1 00:00:01,066 --> 00:00:02,266 [ Clock ticking ] 2 00:00:02,300 --> 00:00:05,066 {\an1}-If you were born in 1900, 3 00:00:05,100 --> 00:00:09,666 {\an1}you could expect to live on average just 32 years. 4 00:00:09,700 --> 00:00:13,800 {\an1}Today, global life expectancy is more than twice that. 5 00:00:13,833 --> 00:00:17,300 {\an1}It's one of the greatest achievements in human history. 6 00:00:17,333 --> 00:00:19,566 ♪ 7 00:00:19,600 --> 00:00:22,400 {\an1}-This is the story of the ideas that have in the space of 8 00:00:22,433 --> 00:00:27,566 {\an1}just a century or two changed what it is to be us 9 00:00:27,600 --> 00:00:32,966 {\an1}by transforming the kind of lives we might live -- 10 00:00:33,000 --> 00:00:36,366 {\an1}no longer short and under the shadow of disease, 11 00:00:36,400 --> 00:00:40,100 {\an1}but healthy and long. 12 00:00:40,133 --> 00:00:42,900 {\an1}I'm David Olusoga, a historian. 13 00:00:42,933 --> 00:00:45,566 {\an1}I have to say, it does look like the sort of laboratory 14 00:00:45,600 --> 00:00:48,600 {\an1}you see in the "Frankenstein" movies. 15 00:00:48,633 --> 00:00:51,266 {\an1}-And I'm science writer Steven Johnson. 16 00:00:51,300 --> 00:00:53,333 {\an1}-The average Black American lives 17 00:00:53,366 --> 00:00:56,700 {\an1}three and a half years less than the average American. 18 00:00:56,733 --> 00:00:58,800 -That to me is just really shocking. 19 00:00:58,833 --> 00:01:01,266 {\an1}-We're investigating the forgotten heroes 20 00:01:01,300 --> 00:01:03,266 {\an1}of global health -- 21 00:01:03,300 --> 00:01:06,300 people whose life saving discoveries have tamed 22 00:01:06,333 --> 00:01:09,366 {\an1}some of the world's most deadly diseases. 23 00:01:09,400 --> 00:01:13,166 {\an1}-We were at a very exciting era of biochemistry 24 00:01:13,200 --> 00:01:15,233 and it was only a question of time 25 00:01:15,266 --> 00:01:17,866 {\an1}before we would hit the gold. 26 00:01:17,900 --> 00:01:22,233 {\an1}-One of their biggest innovations was medical drugs. 27 00:01:22,266 --> 00:01:26,133 {\an1}Today, as the world grapples with another deadly pandemic, 28 00:01:26,166 --> 00:01:29,800 {\an1}we reveal how drugs became one of the most powerful tools 29 00:01:29,833 --> 00:01:32,900 {\an1}we have in the fight for extra life. 30 00:01:32,933 --> 00:01:38,866 {\an8}♪ 31 00:01:40,700 --> 00:01:46,733 {\an8}♪ 32 00:01:46,766 --> 00:01:51,066 -I'm in the U.S., and David is in the U.K. 33 00:01:51,100 --> 00:01:52,466 {\an1}In the current climate, 34 00:01:52,500 --> 00:01:54,366 {\an1}this is the only way we could meet. 35 00:01:56,166 --> 00:01:59,000 David. -Steven, how are you doing? 36 00:01:59,033 --> 00:02:00,333 -Good. -Good to see you. 37 00:02:00,366 --> 00:02:02,000 {\an1}-Good to see you, too. 38 00:02:02,033 --> 00:02:05,333 {\an1}-This is the new normal -- life in 2021. 39 00:02:05,366 --> 00:02:08,166 {\an1}-Couple of pals hanging out, just having a little chat. 40 00:02:08,200 --> 00:02:11,000 [ Laughter ] 41 00:02:11,033 --> 00:02:13,166 {\an1}You want to kick it off, David? 42 00:02:13,200 --> 00:02:16,066 -I take a drug because of a thyroid disease 43 00:02:16,100 --> 00:02:17,066 {\an1}every day of my life. 44 00:02:17,100 --> 00:02:19,166 {\an1}If I don't take that drug, I'll die. 45 00:02:19,200 --> 00:02:22,266 If I go and look at the census records for people 46 00:02:22,300 --> 00:02:24,966 {\an1}with the same condition 100 years ago, 47 00:02:25,000 --> 00:02:28,233 {\an1}their life expectancy, their outcomes are appalling. 48 00:02:28,266 --> 00:02:29,500 It killed people. 49 00:02:29,533 --> 00:02:32,600 {\an1}-The repertoire of magic bullets, 50 00:02:32,633 --> 00:02:34,433 {\an1}of life-saving medicines 51 00:02:34,466 --> 00:02:37,366 {\an1}that have been developed over the past few decades 52 00:02:37,400 --> 00:02:41,233 {\an1}is really one of the most consequential developments 53 00:02:41,266 --> 00:02:42,200 of modern life. 54 00:02:42,233 --> 00:02:43,866 {\an1}I mean, in the United States, 55 00:02:43,900 --> 00:02:48,466 {\an1}compared to 1900, people live about 30 years longer. 56 00:02:48,500 --> 00:02:51,333 {\an1}We expect that our children will live into adulthood, 57 00:02:51,366 --> 00:02:54,100 {\an1}that will get to meet our grandchildren. 58 00:02:54,133 --> 00:02:57,133 {\an1}-We do take it for granted. I take it for granted. 59 00:02:57,166 --> 00:02:59,833 {\an1}I like to think of my work as an historian that I'm somebody 60 00:02:59,866 --> 00:03:03,966 {\an1}who is really cognizant of the centrality of the story 61 00:03:04,000 --> 00:03:05,200 {\an1}of disease and medicine. 62 00:03:05,233 --> 00:03:06,400 {\an1}But in making this program, 63 00:03:06,433 --> 00:03:09,766 I've realized that I've still not grasped 64 00:03:09,800 --> 00:03:13,066 {\an1}the scale of how medicine has been 65 00:03:13,100 --> 00:03:15,833 {\an1}just one of the greatest revolutions in human history. 66 00:03:15,866 --> 00:03:18,100 {\an1}-I've always been fascinated with this -- 67 00:03:18,133 --> 00:03:20,500 {\an7}this story of rising life expectancy. 68 00:03:20,533 --> 00:03:23,333 {\an8}One of the things that was most surprising to me 69 00:03:23,366 --> 00:03:28,500 {\an7}is the invention of actual functional medical drugs 70 00:03:28,533 --> 00:03:31,633 {\an1}arrives on the historical stage surprisingly late. 71 00:03:31,666 --> 00:03:36,333 {\an1}We invented, you know, automobiles and planes 72 00:03:36,366 --> 00:03:38,333 {\an1}and radio and television. 73 00:03:38,366 --> 00:03:40,733 {\an1}But medicine was actually lagging behind 74 00:03:40,766 --> 00:03:42,200 {\an1}those more conventional 75 00:03:42,233 --> 00:03:44,433 kind of markers of technological progress. 76 00:03:44,466 --> 00:03:47,900 {\an1}-I think that revolution had given us a sense of impunity, 77 00:03:47,933 --> 00:03:50,366 {\an1}that there would always be a medicine. 78 00:03:50,400 --> 00:03:52,333 {\an1}And despite all the tragedies we've been through 79 00:03:52,366 --> 00:03:53,766 {\an1}and the terrible cost of this pandemic, 80 00:03:53,800 --> 00:03:55,166 {\an1}maybe there is a positive in this 81 00:03:55,200 --> 00:03:57,700 that we realize we desperately need 82 00:03:57,733 --> 00:04:00,600 to recognize the incredible revolution 83 00:04:00,633 --> 00:04:03,233 {\an1}and the heroes behind it that have given us all of this, 84 00:04:03,266 --> 00:04:05,266 {\an1}given this this extra life. 85 00:04:05,300 --> 00:04:07,533 ♪ 86 00:04:07,566 --> 00:04:10,800 {\an1}-At the beginning of the last century, a medical revolution 87 00:04:10,833 --> 00:04:15,466 {\an1}began that would lead to safe and effective drugs for all, 88 00:04:15,500 --> 00:04:20,400 {\an1}causing life expectancy here in the U.S. to rocket upwards. 89 00:04:20,433 --> 00:04:23,733 {\an1}We take it for granted today that when we go to the pharmacy 90 00:04:23,766 --> 00:04:26,366 {\an1}to treat a bee sting or an eye infection 91 00:04:26,400 --> 00:04:29,300 or a headache, the remedy will work. 92 00:04:32,166 --> 00:04:34,633 {\an1}But even in the early 20th century, 93 00:04:34,666 --> 00:04:38,000 {\an1}taking medicines was gambling with your life. 94 00:04:38,033 --> 00:04:41,800 {\an1}-What's important to remember here is that throughout history 95 00:04:41,833 --> 00:04:46,300 {\an1}and until relatively recently, many medical treatments were, 96 00:04:46,333 --> 00:04:47,766 to put it kindly, 97 00:04:47,800 --> 00:04:50,266 {\an1}a bit questionable. 98 00:04:50,300 --> 00:04:54,200 {\an1}-Duffield's Concentrated Medicinal Fluid Extracts, 99 00:04:54,233 --> 00:05:00,166 {\an1}which contains belladonna from the deadly plant nightshade, 100 00:05:00,200 --> 00:05:02,700 arsenic... 101 00:05:02,733 --> 00:05:04,733 and mercury -- 102 00:05:04,766 --> 00:05:08,033 {\an7}all of which are deadly toxins. 103 00:05:08,066 --> 00:05:12,766 {\an7}-It was all rather unscientific and until recently there was 104 00:05:12,800 --> 00:05:16,400 {\an1}no system to determine if medications were safe 105 00:05:16,433 --> 00:05:21,600 or if they had any positive effects. 106 00:05:21,633 --> 00:05:27,066 {\an1}-1900, an era of quack cures and bogus remedies 107 00:05:27,100 --> 00:05:29,833 {\an1}and life expectancy in the United States 108 00:05:29,866 --> 00:05:32,000 was just... 109 00:05:32,033 --> 00:05:35,400 49 years. 110 00:05:35,433 --> 00:05:39,800 {\an1}But then 34 years after this catalog was published, 111 00:05:39,833 --> 00:05:41,400 {\an1}there would come a discovery 112 00:05:41,433 --> 00:05:44,833 {\an1}that would change drugs and medicine forever. 113 00:05:47,866 --> 00:05:50,166 Penicillin. 114 00:05:50,200 --> 00:05:52,033 {\an7}The discovery of penicillin 115 00:05:52,066 --> 00:05:54,233 {\an8}was a catalyst for dramatic increases 116 00:05:54,266 --> 00:05:57,166 {\an7}in life expectancy across the whole world. 117 00:05:57,200 --> 00:06:02,600 {\an8}♪ 118 00:06:02,633 --> 00:06:04,433 {\an1}The numbers are staggering. 119 00:06:04,466 --> 00:06:07,233 {\an1}In the United States before antibiotics, 120 00:06:07,266 --> 00:06:11,866 30% of all deaths were related to infections. 121 00:06:11,900 --> 00:06:15,466 {\an1}You could get a simple scrape, just a minor cut, 122 00:06:15,500 --> 00:06:19,300 {\an1}and an infection would develop and you could be dead in a week. 123 00:06:19,333 --> 00:06:21,300 {\an1}The magnitude of mortality 124 00:06:21,333 --> 00:06:24,766 {\an1}caused by those kinds of infections was just terrifying. 125 00:06:24,800 --> 00:06:28,633 {\an1}-We've forgotten the scale of the horror because antibiotics, 126 00:06:28,666 --> 00:06:31,766 which is such an incredible magic bullet 127 00:06:31,800 --> 00:06:35,200 {\an1}that made all of that suddenly brush that whole world away 128 00:06:35,233 --> 00:06:37,200 {\an1}that our ancestors just took for granted. 129 00:06:37,233 --> 00:06:38,966 And I just mean our grandparents' generation. 130 00:06:39,000 --> 00:06:41,133 I don't mean back hundreds of years. 131 00:06:41,166 --> 00:06:44,433 {\an1}-What I love about the story is that it is truly 132 00:06:44,466 --> 00:06:46,866 a story of international collaboration, 133 00:06:46,900 --> 00:06:49,800 {\an1}a broad network of people with different talents 134 00:06:49,833 --> 00:06:54,766 {\an1}coming together to solve this truly life-transforming problem. 135 00:06:54,800 --> 00:06:57,100 {\an1}-But that incredible story of all of these people 136 00:06:57,133 --> 00:06:59,166 coming together with these specialist skills, 137 00:06:59,200 --> 00:07:01,066 that's not what I learned at school. 138 00:07:01,100 --> 00:07:03,333 All I was taught about the breakthrough 139 00:07:03,366 --> 00:07:06,533 {\an1}that was penicillin was one moment and one guy. 140 00:07:06,566 --> 00:07:13,066 ♪ 141 00:07:13,100 --> 00:07:16,200 {\an1}Everybody has heard the name Alexander Fleming. 142 00:07:16,233 --> 00:07:19,200 He's somebody we all study at school. 143 00:07:19,233 --> 00:07:22,933 {\an1}What he was fascinated by was the hidden micro world 144 00:07:22,966 --> 00:07:26,300 {\an1}that lies beyond our vision. 145 00:07:26,333 --> 00:07:29,800 {\an1}He became obsessed with microbes, bacteria, 146 00:07:29,833 --> 00:07:32,366 {\an1}and he studied them relentlessly. 147 00:07:34,566 --> 00:07:37,800 {\an1}During the First World War, Fleming had served 148 00:07:37,833 --> 00:07:39,833 in the Royal Army Medical Corps, 149 00:07:39,866 --> 00:07:43,600 {\an1}and in France, in the hospitals behind the Western Front, 150 00:07:43,633 --> 00:07:47,600 {\an1}he had seen at first hand the consequences 151 00:07:47,633 --> 00:07:50,600 {\an1}of bacterial infection -- 152 00:07:50,633 --> 00:07:52,300 septicemia... 153 00:07:52,333 --> 00:07:55,133 gangrene. 154 00:07:55,166 --> 00:07:58,500 {\an1}Of the millions of soldiers who died in World War One, 155 00:07:58,533 --> 00:08:01,733 {\an1}it's estimated that around a third were not killed 156 00:08:01,766 --> 00:08:06,066 {\an1}by shellfire or machine guns, but by disease. 157 00:08:06,100 --> 00:08:09,400 {\an1}Fleming understood as well as anybody possibly could 158 00:08:09,433 --> 00:08:13,033 the desperate, urgent need for new treatments 159 00:08:13,066 --> 00:08:17,366 {\an1}to combat bacterial infection. 160 00:08:17,400 --> 00:08:22,400 London 1928 -- Fleming is working in his lab. 161 00:08:22,433 --> 00:08:29,266 ♪ 162 00:08:29,300 --> 00:08:31,266 {\an1}The story of Alexander Fleming 163 00:08:31,300 --> 00:08:34,800 {\an1}gives hope to anyone with an untidy desk 164 00:08:34,833 --> 00:08:36,900 {\an1}because his untidiness 165 00:08:36,933 --> 00:08:41,366 {\an1}was actually critical to what happened. 166 00:08:41,400 --> 00:08:43,133 {\an1}In the summer of 1928, 167 00:08:43,166 --> 00:08:46,466 {\an1}Fleming left a petri dish contaminated 168 00:08:46,500 --> 00:08:51,500 {\an1}with the bacteria staphylococcus on his desk uncovered. 169 00:08:54,133 --> 00:08:56,766 {\an1}He then went off on a vacation, 170 00:08:56,800 --> 00:09:00,400 but he left... 171 00:09:00,433 --> 00:09:03,900 {\an1}one of the windows of his laboratory wide open. 172 00:09:03,933 --> 00:09:11,233 ♪ 173 00:09:11,266 --> 00:09:18,533 ♪ 174 00:09:18,566 --> 00:09:23,833 {\an1}A microscopic fungal spore is blown in through a window, 175 00:09:23,866 --> 00:09:27,200 {\an1}perhaps escaped from a downstairs laboratory. 176 00:09:31,333 --> 00:09:36,233 {\an1}Pivoting and floating on a sea of turbulent air, 177 00:09:36,266 --> 00:09:38,300 {\an1}it sinks down onto 178 00:09:38,333 --> 00:09:41,400 one of Fleming's uncovered petri dishes. 179 00:09:41,433 --> 00:09:48,633 ♪ 180 00:09:48,666 --> 00:09:55,833 ♪ 181 00:09:55,866 --> 00:09:59,700 {\an1}On the 3rd of September 1928, Alexander Fleming 182 00:09:59,733 --> 00:10:05,666 {\an1}returns to his laboratory and to his untidy desk. 183 00:10:05,700 --> 00:10:08,133 This is the groundbreaking moment... 184 00:10:11,133 --> 00:10:13,566 {\an1}...because Fleming starts to look through 185 00:10:13,600 --> 00:10:17,100 {\an1}all the petri dishes he left on his desk, 186 00:10:17,133 --> 00:10:19,633 {\an1}and something catches his eye. 187 00:10:19,666 --> 00:10:25,700 ♪ 188 00:10:25,733 --> 00:10:31,733 {\an1}On one of the dishes, he sees that a mold has grown. 189 00:10:31,766 --> 00:10:36,866 {\an1}And around the mold, there was no staphylococcus bacteria. 190 00:10:36,900 --> 00:10:42,766 ♪ 191 00:10:42,800 --> 00:10:44,533 {\an1}What Fleming concludes 192 00:10:44,566 --> 00:10:48,933 {\an1}is that the bacteria has been killed by something produced 193 00:10:48,966 --> 00:10:50,700 by the mold, 194 00:10:50,733 --> 00:10:53,800 {\an1}and so this naturally occurring mold, 195 00:10:53,833 --> 00:10:56,533 {\an1}something that's literally in the air, 196 00:10:56,566 --> 00:11:00,466 {\an1}could be a bacteria killer. 197 00:11:00,500 --> 00:11:03,833 {\an1}This was a discovery of enormous significance, 198 00:11:03,866 --> 00:11:07,666 {\an1}one that was eventually to win Alexander Fleming 199 00:11:07,700 --> 00:11:10,400 the Nobel Prize. 200 00:11:10,433 --> 00:11:13,166 {\an1}-And I think a lot of people assume when they hear 201 00:11:13,200 --> 00:11:14,433 the Fleming story 202 00:11:14,466 --> 00:11:17,833 {\an1}that after Fleming makes this accidental discovery, 203 00:11:17,866 --> 00:11:21,200 {\an1}within a couple of years penicillin is available 204 00:11:21,233 --> 00:11:23,100 as a medicine changing the world. 205 00:11:23,133 --> 00:11:27,866 {\an1}But in fact, the development of the drug itself 206 00:11:27,900 --> 00:11:31,300 {\an1}effectively gets paused for a decade 207 00:11:31,333 --> 00:11:34,200 after Fleming's accidental discovery. 208 00:11:34,233 --> 00:11:35,566 {\an1}-We so much want to believe 209 00:11:35,600 --> 00:11:39,100 {\an1}and that sort of Hollywood story of accidental discovery, 210 00:11:39,133 --> 00:11:42,033 kind of addicted to that sort of narrative. 211 00:11:42,066 --> 00:11:43,533 {\an1}You know, Fleming's amazing guy, 212 00:11:43,566 --> 00:11:44,833 and we shouldn't take it away from him. 213 00:11:44,866 --> 00:11:47,133 {\an1}He understood he discovered something significant, 214 00:11:47,166 --> 00:11:49,500 {\an1}but he didn't have all the skills needed. 215 00:11:49,533 --> 00:11:50,700 {\an1}He wasn't a chemist. 216 00:11:50,733 --> 00:11:52,100 {\an1}He couldn't have taken things much further. 217 00:11:52,133 --> 00:11:54,566 {\an1}And I think more importantly, he didn't have the network 218 00:11:54,600 --> 00:11:58,033 {\an1}needed to transform an accident in a petri dish 219 00:11:58,066 --> 00:11:59,766 to the drug that changed the world. 220 00:11:59,800 --> 00:12:03,000 {\an1}-You need to have networks of people with different skills, 221 00:12:03,033 --> 00:12:04,233 {\an1}different fields of expertise 222 00:12:04,266 --> 00:12:05,700 coming together to solve a problem. 223 00:12:05,733 --> 00:12:08,200 And in fact, that's exactly what happens 224 00:12:08,233 --> 00:12:09,633 {\an1}in the history of penicillin. 225 00:12:09,666 --> 00:12:15,100 ♪ 226 00:12:15,133 --> 00:12:21,100 {\an1}-So, let's pick up the story here in Oxford in 1938. 227 00:12:21,133 --> 00:12:23,600 Just two decades after a conflict 228 00:12:23,633 --> 00:12:26,966 {\an1}in which millions had died of bacterial infection, 229 00:12:27,000 --> 00:12:30,633 {\an1}Europe is teetering on the edge of another war. 230 00:12:30,666 --> 00:12:36,333 ♪ 231 00:12:36,366 --> 00:12:38,966 {\an1}Howard Florey, a very driven 232 00:12:39,000 --> 00:12:41,166 and very talented Australian scientist, 233 00:12:41,200 --> 00:12:45,566 {\an1}is running an institute of pathology. 234 00:12:45,600 --> 00:12:48,133 He and his team are studying the pathogens 235 00:12:48,166 --> 00:12:51,800 {\an1}that cause disease in humans. 236 00:12:51,833 --> 00:12:54,200 {\an1}They are searching for substances 237 00:12:54,233 --> 00:12:56,366 {\an1}that might kill bacteria. 238 00:12:59,066 --> 00:13:03,166 {\an1}In an age before computers, this means poring over reams 239 00:13:03,200 --> 00:13:08,466 {\an1}of scientific journals in dusty libraries. 240 00:13:08,500 --> 00:13:10,733 One day in 1938, 241 00:13:10,766 --> 00:13:15,266 {\an1}a member of Florey's team uncovers a decade-old paper. 242 00:13:17,733 --> 00:13:21,766 {\an1}When Florey reads Alexander Fleming's now-obscure paper, 243 00:13:21,800 --> 00:13:24,233 {\an1}and we think that happens in this office 244 00:13:24,266 --> 00:13:25,966 {\an1}that was then his office, 245 00:13:26,000 --> 00:13:28,266 {\an1}he doesn't necessarily recognize 246 00:13:28,300 --> 00:13:31,500 {\an1}the enormous potential of penicillin mold. 247 00:13:31,533 --> 00:13:34,833 {\an1}He wasn't thinking that he'd stumbled upon the  drug 248 00:13:34,866 --> 00:13:36,466 {\an1}that was to change history. 249 00:13:36,500 --> 00:13:40,633 {\an1}Rather, he just found what he was reading interesting. 250 00:13:40,666 --> 00:13:45,533 {\an1}Now, Florey had hired two brilliant biochemists, 251 00:13:45,566 --> 00:13:48,100 {\an1}Ernst Chain and Norman Heatley. 252 00:13:48,133 --> 00:13:52,000 {\an1}They were a perfect team -- three people in the right place 253 00:13:52,033 --> 00:13:54,733 at the right time with complementary skills. 254 00:13:54,766 --> 00:13:57,533 {\an1}And under the firm direction of Florey, 255 00:13:57,566 --> 00:14:01,833 {\an1}they began their investigations. 256 00:14:01,866 --> 00:14:05,733 {\an1}But the first task was to hunt down the exact same mold 257 00:14:05,766 --> 00:14:09,466 {\an1}that Fleming had stumbled across all those years earlier -- 258 00:14:09,500 --> 00:14:12,666 {\an1}the difficulty being that there are tens of thousands 259 00:14:12,700 --> 00:14:15,200 {\an1}of known species of mold. 260 00:14:15,233 --> 00:14:18,500 ♪ 261 00:14:18,533 --> 00:14:20,400 {\an1}In an amazing stroke of luck, 262 00:14:20,433 --> 00:14:23,066 {\an1}the team find some suitable mold growing 263 00:14:23,100 --> 00:14:25,433 {\an1}in a laboratory in the building. 264 00:14:25,466 --> 00:14:28,033 {\an1}Now, this is really fortuitous 265 00:14:28,066 --> 00:14:30,266 {\an1}because otherwise it might have taken them months 266 00:14:30,300 --> 00:14:32,766 to source this specific type of mold. 267 00:14:32,800 --> 00:14:35,633 But this is where their luck runs out. 268 00:14:35,666 --> 00:14:44,833 ♪ 269 00:14:44,866 --> 00:14:48,500 {\an1}So, they'd found some mold in the laboratory. 270 00:14:48,533 --> 00:14:50,266 {\an1}What's the next step? 271 00:14:50,300 --> 00:14:52,533 {\an7}-First of all, they had to grow the mold up in great volumes 272 00:14:52,566 --> 00:14:55,433 {\an7}and great amounts, and that was no easy feat. 273 00:14:55,466 --> 00:14:57,700 {\an7}-And the penicillin is not the mold itself. 274 00:14:57,733 --> 00:14:59,433 {\an7}It is something produced by the mold. 275 00:14:59,466 --> 00:15:00,700 {\an7}-Yeah, that's absolutely right. 276 00:15:00,733 --> 00:15:03,100 {\an7}You can grow the fungus up, 277 00:15:03,133 --> 00:15:06,566 {\an7}but then you have to get the mold to produce the drug 278 00:15:06,600 --> 00:15:10,233 {\an8}and then you have to purify the drug. 279 00:15:10,266 --> 00:15:14,433 {\an7}-Producing and refining the new drug was a complicated process 280 00:15:14,466 --> 00:15:18,133 {\an7}of trial and error -- a multi-staged operation, 281 00:15:18,166 --> 00:15:21,700 {\an7}each stage having to be tinkered with and refined 282 00:15:21,733 --> 00:15:26,100 {\an8}until it was as efficient as possible. 283 00:15:26,133 --> 00:15:28,400 {\an8}After months of intense research, 284 00:15:28,433 --> 00:15:31,466 {\an8}the team managed to produce a tiny amount 285 00:15:31,500 --> 00:15:34,766 {\an1}with which to begin experimentation. 286 00:15:34,800 --> 00:15:37,866 {\an1}-And the critical experiment was to see 287 00:15:37,900 --> 00:15:40,566 {\an1}whether it could cure infection in vivo. 288 00:15:40,600 --> 00:15:43,100 In other words, an infected mouse. 289 00:15:44,533 --> 00:15:46,066 Early in 1940, 290 00:15:46,100 --> 00:15:48,466 {\an1}they gave eight animals a lethal injection, 291 00:15:48,500 --> 00:15:50,666 the bacterium called streptococcus, 292 00:15:50,700 --> 00:15:54,833 {\an1}and four those animals received penicillin treatment. 293 00:15:54,866 --> 00:15:57,300 ♪ 294 00:15:57,333 --> 00:15:59,800 {\an1}-So, all eight mice have been injected 295 00:15:59,833 --> 00:16:01,666 {\an1}with a lethal dose of bacteria. 296 00:16:01,700 --> 00:16:05,066 {\an1}Four have been given penicillin 297 00:16:05,100 --> 00:16:06,866 {\an1}and four haven't, so they're the control animal. 298 00:16:06,900 --> 00:16:08,066 -Absolutely. Yes. 299 00:16:08,100 --> 00:16:10,233 {\an1}-So what was the result of that experiment? 300 00:16:10,266 --> 00:16:11,766 {\an1}-Within a few hours, 301 00:16:11,800 --> 00:16:13,900 {\an1}the control animals who didn't receive penicillin 302 00:16:13,933 --> 00:16:17,333 {\an1}started showing signs of systemic infection. 303 00:16:17,366 --> 00:16:23,866 {\an1}And within about 15 hours, all of them had died. 304 00:16:23,900 --> 00:16:27,933 {\an1}But all the animals treated with penicillin were perfectly happy. 305 00:16:29,933 --> 00:16:32,800 {\an1}Alongside Fleming and the famous story of the petri dish, 306 00:16:32,833 --> 00:16:36,366 {\an1}this is the other eureka moment in the story of penicillin, 307 00:16:36,400 --> 00:16:39,166 {\an1}because if you imagine being part of the Oxford team 308 00:16:39,200 --> 00:16:43,133 {\an1}when seeing those results -- half of the poor mice have died, 309 00:16:43,166 --> 00:16:45,166 but half of them have survived -- 310 00:16:45,200 --> 00:16:46,966 {\an1}and what that strongly suggests 311 00:16:47,000 --> 00:16:49,866 {\an1}is that this does fight bacterial infection. 312 00:16:49,900 --> 00:16:52,300 {\an1}But where are they really? 313 00:16:52,333 --> 00:16:55,300 All they've done is they've proved principle. 314 00:16:55,333 --> 00:16:57,533 {\an1}They're nowhere near having a workable drug. 315 00:16:57,566 --> 00:16:59,433 {\an1}-What's completely up for grabs at this point 316 00:16:59,466 --> 00:17:01,100 {\an1}is the crucial question 317 00:17:01,133 --> 00:17:03,333 {\an1}of whether they can make enough of this stuff 318 00:17:03,366 --> 00:17:04,766 {\an1}to make a difference in humans. 319 00:17:04,800 --> 00:17:06,500 {\an1}Florey remarks at some point 320 00:17:06,533 --> 00:17:09,766 {\an1}that he would need 3,000 times as much penicillin 321 00:17:09,800 --> 00:17:13,833 {\an1}as they currently have to test it on just a single person. 322 00:17:13,866 --> 00:17:15,566 {\an1}And so what you get into at this point 323 00:17:15,600 --> 00:17:17,733 {\an1}is a very different kind of challenge, right? 324 00:17:17,766 --> 00:17:21,166 {\an1}This is about scaling it up and mass producing it. 325 00:17:21,200 --> 00:17:23,300 {\an1}-Let's remember the date. This is May 1940. 326 00:17:23,333 --> 00:17:25,533 {\an1}This is one of the darkest moments in the Second World War. 327 00:17:25,566 --> 00:17:27,866 {\an1}There are soldiers dying on operating theaters 328 00:17:27,900 --> 00:17:29,500 from infections right at that moment. 329 00:17:29,533 --> 00:17:34,400 {\an1}So the potential and the journey they have still to go 330 00:17:34,433 --> 00:17:37,366 {\an1}are just both enormous. 331 00:17:37,400 --> 00:17:41,100 {\an1}Severely lacking in resources, Florey, Chain, and Heatley 332 00:17:41,133 --> 00:17:43,266 {\an1}tried to scale up production 333 00:17:43,300 --> 00:17:45,800 {\an1}with whatever they had to hand. 334 00:17:45,833 --> 00:17:48,400 {\an1}Is that a milk churn? -It's a milk churn 335 00:17:48,433 --> 00:17:50,766 {\an1}because they didn't have any other large volume receptacles 336 00:17:50,800 --> 00:17:53,600 {\an1}and it's being poured into a cast iron bathtub there. 337 00:17:53,633 --> 00:17:55,100 -Bathtub. 338 00:17:56,666 --> 00:18:00,533 {\an1}-This is remarkably... low tech. 339 00:18:00,566 --> 00:18:01,933 {\an1}-It is. Very simple. 340 00:18:01,966 --> 00:18:03,800 {\an1}-All this equipment and material 341 00:18:03,833 --> 00:18:05,200 {\an1}is suspended on bits of wood 342 00:18:05,233 --> 00:18:09,466 {\an1}which have been hammered and screw together. 343 00:18:09,500 --> 00:18:11,300 {\an1}-I have to say, it does look like the sort of laboratory 344 00:18:11,333 --> 00:18:12,866 you see in a "Frankenstein" movie. 345 00:18:12,900 --> 00:18:14,766 -[ Chuckles ] 346 00:18:14,800 --> 00:18:16,500 -So, this is what it's all about. 347 00:18:16,533 --> 00:18:18,400 {\an1}-This is what it's all about. 348 00:18:18,433 --> 00:18:21,166 {\an1}-And this is still not anywhere near the scale you're going to 349 00:18:21,200 --> 00:18:23,000 need to have. Clearly, if you're going to 350 00:18:23,033 --> 00:18:25,400 produce a drug which would be given worldwide, 351 00:18:25,433 --> 00:18:29,833 {\an1}then you need to do this on a huge scale. 352 00:18:29,866 --> 00:18:32,700 {\an1}-After seven months, the Oxford team now 353 00:18:32,733 --> 00:18:36,900 have a few precious grams of penicillin, 354 00:18:36,933 --> 00:18:39,866 {\an1}enough to test on a human being. 355 00:18:43,033 --> 00:18:45,766 {\an1}Rural Oxfordshire -- 356 00:18:45,800 --> 00:18:48,300 {\an1}a 43-year-old police constable, 357 00:18:48,333 --> 00:18:51,800 Albert Alexander, is tending to his roses. 358 00:18:54,233 --> 00:18:56,666 {\an1}Bacteria surround us in the world. 359 00:18:56,700 --> 00:18:58,933 {\an1}We just can't see them. 360 00:18:58,966 --> 00:19:00,633 Beautiful roses 361 00:19:00,666 --> 00:19:02,666 {\an1}and their thorns are covered 362 00:19:02,700 --> 00:19:06,133 with millions of potentially deadly bacteria. 363 00:19:09,000 --> 00:19:12,666 {\an1}A rose thorn slices across his face. 364 00:19:15,100 --> 00:19:18,533 {\an1}Bacteria make their way into the wound. 365 00:19:21,733 --> 00:19:23,466 {\an1}And over the next few days, 366 00:19:23,500 --> 00:19:27,333 {\an1}he begins to get sick. 367 00:19:27,366 --> 00:19:33,600 {\an1}-Sometimes the first symptom is a high-temperature fever, 368 00:19:33,633 --> 00:19:35,500 {\an7}because a high temperature 369 00:19:35,533 --> 00:19:39,000 {\an7}generally inhibits the growth of bacteria. 370 00:19:39,033 --> 00:19:41,366 {\an7}-So it's a defense mechanism when we have a high temperature. 371 00:19:41,400 --> 00:19:43,200 -Absolutely. This high temperature 372 00:19:43,233 --> 00:19:47,933 {\an1}is used by our body to kill the pathogen. 373 00:19:47,966 --> 00:19:49,866 {\an1}-What else can the body do at that moment? 374 00:19:49,900 --> 00:19:52,566 {\an1}-Then white blood cells are recruited 375 00:19:52,600 --> 00:19:55,300 {\an1}in the area of the infection, 376 00:19:55,333 --> 00:19:58,633 {\an1}which is basically to the production of pus. 377 00:19:58,666 --> 00:20:00,766 {\an1}It's a thick fluid that is composed 378 00:20:00,800 --> 00:20:04,066 {\an1}by that white blood cells and bacteria. 379 00:20:04,100 --> 00:20:05,466 {\an1}-So, the person who's sick, do they 380 00:20:05,500 --> 00:20:06,633 {\an1}stay conscious through this 381 00:20:06,666 --> 00:20:08,466 or do they start losing consciousness? 382 00:20:08,500 --> 00:20:11,666 -Generally, they will lose consciousness. 383 00:20:11,700 --> 00:20:15,333 {\an1}Oxygen in the blood will decrease. 384 00:20:15,366 --> 00:20:19,366 {\an1}Some organs might start to fail. 385 00:20:19,400 --> 00:20:23,433 {\an1}And this will highly likely 386 00:20:23,466 --> 00:20:26,433 lead to death. 387 00:20:26,466 --> 00:20:27,566 -For four months, 388 00:20:27,600 --> 00:20:32,400 bacteria rampage through Albert Alexander's body. 389 00:20:32,433 --> 00:20:35,433 {\an1}He's lost one of his eyes to the infection 390 00:20:35,466 --> 00:20:36,966 {\an1}and, too weak to move, 391 00:20:37,000 --> 00:20:39,366 he is near death. 392 00:20:39,400 --> 00:20:43,500 February 1941 -- the new test compound, 393 00:20:43,533 --> 00:20:47,200 {\an1}penicillin, is administered to Alexander. 394 00:20:47,233 --> 00:20:50,433 {\an1}Nearly two years of the Oxford team's work rests 395 00:20:50,466 --> 00:20:52,233 on this moment. 396 00:20:52,266 --> 00:20:55,266 ♪ 397 00:20:55,300 --> 00:20:57,600 [ Heart beating ] 398 00:20:57,633 --> 00:21:00,633 ♪ 399 00:21:00,666 --> 00:21:06,166 {\an1}Within hours, his temperature falls, his appetite returns -- 400 00:21:06,200 --> 00:21:10,800 {\an1}the wonder drug is beating the rioting bacteria. 401 00:21:10,833 --> 00:21:14,733 {\an1}But the penicillin is running out. 402 00:21:14,766 --> 00:21:18,600 {\an1}Even after being reconnected from Alexander's urine, 403 00:21:18,633 --> 00:21:22,733 {\an1}Florey, Chain, and Heatley simply cannot produce enough 404 00:21:22,766 --> 00:21:27,633 {\an1}and he dies in March 1941. 405 00:21:27,666 --> 00:21:31,533 {\an1}-I've always been haunted by that story of Albert Alexander. 406 00:21:31,566 --> 00:21:35,133 {\an1}I mean, it just is such a representative example 407 00:21:35,166 --> 00:21:38,233 {\an1}of what life was like before the invention of penicillin. 408 00:21:38,266 --> 00:21:40,500 {\an1}-It's one of those stories that shows the difference between 409 00:21:40,533 --> 00:21:43,233 {\an1}sort of movies and reality, because if this was a movie, 410 00:21:43,266 --> 00:21:45,966 the first person treated with antibiotics 411 00:21:46,000 --> 00:21:48,066 {\an1}would be the first person saved. 412 00:21:48,100 --> 00:21:50,200 {\an1}But it doesn't work like that. 413 00:21:50,233 --> 00:21:52,600 {\an1}But they have shown that it was effective, 414 00:21:52,633 --> 00:21:55,933 {\an1}and now they face this almost impossible task of trying 415 00:21:55,966 --> 00:21:58,400 to produce enough to treat more people. 416 00:21:58,433 --> 00:21:59,800 {\an1}And they're in the middle of a war. 417 00:21:59,833 --> 00:22:01,566 {\an1}These are scientists cycling 418 00:22:01,600 --> 00:22:03,400 back and forth from their laboratory 419 00:22:03,433 --> 00:22:05,900 {\an1}to the hospital where poor Albert Alexander is dying. 420 00:22:05,933 --> 00:22:08,866 {\an1}If this was today, they would have huge companies 421 00:22:08,900 --> 00:22:12,233 {\an1}and governments pouring millions of dollars into their efforts. 422 00:22:12,266 --> 00:22:14,500 {\an1}They'd be doing huge clinical trials. 423 00:22:14,533 --> 00:22:16,200 {\an1}-And that's the question for us today, right? 424 00:22:16,233 --> 00:22:17,666 {\an1}Particularly in the middle of a pandemic 425 00:22:17,700 --> 00:22:20,066 {\an1}is given all the resources and expertise 426 00:22:20,100 --> 00:22:23,166 {\an1}that we have now that Florey and his team didn't have, 427 00:22:23,200 --> 00:22:26,766 can we accelerate that timetable? 428 00:22:26,800 --> 00:22:31,600 {\an1}-Today, scientists are finding new ways to fast track drugs 429 00:22:31,633 --> 00:22:33,466 to patients. 430 00:22:33,500 --> 00:22:34,800 {\an1}At Oxford University, 431 00:22:34,833 --> 00:22:38,400 {\an1}one of the leading government advisers on COVID-19, 432 00:22:38,433 --> 00:22:42,833 {\an1}Professor Horby, helped to establish the Recovery Trial. 433 00:22:42,866 --> 00:22:46,333 {\an1}It's one of the fastest drug trials ever set up, 434 00:22:46,366 --> 00:22:49,900 {\an1}and initially it looked at whether already available drugs 435 00:22:49,933 --> 00:22:53,366 {\an1}could be repurposed for the pandemic. 436 00:22:53,400 --> 00:22:55,233 {\an1}I think people imagine when you say the phrase 437 00:22:55,266 --> 00:22:58,100 {\an1}"clinical trial" is that you're trying a new drug. 438 00:22:58,133 --> 00:23:00,200 {\an1}Now, that's not what the Recovery Trial was doing. 439 00:23:00,233 --> 00:23:03,200 {\an8}-We started with existing drugs that were in 440 00:23:03,233 --> 00:23:06,166 {\an7}the cupboard licensed for other indications. 441 00:23:06,200 --> 00:23:08,400 {\an7}If these drugs are shown to work in COVID, 442 00:23:08,433 --> 00:23:10,466 {\an1}then you can just get them out the pharmacy and out 443 00:23:10,500 --> 00:23:12,033 {\an1}of the pharmacy cupboard straight away. 444 00:23:12,066 --> 00:23:15,100 {\an1}-So, if your trial hits upon a preexisting drug 445 00:23:15,133 --> 00:23:17,533 {\an1}that has some efficacy with COVID, 446 00:23:17,566 --> 00:23:19,033 then it's already on people's shelves. 447 00:23:19,066 --> 00:23:20,333 {\an1}It's literally already in the factories 448 00:23:20,366 --> 00:23:22,200 {\an1}and we know how to make it. -Yeah, that's right. 449 00:23:22,233 --> 00:23:24,666 {\an1}And you can -- the doctors just can reach for that new drug 450 00:23:24,700 --> 00:23:26,266 {\an1}and they can do that pretty much 451 00:23:26,300 --> 00:23:27,800 in any hospital around the world. 452 00:23:27,833 --> 00:23:31,000 {\an1}So, we would have it benefit not just for high-income countries, 453 00:23:31,033 --> 00:23:33,666 {\an1}but countries everywhere. 454 00:23:33,700 --> 00:23:36,300 {\an1}-How did you select these preexisting drugs? 455 00:23:36,333 --> 00:23:38,433 {\an1}-Initially it was a part of a government committee 456 00:23:38,466 --> 00:23:40,566 {\an1}that I sit on where we got some experts together 457 00:23:40,600 --> 00:23:42,033 {\an1}and we went through the list 458 00:23:42,066 --> 00:23:45,233 {\an1}and one of them is a steroid, dexamethasone. 459 00:23:45,266 --> 00:23:49,466 {\an1}-This anti-inflammatory steroid used for allergies and asthma 460 00:23:49,500 --> 00:23:54,566 {\an1}turned out to have a surprising effect on COVID-19 patients. 461 00:23:54,600 --> 00:23:57,666 {\an1}-Dexamethasone reduces mortality quite significantly, 462 00:23:57,700 --> 00:23:59,333 {\an1}particularly in patients on a ventilator, 463 00:23:59,366 --> 00:24:01,966 {\an1}so severely on patients in intensive care, 464 00:24:02,000 --> 00:24:04,066 which for us was just jaw-dropping 465 00:24:04,100 --> 00:24:07,766 {\an1}but also fantastic news because it's an incredibly cheap drug 466 00:24:07,800 --> 00:24:09,566 that is available in every country in the world. 467 00:24:09,600 --> 00:24:12,066 {\an1}And literally people could get it off the shelf 468 00:24:12,100 --> 00:24:14,100 the same day that we announced the results. 469 00:24:14,133 --> 00:24:16,900 {\an1}-So, there are people who have survived COVID 470 00:24:16,933 --> 00:24:18,433 {\an1}who wouldn't have done had this trial 471 00:24:18,466 --> 00:24:20,833 not identified that particular steroid 472 00:24:20,866 --> 00:24:22,266 as something that could help them? 473 00:24:22,300 --> 00:24:24,133 {\an1}-Their estimate is that from the date 474 00:24:24,166 --> 00:24:27,133 {\an1}we announced the result until the end of 2020, 475 00:24:27,166 --> 00:24:30,166 {\an1}we would have saved around 12,000 lives in the U.K. 476 00:24:30,200 --> 00:24:32,300 {\an1}And if you extrapolate that globally, 477 00:24:32,333 --> 00:24:35,333 {\an1}it could have saved half a million lives. 478 00:24:35,366 --> 00:24:36,300 -Here she comes. 479 00:24:36,333 --> 00:24:38,333 {\an1}A big round of applause, everybody. 480 00:24:38,366 --> 00:24:41,000 {\an1}[ Cheers and applause ] 481 00:24:41,033 --> 00:24:43,366 {\an1}-By testing off-the-shelf drugs 482 00:24:43,400 --> 00:24:46,033 available via existing supply chains, 483 00:24:46,066 --> 00:24:50,066 {\an1}Horby and his team found treatments for COVID-19 484 00:24:50,100 --> 00:24:52,733 {\an1}within just months. 485 00:24:52,766 --> 00:24:56,533 Back in 1941, with the war intensifying, 486 00:24:56,566 --> 00:24:57,900 {\an1}Florey and his team 487 00:24:57,933 --> 00:25:02,833 {\an1}were still nowhere near a workable mass market drug. 488 00:25:02,866 --> 00:25:05,200 {\an1}It had already taken over a decade 489 00:25:05,233 --> 00:25:09,166 {\an1}to progress the promising find into enough of the drug 490 00:25:09,200 --> 00:25:13,466 to trial on a single patient. 491 00:25:13,500 --> 00:25:16,966 {\an1}Penicillin-producing mold was such medical gold dust 492 00:25:17,000 --> 00:25:21,200 that staff took some of the spores 493 00:25:21,233 --> 00:25:26,133 {\an1}and they smeared them down the insides of their coats 494 00:25:26,166 --> 00:25:28,666 {\an1}so that in the event of a German invasion, 495 00:25:28,700 --> 00:25:32,466 {\an1}they could escape and they could grow fresh cultures abroad. 496 00:25:32,500 --> 00:25:40,400 ♪ 497 00:25:40,433 --> 00:25:43,600 {\an1}But despite throwing everything they had at the problem, 498 00:25:43,633 --> 00:25:45,500 {\an1}in this volatile time, 499 00:25:45,533 --> 00:25:49,366 {\an1}the team simply could not make enough penicillin. 500 00:25:49,400 --> 00:25:52,166 Florey grew increasingly frustrated. 501 00:25:52,200 --> 00:25:53,733 {\an1}He knew that he was on to something, 502 00:25:53,766 --> 00:25:56,566 {\an1}but the British government didn't have the resources 503 00:25:56,600 --> 00:25:59,300 {\an1}to offer help, and the pharmaceutical companies, 504 00:25:59,333 --> 00:26:02,200 {\an1}they were working flat out for the war effort. 505 00:26:02,233 --> 00:26:05,400 {\an1}To them, working on penicillin just didn't seem 506 00:26:05,433 --> 00:26:09,733 important enough to commit scarce resources. 507 00:26:09,766 --> 00:26:11,466 And so to Florey, 508 00:26:11,500 --> 00:26:14,466 {\an1}the United States began to look like a safe haven 509 00:26:14,500 --> 00:26:19,933 {\an1}where he and his team could continue with their research. 510 00:26:19,966 --> 00:26:24,466 {\an1}July in 1941, in a scene straight out of "Casablanca," 511 00:26:24,500 --> 00:26:25,833 {\an1}Florey and Heatley 512 00:26:25,866 --> 00:26:28,800 {\an1}pack much of the world's supply of penicillin 513 00:26:28,833 --> 00:26:32,900 {\an1}into a briefcase and take a Pan Am Clipper to New York. 514 00:26:32,933 --> 00:26:34,600 {\an1}They tell U.S. Immigration 515 00:26:34,633 --> 00:26:36,566 they're on important medical business 516 00:26:36,600 --> 00:26:38,700 {\an1}for the war effort. 517 00:26:38,733 --> 00:26:40,566 {\an1}It's at this point in the story that a feature 518 00:26:40,600 --> 00:26:44,600 {\an1}of Howard Florey's personality becomes central 519 00:26:44,633 --> 00:26:46,200 because he brings people together. 520 00:26:46,233 --> 00:26:49,266 {\an1}He meets people and creates this sort of complicated network 521 00:26:49,300 --> 00:26:52,266 {\an1}of specialisms and skills and convinces people, 522 00:26:52,300 --> 00:26:54,533 {\an1}including the government, that this is a project 523 00:26:54,566 --> 00:26:56,533 that they absolutely have to support. 524 00:26:56,566 --> 00:27:01,533 {\an1}-And that ultimate project is really an incredibly powerful 525 00:27:01,566 --> 00:27:05,600 {\an1}story of scientific discovery and global collaboration. 526 00:27:05,633 --> 00:27:09,733 {\an1}And yet the top secret military project during World War Two 527 00:27:09,766 --> 00:27:12,866 {\an1}that we always hear about is the Manhattan Project, 528 00:27:12,900 --> 00:27:14,833 the development of the atomic bomb. 529 00:27:14,866 --> 00:27:17,966 {\an1}But to me, the penicillin story, it deserves far more attention 530 00:27:18,000 --> 00:27:20,066 {\an1}because it's actually the story about inventing 531 00:27:20,100 --> 00:27:21,366 {\an1}a life-saving drug 532 00:27:21,400 --> 00:27:23,766 and not a weapon of mass destruction. 533 00:27:23,800 --> 00:27:25,500 {\an1}-Even with all of those resources 534 00:27:25,533 --> 00:27:28,500 {\an1}and all of those experts and industrialists 535 00:27:28,533 --> 00:27:31,300 {\an1}that Florey brings together, it still takes them years 536 00:27:31,333 --> 00:27:33,066 {\an1}to get from Florey's discovery 537 00:27:33,100 --> 00:27:36,200 {\an1}to a mass-produced penicillin drug. 538 00:27:36,233 --> 00:27:38,600 {\an1}-The American company Pfizer, up until then known 539 00:27:38,633 --> 00:27:41,266 {\an1}for making the citric acid in sodas, 540 00:27:41,300 --> 00:27:43,700 {\an1}decides to take on the challenge. 541 00:27:43,733 --> 00:27:48,600 ♪ 542 00:27:48,633 --> 00:27:51,900 {\an1}The problem was to grow the Penicillium mold 543 00:27:51,933 --> 00:27:55,933 {\an1}required nutrients and oxygen from the air, 544 00:27:55,966 --> 00:27:58,833 {\an1}but that could only happen here at this thin film 545 00:27:58,866 --> 00:28:04,266 at the surface, a relatively tiny area. 546 00:28:04,300 --> 00:28:09,233 {\an1}So the big idea was to blow air through a nutrient-rich broth. 547 00:28:09,266 --> 00:28:17,400 ♪ 548 00:28:17,433 --> 00:28:20,633 {\an1}So instead of just growing the antibiotic-producing mold 549 00:28:20,666 --> 00:28:22,000 at the surface, 550 00:28:22,033 --> 00:28:24,533 {\an1}they hope to grow it through the entire broth, 551 00:28:24,566 --> 00:28:26,833 {\an1}a so-called submerged culture. 552 00:28:28,900 --> 00:28:31,133 {\an1}That, at least, was the plan. 553 00:28:31,166 --> 00:28:34,866 {\an1}Executing it on an industrial scale was another matter. 554 00:28:37,833 --> 00:28:41,933 They convert an old Brooklyn ice factory, 555 00:28:41,966 --> 00:28:44,966 {\an1}scrounging an industrial boiler from Indiana 556 00:28:45,000 --> 00:28:48,566 {\an1}and an old elevator from Long Island. 557 00:28:48,600 --> 00:28:53,333 {\an1}Engineers installed 14 giant fermentation tanks, 558 00:28:53,366 --> 00:28:58,766 {\an1}each with a 7,500-gallon capacity. 559 00:28:58,800 --> 00:29:03,433 {\an1}The vats were filled with a sugar-rich corn steep liquor 560 00:29:03,466 --> 00:29:07,533 and a little bit of penicillin mold. 561 00:29:07,566 --> 00:29:11,266 {\an1}The air was turned on. 562 00:29:11,300 --> 00:29:15,466 {\an1}Nobody knew the right amount of oxygen to put into the system. 563 00:29:15,500 --> 00:29:17,433 Nobody knew what was going to happen. 564 00:29:17,466 --> 00:29:27,100 ♪ 565 00:29:27,133 --> 00:29:31,466 But the results were spectacular. 566 00:29:31,500 --> 00:29:34,800 {\an1}The yield was five times the highest estimate. 567 00:29:37,400 --> 00:29:41,500 {\an1}A few months later, when allied troops landed at D-Day, 568 00:29:41,533 --> 00:29:44,366 {\an1}they had penicillin in their packs -- 569 00:29:44,400 --> 00:29:49,100 {\an1}penicillin made in this room. 570 00:29:49,133 --> 00:29:53,200 It was the dawn of the antibiotic age. 571 00:29:53,233 --> 00:29:55,800 {\an1}What had been incurable was now curable. 572 00:29:55,833 --> 00:30:01,700 {\an1}What could have been fatal was now just a minor illness. 573 00:30:01,733 --> 00:30:05,100 {\an1}-One of the immediate effects of the arrival of penicillin 574 00:30:05,133 --> 00:30:07,700 {\an1}was that it takes diseases 575 00:30:07,733 --> 00:30:10,766 {\an1}that had destroyed millions of lives 576 00:30:10,800 --> 00:30:15,333 {\an1}and it transforms them overnight to being treatable conditions. 577 00:30:15,366 --> 00:30:17,166 {\an1}And that's -- that's miraculous. 578 00:30:17,200 --> 00:30:20,633 {\an1}-Diseases like tuberculosis and syphilis that basically 579 00:30:20,666 --> 00:30:23,133 {\an1}antibiotics kind of took off the table as a threat. 580 00:30:23,166 --> 00:30:26,300 {\an1}And all of that had a massive impact 581 00:30:26,333 --> 00:30:29,033 {\an7}on life expectancy in the antibiotic era. 582 00:30:29,066 --> 00:30:32,166 {\an7}Global life expectancy was extended by two decades. 583 00:30:32,200 --> 00:30:34,933 {\an1}-And there's another effect that it's easy to overlook, 584 00:30:34,966 --> 00:30:38,333 {\an1}which is that it doesn't just gift us with these extra years. 585 00:30:38,366 --> 00:30:42,366 {\an1}It opens up the possibilities of elective surgery, 586 00:30:42,400 --> 00:30:45,500 and people who wouldn't have dreamed 587 00:30:45,533 --> 00:30:48,833 {\an1}of going under the surgeon's knife in an age 588 00:30:48,866 --> 00:30:50,233 {\an1}when infection was, you know, 589 00:30:50,266 --> 00:30:53,200 {\an1}sometimes killing a quarter of people on the operating table 590 00:30:53,233 --> 00:30:57,133 {\an1}could suddenly contemplate these life-improving operations. 591 00:30:57,166 --> 00:30:58,700 {\an1}-And it opened the door 592 00:30:58,733 --> 00:31:01,700 {\an1}for the next generation of medical drugs. 593 00:31:01,733 --> 00:31:10,466 ♪ 594 00:31:10,500 --> 00:31:14,733 {\an1}The discovery that penicillin could kill bacteria ranks 595 00:31:14,766 --> 00:31:16,833 up there with splitting the atom, 596 00:31:16,866 --> 00:31:19,700 {\an1}with the moon landing -- a giant leap forward 597 00:31:19,733 --> 00:31:23,500 in human progress and life expectancy. 598 00:31:23,533 --> 00:31:26,400 {\an1}But there were other wonder drugs to be discovered 599 00:31:26,433 --> 00:31:28,866 that could attack other great pathogens 600 00:31:28,900 --> 00:31:33,066 {\an1}that had plagued humanity for millennia. 601 00:31:33,100 --> 00:31:35,933 {\an1}We've all been living through a new threat to our lives, 602 00:31:35,966 --> 00:31:39,033 {\an1}this time caused by a virus. 603 00:31:39,066 --> 00:31:40,966 {\an1}During the coronavirus pandemic, 604 00:31:41,000 --> 00:31:46,166 {\an1}life expectancy in the U.S. fell by one year. 605 00:31:46,200 --> 00:31:48,600 {\an1}Viruses are much smaller than bacteria -- 606 00:31:48,633 --> 00:31:51,266 100 million can fit on a pinhead -- 607 00:31:51,300 --> 00:31:55,033 and antibiotics can't attack them. 608 00:31:55,066 --> 00:31:57,433 {\an1}Slipping inside a host cell, 609 00:31:57,466 --> 00:32:01,400 {\an1}they reproduce by hijacking the cells own machinery, 610 00:32:01,433 --> 00:32:04,833 {\an1}and most viruses eventually destroy their host cell. 611 00:32:04,866 --> 00:32:10,000 ♪ 612 00:32:10,033 --> 00:32:15,233 {\an1}Influenza, Ebola, and COVID-19 are all caused by viruses, 613 00:32:15,266 --> 00:32:20,566 {\an1}notoriously hard to study and even harder to treat. 614 00:32:20,600 --> 00:32:24,300 But by the 1970s, a pioneer called Gertrude Elion 615 00:32:24,333 --> 00:32:26,633 began using new scientific methods 616 00:32:26,666 --> 00:32:31,900 {\an1}to custom build effective antiviral drugs. 617 00:32:31,933 --> 00:32:36,033 {\an1}Gertrude Elion was born in New York City in 1918 618 00:32:36,066 --> 00:32:37,700 {\an1}to immigrant parents. 619 00:32:39,866 --> 00:32:42,100 {\an1}She lost her grandfather to cancer 620 00:32:42,133 --> 00:32:43,266 and her fiancé 621 00:32:43,300 --> 00:32:46,566 {\an1}to a bacterial infection of the heart. 622 00:32:46,600 --> 00:32:49,566 -I had determined when I was 15 years old 623 00:32:49,600 --> 00:32:52,333 that I was going to be a scientist. 624 00:32:52,366 --> 00:32:56,533 {\an1}I entered college at that age and I was going to be a chemist. 625 00:32:56,566 --> 00:33:00,000 {\an1}And what's more, I was going to find a cure for cancer. 626 00:33:00,033 --> 00:33:02,633 {\an1}In 1944, Elion joined 627 00:33:02,666 --> 00:33:05,166 {\an1}the pharmaceutical company Burroughs Wellcome. 628 00:33:05,200 --> 00:33:09,533 {\an1}-We were at a very exciting era of biochemistry. 629 00:33:09,566 --> 00:33:12,600 {\an1}We were finding out things so rapidly 630 00:33:12,633 --> 00:33:16,600 {\an1}and things were progressing with such excitement. 631 00:33:16,633 --> 00:33:18,833 {\an1}And it was only a question of time 632 00:33:18,866 --> 00:33:24,033 {\an1}before we would really hit the gold. 633 00:33:24,066 --> 00:33:26,866 {\an1}-She started working with Dr. George Hitchings. 634 00:33:26,900 --> 00:33:30,333 Together, they were amazingly prolific. 635 00:33:30,366 --> 00:33:32,600 {\an1}In terms of drug development, 636 00:33:32,633 --> 00:33:34,500 {\an1}they were a dream team. 637 00:33:34,533 --> 00:33:37,633 {\an1}So how did they do it? 638 00:33:37,666 --> 00:33:40,200 {\an1}Thank you so much. 639 00:33:40,233 --> 00:33:44,700 {\an1}Alright, this is my molecule building kit. 640 00:33:44,733 --> 00:33:50,200 {\an1}So, we're gonna need five nitrogen. 641 00:33:50,233 --> 00:33:51,600 {\an1}Hitchings and Elion realized 642 00:33:51,633 --> 00:33:55,233 {\an1}that through careful study of how our cells interact 643 00:33:55,266 --> 00:33:59,266 with compounds and pathogens like viruses, 644 00:33:59,300 --> 00:34:01,566 they could build highly efficient, 645 00:34:01,600 --> 00:34:05,166 targeted drugs to do specific tasks. 646 00:34:05,200 --> 00:34:11,500 {\an1}So, first we connect these three nitrogens... 647 00:34:11,533 --> 00:34:13,366 {\an1}This was a revelation -- 648 00:34:13,400 --> 00:34:16,066 {\an1}building synthetic drugs atom 649 00:34:16,100 --> 00:34:19,466 {\an1}by atom from the ground up. 650 00:34:19,500 --> 00:34:23,900 {\an1}In the 1970s, Elion and her team built a new drug 651 00:34:23,933 --> 00:34:28,666 {\an1}that would revolutionize our approach to tackling viruses. 652 00:34:28,700 --> 00:34:32,433 {\an1}Picture this -- Atlanta 1978. 653 00:34:32,466 --> 00:34:34,933 Trudy Elion is at a conference 654 00:34:34,966 --> 00:34:38,866 filled with expectant scientists. 655 00:34:38,900 --> 00:34:42,533 {\an1}It's the creme de la creme of drug makers and creators 656 00:34:42,566 --> 00:34:44,733 {\an1}from around the world. 657 00:34:44,766 --> 00:34:48,600 {\an1}She presents a paper on a miraculous new compound. 658 00:34:48,633 --> 00:34:52,900 {\an1}It's the first highly selective antiviral drug 659 00:34:52,933 --> 00:34:55,000 {\an1}targeting the herpes virus. 660 00:34:55,033 --> 00:34:57,966 {\an1}It's called acyclovir. 661 00:34:58,000 --> 00:35:00,733 {\an1}It's unlike anything the world has ever seen before. 662 00:35:00,766 --> 00:35:02,233 {\an1}Thank you. Thank you so much. 663 00:35:04,133 --> 00:35:07,000 {\an1}Was there a sudden burst of applause? 664 00:35:07,033 --> 00:35:08,766 {\an1}Did the audience realize 665 00:35:08,800 --> 00:35:11,233 the magnitude of what they were seeing? 666 00:35:11,266 --> 00:35:15,400 {\an1}I like to think so because this speech marked a milestone 667 00:35:15,433 --> 00:35:18,266 {\an1}in the history of human health. 668 00:35:18,300 --> 00:35:21,700 {\an1}And like the discovery of penicillin 50 years before, 669 00:35:21,733 --> 00:35:24,900 {\an1}it ushered in a new age of medicine, 670 00:35:24,933 --> 00:35:27,333 {\an1}this time targeting viruses. 671 00:35:27,366 --> 00:35:30,733 [ Applause ] 672 00:35:30,766 --> 00:35:34,066 {\an1}Together, the work of Elion and Hitchings paved the way 673 00:35:34,100 --> 00:35:35,733 {\an1}for designer drugs, 674 00:35:35,766 --> 00:35:39,233 {\an1}helping to treat a huge range of illnesses from leukemia 675 00:35:39,266 --> 00:35:43,033 {\an1}to malaria to arthritis. 676 00:35:43,066 --> 00:35:45,933 {\an1}The techniques Trudy Elion developed over her career 677 00:35:45,966 --> 00:35:50,300 {\an1}provided a foundation for many other researchers. 678 00:35:50,333 --> 00:35:52,566 -Unfortunately, I never got to meet her, 679 00:35:52,600 --> 00:35:55,733 {\an1}but I think her work certainly is inspirational. 680 00:35:55,766 --> 00:35:57,933 {\an1}Fleming gets the credit for, 681 00:35:57,966 --> 00:36:01,666 {\an1}you know, discovering penicillin by serendipity. 682 00:36:01,700 --> 00:36:06,133 {\an1}But these folks did it by rational design. 683 00:36:06,166 --> 00:36:09,033 {\an1}-Professor David Ho would use antiviral drugs 684 00:36:09,066 --> 00:36:11,300 {\an1}made using rational design 685 00:36:11,333 --> 00:36:13,700 to solve one of the great medical mysteries 686 00:36:13,733 --> 00:36:17,200 {\an1}and save millions of lives. 687 00:36:17,233 --> 00:36:24,100 {\an7}-1980, when I was just finishing up my medical training, 688 00:36:24,133 --> 00:36:29,300 {\an1}when I had a patient who presented to the hospital 689 00:36:29,333 --> 00:36:32,066 {\an1}with a multitude of infections. 690 00:36:32,100 --> 00:36:35,433 He was treated, went home for a while 691 00:36:35,466 --> 00:36:41,100 {\an1}and then shortly after died of other infections. 692 00:36:41,133 --> 00:36:45,966 {\an1}He was a young gay man, and we did not know 693 00:36:46,000 --> 00:36:47,700 {\an1}how to explain his case. 694 00:36:47,733 --> 00:36:49,266 {\an1}And a few weeks later, 695 00:36:49,300 --> 00:36:53,200 {\an1}a similar young man came to the hospital again, 696 00:36:53,233 --> 00:36:54,800 {\an1}and so we were staring 697 00:36:54,833 --> 00:36:59,400 {\an1}at a potentially infectious lethal disease, 698 00:36:59,433 --> 00:37:02,566 {\an1}and that is quite scary. 699 00:37:02,600 --> 00:37:05,400 {\an1}-Ho was witnessing the start of the AIDS epidemic 700 00:37:05,433 --> 00:37:06,733 sweeping America. 701 00:37:06,766 --> 00:37:08,500 {\an1}The new virus was fatal 702 00:37:08,533 --> 00:37:11,166 {\an1}to almost every person it infected. 703 00:37:11,200 --> 00:37:13,700 {\an1}-San Francisco, Los Angeles and New York 704 00:37:13,733 --> 00:37:16,366 {\an1}report the highest number of AIDS cases. 705 00:37:16,400 --> 00:37:20,666 {\an7}But all across the country, the disease is on the rise 706 00:37:20,700 --> 00:37:22,866 {\an1}-At the Center for Disease Control in Atlanta, 707 00:37:22,900 --> 00:37:24,800 where 400 cases have been reported, 708 00:37:24,833 --> 00:37:27,100 {\an1}a special task force has now been set up -- 709 00:37:27,133 --> 00:37:31,666 {\an1}a disease experts are now calling a national epidemic. 710 00:37:31,700 --> 00:37:34,200 {\an1}-It's so interesting to look back at that period 711 00:37:34,233 --> 00:37:37,800 {\an1}from the perspective of the current pandemic, 712 00:37:37,833 --> 00:37:39,900 because HIV was a death sentence. 713 00:37:39,933 --> 00:37:41,233 {\an1}I mean, the infection 714 00:37:41,266 --> 00:37:44,600 mortality rate was very close to 100%. 715 00:37:44,633 --> 00:37:46,533 {\an1}-You and I must have been both kids 716 00:37:46,566 --> 00:37:48,433 {\an1}in the '80s when HIV emerged. 717 00:37:48,466 --> 00:37:52,100 {\an1}Even at that age, I imagine that science and doctors 718 00:37:52,133 --> 00:37:53,600 {\an1}had an answer to every disease 719 00:37:53,633 --> 00:37:54,866 {\an1}and it seemed the end of diseases -- 720 00:37:54,900 --> 00:37:56,866 {\an1}not the emergence of a new one. 721 00:37:56,900 --> 00:37:59,666 {\an1}So it was absolutely terrifying. 722 00:37:59,700 --> 00:38:01,233 {\an1}-And it took years for them 723 00:38:01,266 --> 00:38:03,600 {\an1}to ultimately identify that HIV virus. 724 00:38:03,633 --> 00:38:05,933 {\an1}And you compare that to COVID-19, 725 00:38:05,966 --> 00:38:10,000 {\an1}and within weeks of this, the virus is identified 726 00:38:10,033 --> 00:38:11,700 {\an1}and its genome is sequenced. 727 00:38:11,733 --> 00:38:13,500 {\an1}And so the pace of discovery 728 00:38:13,533 --> 00:38:15,500 and understanding is so much faster today 729 00:38:15,533 --> 00:38:17,600 than it was back in the early '80s. 730 00:38:17,633 --> 00:38:19,166 {\an1}-I think it's important to remember that, you know, 731 00:38:19,200 --> 00:38:21,933 medical science got there in a way 732 00:38:21,966 --> 00:38:25,200 {\an1}because now there's all sorts of antiviral treatments for HIV. 733 00:38:25,233 --> 00:38:28,400 {\an1}But it's sometimes disturbing the way people talk about it, 734 00:38:28,433 --> 00:38:30,066 as if it's in the rearview mirror, 735 00:38:30,100 --> 00:38:32,266 {\an1}as if it's something of the past. 736 00:38:32,300 --> 00:38:35,566 {\an1}HIV is still very, very much with us. 737 00:38:35,600 --> 00:38:37,766 And in the time since it's emerged, 738 00:38:37,800 --> 00:38:41,100 it's claimed over 40 million lives. 739 00:38:44,300 --> 00:38:46,566 {\an1}-First recognized in 1981, 740 00:38:46,600 --> 00:38:50,300 the HIV virus swiftly spread around the world. 741 00:38:50,333 --> 00:38:52,133 {\an1}The race was on for new, 742 00:38:52,166 --> 00:38:56,300 more effective antivirals to tackle it. 743 00:38:56,333 --> 00:39:02,366 {\an1}-In the early '90s, we were studying a new class of drugs 744 00:39:02,400 --> 00:39:07,800 {\an1}that attack HIV called protease inhibitors. 745 00:39:07,833 --> 00:39:10,766 {\an1}-Protease inhibitors are carefully designed drugs 746 00:39:10,800 --> 00:39:14,200 {\an1}that stop the virus replicating in our cells. 747 00:39:14,233 --> 00:39:17,866 {\an1}-When you intervene with a drug like the protease inhibitor, 748 00:39:17,900 --> 00:39:21,666 we essentially shut off production. 749 00:39:21,700 --> 00:39:24,733 {\an1}-But the real revelation came when Ho applied math 750 00:39:24,766 --> 00:39:26,500 {\an1}to what they were witnessing. 751 00:39:26,533 --> 00:39:29,833 {\an1}-We were able to come to a major conclusion 752 00:39:29,866 --> 00:39:33,866 {\an1}about the dynamics of HIV replication. 753 00:39:33,900 --> 00:39:37,900 {\an1}-The virus was making billions of copies of itself every day. 754 00:39:37,933 --> 00:39:39,733 {\an1}Crucially, in doing so, 755 00:39:39,766 --> 00:39:43,633 {\an1}it was also making millions of mutations. 756 00:39:43,666 --> 00:39:49,033 {\an1}-We discerned that the virus was making so many mutations 757 00:39:49,066 --> 00:39:50,433 {\an1}and it was a given 758 00:39:50,466 --> 00:39:54,100 that the virus will quickly escape our drugs 759 00:39:54,133 --> 00:39:57,066 {\an1}if we administer them one at a time. 760 00:39:57,100 --> 00:39:59,333 {\an1}But then we could do the math further to show 761 00:39:59,366 --> 00:40:01,933 {\an1}that if you were to administer three at a time 762 00:40:01,966 --> 00:40:03,666 {\an1}or four at a time, 763 00:40:03,700 --> 00:40:09,466 {\an1}it became exceedingly difficult for HIV to escape. 764 00:40:09,500 --> 00:40:13,866 {\an1}The first phase of the AIDS pandemic really ended 765 00:40:13,900 --> 00:40:19,300 {\an1}with the combination antiretroviral therapy. 766 00:40:19,333 --> 00:40:21,200 {\an1}-Now Professor Ho and his team 767 00:40:21,233 --> 00:40:23,066 {\an1}are using their extensive expertise, 768 00:40:23,100 --> 00:40:27,933 {\an1}tackling new viruses on SARS-CoV-2. 769 00:40:27,966 --> 00:40:30,366 {\an1}Can you tell me about the sense of urgency 770 00:40:30,400 --> 00:40:31,833 {\an1}in this lab right now? 771 00:40:31,866 --> 00:40:33,900 {\an1}-When China shut down Wuhan, 772 00:40:33,933 --> 00:40:37,233 {\an1}we knew this was going to be a big matter, 773 00:40:37,266 --> 00:40:41,600 {\an1}and very soon the first case was identified in New York, 774 00:40:41,633 --> 00:40:43,200 {\an1}here at our hospital, 775 00:40:43,233 --> 00:40:46,300 {\an1}and our team mobilized. 776 00:40:46,333 --> 00:40:50,333 {\an1}They've been, you know, working 14-, 15-hour days 777 00:40:50,366 --> 00:40:52,633 {\an1}and working through the weekend. 778 00:40:52,666 --> 00:40:55,133 {\an1}That's the level of dedication. 779 00:40:57,666 --> 00:41:00,033 {\an1}-Is there something about SARS-CoV-2 780 00:41:00,066 --> 00:41:01,866 {\an1}in the way that it mutates? 781 00:41:01,900 --> 00:41:05,933 {\an1}-SARS-CoV-2 does mutate, but its mutation rate 782 00:41:05,966 --> 00:41:09,333 {\an1}as compared to HIV seems to be slower. 783 00:41:09,366 --> 00:41:14,033 {\an1}So overall, the mutational challenge posed by SARS-CoV-2 784 00:41:14,066 --> 00:41:17,800 {\an1}is probably not as great as that of HIV. 785 00:41:17,833 --> 00:41:19,500 {\an1}-So less of a need for a cocktail. 786 00:41:19,533 --> 00:41:23,333 -Less of a need, but there may still be a need. 787 00:41:23,366 --> 00:41:27,233 {\an1}You may not need three drugs, but you might need two. 788 00:41:27,266 --> 00:41:29,200 {\an1}-Do you think we're ever heading towards a future 789 00:41:29,233 --> 00:41:35,333 {\an1}where there's just one pill that can combat any emerging virus? 790 00:41:35,366 --> 00:41:37,966 {\an1}-That would be really nice to have one pill 791 00:41:38,000 --> 00:41:40,800 {\an1}that takes care of viruses. 792 00:41:40,833 --> 00:41:45,333 {\an1}I think maybe -- maybe a long time from now we could do that. 793 00:41:45,366 --> 00:41:47,233 {\an1}But in the short term, what we could do 794 00:41:47,266 --> 00:41:49,800 {\an1}is perhaps one pill or one antibody 795 00:41:49,833 --> 00:41:54,366 {\an1}that could take care of a pretty large family of coronaviruses. 796 00:41:54,400 --> 00:41:56,633 {\an1}But it's going to be a continual struggle. 797 00:41:56,666 --> 00:41:59,766 {\an1}As we make progress, 798 00:41:59,800 --> 00:42:04,633 {\an1}the pathogens have an enormous capability to evolve and adapt 799 00:42:04,666 --> 00:42:10,000 {\an1}and escape from our vaccines, our antibodies, our drugs. 800 00:42:10,033 --> 00:42:14,500 {\an1}-Mutant strains of SARS-CoV-2 to continue to appear. 801 00:42:14,533 --> 00:42:18,700 {\an1}Both viruses and bacteria are ever-moving targets. 802 00:42:18,733 --> 00:42:22,400 {\an1}Were caught in a game of cat and mouse, 803 00:42:22,433 --> 00:42:26,000 {\an1}and already we're seeing our current deck of antibiotics 804 00:42:26,033 --> 00:42:28,900 begin to fail. 805 00:42:28,933 --> 00:42:30,266 {\an1}-In the story of antibiotics, 806 00:42:30,300 --> 00:42:32,933 {\an1}we've also become victims of our own success 807 00:42:32,966 --> 00:42:35,100 {\an1}because the great specter hanging over all of this 808 00:42:35,133 --> 00:42:39,266 {\an1}and hanging over all of us is antibiotic resistance. 809 00:42:39,300 --> 00:42:44,433 {\an1}-We think that something like 700,000 people a year are dying 810 00:42:44,466 --> 00:42:46,633 because of antimicrobial resistance, 811 00:42:46,666 --> 00:42:48,666 {\an1}because of these new superbugs. 812 00:42:48,700 --> 00:42:50,600 {\an1}And that number is projected to reach as high 813 00:42:50,633 --> 00:42:54,400 {\an1}as 10 million a year by 2050 if we don't do something about it. 814 00:42:54,433 --> 00:42:57,666 {\an1}-The idea of returning to the world before antibiotics, 815 00:42:57,700 --> 00:42:59,333 a world where if you cut yourself 816 00:42:59,366 --> 00:43:00,633 {\an1}on a rose in the garden, 817 00:43:00,666 --> 00:43:01,966 {\an1}you could be dead in weeks, 818 00:43:02,000 --> 00:43:04,300 {\an1}or a world where surgeries become impossible 819 00:43:04,333 --> 00:43:06,800 {\an1}because of infections in the operating theater, 820 00:43:06,833 --> 00:43:08,200 {\an1}the idea of returning to that world, 821 00:43:08,233 --> 00:43:10,566 {\an1}the world of our ancestors, 822 00:43:10,600 --> 00:43:13,900 {\an1}it's just -- it's too horrific to imagine. 823 00:43:13,933 --> 00:43:16,966 {\an1}-I think there's a tendency to assume that the progress 824 00:43:17,000 --> 00:43:19,666 we've made over the last 100 years or so 825 00:43:19,700 --> 00:43:21,300 {\an1}will just continue on 826 00:43:21,333 --> 00:43:23,566 {\an1}because enlightenment science is doing its thing. 827 00:43:23,600 --> 00:43:26,566 {\an1}But these are battles that have to be kind of continually fought 828 00:43:26,600 --> 00:43:28,033 and new threats inevitably emerge. 829 00:43:28,066 --> 00:43:30,866 {\an1}COVID-19 is only the latest reminder of that. 830 00:43:30,900 --> 00:43:35,033 And so in a way, what we need now is -- 831 00:43:35,066 --> 00:43:37,933 {\an1}is not just the innovation of a new pill, a new medicine, 832 00:43:37,966 --> 00:43:39,266 {\an1}as important as that would be, 833 00:43:39,300 --> 00:43:41,766 {\an1}but we may need a different kind of innovation, 834 00:43:41,800 --> 00:43:43,733 {\an1}which is a new kind of institution 835 00:43:43,766 --> 00:43:47,800 {\an1}capable of developing, testing and distributing 836 00:43:47,833 --> 00:43:51,233 {\an1}at scale, at a global scale, a new class of antibiotics 837 00:43:51,266 --> 00:43:55,200 {\an1}that can fight off these superbugs. 838 00:43:55,233 --> 00:43:57,200 In early 2019, 839 00:43:57,233 --> 00:44:00,533 {\an1}a cross-disciplinary team of scientists at MIT 840 00:44:00,566 --> 00:44:04,400 {\an1}came together to tackle antibiotic resistance. 841 00:44:04,433 --> 00:44:08,200 {\an7}-What drives me to go to work every day? 842 00:44:08,233 --> 00:44:13,866 {\an7}The prospect of saving people's lives, full stop. 843 00:44:13,900 --> 00:44:18,633 {\an1}To contribute long-lasting and meaningful solutions 844 00:44:18,666 --> 00:44:21,100 to the antibiotic resistance crisis. 845 00:44:21,133 --> 00:44:23,766 {\an1}We discovered antibiotics so quickly and got so good at it 846 00:44:23,800 --> 00:44:26,833 {\an1}that we stopped thinking about it as a problem, 847 00:44:26,866 --> 00:44:28,800 {\an1}and that caught up with us in a big way. 848 00:44:28,833 --> 00:44:31,766 You know, the evolution of resistance 849 00:44:31,800 --> 00:44:36,033 {\an1}in bacterial pathogens didn't stop, even though we did. 850 00:44:36,066 --> 00:44:38,366 {\an1}-The last time we successfully introduced 851 00:44:38,400 --> 00:44:43,533 {\an1}a new class of antibiotic drugs was over 30 years ago. 852 00:44:43,566 --> 00:44:45,466 {\an7}-We really need to ramp up efforts 853 00:44:45,500 --> 00:44:48,566 {\an7}both within the academic world and the commercial world 854 00:44:48,600 --> 00:44:51,966 {\an8}to replenish our antibiotic arsenal. 855 00:44:52,000 --> 00:44:53,833 {\an1}-But finding new antibiotics 856 00:44:53,866 --> 00:44:57,833 {\an1}is not always cost-effective for drug companies. 857 00:44:57,866 --> 00:45:00,900 {\an1}-Discovering drugs is hard. -It's time-intensive. 858 00:45:00,933 --> 00:45:02,766 It's laborious. 859 00:45:02,800 --> 00:45:05,466 {\an1}-So if you're a drug company, I can make, you know, 860 00:45:05,500 --> 00:45:08,500 {\an1}an anticoagulant that someone's going to take every day 861 00:45:08,533 --> 00:45:11,400 {\an1}for the rest of their life, perhaps, 862 00:45:11,433 --> 00:45:18,133 {\an1}or I can develop an antibiotic that might be used for a week. 863 00:45:18,166 --> 00:45:20,700 {\an1}How do you get your money back? 864 00:45:20,733 --> 00:45:23,866 We can't rely on the free market economy 865 00:45:23,900 --> 00:45:26,333 to encourage antibiotic development. 866 00:45:26,366 --> 00:45:27,866 {\an1}So it has to be treated, in my opinion, 867 00:45:27,900 --> 00:45:33,033 {\an1}more like a public health problem, much like COVID-19. 868 00:45:35,000 --> 00:45:36,566 {\an1}-Jim designs drugs, 869 00:45:36,600 --> 00:45:40,933 {\an1}and as a biochemist, John test new antibiotics in the lab. 870 00:45:43,100 --> 00:45:45,900 {\an1}But to help them find new antibiotics faster 871 00:45:45,933 --> 00:45:47,866 and cheaper than ever before, 872 00:45:47,900 --> 00:45:49,533 they're working with a specialist 873 00:45:49,566 --> 00:45:53,266 {\an1}in artificial intelligence. 874 00:45:53,300 --> 00:45:56,600 {\an7}-I believe that we are just in the very beginning 875 00:45:56,633 --> 00:46:01,000 {\an7}of seeing the advantages of A.I. in drug discovery. 876 00:46:01,033 --> 00:46:03,233 {\an1}-Artificial intelligence has permeated 877 00:46:03,266 --> 00:46:05,466 {\an1}every aspect of our life. 878 00:46:05,500 --> 00:46:08,666 {\an1}It tells us what we might want to watch 879 00:46:08,700 --> 00:46:11,066 {\an1}and what we might want to buy, 880 00:46:11,100 --> 00:46:14,500 {\an1}and it helps self-driving cars not crash into each other, 881 00:46:14,533 --> 00:46:16,133 so it's just a natural progression 882 00:46:16,166 --> 00:46:17,866 {\an1}that A.I. was going to 883 00:46:17,900 --> 00:46:21,866 increasingly influence drug discovery 884 00:46:21,900 --> 00:46:25,100 {\an1}and health care in general. 885 00:46:25,133 --> 00:46:27,600 {\an1}-Regina's expertise in A.I. 886 00:46:27,633 --> 00:46:29,533 enabled the team to open the door 887 00:46:29,566 --> 00:46:33,733 {\an1}to a whole new way of discovering drugs. 888 00:46:33,766 --> 00:46:36,466 {\an1}-So the question is, can we design molecule 889 00:46:36,500 --> 00:46:40,400 {\an1}which would be hard for pathogen to adapt to? 890 00:46:40,433 --> 00:46:42,300 {\an1}And when we started it, we really didn't 891 00:46:42,333 --> 00:46:43,333 {\an1}even have a budget. 892 00:46:43,366 --> 00:46:45,166 {\an1}It was like, just try 893 00:46:45,200 --> 00:46:48,033 {\an1}and see how far you can push the boundaries. 894 00:46:48,066 --> 00:46:51,166 {\an1}-What we were able to do was train a computer model 895 00:46:51,200 --> 00:46:54,500 to learn features of molecular structures 896 00:46:54,533 --> 00:46:57,233 {\an1}that were associated with antibacterial activity. 897 00:46:59,733 --> 00:47:03,766 {\an1}-The computer was given 2,500 molecules, 898 00:47:03,800 --> 00:47:06,333 {\an1}and it began to learn which chemical structures 899 00:47:06,366 --> 00:47:09,066 were linked to antibacterial properties. 900 00:47:09,100 --> 00:47:11,366 {\an1}And then when the computer was given a molecule 901 00:47:11,400 --> 00:47:13,000 {\an1}it hadn't seen before, 902 00:47:13,033 --> 00:47:16,366 {\an1}it could check the chemical structure and accurately predict 903 00:47:16,400 --> 00:47:18,600 if it was likely to kill bacteria. 904 00:47:21,333 --> 00:47:24,533 {\an1}-We were able to scan hundreds of millions of molecules 905 00:47:24,566 --> 00:47:27,500 {\an1}in silico to identify the one 906 00:47:27,533 --> 00:47:29,566 {\an1}who was promising properties. 907 00:47:29,600 --> 00:47:31,533 {\an1}-Our algorithm ran predictions 908 00:47:31,566 --> 00:47:34,400 {\an1}on 107 million molecules 909 00:47:34,433 --> 00:47:36,700 {\an1}on three to four days. 910 00:47:36,733 --> 00:47:38,500 {\an1}To put that in perspective, 911 00:47:38,533 --> 00:47:41,400 {\an1}if I were to test those 107 million molecules 912 00:47:41,433 --> 00:47:43,733 {\an1}in the laboratory, I calculated it out. 913 00:47:43,766 --> 00:47:46,533 {\an1}That would have taken me something like 14 years 914 00:47:46,566 --> 00:47:50,233 {\an1}if I did it all day, every day. 915 00:47:50,266 --> 00:47:53,700 {\an1}-The computer model found about 120 molecules, 916 00:47:53,733 --> 00:47:58,266 {\an1}potential drugs, that showed promising antibiotic properties. 917 00:47:58,300 --> 00:48:01,733 {\an1}John Stokes then tested the short list, and within days, 918 00:48:01,766 --> 00:48:04,733 {\an1}the team had identified one particular molecule 919 00:48:04,766 --> 00:48:05,900 that could become 920 00:48:05,933 --> 00:48:09,533 first new class of antibiotics in decades. 921 00:48:13,066 --> 00:48:16,333 {\an1}-I first observed that this molecule was inhibiting 922 00:48:16,366 --> 00:48:19,400 {\an1}the growth of E. coli in a dish. 923 00:48:19,433 --> 00:48:21,100 {\an1}It had a structure that wasn't similar 924 00:48:21,133 --> 00:48:23,700 {\an1}to known antibiotics, really. 925 00:48:23,733 --> 00:48:25,333 Cool. 926 00:48:25,366 --> 00:48:27,133 {\an1}That wasn't exciting. 927 00:48:27,166 --> 00:48:29,333 Not yet. 928 00:48:29,366 --> 00:48:34,600 {\an1}-The molecule SU3327 was renamed halicin. 929 00:48:34,633 --> 00:48:37,866 {\an1}-We named halicin after HAL, the A.I.-based computer 930 00:48:37,900 --> 00:48:42,000 {\an1}in the movie "2001: A Space Odyssey." 931 00:48:42,033 --> 00:48:45,000 {\an1}-The next question was, well, does it work against 932 00:48:45,033 --> 00:48:49,800 {\an1}other pathogenic species that are problematic? 933 00:48:49,833 --> 00:48:51,633 {\an1}-John Stokes tested halicin 934 00:48:51,666 --> 00:48:55,700 on a number of antibiotic-resistant superbugs. 935 00:48:55,733 --> 00:48:58,100 {\an1}-John had reported to us the results, 936 00:48:58,133 --> 00:49:00,766 {\an1}and he was very excited about the results. 937 00:49:00,800 --> 00:49:03,400 {\an1}-halicin is one of the more potent antibiotics 938 00:49:03,433 --> 00:49:07,366 {\an1}discovered to date, and it has remarkable activity 939 00:49:07,400 --> 00:49:09,266 {\an1}against a wide range of pathogens, 940 00:49:09,300 --> 00:49:12,800 {\an1}including multi-drug-resistant, extensively drug-resistant, 941 00:49:12,833 --> 00:49:14,366 {\an1}and pan-resistant pathogens. 942 00:49:14,400 --> 00:49:16,300 {\an1}And so it opens up tremendous possibilities 943 00:49:16,333 --> 00:49:20,366 and expands our capabilities dramatically. 944 00:49:20,400 --> 00:49:23,400 {\an1}-I feel like the discovery of halicin 945 00:49:23,433 --> 00:49:28,166 {\an1}was perhaps a defining moment in showing that machine 946 00:49:28,200 --> 00:49:33,733 {\an1}learning has real promise in drug discovery, period. 947 00:49:33,766 --> 00:49:35,533 {\an1}-In the hunt for new drugs, 948 00:49:35,566 --> 00:49:39,966 {\an1}A.I. has potential far beyond just antibiotics. 949 00:49:40,000 --> 00:49:43,033 {\an1}-This technology can change life sciences. 950 00:49:43,066 --> 00:49:47,533 {\an1}-Human intelligence and machine intelligence, right? 951 00:49:47,566 --> 00:49:49,866 {\an1}-We are very hopeful that this platform 952 00:49:49,900 --> 00:49:52,366 can be extended to other infectious diseases, 953 00:49:52,400 --> 00:49:56,866 {\an1}including SARS-CoV-2 and other viral infections, 954 00:49:56,900 --> 00:49:59,533 {\an1}as well as to complex disease like cancer, 955 00:49:59,566 --> 00:50:02,200 {\an1}metabolic disorders, neurological conditions. 956 00:50:02,233 --> 00:50:03,600 {\an1}Over the coming decades, 957 00:50:03,633 --> 00:50:05,133 {\an1}the progress we're going to make against 958 00:50:05,166 --> 00:50:07,433 these diseases is going to be tremendous. 959 00:50:10,566 --> 00:50:12,400 {\an1}-This question, I think, that people need to ask, 960 00:50:12,433 --> 00:50:15,166 {\an1}which is, you know, if you open up your cabinet 961 00:50:15,200 --> 00:50:16,600 in the bathroom and there's some drug 962 00:50:16,633 --> 00:50:18,900 that you take that makes you healthier, 963 00:50:18,933 --> 00:50:21,666 that maybe even is keeping you alive, 964 00:50:21,700 --> 00:50:23,533 {\an1}how many people actually stop and say, 965 00:50:23,566 --> 00:50:24,833 {\an1}"Where did this come from?" 966 00:50:24,866 --> 00:50:28,600 {\an1}Right? What is the story of this magic bullet? 967 00:50:28,633 --> 00:50:29,933 {\an1}-The heroes in this story, 968 00:50:29,966 --> 00:50:32,466 {\an1}the key characters in this revolution, 969 00:50:32,500 --> 00:50:34,000 {\an1}most of us don't know their names 970 00:50:34,033 --> 00:50:35,266 {\an1}because they're not celebrated. 971 00:50:35,300 --> 00:50:38,033 {\an1}Walk around your city or your town 972 00:50:38,066 --> 00:50:41,633 {\an1}and the statues will be to politicians and to generals. 973 00:50:41,666 --> 00:50:45,166 They won't be to medical pioneers. 974 00:50:45,200 --> 00:50:50,333 {\an1}-But the history of how we ended up living longer lives 975 00:50:50,366 --> 00:50:51,933 {\an1}is so vitally important. 976 00:50:51,966 --> 00:50:54,300 {\an1}Took effectively 16 years for penicillin 977 00:50:54,333 --> 00:50:55,966 {\an1}to go from the initial discovery 978 00:50:56,000 --> 00:50:58,300 to a drug that was actually functioning. 979 00:50:58,333 --> 00:51:00,766 {\an1}It took about less than 10 years for the antivirals 980 00:51:00,800 --> 00:51:03,066 {\an1}to be developed for HIV. 981 00:51:03,100 --> 00:51:05,866 {\an1}Where will we be with antivirals for COVID-19? 982 00:51:05,900 --> 00:51:08,700 {\an1}We don't know yet, but I suspect it will be faster. 983 00:51:08,733 --> 00:51:10,733 But Big Pharma is much more interested 984 00:51:10,766 --> 00:51:12,666 in pursuing new cancer treatments 985 00:51:12,700 --> 00:51:14,266 that are just far more profitable. 986 00:51:14,300 --> 00:51:16,733 {\an1}I mean, it's a kind of market failure, right? 987 00:51:16,766 --> 00:51:18,533 {\an1}We have this urgent health problem, 988 00:51:18,566 --> 00:51:20,800 {\an1}but the private sector on its own 989 00:51:20,833 --> 00:51:22,866 is not going to solve the problem. 990 00:51:22,900 --> 00:51:25,400 {\an1}-One of the many differences between modern drug development 991 00:51:25,433 --> 00:51:27,400 and what happened with Fleming and penicillin 992 00:51:27,433 --> 00:51:29,666 {\an1}is there's no place for accident anymore. 993 00:51:29,700 --> 00:51:31,333 We're not reliant on the serendipity 994 00:51:31,366 --> 00:51:32,900 {\an1}or finding a petri dish 995 00:51:32,933 --> 00:51:35,166 {\an1}with this remarkable mold in it. 996 00:51:35,200 --> 00:51:36,200 {\an1}It's much more these days 997 00:51:36,233 --> 00:51:38,366 {\an1}a story of rational drug development 998 00:51:38,400 --> 00:51:41,966 {\an1}and also of the sharing of information globally, 999 00:51:42,000 --> 00:51:45,333 {\an1}instantly among medical teams. 1000 00:51:45,366 --> 00:51:48,433 {\an1}-And it also opens the door for this idea 1001 00:51:48,466 --> 00:51:50,133 {\an1}that medicine is now something 1002 00:51:50,166 --> 00:51:54,600 {\an1}that human beings are capable of creating at scale. 1003 00:51:54,633 --> 00:51:58,100 {\an1}-This is arguably the biggest story in human history -- 1004 00:51:58,133 --> 00:51:59,966 {\an1}how we doubled our life expectancy. 1005 00:52:06,900 --> 00:52:09,400 {\an7}-As the world grapples with another deadly pandemic, 1006 00:52:09,433 --> 00:52:12,966 {\an7}we reveal how data became one of the most powerful tools 1007 00:52:13,000 --> 00:52:16,300 {\an7}we have in the fight for extra life. 1008 00:52:16,333 --> 00:52:19,400 {\an7}-Cholera was finally driven from the city of London, 1009 00:52:19,433 --> 00:52:23,400 {\an7}not by a new medicine, but by data. 1010 00:52:23,433 --> 00:52:25,600 {\an7}-This person's been ill for nine and a half days 1011 00:52:25,633 --> 00:52:27,466 {\an7}without knowing it, spreading the virus, 1012 00:52:27,500 --> 00:52:30,100 {\an7}when he could have been caught with a smart watch. 1013 00:52:30,133 --> 00:52:32,933 {\an7}-This is arguably the biggest story in human history -- 1014 00:52:32,966 --> 00:52:34,700 {\an8}how we doubled our life expectancy. 1015 00:52:36,866 --> 00:52:46,333 {\an8}♪ 1016 00:52:46,366 --> 00:52:55,900 {\an8}♪ 1017 00:52:55,933 --> 00:53:05,533 {\an8}♪