The thymus, a relatively obscure organ that sits between the heart and rib cage, was believed by some ancient Greek scholars to be the seat of the human soul. Jacques Miller changed immunology forever in 1961 when he showed that the thymus is critical for the development and function of the immune system.

Emeritus Professor Miller joined WEHI in 1966 and soon led a second groundbreaking discovery: identifying two critical components of the immune system, B cells and T cells. 

Almost 60 years later, Kelin Zhao began her PhD research at WEHI, focusing on the thymus. Her 3D image of a lobe of the thymus, ‘Thymic Coral Reef’, won the Moving Image category in WEHI’s 2022 Art of Science competition. 

Jacques: 

When I began my PhD in the late 1950s, the thymus was considered a vestigial organ with no known function. It was believed to have become redundant over the course of evolution and just seen as a graveyard for dying white blood cells called lymphocytes. 

My experiments led me to conclude that the thymus at birth had a role and function that must be essential to life, but I had no idea at that time it would turn out to be just so important. 

A few years later, Gus Nossal – who I had known since our school days in Sydney – invited me to join WEHI. 

Working with my first PhD student, Graham Mitchell, we were able to show that there were two kinds of lymphocytes with different functions: those derived from the thymus, now called T cells, and others derived from bone marrow, now called B cells. 

We got spectacular results using no more sophisticated equipment than Petri dishes!

Incredible images 

Now, thanks to far more advanced techniques and incredible imaging technology, we know the thymus produces and trains T cells that play a role across the entire spectrum of tissue physiology and pathology: in inflammation and tissue repair, infections, vaccination, allergies, immunodeficiency, autoimmune diseases, tissue and organ transplant rejection, and many others. 

And there are so many different types of T cells now, beyond my ability to keep up – if you don’t work in the lab every day, you lose track! 

I try to stay engaged with the latest research about the thymus, so I was very excited when Associate Professor Daniel Gray showed me his PhD student Kelin’s remarkable images of the three-dimensional structure of the thymus. 

Not only are they very beautiful but they remind us that there’s so much still to be discovered about the thymus; the science becomes more complex and interesting all the time. 

The research that Kelin and her colleagues are doing helps us know more about the framework of the thymus, how different cells interact and communicate within the organ, and also how this activity changes from birth to adulthood. 

Kelin: 

During my Masters degree in molecular biology at the University of Queensland, I had some contact and collaboration with WEHI. I applied to do my PhD at WEHI because of its strong history and reputation in immunology, and I was very excited to be accepted to work in Daniel Gray’s lab. 

Jacques still visits the lab regularly and, although I didn’t know his history initially, I learned from Daniel that Jacques was the first scientist to identify the function of the thymus. 

My research has involved imaging the whole thymus gland in three dimensions for the first time, and the images I entered into Art of Science come from that work. 

I was surprised and pleased that Jacques was very interested in the images and our early data, particularly our findings about thymic epithelial cells (TEC).

We identified a population of TEC that is linked to ageing and shrinkage of the gland, and Jacques offered ideas that have really helped us develop the direction of the research. He also had some interesting suggestions about how we might apply our imaging techniques to understanding the development and changing function of the thymus with age. 

Thymic regeneration 

Research is starting to reveal the interrelationships and “cross-talk” between thymocytes (the cells that are transformed into T cells), blood vessels and TEC within the thymus. 

We’re very keen to understand this better so that we can find ways to support thymic regeneration after damage, for example, as a side effect of cancer treatments. 

The structure and culture of WEHI really supports interaction, communication and collaboration in a way I don’t think I’ve seen at other institutions, and I think that’s really important for actively producing leading research. 

It’s wonderful for me that WEHI has such diversity and encourages groundbreaking scientists like Jacques to remain actively involved in the work of younger researchers. 

Jacques is a brilliant scientist with so much experience and so many ideas that he’s willing to share. I will definitely invite Jacques to my final seminar presentations, and I hope he will be there!