The data sciences (statistics, and recently machine learning) have always been part of the underpinning of all of the natural sciences. `Massive datasets' represent potentially unprecedented capabilities in a growing number of fields, but most of this potential remains untapped, due to the computational intractability of the most powerful statistics and learning methods. The computational problems underlying many of these methods are related to some of the hardest problems of applied mathematics, but have unique properties which make classical solution classes inappropriate. I will describe the beginnings of a unified framework for a large class of problems, which I call generalized N-body problems. The resulting algorithms, which I call multi-tree methods, appear to be the fastest practical algorithms to date for several foundational problems. I will describe four examples -- all-nearest-neighbors, kernel density estimation, distribution-free Bayes classification, and spatial correlation functions, and touch on two more recent projects, kernel matrix-vector multiplication and high-dimensional integration. I'll conclude by showing examples where these algorithms are enabling previously intractable data analyses at the heart of major modern scientific questions in cosmology and fundamental physics, which have been featured in Science and Nature.