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.
Ovo je govor o šećeru i raku. Počela sam se zanimati za šećer kada sam bila na fakultetu. Ne ova vrsta šećera. Šećer o kojemu su nas podučavali naši profesori biologije u kontekstu premazivanja stanica. Možda niste znali da su vaše stanice premazane šećerom. Nisam ni ja, također, sve dok nisam slušala te kolegije, ali tada -- i to je bilo u, recimo samo 1980-ima -- ljudi nisu znali mnogo o tome zašto su naše stanice premazane šećerom. I kada sam kopala po svojim bilješkama, primijetila sam da sam zapisala da je šećerni premaz na našim stanicama isti kao šećerni premaz na kikirikiju M&M-a. A ljudi su mislili da je šećerni premaz na našim stanicama kao zaštitni premaz koji je nekako naše stanice učinio snažnijima ili jačima.
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 danas znamo, nakon mnogo desetljeća, da je to mnogo složenije i da su šećeri na našim stanicama u stvari jako složeni. I kada biste se mogli pretvoriti u minijaturni avion, i preletjeti iznad površine svojih stanica, to bi izgledalo nekako ovako -- s geografskim značajkama. Složeni šećeri su ovo drveće i grmlje, tužne vrbe koje se njišu na vjetru i ljuljaju s valovima. I kada sam počela razmišljati o svim tim složenim šećerima kao o vrsti pokrova na našim stanicama, to je postao jedan od najzanimljivijih problema na koji sam naišla kao biolog i kao kemičar. I sada nastojimo razmišljati o šećerima koji nastanjuju površinu naših stanica, kao o jeziku. Sadrže mnogo informacija u svojim složenim strukturama.
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.
Ali što nam pokušavaju reći? Mogu vam reći da znamo neke informacije koje dolaze od tih šećera i ispada da su nevjerojatno važne u svijetu medicine.
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.
Na primjer, jedna stvar koju nam šećeri govore je vaša krvna grupa. Vaše krvne stanice, crvene krvne stanice, prevučene su šećerom i kemijska struktura tih šećera određuje vašu krvnu grupu. Tako na primjer, znam da je moja krvna grupa 0. Koliko još ljudi ima krvnu grupu 0? Dignite ruke. Prilično je česta pa kada je ovako malo ruku u zraku, ili ne obraćate pozornost, ili ne znate vašu krvnu grupu, u oba slučaja to je loše.
(Laughter)
(Smijeh)
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.
Ali za vas koji dijelite krvnu grupu 0 sa mnom, to znači da imamo ovakvu kemijsku strukturu na površini naših krvnih stanica: tri jednostavna šećera povezana u složeniji šećer. I to je, po definiciji, krvna grupa 0.
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.
Sada, koliko ljudi ima krvnu grupu A? Eto. To znači da vi imate enzim u vašim stanicama, koji dodaje još jedan gradivni dio, taj crveni šećer, koji čini još složeniju strukturu. I koliko ljudi ima krvnu grupu B? Dobar dio. Vi imate nešto drugačiji enzim nego osobe iz A grupe pa vi imate nešto drugačiju strukturu, a vi koji imate AB grupu imate jedan enzim od svoje majke, drugi enzim od vašeg oca i sada imate obje te strukture u približno jednakim omjerima. I kada je to otkriveno, sada već u prošlom stoljeću, to je omogućilo jedan od najvažnijih medicinskih postupaka u svijetu, a to je, naravno, transfuzija krvi. I poznavajući svoju krvnu grupu, možemo biti uvjereni, da ako ikad budete trebali transfuziju, da i vaš donor ima istu krvnu grupu, kako se vaše tijelo ne bi susrelo sa stranim šećerima, koji mu se ne bi svidjeli i koje bi sigurno odbacio.
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?
Što nam još šećeri na površini stanica pokušavaju reći? Pa, ti šećeri bi nam mogli reći da imate rak. Tako su se prije nekoliko desetljeća počele pojavljivati korelacije u analizi kancerogenog tkiva. I tipičan scenarij je da se pacijentu otkrije tumor, tkivo bude uklonjeno biopsijom i poslano u laboratorij patologije, gdje bi bilo analizirano u potrazi za kemijskim promjenama, koje bi mogle informirati onkologa o najboljem tijeku liječenja. Ono što je bilo otkriveno u takvim studijama, je da su se šećeri promijenili kada su se stanice transformirale iz zdravih u bolesne. I te su se korelacije uvijek iznova pojavljivale. Ali veliko pitanje bilo je: Zašto? Zašto rak ima drugačije šećere? U čemu je važnost toga? Zašto se to događa i što mi možemo učiniti s tim ako se ispostavi da su povezani s procesom bolesti?
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.
Pa, jedna od promjena koje smo proučavali je povećanje gustoće određenog šećera, koji se zove sijalična kiselina. I ja mislim da će to biti jedan od najvažnijih šećera našeg vremena, pa bih ohrabrila sve da zapamte tu riječ. Sijalična kiselina nije onaj šećer koji jedemo. To su drugačiji šećeri. Ovo je vrsta šećera koja je zapravo nađena u određenim razinama na svim stanicama u vašem tijelu. Zapravo je jako učestala na vašim stanicama. Ali iz nekog razloga, stanice raka, barem u uspješnoj, progresivnoj bolesti, naginju većim razinama sijalične kiseline od normalnih, zdravih stanica. Zašto? Što to znači? Pa, ono što smo naučili je da je to povezano s vašim imunološkim sustavom.
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.
Reći ću vam malo o važnosti vašeg imunološkog sustava tijekom raka. I to je nešto što je, čini mi se, često u vijestima ovih dana. Znate, ljudi se počinju upoznavati s izrazom "imunoterapija u liječenju raka." I neki od vas možda i znaju ljude koji imaju koristi od tih posve novih načina tretiranja raka. Ono što znamo sada je da vas vaše imunološke stanice, bijele krvne stanice, koje teku vašim krvotokom, štite na dnevnoj bazi od toga da sve pođe po krivu, uključujući i rak. Na ovoj slici, ove male zelene kuglice su vaše imunološke stanice, a ova velika ružičasta stanica je stanica raka. Te imunološke stanice idu uokolo i kušaju sve stanice u vašem tijelu. To je njihov posao. I u većini slučajeva, stanice su OK.
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.
Ali ponekad, neka stanica nije u redu. Nadajmo se da je to stanica raka i kada te imunološke stanice osjete loš okus, lansiraju totalan napad i ubiju te stanice. To je ono što znamo. Također znamo da ako možete potencirati to kušanje, ako možete ohrabriti te imunološke stanice da uistinu zagrizu te stanice raka, imate više šanse u zaštiti od raka svaki dan, a možda čak i u njegovom liječenju. Trenutno je na tržištu nekoliko lijekova koji se koriste u liječenju raka, a koji se ponašaju točno tako. Aktiviraju imunološki sustav kako bi nas on snažnije štitio od raka.
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.
Zapravo, jedan od tih lijekova možda je malo produžio život predsjedniku Jimmyju Carteru. Sjećate li se, predsjednik Carter je imao maligni melanom, koji je metastazirao u mozak i dijagnoza mu je bila jedna od onih obično popraćenih brojkama kao što su "mjeseci života." Ali je bio liječen jednim od tih imunostimulatora i sada je njegov melanom u fazi remisije, što je izvanredno, uzimajući u obzir situaciju od prije samo par godina. Zapravo, to je toliko izvanredno, da provokativne izjave poput ove: "Rak doživljava penicilinski trenutak," govore ljudi o tim novim imunoterapijskim lijekovima. Mislim, nevjerojatno je odvažno reći tako nešto o bolesti, s kojom se dugo borimo i protiv koje najčešće gubimo bitku. Pa, ovo je jako uzbudljivo.
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.
Sada, kakve to ima veze s šećerima? Pa, reći ću vam što smo naučili. Kada se imunološka stanica priljubi uz stanicu raka kako bi je probala, ona traži znakove bolesti, i ako pronađe takve znakove, stanica se aktivira i pokreće raketni udar te ubije stanicu. Ali ako ta stanica raka ima gustu šumu tog šećera, sijalične kiseline, njen okus počinje biti prilično dobar. Postoji protein na imunološkim stanicama koji grabi sijaličnu kiselinu, i ako se taj protein zadrži na toj sinapsi između imunološke stanice i stanice raka, on uspava imunološku stanicu. Sijalične kiseline govore imunološkoj stanici, "Hej, ova stanica je u redu. Nemaš što za vidjeti, nastavi dalje. Pogledaj negdje drugdje." Drugim riječima, sve dok naše stanice imaju debeli omotač sijalične kiseline, izgledaju fenomenalno, zar ne? To je nevjerojatno. A što ako biste mogli skinuti taj omotač i maknuti taj šećer? Pa, vaš imunološki sustav bi možda mogao vidjeti tu stanicu raka onakvom kakva je ona zaista: kao nešto što treba biti uništeno.
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.
I to je ono što mi radimo u mom laboratoriju. Razvijamo nove lijekove koji su u osnovi površinske stanične kosilice, molekule koje dolaze do površine tih stanica raka i samo odrežu tu sijaličnu kiselinu, kako bi imunološki sustav dostigao svoj puni potencijal u eliminiranju tih stanica raka iz našeg tijela.
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."
I za kraj, samo da vas podsjetim: vaše stanice su premazane šećerima. Šećeri govore stanicama oko te stanice je li ta stanica dobra ili loša. I to je važno, jer naš imunološki sustav treba ostaviti dobre stanice na miru. U suprotnom, imali bismo autoimune bolesti. Ali, s vremena na vrijeme, rak dobije mogućnost da manifestira te nove šećere. I sada kada razumijemo kako ti šećeri obmanjuju imunološki sustav, možemo osmisliti nove lijekove da probude te imunološke stanice, da im kažu, "Ignorirajte šećere, pojedite stanicu i uzmite ukusan zalogaj raka."
Thank you.
Hvala vam.
(Applause)
(Pljesak)