TED2014
Stephen Friend: The hunt for "unexpected genetic heroes"
Stiven Frend (Stephen Friend): Lov na "neočekivane genetske heroje"
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Šta možemo da naučimo od ljudi sa genetskom predispozicijom da se razbole, ali se to ipak ne desi? U najvećem broju naslednih bolesti, samo neki članovi porodice se razbole, dok se drugi sa istim genetskim rizikom izvuku. Stiven Frend predlaže da počnemo da proučavamo one koji ostanu zdravi. Poslušajte priču o Projektu otpornosti, ogromnom naporu da se sakupi genetski materijal koji može pomoći u dekodiranju naslednih poremećaja.
Stephen Friend - Open-science advocate
Inspired by open-source software models, Sage Bionetworks co-founder Stephen Friend builds tools that facilitate research sharing on a massive and revolutionary scale. Full bio
Inspired by open-source software models, Sage Bionetworks co-founder Stephen Friend builds tools that facilitate research sharing on a massive and revolutionary scale. Full bio
Double-click the English transcript below to play the video.
00:12
Approximately 30 years ago,
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Pre otprilike 30 godina,
00:14
when I was in oncology at the Children's Hospital
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dok sam bio na onkologiji
u Dečjoj bolnici
u Dečjoj bolnici
00:17
in Philadelphia,
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u Filadelfiji,
00:19
a father and a son walked into my office
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u moju kancelariju ušli su otac i sin
00:22
and they both had their right eye missing,
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i obojica nisu imali desno oko.
00:25
and as I took the history, it became apparent
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Iz istorije bolesti postalo mi je jasno
00:28
that the father and the son had a rare form
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da su otac i sin imali redak oblik
00:30
of inherited eye tumor, retinoblastoma,
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naslednog tumora oka, retinoblastom,
00:34
and the father knew that he had passed that fate
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i otac je znao da je preneo bolest
00:37
on to his son.
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svome sinu.
00:39
That moment changed my life.
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Taj trenutak mi je promenio život.
00:41
It propelled me to go on
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Motivisao me je da nastavim
00:43
and to co-lead a team that discovered
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i povedem tim koji je otkrio
00:47
the first cancer susceptibility gene,
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prvi gen koji je prijemčiv na rak.
00:50
and in the intervening decades since then,
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U proteklim decenijama
00:53
there has been literally a seismic shift
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desio se seizmički preokret
00:56
in our understanding of what goes on,
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u našem poimanju onoga što se dešava,
00:58
what genetic variations are sitting behind
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kakve se to genetske varijacije kriju iza
01:01
various diseases.
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raznih bolesti.
01:03
In fact, for thousands of human traits,
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Zapravo, za hiljade ljudskih osobina,
01:06
a molecular basis that's known for that,
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molekularna osnova koja stoji iza toga
01:08
and for thousands of people, every day,
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i za hiljade ljudi, svakodnevno
01:11
there's information that they gain
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postoje informacije koje dobijaju
01:14
about the risk of going on to get this disease
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o riziku da obole od ove
01:16
or that disease.
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ili one bolesti.
01:18
At the same time, if you ask,
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Istovremeno, ako se zapitate:
01:21
"Has that impacted the efficiency,
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"Da li je to uticalo na efikasnost,
01:23
how we've been able to develop drugs?"
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na našu sposobnost pravljenja lekova?"
01:25
the answer is not really.
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Odgovor je: ne baš.
01:27
If you look at the cost of developing drugs,
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Ako pogledate troškove pravljenja lekova,
01:29
how that's done, it basically hasn't budged that.
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u osnovi se nije ništa promenilo.
01:33
And so it's as if we have the power to diagnose
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Tako da imamo moć da dijagnostikujemo,
01:37
yet not the power to fully treat.
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ali ne i moć da izlečimo.
01:40
And there are two commonly given reasons
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A postoje dva razloga koji se navode
01:43
for why that happens.
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za to zašto se ovo dešava.
01:44
One of them is it's early days.
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Jedan od njih je da tek počinjemo.
01:48
We're just learning the words, the fragments,
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Tek učimo reči, fragmente,
01:51
the letters in the genetic code.
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slova u genetskom kodu.
01:53
We don't know how to read the sentences.
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Ne umemo da čitamo rečenice.
01:55
We don't know how to follow the narrative.
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Ne umemo da pratimo priču.
01:58
The other reason given is that
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Drugi navedeni razlog je da je
02:00
most of those changes are a loss of function,
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većina ovih promena gubitak funkcije,
02:02
and it's actually really hard to develop drugs
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a veoma je teško stvoriti lekove
02:05
that restore function.
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koji vraćaju funkciju.
02:07
But today, I want us to step back
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Ali danas želim
da se vratimo korak unazad
da se vratimo korak unazad
02:09
and ask a more fundamental question,
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i upitamo se jedno osnovnije pitanje:
02:11
and ask, "What happens if we're thinking
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"Šta se dešava ako ovo posmatramo
02:14
about this maybe in the wrong context?"
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možda u pogrešnom kontekstu?"
02:16
We do a lot of studying of those who are sick
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Mnogo proučavamo one koji su bolesni
02:19
and building up long lists
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i pravimo duge spiskove
02:22
of altered components.
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izmenjenih komponenti.
02:25
But maybe, if what we're trying to do
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Ali možda, ako pokušavamo da
02:28
is to develop therapies for prevention,
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napravimo terapiju za prevenciju,
02:31
maybe what we should be doing
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možda bi trebalo
02:32
is studying those who don't get sick.
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da proučavamo one koji se ne razbole.
02:35
Maybe we should be studying those
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Možda bi trebalo da proučavamo one
02:37
that are well.
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koji su zdravi.
02:39
A vast majority of those people
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Velika većina tih ljudi
02:41
are not necessarily carrying a particular
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ne nosi nužno neko posebno
02:43
genetic load or risk factor.
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genetsko opterećenje ili faktor rizika.
02:45
They're not going to help us.
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Oni nam neće pomoći.
02:47
There are going to be those individuals
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To će biti oni pojedinci
02:49
who are carrying a potential future risk,
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koji nose potencijalni budući rizik,
02:52
they're going to go on to get some symptom.
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oni će ispoljiti neki simptom.
02:53
That's not what we're looking for.
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To nije ono što tražimo.
02:55
What we're asking and looking for is,
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Ono što mi želimo i tražimo
02:57
are there a very few set of individuals
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je mali broj pojedinaca
03:00
who are actually walking around
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koji zapravo žive
03:03
with the risk that normally would cause a disease,
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sa rizikom koji bi
normalno izazvao bolest,
normalno izazvao bolest,
03:07
but something in them, something hidden in them
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ali ih nešto u njima, nešto skriveno,
03:10
is actually protective
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u stvari štiti
03:11
and keeping them from exhibiting those symptoms?
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i sprečava te simptome da se ispolje.
03:15
If you're going to do a study
like that, you can imagine
like that, you can imagine
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U takvom istraživanju,
možete da zamislite,
možete da zamislite,
03:17
you'd like to look at lots and lots of people.
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treba da pregledate zaista mnogo ljudi.
03:20
We'd have to go and have a pretty wide study,
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Trebalo bi da sprovedemo
prilično široko istraživanje
prilično široko istraživanje
03:23
and we realized that actually
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i shvatili smo da je
03:25
one way to think of this is,
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jedan od načina da pristupimo ovome
03:26
let us look at adults who are over 40 years of age,
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da uzmemo odrasle ljude
iznad 40 godina starosti
iznad 40 godina starosti
03:30
and let's make sure that we look at those
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i da se pobrinemo da to budu oni
koji su bili zdravi u detinjstvu.
03:33
who were healthy as kids.
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03:35
They might have had individuals in their families
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Moguće je da su imali članove porodice
03:37
who had had a childhood disease,
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koji su bili bolesni u detinjstvu,
03:39
but not necessarily.
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ali to nije nužno.
03:41
And let's go and then screen those
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I hajde da na njima uradimo skrining
03:43
to find those who are carrying genes
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kako bismo pronašli one koji nose gene
03:45
for childhood diseases.
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za dečje bolesti.
03:47
Now, some of you, I can see you
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E sad, mogu da vidim neke od vas
03:49
putting your hands up going, "Uh, a little odd.
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kako podižete ruke u stilu:
"Ovaj, pomalo čudno.
"Ovaj, pomalo čudno.
03:52
What's your evidence
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Šta dokazuje
03:53
that this could be feasible?"
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da je ovo izvodljivo?"
03:55
I want to give you two examples.
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Želim da vam dam dva primera.
03:57
The first comes from San Francisco.
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Prvi dolazi iz San Franciska.
04:00
It comes from the 1980s and the 1990s,
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Dolazi iz 1980-ih i 1990-ih,
04:03
and you may know the story where
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a možda vam je poznata priča
04:05
there were individuals who had very high levels
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o pojedincima koji su imali
vrlo visoke nivoe
vrlo visoke nivoe
04:08
of the virus HIV.
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virusa HIV.
04:09
They went on to get AIDS.
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Oni su dobili sidu.
04:11
But there was a very small set of individuals
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Ali postojao je mali broj ljudi
04:14
who also had very high levels of HIV.
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koji su isto imali visok nivo HIV-a.
04:17
They didn't get AIDS.
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Oni nisu oboleli od side.
04:18
And astute clinicians tracked that down,
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Pronicljivi lekari su ovo istražili
04:21
and what they found was
they were carrying mutations.
they were carrying mutations.
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i otkrili da su ti ljudi nosioci mutacija.
04:24
Notice, they were carrying mutations from birth
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Obratite pažnju da su one tu od rođenja.
04:28
that were protective, that were protecting them
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Mutacije su služile kao zaštita
04:30
from going on to get AIDS.
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od dobijanja side.
04:31
You may also know that actually a line of therapy
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Možda vam je poznato da su razne terapije
04:34
has been coming along based on that fact.
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nastale upravo na osnovu tog saznanja.
04:37
Second example, more recent, is elegant work
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Drugi, noviji, primer je elegantno delo
04:41
done by Helen Hobbs,
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Helen Hobs
04:42
who said, "I'm going to look at individuals
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koja je rekla: "Pregledaću pojedince
04:45
who have very high lipid levels,
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koji imaju visok nivo lipida
04:47
and I'm going to try to find those people
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i pokušaću da nađem one ljude
04:49
with high lipid levels
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sa visokim nivoom lipida
04:51
who don't go on to get heart disease."
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koji ne dobiju srčano oboljenje."
04:53
And again, what she found was
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I opet, otkrila je
04:56
some of those individuals had mutations
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da neki od tih pojedinaca imaju mutacije
04:58
that were protective from birth that kept them,
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koje su ih štitile od rođenja
05:01
even though they had high lipid levels,
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uprkos visokom nivou lipida.
05:03
and you can see this is an interesting way
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Možete da vidite
da je ovo zanimljiv način
da je ovo zanimljiv način
05:06
of thinking about how you could develop
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razmišljanja o tome kako napraviti
05:08
preventive therapies.
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preventivnu terapiju.
05:10
The project that we're working on
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Projekat na kome radimo
05:12
is called "The Resilience Project:
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zove se "Projekat otpornosti:
Potraga za neočekivanim herojima",
05:15
A Search for Unexpected Heroes,"
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05:16
because what we are interested in doing is saying,
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jer želimo da otkrijemo
05:18
can we find those rare individuals
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da li možemo da nađemo
one retke pojedince
one retke pojedince
05:21
who might have these hidden protective factors?
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koji imaju ove skrivene zaštitne faktore.
05:25
And in some ways, think of it as a decoder ring,
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Posmatrajte to kao krug dešifrovanja,
05:28
a sort of resilience decoder ring
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nekakav krug dešifrovanja za otpornost
05:30
that we're going to try to build.
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koji želimo da izgradimo.
05:32
We've realized that we should
do this in a systematic way,
do this in a systematic way,
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Shvatamo da ovo treba
uraditi sistematično,
uraditi sistematično,
05:36
so we've said, let's take every single
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tako da smo odlučili
da uzmemo svaku moguću
da uzmemo svaku moguću
05:38
childhood inherited disease.
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naslednu dečju bolest.
05:40
Let's take them all, and let's
pull them back a little bit
pull them back a little bit
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Hajde sve da ih uzmemo i malo izuzmemo
05:42
by those that are known to have severe symptoms,
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one koji imaju teške simptome,
05:45
where the parents, the child,
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gde roditelji, dete,
05:47
those around them would know
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oni oko njih znaju
05:48
that they'd gotten sick,
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da su se razboleli.
05:50
and let's go ahead and then frame them again
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I hajde da ponovo uzmemo te bolesti
05:53
by those parts of the genes where we know
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i posmatramo one delove gena
za koje znamo
za koje znamo
05:56
that there is a particular alteration
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da imaju neku posebnu promenu
05:58
that is known to be highly penetrant
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za koju se zna da je veoma prodorna
06:01
to cause that disease.
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u izazivanju te bolesti.
06:04
Where are we going to look?
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Gde ćemo gledati?
06:05
Well, we could look locally. That makes sense.
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Pa, mogli bismo lokalno. To ima smisla.
06:08
But we began to think, maybe we should look
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Ali palo nam je na pamet, možda treba
06:10
all over the world.
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da gledamo širom sveta.
Možda ne treba da gledamo samo ovde
06:11
Maybe we should look not just here
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06:13
but in remote places where their might be
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nego u udaljenim mestima
gde možda postoji
gde možda postoji
06:15
a distinct genetic context,
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poseban genetski kontekst,
06:18
there might be environmental factors
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možda postoje faktori sredine
06:20
that protect people.
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koji štite ljude.
06:21
And let's look at a million individuals.
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I hajde da pregledamo milion pojedinaca.
06:25
Now the reason why we think it's a good time
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A razlog zašto mislimo da je pravo vreme
06:28
to do that now
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da to uradimo sada
06:30
is, in the last couple of years,
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je činjenica da se u poslednjih par godina
06:31
there's been a remarkable plummeting in the cost
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desio neverovatan pad troškova
06:34
to do this type of analysis,
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ovakvog tipa analize,
06:36
this type of data generation,
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ovakvog tipa izdvajanja podataka
06:38
to where it actually costs less to do
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gde zapravo manje košta
06:40
the data generation and analysis
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izdvajanje i analiza podataka
06:43
than it does to do the sample
processing and the collection.
processing and the collection.
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nego obrada i prikupljanje uzoraka.
06:46
The other reason is that in the last five years,
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Drugi razlog je to što su se u poslednjih
06:50
there have been awesome tools,
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pet godina pojavili sjajni alati,
06:52
things about network biology, systems biology,
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stvari u vezi sa mrežnom
i sistemskom biologijom
i sistemskom biologijom
koje su se pojavile
i navele nas da pomislimo
i navele nas da pomislimo
06:55
that have come up that allow us to think
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06:57
that maybe we could decipher
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da možda možemo da odgonetnemo
06:59
those positive outliers.
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te pozitivne izuzetke.
07:01
And as we went around talking to researchers
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I kako smo počeli
da pričamo sa naučnicima
da pričamo sa naučnicima
07:03
and institutions
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i institucijama
07:05
and telling them about our story,
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i ispričali im našu priču,
07:07
something happened.
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nešto se desilo.
07:08
They started saying, "This is interesting.
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Govorili su nam: "To je zanimljivo.
07:11
I would be glad to join your effort.
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Rado bismo se priključili vašem naporu.
07:14
I would be willing to participate."
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Rado bismo učestvovali."
07:16
And they didn't say, "Where's the MTA?"
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Nisu rekli:
"Gde je sporazum o transferu materijala?"
"Gde je sporazum o transferu materijala?"
07:19
They didn't say, "Where is my authorship?"
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Nisu rekli:
"Gde je moje autorstvo?"
"Gde je moje autorstvo?"
07:22
They didn't say, "Is this data going
to be mine? Am I going to own it?"
to be mine? Am I going to own it?"
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Nisu rekli:
"Hoće li podaci biti moje vlasništvo?"
"Hoće li podaci biti moje vlasništvo?"
07:26
They basically said, "Let's work on this
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Samo su rekli:
"Hajde da radimo na ovome
"Hajde da radimo na ovome
07:29
in an open, crowd-sourced, team way
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otvoreno, zajednički i timski
07:32
to do this decoding."
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kako bismo uspeli u dekodiranju."
07:35
Six months ago, we locked down
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Pre šest meseci, utvrdili smo
07:37
the screening key for this decoder.
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skrining ključ za ovaj dekoder.
07:41
My co-lead, a brilliant scientist, Eric Schadt
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Moj saradnik, briljantni naučnik, Erik Šat
07:45
at the Icahn Mount Sinai
School of Medicine in New York,
School of Medicine in New York,
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sa Medicinskog fakulteta
Ajkan Maunt u Njujorku
Ajkan Maunt u Njujorku
07:48
and his team,
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i njegov tim,
07:50
locked in that decoder key ring,
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otkrili su taj ključ za dekodiranje.
07:53
and we began looking for samples,
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A mi smo počeli da tražimo uzorke
07:55
because what we realized is,
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jer smo shvatili
07:57
maybe we could just go and look
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da možda možemo da odemo i potražimo
07:58
at some existing samples to
get some sense of feasibility.
get some sense of feasibility.
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postojeće uzorke i vidimo
koliko je sve to izvodljivo.
koliko je sve to izvodljivo.
08:01
Maybe we could take two, three
percent of the project on,
percent of the project on,
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Možda bismo mogli
da uradimo 2-3% projekta
da uradimo 2-3% projekta
08:04
and see if it was there.
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i vidimo kako ide.
08:05
And so we started asking people
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Tako smo počeli da pitamo ljude
08:07
such as Hakon at the Children's Hospital in Philadelphia.
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kao što su Haken
iz Dečje bolnice u Filadelfiji.
iz Dečje bolnice u Filadelfiji.
08:11
We asked Leif up in Finland.
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Pitali smo Lejfa iz Finske.
08:13
We talked to Anne Wojcicki at 23andMe,
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Razgovarali smo
sa En Vodžiki iz 23andMe
sa En Vodžiki iz 23andMe
08:17
and Wang Jun at BGI,
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i sa Vong Džun sa PGI-a.
08:19
and again, something remarkable happened.
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I ponovo se desilo nešto neverovatno.
08:21
They said, "Huh,
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Rekli su nam:
08:23
not only do we have samples,
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"Ne samo da imamo uzorke,
08:24
but often we've analyzed them,
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nego smo ih neretko i analizirali
08:27
and we would be glad to go into
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i rado ćemo pregledati
08:28
our anonymized samples
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naše anonimne uzorke
08:29
and see if we could find those
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i probati da nađemo one
08:32
that you're looking for."
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koji vam trebaju."
08:33
And instead of being 20,000 or 30,000,
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I umesto da ih je 20 ili 30 hiljada,
08:35
last month we passed one half million samples
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prošlog meseca prešli smo
pola miliona uzoraka
pola miliona uzoraka
08:39
that we've already analyzed.
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koje smo već analizirali.
08:40
So you must be going,
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Mora da se pitate:
08:42
"Huh, did you find any unexpected heroes?"
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"Da li ste našli
nekog neočekivanog heroja?"
nekog neočekivanog heroja?"
08:48
And the answer is, we didn't find one or two.
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A nismo pronašli jednog ili dva,
08:50
We found dozens of these strong candidate
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već desetine jakih kandidata
08:53
unexpected heroes.
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za neočekivane heroje.
08:55
So we think that the time is now
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Tako da mislimo da je sad pravi trenutak
08:58
to launch the beta phase of this project
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da izbacimo beta verziju ovog projekta
09:00
and actually start getting prospective individuals.
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i zaista počnemo sa mogućim kandidatima.
09:03
Basically all we need is information.
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Sve što nama u stvari treba
je informacija.
je informacija.
09:06
We need a swab of DNA
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Treba nam uzorak DNK
09:08
and a willingness to say, "What's inside me?
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i želja da saznaju:
"Šta se to nalazi u meni?
"Šta se to nalazi u meni?
09:11
I'm willing to be re-contacted."
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Hteo bih da mi se ponovo javite."
09:15
Most of us spend our lives,
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Većina nas provodi život,
09:18
when it comes to health and disease,
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kad govorimo o zdravlju i bolestima,
09:20
acting as if we're voyeurs.
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u ulozi posmatrača.
09:23
We delegate the responsibility
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Prepuštamo odgovornost
09:26
for the understanding of our disease,
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razumevanja naših bolesti
09:28
for the treatment of our disease,
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i lečenja naših bolesti
09:30
to anointed experts.
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bogom danim stručnjacima.
09:33
In order for us to get this project to work,
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Da bi ovaj projekat uspeo,
09:37
we need individuals to step up
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pojedinci treba da se pokažu
09:39
in a different role and to be engaged,
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u drugačijoj ulozi i da se uključe
09:43
to realize this dream,
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kako bi se ostvario ovaj san,
09:45
this open crowd-sourced project,
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ovaj otvoreni, zajednički projekat,
09:49
to find those unexpected heroes,
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kako bi se pronašli ti neočekivani heroji
09:52
to evolve from the current concepts
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i napredovalo sa sadašnjih ideja
09:55
of resources and constraints,
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o resursima i ograničenjima,
09:57
to design those preventive therapies,
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kako bi se osmislila preventivna terapija
10:01
and to extend it beyond childhood diseases,
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i proširila van granica dečjih bolesti
10:03
to go all the way up to ways
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tako da se smisle načini
10:05
that we could look at Alzheimer's or Parkinson's,
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posmatranja Alchajmerove
ili Parkinsonove bolesti.
ili Parkinsonove bolesti.
10:09
we're going to need us
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Trebaćemo sami sebi
10:11
to be looking inside ourselves and asking,
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da se zagledamo u sebe i zapitamo:
10:14
"What are our roles?
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"Koje su naše uloge?
10:16
What are our genes?"
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Kakvi su naši geni?"
10:18
and looking within ourselves for information
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Unutar sebe da tražimo informacije
10:21
we used to say we should go to the outside,
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koje smo pre tražili spolja,
10:23
to experts,
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od stručnjaka.
10:25
and to be willing to share that with others.
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I da budemo spremni
da to podelimo sa drugima.
da to podelimo sa drugima.
10:29
Thank you very much.
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Mnogo vam hvala.
10:32
(Applause)
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(Aplauz)
ABOUT THE SPEAKER
Stephen Friend - Open-science advocateInspired by open-source software models, Sage Bionetworks co-founder Stephen Friend builds tools that facilitate research sharing on a massive and revolutionary scale.
Why you should listen
While working for Merck, Stephen Friend became frustrated by the slow pace at which big pharma created new treatments for desperate patients. Studying shared models like Wikipedia, Friend realized that the complexities of disease could only be understood -- and combated -- with collaboration and transparency, not by isolated scientists working in secret with proprietary data
In his quest for a solution, Friend co-founded Sage Bionetworks, an organization dedicated to creating strategies and platforms that empower researchers to share and interpret data on a colossal scale -- as well as crowdsource tests for new hypotheses.
As he wrote on CreativeCommons.org, "Our goal is ambitious. We want to take biology from a place where enclosure and privacy are the norm, where biologists see themselves as lone hunter-gatherers working to get papers written, to one where the knowledge is created specifically to fit into an open model where it can be openly queried and transformed."
Stephen Friend | Speaker | TED.com