Imagine you want to live 150 years. That’s not unreasonable in the abstract. It’s a small enough number to sound possible in the future, it’s not just sci-fi, but big enough that it won’t happen by chance. How do we actually achieve it? Well, first of all: forget everything you’ve been told about exercise, diet, and healthy lifestyles. Those are great for extending your lifespan, but not to 150. If lifestyle alone could do it, someone would have already cracked the code. So, what can we do? There’s no way around molecular biology, of course.

First, keep in mind that we humans are amateurs at longevity. Take the bowhead whale, which casually swims around for over 200 years like it’s no big deal. Or the Greenland shark, they were already ancient when Beethoven was composing his symphonies. And don’t get me started on hydras, those tiny, jelly-like creatures that seem to have decided aging is for suckers. Turtles? Sure, they’re slow, but they will live for over two hundred years. And while we’re admiring these overachievers, let’s not forget some trees outlive civilizations. A bristlecone pine would probably laugh at your 150 year ambition if it could be bothered to.

Beyond taking inspiration from nature, there are lots of recent discoveries that inspire research on longevity, and in particular the types of damages that happen in humans that eventually aggregate into what we call aging. For example, how senescent cells (zombie cells that refuse to die) clog up normal function, stem cells lose their regenerative properties, mitochondrial dysfunction starts sapping energy out of cells, and cellular garbage like amyloids builds up over time and so on. If you think the cells in your body are tidy, think again. Aging is like hoarding, but instead of old newspapers and cat statues, your cells are stockpiling toxic junk.

But we sure know many treatments that extend lifespan in other species. Caloric restriction, for example, it has extended the lives of lab mice and maybe a few humans with extraordinary willpower. Senolytic compounds target and kill senescent cells, clearing the way for healthier function, it’s like spring cleaning for your tissues. And let’s not forget the myriad interventions that have doubled, tripled, or even quintupled the lifespans of certain worms and flies. Granted, it’s a long way from flies to humans, but progress is progress.

Now let’s talk about how drug discovery works. If you wanted to bring this knowledge about extending lifespan in other species back to humans, how would you do that? You start with whatever experiments are already happening, probably in worms or flies. Maybe there’s a promising animal study, a known biological target, or a hunch that tweaking this or that might lead to something interesting. Next comes in-silico modeling. This is where computers simulate how thousands, sometimes millions, of compounds might interact with the chosen target. Think of it like a dating app for molecules. Docking simulations and molecular dynamics can filter out obvious mismatches and flag the ones that might actually “swipe right” on your target. Now you’re in the trenches: preclinical testing. This means animal models, in vitro assays, and a relentless cycle of tweaking molecular structures. Here, the goal is to optimize a compound’s properties—making it more effective, more bioavailable, less toxic, until you have a candidate that’s ready to move forward. This is what’s called preclinical research.

Once you have some solid data, it’s time to prepare an IND (Investigational New Drug) application. This involves compiling every shred of preclinical data into a package, submitting it to regulatory authorities, and crossing your fingers that they give you the green light to proceed to human trials. This is the stage where you need to hope your molecule doesn’t accidentally kill someone (unfortunately, this is quite literal). Clinical trials are where the rubber meets the road. Phase I checks safety. Phase II looks for early signs of efficacy. Phase III proves it works on a large enough scale. Each phase comes with its own hurdles, and the vast majority of drugs don’t make it past all three. At this point, you’re juggling more flaming torches than a circus performer, and the stakes are significantly higher.

If you’re still standing after all of that, you file for approval. Congratulations! You probably have spent a small fortune getting there. But here is a key insight: solid preclinical data will attract investors, because if the drug is approved it can make a lot of money back. Once you’ve got solid preclinical data, it’s easier to convince people that you’re not just shooting in the dark. Investors see the early numbers and say, “Okay, let’s put up the cash.” With that money, you can keep pushing forward—filing your IND, starting clinical trials. And if you get past Phase I and II, you’ve shown that your drug is both safe enough and has some real chance of working. At that point, it’s not just small-time believers, big pharma might step in, run the expensive Phase III, and handle the final push to approval.

So here is my main point. The bottleneck across this process is not the clinical work, even if it takes the longest time. Investors and pharmas will look at data and fund these trials if they show promise to treat diseases of aging. Also, the bottleneck is not coming up with potential ideas for aging, we already have hundreds or thousands of those. The bottleneck is in the translation. Converting those ideas into molecules that can be tested.

Here’s where constraint theory comes in. I spent a few years in supply chain, where one book came up quite often: The Goal. It’s a story about factories, production jams, and how to solve them step by step. No dense theory—just practical lessons on identifying the biggest constraint, fixing that first, and moving on. It became a hit because it gave people a clear, actionable framework they could apply immediately. And that’s exactly how I think we should approach the development of longevity therapeutics. We can spend millions or billions in basic research, and running trials, but none of those things is going to move the needle nearly as much as tackling the limiting step in the process, which is the translation from idea to molecule.

The biggest constraint isn’t ideas—we’ve got plenty of those. It’s the translation, turning concepts into testable therapies. If we fix that, we will have the biggest impact on bringing therapies for aging to the market. That’s what we are doing at Pauling. Building the tools that will help us go from ideas to molecules much, much, much faster and better than we can today. If we really want to live to 150 it’s not enough to have ambition, we need to put up a plan and solve the actual problems that stand in the way. And if we can pull that off, we might just fulfill one of humanity’s dreams.