New Super Tool for Cell Biology

Researchers from Stefan Hell’s department at the Max Planck Institute for Biophysical Chemistry in Göttingen have achieved yet another breakthrough in light microscopy: With their new MINFLUX microscope they can separate molecules that are only a few nanometres apart, meaning its resolution is 100 times higher than conventional light microscopy, and about 20 times higher than super-resolution light microscopy.

The 2014 Nobel Prize in Chemistry was dedicated to the breaking of the optical diffraction limit. For more than a century, half the wavelength of light – about 200 nanometres – was considered the absolute limit for light microscopes. When Stefan Hell was studying physics in Heidelberg, this limit was still taught – but Hell couldn’t accept it. By developing stimulated emission depletion (STED) microscopy the following years, he was the first researcher to successfully venture beyond this limit in the 1990s, both theoretically and experimentally. Based on these breakthroughs he received the 2014 Nobel Prize in Chemistry, together with the American physicists Eric Betzig and William E. Moerner, “for the development of super-resolved fluorescence microscopy”.

But how does STED work, and how does it lay the foundations for MINFLUX? Hell explains STED in his own words: “If I cannot resolve two points because they are too close together and they are both emitting fluorescence, I need to darken one of them – and suddenly, you’re able to see the other point. If I make sure that all molecules are dark, except the one or the few that I’m interested in, then I can finally resolve this one, or these few.” The darkening is achieved by optical interference: Since a laser beam is used to excite fluorescence in molecules, it’s also possible to darken some molecules in the probe with a second laser beam whose wave properties cancel out the first beam. This second laser beam is doughnut-shaped, leaving only a small centre spot still emitting fluorescence. Thus STED functions by depleting a circular region of the sample, while leaving a small focal point (see graph below).

 

How a STED microscope works: with a laser excitation focus (left), a doughnut-shaped de-excitation focus (centre) and remaining fluorescence (right). Credit: Marcel Lauterbach, CC BY-SA 3.0

How a STED microscope works: with a laser excitation focus (left), a doughnut-shaped de-excitation focus (centre) and remaining fluorescence (right). Credit: Marcel Lauterbach, CC BY-SA 3.0

With the MINFLUX microscope, Hell’s research group combined the advantages of STED microscopy with the principles of PALM (photo-activated localization microscopy) developed by Eric Betzig. In PALM, also called PALM/STORM, single molecules are also excited by switching them on and off, but these molecules light up randomly, they’re not targeted. Betzig and his colleagues would use a very short laser pulse, thus exciting only a few molecules which could then be localised. As these molecules bleach out, the researchers turn the laser on again to see the next batch and so forth. Finally, the entire probe has been activated, seen and plotted. The result is a graphic resolution far beyond the diffraction limit.

With this approach, PALM already operates on the single-molecule level but the exact location of each molecules isn’t easily determined. With STED, the location of an excited molecule is well known, but the laser beam isn’t able to confine its emission to a single molecule. MINFLUX, on the other hand, switches individual molecules randomly on and off. Simultaneously, their exact positions are determined with a doughnut-shaped laser beam, something we know from STED. But in contrast to STED, this doughnut beam excites the fluorescence instead of darkening it. So if a molecule is located on the ring, it will glow; if it is exactly at the dark centre, it will not glow – but its exact position will be known.

Dr. Francisco Balzarotti, a researcher in Hell’s department, developed an algorithm to locate this centre position fast and with high precision. “With this algorithm, it was possible to exploit the potential of the doughnut excitation beam,” the first lead author of the Science paper explains. Klaus Gwosch, a PhD student in Hell’s group and third lead author, obtained the molecular-resolution images: “It was an incredible feeling as we, for the first time, were able to distinguish details with MINFLUX on the scale of a few nanometres”, the young physicist describes the team’s reaction to the potential of studying life at the molecular level.

 

Stefan Hell gemeinsam mit den Erstautoren der Studie Dr. Francisco Balzarotti, Yvan Eilers und Klaus Gwosch am Mikroskop (von links). Foto: Irene Böttcher-Gajewski, Max-Planck-Institut für biophysikalische Chemie

Stefan Hell and the three lead authors of the MINFLUX Science publication, Dr. Francisco Balzarotti, Yvan Eilers and Klaus Gwosch (from left) with their ground-breaking microscope. Photo: Irene Böttcher-Gajewski, Max Planck Institute for Biophysical Chemistry

In addition to the high optical resolution, this new microscope has another advantage over both STED and PALM: high temporal resolution. Stefan Hell: “MINFLUX is much faster in comparison. Since it works with a doughnut laser beam, it requires much lower light signal, i.e. fewer fluorescence photons, per molecule as compared to PALM/STORM for attaining the ultimate resolution.” MINFLUX stands for “MINimal emission FLUXes”, alluding to this reduced light requirement. Already with STED, researchers had been able to record real-time videos from the inside of living cells. But now it is possible to trace the movement of molecules in a cell with a 100 times better temporal resolution.

Yvan Eilers, another PhD student involved and the second lead author of the Science paper, was responsible for ‘filming’ protein actitivity within a living cell. He filmed the movements of ribosome subunits inside a living E. coli bacterium. “The past has shown that major resolution enhancements have led to new insights into the biology of cells, as STED and PALM have demonstrated,” Eilers elaborates. “Now everybody here is optimistic that this will hold true for MINFLUX as well.” The researchers in Hell’s group are convinced that in the future, even extremely fast changes in living cells will be investigated with the help of their new microscope, for instance the folding of proteins.

I asked Klaus Gwosch whether other research groups had already been in touch to acquire a MINFLUX microscope. “The Science publication has of course reached a large international audience,” he replied. “Currently, the department of NanoBiophotonics in Göttingen has the only MINFLUX microscope, but we expect other research groups to adopt and implement our approach.” His boss Stefan Hell agrees: “I am convinced that MINFLUX microscopes have the potential to become one of the most fundamental tools of cell biology. This could revolutionise our knowledge of the molecular processes occurring in living cells.”

Both Yvan Eilers and Klaus Gwosch will participate in the 67th Lindau Nobel Laureate Meeting this summer as young scientists, together with their doctoral adviser Stefan Hell. William Moerner, the third recipient of the 2014 Nobel Prize in Chemistry, will also attend and talk about super-resolution microscopy. We are looking forward to an interesting and inspiring week in Lindau!

 

 

MINFLUX microscopy separates molecules optically that are only a few nanometers apart. On the left, a schematic graph of the fluorescent molecules. PALM microscopy (right) only delivers a diffuse image of the molecules, whereas the position of each molecules can easily be discerned with MINFLUX (centre). Image: Klaus Gwosch, Max Planck Institute for Biophysical Chemistry

MINFLUX microscopy optically separates molecules that are only a few nanometers apart. A schematic graph of the target molecules is shown on the left. PALM microscopy (right) only delivers a diffuse image of these molecules, whereas the position of each molecule can easily be discerned with MINFLUX (centre). Image: Klaus Gwosch, Max Planck Institute for Biophysical Chemistry

Membranproteinen ihre Geheimnisse entlocken

Vor ungefähr 2,3 Milliarden Jahren kam es „zum wohl größten Massensterben der Erdgeschichte“, so Hartmut Michel zu Beginn seines Vortrags auf der Lindauer Nobelpreisträgertagung 2015. Er beschreibt die sogenannte Große Sauerstoffkatastrophe (englisch GOE, für Great Oxygenation Event), die sich ereignete, als erstmals große Mengen an freiem Sauerstoff in die Atmosphäre gelangten – für die Mehrzahl der damals existierenden Organismen ein tödliches Gift. Doch wie kam es dazu? Die Vorfahren der heutigen Cyanobakterien entwickelten die Photosynthese: Mit Hilfe von Licht, Wasser und Kohlendioxid stellten sie Sauerstoff und Kohlenhydrate in bislang nie dagewesenen Mengen her.

Hartmut Michel erhielt den Chemienobelpreis 1988 „für die Ermittlung der dreidimensionalen Struktur eines Photosynthesezentrums“, zusammen mit Johann Deisenhofer und Robert Huber. Das Nobelpreiskomitee nannte die Photosynthese „die wichigste chemische Reaktion auf Erden“, weil sie Atemluft und Nahrung für Mensch und Tier bereitstellt. Zudem ist sie für die Entstehung der meisten fossilen Energiequellen wie Kohle, Öl und Gas verantwortlich, allerdings mit ein paar Millionen Jahren Verzögerung.

Vor Milliarden Jahren standen die Kleinstlebewesen vor der Herausforderung, mit den großen Sauerstoffmengen zurechtzukommen. Außerdem mussten sie mit den Molekülen der sogenannten reaktive Sauerstoffspezies umgehen können (englisch ROS, für reactive oxygen species). Ein sehr effizienter Weg, freien Sauerstoff unschädlich zu machen, sind Sauerstoff-Reduktasen, also spezielle Enzyme, die Sauerstoff zu Wasser reduzieren. Sie werden auch Oxidoreduktasen genannt. Gleichzeitig helfen sie, die Energie zu speichern, die bei solchen Reaktionen freigesetzt wird. Seit über zehn Jahren analysiert Hartmut Michel nun solche Reduktasen am Max-Planck-Institut für Biophysik in Frankfurt am Main, wo er seit 1987 Direktor ist.

 

Schematische Darstellung des Elektronentransport der inneren Mitochondrienmembran. Die Cytochrom-c-Oxidase ist Teil des Komplex IV. Grafik: T-Fork, auf der basis der Grafik von LadyofHats, beide public domain

Schematische Darstellung des Elektronentransports in der inneren Mitochondrienmembran. Die Cytochrom-c-Oxidase ist Teil von Komplex IV. Grafik: T-Fork, auf der basis der Grafik von LadyofHats, beide public domain

 

In den vergangenen Jahren analysierte Hartmut Michel zusammen mit seiner Forschungsgruppe vor allem zwei Sorten von Oxidoreduktasen: Die Superfamilie der Häm-Kupfer-Oxidasen und die Cytochrom-bd-Oxidase. All diese Oxidasen befinden sich in Membranen. Ein bekanntes Beispiel der Superfamilie ist die Cytochrom-c-Oxidase, das letzte Enzym im Elektronentransport der inneren Mitochondrienmembran (siehe Grafik oben). Diese Oxidase erhält jeweils ein Elektron von vier Cytochrom-c-Molekülen und transportiert diese zu Sauerstoffmolekülen. Aus diesen Zutaten werden zwei Wassermoleküle gebildet. Sie ist außerdem behilflich, zwei Protonen, die für die Bildung von ATP nötig sind, durch die Membran hindurch zu pumpen. „ATP ist die allgemeine Energiewährung des Lebens“, erklärt Michel in seinem Lindau-Vortrag von 2015. Wussten Sie, dass Ihr Körper täglich bis zu 75 kg ATP produziert, damit wir zum Atmen, Verdauen und Bewegen ausreichend Energie zur Verfügung haben? Außerdem müssen wir unsere Körpertemperatur halten, und es gibt viele weitere Prozesse im Körper, die viel Energie benötigen.

 

Hartmut Michel während seines Vortrags in Lindau beim 64. Nobelpreisträgertreffen 2014. Foto: Christian Flemming/Lindau Nobel Laureate Meeting

Hartmut Michel während seines Vortrags in Lindau bei der 64. Nobelpreisträgertagung 2014. Foto: Christian Flemming/Lindau Nobel Laureate Meetings

Interessanterweise waren Oxidoreduktasen wohl bereits vorhanden, bevor sich freier Sauerstoff massenhaft in der Atmosphäre anreicherte. Aber welche Funktion hatten sie damals? Dieses ‘Paradox’ hat die Forschung bislang nicht aufklären können. Ein weiteres interessantes Ergebnis von Michel ist, dass sich die beiden Oxidase-Gruppen zwar strukturell deutlich unterscheiden, aber doch etliche Gemeinsamkeiten aufweisen: Beispielsweise transportieren beide Systeme häufig vier Elektronen gleichzeitig – so wird die Bildung von ROS effektiv verhindert. „Es scheint, als habe Mutter Natur dieselbe Erfindung gleich zweimal gemacht“, folgert Michel in seinem Vortrag.

Das photosynthetische Reaktionszentrum, für dessen Beschreibung Michel, Deisenhofer und Huber den Nobelpreis erhielten, ist ebenfalls ein Membranprotein – das allererste, dessen Struktur bestimmt werden konnte. Als Hartmut Michel noch Student in Tübingen und Würzburg war, galt die Lehrmeinung, dass Membranproteine grundsätzlich nicht kristallisiert werden können. Damals wie heute ist die Röntgenstrukturanalyse die beste Methode, um die molekulare Struktur, und damit die Funktion von Proteinen, zu ermitteln. Ohne Kristallisation kann sie jedoch nicht angewendet werden. Für die Entwicklung und Verbesserung der Röntgenstrukturanalyse wurden in den letzten hundert Jahren übrigens etliche Nobelpreise verliehen.

Doch Hartmut Michel wollte sich nicht mit der herrschenden Lehrmeinung abfinden. Also machte er sich daran, das erste Membranprotein zu kristallisieren. Ein großes Problem hierbei war die Tatsache, dass es sich bei diesen Proteinen eigentlich um eine Mischung aus Lipiden und Proteinen handelt, was dazu führt, dass sie teilweise hydrophob sind, also wasserabweisend, und sie deshalb nicht in wässrigen Flüssigkeiten gelöst werden können. Also braucht man Lösungsmittel, und Michel machte sich auf die Suche nach passenden sogenannten Detergenzien. Viele von ihnen bilden jedoch Mizellen. Das sind Zusammenballungen von Seifenmolekülen, die ihre hydrophilen Enden nach außen und die hydrophoben nach innen ausrichten. Der Nachteil hierbei ist, dass die gelösten Proteine in den dichten Mizellen ‘versteckt’ werden können.

 

Die Struktur eines Proteins mit Hilfe der Röntgenstrukturanalyse zu ermitteln ist ein aufwändiges Verfahren: Zunächst einmal muss das Protein kristallisiert werden, das ist bei Membranproteinen besonders schwierig. Dann wird mit Röntgenstrahlen ein Beugungsbild erstellt (diffraction pattern). Mit fortgeschrittener Analysis wird aus diesem Bild eine Elektronendichtekarte ermittelt, schließlich kann auch eine Struktur des Moleküls errechnet werden. Grafik: Thomas Splettstoesser, www.scistyle.com, CC BY-SA 3.0

Die Röntgenstrukturanalyse ist ein aufwändiges Verfahren: Zunächst einmal muss das Protein kristallisiert werden. Das ist bei Membranproteinen besonders schwierig. Dann wird mit Röntgenstrahlen ein Beugungsbild erstellt (diffraction pattern). Mit fortgeschrittener Analysis wird aus diesem Bild eine Elektronendichtekarte ermittelt. Schließlich kann auch die Struktur des Moleküls errechnet werden. Grafik: Thomas Splettstoesser, www.scistyle.com, CC BY-SA 3.0

Endlich fand Michel ein passendes Lösungsmittel, Heptan-1,2,3-triol, das kleinere Molekül-Verklumpungen bildet, sodass die Proteine herausgelöst, kristallisiert und analysiert werden können. Als nächstes musste er sich für ein bestimmtes Membranprotein entscheiden. Nach mehreren Fehlversuchen entschied er sich für das Purpurbakterium Rhodopseudomonas viridis, wörtlich „eine rote, falsche Zelle, die grün ist“. Diese Bakterien sind Photosynthese-fähig, genau wie Pflanzen, und ihr Reaktionszentrum hierfür kann isoliert werden. Auf diese Weise gelang Michel 1981 die Kristallisation des ersten Membranproteins.

Doch mit der Kristallisation war es nicht getan: Die Röntgenstrukturanalyse erfordert eine anspruchsvolle höhere Mathematik, um aus dem Beugungsbild der Röntgenstrahlen an den Elektronen des Kristalls eine dreidimensionale Struktur zu errechnen (siehe Schaubild rechts). Der Beitrag von Deisenhofer und Huber an diesem Projekt waren diese mathematischen Methoden. Die drei Forscher publizierten ihre Ergebnisse 1985. Nur drei Jahre später erhielten sie dafür den Chemienobelpreis. In den frühen 1980er Jahren brauchte Hartmut Michel noch ungefähr vier Monate, um einen kompletten Datensatz mit vielen Röntgenbildern zu erstellen. Heute entsteht ein solcher Datensatz automatisch innerhalb von Sekunden.

Seit dieser ersten Entdeckung entschlüsselten Forscher die Strukturen von über 600 Membranproteinen. Ungefähr fünfzig davon sind menschliche Membranproteine – doch es gibt insgesamt mehrere tausend! Hier ist also noch eine Menge zu tun.
Warum ist es überhaupt so wichtig, die Struktur und Funktion von diesen Proteinen zu kennen? 80 Prozent aller Arzneimittel wirken auf Membranproteine, und über 50 Prozent von ihnen haben diese Proteine als Zielstruktur. Das hat einen Grund: Sie spielen bei vielen Infektionen eine Schlüsselrolle, sowohl bei Viren als auch bei Bakterien, und sie sind an vielen Krebserkrankungen beteiligt. Diese Tatsache fasst Michel in seinem 2016er Lindau-Vortrag folgendermaßen zusammen: „Die meisten Krankheiten entstehen entweder durch eine Fehlfunktion, oder durch eine Über- oder Unterstimulierung eines bestimmten Membranproteins.“

Hartmut Michel ist ein langjähriger Unterstützer der Lindauer Nobelpreisträgertagungen. Er nahm bisher an zwanzig Tagungen teil, Videos seiner Vorträge finden Sie hier. Und er ist Mitglied im Kuratorium der Lindauer Nobelpreisträgertagungen. Wir freuen uns sehr, ihn im Juni 2017 bei der 67. Tagung, die dem Fach Chemie gewidmet ist, begrüßen zu dürfen.

 

 

 

Roger Tsien: “All Colours of the Rainbow”

Roger Tsien was one of the most productive and creative contemporary chemists. He’d been awarded the 2008 Nobel Prize in Chemistry “for the discovery and development of the green fluorescent protein, GFP”, together with Martin Chalfie and Osamu Shimomura. GFPs enable researchers to watch live cells at work: If they’re interested in a certain protein that can be expressed by an organism, they can fuse the GFP gene with the protein-encoding gene. From now on, each protein molecule can be traced through all its stages with the help of blue to ultraviolet light via fluorescence.

The advantage over many other markers is the fact that GFP is non-toxic, and also the light to see its fluorescence is non-toxic. GFPs have been widely used in many species, from yeast to insects, fish and mammals, as well as in human cells. The original GFP molecule was discovered in the jellyfish Aequorea victoria. This is why Roger Tsien thanked the jellyfish in his banquet speech at the official Nobel Prize Banquet Dinner on December 10th, 2008: “So my final thanks are to both the jellyfish and corals: long may they have intact habitats in which to shine!” Some of the fluorescent dyes developed by his research group were also derived from corals, others from bacteria.

 

With the help of genetic engineering, the GFP gene can be fused to target genes that will glow in ultraviolet light - also generations later! Slide from Roger Tsien's LNLM lecture in 2010. Photo: Bastian Greshake, CC BY-SA 2.0

With the help of genetic engineering, one of this mouse’s genes was fused with the GFP gene so that it glows under ultraviolet light. Also generations later, this mouse’s offspring will shine! Slide from Roger Tsien’s Lindau lecture in 2010. Photo: Bastian Greshake, CC BY-SA 2.0

 

Already as a PhD student of physiology in Cambridge, UK, Roger Tsien had developed his first tracking dyes for calcium activity in living cells. He hadn’t told his PhD supervisor about his new research adventure because he was sure that he would only explain how important it was to finish one project before starting a new one. Some of these dyes are still used today, like BAPTA and Fura-2; the latter was developed when Tsien had already become an assistant professor at the Department of Physiology-Anatomy at Berkeley.

After his move to UCSD in San Diego in 1989, mostly for better lab equipment, the Tsien group found fluorescent indicators that “glow in all colours of the rainbow”, as the Nobel Prize committee wrote. Over the years, his research group has also developed fluorescent indicators for ions like magnesium, copper, iron, lead, cadmium, and many more.

From an early age, Roger Tsien had been fascinated with the chemistry of colours. “I’ve always been attracted to colours,” he told the San Diego Union-Tribune when he learned that he had ben awarded the Nobel Prize. “If I had been born colour-blind, I probably never would have gone into this.” And in his autobiography for the website Nobelprize.org he wrote how his first chemical experiments in the basement of his parent’s house in Livingston, New Jersey, reflect “an early and long-lasting obsession with pretty colours”. He captions this essay with the following joke: “What do elementary school pupils and Nobel Laureates have in common? They both have to write autobiographical essays on command.”

 

 

Roger Tsien’s father was an aviation engineer with a degree from MIT, but couldn’t find a suitable job because as a Chinese, he didn’t get the necessary security clearance. After several different jobs, he found work in the vaccum tube division of RCA, Radio Corporation of America, in New Jersey. When his parents wanted to buy a house in New Jersey, the developer wouldn’t sell it to them because they were Chinese, fearing that other families wouldn’t buy property next to them. His parents wrote to the New Jersey governor to complain, and the governor in turn wrote to the developer that racial discrimination was illegal. Not only could the Tsien family then buy the house – years later, the same developer used Roger’s photo as the winner of the nationwide Westinghouse Science Talent Search to advertise how good the Livingston schools were.

Only sixteen years old, much younger than most other contestants, Roger Tsien had written up his results from an NSF-sponsored summer programme at Ohio University that he had attended in the summer of 1967, his “first exposure to a research environment”. He was assigned a project where he had to analyse how metals bind to thiocyanate. “For lack of any alternatives, I wrote up my Ohio University project, trying my best to draw some conclusions from a mess of dubious data.” To his own surprise, Roger Tsien won the first prize.

 

San Diego beach scene drawn with an eight colour palette of bacterial colonies expressing fluorescent proteins derived from GFP and the red-fluorescent coral protein. Artwork by Nathan Shaner, photography by Paul Steinbach, created in the lab of Roger Tsien in 2006. Credit: Nathan Shaner, CC BY-SA 3.0

San Diego beach scene drawn with an eight colour palette of bacterial colonies expressing fluorescent proteins derived from GFP and red-fluorescent coral protein. Artwork by Nathan Shaner, photo by Paul Steinbach, created in the lab of Roger Tsien in 2006. Credit: Nathan Shaner, CC BY-SA 3.0

The same year, he started college at Harvard University with a scholarship, where he earned a Bachelor of Science in chemistry and physics, followed by a PhD in physiology from the University of Cambridge – and a productive career in the lab discovering and applying fluorescent dyes. Roger Tsien came to five Lindau Meetings, and the five lectures he gave demonstrate his wide interest in many scientific topics. In his 2015 lecture for instance (see above video), he explains his recent interest in two seemingly very different research areas: cancer therapy and long-term memory storage. But interestingly, both topics touch upon the same enzymes called proteases: enzymes that can cut proteins. Tsien himself explains his motivation for cancer research with the fact that his father died of pancreatic cancer. Together with medical doctor Quyen T. Nguyen he developed ‘fluorescence-guided surgery’ that helps the surgeon not only to find most cancer cells around a tumour, but also to preserve as many nerves and other important structures as possible.

The second topic of his 2015 lecture concerns memory storage in the perineuronal net, or PNN, an extracellular matrix structure that stabilises the adult brain. After a lifetime of studying intracellular activities, “here I’m forced to learn about extracellular matrix!” Tsien said in 2015. ‘Holes’ in the PNN act as the storage medium, “like a 3D punch card”, he explains, only to realise that today’s young scientists have never handled a punch card. In a mouse model, he was able to delete many long-term memories with the help of a certain matrix metalloproteinase, or MMP. He expects an even larger deletion share if more enzymes involved are understood. Sounds like the ‘neuralyzer’ from the Men in Black movies that can delete memories, doesn’t it?

On August 24th, 2016 Roger Tsien died unexpectedly on a bike trail in Eugene, Oregon, aged only 64. On this day, the world lost a brilliant scientist as well as a wonderful person with a great sense of humour.

 

Roger Tsien with young scientists on the annual boat trip to Mainau island on the last day of the 2009 Lindau Nobel Laureate Meeting, dedicated to chemistry. Photo: Christian Flemming

Roger Tsien (1952 – 2016) with young scientists on the annual boat trip to Mainau island on the last day of the 2009 Lindau Nobel Laureate Meeting, dedicated to chemistry. Photo: Christian Flemming/Lindau Nobel Laureate Meetings

Roger Tsien über Leuchtfarben, Quallen und Korallen

Roger Tsien gehörte zweifellos zu den kreativsten und produktivsten Forschern der Gegenwart. Er erhielt den Chemienobelpreis 2008 „für die Entdeckung und Entwicklung des grün fluoreszierenden Proteins GFP“, gemeinsam mit Martin Chalfie und Osamu Shimomura. Mit der Hilfe von GFP können Forscher lebene Zellen in Echtzeit bei ihrer ganz normalen Zellaktivität beobachten. Haben sie an einem bestimmten Protein Interesse, das ein Organismus herstellen kann, können sie das GFP-Gen mit jenem Gen verbinden, das genau dieses Protein herstellt. Ab diesem Moment kann der ganze Weg dieses Proteins verfolgt werden, weil es unter blauem oder ultravioletten Licht leuchtet, also fluoresziert.

Die Vorteile gegenüber anderern Markierungsmethoden liegt auf der Hand: GFP ist für den Organismus ungifitig, und auch das Licht, das man braucht um es zu sehen, ist unschädlich, anders als beispielsweise radioaktive Strahlung. GFPs und ähnliche fluoreszierende Marker sind schon in zahlreiche Organismen eingefügt worden, von Hefepilzen über Fische und Insekten bis hin zu Säugetieren und menschlichen Zellkulturen. Ursprünglich stammt das GFP-Gen von der Qualle Aeguorea victoria, daher bedankte sich Tsien in seiner Festrede beim offiziellen Nobelpreisbankett am 10. Dezember 2008 in Stockholm bei diesem Tier: „Meine letzte Danksagung gilt sowohl den Quallen als auch den Korallen: Möget ihr für lange Zeit intakte Habitate haben, in denen ihr ungestört leuchten könnt!“ Weitere Fluoreszensmarker stammen nämlich von Korallen, andere wiederum von speziellen Bakterien.

 

Ein Gen dieser Maus ist dem GFP-Gen markiert worden. Nun leuchtet sie grün unter ultrabviolettem Licht - und alle ihre Nachkommen! Die Abbildung stammt aus dem 2010er Vortrag von Roger Tsien in Lindau. Foto: Bastian Greshake, CC BY-SA 2.0

Ein Gen dieser Maus ist dem GFP-Gen markiert worden. Nun leuchtet sie grün unter ultrabviolettem Licht – und alle ihre Nachkommen! Die Abbildung stammt aus dem 2010er Vortrag von Roger Tsien in Lindau. Foto: Bastian Greshake, CC BY-SA 2.0

 

Bereits als Physiologie-Doktorand in Cambridge in Großbritannien entwickelte Roger Tsien seine ersten Farbstoffe, zunächst für die Kennzeichnung der Kalziumaktivität in Zellen. Sicherheitshalber hatte er seinem Doktorvater nichts von seinem neuen Steckenpferd erzählt, weil er befürchten musste, dieser würde ihm einen langen Vortrag darüber halten, wie wichtig es sei, zuerst das eine Projekt abzuschließen bevor man das nächste beginnt. Manche dieser Farbstoffe werden heute noch verwendet, zum Beispiel BAPTA und Fura-2; letzteren entwickelte Tsien als Assistenzprofessor in Berkeley.

Im Jahr 1989 wechselte er dann an die University of California in San Diego, in erster Linie wegen der deutlich besseren Laborausstattung dort. In den folgenden Jahren entwickelte seine Arbeitsgruppe zahlreiche Fluoreszenzfarbstoffe die “in allen Farben des Regenbogens leuchten”, so das Nobelpreiskomitee in Stockholm. Seine Forschungsgruppe fand außerdem Fluoreszenzindikatoren für zahlreiche Ionen wie Kupfer, Magnesium, Eisen, Blei, Kadmium und viele weitere.

Anlässlich der Nobelpreisverleihung 2008 erzählte er der Zeitung San Diego Union-Tribune, dass er schon als Kind von Farben fasziniert war. „Wäre ich farbenblind auf die Welt gekommen, hätte ich mir bestimmt ein anderes Thema gesucht.“ Schon als Schulkind führte er im Keller seiner Eltern in Livingston, New Jersey zahlreiche chemische Experimente durch, so schreibt er in seinem autobiografischen Essay für die Website Nobelprize.org, und auch damals motivierte ihn „eine frühe und langanhaltende Begeisterung für schöne Farben“. Am Anfang dieses Essays steht ein Witz: „Was haben Grundschüler und Nobelpreisträger gemeinsam? Beide müssen auf Knopfdruck autobiografische Aufsätze schreiben.“

 

Roger Tsien giving his 2014 lecture at the 64. Lindau Nobel Laureate Meeting. Photo: Rolf Schultes/Lindau Nobel Laureate Meetings

Roger Tsien giving his 2014 lecture at the 64. Lindau Nobel Laureate Meeting. Photo: Rolf Schultes/Lindau Nobel Laureate Meetings

Roger Tsiens Vater war ein Luftfahrtingenieur, der in den USA keine passende Anstellung finden konnte, trotz eines Abschluss von der amerikanischen Eliteuniversität MIT, weil er als Chinese keine Sicherheitsfreigabe bekam. Nach verschiedenen Jobs fand er schließlich eine Anstellung in der Abteilung für Vakuumröhren der Firma RCA, kurz für Radio Corporation of America, in New Jersey. Nun wollten die Eltern ein Haus in der Nähe kaufen, Roger war zu dieser Zeit sieben Jahre alt. Doch der Bauunternehmer wollte ihnen das Haus ihrer Wahl nicht verkaufen mit dem Argument, dann würden die anderen Häuser unverkäuflich, weil niemand neben Chinesen wohnen wollte. Daraufhin schrieb das Ehepaar Tsien einen Brief an den Gouverneur von New Jersey, der wiederum dem Bauunternehmer schriftlich mitteilte, dass Diskriminierung aufgrund der Herkunft in den USA illegal sei. So kam die Familie Tsien schließlich zu ihrem Haus.

Und nur neun Jahre später machte derselbe Bauunternehmer mit einem Foto von Roger Tsien Werbung für seine Häuser! Anlass war der erste Preis eines landesweiten Forschungswettbewerbs, den der sechzehnjährige Roger gewonnen hatte. Der Bauunternehmer wollte mit seinem Foto für die guten öffentlichen Schulen werben, dabei hatte sich Roger die anorganische Chemie anhand von Lehrbüchern überwiegend selbst beigebracht. Für den Westinghouse-Talentwettbewerb hatte er die Ergebnisse eines kleinen Projekts zusammengefasst, das er im Rahmen eines NSF-Nachwuchsprogramms an der Ohio University durchführen durfte. Er hatte dort die Aufgabe zu erforschen, wie sich verschiedene Metalle an Thiocyanate binden. „Weil ich nichts anderes vorzuweisen hatte, versuchte ich, aus dem Chaos unklarer Daten irgendwelche Schlüsse zu ziehen,“ schrieb er bescheiden im Nachhinein. Zu seiner großen Überraschung gewann er damit den ersten Preis.

 

Kunst aus der Petrischale: Mit verschiedenen fluoreszierenden Bakterien hat Nathan Shaner im Jahr 2006 im Labor von Roger Tsien in San Diego eine Strandszene in eine Petrischale 'gemalt'. Verwendet werden Farbstoffe, die auf dem GFP-Gen basieren, sowie Korallenfarbstoffe. Photo: Paul Steinbach, Credit: Nathan Shaner, CC BY-SA 3.0

Kunst aus der Petrischale: Mit verschiedenen fluoreszierenden Bakterien hat Nathan Shaner im Jahr 2006 im Labor von Roger Tsien eine Strandszene in eine Petrischale ‘gemalt’; das Labor befindet sich in San Diego, daher das Motiv. Verwendet wurden Farbstoffe, die auf dem GFP-Gen basieren, sowie Korallenfarbstoffe. Photo: Paul Steinbach, Credit: Nathan Shaner, CC BY-SA 3.0

Im selben Jahr, mit gerade mal 16 Jahren, begann Roger Tsien mit Hilfe eines Stipendiums in Harvard zu studieren. Mit einem Bachelor of Science in Chemie und Physik schloss er dieses Studium ab und ging nach England, um dort im Fach Physiologie zu promovieren. Er interessierte sich für die Schnittstelle zwischen Chemie und Biologie und wollte sich nicht auf ein Fach festlegen. Danach entfaltete sich seine unglaublich produktive Forscherkarriere. Roger Tsien nahm an fünf Lindauer Nobelpreisträgertreffen teil, und seine fünf Vorträge dort spiegeln sein breites Interesse an verschiedenen Forschungsthemen wider. In seinem 2015er Vortrag beispielsweise sprach er über zwei ganz unterschiedliche Themen: Krebsforschung und Langzeitgedächtnis. Auch wenn beide Themen scheinbar nichts mit einander zu tun haben, so handeln doch beide auf molekularer Ebene von Proteasen, also von Enzymen, die andere Proteine spalten können. Tsien selbst erklärt, dass seine Motivation, sich mit Krebsforschung zu beschäftigen durch den Krebstod seines Vaters ausgelöst wurde. Gemeinsam mit dem Arzt Quyen T. Nguyen entwickelte er eine fluoreszensgestützten Operationstechnik, bei der nicht nur alle Tumorzellen eingefärbt werden, damit der Chirurg sie möglichst vollständig entfernen kann, sondern auch alle wichtigen Strukturen wie Nerven, die nicht verletzt werden dürfen, gefärbt werden.

Das zweite Thema seines Vortrags war die Speicherung von Langzeiterinnerungen im sogenannten Perineuronalen Netz, kurz PNN, das als Matrix zwischen den Zellen für die Stabilität des erwachsenen menschlichen Gehirns sorgt. Nachdem Tsien sich sein ganzes Forscherleben hindurch mit Vorgängen innerhalb von Zellen befasst hat, „musste ich mich jetzt plötzlich mit der extrazellulärer Matrix beschäftigen“, ergänzte er in seinem Vortrag. Löcher in der PNN sind die eigentlichen Speichermedien, „wie in einer 3D Lochkarte“ – erst da wurde ihm klar, dass die meisten Nachwuchsforscher im Raum noch nie eine Lochkarte benutzt hatten. Im Mausmodell gelang ihm, ungefähr die Hälfte aller Langzeiterinnerungen durch die Gabe einer bestimmten Matrix-Metalloprotease (MMP) zu löschen. Er geht davon aus, dass ein deutlich größerer Anteil gelöscht werden kann, wenn die weiteren beteiligten Proteasen bekannt sind. Klingt ein bisschen nach dem ‘Neuralyzer’ aus dem Film Men in Black, oder?

Am 24. August 2016 starb Roger Tsien völlig unerwartet auf einem Radwanderweg in Eugene, Oregon im Alter von nur 64 Jahren. An diesem Tag verlor die Welt einen genialen Forscher sowie eine faszinierende Persönlichkeit mit einem großartigen Sinn für Humor.

 

Roger Tsien (1952 - 2016) während der traditionellen Bootsfahrt zur Insel Mainau am letzten Tag des Lindauer Nobelpreisträgertreffens 2009. Foto: Christian Flemming/Lindau Nobel Laureate Meetings

Roger Tsien (1952 – 2016) mit Nachwuchsforschern während der traditionellen Bootsfahrt zur Insel Mainau am letzten Tag des Lindauer Nobelpreisträgertreffens 2009. Foto: Christian Flemming/Lindau Nobel Laureate Meetings

Marie Curie’s American Adventure

Thanks to a lucky twist of fate, Marie Meloney, a prominent American journalist, took it into her head to persuade Nobel Laureate Marie Curie to do an interview with her and refused to be put off by Curie’s stubborn refusal. Meloney had started her career in journalism at the Washington Post at the age of just 15, worked as a correspondent for the Denver Post at 18 and was later the editor of various major magazines. She also hosted glamorous receptions, had political ambitions and was a feminist. Meloney was a confidante of Eleanor Roosevelt, who admired her for her determination.

Marie Curie in her chemistry laboratory at the Radium Institute in France, April 1921.

Marie Curie in her chemistry laboratory at the Radium Institute in France, April 1921. Source: Nationaal Archief of the Netherlands / No known copyright restrictions

When the long-desired meeting with Curie finally took place in 1920, despite her 20 years experience as a journalist, Meloney’s courage initially failed her: “The door opened and I saw a pale, timid little woman … with the saddest face I had ever looked upon. (…) Suddenly I felt like an intruder.”

Meloney perceived Curie as ‘helpless’ and took refuge in a discussion about the admiration of American women for her work. Without beating about the bush, Marie Curie got straight to the topic closest to her heart: radium. She knew the precise locations in America where a great deal of it was available. Meloney was completely astonished by the spartan working conditions of the two-time Nobel Laureate. Pierre and Marie Curie had registered no patents and had decided that their research findings should be available to all of humanity and not individuals. This meant that they were reliant on other sources of income.

During the interview Marie Meloney asked a question that went on to have far-reaching consequences: What would Marie Curie wish for, if she could wish for anything? The answer came without hesitation: a gram of radium! The reason for this was that the entire radium stocks of her French institute were used for medical applications, and Marie Curie was literally empty-handed.

Meloney devised a cunning plan: a gram of radium had a market value of 100,000 dollars in the USA – and she would raise the money for it. When an initial attempt to raise the money privately failed, Meloney launched the fundraising campaign later known as the “Marie Curie Radium Fund”, which was aimed at all American women who wanted to support Marie Curie’s work. And one year after the visit, the necessary funds had been raised.

Meloney-with-Irene-Marie-and-Eve_Curie-1921

Meloney, left, with Irène, Marie and Ève Curie. Credits: Public Domain

Meloney wrote to Curie and asked her to come to the USA and receive the gift in person. Warren Harding, the President of the United States of America, would present her with the radium himself. Her daughters could accompany her, and every attempt would be made to shield them from too much publicity. What the publicity-shy scientist feared most was to be paraded in public as an individual. Curie had single-mindedly avoided public appearances up to then; life for her was all about science and her family. But this was an offer she could not refuse, so at the age of 54 she embarked on her first major official trip abroad in spring 1921. A jubilant crowd and a horde of photographers awaited her on her arrival in New York.

The generous donors to the Radium Fund were women of very different origins and class – Curie was feted as a cancer healer, a role model for female scientists and a working mom. Marie Curie was an ideal representative of the type of woman with whom women in America identified in the 1920s. Her veneration in the academic world, which was also strongly masculine in its orientation in America, did not detract from this: Marie Curie was showered with honorary doctorates and other awards. Although Harvard – unlike Yale – denied her this honour, the majority of American academics could not understand why Marie Curie was not similarly honoured and supported in France.

The schedule for the visit proved to be a heavy burden on the scientist, whose state of health was already very frail, and her host and the press were concerned about her. Her modest appearance and cerebral air seemed to fuel the enthusiasm for her even more, however. The most important commitments, which Curie was unable to fulfil herself, were assumed by her daughters Irène and Ève.

The tour started with visits to women’s colleges and the crowds of enthusiastic female students who feted Curie, and an overwhelming reception in Carnegie Hall. Marie Curie entered the event to the thunderous applause of over 3,500 members of the International Federation of University Women. The French and Polish ambassadors were also in attendance. This was followed by a party at the Waldorf Astoria with over 500 representatives of scientific organisations – all before the presentation of the gift on 20 May 1921 at the White House.

Marie Curie with President Warren Harding at the White House in Washington DC. Credits: World History Archive / Alamy Stock Photo

Marie Curie with President Warren Harding at the White House in Washington DC. Credits: World History Archive / Alamy Stock Photo

Every trick in the publicity book was used for the presentation ceremony: Marie Curie entered on the arm of President Warren Harding and was presented with a parchment scroll (the deed of donation) and silk scarf tied with a small key – the key to the casket containing the radium; the latter was fake, however, as the radium remained in the factory so that it did not pose a threat to anyone present. In his address, President Warren Harding referred to Marie Curie as a “…noble creature, the devoted wife and loving mother who, aside from her crushing toil, had fulfilled all the duties of womanhood”. Curie thanked him for his kind words saying she had been honoured “… as no woman has ever been honoured in America before”.

Marie Curie’s trip to the USA was a great personal success and undoubtedly made an important contribution to providing security for her further scientific work, her institute and all the young researchers working there. It also gave her greater latitude in her private life. In her biography of her mother, Ève Curie wrote: “I believe the journey to America taught my mother something. It had shown her that the voluntary isolation in which she confined herself was paradoxical. (…) Marie was responsible for a new science and a new system of therapeutics. The prestige of her name was such that by a simple gesture, by the mere act of being present, she could assure the success of some project of general interest that was dear to her.”

Thanks to Marie Meloney, Marie Curie enjoyed greater fortune in the following years and the two women remained friends for life. In May 1922 Marie Curie became a member of the International Committee for Intellectual Cooperation and was its Vice-President until 1934. During her 12 years of activity for this League of Nations’ committee she supported, among other things, the establishment of an international bibliography of scientific publications and a copyright system for scientists and their inventions.

A video presenting an overview of Marie Curie’s life and scientific achievements is available in the Mediatheque.


Madame Curie. A Biography, Ève Curie

A Devotion to their Science. Pioneer Women in Radioactivity, Marelene and Geoffrey Rayner-Canham

Marie Curie. A Life, Susan Quinn

The private lives of Science’s first family. Marie Curie and her daughters, Shelley Emling

 

Nobel Laureate Oliver Smithies passed away

The Lindau Nobel Laureate Meetings mourn the death of Nobel Laureate in Physiology or Medicine Oliver Smithies. He died on Tuesday, 10 January at the age of 91. Smithies was awarded the Nobel Prize in 2007 alongside Mario Cappecchi and Martin Evans “for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells”. Oliver Smithies was a prolific inventor and devised the method of using potato starch as medium for electrophoresis gel. During his four participations in Lindau Meetings he was especially beloved by the young scientists. For them, his lectures have always been an incredible source of inspiration regardless of their scientific discipline.

To learn more about the life of Oliver Smithies, visit his profile in the mediatheque. A virtual tour through his lab and workshop is available as part of the Nobel Labs 360° series.

 

Oliver Smithies at his discussion session in Lindau 2010. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings

Oliver Smithies at his discussion session in Lindau 2010. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings

 

Smithies with his wife Prof. Nobuyo Maeda at the

Smithies with his wife Prof. Nobuyo Maeda at the “Discoveries” exhibition on Mainau Island in 2010. Photo: Ch Flemming/Lindau Nobel Laureate Meetings

 

Sharing advice and inspiration with young scientists. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings

Sharing advice and inspiration with young scientists. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings

 

A dedicated hobby aviator, Oliver Smithies always kept looking for new horizons. Photo: R. Schultes/Lindau Nobel Laureate Meetings

A dedicated hobby pilot, Oliver Smithies always kept looking for new horizons. Photo: R. Schultes/Lindau Nobel Laureate Meetings

 

 

Obituary for Roman Herzog (1934 – 2017)

Roman Herzog was the first German President to visit a Lindau Meeting in 1995. “Since then we have known him as a loyal and also scrutinising companion. He has encouraged us to further develop the meetings boldly and purposefully,“ said Countess Bettina Bernadotte, President of the Council for the Lindau Nobel Laureate Meetings, when she presentend the Lennart Bernadotte Medal to Roman Herzog in 2010. The award ceremony was held at Jagsthausen Castle near Heilbronn, where Herzog lived with his wife Alexandra Freifrau von Berlichingen.

 

Roman Herzog (left) 2001 in Lindau alongside former CEO and chairman of NOvartis AG Daniel Vasella. Photo: Peter Badge/Lindau Nobel Laureate Meetings

Roman Herzog (left) 2001 in Lindau alongside former CEO and chairman of Novartis AG Daniel Vasella. Photo: Peter Badge/Lindau Nobel Laureate Meetings

Herzog knew and appreciated the Lindau Nobel Laureate Meetings from his time as minister for education and cultural affairs of the German federal state of Baden-Württemberg in the late 1970s. He shared Count Lennart Bernadotte’s vision and lifetime achievement. Starting in 1999, after his presidency, Herzog increased his active support for the meetings that invite many Nobel Laureates and hundreds of young scientists to Lake Constance each year, to exchange knowledge, ideas, and experience, to hear inspiring lectures and take part in lively discussions. But in the late 1990s, the need to reform the meetings became obvious: they required a more solid financial footing, and they also needed to become more visible in Germany and abroad, plus they were supposed to develop into a European flagship project for science promotion.

“The establishment of the Lindau Foundation, inspired by Roman Herzog, was the crucial milestone to give the Lindau dialogue a sustainable and longterm perspective,” Countess Bernadotte continued. On the one hand, he developed ideas and plans to render the Lindau Meetings more future-proof. On the other, he introduced distinguished professionals to the Council that soon would play a crucial role in reinventing the Lindau Meetings, namely Wolfgang Schürer and Thomas Ellerbeck. In 1999, Ellerbeck headed the personal office of Roman Herzog. As a member of the Council since 2000, and subsequently of the Foundation’s Board of Directors, one of his tasks was to heighten the profile of the meetings and explain them to a broader public.

Professor Wolfang Schürer served the meetings as Chairman of the Foundation’s Board of Directors from 2000 to 2015. After the foundation was established late in the year 2000, Roman Herzog became its Honorary President, as well as a member of its Honorary Senate. “His unique way to approach topics and to apply himself has always impressed me profoundly, be it as our Federal President or in his support for the Lindau Meetings,” Countess Bettina remembers. “Encountering this brilliant, modest and witty man in person was always very inspiring.”

 

Roman Herzog (right) with Nobel Laureate Zhores Alferov in Lindau in 2001. Photo: Zhores Alferov

Roman Herzog (right) with Nobel Laureate Zhores Alferov in Lindau in 2001. Photo: Peter Badge/Lindau Nobel Laureate Meetings

 

When people talk or write about Roman Herzog today, they never fail to mention his legendary speech in 1997, in which he said that the Germans needed a ‘jolt’ to leave their comfort zone, and that they had to say goodbye to some aspects of their beloved status quo: “We need more flexibility! In the 21st century knowledge society, we need lifelong learning and new skills. And we have to get used to the idea that we may pursue two, three or even four different careers in our lifetime.” Nowadays this topic still seems important, but by now many people have become used to career changes. But almost twenty years ago, this speech was considered ‘disruptive’ and much debated – and it’s still being quoted. Already in the mid-1990s, Herzog emphasised the importance of an inter-cultural dialogue between Western and Islamic countries. Inter-cultural dialogue is also one of the hallmarks of the Lindau Meetings where young and experienced scientists from different nations, cultures and religions interact.

Roman Herzog cared deeply about science, technical and economic innovation, as well as about educating the young. As a former German Federal President, and also as a former President of Germany’s Federal Constitutional Court, he had numerous assignments and functions in Germany and abroad, and he supported the Lindau Nobel Laureate Meetings actively. “The Nobel Laureates, all members of the Lindau committees, and the Bernadotte family are very grateful to him,” says Countess Bettina Bernadotte.

Roman Herzog died on 10 January 2017. In this time of mourning, we extend our deep sympathy to his wife and family.

Exploring the Connections Between Sports and Science with Kurt Wüthrich

When reading the biography of Nobel Laureate Kurt Wüthrich, it quickly becomes clear that he embodies the concept of a Renaissance man. Not only did he excel in academic work, winning the 2002 Nobel Prize in Chemistry for his advancement of nuclear magnetic resonance spectroscopy, but Wüthrich was also an avid sportsman.

As a young man attending the University of Basel, he worked towards degrees in both chemistry and sports — the latter requiring about 25 hours per week of intense physical exercise, as well as courses in human anatomy and physiology. Even though he chose science in the end, sports continued to play an important role in Wüthrich’s life. He enjoyed skiing, fishing, and even played in a competitive soccer league well beyond the age of 50.

Kurt Wüthrich speaking at #LiNo16

Kurt Wüthrich speaking at #LiNo16. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings

Given his interdisciplinary background, it came as no surprise that much of his master class at the 66th Lindau Nobel Laureate Meeting focused on the science of sports. In fact, two young scientists who gave talks at the master class — Dominique Gisin and Bettina Heim — have been blessed with a similar combination of both mental and physical talents as Wüthrich himself.

Dominique Gisin, currently a Bachelor’s student in physics at ETH Zürich in Switzerland, spoke about the mechanics of alpine skiing and its impact on the human body. Gisin started her degree at the University of Basel but interrupted coursework to concentrate on skiing, making her Alpine Ski World Cup debut in 2005. Four years later, she got her first World Cup victory in women’s downhill skiing, and at the 2014 Sochi Winter Olympics, nabbed a gold medal in the same event.

To start off her talk, she played a series of video clips depicting the many crashes and falls she has suffered throughout her storied career, as the audience winced. In an average year, about 35% of all alpine athletes are injured — Gisin herself has gone through knee surgery a whopping nine times as a result of injuries.

In terms of physics, the variables that matter when it comes to modeling the dynamics of a downhill skier are numerous: the mass of the athlete, her velocity, the radius of a turn, snow temperature, air temperature, course condition, the mechanical characteristics of the equipment, visibility, and the mental/physical state of the athlete. These factors need to be considered when thinking about how to lower the rate of injury for the sport.

For instance, a tighter course setting would help reduce the athlete’s velocity, which could make crashes and falls less dangerous. But as Gisin notes, such a change would also cause skiers to move closer to the nets and potentially get tangled up in them. Another idea that might be interesting to pursue is uniform “anti-aerodynamic” racing suits that reduce athletes’ velocity and provide increased protection. Also, as seen in other sports, alpine skiing could benefit from the development of better protection equipment such as helmets and back protectors.

Kurt Wüthrich and Bettina Heim at the Rolex Science Breakfast

Kurt Wüthrich and Bettina Heim at the Rolex Science Breakfast. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings

Also representing ETH Zürich at the master class was Bettina Heim, a Master’s candidate in physics with a background in competitive figure skating. Her achievements in the sport include competing at two World Junior Championships, two World Championships, and becoming Swiss national champion in 2011. Only a short time after, Heim decided to hang up her skates and study physics full-time.

Her Bachelor’s studies culminated in a paper published by the prestigious journal Science in 2015, titled “Quantum versus classical annealing of Ising spin glasses.” It shows that evidence of quantum speed-up may depend on how the problem is described, as well as how the optimization routine is implemented. Today, Heim continues her research in the field of quantum computing, mostly in the realm of adiabatic quantum computing and quantum error correction, at ETH Zürich’s Institute of Theoretical Physics.

However, her focus during Wüthrich’s master class remained firmly in the world of sport and not quantum computers — in particular, she discussed the physics behind her specialty of figure skating. For instance, an athlete must gain a lot of speed going into a spin, and then one side of the body has to stop so the other can pass. This translates velocity into rotation, which results in the many types of spin moves performed by figure skaters.

As in downhill skiing, injuries remain prevalent in figure skating despite not being a contact sport. Common injuries for skaters include stress fractures, acute injuries involving tendons or ligaments, and back injuries. Heim noted that back injuries often originate from jump impacts (which can be hard on the spinal discs) and extreme positions that require flexibility (tough on muscles and ligaments).

As Wüthrich’s fascinating master class reiterated, the connections between sports and science go way beyond the physics of motion. Sometimes, an athlete and a scientist can be found within the same person.