Some day in the future "He" will come down and
let us all know how foolish or clever we have been.
Until that day -- settled science might be settled in the context
of known data. Add a body of "new" knowledge and data
then revisit what is known.
Newtonian physics is a good example. It solved most if not all of the
problems at hand within the reach of instrumentation of the day. There
were however a number of later measurements that were unexplained as
methods improved. Orbit of Mercury was one IIRC... at which
point Albert and friends explored new solutions.
Today... with the exception of dark matter and dark energy there are
rare examples of unexplained data. Some particle physics research
has taken a different approach and by the exploration of a model attempt
to discover something that has yet to be observed.
Molecular biology is odd in that we know that we do not know very much at all.