:40
CA: Well, it's mind-boggling stuff.
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17:42
Finally, Mike, give us just one other story
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o tome kako ovaj bioelektrični sloj deluje.
17:45
about medicine that might be to come
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ML: Da, ovo je izuzetno uzbudljivo jer, ako razmisliš o tome,
17:48
as you develop this understanding
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većina problema u biomedicini -
17:51
of how this bioelectric layer works.
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urođeni defekti, degenerativne bolesti, starenje, traumatske povrede, čak i rak -
17:54
ML: Yeah, this is incredibly exciting because, if you think about it,
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sve se svode na jedno:
17:58
most of the problems of biomedicine --
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ćelije ne grade što biste želeli da grade.
18:00
birth defects, degenerative disease, aging, traumatic injury, even cancer --
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Stoga, ako bismo razumeli kako da komuniciramo sa ovim kolektivima
i da zaista menjamo njihove ciljne morfologije,
18:06
all boil down to one thing:
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18:07
cells are not building what you would like them to build.
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18:10
And so if we understood how to communicate with these collectives
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bili bismo u stanju da normalizujemo tumore,
da popravljamo urođene defekte,
18:14
and really rewrite their target morphologies,
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da pokrećemo regeneraciju udova i drugih organa,
a ovo smo sve već uradili na žabljim modelima.
18:18
we would be able to normalize tumors,
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Pa je sad sledeći zaista uzbudljiv korak
18:21
we would be able to repair birth defects,
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18:23
induce regeneration of limbs and other organs,
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da ovo prenesemo na ćelije sisara
18:25
and these are things we have already done in frog models.
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i da ovo uistinu pretvorimo u sledeću generaciju regenerativne medicine
18:29
And so now the next really exciting step
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gde učimo da se bavimo svim ovim biomedicinskim potrebama
18:31
is to take this into mammalian cells
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18:35
and to really turn this into the next generation of regenerative medicine
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komunicirajući sa ćelijskim kolektivima
i menjajući njihovu bioelektričnu šablonsku memoriju.
18:39
where we learn to address all of these biomedical needs
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I posljednje što bih želeo da kažem je da se važnost ove oblasti
18:43
by communicating with the cell collectives
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ne ogleda samo u biomedicini.
18:45
and rewriting their bioelectric pattern memories.
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Vidite, kao što sam rekao na početku,
ova sposobnost ćelija u novim sredinama
18:49
And the final thing I'd like to say is that the importance of this field
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da grade svakakve stvari pored onog što im genom saopštava
18:52
is not only for biomedicine.
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18:54
You see, this, as I started out by saying,
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je primer inteligencije,
18:56
this ability of cells in novel environments
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a biologija je inteligentno rešavala probleme
18:59
to build all kinds of things besides what their genome tells them
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još mnogo pre pojave mozgova.
Pa su ovo i počeci nove inspiracije za mašinsko učenje
19:03
is an example of intelligence,
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19:05
and biology has been intelligently solving problems
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koje oponaša veštačku inteligenciju telesnih ćelija, ne samo mozgova,
19:07
long before brains came on the scene.
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19:09
And so this is also the beginnings of a new inspiration for machine learning
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za primene u kompjuterskoj inteligenciji.
19:14
that mimics the artificial intelligence of body cells, not just brains,
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KA: Majk Levin, hvala ti za tvoj izuzetan rad
19:19
for applications in computer intelligence.
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i što si ga tako ubedljivo podelio sa nama.
Hvala ti.
ML: Mnogo vam hvala. Hvala, Kris.
19:24
CA: Mike Levin, thank you for your extraordinary work
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19:27
and for sharing it so compellingly with us.
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19:30
Thank you.
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19:31
ML: Thank you so much. Thank you, Chris.
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