With directed evolution, scientists find a mutated enzyme that works without knowing why. Even with the "answer"—the exact genetic changes—the complexity of protein interactions makes it incredibly difficult to reverse-engineer the underlying mechanism. The solution often precedes the understanding.
Caltech professor Frances Arnold developed her Nobel-winning "directed evolution" method out of desperation. Realizing her biochemistry knowledge was limited compared to peers using "rational design," she embraced a high-volume, random approach that let the experiment, not her intellect, find the solution.
Wet lab experiments are slow and expensive, forcing scientists to pursue safer, incremental hypotheses. AI models can computationally test riskier, 'home run' ideas before committing lab resources. This de-risking makes scientists less hesitant to explore breakthrough concepts that could accelerate the field.
Unlike traditional engineering, breakthroughs in foundational AI research often feel binary. A model can be completely broken until a handful of key insights are discovered, at which point it suddenly works. This "all or nothing" dynamic makes it impossible to predict timelines, as you don't know if a solution is a week or two years away.
The success of iterative design processes hinges entirely on the metric being measured. An enzyme evolved for temperature stability won't necessarily remove clothing stains unless stain removal is the specific property being screened for. This highlights the critical importance of defining the right success metric from the start.
It is a profound mystery how evolution hardcodes abstract social desires (e.g., reputation) into our genome. Unlike simple sensory rewards, these require complex cognitive processing to even identify. Solving this could unlock powerful new methods for instilling robust, high-level values in AI systems.
Building the first large-scale biological datasets, like the Human Cell Atlas, is a decade-long, expensive slog. However, this foundational work creates tools and knowledge that enable subsequent, larger-scale projects to be completed exponentially faster and cheaper, proving a non-linear path to discovery.
The traditional method of engineering enzymes by making precise, knowledge-based changes (“rational design”) is largely ineffective. Publication bias hides the vast number of failures, creating a false impression of success while cruder, high-volume methods like directed evolution prove superior.
Frances Arnold, an engineer by training, reframed biological evolution as a powerful optimization algorithm. Instead of a purely biological concept, she saw it as a process for iterative design that could be harnessed in the lab to build new enzymes far more effectively than traditional methods.
Afeyan proposes that AI's emergence forces us to broaden our definition of intelligence beyond humans. By viewing nature—from cells to ecosystems—as intelligent systems capable of adaptation and anticipation, we can move beyond reductionist biology to unlock profound new understandings of disease.
Beyond optimizing existing biological functions, Frances Arnold's lab uses directed evolution to create enzymes for entirely new chemical reactions, like forming carbon-silicon bonds. This demonstrates that life's chemical toolkit is a small subset of what's possible, opening up a vast "non-natural" chemical universe.