What I'm going to show you are the astonishing molecular machines that create the living fabric of your body. Now molecules are really, really tiny. And by tiny, I mean really. They're smaller than a wavelength of light, so we have no way to directly observe them. But through science, we do have a fairly good idea of what's going on down at the molecular scale. So what we can do is actually tell you about the molecules, but we don't really have a direct way of showing you the molecules.
Pokazal vam bom osupljive molekularne naprave, ki sestavljajo živo tovarno vašega telesa. Molekule so res izjemno majhne. Ko rečem majhne, to dejansko to pomeni. Manjše so, kot meri valovna dolžina svetlobe, zato jih ne moremo neposredno opazovati. A znanost nam omogoča, da si lahko predstavljamo, kaj se dogaja na molekularni ravni. Lahko vam torej o molekulah pripovedujemo, ne moremo pa jih vam neposredno pokazati.
One way around this is to draw pictures. And this idea is actually nothing new. Scientists have always created pictures as part of their thinking and discovery process. They draw pictures of what they're observing with their eyes, through technology like telescopes and microscopes, and also what they're thinking about in their minds. I picked two well-known examples, because they're very well-known for expressing science through art.
Lahko si jih predstavljamo z risanjem. Ta ideja pa pravzaprav ni nova. Za znanstvenike je risanje vedno predstavljalo del miselnega in raziskovalnega postopka. Narišejo, kar vidijo z očmi preko tehnoloških naprav, kot so teleskopi in mikroskopi, in k temu dodajo svoje misli in ideje. Izbral sem dva znana primera, saj predstavljata znanstveno izražanje skozi umetnost.
And I start with Galileo, who used the world's first telescope to look at the Moon. And he transformed our understanding of the Moon. The perception in the 17th century was the Moon was a perfect heavenly sphere. But what Galileo saw was a rocky, barren world, which he expressed through his watercolor painting.
Začel bom z Galileom, ki je s prvim teleskopom na svetu opazoval Luno. S tem je spremenil naše dojemanje Lune. V 17. stoletju so verjeli, da je Luna popolno nebesno telo. Galileo pa je videl kamnit, nerodoviten svet, ki ga je izrazil skozi akvarelno slikanje.
Another scientist with very big ideas, the superstar of biology is Charles Darwin. And with this famous entry in his notebook, he begins in the top left-hand corner with, "I think," and then sketches out the first tree of life, which is his perception of how all the species, all living things on Earth are connected through evolutionary history -- the origin of species through natural selection and divergence from an ancestral population.
Drug znanstvenik z izjemnimi idejami, superzvezdnik biologije, je Charles Darwin. Ta znamenit zapis v njegovi beležnici začne v zgornjem levem kotu z besedo "Mislim," zraven pa je skica prvega rodoslovnega drevesa, njegove predstave, da so vse vrste, vsa živa bitja na Zemlji, povezana z evolucijsko zgodovino -- izvorom vrst preko naravnega izbora in odstopanjem od populacije prednikov.
Even as a scientist, I used to go to lectures by molecular biologists and find them completely incomprehensible, with all the fancy technical language and jargon that they would use in describing their work, until I encountered the artworks of David Goodsell, who is a molecular biologist at the Scripps Institute. And his pictures -- everything's accurate and it's all to scale. And his work illuminated for me what the molecular world inside us is like.
Čeprav sem sam znanstvenik, so se mi predavanja molekularnih biologov zdela popolnoma nerazumljiva zaradi posebnega tehničnega jezika in žargona, s katerim so opisovali svoje delo, dokler nisem odkril umetnin Davida Goodsella, molekularnega biologa na inštitutu Scripps. Na njegovih slikah je vse točno in v pravem merilu. Njegovo delo mi je osvetlilo razumevanje molekularnega sveta znotraj nas.
So this is a transection through blood. In the top left-hand corner, you've got this yellow-green area. The yellow-green area is the fluid of blood, which is mostly water, but it's also antibodies, sugars, hormones, that kind of thing. And the red region is a slice into a red blood cell. And those red molecules are hemoglobin. They are actually red; that's what gives blood its color. And hemoglobin acts as a molecular sponge to soak up the oxygen in your lungs and then carry it to other parts of the body.
To je prikaz krvi. V zgornjem levem delu je rumeno-zeleno območje. Gre za tekočino v krvi, ki je večinoma iz vode, a tudi iz protiteles, sladkorjev, hormonov in podobnega. Rdeče območje predstavlja prerez rdeče krvničke. Te rdeče molekule so hemoglobin. V resnici so rdeče in to daje krvi barvo. Hemoglobin deluje kot molekularna spužva, ki vsrka kisik iz vaših pljuč in ga prenaša po drugih delih telesa.
I was very much inspired by this image many years ago, and I wondered whether we could use computer graphics to represent the molecular world. What would it look like? And that's how I really began. So let's begin.
Ta slika me je pred mnogo leti izjemno navdušila, da sem prišel na idejo uporabe računalniške grafike za predstavitev molekularnega sveta. Kako bi izgledal? Tako sem torej začel. Pa poglejmo. To je DNK v običajni obliki dvojne vijačnice.
This is DNA in its classic double helix form. And it's from X-ray crystallography, so it's an accurate model of DNA. If we unwind the double helix and unzip the two strands, you see these things that look like teeth. Those are the letters of genetic code, the 25,000 genes you've got written in your DNA. This is what they typically talk about -- the genetic code -- this is what they're talking about. But I want to talk about a different aspect of DNA science, and that is the physical nature of DNA. It's these two strands that run in opposite directions for reasons I can't go into right now. But they physically run in opposite directions, which creates a number of complications for your living cells, as you're about to see, most particularly when DNA is being copied.
Strukturo smo določili z rentgensko kristalografijo, zato gre za pravilen model DNK. Če dvojno vijačnico odvijemo in razpremo niza, vidite majhne zobce. To so črke genskega zapisa, 25.000 genov, zapisanih v vašem DNK. V mislih imamo torej to, ko govorimo o genskem zapisu. A želel bi predstaviti drugačen pogled na znanost DNK, in sicer fizikalno naravo DNK. Ta dva niza tečeta v nasprotnih smereh, a o razlogih za to kdaj drugič. Fizično torej potekata v nasprotnih smereh, kar ustvari mnogo zapletov za vaše žive celice, kar boste tudi videli, še posebej pri kopiranju DNK.
And so what I'm about to show you is an accurate representation of the actual DNA replication machine that's occurring right now inside your body, at least 2002 biology. So DNA's entering the production line from the left-hand side, and it hits this collection, these miniature biochemical machines, that are pulling apart the DNA strand and making an exact copy. So DNA comes in and hits this blue, doughnut-shaped structure and it's ripped apart into its two strands. One strand can be copied directly, and you can see these things spooling off to the bottom there. But things aren't so simple for the other strand because it must be copied backwards. So it's thrown out repeatedly in these loops and copied one section at a time, creating two new DNA molecules.
Pokazal vam bom natačno predstavitev dejanskega mehanizma podvojevanja DNK, ki se trenutno odvija v vašem telesu, vsaj pri biologiji, znani leta 2002. DNK torej z leve strani vstopi na tekoči trak in trči ob ta skupek, te majcene biokemične naprave, ki razpirajo verigo DNK in ustvarjajo natančno kopijo. DNK torej vstopi in trči ob modro strukturo v obliki krofa, kjer se razpre na dva niza. En niz se lahko prepiše neposredno in vidite, kako se navija navzdol. A pri drugem nizu je postopek bolj zapleten, saj mora biti prepisan v nasprotni smeri. Ta niz se v zankah prepisuje po delčkih in ustvarja dve novi molekuli DNK.
Now you have billions of this machine right now working away inside you, copying your DNA with exquisite fidelity. It's an accurate representation, and it's pretty much at the correct speed for what is occurring inside you. I've left out error correction and a bunch of other things.
Milijarde takih naprav trenutno neumorno delajo v vaših telesih in prepisujejo vaš DNK z izjemno natačnostjo. Ta natančna predstavitev prikazuje tudi bolj ali manj točno hitrost dejanskega postopka. Izpustil sem popravo napak in precej drugih podatkov.
(Laughter)
To je delo izpred mnogo let.
This was work from a number of years ago-- Thank you.
Hvala. To je delo izpred mnogo let, sedaj pa vam bom
(Applause)
This is work from a number of years ago, but what I'll show you next is updated science, it's updated technology. So again, we begin with DNA. And it's jiggling and wiggling there because of the surrounding soup of molecules, which I've stripped away so you can see something. DNA is about two nanometers across, which is really quite tiny. But in each one of your cells, each strand of DNA is about 30 to 40 million nanometers long. So to keep the DNA organized and regulate access to the genetic code, it's wrapped around these purple proteins -- or I've labeled them purple here. It's packaged up and bundled up. All this field of view is a single strand of DNA. This huge package of DNA is called a chromosome. And we'll come back to chromosomes in a minute.
pokazal posodobljeno znanost in tehnologijo. Še enkrat, začnemo z DNK. Tako miga zaradi mešanice molekul okrog nje, ki pa smo jih odstranili, da lahko vidite bistveno. DNK v premeru meri okrog dva nanometra, kar je resnično malo. A v vsaki vaši celici je vsak niz DNK dolg od 30 do 40 milijonov nanometrov. Da je DNK urejena in s tem tudi dostop do genskega zapisa, je zavita okrog teh vijoličnih beljakovin, kot so označene tukaj. Zavita in zamotana je okrog njih. Pri tem gre le za en sam niz DNK. Ta celoten velik paket DNK pa se imenuje kromosom. K njim se bomo vrnili čez minuto.
We're pulling out, we're zooming out, out through a nuclear pore, which is the gateway to this compartment that holds all the DNA, called the nucleus. All of this field of view is about a semester's worth of biology, and I've got seven minutes, So we're not going to be able to do that today? No, I'm being told, "No."
S pogledom se torej oddaljujemo skozi jedrno poro, ki predstavlja pot do tega oddelka, kjer se nahaja DNK, imenovan jedro. To celotno področje zahteva kak semester pri biologiji, jaz pa imam le sedem minut. Torej tega ne bomo mogli pokazati danes? Ne, rekli so mi, da ne.
This is the way a living cell looks down a light microscope. And it's been filmed under time-lapse, which is why you can see it moving. The nuclear envelope breaks down. These sausage-shaped things are the chromosomes, and we'll focus on them. They go through this very striking motion that is focused on these little red spots. When the cell feels it's ready to go, it rips apart the chromosome. One set of DNA goes to one side, the other side gets the other set of DNA -- identical copies of DNA. And then the cell splits down the middle. And again, you have billions of cells undergoing this process right now inside of you.
Tako je videti živa celica skozi svetlobni mikroskop. Posneta je pospešeno, zato jo vidite v gibanju. Jedrna ovojnica se pretrga, zanimajo pa nas te podolgovate stvari oz. kromosomi. Njihovo gibanje je presenetljivo, označeno pa je z rožnato barvo. Ko celice čutijo, da so pripravljene, pretrgajo kromosom. En niz DNK gre na eno stran, druga stran pa dobi novega oz. identično kopijo DNK. Nato se celice razpolovijo. Še enkrat, milijarda celic gre prav zdaj skozi ta postopek v vašem telesu.
Now we're going to rewind and just focus on the chromosomes, and look at its structure and describe it. So again, here we are at that equator moment. The chromosomes line up. And if we isolate just one chromosome, we're going to pull it out and have a look at its structure. So this is one of the biggest molecular structures that you have, at least as far as we've discovered so far inside of us. So this is a single chromosome. And you have two strands of DNA in each chromosome. One is bundled up into one sausage. The other strand is bundled up into the other sausage.
Vrnili se bomo nazaj in osredotočili na kromosome ter opisali njihovo strukturo. Spet smo pri tem trenutku delitve. Kromosomi se poravnajo. Osredotočimo se le na en kromosom, ga izvzamemo in si ogledamo njegovo strukturo. To je ena od večjih molekularnih struktur v vašem telesu, vsaj kar smo jih odkrili doslej. To je en kromosom. V vsakem imate dva niza DNK. En je zavit v en sveženj, drug pa v drugega.
These things that look like whiskers that are sticking out from either side are the dynamic scaffolding of the cell. They're called microtubules, that name's not important. But we're going to focus on the region labeled red here -- and it's the interface between the dynamic scaffolding and the chromosomes. It is obviously central to the movement of the chromosomes. We have no idea, really, as to how it's achieving that movement.
To, kar izgleda kot mačje brčice na vsaki strani, je dinamični gradbeni oder celice. Imenujejo se mikrotubuli. Ime ni tako pomembno. Osredotočili se bomo na to rdeče označeno območje, ki predstavlja stičišče med dinamičnim gradbenim odrom in kromosomi. To je ključno za gibanje kromosomov. Ne vemo, kako pride do tega gibanja.
We've been studying this thing they call the kinetochore for over a hundred years with intense study, and we're still just beginning to discover what it's about. It is made up of about 200 different types of proteins, thousands of proteins in total. It is a signal broadcasting system. It broadcasts through chemical signals, telling the rest of the cell when it's ready, when it feels that everything is aligned and ready to go for the separation of the chromosomes. It is able to couple onto the growing and shrinking microtubules.
Ta kinetični lok je predmet intenzivnega preučevanja že več kot sto let in šele začenjamo odkrivati, za kaj gre. Sestavlja ga okrog 200 različnih vrst beljakovin, skupaj na tisoče beljakovin. Je sistem širjenja signala. Preko kemičnih signalov sporoča preostali celici, kdaj je pravi čas, kdaj čuti, da je vse na pravem mestu in pripravljeno za delitev kromosomov. Lahko se pripne na mikrotubule, ki rastejo in se krčijo.
It's involved with the growing of the microtubules, and it's able to transiently couple onto them. It's also an attention-sensing system. It's able to feel when the cell is ready, when the chromosome is correctly positioned. It's turning green here because it feels that everything is just right. And you'll see, there's this one little last bit that's still remaining red. And it's walked away down the microtubules. That is the signal broadcasting system sending out the stop signal. And it's walked away -- I mean, it's that mechanical. It's molecular clockwork.
Sodeluje pri rasti mikrotubulov in nanje se lahko začasno pripne. Je tudi sistem zaznavanja pripravljenosti. Zaznava, kdaj je celica pripravljena, kdaj je kromosom pravilno postavljen. Tu se obarva zeleno, saj zazna, da je vse na pravem mestu. Kot vidite, je tu še majhen del, ki je še vedno rdeč. Pomika se vzdolž mikrotubulov. Ta sistem sporoča signal zaustavitve. Odhaja stran. Dobesedno tako mehansko je. To je urni mehanizem molekule.
This is how you work at the molecular scale. So with a little bit of molecular eye candy,
Tako deluje vaše telo na molekularni ravni. Da bi bila molekula še bolj privlačna,
(Laughter)
so tu še kinezini v oranžni barvi,
we've got kinesins, the orange ones. They're little molecular courier molecules walking one way. And here are the dynein, they're carrying that broadcasting system. And they've got their long legs so they can step around obstacles and so on. So again, this is all derived accurately from the science. The problem is we can't show it to you any other way.
majhne molekularne kurirske celice, ki se pomikajo v eni smeri. Imamo tudi dineine, ki nosijo ta informacijski sistem. S svojimi dolgimi nogami se lahko izognejo oviram. Vse to je točen prikaz znanstvenih odkritij. Težava je, da tega ne moremo prikazati drugače.
Exploring at the frontier of science, at the frontier of human understanding, is mind-blowing. Discovering this stuff is certainly a pleasurable incentive to work in science. But most medical researchers -- discovering the stuff is simply steps along the path to the big goals, which are to eradicate disease, to eliminate the suffering and the misery that disease causes and to lift people out of poverty.
Raziskovanje novega področja znanosti, novega področja človeškega razumevanja, je noro. Odkrivanje teh stvari je gotovo prijetna spodbuda za delo v znanosti. A večina raziskovalcev v medicini -- Odkrivanje teh stvari so le koraki na poti do velikih ciljev, kot je izkoreninjanje bolezni, trpljenja in nesreče, ki jih povzročajo, ter popeljati ljudi iz revščine.
Thank you.
Hvala vam.
(Applause)
(Aplavz)