Ovo je prica o seceru i raku. Postala sam zainteresovana za secer dok sam bila na koledzu. Ne ovu vrstu secera. Radi se o seceru o kojem su nas profesori biologije ucili u kontekstu oblaganja celija. Mozda niste znali da su vase celije oblozene secerom. Ni ja to nisam znala, dok nisam pocela pohadati te predmete na koledu ali tada a to je bilo, recimo 1980ih-- ljudi nisu znali mnogo o tome zasto secer prekriva nase celije. I dok sam kopala po svojim biljeskama, primjetila sam da sam zabiljezila da secer koji obavija nase celije izgleda kao secerni premaz na kikirikiju M&M`a. I ljudi su mislili da je secerni omotac na nasim celijama kao zastitni omotac koji nekako nase celije cini jacima i otpornijima.
This is a talk about sugar and cancer. I became interested in sugar when I was in college. Not this kind of sugar. It was the sugar that our biology professors taught us about in the context of the coating of your cells. Maybe you didn't know that your cells are coated with sugar. And I didn't know that, either, until I took these courses in college, but back then -- and this was in, let's just call it the 1980s -- people didn't know much about why our cells are coated with sugar. And when I dug through my notes, what I noticed I had written down is that the sugar coating on our cells is like the sugar coating on a peanut M and M. And people thought the sugar coating on our cells was like a protective coating that somehow made our cells stronger or tougher.
Ali sada znamo, mnogo decenija kasnije, da je to mnogo komplikovanije od toga, i da su seceri na nasim celijama u stvari mnogo kompleksniji. I kad bi mogli smanjiti sebe na nivo minijaturnog aviona i letjeti duz povrsine svojih celija, to bi izgledalo kao nesto poput ovoga sa geografskim karakteristikama. I sad, kompleksni seceri su drveca i grmlje, tuzne vrbe koje se njisu na vjetru i krecu se sa valovima. I kad sam pocela razmisljati o svim tim slozenim secerima koji su kao ovi listovi na nasim celijama, to je postao jedan od najinteresantnijih problema sa kojima sam se srela kao biolog i hemicar. I sad tezimo da mislimo o tim secerima sto naseljavaju povrsinu nasih celija kao o jeziku. Imaju mnostvo informacija sadrzanih u njihovoj kompleksnoj strukturi.
But we now know, many decades later, that it's much more complicated than that, and that the sugars on our cells are actually very complex. And if you could shrink yourself down to a little miniature airplane and fly right along the surface of your cells, it might look something like this -- with geographical features. And now, the complex sugars are these trees and bushes -- weeping willows that are swaying in the wind and moving with the waves. And when I started thinking about all these complex sugars that are like this foliage on our cells, it became one of the most interesting problems that I encountered as a biologist and also as a chemist. And so now we tend to think about the sugars that are populating the surface of our cells as a language. They have a lot of information stored in their complex structures.
Ali sta nam pokusavaju reci? Mogu vam reci da znamo neke informacije koje dolaze od tih secera, i cini se da su vec nevjerovatno vazne u svijetu medicine.
But what are they trying to tell us? I can tell you that we do know some information that comes from these sugars, and it's turned out already to be incredibly important in the world of medicine.
Npr. jedna stvar koju nam vasi seceri govore je vasa krvna grupa. Znaci, vasa krvna zrnca, vasa crvena krvna zrnca su prekrivena secerima i hemijski spojevi tih secera odredjuju vasu krvnu grupu. Npr. ja znam da sam krvna krupa 0. Koliko je ljudi takodjer nulta grupa? Podignite ruke. Poprilicno je cesta, tako da,kad imamo samo par dignutih ruku il ne prdajete paznju ili ne znate svoju krvnu grupu, a oboje je lose.
For example, one thing your sugars are telling us is your blood type. So your blood cells, your red blood cells, are coated with sugars, and the chemical structures of those sugars determine your blood type. So for example, I know that I am blood type O. How many people are also blood type O? Put your hands up. It's a pretty common one, so when so few hands go up, either you're not paying attention or you don't know your blood type, and both of those are bad.
(Smijeh)
(Laughter)
Ali za one koji dijele krvnu grupu 0 sa mnom, znaci da mi imamo takve hemijske spojeve na povrsini nasih celija: tri jednostavna secera spojena zajedno tvore slozeniji secer. I to je, po definiciji, nulta krvna grupa.
But for those of you who share the blood type O with me, what this means is that we have this chemical structure on the surface of our blood cells: three simple sugars linked together to make a more complex sugar. And that, by definition, is blood type O.
Sad, koliko ljudi je krvna grupa A? Ovdje. To znaci da imate enzim u vasi celijama koji dodaje jedan gradivni element vise, taj crveni secer, kako bi izgradio slozeniju strukturu. A koliko je ljudi krvna grupa B? Poprilicno dosta. Vi imate malkice drugaciji enzim od ljudi sa A grupom, tako da tvorite malkice drugaciju strukturu, i vi koji ste AB grupa imate enzim od majke, drugi enzim od oca, i pravite obe ove strukture u priblizno istim proporcijama. Kad se saznalo za ovo, a to je bilo u prethodnom stoljecu, omogucilo je jedan od najvaznijih medicinskih zahvata na svijetu, a to je, naravno, transfuzija krvi. I znajuci koja ste krvna grupa, mozemo biti sigurni da, ako ikad zatrebate transfuziju, da vas donor ima istu krvnu grupu, tako da vasa krv ne vidi tudje secere koji joj se ne bi svidjeli i sigurno bi ih odbacila.
Now, how many people are blood type A? Right here. That means you have an enzyme in your cells that adds one more building block, that red sugar, to build a more complex structure. And how many people are blood type B? Quite a few. You have a slightly different enzyme than the A people, so you build a slightly different structure, and those of you that are AB have the enzyme from your mother, the other enzyme from your father, and now you make both of these structures in roughly equal proportions. And when this was figured out, which is now back in the previous century, this enabled one of the most important medical procedures in the world, which, of course, is the blood transfusion. And by knowing what your blood type is, we can make sure, if you ever need a transfusion, that your donor has the same blood type, so that your body doesn't see foreign sugars, which it wouldn't like and would certainly reject.
Sta nam jos pokusavaju reci seceri sa nasih celija? Pa, ti seceri bi nam mogli poruciti da imate rak. Prije nekoliko decenija, korelacije su se pocele javljati iz analiza tumorskih tkiva. I tipican scenario je da pacijentu otkrivaju tumor, i tkivo bi se uklonilo biopsijom i onda poslano na patologiju gdje bi se tkivo analiziralo i traze se hemijske promjene koje bi mogle informisati onkologa o najboljem nacinu lijecenja. Ono sto je otkriveno iz studija kao ove je da su se ti seceri promijenili nakon sto se celija pretvori iz zdrave u bolesnu. I te korelacije su se pojavljivale iznova i iznova Ali je veliko pitanje na tom polju bilo: Zasto? Zasto tumori imaju drugacije secere? Koja je vaznost toga? Zasto se to desava i sta mozemo uciniti povodom toga ako se ispostavi da je povezano sa procesom bolesti?
What else are the sugars on the surface of your cells trying to tell us? Well, those sugars might be telling us that you have cancer. So a few decades ago, correlations began to emerge from the analysis of tumor tissue. And the typical scenario is a patient would have a tumor detected, and the tissue would be removed in a biopsy procedure and then sent down to a pathology lab where that tissue would be analyzed to look for chemical changes that might inform the oncologist about the best course of treatment. And what was discovered from studies like that is that the sugars have changed when the cell transforms from being healthy to being sick. And those correlations have come up again and again and again. But a big question in the field has been: Why? Why do cancers have different sugars? What's the importance of that? Why does it happen, and what can we do about it if it does turn out to be related to the disease process?
Dakle, jedna od promjena koje izucavamo je porast u gustoci pojedinog secera kojeg nazivamo sialna kiselina. I mislim da ce ovo biti jedan od najznacajnijih secera naseg doba, i zelim potakuti svakoga da se upozna sa ovim nazivom. Sialna kiselina nije tip secera koji jedemo. To su drugaciji seceri. Ovo je secer koji je u stvari pronadjen u odredjenoj razini na svim nasim celijama u tijelu. Ustavri je poprilicno cest na vasim celijama. Ali iz nekog razloga, celije tumora, barem u uspjesnoj, progresivnoj bolesti teze da imaju vise sialne kiseline nego sto ima normalna, zdrava celija. I zasto? Sta to znaci? Pa, ono sto smo naucili je da je to povezano sa vasim imunim sistemom.
So, one of the changes that we study is an increase in the density of a particular sugar that's called sialic acid. And I think this is going to be one of the most important sugars of our times, so I would encourage everybody to get familiar with this word. Sialic acid is not the kind of sugar that we eat. Those are different sugars. This is a kind of sugar that is actually found at certain levels on all of the cells in your body. It's actually quite common on your cells. But for some reason, cancer cells, at least in a successful, progressive disease, tend to have more sialic acid than a normal, healthy cell would have. And why? What does that mean? Well, what we've learned is that it has to do with your immune system.
Dozvolite mi da vam kazem malo vise o znacaju vaseg imunog sistema u tumoru. I ovo je nesto sto je, mislim, mnogo prisutno u danasnjim vijestima. Znate, ljudi se pocinju upoznavati sa terminima "imunoterapija tumora." I neki od vas bi cak mogli znati ljude kojima je koristio ovakav nacin lijecenja raka. Ono sto sada znamo je da vase celije imuniteta, a to su bijela krvna zrnca koja proticu vasim krvotokom stite vas svakodnevno od losih stvari-- ukljucujuci tumor. I tako na ovoj slici, te male zelene loptice su vase celije imuniteta, a ta velika roza celija je celija raka. Te celije imuniteta idu okolo i probaju sve celije u vasem tijelu. To je njihov posao. I vecinu vremena, celije imaju dobar okus.
So let me tell you a little bit about the importance of your immune system in cancer. And this is something that's, I think, in the news a lot these days. You know, people are starting to become familiar with the term "cancer immune therapy." And some of you might even know people who are benefiting from these very new ways of treating cancer. What we now know is that your immune cells, which are the white blood cells coursing through your bloodstream, protect you on a daily basis from things gone bad -- including cancer. And so in this picture, those little green balls are your immune cells, and that big pink cell is a cancer cell. And these immune cells go around and taste all the cells in your body. That's their job. And most of the time, the cells taste OK.
Ali s vrmena na vrijeme, celija moze imat ruzan okus. Nadajmo se da su to celija raka, i kad do tih celije imuniteta dopre los okus, one lansiraju napad i ubiju te celije. Znamo to. Takodjer znamo da ako mozete potencirati taj okus, ako mozete ohrabriti te celije imuniteta da odgriznu veliki komad celije raka, dobijete bolji posao stiteci sebe od raka svakodnevno i mozda cak i izlijecite rak. Sada postoji nekoliko lijekova na trzistu koji s koriste u lijecenju pacijenta s rakom koji djeluju isto kao ovaj proces. Aktiviraju imuni sistem tako da imuni sistem postane snazniji kako bi nas zastitio od raka.
But once in a while, a cell might taste bad. Hopefully, that's the cancer cell, and when those immune cells get the bad taste, they launch an all-out strike and kill those cells. So we know that. We also know that if you can potentiate that tasting, if you can encourage those immune cells to actually take a big old bite out of a cancer cell, you get a better job protecting yourself from cancer every day and maybe even curing a cancer. And there are now a couple of drugs out there in the market that are used to treat cancer patients that act exactly by this process. They activate the immune system so that the immune system can be more vigorous in protecting us from cancer.
U stvari, jedan od tih lijekova je mozda spasio i zivot predjednika Dzimija Kartera. Sjecate se, Predsjednik Karter je imao maligni melanom koji je metastazirao do njegovog mozga i da je dijagnoza obicno popracena brojevima poput "..mjeseci zivota." Ali su njega lijecili jednim od ovih novih imuno-stimulirajucih lijekova, i sad se cini da je njegov melanom u remisiji sto je nevjerovatno, imajuci u vidu situaciju od prije samo par godina. U stvari, to je tako zadivljujuce da provokativne izjave poput ove: "Rak ima momenat penicilina" s ovim novim imunoterapijskim lekovima Mislim, zaista je smjelo reci takvo nesto za jednu bolest sa kojom se borimo dugo vremena i uglavnom gubimo borbu sa njom. Ovo je veoma uzbudljivo.
In fact, one of those drugs may well have spared President Jimmy Carter's life. Do you remember, President Carter had malignant melanoma that had metastasized to his brain, and that diagnosis is one that is usually accompanied by numbers like "months to live." But he was treated with one of these new immune-stimulating drugs, and now his melanoma appears to be in remission, which is remarkable, considering the situation only a few years ago. In fact, it's so remarkable that provocative statements like this one: "Cancer is having a penicillin moment," people are saying, with these new immune therapy drugs. I mean, that's an incredibly bold thing to say about a disease which we've been fighting for a long time and mostly losing the battle with. So this is very exciting.
Sad, kakve veze ovo ima sa secerima? Pa, reci cu vam sta smo naucili. Kad se celija imuniteta priljubi uz celiju raka da je okusi, ona trazi znakove bolesti, i ako nadje te znakove, celija se aktivira i lansira raketni napad te ubije celiju. Ali ako ta celija ima gustu sumu tog secera, sialne kiseline, pa, pocinje da ima stvarno dobar okus. A tu je i protein na celijama imuniteta koji grabi sialnu kiselinu i ako taj protein bude zadrzan na toj sinapsi izmedju celije imuniteta i celije raka, stavi tu celiju imuniteta na spavanje. Sialne kiseline govore celijama imuniteta, "Hej, ova celija je uredu. Nema se sta vidjeti ovdje, produzi dalje. Gledaj negdje drugdje." Drugim rijecima, dok god nase celije nose debeli sloj sialne kiseline, izgledaju fantasticno, zar ne? To je nejvejrovatno. I sta kad bi mogli skinuti taj omotac i skloniti taj secer? Pa, vas imuni sistem bi mogao vidjeti celiju raka onakvom kakva stvarno jest: Nesto sto mora biti unisteno.
Now what does this have to do with sugars? Well, I'll tell you what we've learned. When an immune cell snuggles up against a cancer cell to take a taste, it's looking for signs of disease, and if it finds those signs, the cell gets activated and it launches a missile strike and kills the cell. But if that cancer cell has a dense forest of that sugar, sialic acid, well, it starts to taste pretty good. And there's a protein on immune cells that grabs the sialic acid, and if that protein gets held at that synapse between the immune cell and the cancer cell, it puts that immune cell to sleep. The sialic acids are telling the immune cell, "Hey, this cell's all right. Nothing to see here, move along. Look somewhere else." So in other words, as long as our cells are wearing a thick coat of sialic acid, they look fabulous, right? It's amazing. And what if you could strip off that coat and take that sugar away? Well, your immune system might be able to see that cancer cell for what it really is: something that needs to be destroyed.
To je ono sto radimo u mom laboratoriju. Razvijamo nove lijekove koji su ustvari kosilice za povrsinu celije-- Molekule koje idu dole do povrsine tih celija raka i samo pokidaju te sialne kiseline, tako da imuni sistem moze dosegnuti svoj puni potencijal u eliminaciji tih celija iz naseg tijela.
And so this is what we're doing in my lab. We're developing new medicines that are basically cell-surface lawnmowers -- molecules that go down to the surface of these cancer cells and just cut off those sialic acids, so that the immune system can reach its full potential in eliminating those cancer cells from our body.
Za kraj, dopustite mi samo da vam napomenem jos jednom: vase celije su prekrivene secerima. Ti seceri govore celijama oko tih celija jesu li dobre ili lose celije. I to je vazno, jer nas imuni sistem treba da pusti dobre celije na miru. U protivnom, imali bismo autoimune bolesti Ali povremeno, tumori dobiju sposobnost da izraze te nove secere. I sad kad razumijemo kako ti seceri ocaravaju imuni sistem, mozemo pronaci nove lijekove kako bi probudili te celije imuniteta, i rekli im, "Ignorisite secere, jedite celije i uzivajte u ukusu tog raka."
So in closing, let me just remind you again: your cells are coated with sugars. The sugars are telling cells around that cell whether the cell is good or bad. And that's important, because our immune system needs to leave the good cells alone. Otherwise, we'd have autoimmune diseases. But once in a while, cancers get the ability to express these new sugars. And now that we understand how those sugars mesmerize the immune system, we can come up with new medicines to wake up those immune cells, tell them, "Ignore the sugars, eat the cell and have a delicious snack, on cancer."
Hvala vam.
Thank you.
(Aplauz)
(Applause)