Antibiotika und multiresistente Erreger: ein erbitterter Wettlauf

Antibiotika sind ein wesentlicher Bestandteil der modernen Medizin, und zwar nicht nur zur Behandlung hartnäckiger Hals- oder Ohrenentzündungen – sie spielen auch eine wichtige Rolle bei Routineoperationen wie Kaiserschnitten und Blinddarmoperationen, ebenso im Rahmen von Chemotherapien.

Wenn heute ein Antibiotikum verschrieben wird, ist es meist ein Präparat aus dem 20. Jahrhundert. Und da „Bakterien leben wollen, aber klüger sind als wir“, wie Nobelpreisträgerin Ada Yonath so treffend bemerkt, haben viele Krankeitserreger bereits Resistenzen gegen die häufigsten Antibiotika entwickelt. Im September wandte sich deshalb die Weltgesundheitsorganisation WHO mit einem eindringlichen Appell an Regierungen und Pharmahersteller, sie sollten dringend die Ausgaben für die Antiobitikaforschung erhöhen: Es gäbe einfach zu wenig neue Mittel, an denen zurzeit geforscht würde, um die wachsende Zahl multiresistenter Keime zu bekämpfen. Jedes Jahr sterben geschätzte 700 000 Patienten an den Folgen einer Infektion mit einem solchen Keim, und diese Zahl wird eher wachsen als schrumpfen.

Allein eine Viertelmillion Todesfälle gehen auf multiresistente Tuberkulose-Erreger zurück, weshalb diese Erreger den Experten besonders viele Sorgen bereiten. Wenn man einen solchen Erreger mit den verfügbaren Mitteln besiegen möchte, muss die Therapie konsequent über bis zu 20 Monate durchgehalten werden – in ärmeren Ländern oder auch in Haftanstalten wird die Behandlung aber häufig abgebrochen. Das Ergebnis sind neue Resistenzen (siehe Grafik am Ende des Artikels).

Kopfzerbrechen bereitet den Experten auch das mulitresistente Bakterium Neisseria gonorrhoea, das die Geschlechtskrankheit Gonorrhoe verursacht. Diese Bakterien sind gramnegativ, das bedeutet, dass ihre Oberflächen keine Gram-Färbung annehmen. Diese widerspenstige Oberfläche ist auch der Hauptgrund, weshalb solche Bakterien schwer zu behandeln sind, auch ohne Resistenzen. In den letzten Monaten gab es weltweit mehrere Gonorrhoe-Ausbrüche, für die resistente Keime verantwortlich sind.

 

Antibiotikaresistenz-Tests: Ein Bakterienstamm wird in ein Kulturmedium eingebracht. Die Bakterienkultur in der linken Schale ist gegenüber allen getesteten Antibiotika empfindlich, während die Kultur in der rechten Schale nur gegenüber drei der sieben getesteten Antibiotika empfindlich ist. Foto: Dr. Graham Beards, 2011, CC BY-SA 4.0

Antibiotikaresistenz-Tests: Ein Bakterienstamm wird in ein Kulturmedium eingebracht. Die Bakterienkultur in der linken Schale ist gegenüber allen getesteten Antibiotika empfindlich, während die Kultur auf der rechten Seite nur gegenüber drei der sieben getesteten Antibiotika empfindlich ist. Foto: Dr. Graham Beards, 2011, CC BY-SA 4.0

 

Solche Ausbrüche beleuchten ein weiteres Problem: Resistente Keime reisen schnell. Ganz egal, wo auf der Erde sich die Resistenzen entwickeln, durch moderne Verkehrsmittel wie Langstreckenflüge kann sich ein resistentes Bakterium innerhalb weniger Tage weltweit verbreiten. Die WHO hat eine aktuelle Liste mit 12 resistenten Bakterienstämmen erstellt, die als besonders gefährlich gelten. Diese Liste enthält nicht nur die Gonorrhoe-Erreger, sondern auch den gefürchteten Krankenhauskeim MRSA (die Abkürzung steht für Methicillin-resistenter Staphylococcus aureus).

 

Abhilfe durch bildgebende Verfahren?

Lösungsvorschläge werden möglicherweise von unerwarteter Seite kommen, zum Beispiel von Forschern, die mit Kryo-Elektronenmikroskopie arbeiten, kurz Kryo-EM. Der Chemienobelpreis 2017 würdigt diese Entwicklung. Mit Hilfe dieser Methode erhalten die Forscher eine derart hohe Auflösung des Zellgeschehens, dass sie sogar diejenigen Proteine beobachten können, die Resistenzen gegen Antiobitika weitergeben. Kryo-EM baut auf den Erfahrungen der Kristallstrukturanalyse auf, sowie auf der Methode der klassischen Elektronenmikroskopie.

Das Beobachten von Vorgängen ist in der Wissenschaft häufig der erste Schritt zu einem tiefgreifenden Verständnis, das erklärt die große Bedeutung von bildgebenden Verfahren für die Lebenswissenschaften. Wenn nämlich die Forscher Proteine ‘sehen’ können, die Resistenzen weitergeben, dann kann dies der Startpunkt für die Entwicklung von Medikamenten sein, die dieses Geschehen unterdrücken. Nun eignet sich die Kryo-EM besonders gut für Oberflächenproteine, sie stellt also genau jene Orte gut dar, an denen Infektionen oder Gentransfers ihren Anfang nehmen.

Gleichzeitig entwickelt sich auch die optische Mikroskopie immer weiter, mittlerweile kann man ‘live’ beobachten, wie Proteine in einer Zelle synthetisiert werden. Der Chemienobelpreis 2014 war ganz der Überwindung der Auflösungsgrenze in der Lichtmikroskopie gewidmet: Stefan Hell erhielt ihn für die Entwicklung seiner STED-Mikroskopie, der amerikanische Physiker Eric Betzig entwickelte die PALM-Methode, William E. Moerner war der dritte Preisträger 2014. Kurz nachdem er den Nobelpreis erhalten hatte, erfand Hell die MINFLUX-Mikroskopie, eine Kombination aus STED und PALM. Damit kann er nun erstmals kleine Filme erstellen, die zeigen, wie Proteine tatsächlich innerhalb von Zellen gebildet werden.
Alle diese Methoden zusammen führen zu einer „Auflösungs-Revolution“, die helfen wird, neue Antibiotika zu entwickeln.

 

Chemienobelpreisträgerin Ada Yonath bei einer Diskussionsveranstaltung mit Nachwuchsforschern auf der Lindauer Nobelpreisträgertagung 2016. Yonath erforscht seit Jahren die Ribosomen resistenter Bakterien. Foto: LNLM/Christian Flemming

Chemienobelpreisträgerin Ada Yonath bei einer Diskussionsveranstaltung mit Nachwuchsforschern auf der Lindauer Nobelpreisträgertagung 2016. Yonath erforscht seit Jahren die Ribosomen resistenter Bakterien. Foto: LNLM/Christian Flemming

 

Die Nobelpreisträgerin Ada Yonath, die den Chemienobelpreis 2009 für die Struktur des Ribosoms herhalten hatte, arbeitet bereits an neuartigen Antibiotika, und zwar an solchen, die nur gegen jeweils einen bestimmten Bakterienstamm wirken sollen, das nennt man ‘speziesspezifisch’. Ihr Ansatzpunkt sind die Ribosomen, also „die zellulären Maschinen, die Gene in Proteine umsetzen“, weil viele der bekannten Antibiotika die Aktivität der Ribosomen unterbinden. Zunächst studierte sie die Ribosomen ‘guter’, also harmloser Bakterien, inzwischen arbeitet sie mit MRSA-Keimen. Würde es gelingen, auf diesem Weg einen Wirkstoff zu finden, der alle Krankheitserreger abtötet, aber alle anderen Bakterien schont, wäre nicht nur die Behandlung wesentlich verträglicher – es würden auch deutlich weniger Resistenzen entstehen, unter anderem, weil deutlich weniger Bakterien überhaupt von einem solchen Wirkstoff betroffen wären.

 

Wirkstoff wird resistenter gegen Resistenzen

Eine weitere Strategie ist, an Orten nach neuen Wirkstoffklassen zu suchen, die in der Vergangenheit wenig aussichtsreich erschienen. Am Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie in Jena wurde beispielsweise ein Stoff isoliert, der sich im Labor bereits erfolgreich bei der Bekämpfung von MRSA erwies, weshalb Closthioamid 2014 zum Leibniz-Wirkstoff des Jahres gewählt wurde. Der Wirkstoff stammt von einem anaeroben Bakterium, nämlich Clostridium cellulolyticum. Diese Kategorie ist bei der Suche nach neuen Antibiotika bislang eher vernachlässigt worden. „Durch unsere Arbeit wird klar, dass das Potential einer riesigen Organismengruppe bislang völlig übersehen wurde“, so Christian Hertweck, stellvertretender Direktor des Leibniz-Instituts und Arbeitsgruppenleiter. Erst kürzlich konnten Forscher des Imperial College London, zusammen mit einem Team der ‘London School of Hygiene and Tropical Medicine’, mulitresistente Gonorrhoe-Bakterien mit Hilfe von Closthioamid abtöten. In der Petrischale reichten bereits kleine Mengen, klinische Studien sollen folgen.

In einer weiteren Strategie versucht man, existierende Antibiotika im Labor so zu verändern, dass sie ‘resistenter’ gegen Resistenzbildung werden. So brauchten Bakterien erstaunliche 60 Jahre, um gegen das Antibiotikum Vancomycin resistent zu werden. Nun haben Forscher am Scripps Research Institut (TSRI) eine verbesserte Variante dieses Wirkstoffs entwickelt, der nun Bakterien von drei Seiten gleichzeitig angreift. Das verbesserte Mittel wurde bereits erfolgreich an Enterokokken getestet, die gegen das klassische Vancomycin resistent waren. Studienleiter Dale Boger kommentiert, dass diese TSRI-Entwicklung das erste Antbiotikum sei, dass drei unabhängige Wirkmechanismen hätte, um Bakterien auszuschalten. „Dieses Merkmal wird dazu führen, die Lebensdauer des Wirkstoffs deutlich zu verlängern“, gemeint ist die Zeitspanne, in der das Mittel erfolgreich eingesetzt werden kann. „Mikroorganismen schaffen es einfach nicht, sich gleichzeitig an drei verschiedenen Fronten zu wehren. Selbst wenn sie es schnell schaffen, einen Wirkmechanismus auszuschalten, bleiben immer noch zwei übrig, die sie schließlich abtöten werden.“

 

Resistenzen ‘springen’ von einem Erreger zum anderen

Leider sind an diesem fulminanten Wettlauf nicht nur Forscher und Erreger beteiligt – eine solche Konstellation wäre noch halbwegs überschaubar. Doch die Tatsache, dass mulitresistente Keime heute sowohl unsere Umwelt als auch unsere Nahrung besiedeln, macht die Lage erst bedrohlich. Ein Beispiel hierfür ist das Antiobitikum Colistin: Bereits in den 1950er Jahren entwickelt, wurde es nie auf breiter Front gegen Infektionen beim Menschen eingesetzt, weil es zu starke Nebenwirkungen hat. Doch in den letzten Jahren ist es genau aus diesem Grund als Reserveantibiotikum interessant geworden. Da es sich aber um einen alten Wirkstoff handelt, ist der Patentschutz lange abgelaufen, die Produktion ist also preiswert – und deshalb wird es in China in großen Mengen in der Schweinemast eingesetzt.

Wie nicht anders zu erwarten, haben sich in diesen Schweinen Colistin-resistente Bakterienstämme entwickelt, deren Entdeckung erst 2015 publiziert wurde. Diese speziellen Resistenzen haben es in sich: Weil sich die Resistenz-Gene in einem Plasmid befinden, Bakterien jedoch sehr leicht Plasmide untereinander austauschen können, sind sie somit auch ein der Lage, praktisch mühelos Resistenzen auszutauschen, auch von einem Bakterienstamm zum nächsten. Bereits 2015 wurde das verantwortliche Gen namens mcr-1 in chinesischen Supermärkten entdeckt, ebenso in vereinzelten Patientenproben von dortigen Krankenhäusern. Nur 18 Monate später konnten in einem Viertel aller Krankenhauspatienten in bestimmten Regionen Chinas nun Bakterien mit diesem Resistenz-Gen nachgewiesen werden. Das Fazit lautet: Resistenzen breiten sich mittlerweile in einem beispiellosen Tempo aus.

Ein weiteres Beispiel für die Umweltverschmutzung sind große Mengen moderner Antiobitika und Antimykotika, also Anti-Pilzmittel, die in den Abwässern indischer Pharmahersteller gefunden wurden. In warmen Abwässern finden Bakterien ideale Lebensbedingungen – und wenn es dort Antibiotika gibt, werden sie sich anpassen und Resistenzen entwickeln. Schon heute haben Indienreisende bei ihrer Rückkehr häufig mulitresistente Keime im Gepäck, von denen sie meist nichts wissen, die ihnen jedoch bei einer späteren Erkrankung zum Verhängnis werden können – oder anderen Patienten.

Der erbitterte Kampf zwischen Bakterien auf der einen und Antibiotika auf der anderen Seite tobt jetzt seit 90 Jahren, seitdem Nobelpreisträger Alexander Fleming das Penicillin entdeckte. Dieser Kampf wird in Krankenhäusern, Forschungslaboren und Arztpraxen geführt. Die erwähnten Beispiele der Schweinemastbetriebe und der Abwässer von Pharmaherstellern stellen die Verantwortlichen jedoch vor völlig neue Herausforderungen, denen mit innovativen und vielseitigen Strategien begegnet werden muss. Erst vergangene Woche traf sich eine Arbeitsgruppe der Vereinten Nationen in Berlin, um diese Fragen zu erörtern. Denn eins ist klar: Die meisten von uns leben zwar nicht an indischen Abwasserkanälen, aber die Mirkoben von dort erreichen uns alle.

 

Schautafel der US-Gesundheitsbehörde CDC über die Entstehung von Resistenzen. Das Problem der verseuchten Abwässer ist hier nicht berücksichtigt. Copyright: Centers for Disease Control and Prevention, 2013 Public Domain

Schautafel der US-Gesundheitsbehörde CDC über die Entstehung von Resistenzen. Das Problem der verseuchten Abwässer ist hier allerdings nicht berücksichtigt. Copyright: Centers for Disease Control and Prevention, 2013 Public Domain

Resistant Bacteria vs. Antibiotics: A Fiercely Fought Battle

Antibiotics are an integral part of today’s medicine, not only to treat a strep throat or an ear infection – they also play a huge role in routine operations like appendecotomies or cecareans, and they are indispensable as co-treatment for many chemotherapies.

If you take an antibiotic today, it has most probably been developed and approved of in the last century. And since “bacteria want to live, and they are cleverer than us,” as Nobel laureate Ada Yonath describes them succinctly, many pathogens have become resistant to these common drugs. In September 2017, the World Health Organization (WHO) published an urgent appeal to increase funding for research into new antibiotics: not enough new drugs are in the ‘pipeline’ to combat the growing problem of multi-resistant strains. Currently, an estimated number of 700,000 patients die from infections with these strains every year – and this death toll might rise.

The WHO and other experts are especially concerned about multi-resistant tuberculosis that causes about 250,000 deaths per year, and less than half of all patients receive the necessary treatment that can take up to 20 months. The problem is that disrupted treatment inevitably leads to more resistances. Another very worrisome development is the emergence of multi-resistant Neisseria strains that cause the STD gonorrhoea. Neisseria gonorrhoeae are gram-negative bacteria, meaning that their surface is not coloured by gram staining. This resilient surface is also the reason why it is hard to treat gonorrhoea infections in the first place, even without resistances. Only this year, there have been several outbreaks of this multi-resistant variant around the world.

 

Antibiotic resistance tests: the bacteria in the culture on the left are sensitive to all seven antibiotics contained in the small white paper discs. The bacteria on the right are resistant to four of these seven antibiotics. Photo: Dr Graham Beards, 2011, CC BY-SA 4.0

Antibiotic resistance tests: the bacteria in the culture on the left are sensitive to all seven antibiotics contained in the small white paper discs. The bacteria on the right are resistant to four of these seven antibiotics. Photo: Dr Graham Beards, 2011, CC BY-SA 4.0

 

This brings us to another problem: resistant bugs travel fast. No matter where they develop, with modern travel they can spread around the world within days. The WHO also published a list with 12 pathogens that pose the greatest risks. This list includes Neisseria as well as the well-known and much-feared ‘hospital bug’ methicillin-resistant Staphylococcus aureus, or MRSA.

 

Imaging technologies help to develop new drugs

Relief from this dire situation might come from unexpected sources, like the technology honoured by the Nobel Prize in Chemistry 2017: cryo-electron microscopy, or cryo-EM. With the help of this new method, researchers can ‘see’ “proteins that confer resistance to chemotherapy and antibiotics”. This method was difficult to develop, and it leaned heavily on the experiences from X-ray crystallography and classic electron microscopy.

Often in research, being able to ‘see’ something is the first step of understanding its function, hence the strong interest in imaging technology in the life sciences: if a researcher can ‘see’ the workings of a resistance-inducing protein, he or she can start working on strategies to inhibit this process. Cryo-EM is especially good at depicting surface proteins, i.e., the location where infections or gene transfers usually start.

At the same time, optical microscopy is moving ahead as well, being able to ‘watch’ proteins being coded in living cells.  The Nobel Prize in Chemistry 2014 was dedicated to the breaking of the optical diffraction limit. Stefan Hell developed STED microscopy, American physicists Eric Betzig invented PALM microscopy, and both were awarded the Nobel Prize, together with William E. Moerner, “for the development of super-resolved fluorescence microscopy”. Shortly after receiving the most prestigious science award, Stefan Hell combined STED and PALM microscopy to develop the MINFLUX microscope: the very technology that can show proteins being coded. All these methods together will result in a “resolution revolution” that may contribute to the development of new classes of antibiotics.

 

Nobel laureate Ada Yonath during a discussion with young scientists at the 2016 Lindau Nobel Laureate Meeting. Photo: LNLMM/Christian Flemming

Nobel laureate Ada Yonath during a discussion with young scientists at the 2016 Lindau Nobel Laureate Meeting. Yonath has been studying bacterial ribosomes for many years. Photo: LNLM/Christian Flemming

Nobel Laureate Ada Yonath, who was awarded the 2009 Nobel Prize in Chemistry “for studies of the structure and function of the ribosome“ with X-ray crystallography, is currently researching species-specific antibiotics. Her starting point is that many antibiotics target bacteria’s’ ribosomes, “the universal cellular machines that translate the genetic code into proteins.” First, her team studied the inhibition of ribosome activity in eubacteria, i.e., ‘good’ bacteria. Next, she extended her studies to ribosomes from multi-resistant pathogens like MRSA. Her goal is to design species-specific drugs, meaning specific to a certain pathogen. These will minimise the harm done to the human microbiome by today’s antibiotics, resulting in a more efficient cure and a lower risk of antibiotic resistance, because fewer bacteria are affected.

 

Finding new drugs in unexpected places

Another attack strategy is to look for new antibiotic agents in places that never seemed very promising. For example, in 2010 the Leibniz Institute for Natural Product Research and Infection Biology in Jena (Germany) published a new antibiotic agent found in the soil bacterium Clostridium cellulolyticum. It belongs to the group of anearobic bacteria, a group that has long been neglected in the search for antibiotics. “Our research shows how the potential of a huge group of organisms has simply been overlooked in the past,” says Christian Hertweck, head of Biomolecular Chemistry. Just recently, scientists at the Imperial College London and the London School of Hygiene and Tropical Medicine have treated resistant Gonorrhoea bacteria with Closthioamide, the agent from Jena. They found that even small quantities were highly effective in the Petri dish; clinical trials will follow.

Yet another research strategy is to make antibiotics more ‘resistant’ to resistance formation. For instance, it has taken 60 years for bacteria to become resistant to vancomycin. Now, researchers at The Scripps Research Institute (TSRI) have successfully tested an improved version of vancomycin on vancomycin-resistant Enterococci that are on the WHO list of the most dangerous pathogenes. This improved drug attacks bacteria from three different sides. The study was led by Dale Boger, co-chair of TSRI’s department of chemistry, who said the discovery made the new version of vancomycin the first antibiotic to have three independent ‘mechanisms of action’ to kill bacteria. “This increases the durability of this antibiotic,” he said. “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”

 

Drug resistance can ‘jump’ between pathogens

Unfortunately, researchers and bacteria are not the only combatants, and this fiercly fought battle is not confined to clearly marked battlegrounds. Increasingly, multi-resistant bacteria can be found in our food, mostly due to the use of antibiotics in animal farming, and even in our natural environment. One such troubling example is Colistin, an antibiotic from the 1950s, which had never been widely used in humans due to toxic side-effects; however, in recent years it has been rediscovered as a last-resort antibiotic against multi-resistant bugs. Since it is an old drug, it’s also inexpensive and widely used – on pig farms in China.

As expected, Colistin-resistant bacteria developed in pigs, which was first discovered and published in 2015. But what makes this resistance perilous is the fact that the relevant gene is plasmid-mediated, meaning it can spread easily from one bacterium to another, possibly even from one species to another. In 2015, this resistance gene, called mcr-1, was also found in pork in Chinese supermarkets and in a few probes from hospital patients. Only 18 months later, 25 percent of hospital patients in certain areas in China tested positive for bacteria with this gene: resistances start spreading at unprecedented speeds.

Another highly disturbing example are large quantities of modern antibiotics and antimycotics found in the sewage from pharmaceutical production in India. In warm water, many bacteria find ideal conditions not only to live, but also to adapt to these novel antibiotics by quickly becoming resistant. Already travellers returning from some developing countries are considered a potential health threat, because many of them are unwitting carriers of multi-resistant pathogenes.

Since the discovery of Penicillin in 1928 by Nobel Laureate Alexander Fleming, the battle between bacteria and antibiotics is fierce and ongoing. This battle is fought in the laboratories, the hospitals and doctors’ offices all over the world, with some people seeming about as determined and creative as their opponents.

But resistance-breeding grounds like Chinese pig farms or sewage pipes from pharmaceutical companies present yet another battleground and call for a strategy that needs to be innovative as well as multifaceted. Only last week, a United Nations ad-hoc group met in Berlin to discuss these challenges. To sum it up: most of us do not live next to Indian sewer pipes, but the resistant bacteria bred there may reach us all.

 

Sign by the US Centers for Disease Control and Prevention CDC how antibiotic resistances occur - you use them and you lose them. But in this graph, large-scale pollution with resistant bacteria is not even included. Image: Centers for Disease Control and Prevention, 2013 Public Domain

Sign by the US Centers for Disease Control CDC how antibiotic resistance occurs: “you use it and you lose it”. Sewage pollution with resistant bacteria from pharmaceutical production is not included in this graph. Image: Centers for Disease Control and Prevention, 2013 Public Domain

#LiNo17 Daily Recap – Friday, 30 June

The 67th Lindau Nobel Laureate Meeting ended with the Baden-Württemberg Boat Trip to Mainau Island. It was a day full of science, discussions, joy, genuine delight and even some tears. Enjoy the highlights of the last day of #LiNo17.

 

Video of the day:

 

“I felt like I had the world in my hands.” – Young scientist Hlamulo Makelane

A definite highlight of the day were the heartfelt closing remarks made in the courtyard of Mainau Castle. You can watch the entire Farewell in our Mediatheque.

Hlamulo

Browse through our mediatheque to find all lectures, discussions and more educational videos from the Lindau Meetings.

 

Picture of the day:

Nobel Laureate Rudolph A. Marcus enjoying the Baden-Württemberg Boat Trip to Mainau Island whilst conversing with young scientists. 

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Boattrip to Mainau Island

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

For Nobel Laureate Jean-Pierre Sauvage, novelty, teamwork and adventure drove advances in synthesising molecular chains and knots. Read about his work and his advice for the young scientists.

Sauvage

Do take a look at more of our inspring blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

This is the last daily recap of the 67th Lindau Nobel Laureate Meeting. The idea behind it was to bring to you the day’s highlights in a blink of an eye. We hope you enjoyed the meeting and wish you all safe travels home.

#LiNo17 Daily Recap – Thursday, 29 June

Thursday was the last day in Lindau but not the last day of the meeting. Friday is going to take the participants to Mainau Island, so while they are enjoying their last day on the picturesque island, let’s take a look at what happened yesterday. Here are our highlights from Thursday:

 

Video of the day:

All six panelists – Nobel Laureates Sir John E. Walker and Dan Shechtman, Wiltrud Treffenfeldt (Chief Technology Officer of Dow Europe GmbH), May Shana’a (Head of Research & Developmen of Beiersdorf AG) and young scientist Thomas L. Gianetti from ETH Zurich as well as chairwoman Alaina G. Levine – have strong opinions on “Science Careers” and gave excellent advise for #LiNo17 participants.

You are welcome to browse through our mediatheque for more panel discussions, lectures and other informative videos.

 

Picture of the day:

Nobel Laureate Peter Agre’s lecture on “Aquaporin Water Channels” was not only educational, but also made the young scientists laugh. Most definitely one of the best pictures of Thursday.

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Audience in Peter Agre's lecture

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

When Nobel Laureates come to Lindau, photographer Volker Steger presents each with a surprise task. Find out what it is and how the laureates “sketch their science”.

Sketches of Science Slider

Do take a look at more of our inspring blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

We will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

 

Julie Fenton Loves a Challenge, Regardless of Scale

Interview with #LiNo17 young scientist Julie L. Fenton

This interview is part of a series of interviews of the “Women in Research” blog that features young female scientists participating in the 67th Lindau Nobel Laureate Meeting, to increase the visibility of women in research (more information for and about women in science by “Women in Research” on Facebook and Twitter). Enjoy the interview with Julie and get inspired.

 

Julie_1

Julie L. Fenton, 25, from the United States of America is a Graduate Student & PhD Candidate in Chemistry at the Pennsylvania State University, US. She is working in inorganic/materials chemistry. Nanomaterials have garnered intense interest in the scientific community, due in part to their unique shape-, size-, and composition-dependent properties, and emerging technological applications that leverage these properties require nanomaterials with very specific architectures and well-defined characteristics. Colloidal synthetic methods are among the most effective for delivering high-quality inorganic nanomaterials with desirable properties in high yield. However, the complexities of solution-based chemistry limit the ability to predict and rationally target desired products, rendering some materials and morphologies of interest inaccessible. Her work has focused on developing new synthetic and post-synthetic modification strategies in order to produce inorganic nanomaterials with precise control over product morphology, elemental composition, and crystal structure in a variety of material systems. These advances allow them to access metastable materials, morphologic features, and/or complex heterostructures with desired physical and chemical properties, many of which are not amenable to previous synthetic methods.

 

What inspired you to pursue a career in science/chemistry?

I have always had an interest in problem solving and puzzles – I love a challenge, regardless of scale. When I came up against my first chemistry class in high school, thinking about the world on a molecular level intrigued me, and I was hooked. To me, the chemical discipline represented solving some of the most complex and intriguing problems in the world, except that the answer was previously unknown. This was exciting to me as a young person, and the passion only deepened through higher-level study of chemistry through college, and now well into graduate school.

 

Who are your role models?

I have been fortunate enough to benefit from a number of fantastic mentors and role models, scientific and otherwise, throughout my life. My first (and best) role models have been my parents. Through a strong work ethic coupled with the highest value placed on integrity and respect for others, they have demonstrated to me what success in life looks like (which is not specifically linked to career success). Though my parents, who are not scientists, don’t always understand exactly what it is that I’m doing on a day-to-day basis, they are supportive at every step, encouraging me to be the best version of myself in scientific pursuits, but reminding me that the world is larger than just science, and that it’s important to stay grounded in my personal values.

Academically, I am grateful to have benefitted from and been inspired by too many people to name in this discussion, so I will name just two: my current graduate research advisor, Dr. Raymond Schaak, and my first research advisor as an undergraduate, Dr. Richard Schaeffer. These two have been phenomenally encouraging to me, helping me to develop and to think creatively as a scientist, while giving me the space to work independently on projects that I have cared about. Beyond that, they have modelled how one can balance the demands of a career in chemistry with other priorities in life. Conversations with these two have helped me to think broadly about the world and my place in it, going far beyond the expectations I could have asked for from an academic advisor.

 

How did you get to where you are in your career path?

I grew up in rural Lancaster County, Pennsylvania, USA and did my undergraduate work in chemistry at Messiah College, a small school (~2800 undergraduates only) in Grantham, Pennsylvania, USA. During my second semester as an undergraduate, I began to do research for the first time… I was enthralled by the challenge of research on the cutting edge of science. Research gave me an opportunity to think creatively about the world and the ways in which it works, and my advisor (Richard Schaeffer) gave me ample space to explore and problem-solve independently.

I anticipate working toward developing mentoring programmes to help foster students’ interest in STEM fields at an early age

Like many aspiring U.S. scientists, I participated in a National Science Foundation Research Experience for Undergraduates (NSF REU), between my third and fourth years of college. As a student coming from a small undergraduate institution, this was my first opportunity to do research full-time, working alongside graduate students and primarily research-active faculty members. As such, this experience was amongst the most formative of my young life as a chemist, igniting a passion for academic research and scientific problem solving on the highest level that will never be quenched. Unlike most undergraduate researchers, however, my REU was conducted at the Université de Strasbourg in Strasbourg, France, affording me the unique opportunity to live and to conduct research outside of the United States, where I have lived, worked, and learned for my entire life. Even though significant language and cultural barriers existed between the French research group and myself, we forged relationships and collaborations through the common language of chemistry. This is where I first understood and appreciated the international impact that work in science can have: increasingly, we are participating in an endeavour that transcends our national and cultural boundaries, aided by the ease of communication and collaboration. It was (and still is) incredibly exciting to me to contribute, in some small way, to something much greater than myself.

These experiences propelled me into graduate school, beginning in the summer of 2014, where I have been ever since, and will continue to motivate me as I move into the next stages of my career. I’m currently working towards my Ph.D. in materials/inorganic chemistry at the Pennsylvania State University in University Park, Pennsylvania, USA under the direction of Ray Schaak.

 

What is the coolest project you have worked on and why?

I’m probably totally biased, but the coolest work that I have worked on is my current dissertation work. Although it’s really important to be able to control the way that atoms arrange themselves in solid-state materials (because the atomic arrangement, or crystal structure, dictates the properties), the typical high-temperature synthetic methods for making solid-state materials are often limited to obtaining only the most stable arrangements of atoms in a solid. By using a lower-temperature, solution-based cation exchange method, we can transform a performed material template into a material with targeted composition. Interestingly, these transformations can be accomplished with the retention of some qualities of the template material, including features of the original crystal structure, circumventing some of the primary difficulties encountered in traditional solid-state chemistry. Using this approach, we have been able to target and isolate some unusual crystal structures in a predictable fashion, which begins to point towards the ability to generalise these approaches for polymorphic structure targeting in solid-state chemistry.

I think the most exciting thing about chemistry (and science in general) is that the great breakthroughs can be serendipitous and unexpected

What’s a time you felt immense pride in yourself/your work?

In different ways, I have found pride in sharing my work with others. Outside of my lab or the community of solid-state chemists, there is something really exciting about communicating the major points of my science to non-technical audiences in a way that appeals to them (without oversimplifying the science behind it), in formal presentations and informal conversations. Additionally, I have found great satisfaction and pride in seeing some of my efforts come to fruition in published form. Getting to a paper is a grind – it represents many hours in lab and many, many failed experiments, significant data analysis and interpretation, as well as the actual time spent writing the manuscript and putting together figures and data in a way that communicates the significance more broadly. It is exhilarating to contribute to the scientific community, even in very small ways.

 

Julie_2

What is a “day in the life” of Julie like?

I’m a synthetic chemist, so the majority of my work-life time is spent in the hood or nearby in the lab, weighing powders, pipetting solvents, heating/degassing a reaction, injecting precursors or decomposition agents, or cleaning and working up reactions. I spend “down” time reading papers, chatting science with my lab mates or advisor, or getting other work done (at the beginning of my graduate career, this was class assignments or grading for my teaching assignments… lately, it’s writing!). If I’m not in the synthesis lab, you could probably find me in the Penn State Materials Characterization Lab using one of the transmission electron microscopes (TEM) to take a look at the morphology of my nanoparticle samples, to analyse their crystal structures (using selected-area electron diffraction or high-resolution TEM), or to assess their elemental composition using STEM-EDS (energy dispersive spectroscopy) mapping.

 

What are you seeking to accomplish in your career?

To merge my passion for chemistry and my desire to engage others in STEM, I plan to pursue an academic research career after completing my graduate work. As a young person, I had few female academic role models; as a professional, I anticipate working toward developing mentoring programmes to help foster students’ interest in STEM fields at an early age. I look forward to leveraging my career to help bridge the gap between technical and non-technical audiences and to increase scientific literacy at all levels of academia, politics and normal life. Thus far, I have observed and begun to appreciate the unique set of opportunities available to academic scientists: engagement with top-calibre colleagues, students and mentors, involvement with a built-in community of equally passionate researchers, opportunity to converse and collaborate across disciplines and institutions, and utilisation of cutting-edge instrumentation and laboratories. Leading scientists in top academic institutions enjoy the ideal setting for making discoveries, establishing meaningful collaborations and mentoring future generations of scientists. For an ambitious and creative scientist, academic research positions provide the latitude and flexibility to innovate, the environment to pursue individual research interests (sometimes several different ones), and the opportunity to truly impact the scientific world and the world at large.

 

What do you like to do when you’re not doing research?

I enjoy traveling to new places (or familiar ones), outdoor activities, reading, board games, and spending time with family and friends. I also make some attempts to cook, though I have found that synthetic skills in chemistry do not directly translate to cooking skills (although it feels like they should).

 

What advice do you have for other women interested in science/chemistry?

Although we live in a world of instant gratification and quick answers, progress in science is often quite slow. It requires a significant investment of time, energy and thought, and even with this discipline, projects stalling or hypotheses failing is inevitable in these disciplines. This can be discouraging to anyone, but particularly to young scientists. Eventually, progress is made: an interesting discovery, fresh eyes to interpret formerly frustrating results, or new ideas and hypotheses that can be tested and proven true, but this takes time. My advice is to keep pushing towards the goal of understanding, and to stay positive — try not to let temporary frustrations get in the way of that. I would encourage young women in particular to not be intimidated by male-dominated academic science. If you want it and are willing to work hard, you are capable of achieving every success in science.

 

In your opinion, what will be the next great breakthrough in science/chemistry?

I think the most exciting thing about chemistry (and science in general) is that the great breakthroughs can be serendipitous and unexpected – although we would like to know exactly where they will come from, we don’t and we shouldn’t expect to. As a materials chemist, however, I think some of the scientific discoveries with the potential for the greatest impact on society will come from the development of new materials. I expect that the next decade and beyond will give us numerous breakthroughs in materials for a wide variety of applications, particularly those important for solar energy harvesting, fuel cells, batteries, other electronics and beyond (perhaps for applications we haven’t even thought of yet).

We should continue to reach out to and encourage aspiring scientists as children and teens, and at the undergraduate level

What should be done to increase the number of female scientists and female professors?

This is a difficult question, and one that I think (rightly) is starting to be addressed at every level of academic training and careers. I think that we, as a community, are taking steps in the right direction towards an academy that looks more representative of broader society (including more women and other under-represented groups). While progress is good, this process will take time! 30, 40 and 50 years ago, the pool of trainees looked much different than it does today, which is still reflected in the way the academy (or even in high levels of scientific industry) looks today. I think it’s important not to do this artificially at the highest levels of science, but to build up to that slowly, over a period of time. We should continue to reach out to and encourage aspiring scientists as children and teens, and at the undergraduate level, and help to change the perception of what a scientist looks like and does. At the graduate level, mentorship is extremely important, as learning from the mistakes and triumphs of others who have gone before you is valuable for making informed decisions about your career (and basically everything else).

#LiNo17 Daily Recap – Wednesday, 28 June

With Wednesday ending, we are striding towards the last two days of the 67th Lindau Nobel Laureate Meeting – but that does most certainly not mean that the next days are getting less exciting than the previous ones. Talking about exciting days, let’s take a look at the highlights of yesterday.

 

Video of the day:

Yesterday, Nobel Laureates Stefan Hell and Richard R. Schrock discussed “Current and Future Game Changers in Chemistry” with Jörg Huslage from the Corporate Research & Development Department of Volkswagen Group and Siddulu Talapaneni, an Indian Young Scientist from the University of South Australia at the Panel Discussion moderated by Geoffrey Carr, Science Editor from The Economist.

Obviously, this is not the only video from the last days and today! You are more than welcome to browse through our mediatheque for more.

 

Picture of the day:

Nobel Laureate Ferid Murad enjoying his coffee break while talking to some of the young scientists.

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Ferid Murad in talk with young researchers

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

Focus on Africa: Advancing Science to Advance Humankind – Alaina G. Levine talks with a rising star of Kenyan science, Titus Masese, on the present, presence, and presents of African Science across the globe.

Focus on Africa Slider

Do take a look at more of our inspring blog posts.

 

Tweets of the day:

 

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

Over the course of the next three days, we will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

Chemists Respond to Climate Change with Sustainable Fuel and Chemical Production

Climate change is a common lecture topic at the Lindau Nobel Laureate Meetings. At the opening of the 67th Lindau Meeting, William E. Moerner presented the keynote speech prepared by Steven Chu, 1997 Nobel Laureate in physics and former U.S. Secretary of Energy. In his speech, Chu described how clean energy technologies provide an insurance policy against the societal risks of climate change.

At previous meetings, Nobel Laureates Mario Molina, Paul J. Crutzen, and F. Sherwood Rowland have detailed how greenhouse gases produced by burning fossil fuels alter atmospheric chemistry and warms the planet. Reducing greenhouse gases, particularly carbon dioxide emissions, is key to stopping the planet’s warming temperature. But instead of viewing carbon dioxide as a problem, what happens if it is also part of a solution to climate change?

 

Science Breakfast Austria during the 67th Lindau Nobel Laureate Meeting, Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meeting

Science Breakfast Austria during the 67th Lindau Nobel Laureate Meeting, Credit: Julia Nimke/Lindau Nobel Laureate Meeting

 

Research discussed by Nobel Laureates and young scientists at the 67th Lindau Meeting included ways to use carbon dioxide as a renewable source of synthetic fuel and useful chemicals. Currently, fuels and chemicals come from refined and processed oil and natural gas. Producing these compounds from carbon dioxide captured from the atmosphere or factory emissions could be environmentally sustainable because carbon dioxide released during production or consumption is recycled to make new fuel or material. Sustainable and renewable feedstocks are one aspect of green chemistry, a key topic at this year’s meeting.

During a science breakfast hosted by the Austrian Federal Ministry of Science, Research, and Economy on Tuesday morning, Bernard L. Feringa, 2016 Nobel Laureate in Chemistry, outlined three challenges for carbon capture and utilisation: separating carbon dioxide from other gases, efficiently concentrating it, and catalytically converting the inert molecule to useful fuel and chemicals.

In addition to his Nobel-winning work on molecular machines, Feringa also studies catalysis. While working at Shell in the early 1980s, he developed lithium catalysts to reduce carbon dioxide. The project ended after a couple of years, however, when the researchers realised they would need all the lithium in the world just to make a reasonable amount of fuel.

 

and Melissae Fellet during a Poster Session at the 67th Lindau Nobel Laureate Meeting, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

Biswajit Mondal and Melissae Fellet during the Poster Session at the 67th Lindau Meeting, Credit: Christian Flemming/Lindau Nobel Laureate Meetings

Since then, researchers around the world have developed various electrochemical and photothermal catalysts that reduce carbon dioxide into compounds such as carbon monoxide, formic acid, ethylene and methane. Several young scienists attending the meeting are studying these catalysts, and two presented their work during the poster session.

Biswajit Mondal, at the Indian Association for the Cultivation of Science, studies the mechanism of iron-porphyrin electrocatalysts for carbon dioxide reduction. With an understanding of the precise molecular changes during every step of the reduction reaction, researchers can then tailor the catalyst structure to enhance the reaction efficiency.

Dayne F. Swearer, at Rice University, combines two reactive functions in one aluminum nanoparticle to unlock new catalytic mechanisms for known reactions. In his nanoparticles, the aluminium core absorbs light and generates an energy carrier called a plasmon, which can alter and enhance the activity of a metal catalyst on the outside of the nanoparticle. For example, a particle with a shell of copper oxide its aluminium core reduces carbon dioxide to carbon monoxide faster and more efficiently than particles made of either material alone.

Back at the science breakfast, Feringa encouraged young scientists to investigate photoredox catalysts that reduce carbon dioxide using absorbed light energy. These catalysts can create a variety of reactive intermediates, including radical anions and cations, which could be used to add carbon dioxide to hydrocarbons. Such reactions provide renewable ways to make building blocks for plastics and other common polymers.

 

Young scientist Anna Eibel during the Science Breakfast, Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Young scientist Anna Eibel during the Science Breakfast, Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Renewable routes to acrylic acid, the building block of acrylate polymers common in dental work, are interesting to Anna Eibel, a young scientist at the Graz University of Technology in Austria and a speaker at the science breakfast. She develops new molecules to induce acrylate polymerisation with light at longer wavelengths than the ultraviolet used now.

To really address carbon dioxide emissions, however, renewable routes to synthetic fuels such as methane and methanol are needed. In 1998, George Olah, the 1994 Nobel Laureate in Chemistry, talked about synthetic methanol production from carbon dioxide at the 48th Lindau Meeting, and the topic reappeared at the science breakfast this year.

Chemists are in a unique position to advance renewable fuels and chemicals, Feringa said. The main research questions in this area involve problems of catalysis, electrochemistry, photochemistry, material synthesis and chemical conversions. Feringa encouraged the young scientists to take opportunities to tackle these questions. “Of course you may contribute only a small step, but of course we have to do it. It is our duty to society […] to open opportunities for the future.”

#LiNo17 Daily Recap – Tuesday, 27 June 2017

We are already three days into this year’s chemistry meeting and there are so many interesting things happening. We have collected a huge amount of exhilarating pictures, exceptional lectures and thought-provoking blog contributions. So you can guess that there is so much more that you should definitly check out on our mediatheque than we present to you in our daily recap . Enjoy the following highlights!

 

Video of the day:

“This meeting is about mentorship, and it’s about the future, it’s not about the Nobel Laureates, it is [in fact] about mentoring the next generation of scientists – OUR BEST HOPE FOR THE FUTURE” – Brian Malow has provided us with a live video featuring seven young scientists.

 

 

Picture of the day:

After having the Poster Flashes on Monday, our Poster Session proved to be a success. Frank Biedermann, a young scientist explaining his research about “Supramolecular Sensing Ensembles” to Nobel Laureate Erwin Neher.

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Poster Session

 

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

“When scientific issues become publicly controversial, Nobel Laureates have a history of making strong statements at the Lindau Nobel Laureate Meetings,” writes Melissae Fellet in her new article on science in a post-truth era. Politics and the question of what scientists can do to rebuild trust is one of the main topics being discussed by the participants of the 67th Lindau Meeting.

Post-truth_Slider

Press Talk on ‘Science in a Post-Truth Era’ hosted by Deutsche Welle during the 67th Lindau Meeting. Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Do take a look at more of our exciting blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

 

Over the course of the next four days, we will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

#LiNo17 Daily Recap – Sunday, 25 June 2017

“I close my remarks by asking the young students gather this week at the Lindau Nobel Laureate Meeting to consider joining the effort to combat climate change.” – Steven Chu

Yesterday, the 67th Lindau Nobel Laureate Meeting started in grand fashion with the festive opening ceremony featuring the warm and heartfelt welcome address by Countess Bettina Bernadotte and a very poignant and moving keynote by Steven Chu. The Nobel Laureate himself was, unfortunately, unable to attend, but his fellow laureate William E. Moerner luckily stepped in to deliver the powerful speech on “Science as an Insurance Policy to the Risks of Climate Change”.

 

Video of the day:

“A changing climate does not respect national boundaries.”
First highlight is Steven Chu’s keynote, read by William Moerner. Chu addressed the highly topical issue of climate change and reminded all of us how important it is to treat the earth well.

Obviously, this is not the only video from yesterday and today! You are more than welcome to browse through our mediatheque for more.

 

Picture of the day:

Standing Ovations
William Moerner’s presentation of Steven Chu’s keynote was one of the most moving moments.

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, Germany

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, Germany

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog post of the day:

“A Stellar Meeting Where the Stars Shine Bright, the Science Is Chill, and the Networking Is Chem-Tastic.”
Another highlight is the blog post from science writer Alaina G. Levine. She is back in Lindau for #LiNo17 and gives a preview of the panel discussion on science careers that she will chair on Thursday (replacing Karan Khemka).

Do take a look at more exciting blog posts.

 

Tweets of the day:

 

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

 

Over the course of the next six days, we will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

Ben Feringa: Molecular Machines of the Future

Ben Feringa giving the first lecture at the 67th Lindau Nobel Laureate Meeting. Photo/Credit: Jula Nimke/Lindau Nobel Laureate Meetings

Nobel Laureate Ben Feringa giving the first lecture at the 67th Lindau Nobel Laureate Meeting. Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

The Nobel Laureate gave the #LiNo17 opening lecture with the title ‘The Joy of Discovery’. Ben Feringa grew up on a farm near Groningen, the second of ten siblings. Today, he is professor in Groningen and also received his MSc and PhD degrees there. And just as much as he enjoyed nature as a child, he now enjoys the inifinite possibilities of molecules. In his own words: “We enjoy the adventure into the unkown.” Before starting his lecture, he has some advice in store for the young scientists at the Lindau Nobel Laureate Meeting: Always look for a challenge, and find teachers who challenge you, persevere, follow your intuition and your dreams – but ‘walk on two feet’, meaning remain realistic, and find a balance between life and research. Looking at his impressive career, and appreciating his obvious delight in his work, it seems that Feringa took his own advice to heart.

It’s truly mind-blowing to see what Ben Feringa and his research group are capable of: they synthesise molecules from inanimate matter that can move autonomously. One striking example are the small ‘spiders’ that you can see crawling around under a microscope. These ‘spiders’ can self-assemble, meaning that several molecules form clusters, and these clusters move completely autonomously as long as ‘fuel’ is provided, in their case sugar. (You can watch the crawling ‘spiders’ in a solution, also called nano-swimmers, on the website of Feringa’s research group, or at the end of his #LiNo17 lecture). Other molecules at Feringa’s Molecular Nanoscience group at the University of Groningen have been fitted with light-sensitive switches, so light of a certain wavelength turns them on and off and also acts as their ‘fuel’.

As Feringa points out himself in his lecture: chemists are great at creating molecules, but it’s extremely difficult to control their dynamic functions – movement, rotation, switches, responses, etc. His most noted invention is his version of the ‘nanocar’ – it was also strongly featured in the 2016 Nobel Prize media coverage. For a nanocar’s engine, you need unidirectional rotation. Feringa and his research group discovered the first man-made molecular rotor that could perform a 360 degree rotation ‘a bit by accident’ in the 1990s. They had been working on an alkene molecule (alkenes are unsaturated hydrocarbons containing at least one carbon-carbon double bond). This specific alkene could perform a quarter turn in a process called isomerisation: a process in which one molecule is transformed into another with exactly the same atoms, only these atoms are now arranged differently. Suddenly the researchers realised that the molecule had in fact performed a 180 degree turn and hadn’t switched back. Then they wondered: “Maybe we can get it to perform a 360 degree turn.”

 

How the molecular rotor works: double-bond isomerisation and thermal helix inversion (heat) alternate. Image: Ben Feringa group. Source: The Swedish Academy of Sciences

How the molecular rotor works: double-bond isomerisation and thermal helix inversion (heat) alternate. Image: Ben Feringa group. Source: The Royal Swedish Academy of Sciences

 

Finally, the researchers managed a full rotation with two double-bond isomerisations and two helix inversions induced by heat (see graph above). On the one hand, ‘unidirectional rotation marks the most fundamental breakthrough‘ in the search for molecular motors; on the other hand, the molecule was still too slow – it needed about one hour for the 360 degree turn. Now the researchers set out to build much faster molecules. About sixty different motor designs later, they reached an astounding speed of 10 million rotations per second. But in reality there are some restrictions: for instance, you often cannot get enough energy into these nanosystems to perform at top speed, and the surfaces on which the motors are supposed to perform limit their speed. So realistically, these tiny motors now rotate at about 4000 cycles per second. Next, the researchers fitted four of the enhanced molecules on to axles and added a stator: a molecular four-wheel drive was put on the ‘road’, usually a metal surface.

Today, several research groups around the world build nanocars. And although Feringa’s team received much recognition for their own nanocar, they’re exploring many other possible applications of molecular machines, for instance in medicine: imagine smart drugs that can be ‘switched on’ only at their target area, for instance a tumour. These would be high-precision drugs with very few or even no side-effects, because other body cells would not be affected. In his Lindau lecture, as well as in his Nobel lecture in Stockholm in December 2016, Feringa gave two prominent examples: photo-controlled antibiotics and photo-controlled chemotherapeutics. Into one drug from each category, the Feringa group inserted a light-switch, meaning that the drugs only start working if they’re activated by a certain wavelength of light. The researchers are now working with near-infrared light that has a deep penetration depth, meaning it can even reach remote places deep inside the human body.

 

Nanocar JPG (797x451)

 

With photo-controlled antibiotics, the goal is to ‘train’ the molecules to find their target structures autonomously. Next, their activity would be switched on with an infrared light. Now the drugs would work against a bacterial infection at the target point – no other body cells or bacteria would be affected, making antibiotic restistance more unlikely. And even if the drug leaves the body after treatment, contamination of ground or drinking water would be prevented by precisely engineered half-times of the molecules: they would simply stop being active after a certain amount of time, rendering the build-up of antibiotic restistance outside the human body unlikely as well.

The same holds true for chemotherapeutics: only after a photo-controlled chemotherapeutic reached a tumour, its activity would be switched on, meaning all other body cells would be spared the often severe side-effects. In his Nobel lecture, Feringa describes his dream for future cancer treatments: new imaging technologies like MRI would be linked to a specific laser. First, the patient receives an injection of a photo-controlled chemotherapeutic. Next, the MRI technology would detect a tiny tumour. Now the MRI feeds this information automaticaly to a laser that is callibrated to a specific wavelength that activates the drug. The result is “high temporal and local precision”.

Those are only two examples of the ‘endless opportunities’ of molecular machines, in Feringa’s words – and applications are not limited to pharmaceuticals. Feringa himself talks about self-healing car coatings or wall paint, also called ‘smart coatings’. With a growing world population and a scarcity of materials, smart coatings could help to form longterm coatings, help to spare natural resources, or they could integrate information technology like sensors into the coatings. Other experts envision self-healing infrastructure, for instance plastic water pipes that are able to repair their own leaks. Fraser Stoddart, Feringa’s American-Scottish co-recipient of the 2016 Noble Prize, went into yet another research direction and now builds highly efficient data storage devices based on molecular machines.

 

Ben Feringa giving the first lecture at the 67th Lindau Nobel Laureate Meeting. Picture/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Ben Feringa during his lecture at the 67th Lindau Nobel Laureate Meeting. Picture/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

 

In October 2016, the Royal Swedish Academy of Sciences announced “the dawn of a new industrial revolution of the twenty-first century” based on molecular machines. Feringa himself often emphasises that he is conducting basic research, and he likes to point out that inventions like electric machines, airplanes or smartphones where all the results of basic research – and that they often needed several years or decades to find widespread application. He estimates that in maybe fifty years, doctors will be able to use photo-controlled drugs as described in his Nobel lecture.