1 99:59:59,999 --> 99:59:59,999 Science. 2 99:59:59,999 --> 99:59:59,999 The very word for many of you conjures unhappy memories of boredom 3 99:59:59,999 --> 99:59:59,999 in high school biology or physics class. 4 99:59:59,999 --> 99:59:59,999 But let me assure that what you did there 5 99:59:59,999 --> 99:59:59,999 had very little to do with science. 6 99:59:59,999 --> 99:59:59,999 That was really the "what" of science. 7 99:59:59,999 --> 99:59:59,999 It was the history of what other people had discovered. 8 99:59:59,999 --> 99:59:59,999 What I'm most interested in as a scientist 9 99:59:59,999 --> 99:59:59,999 is the "how" of science. 10 99:59:59,999 --> 99:59:59,999 Because science is knowledge in process. 11 99:59:59,999 --> 99:59:59,999 We make an observation, guess an explanation for that observation, 12 99:59:59,999 --> 99:59:59,999 and then make a prediction that we can test 13 99:59:59,999 --> 99:59:59,999 with an experiment or other observation. 14 99:59:59,999 --> 99:59:59,999 A couple of examples. 15 99:59:59,999 --> 99:59:59,999 First of all, people noticed that the Earth was below, the sky above, 16 99:59:59,999 --> 99:59:59,999 and both the Sun and the Moon seemed to go around them. 17 99:59:59,999 --> 99:59:59,999 Their guessed explanation was that the Earth must be the center 18 99:59:59,999 --> 99:59:59,999 of the Universe. 19 99:59:59,999 --> 99:59:59,999 The prediction: everything should circle around the Earth. 20 99:59:59,999 --> 99:59:59,999 This was first really tested when Galileo got his hands 21 99:59:59,999 --> 99:59:59,999 on one of the first telescopes, 22 99:59:59,999 --> 99:59:59,999 and as he gazed into the night sky, 23 99:59:59,999 --> 99:59:59,999 what he found there was a planet, Jupiter, 24 99:59:59,999 --> 99:59:59,999 with four moons circling around it. 25 99:59:59,999 --> 99:59:59,999 He then used those moons to follow the path of Jupiter 26 99:59:59,999 --> 99:59:59,999 and found that Jupiter also was not going around the Earth 27 99:59:59,999 --> 99:59:59,999 but around the Sun. 28 99:59:59,999 --> 99:59:59,999 So the prediction test failed. 29 99:59:59,999 --> 99:59:59,999 And this led to the discarding of the theory 30 99:59:59,999 --> 99:59:59,999 that the Earth was the center of the Universe. 31 99:59:59,999 --> 99:59:59,999 Another example: Sir Isaac Newton noticed that things fall to the Earth. 32 99:59:59,999 --> 99:59:59,999 The guessed explanation was gravity, 33 99:59:59,999 --> 99:59:59,999 the prediction that everything should fall to the Earth. 34 99:59:59,999 --> 99:59:59,999 But of course, not everything does fall to the Earth. 35 99:59:59,999 --> 99:59:59,999 So did we discard gravity? 36 99:59:59,999 --> 99:59:59,999 No. We revised the theory and said, gravity pulls things to the Earth 37 99:59:59,999 --> 99:59:59,999 unless there is an equal and opposite force in the other direction. 38 99:59:59,999 --> 99:59:59,999 This led us to learn something new. 39 99:59:59,999 --> 99:59:59,999 We began to pay more attention to the bird and the bird's wings, 40 99:59:59,999 --> 99:59:59,999 and just think of all the discoveries 41 99:59:59,999 --> 99:59:59,999 that have flown from that line of thinking. 42 99:59:59,999 --> 99:59:59,999 So the test failures, the exceptions, 43 99:59:59,999 --> 99:59:59,999 the outliers, teach us what we don't know 44 99:59:59,999 --> 99:59:59,999 and lead us to something new. 45 99:59:59,999 --> 99:59:59,999 This is how science moves forward. This is how science learns. 46 99:59:59,999 --> 99:59:59,999 Sometimes in the media, and even more rarely, 47 99:59:59,999 --> 99:59:59,999 but sometimes even scientists will say 48 99:59:59,999 --> 99:59:59,999 that something or has been scientifically proven. 49 99:59:59,999 --> 99:59:59,999 But I hope that you understand that science never proves anything 50 99:59:59,999 --> 99:59:59,999 definitively forever. 51 99:59:59,999 --> 99:59:59,999 Hopefully science remains curious enough 52 99:59:59,999 --> 99:59:59,999 to look for 53 99:59:59,999 --> 99:59:59,999 and humble enough to recognize 54 99:59:59,999 --> 99:59:59,999 when we have found 55 99:59:59,999 --> 99:59:59,999 the next outlier, 56 99:59:59,999 --> 99:59:59,999 the next exception, 57 99:59:59,999 --> 99:59:59,999 which, like Jupiter's moons, 58 99:59:59,999 --> 99:59:59,999 teaches us what we don't actually know. 59 99:59:59,999 --> 99:59:59,999 We're going to change gears here for a second. 60 99:59:59,999 --> 99:59:59,999 The caduceus, or the symbol of medicine, 61 99:59:59,999 --> 99:59:59,999 means a lot of different things to different people, 62 99:59:59,999 --> 99:59:59,999 but most of our public discourse on medicine 63 99:59:59,999 --> 99:59:59,999 really turns it into an engineering problem. 64 99:59:59,999 --> 99:59:59,999 We have the hallways of Congress, 65 99:59:59,999 --> 99:59:59,999 and the boardrooms of insurance companies 66 99:59:59,999 --> 99:59:59,999 that try to figure out how to pay for it. 67 99:59:59,999 --> 99:59:59,999 The ethicists and epidemiologists try to figure out how best 68 99:59:59,999 --> 99:59:59,999 to distribute medicine, 69 99:59:59,999 --> 99:59:59,999 and the hospitals and physicians are absolutely obsessed 70 99:59:59,999 --> 99:59:59,999 with their protocols and checklists, 71 99:59:59,999 --> 99:59:59,999 trying to figure out how best to safely apply medicine. 72 99:59:59,999 --> 99:59:59,999 These are all good things. 73 99:59:59,999 --> 99:59:59,999 However, they also all assume 74 99:59:59,999 --> 99:59:59,999 at some level 75 99:59:59,999 --> 99:59:59,999 that the textbook of medicine is closed. 76 99:59:59,999 --> 99:59:59,999 We start to measure the quality of our healthcare 77 99:59:59,999 --> 99:59:59,999 by how quickly we can access it. 78 99:59:59,999 --> 99:59:59,999 It doesn't surprise me that in this climate, 79 99:59:59,999 --> 99:59:59,999 many of our institutions for for the provision of healthcare 80 99:59:59,999 --> 99:59:59,999 start to look a heck of a lot like Jiffy Lube. 81 99:59:59,999 --> 99:59:59,999 (Laughter) 82 99:59:59,999 --> 99:59:59,999 The only problem is that when I graduated from medical school, 83 99:59:59,999 --> 99:59:59,999 I didn't get one of those little doohickeys 84 99:59:59,999 --> 99:59:59,999 that your mechanic has to plug into your car 85 99:59:59,999 --> 99:59:59,999 and find out exactly what's wrong with it, 86 99:59:59,999 --> 99:59:59,999 because the textbook of medicine 87 99:59:59,999 --> 99:59:59,999 is not closed. 88 99:59:59,999 --> 99:59:59,999 Medicine is science. 89 99:59:59,999 --> 99:59:59,999 Medicine is knowledge in process. 90 99:59:59,999 --> 99:59:59,999 We make an observation, 91 99:59:59,999 --> 99:59:59,999 we guess an explanation of that observation, 92 99:59:59,999 --> 99:59:59,999 and then we make a prediction that we can test. 93 99:59:59,999 --> 99:59:59,999 Now the testing ground 94 99:59:59,999 --> 99:59:59,999 of most predictions in medicine 95 99:59:59,999 --> 99:59:59,999 is populations, 96 99:59:59,999 --> 99:59:59,999 and you may remember from those boring days in biology class 97 99:59:59,999 --> 99:59:59,999 that populations tend to distribute 98 99:59:59,999 --> 99:59:59,999 around a mean 99 99:59:59,999 --> 99:59:59,999 as a Gaussian or a normal curve. 100 99:59:59,999 --> 99:59:59,999 Therefore, in medicine, 101 99:59:59,999 --> 99:59:59,999 after we make a prediction from a guessed explanation, 102 99:59:59,999 --> 99:59:59,999 we test it in a population. 103 99:59:59,999 --> 99:59:59,999 That means that what we know in medicine, 104 99:59:59,999 --> 99:59:59,999 our knowledge and our knowhow, 105 99:59:59,999 --> 99:59:59,999 comes from populations, 106 99:59:59,999 --> 99:59:59,999 but extends only as far 107 99:59:59,999 --> 99:59:59,999 as the next outlier, 108 99:59:59,999 --> 99:59:59,999 the next exception, 109 99:59:59,999 --> 99:59:59,999 which, like Jupiter's moons, 110 99:59:59,999 --> 99:59:59,999 will teach us what we don't actually know. 111 99:59:59,999 --> 99:59:59,999 Now I am a surgeon 112 99:59:59,999 --> 99:59:59,999 who looks after patients with sarcoma. 113 99:59:59,999 --> 99:59:59,999 Sarcoma is a very rare form of cancer. 114 99:59:59,999 --> 99:59:59,999 It's the cancer of flesh and bones. 115 99:59:59,999 --> 99:59:59,999 And I would tell you that every one of my patients is an outlier, 116 99:59:59,999 --> 99:59:59,999 is an exception. 117 99:59:59,999 --> 99:59:59,999 There is no surgery I have ever performed for a sarcoma patient 118 99:59:59,999 --> 99:59:59,999 that has ever been guided 119 99:59:59,999 --> 99:59:59,999 by a randomized controlled clinical trial, 120 99:59:59,999 --> 99:59:59,999 what we consider the best kind of population-based evidence in medicine. 121 99:59:59,999 --> 99:59:59,999 People talk about thinking outside the box, 122 99:59:59,999 --> 99:59:59,999 but we don't even have a box 123 99:59:59,999 --> 99:59:59,999 in sarcoma. 124 99:59:59,999 --> 99:59:59,999 What we do have as we take a bath in the uncertainty 125 99:59:59,999 --> 99:59:59,999 and unknowns and exceptions and outliers that surround us in sarcoma 126 99:59:59,999 --> 99:59:59,999 is easy access to what I think are those two more important values 127 99:59:59,999 --> 99:59:59,999 for any science: 128 99:59:59,999 --> 99:59:59,999 humility and curiosity. 129 99:59:59,999 --> 99:59:59,999 Because if I am humble and curious, 130 99:59:59,999 --> 99:59:59,999 when a patient asks me a question, 131 99:59:59,999 --> 99:59:59,999 and I don't know the answer, 132 99:59:59,999 --> 99:59:59,999 I'll ask a colleague who may have a similar albeit distinct patient 133 99:59:59,999 --> 99:59:59,999 with sarcoma. 134 99:59:59,999 --> 99:59:59,999 We'll even establish international collaborations. 135 99:59:59,999 --> 99:59:59,999 Those patients will start to talk to each other through chatrooms 136 99:59:59,999 --> 99:59:59,999 and support groups. 137 99:59:59,999 --> 99:59:59,999 It's through this kind of humbly curious communication 138 99:59:59,999 --> 99:59:59,999 that we begin to try and learn new things. 139 99:59:59,999 --> 99:59:59,999 As an example, this is a patient of mine 140 99:59:59,999 --> 99:59:59,999 who had a cancer near his knee. 141 99:59:59,999 --> 99:59:59,999 Because of humbly curious communication 142 99:59:59,999 --> 99:59:59,999 in international collaborations, 143 99:59:59,999 --> 99:59:59,999 we have learned that we can repurpose the ankle to serve as the knee 144 99:59:59,999 --> 99:59:59,999 when we have to remove the knee with the cancer. 145 99:59:59,999 --> 99:59:59,999 He can then wear a prosthetic and run and jump and play. 146 99:59:59,999 --> 99:59:59,999 This opportunity was available to him 147 99:59:59,999 --> 99:59:59,999 because of international collaborations. 148 99:59:59,999 --> 99:59:59,999 It was desirable to him 149 99:59:59,999 --> 99:59:59,999 because he had contacted other patients 150 99:59:59,999 --> 99:59:59,999 who had experienced it. 151 99:59:59,999 --> 99:59:59,999 And so exceptions and outliers in medicine 152 99:59:59,999 --> 99:59:59,999 teach us what we don't know, but also lead us to new thinking. 153 99:59:59,999 --> 99:59:59,999 Now very importantly, 154 99:59:59,999 --> 99:59:59,999 all the new thinking that outliers 155 99:59:59,999 --> 99:59:59,999 and exceptions lead us to in medicine 156 99:59:59,999 --> 99:59:59,999 does not only apply to the outliers and exceptions. 157 99:59:59,999 --> 99:59:59,999 It is not that we only learn from sarcoma patients 158 99:59:59,999 --> 99:59:59,999 ways to manage sarcoma patients. 159 99:59:59,999 --> 99:59:59,999 Sometimes, the outliers 160 99:59:59,999 --> 99:59:59,999 and the exceptions 161 99:59:59,999 --> 99:59:59,999 teach us things that matter quite a lot to the general population. 162 99:59:59,999 --> 99:59:59,999 Like a tree standing outside a forests, the outliers and the exceptions 163 99:59:59,999 --> 99:59:59,999 draw our attention 164 99:59:59,999 --> 99:59:59,999 and lead us into a much greater sense 165 99:59:59,999 --> 99:59:59,999 of perhaps what a tree is. 166 99:59:59,999 --> 99:59:59,999 We often talk about losing the forests for the trees, 167 99:59:59,999 --> 99:59:59,999 but one also loses a tree 168 99:59:59,999 --> 99:59:59,999 within a forest. 169 99:59:59,999 --> 99:59:59,999 But the tree that stands out by itself 170 99:59:59,999 --> 99:59:59,999 makes those relationships 171 99:59:59,999 --> 99:59:59,999 that define a tree, 172 99:59:59,999 --> 99:59:59,999 the relationships between trunk and roots and branches, 173 99:59:59,999 --> 99:59:59,999 much more apparent. 174 99:59:59,999 --> 99:59:59,999 Even if that tree is crooked 175 99:59:59,999 --> 99:59:59,999 or even if that tree 176 99:59:59,999 --> 99:59:59,999 has very unusual relationships between trunk and roots and branches, 177 99:59:59,999 --> 99:59:59,999 it nonetheless draws our attention 178 99:59:59,999 --> 99:59:59,999 and allows us to make observation 179 99:59:59,999 --> 99:59:59,999 that we can then test in the general population. 180 99:59:59,999 --> 99:59:59,999 I told you that sarcomas are rare. 181 99:59:59,999 --> 99:59:59,999 They make up about 1 percent of all cancers. 182 99:59:59,999 --> 99:59:59,999 You also probably know that cancer is considered a genetic disease. 183 99:59:59,999 --> 99:59:59,999 By genetic disease, we mean that cancer is caused by oncogenes 184 99:59:59,999 --> 99:59:59,999 that are turned on in cancer 185 99:59:59,999 --> 99:59:59,999 and tumor suppressor genes that are turned off to cause cancer. 186 99:59:59,999 --> 99:59:59,999 You might think that we learned about oncogenes 187 99:59:59,999 --> 99:59:59,999 and tumor suppressor genes from common cancers 188 99:59:59,999 --> 99:59:59,999 like breast cancer and prostate cancer and lung cancer, 189 99:59:59,999 --> 99:59:59,999 but you'd be wrong. 190 99:59:59,999 --> 99:59:59,999 We learned about oncogenes and tumor suppressor genes 191 99:59:59,999 --> 99:59:59,999 for the first time 192 99:59:59,999 --> 99:59:59,999 in that itty bitty little one percent cancers called sarcoma. 193 99:59:59,999 --> 99:59:59,999 In 1966, Peyton Rous