 Abstract tissues use feedback circuits in which cells send signals to each other to control their growth and survival. These circuits are inherently unstable due to mutations that misinterpret the signal level, causing a growth advantage for the mutation and making it difficult to eliminate with existing cell intrinsic mechanisms. To counteract this instability, tissues employ biphasic responses in which the signal is toxic at both high and low levels, creating a frequency-dependent selective disadvantage for the mutation and allowing it to be eliminated from the population. However, this also creates a new unstable fixed point beyond which runaway processes can occur, resulting in increased risk of diseases such as diabetes and neurodegenerative disease. This article was authored by Omar Karan and Yuri alone.