Key Takeaways

  • Truly disruptive technologies, often called "orthogonal" discoveries, rarely begin as solutions to immediate commercial problems. Think CRISPR, which emerged from studying bacterial defense mechanisms.
  • These breakthroughs stem from curiosity-driven basic research. Dr. Max Krummel emphasizes studying things that are “at some point curiosities,” rather than just engineering known solutions.
  • The path to such discoveries is paved with failure. Krummel estimates that if an experiment has a 10% chance of yielding something interesting, you need to run "at least 10" (and often more) experiments to even meet statistical odds.
  • Early-stage scientific exploration often lacks a clear commercial vision. When Krummel began his T-cell work, people questioned why he'd do immunology, but the eventual ability to "turn things off" opened everything.

Your Next Breakthrough Won't Be Obvious

Most founders are wired to solve problems. Find a pain point, build a solution, ship it. But what if the biggest wins don't come from direct problem-solving? Dr. Max Krummel, from the Huberman Lab podcast, argues that the most impactful scientific leaps—the ones that reshape entire industries—spring from something far less predictable: pure, unadulterated curiosity.

Take CRISPR. Today, it's a household name in genetic engineering, promising cures for diseases and powerful biotech tools. Its origin story, Krummel points out, is far removed from human therapeutics. “That was people were studying like how do bacteria defend against other bacteria?” he explains. Researchers simply wanted to understand bacterial immune systems. They found an enzyme that remembers invading viruses and can cut them out. “Well, that same…enzyme then which we now use for all this human engineering came out of a basic like how do bacteria defend themselves.” No one was trying to cure cancer. They were just curious about bacteria.

This isn't an isolated case. GLP-1 agonists, now revolutionizing metabolic health and weight loss, famously came from studying the saliva of Gila monsters. These "orthogonal" discoveries, as Krummel calls them, reveal a recurring pattern: foundational knowledge, pursued for its own sake, unlocks applications no one could foresee.

Embrace the 90% Failure Rate

This kind of research isn't clean or efficient. It's often frustrating. Krummel tells his students, “if an experiment you'll do in lab has a 10% chance of yielding anything interesting you got to do at least 10.” That means most of your attempts will lead to dead ends. This high failure rate is not a bug; it's a feature of exploration.

He recounts his own early work with T-cells. His mentor, Jim, questioned the focus. “Why would you do immunology?” people asked. Krummel and his team simply found a molecule on T-cells and decided to “just see what it does.” There was no grand plan to disrupt medicine. Yet, once they understood how to manipulate those cells, “then everything became possible.” It's a stark contrast to the pressure on startups to prove ROI on day one.

This process challenges the idea that everything can be engineered with ease. While tools like CRISPR make many complex tasks simpler after the discovery, the initial, foundational leap isn't something easily conceived or planned for. It requires patience, a tolerance for ambiguity, and an unwavering commitment to asking "what if?" even when the answer isn't immediately profitable.

What to Do With This

Carve out a curiosity budget: Dedicate 5-10% of your R&D budget or team's time to projects with no immediate product roadmap. Task your smartest engineers or researchers with pursuing "what if?" questions or exploring adjacent scientific fields, even if the application isn't clear. This isn't about solving a known problem; it's about uncovering unknown possibilities.