Mina Bissell: Experiments that point to a new understanding of cancer

Translator: Morton Bast Reviewer: Thu-Huong Ha

Prevoditelj: Senzos Osijek Recezent: Suzana Baric

Now, I don't usually like cartoons,

Inače ne volim karikature,

I don't think many of them are funny,

mnoge od njih ne smatram smiješnima,

I find them weird. But I love this cartoon from the New Yorker.

mislim da su čudne. Ali volim ovu karikaturu iz New Yorkera.

(Text: Never, ever think outside the box.) (Laughter)

(Tekst: Nikad, nikad nemoj misliti izvan kutije.) (Smijeh)

So, the guy is telling the cat,

Dakle, čovjek govori mački:

don't you dare think outside the box.

Da se nisi usudila pomisliti izvan kutije.

Well, I'm afraid I used to be the cat.

Pa, bojim se da sam ja nekad bila mačka.

I always wanted to be outside the box.

Uvijek sam htjela biti izvan kutije.

And it's partly because I came to this field

I to je dijelom zato što sam došla na ovo područje

from a different background, chemist and a bacterial geneticist.

s drugačijom pozadinom, kemičara i bakterijskog genetičara.

So, what people were saying to me

Stoga, ono što su mi ljudi govorili

about the cause of cancer, sources of cancer,

o uzroku raka, izvoru raka, ili, u tom slučaju,

or, for that matter, why you are who you are,

zašto smo onakvi kakvi jesmo,

didn't make sense.

nije imalo smisla.

So, let me quickly try and tell you why I thought that

Dakle, dopustite mi da vam pokušam na brzinu reći zašto

and how I went about it.

sam to mislila i kako sam tome pristupila.

So, to begin with, however,

Kako bih počela, međutim,

I have to give you a very, very quick lesson

moram vam dati vrlo, vrlo brzu lekciju

in developmental biology,

iz razvojne biologije.

with apologies to those of you who know some biology.

Ispričavam se onima od vas koji znaju nešto biologije.

So, when your mom and dad met,

Dakle, kada su se vaše majke i očevi upoznali,

there is a fertilized egg,

oplođeno je jajašce,

that round thing with that little blip.

ta okrugla stvar s malom nepravilnošću.

It grows and then it grows,

Ono raste i raste

and then it makes this handsome man.

i onda postane ovaj zgodni muškarac.

(Applause)

(Pljesak )

So, this guy, with all the cells in his body,

Dakle, sve stanice u tijelu ovog momka

all have the same genetic information.

imaju iste genetičke informacije.

So how did his nose become his nose, his elbow his elbow,

Kako je onda njegov nos postao njegov nos, njegov lakat postao njegov lakat,

and why doesn't he get up one morning

i zašto se ne ustane jedno jutro

and have his nose turn into his foot?

s nosom pretvorenim u stopalo?

It could. It has the genetic information.

Mogao bi. Ima genetičku informaciju.

You all remember, dolly,

Svi se sjećate Dolly,

it came from a single mammary cell.

došla je iz jedne jedine mliječne stanice.

So, why doesn't it do it?

Dakle, zašto se to ne dogodi?

So, have a guess of how many cells he has in his body.

Pokušajte pogoditi koliko on ima stanica u svom tijelu.

Somewhere between 10 trillion to 70 trillion cells in his body.

Negdje između 10 bilijuna do 70 bilijuna stanica u tijelu.

Trillion!

Bilijuna!

Now, how did these cells, all with the same genetic material,

Kako su te stanice, sve s istim genetičkim materijalom,

make all those tissues?

napravile sva ta tkiva?

And so, the question I raised before

Tako, pitanje koje sam prethodno postavila

becomes even more interesting if you thought about

postaje još zanimljivije ako razmislite

the enormity of this in every one of your bodies.

o veličini svega toga u svim vašim tijelima.

Now, the dominant cancer theory would say

Prevladavajuća teorija o raku kaže

that there is a single oncogene

da postoji jedan jedini onkogen

in a single cancer cell, and it would make you

u jednoj stanici raka, i to će vas učiniti

a cancer victim.

žrtvom raka.

Well, this did not make sense to me.

Pa, ovo meni nije imalo smisla.

Do you even know how a trillion looks?

Znate li uopće kako bilijun izgleda?

Now, let's look at it.

Pogledajmo ga.

There it comes, these zeroes after zeroes after zeroes.

Evo ga, nula za nulom za nulom.

Now, if .0001 of these cells got mutated,

Ako 0.0001 ovih stanica mutira

and .00001 got cancer, you will be a lump of cancer.

i 0.00001 dobije rak, bili biste gruda raka.

You will have cancer all over you. And you're not.

Imali biste rak posvuda po sebi. A niste.

Why not?

Zašto ne?

So, I decided over the years,

Odlučila sam tijekom godina,

because of a series of experiments

zbog niza pokusa

that this is because of context and architecture.

da je tako zbog okruženja i arhitekture.

And let me quickly tell you

I dopustite mi da vam na brzinu ispričam

some crucial experiment that was able to actually show this.

o ključnom pokusu koji je zapravo mogao ovo pokazati.

To begin with, I came to work with this virus

Za početak, počela sam raditi s ovim virusom

that causes that ugly tumor in the chicken.

koji uzrokuje taj gadni tumor kod kokoši.

Rous discovered this in 1911.

Rous je otkrio ovo 1911. godine.

It was the first cancer virus discovered,

Bio je to prvi otkriveni virus koji izaziva rak,

and when I call it "oncogene," meaning "cancer gene."

i kada ga nazovem „onkogen“ ima značenje „gen raka“.

So, he made a filtrate, he took this filter

Dakle, napravio je filtrat, uzeo je taj filter

which was the liquid after he passed the tumor through a filter,

koji je bio tekućina koju je dobio nakon što je filtrirao tumor

and he injected it to another chicken, and he got another tumor.

i ubrizgao ga u drugu kokoš te dobio je drugi tumor.

So, scientists were very excited,

Znanstvenici su bili jako uzbuđeni,

and they said, a single oncogene can do it.

i rekli su: Jedan jedini onkogen može to izazvati.

All you need is a single oncogene.

Sve što trebate je jedan onkogen.

So, they put the cells in cultures, chicken cells,

Dakle, uzgojili su kokošje stanice,

dumped the virus on it,

bacili virus na njih,

and it would pile up,

i one bi se nagomilale,

and they would say, this is malignant and this is normal.

a oni bi rekli: Ovo je maligno, a ovo je normalno.

And again this didn't make sense to me.

I opet, ovo meni nije imalo smisla.

So for various reasons, we took this oncogene,

Stoga, zbog raznih razloga, uzeli smo taj onkogen,

attached it to a blue marker,

vezali ga uz plavi marker,

and we injected it into the embryos.

i ubrizgali ga u embrije.

Now look at that. There is that beautiful feather in the embryo.

Pogledaje to. Ovdje je to prekrasno pero u embriju.

Every one of those blue cells are a cancer gene

Svaka od tih plavih stanica su geni raka

inside a cancer cell, and they're part of the feather.

unutar stanica raka i dio su pera.

So, when we dissociated the feather and put it in a dish,

Kada smo odvojili pero i stavili ga u posudicu,

we got a mass of blue cells.

dobili smo masu plavih stanica.

So, in the chicken you get a tumor,

Dakle, u kokoši dobijete tumor,

in the embryo you don't,

u embriju ne,

you dissociate, you put it in a dish, you get another tumor.

odvojite, stavite u posudicu, dobijete još jedan tumor. .

What does that mean?

Što to znači?

That means that microenvironment

To znači da mikrookoliš

and the context which surrounds those cells

i okoliš koji okružuje te stanice

actually are telling the cancer gene and the cancer cell what to do.

zapravo govori genima raka i stanicama raka što da rade.

Now, let's take a normal example.

Uzmimo sada normalan primjer.

The normal example, let's take the human mammary gland.

Kao normalan primjer, uzmimo ljudsku mliječnu žlijezdu.

I work on breast cancer.

Ja radim na raku dojke.

So, here is a lovely human breast.

Dakle ovdje je ljupka ljudska dojka.

And many of you know how it looks,

I mnogi od vas znaju kako izgleda,

except that inside that breast, there are all these

osim da unutar te dojke postoje sve te

pretty, developing, tree-like structures.

lijepe, razvijajuće, drvolike strukture.

So, we decided that what we like to do

Odlučili smo da bismo htjeli

is take just a bit of that mammary gland,

uzeti samo djelić te mliječne žlijezde,

which is called an "acinus,"

koji se zove acinus,

where there are all these little things inside the breast

gdje su sve ove male stvari unutar dojke

where the milk goes, and the end of the nipple

gdje ide mlijeko, i završetak bradavice

comes through that little tube when the baby sucks.

ide kroz tu malu cijev kada beba siše.

And we said, wonderful! Look at this pretty structure.

I rekli smo, prekrasno! Pogledajte te lijepe strukture.

We want to make this a structure, and ask the question,

Želimo od ovoga napraviti strukturu i postaviti pitanje:

how do the cells do that?

Kako to stanice rade?

So, we took the red cells --

Stoga smo uzeli crvene stanice –

you see the red cells are surrounded by blue,

vidite da su crvene stanice okružene plavima,

other cells that squeeze them, and behind it

drugim stanicama koje ih stišću. Iza njih

is material that people thought was mainly inert,

je materijal za koji su ljudi mislili kako je uglavnom inertan

and it was just having a structure to keep the shape,

i da ima strukturu samo kako bi održao oblik.

and so we first photographed it

Prvi put smo ga fotografirali

with the electron microscope years and years ago,

s elektronskim mikroskopim prije mnogo godina,

and you see this cell is actually quite pretty.

i vidite da je ova stanica zapravo dosta lijepa.

It has a bottom, it has a top,

Ima dno, ima vrh,

it is secreting gobs and gobs of milk,

izlučuje velike količine mlijeka

because it just came from an early pregnant mouse.

jer je došla iz miša u ranoj trudnoći.

You take these cells, you put them in a dish,

Uzmete ove stanice, stavite ih u posudicu

and within three days, they look like that.

i kroz tri dana ovako izgledaju.

They completely forget.

Posve su zaboravile.

So you take them out, you put them in a dish,

Dakle izvadite ih, stavite ih u posudicu

they don't make milk. They completely forget.

i one ne prave mlijeko. Posve zaborave.

For example, here is a lovely yellow droplet of milk

Kao primjer, ovdje je lijepa žuta kapljica mlijeka

on the left, there is nothing on the right.

na lijevoj strani, a na desnoj ništa.

Look at the nuclei. The nuclei in the cell on the left

Pogledajte jezgre. Jezgre u stanicama na lijevoj strani

is in the animal, the one on the right is in a dish.

su iz životinje, na desnoj su iz posudice.

They are completely different from each other.

Posve se razlikuju jedne od drugih.

So, what does this tell you?

Što vam to govori?

This tells you that here also, context overrides.

To vam govori da i ovdje okoliš nadjačava.

In different contexts, cells do different things.

U drukčijem okolišu, stanice rade drukčije stvari.

But how does context signal?

Ali kako taj okoliš signalizira?

So, Einstein said that

Einstein je rekao:

"For an idea that does not first seem insane, there is no hope."

"Ako se ideja isprva ne čini apsurdnom tada nema nade za nju,"

So, you can imagine the amount of skepticism

Možete zamisliti količinu skepticizma

I received -- couldn't get money,

koju sam doživjela – nisam mogla dobiti novac,

couldn't do a whole lot of other things,

nisam mogla napraviti hrpu drugih stvari,

but I'm so glad it all worked out.

ali tako mi je drago da je sve ispalo u redu.

So, we made a section of the mammary gland of the mouse,

Secirali smo mliječnu žlijezdu miša

and all those lovely acini are there,

i svi ti ljupki acinusi su tamo,

every one of those with the red around them are an acinus,

svi oni sa crvenim oko sebe su acinusi,

and we said okay, we are going to try and make this,

i rekli smo: U redu, pokušat ćemo to napraviti.

and I said, maybe that red stuff

Rekla sam: Možda ta crvena tvar

around the acinus that people think there's just a structural scaffold,

oko acinusa za koju ljudi misle da je samo strukturna podloga

maybe it has information,

sadrži informacije,

maybe it tells the cells what to do, maybe it tells the nucleus what to do.

možda govori stanicama što da rade, možda govori jezgri što da radi.

So I said, extracellular matrix, which is this stuff

Stoga sam rekla: izvanstanični matriks, što je ova stvar

called ECM, signals and actually tells the cells what to do.

nazvana ECM, signalizira i zapravo govori stanicama što da rade.

So, we decided to make things that would look like that.

Odlučili smo napraviti stvari koje će tako izgledati.

We found some gooey material

Našli smo gnjecav materijal

that had the right extracellular matrix in it,

koji je imao odgovarajući izvanstanični matriks u sebi,

we put the cells in it, and lo and behold,

stavili smo stanice u njega, i

in about four days, they got reorganized

u otprilike 4 dana, reorganizirale su se

and on the right, is what we can make in culture.

i nadesno je što možemo napraviti u kulturi.

On the left is what's inside the animal, we call it in vivo,

Nalijevo je unutar životinje, zovemo ga in vivo,

and the one in culture was full of milk,

i onaj u kulturi bio je pun mlijeka,

the lovely red there is full of milk.

prekrasna crvena tamo je puna mlijeka.

So, we Got Milk, for the American audience.

Dakle, imamo mlijeko, za američku publiku.

All right. And here is this beautiful human cell,

U redu. Ovdje je ta prekrasna ljudska stanica,

and you can imagine that here also, context goes.

možete zamisliti da ovdje također okoliš ima utjecaja.

So, what do we do now?

Dakle, što sada učiniti?

I made a radical hypothesis.

Postavila sam radikalnu hipotezu.

I said, if it's true that architecture is dominant,

Rekla sam, ako je istina da je arhitektura dominantna,

architecture restored to a cancer cell

obnovljena arhitektura stanice raka

should make the cancer cell think it's normal.

trebala bi natjerati je da misli da je normalna.

Could this be done?

Je li ovo izvedivo?

So, we tried it.

Pokušali smo.

In order to do that, however,

Da bismo to napravili, međutim,

we needed to have a method of distinguishing normal from malignant,

morali smo imati metode razlikovanja normalnih od malignih,

and on the left is the single normal cell,

nalijevo je jedina normalna stanica,

human breast, put in three-dimensional gooey gel

ljudska dojka, stavljena u trodimenzionalni gnjecavi gel

that has extracellular matrix, it makes all these beautiful structures.

koji sadrži izvanstanični matriks i radi sve ove prekrasne strukture.

On the right, you see it looks very ugly,

Nadesno, vidite da izgleda vrlo ružno,

the cells continue to grow,

stanice nastavljaju rasti,

the normal ones stop.

normalne prestaju.

And you see here in higher magnification

I ovdje vidite na većem povećanju

the normal acinus and the ugly tumor.

normalni acinus i ružni tumor.

So we said, what is on the surface of these ugly tumors?

Rekli smo: Što je na površini ovih ružnih tumora?

Could we calm them down --

Možemo li ih smiriti –

they were signaling like crazy and they have pathways all messed up --

signalizirale su kao lude i svi putovi su im bili pomiješani –

and make them to the level of the normal?

i vratiti ih na razinu normale?

Well, it was wonderful. Boggles my mind.

Pa, bilo je veličanstveno. Šokiralo me.

This is what we got.

Ovo je što smo dobili.

We can revert the malignant phenotype.

Možemo povratiti maligni fenotip na staro.

(Applause)

(Pljesak)

And in order to show you that the malignant phenotype

Kako bih vam pokazala taj maligni fenotip,

I didn't just choose one,

nisam samo izabrala jedan,

here are little movies, sort of fuzzy,

ovdje su kratki filmići, pomalo nejasni,

but you see that on the left are the malignant cells,

ali vidite da su nalijevo maligne stanice,

all of them are malignant,

sve su maligne,

we add one single inhibitor in the beginning,

dodamo jedan jedini inhibitor na početku

and look what happens, they all look like that.

i pogledajte što se dogodi, sve izgledaju tako.

We inject them into the mouse, the ones on the right,

Ubrizgamo ih u miša, one na desnoj strani,

and none of them would make tumors.

i nijedna neće postati tumor.

We inject the other ones in the mouse, 100 percent tumors.

Ubrizgamo druge u miša i 100% postanu tumori.

So, it's a new way of thinking about cancer,

To je novi način razmišljanja o raku,

it's a hopeful way of thinking about cancer.

to je način razmišljanja o raku pun nade.

We should be able to be dealing with these things at this level,

Trebali bismo se moći nositi s tim stvarima na ovoj razini,

and these conclusions say that growth and malignant behavior

i ovi zaključci nam govore da su rast i maligno ponašanje

is regulated at the level of tissue organization

regulirani na razini tkivne organizacije

and that the tissue organization is dependent

i da tkivna organizacija ovisi

on the extracellular matrix and the microenvironment.

o izvanstaničnom matriksu i mikrookolišu.

All right, thus form and function interact dynamically and reciprocally.

Dakle, oblik i funkcija djeluju međusobno dinamično i recipročno.

And here is another five seconds of repose,

I ovdje je još jednih pet sekundi odmora,

is my mantra. Form and function.

moja mantra. Oblik i funkcija.

And of course, we now ask, where do we go now?

Naravno, pitamo se što napraviti sada.

We'd like to take this kind of thinking into the clinic.

Htjeli bismo prenijeti ovaj način razmišljanja u kliniku.

But before we do that, I'd like you to think

Ali prije nego što to napravimo, htjela bih da razmislite

that at any given time when you're sitting there,

kako u svakom trenutku dok sjedite ovdje

in your 70 trillion cells,

u vaših 70 bilijuna stanica,

the extracellular matrix signaling to your nucleus,

izvanstanični matriks signalizira vašim jezgrama,

the nucleus is signaling to your extracellular matrix

jezgre signaliziraju vašem izvanstaničnom matriksu

and this is how your balance is kept and restored.

i na taj način vaša je ravnoteža održavana i obnovljena.

We have made a lot of discoveries,

Došli smo do mnogih otkrića,

we have shown that extracellular matrix talks to chromatin.

pokazali smo da izvanstanični matriks govori kromatinu.

We have shown that there's little pieces of DNA

Pokazali smo da postoje mali dijelovi DNK

on the specific genes of the mammary gland

na specifičnim genima mliječne žlijezde

that actually respond to extracellular matrix.

koji zapravo odgovaraju izvanstaničnom matriksu.

It has taken many years, but it has been very rewarding.

Bile su potrebne mnoge godine, ali isplatilo se.

And before I get to the next slide, I have to tell you

Prije nego što prijeđem na sljedeći slajd, moram vam reći

that there are so many additional discoveries to be made.

da postoji toliko dodatnih otkrića do kojih se treba doći.

There is so much mystery we don't know.

Postoje tolike zagonetke koje ne znamo.

And I always say to the students and post-docs I lecture to,

Uvijek govorim studentima i doktorandima kojima predajem

don't be arrogant, because arrogance kills curiosity.

da ne budu arogantni jer arogancija ubija radoznalost.

Curiosity and passion.

Radoznalost i strast.

You need to always think, what else needs to be discovered?

Uvijek morate razmišljati o tome što sljedeće treba otkriti.

And maybe my discovery needs to be added to

I možda mojem otkriću treba nešto dodati

or maybe it needs to be changed.

ili možda ga treba promijeniti.

So, we have now made an amazing discovery,

Dakle, sada smo došli do nevjerojatnog otkrića,

a post-doc in the lab who is a physicist asked me,

doktorandica u mojem laboratoriju koja je fizičar, pitala me

what do the cells do when you put them in?

što stanice rade kada ih se ubaci.

What do they do in the beginning when they do?

Što rade na početku rada?

I said, I don't know, we couldn't look at them.

Rekla sam da ne znam, nismo to mogli vidjeti.

We didn't have high images in the old days.

Nismo imali slike s visokom rezolucijom prijašnjih godina.

So she, being an imager and a physicist,

Stoga je ona, kao vizionar i fizičar,

did this incredible thing.

napravila ovu nevjerojatnu stvar.

This is a single human breast cell in three dimensions.

Ovo je jedna stanica ljudske dojke u tri dimenzije.

Look at it. It's constantly doing this.

Pogledajte je. Ona neprestano radi ovo.

Has a coherent movement.

Ima koherentno kretanje.

You put the cancer cells there, and they do go all over,

Stavite stanice raka tamo i one idu posvuda,

they do this. They don't do this.

rade ovo. Ne rade ovo.

And when we revert the cancer cell, it again does this.

A kada ih vratite u početno stanje, ponovno rade ovo.

Absolutely boggles my mind.

To me potpuno šokira.

So the cell acts like an embryo. What an exciting thing.

Dakle, stanica se ponaša kao embrio. Kako uzbudljiva stvar.

So I'd like to finish with a poem.

Htjela bih završiti s pjesmom.

Well I used to love English literature,

Nekad sam voljela englesku književnost

and I debated in college, which one should I do?

i debatirala sam na fakultetu, što bih trebala raditi?

And unfortunately or fortunately, chemistry won.

I na sreću ili nesreću, kemija je pobijedila.

But here is a poem from Yeats. I'll just read you the last two lines.

Ali evo jedne pjesme od Yeatsa. Pročitat ću vam samo posljednja dva stiha.

It's called "Among the School Children."

Zove se "Među školskom djecom".

"O body swayed to music / O brightening glance /

"O tijelo glazbom pokrenuto, oko sjajno,

How [can we know] the dancer from the dance?"

kako razaznati svoj ples od plesača?“

And here is Merce Cunningham,

Ovdje je Merce Cunningham,

I was fortunate to dance with him when I was younger,

bila sam dovoljno sretna da plešem s njim dok sam bila mlađa,

and here he is a dancer,

i ovdje je on plesač

and while he is dancing, he is both the dancer and the dance.

i dok pleše on je u istodobno i plesač i ples.

The minute he stops, we have neither.

U trenu kada stane, nije niti nijedno.

So it's like form and function.

Dakle, isto je kao oblik i funkcija.

Now, I'd like to show you a current picture of my group.

Htjela bih vam pokazati trenutnu sliku moje grupe.

I have been fortunate to have had these magnificant

Imala sam sreće raditi s ovim divnim

students and post-docs who have taught me so much,

studentima i doktorandima koji su me toliko naučili

and I have had many of these groups come and go.

i mnoge od ovih grupa došle su i otišle.

They are the future and I try to make them not be afraid

Oni su budućnost i trudim se naučiti ih da se ne boje

of being the cat and being told,

biti mačka i da im bude rečeno

don't think outside the box.

da ne misle izvan kutije.

And I'd like to leave you with this thought.

Htjela bih vas ostaviti s ovom mišlju.

On the left is water coming through the shore,

Nalijevo je voda koja prolazi obalom,

taken from a NASA satellite.

uzeta sa NASA-inog satelita.

On the right, there is a coral.

Desno je koralj.

Now if you take the mammary gland and spread it

Ako uzmete mliječnu žlijezdu, raširite je

and take the fat away, on a dish it looks like that.

i maknete mast, na posudici izgleda ovako.

Do they look the same? Do they have the same patterns?

Izgledaju li jednako? Imaju li iste uzorke?

Why is it that nature keeps doing that over and over again?

Zašto priroda to radi opet i iznova?

And I'd like to submit to you

Htjela bih vas izvijestiti

that we have sequenced the human genome,

da smo sekvencionirali ljudski genom,

we know everything about the sequence of the gene,

znamo sve o slijedu gena,

the language of the gene, the alphabet of the gene,

jeziku gena, abecedi gena,

But we know nothing, but nothing,

ali ne znamo ništa, ali ništa

about the language and alphabet of form.

o jeziku i abecedi oblika.

So, it's a wonderful new horizon,

Dakle, to je predivan novi horizont,

it's a wonderful thing to discover for the young

to je predivna stvar za otkrivanje za mlade

and the passionate old, and that's me.

i za strastvene stare, kao što sam ja.

So go to it!

Stoga krenimo na to!

(Applause)

(Pljesak)