YouTube: https://youtube.com/watch?v=NdukJ8iG84s
Previous: The Virus Eaters
Next: An Ode to Salps: Our Gelatinous Marine Cousins

Categories

Statistics

View count:1,416
Likes:173
Dislikes:9
Comments:32
Duration:28:43
Uploaded:2020-12-16
Last sync:2020-12-16 23:15
Earlier this month, we talked with Daniel Skovronksy, the Chief Scientific Officer of Eli Lilly, about their colorfully-named COVID-19 treatments. We also discussed the challenges of mass-producing antibodies and how medicine might change going forward.

Hosted by: Hank Green & Alexis Dahl

SciShow has a spinoff podcast! It's called SciShow Tangents. Check it out at http://www.scishowtangents.org
----------
Support SciShow by becoming a patron on Patreon: https://www.patreon.com/scishow
----------
Huge thanks go to the following Patreon supporters for helping us keep SciShow free for everyone forever:

Marwan Hassoun, Jb Taishoff, Bd_Tmprd, Harrison Mills, Jeffrey Mckishen, James Knight, Christoph Schwanke, Jacob, Matt Curls, Sam Buck, Christopher R Boucher, Eric Jensen, Lehel Kovacs, Adam Brainard, Greg, Ash, Sam Lutfi, Piya Shedden, KatieMarie Magnone, Scott Satovsky Jr, charles george, Alex Hackman, Chris Peters, Kevin Bealer
----------
Looking for SciShow elsewhere on the internet?
Facebook: http://www.facebook.com/scishow
Twitter: http://www.twitter.com/scishow
Tumblr: http://scishow.tumblr.com
Instagram: http://instagram.com/thescishow
----------
Sources:
https://www.istockphoto.com/vector/infographic-depicting-the-external-and-internal-coronavirus-structure-gm1202867079-345507611
https://www.istockphoto.com/vector/concepts-of-monoclonal-antibody-for-coronavirus-treatment-gm1279978172-378415156

 (00:00) to (02:00) [upbeat electronic music]


HANK: Hello, and welcome to a special and strange episode of SciShow. I'm Hank Green. We are always trying to bring you science news and also just engage with the constant and never-ending curiosity that we should all have about the world, but also, when we get a chance to talk to somebody who is at the edge of possibly the most important science story of the decade, you can't just keep that to yourself.

So, today I'm joined by Alexis Dahl, SciShow's Content Manager, and also Dr. Daniel Skovronsky, the Chief Science- the Chief of Science. Chief of Science, is that really your title?

DANIEL: No, Chief Scientific Officer. 

HANK: Okay, Chief- That still sounds great. The Chief Scientific Officer of Eli Lilly. Thank you so much for joining us.

DANIEL: Thank you, Hank. It's great to be here.

HANK: I assume that you are 60 or 70 years old but Eli Lilly is just giving you a really great drug to make you look so young for such a prestigious job you've got.

DANIEL: Thanks, I'm 47 years old.

HANK: God, well, first, you do actually look very young, but second, that seems young for the Chief Science Officer at Eli Lilly, but what do I know.

DANIEL: Well, it's a privilege to have this job. I lead a large organization. We have about 6000 scientists and drug developers at Lilly trying to discover new medicines for patients, and we invest about $6 billion a year in research and development of new drugs. So it's a great honor and a privilege to lead this organization.

HANK: And everybody just calls them Skovronsky bucks, right, because they know that you're in charge of all those dollars?

DANIEL: Well, we have $6 billion to invest. We have $12 billion of good ideas for new medicine, so it is competitive to try and pick through all of our ideas and figure out what's gonna work.

ALEXIS: So, what does your life look like as Chief Scientific Officer? What's a day in your world like?

 (02:00) to (04:00)


DANIEL: Well, although I'm a physician and scientist, I don't see patients, and I don't work in the lab anymore, so I work with scientists who are doing experiments and work with drug developers who are designing clinical trials, help pick which medicines, which trials we should work on, and help interpret the data and plot the future forward.

ALEXIS: So, you know, normal day making gigantic decisions.

HANK: Yeah, that doesn't sound stressful at all.

ALEXIS: [laughing] No.

DANIEL: Well, I have a great team, so it's not me alone. 

HANK: Yeah, I believe that. So, today we wanted to talk to you because of that Eli Lilly is working on a couple of COVID medicines that have gotten emergency use authorizations, and there are two of them that are exciting. There's bamlanivimab, and there's baricitinib. Have I done it correctly?

DANIEL: Yes, that's good enough. Bamlanivimab and baricitinib, yes. I can say it faster than you.

HANK: I hope so. And the reason that we actually got put together is that I was tweeting about what a ridiculous job people are doing at naming drugs these days and someone must know how on Earth we end up with these ridiculous names, and someone was like, "Do you wanna talk to the Chief Science Officer at Eli Lilly about it?" And I was like, "Well, maybe about some other stuff, too." But I have to do my due diligence now and fulfill my obligation. What's going on with these names?

DANIEL: Yeah, we enjoyed reading all of the humorous tweets as well. But, actually, we don't get to pick the names. So there's a group in the United States, it's affiliated with the American Medical Association, that actually nominates the names, and then we take them to the World Health Organization for finalization. We can give some input, but parts of the names of drugs actually tell you what they do.

So, for example, bamlanivimab, the "mab" part, M-A-B at the end, means it's a monoclonal antibody. All monoclonal antibodies end in "mab."

 (04:00) to (06:00) And then the "vi" part in the middle tells you it's a virus neutralizing monoclonal antibody, so it's against a virus. And then the beginning part is a little bit whimsical. It's up to people's imagination.


But, in this process, they try and make it so that no two drugs sound the same, and it's not confusing, and it doesn't mean anything in any languages. So a committee of people outside the company helped to create this name, and then it went to another committee who added more syllables, and that's how we get the lovely name. But it's turned out to be great, because a lot of people now have twisted their tongues saying bamlanivimab and, hopefully, creating some awareness that there's a new medicine that's FDA emergency use authorization for COVID-19.

ALEXIS: So, you mentioned there were some names, some options you were presented with. Were there any that you were just flat out like, "Nope, it's not gonna be called this"?

DANIEL: Probably just the one we've got.

ALEXIS: [laughing] Alright. 

DANIEL: But sometimes, in drug development, you can negotiate and say, "Well, how about this one?" and go back and forth. We don't have time for that when we're fighting a pandemic, nor is it really that important. What companies often do is they'll have a great-sounding name that's the trade name. So we have drugs that are called things like trulicity or taltz, and those are great-sounding names that roll off the tongue.

In this case, we didn't think that was needed or appropriate. This is a really early stage. This is an emergency use. We're not gonna be putting commercials on TV. We're trying to respond to, really, a medical crisis here, and so that's why we thought having a name like this is perfectly okay. 

HANK: So what is a monoclonal antibody?

 DANIEL: Yeah, thank you for asking that. Our bodies have immune systems which make a protein to neutralize invaders called an antibody. (06:00) to (08:00) And, within our body, our cells, our immune cells, they sort of evolve in response to an attack to make better and better antibodies that can bind more and more tightly. So that's why, when you get sick, after a couple of days, you start to make these antibodies, and then, over time, you can clear out the invader, and then your immune cells actually can lie dormant. But, if you see that same threat again, your body will pump out a lot more of that antibody.


Now, when your body does this normally, it makes all different kinds of antibodies to bind that virus or bacteria or whatever the threat is. What we've done here in the lab is we found just one from an individual patient that was the most potent, that bound this virus the most tightly on a particular part of the virus that we can talk about, and then we cloned it in our lab so that we can make millions and billions and trillions of copies of it in our factories.

And so we've turned something that came out of a patient into a medicine that is mass produced and completely uniform and can be given to patients at very high doses. And the theory here was that this antibody from this one patient who was one of the first people in North America to recover from this disease, that this one antibody was probably one of the factors that helped this individual recover. And so, can it help other people recover if we mass produce it in our factory? So that's exactly what we did over the course of the last eight months, which is just incredibly fast for what we do.

HANK: Yeah, I mean, it sounds very fast. And I actually had got it in my head that this was something that you were taking out of people, like, they took something out of Tom Hanks and put it in someone else, but you've figured out how to make that thing.

DANIEL: Yeah, so people might know about convalescent plasma, which is something that you take out of a volunteer. Very early in the response to this disease, a lot of doctors were doing that. You take plasma from a person who's recovered, and it's got lots of different antibodies,

 (08:00) to (10:00) some of them are probably good, I guess, and then you give it to another patient, and hopefully it helps them. That's not very uniform. Some batches might be better than others. You need donors. It's hard to standardize.


So, what we've done is translate that into a medicine that can be made in a factory, but it's a similar principle, just not usually able to do it this quickly. And in this case, I think we were quite lucky. This was in the very early days, in late February and early March, when the disease was just first coming in the United States, the National Institute of Health was able to obtain from this volunteer this sample of blood, and then, working with scientists from the National Institute of Health as well as from a private technology company, Epseleron, that we collaborated with, we were able to isolate millions of cells from this one patient and then sequence all of the monoclonal antibodies and find the one that had this ability to bind to the virus really, really well. 

And it binds to an interesting part of the virus called the spike protein, and the spike is like the key that the virus uses to unlock the human cells and enter the cells. And so what we thought was that, if we made an antibody that could bind that spike protein, then it could block the spike from entering the cell. And it works in tissue culture, and then we tested it in animals, and it worked in animals, and then we took it into clinical trials and started to get promising data that led to the emergency use from the FDA.

ALEXIS: That is unbelievably cool.

HANK: Yeah.

 DANIEL: At times, it felt like something out of a movie, right, where there's a pandemic, and everyone's rushing to find that first patient who somehow got better and isolate the cells from the blood that made them better. That's literally what we did. It was just incredible to be part of it.  (10:00) to (12:00) We did it here in the United States, and then also, in China, a similar effort was underway. They had a head start, because the pandemic was there first, but the Chinese National Academy of Sciences collaborated with a Chinese pharmaceutical company and found another antibody from another patient in China.


And so we actually have both of these antibodies now. The first one, bamlanivimab, authorized by the FDA. The second one probably on its way soon. It's been submitted to the FDA, and we can use the first one as an individual antibody, or perhaps the two as a combination could be interesting as well.

ALEXIS: So, I'm curious. How do you mass produce an antibody? Just, how do you go from, yeah, how do you get there?

HANK: Yeah, you say a factory, and I'm just like, "What does a factory of antibodies look like?"

DANIEL: [laughing] Yeah. Actually, we have five or six factories mass producing this antibody, and I'll tell you why in a few minutes. But how do you go about making an antibody? Most of the medicines that you take in pills are chemicals that are made in chemistry labs, in big vats of mixing chemicals together. Antibodies are not that at all. They're what we call biologics. They're made by living cells, so it's more, well, the factories are huge stainless steel vats where we're literally growing cells.

 And this is why it takes a long time, because you start with one cell, and then it divides into two and four and eight. And these cells are all now engineered by us to make this antibody, and so you start growing them in a small vial, and, as the cells reproduce, you transfer them to a bigger vial, until they're huge stainless steel vats, thousands and thousands of liters at the same time. And then, when it's ready, you harvest the cells, isolate the antibody, (12:00) to (14:00) purify it out, and then dispense in a very sterile way into little vials. And so we have operators in what look like space suits in an extremely sterile environment working with this to make sure that the doses are pure and sterile, etc.


Now, the world has a certain capacity of these factories that can do this, and they're mostly busy making other medicines, because we use monoclonal antibodies to treat cancer or immune diseases. And so we have about enough factories to make the medicines people need, and then suddenly COVID-19 came, and we saw that, "Holy smokes, we're gonna need a lot more antibody."

So we started rearranging things at our own factories, trying to free up capacity without stopping to make the important drugs for cancer or anything like that. And then we started working with partners, so companies like Samsung, which has the largest antibody manufacturing facility in the world in South Korea, which has-

HANK: [laughing] I didn't know that you could use monoclonal antibodies in phones, but I guess who knows? 

DANIEL: [laughing] Yeah, they're a big company. They do lots of different things. Amgen, who's one of the largest biotechnology companies. And so, together we found all of the excess capacity, and we turned it all over to making these antibodies, because we give relatively high doses, and there's a lot of people affected, and we need to do it quickly. So what you're seeing from us and other companies that are working on similar technology is this massive mobilization, probably the largest mobilization ever of biotechnology manufacturing capacity, to pump out these antibodies for patients, which is just a pretty amazing thing to see.

HANK: Yeah, and, once you have them, we are learning more that distribution is a whole thing.

 (14:00) to (16:00) And has that- You know, obviously, you're mobilizing that at the same time as you're trying to figure out factory capacity. Has that been a challenge as well?


DANIEL: Yeah, it's been a huge challenge. Everything I can think is challenging. At first, it just seemed like, "Wow, if we could just find an antibody, right-"

HANK: Right.

DANIEL: "-that had these properties, that would be great." And then we did it, and we said, "Well, if we could just test it in patients and it worked, then we'd be home free." We did that. "If we could just manufacture it." Okay, we did that.

And now you're raising the latest problem, which is getting it into patients that need it, because this is- It's not a vaccine for people who are healthy. It's not a treatment for people who are in the hospital. It's for people who are recently diagnosed, so people who've gotten tested, which is its own challenge. They now know they have COVID-19. They're starting to get sick, but they're not severely ill yet, and they have to be able to go see a doctor, get this prescription, and then get it infused. So it's not a pill that they can just swallow at home. It's an infusion, where someone has to put an intravenous line into their wrist, and then they have to sit there and wait about an hour for it to flow into their vein.

This is normal in medicine. We do this all the time for some of these other diseases, but, for COVID-19, now you have people who are infectious, if they cough they could get someone else sick, and, just like we didn't have factories sitting idle to make this, hospitals and medical facilities don't have rooms and staff sitting idle to wait for people with COVID-19 to come and give them the infusion. So, mobilizing that infusion capacity and connecting doctors and patients with that has been a huge challenge. 

 Initially, we were working with hospitals to allocate part of their space to do that, but hospitals are really busy, particularly in the parts (16:00) to (18:00) of the country where the COVID is the worst. Those hospitals are starting to get overwhelmed, and now we're asking them, "Well, I know you're really busy with very, very sick people, but I've got some people who in two weeks might be really sick. We need you to treat them now." That's hard for them. They're doing it. We're working with outpatient infusion centers, but then they say, "Well, I've got people with cancer or with immune diseases. How do I put them next to a COVID patient?"


And so we're starting to ramp up now custom-built, dedicated spaces that we're just standing up for infusing COVID-19 patients. We're doing it. Hospitals are doing it. We're also towards home infusion, so to have a nurse come to a patient's house with the equipment needed and the medicine and just infuse them in their own home. So those kinds of things have to happen. It's taking a few weeks, but there's progress there, and I'm optimistic that we'll solve this problem just like we've solved all the other ones.

HANK: This is a broad question, but, you know, you're talking a bit about new ways of considering healthcare infrastructure, new ways of scaling up capacity for drug development, new ways to do drug development. I'm wondering if, you know, if there are ways that our response to this pandemic will change how we do medicine forever.

 DANIEL: I hope so. So there are a couple of things that are changing for the better, and it's hard to talk about a silver lining to something as deadly as this COVID-19, but I think it's there, and we're seeing it. So, one is this speed and this sense of urgency. What I've described to you, going from an idea to a medicine that's now mass produced around the world and going into patients in eight months, or nine months now maybe, that usually takes eight or nine years. (18:00) to (20:00) So, somehow, we compressed all of that down. Now, we probably can't do that every time, but that sense of urgency and sense of speed for COVID-19 we can apply to diseases like cancer or Alzheimer's disease. People are dying every day. It may not be in the newspapers, but those are deadly diseases as well. So, one is speed.


The other is collaboration. So, here we immediately collaborated with biotech companies, with the National Institute of Health, with a number of academic medical centers, with other pharmaceutical companies in a way that we don't usually do, and it was because nobody felt like we were in this to win or to make money or compete with each other. Everyone just looked at each other and said, "We have to do this to save people's lives. This is a major crisis." And then we learned that we can work together so well and so smoothly, and again, I hope that comes to other diseases.

The last thing is maybe the most interesting. It turns out, because of COVID-19, a lot of people don't want to go see their doctor. They wanted to stay home, stay away from hospitals. So, when we do our clinical trials, suddenly we started to rely on technologies like we're using right now. Why can't the patient see their doctor by telemedicine, and, instead of having them come into the hospital for a blood draw, let's send a nurse to their house and do the blood draw there or do the infusion there. So the idea of bringing clinical research and bringing medicines to patients in their homes is something we had to do because of COVID-19, but I hope it's something that sticks with us, because it makes it so much better and more convenient for the patients we're trying to help. 

HANK: Yeah.

 ALEXIS: For me, it's really lovely and refreshing to hear about that side of things, I think just as a person who, I guess, consumes the news, like, I get one side of it.  (20:00) to (22:00) So it's great to hear your perspective of, you know, there are things that are going well, and things are happening that are good.


DANIEL: Yeah, it's not perfect.

[Hank laughing]

ALEXIS: Well, yeah.

DANIEL: There are so many challenges, but things are getting better, and of course, you know, we're working on therapies, but we're rooting for the people who are working on vaccines, because ultimately the vaccines are a huge part of the solution here. And the progress there has been great, too. I suspect we'll continue to need vaccines and therapies for some time.

HANK: Yeah.

DANIEL: But hopefully, and we say this all the time, hopefully we'll be out of this business. We don't wanna be treating COVID-19 years from now. I hope, over the next year or so, we'll be able to finish our mission and go back to working on Alzheimer's and diabetes and cancer.

HANK: Yeah. Is Lilly working on anything else for COVID? Also, we haven't talked about baracitinib at all.

DANIEL: Yeah, so you mentioned baracitinib. So this is quite a different story. Baracitinib isn't a drug that we built to fight COVID-19. It's something we had on our shelves. We were using it- It's approved for use in arthritis, in rheumatoid arthritis, because it sort of dampens your immune system. And, in rheumatoid arthritis, it's a disease where your own immune system is attacking your joints, so you want less of that.

 So why would that work in a virus infection? That doesn't make any sense. Well, it turns out that, late in the disease, when people are in the hospital and they need oxygen, what they're having is an over-exuberant immune response. So, their own immune system finally got revved up against the virus. They've probably cleared out most of the virus out of their body, but their immune system itself is now making them sick and causing inflammation in their lungs and making it hard for them to breathe. And so, the thought was that drugs that decrease the immune system in that late stage of disease could be helpful. (22:00) to (24:00) So we tested baricitinib, again in collaboration with the NIH, the National Institute of Health, We tested baricitinib in these hospitalized patients, and, sure enough, we found that people who took this medicine had shorter hospital stays and better outcomes. And so, together with the NIH, we took that to the FDA, and also that got an emergency use authorization.


I think we could be the only company that has two different medicines for two different stages of the disease that work almost in opposite ways, one boosting your immune response early in the disease, one decreasing your immune response late in the disease. We tried at least one other medicine for COVID-19. It didn't work, so it's not always success.

HANK: Well, I'm surprised that that list is that short. I would expect that there would be a lot that you've tried or looked at.

DANIEL: Yeah, that's the list right now, two different antibodies, baricitinib, and then another approach. And I think that's it, because the time window here is now. When we started this project back in March, we said, "We need to work as hard as we can as fast as we can, because, in the fall and early winter, there's gonna be a second wave." That's how we all spoke in March, that there's gonna be a second wave in the fall and winter.

Back then, we were confident the first wave would be tamped down, which happened, of course, in Europe and Asia but not in the United States. So now here we are in the third surge. We predicted it would be bad in the winter. I think we, unfortunately, were right. Maybe we didn't realize how bad it would be. 

 So this is the time where we need the therapies. I think, in another six months, as the vaccines start to become more widely available, therapies will be less important. (24:00) to (26:00) So it doesn't make sense to start a new therapy now, given the timelines. 


HANK: How are you doing? 

[all laughing]

ALEXIS: I was just gonna say, I was like, eight to nine months later.

HANK: Yeah, yeah, you as a-

DANIEL: I'm okay.

HANK: -as a person, I mean it's a-

DANIEL: I think, you know, for me and for many people on my team, I think we'll all say we've never worked harder-

HANK: Yeah.

DANIEL: -in our lives. On the other hand, I think we'll all say we've never felt more connected to our purpose as scientists and physicians and drug developers. This is what we've been preparing for. We may not have known it, but it's been a call to action that's energized us. I think, although we're tired, and we miss our families in different ways, I think we're also wondering, "How can we ever go back to the normal place of work?" 

This is something special, and it's a moment where science, I think, comes to the rescue of society, and it's a privilege, as I said, to be part of that. And then the question is, next year, let's replicate this for patients with other diseases. I hope that we can bring some of the energy. 

At the same time, though, we've been fighting this disease that has been fighting us back. So, many of us have had COVID. You know, we've been working, and we've been about and exposed in different ways. That slowed us down, and then, at the same time, the physicians we work with in clinical trials, some of them had COVID.

 The infrastructure that we use to run clinical trials has been so impacted by this disease. Every supply we need, we discovered, "Oh, there's a shortage. We can't get that. We have to wait for that, find a different item, (26:00) to (28:00) because our hospitals are often overwhelmed, because there's not enough gloves or not enough masks or whatever it is." So we're fighting this disease that's fighting us back, and we're doing it with one hand tied behind our back. But, so far, we've managed to find ways to overcome these things. 


HANK: Yeah. We really appreciate you spending some time chatting with us. My last thought is do you think we'll be better at handling the next pandemic?

DANIEL: Yes. We will be. I think, as energized as we are and as proud as I am of the progress that we're making, we- The scientific and pharmaceutical industry and the biotechnology, we're all in this together. I'm proud of what we're doing, but I've also realized, with great humility, that we could've been better prepared, and, for a lot of different reasons, there hasn't been enough investment in preparing for pandemics. That'll change.

So we'll never be complacent again. We'll continue to be ready, I think, in our way, to fight the next pandemic, and we'll be watching even more closely. I think here it was good and lucky that we jumped on this in late February and early March. Next time, I think we could do it two months earlier and maybe a couple months faster and save more lives. And we will. We learned from this.

Still, this is not something we could have done 5 or 10 years ago, just the technology wasn't there.

HANK: Yeah, I mean, biologics in general are very new, so the fact that we've got a powerful biologic for this disease is something that could not have happened not long ago. 

DANIEL: Yeah, that's absolutely true, and the same can be said for

 (28:00) to (28:43) the ability of [audio issue] vaccines. We all feel, I think, unlucky to be alive in 2020 when there's this horrible thing happening in the world. On the other hand, we're lucky it happened in 2020 and not in 2010. 


HANK: Well, Dr. Skovronsky, thank you so much for taking the time to chat with us. We could talk all day, but we won't. I really appreciate it, and I appreciate all the work that you and your team are doing to lessen the impact of this disease.

DANIEL: Thank you both. 

ALEXIS: Yeah, this was wonderful.

[upbeat electronic music]