To evolve AI from pattern matching to understanding physics for protein engineering, structural data is insufficient. Models need physical parameters like Gibbs free energy (delta-G), obtainable from affinity measurements, to become truly predictive and transformative for therapeutic development.

Instead of targeting individual gene mutations in diseases like ALS, condensate science focuses on shared cellular structures where genetic risks converge. This approach creates a broader therapeutic target, potentially treating more patients with diverse genetic profiles.

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.

As biologics evolve into complex multi-specific and hybrid formats, the number of design parameters (valency, linkers, geometry) becomes too vast for experimental testing. AI and computational design are becoming essential not to replace scientists, but to judiciously sample the enormous design space and guide engineering efforts.

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.

While acknowledging the power of Large Language Models (LLMs) for linear biological data like protein sequences, CZI's strategy recognizes that biological processes are highly multidimensional and non-linear. The organization is focused on developing new types of AI that can accurately model this complexity, moving beyond the one-dimensional, sequential nature of language-based models.

A more effective way to define life is not by its internal components (like RNA or metabolism) but by its unique capability. Life is any system that can recursively produce many identical copies of highly complex objects, a feat only achievable through evolution.

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.

Traditional science failed to create equations for complex biological systems because biology is too "bespoke." AI succeeds by discerning patterns from vast datasets, effectively serving as the "language" for modeling biology, much like mathematics is the language of physics.