The invention of the microscope can be traced back to the 14th Century to the Italian art of grinding lenses for spectacles. This technology was then taken up by Dutch lens grinders Hans and Zacharias Janssen in 1590 to make the first microscope by placing two lenses in a tube. In 1675 Anton van Leeuwenhoek used a simple microscope with only one lens to look at blood in fine detail and became the first person to describe cells – the red blood cells that carry oxygen around the body.
Over the centuries, microscopes have been integral to the development of immunological research but perhaps the most formative moment came in 1878 when Paul Ehrlich, a young scientist from Strehlen (now Strzelin) in Prussia (now Poland) described in his doctoral thesis the discovery of a new constituent of blood which he called mast cells. He found that the granulated protoplasm of what were thought to be simply plasma cells could be made visible under a microscope by adding an alkaline dye.
He thought these granulated cells were a sign of good nutrition, hence he named them after the German word for an animal-fattening feed called Mast. In fact, with the help of his microscope, Ehrlich had discovered a key cell type belonging to the human immune system, the first of many. Mast cells are now known to release histamine and other substances during inflammatory and allergic reactions.
Ehrlich’s interest in microscope dyes that could differentially stain tissues also led him to be the first person to distinguish between lymphocytes and leucocytes, the two main groups of white blood cells – vital players in the immune system. He went on to conduct many more seminal discoveries in immunology, such as his experiments on immunising mice against poisons, notably the ricin toxin, and the idea of a “magic bullet” based on specific antibodies to target specific diseases. His work led to a Nobel prize in 1908 in recognition of his work on immunology and in his acceptance lecture he acknowledged the importance of the microscope in the understanding of life.
But, curiously, he thought the age of the microscope had reached its zenith. “I am inclined to think that the limit of what the microscope could and has done for us is now approaching and that for a further penetration into the important, all-governing problem of cell life even the most highly refined optical aids will be of no use to us,” he said.
He wasn’t to know that further advances in labelling, such as immunofluorescence, and in microscopic technology, such as the electron microscope and the scanning-tunnelling microscope, were to shed even further light on the complex workings of the immune system.