One way to tell the story of human history is to just look at how people die. I know that's a bit grizzly, but just bear with me for a moment. In the last 5,000 years, the single most deadly disease was smallpox. Some scientists estimate that it killed billions of people before the 21st century. But in the 1790s, a British physician named Edward Jenner took material from a cow infected with cowpox and used it to inoculate a young boy. Since that fortunate but incredibly unethical science experiment, vaccination, the word itself coming from the Latin for cow, vacca, has spared millions of lives from an early death.
By the early 1900s, in rich countries like the US, where smallpox was fading out, another killer emerged as the apex predator of humanity: bacterial infection. According to the best records we have, almost all of the top causes of death in the late 19th century were bacterial. Whether it was the gunky stuff in your lungs or the little buggers in your gut. But thanks to the accidental discovery of penicillin in the 1920s and a heroic effort by the US to scale up that drug during World War II, bacterial infections have since plummeted. Today, the top causes of death in the US are not poxes or bacteria. They are heart disease, cancer, stroke, and Alzheimer's. These diseases are not typically premature killers. In many cases, they are more like mortality's consolation prize. They are the consequences of not dying young. And this frames the challenge we face in modern medicine.
While we have made progress against this new class of villains, statins for our hearts, immunotherapy for cancer, these killers are still killing us with remarkable frequency. There is an idea in progress studies called the burden of knowledge. Sometimes it looks like progress in a field like science is slowing down. Not because we're getting dumber over time, but ironically because we're getting smarter. Every time we solve a problem in medicine, it's like plucking a fruit from a tree. And if you pluck all of the low-hanging fruit, what you're left with is only the tallest challenges.
One of the tallest challenges for medicine in the last few decades has been dealing with the complications of obesity. Americans who overeat are at higher risk of a number of illnesses and discomforts: inflammation, cancer, knee pain, sleep apnea. But for a long time, as obesity rates skyrocketed, we didn't have reliable technology to help people eat less in an environment of food abundance. Science needed new fruits to pluck. But first, we needed a taller ladder to find them. In the last few years, that taller ladder has arrived. It's the GLP-1 drug revolution, which has taken the medical world by storm.
I've done several episodes on the science of GLP-1s on this show, on the promise and the negative side effects, the positive side effects, and the potential dangers, but we've never done an episode like this one before, where we talk to one of the most important people in charge of guiding the future of GLP-1s. Our guest today is David Ricks, the chief executive of Eli Lilly, the largest pharmaceutical company in the world. First, we talk about what makes the GLP-1 drug category special and the science that Lilly is doing to improve these drugs. Then, we talk more broadly about the pharmaceutical industry, how it works, how it could work better to make more drugs, to make cheaper drugs. And I don't want to shy away from this fundamental question, which I think CEOs need to take much more seriously: If the pharmaceutical industry is theoretically more devoted than any other economic category to saving people's lives, why do Americans distrust it more than literally every other industry in the entire economy? I'm Derek Thompson. This is Plain English.
David Ricks, welcome to the show.
Yeah, thanks for having me. Good to be here today.
So today you are the largest pharmaceutical company in the world in significant part because of your GLP-1 drug. 20 years ago Lilly helped launch the first approved GLP-1 drug. I'm fascinated by the history here and I'd like you to start wherever you think this story should start. 2005, 1970s, dawn of man. Truly it's up to you. How did this drug category get kicked off through the lens of Eli Lilly?
Yeah. Well, I think this is like a great cocktail party intro because I get this question all the time. And everyone knows the story and I think you've even told the story of the Gila Monsters and we'll get to that in a second. But the real first like scientific breakthrough that happened was in the early 70s. There were actually two papers that looked at something that was called at that point the incretin effect. And now incretin is what we call this class of hormones or proteins that your gut excretes like GLP-1. And what was noticed was that if you ingested food or calories of any kind orally through your GI tract versus intravenously, there were very different amounts of that nutrient that would spike in your blood and would be absorbed or not absorbed effectively by the GI tract more effectively. So blood glucose was less where if you took it intravenously it would spike and stay up. So it was hypothesized there were some suite of mechanisms by which your gut actually signaled the rest of your body that you had eaten something and then that work led to identification of what those things were. The first one identified was actually called GIP, which is actually the backbone of tirzepatide or Zepbound, our bestselling drug. But of course GLP was another one early identified as well. And that's like the point of origin for this. The companies that worked on this then in the 70s, 80s included Lilly and Novo actually, but it wasn't until the Gila monster story kicked in in the late 80s. I think this guy named John Eng in the Bronx was interested in why certain animals didn't need to eat very often and identified this mimic of the human peptide but used for this lizard's own purposes, exendin, which mimics GLP-1. And this was useful because you could ask, well, why in the 70s didn't you just make this drug then if you knew about this? And the answer is that peptide chemistry wasn't very mature. And if you give humans a native sequence of GLP-1 or GIP, they both have like a half-life in your body of seven or eight minutes. So it wouldn't be a very convenient drug. You'd have to walk around having like an IV bag infusing it all day long to mimic what we have with the drugs we have today. The Gila monster one was interesting because you could get it to go about 8 to 10 hours. So it was a twice a day shot which barely cleared the hurdle of good enough to be a drug. But we made it into a drug along with a partner, Amylin, and launched that in 2006. So it's been going on for a while. The effect is really sort of the insight into the natural system by which we regulate calories, which is kind of core to our existence. And drugging this target has proven hard. It took a lot of advancements in peptide chemistry and drug making to get to where we are today with pretty convenient, long-acting, and now dual-acting versions of this pathway, the incretin.
Your story stopped off with exenatide, which is the drug that was derived from the Gila monster incretin. That was a type 2 diabetes drug. How long did it take Lilly to recognize that what had begun as a type 2 diabetes drug was in fact an incredibly powerful weight loss drug? Because now here we are 21 years later, which is not a short amount of time. So, how long did it take for you to realize this underlying mechanism which is now what the drug is more famous for?
Yeah, you know, it's interesting because when we go back and look in on the cover of our annual report from that year, there's a patient, Maria, and she's talking about her experience with Byetta, the brand name for exenatide, and she says it's controlling her blood sugar, and there's a quote, and that her friends noticed she's losing some weight. So there it was like sitting there in 2007 in April when we put out that annual report. We were doing studies, but we had a problem. The problem was the side effects associated particularly with GLP-1 are what we call peak to trough. So the difference between the highest amount of drug and the lowest and then going back up again to the highest caused by this twice a day dosing which you can imagine someone sort of bouncing around maybe two to three times the drug at peak then trough causes a lot of GI distress. So we've read about those feelings of nausea, sometimes diarrhea, sometimes vomiting. So the more we pushed the dose up, the more we ran into these things with that particular drug and so we stopped because it was very unpleasant to take and the weight loss effects were there but more modest. What happened that started to, you know, the weight loss part was being able to get the dosing levels up. So we're here we're taking a system, the incretin system, GLP-1 or GIP or coming soon glucagon, and we're kind of boosting it in people who have regular levels. So it's not that people are deficient necessarily in these hormones. It's that we're boosting them to a supranormal level and it suppresses appetite, kicks in the metabolism, etc. So to do that you need to get to higher levels than we were originally to see the weight loss effects whereas it did have some blood sugar control levels. We produced a once-weekly GLP-1 launched in 2014 called Trulicity. Anyone who was in the diabetes world would know that. Very few people in the lay media would remember that drug although it was our bestselling drug at one time and it was a weekly. We did a trick of protein engineering. We made it last a week. And people lost more weight. Our competitor, Novo, then did a similar trick and made a weekly. They launched that in 2017. It was called Ozempic. Oh, we know that word. And that really only got so famous when they took the chance to study that at an even higher dose in people who didn't have diabetes but had dysmetabolism and obesity. And that came out in '21, I think. And then this whole thing started running. But you know even while they were doing that we had switched away from this single-acting GLP. We invented this drug called tirzepatide which happened in 2014 and we started doing studies and by I would say 2018, 2019 we knew this was going to be the most effective obesity drug we've ever seen. And of course since then we've been improving upon that. So it's a case of sort of leapfrogging and iterative improvement. And the story interesting here people think about the long-acting as convenience but actually the long-acting gave us a flatter, steadier drug profile so that the side effects were less bothersome. You could dose up without having that sort of peak trough signal, kind of sawtooth, which causes GI distress and made the drugs intolerable without a very flat profile.
Just a pit stop on the business here before I get into the science. I mean what share of Lilly's revenue and profit at the moment is related to, you know, there's single agonist Ozempic, there's dual agonist GLP plus GIP which is tirzepatide and we'll get to the triple agonist in a second but what share of your revenue, what share of your profit depends on this class of drugs right now?
Well last year it was a little less than half the total company revenue. This year we don't give out like product level guidance but it's projected to exceed half. It's the fastest growing part of the company by far.
And getting to the science, I mean, to me, the most mysterious, the most tantalizing, the most even confounding aspect of these drugs is that they seem to do so many things at once. They increase feelings of fullness, which is probably the most fundamental thing that they do in terms of helping people lose weight. They help people control non-food addictions as well, it seems. They help people stop smoking or stop gambling. In some cases they reduce knee pain. You've studied this directly. They seem to reduce inflammation. They seem in some cases to protect against heart disease among people who aren't even losing weight, which suggests some mechanism that is maybe slightly unrelated to the satiety obesity mechanism. They might even have brain benefits. They're being studied for dementia and all this stuff. Just at the highest level, like you are as close to the best scientists studying GLP-1s as anybody in the world. What the hell is going on here? What is their theory for how one thing can do so many different things?
Yeah, I mean it is a surprising thing that most of what you said there has either been proven or will be proven. I'd add one more category which is cancer reduction. So there's a lot of interesting studies about population-wide cancer risk reduction. Maybe more directly associated with losing weight or maybe the inflammation story. But okay so just to take it all the way back, I mean a core behavior to keep organisms alive is feeding, right? We can all understand that and humans and other animals have grown up in an environment of scarcity so most of the feeding cycles in our body are focused on acquiring more calories, right? There are very few counter-regulatory processes that we've evolved with because our ancestors evolved in scarcity. We spent most our day, you know, looking for food. As you can imagine, you know, wild animal today grazing or hunting or whatever. There wasn't really a biologic need. It was unnecessary to put in our genome something that says, 'Okay, you're full.' Because it was so rare. But this system was put in as sort of the, so as a pathway it's a little bit unique. I think the signal from the gut to the brain and the rest of your body for metabolism has evolved in a way that we don't really know of many other ways to actually reduce satiety effectively. So it's core for that but also feeding drives a number of other processes in our body and overfeeding turns out is not good for us. Although our ancestors didn't experience that because they were starving most of the time. So in a modern world like a lot of chronic conditions we have, the human beings have evolved into an environment we weren't built for. And this is an environment of excess, of abundance, to maybe hit that note for you here, food abundance, right? And so what does that do? I think of course the core benefits which are pretty well documented are these metabolic effects and that is about of course weight, diabetes, which is type 2 diabetes we're talking about here. There's another type of diabetes which is really contracted when we're young and it's an autoimmune disease but most people with diabetes have this adult onset diabetes which is a disease of what we call insulin resistance. So you're too heavy and your insulin which helps you process sugar no longer works effectively because essentially there's resistance from your body from having too much sugar for too long. So these drugs can break that cycle. You reduce weight, you actually increase insulin sensitivity. We can reduce type 2 diabetes. We have a study where we watch people on tirzepatide for three years and they had 92% less diabetes at the end of the study. So essentially I mean nearly staving off diabetes completely. That's a remarkable finding. We know if you add this to people with diabetes or not diabetes and they have heart risk it reduces their heart risk. That's a story as you're saying that may not just be about weight loss. These drugs also reduce inflammatory factors that may be related to over calorie consumption or may be separate. I think our scientists debate that still. But there's a key signal called hsCRP which is C-reactive protein. It sort of measures general inflammation and on these drugs that drops 50 to 70% and it drops a lot faster than your weight. So pretty quickly in the course of treatment, your inflammatory factors go down. And when you're having a heart attack, we know that's not just about cholesterol building up in your arteries and the clogging of the arteries that causes. It's actually the response to that clogging that can cause the blockage, which is an inflammatory event. So you're sort of reducing the risk in two ways. Improving cholesterol and metabolism, but then also in an acute phase with the inflammation. Speaking of inflammation, you raise joints and we did a study with retatrutide, the next generation product we're working on, that reduced knee pain. Well, half the people in the study had no knee pain at the end of the study. I mean, it was the most effective osteoarthritis knee pain drug I think ever studied. Which is also interesting. Here you have probably two effects, the inflammatory factors like I just mentioned, but also the offloading of weight. So there's a mechanical wear problem and if you talk to orthopedic surgeons, they'd say more than half their knee replacement patients have been obese or overweight most of their life. And so there is a mechanical loading challenge people face with their joints that causes a lot of this pain. But it's not just that because we also recently read out a couple studies on top of a drug called Taltz which is for psoriasis and psoriatic arthritis. Psoriasis, a skin inflammation disease. Psoriatic arthritis, a version of that that appears in your joints. Here again, the drug Zepbound boosted that performance by 50% almost as good as adding an entirely new drug class to that category. So pretty miraculous. In addition to like suppressing our appetite for sugary foods, it does also seem to suppress our appetite for vices that are maybe sort of driven by anxiety or driven by kind of a cycle in our brain of like trying to scratch an itch or you know have a craving. So tobacco use and alcohol use are the most noted in the literature. We're actually doing prospective studies to prove both those things. But people also, you know, report like less online shopping and less gambling while on these drugs, which I think wasn't the initial, no one would have hypothesized that at the beginning.
Yeah. What's spookiest about this to me, almost at like a philosophical level, is the degree to which these drugs almost act as a system-wide mechanism for increasing moderation, which is a weird thing for a drug to be able to do. That it moderates our impulse to eat. It moderates our impulse to gamble. In some ways, it even seems to like give patients a kind of agency to align their behavior with what they would report wanting to do in the day before their dopamine takes over. I mean, have you talked to scientists? Are you studying? Do you have theories about how a drug might like even at like the dopaminergic level, like how a drug might allow patients to essentially align their behavior with what they would describe as moderate behavior. That's just a, that's a spooky strange thing for certainly a type 2 diabetes drug to accidentally cause.
Yeah. Let alone a lizard saliva-derived protein. Yeah. I, yes. So I guess one thing to point out and then the difficulty of actually defining the exact mechanisms of this in the human brain. There have been drugs that reduce say and reduce these impulses before. We have them marketed as neuropsych drugs. The problem is they're very dose-sensitive and they are two-way doors. Meaning if you push dopamine down too much, you can reach really unhealthy levels that cause other brain disorders. What seems to be magical here or really quite unique in this pathway is we do tend to suppress these kind of urges without inducing depression or other things that change brain chemistry in a way that's quite negative. And there are lots of neuropsych drugs that help people with extreme and you know clinical neuropsychiatric conditions but they almost all have this notion that if you pick the wrong one or you dose too far there's untoward effects that can be worse than the disease itself. We really don't observe that here. And that makes for a very useful primary care drug because you don't have to worry about carefully titrating doses or about flipping people into you know very negative cycles of depression or you know anxiety or other things. So that's a unique property here to actually when we study in rats and rodents for instance in the lab our scientists are doing that now like of course if you have a sugar stimulus we can reduce that. Well, what about nicotine? We have like simulation for nicotine. It does directly reduce the desire for nicotine. It's harder to see if rats want to gamble less, but they do do these studies and they measure then the neurotransmitters. It's not just dopamine. There seems to be some other signaling going on. And of course, the human brain is very complicated and pretty poorly understood relative to other organ systems. So we're still trying to figure out exactly the mechanisms of these. What we can say is empirically people report it and we will do and are doing prospective studies to take people without obesity but with these problems you mentioned. Too much gambling, too much, we're even doing opioid use disorder just to see well can we help? These are such common and challenging conditions to treat. If something like a type 2 diabetes drug that became good for obesity can do it, we should try to prove that and help those people.
Yeah. I think there's this theory of science that we develop a perfect theory of how the world works and then we develop technology that applies that theory to the physical world. But it always almost always seems to be the opposite way around. Like the classic example I think from tech history is theoretically you would want to understand the principles of thermodynamics to invent the steam engine. But we invented the steam engine and then from it derived the principles of thermodynamics. And so maybe in a similar way, it would be lovely if we accidentally fell into a synthesized Gila monster molecule that taught us the secrets of the gut-brain axis rather than having some perfect theory of how our brains worked and then said, 'Oh, we should be doing is targeting glucagon and GIP in the gut.' So it would be lovely if this technology opened up some big secrets of the brain. But because you use the word magical, I have to interject now as a journalist and say that, you know, for all the good that these drugs can do, I believe according to the most recent data, more than half the folks who start on GLP-1 drugs discontinue them before 2 years is up. So there's still a pretty significant adherence problem made even more significant by the fact that it's not like GLP-1 is a drug where you take it once and you extend the weight loss benefits over the course of your life. People who discontinue these drugs often gain the weight back and theoretically inflammation and everything else can come back as well. So let's take some time to talk about this phenomenon here. Why do you think the discontinuation rate, the fact that people aren't adhering to these drugs year after year, why is it so high and what would bring it down?
Yeah. No, thanks. It's important to flag that. And before we even get to discontinuation, all prescription drugs have untoward effects for some people. I think these drugs have been used for 20 years in people and we have a lot of data to profile that. But people really should talk to their doctor before initiating these. And I say that because there's lots of kind of bypasses to that available online and I think it's really best to if you're interested in this to go to your primary care doctor who knows your health history and consult there just as a public service announcement here. It's very important and some people do have untoward effects. That's not the most common cause for discontinuation. And in our studies, somewhere between 5 and 10% of people across most our drugs do discontinue due to side effects or other untoward thing. That's not the most common thing. The most common reason people discontinue any chronic medication is actually sort of life getting in the way. And the data so far we see for a product like Mounjaro or Zepbound otherwise known as tirzepatide is it's not, you mentioned it's so high, it's actually pretty similar to other chronic medications that we sell. There was a period of time where it was higher but that's when we had shortages going on and so people were actually having to discontinue because they couldn't find the medicine. That's I think quite a different thing than what we see for instance all of last year. So that's worrisome I think for two reasons. One, most of the health gains will reverse pretty quickly for most people. Not unlike taking an antihypertensive or a statin for your cholesterol if you remove the drug. The condition just returns. It's not curing anything here. We're working on those ideas, but or permanent changes that would allow people to live without obesity and without drugs, but right now you need to take the drug to get the benefits. Some people do report being able to go off them or titrate down into very infrequent or different regimens. That's not in our label, but they seem to make a lot of changes to their lifestyle and once they become lighter weight, they're able to do that. That's a good kind of discontinuation if that's you. Most people that's not the case. I think what's getting in the way is either some other medical problem where they discontinue the drug to manage that. That's quite common, especially in the elderly. Financial costs, right? And we can talk about this if you'd like, but a lot of people, more than any other drug class in America, are paying out of pocket even though they've bought insurance. So, they're paying their health premium, but they're not getting covered for this drug. And that is difficult because you know, these drugs are not cheap. And then you know I think people have sometimes experienced so much success that they want to try going off and then they bounce back on and go off and back on. Or there's episodic things like you know seasons that they're more interested in losing weight in. So that's you know I think explaining the data but the major point is it's not so different than the rest of the chronic drugs we see being used. We wish it was better because the profound positive effects we just discussed.
Yeah, you mentioned cost and I definitely want to get back to cost not only for tirzepatide and this category of drugs but also for the pharmaceutical category at large. One more beat on the frontier of GLP-1 drugs. There's a lot of different directions I can imagine you trying to push this class of medication. On the one hand, you can push on the weight loss effects and in fact the most recent version of these drugs, retatrutide, which is a triple agonist, as I said, had even greater weight loss effects in the readout that you guys had in December than tirzepatide. So you can push on weight loss effects. Another direction I can imagine you pushing on is holding the weight loss effects but reducing the side effects. So how can we continue with you know say 20, 25% weight loss but we reduce that peak to trough effect. So there's less nausea, there's less GI distress. And maybe a third direction that you can push in is like trying to accentuate a certain non-weight loss benefit of this drug category. Like is there a GLP-1 drug? Is there a Zepbound for inflammation specifically? Is there a Mounjaro for reducing Alzheimer's plaque in the long run specifically? And so you're not, you're engineering the drug specifically to essentially accentuate one of what we're now calling side effects, but in some future category would be the main effect. So I guess I gave you three pathways here. Accentuate weight loss. De-emphasize side effects and you know door number three some other third thing. Make one of the side effects the main effect. What are you investing in the most here right now?
Well, I mean you've hit on three key ones. We've also, that's occurred to us and we've been developing drugs for some time. In fact, all three of those ideas are in the latest phase of testing for us. So, in the next 3 years or so, we'll have some answers. We have to do studies. They're controlled and blinded. We don't know the results. But those are all some good ideas. The only one I would add and I'll loop back on the alternate uses because I think that's perhaps again back to this why does this work for so many things is convenience. You know, I think people enjoy being able to work it into their daily routine a little easier. You know, a weekly shot has proven not to be so difficult. It's sub-Q. You administrate yourself. Ours come in a pretty convenient auto-injector. And even if you're afraid of needles, you never really see the needle. But people are interested in oral. We have that coming very soon. People are interested in much longer acting. Oh, could I just do this once every three months or maybe on the future horizon even once a year type of therapy. So, it's more like getting your annual flu shot. That's obviously very appealing to consumers. The technology is harder and harder to do that, but that's another vector that we're working on. Looping back to what's in the pipeline. Retatrutide is our triple acting. So, if you think Ozempic GLP-1 is single acting, tirzepatide improved on that. Zepbound with dual acting. So, why not three? So we have a triple acting single protein that's in late phase development. We'll get most of the data this year and submit it end of the year and probably launch it in '27. This promises to get you know between you maybe 28, maybe up to 30% weight loss. So that's the equivalent to gastric bypass surgery. And I think for people who have a lot of overweight and obesity and unfortunately there's I think 8% of Americans have a BMI over 40. So even if you lose 25% of your body weight and your BMI is 40, you're still classified as obese. So having more matters, particularly for people who really struggle with their weight. The second thing you mentioned is the lose the side effects. That's bothersome to many and as I said maybe 5 to 10% of people discontinue just because of that. And most people actually don't go to the highest doses available of our drug or our competitors because of side effects. So we have a drug in our pipeline called amycretin. This is actually not a GLP-1 or a GIP. It's actually a separate, a different gut secreted hormone called amylin that this is based on that appears to suppress appetite without really much GI side effect at all. And that would be super promising. Get about 18 to 20% weight loss with almost no GI side effects. That's of course under development and needs to be evaluated further but we've started phase three testing there. And then I think this alternate use one is worth exploring. So we put a drug into phase three that in many ways is like tirzepatide but maybe has a few different properties that might make it better for some of these other chronic conditions. And we're studying it, that's the one we're in phase three for alcohol use disorder but also we're studying it in asthma. Okay. So there you look at asthma. Well, asthma is an inflammatory condition. It is very comorbid with overweight and obesity and it's a major problem in the US. And so that's another indication along with tobacco use disorder and bipolar disorder. So here we're taking a drug that appears to have a little more brain properties that might be ideally suited for these not necessarily just weight loss but other conditions. It also appears a little more tolerable and longer acting than tirzepatide. So we've selected that one to further explore that pathway.
I'm going to close the door on this chapter of the conversation about GLP-1.
We can return at the end to sort of some of the moonshots that Eli Lilly is looking at, but there's a second chapter of this conversation that I think is really important. I would love for you to explain at a high level, and I apologize if this sounds like a weird question, but how the pharmaceutical industry works. I think it's a very unique industry for a lot of reasons, some of which I won't get into before asking this question in that you spend so much money on each individual product and there seems to be this limited patent-enforced window where you can make the largest profit on that product. And so you're in this cycle of R&D and profit window that is very, very distinct from I think most other industries that people are familiar with in the US. So maybe before I get into some of my critiques and suggestions, can you just tell me, explain to our audience like how you like to explain how the pharmaceutical industry actually works?
Yeah. Well, I could answer this on many levels, but I think you're pointing out kind of the from inside the industry the key challenge and maybe from outside the key misunderstanding, which is that once we have a medicine that's successful selling a lot and that means it's widely useful, otherwise no one would be buying it. It seems like this is a great business to be in. But that period is fixed. So, and why is it fixed? Because we rely on patent protection to have a government-enforced monopoly for our invention. When that patent protection ends, we tend to lose almost all that business. It's not unusual within one month of our patent expiry for a major product to have 99% of our volume go to competitors. So really, you have a quite a fixed and almost predetermined period to recoup investments. That period can be long and I think to the general public seems long. We get 20 years of patent life. About half of that we consume in the drug development process. So you end up with like 10 years and that's a long time of someone paying full price during those 10 years to think boy hasn't this company had a good return on the investment for my medicine. But the answer is actually rarely. So our industry although profitable in terms of operating profit etc trades at one of the lowest multiples of any sector in the S&P 500. What does that mean? That means the expectations for growth are amongst the lowest of any industry. That's not a great thing because I think if it was a better performing financial industry, we'd attract more capital to invent more drugs. But that's a tough exercise. In part because the return cycle we just discussed every like here's an example. We invented Prozac in the 1980s and sold it and became a mega blockbuster. Kind of made the modern company. Went generic in 2001. The next year we sold 10% of the prior year and the year after that 1%. So it literally just evaporated. Yet many people are on Prozac today. And so that public benefit goes on and on. It just takes place over kind of a long horizon for people to really appreciate.
And before we get to a lot of Americans' frustration with that business model, what percent of your sales are going back into R&D?
