Over the next several weeks, Distillations will be talking to people who have special insight into the coronavirus crisis—biomedical researchers, physicians, public health experts, and historians.

In this episode, we talk with Robert Langer, a chemical engineer and an entrepreneur who runs the largest biomedical engineering research laboratory in the world at MIT. He has also started numerous biotech companies, including Moderna Therapeutics, a company that’s been making headlines for the COVID-19 vaccine they’re developing.

Langer told us about his work with the Gates Foundation to develop a way for vaccines to self-boost in the body, his work with the sneaker company New Balance to create masks and his thoughts about how diagnostic testing could be better.

Credits

Host: Alexis Pedrick
Senior Producer: Mariel Carr
Producer: Rigoberto Hernandez
Researcher: Jessica Wade
Audio Engineer: Jonathan Pfeffer
Original music by Zach Young

Transcript

Alexis: Hello, and welcome to Distillations. I’m one of your hosts, Alexis Pedrick. In response to the coronavirus pandemic we’ve launched a brand-new series focused entirely on COVID-19. Over the next several weeks we’ll be bringing you interviews with people working at the heart of the crisis, including biomedical researchers, physicians, and public health experts.

In this episode our senior producer, Mariel Carr, talks with Robert Langer, a chemical engineer and entrepreneur who runs the largest biomedical engineering research laboratory in the world at MIT.

He’s also started numerous biotech companies, including Moderna Therapeutics, a company that’s been making headlines for the COVID vaccine they’re developing.

Langer told us about his work with the Gates Foundation to develop a way for vaccines to self-boost themselves, his work with the sneaker company New Balance to create masks, and how he thinks diagnostic testing could be better.

Mariel: Thanks for joining me.

Bob Langer: My pleasure.

Mariel: So I know that you have a lab at MIT. Is your lab doing anything specifically COVID-related now, or has it changed at all as a result of the pandemic?

Bob Langer: Yeah. Well, let’s see, there’s a lot that we’re doing. I mean, so let’s see how to answer all those. First, I mean, MIT, as are many universities, is I don’t want to say shut down, but greatly diminished in terms of, you know, allowing people to work in the laboratory.

So for the last few months, if you weren’t doing something COVID related, you know, the people aren’t able to come in. But we are doing a number of things which I’ll go over. And we’re also doing a number of things—I’ve been involved in spinning out some of our technology into various companies.

Mariel: And Moderna is one of those companies, right?

Bob Langer: Yeah. Moderna is a company I cofounded, and there we’re developing a new vaccine based on messenger RNA and nanoparticles. That’s actually now in phase 2 trials and will probably be in phase 3 trials in July.

Also in our lab we’ve been doing a lot of work with the Gates Foundation. And there what we’ve been doing is developing a way to give a single vaccine that self-boosts itself. We’ve got different micro or nanoparticles that we encapsulate a vaccine in, and they burst at different times, like at zero, one month, two months, a year, whatever you actually design it to be. And of course, if you look at the vaccines that are being used, including the Moderna vaccine, right now you give two injections and some of the others, you give three injections.

We don’t know yet whether people have to go in for boosters. So that’s been a project we’ve actually had in our lab with the Gates Foundation. And we published an article in Science on this and other journals too over time. We’re also working on new masks. They’ve been developing new masks. And I’ve also helped New Balance, which is actually a sneaker company. They’ve done a great job actually using a lot of the sneaker technology to make masks for some of the big hospitals in Boston.

We’ve also worked on ventilators. Shriya Srinivasan from our lab has been working on an ultra-inexpensive ventilator, like it might cost $200 and it’s portable. And we also published, several people in our group and myself, we published a paper in Science Translational Medicine just a couple of weeks ago on a very safe way to split ventilators, with alarms and things like that.

And then we’ve also been working on new blood tests. One of the companies that I cofounded is called Seventh Sense. But by the way of background, you may know that one of the problems with all the testing—and it’s been terrible—is false-negatives and actually false-positives. But they’re all using things like nasal swabs and things and stuff like that, which I think is going to be very hard to accurately, you know, get things.

So we actually came up with using microneedles as a way to actually minimally invasively with essentially no pain draw blood, which could be used for serology tests. And the FDA actually has approved this technology for at-home use for diabetes, but has not yet approved it for COVID. But I don’t see any reason, you know, given that the safety is well established, and I’ve even, I’m a baby myself, and it didn’t even hurt me when I did it. So that was actually very encouraging.

I mean, the testing sadly in the United States is incompetent, you know? I mean, not only do you get false-positives and false-negatives, like my son’s girlfriend went in to get a test in April, and they still haven’t given us the results yet.

I mean, so their testing is just terrible. They’re charging us money for it, which we aren’t paying until we get the results, not because I’m concerned about the $36, but because I just am so disappointed that they can’t get test results back. But at any rate, so those are some of the things that we’re working on, I mean, in the lab and in the companies.

Mariel: That’s like you’ve listed sort of every aspect of this virus, you have your hands in.

Bob Langer: Also, you know, this is a very underserved thing, but vials, you know, when you develop these vaccines, you need to actually package them. That’s actually a big deal—the manufacturing, the packaging, the distribution.

You know, there’s a lot of steps on any of these things. So whether it’s Moderna or other companies, they need to package the vaccine and distribute it. But one of the problems with a lot of vials is that, I mean, it doesn’t happen often but it does happen, is if you use the glass vial, sometimes they break and you get shards of glass.

And if you use a plastic vial, a lot of times oxygen can get through and cause problems with the vaccine. So here, what SiO2, did, this is run by Bobby Abrams and based on some technology that Dow originally developed. It’s in Alabama. But they figured out a way to coat these so that you get the best features of both the glass and the plastic.

And they just got a giant BARDA [Biomedical Advanced Research and Development Authority] grant, over a hundred million dollars, just announced today, to make, you know, many, many millions of vials for these too.

Mariel: Oh, wow, and that’s one of your companies?

Bob Langer: I don’t want to give myself credit. I’m an adviser to them. But interestingly Bobby Abrams, who started it, is from Albany, New York, which is my hometown too. So there I’ve been an adviser to his companies for about 25 years.

Mariel: Okay. So the list that you’ve just given me is like every aspect of this virus you in some way are involved in, and yet it’s only been a few months. So tell me, like what has it been like in the past few months to, I imagine you were working on other things and then you had to pivot? Tell me what that’s been like.

Bob Langer: Well, I didn’t have to pivot that much. You know, first of all, I mean, like all those companies that I mentioned I’ve been working with anyhow I helped start. And SiO2, as I mentioned, I’ve been working with from 1995. Seventh Sense, which was doing the blood draws, is, you know, I helped start that about 10 years ago.

And the vaccine work, Bill Gates, as you may know, he actually predicted that all these things might happen. He has a TED talk from 2015, and I remember when he came to see me in 2012. He kept bringing up, you know, vaccines. And we actually came up with a number of ideas that our labs have been working on, which they’ve been funding and they’ve been terrific, including Bill.

And so, you know, so a lot of these things we’ve been working on. But some of the things are newer like the, like I said, some of the masks that—I’ve been a big believer in masks from the beginning of this crisis, way back in, you know, when it was starting in January and April, January, February.

And so, you know, so some of the things are new, but it really isn’t that much of a pivot. I mean, and in a way, I mean, there’s just a couple of new things, and one of the things about this crisis is scientists all over, not just ourselves, are doing whatever they can to try to help out on the crisis.

So what doesn’t get done sadly is some of the other things that we’ve been doing, like the cancer research, you know, other things that are also very, very important. I mean, so that slows down and that’s of course tragic. I mean, because, you know, just fewer people are in the lab.

Mariel: Yeah, I hadn’t actually thought about that yet, but that’s an important point.

Was there sort of an alternate reality where we were more prepared in a way and that it didn’t have to be this sort of like mad crunch that everyone’s shifting to, or that kind of would have happened anyway?

Bob Langer: Well, I think that this whole thing could have been handled better. I’m not limiting it to just our country. I think that just people didn’t anticipate this. And, you know, some countries have done a better job than others. Of course, some countries are probably easier to do than others because of their size.

I think sadly both the Centers for Disease Control and the World Health Organization gave very bad information about not using masks, which I think if people did that sooner, I mean, would have been much, much better, you know. And I think that people, some of the policies on social distancing, which are now, you know, more firmly in place are much better.

I don’t know that we could have, you know, I just think we could have done a lot better. Whether we could have ever anticipated that it would happen, you know, in January or whenever of 2020, that I doubt. I think that, but I certainly think we could have done a better job on testing and masks and other things like that.

Mariel: Yeah. I want to ask you about, so a lot of people that I’ve spoken with and a lot of things that I’ve read and I’m sure you’ve read talk about how this is sort of an unusual moment where everyone is watching science happen in real time. And they’re watching, I mean, not up close necessarily, but we’re normally, we’re just sort of told about like the nice, shiny results at the end. And we don’t get to see any of the part in the middle. And I was actually rewatching the Scientists You Must Know video that features you this morning. And I, something that you said stood out to me about how you’ve run thousands of tests or a thousand tests.

SYMK Archive:  Being the only engineer there, I would see all these surgery problems, and they were trying to solve it certain ways. But I thought, gee, you could solve this by chemical ways or engineering ways.

And so I got all kinds of ideas, new ways of drug delivery, new ways of using enzymes to do things in the body, new ways of growing tissues and organs, new types of materials.

But we did thousands of experiments, and it did, it took a lot of persistence. Most of the time, of course, I’d fail.

Mariel: It struck me that people don’t really know about that part. I guess what I’m asking is does it seem like it’s different this time, and do you think this is a good thing or a bad thing that sort of the public is getting in on this a little bit?

Bob Langer: Well, I think, I mean, does it happen? This time sure there’s going to be lots and lots of failures. I think in terms of the public, I think, it’s so hard to say.  I think it’s good for people to understand what’s going on. The problem, I think is that, you know, some newspaper writers try to stir up controversy.

I mean, most of them I think have been very, very good, but some of them try to, you know, I mean they have an agenda and they pick the facts that will fit their agenda. I think it’s just unfortunate. So, you know, the question is sometimes people don’t know what to believe.

Mariel: So I guess that kind of leads me into asking you about Moderna because there obviously has been some of that sort of press about it. Can you tell me anything about their vaccine?

Bob Langer: Sure. Well, I mean, just historically, you know, what people have done with vaccines is usually you might use viruses and attenuate them or inactivate them, or you grow up eggs and make proteins. But the point is classically you would spend a really long time and have giant manufacturing plants to make the tons and tons of vaccine or protein.

But there’s a central dogma of molecular biology, which is that DNA makes RNA makes protein. And so rather than do protein, the beauty of RNA is that you could figure out an RNA that might inactivate the virus. In this case, the RNA is aimed at what’s called the spike protein, which is a part of this particular virus.

And you could make this RNA. And depending on how you did the chemistry of both the RNA and the nanoparticle that you’re going to use to deliver it, you can then inject it into the patient. It goes into the patient’s cells. And rather than have this giant manufacturing plant, you know, make the protein, you have the person make the protein.

So, and that’s like I say, the real paradigm shift that DNA makes RNA makes protein. So by using the RNA, you’re able to have the body be the factory that makes the vaccine. And that’s actually Moderna’s in I think something like eight different clinical trials for vaccines and actually many other trials for other diseases.

But the beauty of it then is that you could use a much smaller manufacturing plant, and you could do it much faster, right. In fact, that’s what Moderna did. That’s why they were in clinic, or we were in the clinic so quickly because you could make the messenger RNA, and then, like I say, have the body do all the work for you.

So that is the strategy that Moderna is using. And basically in the phase 1 trials, where it was reported—that’s largely a safety trial—is that the two lowest doses, 45 out of 45 people had antibodies, and 8 out of 8, which was all that was tested, had what are called neutralizing antibodies.

Antibodies, for example, might be tested by what’s called an immunoassay: that just shows they’re present, but the neutralizing antibodies show that it actually kills the virus. And both times the levels were at least, according to what I’ve heard, at least as high, if not higher than people that were convalescing with the disease.

And in terms of safety, at the two lowest doses, it seemed to be very safe. At the highest doses there were some side effects. So what’ll happen now in the phase 2 trial is you’ll go with the second-highest dose, which was safe and effective, and probably that’ll be done in the phase 3 trial too.

Mariel: Okay. So a lot of, or not a lot of, but a big part of any kind of trial like this is figuring out the right dose. Is that right?

Bob Langer: That’s correct. I mean, in fact, that’s sort of the standard with any trial, an FDA-sponsored trial, is that the first trial is usually to find the highest safe dose that you can use.

Mariel: So why were only eight people tested?

Bob Langer: Actually all 45 will be tested. But what happens when you do escalating dose is you start out, you know, with the lowest dose, and then you give an injection; then you have to give a second injection. So it’s just a timing thing. All 45 will ultimately get tested.

But it just took longer to get, to do the test for neutralizing antibodies, but all of them got tested. It was just, that was just a point in time.

Mariel: I see what you’re saying. Okay. Could you tell me a little bit about the messenger RNA and how that works? Is that specific to Moderna, that mRNA?

Bob Langer: There’s about four companies working on it.

All of them are trying to come up with ways to do it. I mean, you can modify messenger RNA differently, and you can use different types of nanoparticles to deliver it. But no, there’s a, you know, in fact, Translate Bio, which has licensed some of our MIT patents, you know, so their nanotechnology for delivering messenger RNA. So they’re working on it. I can’t remember if they’re working with Sanofi, or if not, then there were a couple of others. CureVac is working on messenger RNA. And I know there’s at least one other company too, working on it. So I mean, there’s a variety of places working on them.

I think that Moderna, you know, we’ve made a huge effort for 10 years to really develop the technology and expertise to, you know, manufacture it accurately, and make a lot of it, and, you know, work on the nanoparticles so that you could make different nanoparticles with different properties. But other companies are working on it too.

I mean, and to me, I think all this is a good thing, that there’s lots of companies working on it. And then there are other vaccine strategies as well, with DNA and things like that. 

Mariel: Do we currently have any vaccines that use this RNA approach?

Bob Langer: There’s none approved because it’s so new, but there are clinical trials that at least have shown safety and efficacy for different diseases for the limited number of patients that have been studied.

Mariel: So there’s been a lot of criticism in the media about Moderna and the way they’ve been developing their vaccine, sort of, I guess the criticism is that it’s been too secretive. What are your thoughts on that?

Bob Langer: Well, my feeling is, this goes to what I said before. I mean, I think by and large most people are positive about it. You know, I think you have to look at what the criticism is and who says it. I mean, you know, there can certainly be, I mean, you know, there’s different types of criticism that I’ve seen, but there’s different types of criticism for everything.

I mean, I’ve certainly seen some places that will give criticism. It’s interesting. One, I think—I don’t know if it was CNN or Stat—one of them said that, well, Moderna is very secretive, but then the article that was written said, well, this former executive said this and this person, anonymous person, said that. And this person without a name said this, and I remember reading something at the bottom where, you know, people write in responses. A person wrote in response, boy, they’re calling Moderna secretive and they don’t mention anything. You know, I don’t think it’s a question of how—that goes to what I said before.

I think some of these articles just try to be deliberately provocative without really backing it up. I mean, you can go out and find people who will say almost anything. But then you have to decide whether you want to write a balanced article, which I think would say some positive things or some negatives, or you want to write an article that just criticizes people.

And I mean, that’s very easy to do. But I would say I’ve seen both. And I think, you know, ultimately to me, the answer will be, does it work or not? You know, in patients. Will it be useful for patients or not? You know, I mean, myself, I have seen some of the data. I think it’s encouraging, but it’s still very early and we need to see more.

I see very little value in some of the criticisms that I’ve seen. But you know, I mean, to me, everybody’s like at Moderna and lots of other places are working incredibly hard to try to do the best science they can. To me, that’s what the important thing is. Can we really help people’s, you know, can we really help patients?

And certainly that’s been my goal. And I think that’s certainly the goal of the people at Moderna.

Mariel: So another thing that, I guess this was part of the same section of the video I was watching earlier, the response to your controlled-release drug delivery. At first there was, it was met with a lot of skepticism. Is that right?

Bob Langer: That’s absolutely correct. Yeah. I almost didn’t get tenure at MIT, and I got my first nine grants turned down.

Yeah. So that’s kind of what I meant when you were asking about Moderna. I mean, sadly you get used to criticism in different ways, and you know, people can, you know, but history will ultimately decide what’s right and what isn’t.

Mariel: Yeah, it just made me think like, at some point the science will either work or it won’t. So we’ll all have our answer, I guess.

Bob Langer: That’s what I feel, you know, and again, things may not be perfect. But you know, trying to come up with cures is a very tough thing. But you could look at the flu vaccines, which work some percentage of the time, but not all. I mean, but you’re right.

I mean, ultimately that’s the way I look at it. I mean, I think that myself, and I think, you know, our lab and the people I work with, we’re working as hard as possible just to do the best we can. And that’s all we can do is the best science we can do.

Mariel: How do you think this will all end?

Bob Langer: Yeah. Well, I wish I knew. I just hope it ends soon for a lot of reasons. But I think, I mean, I’m concerned that we’re moving too fast in terms of reopening things. I hope I’m wrong. You know, I worry about, you know, getting surges because that’s certainly happened in the past. But you know, ultimately, I mean, sadly already we’re close to doubling the number of deaths that we had in the Vietnam War, and there’s certainly going to be more to come.

So this is, and lots of people have lost jobs. I mean, it’s a real tragedy. So I think you want to, so I don’t know exactly how it will end, but whatever, however it does, and whenever it does, it’s this tragedy. So you just want to do whatever you can to make it end as fast as possible and to have as few people affected as possible.

Mariel: Yeah. Do you think that we’ll have a vaccine in the next year?

Bob Langer: I hope so. I don’t know for sure. I mean, I think, you know, I never want to create false hope. I think the goal, I think some of the strategies, I mean, there’s many, many companies working on it, which is good. There are a lot of different strategies, which is good.

So I really hope so, but you know, there’s certainly unanswered questions.

Mariel: Do you think this will happen again? And what could we do differently next time?

Bob Langer: Bill Gates, who I mentioned, he gave this TED talk in 2015, and he was saying, look, we spend so much money on the military and this and that. We spend almost no money on things like these pandemics. And we should be aware that it’s not these big bombs that are going to kill us. It’s going to be these tiny nano microbes that are going to kill us. And we should be prepared to spend money on that. And I, so I do think he’s right. I think that that’s a danger, but I think we can certainly be far, far better prepared than we have been this time. I mean, as a nation and as a planet. And I think if we are, we’ll do much better.

Alexis: Thanks for listening to this episode of Pandemic Perspectives. We’ll be bringing you more interviews from all sides of the crisis. So stay tuned and watch your feeds.

As always, you can find all of our episodes plus transcripts and show notes at distillations.org. And you can find tons of educational resources on our website at sciencehistory.org/learn.

The Science History Institute remains committed to revealing the role of science in our world. Please support our efforts at sciencehistory.org/give now. For Distillations, I’m Alexis Pedrick.