WEBVTT 00:00:00.000 --> 00:00:01.919 Welcome back to the Deep Doc. Today we are wrestling 00:00:01.919 --> 00:00:05.160 with one of modern science's most confounding 00:00:05.160 --> 00:00:08.960 and frankly explosive figures, Cary Banks Mollis. 00:00:09.320 --> 00:00:13.419 Born in 1944, passing away in 2019, Mollis was 00:00:13.419 --> 00:00:16.140 the American biochemist who gave the world an 00:00:16.140 --> 00:00:19.019 invention that, and this isn't an exaggeration, 00:00:19.120 --> 00:00:21.140 fundamentally changed the physical science. It 00:00:21.140 --> 00:00:22.960 really did. We're talking about the polymerase 00:00:22.960 --> 00:00:25.960 chain reaction or PCR. CCR. It's the ultimate 00:00:25.960 --> 00:00:28.649 tool. for amplification, not just scientifically, 00:00:28.789 --> 00:00:30.969 but, I mean, metaphorically, too, when you look 00:00:30.969 --> 00:00:32.469 at his life. That's a great way to put it. The 00:00:32.469 --> 00:00:34.090 New York Times, when they were discussing his 00:00:34.090 --> 00:00:37.710 work, used this just a magnificent line. They 00:00:37.710 --> 00:00:39.869 said his invention virtually divided the field 00:00:39.869 --> 00:00:44.119 of biology into two distinct epochs. Before PCR 00:00:44.119 --> 00:00:47.219 and after PCR. And that's not hyperbole. Not 00:00:47.219 --> 00:00:50.020 at all. PCR is the bedrock of, well, almost everything 00:00:50.020 --> 00:00:52.840 we do today. Forensics, rapid diagnostic testing, 00:00:53.100 --> 00:00:56.000 cutting edge genetic research, even phylogenetic 00:00:56.000 --> 00:00:58.280 studies. It's everywhere. But the core mission 00:00:58.280 --> 00:01:00.740 of this deep dive isn't just to celebrate the 00:01:00.740 --> 00:01:03.140 Nobel Prize winner. It's to try and understand 00:01:03.140 --> 00:01:05.659 the man behind the invention. Right. Because 00:01:05.659 --> 00:01:09.760 Cary Mullis presented this. intense, almost unbearable 00:01:09.760 --> 00:01:13.640 contrast between his certified Nobel -winning 00:01:13.640 --> 00:01:16.500 scientific genius, I mean a total mastery over 00:01:16.500 --> 00:01:19.840 molecular structure, and his highly unconventional, 00:01:19.840 --> 00:01:22.480 often deeply controversial views. We've used 00:01:22.480 --> 00:01:24.599 an exhaustive biographical account to really 00:01:24.599 --> 00:01:27.140 explore this full spectrum. We'll trace his path 00:01:27.140 --> 00:01:30.579 from high school rocketry and some clandestine 00:01:30.579 --> 00:01:32.719 chemistry. You'll get to that. Oh, we will. All 00:01:32.719 --> 00:01:34.040 the way to his breakthrough at Cetus Corporation. 00:01:34.159 --> 00:01:37.079 And then we have to dive deep into his profound 00:01:37.079 --> 00:01:40.099 and sometimes dangerous skepticism on huge public 00:01:40.099 --> 00:01:43.299 health issues like HIV AIDS, environmental science 00:01:43.299 --> 00:01:46.079 like climate change, and even his documented 00:01:46.079 --> 00:01:49.359 belief in the, well, the outright paranormal. 00:01:49.739 --> 00:01:51.450 We're talking about a man who gave us... the 00:01:51.450 --> 00:01:54.090 ultimate instrument for revealing objective truth 00:01:54.090 --> 00:01:56.870 at the molecular level. Yes. Who, in his personal 00:01:56.870 --> 00:01:58.810 life, was completely comfortable entertaining 00:01:58.810 --> 00:02:01.870 this scientifically implausible. This includes 00:02:01.870 --> 00:02:04.650 a widely publicized account of an encounter with 00:02:04.650 --> 00:02:07.689 a fluorescent talking raccoon. A fluorescent 00:02:07.689 --> 00:02:09.849 talking raccoon, he suggested, might have been 00:02:09.849 --> 00:02:12.349 an extraterrestrial alien. You can't make this 00:02:12.349 --> 00:02:15.219 stuff up. You really can't. It's a true study 00:02:15.219 --> 00:02:18.580 and paradox. The genius who, as one biologist 00:02:18.580 --> 00:02:22.199 put it, superpowered molecular biology, was at 00:02:22.199 --> 00:02:24.979 the same time guided by anecdotal evidence and 00:02:24.979 --> 00:02:27.259 personal belief whenever he stepped outside his 00:02:27.259 --> 00:02:29.199 own domain. And that's why this deep dive is 00:02:29.199 --> 00:02:31.180 so crucial for you, the learner. We're trying 00:02:31.180 --> 00:02:33.860 to help you understand a true intolerable genius, 00:02:34.139 --> 00:02:36.780 a case study in how world -changing innovation 00:02:36.780 --> 00:02:39.639 sometimes springs from the most unexpected and, 00:02:39.659 --> 00:02:43.060 yeah, sometimes erratic. So what does it mean 00:02:43.060 --> 00:02:45.900 when the man who gave us the power of molecular 00:02:45.900 --> 00:02:49.580 certainty was himself so, so uncertain about 00:02:49.580 --> 00:02:51.599 established reality? Yeah. OK, let's unpack this 00:02:51.599 --> 00:02:54.120 life story starting right at the beginning. So 00:02:54.120 --> 00:02:56.340 Carey Mullis was born in Lenoir, North Carolina, 00:02:56.500 --> 00:02:58.780 but he spent his formative years growing up in 00:02:58.780 --> 00:03:01.599 Columbia, South Carolina. And his early life, 00:03:01.620 --> 00:03:03.460 it was really marked by this deep fascination 00:03:03.460 --> 00:03:06.000 with the natural world. He spent a lot of time 00:03:06.000 --> 00:03:08.319 just observing organisms, which, you know, reflects 00:03:08.319 --> 00:03:10.479 a foundational interest in biological systems. 00:03:10.620 --> 00:03:12.979 His family had a farming background, but his 00:03:12.979 --> 00:03:15.060 own curiosity just pulled him toward the hands 00:03:15.060 --> 00:03:17.479 -on world of chemistry. And when you say hands 00:03:17.479 --> 00:03:20.060 -on, his chemistry interests were anything but 00:03:20.060 --> 00:03:22.860 theoretical. We're talking about the 1960s here. 00:03:22.960 --> 00:03:25.900 Personal rocketry was a pretty big hobby for 00:03:25.900 --> 00:03:29.000 aspiring young scientists back then. Mullis wasn't 00:03:29.000 --> 00:03:31.240 just reading about it. He was actively involved 00:03:31.240 --> 00:03:34.800 in chemically synthesizing and building solid 00:03:34.800 --> 00:03:37.479 fuel propulsion rockets. In high school. In high 00:03:37.479 --> 00:03:40.860 school. This early mix of intellectual rigor, 00:03:41.060 --> 00:03:44.280 practical chemistry, and a willingness to embrace 00:03:44.280 --> 00:03:47.180 risk, or maybe just the sheer fun of making things 00:03:47.180 --> 00:03:49.960 go boom, it feels like a crucial foundation for 00:03:49.960 --> 00:03:52.460 how he approached problem solving later on. Absolutely. 00:03:52.719 --> 00:03:54.979 And he channeled that energy into formal academics. 00:03:55.340 --> 00:03:57.780 He got a Bachelor of Science in Chemistry from 00:03:57.780 --> 00:03:59.900 the Georgia Institute of Technology in 1966. 00:04:00.659 --> 00:04:02.780 And it's worth noting, his life was already moving 00:04:02.780 --> 00:04:04.719 fast. He was married for the first time while 00:04:04.719 --> 00:04:06.939 he was still an undergraduate. And he was already 00:04:06.939 --> 00:04:08.860 dabbling in starting these small businesses. 00:04:09.199 --> 00:04:13.080 His path was accelerated and nonlinear from the 00:04:13.080 --> 00:04:15.139 get -go. He didn't slow down for grad school 00:04:15.139 --> 00:04:17.800 either. He heads to UC Berkeley for a PhD in 00:04:17.800 --> 00:04:21.540 biochemistry. A big deal. A very big deal. And 00:04:21.540 --> 00:04:24.040 his doctoral work, which he finished in 1973, 00:04:24.420 --> 00:04:28.000 was highly specialized. It focused on the synthesis 00:04:28.000 --> 00:04:31.019 and structure of bacterial iron transporter molecules, 00:04:31.439 --> 00:04:34.339 technically called siderophores. Specifically, 00:04:34.519 --> 00:04:36.699 he characterized one called schizokinin. Okay, 00:04:36.720 --> 00:04:38.879 let's break that down. Siderophores, what are 00:04:38.879 --> 00:04:41.319 they doing exactly? So think of them as molecules 00:04:41.319 --> 00:04:44.360 that microorganisms like bacteria secrete to 00:04:44.360 --> 00:04:46.920 basically scavenge for iron in their environment. 00:04:47.160 --> 00:04:49.160 Like little molecular claw machines. That's a 00:04:49.160 --> 00:04:51.959 perfect analogy. Iron is essential for microbial 00:04:51.959 --> 00:04:53.980 growth, but it's often locked up in forms they 00:04:53.980 --> 00:04:56.720 can't use. Siderophores go out, grab the iron, 00:04:56.800 --> 00:04:59.089 and transport it back into the cell. Melissa's 00:04:59.089 --> 00:05:01.069 work was on characterizing the structure of one 00:05:01.069 --> 00:05:03.310 of these. It was precise, rigorous chemistry. 00:05:03.689 --> 00:05:05.829 So he's clearly operating at this really high 00:05:05.829 --> 00:05:08.490 level of chemical complexity. And yet there's 00:05:08.490 --> 00:05:11.250 this recurring story that he really struggled 00:05:11.250 --> 00:05:13.589 with the formal academic structure at Berkeley. 00:05:14.029 --> 00:05:17.310 He did. His time there was notoriously difficult 00:05:17.310 --> 00:05:19.949 in terms of him fitting the mold. Colleagues 00:05:19.949 --> 00:05:22.250 noted his unique style, but also his struggles 00:05:22.250 --> 00:05:25.310 with standardized things like oral exams. Yeah. 00:05:25.449 --> 00:05:27.670 One recalled that he struggled badly with his 00:05:27.670 --> 00:05:30.670 oral exams. He said Mullis, quote, didn't get 00:05:30.670 --> 00:05:32.910 his propositions right. He didn't know general 00:05:32.910 --> 00:05:35.509 biochemistry. The formal discipline of academia 00:05:35.509 --> 00:05:39.069 just it chafed against his intuitive, unconventional 00:05:39.069 --> 00:05:41.439 way of thinking. And this tension became very 00:05:41.439 --> 00:05:43.939 real when it was time to submit his thesis. We 00:05:43.939 --> 00:05:46.379 have this incredible detail that his dissertation 00:05:46.379 --> 00:05:49.319 was only accepted after his friends had to intervene. 00:05:49.500 --> 00:05:51.480 They literally had to cut all the wacko stuff 00:05:51.480 --> 00:05:53.459 out of it. Which beats volumes, right? It really 00:05:53.459 --> 00:05:56.360 does. The core chemistry on Skissikinen was solid, 00:05:56.480 --> 00:05:59.560 but Mullis's tendency to integrate these, you 00:05:59.560 --> 00:06:02.620 know, far out philosophical or totally unrelated 00:06:02.620 --> 00:06:05.339 scientific tangents into his formal work was 00:06:05.339 --> 00:06:08.160 already there. He was a brilliant chemist, but 00:06:08.160 --> 00:06:10.430 he resisted the structure. structured confines 00:06:10.430 --> 00:06:12.470 of the scientific establishment from day one. 00:06:12.649 --> 00:06:14.949 And if we need any more proof of just how eclectic 00:06:14.949 --> 00:06:17.949 his mind was, think about this. Four years before 00:06:17.949 --> 00:06:20.790 he even got that biochemistry PhD, back in 1968, 00:06:21.189 --> 00:06:24.269 he published a sole author paper in Nature. Which 00:06:24.269 --> 00:06:26.250 is almost unheard of for a grad student. In Nature. 00:06:26.449 --> 00:06:28.589 And the topic was a whole different ballgame. 00:06:28.730 --> 00:06:31.949 It was astrophysics. The title was Cosmological 00:06:31.949 --> 00:06:35.170 Significance of Time Reversal. A biochemist writing 00:06:35.170 --> 00:06:37.850 theoretical astrophysics in nature. It shows 00:06:37.850 --> 00:06:40.629 he was either breathtakingly confident or a genuine 00:06:40.629 --> 00:06:43.550 polymath or, you know, maybe a bit of both. And 00:06:43.550 --> 00:06:46.509 yet after he gets his Ph .D. in 73, his career 00:06:46.509 --> 00:06:49.850 path just takes these surprising, almost aimless 00:06:49.850 --> 00:06:53.329 detours. It really does. He did a couple of postdoctoral 00:06:53.329 --> 00:06:56.329 fellowships, first in pediatric cardiology, then 00:06:56.329 --> 00:06:59.180 pharmaceutical chemistry. Then he just. leaves 00:06:59.180 --> 00:07:02.040 science. Completely. He managed a bakery for 00:07:02.040 --> 00:07:04.860 two years. A bakery. A bakery. And then he left 00:07:04.860 --> 00:07:07.399 the technical world entirely to try and write 00:07:07.399 --> 00:07:10.500 fiction. This is not the resume you expect from 00:07:10.500 --> 00:07:12.939 a future Nobel Prize winner. It really emphasizes 00:07:12.939 --> 00:07:15.779 how much chance and a little push from a friend 00:07:15.779 --> 00:07:17.779 played a role in bringing him back to the lab. 00:07:17.899 --> 00:07:20.800 And that return to science was directly orchestrated 00:07:20.800 --> 00:07:23.379 by his friend and former colleague, Thomas White. 00:07:23.540 --> 00:07:26.060 Okay, so White's a key figure here. He was instrumental. 00:07:26.360 --> 00:07:29.100 First, he helped Mullis get a postdoctoral position 00:07:29.100 --> 00:07:32.439 at UCSF, and then he facilitated his move to 00:07:32.439 --> 00:07:34.519 Cetus Corporation in Emeryville, California. 00:07:35.300 --> 00:07:39.339 Cetus was one of the early major powerhouses 00:07:39.339 --> 00:07:41.759 of the biotech industry. And Mullis arrived there 00:07:41.759 --> 00:07:45.959 in 1979 as a DNA chemist. It's important to remember, 00:07:46.060 --> 00:07:48.839 as we said, he had very little formal molecular 00:07:48.839 --> 00:07:51.060 biology experience at this point. Right, but 00:07:51.060 --> 00:07:53.600 he was a highly capable synthetic chemist. He 00:07:53.600 --> 00:07:56.220 ended up heading... their DNA synthesis lab. 00:07:56.459 --> 00:07:58.620 He spent four years there, and then in 1983, 00:07:58.939 --> 00:08:02.060 we get the legendary Eureka moment. This is the 00:08:02.060 --> 00:08:03.980 moment that changed everything, and the setting 00:08:03.980 --> 00:08:06.540 is almost mythological now. Mullis was driving 00:08:06.540 --> 00:08:08.720 late one Friday night. He mentions the time was 00:08:08.720 --> 00:08:11.180 about 10 .30 p .m., heading out of Berkeley toward 00:08:11.180 --> 00:08:13.560 his country home in Mendocino County. He was 00:08:13.560 --> 00:08:15.120 with his girlfriend at the time, Jennifer, who 00:08:15.120 --> 00:08:17.160 was also a chemist at Cetus. He's driving on 00:08:17.160 --> 00:08:20.060 Highway 128, going past a winery, and then the 00:08:20.060 --> 00:08:22.120 idea just hits him. So what was the specific 00:08:22.120 --> 00:08:24.019 problem he was trying to solve in his head? He 00:08:24.019 --> 00:08:26.139 was trying to figure out a method to detect a 00:08:26.139 --> 00:08:29.519 single, very specific base sequence within a 00:08:29.519 --> 00:08:32.740 massive, complex sample of DNA, like the entire 00:08:32.740 --> 00:08:35.419 human genome. Which was the holy grail at the 00:08:35.419 --> 00:08:38.379 time. It was. Before PCR, if you wanted to study 00:08:38.379 --> 00:08:40.879 a particular gene, you had two main options. 00:08:41.139 --> 00:08:44.080 You could either grow the DNA inside living organisms, 00:08:44.259 --> 00:08:47.960 a process called cloning, which was slow, labor 00:08:47.960 --> 00:08:50.500 -intensive, and needed specialized cell cultures. 00:08:50.700 --> 00:08:53.620 Or you could use these time -consuming, chemically 00:08:53.620 --> 00:08:56.399 complex sequencing methods that could only analyze 00:08:56.399 --> 00:08:59.500 tiny little snippets. Getting enough clean, specific 00:08:59.500 --> 00:09:02.080 DNA to study was the bottleneck. It was like 00:09:02.080 --> 00:09:04.639 trying to find one specific word in a thousand 00:09:04.639 --> 00:09:07.000 -volume library, and the only way to read it 00:09:07.000 --> 00:09:09.559 was to copy the entire library out by hand first. 00:09:09.840 --> 00:09:11.860 Precisely. And Mullis realized he didn't need 00:09:11.860 --> 00:09:13.759 to copy the whole library. The essential insight 00:09:13.759 --> 00:09:16.419 was this. He could use a pair of short, synthetic 00:09:16.419 --> 00:09:19.460 DNA fragments, he called them primers, to bracket 00:09:19.460 --> 00:09:22.230 the... exact DNA sequence he wanted. So the primer 00:09:22.230 --> 00:09:25.009 basically tells the copying enzyme, the DNA polymerase, 00:09:25.110 --> 00:09:27.950 exactly where to start and stop copying. Exactly. 00:09:28.250 --> 00:09:31.629 And the true genius was in the cycling. He realized 00:09:31.629 --> 00:09:34.950 if he heated the mixture, the DNA double helix 00:09:34.950 --> 00:09:37.929 would separate into two strands. Then as it cooled 00:09:37.929 --> 00:09:40.289 a bit, the primers would attach to their specific 00:09:40.289 --> 00:09:43.230 spots. Finally, at the right temperature, the 00:09:43.230 --> 00:09:45.509 DNA polymerase would just zoom along and copy 00:09:45.509 --> 00:09:47.830 the target segment between the primers. But here's 00:09:47.830 --> 00:09:50.470 where the conceptual leap happened. He realized 00:09:50.470 --> 00:09:52.950 that the newly synthesized strands could, in 00:09:52.950 --> 00:09:55.429 turn, become the templates for the next round 00:09:55.429 --> 00:10:00.009 of copying. Yes. The process just repeats. Separate, 00:10:00.009 --> 00:10:02.190 attach, copy. In the first cycle, you get two 00:10:02.190 --> 00:10:04.149 copies. In the second, you get four. The third, 00:10:04.210 --> 00:10:07.029 eight. This is the power of exponential amplification. 00:10:07.289 --> 00:10:08.950 Let's be really clear about what exponential 00:10:08.950 --> 00:10:10.929 amplification means, because that's the magic 00:10:10.929 --> 00:10:13.029 the New York Times quote was getting at. If you 00:10:13.029 --> 00:10:15.610 start with just one molecule of DNA and run, 00:10:15.710 --> 00:10:19.309 say, 30 cycles. How many molecules do you end 00:10:19.309 --> 00:10:21.149 up with? Assuming the process is 100 percent 00:10:21.149 --> 00:10:23.450 efficient, 30 cycles will yield approximately 00:10:23.450 --> 00:10:25.850 one billion copies of that initial single segment. 00:10:25.990 --> 00:10:28.149 One to one billion. That transformation from 00:10:28.149 --> 00:10:30.389 one molecule to a billion means that suddenly 00:10:30.389 --> 00:10:33.629 the tiniest trace amount of DNA from a single 00:10:33.629 --> 00:10:36.769 hair follicle or a tiny blood spot becomes visible 00:10:36.769 --> 00:10:39.370 and measurable. It was a feat that was utterly 00:10:39.370 --> 00:10:42.750 impossible before 1983. It turned DNA from this 00:10:42.750 --> 00:10:45.590 highly limited resource into an abundant one. 00:10:45.809 --> 00:10:48.289 And Mullis managed to demonstrate. PCR on December 00:10:48.289 --> 00:10:52.490 16th, 1983. But despite the undeniable mathematical 00:10:52.490 --> 00:10:55.450 logic, the sources say the staff at Cetus were 00:10:55.450 --> 00:10:58.649 skeptical. They were. It was partly methodological 00:10:58.649 --> 00:11:00.830 and partly cultural. Colleagues were cautious, 00:11:01.049 --> 00:11:03.309 noting that Mullis's initial results were a bit 00:11:03.309 --> 00:11:06.250 ambiguous. They pointed to what they saw as methodological 00:11:06.250 --> 00:11:08.750 problems, specifically a lack of appropriate 00:11:08.750 --> 00:11:11.110 controls and repetition. So his execution was 00:11:11.110 --> 00:11:13.570 maybe a little sloppy, even if the idea was brilliant. 00:11:13.750 --> 00:11:16.210 His mind was often ahead of his hands. His supervisor, 00:11:16.490 --> 00:11:18.570 Thomas White, actually had to reassign Mullis 00:11:18.570 --> 00:11:20.710 from his other projects to focus entirely on 00:11:20.710 --> 00:11:22.950 perfecting PCR because the technique was meeting 00:11:22.950 --> 00:11:25.450 so much internal resistance. It's just so interesting 00:11:25.450 --> 00:11:27.149 that this monumental scientific breakthrough 00:11:27.149 --> 00:11:29.570 didn't solve his personal problem. problems. 00:11:29.710 --> 00:11:32.490 He said in his Nobel lecture that while all this 00:11:32.490 --> 00:11:35.250 was happening, he felt lonesome because his girlfriend 00:11:35.250 --> 00:11:37.210 had just broken up with him. That detail really 00:11:37.210 --> 00:11:40.289 speaks to the kind of whirlwind his life always 00:11:40.289 --> 00:11:43.970 was. So PCR was invented. The exponential amplification 00:11:43.970 --> 00:11:47.049 was proven. But the process was still incredibly 00:11:47.049 --> 00:11:50.429 labor intensive and expensive. It was. It was 00:11:50.429 --> 00:11:52.990 an amazing scientific proof of concept, but it 00:11:52.990 --> 00:11:55.549 wasn't a global workhorse yet. Which brings us 00:11:55.549 --> 00:11:57.309 to the critical improvement that made it commercially 00:11:57.309 --> 00:12:00.370 viable. What was the major practical drawback 00:12:00.370 --> 00:12:02.769 of the original method? The fundamental problem 00:12:02.769 --> 00:12:05.309 was thermal stability. As we said, you need high 00:12:05.309 --> 00:12:07.870 heat, we're talking near boiling, around 95 degrees 00:12:07.870 --> 00:12:11.389 Celsius, to separate the DNA double helix into 00:12:11.389 --> 00:12:14.149 single strands. Well, the DNA polymerase enzyme, 00:12:14.330 --> 00:12:16.049 the thing that does the actual copying, is a 00:12:16.049 --> 00:12:19.190 protein. And most proteins, they just denature. 00:12:19.289 --> 00:12:21.429 They get destroyed by that much heat. So the 00:12:21.429 --> 00:12:23.519 enzyme was like ice cream in a sauna. Perfect 00:12:23.519 --> 00:12:26.840 analogy. It melted. So for every single replication 00:12:26.840 --> 00:12:29.620 cycle, heating up to 95 degrees and cooling back 00:12:29.620 --> 00:12:32.779 down, you had to manually stop, open the tube, 00:12:32.860 --> 00:12:35.340 and add a fresh dose of this expensive enzyme. 00:12:35.720 --> 00:12:37.820 So if you wanted 30 cycles to get your billion 00:12:37.820 --> 00:12:40.259 copies. You had to manually add the enzyme 30 00:12:40.259 --> 00:12:43.139 times. It was tedious, it was prone to contamination, 00:12:43.539 --> 00:12:46.500 and it was prohibitively expensive for mass use. 00:12:46.759 --> 00:12:48.620 You still needed a highly trained technician 00:12:48.620 --> 00:12:51.039 babysitting machine all day. The breakthrough 00:12:51.039 --> 00:12:53.690 was intellectual. But the application was still 00:12:53.690 --> 00:12:56.730 stuck in the age of manual labor. Exactly. The 00:12:56.730 --> 00:13:00.629 game changer arrived in 1986, three years after 00:13:00.629 --> 00:13:03.090 Mullis' breakthrough. And it came from another 00:13:03.090 --> 00:13:06.789 CETA scientist, Randall Saiki. Right. Saiki introduced 00:13:06.789 --> 00:13:09.730 a DNA polymerase that was sourced from a bacterium 00:13:09.730 --> 00:13:12.850 called Thermophilus aquaticus. Mercifully, they 00:13:12.850 --> 00:13:15.149 shortened it to TAC. And this bacterium lives 00:13:15.149 --> 00:13:18.230 where? It lives naturally in the extremely high 00:13:18.230 --> 00:13:20.070 temperatures of hot springs like the ones in 00:13:20.070 --> 00:13:22.070 Yellowstone National Park. It's a thermophile. 00:13:22.250 --> 00:13:24.909 It loves the heat. So its enzymes evolved to 00:13:24.909 --> 00:13:27.250 love the heat too. They did. Taq polymerase is 00:13:27.250 --> 00:13:29.350 naturally heat resistant. It could survive the 00:13:29.350 --> 00:13:31.909 95 degree separation phase without denaturing. 00:13:32.450 --> 00:13:34.610 You only needed to add the enzyme once at the 00:13:34.610 --> 00:13:36.789 very beginning. You could put your mixture into 00:13:36.789 --> 00:13:39.889 an automated thermal cycler, set it to run 20, 00:13:40.049 --> 00:13:43.230 30, 40 cycles and just walk away. The Taq polymerase 00:13:43.230 --> 00:13:45.029 would patiently wait for the temperature to drop 00:13:45.029 --> 00:13:47.759 and get back. to work again and again. That one 00:13:47.759 --> 00:13:50.919 small molecular detail, the heat stability of 00:13:50.919 --> 00:13:53.460 one enzyme, fundamentally changed the entire 00:13:53.460 --> 00:13:56.820 process. It made PCR cheap, fully automatable, 00:13:56.919 --> 00:13:59.580 and viable for pretty much any lab on the planet. 00:13:59.879 --> 00:14:02.580 The impact is, as David Bilder from UC Berkeley 00:14:02.580 --> 00:14:04.879 stated, just hard to overstate. He called it 00:14:04.879 --> 00:14:07.960 magical. He said it superpowered molecular biology 00:14:07.960 --> 00:14:11.179 and it transformed fields from ecology, where 00:14:11.179 --> 00:14:13.279 you can now analyze DNA from animal scat, to 00:14:13.279 --> 00:14:15.919 evolutionary biology, where tiny preserved samples 00:14:15.919 --> 00:14:19.259 can be amplified. PCR, thanks to TAC, became 00:14:19.259 --> 00:14:21.620 the indispensable workhorse that made molecular 00:14:21.620 --> 00:14:24.379 biology accessible to everyone. The second that 00:14:24.379 --> 00:14:26.659 technique became automated and commercially viable, 00:14:26.879 --> 00:14:29.039 the story really shifts, doesn't it? It goes 00:14:29.039 --> 00:14:32.840 from scientific discovery to... A corporate battleground. 00:14:33.019 --> 00:14:35.399 Yeah. When an invention can diagnose disease, 00:14:35.539 --> 00:14:37.840 solve crimes, and generate billions of dollars, 00:14:38.080 --> 00:14:41.259 the credit lines get very blurry very fast. Okay, 00:14:41.320 --> 00:14:43.820 so let's start with Mullis' compensation for 00:14:43.820 --> 00:14:46.700 this billion -dollar idea. He received a one 00:14:46.700 --> 00:14:51.379 -time bonus from Cetus for $10 ,000. $10 ,000 00:14:51.379 --> 00:14:54.399 for a foundational technology that would eventually 00:14:54.399 --> 00:14:57.379 be sold for hundreds of millions? That feels 00:14:57.379 --> 00:14:59.600 like a massive insult. It was certainly a source 00:14:59.600 --> 00:15:02.759 of deep, lasting bitterness for Mullis. But the 00:15:02.759 --> 00:15:05.679 tension was also fueled by Cetus's decision to 00:15:05.679 --> 00:15:08.399 bring in other researchers. Right. The company, 00:15:08.559 --> 00:15:10.820 understanding the immense commercial value here, 00:15:11.120 --> 00:15:14.779 assigned what the sources call top -notch experimentalists, 00:15:14.919 --> 00:15:17.340 people like Randall Psyche, Henry Ehrlich, and 00:15:17.340 --> 00:15:20.240 Norman Arnheim, to work on parallel PCR projects. 00:15:20.639 --> 00:15:22.960 So they weren't brought in to invent the concept, 00:15:23.220 --> 00:15:26.000 but to provide the rigor and the data that Mullis, 00:15:26.039 --> 00:15:29.259 with his, let's say, erratic style, hadn't formalized 00:15:29.259 --> 00:15:32.519 yet. Precisely. They were tasked with generating 00:15:32.519 --> 00:15:35.440 the critical, clean data to prove the technique 00:15:35.440 --> 00:15:38.779 worked flawlessly. Specifically, showing that 00:15:38.779 --> 00:15:42.139 PCR could reliably amplify a human gene, beta 00:15:42.139 --> 00:15:45.259 -globin, from a whole genome. And they did. Sahiki 00:15:45.259 --> 00:15:47.799 generated that data, and Ehrlich authored the 00:15:47.799 --> 00:15:49.980 first paper describing a practical use of the 00:15:49.980 --> 00:15:53.500 technique in 1985. Mullis, who was still working 00:15:53.500 --> 00:15:56.000 on his own paper describing the fundamental process, 00:15:56.440 --> 00:15:58.860 felt aggressively marginalized. And he didn't 00:15:58.860 --> 00:16:00.559 hold back his feelings about it? Not at all. 00:16:00.639 --> 00:16:03.259 The sources detail his condemnation of his supervisor, 00:16:03.559 --> 00:16:05.620 Thomas White, and the members of that parallel 00:16:05.620 --> 00:16:09.009 team. He referred to them as vultures. Vultures. 00:16:09.110 --> 00:16:11.509 This is the core conflict, right? The inventor, 00:16:11.690 --> 00:16:13.950 driven by intuition, versus the organization 00:16:13.950 --> 00:16:16.690 that needs methodological rigor and speed to 00:16:16.690 --> 00:16:18.789 secure a market advantage. And the financial 00:16:18.789 --> 00:16:22.110 stakes were huge. Cetus eventually sold the entire 00:16:22.110 --> 00:16:24.830 PCR patent, the initial invention, and the crucial 00:16:24.830 --> 00:16:27.549 tech element to Roche Molecular Systems for a 00:16:27.549 --> 00:16:30.690 staggering $300 million. $300 million. And while 00:16:30.690 --> 00:16:33.549 Mullis shared the 1993 Nobel Prize in Chemistry 00:16:33.549 --> 00:16:36.889 with Michael Smith for his conceptual work, that 00:16:36.889 --> 00:16:39.830 corporate compensation or lack of it, it just 00:16:39.830 --> 00:16:42.950 fueled his volatile reputation. It fed his cynicism 00:16:42.950 --> 00:16:45.129 about institutional science. Let's talk about 00:16:45.129 --> 00:16:47.370 the patent challenge, because DuPont tried to 00:16:47.370 --> 00:16:50.470 contest it, arguing there was prior art from 00:16:50.470 --> 00:16:53.210 years earlier. Who did they cite? They cited 00:16:53.210 --> 00:16:56.190 Nobel laureate H. Gabun Karana and a Norwegian 00:16:56.190 --> 00:17:00.299 scientist, K. Jell Klepp. Way back in 1971, that's 00:17:00.299 --> 00:17:03.080 17 years before Mullis' breakthrough, they'd 00:17:03.080 --> 00:17:05.440 published work on a conceptually similar idea 00:17:05.440 --> 00:17:08.079 they called repair replication. Okay. Their work 00:17:08.079 --> 00:17:10.559 demonstrated duplicating and even quadrupling 00:17:10.559 --> 00:17:13.819 a small synthetic molecule using two primers 00:17:13.819 --> 00:17:17.039 and a polymerase. So conceptually, the essential 00:17:17.039 --> 00:17:19.180 elements, primers, polymerase, they were there. 00:17:19.789 --> 00:17:22.089 Why didn't that invalidate Mullis' patent? The 00:17:22.089 --> 00:17:24.970 key was application and context. Karana's experiment 00:17:24.970 --> 00:17:27.390 worked on a small, synthetic, highly controlled 00:17:27.390 --> 00:17:30.670 molecule. It was a very specific chemical environment. 00:17:31.069 --> 00:17:33.269 Mullis' breakthrough was demonstrating that the 00:17:33.269 --> 00:17:35.710 exponential nature worked on complex biological 00:17:35.710 --> 00:17:38.450 mixtures like genomic DNA. That's a whole different 00:17:38.450 --> 00:17:41.990 ballgame. And Carana himself refused to testify 00:17:41.990 --> 00:17:44.390 for DuPont. He perhaps saw the patent battle 00:17:44.390 --> 00:17:46.950 as a distraction, or maybe he recognized the 00:17:46.950 --> 00:17:49.089 huge practical difference between his conceptual 00:17:49.089 --> 00:17:51.589 demonstration and Mullis' functional application. 00:17:52.049 --> 00:17:55.769 A jury upheld the Mullis patent in 1991. But 00:17:55.769 --> 00:17:57.910 the legal battles weren't over, especially regarding 00:17:57.910 --> 00:18:01.210 the tack component. That's right. In 1999, years 00:18:01.210 --> 00:18:04.390 after the Nobel, the Roche patent Specifically, 00:18:04.390 --> 00:18:06.569 the part concerning the use of TAC polymerase 00:18:06.569 --> 00:18:09.410 was actually found unenforceable. On what grounds? 00:18:09.750 --> 00:18:12.640 It was based on evidence of prior art. There 00:18:12.640 --> 00:18:15.000 were articles published on the heat -stable polymerase 00:18:15.000 --> 00:18:18.579 itself back in 1976 and 1980, which predated 00:18:18.579 --> 00:18:21.160 the work done by the CETIS team that had patented 00:18:21.160 --> 00:18:23.599 its purification process. It just highlights 00:18:23.599 --> 00:18:26.460 the layered nature of scientific progress. Mollis 00:18:26.460 --> 00:18:28.740 had the conceptual leap. Psyche provided the 00:18:28.740 --> 00:18:30.799 critical enabler with TAC. But the underlying 00:18:30.799 --> 00:18:33.940 component, TAC polymerase, was already part of 00:18:33.940 --> 00:18:35.940 the public scientific record. So the invention 00:18:35.940 --> 00:18:38.099 that revolutionized biology was the product of 00:18:38.099 --> 00:18:40.460 a singular moment of genius, years of testing, 00:18:40.660 --> 00:18:47.430 complex corpor - And even if you set aside the 00:18:47.430 --> 00:18:50.569 patent drama, Mullis's reputation for erratic 00:18:50.569 --> 00:18:53.849 behavior at CETUS was profound. His supervisor, 00:18:54.230 --> 00:18:57.069 Thomas White, noted that his behavior was so 00:18:57.069 --> 00:19:00.029 outrageous that colleagues thought White only 00:19:00.029 --> 00:19:02.430 kept him on because they were friends. That tells 00:19:02.430 --> 00:19:04.109 you something about the corporate culture. They 00:19:04.109 --> 00:19:07.049 tolerated extreme volatility because the genius 00:19:07.049 --> 00:19:09.490 was just undeniable. What specifically are we 00:19:09.490 --> 00:19:11.289 talking about when we say outrageous behavior? 00:19:11.549 --> 00:19:13.670 Well, the sources cite specific examples that 00:19:13.670 --> 00:19:17.089 paint a picture of intense instability. Mullis 00:19:17.089 --> 00:19:19.490 once allegedly threatened to bring a gun to work. 00:19:19.670 --> 00:19:22.630 Wow. OK. He engaged in these highly public lovers 00:19:22.630 --> 00:19:24.809 quarrels with his girlfriend, who, again, was 00:19:24.809 --> 00:19:27.109 a chemist working on the same floor. So uncomfortable 00:19:27.109 --> 00:19:29.630 for everyone else. Immensely. And the source 00:19:29.630 --> 00:19:32.599 also details how he. nearly came to blows with 00:19:32.599 --> 00:19:34.980 another scientist at a company party. His emotional 00:19:34.980 --> 00:19:37.400 intensity just bled over into his professional 00:19:37.400 --> 00:19:40.119 life, which made him a truly difficult yet indispensable 00:19:40.119 --> 00:19:42.859 colleague. He eventually resigned from Cetus 00:19:42.859 --> 00:19:46.920 in 1986, right after the TAC discovery, but he 00:19:46.920 --> 00:19:49.599 didn't stop working. He continued inventing and 00:19:49.599 --> 00:19:52.200 consulting, often blending this high -level science 00:19:52.200 --> 00:19:55.019 with some really unconventional commercial ventures. 00:19:55.140 --> 00:19:57.839 His next stop was a company called Zytron Inc. 00:19:58.319 --> 00:20:00.680 in san diego he was the director of molecular 00:20:00.680 --> 00:20:03.920 biology there for two years he invented a uv 00:20:03.920 --> 00:20:06.480 sensitive ink a practical chemistry application 00:20:06.480 --> 00:20:10.119 but you know a far cry from dna right and it 00:20:10.119 --> 00:20:11.720 was during this period that the source notes 00:20:11.720 --> 00:20:14.079 he became actively skeptical of the existence 00:20:14.079 --> 00:20:16.859 of the ozone hole which was a major environmental 00:20:16.859 --> 00:20:19.740 concern at the time this marks a really early 00:20:19.740 --> 00:20:22.400 concrete shift toward him questioning scientific 00:20:22.400 --> 00:20:25.380 consensus outside his own domain he then transitioned 00:20:25.380 --> 00:20:28.279 into consulting focusing on nucleic acid chemistry 00:20:28.279 --> 00:20:30.980 and becoming this high -profile expert witness 00:20:30.980 --> 00:20:34.359 in DNA profiling. A field that, ironically, depended 00:20:34.359 --> 00:20:36.740 entirely on his own invention to even function. 00:20:36.940 --> 00:20:39.880 And this brings us to one of his more bizarre 00:20:39.880 --> 00:20:42.839 commercial ventures. In 1992, around the time 00:20:42.839 --> 00:20:45.180 he was cementing his reputation as a DNA forensics 00:20:45.180 --> 00:20:47.799 expert, he founded a business to sell celebrity 00:20:47.799 --> 00:20:51.660 DNA jewelry. You have to explain this. Amplified 00:20:51.660 --> 00:20:55.140 DNA inside a trinket. That's it. He wanted to 00:20:55.140 --> 00:20:57.220 sell pieces of jewelry containing the amplified 00:20:57.220 --> 00:21:00.160 DNA of deceased famous people. He cited Elvis 00:21:00.160 --> 00:21:02.539 Presley and Marilyn Monroe as examples. That 00:21:02.539 --> 00:21:05.180 is almost surreal. It's taking the pinnacle of 00:21:05.180 --> 00:21:08.380 high -tech molecular biology, the ability to 00:21:08.380 --> 00:21:10.940 amplify the smallest trace of life, and using 00:21:10.940 --> 00:21:14.059 it to create morbid novelty items. It just reveals 00:21:14.059 --> 00:21:16.859 this incredible commercial impulsivity combined 00:21:16.859 --> 00:21:19.630 with his unique technical skill. But in the same 00:21:19.630 --> 00:21:22.670 year, he also founded Atomic Tags, which shows 00:21:22.670 --> 00:21:24.970 his mind was still operating at the absolute 00:21:24.970 --> 00:21:28.119 cutting edge. Atomic tags was a serious, complex 00:21:28.119 --> 00:21:31.319 idea. It was a venture to develop highly multiplexed 00:21:31.319 --> 00:21:34.259 amino assays using advanced tech, specifically 00:21:34.259 --> 00:21:36.900 atomic force microscopy, where you'd tag antibodies 00:21:36.900 --> 00:21:39.119 with heavy metals. And the goal was? The goal 00:21:39.119 --> 00:21:41.440 was to identify multiple disease markers at the 00:21:41.440 --> 00:21:43.859 same time with incredible precision. So within 00:21:43.859 --> 00:21:46.440 the same calendar year, Carey Mullis was simultaneously 00:21:46.440 --> 00:21:49.339 trying to sell Elvis's DNA and launch a highly 00:21:49.339 --> 00:21:52.339 sophisticated next generation diagnostic platform. 00:21:52.680 --> 00:21:56.130 The contrast is just astonishing. Years later, 00:21:56.230 --> 00:22:00.289 in 2011, Mullis founded Ultramune LLC to pursue 00:22:00.289 --> 00:22:03.250 ideas about the immune system. This concept, 00:22:03.369 --> 00:22:06.009 far removed from DNA synthesis, it just shows 00:22:06.009 --> 00:22:09.009 his continued ability to conceptualize these 00:22:09.009 --> 00:22:11.730 innovative molecular solutions. Let's try to 00:22:11.730 --> 00:22:13.930 unpack this claimed breakthrough, Ultramune. 00:22:14.220 --> 00:22:16.500 Ultramune is a highly complex mechanism that 00:22:16.500 --> 00:22:20.819 proposes to revolutionize immunotherapy by leveraging 00:22:20.819 --> 00:22:22.960 the immune system's pre -existing memory. So 00:22:22.960 --> 00:22:25.240 not waiting for it to develop new memory, which 00:22:25.240 --> 00:22:27.220 is what a traditional vaccine does. Exactly. 00:22:27.339 --> 00:22:29.980 The basic idea is molecular redirection. So instead 00:22:29.980 --> 00:22:32.180 of creating new antibodies to fight a new flu 00:22:32.180 --> 00:22:34.140 strain, you trick the antibodies you already 00:22:34.140 --> 00:22:36.180 have into fighting the flu for you. That's it. 00:22:36.339 --> 00:22:38.740 The core tool is a synthetic chemical linker 00:22:38.740 --> 00:22:41.589 he called an alphamer. The goal is to divert 00:22:41.589 --> 00:22:44.349 a robust pre -existing immune response toward 00:22:44.349 --> 00:22:47.329 a new immediate threat. The analogy is like this. 00:22:47.569 --> 00:22:49.890 Imagine your body has a standing army that is 00:22:49.890 --> 00:22:52.250 already highly trained to fight one specific 00:22:52.250 --> 00:22:55.069 rare enemy. Let's call them alpha gulls. This 00:22:55.069 --> 00:22:57.869 army is massive. It's deployed and it's waiting. 00:22:58.069 --> 00:23:00.349 And every human has this alpha gull standing 00:23:00.349 --> 00:23:03.950 army. Yes. All humans have a strong natural immunity 00:23:03.950 --> 00:23:06.930 to something called alpha -1 ,3 -galactosyl galactose 00:23:06.930 --> 00:23:09.549 bonds or alpha -gal bonds. They're found in certain 00:23:09.549 --> 00:23:12.589 animal products. So the linker, the alphamer, 00:23:12.750 --> 00:23:15.069 is synthesized with an alpha -gal bond on one 00:23:15.069 --> 00:23:18.029 end. Okay. That alpha -gal end instantly attracts 00:23:18.029 --> 00:23:21.059 and binds to that massive... pre -existing antibody 00:23:21.059 --> 00:23:23.359 army. And the other end of this molecular bridge? 00:23:23.519 --> 00:23:25.799 The other end of the linker is designed to bind 00:23:25.799 --> 00:23:29.519 specifically to the new target, say, a surface 00:23:29.519 --> 00:23:32.680 protein on a deadly new strain of flu or maybe 00:23:32.680 --> 00:23:35.539 an anthrax spore. So the alphamer acts as a chemical 00:23:35.539 --> 00:23:37.839 bridge. It connects the massive pre -existing 00:23:37.839 --> 00:23:40.519 anti -alpha -gal antibodies directly to the surface 00:23:40.519 --> 00:23:42.859 of the new threatening pathogen. So you have 00:23:42.859 --> 00:23:45.910 literally as Mullis claimed, fooled your immune 00:23:45.910 --> 00:23:48.750 system into thinking that the deadly new pathogen 00:23:48.750 --> 00:23:50.710 is the common safe target it was already trained 00:23:50.710 --> 00:23:53.549 to destroy. And that offers immediate mass scale 00:23:53.549 --> 00:23:56.690 immunity. That's the theory. He claimed significant 00:23:56.690 --> 00:23:59.569 success. He stated the U .S. government paid 00:23:59.569 --> 00:24:03.210 $500 ,000 to use this technology against anthrax 00:24:03.210 --> 00:24:05.970 in preliminary trials. He claimed it resulted 00:24:05.970 --> 00:24:09.369 in a 100 % effective treatment, which was a huge 00:24:09.369 --> 00:24:12.230 increase from the previous treatment's 40 % effectiveness. 00:24:12.569 --> 00:24:15.369 Wow. He was also personally driven to apply it 00:24:15.369 --> 00:24:17.410 against a pathogenic strep bacterium because 00:24:17.410 --> 00:24:19.569 it had tragically killed a close friend of his. 00:24:20.130 --> 00:24:22.829 This invention just demonstrates that even late 00:24:22.829 --> 00:24:26.190 in his career, Mullis' capacity for high -level 00:24:26.190 --> 00:24:28.609 foundational molecular innovation was absolutely 00:24:28.609 --> 00:24:31.690 intact. He maintained his technical genius even 00:24:31.690 --> 00:24:34.390 as his personal philosophical views drifted further 00:24:34.390 --> 00:24:37.349 and further into controversy. And now we arrive 00:24:37.349 --> 00:24:39.289 at the heart of the paradox. This is the most 00:24:39.289 --> 00:24:42.450 difficult section to reconcile. Cary Mullis was 00:24:42.450 --> 00:24:44.849 undeniably brilliant, operating at the highest 00:24:44.849 --> 00:24:47.130 level of chemistry and molecular biology. No 00:24:47.130 --> 00:24:49.450 question. Yet at the same time, he was guided 00:24:49.450 --> 00:24:52.170 by this profound and sometimes dangerous skepticism 00:24:52.170 --> 00:24:54.470 that led him to embrace views that weren't just 00:24:54.470 --> 00:24:57.190 scientifically rejected, but they carried real 00:24:57.190 --> 00:24:59.710 world tragic consequences. The scientific community 00:24:59.710 --> 00:25:01.890 actually has a term for this phenomenon, which 00:25:01.890 --> 00:25:04.829 is highly relevant here. The skeptical inquirer 00:25:04.829 --> 00:25:08.130 coined the term Nobel disease. Nobel disease. 00:25:08.269 --> 00:25:10.869 That sounds ominous. What exactly is it? It's 00:25:10.869 --> 00:25:12.730 not. Not a medical condition, it's a tendency, 00:25:12.789 --> 00:25:15.470 an intellectual hazard that's been observed in 00:25:15.470 --> 00:25:18.930 some Nobel laureates. These are individuals who 00:25:18.930 --> 00:25:21.269 have reached the absolute pinnacle of achievement 00:25:21.269 --> 00:25:24.670 in one incredibly specialized field. Okay. And 00:25:24.670 --> 00:25:27.009 having received that ultimate validation, they 00:25:27.009 --> 00:25:28.970 often begin to believe that their specialized 00:25:28.970 --> 00:25:31.470 insight and critical genius applies universally 00:25:31.470 --> 00:25:34.809 to everything well outside their domain of expertise. 00:25:35.170 --> 00:25:37.049 So their certainty in one area becomes intellectual 00:25:37.049 --> 00:25:39.960 hubris in others. Precisely. They start to embrace 00:25:39.960 --> 00:25:43.019 scientifically implausible, often marginal or 00:25:43.019 --> 00:25:46.440 unsubstantiated ideas. And what guides this shift? 00:25:46.599 --> 00:25:49.640 It's rarely new, rigorous data. The Nobel disease 00:25:49.640 --> 00:25:52.559 often manifests as adopting views based on anecdotal 00:25:52.559 --> 00:25:54.839 evidence, conspiracy theories, or personal bias 00:25:54.839 --> 00:25:57.380 that overrides the very skepticism that defined 00:25:57.380 --> 00:25:59.900 their award -winning work. And Mullis is cited 00:25:59.900 --> 00:26:02.299 as a classic example of this. His ability to 00:26:02.299 --> 00:26:05.500 synthesize complex molecular data just seemed 00:26:05.500 --> 00:26:07.920 to vanish when he decided to weigh in on public 00:26:07.920 --> 00:26:10.740 health or environmental science. Let's start 00:26:10.740 --> 00:26:13.349 with the most serious implication. His views 00:26:13.349 --> 00:26:16.289 on HIV AIDS. Wallace became a vocal and influential 00:26:16.289 --> 00:26:19.769 figure in the HIV AIDS denialist movement. It's 00:26:19.769 --> 00:26:21.690 a position that placed him in direct opposition 00:26:21.690 --> 00:26:24.930 to the global scientific consensus. He expressed 00:26:24.930 --> 00:26:28.089 profound doubt that the HIV virus causes AIDS. 00:26:28.309 --> 00:26:30.470 And it's crucial to underscore this point, which 00:26:30.470 --> 00:26:33.029 really speaks to the Nobel disease. He never 00:26:33.029 --> 00:26:35.569 conducted any scientific research on either HIV 00:26:35.569 --> 00:26:39.210 or AIDS himself. None. His skepticism was entirely 00:26:39.210 --> 00:26:41.609 philosophical, not empirical. So what was his 00:26:41.609 --> 00:26:44.609 reasoning? In his 1998 autobiography, he explained 00:26:44.609 --> 00:26:46.829 it was highly anecdotal. He claimed he started 00:26:46.829 --> 00:26:48.670 questioning the consensus when he was compiling 00:26:48.670 --> 00:26:50.670 a report and couldn't find a single published 00:26:50.670 --> 00:26:53.450 reference that definitively stated HIV was the 00:26:53.450 --> 00:26:56.390 cause of AIDS. A reference he insisted should 00:26:56.390 --> 00:26:58.569 have been easy to locate if the science was settled. 00:26:58.849 --> 00:27:01.410 For him, the lack of an immediate simple citation 00:27:01.410 --> 00:27:03.869 became proof that the entire scientific establishment 00:27:03.869 --> 00:27:06.940 was wrong. That sounds less like scientific inquiry 00:27:06.940 --> 00:27:09.819 and more like a massive confirmation bias. His 00:27:09.819 --> 00:27:12.279 personal inability to find the exact source he 00:27:12.279 --> 00:27:15.200 wanted instantly led him to reject decades of 00:27:15.200 --> 00:27:17.140 evidence. That's the danger of the Nobel disease. 00:27:17.559 --> 00:27:20.460 He published an alternative hypothesis in 1994 00:27:20.460 --> 00:27:23.240 claiming AIDS was just an arbitrary diagnosis 00:27:23.240 --> 00:27:25.960 used when HIV antibodies were found in a patient's 00:27:25.960 --> 00:27:28.619 blood. He just dismissed the vast complexity 00:27:28.619 --> 00:27:31.039 of retroviral infection and immune collapse. 00:27:31.869 --> 00:27:34.269 And his position put him in alignment with other 00:27:34.269 --> 00:27:37.210 controversial figures. Yes. Seth Kalichman, an 00:27:37.210 --> 00:27:40.150 AIDS researcher who tracks denialism, named Mullis 00:27:40.150 --> 00:27:43.009 among the who's who of AIDS pseudoscientists. 00:27:43.170 --> 00:27:45.670 He was a vocal supporter of Peter Duisburg, another 00:27:45.670 --> 00:27:47.990 molecular biologist who championed denialism. 00:27:48.130 --> 00:27:50.349 And this is where the story shifts from personal 00:27:50.349 --> 00:27:53.829 eccentricity to profound tragedy. His scientific 00:27:53.829 --> 00:27:57.369 notoriety gave his fringe views a massive, destructive 00:27:57.369 --> 00:28:00.109 megaphone. The source material details some very 00:28:00.109 --> 00:28:02.589 serious implications. Specifically, the influence 00:28:02.589 --> 00:28:05.309 he had over the world leader. Yes. Mullis' HIV 00:28:05.309 --> 00:28:07.509 skepticism allegedly influenced the thinking 00:28:07.509 --> 00:28:09.930 of Thabo Mbeki, who was the president of South 00:28:09.930 --> 00:28:13.589 Africa from 1999 to 2008. And Mbeki, listening 00:28:13.589 --> 00:28:16.250 to denialists like Mullis, refused to implement 00:28:16.250 --> 00:28:19.170 life -saving antiretroviral drug programs nationwide. 00:28:19.369 --> 00:28:21.970 He preferred to focus on traditional, unproven 00:28:21.970 --> 00:28:24.740 remedies instead. And the cost of that policymaking, 00:28:24.960 --> 00:28:27.720 fueled in part by the intellectual weight Mull 00:28:27.720 --> 00:28:30.519 has provided to the movement, was just staggering. 00:28:30.779 --> 00:28:33.640 It's hard to calculate the full scope, but estimates 00:28:33.640 --> 00:28:36.599 from sources analyzing this period suggest Menelik's 00:28:36.599 --> 00:28:40.680 policies contributed to as many as 330 ,000 unnecessary 00:28:40.680 --> 00:28:44.660 deaths in South Africa. 330 ,000? The inventor 00:28:44.660 --> 00:28:47.079 of PCR, the tool that could rapidly diagnose 00:28:47.079 --> 00:28:50.299 HIV, became one of the most visible voices denying 00:28:50.299 --> 00:28:52.460 the cause of one of the 20th century's deaths. 00:29:00.000 --> 00:29:03.619 And his skepticism wasn't just limited to virology. 00:29:03.619 --> 00:29:06.640 He also took aim at environmental science, expressing 00:29:06.640 --> 00:29:08.579 disagreement with the scientific evidence for 00:29:08.579 --> 00:29:11.079 our role in climate change and ozone depletion. 00:29:11.160 --> 00:29:13.700 He had a specific cynicism about the motivations 00:29:13.700 --> 00:29:16.500 of scientists themselves. His perspective was 00:29:16.500 --> 00:29:19.269 fundamentally conspiratorial. He claimed that 00:29:19.269 --> 00:29:21.269 theories on these topics were the product of 00:29:21.269 --> 00:29:24.410 scientists and government bureaucrats conspiring 00:29:24.410 --> 00:29:27.349 to secure funding. So a jobs program for scientists. 00:29:27.670 --> 00:29:30.109 Essentially. He said, quote, science is being 00:29:30.109 --> 00:29:32.109 practiced by people who are dependent on being 00:29:32.109 --> 00:29:34.109 paid for what they're going to find out instead 00:29:34.109 --> 00:29:37.430 of searching for truth. For Mullis, the consensus 00:29:37.430 --> 00:29:39.769 on climate change wasn't the result of overwhelming 00:29:39.769 --> 00:29:43.009 evidence, but a collective economic effort to 00:29:43.009 --> 00:29:45.579 keep research grants flowing. To understand the 00:29:45.579 --> 00:29:48.400 source of this highly idiosyncratic worldview, 00:29:48.720 --> 00:29:52.720 this extreme skepticism toward consensus, combined 00:29:52.720 --> 00:29:55.279 with a deep acceptance of personal unverified 00:29:55.279 --> 00:29:57.940 experience, we really have to look at his own 00:29:57.940 --> 00:30:00.240 detailed accounts of altered states of consciousness. 00:30:00.579 --> 00:30:02.220 We've already noted his background in chemistry 00:30:02.220 --> 00:30:05.279 at UC Berkeley. Mullis practiced clandestine 00:30:05.279 --> 00:30:07.779 chemistry throughout his graduate studies. Specifically, 00:30:07.900 --> 00:30:10.740 he was synthesizing LSD. And his friend, Tom 00:30:10.740 --> 00:30:13.369 White, the one who got him the Cetus job. knew 00:30:13.369 --> 00:30:16.529 about this he was not only aware of it he cited 00:30:16.529 --> 00:30:19.789 it as evidence of mollusk's chemical skill he 00:30:19.789 --> 00:30:21.829 knew mollusk was a good chemist because quote 00:30:21.829 --> 00:30:24.670 he'd been synthesizing hallucinogenic drugs at 00:30:24.670 --> 00:30:27.950 uc berkeley that's an incredible inversion mastery 00:30:27.950 --> 00:30:30.430 of illicit chemistry proving his fitness for 00:30:30.430 --> 00:30:33.369 a professional biotech job and he didn't just 00:30:33.369 --> 00:30:36.230 synthesize psychedelics He was a very active 00:30:36.230 --> 00:30:38.670 user. He detailed it all in his autobiography, 00:30:38.910 --> 00:30:41.450 synthesizing and testing various psychedelic 00:30:41.450 --> 00:30:43.890 amphetamines. He talked about a particularly 00:30:43.890 --> 00:30:46.869 difficult trip on something called D .E .T. And 00:30:46.869 --> 00:30:49.650 he spoke openly about how important these experiences 00:30:49.650 --> 00:30:52.369 were for him. He said in a 1994 interview that 00:30:52.369 --> 00:30:55.009 taking LSD in the 60s and 70s was a mind opening 00:30:55.009 --> 00:30:57.789 experience. But what's really significant is 00:30:57.789 --> 00:30:59.829 the direct connection he made to his Nobel winning 00:30:59.829 --> 00:31:02.150 invention. Right. He said what? He said taking 00:31:02.150 --> 00:31:04.509 LSD was certainly much more important than any. 00:31:04.680 --> 00:31:06.480 courses I ever took. And he made this connection 00:31:06.480 --> 00:31:09.519 public. Oh, yes. During a symposium in Switzerland 00:31:09.519 --> 00:31:12.480 for Albert Hoffman, the man who first synthesized 00:31:12.480 --> 00:31:15.180 LSD Hoffman publicly recounted that Mullis had 00:31:15.180 --> 00:31:17.819 told him directly that LSD had helped him develop 00:31:17.819 --> 00:31:20.420 the polymerase chain reaction. He explicitly 00:31:20.420 --> 00:31:23.400 credited a psychedelic experience with one of 00:31:23.400 --> 00:31:25.440 the most crucial scientific inventions of the 00:31:25.440 --> 00:31:28.119 20th century. This profoundly nontraditional 00:31:28.119 --> 00:31:30.960 path to innovation is just central to his entire 00:31:30.960 --> 00:31:35.039 story. And if synthesizing LSD and crediting 00:31:35.039 --> 00:31:37.940 it with PCR wasn't enough to define his worldview 00:31:37.940 --> 00:31:41.039 as non -traditional, his interest went even further 00:31:41.039 --> 00:31:43.740 into the realm of the truly paranormal. He was 00:31:43.740 --> 00:31:46.759 definitely open to esoteric ideas. He professed 00:31:46.759 --> 00:31:48.799 a belief in astrology, for example, which is 00:31:48.799 --> 00:31:51.460 a pretty big departure from conventional scientific 00:31:51.460 --> 00:31:54.200 thinking. But the anecdotes in his autobiography, 00:31:54.420 --> 00:31:57.099 Dancing Naked in the Minefield, there would really 00:31:57.099 --> 00:31:59.400 stick with you. That title alone tells you so 00:31:59.400 --> 00:32:02.319 much. It does. He detailed two specific paranormal 00:32:02.319 --> 00:32:05.240 anecdotes that just defy logic. The first involves 00:32:05.240 --> 00:32:08.359 a ghostly visitation. He detailed witnessing 00:32:08.359 --> 00:32:11.059 what he called the non -substantial form of his 00:32:11.059 --> 00:32:13.460 deceased grandfather. And what did he do? He 00:32:13.460 --> 00:32:16.119 casually offered the apparition a beer. Offering 00:32:16.119 --> 00:32:19.200 a ghost a beer. That incredible comfort level 00:32:19.200 --> 00:32:22.059 with something outside empirical reality, a total 00:32:22.059 --> 00:32:24.859 suspension of disbelief, is amazing. It's the 00:32:24.859 --> 00:32:27.339 exact opposite of the hyperskepticism he applied 00:32:27.339 --> 00:32:29.799 to climate change data. And the second anecdote 00:32:29.799 --> 00:32:32.019 is the one that has truly entered the scientific 00:32:32.019 --> 00:32:35.319 folklore surrounding Carey Mullis. His encounter 00:32:35.319 --> 00:32:39.230 with a fluorescent... Talking raccoon. A talking, 00:32:39.269 --> 00:32:42.809 glowing raccoon. Mullis, the Nobel laureate, 00:32:42.849 --> 00:32:45.529 detailed this in his autobiography and suggested 00:32:45.529 --> 00:32:47.710 the animal might have been an extraterrestrial. 00:32:47.890 --> 00:32:51.309 The detail itself is just astounding. He recounts 00:32:51.309 --> 00:32:53.890 being at his cabin in the woods, and this raccoon 00:32:53.890 --> 00:32:56.750 walks up and starts speaking to him. The raccoon, 00:32:56.809 --> 00:32:59.769 he noted, was fluorescent. And Mullis didn't 00:32:59.769 --> 00:33:02.109 dismiss this as a hallucination or some elaborate 00:33:02.109 --> 00:33:05.670 joke. He integrated it into his reality, suggesting 00:33:05.670 --> 00:33:08.150 it was pre - that reality itself is far stranger 00:33:08.150 --> 00:33:11.210 than consensus science allows. This detail just 00:33:11.210 --> 00:33:13.589 perfectly encapsulates the fundamental conflict 00:33:13.589 --> 00:33:16.119 in his life. He was a molecular master whose 00:33:16.119 --> 00:33:18.460 scientific discipline gave him exponential certainty 00:33:18.460 --> 00:33:20.960 in the lab. Yet his personal philosophy was a 00:33:20.960 --> 00:33:23.299 free -for -all, embracing the most far -fetched 00:33:23.299 --> 00:33:25.740 possibilities imaginable. As we conclude this 00:33:25.740 --> 00:33:28.220 deep dive, the figure of Carey Mullis remains 00:33:28.220 --> 00:33:31.359 profoundly difficult to categorize. On one side, 00:33:31.400 --> 00:33:34.420 you have the recipient of the 1993 Nobel Prize 00:33:34.420 --> 00:33:37.539 in Chemistry and the Japan Prize, honored for 00:33:37.539 --> 00:33:39.579 providing a technology that fundamentally changed 00:33:39.579 --> 00:33:42.079 medicine and forensics. Indispensable technology. 00:33:42.500 --> 00:33:44.319 And on the other side, you have... a man who 00:33:44.319 --> 00:33:47.680 wielded his scientific authority to promote scientifically 00:33:47.680 --> 00:33:51.400 unfounded claims especially his aids denialism 00:33:51.400 --> 00:33:54.640 which through political influence likely resulted 00:33:54.640 --> 00:33:57.000 in hundreds of thousands of avoidable deaths 00:33:57.000 --> 00:33:59.640 he was a character defined by these massive contradictory 00:33:59.640 --> 00:34:02.400 energies right up until his death in 2019 at 00:34:02.400 --> 00:34:04.859 the age of 74 from complications of pneumonia 00:34:04.859 --> 00:34:07.140 we know he loved surfing he was married four 00:34:07.140 --> 00:34:10.179 times played guitar and sang he was constantly 00:34:10.179 --> 00:34:12.829 moving The story of Cary Mullis really forces 00:34:12.829 --> 00:34:15.190 you, the learner, to confront the crucial difference 00:34:15.190 --> 00:34:18.369 between domain expertise and general critical 00:34:18.369 --> 00:34:20.929 thinking. Mullis was a world -class technician. 00:34:21.289 --> 00:34:23.849 His ability to innovate within molecular chemistry 00:34:23.849 --> 00:34:27.409 was peerless. It gave us PCR and the highly innovative 00:34:27.409 --> 00:34:30.469 ultramune concept. But his skepticism outside 00:34:30.469 --> 00:34:32.789 his precise field was not guided by the same 00:34:32.789 --> 00:34:35.389 level of evidence and rigor. When he talked about 00:34:35.389 --> 00:34:38.030 broader public issues, he was guided by anecdote, 00:34:38.309 --> 00:34:54.590 personal convenience, and a consistency. And 00:34:54.590 --> 00:34:59.329 that brings us to our final provocative thought 00:34:59.329 --> 00:35:02.360 for you to chew on. PCR is a tool of almost surgical 00:35:02.360 --> 00:35:05.000 precision. It allows scientists to analyze the 00:35:05.000 --> 00:35:07.340 smallest traces of DNA to determine objective 00:35:07.340 --> 00:35:10.059 truth in medicine, in forensics, in genetics. 00:35:10.260 --> 00:35:13.199 It leaves almost no room for ambiguity. Given 00:35:13.199 --> 00:35:16.119 Carey Mullis' deep personal belief in the paranormal, 00:35:16.360 --> 00:35:19.099 in astrology, and in a fluorescent talking raccoon 00:35:19.099 --> 00:35:21.480 that might have been an alien, what does it truly 00:35:21.480 --> 00:35:24.119 mean when the man who invented one of our greatest 00:35:24.119 --> 00:35:26.239 instruments for revealing scientific certainty 00:35:26.239 --> 00:35:30.119 was so actively comfortable embracing the scientifically 00:35:30.119 --> 00:35:32.800 implausible in his own life? It makes you wonder 00:35:32.800 --> 00:35:35.460 if that very willingness to entertain the absurd, 00:35:35.539 --> 00:35:38.059 to discard conventional wisdom entirely, was 00:35:38.059 --> 00:35:40.159 a necessary prerequisite for the brilliance that 00:35:40.159 --> 00:35:41.400 led to PCR in the first place.