1 00:00:00,813 --> 00:00:04,064 This is a talk about sugar and cancer, 2 00:00:04,064 --> 00:00:07,364 and I became interested in sugar when I was in college. 3 00:00:07,364 --> 00:00:09,610 Not this kind of sugar. 4 00:00:09,610 --> 00:00:12,691 It was the sugar that our biology professors 5 00:00:12,691 --> 00:00:14,247 taught us about 6 00:00:14,247 --> 00:00:17,005 in the context of the coating 7 00:00:17,005 --> 00:00:18,937 of your cells, 8 00:00:18,937 --> 00:00:20,589 and maybe you didn't know 9 00:00:20,589 --> 00:00:23,070 that your cells are coated with sugar. 10 00:00:23,070 --> 00:00:24,668 And I didn't know that either 11 00:00:24,668 --> 00:00:26,743 until I took these courses in college, 12 00:00:26,743 --> 00:00:28,178 but back then, 13 00:00:28,178 --> 00:00:32,728 and this was in, let's just call it the 1980s, 14 00:00:32,728 --> 00:00:34,925 people didn't know much about why 15 00:00:34,925 --> 00:00:37,249 our cells are coated with sugar. 16 00:00:37,249 --> 00:00:38,982 And when I dug through my notes, 17 00:00:38,982 --> 00:00:41,058 what I noticed I had written down 18 00:00:41,058 --> 00:00:43,886 is that the sugar coating on our cells 19 00:00:43,886 --> 00:00:47,539 is like the sugar coating on a peanut M&M. 20 00:00:47,539 --> 00:00:50,888 And people thought the sugar coating on our cells 21 00:00:50,888 --> 00:00:52,960 was like a protective coating 22 00:00:52,960 --> 00:00:57,204 that somehow made our cells stronger or tougher. 23 00:00:57,204 --> 00:00:59,203 But we now know, many decades later, 24 00:00:59,203 --> 00:01:02,136 that it's much more complicated than that 25 00:01:02,136 --> 00:01:07,286 and that the sugars on our cells are actually very complex 26 00:01:07,286 --> 00:01:09,854 and if you could shrink yourself down 27 00:01:09,854 --> 00:01:12,863 to a little miniature airplane 28 00:01:12,863 --> 00:01:16,525 and fly right along the surface of your cells, 29 00:01:16,525 --> 00:01:19,419 it might look something like this, 30 00:01:19,419 --> 00:01:21,949 with geographical features, 31 00:01:21,949 --> 00:01:25,575 and now the complex sugars are these trees and bushes, 32 00:01:25,575 --> 00:01:27,861 weeping willows that are swaying in the wind 33 00:01:27,861 --> 00:01:30,045 and moving with the waves. 34 00:01:30,045 --> 00:01:33,953 And when I started thinking about all these complex sugars 35 00:01:33,953 --> 00:01:36,902 that are like this foliage on our cells, 36 00:01:36,902 --> 00:01:39,943 it became one of the most interesting problems that I encountered 37 00:01:39,943 --> 00:01:43,990 as a biologist and also as a chemist. 38 00:01:43,990 --> 00:01:47,883 And so now we tend to think about the sugars that are populating 39 00:01:47,883 --> 00:01:49,908 the surface of our cells 40 00:01:49,908 --> 00:01:52,628 as a language. 41 00:01:52,628 --> 00:01:54,293 They have a lot of information stored in their complex structures. 42 00:01:54,293 --> 00:02:00,771 But what are they trying to tell us? 43 00:02:00,771 --> 00:02:03,887 I can tell you that we do know some information 44 00:02:03,887 --> 00:02:05,776 that comes from these sugars, 45 00:02:05,776 --> 00:02:08,591 and it's turned out already to be incredibly important 46 00:02:08,591 --> 00:02:11,040 in the world of medicine. 47 00:02:11,040 --> 00:02:14,724 For example, one thing your sugars are telling us 48 00:02:14,724 --> 00:02:17,224 is your blood type. 49 00:02:17,224 --> 00:02:19,461 So your blood cells, your red blood cells 50 00:02:19,461 --> 00:02:21,404 are coated with sugars, 51 00:02:21,404 --> 00:02:24,131 and the chemical structures of those sugars 52 00:02:24,131 --> 00:02:26,097 determine your blood type. 53 00:02:26,097 --> 00:02:30,132 So for example, I know that I am blood type O, 54 00:02:30,132 --> 00:02:33,124 and how many people are also blood type O? 55 00:02:33,124 --> 00:02:35,578 Put your hands up. It's a pretty common one, 56 00:02:35,578 --> 00:02:37,918 and so when so few hands go up, either you're not paying attention 57 00:02:37,918 --> 00:02:41,645 or you don't know your blood type, and both of those are bad, okay? 58 00:02:41,645 --> 00:02:44,945 But for those of you who share the blood type O with me, 59 00:02:44,945 --> 00:02:47,988 what this means is that we have this chemical structure 60 00:02:47,988 --> 00:02:49,801 on the surface of our blood cells: 61 00:02:49,801 --> 00:02:54,663 three simple sugars linked together to make a more complex sugar. 62 00:02:54,663 --> 00:02:57,740 And that, by definition, is blood type O. 63 00:02:57,740 --> 00:03:00,876 Now, how many people are blood type A? 64 00:03:00,876 --> 00:03:01,872 Right here. 65 00:03:01,872 --> 00:03:03,909 So that means you have an enzyme in your cells 66 00:03:03,909 --> 00:03:07,450 that adds one more building block, 67 00:03:07,450 --> 00:03:08,848 that red sugar, 68 00:03:08,848 --> 00:03:11,315 to build a more complex structure. 69 00:03:11,315 --> 00:03:14,536 And how many people are blood type B? 70 00:03:14,536 --> 00:03:15,623 Quite a few. 71 00:03:15,623 --> 00:03:18,441 You have a slightly different enzyme than the A people, 72 00:03:18,441 --> 00:03:20,308 so you build a slightly different structure, 73 00:03:20,308 --> 00:03:22,692 and those of you that are AB 74 00:03:22,692 --> 00:03:25,905 have the enzyme from your mother, the other enzyme from your father, 75 00:03:25,905 --> 00:03:29,705 and now you make both of these structures in roughly equal proportions. 76 00:03:29,705 --> 00:03:32,257 And when this was figured out, 77 00:03:32,257 --> 00:03:34,981 which is now back in the previous century, 78 00:03:34,981 --> 00:03:38,521 this enabled one of the most important medical procedures in the world, 79 00:03:38,521 --> 00:03:40,922 which of course is the blood transfusion, 80 00:03:40,922 --> 00:03:43,158 and by knowing what your blood type is, 81 00:03:43,158 --> 00:03:45,529 we can make sure, if you ever need a transfusion, 82 00:03:45,529 --> 00:03:48,073 that your donor has the same blood type 83 00:03:48,073 --> 00:03:51,823 so that your body doesn't see foreign sugars 84 00:03:51,823 --> 00:03:56,241 which it wouldn't like and would certainly reject. 85 00:03:56,241 --> 00:03:59,118 What else are the sugars on the surface of your cells 86 00:03:59,118 --> 00:04:01,454 trying to tell us? 87 00:04:01,454 --> 00:04:03,221 Well, those sugars 88 00:04:03,221 --> 00:04:06,812 might be telling us that you have cancer. 89 00:04:06,812 --> 00:04:09,087 So a few decades ago, 90 00:04:09,087 --> 00:04:12,918 correlations began to emerge from the analysis 91 00:04:12,918 --> 00:04:14,669 of tumor tissue, 92 00:04:14,669 --> 00:04:19,203 and the typical scenario is a patient would have a tumor detected 93 00:04:19,203 --> 00:04:21,327 and the tissue would be removed 94 00:04:21,327 --> 00:04:22,940 in a biopsy procedure 95 00:04:22,940 --> 00:04:25,582 and then sent down to a pathology lab, 96 00:04:25,582 --> 00:04:28,204 where that tissue would be analyzed 97 00:04:28,204 --> 00:04:29,984 to look for chemical changes 98 00:04:29,984 --> 00:04:35,226 that might inform the oncologist about the best course of treatment. 99 00:04:35,226 --> 00:04:38,133 And what was discovered from studies like that 100 00:04:38,133 --> 00:04:41,020 is that the sugars have changed 101 00:04:41,020 --> 00:04:44,263 when the cell transforms 102 00:04:44,263 --> 00:04:47,038 from being healthy to being sick. 103 00:04:47,038 --> 00:04:49,247 And those correlations 104 00:04:49,247 --> 00:04:52,855 have come up again and again and again, 105 00:04:52,855 --> 00:04:55,937 but a big question in the field 106 00:04:55,937 --> 00:04:57,209 has been why. 107 00:04:57,209 --> 00:04:59,723 Why do cancers have different sugars? What's the importance of that? 108 00:04:59,723 --> 00:05:03,517 Why does it happen, and what can we do about it if it does turn out 109 00:05:03,517 --> 00:05:10,014 to be related to the disease process? 110 00:05:10,014 --> 00:05:13,248 So one of the changes that we study 111 00:05:13,248 --> 00:05:17,011 is an increase 112 00:05:17,011 --> 00:05:18,759 in the density of a particular sugar 113 00:05:18,759 --> 00:05:21,112 that's called sialic acid. 114 00:05:21,112 --> 00:05:24,561 And I think this is going to be 115 00:05:24,561 --> 00:05:26,677 one of the most important sugars of our time, 116 00:05:26,677 --> 00:05:31,645 so I would encourage everybody to get familiar with this word. 117 00:05:31,645 --> 00:05:34,633 Sialic acid is not the kind of sugar that we eat. 118 00:05:34,633 --> 00:05:36,210 Those are different sugars. 119 00:05:36,210 --> 00:05:39,859 This is a kind of sugar that is actually found 120 00:05:39,859 --> 00:05:43,010 at certain levels on all of the cells in your body. 121 00:05:43,010 --> 00:05:46,759 It's actually quite common on your cells. 122 00:05:46,759 --> 00:05:48,761 But for some reason, 123 00:05:48,761 --> 00:05:54,405 cancer cells, at least in a successful, progressive disease, 124 00:05:54,405 --> 00:05:57,414 they tend to have more sialic acid 125 00:05:57,414 --> 00:05:59,626 than a normal, healthy cell would have. 126 00:05:59,626 --> 00:06:03,475 And why? What does that mean? 127 00:06:03,475 --> 00:06:05,391 Well, what we've learned is that 128 00:06:05,391 --> 00:06:09,056 it has to do with your immune system. 129 00:06:09,056 --> 00:06:12,653 So let me tell you a little bit about the importance 130 00:06:12,653 --> 00:06:14,722 of your immune system in cancer. 131 00:06:14,722 --> 00:06:17,423 And this is something that's I think in the news a lot these days. 132 00:06:17,423 --> 00:06:20,249 You know, people are starting to become familiar with the term 133 00:06:20,249 --> 00:06:23,282 "cancer immune therapy." 134 00:06:23,282 --> 00:06:24,937 And some of you might even know people 135 00:06:24,937 --> 00:06:29,773 who are benefiting from these very new ways of treating cancer. 136 00:06:29,773 --> 00:06:33,318 What we now know is that your immune cells, 137 00:06:33,318 --> 00:06:37,275 which are the white blood cells coursing through your bloodstream, 138 00:06:37,275 --> 00:06:39,633 they protect you on a daily basis 139 00:06:39,633 --> 00:06:41,953 from things gone bad, 140 00:06:41,953 --> 00:06:44,102 including cancer. 141 00:06:44,102 --> 00:06:46,237 And so in this picture, 142 00:06:46,237 --> 00:06:48,820 those little green balls are your immune cells, 143 00:06:48,820 --> 00:06:52,766 and that big pink cell is a cancer cell. 144 00:06:52,766 --> 00:06:56,536 And these immune cells, they go around 145 00:06:56,536 --> 00:06:57,469 and they taste all the cells in your body. 146 00:06:57,469 --> 00:06:59,072 That's their job. 147 00:06:59,072 --> 00:07:02,002 And most of the time, the cells taste okay. 148 00:07:02,002 --> 00:07:04,935 But once in a while, a cell might taste bad. 149 00:07:04,935 --> 00:07:06,419 Hopefully, that's the cancer cell, 150 00:07:06,419 --> 00:07:08,719 and when those immune cells get the bad taste, 151 00:07:08,719 --> 00:07:12,853 they launch an all-out strike and they kill those cells. 152 00:07:12,853 --> 00:07:14,194 So we know that. 153 00:07:14,194 --> 00:07:18,501 We also know that if you can potentiate that tasting, 154 00:07:18,501 --> 00:07:22,266 if you can encourage those immune cells to actually take a big old bite 155 00:07:22,266 --> 00:07:23,532 out of a cancer cell, 156 00:07:23,532 --> 00:07:27,146 you get a better job protecting yourself from cancer every day 157 00:07:27,146 --> 00:07:29,684 and maybe even curing a cancer. 158 00:07:29,684 --> 00:07:32,553 And there are now a couple of drugs out there in the market 159 00:07:32,553 --> 00:07:34,647 that are used to treat cancer patients 160 00:07:34,647 --> 00:07:37,898 that act exactly by this process. 161 00:07:37,898 --> 00:07:39,799 They activate the immune system so that the immune system 162 00:07:39,799 --> 00:07:44,012 can be more vigorous in protecting us from cancer. 163 00:07:44,012 --> 00:07:49,734 And in fact, one of those drugs 164 00:07:49,734 --> 00:07:54,176 may well have spared President Jimmy Carter's life. 165 00:07:54,176 --> 00:07:55,342 Do you remember, President Carter 166 00:07:55,342 --> 00:07:56,180 had malignant melanoma 167 00:07:56,180 --> 00:07:56,902 that had metastasized to his brain, 168 00:07:56,902 --> 00:08:00,530 and that diagnosis is one that is usually accompanied by numbers 169 00:08:00,530 --> 00:08:03,326 like "months to live." 170 00:08:03,326 --> 00:08:07,701 But he was treated with one of these new immune-stimulating drugs, 171 00:08:07,701 --> 00:08:11,083 and now his melanoma appears to be in remission, 172 00:08:11,083 --> 00:08:12,747 which is remarkable 173 00:08:12,747 --> 00:08:16,211 considering the situation only a few years ago, 174 00:08:16,211 --> 00:08:20,501 in fact so remarkable that provocative statement like this one -- 175 00:08:20,501 --> 00:08:23,491 "Cancer is having a penicillin moment," people are saying 176 00:08:23,491 --> 00:08:26,277 with these new immune therapy drugs. 177 00:08:26,277 --> 00:08:28,693 I mean, that's an incredibly bold thing to say 178 00:08:28,693 --> 00:08:32,003 about a disease which we've been fighting for a long time 179 00:08:32,003 --> 00:08:35,125 and mostly losing the battle with. 180 00:08:35,125 --> 00:08:37,176 So this is very exciting. 181 00:08:37,176 --> 00:08:39,526 Now what does this have to do with sugars? 182 00:08:39,526 --> 00:08:42,444 Well, I'll tell you what we've learned. 183 00:08:42,444 --> 00:08:47,857 When an immune cell snuggles up against a cancer cell 184 00:08:47,857 --> 00:08:49,455 to take a taste, 185 00:08:49,455 --> 00:08:52,127 it's looking for signs of disease, 186 00:08:52,127 --> 00:08:54,069 and if it finds those signs, 187 00:08:54,069 --> 00:08:59,492 the cell gets activated and it launches a missile strike and kills the cell. 188 00:08:59,492 --> 00:09:02,553 But if that cancer cell 189 00:09:02,553 --> 00:09:05,922 has a dense forest of that sugar, sialic acid 190 00:09:05,922 --> 00:09:09,872 well it starts to taste pretty good, 191 00:09:09,872 --> 00:09:12,310 and there's a protein on immune cells 192 00:09:12,310 --> 00:09:14,418 that grabs the sialic acid, 193 00:09:14,418 --> 00:09:18,104 and if that protein gets held at that synapse 194 00:09:18,104 --> 00:09:21,402 between the immune cell and the cancer cell, 195 00:09:21,402 --> 00:09:23,992 it puts that immune cell to sleep. 196 00:09:23,992 --> 00:09:27,135 The sialic acids are telling the immune cell, "Hey, 197 00:09:27,135 --> 00:09:28,938 this cell's all right, 198 00:09:28,938 --> 00:09:30,646 nothing to see here, move along. 199 00:09:30,646 --> 00:09:33,003 Look somewhere else." 200 00:09:33,003 --> 00:09:35,671 So in other words, as long as our cells 201 00:09:35,671 --> 00:09:39,471 are wearing a thick coat of sialic acid, 202 00:09:39,471 --> 00:09:42,219 they look fabulous, right? 203 00:09:42,219 --> 00:09:44,707 It's amazing. 204 00:09:44,707 --> 00:09:47,884 And what if you could strip off that coat 205 00:09:47,884 --> 00:09:50,320 and take that sugar away? 206 00:09:50,320 --> 00:09:53,095 Well, your immune system 207 00:09:53,095 --> 00:09:57,319 might be able to see that cancer cell for what it really is, 208 00:09:57,319 --> 00:10:01,066 something that needs to be destroyed. 209 00:10:01,066 --> 00:10:03,839 And so this is what we're doing in my lab. 210 00:10:03,839 --> 00:10:06,184 We're developing new medicines 211 00:10:06,184 --> 00:10:09,503 that are basically cell surface lawnmowers, 212 00:10:09,503 --> 00:10:14,149 molecules that go down to the surface of these cancer cells 213 00:10:14,149 --> 00:10:16,801 and just cut off those sialic acids 214 00:10:16,801 --> 00:10:21,042 so that the immune system 215 00:10:21,042 --> 00:10:22,218 can reach its full potential 216 00:10:22,218 --> 00:10:25,325 in eliminating those cancer cells from our body. 217 00:10:25,325 --> 00:10:28,097 So in closing, 218 00:10:28,097 --> 00:10:30,273 let me just remind you again, 219 00:10:30,273 --> 00:10:32,972 your cells are coated with sugars. 220 00:10:32,972 --> 00:10:38,013 The sugars are telling cells around that cell 221 00:10:38,013 --> 00:10:40,842 whether the cell is good or bad, 222 00:10:40,842 --> 00:10:43,288 and that's important because our immune system needs 223 00:10:43,288 --> 00:10:45,410 to leave the good cells alone. 224 00:10:45,410 --> 00:10:48,379 Otherwise, we'd have autoimmune diseases. 225 00:10:48,379 --> 00:10:51,648 But once in a while, cancers get the ability 226 00:10:51,648 --> 00:10:53,361 to express these new sugars, 227 00:10:53,361 --> 00:10:56,264 and now that we understand how those sugars 228 00:10:56,264 --> 00:10:57,806 mesmerize the immune system, 229 00:10:57,806 --> 00:11:00,249 we can come up with new medicines 230 00:11:00,249 --> 00:11:02,236 to wake up those immune cells, 231 00:11:02,236 --> 00:11:05,306 tell them, "Ignore the sugars, eat the cell, 232 00:11:05,306 --> 00:11:08,733 and have a delicious snack on cancer." 233 00:11:08,733 --> 00:11:10,407 Thank you. 234 00:11:10,407 --> 00:11:12,775 (Applause)