Miller, who was born at Nice in the south of France, was educated at the University of Sydney, Australia, and at University College, London, where he obtained his PhD in 1960. He then held brief appointments at the Chester Beatty Research Institute in London and the National Cancer Institute in Bethesda, Maryland. Miller returned to Australia in 1966 to serve as head of the experimental pathology department at the Hall Institute of Medical Research, Melbourne.

In 1961 Miller succeeded in solving an ancient medical mystery. The thymus gland is a large organ placed in the chest beneath the breastbone. Surprisingly, until 1961 scientists lacked any clear idea of the role played by such a prominent body. The normal technique in such a situation is to watch for any changes in the behavior of the subject when the organ has been removed. In this case thymectomy seemed to make no discernible difference to the behavior of any experimental animal.

Working within this tradition Miller performed a surgical operation of great skill, the removal of the thymus from one-day-old mice. As the mice weigh no more than a gram and are no bigger than an inch it is not difficult to see why such an operation had been little attempted before. In this case, however, the excision did lead to dramatic and obvious changes. The mice failed to develop properly and usually died within two to three months of the operation. Just what was wrong with them became clear when Miller went on to test their ability to reject skin grafts, a sure sign of a healthy immune system. Miller's mice could tolerate grafts from unrelated mice and sometimes even from rats. This made it quite clear that the thymus was deeply involved in the body's immune system but just what precise role it played was to occupy immunologists for a decade or more.

Much of Miller's work was performed independently, also in 1961, by a team under the direction of Robert Good at Minnesota.