How early life experience is written into DNA | Moshe Szyf

Prevodilac: Milenka Okuka Lektor: Mile Živković

So it all came to life

Dakle, sve se začelo

in a dark bar in Madrid.

u mračnom baru u Madridu.

I encountered my colleague from McGill, Michael Meaney.

Sreo sam kolegu sa Mekgila, Majkla Minija.

And we were drinking a few beers,

Popili smo nekoliko piva,

and like scientists do,

i, kao i svaki naučnik,

he told me about his work.

ispričao mi je o svom radu.

And he told me that he is interested in how mother rats lick their pups

A rekao mi je da ga interesuje kako majke pacovi ližu svoje mlade

after they were born.

nakon što su rođeni.

And I was sitting there and saying,

A ja sam sedeo tu i govorio:

"This is where my tax dollars are wasted --

"Na to traćite moj novac od poreza -

(Laughter)

(Smeh)

on this kind of soft science."

na ovaj vid meke nauke."

And he started telling me

A on je počeo da mi govori

that the rats, like humans,

kako pacovi, poput ljudi,

lick their pups in very different ways.

ližu svoje mlade na veoma različite načine.

Some mothers do a lot of that,

Neke majke to često rade,

some mothers do very little,

neke majke veoma retko,

and most are in between.

a većina je negde između.

But what's interesting about it

Međutim, zanimljivo je to

is when he follows these pups when they become adults --

da kada prati te mlade, nakon što postanu odrasli -

like, years in human life, long after their mother died.

godinama u ljudskom životu, dugo nakon što im je majka uginula.

They are completely different animals.

To su potpuno različite životinje.

The animals that were licked and groomed heavily,

Životinje koje su lizali i timarili često,

the high-licking and grooming,

visoko lizani i timareni,

are not stressed.

nisu pod stresom.

They have different sexual behavior.

Imaju drugačije seksualno ponašanje.

They have a different way of living

Imaju drugačiji način života

than those that were not treated as intensively by their mothers.

od onih koje majke nisu tako snažno pazile.

So then I was thinking to myself:

Potom sam pomislio u sebi:

Is this magic?

da li je ovo magija?

How does this work?

Kako ovo funkcioniše?

As geneticists would like you to think,

Genetičari bi vam rekli

perhaps the mother had the "bad mother" gene

da je majka možda imala gen "loše majke"

that caused her pups to be stressful,

koji je uzrokovao da njeni mladi budu pod stresom,

and then it was passed from generation to generation;

a potom se preneo s generacije na generaciju;

it's all determined by genetics.

sve je genetski predodređeno.

Or is it possible that something else is going on here?

Ili je moguće da se nešto drugo ovde dešava?

In rats, we can ask this question and answer it.

Kod pacova možemo da postavimo i da odgovorimo na ovo pitanje.

So what we did is a cross-fostering experiment.

Pa smo napravili eksperiment unakrsnog roditeljstva.

You essentially separate the litter, the babies of this rat, at birth,

U suštini razdvojite leglo, mlade ovog pacova po rođenju,

to two kinds of fostering mothers --

kod dve vrste majki starateljki -

not the real mothers, but mothers that will take care of them:

ne stvarnih majki, već majki koje će o njima da brinu:

high-licking mothers and low-licking mothers.

majki koje često ližu majki koje retko ližu.

And you can do the opposite with the low-licking pups.

I možete da uradite suprotno sa mladima koji retko ližu.

And the remarkable answer was,

A izvanredan rezultat je bio:

it wasn't important what gene you got from your mother.

nije bilo važno koje ste gene dobili od vaše majke.

It was not the biological mother that defined this property of these rats.

Nije biološka majka određivala ovo svojstvo kod pacova.

It is the mother that took care of the pups.

Već majka koja se brinula o mladima.

So how can this work?

Pa, kako je ovo moguće?

I am an a epigeneticist.

Ja sam epigenetičar.

I am interested in how genes are marked

Zanima me kako se geni obeležavaju

by a chemical mark

hemijskim obeležjima

during embryogenesis, during the time we're in the womb of our mothers,

tokom embriogeneze, tokom vremena dok smo u utrobi naših majki,

and decide which gene will be expressed

i kako se donosi odluka koji geni će se manifestovati

in what tissue.

u kom tkivu.

Different genes are expressed in the brain than in the liver and the eye.

Različiti geni se manifestuju u mozgu nego u jetri i oku.

And we thought: Is it possible

Pa smo pomislili: da li je moguće

that the mother is somehow reprogramming the gene of her offspring

da majka nekako reprogramira gen svog potomka

through her behavior?

svojim ponašanjem?

And we spent 10 years,

Pa smo proveli 10 godina

and we found that there is a cascade of biochemical events

i otkrili smo da postoji obilje biohemijskih događaja

by which the licking and grooming of the mother, the care of the mother,

kojima lizanje i timarenje majke, briga majke,

is translated to biochemical signals

se prevodi u biohemijske signale

that go into the nucleus and into the DNA

koji idu do jedra i u DNK

and program it differently.

i drugačije ga programiraju.

So now the animal can prepare itself for life:

Dakle, sada životinja može da se pripremi za život:

Is life going to be harsh?

da li će život da bude težak?

Is there going to be a lot of food?

Da li će da bude mnogo hrane?

Are there going to be a lot of cats and snakes around,

Da li će da bude mnogo mačaka i zmija u blizini

or will I live in an upper-class neighborhood

ili ću da živim u komšiluku više klase

where all I have to do is behave well and proper,

gde samo treba da se ponašam lepo i pristojno

and that will gain me social acceptance?

i to će da mi obezbedi društvenu prihvaćenost?

And now one can think about how important that process can be

I sad neko može da pomisli koliko je ovaj proces važan

for our lives.

u našim životima.

We inherit our DNA from our ancestors.

Nasleđujemo našu DNK od naših predaka.

The DNA is old.

DNK je stara.

It evolved during evolution.

Evoluirala je tokom evolucije.

But it doesn't tell us if you are going to be born in Stockholm,

Ali nam ne saopštava da li ćemo se roditi u Stokholmu,

where the days are long in the summer and short in the winter,

gde su dani tokom leta dugi, a kratki tokom zime

or in Ecuador,

ili u Ekvadoru,

where there's an equal number of hours for day and night all year round.

gde dan i noć imaju jednak broj sati tokom čitave godine.

And that has such an enormous [effect] on our physiology.

A to ima ogroman uticaj na našu fiziologiju.

So what we suggest is, perhaps what happens early in life,

Mi pretpostavljamo da možda, rano u životu,

those signals that come through the mother,

ti signali koji se prenose preko majke,

tell the child what kind of social world you're going to be living in.

saopštavaju detetu u kakvom društvenom svetu će da živi.

It will be harsh, and you'd better be anxious and be stressful,

Ako će da bude težak, bolje je biti anksiozan i pod stresom

or it's going to be an easy world, and you have to be different.

ili će da bude lagodan svet i morate da budete drugačiji.

Is it going to be a world with a lot of light or little light?

Da li će to da bude svet s mnogo ili malo svetla?

Is it going to be a world with a lot of food or little food?

Da li će da bude svet s mnogo ili malo hrane?

If there's no food around,

Ako nema hrane u blizini,

you'd better develop your brain to binge whenever you see a meal,

bolje da vam se razvije mozak koji navaljuje svaki put kad vidi obrok

or store every piece of food that you have as fat.

ili koji skladišti u vidu masti svu hranu koja vam je dostupna.

So this is good.

Dakle, ovo je dobro.

Evolution has selected this

Evolucija je odabrala ovo

to allow our fixed, old DNA to function in a dynamic way

kako bi omogućila našoj fiksiranoj, staroj DNK da funkcioniše dinamično

in new environments.

u novim sredinama.

But sometimes things can go wrong;

Međutim, ponekad stvari krenu po zlu;

for example, if you're born to a poor family

na primer, ako ste rođeni u siromašnoj porodici

and the signals are, "You better binge,

a signali su: "Bolje navalite,

you better eat every piece of food you're going to encounter."

bolje bi vam bilo da pojedete svu hranu na koju naletite."

But now we humans and our brain have evolved,

Međutim, nama ljudima su evoluirali mozgovi

have changed evolution even faster.

i to je čak i brže izmenilo evoluciju.

Now you can buy McDonald's for one dollar.

Sad možete da jedete u Mekdonaldsu za jedan dolar.

And therefore, the preparation that we had by our mothers

I, stoga, pripreme koje smo dobili od majki

is turning out to be maladaptive.

postaju loše prilagođene.

The same preparation that was supposed to protect us from hunger and famine

Ista spremnost koja je trebalo da nas zaštiti od gladovanja i gladi

is going to cause obesity,

će da uzrokuje gojaznost,

cardiovascular problems and metabolic disease.

kardiovaskularne probleme i oboljenja metabolizma.

So this concept that genes could be marked by our experience,

Dakle, ovaj koncept da naša iskustva mogu da obeleže gene,

and especially the early life experience,

a naročito rana iskustva,

can provide us a unifying explanation

može da nam obezbedi objedinjujuće objašnjenje

of both health and disease.

i za zdravlje i za bolest.

But is true only for rats?

Međutim, da li je istinito samo kod pacova?

The problem is, we cannot test this in humans,

Problem je što ovo ne možemo da testiramo na ljudima

because ethically, we cannot administer child adversity in a random way.

jer etički ne možemo da izazivamo dečje nedaće nasumično.

So if a poor child develops a certain property,

Pa, ako siromašno dete razvije određeno svojstvo,

we don't know whether this is caused by poverty

ne znamo da li je siromaštvo to uzrokovalo

or whether poor people have bad genes.

ili siromašni ljudi imaju loše gene.

So geneticists will try to tell you that poor people are poor

Pa će genetičari pokušati da vam kažu kako siromašni su siromašni

because their genes make them poor.

jer im geni uzrokuju siromaštvo.

Epigeneticists will tell you

Epigenetičari će da vam kažu

poor people are in a bad environment or an impoverished environment

da su siromašni u lošem okruženju ili u osiromašenom okruženju

that creates that phenotype, that property.

koje stvara taj fenotip, to svojstvo.

So we moved to look into our cousins, the monkeys.

Pa smo krenuli da proverimo kod naših rođaka majmuna.

My colleague, Stephen Suomi, has been rearing monkeys

Moj kolega Stiven Sumi uzgaja majmune

in two different ways:

na dva različita načina:

randomly separated the monkey from the mother

nasumično razdvaja majmuna od majke

and reared her with a nurse

i podiže ga uz pomoć negovateljice

and surrogate motherhood conditions.

u uslovima surogat majke.

So these monkeys didn't have a mother; they had a nurse.

Ovi majmuni nisu imali majku; imali su negovateljicu.

And other monkeys were reared with their normal, natural mothers.

A druge majmune su podizale njihove normalne, prirodne majke.

And when they were old, they were completely different animals.

A kad su ostarili, bili su potpuno različite životinje.

The monkeys that had a mother did not care about alcohol,

Majmuni koji su imali majku nisu marili za alkohol,

they were not sexually aggressive.

nisu bili seksualno agresivni.

The monkeys that didn't have a mother were aggressive, were stressed

Majmuni koji nisu imali majku su bili agresivni, pod stresom

and were alcoholics.

i bili su alkoholičari.

So we looked at their DNA early after birth, to see:

Pa smo pogledali njihovu DNK rano po rođenju kako bismo videli:

Is it possible that the mother is marking?

da li je moguće da majka obeležava?

Is there a signature of the mother in the DNA of the offspring?

Da li postoji potpis majčin u DNK potomka?

These are Day-14 monkeys,

Ovo su majmuni Dan-14,

and what you see here is the modern way by which we study epigenetics.

i ovde vidite savremeni način na koji izučavamo epigenetiku.

We can now map those chemical marks, which we call methylation marks,

Sad možemo da mapiramo ova hemijska obeležja,

koje nazivamo metilacionim obeležjima,

on DNA at a single nucleotide resolution.

na DNK u rezoluciji jednog nukleotida.

We can map the entire genome.

Možemo da mapiramo čitav genom.

We can now compare the monkey that had a mother or not.

Sad možemo da uporedimo majmuna koji je imao majku ili nije.

And here's a visual presentation of this.

A ovo je vizuelna prezentacija toga.

What you see is the genes that got more methylated are red.

Vidite da su crveni oni geni koji su više metilizovani.

The genes that got less methylated are green.

Geni koji su manje metilizovani su zeleni.

You can see many genes are changing,

Možete da vidite da se mnogi geni menjaju

because not having a mother is not just one thing --

jer nemati majku nije prosta stvar -

it affects the whole way;

utiče na sve;

it sends signals about the whole way your world is going to look

šalje signale o čitavom načinu na koji će vaš svet da izgleda

when you become an adult.

kada odrastete.

And you can see the two groups of monkeys

I možete da vidite dve grupe majmuna

extremely well-separated from each other.

izuzetno razdvojene jedne od drugih.

How early does this develop?

Koliko rano se ovo razvije?

These monkeys already didn't see their mothers,

Ovi majmuni već nisu videli svoje majke,

so they had a social experience.

dakle imali su društveno iskustvo.

Do we sense our social status, even at the moment of birth?

Da li osećamo naš društveni status čak i u trenutku rođenja?

So in this experiment, we took placentas of monkeys

Pa smo u ovom eksperimentu uzeli posteljice majmuna

that had different social status.

koji su imali različit društveni status.

What's interesting about social rank is that across all living beings,

Zanimljivo kod društvenog ranga je da će sva živa bića

they will structure themselves by hierarchy.

da se organizuju prema hijerarhiji.

Monkey number one is the boss;

Majmun broj jedan je šef;

monkey number four is the peon.

majmun broj četiri je pion.

You put four monkeys in a cage,

Stavite četiri majmuna u kavez,

there will always be a boss and always be a peon.

uvek ćete da imate šefa i piona.

And what's interesting is that the monkey number one

A zanimljivo je da je majmun broj jedan

is much healthier than monkey number four.

daleko zdraviji od majmuna broj četiri.

And if you put them in a cage,

A ako ih stavite u kavez,

monkey number one will not eat as much.

majmun broj jedan neće da jede mnogo.

Monkey number four will eat [a lot].

Majmun broj četiri će da jede mnogo.

And what you see here in this methylation mapping,

A ovde vidite kod mapiranja metilacije,

a dramatic separation at birth

drastično razdvajanje po rođenju

of the animals that had a high social status

životinja koje su imale visok društveni status

versus the animals that did not have a high status.

nasuprot životinjama koje nisu imale visok status.

So we are born already knowing the social information,

Dakle, rođeni smo unapred znajući društvene informacije,

and that social information is not bad or good,

a te društvene informacije nisu loše ili dobre,

it just prepares us for life,

prosto nas pripremaju za život

because we have to program our biology differently

jer moramo da programiramo našu biologiju drugačije,

if we are in the high or the low social status.

ukoliko smo visokog ili niskog društvenog statusa.

But how can you study this in humans?

Ali kako da ovo izučavate kod ljudi?

We can't do experiments, we can't administer adversity to humans.

Ne možemo da vršimo eksperimente, ne možemo da ljude izlažemo nedaćama.

But God does experiments with humans,

Ali bog vrši eksperimente nad ljudima

and it's called natural disasters.

i oni se nazivaju prirodnim katastrofama.

One of the hardest natural disasters in Canadian history

Jedna od najtežih prirodnih katastrofa u istoriji Kanade

happened in my province of Quebec.

se desila u mojoj provinciji Kvebek.

It's the ice storm of 1998.

Radi se o ledenoj oluji iz 1998.

We lost our entire electrical grid because of an ice storm

Izgubili smo kompletnu elektromrežu zbog ledene oluje,

when the temperatures were, in the dead of winter in Quebec,

kada su temperature bile, u sred zime u Kvebeku,

minus 20 to minus 30.

minus 20 do minus 30.

And there were pregnant mothers during that time.

A tokom tog perioda bilo je trudnih majki.

And my colleague Suzanne King followed the children of these mothers

A moja koleginica Suzan King je pratila decu tih majki

for 15 years.

15 godina.

And what happened was, that as the stress increased --

A dešavalo se to da dok se stres povećavao -

and here we had objective measures of stress:

a ovde smo imali objektivna merenja stresa:

How long were you without power? Where did you spend your time?

koliko dugo ste bili bez struje? Gde ste provodili vreme?

Was it in your mother-in-law's apartment or in some posh country home?

Da li je to bilo u stanu vaše svekrve ili u nekom otmenom seoskom domu?

So all of these added up to a social stress scale,

Dakle, sve ovo je dodato na društvenu lestvicu stresa,

and you can ask the question:

i možete da upitate:

How did the children look?

kako su deca izgledala?

And it appears that as stress increases,

A izgleda da kako se stres povećava,

the children develop more autism,

kod dece se više razvija autizam,

they develop more metabolic diseases

više se razvijaju bolesti metabolizma

and they develop more autoimmune diseases.

i više se razvijaju autoimune bolesti.

We would map the methylation state,

Mapirali bismo stanje metilacije

and again, you see the green genes becoming red as stress increases,

i, opet, vidite kako zeleni geni postaju crveni kako se stres povećava,

the red genes becoming green as stress increases,

crveni geni postaju zeleni kako se stres povećava,

an entire rearrangement of the genome in response to stress.

celokupno preuređenje genoma kao odgovor na stres.

So if we can program genes,

Pa, ako možemo da programiramo gene,

if we are not just the slaves of the history of our genes,

ako nismo puki robovi istorije naših gena,

that they could be programmed, can we deprogram them?

ako mogu da se programiraju, možemo li da ih otprogramiramo?

Because epigenetic causes can cause diseases like cancer,

Zato što epigenetski uzroci mogu da uzrokuju bolesti poput raka,

metabolic disease

bolesti metabolizma

and mental health diseases.

i mentalna oboljenja.

Let's talk about cocaine addiction.

Razgovarajmo o zavisnosti od kokaina.

Cocaine addiction is a terrible situation

Kokainska zavisnost je grozna situacija

that can lead to death and to loss of human life.

koja može da dovede do smrti i gubitka ljudskog života.

We asked the question:

Postavili smo pitanje:

Can we reprogram the addicted brain

možemo li da reprogramiramo mozak zavisnika

to make that animal not addicted anymore?

kako životinja ne bi više bila zavisnik?

We used a cocaine addiction model

Koristili smo model kokainske zavisnosti

that recapitulates what happens in humans.

koji simulira šta se dešava kod ljudi.

In humans, you're in high school,

Kod ljudi, u srednjoj ste školi,

some friends suggest you use some cocaine,

neki prijatelji vam predlože da uzmete kokain,

you take cocaine, nothing happens.

uzmete kokain, ništa se ne desi.

Months pass by, something reminds you of what happened the first time,

Meseci prođu, nešto vas podseti šta se desilo prvi put,

a pusher pushes cocaine,

nametljivac vam nametne kokain

and you become addicted and your life has changed.

i postajete zavisni i vaš se život menja.

In rats, we do the same thing.

Kod pacova radimo to isto.

My colleague, Gal Yadid,

Moj kolega, Gal Jadid,

he trains the animals to get used to cocaine,

dresira životinje da se naviknu na kokain,

then for one month, no cocaine.

onda jedan mesec nema kokaina.

Then he reminds them of the party when they saw the cocaine the first time

Onda ih podseća na zabavu na kojoj su prvi put videli kokain

by cue, the colors of the cage when they saw cocaine.

nagoveštajem, bojom kaveza kad su videli kokain.

And they go crazy.

I oni polude.

They will press the lever to get cocaine

Pritiskaće polugu da dobiju kokain

until they die.

dok umru.

We first determined that the difference between these animals

Prvo smo utvrdii da je razlika između ovih životinja

is that during that time when nothing happens,

ta da tokom perioda kad se ništa ne dešava,

there's no cocaine around,

kad nema kokaina,

their epigenome is rearranged.

njihov epigenom se preuređuje.

Their genes are re-marked in a different way,

Njihovi geni su nanovo obeleženi na drugačiji način,

and when the cue comes, their genome is ready

a kad dođe do nagoveštaja, njihov genom je spreman

to develop this addictive phenotype.

da razvije ovaj fenotip zavisnosti.

So we treated these animals with drugs that either increase DNA methylation,

Pa smo tretirali ove žvotinje lekovima koji uvećavaju DNK metilaciju,

which was the epigenetic marker to look at,

to je bio epigenetski obeleživač koji smo posmatrali,

or decrease epigenetic markings.

ili smo umanjivali epigenetska obeležja.

And we found that if we increased methylation,

A otkrili smo da ako povećamo metilaciju,

these animals go even crazier.

ove životinje još više polude.

They become more craving for cocaine.

Još su željnije kokaina.

But if we reduce the DNA methylation,

Međutim, ako umanjimo DNK metilaciju,

the animals are not addicted anymore.

životinje više nisu zavisne.

We have reprogrammed them.

Reprogramirali smo ih.

And a fundamental difference between an epigenetic drug

A temeljna razlika između epigenetskog leka

and any other drug

i bilo kog drugog leka

is that with epigenetic drugs,

je da kod epigenetskih lekova

we essentially remove the signs of experience,

u suštini uklanjamo znakove iskustva,

and once they're gone,

i čim oni nestanu,

they will not come back unless you have the same experience.

neće se vraćati, ukoliko ne ponovite isto iskustvo.

The animal now is reprogrammed.

Sada je životinja reprogramirana.

So when we visited the animals 30 days, 60 days later,

Pa, kad smo posetili životinje 30 dana, 60 dana kasnije,

which is in human terms many years of life,

to je u ljudskom okviru mnogo godina života,

they were still not addicted -- by a single epigenetic treatment.

i dalje nisu bile zavisne - zbog samo jednog epigenetskog tretmana.

So what did we learn about DNA?

Pa, šta smo naučili o DNK?

DNA is not just a sequence of letters;

DNK nije puki niz slova;

it's not just a script.

nije puki scenario.

DNA is a dynamic movie.

DNK je dinamičan film.

Our experiences are being written into this movie, which is interactive.

Naša iskustva se ispisuju na ovom filmu, koji je interaktivan.

You're, like, watching a movie of your life, with the DNA,

Vi kao da gledate film o svom životu, sa DNK,

with your remote control.

uz svoj daljniski upravljač.

You can remove an actor and add an actor.

Možete da uklonite glumca i da dodate glumca.

And so you have, in spite of the deterministic nature of genetics,

Te imate, uprkos determinističkoj prirodi genetike,

you have control of the way your genes look,

imate kontrolu nad time kako vaši geni izgledaju,

and this has a tremendous optimistic message

a to nosi krajnje optimističnu poruku

for the ability to now encounter some of the deadly diseases

zbog mogućnosti da se sada suočimo sa nekim smrtonosnim bolestima

like cancer, mental health,

poput raka, mentalnih bolesti,

with a new approach,

novim pristupom,

looking at them as maladaptation.

posmatrajući ih kao lošu adaptaciju.

And if we can epigenetically intervene,

A ako možemo da epigenetski intervenišemo,

[we can] reverse the movie by removing an actor

možemo da preokrenemo film, uklanjajući glumca

and setting up a new narrative.

i podešavajući novi narativ.

So what I told you today is,

Dakle, danas sam vam saopštio

our DNA is really combined of two components,

da je naša DNK uistinu sačinjena od dve komponente,

two layers of information.

dva sloja informacija.

One layer of information is old,

Jedan sloj informacija je star,

evolved from millions of years of evolution.

evoluirao je milionima godina evolucije.

It is fixed and very hard to change.

Okoštao je i veoma teško ga je promeniti.

The other layer of information is the epigenetic layer,

Drugi sloj informacija je epigenetski sloj,

which is open and dynamic

koji je otvoren i dinamičan

and sets up a narrative that is interactive,

i podešava narativ koji je interaktivan,

that allows us to control, to a large extent, our destiny,

koji nam omogućuje da kontrolišemo, u velikoj meri, našu sudbinu,

to help the destiny of our children

kako bismo unapredili sudbinu naše dece

and to hopefully conquer disease

i uspeli, nadamo se, da pobedimo bolesti

and serious health challenges

i ozbiljne zdravstvene izazove

that have plagued humankind for a long time.

koji haraju čovečanstvom već dugo vremena.

So even though we are determined

Dakle, iako smo određeni

by our genes,

našim genima,

we have a degree of freedom

imamo stepen slobode

that can set up our life to a life of responsibility.

koji može da podesi naš život da bude odgovoran život.

Thank you.

Havala vam.

(Applause)

(Aplauz)