In this talk, titled “What Can you Learn with a Light Microscope”, Prof. Ron Vale (UCSF, HHMI, founder of iBiology and the scientist who discovered the motor protein kinesin) provides an excellent overview of Light Microscopy. Against a backdrop of beautiful images from the world of microscopy, including some from his own work, Prof. Vale captures the wonder of discovery beginning with the historical context of microscopy. He shows 19th century images taken with microscopes by Golgi and Cajal (who shared the Nobel Prize in 1906 for their work) and remarks on how similar those images are to those found in modern textbooks.
He then outlines how the late Prof. Shinya Inoué (RIP), a pioneer in polarization light microscopy and video microscopy, was able to image mitosis in Live Cells during the 1950s. By observing cell division and the movement of chromosomes, Dr. Inoué deduced structural information from the movement of chromosomes and fibers involved in mitosis. Given what was subsequently discovered about the protein molecules that make up these structures, this example illuminates the critical sequence of observation and deduction in scientific discovery. It is in this context that one grasps the importance of the evidence provided by Light Microscopy in the evolution of human knowledge of the Life Sciences.
Prof. Vale goes on to describe the pathbreaking deductions made by Hugh Huxley and Andrew Huxley from Phase Contrast Microscopy images of sarcomeres, units of striated muscle tissue. Their observation of the changing banding patterns in sarcomeres was the basis of the “sliding filament theory” of muscle contraction. In a segment titled “Watching Biochemistry in Action”, Prof. Vale also recounts his own personal research in 1984 in which he was able to use video microscopy to image an enzyme (kinesin) transporting artificial beads along microtubules. Previously biochemistry had been the domain of spectral photometry. But now, scientists now could use video microscopy to watch proteins in action.
The discovery of Green Fluorescent Protein (GFP) by Osamu Shimomura, Martin Chalfie and Roger Tsien (Nobel Prize winners in 2008) is described by Prof. Vale as a combination of Light Microscopy and Genomics. Based on their discovery, scientists can fuse GFP that is found in jellyfish to any protein in the genome and follow the dynamics of the protein. This enabled a new aspect of discovery as to how proteins behave in living cells.
The grand finale of this talk is a summary of the modern advances in Light Microscopy. Viewers are introduced to Super Resolution Microscopy, in which it is possible to get beyond the diffraction limit, Quantitative Image Analysis, and the use of holographic optical traps to manipulate objects and molecules with light. The video concludes with a beautiful, complex 3D pattern of neurons of the mouse somatosensory cortex image demonstrating the technique known as Array Tomography.
In this iBiology lecture, titled “Early History of Microscopy”, Prof. Joseph Gall (Carnegie Institution for Science) details the evolution of microscopy from the early 17th century to the present day. The lecture is full of fascinating details, such as why there was a time lag between the developments in astronomical telescopes and microscopy, even though the compound microscope was invented in the 17th century. One also learns of the tremendous pace of developments in microscopy during the pivotal 19th century, many of which are still part of modern Light Microscopy.