I
was born on September 12, 1940 in Weidenau/Sieg, Germany. Since 1972 the town has been part of Siegen, a city with currently some 100,000 inhabitants, situated at the southern tip of North Rhine Westphalia. The mountainous area around it is called Siegerland, for centuries home of the iron mining, processing and manufacturing industry. Mining of iron went all the way back to the Celts, two thousand years ago. After mining and processing moved to the Ruhr area, only the iron manufacturing part remained − boilers, metal pipes, railroad tracks, buckets and many other parts made of iron and steel. Weidenau’s most prominent landmark is called the Fujiyama, a giant heap of slag from iron mining, matching the shape of the famous mountain in Japan. Siegen was also the seat of the House of Orange Nassau, related to the Dutch royal family.

The city of Siegen prides itself of being the birthplace of Peter Paul Rubens. However, the only reason he was born there and not in Cologne, his parents’ place of residence, was that his father got arrested as he was passing Siegen in a carriage with his pregnant wife, in a case of mistaken identity. The dispute between three cities claiming Ruben as their son – Siegen, Cologne and Antwerp – is immortalized in a fountain sculpture at Siegen’s Upper Castle showing three mothers holding, and fighting over, baby Peter Paul.

My father Wilhelm Frank was a judge (Amtsgerichtsrat) at the District Court in Siegen. He was born in 1896 in Weidenau. His study of law was interrupted by the draft to fight in Verdun in WWI where he was wounded, losing most of his left hand. His mother came from a wealthy local family, the Schleifenbaums, that owned a flourishing iron-manufacturing business, and his father was a high school teacher who came from a rural family in Banfe, in nearby Wittgenstein. My mother Charlotte came from the distinguished Manskopf family that traced its origins in Siegen back to the 15th century. A branch of her family settled in Frankfurt in the 18th century and gained wealth and notoriety from international wine trading. They were friends with Johann Wolfgang von Goethe’s family around the beginning of the 19th century.

My mother, educated in Stift Keppel, a high school for girls with a history going back to the 13th century, stayed at home, taking care of her four children – myself, my four year younger sister Renate and two older siblings: Ingeborg and Helmut. Our house was large and stately, solidly built from red double-glazed bricks by my grandparents in 1905. It was set on a good-sized plot bordered from the street by a wrought-iron fence. The house had verandas on the first and second floor overlooking the backyard. Walking paths were seamed with boxwood and covered with ornamental gravel.

The war

As I was born during WWII, my whole childhood was marked by the war. Siegen’s iron manufacturing industry made the city a target of the Allied raids, and eventually, by the end of the war, led to the destruction of 80% of all buildings. My first memories, at age four, were of houses in the neighborhood going up in flames. In one of the early raids in February of 1944, my parents’ house was fire-bombed. Since the roof and upper floor of our house were destroyed, and the rest rendered uninhabitable by extensive water damage, we had to move for over a year to Hilchenbach, a town 20 kilometers to the north, where a colleague of my father offered us room in his large apartment. This apartment was located in the Williamsburg, an 18th century water castle that served as the court building at the time. The memory of sitting in the bomb shelter, in the basement of the large building, surrounded by crying babies, and listening to the sounds of planes, air raids, and radio announcements were the stuff of nightmares well into my adolescence.

The time immediately after the war was one of great hardship. My mother went on “hamstering” trips into the country by train, traveling with zinc-plated buckets, manufactured by the company of her in-laws and much treasured by the farmers. She bartered them for butter, ham, big loafs of bread, flour, and eggs. Back home, she would mix “real butter” with margarine in a large bowl to stretch out the experience of tasting traces of real butter into weeks. We had a good-sized garden with apple, pear and cherry trees. For a while we grew sugar beets to make syrup and tobacco plants to support my father’s smoking habits. We kept chickens in the backyard, and even kept a pig at one time in the space under the veranda. Helping my 10-year older brother with the garden work and spending time with the chickens made me appreciate nature from a close range.

The sight of rubble of houses burned and collapsed in our neighborhood had a peculiar effect on me, a mixture of fright and fascination. The fright was the natural reaction to the sights of chaos and destruction, which implied to a child that nothing still standing is safe. The fascination part came from the experience of playing, together with other boys my age, on desolate lots filled with bricks, pots, twisted wires and Bakelite insulators. Here and there we uncovered a family of mice with pink stillblind babies.

School years

My elementary school, where I spent my first four years, was right across the street from our house. I was eight years old when I started my first experiments in the dark place underneath the veranda where our little pig once roamed. It was natural curiosity that made me do it, before I had any concept of science. I built a shelf, collected little Magenbitter liqueur bottles and filled them with every liquid I could get hold of: oil, water, gasoline and, when I was a little older, hydrochloric acid. In bouts of intuition I mixed the fluids, exposed metals to them and recorded the results. I watched calcium carbide dissolve in water and enjoyed watching the violent reaction and the smell of the escaping gas. I watched zinc dissolve and bubble up in hydrochloric acid. I heated up coal in a metal container connected to a tube since I’d heard that a flammable gas would escape.

My parents’ house contained one amazing treasure that would accompany me through all of my boyhood and adolescence, as soon as I was able to read: Meyers Konversations-Lexikon, an encyclopedia in 20 volumes published in 1905. Each volume measured about 1000 pages, filled with scholarly articles, technical drawings, colorful photogravures, and maps from all over the world. Quite possibly I read them all over the course of the years. As a whole, this large encyclopedia reflected the belief that all that ever needed to be studied was known already, and that progress from then on would be at most incremental. Ironically, 1905 happened to be the exact year when Albert Einstein published a paper on the photoelectric effect, with its evidence for the quantization of energy, the precursor of Quantum Mechanics. It would leave little of the old wisdom untouched. I would later claim the collection as my only bid for a tangible heirloom in my parents’ house.

Starting with fifth grade I went to the Fürst Johann Moritz Gymnasium, named after one of the prominent Orange Nassau dukes. I was one of only four to step up from my elementary class of twenty students. In the Gymnasium, which in the German system combines middle and high school, I immediately took an interest in science classes, particular physics. Meanwhile my tinkering at home had migrated from the place under the veranda to the attic of our house and expanded to include radios, which I rebuilt from used and mail-ordered parts. This obsession with radios started after my brother showed me how to build a crystal radio. I constructed several fancy miniature radios fitting in soap boxes. Most of my savings went into the purchase of valves, transistors, resistors, and capacitors. The attic was filled with the exciting smell of vapor from the soldering rosin. I made a friend in school who shared my hobby and lived across the street.

I should add at this point that all three of my siblings went to the same Gymnasium.

After receiving his Abitur (high school diploma) my brother finished his Ph.D. in Engineering and became a civil servant for Occupational Safety. Both my sisters left at the “Einjaehrige,” an early departure point from high school for a switch to a trade school, in their case a school for physical therapists. My elder sister finished her Abitur many years later after she married and her kids had grown up, proceeding to college and obtaining a Ph.D. in Biochemistry. My younger sister, after working as a physical therapist, became an artist and made many beautiful quilts until her early death in 1998, from cancer.

College

For me the choice of physics for study in college was always a foregone conclusion, though my father needed extra reassurance, as he doubted this would lead to a career that would ever earn me a living. In 1960, after finishing my Abitur I went to the University in Freiburg. The move into the little quiet university town with its large Gothic cathedral and charming medieval buildings was nevertheless a huge step for me coming from the provincial town I grew up in. I took Calculus and Linear Algebra, and learned how to write rigorous mathematical proofs. I also took courses in Special Functions of Mathematical Physics and Statistical Mechanics.

Following the example set by my brother, who had studied Engineering in Aachen, I joined a fraternity, Corps Suevia, and made several friends there. Later, though, influenced and enlightened by the political upheavals in the sixties, I decided to quit the Corps since I recognized the nationalistic, right-wing roots of German student organizations. Freiburg was also the place where Martin Heidegger, as rector of the university, had infamously aligned himself with the Führer. During my time there I saw the aged Heidegger, a little man, give one of his rare public speeches in front of the University, barely visible as a throng of students surrounded him.

Based on my performance in the Vordiplom (B.S. equivalent) exam, I was nominated for the Studienstiftung des Deutschen Volkes, a special fellowship that would prove instrumental in widening my horizon to include other fields of science and humanity. The Studienstiftung fostered interdisciplinary discourse by organizing meetings at the forefront of science. In one of these meetings, in 1964, I first learned about the tenets of the Central Dogma and the structure of DNA. I was also here that I met Wolf Singer, a neurophysiologist, starting a close friendship that would last until today. With him and like-minded students, I founded a discussion group focused on Cybernetics, the hot subject of the time.

Graduate studies

I went to the Physics Department at the University of Munich to do work toward my Diploma thesis, the equivalent of a Masters degree. The thesis project had to do with the back-scattering of electrons on gold in the liquid phase, an esoteric subject vaguely related to the then-emerging technology of machining with high-intensity electron beams. My mentor, Ernst Kinder, had done early work with the electron microscope, tracing the colorful patterns of butterfly wings to light interference created by submicroscopic arrangements of tiny scales. He still kept an ancient electron microscope in his office.

After finishing my diploma, when it came to choosing a Ph.D. thesis mentor, I was therefore prepared and open to the idea of working on a project that involved electron microscopy. The mentor I chose was Walter Hoppe, an X-ray crystallographer-turned electron microscopist at the Max-Planck Institut für Eiweissund Lederforschung on the Schillerstrasse in the center of Munich, which later relocated to Martinsried and became the Max-Planck Institute for Biochemistry. Hoppe looked for ways to use the electron microscope for imaging biological molecules in three dimensions. My thesis focused on an exploration of the properties of electron micrographs using methods gleaned from other fields, such as Statistical Optics. My first paper, in the journal Optik, examined the optical diffraction patterns of micrographs affected by specimen drift, and interpreted the stripes observed in terms of Fourier theory (Frank, 1969). I was proud when Hoppe refused to put his name on it, recognizing it as a totally independent piece of work.

My first experience in computer programming was with the programming language ALGOL, and involved a 20-minute walk to the Technical University for every compilation and every run of a newly written program. I later learned to program in FORTRAN on an IBM 1130 machine tucked in a little basement room of our Institute, where I sometimes worked late into the night. The Institute, located just minutes’ walk away from the Wiesn, the site of the Oktoberfest, had its own social life with distinct Bavarian color. Early-morning mushroom picking raids were organized when they were in season. The porcinos and pfefferlings brought back by the teams of three or four students – always including at least one expert – wound up boiling in Erlenmeyer flasks in the exhaust hood. They were sprinkled with salt and served with pieces from a big loaf of Bavarian bread. We celebrated the acceptance of papers with a keg of beer and big hunks of meatloaf in the library room.

Munich at the time, as now, was a city rich with cultural events. There were so many venues; it was possible to go to a classical concert every day. One of my friends, who also made the move from Freiburg to Munich, was a classical music aficionado and lured me to many outstanding performances. It was then that I learned to recognize many classical symphonies from a few opening notes. Little experimental theaters were abounding. The Munich Opera House offered a grand experience for affordable ticket prices. I spent my time with two circles of friends, one around Wolf Singer, whom I’d met through the Studienstiftung, the other around Jan Groneberg, a firebrand college dropout with utopian ideas who lived in a little cottage outside of Munich. It was in Wolf Singer’s circle of friends where I met my first wife, Cathy Engelberger. We married in 1969, but the marriage would last less than 10 years.

During this time, a meeting in Hirschegg, in 1968, gave me the opportunity to meet several people who later became important in the field. The workshop (as well as later ones) was co-organized by Walter Hoppe and Max Perutz from the Laboratory of Molecular Biology of the MRC in Cambridge, known for his pioneering work in protein X-ray crystallography. Among the people I met there were Harold Erickson, Richard Henderson, Ken Holmes, Hugh Huxley, and Nigel Unwin. With afternoons free for skiing, and both mornings and evenings reserved for the lectures and discussions, the format resembled that of the Gordon Conferences. Two papers (in German) related to my thesis were later published in the proceedings of the meeting, in a special issue of Berichte der Bunsengesellschaft für Physikalische Chemie (Frank et al., 1970; Langer et al., 1970).

Postdoctoral studies

After my thesis defense at the Technical University Munich in early summer of 1970 I was awarded a Harkness Fellowship, which allowed me to spend two years in the USA at labs of my choice. I chose the Jet Propulsion Lab (JPL) at Caltech in Pasadena, the Donner lab in Berkeley, and Cornell University. Coming from Europe, the culture shock of being placed into the Hollywood-like landscape of Pasadena with its restless freeways and little houses with palm trees and little old ladies with tennis shoes could not be greater.

In hindsight, all three labs gave me important impulses toward my future direction. The JPL at the time had the world’s best image processing equipment, and had developed a modular image processing system, VICAR, that I could hook my own programs to. This package would later serve as a model for developing my own system, SPIDER. At Donner lab, which was part of the Lawrence Berkeley labs on the hill, I spent time with the group of Bob Glaeser, who focused on two quintessential problems faced by structure research with the EM: radiation damage, and the need for a hydrated environment. He and his student Ken Taylor were already experimenting with the preparation of frozen-hydrated samples, but the decisive invention of the vitrification technique in Jacques Dubochet’s hands had yet to come. At Cornell University, in the group of Benjamin Siegel in Clark Hall, I made the acquaintance of Ken Downing and William Goldfarb. I later asked William to join me in Albany as part of my team.

While in Ithaca, in 1972, my son Hosea Jan Frank was born.

Returning from the USA, I spent a brief time back at the Max-Planck Institute, in the winter of 1972/73, working on the theory of partial coherence in electron microscopy. This work brought me in contact with Peter Hawkes, a world expert in Electron Optics. In 1973 I joined the group of Vernon Ellis Cosslett at the Cavendish Laboratory in Cambridge, still at its old location in Free School Lane, as a Senior Research Assistant.

Among the people I interacted with were Owen Saxton and Peter Hawkes. During my years at the Cavendish I worked further on partial coherence and found a way to obtain the signal-to-noise ratio of electron micrographs by computing the cross-correlation of two successive images of the same field.

This was the time when the vision of single-particle averaging and reconstruction took hold in my mind – the idea of spreading out electron dose among multiple “copies” of a molecule randomly arranged on the grid. In 1975 I published a concept paper presenting the idea that the structure of a molecule could be retrieved by taking advantage of multiple occurrences of this molecule in solution (Frank, 1975). Together with Owen Saxton I analyzed the conditions under which bright field images of biological molecules can be aligned with sufficient accuracy for the image average to reach a given resolution. The result of this study, which we jointly published in 1977 (Saxton and Frank, 1977), gave me confidence that the single-particle approach would work even under weak native contrast (i.e., protein vs. water) conditions.

Albany, and the Wadsworth Center

In 1975 I received a job offer from Don Parsons at the Division of Labs and Research (later renamed Wadsworth Center) of the New York State Department of Health in Albany, New York. While the original mission was tomographic reconstruction of cell sections, I focused on the implementation of the single-particle approach. In both areas I recognized the need for a workbench of programs to gain flexibility in the design of programs, and started on the development of SPIDER, an image processing system of modular design (Frank et al., 1981). As the single-particle techniques developed, SPIDER became the vehicle for disseminating the technique to the community. It was initially distributed under a license agreement, for a one-time fee, and later became available for free under a creative commons license.

It would still take a few years until proof of concept would be available with actual images of biological molecules. These were glutamine synthetase, provided by David Eisenberg at UCLA, acetylcholine receptor, by Peter Zingsheim in Goettingen, and ribosomes, by Miloslav Boublik, at Roche in New Jersey. Martin Kessel, an early convert and close friend, helped me in some of these studies as he took a Sabbatical leave from Hadassah University Medical Center. In each case, reproducibility of two-dimensional averages demonstrated that the approach was sound. Still, there was a lot of skepticism among practitioners of electron microscopy. A turning point came with the addition of a method addressing the problem of heterogeneity, which I developed jointly with Marin van Heel, a student visiting from the Netherlands in 1980 (van Heel and Frank, 1981). Looking for other suitable challenging molecules to try the technique on, I started a collaboration with Jean Lamy and his student Nicolas Boisset in Tours, France, to image a variety of arthropod hemocyanins. (I stayed in touch with Nicolas over the years until his untimely death in 2008. He had a meticulous way of record keeping and developed beautiful slides for teaching the principles of single-particle reconstruction).

Albany is the capital of New York State but has a distinctly provincial character, especially lying as it does in the shadow of New York City. The town is surrounded by beautiful countryside, and hikes into the Adirondack mountains are not far away.

The move to Albany not only gave me my first independent position, it also unleashed an urge in me for creative expression in areas not associated with science. I joined an artists’ collective, called WORKSPACE, founded by Jacy Garrett. At the time, performance art was being redefined across the country, and artists’ collectives were springing up everywhere. The FLUXUS movement directed attention to the peripheral, the accidental. I enjoyed being accepted by the collective without formal credentials, just by virtue of my creative contributions. I participated in mail art correspondence and, for several years, either edited or co-edited a small literary magazine called PROP.

At the end of the 70s my first marriage ended. The divorce agreement gave us joint custody over our son, an arrangement that would keep me in town for quite some time, as I would see Hosea grow and become a multitalented artist who renamed himself Ze. I was to meet my present wife, Carol Saginaw, in Albany in 1982. Carol worked initially at the New York State Office of Mental Health, then over the years was executive director of several statewide non-profit organizations in mental health and later in early care and education. Carol was from Michigan, from a Jewish family that had lost many of their members in death chambers constructed by the country I was from. Although our diverse backgrounds presented a challenge, we were married in 1983, and we have been happily together ever since. In good part it was Carol’s continuous support, and her faith in me, that made me prevail and come to the present point in my career.

At that time, I also started writing fiction in English and was quite flattered when William Kennedy, and later Steven Millhauser and Eugene Garber, gave me very positive feedback on my manuscripts. To me the idea that I might be able to express myself creatively in my second language was thrilling as I was unsure at this stage if I would ever return to live in Germany. After a course in fiction writing with Eugene Garber at SUNY Albany, the participants of his class, myself included, decided to continue meeting as a writers’ group. Constructive criticism by this group, and other groups that I joined later on, honed my writing and helped me recognize “my voice,” and writing became part of my life (www.franxfiction.com).

Looking back now, I see that my early contributions to single-particle EM were made possible mainly by three factors: the peace and quiet of the place where I worked, the absence of any teaching requirements, and the steady support by the National Institute of General Medical Sciences, of NIH, which lasts until the present day. I was quite fortunate to have Michael Radermacher join my team in 1982, a German student who had also trained under Walter Hoppe and had a special background in three-dimensional reconstruction with arbitrary geometries. Michael was the one who single-handedly designed the random-conical reconstruction programs in my lab that, in 1986, yielded the first three-dimensional reconstruction of a totally asymmetric molecule, the large subunit of the E. coli ribosome. By adopting the novel plunge-freezing and vitrification technique of Jacques Dubochet, we were soon able to reconstruct biological molecules in their hydrated, native state as well. From that point on, in the late 1980s, the technique we had been working on so hard was evidently headed for success, though it was still uncertain if it would ever be able to compete with X-ray crystallography in resolution and propensity to yield atomic structures.

Meanwhile, in 1985, our daughter Mariel Beth was born and became the center of our life. When she was two years old, I received the invitation for a Sabbatical stay at the Medical Research Council (MRC)’s Laboratory for Molecular Biology (LMB) in Cambridge, England, with Richard Henderson as host. We rented a charming little home, King’s Cottage in Little Shelford, with a flower garden where Mariel played with other children. We made punting trips on the river Cam and walked in the beautiful parks in the surroundings of Cambridge. Most of my interactions in the lab were with Wah Chiu, whom I first met as a student during my visit at Bob Glaeser’s lab, and who visited the LMB at that same time. With his help, and using his data on two-dimensional crystals of crotoxin, I developed and demonstrated patch averaging, a method of structure recovery that made use of “local” averages of a crystal divided into small areas – essentially the single-particle approach applied to pieces of a crystal.

Back in Albany, among the first molecules we reconstructed in 3D were hemocyanins, in continuation of our collaboration with Jean Lamy’s group in France. Another collaboration, with Sydney Fleischer of Vanderbilt University, gave me the first opportunity to work on the structure of the ryanodine receptor. Still, the work on the structure of the ribosome continued to fascinate me most. As early as 1990 I became convinced that my lab would be able to contribute significantly to the structure and function of the ribosome, and I started hiring biochemists with ribosome background. Rajendra Agrawal, trained in the Burma lab at the Baranas Hindu University, was the first to bring real “ribosomologist” expertise into the lab. Others would follow later, among these Christian Spahn, trained in the lab of Knud Nierhaus in Berlin.

A major factor promoting discussions in the growing cryo-EM community and the dissemination of the new technologies of sample preparation, instrumentation and data processing has been the Gordon Conference on three-dimensional electron microscopy (3DEM). Established in 1985, it met every two years initially and later switched to the present annual cycle. My election in 1987 to be Vice-chair in 1989 with David DeRosier and to be Chair in 1991 was a big step marking recognition of the single-particle techniques by the whole community.

A Humboldt-funded Sabbatical stay in 1994 at the Max-Planck Institute for Medical Research in Heidelberg, hosted by Ken Holmes and Rasmus Schröder offered me the first opportunity to work in Germany again. Through the efforts of my graduate student Jun Zhu and my postdoc Pawel Penczek, the first detailed map of the E. coli ribosome emerged, well before the X-ray structures came out. The putative placements, by Raj Agrawal, of tRNAs and mRNA into this map of the ribosome have stood the test of time. It was also in Heidelberg that I completed writing my book on 3D electron microscopy, which would be published in 1996 and, in a second edition, in 2006 (Frank, 2006).

In 1998 I was appointed a Howard Hughes Medical Institute (HHMI) investigator, a position that would last for 19 years and was only recently terminated. The funding by HHMI during these years was absolutely crucial for my lab to continue development of cryo-EM and realize very challenging biological projects with several collaborators. At about that time the Wadsworth Center joined eight institutions in New York City to form a consortium for structural research, called the New York Structural Biology Center, which supports NMR, X-ray crystallography, and cryo-electron microscopy. This connection provided entrées for me at Columbia University and other leading institutions in New York.

In 2000, on my 60th birthday, I organized a meeting in Rensselaerville, in continuation of a series of conferences started by Anders Liljas in Sweden on the Structural Basis of Translation. The conference site in Rensselaerville is set in a beautiful park, an hour driving distance from Albany. As I spent time during this meeting with Måns Ehrenberg we made concrete plans for collaboration on ribosome structure and function. This turned out to be the beginning of an exhilarating journey that has lasted until now, as we investigated the structural basis for initiation, decoding, mRNA-tRNA translocation, termination, and the recycling process, thereby contributing to the rich knowledge base on the mechanism of translation available today.

My children at this point were grown and on their own. My son Ze Frank had majored in neuroscience at Brown University and started a band, playing the guitar. His special talents for music and the arts had been in evidence early on. He subsequently moved to New York and began doing web design. Through a fortuitous route, which he recounted in his first TED Talk, he became an internet personality virtually overnight. Most recently he was a media executive at Buzzfeed. He now lives with his wife and two children in Los Angeles. My daughter Mariel Frank majored in linguistics at Barnard College. Speaking multiple languages, she taught English in Japan, worked for a Latinx non-profit organization and is now a programmer and curriculum developer at Code academy. She is married and lives in Brooklyn.

Columbia University

In 2008 I joined Columbia University as a faculty member of both the Department of Biochemistry and Molecular Biophysics, and the Department of Biological Sciences. After more than 30 years, this move from pastoral Albany to New York City was quite exciting as it offered many opportunities for collaborations. I brought the HHMI-owned FEI Polara microscope with me and, together with the FEI F20 microscope purchased as part of the startup, established cryo-EM at Columbia University. One area of collaboration I was immediately attracted to was single-molecule FRET, which had just been set up by Ruben Gonzalez coming from the Puglisi lab at Stanford.

For the first four years at Columbia, progress with our cryo-EM projects was slow as it was still limited by the poor quality of recording media. The situation changed radically when direct electron detection cameras were introduced commercially, transforming the field profoundly and opening up many new avenues in my lab for exciting collaborations, particularly on channel structures. A Columbia-wide cryo-EM resource facility has been recently created and, thanks to generous gifts by donors and the cooperation by the deans of all three campuses, Columbia is now headed toward becoming one of the world’s leading centers for cryo-EM.

Beyond the benefits to Columbia and the USA, looking at the way the new technology has recently spread across the entire industrialized world, I’m gratified to see that single-particle cryo-EM is now able to fill a huge gap in molecular structure research as membrane-bound channels and receptors, and also many large molecules with flexible regions can be tackled, promising to add significantly to the war chest of human medicine in years to come.

Acknowledgments and final note

The emergence of many near-atomic structures in the last five years in several labs has drawn the world’s attention to the many preceding years of work not just by the Nobel Laureates now honored and their groups, but by the whole cryo-EM community. Because, for perspective, it is necessary to note that since about 1990, when the technique started to receive recognition within the cryo-EM community, there have been major contributions by many groups to every aspect: sample preparation, automation of data collection, computation, validation and atomic model building. These contributions are too numerous to list, but instead I refer to a recent review of the whole field (Frank, 2015).

I have been very fortunate throughout the journey that has brought me to this point. I would like to express my gratitude to my family, particularly my wife Carol, for their steady support over this long time. My sister Ingeborg Berg, with her training in biochemistry, was the one person in my family who could appreciate the enthusiasm I expressed in letters to her early on. Among my friends I need to single out Martin Kessel for his early encouragement and support and Jose-Maria Carazo for so many brainstorms along the way.

As a final note, the recognition by the Nobel Prize is an experience both extremely thrilling and humbling. A lifetime achievement benefiting the whole of humankind – in the words of Alfred Nobel’s will − seems an idea so grandiose that only few can live up to it. Ernest Rutherford? Linus Pauling? Marie Curie? Their shoes are difficult to fill. The event is also transformative since all of a sudden my life is defined, or confined, by the perceptions of many people I have never met. It dawns on me that there is no way back – for better or worse − to the life I was living before. This is why I’m grateful for this opportunity to tell my own story, in my own words.

References

Frank, J. (1975). “Averaging of low exposure electron micrographs of non-periodic objects.” Ultramicroscopy 1, 159–162.

Frank, J., Shimkin, B., and Dowse, H. (1981). “SPIDER — A modular software system for image processing.” Ultramicroscopy 6, 343–358.

Frank, J. (2006). Three-Dimensional Electron Microscopy of Macromolecular Assemblies (New York, Oxford U. Press).

Frank, J. (2015). “Generalized single-particle cryo-EM – a historical perspective.”

Microscopy 65, 3–8.

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/ Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.