WEBVTT - HIV: Racing to Identify a Killer 0:00:06.240 --> 0:00:09.240 HIV was one of the most important viruses of the 0:00:09.240 --> 0:00:13.640 past century. It caused profound suffering, It led to intense 0:00:13.720 --> 0:00:19.320 political and social confrontations and eventually transformations. And for scientists, 0:00:19.880 --> 0:00:23.439 HIV posed a complicated set of problems that still have 0:00:23.560 --> 0:00:27.400 not been entirely solved. On today's show, we're going to 0:00:27.400 --> 0:00:31.320 focus on the scientists and the science. I'm Jacob Goldstein, 0:00:31.400 --> 0:00:34.479 and this is Incubation, a show about viruses. In the 0:00:34.479 --> 0:00:36.800 first half of the show, we'll talk with a virologist. 0:00:37.159 --> 0:00:39.600 She was working at a hospital in the early nineteen 0:00:39.640 --> 0:00:42.239 eighties when the first patients began to show up with 0:00:42.320 --> 0:00:46.040 this deadly disease that no one understood. She was part 0:00:46.040 --> 0:00:49.320 of a team that rushed to identify the virus behind 0:00:49.360 --> 0:00:52.360 the disease. Then, in the second half of the show, 0:00:52.600 --> 0:00:55.560 we'll hear from a physician who's been working for over 0:00:55.680 --> 0:01:02.560 twenty years to develop an HIV vaccine. We're going to 0:01:02.640 --> 0:01:07.479 start today with my conversation with Christine Ruzu. Christine became 0:01:07.560 --> 0:01:10.800 part of a famous team that ultimately wound up in 0:01:10.840 --> 0:01:15.640 an international fight over who discovered HIV in nineteen eighty one. 0:01:15.920 --> 0:01:19.479 Christine was a young researcher in the virology lab at 0:01:19.560 --> 0:01:23.199 Bishaw Claude Bernard Hospital. It's a hospital in Paris that's 0:01:23.240 --> 0:01:28.000 dedicated to infectious diseases. Christine remembers when the first patients 0:01:28.040 --> 0:01:31.160 with this mysterious new illness started coming to the hospital. 0:01:31.600 --> 0:01:36.080 We start to see those patients. They were young, they 0:01:36.120 --> 0:01:41.520 were gay, and they had a lot of infections and 0:01:41.640 --> 0:01:42.560 they were dying. 0:01:43.720 --> 0:01:45.840 Like did you see yourself in them at all? Like 0:01:45.920 --> 0:01:49.280 here of just some young healthy person, suddenly they get 0:01:49.320 --> 0:01:50.280 sick and die. 0:01:50.840 --> 0:01:55.880 Yeah, we had patients with our age. I was thirty 0:01:56.680 --> 0:02:03.920 at the beginning. Those who were hospitalized died rapidly. They 0:02:03.920 --> 0:02:07.720 come to the hospital very late in the disease, and 0:02:08.800 --> 0:02:14.080 within the gay community, I could see progressively some of 0:02:14.120 --> 0:02:17.800 them with big lymphnods, some of them with the caposis 0:02:17.880 --> 0:02:19.800 are comma very difficult. 0:02:20.160 --> 0:02:23.240 And so what are you what are you thinking when 0:02:23.400 --> 0:02:27.799 these when these people start showing up with these strange symptoms. 0:02:28.120 --> 0:02:32.120 From the beginning, the sign of our infection was there. 0:02:33.000 --> 0:02:37.000 When you look at the number in blood of cells, 0:02:37.160 --> 0:02:41.520 you can make the difference between bacteria and virus. Is infection. 0:02:42.360 --> 0:02:48.160 And we we discuss with the different teams and we 0:02:48.240 --> 0:02:52.840 start with the ideas that could be a retrovirus, a 0:02:52.960 --> 0:02:55.160 very specific retrovirus. 0:02:55.680 --> 0:02:58.400 Why do you think retrovirus? We should say, by the way, 0:02:58.440 --> 0:03:01.560 retrovirus is a virus that use is RNA instead of DNA. 0:03:01.600 --> 0:03:02.400 Why do you think it's that? 0:03:03.400 --> 0:03:07.720 So how can I say it was vious. 0:03:07.400 --> 0:03:10.640 Alamodo alamode like it was sort of the fashionable virus. 0:03:10.639 --> 0:03:13.920 It was the it kind of virus, fashionable virus. Yes, 0:03:14.280 --> 0:03:17.560 you and your colleagues have this hypothesis, we think this 0:03:17.600 --> 0:03:19.960 is a retrovirus. What is the first thing you do? 0:03:20.960 --> 0:03:23.600 We went to see Luke Montagnier and Francos virus and 0:03:23.600 --> 0:03:24.560 you see in Pastor in. 0:03:24.520 --> 0:03:29.240 Situew Luke Montaigne worked with Francois Barressing. You see at 0:03:29.240 --> 0:03:32.679 the Pastor Institute, these two scientists who will become very famous. 0:03:32.960 --> 0:03:36.240 Yeah, yeah, And we asked them, do you think that 0:03:36.280 --> 0:03:40.600 it's possible to try to isolate the virus retrovirus? And 0:03:40.640 --> 0:03:46.280 he said, that's a good idea. Maybe we can try. Maybe, Okay, 0:03:46.560 --> 0:03:50.080 we'll do the work. So we come back to the 0:03:50.160 --> 0:03:53.360 working group and we decide to take the lymph nodes 0:03:53.400 --> 0:03:57.000 because they were very big, and to take a blood 0:03:57.600 --> 0:04:00.720 in a nearly a symptomatic patients. 0:04:01.120 --> 0:04:04.800 Okay, So You're at the hospital seeing these patients sick 0:04:05.000 --> 0:04:08.080 with what you think might be a retrovirus, and you're 0:04:08.120 --> 0:04:11.840 taking samples from patients at what seemed like different stages 0:04:11.880 --> 0:04:15.720 of the disease and sending them to these academic researchers 0:04:15.720 --> 0:04:17.080 at the Pastor Institute. 0:04:17.400 --> 0:04:24.839 What happens next fifteen days after Luc Montaignefon and we 0:04:25.000 --> 0:04:29.440 have something. We have something, We have something. 0:04:29.800 --> 0:04:33.480 Front Soise Barre Snusi. That researcher who was working with 0:04:33.520 --> 0:04:37.800 Montagnier had discovered evidence that suggested a retrovirus was in 0:04:37.839 --> 0:04:41.520 fact the culprit for this mysterious disease. The team developed 0:04:41.520 --> 0:04:45.480 a blood test to identify patients with antibodies to this virus. 0:04:46.200 --> 0:04:49.600 Test allowed researchers to diagnose the virus not only in 0:04:49.640 --> 0:04:53.960 gay men, but also in IV drug users and hemophiliacs, 0:04:54.440 --> 0:04:57.680 But the illness was still a mystery, and in particular, 0:04:58.200 --> 0:05:00.880 even though they knew it was a retrovisvirus, no one 0:05:00.880 --> 0:05:05.080 had actually seen and correctly identified it. So now researchers 0:05:05.080 --> 0:05:08.039 around the world are in this race both to help 0:05:08.120 --> 0:05:11.960 patients and to find the virus. On the team, Christine 0:05:12.000 --> 0:05:16.240 was working with an electron microscopist a specialist in looking 0:05:16.279 --> 0:05:20.000 for things through an electron microscope, spent his days trying 0:05:20.040 --> 0:05:21.360 to find this virus. 0:05:22.080 --> 0:05:25.760 He said, for the first days, no, I can't see nothing. 0:05:26.279 --> 0:05:29.599 And then after three days he said, come and see. 0:05:29.680 --> 0:05:31.200 I'm sure there is something. 0:05:31.920 --> 0:05:34.400 What is the microscopycy happening in the cell? 0:05:35.200 --> 0:05:37.680 He sees the budding of the virus at the surface 0:05:37.720 --> 0:05:38.760 of the lymphosize. 0:05:38.960 --> 0:05:42.160 Uh huh, And so does that mean coming out, going in? 0:05:42.240 --> 0:05:43.200 What does budding mean? 0:05:43.360 --> 0:05:48.440 In that kind of budding is when the virus has 0:05:48.480 --> 0:05:52.080 been within the cells he has to get out, and 0:05:52.320 --> 0:05:55.840 he could see free virl particles and he could see 0:05:55.880 --> 0:06:01.120 also that those particles came from those infected cells. Budding 0:06:01.279 --> 0:06:03.960 is a Commondi budding. 0:06:04.160 --> 0:06:07.320 It's sort of exploding out of the cell or leaving the. 0:06:07.279 --> 0:06:10.320 Cell, exactly, the moment of leaving the cell. 0:06:10.440 --> 0:06:12.920 That's so this is like a big moment, right. You're 0:06:12.960 --> 0:06:15.680 not only seeing the virus, but you're actually seeing it 0:06:15.839 --> 0:06:16.560 as it's. 0:06:16.480 --> 0:06:18.520 Leaving the host cell exactly. 0:06:19.320 --> 0:06:21.440 Do you remember when you saw that image for the 0:06:21.480 --> 0:06:22.080 first time. 0:06:22.640 --> 0:06:26.479 Ah, yes, I remember very well, because at that time 0:06:26.960 --> 0:06:31.320 we say, oh, now what we have to do with that. 0:06:32.520 --> 0:06:34.120 We have to organize everything. 0:06:35.080 --> 0:06:37.720 So your response is not Wow, we did it, it's 0:06:37.800 --> 0:06:39.640 oh my god, We've got so much work to do. 0:06:40.000 --> 0:06:44.400 Yeah. You know, in France we say we have the 0:06:44.560 --> 0:06:48.000 nose in the bicycle, I mean. 0:06:49.720 --> 0:06:53.520 The steering the handlebars, just looking at not looking at 0:06:53.760 --> 0:06:56.680 your head down those to the handlebars. 0:06:57.040 --> 0:06:57.840 Yeah, exactly. 0:06:58.080 --> 0:07:01.240 And so that's the moment when you're basic saying we 0:07:01.440 --> 0:07:04.760 found it, we found the virus that is causing this 0:07:04.880 --> 0:07:05.960 mysterious disease. 0:07:06.320 --> 0:07:09.400 Yeah, and a paper with the publish in science. 0:07:10.280 --> 0:07:13.680 Meanwhile, in the United States there is another team working 0:07:13.720 --> 0:07:17.280 to study the disease. It's led by Robert Gallo, a 0:07:17.320 --> 0:07:21.360 famous virologist at the National Institutes of Health. And this 0:07:21.600 --> 0:07:25.320 is where a story of discovery becomes a story of 0:07:25.360 --> 0:07:29.480 a competition, of a fight over who really discovered the virus. 0:07:30.040 --> 0:07:32.680 But it didn't start out as a fight. It started 0:07:32.720 --> 0:07:33.960 out as a collaboration. 0:07:35.280 --> 0:07:38.520 Luke Montagne decided, because he knows very well Bob Gelou 0:07:38.600 --> 0:07:41.800 at that time, he decided to collaborate and to cooperate, 0:07:42.440 --> 0:07:46.679 and he sent samples with the virus to Bob Galu. Okay, 0:07:46.800 --> 0:07:48.040 can you imagine that? 0:07:48.360 --> 0:07:51.520 Well, that's like the ideal of science, right, They're not rivals. 0:07:51.520 --> 0:07:56.360 They're working together to increase humanity's understanding exactly. 0:07:57.080 --> 0:08:04.560 Yeah. Yeah. And then Bob Galou publish a discovery of 0:08:04.760 --> 0:08:05.600 AS virus. 0:08:05.960 --> 0:08:08.960 H huh, you're using air quotes as you say discovery. 0:08:09.040 --> 0:08:15.640 Yeah, yeah, in April nineteen eighty four, and he said, 0:08:16.080 --> 0:08:18.520 we discovers the virus. 0:08:18.600 --> 0:08:21.400 Just from Gallo's point of view, what is his claim 0:08:21.560 --> 0:08:23.680 in eighty four of discovery. 0:08:23.720 --> 0:08:29.760 He claims that the virus was not completely identical to 0:08:30.080 --> 0:08:34.640 our virus, and he says mine is really AS virus 0:08:34.679 --> 0:08:35.560 in the United States. 0:08:35.600 --> 0:08:38.720 So Gallo was saying he discovered the AIDS virus in 0:08:38.760 --> 0:08:42.960 the United States. From your perspective, your lab already discovered 0:08:42.960 --> 0:08:46.200 the virus. What do you think when you read this paper? 0:08:47.800 --> 0:08:50.760 It was a very difficult period of time for us. 0:08:51.160 --> 0:08:54.960 And in France he said, you can't imagine. Of course, 0:08:55.000 --> 0:08:57.600 Bob Gallo is right and your virus is not the 0:08:57.720 --> 0:08:58.160 right one. 0:08:58.559 --> 0:09:01.079 Oh, I would not have guessed that. Wait, even even 0:09:01.120 --> 0:09:03.400 in France they said that. I am surprised. 0:09:03.640 --> 0:09:07.400 Even in France. You know, we were young frenchie. Yeah yeah, 0:09:08.720 --> 0:09:13.719 those little frenchie compared to the bag Gallo, it's not possible. 0:09:14.960 --> 0:09:18.959 Bob Gallo is very important in the nine i H 0:09:19.640 --> 0:09:23.240 compared to us. We are not professor, We were just 0:09:23.400 --> 0:09:26.440 assistant in labs. We are so young. 0:09:27.120 --> 0:09:29.360 What do you think when this is happening and people 0:09:29.440 --> 0:09:31.440 are saying this you personally, we. 0:09:31.800 --> 0:09:37.120 Thought that we had to go more rapidly for the 0:09:37.200 --> 0:09:44.160 demonstration of our RUS and with particularly with zero logical tests. 0:09:44.200 --> 0:09:46.439 I'm in the screening with my test. 0:09:46.880 --> 0:09:48.240 Yeah, you know, we. 0:09:48.040 --> 0:09:52.880 Were working and working and working publishing with US, with Italian, 0:09:53.000 --> 0:09:57.560 with CDC. We have to work more and more to 0:09:57.679 --> 0:10:01.600 show that we were right at that time. So we 0:10:01.840 --> 0:10:07.080 progress a lot with the number of patients which increased. 0:10:07.080 --> 0:10:08.680 That'side time everywhere. 0:10:11.080 --> 0:10:14.600 In nineteen eighty five, the Pastor Institute sued the United 0:10:14.640 --> 0:10:17.920 States government, claiming that Bob Gallo's team had used the 0:10:17.960 --> 0:10:21.520 French samples to isolate the virus and create an HIV 0:10:21.600 --> 0:10:25.480 blood test. The lawsuit was eventually settled, and in April 0:10:25.559 --> 0:10:28.440 nineteen eighty seven, Ronald Reagan, the President of the US, 0:10:28.520 --> 0:10:31.560 and Jacques Chirack, the Prime Minister of France, actually held 0:10:31.640 --> 0:10:35.160 a joint press conference where they announced that both countries 0:10:35.160 --> 0:10:39.080 would share the discovery. That same month, Bob Gallo and 0:10:39.160 --> 0:10:42.839 Luke Montagnier co published a paper explaining the sequence of 0:10:42.880 --> 0:10:45.520 events and sharing credit for discoveries. 0:10:46.480 --> 0:10:53.160 But maybe few years after we had the technology for 0:10:53.880 --> 0:10:58.280 genome sequencing, and you know, the story is the end 0:10:58.320 --> 0:11:02.760 of the story. Genetics sequencing of the virus from Bob 0:11:02.800 --> 0:11:06.600 Gallow's lab and from our LAMB show that the Bob's 0:11:06.640 --> 0:11:10.200 Gatherous lab was exactly the same that our virus. 0:11:12.679 --> 0:11:16.119 After that, genetic sequencing proved that the viruses were identical. 0:11:16.480 --> 0:11:18.760 Bob Gallow's lab said the whole thing was a kind 0:11:18.760 --> 0:11:21.960 of a mix up, the result of an accidental contamination. 0:11:22.920 --> 0:11:25.440 The final verdict in the fight over the discovery of 0:11:25.559 --> 0:11:27.719 HIV came decades later. 0:11:28.240 --> 0:11:32.160 And we waited until two thousand and eight against the 0:11:32.200 --> 0:11:37.000 Nobel price, and Bob Gallo did not receive the Nobel price. 0:11:37.600 --> 0:11:40.520 And the people from the Nobel Price, the jury of 0:11:40.679 --> 0:11:45.160 a Nobel Price, explain us they look for They looked 0:11:45.160 --> 0:11:49.920 at everything in Bob Gatherous lab, everything in Luc Montagni labs, 0:11:49.960 --> 0:11:52.679 and they understood very well as the story with a 0:11:52.679 --> 0:11:57.600 sequencing showing that the virus was our virus. 0:11:58.920 --> 0:12:01.960 Bob Gallo is still all credited with important research on 0:12:02.000 --> 0:12:05.600 the links between HIV and AIDS, and even when the 0:12:05.640 --> 0:12:09.000 Nobel was announced, Luke Montaigner was quoted as saying that 0:12:09.040 --> 0:12:12.160 the Gallo team deserved to share. How did you feel 0:12:12.200 --> 0:12:14.319 when you found out about the Nobel Prize? 0:12:15.800 --> 0:12:21.319 Very well satisfied because you know, we started with history 0:12:21.320 --> 0:12:24.440 in nineteen eighty three and it was a long time 0:12:24.559 --> 0:12:28.720 ago after, yeah, and it was very important to be 0:12:28.920 --> 0:12:30.760 recognized even later. 0:12:31.600 --> 0:12:36.560 Yes, I mean the Nobel Prize is legit recognition. It's 0:12:36.640 --> 0:12:39.640 for real, Like if you want to be vindicated in science, 0:12:39.679 --> 0:12:41.440 it's tough to beat the Nobel Prize. 0:12:41.679 --> 0:12:47.319 Yeah. After yeah, after fighting a lot with US people 0:12:47.559 --> 0:12:52.160 with even in France, it was a Greek moment in Stockholm. 0:12:52.640 --> 0:12:59.240 But we built a working group with the physicians, semanologist 0:12:59.320 --> 0:13:06.520 and self biologists in order to try to understand what 0:13:06.640 --> 0:13:09.640 I want with those patients. And that's a very important 0:13:09.679 --> 0:13:14.320 point of the story because we were a multidisciplinary working 0:13:14.400 --> 0:13:18.800 group and you know it's a listen learned. You can't 0:13:19.120 --> 0:13:23.080 do such a research alone, you can't. 0:13:24.000 --> 0:13:27.120 Wonderful, Thank you so much for your time. It was 0:13:28.000 --> 0:13:28.920 great to talk with you. 0:13:29.240 --> 0:13:30.120 Thank you very much. 0:13:31.640 --> 0:13:35.800 Christine, whoso has spent the last forty years studying HIV 0:13:36.000 --> 0:13:39.600 and AIDS, including work on preventing transmission of the virus 0:13:39.640 --> 0:13:43.480 from mothers to children. She's currently a professor of virology 0:13:43.559 --> 0:13:57.959 at Paris Descartes University. So can we talk about HIV? 0:13:58.640 --> 0:13:59.960 Sure, that would be wonderful. 0:14:01.080 --> 0:14:02.880 My guest for the second half of the show is 0:14:03.000 --> 0:14:06.960 Richard Koup. Richard is the Deputy director of the Vaccine 0:14:07.040 --> 0:14:10.320 Research Center at the National Institutes of Health. He has 0:14:10.360 --> 0:14:14.720 spent his career studying and testing HIV vaccines, and, as 0:14:14.720 --> 0:14:20.040 he explains, creating a vaccine against HIV is this extraordinarily 0:14:20.120 --> 0:14:23.520 hard problem that goes to the heart of why this 0:14:23.760 --> 0:14:28.160 virus is so insidious? Why did you become an infectious 0:14:28.200 --> 0:14:28.880 disease doctor? 0:14:29.600 --> 0:14:33.080 You know, when I was in medical school and my training, 0:14:34.160 --> 0:14:38.320 I noticed that almost all of the different specialties in 0:14:38.400 --> 0:14:42.040 medicine dealt with chronic illness, and infectious disease was the 0:14:42.280 --> 0:14:46.920 one specialty where you didn't have to deal with chronic illnesses. 0:14:46.960 --> 0:14:51.960 What you actually did was you cured people. So people 0:14:52.000 --> 0:14:55.440 would come in with infections, you gave them antibiotics and 0:14:55.480 --> 0:14:58.520 they were cured, and that felt very good. 0:14:59.400 --> 0:15:02.760 Like Christine lose you. Richard Kaup started his career at 0:15:02.760 --> 0:15:06.400 the beginning of the AIDS epidemic, and over time HIV 0:15:06.560 --> 0:15:09.800 would in fact become a chronic disease, but that was 0:15:09.840 --> 0:15:10.440 in the future. 0:15:10.800 --> 0:15:16.360 What we knew then was the genetics of the virus, 0:15:16.360 --> 0:15:20.480 but we didn't really know much about the immune response, 0:15:20.920 --> 0:15:24.040 so we were just sort of mapping out what they 0:15:24.080 --> 0:15:25.160 were responding to. 0:15:25.720 --> 0:15:28.840 It was like we knew what the virus was, but 0:15:28.920 --> 0:15:32.120 we didn't really understand what it did, how it worked. 0:15:32.520 --> 0:15:36.000 Yeah, not really, And we knew that for most viruses, 0:15:36.200 --> 0:15:40.080 in a vaccine, you want to target the envelope protein, 0:15:40.200 --> 0:15:42.800 the protein that's on the surface of the virus that 0:15:42.960 --> 0:15:46.320 is used to enter cells, and so that's what most 0:15:46.360 --> 0:15:48.920 of the first vaccines were directed against. 0:15:49.040 --> 0:15:52.760 Which is like very reasonable, right, Like that's what scientists 0:15:52.960 --> 0:15:55.000 just did with COVID, and it's like that is sort 0:15:55.040 --> 0:15:58.240 of what's floating around in your body and it's what 0:15:58.360 --> 0:16:00.720 the immune system sees. So it seemed it's logical that 0:16:00.720 --> 0:16:05.040 you would want to do that. What happened when when 0:16:05.120 --> 0:16:08.120 you and other researchers tried that with HIV. 0:16:08.720 --> 0:16:12.960 Well, you generated an immune response, so you've got antibodies 0:16:12.960 --> 0:16:15.920 against the envelope protein. 0:16:16.400 --> 0:16:18.680 Seems good, that's what you want, Yeah. 0:16:18.600 --> 0:16:23.720 But those antibodies didn't do anything, they didn't neutralize the virus. 0:16:23.960 --> 0:16:26.720 What was the next thought, What was the next idea? 0:16:27.280 --> 0:16:30.440 The thought then was, well, what we should do is 0:16:30.560 --> 0:16:35.840 stimulate T cells, so T cells recognize virally infected cells 0:16:35.840 --> 0:16:38.800 and kill them. And there were there was a lot 0:16:38.840 --> 0:16:42.040 of data to suggest that people who were long term 0:16:42.120 --> 0:16:45.680 non progressors, so these are people who are infected with 0:16:45.880 --> 0:16:52.120 HIV but they don't progress to full blown AIDS, they 0:16:52.160 --> 0:16:56.000 had really good T cells that were attacking the virus. 0:16:56.760 --> 0:17:01.880 So basically there is this universe of people who have HIV, 0:17:02.000 --> 0:17:06.080 who are HIV positive, but who are not getting really sick. 0:17:06.119 --> 0:17:08.120 And this is an era when most people who get 0:17:08.280 --> 0:17:12.480 HIV get AIDS and die essentially right, get very sick. 0:17:12.520 --> 0:17:15.320 And so you look at these patients and you see 0:17:15.960 --> 0:17:19.000 that there is a particular kind of a cell in 0:17:19.040 --> 0:17:22.000 their immune system that seems to be fighting the disease. 0:17:22.080 --> 0:17:25.680 Is that right, That's absolutely correct. You hit the nail 0:17:25.720 --> 0:17:30.720 on the head there. And so with this insight, people said, 0:17:30.840 --> 0:17:36.080 what we should do is stimulate with a vaccine, not antibodies, 0:17:36.480 --> 0:17:38.720 but CD eight positive T cells. 0:17:39.280 --> 0:17:41.840 So basically, like the first idea was sort of a 0:17:41.880 --> 0:17:45.240 classic vaccine idea like let's create a vaccine based on 0:17:45.240 --> 0:17:48.560 antibodies that didn't work, and so then the second idea 0:17:48.720 --> 0:17:52.240 is to stimulate T cells, this particular part of the 0:17:52.240 --> 0:17:55.200 immune response that vaccines don't usually deal with. 0:17:55.560 --> 0:17:59.400 Instead, it was felt that those vaccines may not keep 0:17:59.440 --> 0:18:04.160 people from getting infected, but if they had the vaccine 0:18:04.320 --> 0:18:07.280 and the people got infected, that they may all become 0:18:07.400 --> 0:18:10.399 long term non progressors, so they wouldn't get sick. 0:18:10.800 --> 0:18:13.240 Which is actually what you care about, right, what you 0:18:13.280 --> 0:18:16.119 want is for people to live long, healthy lives. 0:18:16.520 --> 0:18:17.840 That's absolutely correct. 0:18:18.119 --> 0:18:21.679 So you do this trial and what do you find? 0:18:22.359 --> 0:18:24.760 It did not do what we had hoped it would do. 0:18:25.480 --> 0:18:27.640 And what year more or less is this. 0:18:27.960 --> 0:18:32.320 We've been doing this for twenty years of efficacy trials, 0:18:32.680 --> 0:18:35.760 and seven different trials have been done and none of 0:18:35.800 --> 0:18:38.360 them have shown really good protection. 0:18:39.080 --> 0:18:43.880 So a long time into the history of this disease. 0:18:44.000 --> 0:18:47.639 This is decades of work in and if you'll allow 0:18:47.720 --> 0:18:51.320 me this sort of dumb journaloius question, what was that like? 0:18:52.920 --> 0:18:58.159 It's terribly disappointing. You know, you put a lot of 0:18:58.200 --> 0:19:03.520 effort into this, your hoping that finally something will work 0:19:03.560 --> 0:19:08.240 against this illness. And when it doesn't work at all, 0:19:09.200 --> 0:19:13.160 you're really back to square one. So it's extremely disheartening. 0:19:13.960 --> 0:19:15.960 Why is it so hard to vaccinate against HIV? 0:19:16.520 --> 0:19:22.440 So unlike most viruses, most viruses enter cells of your body, 0:19:22.560 --> 0:19:26.520 they use the machinery of those cells to replicate, and 0:19:26.560 --> 0:19:29.560 then they leave your body and they're gone. They leave, 0:19:30.040 --> 0:19:33.080 and you're no longer sick. When they're not there. 0:19:33.440 --> 0:19:35.680 You get a cold and then you get better. 0:19:35.640 --> 0:19:40.040 Right, and there's no cold virus left in the cells 0:19:40.080 --> 0:19:40.520 of your. 0:19:40.359 --> 0:19:44.840 Body because your immune system destroys all the virus, right. 0:19:45.000 --> 0:19:48.200 And so with a vaccine, all you need to do, 0:19:48.280 --> 0:19:50.800 actually you don't need to prevent the infection. All you 0:19:50.840 --> 0:19:54.120 have to do is knock down the amount of virus 0:19:54.160 --> 0:20:01.080 it's replicating to decrease your symptoms until the virus goes away. 0:20:01.680 --> 0:20:02.080 Okay. 0:20:02.640 --> 0:20:08.960 HIV is different in that it infects certain cells of 0:20:09.000 --> 0:20:13.879 your body and it actually integrates its genome into the 0:20:13.960 --> 0:20:17.520 genome of those cells and it never goes away. 0:20:18.040 --> 0:20:18.840 Huh. 0:20:18.920 --> 0:20:21.200 I like to think of it like playing whack a mole. 0:20:21.800 --> 0:20:25.679 So it's basically hibernating in those cells, and then the 0:20:25.800 --> 0:20:28.159 virus will will pop out every now and then, and 0:20:28.240 --> 0:20:31.280 you need to try and knock it down, and our 0:20:31.480 --> 0:20:37.960 antiretroviral therapy that we give to individuals doesn't do anything 0:20:38.800 --> 0:20:44.840 to the virus that's sitting there hibernating. It's only when 0:20:45.080 --> 0:20:49.240 when it reactivates and pops itself up that the antiretrovirals 0:20:49.320 --> 0:20:50.160 have any effect. 0:20:50.640 --> 0:20:53.600 This is why the antiretrovirals can keep you from getting sick, 0:20:53.640 --> 0:20:55.680 but they cannot cure you per se. 0:20:55.880 --> 0:20:58.520 Yeah, because it it'll never get rid of all of 0:20:58.560 --> 0:21:00.920 those hibernating viruses. 0:21:01.080 --> 0:21:03.880 Uh huh. So what does that mean from the point 0:21:03.880 --> 0:21:05.760 of view of developing a vaccine. 0:21:06.280 --> 0:21:10.359 That means that you have to block every single infection 0:21:10.560 --> 0:21:11.320 from occurring. 0:21:11.640 --> 0:21:16.160 That seems wildly difficult. Tell me, give me some hope. 0:21:16.160 --> 0:21:19.000 Now I am here sitting here thinking there is no way. 0:21:20.520 --> 0:21:22.240 You know, but I don't know anything. Tell me why 0:21:22.240 --> 0:21:22.840 there is a way. 0:21:23.880 --> 0:21:27.719 So certain individuals who are infected with HIV develop what 0:21:27.760 --> 0:21:33.960 we call broadly neutralizing antibodies. So these are antibodies that 0:21:34.359 --> 0:21:41.119 can neutralize seventy eighty ninety ninety five percent of hivs 0:21:41.160 --> 0:21:43.120 that are circulating in the world. 0:21:43.400 --> 0:21:45.840 These are just patients who have HIV who have this 0:21:45.960 --> 0:21:50.120 particularly robust natural immune response absolutely. 0:21:50.400 --> 0:21:54.000 So we know two things. One that there is a 0:21:54.000 --> 0:21:57.920 way that the immune system can develop these types of antibodies. 0:21:58.720 --> 0:22:02.120 The other thing that we know is that these antibodies 0:22:02.200 --> 0:22:08.800 target multiple different sites on the HIV envelope protein. So 0:22:08.840 --> 0:22:12.960 there are multiple targets on the HIV envelope that can 0:22:13.000 --> 0:22:16.680 be used in the vaccine to stimulate these types of antibodies. 0:22:17.400 --> 0:22:20.920 And we have actually done a clinical trial called the 0:22:20.960 --> 0:22:24.280 AMP trial, where we took one of these broadly neutralizing 0:22:24.280 --> 0:22:27.000 antibodies and we gave it to people who were at 0:22:27.080 --> 0:22:32.040 risk of HIV infection, and at a certain level, those 0:22:32.200 --> 0:22:34.960 individuals were protected against infection. 0:22:35.800 --> 0:22:39.800 And as I understand it, that technique works to protect 0:22:39.800 --> 0:22:43.840 people against some strains of HIV, but not all, right, 0:22:44.080 --> 0:22:48.000 And so what percentage of strains were people protected against 0:22:48.040 --> 0:22:49.000 in that trial. 0:22:49.000 --> 0:22:53.000 For this antibody, It was it was about thirty percent 0:22:53.080 --> 0:22:53.879 of viruses. 0:22:54.119 --> 0:22:58.880 Okay, so that not that broadly neutralizing in that instance. 0:22:59.240 --> 0:23:02.640 No, but this was one of the very first broadly 0:23:02.680 --> 0:23:06.000 neutralizing antibodies that we had that we did this trial with. 0:23:06.119 --> 0:23:11.959 There are much broader and better neutralizing antibodies that are 0:23:11.960 --> 0:23:15.520 available now. But what this is also showing us is 0:23:15.600 --> 0:23:19.760 the roadmap of if we can develop a vaccine that 0:23:19.880 --> 0:23:25.760 will recapitulate the development of these broadly neutralizing antibodies in 0:23:25.880 --> 0:23:30.520 people through immunization rather than through infection. If we can 0:23:30.600 --> 0:23:35.080 get that level of antibody high enough, then we know 0:23:35.200 --> 0:23:36.680 that they should be protected. 0:23:38.880 --> 0:23:41.840 So the basic idea is, like, we have these antibodies 0:23:41.840 --> 0:23:44.560 that seem to work, let's develop a vaccine that can 0:23:44.680 --> 0:23:46.480 induce people to develop these antibodies. 0:23:47.040 --> 0:23:51.880 Yes, that's exactly it. So there's still many big hurdles 0:23:51.880 --> 0:23:54.800 to get over, but the initial studies have shown that 0:23:54.840 --> 0:24:00.560 we can actually get the immune cells in the body 0:24:00.600 --> 0:24:03.960 to start producing the correct type of antibodies. 0:24:04.320 --> 0:24:07.160 These broadly neutralizing antibodies that we want. 0:24:07.080 --> 0:24:11.840 Well, they're sort of the precursors of the broadly neutralizing anivites. 0:24:11.920 --> 0:24:14.800 They're on the JV team. With some work, they can 0:24:14.920 --> 0:24:15.800 make the varsity. 0:24:16.160 --> 0:24:20.720 We need to shepherd them along, mentor them, tutor them, 0:24:20.760 --> 0:24:23.000 and get them to be broadly neutralizing. 0:24:23.359 --> 0:24:26.640 So still a long way away. Clearly, it's a profoundly 0:24:26.680 --> 0:24:31.679 difficult virus to vaccinate against. Drug treatment for HIV, on 0:24:31.760 --> 0:24:35.920 the other hand, has been quite successful, right, and now 0:24:35.960 --> 0:24:42.240 you can do prophylaxis with drugs, which is great. Obviously, 0:24:42.359 --> 0:24:45.800 it reduces human suffering a tremendous amount. Do we need 0:24:45.880 --> 0:24:48.359 vaccines less because the drugs work so well. 0:24:49.240 --> 0:24:53.399 It gives us a bit of a breather in that 0:24:53.440 --> 0:24:57.240 we know that there are other ways to protect people 0:24:57.280 --> 0:25:01.359 who are at risk of HIV infection. But there's a 0:25:01.520 --> 0:25:07.080 lot of healthcare delivery that would need to go into 0:25:07.160 --> 0:25:12.000 protecting the world against HIV in the absence of a vaccine, 0:25:12.400 --> 0:25:15.359 and you need the infrastructure to do that, And in 0:25:15.400 --> 0:25:17.439