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NCERT lists the thymus as a primary lymphoid organ where immature lymphocytes become antigen-sensitive, and notes that it is large at birth and shrinks by puberty (NCERT Class 12 Biology, Chapter 7). That sentence would have surprised many doctors around 1960, who thought the thymus did nothing. This post covers how Jacques Miller found out what it does, the objection he had to answer, and what to take from his method.
What did people think the thymus did?
The Lasker Foundation's account of the 2019 Basic Medical Research Award sets the scene. The thymus was full of lymphocytes, but those cells could not transfer immune responses to other animals, and removing the thymus from adult animals did no visible harm. "The thymus, according to prevailing wisdom, was dispensable, an evolutionary relic."
How did a leukaemia project change direction?
Miller was not looking for the thymus's job. According to the Lasker account, during his PhD work in London he was studying a virus that caused leukaemia in mice when given at birth, and wanted to know whether it could multiply only in the newborn thymus. So he removed the thymus in newborn mice before injecting the virus. WEHI's page on his career places this work at the Chester Beatty Research Institute in London in 1958.
He never got the answer to his virus question. The mice without a thymus stayed healthy at first, but after weaning they developed diarrhoea and wasted away. They were short of lymphocytes in blood, lymph nodes and spleen, made a poor antibody response, and failed to reject skin grafted from unrelated mice and even rats. Two-thirds died early. He reported the result in The Lancet in 1961 as Immunological function of the thymus.
How did he show the thymus supplied the immune cells?
He then put thymus tissue back. Neonatally thymectomised mice that received a thymus graft rejected skin from unrelated donors but accepted skin from the strain that had given the thymus, the Lasker account explains. Many of the dividing cells in the spleen came from the donor thymus. Cells from the thymus could leave it and mature elsewhere.
Worked example: reading the experiment
Lay out the groups the way an exam answer would. These are the groups described in the Lasker account, not new data.
Group 1, thymus removed at birth: few lymphocytes, weak antibody response, accepts foreign skin. Conclusion: the thymus is needed for immunity to develop.
Group 2, thymus removed, then thymus grafted: rejects unrelated skin, accepts skin from the thymus donor's strain. Conclusion: the graft restores immune function and carries the donor's identity.
Group 3, germ-free mice with thymus removed: still accept foreign skin. Conclusion: the effect comes from losing the thymus, not from infections in the animal house.
Common mistakes:
Saying the thymus makes antibodies. Antibodies come from B cells and plasma cells; T cells help them.
Saying all lymphocytes are born in the thymus. NCERT says the bone marrow produces all blood cells, including lymphocytes; the thymus provides an environment for T cells to develop.
Concluding the thymus is useless in adults. Miller showed it can be essential in adults too, to rebuild the immune system after irradiation.
Why did his critics doubt him?
Leading immunologists, including Peter Medawar and Macfarlane Burnet, at first resisted his interpretation, the Lasker account says. How could a disposable organ be vital? The sharpest objection was practical: his laboratory was a converted horse stable, and perhaps the mice were already sick and stressed. To rule this out, Miller went to the US National Institutes of Health, then the only place with germ-free mice, repeated the experiment and got the same result.
For Medawar's own work on graft rejection, see our post on Peter Medawar and immune tolerance.
How were T cells and B cells told apart?
WEHI records that Miller moved to the Walter and Eliza Hall Institute in Melbourne in 1966, invited by its director Gustav Nossal to head the Experimental Pathology Unit. With his PhD student Graham Mitchell he gave mice thymus-derived cells, bone marrow cells, or both. Only mice that got both made antibody, and the antibody came from the bone-marrow cells, with help from the thymus cells. The Lasker account says this exposed "what we now know as helper T cells". Max Cooper, working in chickens, had separately shown two lymphocyte lines, and the two shared the 2019 Lasker Award "for their discovery of the two distinct classes of lymphocytes, B and T cells".
WEHI lists his other honours, including the Copley Medal of the Royal Society and the Prime Minister's Prize for Science (2003), and notes that he is credited as the last person to have identified the function of a major organ.
What can a student take from his way of working?
Follow the surprise. A virus project turned into a discovery about the immune system.
Remove, then restore. Taking an organ out and putting it back is a strong test of what it does.
Answer the best objection with an experiment. The germ-free test ended the stable argument.
If B cells, T cells and lymphoid organs blur together, the Fermi Concept Library has every concept in biology with its own lesson, so you can sort them out one at a time.
Next step: draw a flow chart from bone marrow to thymus to spleen, and mark where T cells and B cells mature.
