TEDSummit
Ellen Jorgensen: What you need to know about CRISPR
Elen Jorgensen (Ellen Jorgensen): Šta treba da znate o CRISPR-u
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Da li treba da vratimo runastog mamuta? Ili da izmenimo ljudski embrion? Ili izbrišemo celu vrstu koju smatramo štetnom? CRISRP, tehnologija za izmenu genoma, učinila je ovakva pitanja legitimnim - ali kako ona funkcioniše? Naučnica i zastupnica otvorenih laboratorija, Elen Jorgensen, na misiji je da razjasni mitove i stvarnost CRISPR-a, bez preuveličavanja, za one među nama koji nisu naučnici.
Ellen Jorgensen - Biologist, community science advocate
Ellen Jorgensen is at the leading edge of the do-it-yourself biotechnology movement, bringing scientific exploration and understanding to the public. Full bio
Ellen Jorgensen is at the leading edge of the do-it-yourself biotechnology movement, bringing scientific exploration and understanding to the public. Full bio
Double-click the English transcript below to play the video.
00:12
So, has everybody heard of CRISPR?
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Da li su svi čuli za CRISPR?
00:15
I would be shocked if you hadn't.
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Bila bih šokirana da niste.
00:18
This is a technology --
it's for genome editing --
it's for genome editing --
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Ovo je tehnologija -
za izmenjivanje genoma -
za izmenjivanje genoma -
00:21
and it's so versatile and so controversial
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i toliko je raznovrsna i kontroverzna
00:24
that it's sparking all sorts
of really interesting conversations.
of really interesting conversations.
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da zbog nje počinju
svakakve zanimljive rasprave.
svakakve zanimljive rasprave.
00:28
Should we bring back the woolly mammoth?
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Da li da vratimo runastog mamuta?
00:31
Should we edit a human embryo?
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Da li da izmenimo ljudski embrion?
00:34
And my personal favorite:
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I moje omiljeno:
00:36
How can we justify
wiping out an entire species
wiping out an entire species
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kako možemo da opravdamo
brisanje čitave vrste
brisanje čitave vrste
00:40
that we consider harmful to humans
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koju smatramo štetnom za ljude
00:43
off the face of the Earth,
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sa lica planete Zemlje,
00:44
using this technology?
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koristeći ovu tehnologiju?
00:47
This type of science
is moving much faster
is moving much faster
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Ova vrsta nauke napreduje mnogo brže
00:50
than the regulatory mechanisms
that govern it.
that govern it.
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od mehanizama
koji regulišu upravljanje njome.
koji regulišu upravljanje njome.
00:53
And so, for the past six years,
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I tako, proteklih šest godina,
00:55
I've made it my personal mission
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moja je lična misija
00:57
to make sure that as many people
as possible understand
as possible understand
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da se postaram
da što je više moguće ljudi razume
da što je više moguće ljudi razume
01:00
these types of technologies
and their implications.
and their implications.
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ovu vrstu tehnologije i njene implikacije.
01:04
Now, CRISPR has been the subject
of a huge media hype,
of a huge media hype,
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CRISPR je bio tema
velike medijske pomame
velike medijske pomame
01:09
and the words that are used most often
are "easy" and "cheap."
are "easy" and "cheap."
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i najčešće se koriste
reči "lako" i "jeftino".
reči "lako" i "jeftino".
01:14
So what I want to do is drill down
a little bit deeper
a little bit deeper
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Želim da malo produbim temu
01:17
and look into some of the myths
and the realities around CRISPR.
and the realities around CRISPR.
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i pogledam neke od mitova i realnosti
koji se tiču CRISPR-a.
koji se tiču CRISPR-a.
01:22
If you're trying to CRISPR a genome,
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Ukoliko želite
da izmenite genom CRISPR-om,
da izmenite genom CRISPR-om,
01:25
the first thing that you have to do
is damage the DNA.
is damage the DNA.
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prvo morate da oštetite DNK.
01:29
The damage comes in the form
of a double-strand break
of a double-strand break
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Šteta nastaje tako što prelomite dupli niz
01:32
through the double helix.
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kroz duplu spiralu.
01:33
And then the cellular repair
processes kick in,
processes kick in,
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Onda kreću procesi popravke ćelije
01:37
and then we convince
those repair processes
those repair processes
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i onda te procese ubedimo
01:39
to make the edit that we want,
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da naprave izmenu koju želimo
01:42
and not a natural edit.
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a ne prirodnu izmenu.
01:43
That's how it works.
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Tako funkcioniše.
01:45
It's a two-part system.
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To je sistem od dva dela.
01:47
You've got a Cas9 protein
and something called a guide RNA.
and something called a guide RNA.
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Imate protein Cas9
i nešto što se zove RNK vodič.
i nešto što se zove RNK vodič.
01:51
I like to think of it as a guided missile.
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Volim da ga posmatram
kao raketu na navođenje.
kao raketu na navođenje.
Cas9 onda - volim da stvarima
dajem ljudske karakteristike -
dajem ljudske karakteristike -
01:53
So the Cas9 --
I love to anthropomorphize --
I love to anthropomorphize --
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01:56
so the Cas9 is kind of this Pac-Man thing
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Cas9 liči na nekog Pekmena
01:59
that wants to chew DNA,
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koji želi da žvaće DNK,
02:01
and the guide RNA is the leash
that's keeping it out of the genome
that's keeping it out of the genome
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a RNK vodič je povodac
koji ga drži van genoma
koji ga drži van genoma
02:05
until it finds the exact spot
where it matches.
where it matches.
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dok ne pronađe tačno mesto gde se uklapa.
02:08
And the combination of those two
is called CRISPR.
is called CRISPR.
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Kombinacija ove dve stvari
naziva se CRISPR.
naziva se CRISPR.
02:11
It's a system that we stole
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To je sistem koji smo ukrali
02:13
from an ancient, ancient
bacterial immune system.
bacterial immune system.
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od drevnog bakterijskog imunog sistema.
02:17
The part that's amazing about it
is that the guide RNA,
is that the guide RNA,
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Ono što je neverovatno kod svega
je da RNK vodič,
je da RNK vodič,
02:22
only 20 letters of it,
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samo 20 slova,
02:23
are what target the system.
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je ono što napada sistem.
02:26
This is really easy to design,
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Ovo je lako za osmisliti
02:28
and it's really cheap to buy.
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i veoma je jeftino.
02:30
So that's the part
that is modular in the system;
that is modular in the system;
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Ovo je deo koji je modularan u sistemu,
02:35
everything else stays the same.
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sve ostalo ostaje isto.
02:37
This makes it a remarkably easy
and powerful system to use.
and powerful system to use.
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Ovo ga čini neverovatno moćnim
i lakim sistemom za korišćenje.
i lakim sistemom za korišćenje.
02:42
The guide RNA and the Cas9
protein complex together
protein complex together
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RNK vodič i kompleks Cas9 proteina zajedno
02:46
go bouncing along the genome,
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kruže po genomu
02:48
and when they find a spot
where the guide RNA matches,
where the guide RNA matches,
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i kada naiđu na mesto
gde se vodič RNK podudara,
gde se vodič RNK podudara,
02:51
then it inserts between the two strands
of the double helix,
of the double helix,
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onda se ubacuju između dva niza
duple spirale,
duple spirale,
02:54
it rips them apart,
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kidaju ih,
02:56
that triggers the Cas9 protein to cut,
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to natera protein Cas9 da seče
02:59
and all of a sudden,
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i odjednom
03:01
you've got a cell that's in total panic
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imate ćeliju u panici
03:03
because now it's got a piece
of DNA that's broken.
of DNA that's broken.
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jer sada ima polomljen komad DNK.
03:07
What does it do?
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Šta onda radi?
03:08
It calls its first responders.
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Zove hitnu pomoć.
03:10
There are two major repair pathways.
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Postoje dva glavna načina popravke.
03:13
The first just takes the DNA
and shoves the two pieces back together.
and shoves the two pieces back together.
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U prvom se samo uzima DNK
i dva komada se ponovo prilepe.
i dva komada se ponovo prilepe.
03:18
This isn't a very efficient system,
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Ovo nije veoma efikasan sistem
03:20
because what happens is
sometimes a base drops out
sometimes a base drops out
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jer se dešava da ponekad ispadne baza
03:23
or a base is added.
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ili se doda.
03:25
It's an OK way to maybe, like,
knock out a gene,
knock out a gene,
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To je dobar sistem da se možda
izbaci neki gen,
izbaci neki gen,
03:28
but it's not the way that we really want
to do genome editing.
to do genome editing.
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ali nije način na koji zaista želimo
da menjamo genom.
da menjamo genom.
03:32
The second repair pathway
is a lot more interesting.
is a lot more interesting.
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Drugi način popravke
mnogo je zanimljiviji.
mnogo je zanimljiviji.
03:35
In this repair pathway,
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Kod ovog načina popravke,
03:36
it takes a homologous piece of DNA.
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uzima se odgovarajući komad DNK.
03:39
And now mind you, in a diploid
organism like people,
organism like people,
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I sada, kod diploidnog organizma
poput ljudi,
poput ljudi,
03:42
we've got one copy of our genome
from our mom and one from our dad,
from our mom and one from our dad,
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imamo jedan primerak genoma
od majke i jedan od oca,
od majke i jedan od oca,
03:46
so if one gets damaged,
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pa ako se jedan ošteti,
03:47
it can use the other
chromosome to repair it.
chromosome to repair it.
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drugi hromozom se može
iskoristiti za popravku.
iskoristiti za popravku.
03:50
So that's where this comes from.
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Odatle potiče ovo.
03:52
The repair is made,
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Vrši se popravka
03:54
and now the genome is safe again.
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i genom je opet bezbedan.
03:56
The way that we can hijack this
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Način na koji možemo ovo prisvojiti
03:58
is we can feed it a false piece of DNA,
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je taj da mu damo komad lažne DNK,
04:02
a piece that has homology on both ends
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komad koji je homologan na oba kraja,
04:04
but is different in the middle.
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ali je drugačiji na sredini.
04:06
So now, you can put
whatever you want in the center
whatever you want in the center
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Sada možete staviti
šta god želite u sredinu
šta god želite u sredinu
04:08
and the cell gets fooled.
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i namagarčićete ćeliju.
04:10
So you can change a letter,
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Možete izmeniti slovo,
04:12
you can take letters out,
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možete vaditi slova,
04:13
but most importantly,
you can stuff new DNA in,
you can stuff new DNA in,
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ali što je najbitnije,
možete ubaciti novu DNK,
možete ubaciti novu DNK,
04:16
kind of like a Trojan horse.
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poput trojanskog konja.
04:19
CRISPR is going to be amazing,
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CRISPR će biti neverovatan,
04:21
in terms of the number of different
scientific advances
scientific advances
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što se tiče broja raznih naučnih otkrića
04:24
that it's going to catalyze.
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koje će katalisati.
04:26
The thing that's special about it
is this modular targeting system.
is this modular targeting system.
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Ono što je kod njega posebno
je ovaj modularni sistem za ciljanje.
je ovaj modularni sistem za ciljanje.
04:29
I mean, we've been shoving DNA
into organisms for years, right?
into organisms for years, right?
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Mislim, već godinama trpamo DNK
u različite organizme, zar ne?
u različite organizme, zar ne?
04:33
But because of the modular
targeting system,
targeting system,
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Ali zbog modularnog sistema za ciljanje,
04:35
we can actually put it
exactly where we want it.
exactly where we want it.
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zapravo možemo da je stavimo
tačno tamo gde želimo.
tačno tamo gde želimo.
04:39
The thing is that there's
a lot of talk about it being cheap
a lot of talk about it being cheap
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Stvar je u tome da se mnogo priča
o tome da je CRISPR jeftin
o tome da je CRISPR jeftin
04:45
and it being easy.
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i da je jednostavan.
04:46
And I run a community lab.
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Ja vodim otvorenu laboratoriju.
04:50
I'm starting to get emails from people
that say stuff like,
that say stuff like,
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Počinjem da dobijam mejlove od ljudi
ovakvog sadržaja:
ovakvog sadržaja:
04:53
"Hey, can I come to your open night
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"Hej, mogu li da dođem na otvoreno veče
04:56
and, like, maybe use CRISPR
and engineer my genome?"
and engineer my genome?"
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i da kao, možda koristim CRISPR
i izmenim svoj genom?"
i izmenim svoj genom?"
04:59
(Laugher)
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(Smeh)
05:01
Like, seriously.
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Kao, zaista.
05:03
I'm, "No, you can't."
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Kažem: "Ne, ne možeš."
05:05
(Laughter)
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(Smeh)
05:06
"But I've heard it's cheap.
I've heard it's easy."
I've heard it's easy."
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"Ali čuo sam da je jeftino.
Čuo sam da je jednostavno."
Čuo sam da je jednostavno."
05:08
We're going to explore that a little bit.
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Malo ćemo da istražimo to.
05:10
So, how cheap is it?
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Koliko je jeftino?
05:12
Yeah, it is cheap in comparison.
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Jeftino je u poređenju
sa drugim stvarima, da.
sa drugim stvarima, da.
05:15
It's going to take the cost of the average
materials for an experiment
materials for an experiment
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Trošak materijala za eksperimente koštaće
05:19
from thousands of dollars
to hundreds of dollars,
to hundreds of dollars,
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od na hiljade dolara do na stotine dolara
05:21
and it cuts the time a lot, too.
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i uštedeće dosta vremena.
05:23
It can cut it from weeks to days.
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Skratiće vreme s nedelja na dane.
05:26
That's great.
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To je sjajno.
05:27
You still need a professional lab
to do the work in;
to do the work in;
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Još uvek vam je potrebna
profesionalna laboratorija za rad,
profesionalna laboratorija za rad,
05:30
you're not going to do anything meaningful
outside of a professional lab.
outside of a professional lab.
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nećete uraditi ništa smisleno
van profesionalne laboratorije.
van profesionalne laboratorije.
05:34
I mean, don't listen to anyone who says
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Mislim, ne slušajte bilo koga ko kaže
05:36
you can do this sort of stuff
on your kitchen table.
on your kitchen table.
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da nešto ovako može da se uradi
na vašem kuhinjskom stolu.
na vašem kuhinjskom stolu.
05:39
It's really not easy
to do this kind of work.
to do this kind of work.
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Zaista nije lako baviti se ovakvim poslom.
Da ne spominjem to da se trenutno
vodi bitka oko patenta,
vodi bitka oko patenta,
05:43
Not to mention,
there's a patent battle going on,
there's a patent battle going on,
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05:46
so even if you do invent something,
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pa i da izmislite nešto,
05:48
the Broad Institute and UC Berkeley
are in this incredible patent battle.
are in this incredible patent battle.
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Institut Brod i Univerzitet Berkli
su u neverovatnoj bici oko patenta.
su u neverovatnoj bici oko patenta.
05:54
It's really fascinating
to watch it happen,
to watch it happen,
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Zaista je fascinantno
gledati kako se to dešava
gledati kako se to dešava
05:57
because they're accusing each other
of fraudulent claims
of fraudulent claims
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jer optužuju jedni druge za prevaru
06:00
and then they've got people saying,
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i onda ljudi govore stvari poput:
06:02
"Oh, well, I signed
my notebook here or there."
my notebook here or there."
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"O, pa ja sam potpisao svesku tu i tamo."
06:05
This isn't going to be settled for years.
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Ovo se neće rešiti godinama.
06:07
And when it is,
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A kada se reši,
06:08
you can bet you're going to pay someone
a really hefty licensing fee
a really hefty licensing fee
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možete da se kladite da ćete nekome
plaćati ogromnu svotu za licenciranje
plaćati ogromnu svotu za licenciranje
06:11
in order to use this stuff.
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da biste koristili ove stvari.
06:13
So, is it really cheap?
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Da li je onda zaista jeftino?
06:15
Well, it's cheap if you're doing
basic research and you've got a lab.
basic research and you've got a lab.
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Pa jeftino je ako radite osnovno
istraživanje i imate laboratoriju.
istraživanje i imate laboratoriju.
06:21
How about easy?
Let's look at that claim.
Let's look at that claim.
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A lako? Hajde da istražimo to.
06:24
The devil is always in the details.
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Uvek se neki vrag ispreči.
06:27
We don't really know
that much about cells.
that much about cells.
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Zapravo ne znamo toliko toga o ćelijama.
06:31
They're still kind of black boxes.
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Još su nešto poput crnih kutija.
06:32
For example, we don't know
why some guide RNAs work really well
why some guide RNAs work really well
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Na primer, ne znamo zašto
neki RNK vodiči funkcionišu veoma dobro,
neki RNK vodiči funkcionišu veoma dobro,
06:37
and some guide RNAs don't.
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a neki RNK vodiči ne funkcionišu.
06:39
We don't know why some cells
want to do one repair pathway
want to do one repair pathway
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Ne znamo zašto neke ćelije žele
da poprave niz na jedan način,
da poprave niz na jedan način,
06:43
and some cells would rather do the other.
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a neke ćelije na drugi.
06:46
And besides that,
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Pored toga,
06:47
there's the whole problem
of getting the system into the cell
of getting the system into the cell
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tu je i ceo problem da uopšte ubacite
06:50
in the first place.
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sistem u ćeliju.
06:51
In a petri dish, that's not that hard,
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U petrijevoj posudi, to nije tako teško,
06:53
but if you're trying to do it
on a whole organism,
on a whole organism,
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ali ako to želite da uradite
na celom organizmu,
na celom organizmu,
06:56
it gets really tricky.
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postaje prilično komplikovano.
06:58
It's OK if you use something
like blood or bone marrow --
like blood or bone marrow --
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U redu je ako koristite nešto
poput krvi ili koštane srži -
poput krvi ili koštane srži -
07:01
those are the targets
of a lot of research now.
of a lot of research now.
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to su mete raznih istraživanja trenutno.
07:03
There was a great story
of some little girl
of some little girl
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Bila je sjajna priča o nekoj devojčici
07:05
who they saved from leukemia
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koju su spasili od leukemije
07:07
by taking the blood out, editing it,
and putting it back
and putting it back
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tako što su izvadili krv,
izmenili je i vratili je
izmenili je i vratili je
07:10
with a precursor of CRISPR.
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uz prethodnika CRISPR-a.
07:12
And this is a line of research
that people are going to do.
that people are going to do.
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Ovo je vrsta istraživanja
kakve će ljudi raditi.
kakve će ljudi raditi.
07:15
But right now, if you want to get
into the whole body,
into the whole body,
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Ali trenutno, ako želite
da pristupite celom telu,
da pristupite celom telu,
07:18
you're probably going
to have to use a virus.
to have to use a virus.
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verovatno ćete morati da korstite virus.
07:20
So you take the virus,
you put the CRISPR into it,
you put the CRISPR into it,
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Uzmete virus, u njega ubacite CRISPR,
07:22
you let the virus infect the cell.
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date virusu da zarazi ćeliju.
07:24
But now you've got this virus in there,
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Ali sada tu imate virus,
07:26
and we don't know what the long-term
effects of that are.
effects of that are.
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i ne znamo šta su
dugotrajne posledice ovoga.
dugotrajne posledice ovoga.
07:29
Plus, CRISPR has some off-target effects,
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Pored toga, CRISPR ima neke nuspojave,
07:31
a very small percentage,
but they're still there.
but they're still there.
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veoma mali broj njih, ali ipak su tu.
07:34
What's going to happen
over time with that?
over time with that?
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Šta će se tokom vremena desiti s time?
07:38
These are not trivial questions,
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Ovo nisu trivijalna pitanja
07:40
and there are scientists
that are trying to solve them,
that are trying to solve them,
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i postoje naučnici koji pokušavaju
na njih da odgovore,
na njih da odgovore,
07:42
and they will eventually,
hopefully, be solved.
hopefully, be solved.
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i to će se desiti pre ili kasnije.
07:45
But it ain't plug-and-play,
not by a long shot.
not by a long shot.
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Ali nije prosto kao pritiskanje dugmeta,
ni blizu toga.
ni blizu toga.
07:48
So: Is it really easy?
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Da li je onda zaista lako?
07:51
Well, if you spend a few years
working it out in your particular system,
working it out in your particular system,
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Pa, ako provedete nekoliko godina
radeći na tome u svom posebnom sistemu,
radeći na tome u svom posebnom sistemu,
07:55
yes, it is.
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da, onda jeste.
07:57
Now the other thing is,
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Druga stvar je,
07:59
we don't really know that much about how
to make a particular thing happen
to make a particular thing happen
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zaista ne znamo mnogo o tome
kako da nateramo da se desi jedna stvar
kako da nateramo da se desi jedna stvar
08:05
by changing particular spots
in the genome.
in the genome.
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tako što ćemo izmeniti
određena mesta u genomu.
određena mesta u genomu.
08:09
We're a long way away from figuring out
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Još nam dosta treba da otkrijemo
08:11
how to give a pig wings, for example.
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kako da svinji damo krila, na primer.
08:14
Or even an extra leg -- I'd settle
for an extra leg.
for an extra leg.
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Ili čak nogu viška -
zadovoljila bih se time.
zadovoljila bih se time.
08:17
That would be kind of cool, right?
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To bi bilo kul, zar ne?
08:18
But what is happening
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Ali dešava se to
08:20
is that CRISPR is being used
by thousands and thousands of scientists
by thousands and thousands of scientists
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da CRISPR koriste
hiljade i hiljade naučnika
hiljade i hiljade naučnika
08:24
to do really, really important work,
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da bi obavljali zaista bitan posao
08:27
like making better models
of diseases in animals, for example,
of diseases in animals, for example,
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poput toga da prave bolje modele
bolesti kod životinja, na primer
bolesti kod životinja, na primer
08:32
or for taking pathways
that produce valuable chemicals
that produce valuable chemicals
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ili stvaranja načina za proizvođenje
dragocenih hemikalija
dragocenih hemikalija
08:37
and getting them into industrial
production and fermentation vats,
production and fermentation vats,
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i njihovo dovođenje u bačve
u industrijskoj proizvodnji i fermentaciji
u industrijskoj proizvodnji i fermentaciji
08:42
or even doing really basic research
on what genes do.
on what genes do.
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ili samo jednostavnog istraživanja
o tome šta rade geni.
o tome šta rade geni.
08:46
This is the story of CRISPR
we should be telling,
we should be telling,
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Ovo je priča o CRISPR-u
koju bi trebalo da pričamo
koju bi trebalo da pričamo
08:48
and I don't like it
that the flashier aspects of it
that the flashier aspects of it
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i ne dopada mi se
što blještavije strane svega ovoga
što blještavije strane svega ovoga
08:52
are drowning all of this out.
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ne daju da izađe na videlo ostalo.
08:54
Lots of scientists did a lot of work
to make CRISPR happen,
to make CRISPR happen,
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Mnogo naučnika radilo je na tome
da se desi CRISPR
da se desi CRISPR
08:58
and what's interesting to me
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i meni je zanimljivo to
09:00
is that these scientists
are being supported by our society.
are being supported by our society.
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da ove naučnike podržava naše društvo.
09:05
Think about it.
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Razmislite o tome.
09:06
We've got an infrastructure that allows
a certain percentage of people
a certain percentage of people
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Imamo infrastrukturu koja dozvoljava
određenom broju ljudi
određenom broju ljudi
09:10
to spend all their time doing research.
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da provode vreme baveći se istraživanjem.
09:14
That makes us all the inventors of CRISPR,
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To sve nas čini izumiteljima CRISPR-a,
09:18
and I would say that makes us all
the shepherds of CRISPR.
the shepherds of CRISPR.
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i rekla bih da to sve nas čini
pastirima CRISPR-a.
pastirima CRISPR-a.
09:23
We all have a responsibility.
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Svi imamo odgovornost.
09:25
So I would urge you to really learn
about these types of technologies,
about these types of technologies,
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Pozvala bih vas sve da zaista naučite više
o ovakvim tehnologijama
o ovakvim tehnologijama
09:30
because, really, only in that way
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jer zaista, jedino na taj način
09:32
are we going to be able to guide
the development of these technologies,
the development of these technologies,
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možemo zaista da vodimo razvoj
ovih tehnologija,
ovih tehnologija,
09:36
the use of these technologies
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upotrebu ovih tehnologija
09:38
and make sure that, in the end,
it's a positive outcome --
it's a positive outcome --
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i da se postaramo da sve ima srećan kraj -
09:43
for both the planet and for us.
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i za planetu i za nas.
09:46
Thanks.
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Hvala.
09:47
(Applause)
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(Aplauz)
ABOUT THE SPEAKER
Ellen Jorgensen - Biologist, community science advocateEllen Jorgensen is at the leading edge of the do-it-yourself biotechnology movement, bringing scientific exploration and understanding to the public.
Why you should listen
In 2009, after many years of working as a molecular biologist in the biotech industry, together with TED Fellow Oliver Medvedik, Jorgensen founded Genspace, a nonprofit community laboratory dedicated to promoting citizen science and access to biotechnology. Despite criticism that bioresearch should be left to the experts, the Brooklyn-based lab continues to thrive, providing educational outreach, cultural events and a platform for science innovation at the grassroots level. At the lab, amateur and professional scientists conduct award-winning research on projects as diverse as identifying microbes that live in Earth's atmosphere and (Jorgensen's own pet project) DNA-barcoding plants, to distinguish between species that look alike but may not be closely related evolutionarily. Fast Company magazine named Genspace one of the world's "Top 10 innovative companies in education."
Ellen Jorgensen | Speaker | TED.com