Nobel Prize winner in Chemistry
Fritz Haber (1918), Carl Bosch (1931) Friedrich Bergius (1931) Georg Witt (1979) Stefan Heil (2014)
The Nobel Prize has been awarded since 1901 and is considered the world's highest award for significant achievements in physics, chemistry, physiology and medicine, as well as for literature and peace. The founder of the prize is the Swede Alfred Nobel, who achieved great wealth with the invention of dynamite. In 1895, Nobel stipulated in his will that almost his entire fortune should go into a fund "the interest on which is to be distributed annually as a prize to those who have been of the greatest benefit to mankind in the past year." Nobel went on to explain that it was his express wish that the most worthy should receive the prize, regardless of nationality. The award ceremony is held in Stockholm every year on December 10, the anniversary of Nobel's death. The Nobel Peace Prize is awarded in Oslo.
We can be proud of the fact that our region has also produced numerous Nobel Prize winners. In the chemistry category, these include Carl Bosch, Friedrich Bergius, Richard Kuhn, Stefan Hell and Jacques Dubochet.
Carl Bosch was born in Cologne on August 27, 1874, the first of seven children of Paula and Carl Friedrich Bosch. His father is the co-owner of an installation company and brother of the famous entrepreneur Robert Bosch. Even as a child, Carl was already looking around his father's business and gaining his first experience in the trades. After graduating from secondary school in 1893, he received an apprenticeship at a steelworks in Silesia, where he also acquired knowledge of metallurgy.
After his apprenticeship, Carl Bosch initially studied mechanical engineering at the Charlottenburg Technical University before transferring to the University of Leipzig in the summer semester of 1896 to study chemistry. Just two years later, he received his doctorate in organic chemistry with the distinction "summa cum laude" for his dissertation "On the condensation of disodium acetone dicarboxylic acid diethyl ester with bromoacetophenone".
Carl Bosch then remained in Leipzig for two years as an assistant for analytical chemistry. In his spare time, he studied botany and zoology, as well as mineralogy and entomology. At the end of his life, he had an extensive collection of plants, butterflies and beetles that he had prepared himself. Some of these can be admired today in the Carl Bosch Museum in Heidelberg.
On the recommendation of his doctoral supervisor, Carl Bosch was employed as a chemist at BASF in 1899. He married Else Schilbach in Cologne and moved with her to Ludwigshafen, where their children Carl and Ingeborg were born.
In 1902, Bosch was commissioned by Heinrich von Brunck, then Chairman of the Supervisory Board of BASF, to investigate the problems arising from the binding of atmospheric nitrogen. At the beginning of the 20th century, there was still no process for converting inert atmospheric nitrogen into chemical compounds and thus making it usable as a fertilizer, for example. The development of such a process is a very challenging task.
The famous Justus von Liebig had already pointed out in 1840 in his work on agricultural chemistry that plants absorb the minerals required for the formation of chlorophyll and plant proteins, in particular phosphorus, potassium and nitrogen, from the soil with their roots. However, intensive farming deprives the soil of these minerals over time.
Around 1900, in Germany and many other parts of Europe, crop failures and even famines became increasingly common. Many people emigrated to America during this time. In order to secure the supply of food for the rapidly growing population, the depleted soils had to be supplied with nitrogen in particular.
However, natural fertilization with liquid manure or dung, which releases ammonia through the decomposition of nitrogenous substances, is not enough. At room temperature, ammonia is a poisonous gas with a pungent odor, which we know from ammonia, the aqueous nitrogen solution. The nitrogen atom contained in the ammonia molecule is bound to three hydrogen atoms, hence its formal name "NH3". The N stands for nitrogen, the H for hydrogen.
At that time, saltpetre was used to supplement organic fertilization. This nitrogen-containing salt occurs naturally, but is very expensive because it has to be brought in from overseas, e.g. from Chile. The idea of producing the nitrogen salts that plants can use to build up leaf mass on an industrial scale is an obvious one.
Nitrogen, a colorless and odorless gas, is available in abundance, as it is the main component of the earth's atmosphere, accounting for 78%. However, plants cannot utilize atmospheric nitrogen directly. The nitrogen molecule N2 consists of two nitrogen atoms firmly bonded together. The two atoms can only be separated from each other by applying high levels of energy.
Lightning storms, for example, split the nitrogen molecules due to the high temperatures they generate. The released nitrogen atoms are very reactive and immediately recombine with other atoms or molecules, e.g. with water. In this way, the nitrogen reaches the soil in a form that can be used by plants. Thunderstorms at the beginning of the growing season in spring are particularly effective. It is not for nothing that an old farmer's saying goes: "Thunderstorms in May, the farmer shouts yay!"
Bosch is carrying out a series of experiments at BASF to convert nitrogen into chemical compounds. However, the results are unsatisfactory: the processes used do not provide a sufficient yield, are too uneconomical or cannot be implemented on an industrial scale.
At the same time, the chemist Fritz Haber was investigating the reaction between nitrogen and hydrogen under high pressure and at high temperatures at the Technical University of Karlsruhe. After years of experiments, he discovered that a pressure of around 300 bar, i.e. 300 times the normal air pressure, temperatures of 400 degrees Celsius and, last but not least, suitable catalysts were required for a sufficient reaction rate.
In 1908, his experimental apparatus produced the first synthetically produced ammonia under laboratory conditions. He applies for a patent for his process and turns to BASF for its industrial-scale implementation. However, a major problem was identified there, particularly with regard to the high pressures required. This is because there are still no pressure vessels and pipes that can withstand such loads. In addition, hydrogen diffuses through even the thickest steel walls at high temperatures and pressures because its atoms are tiny.
But Carl Bosch finds a solution. He constructed a double-walled tube from new types of steel. Its interior consists of soft, low-carbon iron, which is barely penetrated by hydrogen, and a jacket of solid steel. The hydrogen still diffusing through the inner tube can escape through holes in the outer tube. After extensive research, Alwin Mitasch, head of the ammonia laboratory at BASF and a close associate of Carl Bosch, develops a suitable catalyst made of iron oxide with aluminum, calcium and potassium components.
The first high-pressure and therefore reliable reactor in the history of process engineering is thus invented and, after five years of research and development, Haber's laboratory result is made usable for large-scale production.
The ammonia synthesis process, named the Haber-Bosch process after its developers, was the first to successfully combine atmospheric nitrogen with hydrogen in huge high-pressure reactors. The resulting ammonia is liquefied and separated by cooling the gas mixture. In 1913, mineral fertilizer production begins at the first synthesis plant in Oppau near Ludwigshafen. By 1914, more than 7,000 tons of inexpensive percolating fertilizer are available.
At BASF's own agricultural research institute in Limburgerhof, Bosch starts field trials in 1914 to determine the optimum quantities, application times and distribution of the fertilizers so that he can provide farmers with the best possible instructions for using the fertilizer. Farmers are introduced to the new artificial fertilizer through amusing advertising.
But then the First World War breaks out. Ammonia becomes an important raw material for the war effort, as the nitric acid obtained from it is a raw material for explosives. BASF promises to supply it with the so-called "saltpetre promise" and switches production from fertilizer to saltpetre, which is then also produced in large quantities in the newly built Leuna works.
In 1919, Bosch becomes Chairman of the Board of Executive Directors of BASF and takes part in the peace negotiations in Versailles as an expert for the chemical industry. He succeeds in preventing the implementation of plans to dismantle the German chemical industry.
After the end of the war, ammonia and nitric acid production grew steadily. Although the risks of production and storage are known, a catastrophe occurs on September 21, 1921, which costs the lives of 561 people when a huge explosion shakes Oppau and largely destroys it. Even in Heidelberg, 25 km away, the blast wave covered the roofs of houses. To this day, it is the biggest chemical disaster in BASF's history.
Carl Bosch, who had a wide range of scientific interests, ran a private observatory on his Heidelberg estate and not only supported the construction of the Einstein Tower in Potsdam, but also sponsored the liberal Frankfurter Zeitung newspaper and made a substantial donation in 1933 to help found the Heidelberg Zoo.
In 1937, Bosch succeeded Max Planck as President of the Kaiser Wilhelm Society, now the Max Planck Society. At the annual meeting of the Deutsches Museum in May 1939, Bosch courageously warned that "science can only flourish freely and without paternalism, and that the economy and the state will inevitably perish if science is forced into such stifling political, ideological and racist restrictions as under National Socialism" (issue 3, page 270, Kultur und Technik 1984). Based on this conviction, he also intervened against the expulsion of Jewish scientists. After more than 100 years, BASF has now shut down ammonia production in Ludwigshafen and relocated it abroad due to high energy costs.
Dr. Carl Bosch does not live to see the terrible end of the Second World War. He died in Heidelberg on April 26, 1940 at the age of 66 and was buried in the Bergfriedhof cemetery. Carl Bosch receives many honors. The most important was the Nobel Prize, which he was awarded in 1931 together with Friedrich Bergius, a student of Fritz Haber, for the invention and development of high-pressure chemical processes.
Friedrich Bergius was born on October 11, 1884 as the only son of Heinrich and Marie Bergius in Breslau in what is now Poland. He grew up there with four sisters in a wealthy and educated family. His father owned a chemical factory where bauxite was processed. Before attending secondary school, Friedrich was taught at home. After leaving school, he completed a six-month internship in a smelting works, where he was able to deepen the experience he had already gained as a pupil in his father's factory in both chemical and technical processes.
In the fall of 1903, he began studying chemistry in Breslau, which he continued after a year of military service in Leipzig, where he received his doctorate in 1907. Dr. Bergius then worked for two semesters as an assistant to Walter Nernst (Nobel Prize 1920) at the Institute of Physical Chemistry in Berlin, where he met the chemist Matthias Pier.
In 1908, Bergius married Margarethe Sachs and moved to Karlsruhe for a semester to acquire additional knowledge from Fritz Haber (Nobel Prize 1918), who was researching in the field of high-pressure chemistry. He continued his studies on coal liquefaction at the Institute of Physical Chemistry at the Technical University of Hanover. A process for producing illuminating gas from coal had already been developed in England. This could be used to light streets and buildings. But Bergius wants to convert coal into liquid rather than gaseous products.
He sees that increasing motorization through car traffic and aviation will require large quantities of fuel, which could be made available if the abundant coal in Germany could be converted into petrol.
In his laboratory, he investigates how high pressure of 100 to 200 bar combined with a high temperature of 500 °C affects chemical reactions. Like Carl Bosch, he first has to construct a container that can withstand both high pressure and high temperatures and is also chemically resistant. The ground coal, enriched with heavy oil to form a slurry for better dosing and to prevent a dust explosion, is pumped into this reaction vessel. Finally, hydrogen is added to the reaction chamber.
With the help of metallic catalysts, the hydrogen reacts at a pressure of 300 bar and a temperature of 450-500 °C and attaches itself to the carbon. In this way, the carbon is liquefied to hydrocarbon 2C+2H2→2CH.
In 1912, the 28-year-old Bergius habilitated with the thesis "Application of high pressures in chemical processes and the reproduction of the formation process of hard coal" and became a lecturer in physical chemistry at the Technical University of Hanover. Just one year later, Prof. Bergius applies for a patent for the production of chain-shaped hydrocarbons using a process for the hydrogenation of coal, known as coal liquefaction.
However, Bergius is not satisfied with using his process only in the laboratory. Coal liquefaction should also succeed on an industrial scale. Further extensive experiments were necessary for this, but his resources were not sufficient. At the beginning of the First World War, Bergius gives up his teaching position and accepts an offer from Dr. Karl Goldschmidt. He became head of the research laboratories at Theodor Goldschmidt A.G. and moved his laboratory to the Essen plant.
In 1916, he not only became a deputy member of the Management Board, but was also put in charge of the newly established test facility in Mannheim-Rheinau for the development of a large-scale coal liquefaction process.
Due to the First World War, time was of the essence and Bergius was under pressure to deliver results quickly. He therefore attempted to develop the coal hydrogenation process for series production directly in industrial applications without lengthy laboratory work. However, this was not successful. The incredibly high sum of five million gold marks invested by Goldschmidt in research is used up and the businessman Karl Goldschmidt is not prepared to provide any further funds. His faith in success is lost, as is his trust in Bergius, whose employment ends in 1919.
Soon afterwards, Bergius founded Deutsche Bergin-AG für Kohle- und Erdölchemie in Berlin. However, the end of the war and the onset of hyperinflation made it impossible for him to raise the capital required for the further development of coal liquefaction. Bergius therefore sells his patent rights to coal liquefaction to BASF, which merges with seven other German chemical companies to form IG Farben in December 1925 under the leadership of Dr. Carl Bosch. There, the chemist Matthias Pier finally succeeds in developing a process for coal liquefaction on an industrial scale, the Bergius-Pier process. From 1927, Leunawerke near Merseburg is able to produce 100,000 tons of synthetic petrol a year with the first hydrogenation plant.
Bergius is no longer involved in this. He moved to Heidelberg with his second wife Ottilie and embarked on a new research project: the extraction of sugar from wood cellulose, or wood saccharification. The great shortage of food and fodder at the beginning of the 19th century had already prompted him to carry out his first research in 1916, which he resumed in Mannheim-Rheinau in 1924. He financed this research with a large part of the proceeds from the sale of the patent rights.
With another part of the proceeds, he acquired two Art Nouveau villas at Albert-Ueberle-Straße 3-5 in Heidelberg in 1923, which he later replaced with a villa in the "New Objectivity" style. The inauguration ceremony in July 1929 was attended by 143 guests, including Gerhart Hauptmann, Walter Jellinek, Thomas and Golo Mann, Carl Zuckmayer and the ministers Gustav Radbruch and Gustav Stresemann. The villa becomes a social hub.
In his laboratory, Bergius achieves his first results with his hydrolysis process. Wood consists of cellulose, the main component of plant cell walls, lignin, which supports the cell walls, and hemicellulose, a mixture of polysaccharides, i.e. multiple sugars. During the wood saccharification process, the previously chopped wood is broken down into lignin and cellulose with the help of a highly concentrated hydrochloric acid solution. The lignin remains as an insoluble residue, while the hemicellulose can be broken down into mono- and disaccharides. The hydrochloric acid is then separated by vacuum distillation, resulting in a viscous solution containing 60-70% sugar and only around 4% hydrochloric acid.
The innovative aspect of Bergius' process is not the saccharification of wood with hydrochloric acid itself, but its complete recovery, which is achieved by evaporation using hot mineral oil. However, as with coal liquefaction, the process engineering implementation on an industrial scale caused great difficulties. It was only later that he finally succeeded in extracting around 66 kg of sugar from 100 kg of wood.
The global economic crisis in 1929 threatened to thwart the continuation of his expensive research. Bergius invested his private assets, took out loans and was soon broke.
After receiving honorary doctorates from the universities of Heidelberg and Hanover and the Liebig Medal, Bergius was awarded the highest scientific honor on December 10, 1931. He and Carl Bosch are awarded the Nobel Prize in Chemistry for their contributions to the invention and development of high-pressure chemical processes.
In his acceptance speech, Bergius admits that he has been unfaithful to the goals of his youth. "The house where I received my first training as a chemist, the laboratory of the University of Wrocław, bore the motto "Seek the truth and ask not what good it does" in its entrance hall. He only followed this teaching for a few years because he was looking for knowledge that would benefit mankind. He goes on to say that after this betrayal of pure science, it was impossible to turn back. "For the problems, once grasped, drag those who are obsessed by them further and further away, deeper and deeper, and entangle them in their bonds and in their service with body and soul, with property and possessions, until the problems are solved or their adept lies defeated on the ground." (From: Nobel Lectures, Chemistry 1922-1941, Elsevier Publishing Company, Amsterdam, 1966). In fact, a bailiff who had traveled to the Nobel Prize ceremony seized the prize money from the destitute Nobel Prize winner.
Only when the Nazi government took an interest in Bergius' research after Hitler came to power and supported it with public funds did his financial situation improve. With the inclusion of wood hydrolysis in the four-year plan to secure raw materials, Bergius was able to continue his research, and a Reich guarantee made it possible to expand the wood hydrolysis plant in Mannheim-Rheinau. Like the chemical industry as a whole, Bergius benefited from the economic upturn, but became increasingly dependent on a state that was developing into a dictatorship.
In the 1934 referendum on merging the offices of Reich Chancellor and Reich President, Bergius campaigns for a vote in favor of Adolf Hitler. However, Friedrich Bergius did not become a member of the NSDAP. In any case, there is no indication of this in the NSDAP membership register.
Perhaps the fact that his daughter Renate, the eldest of his three children, was stripped of her German citizenship in 1935 because of her Jewish mother and emigrated to England in 1938, where she married and later worked very successfully as an art historian, played a role in this context.
In the end, Bergius also had to sell his house in Heidelberg. In 1942, he moved to Berlin and, after his apartment was destroyed in an air raid in September 1944, to Austria. In 1947, he emigrated to Argentina and worked as an advisor to the Argentinian government. On March 29, 1949 (according to his widow), Friedrich Bergius died in Buenos Aires at the age of 64 and was buried in the German cemetery in Chacarita.
After the Second World War, coal liquefaction no longer plays a role. Fuels produced from the now abundant crude oil are considerably cheaper. During the oil crisis in the 1970s, the process is remembered again, but only China produces fuels from coal for its own market.
Richard Kuhn was born in Vienna on December 3, 1900, the son of Richard Clemens Kuhn, an Imperial and Royal Court Councillor and hydraulics engineer. Until the age of 9, Richard was taught at home by his mother Angelika, a primary school teacher. From 1909, he attended grammar school in Döbling. One of his classmates was Wolfgang Pauli, who became his best friend and was awarded the Nobel Prize in Physics in 1945 for his contributions to quantum physics. A family friend was head of the Institute of Medicinal Chemistry and Richard was often allowed to help him prepare experiments, which sparked his interest in biochemistry at an early age.
At the end of the First World War, Kuhn was drafted into the Austrian army signal corps, which was a very emotionally stressful time for him. Just four days after his discharge on November 18, 1918, he enrolled at the University of Vienna to study chemistry. But as early as 1919, he transferred to the Ludwig Maximilian University in Munich together with his school friend Wolfgang Pauli. Richard Kuhn wanted to study under the internationally renowned chemist Richard Willstätter. Willstätter was awarded the Nobel Prize in 1915 for deciphering the structure of chlorophyll.
Kuhn quickly completed his undergraduate studies and was offered a doctoral position with Prof. Willstätter in 1921. Just one year later, Kuhn received his doctorate "summa cum laude" with a thesis on "The specificity of enzymes in carbohydrate metabolism and the mechanism of action of amylases", enzymes that break down polysaccharides.
Kuhn remained at Munich University at his professor's request. However, when Hitler was put on trial in Munich in the spring of 1924 for the failed putsch of November 9, 1923, anti-Semitic sentiment grew so strong that the Jewish Professor Willstätter resigned his chair in protest.
Richard Kuhn completed his habilitation in 1925 and, on Willstätter's recommendation, subsequently became a private lecturer at the Swiss Federal Institute of Technology in Zurich and a year later, at barely 26 years of age, Professor of General and Analytical Chemistry. Even after Kuhn moved to Switzerland, the two scientists, who held each other in high esteem, maintained a lively correspondence.
In Zurich, Kuhn continued his work in the field of enzyme chemistry, publishing a textbook on the "Chemistry, Physical Chemistry and Biology of Enzymes" in 1927 and beginning his research into vitamins and plant carotenoids. In one of his lectures, he met the Swiss student Daisy Hartmann, who became his wife in 1928 and with whom he had six children. In his private life, Richard Kuhn was rather shy, reserved and modest.
As a scientist, the highly intelligent Kuhn was brilliant: an outstanding teacher, a masterful connoisseur of scientific literature and a brilliant theorist, who also carried out his experiments, driven by almost boundless scientific curiosity, with great skill, precision and discipline. It is therefore no wonder that the young scientist quickly made a career for himself and was sought after.
On the recommendation of Prof. Willstätter, Kuhn was appointed Research Director of the Chemistry Department of the Kaiser Wilhelm Institute for Medical Research in Heidelberg in October 1929, which was newly founded at the instigation of Ludolf von Krehl. At the interface between clinical medicine, physics and chemistry, it is intended to serve basic research. It is the first institute in Neuenheimer Feld and the first KWI in southern Germany.
Otto Meyerhof, who has been appointed head of the Institute of Physiology, is delighted with his new colleague, not least because Kuhn has experience with carbohydrate chemistry and the involvement of lactic acid in muscle, topics that play a major role in Meyerhof's own research. Karl-Wilhelm Hausser heads the Department of Physics.
The KWI offers Kuhn a tailor-made laboratory and very good financial resources. Above all, his teaching duties as Professor of Biochemistry leave him enough time for research. Another attractive aspect is that the bureaucracy at the KWI is kept to a minimum.
In his new laboratory, Kuhn and his assistants immediately begin investigating the structure and function of molecules with carbon double bonds, known as polyenes. Polyenes, which include carotenoids, for example, are widespread in nature. These molecules form the basis of many natural pigments in plants and animals. In order to study the structure of carotenoids, a technique for their effective purification must be found. Only in this way is it possible to isolate and produce pure substances and thus also carry out a precise structural and functional analysis.
Kuhn recalls the absorption chromatography invented twenty years earlier by the Russian chemist Michael Tswett, a filter process that enables the separation of different compounds or molecules according to molecular size and weight and can purify chemical and biological samples to an extremely high degree.
Even though most chemists considered it ineffective for fine analysis, Kuhn commissioned one of his youngest assistants, Edgar Lederer, to improve the chromatography methods so that they could be used to purify carotene, which he succeeded in doing after testing several absorption materials. Now the concentration of trace substances can be measured and the homogeneity of substances in a solution can be detected. In this way, Kuhn and his assistants can purify and isolate a large number of natural carotenoids.
Carotene, a pigment that has been known for more than a century and is found in carrots and other plants, is a building block of vitamin A, which the body needs for growth, night vision and to maintain mucous membranes.
The spectroscopy used by Karl Hausser, Research Director of the Physics Department, also plays an important role in the studies. Using the different wavelengths of light, the light absorption spectra of the various carotene molecules could be determined, which not only made it easier to determine the chemical composition of the molecules, but could even reveal significant differences in optical properties.
At the beginning of 1931, Kuhn succeeded in identifying two similar but nevertheless different forms (isomers). He named them beta-carotene and alpha-carotene. Two years later, gamma-carotene and five other types of carotenoids were identified and their composition analyzed. When Hausser died in 1933, Walther Bothe became his successor.
In 1933, Kuhn turned his attention to researching B vitamins. His research group purifies and isolates vitamin B2, riboflavin, which is involved in the metabolism of carbohydrates, fats and proteins, from egg white and milk. Like polyenes, flavins also have double bonds, but with a nitrogen bond instead of carbon.
Kuhn and his research team succeeded in isolating vitamin B6 in yeast, elucidating its chemical composition and structure and finally synthesizing the vitamin. B6 is a co-enzyme which, like vitamin B2, is of great importance for the metabolism of proteins, lipids and carbohydrates and thus for body growth. A vitamin B6 deficiency causes dermatitis, an inflammatory reaction of the skin. Vitamin B6 can therefore be used to treat skin diseases.
Kuhn also became increasingly interested in how vitamins could be used as antibacterial agents and worked on deciphering the biochemical functions of growth factors in order to develop new antibacterial agents.
In 1938, Kuhn was awarded the Nobel Prize in Chemistry for his work on carotenoids and vitamins. However, as the Nazi government forbade German scientists from accepting the Nobel Prize, he was not able to receive the Nobel Medal until ten years later. Kuhn also received countless awards and honorary doctorates, medals and prizes. He also received numerous orders and highest honors and was a member of numerous scientific societies.
Although Kuhn is a member of the Nazi Teachers' Association, he is not a member of the NSDAP. Nevertheless, he seems to have sympathized with the Nazi regime. In 1936, he denounced his Jewish colleague Otto Fritz Meyerhof to the administration of the Kaiser Wilhelm Society for employing non-Aryan scientists.
He also worked on chemical weapons research, which in 1944 led to the development of soman, a nerve gas that was lethal even in the smallest quantities. He is also informed about human experiments by the National Socialists. On December 10, 1943, he wrote about an alleged cure for tuberculosis: "Human trials have already been started in a lung sanatorium near Darmstadt".
After the Second World War, he initially taught in the United States, but returned to Heidelberg in 1953 to his institute, which was soon renamed the Max Planck Institute for Medical Research, and was once again its director. There he researched and identified "resistance" factors effective against infections, such as oligosaccharides (polysaccharides) isolated from breast milk. He recognizes lactaminyl oligosaccharides as a receptor for the influenza virus and can thus explain the virus-inhibiting effect of human milk.
Richard Kuhn dies of cancer on July 31, 1967 in Heidelberg and is buried in the mountain cemetery. Carl Bosch once said: "If you have to choose between a genius and a character, forget the genius."
Stefan Hell was born on December 23, 1962 in Arad, Romania. His parents, an engineer and a primary school teacher, are descended from Banat Swabians and speak German as their mother tongue. He spent his childhood in the village of Sântana near Arad, known as Sankt Anna in German, and attended a German school there. His parents set great store by education and encouraged their inquisitive son. He was also lucky enough to be taught by very dedicated teachers.
After the eighth grade in 1977, Stefan was able to transfer to the German-speaking Nikolaus Lenau Lyceum in Timisoara, one of the best grammar schools in the country with a focus on mathematics and physics. But living conditions in communist Romania under Ceausescu's dictatorship became increasingly problematic, especially for people of German or Jewish origin.
When his mother fell seriously ill, the family applied for an exit visa and, after many difficulties, were finally allowed to leave Romania two years later. Their new home became Ludwigshafen. There, the now fifteen-year-old Stefan attends the Carl-Bosch-Gymnasium. While he had a lot of catching up to do in English, he was at the top of his class in science and German.
In 1981, Stefan Hell began studying physics at the University of Heidelberg, graduating with a degree. He then worked for a short time at "Heidelberg Instruments GmbH", a company founded by his professor to develop optical laser scanning systems. Here he met a biology doctoral student who familiarized him with fluorescence imaging in biology.
In his dissertation on "Imaging transparent microstructures in confocal microscopy", Hell deals with light microscopy and considers whether and how the diffraction limit in optical microscopes can be overcome.
The light microscope has been an important examination instrument since the 17th century. It works like a magnifying glass made up of two lenses, in which the image produced by the objective is magnified again by the eyepiece. If you want to take a closer look at certain structures of an object, you mark them with fluorescent paint, which is made to glow by a light source.
However, the image becomes blurred due to scattered light. With a confocal microscope, the stray light can be suppressed by filtering it out of the fluorescent light using a pinhole diaphragm and deflecting it. The marked structures are now more clearly visible.
Nevertheless, a light microscope only allows a maximum magnification of one thousand times. This is due to the wave nature of light, or more precisely the diffraction of light waves by objects of the same size as the light wavelength. If, for example, a wave hits a slit, it is diffracted there and spreads out behind it in a semicircle. The closer objects are to each other, the more the light is diffracted. This limits the so-called resolving power of optical devices. Two neighboring objects can no longer be perceived separately if they are less than 200 nanometers - around half a wavelength of light - apart. This physical limit was formulated by the physicist Ernst Abbe in 1873.
When Stefan Hell completed his doctorate in the summer of 1990, he became convinced that it must be possible to overcome the limits of resolution set by diffraction and thus develop a high-resolution optical microscope.
Why is this so important to him? There are already microscopes with such a high resolution that they can produce impressively sharp images of even the smallest objects such as viruses or molecules, such as the scanning electron microscope invented by Manfred von Ardenne in 1937. However, this microscope can only examine specimens that have been cut into wafer-thin slices, but not living cells with their countless molecules. Only a light microscope can do that.
Thanks to a postdoctoral fellowship, Hell was able to continue working on this goal at the European Molecular Biology Laboratory (EMBL) in Heidelberg and found the basis for a microscope called "4Pi". This superimposes the light in the focus with the aid of two objectives directed in opposite directions towards a single point and shortens the elongated focal spot to an approximate sphere. This makes it possible to increase the sharpness of the image along the optical axis of the microscope by up to seven times, but not to circumvent the diffraction barrier.
When his scholarship expired in spring 1993, Hell needed new research funding, which he did not receive in Germany. On the recommendation of a Finnish colleague from EMBL, he met Professor Erkki Soini from the University of Turku, who was testing fluorescence methods for medical diagnostics. With his support, Hell submitted a research proposal on 4Pi microscopy to the Academy of Finland. The Academy approved the funding, but only on the condition that Hell conducted his research in Turku. In the summer of 1993, he moved to Turku, where he was appointed group leader in the university's Department of Medical Physics.
While searching for ways to overcome the diffraction limit, he came across the phenomenon of "stimulated emission", which can be used to temporarily switch off molecules that are excited to glow. Dr. Hell immediately realized that he had found the right approach. Structural details of neighboring objects can be made distinguishable by their molecular state.
On paper, the concept of stimulated emission quenching works, and initial experiments make Hell confident that the resolution of a fluorescence microscope can be increased to at least 30 nanometers in this way.
But the three years in Finland soon came to an end, and with them the grant from the Finnish Academy. Hell returned to Heidelberg in 1996, where he completed his habilitation in physics.
At the Max Planck Institute for Biophysical Chemistry in Göttingen, Hell became head of a five-year junior research group in 1997. In the same year, he met Anna, a pediatric orthopaedist, in Göttingen, whom he married in 2000.
A generous budget allows him to set up several research groups: Physicists for questions in the field of optics, chemists to develop suitable dyes and biologists to deal with the applications. In 2000, Hell and his junior research group finally developed the STED (Stimulated Emission Depletion) method and were able to prove that it actually produced ten times sharper images than the light microscopes available at the time.
In STED microscopy, previously defined areas of a specimen are first marked with special fluorescent dyes. A special laser beam then excites these molecules to glow themselves. However, as structures closer than 200 nm to each other all glow at the same time, they become blurred. For example, the light of many flashlights shining close together at the same time outshines the other image information.
These glowing molecules are superimposed with a second ring-shaped, donut-like cut-off beam, so that only the molecules in the center of the hole can glow. An image is then created by scanning. This allows the molecules to emit their fluorescence one after the other and thus become separately perceptible. As the separation of the molecules now takes place via the states of the molecules and no longer via light waves, the sharpness of detail is no longer limited by the diffraction of the light.
But experts remain skeptical and consider it impossible that the diffraction limit can be circumvented. Respected scientific journals do not publish the research results. Once again, Hell has to look for a new job and the necessary funding for his research. But now he receives a whole series of interesting offers, which he turns down, as the Max Planck Society asks him to remain as Director of the Max Planck Institute for Biophysical Chemistry in Göttingen in 2002, which he gladly accepts. After many years in which he only financed his research through grants and did not know whether he would be able to continue it the following year, he had finally arrived.
From 2003, he headed a research group at the German Cancer Research Center in Heidelberg, which investigated ways of applying the latest developments in microscopy to cancer research. He is no longer able to help his mother; she dies of cancer in Ludwigshafen in 2004. In the meantime, high-resolution microscopes have become very important, particularly in cancer research. They can be used to observe how cancer cells communicate with each other and with healthy cells. The first commercial STED microscope was developed back in 2006, helping doctors and biologists in their search for the molecular causes of diseases.
In 2014, the physicist Stefan Hell was awarded the Nobel Prize in Chemistry for the development of super-resolution fluorescence microscopy together with the Americans Eric Betzig and William Moerner. Although STED microscopy is an innovation from optics, a branch of physics, it is also an innovation in the chemistry category, as it switches molecules on and off between two different states using special dyes. The Royal Swedish Academy of Sciences awarded the Nobel Prize in recognition of the fact that STED microscopy provides insights into the processes of living cells that were previously inconceivable.
However, Prof. Hell is not resting on his laurels, but is continuing to develop the potential of the STED principle into a new light microscopy method called MINSTED. Whereas STED microscopy still achieves a selectivity of up to 20 to 30 nanometres, i.e. 20 to 30 millionths of a millimetre, MINSTED can even display directly adjacent structures with nanometre precision by exciting only one molecule at a time to glow and locating it individually with an electronically controlled so-called STED donut beam. This is called a donut beam because there is a hole in the middle of the beam, just like a donut. The process is repeated until the position of all the molecules is recorded and an image can be calculated.
As the new light microscopes make structures up to 2000 times finer than a human hair visible, they offer an immense field of application. They allow insights into DNA strands, the arrangement of proteins in cells, the decoding of chromosome distribution in bacteria, the observation of interactions between viruses and cells in the body and also how proteins clump together in Alzheimer's or Parkinson's disease. It is even possible to record 3D videos of molecular movements. In this way, MINSTED helps to research diseases and develop new medicines.
Jacques Dubochet was born on June 8, 1942 in the small town of Aigle in the Swiss canton of Vaud, the third of four children of civil engineer Jean-Emmanuel Dubochet and his wife Liliane. He spent his childhood in a small Valais village until his family moved to Sion and then to the big city of Lausanne.
At the age of 12, Jacques passed the entrance exam to the Collège du Belvédère. He had a need to understand things and was therefore interested in science from an early age. He even built his own telescopes in art class. Nevertheless, he found his school days terrible. He suffers from dyslexia and the resulting poor grades. When his performance in all subjects steadily deteriorated, he finally had to leave school at the age of sixteen. An academic career does not seem destined for him.
But his parents believed in him and sent him to the cantonal school in Trogen in the canton of Appenzell in 1958 and from 1960 to a private grammar school in Lausanne, where he was supposed to prepare for the university entrance exam. Jacques manages to catch up on the missed learning material in a short time and passes the federal baccalaureate in 1962.
Dubochet completed his military service and then began studying physics at the École polytechnique de l'Université de Lausanne, where his father had already studied. His aim was to understand the world, especially the world of living beings. With the exception of mathematics, he enjoyed his studies, which he completed in 1967 as a physics engineer. He then devoted himself to researching DNA with electron microscopy at the University of Geneva, which later became his specialty. In 1969, he also obtained a degree in molecular biology.
He stayed in Geneva to do his doctorate under Eduard Kellenberger, one of the most important Swiss molecular biologists. Kellenberger was appointed full professor of microbiology at the University of Basel in 1970, and Dubochet followed him there.
Although his work in the laboratory left him little time, he was also committed to environmental protection in Basel. In 1973, he completed his doctorate with a dissertation on dark-field electron microscopy. However, he came to the conclusion that this was unsuitable for observations in biology. After completing his doctorate, Dubochet remained at the Biozentrum of the University of Basel and worked with his doctoral supervisor. He not only learned biophysics from him, but also took on his ethical responsibility as a scientist. A lifelong friendship connected the two researchers.
In 1978, Jacques Dubochet married the art therapist Christine Wiemken, whom he had already met at a party as a doctoral student in Basel. In the same year, he was appointed research group leader at the newly founded European Molecular Biology Laboratory (EMBL) in Heidelberg and moved with his wife to a small village south of Heidelberg. Their son Gilles and daughter Lucy are born in Heidelberg.
Located in a forest above the city of Heidelberg, the European Molecular Biology Laboratory, which today is one of the best-known biological research laboratories in the world, is headed by John Kendrew, its first Director General, and offers young researchers the best possible working conditions. Dubochet's research group has the task of contributing to the development of cryo-electron microscopy. In order to understand biochemical processes, visual representations of the molecules involved in the processes are absolutely essential. Light microscopes are not suitable for investigating the smallest structures because their resolution is far too low. Even though the electron microscopes of Ernst Ruska, Max Knoll and Ernst Brüche have been able to view cells on a nanometer scale since 1933, it is not possible to visualize biomolecules in detail. Electron microscopes "illuminate" the objects with electron beams. The electrons that "shine through" the object (transmission electron microscopy) or reflect it - as in conventional optical reflected light microscopy - are observed. In contrast to light microscopy, electron microscopy has severe limitations. As electrons, unlike photons, the "light particles", cannot move through air, the samples must be examined in a vacuum. There, however, the biological specimens containing water dry out immediately and are burntby the high-energy electron beam. This can be remedied by cooling the samples to be examined to very low temperatures. However, "normal" cooling causes ice crystals to form, which damage the structure of the molecules to be examined. The scattering of the electron beams by the ice crystals also prevents useful imaging.
At EMBL, Dubochet and his research group are now developing amethod with which the samples are cooled so extremely quickly that the water around the molecules turns into a glassy state and no ice crystals form. Vitrification allows biomolecules to be examined almost in their original state.
In this method, the sample is applied as a thin film to a metal grid and cooled down with liquid nitrogen to a temperature of minus 196 °C during the measurements in the electron microscope. The water in the sample solidifies into glass without ice crystals forming. With the help of an image processing method developed by Joachim Frank, the information from thousands of blurred two-dimensional images is assembled into a high-resolution three-dimensional structure, making the smallest biomolecules visible.
Even though Dubochet felt at home in Heidelberg, he returned to Switzerland in 1987 and took up a professorship. Until his retirement in 2007, he headed the Center for Electron Microscopy at the University of Lausanne and remained an honorary professor at the University of Lausanne, where he still has an office.
In 2017, Dubochet was awarded the Nobel Prize in Chemistry together with his colleagues Joachim Frank from the USA and Richard Henderson from the UK "for the development of cryo-electron microscopy for high-resolution structure determination of biomolecules in solution".
Today, cryo-electron microscopy can be used to visualize a wide variety of proteins and organisms and even freeze biomolecules in mid-motion and portray them at atomic resolution. As a result, we now know the nature of proteins that cause antibiotic resistance or the Zika virus and gain important insights into the development of drugs. Just a few weeks after its foundation, the Dubochet Center for Imaging (DCI) will be able to contribute to decoding the omicron variant of the COVID-19 virus at the end of 2021.
Since his student days, Dubochet has been committed to protecting the environment and was also involved as a local councillor in his home town of Morges on Lake Geneva until 2011. "As soon as I open my mouth and speak out on any subject, people listen to me because I'm a Nobel Prize winner," says Dubochet and uses this to draw attention to issues that are important to him, such as the fight against climate change in particular.
