In the physics of thermodynamically large numbers of particles there are known to be collective organizing principles that lead to astonishing behavior, such as superconductivity or the fractional quantum Hall effect. These effects enable one to measure fundamental constants with high precision and are for this reason often thought of as following deductively from microscopics. This is, however, incorrect. They are instead universal and generic – “protected” by principles of large-scale organization of matter, and quite independent of microscopic details. The simple, elegant descriptions we have of the quantum mechanics of sound, quantum magnetism, ferroelectricity, superfluidity, and even the conventional metallic and insulating states, are made possible by the occurrence of quantum protection in these systems, not the other way around. The most timely example is the case of cuprate superconductors, where the principles of protection at low energy scales have turned out to be those operating in conventional superconductors, while the deductive path back to microscopics has not been found and many not exist at all. Principles of protection are at work everywhere in nature, might conceivably be at work at a very fundamental level in the universe itself. But the place where they are most problematical, and potentially of the greatest importance, is at the scale of the macromolecules of life. It is not known one way or the other whether organizational principles are at work in proteins, as they do not contain a thermodynamically large number of particles and thus are not protected by the principles at work in solids or quantum fluids. Yet there are many documented cases of enzymes having the same fold and function when their amino acid sequence is changed significantly. Since independence of microscopic detail is one of the key symptoms of protected behavior, one is tempted to speculate that fundamentally new kinds of protection might be at work at the scale of life. However such principles have never been deduced from microscopics in the past, but have always been discovered serendipitously in the laboratory, and this is unfortunately unlikely in biology while the experimental tools capable of seeing at length scales of 10 Åto 1000 Åare so crude. Thus I propose the great challenge of experimental physics in this upcoming century to be the development of new instruments capable searching for principles of organization in mesoscopic matter, establishing whether protection exists at this scale, and, if it does, determining the role of mesoscopic protection in life.