WEBVTT - Breakthrough, Part Eight: The Future of mRNA 0:00:00.120 --> 0:00:03.520 A black van with tinted windows is parked in front 0:00:03.560 --> 0:00:07.280 of an Art nouveau building not far from Munich's English garden. 0:00:08.400 --> 0:00:13.080 It's September. The COVID nineteen vaccine drive is in full swing, 0:00:13.840 --> 0:00:16.840 with countries around the world debating just who should get 0:00:16.880 --> 0:00:21.079 booster shots. Inside the Munich villa's heavy door is a 0:00:21.200 --> 0:00:25.919 narrow entry foyer that leads up a wooden staircase. There's 0:00:25.920 --> 0:00:30.240 a cluster of people coming down. It's Germany's star scientists 0:00:30.400 --> 0:00:34.159 erz Lam, Too, Duchy and war Shachen. There the husband 0:00:34.159 --> 0:00:38.800 and wife duo behind BioNTech, Weiser's partner for the COVID vaccine, 0:00:39.440 --> 0:00:41.159 and they're on their way out of a meeting with 0:00:41.200 --> 0:00:45.559 the company's chairman, Helmett yuggla ertz Lam and Uer say 0:00:45.600 --> 0:00:49.280 hello politely and then head out the door. Helmett is 0:00:49.320 --> 0:00:53.560 waiting upstairs to talk to me about BioNTech and it's 0:00:53.680 --> 0:00:58.639 race to develop a messenger RNA vaccine. Helmett laughs when 0:00:58.680 --> 0:01:01.920 I asked what they talked about that day. Next generation 0:01:02.080 --> 0:01:08.440 m R and A treatments are in everyone's mind. Next 0:01:08.480 --> 0:01:15.480 generation now next generation No, of course, we have to 0:01:15.520 --> 0:01:18.440 think about how we developed the company because of the 0:01:18.480 --> 0:01:28.080 situation now. Helmont has known the BioNTech founders since two 0:01:28.080 --> 0:01:31.720 thousand seven. He was working then for the strong One Brothers, 0:01:32.240 --> 0:01:35.600 the German billionaires who helped fund the company. He's been 0:01:35.640 --> 0:01:38.480 involved with Biontic since the beginning and chairman of the 0:01:38.520 --> 0:01:42.320 board since two thousand eight. When we talked, it had 0:01:42.319 --> 0:01:45.399 been almost a year since Helmot, Uger, and utz Lum 0:01:45.640 --> 0:01:48.880 found out that the bet on BioNTech and a messenger 0:01:49.000 --> 0:01:52.800 RNA technology had paid off in the biggest possible way. 0:01:53.680 --> 0:01:57.240 Helmote compares it to a moon landing. You plan and 0:01:57.280 --> 0:02:00.320 you work and you prepare, and it's all THEO nicole 0:02:00.400 --> 0:02:03.000 until you step out the door of your spacecraft and 0:02:03.080 --> 0:02:07.400 suddenly you're there. It's almost hard to believe that you've 0:02:07.440 --> 0:02:11.160 actually made it. He tells me that after he heard 0:02:11.200 --> 0:02:13.800 the news from Ugre about how well the vaccine worked 0:02:13.800 --> 0:02:16.520 in a patient trial, he left his phone at home 0:02:16.840 --> 0:02:19.240 and went out for a walk. He lives out in 0:02:19.240 --> 0:02:22.880 the country, and it was a peaceful night. He says. 0:02:22.919 --> 0:02:25.720 He figured it would be his last quiet night for 0:02:25.760 --> 0:02:31.000 a while. That's exactly why I want to enjoy this 0:02:31.040 --> 0:02:37.639 moment quietly myself. Helmont turned out to be right. The 0:02:37.800 --> 0:02:41.480 vaccine isn't just one of human kind's best weapons so 0:02:41.520 --> 0:02:46.200 far against the COVID pandemic. It's also the vindication for 0:02:46.240 --> 0:02:51.680 an entirely new field of medicine. Suddenly, messenger RNA vaccines 0:02:51.880 --> 0:02:55.760 are the world's best selling drugs, and suddenly the young 0:02:55.800 --> 0:03:00.280 biotechs that developed them, Germany's BioNTech and modern of from 0:03:00.320 --> 0:03:04.480 the US, are among the world's most closely scrutinized drug makers. 0:03:05.240 --> 0:03:07.400 Everybody wants to know what their next step will be. 0:03:09.440 --> 0:03:13.200 Welcome to the eighth episode of our series. This time 0:03:13.680 --> 0:03:17.000 we're looking at what's next for the biggest scientific breakthrough 0:03:17.120 --> 0:03:21.600 to emerge out of the COVID pandemic, Messenger RNA vaccines. 0:03:22.639 --> 0:03:25.360 Up until last year, it wasn't even clear that they'd 0:03:25.360 --> 0:03:29.560 work at all. Now everyone from hospitals and drug makers 0:03:29.680 --> 0:03:32.360 to Wall Street are waiting to see where else they 0:03:32.400 --> 0:03:34.760 can be used and what the payoff could be for 0:03:34.840 --> 0:03:39.760 patients and for the company's The technology could help engineer 0:03:39.760 --> 0:03:43.360 a better flu shop, for example, but its potential goes 0:03:43.480 --> 0:03:48.200 far beyond zapping viruses. Messenger RNA is being tested in 0:03:48.280 --> 0:03:52.119 cancer medicines and in heart disease. Some researchers are also 0:03:52.200 --> 0:03:55.200 studying whether it could be useful against autoimmune diseases like 0:03:55.320 --> 0:04:00.160 multiple sclerosis, or even treat genetic illnesses like sickle cell anemia. UH. 0:04:00.760 --> 0:04:03.640 Some argue that we can't even imagine how widely this 0:04:03.760 --> 0:04:08.120 technology will eventually be used, and then eventually there won't 0:04:08.160 --> 0:04:10.000 even be such a thing as an m R and 0:04:10.080 --> 0:04:14.200 a vaccine company. That the technology will become so widespread 0:04:14.800 --> 0:04:17.560 that it's just another piece of the puzzle for drugmakers 0:04:17.800 --> 0:04:21.400 working in all sorts of fields. My name is Naomi 0:04:21.440 --> 0:04:24.200 Kraski and I'm a health reporter for Blue Broke News 0:04:24.880 --> 0:04:47.560 from the Prognosis podcast. This is Breakthrough. That's the sound 0:04:47.600 --> 0:04:51.960 of equipment at BioNTech's headquarters in Minz, Germany. It's about 0:04:51.960 --> 0:04:55.159 a half hour drive west of the Frankfurt airport. Okay, 0:04:55.400 --> 0:04:59.520 what do you see here? Inside? The lab and infrastructure 0:04:59.560 --> 0:05:03.920 director frescois Perrino is showing me around. I've been at 0:05:03.960 --> 0:05:08.440 BioNTech offices before, in late and I'm struck by what 0:05:08.600 --> 0:05:12.960 has changed and what has stayed the same. Now they 0:05:13.040 --> 0:05:15.720 have a fence and a security officer who takes his 0:05:15.800 --> 0:05:19.680 time letting me in, but the building itself doesn't look 0:05:19.720 --> 0:05:23.560 any fancier than it did before. Most farmer headquarters that 0:05:23.640 --> 0:05:26.880 I've visited have a certain class. Eveneer there tends to 0:05:26.960 --> 0:05:30.159 be a lot of modern art soaring atriums and high 0:05:30.200 --> 0:05:35.200 tech elevators. Not by on Tech. We mostly take the stairs, 0:05:35.640 --> 0:05:37.880 which is okay because the building is only a couple 0:05:37.880 --> 0:05:40.520 of stories tall. The labs are on the same floor 0:05:40.640 --> 0:05:44.080 as the CEO's office. They've been adding research space and 0:05:44.160 --> 0:05:47.280 equipment though, so this is a kind of workbench where 0:05:47.360 --> 0:05:50.920 all the stereo processes are performed, kind of The whole 0:05:51.000 --> 0:05:55.120 facility is called cell Culture facility, and within this facility 0:05:55.600 --> 0:05:59.200 we do all our experiments with south sets from human 0:05:59.360 --> 0:06:02.080 For example, when for us while joined by on Tech, 0:06:02.240 --> 0:06:06.720 in about five fifty people worked at the Mind's headquarters. 0:06:07.480 --> 0:06:10.520 Now it's about three times as many, and most of 0:06:10.720 --> 0:06:15.680 the development of the car Are Community Vaccine was performed 0:06:15.720 --> 0:06:20.080 inside police facilities over here. The wholesale culture facility is 0:06:20.160 --> 0:06:25.080 approximately about four d square meters and it's just about psyculturing. 0:06:25.880 --> 0:06:28.240 We're there in the late afternoon, so the labs have 0:06:28.360 --> 0:06:32.200 emptied out quite a bit. A few scientists linger taking 0:06:32.240 --> 0:06:40.160 advantage of the quiet to finished projects. Some of the 0:06:40.240 --> 0:06:43.680 people we meet are working on research that's still far 0:06:43.880 --> 0:06:47.359 from being ready to be tested in patients. The mind's 0:06:47.400 --> 0:06:50.200 facility also makes R and A for use in research 0:06:50.279 --> 0:06:55.880 and development. BioNTech is pouring its COVID vaccine profits into 0:06:55.960 --> 0:07:01.119 its pipeline of new experimental medicines. Company scientists are working 0:07:01.320 --> 0:07:06.599 on some infectious disease projects, including vaccines from malaria, HIV, 0:07:06.839 --> 0:07:10.640 and tuberculosis. None of those are far enough along to 0:07:10.720 --> 0:07:14.160 be tested in humans, though the more advanced part of 0:07:14.200 --> 0:07:19.280 the pipeline is almost entirely potential cancer treatments. The companies 0:07:19.360 --> 0:07:23.600 running nineteen patient trials and cancer About half of these 0:07:23.800 --> 0:07:27.160 are m R and A vaccines. In fact, before the 0:07:27.240 --> 0:07:32.160 COVID pandemic, BioNTech was basically a cancer company. As we 0:07:32.280 --> 0:07:35.000 learned in last week's episode. It didn't work on infectious 0:07:35.000 --> 0:07:38.720 disease vaccines until mid when its signed a deal with 0:07:38.880 --> 0:07:42.800 Fisser to develop a flu shot, but it's already treated 0:07:42.800 --> 0:07:46.640 about six hudd patients and cancer trials. Most were small 0:07:46.720 --> 0:07:52.200 studies designed to look at safety. That's how drug development works. First, 0:07:52.280 --> 0:07:54.760 you test a potential medicine and only a few people, 0:07:55.320 --> 0:07:57.840 and if it's shown to be safe, you can move 0:07:57.920 --> 0:08:01.000 on to testing its efficacy in a bigger it. You 0:08:01.080 --> 0:08:03.920 might see some hints of an impact against disease in 0:08:04.000 --> 0:08:07.120 phase one, but that's not really what those trials are 0:08:07.160 --> 0:08:11.440 designed to find out. But thanks to the COVID vaccine cash, 0:08:11.880 --> 0:08:14.520 BioNTech has been able to move quickly on the bigger 0:08:14.560 --> 0:08:17.760 studies it will need to push its cancer programs forward. 0:08:19.640 --> 0:08:22.880 One of those programs is called Ionest. Essentially, it's a 0:08:22.960 --> 0:08:26.720 personalized m R and a cancer vaccine. We're standing in 0:08:26.880 --> 0:08:29.520 front of a washing machine sized piece of equipment in 0:08:29.600 --> 0:08:32.959 one of the labs. It's crucial to the project and 0:08:33.160 --> 0:08:39.320 this machine is uh, yeah, it's very important. It's very 0:08:39.400 --> 0:08:41.679 important for us because this is one of, let's say, 0:08:41.880 --> 0:08:46.520 kind of the heart for our analysis for the Ionest treatment. 0:08:48.400 --> 0:08:52.319 In order to make a personalized cancer vaccine, BioNTech has 0:08:52.400 --> 0:08:56.160 to sequence the genetic code of each patient's tumor. The 0:08:56.280 --> 0:09:00.840 researchers use this machine to do the sequencing. So every 0:09:01.040 --> 0:09:05.600 every the tumor is caused by different mutations inside the genome, 0:09:05.760 --> 0:09:08.000 and we have to have a look at the TOLO 0:09:08.040 --> 0:09:10.959 genome to be sure that we if we find or 0:09:11.040 --> 0:09:13.839 that we that we identify the mutations and that we 0:09:14.000 --> 0:09:18.880 know how to shape the m RNA computer algorithm helps 0:09:18.920 --> 0:09:22.079 them find the special pattern of mutations that's unique to 0:09:22.120 --> 0:09:25.920 the tumor not found elsewhere in the body. Then bion 0:09:26.000 --> 0:09:28.800 text teams can take that pattern and build a template 0:09:29.000 --> 0:09:32.920 for an m r and A treatment. Remember how the 0:09:33.120 --> 0:09:36.199 m r and A vaccine for COVID works. It delivers 0:09:36.240 --> 0:09:39.439 instructions for cells to make the spike protein of the 0:09:39.520 --> 0:09:44.200 stars copy two virus that jolts the immune system into action, 0:09:45.080 --> 0:09:47.560 so if it encounters the real virus, it can act 0:09:47.600 --> 0:09:51.760 quickly to stop it. The m RNA cancer vaccine would 0:09:51.760 --> 0:09:55.320 train the body's immune system too, but to attack a tumor, 0:09:55.679 --> 0:09:59.640 not a virus. It's a treatment, not a preventative measure, 0:10:00.800 --> 0:10:05.040 and the mr and A is, let's say, the needed 0:10:05.360 --> 0:10:10.199 trigger for your immune system. Bion Tech already has some 0:10:10.320 --> 0:10:13.559 promising results with Ainest in a small trial with just 0:10:13.679 --> 0:10:17.920 thirteen patients. It's now testing the technology and bigger studies 0:10:18.040 --> 0:10:22.160 and melanoma and colorectal cancer. Like for the COVID vaccine, 0:10:22.320 --> 0:10:25.400 they're working with an experienced partner. It's one of the 0:10:25.440 --> 0:10:28.680 biggest cancer drugmakers in the world, a Swiss company called 0:10:28.840 --> 0:10:31.679 Roche Holding. You may have heard of Roche's u S 0:10:31.800 --> 0:10:36.439 unit called Genentech. I wanted to get Roche's view on 0:10:36.679 --> 0:10:39.960 m R and A cancer vaccines, so I called Charlie Fuchs, 0:10:40.400 --> 0:10:44.640 who runs their oncology and hematology product development. He's the 0:10:44.720 --> 0:10:48.160 former director of Yale Cancer Center and as an oncologist, 0:10:48.440 --> 0:10:52.760 he helped run huge clinical trials for other successful cancer immunotherapies. 0:10:54.200 --> 0:10:57.160 Charlie says the COVID vaccine's success is a good sign 0:10:57.360 --> 0:10:59.959 for the likelihood of m R and A technology working 0:11:00.080 --> 0:11:04.640 for cancer too. Seeing that on a population level and 0:11:04.800 --> 0:11:09.080 seeing the validation in patients that this technology really does 0:11:09.640 --> 0:11:13.040 enable a robust immune responses, I think is an important 0:11:13.120 --> 0:11:18.960 step in believing that we can leverage this technology for cancer. Still, 0:11:19.400 --> 0:11:23.280 just because MR and A vaccines worked against COVID doesn't 0:11:23.280 --> 0:11:27.600 mean they'll stop tumors. You know, Viruses are tiny little 0:11:27.679 --> 0:11:33.719 packages of limited genetic code that can create havoc by 0:11:34.679 --> 0:11:38.480 interfering with functions the normal functions of a human cell, 0:11:38.800 --> 0:11:42.840 or for that matter, creating an immune response. That's harmful, 0:11:43.800 --> 0:11:49.120 but um they're very limited. Cancers are a lot more complex. 0:11:49.840 --> 0:11:54.839 They're a lot better at defending themselves. Cancers are human 0:11:54.960 --> 0:12:00.120 cells that have mutated to leverage the full extent of 0:12:00.200 --> 0:12:04.559 the machinery and genetic code of a complex human cell, 0:12:05.440 --> 0:12:10.480 such that it will um become a lignan spread and 0:12:10.760 --> 0:12:14.880 because it has the availability of the entire human genome 0:12:15.800 --> 0:12:19.160 associated with it, that it can actually come up with 0:12:19.400 --> 0:12:24.680 lots of different mechanisms to overcome response to cancer therapy, 0:12:25.280 --> 0:12:30.240 to sustain itself, to avoid the immune surveillance. This is 0:12:30.320 --> 0:12:34.679 one reason that doctors often combine cancer therapies, and that's 0:12:34.760 --> 0:12:38.920 one reason, unfortunately, the cancer treatments sometimes stop helping after 0:12:39.000 --> 0:12:41.880 a few months or years, and so there's just a 0:12:42.080 --> 0:12:46.080 lot more to deal with when you're developing a cancer 0:12:46.200 --> 0:12:49.280 therapy as opposed to a virus, which is a tiny 0:12:49.520 --> 0:12:54.120 little compartment of very limited genetic code, very limited DNA 0:12:54.480 --> 0:12:57.959 r n A. Charlie tells me he thinks they'll have 0:12:58.040 --> 0:13:00.240 a better sense of how well m r n A 0:13:00.360 --> 0:13:03.760 vaccines can help with cancer treatment within the next two years. 0:13:14.520 --> 0:13:17.800 Thinking about Charlie's words, when I talk with BioNTech chief 0:13:17.880 --> 0:13:20.840 medical officer, it's them too, Rechi a few weeks later. 0:13:21.760 --> 0:13:25.839 She and her husband, Ushahi, and the CEO are also oncologists. 0:13:26.559 --> 0:13:30.559 They treated patients for years before they started BioNTech. We 0:13:30.720 --> 0:13:36.199 spent most of our time at the patient's bedside. That 0:13:36.440 --> 0:13:41.480 was the motivation to provide better medicines for those patients 0:13:41.840 --> 0:13:45.280 whom we had to tell that we had nothing to 0:13:45.400 --> 0:13:49.200 offer him. Some agrees that cancer is a tougher target 0:13:49.360 --> 0:13:54.280 than COVID for the immune system Sara's COVIE two is 0:13:54.360 --> 0:13:59.200 foreign cancer as part of us. So it's not about 0:13:59.800 --> 0:14:05.800 a about preventing, it's about melting away a substantial to 0:14:06.000 --> 0:14:10.280 more burden. So there are already immune suppressive mechanisms where 0:14:10.480 --> 0:14:15.040 cancer has installed, and you have to to fight against 0:14:15.120 --> 0:14:19.040 them and fight against immune tolerance because it's not really 0:14:19.080 --> 0:14:22.520 a foreign protein which you are using as target and 0:14:22.960 --> 0:14:27.720 um so this is a very different, higher challenge. All 0:14:27.760 --> 0:14:32.720 those years working to optimize mRNA technology for cancer vaccines 0:14:33.040 --> 0:14:36.000 helped when it came time to make the COVID chat. 0:14:37.160 --> 0:14:40.760 I think the reason why we have been successful for 0:14:41.000 --> 0:14:45.440 in COVID nineteen is that we have sharpened our weapons 0:14:45.680 --> 0:14:51.160 against cancer with all those um yeah, higher thresholds for 0:14:51.400 --> 0:14:57.000 for success. And once they'd optimized mRNA for cancer, Reson 0:14:57.160 --> 0:15:00.080 tells me, they started realizing there would be potential and 0:15:00.200 --> 0:15:04.160 lots of other diseases too. They want to develop mRNA 0:15:04.240 --> 0:15:09.360 treatments for autoimmune diseases illnesses in which the body attacks itself. 0:15:10.280 --> 0:15:14.800 Multiple sclerosis is one example for a disease like MS 0:15:15.560 --> 0:15:17.720 and mr and A vaccine will work in the opposite 0:15:17.800 --> 0:15:22.600 way how it's used against cancer or covids. Some explains. 0:15:23.480 --> 0:15:29.600 We have shown that while for cancer or infects disease vaccines, 0:15:30.200 --> 0:15:36.840 the mrn A is used to deliver two signals or messages, namely, 0:15:36.920 --> 0:15:40.280 on the one hand, to present the target, for example 0:15:40.360 --> 0:15:44.920 the COVID nineteen spike protein or a tumor integen plus, 0:15:45.080 --> 0:15:50.080 to provide um the message that the immune system needs 0:15:50.160 --> 0:15:54.720 to attack, in particular that the c D eight killer 0:15:54.800 --> 0:16:00.640 T cells need to be directed against this the target. 0:16:01.480 --> 0:16:05.760 For autoimmune diseases, m RNA vaccine would still wave a 0:16:05.840 --> 0:16:10.520 flag for the immune system to recognize something, but the 0:16:10.760 --> 0:16:14.680 second message we deliver is that the immune system, once 0:16:14.720 --> 0:16:19.280 it cease this target, needs to calm down and needs 0:16:19.360 --> 0:16:23.520 to accept this target and not a tack, so it's 0:16:23.560 --> 0:16:28.160 telling the body to stop turning against itself. BioNTech has 0:16:28.200 --> 0:16:31.880 had a successful experiment in this area with mice, but 0:16:32.000 --> 0:16:34.360 there's still quite a ways a way from having an 0:16:34.480 --> 0:16:39.040 mr ANDA vaccine to test in people with autoimmune diseases. Moderna, 0:16:39.320 --> 0:16:43.200 the other mRNA code vaccine maker, is also working on 0:16:43.320 --> 0:16:47.680 an autoimmune disease project. Moderna is also working on mRNA 0:16:47.840 --> 0:16:52.480 based cancer vaccines andicistic fibrosis treatment, as well as the 0:16:52.560 --> 0:16:55.680 treatment for heart disease, and it has a broad palette 0:16:55.840 --> 0:17:00.960 of other potential mRNA vaccines for infectious diseases, everything from 0:17:01.040 --> 0:17:05.560 zeka and FLEW to HIV. I caught up with one 0:17:05.600 --> 0:17:09.320 of the early investors in BioNTech, a German venture capitalist, 0:17:09.440 --> 0:17:12.760 in Matthias Cromeyer, at a conference in Berlin to find 0:17:12.760 --> 0:17:16.000 out more about the broader field. And you need to 0:17:16.200 --> 0:17:19.720 keep in mind that m RNA is at the center 0:17:19.840 --> 0:17:22.840 of any biological process. I mean, any gene that gets 0:17:22.920 --> 0:17:29.200 expressed is expressed via m RNA. Matthias's firm, MiG Capital, 0:17:29.600 --> 0:17:32.879 gave BioNTech about fifteen million dollars in seed money in 0:17:32.960 --> 0:17:37.600 two thousand eight. It was migg's best investment ever. Now, 0:17:37.720 --> 0:17:40.400 he says the approach could be useful in any kind 0:17:40.440 --> 0:17:43.159 of genetic disorder where the body doesn't make something that 0:17:43.280 --> 0:17:48.560 it should, from diabetes to hemophilia or rare diseases. But 0:17:48.720 --> 0:17:50.879 the first chance to see the proof of the pudding 0:17:51.160 --> 0:17:56.119 will be the cancer trials oncology. It's definitely oncology because 0:17:56.200 --> 0:17:59.040 this is where the company's are most advanced. So I 0:17:59.040 --> 0:18:04.280 would expect for approvals um provided that these these studies 0:18:04.320 --> 0:18:08.040 work out nicely. First approvals in twenty four or twenty five. 0:18:09.880 --> 0:18:11.800 That's a lot longer than it took to get the 0:18:11.840 --> 0:18:16.040 COVID vaccines approved. But in drug development terms, it's actually 0:18:16.119 --> 0:18:19.439 pretty fast. It just takes longer to see whether an 0:18:19.480 --> 0:18:23.200 experimental treatment can help cancer patients then it does to 0:18:23.280 --> 0:18:26.240 see whether a vaccine can stop a virus from making 0:18:26.320 --> 0:18:30.399 people sick. First of all, you can't recruit twenty cancer 0:18:30.480 --> 0:18:34.080 patients in in a couple of weeks time. Secondly, the 0:18:34.280 --> 0:18:38.280 endpoint in in in the COVID are In the COVID 0:18:38.400 --> 0:18:43.359 nineteen um immune immunized population, it took only weeks to 0:18:43.440 --> 0:18:47.440 reach the endpoint um of a number of events in 0:18:47.560 --> 0:18:51.080 oncologies usually years that you need to wait until people 0:18:51.160 --> 0:18:53.720 have survived or not. So this is why it takes longer. 0:18:53.960 --> 0:19:00.400 It's not because people weren't working as diligently as into 0:19:00.440 --> 0:19:04.399 COVID lntine vaccination areas. If you talk to some of 0:19:04.440 --> 0:19:07.159 the early pioneers in m r and A, sky is 0:19:07.200 --> 0:19:10.679 the limit for what else the technology could do. Remember 0:19:10.720 --> 0:19:13.920 Derek Rossi, the Harvard stem cell scientists who did important 0:19:13.960 --> 0:19:17.960 early experiments with m RNA and founded Materna. He says 0:19:17.960 --> 0:19:21.040 his original vision for the company wasn't vaccines at all. 0:19:21.400 --> 0:19:25.440 Vaccines have been in production for you know, you know, 0:19:25.560 --> 0:19:30.359 a hundred years, and they work. Uh and uh so 0:19:30.600 --> 0:19:34.879 why reinvent the wheel? Well there's turns out, as we 0:19:35.000 --> 0:19:36.960 now know, there is good reasons for that. It's a 0:19:37.119 --> 0:19:40.040 faster technology, it's a more precise technology, it's a better 0:19:40.119 --> 0:19:43.960 technology for vaccination, It's true. But what I imagined was 0:19:44.520 --> 0:19:49.600 application towards genetic disease. Derek tells me there are six 0:19:49.680 --> 0:19:54.520 thousand genetic diseases. He says that six thousand mutations in DNA, 0:19:55.320 --> 0:19:58.119 which leads to bad mr and A, which leads to 0:19:58.160 --> 0:20:02.720 a problem with the protein, leads to disease. Derek's idea 0:20:02.920 --> 0:20:05.600 was to use mr and A vaccines to spur cells 0:20:05.800 --> 0:20:10.840 to make the right proteins instead. Wherever protein is needed, 0:20:11.920 --> 0:20:16.440 it can be applied. So um, that could be six 0:20:16.520 --> 0:20:23.639 thousand genetic diseases. Uh. Oncology, cancer, mutated genes. Projects to 0:20:23.720 --> 0:20:26.240 study how MR and A therapy can be used to 0:20:26.320 --> 0:20:29.879 treat genetic disease are also in the works. In fact, 0:20:30.440 --> 0:20:33.800 Drew Wiseman, the University of Pennsylvania professor who worked with 0:20:33.880 --> 0:20:37.399 Catalan Kerry Co to answer vital early questions around m 0:20:37.520 --> 0:20:40.320 R and A research, is now working on an m 0:20:40.400 --> 0:20:43.359 R and A vaccine for sickle cell anemia, one of 0:20:43.400 --> 0:20:47.359 the most common genetic disorders. The Bill and Melinda Gates 0:20:47.400 --> 0:20:52.479 Foundation is sponsoring the research. Drew tells me some two 0:20:52.920 --> 0:20:56.200 thousand people are born every year with sickle cell disease, 0:20:56.720 --> 0:21:00.240 most of them in Sub Saharan Africa. There's a here, 0:21:01.080 --> 0:21:03.680 but it's way too expensive for a lot of these patients. 0:21:04.960 --> 0:21:07.760 And what they do is they take a patient, they 0:21:07.920 --> 0:21:11.119 take out a lot of bone marrow, they infect the 0:21:11.200 --> 0:21:14.360 bone marrow with a lenty virus, and then they give 0:21:14.440 --> 0:21:19.760 it back. That's probably a half a million dollar per 0:21:19.960 --> 0:21:24.800 person costs for for a cycle cell cure. You can't 0:21:24.840 --> 0:21:30.280 do two hundred bone marrow biopsies in Sub Saharan Africa. 0:21:32.560 --> 0:21:35.760 So Drew's lab has figured out how to target bone 0:21:35.800 --> 0:21:38.600 marrow stem cells with an m R and A treatment. 0:21:39.440 --> 0:21:42.240 It inserts a new gene into the genome of the 0:21:42.280 --> 0:21:47.320 stem cells. Instead of removing a patient's bone marrow, doctors 0:21:47.400 --> 0:21:50.760 would simply need to give them an IVY injection. To 0:21:50.920 --> 0:21:54.080 me that that changes the world, because now you can 0:21:54.600 --> 0:21:59.080 do gene therapy with a simple injection. We should make 0:21:59.119 --> 0:22:03.000 this clear. Program isn't in human trials yet. It's being 0:22:03.080 --> 0:22:06.639 tested now in mice. As Drew has told us several times, 0:22:07.160 --> 0:22:11.760 success in mice doesn't necessarily translate to humans. Drew's lab 0:22:11.880 --> 0:22:15.280 has a laundry list of other projects as well. He's 0:22:15.320 --> 0:22:18.520 working with BioNTech on a range of infectious disease vaccines, 0:22:19.480 --> 0:22:23.520 and he's working on a pan coronavirus vaccine with Duke University, 0:22:24.000 --> 0:22:27.240 the University of North Carolina, and the National Institutes of Health. 0:22:28.280 --> 0:22:31.360 That's a shot that could work against all types of coronavirus, 0:22:31.520 --> 0:22:35.080 is not just stars Kobe two. The idea would be 0:22:35.200 --> 0:22:38.359 to have a vaccine that could cover whatever variant pops 0:22:38.440 --> 0:22:41.359 up in the future, maybe even something that's ready to 0:22:41.440 --> 0:22:44.879 go for the next pandemic. And they're working on an 0:22:45.040 --> 0:22:49.440 MR and a vaccine against HIV. If it succeeds, that 0:22:49.520 --> 0:22:54.160 would be transformative to HIV. The virus that causes AIDS 0:22:54.840 --> 0:23:01.920 has alluded vaccine efforts for decades. It mutates so quickly, 0:23:03.280 --> 0:23:07.120 the way it infects cells is very different. It forms 0:23:07.400 --> 0:23:11.639 a long, live, latent reservoir that's hard to get rid 0:23:11.680 --> 0:23:16.560 of um, and it has so many ways of avoiding 0:23:17.000 --> 0:23:22.000 immune responses. Again, the HIV vaccine is a long way 0:23:22.119 --> 0:23:25.760 from completion. Juice Team is also working with Duke and 0:23:25.960 --> 0:23:28.840 ni H on this project. He says it's due to 0:23:28.880 --> 0:23:32.840 start human trials next year. HIV is a much more 0:23:32.960 --> 0:23:36.160 difficult virus, so that that's going to take a lot 0:23:36.240 --> 0:23:40.480 more work to get it to work correctly. None of 0:23:40.600 --> 0:23:43.600 these new MR and A vaccines and treatments will have 0:23:43.760 --> 0:23:47.800 the same speedy trajectory as the COVID vaccine last year. 0:23:48.800 --> 0:23:53.960 That's partly because the circumstances are so different. As we 0:23:54.080 --> 0:23:56.960 saw in last week's episode, the pandemic was in some 0:23:57.080 --> 0:23:59.960 ways the perfect use case for MR and A vaccine. 0:24:00.840 --> 0:24:03.680 The vaccine makers could draw on years of prior work 0:24:03.760 --> 0:24:06.399 from virologists on what would be the best bit of 0:24:06.480 --> 0:24:09.760 a coronavirus to use for a vaccine. They could run 0:24:09.840 --> 0:24:14.000 relatively quick patient trials. With COVID circulating around the globe. 0:24:14.040 --> 0:24:16.800 There was no shortage of scope for testing the vaccine, 0:24:17.520 --> 0:24:20.159 and the stars Cove two virus is a lot more 0:24:20.200 --> 0:24:25.080 straightforward than cancer or HIV. Now, the companies that raced 0:24:25.160 --> 0:24:28.119 to get COVID vaccines on the market are going to 0:24:28.240 --> 0:24:32.280 need to start playing a more complicated game. They'll need 0:24:32.359 --> 0:24:35.800 to reassure investors that their billions and revenues won't just 0:24:35.920 --> 0:24:39.400 be a one off. They're grappling with a tremendous pace 0:24:39.480 --> 0:24:43.359 of growth. Moderna in particular, has struggled to set up 0:24:43.359 --> 0:24:46.560 a global distribution network without a big partner like Visor. 0:24:47.320 --> 0:24:49.439 It recently said it wouldn't be able to ship as 0:24:49.480 --> 0:24:54.320 many COVID vaccine doses as expected this year. Meanwhile, smaller 0:24:54.359 --> 0:24:56.920 startups around the world are also working on m R 0:24:57.000 --> 0:25:01.359 and A vaccines and treatments. When I asked Helmet Juggla, 0:25:01.600 --> 0:25:05.240 the BioNTech chairman, about the biggest challenges ahead, he says 0:25:05.280 --> 0:25:10.320 the company has to be careful to stay focused. We 0:25:10.480 --> 0:25:12.560 just need to be careful that we don't go after 0:25:12.640 --> 0:25:14.760 too many things at once, and we really need to 0:25:14.880 --> 0:25:19.680 rule Lan's work focus. Um Helmett says he thinks bion 0:25:19.800 --> 0:25:22.159 Tech will have more MR and A products on the 0:25:22.240 --> 0:25:25.520 market in a few years. It reminds me of the 0:25:25.600 --> 0:25:28.240 song by the Hungarian rock singer who appeared on that 0:25:28.400 --> 0:25:31.879 radio interview with Catle and Currico, the pioneering MR and 0:25:31.960 --> 0:25:35.240 A researcher in Budapest. We played some of it in 0:25:35.359 --> 0:25:38.399 episode six. The song is about how you need to 0:25:38.480 --> 0:25:41.040 work hard and stay the course to achieve your goals. 0:25:41.680 --> 0:25:44.560 The diamonds and gold have a nice shine, but you 0:25:44.680 --> 0:25:48.119 have to dig deep to get it. Catalan says her 0:25:48.160 --> 0:25:50.959 favorite part of the song is about what happens when 0:25:51.040 --> 0:25:55.719 you finally hit your target. The lyrics roughly translated from 0:25:55.760 --> 0:25:59.480 Hungarian are but when you reach your goal and could 0:25:59.520 --> 0:26:03.639 be happy, you're already thinking about a new plan, already 0:26:03.680 --> 0:26:09.240 embarking on a new road, and that's the beauty of life. BioNTech, 0:26:09.440 --> 0:26:13.360 MODERNA and their competitors have new plans too, and it's 0:26:13.400 --> 0:26:43.440 all about m R and A. Next week on Breakthrough, 0:26:43.840 --> 0:26:46.439 we'll talk with the public health leaders and scientists who 0:26:46.480 --> 0:26:49.800 are preparing for the next pandemic. Even before this one 0:26:50.080 --> 0:26:53.640 is over. COVID has shown us health vulnerable or health 0:26:53.720 --> 0:26:56.960 systems really are? Will we be ready when the next 0:26:57.000 --> 0:27:02.480 pandemic comes? They are a very moder threat that emerges 0:27:02.640 --> 0:27:06.640 from the way we have organized our societies, and they 0:27:06.960 --> 0:27:12.639 represent a critical threat for the century. This episode of 0:27:12.720 --> 0:27:16.240 Prognosis Breakthrough was written and reported by me Naomi Krasky 0:27:16.800 --> 0:27:20.440 So for Fourheads and Nagus Hendrickson, our senior producers. Carl 0:27:20.520 --> 0:27:24.160 Kevin Robinson Jr. Is our associate producer. Our theme music 0:27:24.280 --> 0:27:28.200 was composed and performed by Hanness Brown. Philip Corne did voiceover, 0:27:28.600 --> 0:27:32.840 and Bob Langrath and Sultan Shimon contributed reporting. Rick Shine 0:27:32.920 --> 0:27:36.600 is our editor. Francesca Levi is the head of Bloomberg Podcasts. 0:27:37.280 --> 0:27:39.760 Be sure to subscribe if you haven't already, and if 0:27:39.800 --> 0:27:42.680 you like this episode, please leave us a review. It 0:27:42.760 --> 0:27:45.639 helps others find out about the show. Thanks for listening.