1 00:00:00,669 --> 00:00:03,444 This is a talk about sugar and cancer. 2 00:00:03,889 --> 00:00:07,166 I became interested in sugar when I was in college. 3 00:00:07,190 --> 00:00:09,042 Not this kind of sugar. 4 00:00:09,066 --> 00:00:14,017 It was the sugar that our biology professors taught us about 5 00:00:14,041 --> 00:00:18,183 in the context of the coating of your cells. 6 00:00:18,733 --> 00:00:22,843 Maybe you didn't know that your cells are coated with sugar. 7 00:00:22,867 --> 00:00:24,442 And I didn't know that, either, 8 00:00:24,466 --> 00:00:26,621 until I took these courses in college, 9 00:00:26,645 --> 00:00:28,057 but back then -- 10 00:00:28,081 --> 00:00:31,640 and this was in, let's just call it the 1980s -- 11 00:00:32,560 --> 00:00:36,814 people didn't know much about why our cells are coated with sugar. 12 00:00:36,838 --> 00:00:40,805 And when I dug through my notes, what I noticed I had written down 13 00:00:40,829 --> 00:00:45,374 is that the sugar coating on our cells is like the sugar coating 14 00:00:45,398 --> 00:00:46,604 on a peanut M and M. 15 00:00:47,198 --> 00:00:50,864 And people thought the sugar coating on our cells 16 00:00:50,888 --> 00:00:52,718 was like a protective coating 17 00:00:52,742 --> 00:00:55,993 that somehow made our cells stronger or tougher. 18 00:00:56,934 --> 00:00:59,060 But we now know, many decades later, 19 00:00:59,084 --> 00:01:01,360 that it's much more complicated than that, 20 00:01:01,906 --> 00:01:06,367 and that the sugars on our cells are actually very complex. 21 00:01:07,183 --> 00:01:12,695 And if you could shrink yourself down to a little miniature airplane 22 00:01:12,719 --> 00:01:16,501 and fly right along the surface of your cells, 23 00:01:16,525 --> 00:01:18,891 it might look something like this -- 24 00:01:18,915 --> 00:01:21,116 with geographical features. 25 00:01:21,140 --> 00:01:25,170 And now, the complex sugars are these trees and bushes -- 26 00:01:25,194 --> 00:01:27,726 weeping willows that are swaying in the wind 27 00:01:27,750 --> 00:01:29,787 and moving with the waves. 28 00:01:29,811 --> 00:01:33,624 And when I started thinking about all these complex sugars 29 00:01:33,648 --> 00:01:36,574 that are like this foliage on our cells, 30 00:01:36,598 --> 00:01:39,715 it became one of the most interesting problems that I encountered 31 00:01:39,739 --> 00:01:42,743 as a biologist and also as a chemist. 32 00:01:43,657 --> 00:01:46,592 And so now we tend to think about the sugars 33 00:01:46,616 --> 00:01:49,884 that are populating the surface of our cells 34 00:01:49,908 --> 00:01:51,703 as a language. 35 00:01:52,342 --> 00:01:56,223 They have a lot of information stored in their complex structures. 36 00:01:57,142 --> 00:01:59,711 But what are they trying to tell us? 37 00:02:00,548 --> 00:02:03,863 I can tell you that we do know some information 38 00:02:03,887 --> 00:02:05,492 that comes from these sugars, 39 00:02:05,516 --> 00:02:08,451 and it's turned out already to be incredibly important 40 00:02:08,475 --> 00:02:10,295 in the world of medicine. 41 00:02:10,777 --> 00:02:14,438 For example, one thing your sugars are telling us 42 00:02:14,462 --> 00:02:15,919 is your blood type. 43 00:02:17,041 --> 00:02:21,195 So your blood cells, your red blood cells, are coated with sugars, 44 00:02:21,219 --> 00:02:25,896 and the chemical structures of those sugars determine your blood type. 45 00:02:25,920 --> 00:02:29,843 So for example, I know that I am blood type O. 46 00:02:29,867 --> 00:02:32,978 How many people are also blood type O? 47 00:02:33,002 --> 00:02:34,160 Put your hands up. 48 00:02:34,184 --> 00:02:35,377 It's a pretty common one, 49 00:02:35,401 --> 00:02:38,336 so when so few hands go up, either you're not paying attention 50 00:02:38,360 --> 00:02:41,250 or you don't know your blood type, and both of those are bad. 51 00:02:41,274 --> 00:02:42,289 (Laughter) 52 00:02:42,313 --> 00:02:44,976 But for those of you who share the blood type O with me, 53 00:02:45,000 --> 00:02:47,715 what this means is that we have this chemical structure 54 00:02:47,739 --> 00:02:49,777 on the surface of our blood cells: 55 00:02:50,296 --> 00:02:54,019 three simple sugars linked together to make a more complex sugar. 56 00:02:54,043 --> 00:02:56,311 And that, by definition, is blood type O. 57 00:02:57,366 --> 00:02:59,496 Now, how many people are blood type A? 58 00:03:00,574 --> 00:03:01,743 Right here. 59 00:03:01,767 --> 00:03:04,728 That means you have an enzyme in your cells 60 00:03:04,752 --> 00:03:07,168 that adds one more building block, 61 00:03:07,192 --> 00:03:08,567 that red sugar, 62 00:03:08,591 --> 00:03:10,415 to build a more complex structure. 63 00:03:11,116 --> 00:03:13,506 And how many people are blood type B? 64 00:03:14,298 --> 00:03:15,463 Quite a few. 65 00:03:15,487 --> 00:03:18,215 You have a slightly different enzyme than the A people, 66 00:03:18,239 --> 00:03:20,355 so you build a slightly different structure, 67 00:03:20,379 --> 00:03:22,492 and those of you that are AB 68 00:03:22,516 --> 00:03:25,708 have the enzyme from your mother, the other enzyme from your father, 69 00:03:25,732 --> 00:03:29,507 and now you make both of these structures in roughly equal proportions. 70 00:03:29,531 --> 00:03:31,935 And when this was figured out, 71 00:03:31,959 --> 00:03:34,697 which is now back in the previous century, 72 00:03:34,721 --> 00:03:38,238 this enabled one of the most important medical procedures in the world, 73 00:03:38,262 --> 00:03:40,640 which, of course, is the blood transfusion. 74 00:03:40,664 --> 00:03:42,560 And by knowing what your blood type is, 75 00:03:42,584 --> 00:03:45,176 we can make sure, if you ever need a transfusion, 76 00:03:45,200 --> 00:03:47,721 that your donor has the same blood type, 77 00:03:47,745 --> 00:03:51,066 so that your body doesn't see foreign sugars, 78 00:03:51,783 --> 00:03:54,220 which it wouldn't like and would certainly reject. 79 00:03:56,113 --> 00:04:00,355 What else are the sugars on the surface of your cells trying to tell us? 80 00:04:01,112 --> 00:04:05,805 Well, those sugars might be telling us that you have cancer. 81 00:04:06,708 --> 00:04:08,960 So a few decades ago, 82 00:04:08,984 --> 00:04:14,377 correlations began to emerge from the analysis of tumor tissue. 83 00:04:14,401 --> 00:04:18,912 And the typical scenario is a patient would have a tumor detected, 84 00:04:18,936 --> 00:04:22,764 and the tissue would be removed in a biopsy procedure 85 00:04:22,788 --> 00:04:25,558 and then sent down to a pathology lab 86 00:04:25,582 --> 00:04:29,713 where that tissue would be analyzed to look for chemical changes 87 00:04:29,737 --> 00:04:34,451 that might inform the oncologist about the best course of treatment. 88 00:04:34,979 --> 00:04:37,863 And what was discovered from studies like that 89 00:04:37,887 --> 00:04:40,751 is that the sugars have changed 90 00:04:40,775 --> 00:04:45,772 when the cell transforms from being healthy to being sick. 91 00:04:46,823 --> 00:04:51,806 And those correlations have come up again and again and again. 92 00:04:52,497 --> 00:04:56,963 But a big question in the field has been: Why? 93 00:04:56,987 --> 00:05:01,231 Why do cancers have different sugars? What's the importance of that? 94 00:05:01,255 --> 00:05:04,616 Why does it happen, and what can we do about it if it does turn out 95 00:05:04,640 --> 00:05:08,395 to be related to the disease process? 96 00:05:09,783 --> 00:05:12,994 So, one of the changes that we study 97 00:05:13,018 --> 00:05:18,563 is an increase in the density of a particular sugar 98 00:05:18,587 --> 00:05:20,916 that's called sialic acid. 99 00:05:21,617 --> 00:05:25,541 And I think this is going to be one of the most important sugars 100 00:05:25,565 --> 00:05:26,723 of our times, 101 00:05:26,747 --> 00:05:30,822 so I would encourage everybody to get familiar with this word. 102 00:05:31,502 --> 00:05:34,467 Sialic acid is not the kind of sugar that we eat. 103 00:05:34,491 --> 00:05:36,047 Those are different sugars. 104 00:05:36,602 --> 00:05:39,566 This is a kind of sugar that is actually found 105 00:05:39,590 --> 00:05:42,718 at certain levels on all of the cells in your body. 106 00:05:42,742 --> 00:05:45,610 It's actually quite common on your cells. 107 00:05:46,393 --> 00:05:47,704 But for some reason, 108 00:05:48,451 --> 00:05:53,939 cancer cells, at least in a successful, progressive disease, 109 00:05:53,963 --> 00:05:57,072 tend to have more sialic acid 110 00:05:57,096 --> 00:05:59,443 than a normal, healthy cell would have. 111 00:05:59,467 --> 00:06:00,909 And why? 112 00:06:00,933 --> 00:06:02,179 What does that mean? 113 00:06:03,276 --> 00:06:04,728 Well, what we've learned 114 00:06:04,752 --> 00:06:08,227 is that it has to do with your immune system. 115 00:06:08,935 --> 00:06:12,501 So let me tell you a little bit about the importance of your immune system 116 00:06:12,525 --> 00:06:13,689 in cancer. 117 00:06:13,713 --> 00:06:17,231 And this is something that's, I think, in the news a lot these days. 118 00:06:17,255 --> 00:06:20,161 You know, people are starting to become familiar with the term 119 00:06:20,185 --> 00:06:22,947 "cancer immune therapy." 120 00:06:22,971 --> 00:06:24,782 And some of you might even know people 121 00:06:24,806 --> 00:06:28,713 who are benefiting from these very new ways of treating cancer. 122 00:06:29,848 --> 00:06:33,089 What we now know is that your immune cells, 123 00:06:33,113 --> 00:06:37,047 which are the white blood cells coursing through your bloodstream, 124 00:06:37,071 --> 00:06:41,727 protect you on a daily basis from things gone bad -- 125 00:06:41,751 --> 00:06:43,092 including cancer. 126 00:06:43,951 --> 00:06:45,942 And so in this picture, 127 00:06:45,966 --> 00:06:48,687 those little green balls are your immune cells, 128 00:06:48,711 --> 00:06:51,659 and that big pink cell is a cancer cell. 129 00:06:52,250 --> 00:06:57,015 And these immune cells go around and taste all the cells in your body. 130 00:06:57,039 --> 00:06:58,334 That's their job. 131 00:06:58,913 --> 00:07:01,668 And most of the time, the cells taste OK. 132 00:07:01,692 --> 00:07:04,196 But once in a while, a cell might taste bad. 133 00:07:04,744 --> 00:07:06,555 Hopefully, that's the cancer cell, 134 00:07:06,579 --> 00:07:08,962 and when those immune cells get the bad taste, 135 00:07:08,986 --> 00:07:11,795 they launch an all-out strike and kill those cells. 136 00:07:12,630 --> 00:07:13,783 So we know that. 137 00:07:13,807 --> 00:07:18,223 We also know that if you can potentiate that tasting, 138 00:07:18,247 --> 00:07:22,075 if you can encourage those immune cells to actually take a big old bite 139 00:07:22,099 --> 00:07:23,342 out of a cancer cell, 140 00:07:23,366 --> 00:07:26,957 you get a better job protecting yourself from cancer every day 141 00:07:26,981 --> 00:07:28,713 and maybe even curing a cancer. 142 00:07:29,509 --> 00:07:32,355 And there are now a couple of drugs out there in the market 143 00:07:32,379 --> 00:07:34,450 that are used to treat cancer patients 144 00:07:34,474 --> 00:07:37,215 that act exactly by this process. 145 00:07:37,726 --> 00:07:39,355 They activate the immune system 146 00:07:39,379 --> 00:07:42,126 so that the immune system can be more vigorous 147 00:07:42,150 --> 00:07:43,902 in protecting us from cancer. 148 00:07:43,926 --> 00:07:45,969 In fact, one of those drugs 149 00:07:45,993 --> 00:07:48,983 may well have spared President Jimmy Carter's life. 150 00:07:49,516 --> 00:07:53,996 Do you remember, President Carter had malignant melanoma 151 00:07:54,020 --> 00:07:56,878 that had metastasized to his brain, 152 00:07:56,902 --> 00:08:00,256 and that diagnosis is one that is usually accompanied by numbers 153 00:08:00,280 --> 00:08:02,125 like "months to live." 154 00:08:03,093 --> 00:08:07,488 But he was treated with one of these new immune-stimulating drugs, 155 00:08:07,512 --> 00:08:10,871 and now his melanoma appears to be in remission, 156 00:08:10,895 --> 00:08:12,536 which is remarkable, 157 00:08:12,560 --> 00:08:16,001 considering the situation only a few years ago. 158 00:08:16,025 --> 00:08:17,845 In fact, it's so remarkable 159 00:08:17,869 --> 00:08:20,669 that provocative statements like this one: 160 00:08:20,693 --> 00:08:24,408 "Cancer is having a penicillin moment," people are saying, 161 00:08:24,432 --> 00:08:26,253 with these new immune therapy drugs. 162 00:08:26,277 --> 00:08:29,475 I mean, that's an incredibly bold thing to say about a disease 163 00:08:29,499 --> 00:08:32,148 which we've been fighting for a long time 164 00:08:32,172 --> 00:08:34,252 and mostly losing the battle with. 165 00:08:34,855 --> 00:08:36,384 So this is very exciting. 166 00:08:36,907 --> 00:08:39,319 Now what does this have to do with sugars? 167 00:08:39,343 --> 00:08:42,063 Well, I'll tell you what we've learned. 168 00:08:42,944 --> 00:08:49,280 When an immune cell snuggles up against a cancer cell to take a taste, 169 00:08:49,304 --> 00:08:51,953 it's looking for signs of disease, 170 00:08:51,977 --> 00:08:53,896 and if it finds those signs, 171 00:08:53,920 --> 00:08:58,166 the cell gets activated and it launches a missile strike and kills the cell. 172 00:08:59,269 --> 00:09:05,079 But if that cancer cell has a dense forest of that sugar, sialic acid, 173 00:09:05,731 --> 00:09:08,699 well, it starts to taste pretty good. 174 00:09:09,507 --> 00:09:14,151 And there's a protein on immune cells that grabs the sialic acid, 175 00:09:14,175 --> 00:09:17,976 and if that protein gets held at that synapse 176 00:09:18,000 --> 00:09:20,424 between the immune cell and the cancer cell, 177 00:09:21,171 --> 00:09:23,156 it puts that immune cell to sleep. 178 00:09:23,809 --> 00:09:27,111 The sialic acids are telling the immune cell, 179 00:09:27,135 --> 00:09:30,336 "Hey, this cell's all right. Nothing to see here, move along. 180 00:09:30,360 --> 00:09:31,854 Look somewhere else." 181 00:09:32,741 --> 00:09:33,963 So in other words, 182 00:09:33,987 --> 00:09:38,731 as long as our cells are wearing a thick coat of sialic acid, 183 00:09:39,399 --> 00:09:41,417 they look fabulous, right? 184 00:09:42,036 --> 00:09:43,388 It's amazing. 185 00:09:44,524 --> 00:09:47,678 And what if you could strip off that coat 186 00:09:47,702 --> 00:09:50,000 and take that sugar away? 187 00:09:50,024 --> 00:09:53,023 Well, your immune system 188 00:09:53,047 --> 00:09:57,248 might be able to see that cancer cell for what it really is: 189 00:09:57,272 --> 00:09:59,496 something that needs to be destroyed. 190 00:10:00,875 --> 00:10:03,186 And so this is what we're doing in my lab. 191 00:10:03,704 --> 00:10:06,026 We're developing new medicines 192 00:10:06,050 --> 00:10:09,107 that are basically cell-surface lawnmowers -- 193 00:10:09,861 --> 00:10:13,514 molecules that go down to the surface of these cancer cells 194 00:10:13,538 --> 00:10:16,403 and just cut off those sialic acids, 195 00:10:16,427 --> 00:10:20,732 so that the immune system can reach its full potential 196 00:10:20,756 --> 00:10:23,413 in eliminating those cancer cells from our body. 197 00:10:24,983 --> 00:10:27,114 So in closing, 198 00:10:27,819 --> 00:10:29,972 let me just remind you again: 199 00:10:29,996 --> 00:10:32,263 your cells are coated with sugars. 200 00:10:32,972 --> 00:10:37,667 The sugars are telling cells around that cell 201 00:10:37,691 --> 00:10:39,611 whether the cell is good or bad. 202 00:10:40,682 --> 00:10:41,847 And that's important, 203 00:10:41,871 --> 00:10:44,927 because our immune system needs to leave the good cells alone. 204 00:10:44,951 --> 00:10:47,421 Otherwise, we'd have autoimmune diseases. 205 00:10:48,315 --> 00:10:51,463 But once in a while, cancers get the ability 206 00:10:51,487 --> 00:10:53,043 to express these new sugars. 207 00:10:53,067 --> 00:10:54,399 And now that we understand 208 00:10:54,423 --> 00:10:57,583 how those sugars mesmerize the immune system, 209 00:10:57,607 --> 00:11:01,792 we can come up with new medicines to wake up those immune cells, 210 00:11:01,816 --> 00:11:05,043 tell them, "Ignore the sugars, eat the cell 211 00:11:05,067 --> 00:11:07,650 and have a delicious snack, on cancer." 212 00:11:08,574 --> 00:11:09,737 Thank you. 213 00:11:10,073 --> 00:11:12,441 (Applause)