1 00:00:14,920 --> 00:00:19,040 Speaker 1: Welcome back, everybody. My next guest is a Harvard medical professor, 2 00:00:19,120 --> 00:00:22,400 Speaker 1: a biologist, a geneticist, a chemist, and an engineer who's 3 00:00:22,440 --> 00:00:25,840 Speaker 1: worked with DNA is transforming our biology and our future. 4 00:00:26,079 --> 00:00:31,920 Speaker 1: Please welcome George Church. When it comes to geneting researchers, 5 00:00:32,280 --> 00:00:35,199 Speaker 1: George Church is the closest person in the field to 6 00:00:35,280 --> 00:00:37,360 Speaker 1: an actual, real world celebrity. 7 00:00:37,920 --> 00:00:43,839 Speaker 2: George Church is a true gentleman scientist wrapped in the 8 00:00:43,840 --> 00:00:47,440 Speaker 2: cloak of being a madman scientist. He has a bushy beard. 9 00:00:47,720 --> 00:00:51,480 Speaker 2: He wants to bring the wooly mammoth back from extinction. 10 00:00:52,200 --> 00:00:55,800 Speaker 2: He talks in this very flamboyant way. He's just as 11 00:00:55,840 --> 00:00:58,560 Speaker 2: comfortable at the lab bench as he is on the 12 00:00:58,640 --> 00:01:00,560 Speaker 2: Colbert TV Show. 13 00:01:00,800 --> 00:01:04,160 Speaker 1: For some he's known as the Godfather of synthetic biology 14 00:01:04,560 --> 00:01:07,720 Speaker 1: for his foundational work on gene editing technology, but for 15 00:01:07,760 --> 00:01:10,199 Speaker 1: most people today, he's best known as the co founder 16 00:01:10,240 --> 00:01:13,960 Speaker 1: of Colossal Biosciences, a company that's embarked on the ambitious 17 00:01:13,959 --> 00:01:18,360 Speaker 1: mission of de extincting species, most recently the dire Wolf. 18 00:01:18,840 --> 00:01:20,759 Speaker 1: And so when there's anything exciting happening in the field 19 00:01:20,800 --> 00:01:23,360 Speaker 1: of gene editing, you can bet George Church has been 20 00:01:23,360 --> 00:01:26,399 Speaker 1: involved with it in some way. Isaacson tells me that 21 00:01:26,440 --> 00:01:28,880 Speaker 1: the development of Crisper was no exception. He was one 22 00:01:28,880 --> 00:01:31,360 Speaker 1: of the researchers working on it and a close adviser 23 00:01:31,440 --> 00:01:32,759 Speaker 1: to Jennifer Dowdner at the time. 24 00:01:33,240 --> 00:01:37,600 Speaker 2: He's become this mentor to a lot of people in 25 00:01:37,640 --> 00:01:41,600 Speaker 2: the biotech world, including Jennifer Dowdner, and I think he 26 00:01:41,800 --> 00:01:46,080 Speaker 2: started maybe three dozen companies. So he's not just a 27 00:01:46,120 --> 00:01:48,400 Speaker 2: great researcher. He applies it. 28 00:01:48,800 --> 00:01:51,760 Speaker 1: He was twenty twelve and now that Dowdner and Charpentier 29 00:01:51,880 --> 00:01:54,720 Speaker 1: had successfully published their paper on how the Crisper CAST 30 00:01:54,840 --> 00:01:57,800 Speaker 1: nine mechanism worked, the next challenge for them was to 31 00:01:57,800 --> 00:02:00,920 Speaker 1: translate their findings from the test tube to the human cell. 32 00:02:01,600 --> 00:02:04,240 Speaker 2: Well the end of the piece, they write they hint 33 00:02:04,440 --> 00:02:08,200 Speaker 2: that this could be used as a tool for editing genes. 34 00:02:08,800 --> 00:02:11,480 Speaker 2: But what they've done is only shown that it works 35 00:02:11,600 --> 00:02:15,400 Speaker 2: in a test tube. They haven't shown it can work 36 00:02:15,480 --> 00:02:19,120 Speaker 2: in a human cell. And so for the next six 37 00:02:19,160 --> 00:02:23,200 Speaker 2: to seven months you have a great race around the 38 00:02:23,240 --> 00:02:29,320 Speaker 2: world of scientists trying to show how this new combination 39 00:02:30,040 --> 00:02:35,840 Speaker 2: of RNA and enzyme a cast enzyme, a little manufactured 40 00:02:35,880 --> 00:02:39,800 Speaker 2: thing can edit human genes. 41 00:02:39,760 --> 00:02:41,920 Speaker 1: And within this global race to figure out how crisper 42 00:02:41,919 --> 00:02:45,920 Speaker 1: could edit ourselves, one competitor came to the forefront, a 43 00:02:45,960 --> 00:02:49,240 Speaker 1: competitor who had also been mentored by George Church, a 44 00:02:49,240 --> 00:02:51,399 Speaker 1: Harvard scientist named Fungjong. 45 00:02:51,960 --> 00:02:56,560 Speaker 2: Fung Jang is a great American story. His mother came 46 00:02:56,639 --> 00:03:01,120 Speaker 2: over from China on some fellowship to Iowa and just 47 00:03:01,240 --> 00:03:04,520 Speaker 2: saw how the labs and the universities and the schools 48 00:03:04,560 --> 00:03:08,480 Speaker 2: and the high schools in Iowa were so good that 49 00:03:09,000 --> 00:03:13,480 Speaker 2: she ends up bringing her young kid, Fung Jiang, to America, 50 00:03:14,120 --> 00:03:17,080 Speaker 2: and he becomes sort of a star in high school 51 00:03:17,440 --> 00:03:21,359 Speaker 2: in Iowa and eventually goes on studies with George Church 52 00:03:21,400 --> 00:03:25,840 Speaker 2: at Harvard and becomes a great biochemist and microbiologist. 53 00:03:26,400 --> 00:03:29,280 Speaker 1: Fun Jong was working at the Broad Institute, a collaboration 54 00:03:29,400 --> 00:03:33,000 Speaker 1: between Harvard and MIT, when the race to apply crisper 55 00:03:33,000 --> 00:03:36,080 Speaker 1: and human cells was heating up, and so a triangle 56 00:03:36,080 --> 00:03:40,600 Speaker 1: of competition was born. George Church, Jennifer DOWDNA, and Fung Jong. 57 00:03:41,080 --> 00:03:44,000 Speaker 1: They were all racing towards the same goal, and Isaacson 58 00:03:44,040 --> 00:03:47,080 Speaker 1: says that Church, faced with competing with two of his protegees, 59 00:03:47,600 --> 00:03:49,040 Speaker 1: found himself in a tricky situation. 60 00:03:50,400 --> 00:03:54,160 Speaker 2: It's complicated because he's very close to Jennifer Dowdner had 61 00:03:54,200 --> 00:03:57,840 Speaker 2: been an advisor and mentor, and he was close to 62 00:03:57,880 --> 00:04:02,200 Speaker 2: Fong Jiang who had worked in his lab, and so 63 00:04:02,440 --> 00:04:06,120 Speaker 2: he's conflicted a bit. He ends up wanting to help Jennifer. 64 00:04:07,560 --> 00:04:10,720 Speaker 2: Fung Jang is working behind his back, doesn't tell George 65 00:04:10,800 --> 00:04:14,640 Speaker 2: Church that he's trying to do this, and all three 66 00:04:14,680 --> 00:04:18,160 Speaker 2: of them at about the same time sort of circle 67 00:04:18,279 --> 00:04:20,800 Speaker 2: in on how do we prove it can work in 68 00:04:20,800 --> 00:04:21,520 Speaker 2: a human cell? 69 00:04:22,920 --> 00:04:25,240 Speaker 1: What came next would feel one of the most disputed 70 00:04:25,320 --> 00:04:29,960 Speaker 1: questions around scientific discovery in the past decades. Who owns Crisper. 71 00:04:31,320 --> 00:04:33,800 Speaker 1: I'm Evan Ratliffe and this is on Crisper The Story 72 00:04:33,839 --> 00:04:45,440 Speaker 1: of Jennifer Dowdner Episode three, Patent Moore's So you have 73 00:04:45,560 --> 00:04:48,039 Speaker 1: these three labs who are chasing this question will this 74 00:04:48,160 --> 00:04:51,640 Speaker 1: work in a human cell? But again you have this 75 00:04:51,760 --> 00:04:56,880 Speaker 1: kind of competition cooperation because Fong Jiang has previously reached 76 00:04:56,920 --> 00:05:00,320 Speaker 1: out to Dowdna, been in contact with her because he 77 00:05:00,920 --> 00:05:02,719 Speaker 1: wants to understand her work. 78 00:05:03,240 --> 00:05:06,600 Speaker 2: Phung Jong originally sends an email to Jennifer down to say, 79 00:05:06,640 --> 00:05:08,680 Speaker 2: I've read your piece. I want to figure out how 80 00:05:08,720 --> 00:05:13,000 Speaker 2: it's going to work, but they soon realize the stakes 81 00:05:13,000 --> 00:05:17,680 Speaker 2: are too high, and they all become more secretive and 82 00:05:17,800 --> 00:05:23,560 Speaker 2: more competitive. The question is, is that a bad thing. Suppose 83 00:05:23,640 --> 00:05:27,680 Speaker 2: there was no real competition thereby worked together, Well, that 84 00:05:27,760 --> 00:05:32,480 Speaker 2: would actually be friendlier and nicer. But maybe we wouldn't 85 00:05:32,480 --> 00:05:36,400 Speaker 2: have pushed science so far so fast if there weren't 86 00:05:36,440 --> 00:05:37,960 Speaker 2: an award forgetting their. 87 00:05:37,800 --> 00:05:41,080 Speaker 1: First Isaacson tells me that if Dowdner and fun Jong 88 00:05:41,160 --> 00:05:44,200 Speaker 1: were racing on a track, Jong would have started in 89 00:05:44,200 --> 00:05:47,520 Speaker 1: the pole position. Even if Dowda might not have realized. 90 00:05:47,200 --> 00:05:51,080 Speaker 2: It, she started off at a disadvantage. She had never 91 00:05:51,320 --> 00:05:55,640 Speaker 2: worked in living cells before, she had only done it 92 00:05:55,680 --> 00:05:58,719 Speaker 2: in a test to now you could have an argument, 93 00:05:58,839 --> 00:06:02,680 Speaker 2: as they did, about what is the more important way 94 00:06:02,839 --> 00:06:06,240 Speaker 2: to show something works. Is it best to be able 95 00:06:06,279 --> 00:06:10,400 Speaker 2: to show it in a living cell in the real world. Well, 96 00:06:10,480 --> 00:06:14,000 Speaker 2: that sounds logical, but actually to be able to show 97 00:06:14,040 --> 00:06:17,120 Speaker 2: it in a working in a test tube means that 98 00:06:17,200 --> 00:06:21,800 Speaker 2: you know the exact components. You know exactly which ingredients 99 00:06:21,839 --> 00:06:24,680 Speaker 2: are necessary or not which If you're doing it in 100 00:06:24,680 --> 00:06:28,120 Speaker 2: the human cell, there's also a messy other things happening. 101 00:06:28,640 --> 00:06:31,359 Speaker 2: So a Jennifer would say, being able to do with 102 00:06:31,400 --> 00:06:36,279 Speaker 2: the biochemistry in a test tube, that's actually the big deal, 103 00:06:36,839 --> 00:06:41,119 Speaker 2: and fong Jiang and others might say, no, no, test 104 00:06:41,160 --> 00:06:45,080 Speaker 2: tubes are easy. Doing it in a living cell is 105 00:06:45,120 --> 00:06:45,919 Speaker 2: the big leap. 106 00:06:46,600 --> 00:06:48,799 Speaker 1: But they both knew that it would be a huge 107 00:06:48,839 --> 00:06:51,479 Speaker 1: discovery whoever got there first in terms of making it 108 00:06:51,560 --> 00:06:53,200 Speaker 1: work in the human cell. 109 00:06:53,600 --> 00:06:57,040 Speaker 2: They both felt it would be a big discovery to 110 00:06:57,120 --> 00:06:59,119 Speaker 2: be able to do it first in the human cell. 111 00:06:59,600 --> 00:07:03,559 Speaker 2: Butjonniffer would argue, and did argue, that's not that big 112 00:07:03,600 --> 00:07:08,159 Speaker 2: of a leap once you know the ingredients that can 113 00:07:08,320 --> 00:07:11,680 Speaker 2: work and attest to. We've always had these things and 114 00:07:11,720 --> 00:07:16,400 Speaker 2: it's always been pretty ordinary in standard to then apply 115 00:07:16,520 --> 00:07:19,200 Speaker 2: them in the human cell. So she would argue the 116 00:07:19,240 --> 00:07:23,160 Speaker 2: big leap is figuring out the exact ingredients and that 117 00:07:23,400 --> 00:07:26,560 Speaker 2: every other gene editing tool. Once she had done that, 118 00:07:26,960 --> 00:07:28,960 Speaker 2: it wasn't that big of a leap to do it 119 00:07:29,040 --> 00:07:32,920 Speaker 2: in a cell. Now I think she's minimizing the importance 120 00:07:32,960 --> 00:07:36,400 Speaker 2: of doing it in a living cell. But that's why 121 00:07:36,480 --> 00:07:38,360 Speaker 2: there was a big dispute afterwards. 122 00:07:38,720 --> 00:07:42,080 Speaker 1: But regardless of their starting positions, both Downa and Jung 123 00:07:42,160 --> 00:07:44,880 Speaker 1: knew that what mattered was who was first of the 124 00:07:44,880 --> 00:07:46,720 Speaker 1: finish line. 125 00:07:47,040 --> 00:07:50,640 Speaker 2: The huge race is to actually be published first, because 126 00:07:50,680 --> 00:07:54,120 Speaker 2: that's the way you put a stamp on. I got 127 00:07:54,120 --> 00:07:59,240 Speaker 2: there first, and Jennifer knew that she was running behind that. 128 00:07:59,640 --> 00:08:03,040 Speaker 2: Jennifer for Dowbtne learns in a phone conversation from George 129 00:08:03,160 --> 00:08:06,480 Speaker 2: Church that not only is George Church trying to make 130 00:08:06,520 --> 00:08:09,480 Speaker 2: it work in human cells, which is logical, he had 131 00:08:09,520 --> 00:08:12,680 Speaker 2: done that his whole career, he had made other types 132 00:08:12,720 --> 00:08:16,200 Speaker 2: of technology work in human cells. But George Church also 133 00:08:16,240 --> 00:08:19,800 Speaker 2: says Pong Jang is doing a tiffic, so Jennifer tries 134 00:08:19,880 --> 00:08:23,760 Speaker 2: to speed up. She finds a publication that's online only 135 00:08:24,440 --> 00:08:29,160 Speaker 2: and that will rush it into publication, but she's still 136 00:08:29,280 --> 00:08:32,839 Speaker 2: She and Martin Yunick have to finish all the experiments 137 00:08:32,880 --> 00:08:35,640 Speaker 2: and show that it can be made to work, and 138 00:08:35,720 --> 00:08:39,600 Speaker 2: so over Christmas she's doing it, and then finally at 139 00:08:39,640 --> 00:08:43,480 Speaker 2: the very beginning of January twenty thirteen, when she's ready 140 00:08:43,480 --> 00:08:48,160 Speaker 2: to send it in Boom Science magazine, the grandest of all. 141 00:08:48,240 --> 00:08:52,560 Speaker 2: The magazine goes online and it has both George Church's 142 00:08:52,600 --> 00:08:57,160 Speaker 2: paper and Fong Jiang's paper showing how it works in humans. 143 00:09:00,240 --> 00:09:05,320 Speaker 2: Before Fong Jang and George church simultaneously a publishing Fong 144 00:09:05,400 --> 00:09:09,680 Speaker 2: Jang casually sends Jennifer an email saying, hey, my papers 145 00:09:09,840 --> 00:09:14,439 Speaker 2: about to be published. So her heart sinks. She knows 146 00:09:15,240 --> 00:09:17,800 Speaker 2: she's going to lose the race by about one or 147 00:09:17,840 --> 00:09:20,800 Speaker 2: two weeks because that's when her paper will be published. 148 00:09:21,240 --> 00:09:24,880 Speaker 2: And that may seem pretty you know, close in time, 149 00:09:25,000 --> 00:09:28,840 Speaker 2: but close doesn't count when it comes to patent surprises. 150 00:09:29,320 --> 00:09:32,160 Speaker 1: Yeah, just the idea that it doesn't matter when you 151 00:09:32,240 --> 00:09:36,440 Speaker 1: knew it. It matters when that paper appears somewhere in 152 00:09:36,480 --> 00:09:36,880 Speaker 1: the world. 153 00:09:37,760 --> 00:09:41,520 Speaker 2: One of the complexities is the winner of the race 154 00:09:41,600 --> 00:09:45,320 Speaker 2: is who published it as a paper first. But the 155 00:09:45,400 --> 00:09:50,080 Speaker 2: winner of a patent is a slightly more complicated task, 156 00:09:50,720 --> 00:09:54,200 Speaker 2: which is, even if you haven't published it, if you 157 00:09:54,320 --> 00:09:57,720 Speaker 2: can show you've made a certain discovery at a certain 158 00:09:57,800 --> 00:10:02,320 Speaker 2: point and you eventually get it on, it can count 159 00:10:02,880 --> 00:10:07,520 Speaker 2: in what's called a priority dispute. And so even now, 160 00:10:07,720 --> 00:10:11,760 Speaker 2: I mean we're ten years later, there's still a patent 161 00:10:11,800 --> 00:10:15,040 Speaker 2: war going on, and they're still showing pages in the 162 00:10:15,120 --> 00:10:18,240 Speaker 2: notebook where they show when they made each experiment. 163 00:10:18,880 --> 00:10:22,800 Speaker 1: The notebook, a simple analog object would become a critical 164 00:10:22,800 --> 00:10:26,320 Speaker 1: piece of evidence in the timeline of Crisper's invention. Isaacson 165 00:10:26,360 --> 00:10:28,480 Speaker 1: tells me that Jennifer Downon knew that she could prove 166 00:10:28,520 --> 00:10:31,400 Speaker 1: that she had discovered the mechanism first just by looking 167 00:10:31,400 --> 00:10:33,680 Speaker 1: back at her notes each day. 168 00:10:34,040 --> 00:10:38,000 Speaker 2: A great scientist who makes any discovery that day will 169 00:10:38,040 --> 00:10:40,720 Speaker 2: put it in a lab notebook and get two people 170 00:10:40,920 --> 00:10:44,240 Speaker 2: to witness it on the bottom of the page. And 171 00:10:44,360 --> 00:10:48,640 Speaker 2: early on with the first Crisper discoveries, Jennifer Dowdnan did 172 00:10:49,080 --> 00:10:53,440 Speaker 2: her husband, who's also a BIOCHEMISTY, that's important enough. You 173 00:10:53,520 --> 00:10:55,520 Speaker 2: got to go back to the lab, put it in 174 00:10:55,600 --> 00:10:59,200 Speaker 2: the notebook, and she got two of her graduate students 175 00:10:59,520 --> 00:11:04,439 Speaker 2: to witness set. So this is how important this claims 176 00:11:04,480 --> 00:11:05,880 Speaker 2: of priority can be. 177 00:11:06,559 --> 00:11:09,640 Speaker 1: Now you've mentioned patents a couple of times, and I 178 00:11:09,679 --> 00:11:13,199 Speaker 1: feel like there was, of course a time when if 179 00:11:13,200 --> 00:11:15,679 Speaker 1: someone made this kind of breakthrough in a lab at university, 180 00:11:15,920 --> 00:11:20,559 Speaker 1: it wouldn't be patented necessarily. So what led to these 181 00:11:20,559 --> 00:11:25,760 Speaker 1: different university associated labs seeking patents on this type of discovery. 182 00:11:26,520 --> 00:11:32,640 Speaker 2: In the early nineteen seventies, Herbert Bowyer and others working 183 00:11:32,679 --> 00:11:37,040 Speaker 2: at Stanford and universities in that area had come up 184 00:11:37,320 --> 00:11:44,719 Speaker 2: with genetic engineering advances how to do recombinant DNA. It 185 00:11:44,760 --> 00:11:49,400 Speaker 2: was called to make new types of organisms. And at 186 00:11:49,440 --> 00:11:53,960 Speaker 2: one point the Stanford lawyers helped some of them get 187 00:11:53,960 --> 00:11:57,679 Speaker 2: a patent, and the other scientists thought, hey, that's not 188 00:11:57,720 --> 00:12:01,160 Speaker 2: what we're doing here. We're doing research for the basic good. 189 00:12:01,880 --> 00:12:05,600 Speaker 2: But that patent ends up becoming the formation of this 190 00:12:05,960 --> 00:12:11,679 Speaker 2: multi billion dollar company, Genentech. So around then patents become 191 00:12:12,080 --> 00:12:18,920 Speaker 2: more important. America has a great system of allowing people 192 00:12:19,000 --> 00:12:23,720 Speaker 2: to patent the type of research they did at universities, 193 00:12:24,200 --> 00:12:28,400 Speaker 2: even if the government helped fund that research. And it 194 00:12:28,440 --> 00:12:32,240 Speaker 2: was two senators, Bob Dole and Birch Buy came up 195 00:12:32,240 --> 00:12:35,280 Speaker 2: with an act that said, how do we allocate it 196 00:12:35,440 --> 00:12:39,439 Speaker 2: if the federal government pays for research at the university. 197 00:12:40,160 --> 00:12:44,000 Speaker 2: And it's a slightly complicated formula, but the professor gets 198 00:12:44,000 --> 00:12:48,040 Speaker 2: a stake, the university gets a stake, the government has 199 00:12:48,080 --> 00:12:52,840 Speaker 2: a right to use the patented material. And it becomes 200 00:12:52,880 --> 00:12:59,959 Speaker 2: a great engine for commercializing basic science. And some people, 201 00:13:00,200 --> 00:13:03,560 Speaker 2: especially in the old days at Harvard or even in 202 00:13:03,600 --> 00:13:07,480 Speaker 2: the early seventies, soelth that's not good. You shouldn't be 203 00:13:07,559 --> 00:13:11,760 Speaker 2: trying to own this intellectual property. By the nineteen seventies 204 00:13:11,760 --> 00:13:16,920 Speaker 2: it was clear, we wanted research labs and research professors 205 00:13:17,280 --> 00:13:20,800 Speaker 2: to be able to make a buck if they made discoveries. 206 00:13:20,559 --> 00:13:23,320 Speaker 1: In order to sort of drive that same competitive spirit. 207 00:13:24,200 --> 00:13:27,120 Speaker 2: If you look around the world at where the greatest 208 00:13:27,120 --> 00:13:31,439 Speaker 2: advance has come in biotech and genetic engineering and the Internet, 209 00:13:32,240 --> 00:13:35,960 Speaker 2: in searches like Google, which were done at a Stanford 210 00:13:36,040 --> 00:13:39,800 Speaker 2: university under a government grant, it tends to happen in 211 00:13:39,840 --> 00:13:45,760 Speaker 2: the US because you're able to get rewarded if you 212 00:13:45,880 --> 00:13:50,600 Speaker 2: make discoveries, but it also funds them. It costs a 213 00:13:50,720 --> 00:13:54,160 Speaker 2: lot of money to build that lab at Berkeley, with 214 00:13:54,320 --> 00:13:56,640 Speaker 2: all of the not just the benches, but the hoods 215 00:13:56,679 --> 00:13:59,439 Speaker 2: and the ventilation and the test tubes and the pipeds 216 00:13:59,520 --> 00:14:03,360 Speaker 2: and the the graduate students being paid to do things. 217 00:14:04,080 --> 00:14:05,960 Speaker 2: That's a huge investment. 218 00:14:07,080 --> 00:14:16,560 Speaker 1: We'll be right back, coming back to our trio of 219 00:14:16,559 --> 00:14:21,240 Speaker 1: scientific racers, DAWNA, Young, and Church. They would all publish 220 00:14:21,240 --> 00:14:24,880 Speaker 1: their papers close together in twenty thirteen detailing how crisper 221 00:14:24,960 --> 00:14:27,800 Speaker 1: could work in human cells, and while the patent question 222 00:14:27,880 --> 00:14:30,240 Speaker 1: was still up in the air, Isaacson says, they began 223 00:14:30,280 --> 00:14:33,240 Speaker 1: to explore the possibility of linking arms and creating a 224 00:14:33,320 --> 00:14:35,680 Speaker 1: joint company to share the ownership. 225 00:14:35,960 --> 00:14:39,400 Speaker 2: After they all figure out how to make it work 226 00:14:39,400 --> 00:14:42,280 Speaker 2: in a human cell in this great race, and in 227 00:14:42,400 --> 00:14:47,640 Speaker 2: January twenty thirteen each published their papers. Initially they start 228 00:14:47,720 --> 00:14:52,200 Speaker 2: to work together, with George Church being the Ben Franklin 229 00:14:52,240 --> 00:14:55,960 Speaker 2: type trying to bring everybody together and starting a company 230 00:14:56,560 --> 00:14:59,440 Speaker 2: in which all of their intellectual property, any patents they 231 00:14:59,480 --> 00:15:02,160 Speaker 2: get in anything in the future, will all be part 232 00:15:02,200 --> 00:15:06,880 Speaker 2: of one consortium and they'll be able to commercialize it 233 00:15:06,960 --> 00:15:11,280 Speaker 2: and make it work. And the venture capitalists in Boston 234 00:15:11,360 --> 00:15:15,720 Speaker 2: in particular, are investing in a big company that's going 235 00:15:15,800 --> 00:15:18,760 Speaker 2: to do it. And yet there was a lot of 236 00:15:18,920 --> 00:15:23,240 Speaker 2: bad feelings, and I think in particular in the book, 237 00:15:23,360 --> 00:15:28,400 Speaker 2: there's this Jennifer describing that she thought fong Jiang was 238 00:15:28,440 --> 00:15:32,680 Speaker 2: working with the venture capitalists behind her back, and it 239 00:15:32,720 --> 00:15:36,880 Speaker 2: turns out he had filed for an expedited patent application 240 00:15:37,000 --> 00:15:41,720 Speaker 2: without telling her and the group, and she just feels 241 00:15:42,360 --> 00:15:45,800 Speaker 2: the guys are ganging up on me, and I don't 242 00:15:45,800 --> 00:15:50,280 Speaker 2: want any part of this, and she pulls out. And 243 00:15:50,320 --> 00:15:53,000 Speaker 2: then she thought, well, maybe I'll do it with Emmanuel Sharpentay. 244 00:15:53,480 --> 00:15:57,600 Speaker 2: But Emmanuel Sharpentay, she's off in her own world. She 245 00:15:57,760 --> 00:16:01,680 Speaker 2: wanted her own thing. I think eventually they're going to 246 00:16:01,760 --> 00:16:06,760 Speaker 2: all have to cross license the patents. But it almost 247 00:16:06,840 --> 00:16:10,680 Speaker 2: worked at the beginning to have one consortium. But now 248 00:16:11,080 --> 00:16:15,000 Speaker 2: if you want to make a treatment for sickle cell 249 00:16:15,040 --> 00:16:19,080 Speaker 2: anemia for other you know, for type of blindness, and 250 00:16:19,120 --> 00:16:23,080 Speaker 2: you're using crisper, sometimes you got to figure out which 251 00:16:23,200 --> 00:16:25,840 Speaker 2: of these patents do I have to license them all? 252 00:16:26,320 --> 00:16:29,120 Speaker 2: The field would be better off if they could settle 253 00:16:29,160 --> 00:16:30,080 Speaker 2: their patent dispute. 254 00:16:30,640 --> 00:16:33,360 Speaker 1: And you, as you're reporting the book, you're you are 255 00:16:33,560 --> 00:16:36,800 Speaker 1: moving as we discussed, you're moving across talking to all 256 00:16:36,840 --> 00:16:39,520 Speaker 1: the players involved. Where did you land in terms of 257 00:16:40,120 --> 00:16:44,600 Speaker 1: pong Jiang's actions pursuing the expedited patent, for example, being 258 00:16:45,520 --> 00:16:50,720 Speaker 1: machiavellian versus having, you know, purer motives around trying to 259 00:16:50,800 --> 00:16:52,280 Speaker 1: accelerate the discovery. 260 00:16:52,880 --> 00:16:55,960 Speaker 2: I think Pong Jang is a decent, good person and 261 00:16:56,040 --> 00:17:00,720 Speaker 2: a great scientist. And what he was doing was in 262 00:17:00,840 --> 00:17:06,359 Speaker 2: the realm of regular ethical conduct, which is trying to 263 00:17:06,359 --> 00:17:10,040 Speaker 2: get the patent first, rushing the patent application, and many 264 00:17:10,080 --> 00:17:14,160 Speaker 2: other things. And what he also did was keeping it secret. 265 00:17:15,480 --> 00:17:20,840 Speaker 2: Well that's not against the ethics rules. But as George 266 00:17:20,920 --> 00:17:25,080 Speaker 2: Church said to me, yes, what he did was in 267 00:17:25,119 --> 00:17:28,800 Speaker 2: the bounds of all the rules of ethics. But it's 268 00:17:28,880 --> 00:17:31,960 Speaker 2: not the way I would have had him do it 269 00:17:32,080 --> 00:17:34,840 Speaker 2: if he had still been part of my lab. That's 270 00:17:34,920 --> 00:17:37,960 Speaker 2: not the way we work. There's a system of honor 271 00:17:38,240 --> 00:17:42,240 Speaker 2: that goes beyond the ethics of are you supposed to 272 00:17:42,320 --> 00:17:45,920 Speaker 2: tell the other side? Or how open do you have 273 00:17:46,040 --> 00:17:51,480 Speaker 2: to be? I don't think Fong Xiang is a manipulative 274 00:17:51,720 --> 00:18:00,359 Speaker 2: or deceitful person, but he did decide toss to his 275 00:18:00,359 --> 00:18:04,159 Speaker 2: own course a little bit secretively, and that rubbed George 276 00:18:04,240 --> 00:18:05,560 Speaker 2: Church the wrong way. 277 00:18:06,080 --> 00:18:08,680 Speaker 1: And is part of it. The way that the incentives 278 00:18:09,200 --> 00:18:11,840 Speaker 1: change when you move from you know, when you're talking 279 00:18:11,840 --> 00:18:15,400 Speaker 1: about trying to understand bacteria in a salt pool somewhere, 280 00:18:15,840 --> 00:18:19,960 Speaker 1: there's discovery incentive and there's curiosity that's driving you. But 281 00:18:20,040 --> 00:18:23,720 Speaker 1: when you reach this point, you have possible financial incentives 282 00:18:23,920 --> 00:18:26,480 Speaker 1: that come into play. These are businesses that are being started. 283 00:18:26,760 --> 00:18:29,520 Speaker 1: Did you feel like that played a role in how 284 00:18:29,600 --> 00:18:31,640 Speaker 1: people responded to the situation. 285 00:18:33,240 --> 00:18:35,560 Speaker 2: One of the things that happened at one of these 286 00:18:35,680 --> 00:18:40,040 Speaker 2: breakfasts in Cambridge or meetings where they're all trying to 287 00:18:40,080 --> 00:18:43,240 Speaker 2: figure out how to pool together their patents and maybe 288 00:18:43,720 --> 00:18:48,760 Speaker 2: have one big company is. Jennifer asked George Church, how 289 00:18:48,800 --> 00:18:51,280 Speaker 2: big of a deal do you think this is? This 290 00:18:52,320 --> 00:18:58,320 Speaker 2: editing genes using Crisper pet and he basically says, grace yourself. 291 00:18:58,920 --> 00:19:01,760 Speaker 2: This is one of the biggest things ever to come 292 00:19:01,800 --> 00:19:05,439 Speaker 2: down the pike. So when the stakes get to be 293 00:19:05,640 --> 00:19:09,120 Speaker 2: so big and you realize this may be the biggest 294 00:19:09,160 --> 00:19:15,199 Speaker 2: discovery of the decade and it may have huge financial implications, 295 00:19:16,160 --> 00:19:19,160 Speaker 2: and that's a little bit different than trying to share 296 00:19:19,280 --> 00:19:24,920 Speaker 2: research on exactly how the sequences of Crisper might work 297 00:19:24,960 --> 00:19:26,120 Speaker 2: in different bacteria. 298 00:19:26,960 --> 00:19:30,119 Speaker 1: So let's try to help people understand why it is 299 00:19:30,160 --> 00:19:34,280 Speaker 1: such a world changing, potentially world changing development because people 300 00:19:34,320 --> 00:19:37,600 Speaker 1: may know, well, we could sort of edit genes before this, 301 00:19:37,800 --> 00:19:40,600 Speaker 1: and they've heard of gene editing, So what is the 302 00:19:40,680 --> 00:19:44,960 Speaker 1: fundamental breakthrough when it comes to human cells and gene 303 00:19:45,040 --> 00:19:47,520 Speaker 1: editing that Crisper allows that we couldn't do before. 304 00:19:48,600 --> 00:19:51,240 Speaker 2: Before when you had to edit, you could do something 305 00:19:51,480 --> 00:19:57,200 Speaker 2: very tailored and complicated, but it wasn't like programming a microchip, 306 00:19:57,400 --> 00:20:00,399 Speaker 2: which we can, you know, do in forty second. If 307 00:20:00,400 --> 00:20:04,399 Speaker 2: we want to fiddle with a program with Crisper, you 308 00:20:04,600 --> 00:20:10,520 Speaker 2: can instantly program it to cut wherever you want. In 309 00:20:10,560 --> 00:20:13,560 Speaker 2: the gene and then if you decide, well there's some 310 00:20:13,640 --> 00:20:15,600 Speaker 2: other place you went up, you're just tap tap, tap 311 00:20:15,880 --> 00:20:18,120 Speaker 2: and you get a new one. So it's very easy, 312 00:20:18,600 --> 00:20:23,760 Speaker 2: and with the combined single RNA guide we talked about, 313 00:20:24,280 --> 00:20:27,160 Speaker 2: it becomes pretty easy to get it into the cell. 314 00:20:27,720 --> 00:20:33,320 Speaker 2: So this is the difference between being a monk doing 315 00:20:33,359 --> 00:20:37,480 Speaker 2: a scribe work on a great manuscript and being able 316 00:20:37,560 --> 00:20:41,320 Speaker 2: to edit it with a quill pen and having a 317 00:20:41,320 --> 00:20:45,359 Speaker 2: amazing cut and paste computer programming type thing where you 318 00:20:45,400 --> 00:20:49,760 Speaker 2: can cut and paste and change. So Crisper at its 319 00:20:49,800 --> 00:20:54,560 Speaker 2: foundation using Crisper cast nine, the enzyme and the tool 320 00:20:54,880 --> 00:20:58,959 Speaker 2: becomes a foundation for even more tools that will allow 321 00:20:59,119 --> 00:21:04,480 Speaker 2: us to rewrite our genetic code. 322 00:21:04,640 --> 00:21:07,200 Speaker 1: At this point in the story, the wider scientific community 323 00:21:07,200 --> 00:21:09,680 Speaker 1: in the public are becoming aware of the importance of Crisper. 324 00:21:10,119 --> 00:21:12,960 Speaker 1: The initial attempt at a consortium has devolved into separate, 325 00:21:13,080 --> 00:21:16,480 Speaker 1: competing companies, and it's also a point where Isaacson becomes 326 00:21:16,600 --> 00:21:20,720 Speaker 1: unexpectedly pulled into the dispute over who pioneered Crisper. It 327 00:21:20,760 --> 00:21:23,600 Speaker 1: all starts with a paper written by Eric Lander, founding 328 00:21:23,640 --> 00:21:26,280 Speaker 1: director of the Broad Institute where Fung Jung works. 329 00:21:27,359 --> 00:21:30,280 Speaker 2: One of the things that Eric Lander Does, who ran 330 00:21:30,359 --> 00:21:34,240 Speaker 2: the Broad Institute where Fong Jang was working, decided he 331 00:21:34,359 --> 00:21:38,840 Speaker 2: wanted to make sure that Fung Jang and his team 332 00:21:38,960 --> 00:21:43,240 Speaker 2: got credit, and he wrote a scientific paper that got 333 00:21:43,280 --> 00:21:49,000 Speaker 2: published called The Heroes of Crisper. It's actually a very 334 00:21:49,280 --> 00:21:53,440 Speaker 2: good paper, and it takes you through every person involved 335 00:21:53,440 --> 00:21:56,920 Speaker 2: in the process, starting with Francesco Molika, the guy in 336 00:21:57,000 --> 00:22:02,600 Speaker 2: Spain who sees it in the original crobes in saltwater ponds, 337 00:22:03,760 --> 00:22:08,919 Speaker 2: but he minimizes what Jennifer Dowden, Emmanuel Sharpenjay does in 338 00:22:09,000 --> 00:22:13,000 Speaker 2: sort of a dismissive part of a paragraph saying a 339 00:22:13,040 --> 00:22:16,800 Speaker 2: good scientist say this, and then paragraph after paragraph on 340 00:22:16,920 --> 00:22:20,439 Speaker 2: how important it was that Phong Xiang was able to 341 00:22:20,480 --> 00:22:25,000 Speaker 2: make it work in the human cell. This causes only 342 00:22:25,400 --> 00:22:28,359 Speaker 2: the type of controversy that can happen when you combine 343 00:22:28,920 --> 00:22:33,040 Speaker 2: basic science with Twitter, in which Twitter mobs are accusing 344 00:22:33,160 --> 00:22:36,480 Speaker 2: Eric Lander are being sexist, and you know, doing to 345 00:22:36,640 --> 00:22:41,320 Speaker 2: Emmanuel Sharpentjay and Jennifer Dowdner what Jim Watson had done 346 00:22:41,880 --> 00:22:45,760 Speaker 2: to Rosalind Franklin and writing them out of history, and 347 00:22:46,320 --> 00:22:50,840 Speaker 2: also not disclosing when he wrote the piece that his 348 00:22:51,000 --> 00:22:53,879 Speaker 2: institute was in a patent battle with all of them, 349 00:22:53,920 --> 00:22:57,960 Speaker 2: so it becomes a mini scandal in the world of science. 350 00:22:59,240 --> 00:23:02,399 Speaker 1: And then one of the people enlisted to help resolve 351 00:23:02,440 --> 00:23:03,520 Speaker 1: that scandal is you. 352 00:23:04,400 --> 00:23:09,560 Speaker 2: At a certain point, the people at Harvard want to 353 00:23:10,080 --> 00:23:14,080 Speaker 2: restrain Eric Lander from going too far, and they know 354 00:23:14,160 --> 00:23:16,480 Speaker 2: it's gotten a bit unseemly. So I got a call 355 00:23:16,560 --> 00:23:21,399 Speaker 2: from somebody who said, can you host Eric Lander and 356 00:23:21,480 --> 00:23:26,080 Speaker 2: a group of science reporters and writers and technicians in 357 00:23:26,320 --> 00:23:31,600 Speaker 2: Washington and walk them through the Crispers story And we're 358 00:23:31,640 --> 00:23:34,880 Speaker 2: going to get him prepared to say nice things about 359 00:23:34,960 --> 00:23:38,680 Speaker 2: Jennifer Downer to try to resolve the controversy. And Eric 360 00:23:38,760 --> 00:23:42,080 Speaker 2: couldn't quite do it. I kept saying, all right, well 361 00:23:42,119 --> 00:23:44,680 Speaker 2: when the role of Jennifer, and he said, oh yeah, 362 00:23:44,760 --> 00:23:47,520 Speaker 2: they did okay. And I could see the person from 363 00:23:47,600 --> 00:23:50,400 Speaker 2: Harvard who was trying to orchesrate this kind of shrug 364 00:23:50,400 --> 00:23:53,800 Speaker 2: and roll their eyes. But I love Eric partly because 365 00:23:53,800 --> 00:23:56,400 Speaker 2: he's just so competitive. 366 00:23:57,480 --> 00:24:00,159 Speaker 1: And was there a part of you that was this 367 00:24:00,240 --> 00:24:03,600 Speaker 1: did getting involved? Did you think, well, that's if I'm involved, 368 00:24:03,640 --> 00:24:06,159 Speaker 1: I'll just write it into the book. Or did you 369 00:24:06,200 --> 00:24:08,680 Speaker 1: say I'm trying to stay out of this. 370 00:24:09,200 --> 00:24:12,159 Speaker 2: As a reporter. I was trained to stay out of it, 371 00:24:12,280 --> 00:24:15,000 Speaker 2: never to put yourself in a story. And over the years, 372 00:24:15,520 --> 00:24:19,080 Speaker 2: I realize you're more honest with the reader. Plus you 373 00:24:19,119 --> 00:24:23,480 Speaker 2: can make it a better understanding if you hold the 374 00:24:23,520 --> 00:24:26,400 Speaker 2: reader's hands and say, well, here's what I was doing 375 00:24:26,480 --> 00:24:29,680 Speaker 2: and how I got involved. And so with the Jennifer 376 00:24:29,760 --> 00:24:33,160 Speaker 2: Dowd in a book, I tried not to insert myself 377 00:24:33,200 --> 00:24:38,560 Speaker 2: in it unnecessarily. But at one point Jennifer Dowdn and 378 00:24:38,560 --> 00:24:41,320 Speaker 2: Emmanuel Sharp and Jay just are barely speaking to each 379 00:24:41,320 --> 00:24:44,359 Speaker 2: other even though that part, and Jennifer says, can you 380 00:24:44,400 --> 00:24:46,720 Speaker 2: call her up? And I had a joint session with 381 00:24:46,760 --> 00:24:50,240 Speaker 2: them on zoom, and I was just trying to see 382 00:24:50,320 --> 00:24:54,320 Speaker 2: if I could make sure that there was no misunderstandings 383 00:24:54,359 --> 00:24:56,520 Speaker 2: between them. And so what I was asked to do 384 00:24:56,600 --> 00:24:59,119 Speaker 2: this thing Ferick Landra, I said, if I'm upfront with 385 00:24:59,200 --> 00:25:02,280 Speaker 2: the reader and I plain exactly why I was doing it, 386 00:25:02,320 --> 00:25:06,240 Speaker 2: and it's actually truer to the situation than if I 387 00:25:06,400 --> 00:25:11,040 Speaker 2: pretend to have not been involved. Even when I'm at 388 00:25:11,080 --> 00:25:14,520 Speaker 2: a crisper conference like in Quebec City and I decide 389 00:25:14,560 --> 00:25:17,399 Speaker 2: to go out instead of with Jennifer Dowd newsgroup, I 390 00:25:17,480 --> 00:25:20,000 Speaker 2: decided to go to a restaurant with Fong Jang's group 391 00:25:20,400 --> 00:25:23,639 Speaker 2: and hear his side of the story. Instead of just 392 00:25:23,720 --> 00:25:27,240 Speaker 2: reporting his side of the story, I make it clear 393 00:25:27,240 --> 00:25:30,200 Speaker 2: they're competing debtors that night, and here's why I decided 394 00:25:30,240 --> 00:25:31,040 Speaker 2: to go to this one. 395 00:25:31,600 --> 00:25:35,320 Speaker 1: You're like an enzyme. Maybe that's supercharging the competition just 396 00:25:35,359 --> 00:25:37,600 Speaker 1: by showing up and saying I'm going to write the 397 00:25:37,640 --> 00:25:38,280 Speaker 1: story about this. 398 00:25:38,760 --> 00:25:42,119 Speaker 2: Yeah. I mean, enzymes are catalysts. They cause things to happen, 399 00:25:42,720 --> 00:25:47,160 Speaker 2: and you have to be careful that you're not distorting 400 00:25:47,200 --> 00:25:50,280 Speaker 2: the narrative by being there, that you're not too much 401 00:25:50,880 --> 00:25:57,399 Speaker 2: of a catalyst. On the other hand, when the story 402 00:25:57,480 --> 00:25:59,360 Speaker 2: is happening around you, when you're a part of it. 403 00:25:59,440 --> 00:26:02,640 Speaker 2: When I'm asked to moderate a panel at the Chris 404 00:26:02,720 --> 00:26:06,080 Speaker 2: Brook one of the later Christopher conferences at Cold Spring Arbor, 405 00:26:07,160 --> 00:26:12,080 Speaker 2: I want to do which best for the reader in 406 00:26:12,359 --> 00:26:14,520 Speaker 2: explaining how the tale unfolds. 407 00:26:16,400 --> 00:26:19,600 Speaker 1: As of this recording, the dispute over who discovered Crisper 408 00:26:19,600 --> 00:26:24,120 Speaker 1: Cast nine is ongoing. In the next episode of On Crisper, 409 00:26:24,280 --> 00:26:27,400 Speaker 1: we delve into the ethical implications that gene editing technology 410 00:26:27,400 --> 00:26:31,240 Speaker 1: brings and how Jennifer Dowdner grappled with them, both professionally 411 00:26:31,920 --> 00:26:35,919 Speaker 1: and personally on Crisper. The Story of Jennifer DOWDNA is 412 00:26:35,920 --> 00:26:39,080 Speaker 1: a production of Kaleidoscope and iHeart. This show is based 413 00:26:39,119 --> 00:26:42,040 Speaker 1: on the writing and reporting of Walter Isaacson. It's hosted 414 00:26:42,040 --> 00:26:44,840 Speaker 1: by me Evan Ratliffe and produced by Adriana Tipia with 415 00:26:44,880 --> 00:26:48,240 Speaker 1: assistance from Alex Jandenveldt. He was mixed by Kyle Murdoch 416 00:26:48,280 --> 00:26:51,760 Speaker 1: and our studio engineer was Thomas Walsh. Our executive producers 417 00:26:51,760 --> 00:26:55,000 Speaker 1: are Kate Osborne and my Gaeshatikador from Kaleidoscope and Katrina 418 00:26:55,040 --> 00:26:58,520 Speaker 1: Dorvel from iHeart Podcasts. If you enjoy hearing stories about 419 00:26:58,600 --> 00:27:01,280 Speaker 1: visionaries and science and technology, check out our other seasons 420 00:27:01,320 --> 00:27:03,879 Speaker 1: based on the biographies that Walter Isaacson has written. On 421 00:27:04,080 --> 00:27:06,600 Speaker 1: Musk for an intimate dive into all facets of Elon 422 00:27:06,720 --> 00:27:10,280 Speaker 1: Musk and on Benjamin Franklin to understand how his scientific 423 00:27:10,280 --> 00:27:12,840 Speaker 1: curiosity shapes society as we know it.