Sticks, Carrots, & Carolina Reapers: Fact-Checking The "Death" Of The US mRNA Industry

Anna Rose Welch: Hello everyone and welcome to Advancing RNA's mRNA Hot Takes, the show where we talk about serious RNA things, but with a spicy twist. I'm your host, Anna Rose Welch, the editorial and community director of Advancing RNA, and I am thrilled to be joined once more by two very brave and very bold — and as I've learned, incredibly competitive, very competitive — legends in the RNA world: Sophia Lugo, CEO of Radar Therapeutics, and Michelle Lynn Hall, general partner of the VC firm, Entrée Bio. So, thank you ladies for continuing to return to me for these episodes every week.

Over the past five episodes, we've met and talked about the scientific and business world of mRNA. But if you've tuned in before, you'll know that our discussions have been anything but ordinary for one particular reason: Each question we've discussed has been paired with a hot pepper, and those peppers have only gotten spicier as we've gone along.

So, over the last few episodes, we've talked about mRNA while tackling jalapenos, Serranos, Thai chilies, habaneros, and the dreaded ghost pepper. We are not messing around on this show; In our last episode, we put our entire psyches to the test for you, ladies and gentlemen, with what turned out to be delightful, but I would still say insanely spicy ghost pepper hot sauce.

How did you guys feel after last episode, by the way? I've learned personally that I need to stop going to hot yoga classes after eating these hot peppers.

Michelle Lynn Hall: I could have told you that.  

Sophia Lugo: Actually, I really do have to say it was a tasty hot sauce. I had more at dinner and yes, I did enjoy it. I have found though that my mouth seems to be fine; my stomach has different opinions. And so, about an hour after the show is when I feel it, and I feel it with saliva gathering in my mouth, unclear if I'm going to make it through.

Welch: Oh, no!

Hall: I'm sorry to hear that. Fortunately, I have not pushed myself nearly as hard as you ladies have. So, my GI system is just fine. Thank you for inquiring.

Welch: Says the woman who immediately drank straight out of the bottle the last episode. Come on.

Lugo: I did have a CEO kindly offer that he could make me a protein that will block the receptor so I won't feel the effects in my stomach or mouth. But I felt that was cheating.

Hall: That’s just ingenious.

Welch: The connections are everything in this space. We have magic at our fingertips.

Well, ladies, the fun does not stop with the ghost pepper. We're obviously still here. Your chance to run away was five minutes ago before we started filming, but we have made it to our final episode of this hot taste mini-series for now. Hint, hint — There will probably be more. But, believe it or not, there are still a couple of peppers that we have to add on to our belt here. So, the ghost pepper may have few rivals in terms of spice, but it does still have a handful, and today we're going to be exploring two of them in combination, namely the Trinidad Scorpion and the Carolina Reaper, which clock in at 1.5 million Scoville units and 2.2 million Scoville units respectively.

So, seeing as it's the dead of winter, we were unable to source the real peppers to eat, so we've had to turn once more to hot sauces.

I've supplied each of us with this hot sauce called The Rapture by Torchbearer Sauces. Yes, we've got a man here holding scorpions. The sauce is a combination of the Trinidad Scorpion, the Carolina Reaper, and our old returning favorites: the Ghost Pepper and Habanero, which, according to the Torchbearer website, is perfect for pairing with burgers and chili —  

Hall: And regret.

Welch: It's also supposedly great for torture. So that's something.

It lists that on the site: Torture.

Hall: I can affirm that that is accurate.

Welch: We're going to find out. Do you guys have your hot sauces and your spoons at ready? We're going to make this magic a reality. Alright. Here we go. We're going to add a little ... Oops, okay. Alight. We’ve got a pretty big dollop here—we’re not messing around.  

[Tastes sauce.] Ooh, that's got a nice kick right away. Yeah, that's got a nice kick. I like it though. It's pretty tasty, but that's definitely ... I think it's spicier than the ghost pepper. I'll be curious to get your take.

Hall: Oh, good.

Welch: Michelle, we're going to start with you this time because I think Sophia took the bullet for the ghost pepper the last time first. So obviously, if we look at the headlines today, there's a lot going on on the policy level in terms of how the US government is approaching mRNA. It would definitely seem as though the US is starting to take a firmly anti-mRNA stance. But I would like to step back a little bit because, as an industry, this is our business. We are constantly focused on what is happening in the space, what barriers could exist. We can occasionally live a little bit in an echo chamber. So, I'd really like to just get your sense: To what extent do you feel this perception that the US is firmly anti-mRNA? How accurate do you think that perception is today? Are we living in an industry echo chamber? Are things truly as bad as they seem based on headlines and discussions that we've had in this space so far?

So, take it away. [Michelle drinks from the bottle.]

Ooh, ladies and gentlemen, she's fearless. She just drank straight from the bottle again.

Hall: Holy. Alright, so I made the mistake of using my lips as a filter.

Lugo: No, no. That's a big mistake.

Welch: That's where you feel it the most.

Hall: It was a very big mistake. My lips are ... Yep, they're burning. And then I can't tell whether my tongue or my bottom palette is burning more at this moment, but I will say it has a very pleasant smell to it. Does it have carrots in it?

Welch: I think so. Carrots and mandarin oranges.

Hall: Yeah, it's pretty good. I mean, it's definitely death in a bottle, but it's pretty good. I'm going to try to make it through this.

So, I will be the first to tell you that I am glued to the news and have watched all the vitriol and misinformation around mRNA probably as closely as a lot of people. However, let's put some things in perspective. The people who sell you the news have a vested interest in making that news sensationalist, because nobody clicks on headlines of “everything's good in the universe.” That's not something we click on. “RFK did something dumb today” is something we will click on. So yes, it is bad. I am not going to deny that. But there is hope.

So, the most recent poll I found was back in the summer, and who knows how things have changed since then, but back in the summer, one third of US adults said that they thought vaccines were mRNA vaccines were generally safe.

One half of that, so about 16% of the US, believe that mRNA vaccines are generally unsafe. 16%. It's not a lot; 2X more people believe they are safe than believe they are unsafe.

And then what was also interesting is about half of the US population said they did not know enough about the technology to say one way or the other. I actually think that's good. I don't know about you, but when I go to my doctor and they say, “Michelle, you should be on medicine X instead of medicine Y,” I don't go, "Well, I would like to see the peer reviewed literature on that." I trust that my MD doctor knows more about MD doctoring than I do. So, I don't actually think it's a bad thing that 50% of Americans don't know. I think it's interesting and noteworthy that 2X more people think it's safe than think it's unsafe.

Now, in our little industry echo chamber, are we all incensed and alarmed at what is, I would argue, the most politicization of science that I've experienced in my life? Yeah, of course we are. But I don't think what you are seeing in terms of, let's say, investor sentiment and a pullback from mRNA technology is a reflection of our thoughts on the technology itself. For better or for worse, it's about economics, and here's what I mean.

So, with the COVID-19 vaccine, the biggest customer of the COVID-19 vaccine was the Trump administration. And if the Trump administration in its second resurgence is going to take a vastly different tone on mRNA vaccines, there goes your largest purchaser. So, as somebody who's an investor or even a leader in a company who has a fiduciary responsibility to the investors to make sure that that company succeeds, that is something you have to take note of.

Now, do I think that will always be the state of affairs? No. And later I'm happy to talk about some of the things that I think will likely change public sentiment. But right now, I don't think things are as bad as we think they are, but I think people are responding in a rational way —  investors & leaders — to an irrational public policy around mRNA.

Welch: Absolutely. I had not seen this survey, so that's amazing to hear that 50% of people still don't have an opinion either way, which I think, as you said, is very optimistic. That just means there are people to educate and to familiarize with this technology over time, whether it be through vaccines or, I think a big conversation in this space so far has been finding ways that mRNA is going to impact people therapeutically. The vaccines may not have necessarily been the best use case to start in the sense of personal impact, because, if the vaccine works, you're not going to experience negative effects of a disease. So, having that therapeutic approach for mRNA is a good way that we could start to see more, I think, education.

Sophia, in a previous episode, you talked about folks that have come in for clinical trials. There was one gentleman who came in for an mRNA trial of a therapeutic as opposed to a vaccine. At first, he was anti-mRNA from a vaccine standpoint, but then when he realized it was an mRNA therapeutic for his cancer, it was a completely different story. So, I think there is some hope to be had there.

I'd love to get your take, Sophia, and have you join in on this hot sauce brigade so that Michelle's lips aren't the only ones burning. So, I'd like to ask you the same question: Do you feel that this perception is accurate? Are we living in an echo chamber, or are things truly as bad as they seem? But I'd also like to get your take, as well, being the CEO of an mRNA company: What measurable impacts, if any, have you faced in the past year or so as at the helm of a company that's working on mRNA?

Welch: I will take more in solidarity with you.

Lugo: Great. That tells me that it's survivable. Except mine's a little chunky. I need to shake this.

Welch: It is a very substantial hot sauce. And if you look closely at it, there are seeds.

Lugo: [Attempts to drink from the bottle] No, nothing came out. Going to go in with the back of the spoon. [Tastes sauce]

Immediate kick is right. It is tasty.

I'd say maybe what's going on with mRNA right now, kind of like this hot sauce, I remember in February of last year feeling gut punched at the rapid spread of misinformation on mRNA. This is personal feeling versus what's happening at the company. There are many groups that I'm a part of; people that have been to elite universities and are highly educated — maybe not in STEM, but highly educated — who were also spreading a lot of misinformation on the vaccine. In Silicon Valley, in the Bay Area, I think everyone likes the idea of government efficiency, but liked particularly the DOGE efforts. I think the Bay Area also has this vibe of wanting to be contrarian, and a lot of these voices who are very highly educated came out with very anti-scientific views. I'd call them misinformed views and anti-scientific views. They were happy for the funding cuts. They were in favor of funding cuts to science, saying science needed to happen at companies, which, I run a company, not an academic institute, and federal funding is what made Moderna so successful. And so, a lot of companies do still rely on this, particularly for higher risk areas. We also rely on getting innovation that was funded. So, I'll start there with saying: I felt gut punched by the amount of people that were entirely misinformed on how drugs are developed and where those sources of funding come from and why the US has been so successful. I have met generalist investors out here in the Bay Area — definitely not the right fit for our company — but generalist investors to VCs, one of which who told me that her blood, when she got the vaccine, her blood turned different colors, and she's never been the same since.

Hall: I'm curious how she knew that. That’s fascinating.

Welch: Did her skin become translucent?

Hall: You know, some of us are melanin-challenged, thank you very much.

Lugo: I don't know, but yeah, she really believed her blood turned different colors and that she's never been the same since, that she's never been able to exercise the same and described symptoms of long COVID. I think it is much more likely that symptoms of long COVID are due to the infectiousness of the virus than the vaccine, even if you were vaccinated. But yeah, she really believed that, and honestly, there was nothing I could say. I had utter confusion as to how the mRNA vaccine possibly could turn her blood different colors and change her DNA, which, once again, my brain believes too much in the science to understand where she's coming from. So, I do hope that more generalist investment comes back into mRNA. Maybe we remember Larry Ellison announcing Stargate’s $500 million investment into AI, and Larry Ellison says we can use AI to make personalized cancer vaccines with mRNA, and then there was backlash to that.

So, I'd say generalist sentiment matters to venture capital firms. I do think that it would be great to get general investment back into biotech more than it is now. A lot of generalist investment has fled. I think on the specialized investor front, we haven't experienced any difference. I think at first, my investors asked me, "Are things going to fall apart?" But I think specialized investors still really believe in the promise of mRNA. So, we haven't experienced any difference on that front. For generalist investors, I do often get the question if mRNA is going to be allowed in the US. I think there is a question ... A lot of pharma and a lot of companies want to use mRNA, not for cancer, but for chronic conditions like autoimmune disease, where mRNA is safer and you don't want to go with viral packaging. Almost every pharma we talk to actually prefers the mRNA-LNP format to a viral format to go after chronic diseases, sensory diseases, diseases that require a higher bar for safety. Here is where I hope that adoption is not hurt by the misinformation over mRNA, because adoption is critical to the eventual success of a drug and, for chronic conditions, you're looking at broader distribution and, again, a higher bar for safety, a different analysis of risk benefit. So, I think that that is a valid question if adoption will change. I think it was asked differently: Is it going to be banned? I don't think it's going to be universally banned. I think some states are trying. Some states are trying to ban it, but it's going to be very hard to ban it. mRNA is in everything, but is it possible it affects adoption? It's possible.

So targeted specialized investors haven't changed. Pharma still really wants it. There's still a huge demand to make mRNA work. There's still a lot of excitement about its potential. We have had some grants where we went back and tried to scrub the language, but honestly, it becomes impossible to scrub the language and call it something else. That's why you see people calling mRNA cancer vaccines personalized immunotherapies. There's some scrubbing of language, but I think what really needs to happen is education. Let's start with the central dogma of biology. I did an MBA program, so I've been around people who are really highly educated, very successful, but have zero STEM knowledge, zero. Something I find interesting about our industry is that there is such a high barrier to entry because of the technical jargon that many people don't want to engage at all. And I think we need to come to some ground where people are able to engage more, because we are an industry that touches people very directly, typically in vulnerable states. So, I don't know how to fix that. I don't know how to fix education.

In terms of the measurable impacts on the company, I think there are certainly psychological ones. There's fear and emotional charge. My scientists are just as exposed to the news as I am. Technical investors, not so much. Big pharma, not so much. But eventually we do touch people. So, I'm hoping that the half of the people on the poll that Michelle mentioned are reached out to by people who know what mRNA is before they're reached out to by people who do not. And those people have great distribution.

Hall: They do. And that's the thing that is just insane to me about Instagram, TikTok, Twitter. I was one of, I assume, many, many Americans who were absolutely glued to Twitter trying to figure out what was going on the weekend Alex Pretti was shot. And what was crazy to me is the number of things that were coming up in my feed that we're absolutely bogus. So, if this is what is happening for somebody like me who is rarely glued to Twitter or Instagram or TikTok, what is happening to everybody else? It's crazy how much health advice and news gets disseminated through those channels.

Welch: Absolutely. Accessing physicians is probably going to be, I would say, the next step. Yes, the general public needs to understand what mRNA is too, but if we're moving into chronic conditions, if we're moving into indications that are therapeutic, you're really going to want to be able to touch that physician landscape. So, getting in front of that population is going to be our next important big step, in addition to trying to educate congressmen and senators and the patient population.

Lugo: I'll just mention that, of the 19-20 physicians that are in Congress, about 15 are Republican. They know the central dog of biology; they can understand the science.

Hall: Yes. And some of them are speaking out against what RFK Jr. is doing.

Lugo: Some of them are speaking out against, but I want to hear them say it louder.

Hall: Also, as soon as they do speak out, Donald Trump threatens to back somebody else against them. I understand why they aren't, and I'm glad that they are nevertheless.

Welch: Every little bit counts here, right?

So, Michelle, I want to jump to you and ask you a similar question that I'd asked Sophia. So, I was asking Sophia, in building an mRNA company, what have the measurable impacts been? She talked about specialist investors still being pretty much on board. You're now in the investment world, but I'd be curious, based off of your experience previously with Big Pharma, heading up a genetic medicines division and now working for a VC firm, what were some of the measurable impacts you observed, first of all, on how business was being run in the nucleic acids field in big pharma as the year progressed post the Trump administration coming to term here? And then what are you thinking too in terms of the investments being made in nucleic acids? What kind of trends are you seeing? Are you seeing that things are continuing full steam ahead or has there been a general slowdown in certain areas?

Hall: So, I think some of that fear that we've seen from different Republican leaders, the reticence to speak out against what is happening because it will fundamentally impact their bottom line, their job security—that's not just them. So, if you think about it, there's been a long tug of war for the last year since Trump took office on drug pricing. So, you can imagine as soon as RFK comes out and says, "MRNA, bad, funding, no," of course, your big pharma folks are alarmed; everybody is alarmed who has an inch of scientific training.

However, this is where strategy becomes important. You can imagine if all of the big pharma CEOs immediately started speaking out and saying, the Trump administration has appointed a buffoon — which would be scientifically objectively accurate — it does not help their end game, which is negotiating drug prices. So, I think there is an internal acknowledgement that what is going on is very unprecedented, but I think that there is also a calm exterior and for very good strategic reasons.

I will say early 2020, pandemic hits, 2021, excitement around mRNA, and, as we all know, infamously, the landscape changed to all you had to have was a pitch deck and a dream, and you got millions of dollars. Obviously, we are now paying the price for that, and I certainly felt like every year, 2022 on to 2025, it was, “next year's going to be better, next year's going to be better.” And it never was. I am cautiously optimistic that it finally is, because I think we paid a price twice. First, it was “platform, pitch deck, and a dream, you get millions of dollars.” Then it was, “I don't even want to talk to you until you're ready to go into clinical trials.” And now I think we're sort of bringing the pendulum back somewhere in the middle where we recognize that assets alone create high but short-term value. Platforms alone are pretty worthless, but that there's a happy middle between those two. And so, I will say it was an interesting time to be in Big Pharma where I joined in 2020 and it was like, “What's an mRNA and what's an LNP? Can't we just do everything we need with siRNAs? Those seem pretty good,” to, all of a sudden, the mRNA vaccines get approved, and it's like, "Have you heard about this thing called an mRNA-LNP? It seems like a really big deal." And I'm like, "Yes. Yes, I have. Thank you. Yeah, we don't actually care unless it's about to be in the clinic or, ideally, already in the clinic.” So, it was just a really weird time, frankly, to have been in Big Pharma. I am really pleased that I appear to have made the switch to investment around the time that I think we're all starting to say, “Maybe we were a little too loose, and then a little too stringent, and maybe we can bring some intelligent and strategic risk-taking to the future.” So that's what I'm super excited about.

Welch: A little bit of a Goldilocks effect here.

Hall: I think so, and it's welcome. I don't know about you, but I certainly saw a lot of companies in 2021 that were funded and I'm like, "You got money for that? You are kidding." But then I think we're way too strict now. I was talking to a CEO who was talking to an investor about a seed round, and they had asked him where his NHP data was — for a seed round! So, I'm really happy to be in the Goldilocks regime, and I really hope that it holds.

Welch: So outside of your own businesses, outside of the VC world, I think one of the most important aspects is there's a supportive infrastructure that we need as well to help us make our drugs. We have CDMOs, there are tech suppliers. Academia is a really big piece of partnerships, especially for the early-stage biology. How are you seeing the supportive infrastructure reacting to this political environment, and do you think that this response is proportional to the challenges that we're facing? Has this impacted your ability to access partners or innovative solutions to help you bring your science into the clinic?

Lugo: I'll take another little spoonful.

Welch: I will join you.

Lugo: It’s hard to get it out, though. It’s very chunky.

Welch: I think that's the mark of a good hot sauce, though. I tried another Carolina Reaper sauce. It was more vinegar-based; It was more fluid. It was not quite as good.  

Lugo: This is very tasty. I think that the ... Oh, okay. One more.

Welch: Michelle is like, “Nah, you guys are nuts."

Lugo: This is tasty.

Hall: I’d like to point out that I would like my GI system to be in good shape after this.

Lugo: I know. I keep forgetting that it’s my GI system that suffers.

Hall: I’m taking proactive measures.

Welch: You guys are rock stars.

Lugo: How is the supportive infrastructure reacting in the political environment: I don't know exactly how to answer that question. I will say that, generally, because the macro is not so great, that is pushing companies to do things in ways that they have perhaps not done before. I think, for example, a lot of companies were thinking about internal manufacturing. CMC is incredibly important. So, a lot of companies that were from COVID era seem to have thought about building internal manufacturing. Now what's in vogue is, can we just run this company entirely digitally? Can we only have enough people to do magic sauce and then everything else gets outsourced? That's what's in vogue. You just work on the core IP, and as much as possible needs to be done elsewhere. This is obviously bad for people because there are so many great scientific minds on the market right now that cannot get a job, and this trend is only getting worse and worse. It is also pushing people to look for infrastructure outside of the country because it is cheaper. So, the more that we punish and whip the science industry and the macro remains bad, the more creative people are going to be. Sometimes, this means actually we've been able to talk to a lot of delivery companies about potential collaborations and going at things together. So, I think for genetic medicines where payload tends to be risky, delivery tends to be risky, and both of you are trying to move forward more quickly, it opens up more avenues for talking about collaborations. It also pushes CEOs to think, how can I go to places where it's cheaper and US is most expensive. So, it has pushed people to ... I think the opposite of what the government wants, it pushes us to find many opportunities for research and manufacturing abroad, particularly in Asia or Europe where it's a lot cheaper.

As a company, I do think that it's a national security issue to be able to have a domestic supply chain built up for mRNA products and have strong research capabilities here. As the leader of Radar Therapeutics, I need to watch my budget. So, I cannot vouch for both goals at once. My budget is limited and therefore, I have to do what's best for the company, and what’s best for the company is not often to build it all up here. And so, I think the government should be aware of that. You're forcing companies to make decisions. You can add more sticks; I think the government has looked at a lot of sticks versus a lot of carrots. It's time for carrots. The more sticks that you do, there's going to be one stick too much that gets companies to move entirely out of the US.

I enjoy being in California where we have CIRM, and we have extra money allocated to regenerative medicine. But —

Welch: As we talked about last time, there's a lot going on overseas. There's quite a bit to want to take part in. So that's something to consider.

Michelle, what were you going to add?

Hall: Oh, so much.

And now that I don't have to get everything I say approved by a corporate communications person, I'm going to say it.

Welch: Please do.

Hall: So, I typically like to look up my facts, but I'm going to do this one from memory. So, apologies if it's wrong. I think something like only one in 10 Americans even has a passport. We are not known for being a very well-traveled or worldly group. I think maybe building on what Sophia is saying, I think a lot of this comes from our feeling that we are the best and we are the only option, and we are going to rapidly find that we are not. And that, also building on Sophia's point, was not the point. I mean, again, all you have to do is go and look back at economic history to see that tariffs don't work. And so exactly what we knew and could predict what happened is happening. So, Americans are paying more to get their drugs manufactured abroad because we're still importing them. We're just now putting tariffs on them. So, I knew that intuitively, but I felt it acutely the other day when I was on a call with an investor in Europe, and he put it to me very plainly. He said he no longer wants to invest in American companies because he does not trust the US. He said, if Donald Trump is going to invade Greenland and divide NATO, it is going to become Europe versus the US, and he is not going to invest his money in that, and he is sticking his money in Europe. Imagine hearing that. And I have to say, I hear you, I respectfully understand that, and the US remains the largest commercial market for drugs. And he correctly countered, “For how much longer?” So, I have been alarmed but also encouraged in some ways. So, for every person who said something like that to me, which was totally fair, other people have said things to me like, our country would welcome you. You're welcome to relocate here. And so, I think, I hope, I pray that cooler heads will prevail. I think a lot of the world does see what's happening and recognize that maybe what the American government is doing is not necessarily a reflection of the entirety of its voter base, and I am hopeful that this will be a temporary blip on the radar.

Welch: Beautiful answer. I want to cool us down a little bit because my lips are on fire.

Hall: Mine too, still.  

Welch: They're still on fire. How are you doing, Sophia? You surviving?

Lugo: You do have to avoid the lips, but yeah, it's definitely a kick and then it goes away. We'll see about the stomach.

Welch: Yeah, I was already feeling slightly weird before filming. So, I can only imagine things are going to continue to —

Hall: No hot yoga after this.

Welch: There's no hot yoga. There is a personal trainer, however, so this could be fun.

Hall: Oh God.

Welch: So, I want to think optimistically here. Michelle, you've already kind of kicked us off really beautifully with your previous response. Cooler heads hopefully will at some point prevail. We've talked a little bit, too, about the hopes that education will take root here in the US and help educate some of that 50% of the populace to take a stance on mRNA. But what advancements do you think — and to keep this a pun — could extinguish some of the political fires we're facing or at the very least could soothe the industry's burns?... There won't necessarily be a magic bullet, of course, but what are some of the advancements on the therapeutic side or in terms of strategy that you think could really help us out here? We can start with you, Michelle.

Hall: The resignation of RFK Jr.

Welch: We've got that one.

Hall: Okay, great. I wanted to make sure that was clear.

Welch: Go back to episode two. I think it was episode two.

Hall: Yeah. Barring that, the impeachment of RFK Junior. No, anyway.

So, I struggle with this because you ask what therapeutic advancements could extinguish this political fire? I don't think it's about therapeutic advancements. This is fundamentally a political fire. This is not about information. This is not about facts. This is about fear, and this is about misinformation. And so I'm not sure any advancements, grand breakthroughs, Wall Street, journal op-eds extolling the virtues of this are going to do the trick at this point. I think this is going to have to be the long game politically. I think measles is at the highest rate it's been in decades. I think when people start to feel the impacts personally, sentiment will change. So that's my thinking. Now, let's just say hypothetically, we could overcome political misinformation with new scientific advances, I would say nothing is going to change perception faster than clear patient benefit.

You hit the nail on the head when you said, you get the COVID vaccine, you don't know that you didn't get COVID. The effects of it are invisible to you, but what is visible to you is, “Ow, my arm hurts. Ooh, I feel a little feverish and fatigued.” So understandably, people didn't feel super enthusiastic about that. But the more, for example, Baby KJ stories we have; the more Moderna personalized cancer vaccine data we have that is positive, I think that will start to really turn people around if combined with a sufficient change in the tone of the Trump administration on mRNA. And so, I'm really hopeful that those two things will happen in parallel.

Welch: Go ahead, Sophia. What do you have for us?

Lugo: Michelle stole the answer. I think she's exactly right. I don't think there is any therapeutic advancement that's going to extinguish this fire. I mean, the mRNA vaccines were such a raving success. The safety and effectiveness of these vaccines was such a raving success. There are many parallel universes where a new modality tried out in vaccine en masse would not have been a success, but it was a success. In fact, they could have even, even if they had been ... I think the J&J vaccine was eventually pulled off the market. Even if they had matched the J&J vaccine with older technology, I think that's a scenario that could have happened in a parallel universe, but it didn't happen. It didn't. There was a raving success that brought mRNA out onto the scene. It was brought out to the scene by a Republican president — 

Hall: Who claimed he should have gotten the Nobel Prize for it.

Lugo: Who claims he should have gotten the Nobel Prize for it, and it won a Nobel Prize. So, it did all the things.

Welch: It checked all the boxes!

Lugo: Yes. I think most authors writing this book would not have ended it with: “And then the same president hired a guy who decided that it was terrible and convinced everyone that actually what they experienced was not what they experienced.” So yeah, this is not a matter of therapeutic advancement. I think a lot of patients will experience it, but if it's not done en masse, they may not understand it.

It's interesting because we do have medications like semaglutide and tirzepatide that are taken en masse by people who probably don't understand how they work. And everyone wants it, likes it, is raving about it. It's probably a lot of the same people who don't like mRNA for some reason that are taking this. And it's novel and it's being introduced en masse and in some circumstances they are not approved medications; they’re being mixed at different compounding pharmacies. I think that what's clear here is that there's immediate benefits to semaglutide and terzepatide that is desirable. So, people find ways to justify that it is desirable. You don't see the government raging about this being untested. So, I think this is an information thing. And I think we're at a point where the Tennessee House had a bill passed or Tennessee House of Representatives had a bill passed where they said — Michelle, you probably saw this — that people were potentially eating mRNA vaccines through lettuce; that this technology was being —

Hall: Oh, yes! You know you are also made of mRNA, as is your food.

Lugo: Lettuce does have mRNA; it’s true. If anyone is listening to this: All of your foods have mRNA.

But they believed that it's possible that some vaccine producers were trying to develop technologies to pump the food supply, to mass-medicate Americans; that they were already being pumped into lettuce. The vaccine was then consumable, and it would change your DNA so that when you got genetic testing before eating the lettuce and after eating the lettuce, your DNA would be different. This passed in Tennessee, and I believe in one other state.

There is no science there. Science did nothing wrong or right in this case about the lettuce. My brain is like, I don't even ... If I were there, I wouldn't know what to say. If I said mRNA is in the lettuce, it might make things worse. If I said that mRNA degrades so freaking quickly, it's hard to deliver this thing. Putting it in a lettuce, like, “Who knew it could be orally available? That's awesome! Pass that on to me” — I can't say that because that'll get me in trouble, too.

We are not structured to deal with this kind of misinformation, so it has to start at the level of how good we are at distributing good information when we know that there is bad information being distributed.

When I saw this thing about Tennessee, this person keeps talking about how he read about it and then he kept reading about it further. Where is he reading about this? I want to know. We need to be just as good at reaching people with good information as whatever lettuce-claiming author did to distribute bad information that got a bill passed in two states. So yes, I really think ...

Hall: And just before people say, “OK, it's three educated women in blue states talking about this,” I just want to say, I think it is a serious discredit to the people of Tennessee that their representatives are doing that, right?

Welch: 100%

Lugo: 100%

Welch: Well, that's a pretty wild place to end this episode, but I almost feel like finding out where the “lettuce people” get their information is a really great, great way to end an episode that has to do with something called The Rapture.

Hall: Just the cost of that lettuce alone would be astronomical. I have a friend of mine who works in ag tech and I'm always harassing him about stuff. And I'm like, " Well, could we engineer plants to do X, Y, Z? Think about climate change, and we need climate resilient crops.” And he's like, "Yeah, Michelle, but I'm not going to pay mRNA prices for that."

So whatever evil philanthropist is funding this very expensive lettuce, I'm super curious.

Welch: And she's an investor, so come forward.

Lugo: I will say that one member of the Tennessee House — I'm saying House, I think it was the House — did say that, “That lettuce would cost so many thousands of dollars. I'm not understanding why someone would be doing this.” I think —  

Hall: They're just an evil henchman hell-set on vaccinating people against their wills. I mean, it's the most parsimonious possible explanation.

Lugo: I mean, maybe we need mRNA for GLP-1s.

Welch: That’s not outside the realm of possibility.

If mRNA will make you lose weight, you're golden, right?

Lugo: Yeah, except that would also be expensive to produce and expensive to distribute, but ...

Welch: So, since this is the end of our reign of Hot Takes, and we are the spice queens, what positive note would you have us end on?

Lugo: mRNA is still an incredible molecule. It's incredible because it is safe. It gets degraded so quickly in the body, and that's the benefit. It’s not changing your genomic architecture unless you encode it to do so by making it into an editor. But the benefit of mRNA is that it's safe, it's powerful, and it’s versatile. You can encode so many different functions. It's a hard molecule; there are many technical challenges to be solved. But it is worth working on them because we can access so many diseases. I heard a statistic that I hope is true that only one in four diseases have any medications for them, and this new modality will open up so many more, and that's exciting.

Welch: That's a beautiful point. Michelle?

Hall: Every generation has something horrifying that they just all shake their heads years later and go, “I cannot believe that we ever did that or thought that or acted like that.” This is ours. This too will pass, but it only passes if we force it to pass. Complacency, silence, that is not going to work. Throughout history, lots and lots of things have changed when enough people were loud enough about them. And so, I think what is unfortunate is I would love a world where we could decouple science from politics. I think we are seeing that that is not the case. So, this is where I would really encourage a lot of us to be strategic. Yes, if you have to go in and negotiate with Donald Trump about drug pricing, probably good to not be as vocal as I'm being right now. However, I am not the person who has to go negotiate with him about drug pricing, and I assume neither are y'all. And so I think it's really incumbent upon us to continue to be loud and vocal, and that is the only way things like this are going to change.

Lugo: And if you are in that room, take the opportunity to be loud and vocal about what's going on and how this is going to have an immediate impact on people's health and your children's health and the US' competitiveness. So, make your voice very, very heard. It is not Donald Trump who is driving this misinformation. There are other voices.

Welch: Well, ladies, we have done it. We've beaten the Spice Challenge. You both have not been vanquished. You should be very proud of yourselves. I am still thrilled and honored and very, very grateful that you guys were willing to embark on this wacky journey with me. And I'm really excited to have been able to share your thoughts and your brain power with the Advancing RNA audience. So, thank you. From the bottom of my heart, thank you. This has been a lot of fun for me and very informative.

Hopefully, we will be back with some more mRNA and RNA-related hot takes in the future with new voices and perhaps some returning faces. So, thank you all for watching and joining us throughout this miniseries, and I hope to catch you the next time. Take it easy.