1 00:00:00,738 --> 00:00:02,952 I have a tendency to assume the worst, 2 00:00:03,757 --> 00:00:06,620 and once in a while, this habit plays tricks on me. 3 00:00:06,644 --> 00:00:09,925 For example, if I feel unexpected pain in my body 4 00:00:09,949 --> 00:00:13,456 that I have not experienced before and that I cannot attribute, 5 00:00:13,480 --> 00:00:18,000 then all of a sudden, my mind might turn a tense back into heart disease 6 00:00:18,024 --> 00:00:20,920 or calf muscle pain into deep vein thrombosis. 7 00:00:21,699 --> 00:00:25,217 But so far, I haven't been diagnosed with any deadly or incurable disease. 8 00:00:25,241 --> 00:00:27,653 Sometimes things just hurt for no clear reason. 9 00:00:29,098 --> 00:00:31,318 But not everyone is as lucky as me. 10 00:00:31,970 --> 00:00:35,215 Every year, more than 50 million people die worldwide. 11 00:00:36,287 --> 00:00:39,820 Especially in high-income economies like ours, 12 00:00:39,844 --> 00:00:44,599 a large fraction of deaths is caused by slowly progressing diseases: 13 00:00:44,623 --> 00:00:48,931 heart disease, chronic lung disease, cancer, Alzheimer's, diabetes, 14 00:00:48,955 --> 00:00:50,325 just to name a few. 15 00:00:51,300 --> 00:00:55,804 Now, humanity has made tremendous progress in diagnosing and treating many of these. 16 00:00:56,859 --> 00:01:00,060 But we are at a stage where further advancement in health 17 00:01:00,084 --> 00:01:03,374 cannot be achieved only by developing new treatments. 18 00:01:03,398 --> 00:01:05,798 And this becomes evident when we look at one aspect 19 00:01:05,822 --> 00:01:08,188 that many of these diseases have in common: 20 00:01:09,418 --> 00:01:12,246 the probability for successful treatment 21 00:01:12,270 --> 00:01:14,912 strongly depends on when treatment is started. 22 00:01:15,370 --> 00:01:18,814 But a disease is typically only detected once symptoms occur. 23 00:01:19,632 --> 00:01:24,025 The problem here is that, in fact, many diseases can remain asymptomatic, 24 00:01:24,049 --> 00:01:26,902 hence undetected, for a long period of time. 25 00:01:27,902 --> 00:01:31,803 Because of this, there is a persisting need for new ways 26 00:01:31,827 --> 00:01:33,775 of detecting disease at early stage, 27 00:01:33,799 --> 00:01:35,937 way before any symptoms occur. 28 00:01:37,135 --> 00:01:39,411 In health care, this is called screening. 29 00:01:39,435 --> 00:01:42,600 And as defined by the World Health Organization, 30 00:01:42,624 --> 00:01:48,282 screening is "the presumptive identification of unrecognized disease 31 00:01:48,306 --> 00:01:50,867 in an apparently healthy [person], 32 00:01:50,891 --> 00:01:54,680 by means of tests ... that can be applied rapidly and easily ..." 33 00:01:55,429 --> 00:01:57,618 That's a long definition, so let me repeat it: 34 00:01:58,237 --> 00:02:01,722 identification of unrecognized disease 35 00:02:01,746 --> 00:02:04,230 in an apparently healthy person 36 00:02:04,254 --> 00:02:08,268 by means of tests that can be applied both rapidly and easily. 37 00:02:08,292 --> 00:02:11,671 And I want to put special emphasis on the words "rapidly" and "easily" 38 00:02:11,695 --> 00:02:13,945 because many of the existing screening methods 39 00:02:13,969 --> 00:02:15,628 are exactly the opposite. 40 00:02:16,189 --> 00:02:18,888 And those of you who have undergone colonoscopy 41 00:02:18,912 --> 00:02:22,111 as part of a screening program for colorectal cancer 42 00:02:22,135 --> 00:02:23,482 will know what I mean. 43 00:02:25,209 --> 00:02:28,285 Obviously, there's a variety of medical tools available 44 00:02:28,309 --> 00:02:29,838 to perform screening tests. 45 00:02:30,298 --> 00:02:33,984 This ranges from imaging techniques such as radiography 46 00:02:34,008 --> 00:02:36,138 or magnetic resonance imaging 47 00:02:36,162 --> 00:02:38,166 to the analysis of blood or tissue. 48 00:02:38,190 --> 00:02:40,106 We have all had such tests. 49 00:02:41,344 --> 00:02:44,917 But there's one medium that for long has been overlooked; 50 00:02:45,674 --> 00:02:48,416 a medium that is easily accessible, 51 00:02:48,440 --> 00:02:50,461 basically nondepletable, 52 00:02:50,485 --> 00:02:53,732 and it holds tremendous promise for medical analysis. 53 00:02:54,994 --> 00:02:56,522 And that is our breath. 54 00:02:58,514 --> 00:03:01,895 Human breath is essentially composed of five components: 55 00:03:02,649 --> 00:03:09,325 nitrogen, oxygen, carbon dioxide, water and argon. 56 00:03:09,349 --> 00:03:12,748 But besides these five, there are hundreds of other components 57 00:03:12,772 --> 00:03:15,155 that are present in very low quantity. 58 00:03:15,179 --> 00:03:17,732 These are called volatile organic compounds, 59 00:03:17,756 --> 00:03:20,089 and we release hundreds, even thousands of them 60 00:03:20,113 --> 00:03:21,872 every time we exhale. 61 00:03:23,110 --> 00:03:26,479 The analysis of these volatile organic compounds in our breath 62 00:03:26,503 --> 00:03:28,204 is called breath analysis. 63 00:03:29,545 --> 00:03:33,309 In fact, I believe that many of you have already experienced breath analysis. 64 00:03:33,333 --> 00:03:36,934 Imagine: you're driving home late at night, 65 00:03:36,958 --> 00:03:39,656 when suddenly, there's a friendly police officer 66 00:03:39,680 --> 00:03:42,472 who asks you kindly but firmly 67 00:03:42,496 --> 00:03:45,899 to pull over and blow into a device like this one. 68 00:03:47,486 --> 00:03:50,709 This is an alcohol breath tester 69 00:03:50,733 --> 00:03:54,440 that is used to measure the ethanol concentration in your breath 70 00:03:54,464 --> 00:03:57,821 and determine whether driving in your condition is a clever idea. 71 00:03:58,509 --> 00:04:00,456 Now, I'd say my driving was pretty good, 72 00:04:00,480 --> 00:04:01,700 but let me check. 73 00:04:02,788 --> 00:04:04,715 (Beep) 74 00:04:08,445 --> 00:04:11,405 Zero point zero, so nothing to worry about, all fine. 75 00:04:11,429 --> 00:04:12,696 (Laughter) 76 00:04:14,298 --> 00:04:16,959 Now imagine a device like this one, 77 00:04:16,983 --> 00:04:19,927 that does not only measure alcohol levels in your breath, 78 00:04:19,951 --> 00:04:23,767 but that detects diseases like the ones I've shown you 79 00:04:23,791 --> 00:04:25,507 and potentially many more. 80 00:04:26,868 --> 00:04:30,666 The concept of correlating the smell of a person's breath 81 00:04:30,690 --> 00:04:32,810 with certain medical conditions, 82 00:04:32,834 --> 00:04:35,254 in fact, dates back to Ancient Greece. 83 00:04:35,905 --> 00:04:40,876 But only recently, research efforts on breath analysis have skyrocketed, 84 00:04:40,900 --> 00:04:44,307 and what once was a dream is now becoming reality. 85 00:04:45,307 --> 00:04:48,321 And let me pull up this list again that I showed you earlier. 86 00:04:49,047 --> 00:04:51,813 For the majority of diseases listed here, 87 00:04:52,495 --> 00:04:54,688 there's substantial scientific evidence 88 00:04:54,712 --> 00:04:58,369 suggesting that the disease could be detected by breath analysis. 89 00:04:59,917 --> 00:05:01,612 But how does it work, exactly? 90 00:05:02,421 --> 00:05:05,199 The essential part is a sensor device 91 00:05:05,223 --> 00:05:08,435 that detects the volatile organic compounds in our breath. 92 00:05:09,364 --> 00:05:12,294 Simply put: when exposed to a breath sample, 93 00:05:12,318 --> 00:05:15,002 the sensor outputs a complex signature 94 00:05:15,026 --> 00:05:19,006 that results from the mixture of volatile organic compounds that we exhale. 95 00:05:20,141 --> 00:05:24,457 Now, this signature represents a fingerprint of your metabolism, 96 00:05:24,481 --> 00:05:25,646 your microbiome 97 00:05:25,670 --> 00:05:29,273 and the biochemical processes that occur in your body. 98 00:05:29,980 --> 00:05:31,573 If you have a disease, 99 00:05:31,597 --> 00:05:33,884 your organism will change, 100 00:05:33,908 --> 00:05:36,868 and so will the composition of your exhaled breath. 101 00:05:37,479 --> 00:05:42,609 And then the only thing that is left to do is to correlate a certain signature 102 00:05:42,633 --> 00:05:45,739 with the presence or absence of certain medical conditions. 103 00:05:47,921 --> 00:05:51,156 The technology promises several undeniable benefits. 104 00:05:51,719 --> 00:05:54,816 Firstly, the sensor can be miniaturized 105 00:05:54,840 --> 00:05:57,686 and integrated into small, handheld devices 106 00:05:57,710 --> 00:05:59,548 like this alcohol breath tester. 107 00:06:00,437 --> 00:06:03,450 This would allow the test to be used in many different settings 108 00:06:03,474 --> 00:06:05,248 and even at home, 109 00:06:05,272 --> 00:06:07,266 so that a visit at the doctor's office 110 00:06:07,290 --> 00:06:10,049 is not needed each time a test shall be performed. 111 00:06:10,946 --> 00:06:14,326 Secondly, breath analysis is noninvasive 112 00:06:14,350 --> 00:06:17,997 and can be as simple as blowing into an alcohol breath tester. 113 00:06:18,900 --> 00:06:23,894 Such simplicity and ease of use would reduce patient burden 114 00:06:23,918 --> 00:06:27,361 and provide an incentive for broad adoption of the technology. 115 00:06:27,973 --> 00:06:32,081 And thirdly, the technology is so flexible 116 00:06:32,105 --> 00:06:34,345 that the same device could be used 117 00:06:34,369 --> 00:06:37,509 to detect a broad range of medical conditions. 118 00:06:38,224 --> 00:06:42,909 Breath analysis could be used to screen for multiple diseases at the same time. 119 00:06:44,195 --> 00:06:47,526 Nowadays, each disease typically requires a different medical tool 120 00:06:47,550 --> 00:06:49,006 to perform a screening test. 121 00:06:49,561 --> 00:06:52,645 But this means you can only find what you're looking for. 122 00:06:54,637 --> 00:06:58,496 With all of these features, breath analysis is predestined 123 00:06:58,520 --> 00:07:01,584 to deliver what many traditional screening tests are lacking. 124 00:07:02,671 --> 00:07:04,310 And most importantly, 125 00:07:04,334 --> 00:07:07,684 all of these features should eventually provide us 126 00:07:07,708 --> 00:07:10,214 with a platform for medical analysis 127 00:07:10,238 --> 00:07:13,943 that can operate at attractively low cost per test. 128 00:07:15,713 --> 00:07:18,963 On the contrary, existing medical tools 129 00:07:18,987 --> 00:07:21,373 often lead to rather high cost per test. 130 00:07:21,920 --> 00:07:24,198 Then, in order to keep costs down, 131 00:07:24,222 --> 00:07:26,832 the number of tests needs to be restricted, 132 00:07:27,562 --> 00:07:30,803 and this means: a) that the tests can only be performed 133 00:07:30,827 --> 00:07:35,511 on a narrow part of the population, for example, the high-risk population; 134 00:07:35,535 --> 00:07:40,690 and b) that the number of tests per person needs to be kept at a minimum. 135 00:07:41,459 --> 00:07:43,303 But wouldn't it actually be beneficial 136 00:07:43,327 --> 00:07:46,287 if the test was performed on a larger group of people, 137 00:07:46,311 --> 00:07:50,559 and more often and over a longer period of time for each individual? 138 00:07:51,845 --> 00:07:55,706 Especially the latter would give access to something very valuable 139 00:07:55,730 --> 00:07:57,997 that is called longitudinal data. 140 00:07:58,950 --> 00:08:03,052 Longitudinal data is a data set that tracks the same patient 141 00:08:03,076 --> 00:08:05,572 over the course of many months or years. 142 00:08:07,318 --> 00:08:12,368 Nowadays, medical decisions are often based on a limited data set, 143 00:08:12,392 --> 00:08:15,584 where only a glimpse of a patient's medical history 144 00:08:15,608 --> 00:08:17,662 is available for decision-making. 145 00:08:18,210 --> 00:08:20,509 In such a case, 146 00:08:20,533 --> 00:08:23,326 abnormalities are typically detected 147 00:08:23,350 --> 00:08:25,916 by comparing a patient's health profile 148 00:08:25,940 --> 00:08:29,212 to the average health profile of a reference population. 149 00:08:30,419 --> 00:08:34,337 Longitudinal data would open up a new dimension 150 00:08:34,361 --> 00:08:37,229 and allow abnormalities to be detected 151 00:08:37,253 --> 00:08:39,950 based on a patient's own medical history. 152 00:08:40,862 --> 00:08:43,685 This will pave the way for personalized treatment. 153 00:08:44,741 --> 00:08:46,305 Sounds pretty great, right? 154 00:08:47,194 --> 00:08:50,169 Now you will certainly have a question that is something like, 155 00:08:50,193 --> 00:08:54,988 "If the technology is as great as he says, then why aren't we using it today?" 156 00:08:55,012 --> 00:08:57,490 And the only answer I can give you is: 157 00:08:57,514 --> 00:09:00,094 not everything is as easy as it sounds. 158 00:09:00,983 --> 00:09:04,470 There are technical challenges, for example. 159 00:09:04,494 --> 00:09:07,508 There's the need for extremely reliable sensors 160 00:09:07,532 --> 00:09:10,800 that can detect mixtures of volatile organic compounds 161 00:09:10,824 --> 00:09:12,917 with sufficient reproducibility. 162 00:09:13,629 --> 00:09:16,064 And another technical challenge is this: 163 00:09:16,088 --> 00:09:21,074 How do you sample a person's breath in a very defined manner 164 00:09:21,098 --> 00:09:23,446 so that the sampling process itself 165 00:09:23,470 --> 00:09:26,123 does not alter the result of the analysis? 166 00:09:27,187 --> 00:09:28,975 And there's the need for data. 167 00:09:29,556 --> 00:09:33,514 Breath analysis needs to be validated in clinical trials, 168 00:09:33,538 --> 00:09:36,030 and enough data needs to be collected 169 00:09:36,054 --> 00:09:40,296 so that individual conditions can be measured against baselines. 170 00:09:41,167 --> 00:09:43,640 Breath analysis can only succeed 171 00:09:43,664 --> 00:09:46,437 if a large enough data set can be generated 172 00:09:46,461 --> 00:09:48,811 and made available for broad use. 173 00:09:51,050 --> 00:09:53,880 If breath analysis holds up to its promises, 174 00:09:54,745 --> 00:09:57,271 this is a technology that could truly aid us 175 00:09:57,295 --> 00:09:59,538 to transform our health care system -- 176 00:10:00,410 --> 00:10:03,564 transform it from a reactive system 177 00:10:03,588 --> 00:10:06,750 where treatment is triggered by symptoms of disease 178 00:10:06,774 --> 00:10:08,789 to a proactive system, 179 00:10:08,813 --> 00:10:12,027 where disease detection, diagnosis and treatment 180 00:10:12,051 --> 00:10:13,935 can happen at early stage, 181 00:10:13,959 --> 00:10:16,058 way before any symptoms occur. 182 00:10:17,590 --> 00:10:20,976 Now this brings me to my last point, and it's a fundamental one. 183 00:10:21,537 --> 00:10:23,526 What, exactly, is a disease? 184 00:10:24,590 --> 00:10:28,625 Imagine that breath analysis can be commercialized as I describe it, 185 00:10:28,649 --> 00:10:31,255 and early detection becomes routine. 186 00:10:32,417 --> 00:10:34,721 A problem that remains is, in fact, a problem 187 00:10:34,745 --> 00:10:37,733 that any screening activity has to face 188 00:10:37,757 --> 00:10:39,578 because, for many diseases, 189 00:10:39,602 --> 00:10:43,426 it is often impossible to predict with sufficient certainty 190 00:10:43,450 --> 00:10:45,992 whether the disease would ever cause any symptoms 191 00:10:46,016 --> 00:10:48,138 or put a person's life at risk. 192 00:10:48,990 --> 00:10:51,549 This is called overdiagnosis, 193 00:10:51,573 --> 00:10:53,211 and it leads to a dilemma. 194 00:10:53,927 --> 00:10:56,011 If a disease is identified, 195 00:10:56,035 --> 00:10:58,079 you could decide not to treat it 196 00:10:58,103 --> 00:11:02,074 because there's a certain probability that you would never suffer from it. 197 00:11:02,955 --> 00:11:04,454 But how much would you suffer 198 00:11:04,478 --> 00:11:07,865 just from knowing that you have a potentially deadly disease? 199 00:11:07,889 --> 00:11:10,813 And wouldn't you actually regret that the disease was detected 200 00:11:10,813 --> 00:11:12,080 in the first place? 201 00:11:13,281 --> 00:11:17,169 Your second option is to undergo early treatment 202 00:11:17,193 --> 00:11:18,843 with the hope for curing it. 203 00:11:19,485 --> 00:11:22,314 But often, this would not come without side effects. 204 00:11:25,623 --> 00:11:27,727 To be precise: 205 00:11:27,751 --> 00:11:30,325 the bigger problem is not overdiagnosis, 206 00:11:30,349 --> 00:11:31,802 it's overtreatment, 207 00:11:31,826 --> 00:11:34,841 because not every disease has to be treated immediately 208 00:11:34,865 --> 00:11:36,925 just because a treatment is available. 209 00:11:39,441 --> 00:11:42,139 The increasing adoption of routine screening 210 00:11:42,163 --> 00:11:43,912 will raise the question: 211 00:11:45,082 --> 00:11:49,173 What do we call a disease that can rationalize treatment, 212 00:11:49,197 --> 00:11:53,785 and what is just an abnormality that should not be a source of concern? 213 00:11:55,404 --> 00:12:00,336 My hopes are that routine screening using breath analysis 214 00:12:00,360 --> 00:12:03,120 can provide enough data and insight 215 00:12:03,144 --> 00:12:07,690 so that at some point, we'll be able to break this dilemma 216 00:12:07,714 --> 00:12:10,144 and predict with sufficient certainty 217 00:12:10,168 --> 00:12:12,858 whether and when to treat at early stage. 218 00:12:14,794 --> 00:12:19,513 Our breath and the mixture of volatile organic compounds that we exhale 219 00:12:19,537 --> 00:12:24,207 hold tremendous amounts of information on our physiological condition. 220 00:12:25,262 --> 00:12:28,602 With what we know today, we have only scratched the surface. 221 00:12:29,993 --> 00:12:34,234 As we collect more and more data and breath profiles across the population, 222 00:12:34,258 --> 00:12:38,790 including all varieties of gender, age, origin and lifestyle, 223 00:12:38,814 --> 00:12:41,147 the power of breath analysis should increase. 224 00:12:42,147 --> 00:12:47,725 And eventually, breath analysis should provide us with a powerful tool 225 00:12:47,749 --> 00:12:52,215 not only to proactively detect specific diseases, 226 00:12:52,239 --> 00:12:55,888 but to predict and ultimately prevent them. 227 00:12:57,110 --> 00:12:59,728 And this should be enough motivation 228 00:12:59,752 --> 00:13:03,935 to embrace the opportunities and challenges 229 00:13:03,959 --> 00:13:06,420 that breath analysis can provide, 230 00:13:06,444 --> 00:13:09,846 even for people that are not part-time hypochondriacs like me. 231 00:13:10,532 --> 00:13:11,689 Thank you. 232 00:13:11,713 --> 00:13:15,730 (Applause)