Going All In: A Strategic Investment in Toxicology.

As vast numbers of new chemicals are introduced to market annually, we are faced with the grand challenge of protecting humans and the environment while minimizing economically and ethically costly animal testing. models promise to be the solution we seek, but we find ourselves at crossroads of future development efforts that would ensure standalone applicability and reliability of these tools. A conscientious effort that prioritizes experimental testing to support the needs of models (versus regulatory needs) is called for to achieve this goal. Using economic analogy in the title of this work, we argue that a prudent investment is to go all-in to support model development, rather than gamble our future by keeping the of a "balanced portfolio" of testing approaches. We discuss two paths to future toxicology-one based on big-data statistics ("broadsword"), and the other based on direct modeling of molecular interactions ("scalpel")-and offer rationale that the latter approach is more transparent, is better aligned with our quest for fundamental knowledge, and has a greater potential to succeed if we are willing to transform our toxicity-testing paradigm.