Adjusting the yin and yang of the cell

Abstract

At the beginning of 2017, Keith Dionne was looking for the next big idea in biotech. He had just joined the life sciences–based venture capital firm Third Rock Ventures, and the investors there were building a company centered on the cellular process of autophagy, the subject of the 2016 Nobel Prize in Physiology or Medicine, announced just months before. Autophagy literally means self-eating, but the cellular housecleaning it accomplishes is more important than its cannibalistic connotations. Cells build structures called autophagosomes around junk they want to recycle—for example, old or damaged organelles, fat deposits, clumps of poisonous proteins, or even microbial invaders. Once that garbage is bagged, cells break it down into reusable building blocks and nutrients. A year earlier, Beth Levine, an autophagy researcher at the University of Texas Southwestern Medical Center, and a few other experts in the field had come to Third Rock to pitch a biotech