Nobel Laureate in Chemistry Joachim Frank Unveils the Legendary Path of Cryo-Electron Microscopy in Transforming Modern Medicine

Prof. Joachim Frank, the 2017 Nobel Laureate in Chemistry, delivered a speech titled "Cryo-electron microscopy, a new foundation for molecular medicine and drug design" at National Taiwan University on May 6, 2026. As a pioneer in the high-resolution applications of cryo-electron microscopy (Cryo-EM), he pointed out that this technology was one of the key contributors in the fight against COVID-19; during the critical moment of the pandemic outbreak, cryo-electron microscopy demonstrated a speed unattainable by X-rays, allowing scientists to directly observe the structure of the "Spike Protein" in an extremely short period of time, which played a decisive role in vaccine development and the screening of neutralizing antibodies.

Prof. Frank currently teaches at Columbia University in the United States and is also a member of both the National Academy of Sciences and the American Academy of Arts and Sciences. He jointly won the 2017 Nobel Prize in Chemistry with Jacques Dubochet and Richard Henderson.

From Basic Research to Frontline Healthcare: The Leap of Cryo-Electron Microscopy
During the speech, Prof. Frank elaborated deeply on how cryo-electron microscopy technology moved from basic research to the frontline, becoming a key weapon against cancer, heart disease, and COVID-19. He stated that the essence of modern medicine is "molecular medicine," and early structural biology mostly separated molecules in vitro, designing drugs by studying their structures. However, life is not static, and the molecules within cells are like precise "molecular machines," executing various physiological functions in motion. To understand these complex molecular operations, scientists need powerful tools capable of capturing every frame of dynamics.

In the early stages of structural biology development, X-ray Crystallography was the mainstream technology; he used Max Perutz and John Kendrew's use of X-rays to build the first hemoglobin model to explain the importance of atomic resolution to the audience, noting that the two scientists also won the 1962 Nobel Prize in Chemistry for this, but this traditional technology is still limited by the challenge that molecules must be crystallized.

Breakthrough in Image Reconstruction Technology: The Birth of “Spider”
After obtaining his Ph.D. from the Technical University of Munich (TUM), Prof. Frank went to the United States for postdoctoral research and was inspired at the Jet Propulsion Laboratory (JPL) of the California Institute of Technology to develop "Spider," a key image processing technology in Cryo-Electron Microscopy (Cryo-EM) that can convert thousands of cluttered, two-dimensional protein projection images captured by electron microscopes into precise three-dimensional spatial models through calculation and reconstruction. This breakthrough broke traditional constraints, not only overcoming the difficulty of biological samples being easily damaged under electron beam irradiation, but also breaking free from the limitation of traditional X-ray crystal diffraction technology which requires a long time to grow high-quality single crystals, enabling scientists to observe the true structures of biological macromolecules at atomic resolution.

Prof. Frank elaborated that cryo-electron microscopy technology allows researchers to directly observe the dynamic changes of proteins in a nearly natural physiological state, providing unprecedented visual evidence for fields such as ribosome operating mechanisms, viral infection pathways, and drug target design. To this day, this technology has become an indispensable navigator in modern drug development and life science research, continuously leading humanity to explore the mysteries of the microscopic world. He also mentioned that the advent of the 300 KV high-end electron microscope symbolizes the perfect integration of computer control and electron optics, pushing the resolution across to the atomic level and completely changing the experimental paradigm of scientists. Contemporary technological development has made it possible to observe the dynamics of ribosomes through cryo-electron microscopy, expanding the research landscape into the field of biomolecular dynamics that traditional crystallography cannot reach.

The Navigator of Precision Medicine: Cancer, Heart Disease, and Epidemic Prevention
At the end of the speech, Prof. Frank demonstrated the outstanding application potential of cryo-electron microscopy in current medical challenges. Through this technology, scientists can clearly observe how small molecule drugs bind to cancer protein targets, and can also resolve the dynamic conformations of ion channels in myocardial cells, providing structural solutions for the treatment of cardiovascular diseases. Today, cryo-electron microscopy has become an indispensable core tool in modern drug development and life science research, and is an important contributor in the fight against cancer, heart disease, and the pandemic. In the subsequent Q&A session, Prof. Frank highly appreciated the depth of knowledge demonstrated by NTU students, and he encouraged the faculty and students present to possess interdisciplinary thinking—integrating physics, computational science, and biology—which is the core key to deciphering complex life science problems.

The Finale of TAIWAN BRIDGES: Connecting the World through Science
Prof. Frank's visit was invited under both "Raymond Soong Chair Professorship of Distinguished Research” and the “TAIWAN BRIDGES” program. The Taiwan Bridges program, collectively held by National Taiwan University, Academia Sinica, and 10 other institutions in collaboration with the International Peace Foundation (IPF) hosted the visits of 31 Nobel Laureates to Taiwan over 7 months for lectures academic exchanges. The initiative promoted knowledge interaction and humanistic dialogue between Taiwanese and global scientists opening up global space for Taiwan's scientific development.