Short answers, pulled from the story.
Mass-energy equivalence is the principle that mass and energy are two expressions of the same physical quantity, related by the square of the speed of light. The formula E equals mc squared states that the energy of an object at rest equals its mass multiplied by the speed of light squared, meaning a tiny amount of mass corresponds to an enormous amount of energy.
Einstein first described mass-energy equivalence on the 21st of November 1905, in his Annus Mirabilis paper titled "Does the inertia of a body depend upon its energy content?" He did not write the familiar formula directly; he stated in German that if a body gives off energy as radiation, its mass diminishes by the corresponding amount. He first published the equation using a lowercase c in 1907.
Several scientists anticipated aspects of the idea before Einstein. Henri Poincaré associated electromagnetic radiation with a fictitious mass in 1900. Nikolay Umov proposed a mass-energy proportionality for ether in 1873. Samuel Tolver Preston in 1875 and Olinto De Pretto in 1903 imagined ether particles moving at the speed of light with a kinetic energy implying a mass-energy relation. None established the general principle Einstein derived from the symmetries of space and time.
During the solar eclipse of the 29th of May 1919, English astronomer Arthur Eddington observed that light from stars passing close to the Sun was bent by the Sun's gravitational field. This confirmed that the energy carried by light behaves as gravitational mass, a direct prediction of mass-energy equivalence combined with the equivalence of gravitational and inertial mass.
Einstein cosigned a letter to the US president in 1939 warning that an atomic bomb was theoretically possible, which persuaded Roosevelt to fund atomic research. Lise Meitner and Otto Robert Frisch used Einstein's equation in late 1938 to confirm that nuclear fission was energetically possible. However, Manhattan Project physicist Robert Serber noted that relativity is not actually required to describe the fission process, which is non-relativistic.
Nuclear fission converts roughly 0.1 percent of the original mass of uranium into energy. Complete conversion requires matter-antimatter annihilation, which in principle releases all rest-energy as radiation. In practice, CERN estimated in 2011 that producing and storing antimatter requires more than a billion times the energy that would be released in its annihilation, making full conversion impractical with known methods.