Grégoire Courtine: The paralyzed rat that walked

Prevodilac: Ivana Krivokuća Lektor: Mile Živković

I am a neuroscientist

Ja sam neurolog

with a mixed background in physics and medicine.

sa mešanim obrazovanjem iz fizike i medicine.

My lab at the Swiss Federal Institute of Technology

Moja laboratorija na Švajcarskom federalnom institutu tehnologije

focuses on spinal cord injury,

fokusirana je na oštećenja kičmene moždine,

koja pogađaju više od 50 000 ljudi

which affects more than 50,000 people

around the world every year,

širom sveta svake godine,

with dramatic consequences for affected individuals,

sa dramatičnim posledicama na pogođene pojedince,

whose life literally shatters

čiji se životi bukvalno ruše

in a matter of a handful of seconds.

u roku od svega nekoliko sekundi.

And for me, the Man of Steel,

A za mene, Čelični čovek,

Christopher Reeve,

Kristofer Riv,

has best raised the awareness

najbolje je podigao svest

on the distress of spinal cord injured people.

o neprijatnostima ljudi sa povredom kičmene moždine.

And this is how I started my own personal journey

A ovako sam započeo svoje sopstveno lično putovanje

u ovom polju istraživanja,

in this field of research,

working with the Christopher and Dana Reeve Foundation.

radeći sa Fondacijom Kristofera i Dane Riv.

I still remember this decisive moment.

Još uvek se sećam ovog presudnog trenutka.

It was just at the end of a regular day of work

Bio je to samo kraj uobičajenog dana na poslu sa fondacijom.

with the foundation.

Chris addressed us, the scientists and experts,

Kris se obratio nama, naučnicima i ekspertima:

"You have to be more pragmatic.

"Morate biti pragmatičniji.

When leaving your laboratory tomorrow,

Kada budete napuštali svoju laboratoriju sutra,

I want you to stop by the rehabilitation center

želim da svratite do rehabilitacionog centra

to watch injured people

da posmatrate povređene ljude

fighting to take a step,

kako se bore da zakorače,

struggling to maintain their trunk.

naprežući se da podrže svoj trup.

And when you go home,

A kada odete kući,

think of what you are going to change in your research

mislite o onome što ćete promeniti u svojem istraživanju

on the following day to make their lives better."

narednog dana kako biste učinili njihove živote boljim."

These words, they stuck with me.

Ove reči prilepile su se za mene.

This was more than 10 years ago,

Ovo je bilo pre više od 10 godina,

but ever since, my laboratory has followed

ali od tada, moja laboratorija je sledila

the pragmatic approach to recovery

pragmatični pristup ozdravljenju

after spinal cord injury.

nakon povrede kičmene moždine.

And my first step in this direction

I moj prvi korak u ovom pravcu

was to develop a new model of spinal cord injury

bio je razviti novi model oštećenja kičmene moždine

that would more closely mimic some of the key features of human injury

koji će približnije oponašati neke od ključnih svojstava ljudske povrede

while offering well-controlled experimental conditions.

dok će istovremeno pružati dobro kontrolisane eksperimentalne uslove.

And for this purpose, we placed two hemisections

I u ovu svrhu, postavili smo dve hemisekcije

on opposite sides of the body.

na različitim stranama tela.

They completely interrupt the communication

One su potpuno prekinule komunikaciju

between the brain and the spinal cord,

između mozga i kičmene moždine,

thus leading to complete and permanent paralysis

time dovevši do potpune i trajne paralize noge.

of the leg.

But, as observed, after most injuries in humans,

Ali, kako je primećeno, nakon većine povreda kod ljudi,

there is this intervening gap of intact neural tissue

postoji intervenišući međuprostor netaknutog nervnog tkiva

through which recovery can occur.

preko kojeg se može dogoditi oporavak.

But how to make it happen?

Ali kako učiniti da se to dogodi?

Well, the classical approach

Pa, klasični pristup

consists of applying intervention

se sastoji u primeni intervencija

that would promote the growth of the severed fiber

koje bi podstakle rast prekinutih vlakana

to the original target.

ka prvobitnom cilju.

And while this certainly remained the key for a cure,

I mada je ovo zasigurno ostalo ključno za ozdravljenje,

this seemed extraordinarily complicated to me.

meni se to činilo kao izuzetno komplikovano.

To reach clinical fruition rapidly,

Da bismo brzo postigli kliničku primenu,

it was obvious:

bilo je očigledno:

I had to think about the problem differently.

morao sam da razmišljam drugačije o problemu.

It turned out that more than 100 years of research

Ispostavilo se da je više od 100 godina istraživanja

on spinal cord physiology,

fiziologije kičmene moždine,

starting with the Nobel Prize Sherrington,

počevši od Nobelovca Šeringtona,

had shown that

pokazalo da

the spinal cord, below most injuries,

kičmena moždina, ispod većine oštećenja,

contained all the necessary and sufficient neural networks

sadrži sve neophodne i dovoljne mreže neurona

to coordinate locomotion,

da bi koordinisala kretanje,

ali pošto su ulazni podaci iz mozga prekinuti,

but because input from the brain is interrupted,

oni su u nefunkcionišućem stanju, kao vrsta uspavanosti.

they are in a nonfunctional state, like kind of dormant.

My idea: We awaken this network.

Moja ideja: probudimo ovu mrežu.

And at the time, I was a post-doctoral fellow in Los Angeles,

U to vreme, bio sam postdoktorant u Los Anđelesu,

after completing my Ph.D. in France,

nakon što sam završio svoje doktorske studije u Francuskoj,

where independent thinking

gde samostalno razmišljanje

is not necessarily promoted.

nije nužno podsticano.

(Laughter)

(Smeh)

I was afraid to talk to my new boss,

Plašio sam se da pričam sa svojim novim šefom,

but decided to muster up my courage.

ali sam rešio da prikupim hrabrost.

I knocked at the door of my wonderful advisor,

Pokucao sam na vrata mog divnog savetnika,

Reggie Edgerton, to share my new idea.

Redžija Edgertona, kako bih podelio svoju novu ideju.

Slušao me je pažljivo,

He listened to me carefully,

and responded with a grin.

i odgovorio sa smeškom.

"Why don't you try?"

"Zašto ne pokušaš?"

And I promise to you,

I kunem vam se,

this was such an important moment in my career,

ovo je bio tako značajan momenat u mojoj karijeri,

when I realized that the great leader

kada sam shvatio da je veliki vođa

believed in young people and new ideas.

verovao u mlade ljude i nove ideje.

And this was the idea:

A ovo je bila ideja:

I'm going to use a simplistic metaphor

koristiću pojednostavljenu metaforu

to explain to you this complicated concept.

da bih vam objasnio ovaj komplikovani koncept.

Imagine that the locomotor system is a car.

Zamislite da je sistem za kretanje automobil.

The engine is the spinal cord.

Motor je kičmena moždina.

The transmission is interrupted. The engine is turned off.

Prenos je prekinut. Motor je isključen.

How could we re-engage the engine?

Kako bismo mogli da reaktiviramo motor?

First, we have to provide the fuel;

Prvo, moramo obezbediti gorivo,

second, press the accelerator pedal;

drugo, pritisnuti pedalu za gas,

third, steer the car.

treće, upravljati autom.

It turned out that there are known neural pathways

Ispostavilo se da postoje poznati nervni putevi

coming from the brain that play this very function

koji dolaze iz mozga i igraju baš ovu funkciju

during locomotion.

za vreme kretanja.

My idea: Replace this missing input

Moja ideja - zameniti ove nedostajuće ulazne informacije

to provide the spinal cord

da bismo kičmenoj moždini pružili

with the kind of intervention

that the brain would deliver naturally in order to walk.

onu vrstu intervencije

koju bi mozak prirodno izveo u cilju hodanja.

For this, I leveraged 20 years of past research in neuroscience,

Radi ovoga, upotrebio sam 20 godina ranijih istraživanja u neurologiji,

najpre da bih zamenio nedostajuće gorivo

first to replace the missing fuel

with pharmacological agents

farmakološkim supstancama

that prepare the neurons in the spinal cord to fire,

koje pripremaju neurone u kičmenoj moždini da se upale,

and second, to mimic the accelerator pedal

a zatim, da bih podražavao pedalu za gas

električnom stimulacijom.

with electrical stimulation.

So here imagine an electrode

Dakle ovde zamislite elektrodu

implanted on the back of the spinal cord

ugrađenu na zadnjem delu kičmene moždine

to deliver painless stimulation.

radi dobijanja bezbolne stimulacije.

It took many years, but eventually we developed

Bilo je potrebno mnogo godina, ali najzad smo razvili

an electrochemical neuroprosthesis

elektrohemijsku neuroprotezu

koja je transformisala neuralnu mrežu

that transformed the neural network

in the spinal cord from dormant to a highly functional state.

u kičmenoj moždini od uspavanog do visoko funkcionalnog stanja.

Immediately, the paralyzed rat can stand.

Istog trenutka, paralisani pacov može da stoji.

Čim pokretna traka počne da se pomera,

As soon as the treadmill belt starts moving,

the animal shows coordinated movement of the leg,

životinja pokazuje koordinisane pokrete nogu,

but without the brain.

ali bez mozga.

Here what I call "the spinal brain"

Evo kako ono što ja nazivam "kičmenim mozgom"

cognitively processes sensory information

kognitivno procesuira senzorne informacije

arising from the moving leg

koje nastaju iz noge u pokretu

and makes decisions as to how to activate the muscle

i donosi odluke kao što je kako aktivirati mišić

in order to stand, to walk, to run,

da bi se stajalo, hodalo, trčalo

and even here, while sprinting,

i čak i ovde, za vreme brzog trčanja,

instantly stand

momentalno staje

if the treadmill stops moving.

ako traka prestaje da se kreće.

This was amazing.

Ovo je bilo neverovatno.

I was completely fascinated by this locomotion

Bio sam potpuno fasciniran kretanjem

without the brain,

bez mozga,

but at the same time so frustrated.

ali istovremeno i toliko frustriran.

This locomotion was completely involuntary.

Ovo kretanje je bilo potpuno nevoljno.

The animal had virtually no control over the legs.

Životinja praktično nije imala kontrolu nad svojim nogama.

Clearly, the steering system was missing.

Očigledno, sistem za upravljanje je nedostajao.

I tada mi je postalo očigledno

And it then became obvious from me

that we had to move away

da moramo da se udaljimo

from the classical rehabilitation paradigm,

od klasične rehabilitacione paradigme,

stepping on a treadmill,

koračanja na pokretnoj traci,

and develop conditions that would encourage

i razviti uslove koji će podstaći

the brain to begin voluntary control over the leg.

mozak da započne voljnu kontrolu nad nogama.

With this in mind, we developed a completely new

Sa ovim na umu, razvili smo potpuno novi

robotički sistem radi podupiranja pacova

robotic system to support the rat

in any direction of space.

u bilo kom pravcu u prostoru.

Imagine, this is really cool.

Zamislite, ovo je stvarno kul.

So imagine the little 200-gram rat

Dakle zamislite malog pacova od 200 grama

attached at the extremity of this 200-kilo robot,

privezanog za ekstremitet ovog robota od 200 kila,

but the rat does not feel the robot.

ali pacov nije svestan robota.

The robot is transparent,

Robot je transparentan,

just like you would hold a young child

isto kao kada biste pridržavali malo dete

during the first insecure steps.

za vreme prvih nesigurnih koraka.

Let me summarize: The rat received

Hajde da rezimiram: pacov je zadobio

a paralyzing lesion of the spinal cord.

paralizujuću leziju kičmene moždine.

Elektrohemijska neuroproteza je omogućila

The electrochemical neuroprosthesis enabled

a highly functional state of the spinal locomotor networks.

visoko funkcionalno stanje mreža za kretanje u kičmi.

The robot provided the safe environment

Robot je obezbedio bezbednu sredinu

to allow the rat to attempt anything

kako bi omogućio pacovu da pokuša bilo šta

to engage the paralyzed legs.

da bi aktivirao paralizovane noge.

And for motivation, we used what I think

A što se tiče motivacije, koristili smo nešto za šta ja smatram

is the most powerful pharmacology of Switzerland:

da je najsnažnija farmakologija u Švajcarskoj:

fine Swiss chocolate.

fina švajcarska čokolada.

(Smeh)

(Laughter)

Actually, the first results were very, very,

Zapravo, prvi rezultati su bili veoma, veoma,

very disappointing.

veoma razočaravajući.

Here is my best physical therapist

Evo mog najboljeg fizikalnog terapeuta

completely failing to encourage the rat

koji postiže potpuni neuspeh u podsticanju pacova

to take a single step,

da pruži jedan korak,

whereas the same rat, five minutes earlier,

dok je isti pacov, pet minuta ranije,

walked beautifully on the treadmill.

lepo hodao na pokretnoj traci.

We were so frustrated.

Bili smo tako frustrirani.

But you know, one of the most essential qualities

Ali znate, jedan od najosnovnijih kvaliteta

of a scientist is perseverance.

naučnika je istrajnost.

Insistirali smo. Preradili smo našu paradigmu,

We insisted. We refined our paradigm,

and after several months of training,

i nakon nekoliko meseci treniranja,

the otherwise paralyzed rat could stand,

inače paralisani pacov mogao je da stoji,

and whenever she decided,

i kada god bi to odlučio,

initiated full weight-bearing locomotion

inicirao bi kretanje celom težinom tela

to sprint towards the rewards.

kako bi pojurio prema nagradi.

This is the first recovery ever observed

Ovo je prvi ikada opserviran oporavak

of voluntary leg movement

dobrovoljnog pokretanja nogu

after an experimental lesion of the spinal cord

nakon eksperimentalne lezije kičmene moždine

leading to complete and permanent paralysis.

koja je dovela do potpune i trajne paralize.

In fact --

U stvari -

(Aplauz)

(Applause)

Thank you.

Hvala vam.

In fact, not only could the rat initiate

U stvari, ne samo da je pacov mogao da inicira

and sustain locomotion on the ground,

i održi kretanje na zemlji,

they could even adjust leg movement,

mogao je čak i da prilagodi pokrete nogu,

for example, to resist gravity

na primer, da bi pružio otpor gravitaciji

in order to climb a staircase.

kako bi se popeo uz stepenice.

I can promise you this was

Mogu vam se zakleti da je ovo bio

such an emotional moment in my laboratory.

tako emotivan trenutak u mojoj laboratoriji.

It took us 10 years of hard work

Bilo nam je potrebno 10 godina teškog rada

da bismo postigli ovaj cilj.

to reach this goal.

But the remaining question was, how?

Ali ostalo je pitanje, kako?

I mean, how is it possible?

Mislim, kako je to moguće?

And here, what we found

A evo, ono što smo otkrili

was completely unexpected.

bilo je potpuno neočekivano.

Ova novouvedena paradigma treniranja

This novel training paradigm

encouraged the brain to create new connections,

podstakla je mozak da stvori nove veze,

nekakva prenosna kola

some relay circuits

that relay information from the brain

koja prenose informacije iz mozga

past the injury and restore cortical control

mimo povrede i obnavljaju kortikalnu kontrolu

over the locomotor networks below the injury.

nad mrežama za kretanje ispod povrede.

And here, you can see one such example,

A ovde, možete videti jedan takav primer,

where we label the fibers coming from the brain in red.

gde vlakna koja dolaze iz mozga označavamo crvenom.

This blue neuron is connected with the locomotor center,

Ovaj plavi neuron je povezan sa centrom za kretanje,

and what this constellation

i ono što ova grupa

of synaptic contacts means

sinaptičkih veza označava

is that the brain is reconnected with the locomotor center

je to da je mozak iznova povezan sa centrom za kretanje

with only one relay neuron.

samo jednim prenosnim neuronom.

But the remodeling was not restricted

Ali preobražaj nije bio ograničen

to the lesion area.

na oblast lezije.

It occurred throughout the central nervous system,

Dogodio se kroz čitav centralni nervni sistem,

including in the brain stem,

uključujući moždano stablo,

where we observed up to 300-percent increase

gde smo uočili i do 300 procenata porasta

in the density of fibers coming from the brain.

gustine vlakana koji dolaze iz mozga.

We did not aim to repair the spinal cord,

Nismo imali za cilj da popravimo kičmenu moždinu,

yet we were able to promote

ali smo mogli da pokrenemo

one of the more extensive remodeling

jedan od znatnijih preobražaja

of axonal projections ever observed

aksonskih projekcija ikada zapaženih

in the central nervous system of adult mammal

u centralnom nervnom sistemu odraslog sisara

after an injury.

nakon oštećenja.

And there is a very important message

Postoji veoma značajna poruka

koja se krije iza ovog otkrića.

hidden behind this discovery.

They are the result of a young team

Ovo su rezultati mladog tima

of very talented people:

veoma talentovanih ljudi:

fizikalnih teraputa, neurobiologa, neurohirurga,

physical therapists, neurobiologists, neurosurgeons,

engineers of all kinds,

inženjera svih vrsta,

who have achieved together

koji su zajedno postigli

what would have been impossible by single individuals.

ono što bi bilo nemoguće da urade kao pojedinci.

Ovo je zaista transdisciplinarni tim.

This is truly a trans-disciplinary team.

They are working so close to each other

Oni rade toliko prisno međusobno

that there is horizontal transfer of DNA.

da postoji horizontalni transfer DNK.

We are creating the next generation

Mi stvaramo sledeću generaciju

of M.D.'s and engineers

doktora medicine i inženjera

capable of translating discoveries all the way

koji su u stanju da prenesu otkrića skroz

from bench to bedside.

od laboratorije do bolničkog kreveta.

And me?

A ja?

I am only the maestro who orchestrated this beautiful symphony.

Ja sam samo maestro koji je orkestrirao ovu divnu simfoniju.

Now, I am sure you are all wondering, aren't you,

A sad, siguran sam da se svi pitate, zar ne,

will this help injured people?

da li će ovo pomoći povređenim ljudima?

Me too, every day.

I ja se pitam, svakoga dana.

The truth is that we don't know enough yet.

Istina je da još uvek ne znamo dovoljno.

Ovo svakako nije lek za povredu kičmene moždine,

This is certainly not a cure for spinal cord injury,

but I begin to believe that this may lead

ali počinjem da verujem da može dovesti

to an intervention to improve recovery

do intervencije za unapređivanje oporavka

and people's quality of life.

i kvaliteta života ljudi.

I would like you all

Hteo bih da svi vi

to take a moment and dream with me.

odvojite momenat i maštate sa mnom.

Imagine a person just suffered a spinal cord injury.

Zamislite osobu koja je upravo pretrpela povredu kičmene moždine.

After a few weeks of recovery,

Nakon nekoliko nedelja oporavka,

we will implant a programmable pump

ugradićemo pumpu koja se može programirati

to deliver a personalized pharmacological cocktail

kako bismo dopremili individualizovani farmakološki koktel

directly to the spinal cord.

direktno do kičmene moždine.

At the same time, we will implant an electrode array,

Istovremeno, ugradićemo niz elektroda,

slično drugoj koži

a sort of second skin

covering the area of the spinal cord controlling leg movement,

koja će pokrivati područje kičmene moždine kontrolišući pokrete nogu,

and this array is attached to an electrical pulse generator

i ovaj niz je povezan sa električnim generatorom pulsa

that delivers stimulations that are tailored

koji donosi senzacije prilagođene

to the person's needs.

potrebama osobe.

This defines a personalized electrochemical neuroprosthesis

Ovo definiše individualizovanu elektrohemijsku protezu

that will enable locomotion

koja će omogućiti kretanje

during training with a newly designed supporting system.

za vreme treninga novodizajniranim sistemom podrške.

And my hope is that after several months of training,

I moja nada je da će nakon nekoliko meseci treninga,

there may be enough remodeling of residual connection

možda biti dovoljno preoblikovanja preostalih veza

to allow locomotion without the robot,

da bi se omogućilo kretanje bez robota,

maybe even without pharmacology or stimulation.

možda čak i bez farmakologije ili stimulacije.

Moja nada je da ćemo biti u stanju da kreiramo

My hope here is to be able to create

the personalized condition

individualizovano stanje

to boost the plasticity of the brain

kako bismo pojačali plastičnost mozga

and the spinal cord.

i kičmene moždine.

Ovo je radikalno novi koncept

And this is a radically new concept

that may apply to other neurological disorders,

koji se može primeniti na druge neurološke poremećaje,

what I termed "personalized neuroprosthetics,"

ono što sam nazvao "individualizovana neuroproteza",

where by sensing and stimulating neural interfaces,

pomoću čula i stimulacije nervnih međuveza,

I implanted throughout the nervous system,

usadio sam kroz čitav nervni sistem,

in the brain, in the spinal cord,

u mozak, u kičmenu moždinu,

even in peripheral nerves,

čak i u periferne nerve,

based on patient-specific impairments.

bazirano na oštećenju specifičnom za pacijenta.

But not to replace the lost function, no --

Ali ne da bih zamenio izgubljenu funkciju, ne -

to help the brain help itself.

da bih pomogao mozgu da pomogne sam sebi.

And I hope this enticed your imagination,

I nadam se da je ovo zaintrigiralo vašu maštu,

because I can promise to you

jer vam mogu obećati

this is not a matter of whether this revolution will occur,

da nije pitanje da li će se ova revolucija dogoditi,

već kada.

but when.

I zapamtite, mi smo veliki samo onoliko

And remember, we are only as great

as our imagination, as big as our dream.

koliko i naša mašta, onoliko veliki kao naš san.

Thank you.

Hvala vam.

(Applause)

(Aplauz)