1 00:00:01,068 --> 00:00:03,269 Viewers like you make this program possible. 2 00:00:03,270 --> 00:00:05,339 Support your local PBS station. 3 00:00:15,850 --> 00:00:17,751 This really is 4 00:00:17,752 --> 00:00:19,619 one of the greatest stories in medicine. 5 00:00:19,620 --> 00:00:21,488 Most people thought that can't be done. 6 00:00:21,489 --> 00:00:23,256 An epic quest... 7 00:00:23,257 --> 00:00:24,524 We're gonna keep going. 8 00:00:24,525 --> 00:00:25,725 We're not gonna stop. 9 00:00:25,726 --> 00:00:27,460 We will find something. 10 00:00:27,461 --> 00:00:30,497 ...to save lives otherwise cut too short. 11 00:00:30,498 --> 00:00:32,165 It was a sure death, 12 00:00:32,166 --> 00:00:34,534 generally in childhood. 13 00:00:34,535 --> 00:00:36,669 Powered not only by scientists, 14 00:00:36,670 --> 00:00:41,875 but by the determination of those with the most to lose. 15 00:00:41,876 --> 00:00:44,778 It was driven by the passion of the parents. 16 00:00:44,779 --> 00:00:47,380 CAM McLOUD: I had to get involved 17 00:00:47,381 --> 00:00:49,016 any way that I could. 18 00:00:50,151 --> 00:00:52,552 An extraordinary scientific breakthrough. 19 00:00:52,553 --> 00:00:54,020 I ran out in the hallway, 20 00:00:54,021 --> 00:00:55,722 "Eureka!" 21 00:00:55,723 --> 00:00:58,525 {\an8}The most exciting announcement in the 50 years... 22 00:00:58,526 --> 00:01:01,461 Wow. This is as clear 23 00:01:01,462 --> 00:01:03,596 as science gets. 24 00:01:03,597 --> 00:01:05,999 Not working, working. 25 00:01:06,000 --> 00:01:08,435 I actually cried. 26 00:01:08,436 --> 00:01:10,036 It just blew my mind. 27 00:01:10,037 --> 00:01:11,237 Ah! 28 00:01:11,238 --> 00:01:13,540 Transforming lives forever. 29 00:01:13,541 --> 00:01:16,609 I'm breathing, like, I'm breathing without pain. 30 00:01:16,610 --> 00:01:18,211 It was something you, 31 00:01:18,212 --> 00:01:19,213 you sort of dream about. 32 00:01:20,214 --> 00:01:23,450 To see children starting to recover, 33 00:01:23,451 --> 00:01:26,786 It's just... it's just unimaginable. 34 00:01:28,622 --> 00:01:30,457 "The Battle to Breathe." 35 00:01:30,458 --> 00:01:32,960 Right now, on "NOVA!" 36 00:01:54,849 --> 00:01:56,382 The fact that I'm running today, 37 00:01:56,383 --> 00:01:59,652 with clear lungs and no coughing at all, 38 00:01:59,653 --> 00:02:01,754 is something that, when I was born, 39 00:02:01,755 --> 00:02:03,090 no one thought would be possible. 40 00:02:05,626 --> 00:02:08,461 I was told kids with this condition 41 00:02:08,462 --> 00:02:11,331 are often not living past 18. 42 00:02:11,332 --> 00:02:13,533 It was very scary. 43 00:02:13,534 --> 00:02:15,735 Jon is out here 44 00:02:15,736 --> 00:02:18,438 thanks to a remarkable scientific breakthrough. 45 00:02:18,439 --> 00:02:21,908 Since the new generation of medications, 46 00:02:21,909 --> 00:02:24,844 I can run and never think about being sick at all, 47 00:02:24,845 --> 00:02:27,347 it's incredible. 48 00:02:27,348 --> 00:02:29,883 A revolution in medical science 49 00:02:29,884 --> 00:02:32,418 has recently transformed 50 00:02:32,419 --> 00:02:34,721 the lives of those like Jon, 51 00:02:34,722 --> 00:02:36,956 born with the rare and deadly genetic disease: 52 00:02:36,957 --> 00:02:38,325 cystic fibrosis. 53 00:02:39,527 --> 00:02:40,894 It's a story of hope 54 00:02:40,895 --> 00:02:42,262 and perseverance 55 00:02:42,263 --> 00:02:44,163 that we've gotten to the place that we're at today. 56 00:02:57,545 --> 00:02:59,746 That tiny little guy... 57 00:02:59,747 --> 00:03:02,282 On May 1, 1989, 58 00:03:02,283 --> 00:03:04,717 a miserable kind of snowy spring day 59 00:03:04,718 --> 00:03:07,153 {\an8}a young attending physician walked in, 60 00:03:07,154 --> 00:03:08,655 {\an8}who we'd never met, 61 00:03:08,656 --> 00:03:11,124 {\an8}uh, looked us straight in the eye 62 00:03:11,125 --> 00:03:13,126 and said, "Your child has cystic fibrosis. 63 00:03:13,127 --> 00:03:15,995 "They will be sick their entire lifetime 64 00:03:15,996 --> 00:03:17,130 "with lung infections, 65 00:03:17,131 --> 00:03:19,265 "culminating in pneumonia, 66 00:03:19,266 --> 00:03:22,769 "uh, about, uh, age of 18, 67 00:03:22,770 --> 00:03:24,037 probably will die." 68 00:03:24,038 --> 00:03:27,173 And that was the diagnosis. 69 00:03:27,174 --> 00:03:30,577 And they, uh, said that we need to immediately test 70 00:03:30,578 --> 00:03:31,978 your other son, Andrew, 71 00:03:31,979 --> 00:03:35,182 and he was, uh, diagnosed positive the next day. 72 00:03:38,652 --> 00:03:42,689 Each year, around 1,000 families in the United States 73 00:03:42,690 --> 00:03:44,691 are told by their physician 74 00:03:44,692 --> 00:03:48,761 that their children have inherited cystic fibrosis-- CF. 75 00:03:48,762 --> 00:03:52,966 Cystic fibrosis is a genetic disorder. 76 00:03:52,967 --> 00:03:55,468 {\an8}You have to have one abnormal copy of the gene 77 00:03:55,469 --> 00:03:56,869 {\an8}from your mother, 78 00:03:56,870 --> 00:03:59,005 {\an8}and one abnormal copy of the gene from your father. 79 00:03:59,006 --> 00:04:01,541 So people are born with this disease, 80 00:04:01,542 --> 00:04:05,211 they have signs and symptoms early as toddlers, 81 00:04:05,212 --> 00:04:08,015 and over time, the disease progresses. 82 00:04:15,389 --> 00:04:17,490 {\an8}Emily Kramer-Golinkoff 83 00:04:17,491 --> 00:04:20,026 {\an8}has lived with CF, against the odds, 84 00:04:20,027 --> 00:04:21,495 {\an8}for 40 years. 85 00:04:23,364 --> 00:04:24,964 {\an8}KRAMER-GOLINKOFF: I spend a lot of my day 86 00:04:24,965 --> 00:04:27,367 {\an8}hooked up to medical devices. 87 00:04:27,368 --> 00:04:29,637 {\an8}I inhale a whole variety of different medications. 88 00:04:31,739 --> 00:04:34,642 {\an8}I have an airway vest, which vibrates my lungs. 89 00:04:37,778 --> 00:04:41,347 {\an8}There's not a minute of a day that goes by 90 00:04:41,348 --> 00:04:43,684 {\an8}where CF is not on my mind. 91 00:04:44,818 --> 00:04:46,786 {\an8}There is this like, 92 00:04:46,787 --> 00:04:49,789 {\an8}constant ticker in my head, 93 00:04:49,790 --> 00:04:52,525 {\an8}um, monitoring every single 94 00:04:52,526 --> 00:04:55,195 bodily sensation, and it is exhausting. 95 00:04:57,798 --> 00:05:01,034 Around 40,000 Americans live with CF, 96 00:05:01,035 --> 00:05:04,170 and it affects people of every race and ethnicity 97 00:05:04,171 --> 00:05:05,772 around the world. 98 00:05:12,780 --> 00:05:14,814 At 25 years old, 99 00:05:14,815 --> 00:05:16,516 Marwan Moheissen 100 00:05:16,517 --> 00:05:18,184 is one of Egypt's oldest known 101 00:05:18,185 --> 00:05:21,054 surviving CF patients. 102 00:05:21,055 --> 00:05:22,956 {\an8}MOHEISSEN 103 00:05:23,991 --> 00:05:26,192 {\an8}A lot of people don't know what this is, 104 00:05:26,193 --> 00:05:28,728 {\an8}and I want them to know. When I'm coughing... 105 00:05:30,297 --> 00:05:31,664 ...it's not gonna hurt them. 106 00:05:33,167 --> 00:05:36,403 It's the opposite. I'm more at risk. 107 00:05:38,439 --> 00:05:41,008 Leaving home now is harder. 108 00:05:42,176 --> 00:05:45,845 My lungs only work at 30% capacity, 109 00:05:45,846 --> 00:05:48,882 and the right lung barely functions. 110 00:05:50,017 --> 00:05:53,820 For Marwan, and everyone who inherits CF, 111 00:05:53,821 --> 00:05:57,023 something that normally protects them turns deadly-- 112 00:05:57,024 --> 00:05:59,560 their mucus. 113 00:06:00,961 --> 00:06:02,595 In the normal state, 114 00:06:02,596 --> 00:06:04,797 mucus is very thin and watery, 115 00:06:04,798 --> 00:06:06,766 so if you inhale something 116 00:06:06,767 --> 00:06:08,301 that you're not supposed to inhale, 117 00:06:08,302 --> 00:06:11,604 like a particle or a virus, your body helps dispel that 118 00:06:11,605 --> 00:06:13,973 by using very thin mucus to get it out. 119 00:06:15,542 --> 00:06:17,310 Whereas in CF, 120 00:06:17,311 --> 00:06:18,978 mucus is very thick and sticky, 121 00:06:18,979 --> 00:06:20,514 sometimes like tar. 122 00:06:22,516 --> 00:06:24,517 In the lungs, the cilia-- 123 00:06:24,518 --> 00:06:26,786 little hairs that usually beat to help you move things 124 00:06:26,787 --> 00:06:28,889 out of the airway... 125 00:06:30,424 --> 00:06:32,625 in that thick, sticky environment, 126 00:06:32,626 --> 00:06:35,428 they can't really function. 127 00:06:35,429 --> 00:06:37,897 So bacteria sets in, 128 00:06:37,898 --> 00:06:40,733 and then your body tries to fight off that infection 129 00:06:40,734 --> 00:06:42,668 with inflammation, 130 00:06:42,669 --> 00:06:45,772 and that makes the mucus even more sticky, 131 00:06:45,773 --> 00:06:48,708 so you get into this vicious cycle. 132 00:06:48,709 --> 00:06:50,476 At the same time, 133 00:06:50,477 --> 00:06:53,579 you get thick sticky mucus in your pancreas, 134 00:06:53,580 --> 00:06:54,781 in your liver, 135 00:06:54,782 --> 00:06:57,150 in your gut... 136 00:06:57,151 --> 00:07:00,019 And ultimately, it's the damage to the lungs 137 00:07:00,020 --> 00:07:02,021 which eventually causes death of most people 138 00:07:02,022 --> 00:07:03,657 with cystic fibrosis. 139 00:07:11,532 --> 00:07:13,166 How we came to understand 140 00:07:13,167 --> 00:07:17,136 and break the vicious, destructive cycle of CF 141 00:07:17,137 --> 00:07:22,175 is one of the greatest success stories in modern medicine. 142 00:07:22,176 --> 00:07:26,012 It began in New York City in 1938, 143 00:07:26,013 --> 00:07:28,447 with an unsung heroine of medical science-- 144 00:07:28,448 --> 00:07:32,318 Dorothy Andersen. 145 00:07:32,319 --> 00:07:34,954 Dorothy Andersen is amazing. 146 00:07:34,955 --> 00:07:36,889 {\an8}She was a real character. 147 00:07:36,890 --> 00:07:38,724 {\an8}I mean, she was a chain smoker, 148 00:07:38,725 --> 00:07:40,293 {\an8}she drank really hard. 149 00:07:40,294 --> 00:07:43,196 And she was a professional doctor 150 00:07:43,197 --> 00:07:46,567 when less than 5% of the doctors were women. 151 00:07:49,203 --> 00:07:51,771 In her hospital, there were these children 152 00:07:51,772 --> 00:07:53,806 who looked like they were starving 153 00:07:53,807 --> 00:07:56,843 and had horrible lung infections 154 00:07:56,844 --> 00:08:00,180 but nobody really knew what exactly was killing them. 155 00:08:02,683 --> 00:08:06,519 When Dorothy Andersen did the autopsies, 156 00:08:06,520 --> 00:08:09,589 {\an8}she discovered they had horrible mucus in the lungs, 157 00:08:09,590 --> 00:08:11,457 {\an8}and they had a hard pancreas, 158 00:08:11,458 --> 00:08:14,695 {\an8}filled with glistening white cysts. 159 00:08:17,364 --> 00:08:19,732 The pancreas is supposed to create all the juices 160 00:08:19,733 --> 00:08:22,068 that you need to digest your food, 161 00:08:22,069 --> 00:08:23,703 but it was dysfunctional. 162 00:08:23,704 --> 00:08:27,206 And so the children couldn't get any nutrition. 163 00:08:27,207 --> 00:08:29,508 When you combined these symptoms, 164 00:08:29,509 --> 00:08:31,811 she realized this was a new disease, 165 00:08:31,812 --> 00:08:34,614 and she named it cystic fibrosis of the pancreas. 166 00:08:39,019 --> 00:08:40,519 {\an8}Dr. Andersen noted 167 00:08:40,520 --> 00:08:41,687 {\an8}that the majority of patients 168 00:08:41,688 --> 00:08:44,858 {\an8}did not survive beyond a year. 169 00:08:48,228 --> 00:08:50,429 Though CF was new to medical science, 170 00:08:50,430 --> 00:08:53,266 one strange symptom of the disease 171 00:08:53,267 --> 00:08:55,601 had been described in European folklore 172 00:08:55,602 --> 00:08:58,070 for centuries-- 173 00:08:58,071 --> 00:09:02,108 "Woe to the child who tastes salty from a kiss on the brow, 174 00:09:02,109 --> 00:09:04,878 for he is cursed and soon will die." 175 00:09:07,414 --> 00:09:09,849 We did have a pulmonologist 176 00:09:09,850 --> 00:09:11,350 {\an8}who I used to think was so strange, 177 00:09:11,351 --> 00:09:13,119 {\an8}because if kids came in to be ruled out 178 00:09:13,120 --> 00:09:15,321 {\an8}for cystic fibrosis in the hospital, 179 00:09:15,322 --> 00:09:16,589 {\an8}he would actually go 180 00:09:16,590 --> 00:09:18,124 {\an8}and he'd kiss them on the forehead, 181 00:09:18,125 --> 00:09:19,792 and he'd be-- he'd come out of the room 182 00:09:19,793 --> 00:09:21,027 and be like, "They don't have CF, 183 00:09:21,028 --> 00:09:22,361 they're not salty." 184 00:09:22,362 --> 00:09:23,829 And I was just like, that is the weirdest thing. 185 00:09:23,830 --> 00:09:25,064 Um, but he was right. 186 00:09:25,065 --> 00:09:27,400 {\an8}You know, you'd be out in the yard goofing, 187 00:09:27,401 --> 00:09:28,868 {\an8}everybody's sweaty, and you give 'em a kiss. 188 00:09:28,869 --> 00:09:30,236 {\an8}There it is. 189 00:09:30,237 --> 00:09:31,804 {\an8}You know, I mean, pungently strong. 190 00:09:31,805 --> 00:09:34,540 {\an8}There would be salt, you know, 191 00:09:34,541 --> 00:09:38,778 {\an8}on his caps, on his, his face. 192 00:09:38,779 --> 00:09:41,014 And I mean, it was very evident. 193 00:09:43,050 --> 00:09:44,650 My mother was always saying 194 00:09:44,651 --> 00:09:47,386 "he's got funny sweat." 195 00:09:47,387 --> 00:09:48,587 You know, I don't know if it was so funny, 196 00:09:48,588 --> 00:09:50,089 but it was strange. 197 00:09:56,730 --> 00:09:59,031 For physiologist Paul Quinton, 198 00:09:59,032 --> 00:10:00,633 salty sweat would become a vital clue 199 00:10:00,634 --> 00:10:03,035 in unravelling the cause 200 00:10:03,036 --> 00:10:04,438 of this mysterious disease. 201 00:10:05,973 --> 00:10:08,808 Diagnosed with chronic bronchitis as a baby, 202 00:10:08,809 --> 00:10:10,109 by the time he was in college, 203 00:10:10,110 --> 00:10:13,446 he'd had part of his lung removed, 204 00:10:13,447 --> 00:10:17,083 and he began to research his condition. 205 00:10:17,084 --> 00:10:19,352 There was one book about chronic bronchitis 206 00:10:19,353 --> 00:10:21,721 {\an8}that had this little footnote that said, 207 00:10:21,722 --> 00:10:23,956 {\an8}"see: in reference to cystic fibrosis." 208 00:10:23,957 --> 00:10:26,892 And I-- and the more I read, 209 00:10:26,893 --> 00:10:28,962 then I began to get a chill down my back. 210 00:10:29,997 --> 00:10:32,698 "Holy crap, this is me!" 211 00:10:32,699 --> 00:10:36,369 A doctor confirmed his self-diagnosis. 212 00:10:36,370 --> 00:10:41,173 At 19, he seemed to be living on borrowed time. 213 00:10:41,174 --> 00:10:43,976 CF kids had been living longer 214 00:10:43,977 --> 00:10:46,746 {\an8}thanks to treatments like better antibiotics. 215 00:10:46,747 --> 00:10:50,316 {\an8}But by 1963, in the U.S., 216 00:10:50,317 --> 00:10:54,286 {\an8}half would still die before the age of ten. 217 00:10:54,287 --> 00:10:56,422 Everybody needs a purpose. 218 00:10:56,423 --> 00:10:58,991 And once I was introduced to this, 219 00:10:58,992 --> 00:11:00,426 that gave a purpose, you know-- 220 00:11:00,427 --> 00:11:01,660 "what, what is this thing? 221 00:11:01,661 --> 00:11:02,995 "What causes it? 222 00:11:02,996 --> 00:11:04,997 "How does the abnormality in the sweat relate 223 00:11:04,998 --> 00:11:06,466 to the abnormalities in the lung?" 224 00:11:08,101 --> 00:11:11,303 Paul started studying sweat ducts, 225 00:11:11,304 --> 00:11:13,272 the tiny tubes that release sweat 226 00:11:13,273 --> 00:11:16,275 onto the skin to keep us cool. 227 00:11:16,276 --> 00:11:18,344 Comparing ones from healthy volunteers 228 00:11:18,345 --> 00:11:21,180 to his own. 229 00:11:21,181 --> 00:11:22,882 I took biopsies from my thighs. 230 00:11:22,883 --> 00:11:26,385 I would just zap my leg in the, in the thigh 231 00:11:26,386 --> 00:11:28,320 and, uh, pull out. 232 00:11:28,321 --> 00:11:30,523 Uh, usually I got maybe four plugs at a time. 233 00:11:30,524 --> 00:11:32,391 If I took my trousers down, 234 00:11:32,392 --> 00:11:35,495 we could probably count, but... 235 00:11:37,030 --> 00:11:40,566 The plan was to fill a tiny section of sweat duct 236 00:11:40,567 --> 00:11:41,767 with salty water, 237 00:11:41,768 --> 00:11:44,136 and do electrical measurements on it. 238 00:11:49,176 --> 00:11:51,844 In everyone, sweat inside the duct 239 00:11:51,845 --> 00:11:54,947 contains salt-- sodium chloride-- 240 00:11:54,948 --> 00:11:56,582 which, dissolved in water, 241 00:11:56,583 --> 00:11:59,485 forms positively charged sodium 242 00:11:59,486 --> 00:12:01,655 and negatively charged chloride. 243 00:12:03,023 --> 00:12:05,825 {\an8}A healthy body wants that salt back, 244 00:12:05,826 --> 00:12:08,227 {\an8}reabsorbing sodium first, 245 00:12:08,228 --> 00:12:11,198 {\an8}which pulls chloride along behind. 246 00:12:13,300 --> 00:12:15,734 {\an8}That brief separation of charge 247 00:12:15,735 --> 00:12:18,238 {\an8}creates a tiny, detectable voltage. 248 00:12:19,840 --> 00:12:21,273 When I hooked my own up 249 00:12:21,274 --> 00:12:23,542 and I got it connected, 250 00:12:23,543 --> 00:12:25,911 I looked at the voltmeter, and it kept-- 251 00:12:25,912 --> 00:12:28,781 it went well past the normal, and it pegged 252 00:12:28,782 --> 00:12:30,382 to the top of the scale. 253 00:12:30,383 --> 00:12:31,617 So I turned it up to the next range, 254 00:12:31,618 --> 00:12:33,419 it pegged again. 255 00:12:33,420 --> 00:12:35,020 It made a negative voltage, 256 00:12:35,021 --> 00:12:37,089 about ten times higher than it normally was. 257 00:12:37,090 --> 00:12:38,657 And I thought, "Woah!" 258 00:12:38,658 --> 00:12:40,392 What that would really suggest 259 00:12:40,393 --> 00:12:42,262 is that the chloride is being held back. 260 00:12:44,064 --> 00:12:45,397 {\an8}Paul had realized 261 00:12:45,398 --> 00:12:47,032 {\an8}that the chloride and sodium 262 00:12:47,033 --> 00:12:48,667 {\an8}were being kept apart, 263 00:12:48,668 --> 00:12:50,469 {\an8}driving the voltage higher. 264 00:12:53,073 --> 00:12:54,874 Since chloride and sodium 265 00:12:54,875 --> 00:12:56,475 like to be together, 266 00:12:56,476 --> 00:12:58,444 sodium also becomes trapped 267 00:12:58,445 --> 00:13:00,012 in the CF duct. 268 00:13:00,013 --> 00:13:02,414 And this is why extra salty sweat 269 00:13:02,415 --> 00:13:04,417 ends up on the skin. 270 00:13:06,253 --> 00:13:08,888 I ran out in the hallway-- "Eureka!" 271 00:13:08,889 --> 00:13:11,056 like some kind of idiot. 272 00:13:11,057 --> 00:13:15,361 But I thought the problem must be chloride impermeability. 273 00:13:15,362 --> 00:13:18,697 Chloride can't get across that, uh, membrane. 274 00:13:18,698 --> 00:13:21,400 And so that's the problem with, with cystic fibrosis. 275 00:13:22,736 --> 00:13:24,570 Paul published the results 276 00:13:24,571 --> 00:13:28,807 of his remarkable self-experimentation in 1983. 277 00:13:28,808 --> 00:13:30,709 "Sweating out cystic fibrosis..." 278 00:13:30,710 --> 00:13:35,014 He'd proved why CF patients have such salty sweat, 279 00:13:35,015 --> 00:13:37,383 and chloride was a vital clue 280 00:13:37,384 --> 00:13:40,686 in the mystery of what causes the disease. 281 00:13:40,687 --> 00:13:43,189 But turning that knowledge into a life-saving treatment 282 00:13:43,190 --> 00:13:46,025 was still a long way off, 283 00:13:46,026 --> 00:13:49,729 and would come from an unlikely source. 284 00:13:51,198 --> 00:13:53,265 Back in the 1950s, 285 00:13:53,266 --> 00:13:56,268 medicine had very little to offer children with CF. 286 00:13:56,269 --> 00:13:59,471 So, a group of parents, desperate to save 287 00:13:59,472 --> 00:14:02,374 their dying kids, felt compelled to act, 288 00:14:02,375 --> 00:14:06,079 {\an8}and formed the Cystic Fibrosis Foundation. 289 00:14:08,582 --> 00:14:13,052 These parents knew that little was known about this disease, 290 00:14:13,053 --> 00:14:14,920 {\an8}and unless they figured that out, 291 00:14:14,921 --> 00:14:16,823 {\an8}there would never ever be a cure. 292 00:14:17,791 --> 00:14:19,792 No one was gonna give them the money, 293 00:14:19,793 --> 00:14:22,361 they had to do it themselves. 294 00:14:22,362 --> 00:14:23,796 So, over time, 295 00:14:23,797 --> 00:14:27,533 they raised it through walks, through bake sales, 296 00:14:27,534 --> 00:14:29,201 through galas, 297 00:14:29,202 --> 00:14:30,569 and with this money, 298 00:14:30,570 --> 00:14:32,538 one of the key things they did 299 00:14:32,539 --> 00:14:33,607 was establish care centers. 300 00:14:38,378 --> 00:14:39,745 You know, you would walk down the corridor, 301 00:14:39,746 --> 00:14:42,314 you could hear the coughing. 302 00:14:42,315 --> 00:14:45,952 They would actually break their ribs. 303 00:14:46,820 --> 00:14:49,455 Can you imagine the pain of having broken ribs, 304 00:14:49,456 --> 00:14:51,157 and yet you have to keep coughing? 305 00:14:53,760 --> 00:14:55,828 Dr. Bonnie Ramsey 306 00:14:55,829 --> 00:14:58,464 led a specialist CF care center in Seattle, 307 00:14:58,465 --> 00:14:59,732 one of a growing network 308 00:14:59,733 --> 00:15:03,303 of over 100 funded by the CF Foundation. 309 00:15:04,271 --> 00:15:05,871 I remember thinking, 310 00:15:05,872 --> 00:15:09,408 {\an8}I can't continue to do this if I don't feel 311 00:15:09,409 --> 00:15:11,844 {\an8}I'm making some sort of difference. 312 00:15:11,845 --> 00:15:15,781 We started looking at nutrition, 313 00:15:15,782 --> 00:15:19,451 working on better ways to give the intravenous antibiotics, 314 00:15:19,452 --> 00:15:22,155 {\an8}and then, later, inhaled antibiotics. 315 00:15:23,623 --> 00:15:27,793 {\an8}I remember one of my patients, and her mom, she said, 316 00:15:27,794 --> 00:15:29,828 "We just wanna thank you, 317 00:15:29,829 --> 00:15:32,331 "because you've given us our lives back 318 00:15:32,332 --> 00:15:34,767 "because, you know, our daughter 319 00:15:34,768 --> 00:15:36,101 can be at home sometimes." 320 00:15:40,073 --> 00:15:41,874 Twice a day, 321 00:15:41,875 --> 00:15:43,075 {\an8}we'd put one of the boys on our lap 322 00:15:43,076 --> 00:15:44,343 {\an8}and we'd do these chest percussions, 323 00:15:44,344 --> 00:15:46,845 to try to loosen that mucus, 324 00:15:46,846 --> 00:15:48,881 so that we keep that infection out of there. 325 00:15:48,882 --> 00:15:50,883 You know, asking "cough, cough, 326 00:15:50,884 --> 00:15:52,851 cough it up, cough it up," like all the time. 327 00:15:52,852 --> 00:15:55,555 There was always a cough in this house. Always. 328 00:15:56,790 --> 00:15:59,591 {\an8}Improving treatments helped control 329 00:15:59,592 --> 00:16:01,760 {\an8}the suffocating buildup of mucus 330 00:16:01,761 --> 00:16:04,363 {\an8}and lung infections. 331 00:16:04,364 --> 00:16:07,132 And in the U.S., by 1980, 332 00:16:07,133 --> 00:16:11,036 kids with CF finally stood a better chance than not 333 00:16:11,037 --> 00:16:12,672 of reaching adulthood. 334 00:16:13,840 --> 00:16:17,276 A lot had happened since the Foundation had been founded. 335 00:16:17,277 --> 00:16:18,477 {\an8}It was driven 336 00:16:18,478 --> 00:16:20,879 {\an8}by the passion of the parents 337 00:16:20,880 --> 00:16:23,882 to raise the money to make the difference. 338 00:16:23,883 --> 00:16:27,620 Progress had been made, but they wanted more. 339 00:16:29,823 --> 00:16:34,226 The CF Foundation's ultimate goal was a cure. 340 00:16:34,227 --> 00:16:37,629 {\an8}And in 1980, they recruited Bob Beall from the N.I.H. 341 00:16:37,630 --> 00:16:39,899 {\an8}to drive that mission forward. 342 00:16:42,068 --> 00:16:43,402 One of my colleagues used to say, 343 00:16:43,403 --> 00:16:45,671 "Money buys science, 344 00:16:45,672 --> 00:16:47,406 science buys lives." 345 00:16:47,407 --> 00:16:49,508 So first thing that we did 346 00:16:49,509 --> 00:16:51,911 is started our research center network. 347 00:16:53,146 --> 00:16:55,547 North Carolina, Alabama, 348 00:16:55,548 --> 00:16:57,616 San Francisco, 349 00:16:57,617 --> 00:16:59,785 and they all had some research money 350 00:16:59,786 --> 00:17:02,756 to be able to explore new ideas. 351 00:17:04,357 --> 00:17:06,692 We were taking shots on goal, 352 00:17:06,693 --> 00:17:08,660 and some of them were not gonna pay off. 353 00:17:08,661 --> 00:17:09,796 Some were gonna pay off. 354 00:17:11,030 --> 00:17:12,898 But as Wayne Gretzky says, 355 00:17:12,899 --> 00:17:15,635 you miss 100% of the shots you don't take. 356 00:17:18,638 --> 00:17:21,940 Because of the way CF runs in families, 357 00:17:21,941 --> 00:17:24,243 it had to be caused by both parents 358 00:17:24,244 --> 00:17:27,346 giving their child a faulty gene. 359 00:17:27,347 --> 00:17:30,249 In the 1980s, 360 00:17:30,250 --> 00:17:32,352 "gene hunting" was brand-new to science. 361 00:17:33,586 --> 00:17:36,322 And it was a shot Bob decided to take. 362 00:17:38,291 --> 00:17:39,825 In 1985, Dr. Francis Collins 363 00:17:39,826 --> 00:17:43,262 and his team at the University of Michigan 364 00:17:43,263 --> 00:17:45,731 were among those to join the hunt 365 00:17:45,732 --> 00:17:49,134 {\an8}for the CF gene; a formidable challenge. 366 00:17:49,135 --> 00:17:51,136 {\an8}Talking about the human genome, 367 00:17:51,137 --> 00:17:53,472 {\an8}your own instruction book. 368 00:17:53,473 --> 00:17:57,176 And it has just four letters in its chemical alphabet-- 369 00:17:57,177 --> 00:18:00,279 A, C, G, and T-- 3 billion of them 370 00:18:00,280 --> 00:18:04,183 and the mistake that might cause cystic fibrosis 371 00:18:04,184 --> 00:18:06,919 could be as subtle as one letter gone wrong. 372 00:18:08,588 --> 00:18:10,923 Yet, by late 1985, 373 00:18:10,924 --> 00:18:14,326 Toronto-based scientist Lap-Chee Tsui had managed to 374 00:18:14,327 --> 00:18:15,761 {\an8}narrow down the hunt 375 00:18:15,762 --> 00:18:17,831 {\an8}to part of our genome called chromosome seven. 376 00:18:20,467 --> 00:18:25,771 Still, there was a vast stretch of DNA to search and, 377 00:18:25,772 --> 00:18:28,674 given the task, Francis Collins and Lap-Chee Tsui 378 00:18:28,675 --> 00:18:32,579 took the unusual step of merging their labs to collaborate. 379 00:18:34,147 --> 00:18:36,950 My buddy, Lap-Chee. 380 00:18:38,451 --> 00:18:42,020 Ah, this is May of '88, it's a phone call with Lap-Chee. 381 00:18:42,021 --> 00:18:44,456 Big star-- must have thought we had something. 382 00:18:44,457 --> 00:18:47,860 We didn't. 383 00:18:47,861 --> 00:18:50,262 That's sort of the way it went. 384 00:18:50,263 --> 00:18:51,463 "It's working." "No, it's not." 385 00:18:51,464 --> 00:18:52,464 "It's working." 386 00:18:52,465 --> 00:18:53,566 "Oh no, it really isn't." 387 00:18:55,268 --> 00:18:57,803 {\an8}But then, in spring 1989, 388 00:18:57,804 --> 00:19:00,772 {\an8}they found what they were looking for. 389 00:19:00,773 --> 00:19:05,444 {\an8}Oh yeah. Here is the real story. 390 00:19:05,445 --> 00:19:08,514 So this is the way we used to read DNA. 391 00:19:08,515 --> 00:19:14,019 A-T-C-T-T-T-G-G, et cetera. 392 00:19:14,020 --> 00:19:15,988 That's the normal. 393 00:19:15,989 --> 00:19:18,390 This is the same stretch of DNA 394 00:19:18,391 --> 00:19:20,158 from somebody with CF. 395 00:19:20,159 --> 00:19:23,729 Again, T-A-T-C-A-T-T-- 396 00:19:23,730 --> 00:19:24,997 wait a minute, that's different. 397 00:19:24,998 --> 00:19:30,602 {\an8}That CTT is missing that you see over here. 398 00:19:30,603 --> 00:19:32,371 {\an8}CTT is, is, is disappeared. 399 00:19:32,372 --> 00:19:36,542 You're looking at the main cause of cystic fibrosis. 400 00:19:36,543 --> 00:19:40,947 That was the moment that we knew we had something. 401 00:19:43,516 --> 00:19:46,919 In around 70% of CF patients tested, 402 00:19:46,920 --> 00:19:49,422 these three DNA letters were missing. 403 00:19:53,092 --> 00:19:56,129 The mutation was named Delta F508, 404 00:19:57,730 --> 00:20:00,967 and the gene it was found in called CFTR. 405 00:20:05,772 --> 00:20:07,439 On August 24, 1989, 406 00:20:07,440 --> 00:20:11,376 the news broke around the world. 407 00:20:11,377 --> 00:20:13,712 REPORTER U.S. and Canadian researchers today announced a breakthrough 408 00:20:13,713 --> 00:20:18,116 which could lead to treatment or a cure for cystic fibrosis. 409 00:20:18,117 --> 00:20:21,853 BEALL The cystic fibrosis gene has indeed been isolated, 410 00:20:21,854 --> 00:20:24,022 and the product of that particular gene, 411 00:20:24,023 --> 00:20:26,024 the protein, has been identified. 412 00:20:27,827 --> 00:20:30,762 Scientists, the world, the parents, everybody thought, 413 00:20:30,763 --> 00:20:33,966 {\an8}"if we know the gene that causes a disease, 414 00:20:33,967 --> 00:20:35,801 {\an8}we can fix it." 415 00:20:35,802 --> 00:20:38,770 There was a lot of excitement at that point 416 00:20:38,771 --> 00:20:41,640 about the concept of gene therapy. 417 00:20:41,641 --> 00:20:43,342 This would be putting 418 00:20:43,343 --> 00:20:45,110 a normal copy of the gene 419 00:20:45,111 --> 00:20:47,479 into the airways of CF patients, 420 00:20:47,480 --> 00:20:49,448 and get things to work normally. 421 00:20:49,449 --> 00:20:52,050 {\an8}Bob, you know, had this vision, 422 00:20:52,051 --> 00:20:55,887 {\an8}and he came to the board and said, "we need to do this." 423 00:20:55,888 --> 00:20:58,590 And of course, all of us were... 424 00:20:58,591 --> 00:21:00,225 totally on board, 425 00:21:00,226 --> 00:21:02,929 and we said, "whatever it takes." 426 00:21:05,698 --> 00:21:07,299 At the time, 427 00:21:07,300 --> 00:21:10,402 Cam McLoud's son Will was seven years old. 428 00:21:10,403 --> 00:21:12,471 She knew gene therapy 429 00:21:12,472 --> 00:21:14,773 might transform his prospects-- 430 00:21:14,774 --> 00:21:17,176 and those of all kids with CF. 431 00:21:19,112 --> 00:21:23,281 And within a year, a healthy copy of the CFTR gene 432 00:21:23,282 --> 00:21:26,152 was successfully put into cells in the lab. 433 00:21:27,887 --> 00:21:29,655 But doing the same in the lungs 434 00:21:29,656 --> 00:21:32,659 of living, breathing people proved much harder. 435 00:21:34,427 --> 00:21:37,963 Your immune system does not like foreign things 436 00:21:37,964 --> 00:21:40,332 appearing in your airway. 437 00:21:40,333 --> 00:21:42,934 And so, as hard as we would try 438 00:21:42,935 --> 00:21:44,803 to block the immune response, 439 00:21:44,804 --> 00:21:48,408 it never got to the point of being efficient enough. 440 00:21:50,176 --> 00:21:53,178 The CF community had vastly underestimated 441 00:21:53,179 --> 00:21:57,282 the challenge of getting their pioneering gene therapy to work. 442 00:21:57,283 --> 00:22:00,052 That was years of effort. 443 00:22:00,053 --> 00:22:01,887 This was not the best time 444 00:22:01,888 --> 00:22:04,456 for all of us who had those dreams 445 00:22:04,457 --> 00:22:06,359 of saving a lot of lives. 446 00:22:09,395 --> 00:22:11,163 I was devastated 447 00:22:11,164 --> 00:22:13,598 when I heard that the gene therapy didn't work, 448 00:22:13,599 --> 00:22:16,601 because that was... 449 00:22:16,602 --> 00:22:19,372 what we had to look forward to at that time. 450 00:22:21,574 --> 00:22:22,874 The parents were full of 451 00:22:22,875 --> 00:22:25,911 anger and resentment and frustration, 452 00:22:25,912 --> 00:22:28,146 because they were told that this was the way 453 00:22:28,147 --> 00:22:29,414 to cure the disease. 454 00:22:29,415 --> 00:22:32,217 "Find the gene, fix the gene, 455 00:22:32,218 --> 00:22:34,954 the patient is cured." But it didn't work 456 00:22:40,393 --> 00:22:42,060 In the wake of this setback, 457 00:22:42,061 --> 00:22:44,629 one question became increasingly urgent. 458 00:22:44,630 --> 00:22:48,400 If CF scientists couldn't fix the gene, 459 00:22:48,401 --> 00:22:50,836 could they instead fix 460 00:22:50,837 --> 00:22:52,571 what the gene instructs the body to build-- 461 00:22:52,572 --> 00:22:55,408 the CFTR protein. 462 00:22:56,642 --> 00:23:01,446 By 1991, physician Mike Welsh and his research team 463 00:23:01,447 --> 00:23:05,150 had demonstrated that this protein forms a pore 464 00:23:05,151 --> 00:23:06,718 {\an8}through the cell membrane. 465 00:23:06,719 --> 00:23:10,288 {\an8}A channel that allows chloride in and out of cells 466 00:23:10,289 --> 00:23:12,825 {\an8}just like in a healthy sweat duct. 467 00:23:14,193 --> 00:23:16,628 {\an8}So once we knew CFTR was a channel, 468 00:23:16,629 --> 00:23:17,829 {\an8}then we wanted to know, 469 00:23:17,830 --> 00:23:20,232 {\an8}what goes wrong in cystic fibrosis? 470 00:23:20,233 --> 00:23:21,534 {\an8}Why, why doesn't it work? 471 00:23:22,802 --> 00:23:24,402 And we thought about that, 472 00:23:24,403 --> 00:23:26,838 just like an assembly line inside of the cells, 473 00:23:26,839 --> 00:23:28,241 lining the airways. 474 00:23:31,110 --> 00:23:34,146 DNA is the code, 475 00:23:34,147 --> 00:23:37,549 and the cell takes a copy of the code, 476 00:23:37,550 --> 00:23:40,886 then it makes a long string 477 00:23:40,887 --> 00:23:43,855 of these little things called amino acids 478 00:23:43,856 --> 00:23:47,392 and it folds it up to make the CFTR protein. 479 00:23:47,393 --> 00:23:50,128 And then it travels to the cell surface, 480 00:23:50,129 --> 00:23:53,231 where the channel opens to get the chloride moving 481 00:23:53,232 --> 00:23:56,536 from one side of the cell membrane to the other. 482 00:23:59,939 --> 00:24:04,943 Researchers found that many different genetic mutations 483 00:24:04,944 --> 00:24:06,444 can cause CF, 484 00:24:06,445 --> 00:24:08,747 and that they can break the protein assembly line 485 00:24:08,748 --> 00:24:10,149 in different ways. 486 00:24:13,686 --> 00:24:16,454 One type of mutation, they never make it. 487 00:24:16,455 --> 00:24:18,257 You never make that assembly line. 488 00:24:21,060 --> 00:24:22,727 And then other mutations, 489 00:24:22,728 --> 00:24:24,896 it just doesn't fold right, 490 00:24:24,897 --> 00:24:27,266 and it's off the assembly line. 491 00:24:29,402 --> 00:24:33,438 There are also mutations where it folds pretty good, 492 00:24:33,439 --> 00:24:35,707 {\an8}but the channel doesn't open 493 00:24:35,708 --> 00:24:37,743 {\an8}for the chloride to move through. 494 00:24:41,414 --> 00:24:44,349 Mike's team focused on the folding problem, 495 00:24:44,350 --> 00:24:48,253 usually caused by the most common CF gene mutation-- 496 00:24:48,254 --> 00:24:51,256 Delta F508. 497 00:24:51,257 --> 00:24:54,993 We knew that the F508 protein was misfolded. 498 00:24:54,994 --> 00:24:57,829 And we also knew 499 00:24:57,830 --> 00:25:00,165 that folding depends on temperature. 500 00:25:00,166 --> 00:25:03,368 What would happen if you cooled it down? 501 00:25:03,369 --> 00:25:05,404 Maybe that would help the folding problem. 502 00:25:07,206 --> 00:25:08,874 That's what we tried to do. 503 00:25:08,875 --> 00:25:11,109 We cooled it down, 504 00:25:11,110 --> 00:25:13,912 {\an8}it folded more correctly, 505 00:25:13,913 --> 00:25:16,081 {\an8}it went to the cell surface 506 00:25:16,082 --> 00:25:18,750 {\an8}and it didn't work completely well. 507 00:25:18,751 --> 00:25:21,353 It maybe only, only worked a quarter as well 508 00:25:21,354 --> 00:25:23,656 or a third as well. But it worked. 509 00:25:25,892 --> 00:25:28,793 This was evidence that the most common 510 00:25:28,794 --> 00:25:33,431 protein defect in CF patients was repairable in the lab. 511 00:25:33,432 --> 00:25:36,368 So could it be done with a medicine? 512 00:25:36,369 --> 00:25:40,105 No one had used a drug to fix a broken protein 513 00:25:40,106 --> 00:25:41,339 in patients before. 514 00:25:43,242 --> 00:25:47,446 Yet an emerging new technology made it at least plausible. 515 00:25:51,183 --> 00:25:53,752 Before screening, we were doing experiments, 516 00:25:53,753 --> 00:25:55,487 essentially in test tubes, right. 517 00:25:55,488 --> 00:25:56,955 One at a time, handling it by hand, 518 00:25:56,956 --> 00:25:58,490 putting it in a rack. 519 00:25:58,491 --> 00:26:01,559 In 1998, Paul Negulescu 520 00:26:01,560 --> 00:26:04,129 was working for Aurora Biosciences, 521 00:26:04,130 --> 00:26:07,699 a small startup trying to accelerate drug discovery 522 00:26:07,700 --> 00:26:09,734 using a new technique 523 00:26:09,735 --> 00:26:12,405 called high throughput screening. 524 00:26:14,006 --> 00:26:17,208 {\an8}The idea of high throughput screening is we, 525 00:26:17,209 --> 00:26:19,511 {\an8}rather than handing them all individually, 526 00:26:19,512 --> 00:26:21,380 {\an8}we do the tests in microtiter plates. 527 00:26:23,082 --> 00:26:25,450 We could run tens of thousands in a day, 528 00:26:25,451 --> 00:26:27,519 to find just a few 529 00:26:27,520 --> 00:26:31,290 chemicals that will potentially do what you want. 530 00:26:33,059 --> 00:26:35,160 This was exactly what Bob Beall 531 00:26:35,161 --> 00:26:37,763 at the CF Foundation had been looking for. 532 00:26:38,965 --> 00:26:41,266 We went to them and said 533 00:26:41,267 --> 00:26:43,668 we want to screen chemical compounds. 534 00:26:43,669 --> 00:26:46,071 {\an8}We want to find one or two molecules 535 00:26:46,072 --> 00:26:48,873 {\an8}that might open up the defective chloride channel. 536 00:26:48,874 --> 00:26:51,009 {\an8}And if they move forward to drugs, 537 00:26:51,010 --> 00:26:53,446 that's also very important for us. 538 00:26:56,048 --> 00:26:59,551 The idea of fixing a defective protein, 539 00:26:59,552 --> 00:27:01,886 that was the part that I think 540 00:27:01,887 --> 00:27:03,922 most people thought that can't be done. 541 00:27:03,923 --> 00:27:06,925 You know, nature has made that protein broken. 542 00:27:06,926 --> 00:27:09,295 How can a small molecule fix that? 543 00:27:10,896 --> 00:27:13,231 Aurora decided to try anyway, 544 00:27:13,232 --> 00:27:16,735 proposing a five-year research project. 545 00:27:16,736 --> 00:27:20,939 They would engineer cells to make the broken CFTR protein, 546 00:27:20,940 --> 00:27:23,341 and screen hundreds of thousands 547 00:27:23,342 --> 00:27:26,611 of chemicals, searching for any that might fix it. 548 00:27:28,481 --> 00:27:30,850 But it would come at a cost. 549 00:27:33,619 --> 00:27:36,388 We got a price tag of $40 million. 550 00:27:36,389 --> 00:27:37,689 Uh, that was big. 551 00:27:37,690 --> 00:27:40,426 How were we going to find $40 million? 552 00:27:42,795 --> 00:27:45,630 One family, closely connected to the Foundation, 553 00:27:45,631 --> 00:27:48,134 was in a unique position to help. 554 00:27:49,568 --> 00:27:51,469 I can remember calling Bonnie 555 00:27:51,470 --> 00:27:54,339 {\an8}one day and just saying, "Look, I gotta do something." 556 00:27:54,340 --> 00:27:57,308 {\an8}Unless there was some dramatic treatment, 557 00:27:57,309 --> 00:27:59,644 Paul knew they were going to lose 558 00:27:59,645 --> 00:28:02,480 their only two children as young adults. 559 00:28:02,481 --> 00:28:03,915 I said, 560 00:28:03,916 --> 00:28:07,018 I think I might be able to, to get some money. 561 00:28:07,019 --> 00:28:10,389 I made an appointment to go see my boss, a guy named Bill Gates. 562 00:28:11,490 --> 00:28:14,426 And you know, I gave him a story and he said, "Look, Paul. 563 00:28:14,427 --> 00:28:16,027 "you know, I, I want to help you. 564 00:28:16,028 --> 00:28:17,862 "I'm trying to start this foundation. 565 00:28:17,863 --> 00:28:19,364 "The only employee is my dad. 566 00:28:19,365 --> 00:28:21,366 So I need you to go talk to my dad." 567 00:28:21,367 --> 00:28:24,169 So we drove up there and there's the three of us, 568 00:28:24,170 --> 00:28:25,870 I think we were in Paul's car. 569 00:28:25,871 --> 00:28:28,139 And that's the most nervous I ever saw Bob. 570 00:28:28,140 --> 00:28:30,675 I'm allergic to cats, and they had cats. 571 00:28:30,676 --> 00:28:33,111 They had cats-- but anyway, 572 00:28:33,112 --> 00:28:34,712 we sat around a table. 573 00:28:34,713 --> 00:28:36,314 So we gave the presentation. 574 00:28:36,315 --> 00:28:38,516 Bill's dad said, "Look, we're 575 00:28:38,517 --> 00:28:40,218 "really trying to focus on diseases 576 00:28:40,219 --> 00:28:41,619 "in developing countries but 577 00:28:41,620 --> 00:28:43,421 "why don't you guys write up a detailed proposal 578 00:28:43,422 --> 00:28:45,790 and give it to me and I'll see what I can do." 579 00:28:45,791 --> 00:28:47,592 One day, about two weeks later, 580 00:28:47,593 --> 00:28:51,262 uh, the, my, my secretary screams. 581 00:28:51,263 --> 00:28:53,198 I get a call, uh, from Bob Beall, 582 00:28:53,199 --> 00:28:56,334 and he said, "Well, my admin just screamed. 583 00:28:56,335 --> 00:28:59,070 "And I went running out to see what was happening, 584 00:28:59,071 --> 00:29:01,439 and she was holding up a check." 585 00:29:01,440 --> 00:29:03,975 Sent through the U.S. Mail 586 00:29:03,976 --> 00:29:07,011 for $20 million. 587 00:29:07,012 --> 00:29:09,148 What a, what a day! 588 00:29:11,150 --> 00:29:12,817 Such a large donation, 589 00:29:12,818 --> 00:29:16,721 plus further funds raised, meant the Foundation could 590 00:29:16,722 --> 00:29:19,358 strike a ground-breaking deal with Aurora. 591 00:29:20,459 --> 00:29:21,626 What resulted 592 00:29:21,627 --> 00:29:24,529 was a concept called venture philanthropy. 593 00:29:24,530 --> 00:29:26,698 We were taking philanthropic dollars 594 00:29:26,699 --> 00:29:28,534 and becoming venture capitalists. 595 00:29:29,902 --> 00:29:31,703 The Foundation would 596 00:29:31,704 --> 00:29:34,472 {\an8}invest in the riskiest part 597 00:29:34,473 --> 00:29:37,143 {\an8}of the drug development, drug discovery process. 598 00:29:38,144 --> 00:29:40,111 And then if it was successful, 599 00:29:40,112 --> 00:29:42,681 there would be a royalty stream. 600 00:29:43,949 --> 00:29:46,651 {\an8}That was very unusual, because this was 601 00:29:46,652 --> 00:29:50,622 {\an8}the first disease-specific non-profit to use 602 00:29:50,623 --> 00:29:54,592 venture philanthropy to try and fund drug development. 603 00:29:54,593 --> 00:29:56,728 Nobody else had ever done that. 604 00:29:56,729 --> 00:29:58,863 This was a huge gamble. 605 00:30:00,766 --> 00:30:03,401 {\an8}With only half of all CF patients in the U.S. 606 00:30:03,402 --> 00:30:05,270 {\an8}reaching their early 30s, 607 00:30:05,271 --> 00:30:08,707 {\an8}the Foundation judged it to be a risk worth taking. 608 00:30:10,576 --> 00:30:12,177 And by mid-2001, 609 00:30:12,178 --> 00:30:14,479 Paul's team, now part 610 00:30:14,480 --> 00:30:16,214 of Vertex Pharmaceuticals, 611 00:30:16,215 --> 00:30:18,817 was screening thousands of chemical compounds a day. 612 00:30:20,753 --> 00:30:22,120 They were adding them 613 00:30:22,121 --> 00:30:25,623 to cells they'd engineered to make the defective CFTR 614 00:30:25,624 --> 00:30:29,060 protein, hunting for an elusive "hit." 615 00:30:29,061 --> 00:30:30,796 A chemical that might fix it. 616 00:30:35,134 --> 00:30:37,569 This is similar to the setup that we had 617 00:30:37,570 --> 00:30:38,937 20 years ago. 618 00:30:38,938 --> 00:30:41,606 Uh, the robots are a little more reliable. 619 00:30:41,607 --> 00:30:43,675 There's enough screening 620 00:30:43,676 --> 00:30:45,578 to keep us busy for years. 621 00:30:46,645 --> 00:30:50,715 The initial screens did not identify any hits 622 00:30:50,716 --> 00:30:53,084 that we could optimize. 623 00:30:53,085 --> 00:30:55,520 And so maybe some of the naysayers were right. 624 00:30:55,521 --> 00:30:58,657 Maybe this is an impossible problem. 625 00:31:02,361 --> 00:31:05,030 The skepticism was well-placed. 626 00:31:06,565 --> 00:31:08,933 After four long years, 627 00:31:08,934 --> 00:31:12,237 searching through hundreds of thousands of chemical compounds, 628 00:31:12,238 --> 00:31:15,407 they had found just a handful that looked promising. 629 00:31:16,508 --> 00:31:18,876 Looking for chemicals, 630 00:31:18,877 --> 00:31:20,913 it's not, it's not easy. 631 00:31:22,147 --> 00:31:24,849 And when you find one that sort of works, 632 00:31:24,850 --> 00:31:26,851 you take that molecule 633 00:31:26,852 --> 00:31:29,621 and then you have a whole group of chemists. 634 00:31:29,622 --> 00:31:31,089 They'll take an atom off here, 635 00:31:31,090 --> 00:31:34,193 add one over here, does the molecule work better? 636 00:31:36,061 --> 00:31:38,396 This painstaking process finally led 637 00:31:38,397 --> 00:31:40,164 to their first candidate drug, 638 00:31:40,165 --> 00:31:42,734 named VX-770. 639 00:31:42,735 --> 00:31:44,302 It had worked 640 00:31:44,303 --> 00:31:46,504 extremely well in their lab tests, 641 00:31:46,505 --> 00:31:48,940 but would have no future unless it also 642 00:31:48,941 --> 00:31:52,044 worked in living cells from human tissue. 643 00:31:54,513 --> 00:31:55,747 So we're looking 644 00:31:55,748 --> 00:32:00,051 at a layer of human lung cells 645 00:32:00,052 --> 00:32:02,353 in a dish, and these are from 646 00:32:02,354 --> 00:32:04,290 a person with cystic fibrosis. 647 00:32:05,624 --> 00:32:08,493 Fred Van Goor was one of the few people 648 00:32:08,494 --> 00:32:10,228 who could culture these living cells, 649 00:32:10,229 --> 00:32:14,932 to look just as they did inside a CF patient's body. 650 00:32:14,933 --> 00:32:17,535 You know all these shapes that you're seeing here. 651 00:32:17,536 --> 00:32:19,937 {\an8}That's that thick, sticky mucus 652 00:32:19,938 --> 00:32:22,607 {\an8}that's just covering the surface. 653 00:32:22,608 --> 00:32:24,175 {\an8}Yeah, totally covered. 654 00:32:24,176 --> 00:32:27,111 And there should be cilia beating, 655 00:32:27,112 --> 00:32:29,247 because that's what helps clear out 656 00:32:29,248 --> 00:32:30,916 the lungs. 657 00:32:31,917 --> 00:32:33,251 You know, they're trying to beat, 658 00:32:33,252 --> 00:32:34,520 but there's not much going on. 659 00:32:38,957 --> 00:32:43,361 In 2006, Fred tested their new compound on these cells 660 00:32:43,362 --> 00:32:45,296 from a CF patient. 661 00:32:45,297 --> 00:32:47,231 Fred came up to 662 00:32:47,232 --> 00:32:48,766 my office and said, 663 00:32:48,767 --> 00:32:50,869 "I think you should see something." 664 00:32:51,937 --> 00:32:55,506 As I bring this into view... wow. 665 00:32:55,507 --> 00:32:56,741 And look at that. 666 00:32:56,742 --> 00:32:59,010 You no longer see that thick, 667 00:32:59,011 --> 00:33:00,678 sticky mucus. 668 00:33:00,679 --> 00:33:03,915 And then the other thing you see is all of this 669 00:33:03,916 --> 00:33:04,982 cilia beating. 670 00:33:04,983 --> 00:33:07,418 And that's an indication of, you know, 671 00:33:07,419 --> 00:33:10,822 both the mucus is now less thick and there's fluid on top. 672 00:33:10,823 --> 00:33:12,757 And that happens because you've 673 00:33:12,758 --> 00:33:16,128 restored the defective CFTR protein. 674 00:33:17,529 --> 00:33:18,930 I just thought it was beautiful. 675 00:33:18,931 --> 00:33:20,164 Yeah. 676 00:33:20,165 --> 00:33:24,336 This is as clear as science gets, you know? 677 00:33:25,437 --> 00:33:27,538 Not working, working. 678 00:33:34,947 --> 00:33:36,781 Good news travels fast, 679 00:33:36,782 --> 00:33:42,019 and people started lining up to see, you know, that little cell, 680 00:33:42,020 --> 00:33:44,522 you know, those little cilia beating. 681 00:33:44,523 --> 00:33:48,393 It was a glimpse of what VX-770 682 00:33:48,394 --> 00:33:50,929 ought to do, inside patients. 683 00:33:52,264 --> 00:33:54,565 With their CFTR channel working, 684 00:33:54,566 --> 00:33:57,368 chloride should reach the airway surface, 685 00:33:57,369 --> 00:33:59,738 and draw water with it by osmosis. 686 00:34:00,873 --> 00:34:04,842 That should thin the mucus, so the cilia beat freely, 687 00:34:04,843 --> 00:34:07,145 clearing the lungs to breathe. 688 00:34:09,715 --> 00:34:13,918 After being used to the general premise in the field that you 689 00:34:13,919 --> 00:34:14,952 fail so often, 690 00:34:14,953 --> 00:34:17,121 to realize this was going to work 691 00:34:17,122 --> 00:34:19,257 was quite a, quite a moment. 692 00:34:21,693 --> 00:34:23,961 After eight years of work, 693 00:34:23,962 --> 00:34:25,831 this was an incredible breakthrough. 694 00:34:27,099 --> 00:34:29,668 But there was a catch. 695 00:34:30,669 --> 00:34:35,340 VX-770 did not correct the most common protein folding problem. 696 00:34:36,475 --> 00:34:39,677 It only addressed a much rarer defect found 697 00:34:39,678 --> 00:34:43,615 in just 5% of patients in the U.S. 698 00:34:45,684 --> 00:34:47,318 The question that was asked, 699 00:34:47,319 --> 00:34:50,755 do we really want to develop a drug 700 00:34:50,756 --> 00:34:53,559 that only works in 5% of our patients? 701 00:34:55,527 --> 00:34:58,062 The, the call that you've gotten a hit, 702 00:34:58,063 --> 00:35:01,232 was something you, you sort of dream about. 703 00:35:01,233 --> 00:35:02,800 Then to find out that, 704 00:35:02,801 --> 00:35:04,569 you know, probably wasn't gonna help, you know, 705 00:35:04,570 --> 00:35:06,538 our boys, it was hard. 706 00:35:07,673 --> 00:35:08,873 And I remember the meeting 707 00:35:08,874 --> 00:35:10,107 and they, you know, they're like 708 00:35:10,108 --> 00:35:12,076 {\an8}this is gonna cost at least 709 00:35:12,077 --> 00:35:14,612 {\an8}tens of millions of dollars, possibly much more. 710 00:35:14,613 --> 00:35:16,180 {\an8}Do we move forward? 711 00:35:16,181 --> 00:35:17,582 And I was quick to say, "Look, 712 00:35:17,583 --> 00:35:19,584 we can't not do a treatment." 713 00:35:19,585 --> 00:35:22,487 Uh, uh, you know, it's just unconscionable 714 00:35:22,488 --> 00:35:23,921 to sit here and make that decision. 715 00:35:26,225 --> 00:35:27,758 Despite the cost, 716 00:35:27,759 --> 00:35:30,095 the Foundation decided to proceed. 717 00:35:32,831 --> 00:35:37,702 They would raise $175 million to continue their hunt 718 00:35:37,703 --> 00:35:39,804 for new drugs and support 719 00:35:39,805 --> 00:35:42,374 clinical trials of VX-770. 720 00:35:47,880 --> 00:35:50,481 LAURA CHEEVERS My name is Laura Cheevers and I'm 11 years old. 721 00:35:50,482 --> 00:35:53,751 My sister Cate also has CF. 722 00:35:53,752 --> 00:35:55,953 We just signed up for what my mom calls a possible 723 00:35:55,954 --> 00:35:57,788 life-changing research study. 724 00:35:57,789 --> 00:36:00,157 Both of Kim Cheevers' 725 00:36:00,158 --> 00:36:03,094 two young daughters, Cate and Laura, 726 00:36:03,095 --> 00:36:05,363 had the rare mutation needed to take part 727 00:36:05,364 --> 00:36:07,064 in the VX-770 trial. 728 00:36:08,400 --> 00:36:11,602 By 2010, she was desperately worried 729 00:36:11,603 --> 00:36:13,805 about their increasingly fragile health. 730 00:36:14,907 --> 00:36:16,140 You started to feel 731 00:36:16,141 --> 00:36:18,309 this sense of urgency, like, okay, now we really 732 00:36:18,310 --> 00:36:20,078 need to get going on these trials. 733 00:36:21,213 --> 00:36:24,615 Both girls would take a pill, twice a day, 734 00:36:24,616 --> 00:36:26,450 but because the trials were blinded, 735 00:36:26,451 --> 00:36:28,953 Kim had no idea if it was the drug 736 00:36:28,954 --> 00:36:30,556 or a placebo. 737 00:36:31,523 --> 00:36:32,790 When Laura started, 738 00:36:32,791 --> 00:36:35,226 you know, we didn't see too much of a difference. 739 00:36:35,227 --> 00:36:37,729 {\an8}We kept waiting for this magic moment to happen. 740 00:36:38,931 --> 00:36:40,998 But within a month, 741 00:36:40,999 --> 00:36:43,000 you saw a difference in Cate. 742 00:36:43,001 --> 00:36:44,835 Less coughing for sure. 743 00:36:44,836 --> 00:36:46,237 I think she gained 744 00:36:46,238 --> 00:36:47,673 seven pounds in six months. 745 00:36:48,740 --> 00:36:51,509 We were kind of like, okay, Cate's on it. 746 00:36:51,510 --> 00:36:53,311 We gotta believe she's on it. 747 00:36:53,312 --> 00:36:56,414 And we really hope that Laura's not on it, 748 00:36:56,415 --> 00:36:59,550 because this is not doing anything for her, like, 749 00:36:59,551 --> 00:37:01,553 that was probably the scariest time. 750 00:37:05,190 --> 00:37:07,024 After more than a year in the dark, 751 00:37:07,025 --> 00:37:10,696 both girls were officially given VX-770. 752 00:37:12,197 --> 00:37:13,331 LAURA CHEEVERS Hello, folks, 753 00:37:13,332 --> 00:37:15,299 and we are back. 754 00:37:15,300 --> 00:37:18,069 Laura went on to the medication and she had 755 00:37:18,070 --> 00:37:20,137 the same type of effects that Cate did. 756 00:37:20,138 --> 00:37:21,772 We could see it. 757 00:37:21,773 --> 00:37:24,308 So this was like really, really amazing. 758 00:37:24,309 --> 00:37:26,612 Amazing, and we were very happy. 759 00:37:28,680 --> 00:37:30,915 The official trial results confirmed 760 00:37:30,916 --> 00:37:33,819 VX-770 worked. 761 00:37:35,153 --> 00:37:36,287 Lung function 762 00:37:36,288 --> 00:37:39,256 improved by about 300 milliliters of air, 763 00:37:39,257 --> 00:37:40,992 so that's about a Coke can 764 00:37:40,993 --> 00:37:44,128 {\an8}of air that people were now able 765 00:37:44,129 --> 00:37:46,497 {\an8}to move in and out of their lung in one second, 766 00:37:46,498 --> 00:37:48,232 {\an8}uh, more than they could before. 767 00:37:48,233 --> 00:37:49,734 And people can feel that. 768 00:37:49,735 --> 00:37:51,535 Oh, this was remarkable. 769 00:37:51,536 --> 00:37:55,741 We really had a shot on goal that worked. 770 00:37:57,876 --> 00:38:00,277 The FDA approved the new drug, 771 00:38:00,278 --> 00:38:04,349 marketed as Kalydeco early in 2012. 772 00:38:05,417 --> 00:38:09,287 And for a small number of patients, it was transformative. 773 00:38:12,991 --> 00:38:17,261 But most were still reliant on standard treatments, 774 00:38:17,262 --> 00:38:19,631 including Cam McLoud's son, Will. 775 00:38:21,967 --> 00:38:24,335 Will was spending more time in the hospital 776 00:38:24,336 --> 00:38:26,971 and was getting weaker. 777 00:38:26,972 --> 00:38:31,208 And he was in the I.C.U. for a while. 778 00:38:31,209 --> 00:38:37,181 And then they were talking about releasing him to the CF floor. 779 00:38:37,182 --> 00:38:41,987 And, um... that night he passed away. 780 00:38:43,822 --> 00:38:46,191 And, um... 781 00:38:48,026 --> 00:38:51,295 ...of course I was there with him. 782 00:38:51,296 --> 00:38:54,066 Um, but, um... 783 00:38:55,267 --> 00:38:59,071 ...we, we didn't get the answers for Will in time. 784 00:39:01,640 --> 00:39:06,310 Will was 34 when he died in 2016. 785 00:39:06,311 --> 00:39:11,382 He lived twice as long as it was projected, 786 00:39:11,383 --> 00:39:13,751 you know, is, is something that I would 787 00:39:13,752 --> 00:39:17,221 always be grateful for, although, you know, 788 00:39:17,222 --> 00:39:19,691 certainly wish he were here right now. 789 00:39:25,697 --> 00:39:27,565 The majority of CF patients 790 00:39:27,566 --> 00:39:29,968 were still in desperate need of a drug. 791 00:39:31,970 --> 00:39:35,339 {\an8}And at Vertex, the hunt went on. 792 00:39:35,340 --> 00:39:37,141 {\an8}Screening over a million chemical 793 00:39:37,142 --> 00:39:39,577 {\an8}compounds to find any that might fix 794 00:39:39,578 --> 00:39:41,445 {\an8}the folding problem caused by 795 00:39:41,446 --> 00:39:44,716 {\an8}the most common mutation, delta F508. 796 00:39:46,351 --> 00:39:49,153 {\an8}Over seven more long years, they developed two other 797 00:39:49,154 --> 00:39:51,389 {\an8}drugs that offered incremental gains. 798 00:39:53,358 --> 00:39:55,359 {\an8}But a third led to their most 799 00:39:55,360 --> 00:39:57,028 {\an8}promising treatment yet. 800 00:40:00,265 --> 00:40:02,900 {\an8}This new drug combined two compounds 801 00:40:02,901 --> 00:40:05,704 to help the protein fold correctly. 802 00:40:06,805 --> 00:40:09,673 And it included the original one from Kalydeco, 803 00:40:09,674 --> 00:40:12,477 which helps it open properly as well. 804 00:40:17,282 --> 00:40:18,983 More than 20 years 805 00:40:18,984 --> 00:40:20,918 after the CF Foundation's most 806 00:40:20,919 --> 00:40:22,419 audacious shot on goal, 807 00:40:22,420 --> 00:40:27,759 Trikafta was approved for use in the United States in 2019. 808 00:40:29,027 --> 00:40:30,961 Trikafta! 809 00:40:30,962 --> 00:40:33,932 My life is about to change forever. 810 00:40:35,233 --> 00:40:38,536 Many thousands of patients began taking their new daily drug. 811 00:40:38,537 --> 00:40:40,070 Whoo-hoo! 812 00:40:40,071 --> 00:40:42,740 Soon experiencing what became known as the purge. 813 00:40:44,309 --> 00:40:47,211 Lots of mucus today. 814 00:40:47,212 --> 00:40:48,712 I've been coughing all day. 815 00:40:50,248 --> 00:40:51,482 And it's gross. 816 00:40:51,483 --> 00:40:53,984 Where mucus could be coming out of, it was. 817 00:40:53,985 --> 00:40:56,053 {\an8}Within a few hours, you might start 818 00:40:56,054 --> 00:40:58,689 {\an8}having massive amounts of mucus from your lungs, 819 00:40:58,690 --> 00:41:00,691 {\an8}from your gut, from all parts of your body. 820 00:41:00,692 --> 00:41:04,028 And you're gonna start feeling better in those few hours. 821 00:41:04,029 --> 00:41:06,263 Like, I'm breathing without pain. 822 00:41:06,264 --> 00:41:07,832 It's unreal. 823 00:41:07,833 --> 00:41:12,303 My energy level has been through the roof. 824 00:41:12,304 --> 00:41:14,939 I can breathe in so much deeper. 825 00:41:16,007 --> 00:41:19,343 {\an8}If Kalydeco was a spark, 826 00:41:19,344 --> 00:41:22,080 {\an8}like, Trikafta was like a bonfire. 827 00:41:23,915 --> 00:41:25,783 For Cate and Laura Cheevers, 828 00:41:25,784 --> 00:41:28,452 the effect of Trikafta went far beyond 829 00:41:28,453 --> 00:41:30,422 their experience with Kalydeco. 830 00:41:32,057 --> 00:41:33,224 I remember my friend, 831 00:41:33,225 --> 00:41:35,759 and he was like, "What happened to your cough?" 832 00:41:35,760 --> 00:41:37,161 And I was like, 833 00:41:37,162 --> 00:41:39,363 {\an8}"Okay, well I just started a new treatment." 834 00:41:39,364 --> 00:41:40,664 {\an8}And he was like, "It's gone?" 835 00:41:40,665 --> 00:41:42,132 {\an8}And I was like, "I think so." 836 00:41:42,133 --> 00:41:45,202 {\an8}It's like so funny 'cause I just don't think about it anymore. 837 00:41:45,203 --> 00:41:47,272 {\an8}At all. 838 00:41:49,174 --> 00:41:51,942 {\an8}In the few years Trikafta has been around, 839 00:41:51,943 --> 00:41:55,379 {\an8}average life expectancy for people with CF in the U.S. 840 00:41:55,380 --> 00:41:58,283 {\an8}has leapt almost 20 years. 841 00:42:01,720 --> 00:42:03,187 Trikafta changed everything. 842 00:42:03,188 --> 00:42:07,459 You know it gave me hours of myself back every single day. 843 00:42:08,627 --> 00:42:09,827 And to have that 844 00:42:09,828 --> 00:42:12,663 {\an8}amount of freedom physically is incredible, 845 00:42:12,664 --> 00:42:15,165 {\an8}but it's a mental weight that is almost heavier 846 00:42:15,166 --> 00:42:16,401 {\an8}that's been lifted off. 847 00:42:18,637 --> 00:42:21,038 Since starting Trikafta six years ago, 848 00:42:21,039 --> 00:42:24,108 Jon's life is entirely transformed. 849 00:42:24,109 --> 00:42:27,444 Yeah, you love the cheek. 850 00:42:27,445 --> 00:42:31,549 And his brother Andy's, too. 851 00:42:32,717 --> 00:42:34,718 The biggest news we have in our family 852 00:42:34,719 --> 00:42:38,456 is that we have a grandson and a new granddaughter. 853 00:42:40,859 --> 00:42:45,329 {\an8}Something that Sue and I had never ever thought about, 854 00:42:45,330 --> 00:42:47,698 {\an8}just didn't consider, 855 00:42:47,699 --> 00:42:49,233 wouldn't let your brain go there, 856 00:42:49,234 --> 00:42:51,503 uh, is now reality. 857 00:42:55,006 --> 00:42:56,807 {\an8}You know, I've talked to the clinic 858 00:42:56,808 --> 00:42:58,342 {\an8}and you know they talk about how many 859 00:42:58,343 --> 00:43:01,278 babies they're having nowadays, it's just all the time. 860 00:43:01,279 --> 00:43:03,781 You know, CF parents having babies. 861 00:43:03,782 --> 00:43:05,449 It's pretty unbelievable. 862 00:43:05,450 --> 00:43:07,686 We're lucky, we're lucky. 863 00:43:09,921 --> 00:43:12,323 And thanks to the new medications, 864 00:43:12,324 --> 00:43:15,259 there are even greater hopes for the future. 865 00:43:15,260 --> 00:43:17,494 If treated early enough, 866 00:43:17,495 --> 00:43:20,331 people born with the most common CF mutation 867 00:43:20,332 --> 00:43:24,235 might soon expect to live a life as long as anyone. 868 00:43:29,007 --> 00:43:31,775 What Vertex and the CF Foundation have achieved 869 00:43:31,776 --> 00:43:34,311 together is extraordinary. 870 00:43:34,312 --> 00:43:38,483 But so, too, is the price of the new treatments. 871 00:43:41,019 --> 00:43:43,120 Vertex announced 872 00:43:43,121 --> 00:43:47,591 {\an8}that it was gonna be over $300,000 per patient per year. 873 00:43:47,592 --> 00:43:49,760 {\an8}And that was mindboggling. 874 00:43:49,761 --> 00:43:51,795 {\an8}You can have great drugs, 875 00:43:51,796 --> 00:43:55,699 {\an8}but unless they're accessible to the community 876 00:43:55,700 --> 00:43:59,804 {\an8}that needs them, they really are not any good. 877 00:44:01,573 --> 00:44:05,342 Vertex defends its pricing, saying it reflects 878 00:44:05,343 --> 00:44:08,345 "more than two decades of work" 879 00:44:08,346 --> 00:44:10,347 and "billions of dollars 880 00:44:10,348 --> 00:44:12,384 invested in research and development." 881 00:44:14,386 --> 00:44:18,389 PROTESTERS Shame on Vertex! 882 00:44:18,390 --> 00:44:20,858 But critics point to the huge sums 883 00:44:20,859 --> 00:44:23,027 U.S. insurers have to pay out. 884 00:44:23,028 --> 00:44:24,595 Vertex, shame on you! 885 00:44:24,596 --> 00:44:27,064 And that Vertex's prices aren't affordable 886 00:44:27,065 --> 00:44:28,899 in many countries around the world. 887 00:44:28,900 --> 00:44:31,269 PROTESTORS Every country, every kid! 888 00:44:34,572 --> 00:44:36,875 {\an8}MOHEISSEN I heard about Trikafta. 889 00:44:38,543 --> 00:44:41,012 {\an8}How it's one of the most expensive drugs in the world. 890 00:44:42,647 --> 00:44:44,415 {\an8}I could work an extra lifetime 891 00:44:44,416 --> 00:44:46,651 {\an8}and still wouldn't be able to afford it! 892 00:44:48,286 --> 00:44:50,320 It doesn't matter if you're poor or rich, 893 00:44:50,321 --> 00:44:52,757 you have the right to, to breathe. 894 00:44:54,259 --> 00:44:58,028 Dr. Samya Nasr is an American physician, who also 895 00:44:58,029 --> 00:45:01,131 works with the CF team at Ain Shams University 896 00:45:01,132 --> 00:45:02,400 Hospital in Cairo. 897 00:45:04,702 --> 00:45:06,904 Life expectancy for CF patients 898 00:45:06,905 --> 00:45:10,140 in Egypt is around eight years of age. 899 00:45:10,141 --> 00:45:14,078 I'm seeing the improvement that this drug can give 900 00:45:14,079 --> 00:45:16,480 {\an8}to patients in the U.S., and I wanted 901 00:45:16,481 --> 00:45:18,816 {\an8}that to be here because I'm really tired of coming in, 902 00:45:18,817 --> 00:45:21,418 {\an8}asking about patients, and they already died. 903 00:45:23,254 --> 00:45:26,623 In 2023, Samya helped persuade Vertex 904 00:45:26,624 --> 00:45:29,293 to add Egypt to their pilot donation program, 905 00:45:29,294 --> 00:45:32,096 which currently offers Trikafta in a few 906 00:45:32,097 --> 00:45:34,232 countries, at no cost. 907 00:45:36,901 --> 00:45:38,302 I actually cried. 908 00:45:38,303 --> 00:45:41,105 The prospect of bringing Trikafta here, 909 00:45:41,106 --> 00:45:43,241 it just blew my mind. 910 00:45:44,843 --> 00:45:47,578 Honestly, you can't believe how happy I am. 911 00:45:47,579 --> 00:45:52,282 In 2025, Marwan got his prescription. 912 00:45:52,283 --> 00:45:54,485 Finally guys, we've got it! 913 00:45:54,486 --> 00:45:55,886 It's unbelievable! 914 00:45:55,887 --> 00:45:58,289 Oh! 915 00:45:59,891 --> 00:46:02,093 He began the process of pills... 916 00:46:03,661 --> 00:46:06,864 ...followed by purge... 917 00:46:08,967 --> 00:46:10,901 ...and three months later, 918 00:46:10,902 --> 00:46:13,203 returned to the hospital to have 919 00:46:13,204 --> 00:46:14,571 his progress assessed. 920 00:46:14,572 --> 00:46:15,840 {\an8}NURSE 921 00:46:26,584 --> 00:46:27,584 14. 922 00:46:27,585 --> 00:46:28,652 14, okay. 923 00:46:28,653 --> 00:46:30,053 Yes, all the numbers are better. 924 00:46:30,054 --> 00:46:32,189 Marwan's lung function 925 00:46:32,190 --> 00:46:33,491 has doubled. 926 00:46:36,427 --> 00:46:37,928 MOHEISSEN I'm so happy. 927 00:46:37,929 --> 00:46:40,531 Because there's a huge difference. 928 00:46:40,532 --> 00:46:43,767 This could be a new start for me, 929 00:46:43,768 --> 00:46:46,004 to change my life! 930 00:46:47,805 --> 00:46:49,273 If Trikafta, 931 00:46:49,274 --> 00:46:52,276 or a generic equivalent, became accessible worldwide, 932 00:46:52,277 --> 00:46:54,478 the lives of more than 933 00:46:54,479 --> 00:46:58,183 90% of people with CF would be transformed. 934 00:47:02,086 --> 00:47:03,620 But there are still some 935 00:47:03,621 --> 00:47:06,291 who will never benefit from such a lifeline. 936 00:47:07,859 --> 00:47:09,259 So this was also that... 937 00:47:09,260 --> 00:47:10,961 KRAMER-GOLINKOFF: I've learned over the past 938 00:47:10,962 --> 00:47:13,830 decades that, you know, you don't 939 00:47:13,831 --> 00:47:16,600 need like, so much hope to keep going. 940 00:47:16,601 --> 00:47:19,036 But you do need these glimmers of hope. 941 00:47:19,037 --> 00:47:21,138 And when those glimmers go away, 942 00:47:21,139 --> 00:47:23,574 and it's just darkness, 943 00:47:23,575 --> 00:47:26,543 those are the moments that it's really hard to endure. 944 00:47:26,544 --> 00:47:27,679 Yeah. 945 00:47:28,813 --> 00:47:30,647 Emily is one of around 10% 946 00:47:30,648 --> 00:47:34,418 of people with CF who don't benefit from Trikafta. 947 00:47:34,419 --> 00:47:37,821 In her case, she has a rare mutation, 948 00:47:37,822 --> 00:47:39,790 which means she makes 949 00:47:39,791 --> 00:47:42,227 no CFTR protein for the drug to fix. 950 00:47:43,761 --> 00:47:46,297 She and her family now live in total isolation. 951 00:47:48,166 --> 00:47:49,967 You know, I think it's when I sort of 952 00:47:49,968 --> 00:47:52,269 entered the 30% lung function phase 953 00:47:52,270 --> 00:47:54,105 that we started to get scared. 954 00:47:55,139 --> 00:47:57,941 To realize that there were no drugs in the pipeline 955 00:47:57,942 --> 00:47:59,943 that would help us. 956 00:47:59,944 --> 00:48:03,347 It was really devastating, for us. 957 00:48:06,317 --> 00:48:07,718 To hold onto hope, 958 00:48:07,719 --> 00:48:09,219 Emily and her family began 959 00:48:09,220 --> 00:48:13,056 their own non-profit, Emily's Entourage. 960 00:48:13,057 --> 00:48:16,660 Raising awareness and over $20 million so far 961 00:48:16,661 --> 00:48:19,530 in pursuit of solutions for the 10%. 962 00:48:21,666 --> 00:48:24,001 KRAMER-GOLINKOFF: We are looking to advance research 963 00:48:24,002 --> 00:48:26,036 for any kind of therapeutic 964 00:48:26,037 --> 00:48:28,105 that, um, addresses those that don't benefit 965 00:48:28,106 --> 00:48:29,539 from existing treatments. 966 00:48:29,540 --> 00:48:31,275 So it can be 967 00:48:31,276 --> 00:48:32,676 gene editing, it can be gene therapy, 968 00:48:32,677 --> 00:48:34,111 it can be small molecules. 969 00:48:34,112 --> 00:48:37,381 We need a toolbox of options 970 00:48:37,382 --> 00:48:40,217 to address all of the things that we live with, 971 00:48:40,218 --> 00:48:43,587 and to get us to one-time cures. 972 00:48:43,588 --> 00:48:45,189 I mean, that is the dream. 973 00:48:49,027 --> 00:48:50,927 You have to understand that with 974 00:48:50,928 --> 00:48:52,729 the drugs that we have now, 975 00:48:52,730 --> 00:48:54,698 we still lose patients. 976 00:48:54,699 --> 00:48:57,668 We're still, sort of, treating the symptoms of CF. 977 00:48:57,669 --> 00:49:00,604 And we would love to be able to give 978 00:49:00,605 --> 00:49:03,173 a patient a one-time drug. 979 00:49:03,174 --> 00:49:05,043 And that would be the cure. 980 00:49:06,778 --> 00:49:08,679 Over the last ten years, 981 00:49:08,680 --> 00:49:10,414 the CF Foundation has 982 00:49:10,415 --> 00:49:11,982 refocused its efforts, 983 00:49:11,983 --> 00:49:14,051 from fixing the CFTR protein, 984 00:49:14,052 --> 00:49:16,487 back to trying to fix the gene. 985 00:49:17,722 --> 00:49:21,091 That's possible because its venture philanthropy gamble 986 00:49:21,092 --> 00:49:22,959 paid off. 987 00:49:22,960 --> 00:49:24,795 Part of venture philanthropy 988 00:49:24,796 --> 00:49:26,330 was that we took royalties 989 00:49:26,331 --> 00:49:28,398 once the drug was approved. 990 00:49:28,399 --> 00:49:30,935 If it wasn't approved, we didn't get anything back. 991 00:49:32,236 --> 00:49:34,137 When Kalydeco was approved, 992 00:49:34,138 --> 00:49:35,405 its high price 993 00:49:35,406 --> 00:49:37,874 and the prospect of more drugs in the pipeline, 994 00:49:37,875 --> 00:49:41,846 delivered in 2014 an unexpected windfall. 995 00:49:43,047 --> 00:49:44,381 Lo and behold, 996 00:49:44,382 --> 00:49:47,918 somebody said, we'll buy all your future royalties. 997 00:49:47,919 --> 00:49:49,720 And they had determined 998 00:49:49,721 --> 00:49:53,991 that was worth $3.3 billion. 999 00:49:56,894 --> 00:50:01,431 The reaction that we had sitting around the board was, 1000 00:50:01,432 --> 00:50:04,134 you know, mouths open. 1001 00:50:04,135 --> 00:50:09,673 What could CFF do with $3.3 billion? 1002 00:50:09,674 --> 00:50:10,942 We could do a lot. 1003 00:50:13,578 --> 00:50:16,179 As of 2026, the Foundation 1004 00:50:16,180 --> 00:50:19,516 is supporting development of several new treatments, 1005 00:50:19,517 --> 00:50:23,388 including a number of different CF gene therapy trials. 1006 00:50:25,356 --> 00:50:27,758 It's incredibly exciting to know 1007 00:50:27,759 --> 00:50:30,060 that we are back, testing gene therapy, 1008 00:50:30,061 --> 00:50:32,463 to try to cure CF. 1009 00:50:33,231 --> 00:50:34,398 In Denver, 1010 00:50:34,399 --> 00:50:38,169 Dr. Jen Taylor oversees two of these trials. 1011 00:50:39,337 --> 00:50:40,537 We have the technology 1012 00:50:40,538 --> 00:50:43,440 to see if we can actually at least fix 1013 00:50:43,441 --> 00:50:46,477 the gene in the lungs of people with cystic fibrosis. 1014 00:50:48,513 --> 00:50:51,314 And the thing that's so amazing about these therapies 1015 00:50:51,315 --> 00:50:53,450 is it wouldn't matter what mutation you have. 1016 00:50:53,451 --> 00:50:57,155 If they work, they'll work for all people with CF. 1017 00:50:59,457 --> 00:51:02,426 If the cystic fibrosis community is successful 1018 00:51:02,427 --> 00:51:03,927 in their quest for a cure, 1019 00:51:03,928 --> 00:51:06,296 they may once again transform 1020 00:51:06,297 --> 00:51:08,098 not only CF, 1021 00:51:08,099 --> 00:51:09,801 but science itself. 1022 00:51:12,703 --> 00:51:14,504 Thanks to the determination 1023 00:51:14,505 --> 00:51:17,340 of parents, patients and scientists, 1024 00:51:17,341 --> 00:51:20,310 pioneering breakthroughs in genetic medicine 1025 00:51:20,311 --> 00:51:23,481 may go on to transform life for most people with CF. 1026 00:51:26,117 --> 00:51:29,085 And they're not giving up, until 1027 00:51:29,086 --> 00:51:31,088 there's a solution for everyone. 1028 00:51:32,657 --> 00:51:34,758 My tattoo says, "Until it's done." 1029 00:51:34,759 --> 00:51:37,727 Because we still have a lot of work to do. 1030 00:51:37,728 --> 00:51:40,498 And that is our mission: until it's done.