Joachim Frank

Joachim Frank
Joachim Frank at the Nobel Prize press conference in Stockholm, December 2017
Joachim Frank
Born	12 9, 1940
Birthplace	Siegen, Germany
Nationality	German-American
Occupation	Biophysicist, academic
Title	Professor of Biochemistry and Molecular Biophysics
Employer	Columbia University
Known for	Single-particle cryo-electron microscopy, ribosome structure and dynamics
Education	Technical University of Munich (Dr. rer. nat.)
Children	2
Awards	Nobel Prize in Chemistry (2017), Benjamin Franklin Medal in Life Science (2014), Wiley Prize in Biomedical Sciences (2014)
Website	[Frank Lab at Columbia University Official site]

Joachim Frank (born September 12, 1940) is a German-American biophysicist and professor at Columbia University who was awarded the Nobel Prize in Chemistry in 2017 for developing single-particle cryo-electron microscopy (cryo-EM), a technique that allows scientists to produce three-dimensional images of biological molecules at near-atomic resolution. He shared the prize with Jacques Dubochet and Richard Henderson, each recognized for distinct contributions to the development of cryo-EM. Frank's specific contribution lay in the computational methods he devised for processing and combining thousands of two-dimensional electron microscope images into sharp three-dimensional structures—a set of techniques that transformed structural biology and opened the door to visualizing molecules that had previously resisted study by traditional methods such as X-ray crystallography. Born in Siegen, Germany, Frank spent much of his career at the University at Albany before joining Columbia, where he holds appointments in the Department of Biochemistry and Molecular Biophysics and the Department of Biological Sciences. In addition to his Nobel Prize–winning work on image processing, Frank has made substantial contributions to understanding the structure and function of the ribosome, the molecular machine responsible for protein synthesis in all living cells.

Early Life

Joachim Frank was born on September 12, 1940, in Siegen, a city in the North Rhine-Westphalia region of Germany. He grew up in postwar Germany, a period that shaped the educational and scientific institutions in which he would later train. The University of Siegen has acknowledged Frank as one of the region's most prominent figures in the sciences.

Details about Frank's family background and childhood remain limited in publicly available sources. What is known is that his early intellectual interests gravitated toward physics and the natural sciences, leading him to pursue university education at several of Germany's leading institutions.

Education

Frank's academic training spanned multiple universities in Germany and included postdoctoral work in the United States. He studied at the University of Freiburg and the Ludwig Maximilian University of Munich (University of Munich) before completing his doctoral studies at the Technical University of Munich under the supervision of Walter Hoppe, a pioneer in electron microscopy and structural analysis. His doctoral thesis, titled Untersuchungen von elektronenmikroskopischen Aufnahmen hoher Auflösung mit Bilddifferenz- und Rekonstruktionsverfahren (Investigations of high-resolution electron microscopic images using image-difference and reconstruction methods), was completed in 1970 and foreshadowed the computational image-processing work that would define his career.

Following the completion of his doctorate, Frank conducted postdoctoral research in the United States. He worked with Robert Glaeser at the University of California, Berkeley, and with Robert Nathan at the Jet Propulsion Laboratory in Pasadena, California, both of whom served as his academic advisors during this period. At Cornell University, he also gained further experience that helped consolidate his expertise in electron microscopy and image analysis. These postdoctoral positions exposed Frank to the computational and optical techniques emerging in American laboratories during the early 1970s and provided the intellectual foundation for the methods he would later develop.

Career

Early Academic Career and the University at Albany

After completing his postdoctoral training, Frank joined the Wadsworth Center, the public health laboratory of the New York State Department of Health, and the Department of Biomedical Sciences at the University at Albany, SUNY. He would remain based in Albany for approximately three decades, during which time he carried out the bulk of the foundational research that would eventually earn him the Nobel Prize. At the Wadsworth Center, Frank assembled a research group dedicated to developing computational techniques for analyzing electron microscope images of biological macromolecules.

The central problem that Frank set out to solve was a fundamental limitation of electron microscopy as applied to biological specimens. While electron microscopes could visualize individual molecules, the resulting images were noisy, two-dimensional projections that captured a molecule in a random orientation. No single image contained enough information to reconstruct the molecule's three-dimensional structure at high resolution. Frank recognized that if thousands of such images could be classified according to their orientations and then mathematically combined, a detailed three-dimensional model could be computed.

Development of Single-Particle Cryo-Electron Microscopy

Beginning in the 1970s and continuing over several decades, Frank developed a suite of computational algorithms and software tools that made single-particle reconstruction possible. His approach involved several key innovations. First, he developed methods for aligning and classifying noisy electron microscope images so that images showing the molecule in similar orientations could be grouped together and averaged, dramatically improving the signal-to-noise ratio. Second, he devised algorithms for determining the three-dimensional orientation of each two-dimensional image, allowing the images to be combined into a coherent three-dimensional reconstruction.

These methods were implemented in software packages that became widely used in the structural biology community. The techniques Frank pioneered did not require that the molecules being studied form crystals—a prerequisite for X-ray crystallography, the dominant method of structural determination at the time. This was a transformative advantage, because many biologically important molecules, including large complexes and membrane proteins, resist crystallization.

The term "single-particle cryo-electron microscopy" reflects the fact that the method images individual molecules (single particles) that have been rapidly frozen (cryo) in a thin layer of ice, preserving them in their native, hydrated state. While Frank focused primarily on the image-processing and computational aspects, the broader cryo-EM methodology also depended on the contributions of his co-laureates: Jacques Dubochet developed the vitrification technique for preparing frozen-hydrated specimens, and Richard Henderson demonstrated that electron microscopy could achieve atomic resolution on biological samples.

Frank's computational framework was essential to making cryo-EM a general-purpose tool for structural biology. By the 2010s, advances in electron detector technology combined with Frank's image-processing methods had brought about what the structural biology community termed the "resolution revolution," enabling cryo-EM to routinely achieve near-atomic resolution.

Ribosome Research

In addition to his methodological contributions, Frank applied his cryo-EM techniques to study the ribosome, the large molecular machine responsible for translating genetic information into proteins. This work constituted a major second strand of his research career.

Using the single-particle methods he had developed, Frank and his collaborators produced increasingly detailed three-dimensional structures of ribosomes from both bacteria and eukaryotic organisms. These structures provided insights into how the ribosome functions during the various stages of translation—the process by which messenger RNA is decoded to build a polypeptide chain. Frank's cryo-EM studies were among the first to capture the ribosome in multiple functional states, revealing the conformational changes and dynamics that accompany each step of the translation cycle.

This line of research had implications beyond basic biology. Because bacterial ribosomes differ structurally from human ribosomes, understanding the ribosome's structure at high resolution is relevant to the design of antibiotics, many of which work by targeting the bacterial ribosome and inhibiting protein synthesis. Frank's structural studies thus contributed to efforts in rational drug design.

Move to Columbia University

Frank joined the faculty of Columbia University in New York City, where he holds the position of Professor of Biochemistry and Molecular Biophysics in the College of Physicians and Surgeons, as well as a position in the Department of Biological Sciences. At Columbia, he continued his research on cryo-EM methodology and ribosome dynamics, leading an active laboratory known as the Frank Lab. The Frank Lab has produced an extensive body of publications spanning cryo-EM methods, ribosome structure, and related topics in structural biology.

Public Engagement and Advocacy

In the years following his Nobel Prize, Frank has been an active public voice on issues related to scientific research funding and academic freedom. In a 2025 opinion article published in The Berkshire Eagle, Frank argued that scientific research "cannot be switched on and off at will" and warned against the consequences of drastic government funding cuts to research. In an opinion piece for U.S. News & World Report in October 2025, he defended universities as institutions that "nurture independent thought" and argued for the importance of protecting academic freedoms.

Frank has also continued to engage with the international scientific community through lectures and speaking engagements. In March 2025, he delivered a lecture at Wayne State University School of Medicine as part of the Bhanu P. Jena Endowed Lecture series. In December 2025, he was announced as a lecturer at the Cochin University of Science and Technology in India.

Personal Life

Joachim Frank has two children, Ze Frank and Mariel Frank. Ze Frank is known as an online performance artist, composer, and humorist who became a prominent figure in early web culture. Frank has resided in the Great Barrington, Massachusetts area, as indicated by his 2025 opinion writing in The Berkshire Eagle.

In September 2022, scientists from around the world gathered at a symposium at Columbia University to celebrate Frank's belated 80th, 81st, and 82nd birthdays—delayed by the COVID-19 pandemic—honoring his contributions to cryo-electron microscopy and structural biology.

Recognition

Frank's contributions to science have been recognized with numerous awards and honors. The most prominent is the Nobel Prize in Chemistry, which he received in 2017 jointly with Jacques Dubochet and Richard Henderson "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution." The announcement by the Royal Swedish Academy of Sciences noted that the three laureates' collective work had moved biochemistry into a new era by enabling researchers to visualize molecular processes in unprecedented detail.

Prior to the Nobel Prize, Frank received the Benjamin Franklin Medal in Life Science from the Franklin Institute in 2014, recognizing his pioneering work in developing computational methods for three-dimensional electron microscopy. That same year, he was awarded the Wiley Prize in Biomedical Sciences, given annually by Wiley to recognize breakthrough research in the biomedical sciences. The 16th annual Wiley Prize honored the pioneering development of cryo-EM techniques.

Frank is a member of several learned societies. He was elected to the National Academy of Sciences of the United States. He is also a Fellow of the American Academy of Arts and Sciences.

Legacy

Joachim Frank's principal legacy lies in the establishment of single-particle cryo-electron microscopy as one of the foundational methods of modern structural biology. Before his work, determining the three-dimensional structures of biological macromolecules at high resolution was largely dependent on X-ray crystallography, which required that molecules be coaxed into forming ordered crystals—a process that was often difficult or impossible for many important biological complexes. Frank's computational image-processing methods provided an alternative pathway that bypassed crystallization entirely, opening up vast new territory for structural investigation.

The impact of cryo-EM, built substantially on Frank's algorithms and software, has been transformative for the life sciences. By the mid-2010s, the method had achieved resolutions rivaling X-ray crystallography for many types of specimens, and it became the method of choice for studying large molecular assemblies, membrane proteins, and molecular machines in multiple functional states. The technique has been applied across fields from virology—where it has been used to determine the structures of viral proteins, including those of SARS-CoV-2—to neuroscience and pharmacology.

Frank's work on the ribosome also represents a lasting scientific contribution. His cryo-EM structures of the ribosome in different functional states have provided a dynamic picture of one of the cell's most essential machines, complementing the earlier crystallographic ribosome structures that earned Venkatraman Ramakrishnan, Thomas A. Steitz, and Ada Yonath the 2009 Nobel Prize in Chemistry.

The celebration of Frank's contributions by colleagues from around the world at the belated birthday symposium at Columbia in 2022 reflected the breadth of his influence across the cryo-EM community. His continued public advocacy for scientific research funding and academic freedom has further extended his influence beyond the laboratory.