Cool Microscope Technology – Nobel Prize in Chemistry 2017

Being able to see something often precedes understanding its function. In the case of molecules and atoms, this requires advanced methods. Visualising biomolecules is crucial for both the basic understanding of the chemistry of life and for the design of pharmaceuticals. Thanks to the ground-breaking work of Jacques Dubochet, Joachim Frank and Richard Henderson to the development of cryo-electron microscopy (cryo-EM), researchers can now freeze biomolecules mid-movement and image cellular processes they have never previously seen.

There have been two powerful imaging methods before cryo-EM, namely, X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. These methods have enabled the structural analysis of thousands of biomolecules. However, both methods suffer from fundamental limitations. NMR only works for relatively small proteins in solution. X-ray crystallography requires that the molecules form well-organised crystals. The images are like black and white portraits from early cameras – their rigid pose reveals very little about the protein’s dynamics.

 

The 2017 Nobel Laureates in Chemistry: Jacques Dubochet, Joachim Frank, and Richard Henderson (from left). Illustrations: Niklas Elmehed. Copyright: Nobel Media AB 2017

TheNobel Laureates in Chemistry 2017: Jacques Dubochet, Joachim Frank, and Richard Henderson (from left). Illustrations: Niklas Elmehed. Copyright: Nobel Media AB 2017

 

Richard Henderson succeeded in using an electron microscope to generate a three-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential. Henderson used this older method for imaging proteins, but setbacks arose when he attempted to crystallise a protein that was naturally embedded in the membrane surrounding the cell. Membrane proteins are difficult to manage, because they tend to clump up into a useless mass once they are removed from their natural environment – the membrane. The first membrane protein that Richard Henderson worked with was difficult to produce in adequate amounts; the second one failed to crystallise. After years of disappointment, he turned to the only available alternative: the electron microscope.

When the electron microscope was invented in the 1930s, scientists thought that it was only suitable for studying dead matter. The intense electron beam necessary for obtaining high resolution images incinerates biological material and, if the beam is weakened, the images lose contrast. In addition, electron microscopy requires a vacuum, a condition in which biomolecules deteriorate because the surrounding water evaporates. When biomolecules dry out, they collapse and lose their natural structure, rendering the images useless.

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Bacteriorhodopsin is a purple protein that is embedded in the membrane of a photosynthesising organism, where it captures the energy from the sun’s rays. Instead of removing the sensitive protein from the membrane, as Richard Henderson had previously tried to do, he and his colleagues took the complete purple membrane and put it under the electron microscope. In this way, the protein retained its structure because it remained membrane-bound. To prevent the sample’s surface from drying out in the vacuum, they covered it with a glucose solution.

The harsh electron beam was a major problem, but the researchers made use of the way in which bacteriorhodopsin molecules are packed in the organism’s membrane. Instead of blasting it with a full dose of electrons, they used a weaker beam. The image’s contrast was poor, and they could not see the individual molecules, but they were able to make use of the fact that the proteins were regularly packed and oriented in the same direction. When all the proteins diffracted the electron beams in an almost identical manner, they could calculate a more detailed image based on the diffraction pattern – they used a similar mathematical approach to that used in X-ray crystallography.

To get the sharpest images, Henderson travelled to the best electron microscopes in the world. All of them had their weaknesses, but they complemented each other. Finally, in 1990, 15 years after he had published the first model, Henderson achieved his goal and was able to present a structure of bacteriorhodopsin at atomic resolution. He thereby proved that cryo-EM could provide images as detailed as those generated using X-ray crystallography, which was a crucial milestone. However, this progress was built upon an exception: the way that the protein naturally packed itself regularly in the membrane. Few other proteins spontaneously order themselves like this. The question was whether the method could be generalised: would it be able to produce high-resolution three-dimensional images of proteins that were randomly scattered in the sample and oriented in different directions?

On the other side of the Atlantic, at the New York State Department of Health, Joachim Frank had long worked to find a solution to just that problem. Joachim Frank made the technology generally applicable. Between 1975 and 1986, he developed an image processing method in which the electron microscope’s fuzzy two-dimensional images are analysed and merged to reveal a sharp three-dimensional structure.

Already in 1975, Frank presented a theoretical strategy where the apparently minimal information found in the electron microscope’s two-dimensional images could be merged to generate a three-dimensional whole. His strategy built upon having a computer discriminate between the traces of randomly positioned proteins and their background in a fuzzy electron microscope image. He developed a mathematical method that allowed the computer to identify different recurring patterns in the image. The computer then sorted similar patterns into the same group and merged the information in these images to generate a sharper image. In this way he obtained a number of high-resolution, two-dimensional images that showed the same protein but from different angles. The algorithms for the software were complete in 1981.

The next step was to mathematically determine how the different two-dimensional images were related to each other and, based on this, to create a three-dimensional image. Frank published this part of the image analysis method in the mid-1980s and used it to generate a model of the surface of a ribosome, the gigantic molecular machinery that builds proteins inside the cell. Joachim Frank’s image processing method was fundamental to the development of cryo-EM.

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Back in 1978, at the same time as Frank was perfecting his computer programmes, Jacques Dubochet was recruited to the European Molecular Biology Laboratory in Heidelberg to solve another of the electron microscope’s basic problems: how biological samples dry out and are damaged when exposed to a vacuum. Henderson had used a glucose solution to protect his membrane from dehydrating in 1975, but this method did not work for water-soluble biomolecules. Other researchers had tried freezing the samples because ice evaporates more slowly than water, but the ice crystals disrupted the electron beams so much that the images were useless. Also, the vaporising water was a major dilemma.

Jacques Dubochet saw a potential solution: cooling the water so rapidly that it solidified in its liquid state to form a glass instead of crystals. A glass appears to be a solid material, but is actually a fluid because it has disordered molecules. Dubochet realised that if he could get water to form glass – also known as vitrified water – the electron beam would diffract evenly and provide a uniform background.

Initially, the research group attempted to vitrify tiny drops of water in liquid nitrogen at –196°C, but were successful only when they replaced the nitrogen with ethane that had, in turn, been cooled by liquid nitrogen. Under the microscope they saw a drop that was like nothing they had seen before. They first assumed it was ethane, but when the drop warmed slightly the molecules suddenly rearranged themselves and formed the familiar structure of an ice crystal. This was a great success, particularly as some researchers had claimed it was impossible to vitrify water drops.

After the breakthrough in 1982, Dubochet’s research group rapidly developed the basis of the technique that is still used in cryo-EM. They dissolved their biological samples – initially different forms of viruses – in water. The solution was then spread across a fine metal mesh as a thin film. Using a bow-like construction they shot the net into the liquid ethane so that the thin film of water vitrified. In 1984, Jacques Dubochet published the first images of a number of different viruses, round and hexagonal, that are shown in sharp contrast against the background of vitrified water. Biological material could now be relatively easily prepared for electron microscopy, and researchers were soon knocking on Dubochet’s door to learn the new technique.

In 1991, when Joachim Frank prepared ribosomes using Dubochet’s vitrification method and analysed the images with his own software, he obtained a three-dimensional structure that had a resolution of 40 Å. This was an amazing step forward for electron microscopy, but the image only showed the ribosome’s contours. In fact, it looked like a blob and the image did not even come close to the atomic resolution of X-ray crystallography.

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The electron microscope has gradually been optimised, greatly due to Richard Henderson stubbornly maintaining his vision that electron microscopy would one day routinely provide images that show individual atoms. Indeed, recent years have witnessed a ‘resolution revolution’. Resolution has improved, Ångström by Ångström, and the final technical hurdle was overcome in 2013, when a new type of electron detector came into use. Researchers can now routinely produce three-dimensional structures of biomolecules. 

There are a number of benefits that make cryo-EM so revolutionary: Dubochet’s vitrification method is relatively easy to use and requires a minimal sample size. Due to the rapid cooling process, biomolecules can be frozen mid-action and researchers can take image series that capture different parts of a process. This way, they produce ‘films’ that reveal how proteins move and interact with other molecules. Using cryo-EM, it is also easier than ever before to depict membrane proteins, which often function as targets for pharmaceuticals. For instance in the Zika virus outbreak in 2015-16, cryo-EM was used to visualise the virus’ membrane within months. As the Nobel Committee’s press release appreciates: “this method has moved biochemistry into a new era.”

Nobel Prize in Physics 2017 – the Discovery of Gravitational Waves

On 14 September 2015, the LIGO detectors in the USA saw space vibrate with gravitational waves for the very first time. Even though the signal was tiny – the time difference between the two light beams in one LIGO interferometer was only 0.0069 seconds, as Olga Botner from the Nobel Committee for Physics points out – it marked the beginning of a new era in astronomy: with Gravitational Wave Astronomy, researchers will be able study the most violent events in the universe, like the merging of black holes. Such a merger was detected in September 2015, and it happened incredible 1.3 billion lightyears away from earth.

 

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The fourth observation of a gravitational wave was only announced on 27 September 2017 at the meeting of G7 science ministers in Turin, Italy. It was also the first to have been picked up by the Virgo detector, located near Pisa. This detection at a third site, besides the two LIGO detectors in the US states of Washington and Louisiana, provides a much better understanding of the three-dimensional pattern of the wave. It is also the result of two merging black holes and was detected on 14 August 2017.

Gravitational waves had been predicted in 1915 by Nobel Laureate Albert Einstein in his General Theory of Relativity. In his mathematical model, Einstein combined space and time in a continuum he called ‘spacetime’. This is where the expression ‘ripples in spacetime’ for gravitational waves comes from.

LIGO, the Laser Interferometer Gravitational Wave Observatory, is a collaborative project with over one thousand researchers from more than twenty countries. Together, they have realised a vision that is almost fifty years old. The 2017 Nobel Laureates all have been invaluable to the success of LIGO. Pioneers Rainer Weiss and Kip S. Thorne, together with Barry C. Barish, the scientist and leader who brought the project to completion, have ensured that more than four decades of effort led to gravitational waves finally being observed.

 

The three new Nobel Laureates: Rainer Weiss, Barry C. Barish, and Kip S. Thorne (from left). Copyright: Nobel Media, Illustration by N. Elmehed

The three new Nobel Laureates in Physics: Rainer Weiss, Kip S. Thorne, and Barry C. Barish (from left). Copyright: Nobel Media, Illustrations by Niklas Elmehed

 

Already in the mid-1970s, both Kip Thorne and Rainer Weiss were firmly convinced that gravitational waves could be detected. Weiss had already analysed possible sources of background noise that would disturb their measurements. He had also designed a detector, a laser-based interferometer, which would overcome this noise. While Rainer Weiss was developing his detectors at MIT in Cambridge, outside Boston, Kip Thorne started working with Ronald Drever, who built his first prototypes in Glasgow, Scotland. Drever eventually moved to join Thorne at Caltech in Los Angeles. Together, Weiss, Thorne and Drever formed a trio that pioneered development for many years. Drever learned about the first discovery, but then passed away in March 2017.

Together, Weiss, Thorne and Drever developed a laser-based interferometer. The principle has long been known: an interferometer consists of two arms that form an L. At the corner and the ends of the L, massive mirrors are installed. A passing gravitational wave affects each interferometer’s arm differently – when one arm is compressed, the other is stretched. The laser beam that bounces between the mirrors can measure the change in the lengths of the arms. If nothing happens, the light beams cancel each other out when they meet at the corner of the L. However, if either of the interferometer’s arms changes length, the light travels different distances, so the light waves lose synchronisation and the resulting light’s intensity changes where the beams meet; the minimal time difference of the two beams can also be detected.

The idea was fairly simple, but the devil was in the details, so it took over forty years to realise. Large-scale instruments are required to measure microscopic changes of lengths less than an atom’s nucleus. The plan was to build two interferometers, each with four-kilometre-long arms along which the laser beam bounces many times, thus extending the path of the light and increasing the chance of detecting any tiny stretches in spacetime. It took years of developing the most sensitive instrument ever to be able to distinguish gravitational waves from all the background noise. This required sophisticated analysis and advanced theory, for which Kip Thorne was the expert.

 

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Running such a project on a small scale was no longer possible and a new approach was needed. In 1994, when Barry Barish took over as leader for LIGO, he transformed the small research group of about forty people into a large-scale international collaboration with more than a thousand participants. He searched for the necessary expertise and brought in numerous research groups from many countries.

In September 2015, LIGO was about to start up again after an upgrade that had lasted several years. Now equipped with tenfold more powerful lasers, mirrors weighing 40 kilos, highly advanced noise filtering, and one of the world’s largest vacuum systems, it captured a wave signal a few days before the experiment was set to officially start. The wave first passed the Livingston, Louisiana, facility and then, seven milliseconds later – moving at the speed of light – it appeared at Hanford, Washington, three thousand kilometres away.

 

Young researcher was first person the ‘see’ a gravitational wave

A message from the computerised system was sent early in the morning on 14 September 2015. Everyone in the US was sleeping, but in Hannover, Germany, it was 11:51 hours and Marco Drago, a young Italian physicist at the Max Planck Institute for Gravitational Physics, also named Albert Einstein Institute and part of the LIGO Collaboration, was getting ready for lunch. The curves he glimpsed looked exactly like those he had practiced recognising so many times. Could he really be the first person in the world to see gravitational waves? Or was it just a false alarm, one of the occasional blind tests about which only a few people knew?

The wave’s form was exactly as predicted, and it was not a test. Everything fit perfectly. The pioneers, now in their 80s, and their LIGO colleagues were finally able to hear the music of their dreams, like a bird chirping. The discovery was almost too good to be true, but it was not until February the following year that they were allowed to reveal the news to anyone, even their families.

What will we learn from the observation of gravitational waves? As Karsten Danzmann, Director of the Albert Einstein Institute and Drago’s boss, explained: “More than 99 percent of the universe are dark to direct observation.” And Rainer Weiss elaborated during a telephone conversation with Thors Hans Hansson of the Nobel Committee: Merging black holes probably send the strongest signal, but there are many other possible sources, like neutron stars orbiting each other, and supernovae explosions. Thus, Gravitational Waves Astronomy opens a new and surprising window to the Universe.

The Workings of Our Inner Clock – Nobel Prize in Physiology or Medicine 2017

2017 Nobel Laureates in Physiology or Medicine: Jeffrey C. Hall, Michael Rosbash and Michael W. Young. Illustration: Niklas Elmehed. Copyright: Nobel Media AB 2017

2017 Nobel Laureates in Physiology or Medicine: Jeffrey C. Hall, Michael Rosbash and Michael W. Young. Illustration: Niklas Elmehed. Copyright: Nobel Media AB 2017

 

Our body functions differently during the day than it does during the night – as do those of many organisms. This phenomenon, referred to as the circadian rhythm, is an adaptation to the drastic changes in the environment over the course of the 24-hour cycle in which the Earth rotates about its own axis. How does the biological clock work? A complex network of molecular reactions within our cells ensures that certain proteins accumulate at high levels at night and are degraded during the daytime. For elucidating these fundamental molecular mechanisms, Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded the Nobel Prize in Physiology or Medicine 2017.

Already in the 18th century, the astronomer Jean Jacque d’Ortous de Mairan observed that plants moved their leaves and flowers according to the time of the day no matter whether they were placed in the light or in the dark, suggesting the existence of an inner clock that worked independently of external stimuli. However, the idea remained controversial for centuries until additional physiological processes were shown to be regulated by a biological clock, and the concept of endogenous circadian rhythms was finally established.

 

Simplified illustration of the feedback regulation of the period gene.  Illustration: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén

Simplified illustration of the feedback regulation of the period gene. Illustration: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén

The first evidence of an underlying genetic programme was found by Seymour Benzer and Ronald Konopka in 1971 when they discovered that mutations in a particular gene, later named period, disturbed the circadian rhythm in fruit flies. In the 1980s, the collaborating teams of the American geneticists Jeffrey C. Hall and Michael Rosbash at Brandeis University as well as the laboratory of Michael W. Young at Rockefeller University succeeded in deciphering the molecular structure of period. Hall and Rosbash subsequently discovered how it was involved in the circadian cycle: they found that the levels of the gene’s product, the protein PER, oscillated in a 24-hour cycle, and suggested that high levels of PER may in fact block further production of the protein in a negative self-regulatory feedback loop. However, how exactly this feedback mechanism might work remained elusive.

Years later, the team of Michael W. Young contributed the next piece to the circadian puzzle with the discovery of another clock gene, named timeless. The protein products of period and timeless bind each other and are then able to enter the cell’s nucleus to block the activity of the period gene. The cycle was closed when, in 1998, the teams of Hall and Rosbash found two further genes, clock and cycle, that regulate the activity of both period and timeless, and another group showed that vice versa the gene products of timeless and period control the activity of clock. Later studies by the laureates and others found additional components of this highly complex self-regulating network and discovered how it can be affected by light.

The ability of this molecular network to regulate itself explains how it can oscillate. However, it does not explain why this oscillation occurs every 24 hours. After all, both gene expression and protein degradation are relatively fast processes. It was thus clear that a delay mechanism must be in place. An important insight came from Young’s team: the researchers found that a particular protein can delay the process and named the corresponding gene doubletime.

It has since been discovered that the physiological clock of humans works according to the same principles as that of fruit flies. To ensure that our whole body is in sync, our circadian rhythm is regulated by a central pacemaker in the hypothalamus. The circadian clock is affected by external cues such as food intake, physical activity or temperature. But how does the circadian clock affect us? Our biological rhythm influences our sleep patterns, how much we eat, our hormone levels, our blood pressure and our body temperature. Dysfunction of the circadian clock is associated with a range of diseases including sleep disorders, depression, bipolar disorders and neurological diseases. There is also some evidence suggesting that a misalignment between lifestyle and the inner biological clock can have negative consequences for our health. An aim of ongoing research in the field of chronobiology is thus to regulate circadian rhythms to improve health.

 

Tackling the Intractable

Depression is one of the most common and debilitating illnesses worldwide, especially because many sufferers do not respond adequately to any of the currently available treatment options. Picture/Credit: SanderStock/iStock.com

Depression is one of the most common and debilitating illnesses worldwide, especially because many sufferers do not respond adequately to any of the currently available treatment options. Picture/Credit: SanderStock/iStock.com

 

The scourge of depression affects more than 300 million people worldwide, and is the leading global cause of disability. The Nobel Prize-winning research of Arvid Carlsson, Paul Greengard and Eric Kandel among others, paved the way for effective drugs to treat the condition.

How do nerve cells communicate with each other? This was the question that fascinated Paul Greengard and which led him to unravel the biochemical basis for how dopamine acts as a neurotransmitter between nerve cells. His scientific discoveries provided part of the underlying scientific rationale for drugs such as Prozac that act to increase the levels of serotonin, another neurotransmitter whose levels are implicated in depression. Indeed, several so-called selective serotonin reuptake inhibitors (SSRIs) have been developed for the treatment of depression and other disorders, and they are the most commonly prescribed anti-depressants in many countries.

However, even though these compounds provide relief to many, a substantial proportion of individuals with depression do not respond adequately either to these drugs or to cognitive behavioural therapy, the other common first-line treatment for depression.  In fact, about one third of people with severe depression do not initially respond adequately to any currently available therapy. Recently revived research into the medicinal potential of psychedelic drugs, which include LSD and psilocybin from mushrooms, indicates that such substances, when combined with appropriate psychiatric care, may be an effective tool in combatting depressive disorders. The stage is now set for the largest ever clinical trial examining the effectiveness of a psychedelic substance to treat depression.

Although psychedelic drugs may revolutionise the treatment of depression, at a molecular level, their mode of action is very similar to that of traditional SSRIs: they decrease the amount of serotonin that is “reabsorbed” by the signalling neuron and thus increase the amount of the neurotransmitter that can be taken up by the neuron which is receiving the signal. The key difference is that psychedelics primarily engage different serotonin receptors, which means that different regions of the brain are affected leading to very different physiological effects. Thus, while traditional SSRIs act to reduce stress, anxiety and aggression and to promote increased resilience and emotional blunting, the goal of treatment with psychedelics is rather to dissolve rigid thinking and provide environmental sensitivity and emotional release. The proponents of psychedelics thus claim that the cumulative effect is to increase well-being, while more traditional medications seek to rather simply decrease the symptoms of depression.

The potential of psychedelics to tackle depression head-on and “wipe the slate clean” instead of simply addressing the symptoms almost sounds too good to be true. Psychedelic drugs are strictly prohibited in most countries around the world. In the UK, for example, both LSD and psilocybin are classified as Class A drugs (those whose consumption is deemed most dangerous). With good reason: in particular, LSD abuse is linked with a range of adverse consequences, including panic attacks, psychosis and perceptual disorders. Many users apply Paracelsus’ maxim: “The dose makes the poison.” The regular ingestion of LSD at amounts that are not sufficient to elicit full-blown hallucinations, but which users claim improves focus and creativity, referred to as micro-dosing, has attracted a huge amount of attention in recent times, in large part due to anecdotal evidence that the practice is rife in Silicon Valley. Micro-dosing with psilocybin is also increasing in popularity. The use of psilocybin, found in “magic mushrooms”, was an element of some pre-historic cultures, and, as with other psychedelics, its use both recreational and medicinal was popular in the 1960s. Prohibitive anti-drug legislation across the globe meant that in subsequent decades research into the drug was severely curtailed. However, the last 20 years have witnessed a gradual renaissance of psilocybin research.

 

Psilocybin, a psychedelic substance found in “magic mushrooms”, has shown promise in tackling treatment-resistant depression and in alleviating the anxiety and depressive symptoms of cancer patients. Picture/Credit: Misha Kaminsky/iStock.com

Psilocybin, a psychedelic substance found in “magic mushrooms”, has shown promise in tackling depression and in alleviating anxiety. Picture/Credit: Misha Kaminsky/iStock.com

 

While regular small doses appear to be one potential approach, most recent clinical studies that have tested the effects of psilocybin for depression in a controlled set-up have adopted a strategy in which a single higher dose of the substance or several such doses are administered over a short period of time. This approach is in sharp contrast to the one taken for classical anti-depressants, which are consumed daily. The single high dose strategy has yielded promising results for patients with treatment-resistant depression and also for those suffering with the anxiety and depression often experienced by individuals with cancer. The majority of patients treated with psilocybin in this way exhibited an improvement in the symptoms of depression for up to six months. However, even though these recent studies have shown positive results, there remain a number of significant caveats: firstly, one of the most recent trials was open-label, meaning that the participants knew in advance that they would be receiving a psychedelic drug; secondly, most of the studies to date have been small with only 50 subjects or less; finally, as in most other trials of this kind, the reporting measures are very subjective in nature and rely upon observation by health care professionals, friends or self-reporting by the patients themselves.

It is thus still too early to draw any definitive conclusions regarding the efficacy of psilocybin in alleviating the symptoms of depression. This might be about to change, however: the British start-up company Compass Pathways is close to sealing final approval to carry out what would be the largest clinical trial to date looking at the efficacy of psilocybin in treating treatment-resistant depression. The two-part trial will incorporate a much larger number of patients than in previous trials (approximately 400), and will be performed with leading clinical research institutions across Europe. The first part will be focused on determining the most effective dosage of psilocybin; in the second part, patients will receive the psilocybin therapy as a single treatment. An important feature of the trial will be the use of more objective digital tracking methods to monitor the effects of psilocybin. In common with previous smaller-scale studies, careful psychological support and monitoring will be crucial. Research has shown that simply administering psychedelic drugs without providing a proper supportive environment, including counselling, greatly reduces the efficacy of psychedelics against depression and may even be counter-productive.

Even though the first clinical data suggest promising effects of psychedelic drugs in the treatment of depression, several questions remain open: it is unclear how representative the study populations have been, as there may have been a bias toward recruiting those who are more favourably disposed to using psychedelics, and positive prior experiences with such substances may affect treatment outcome. Furthermore, it has yet to be determined at which point substances should be introduced as therapy – as a front-line therapy before depressive symptoms become too ingrained and before long-term therapy with classical anti-depressants, or rather as a treatment of last resort when all else fails.

Young Women Economists in Lindau: Powerful Encounters

One of the reasons I applied to attend the 6th Lindau Meeting on Economic Sciences was the expectation of coming back brimming with self-motivation. Moreover, I expected to be deeply fascinated by the commitment of the pioneers of economic sciences, by their bravery in addressing world issues and by their lives as common individuals facing successes and failures. My expectations were by far exceeded.

I have always genuinely aspired to become an active participant in economics and to make a difference. My passion for the subject started with my postgraduate studies and further developed during my work at the United Nations and my academic experiences. A special opportunity offered by this meeting is the possibility of interacting with Nobel Laureates and other young academics, while sharing passions and values, understanding different cultures and exchanging ideas and future collaborations.

But what also fascinated me and made this experience even more magic and overwhelming was the passion, the eagerness and the determination of the many young women economists I had the pleasure of meeting in Lindau.

 

Zeinab Aboutalebi (left) and Angela De Martiis during the 6th Lindau Meeting on Economic Sciences. Picture/Credit: Lisa Vincenz-Donnelly/Lindau Nobel Laureate Meetings

Zeinab Aboutalebi (left) and Angela De Martiis during the 6th Lindau Meeting on Economic Sciences, Picture/Credit: Lisa Vincenz-Donnelly/Lindau Nobel Laureate Meetings

 

One of the ideas that particularly got my attention during the meeting is what Nobel Laureate Bengt Holmström called serendipity. Among the various questions to the laureates, many young economists were eager to know the secret of their success: how did they do it?

A common answer was indeed serendipity. An unexpected discovery that occurs by chance, a valuable finding that was not looked for by others, being in the right place at the right time, or simply luck. Nevertheless, the role of chance – or luck – in science is also driven by passion and determination. Often, such unexpected findings come from an error in the scientist’s own methodology, according to scientists Kevin Dunbar and Jonathan Fugelsang. Passion and determination were in fact the two main elements that I sensed when talking with young women economists about their research interests.

During my week at the meeting, I had the honour of presenting my research in front of five Nobel Laureates – an invaluable experience – and the pleasure of interviewing several young women economists from different countries, cultures and backgrounds. They came from Africa, Russia, Iran, China, the United States, Germany and Italy, and they all have one element in common: passion.

When I asked them about their motivation for doing academic research, the first answer was indeed passion, eagerness to learn, to understand and provide valuable results to inform some of today’s most debated issues – such as climate change, economic sanctions, information asymmetry, inequalities, labour markets, growth theory and monetary policy. The women economists, and women’s participation in the economy more generally, provide a diversity of economic thinking, as Janet Yellen recently emphasised in a speech at Brown University.

This diversity of thinking comes from the fact that, as one of these women economists told me, economics is not just economics. Being an economist implies knowing about mathematics, statistics, natural sciences, law, politics, psychology, history, sociology and more. Economics means dealing with issues that involve institutions and individuals. All these elements together make it a powerful tool for improving people’s welfare and lives.

On the one hand, welfare is one of the motivations driving Linda Glawe, a young German economist from the University of Hagen, to focus on prolonged growth slowdowns in emerging market economies and on the concept of the middle-income trap. In a world in which more than five billion people live in middle-income countries, representing more than 70% of the world’s poor population, a slowdown in emerging markets will have strong implications for low and high-income countries. Therefore, the danger of a middle-income trap is of great relevance for future welfare. After publishing a literature survey on the middle-income trap, Linda’s current research aims to provide a theoretical contribution to discussions of future growth in China.

On the other hand, when we talk about welfare we often refer to the fact that countries have unequal living standards that makes them grow faster or slower than others. Therefore, some countries display higher inequalities in incomes, wealth and human capital. These issues are among the main research interests of Rong Hai, a Chinese young assistant professor in economics at the University of Miami.

In one recent paper, she and laureate James Heckman investigate the determinants of inequality in human capital with an emphasis on the role of credit constraints. The results show that both cognitive and non-cognitive abilities are important determinants of human capital inequality. In addition, credit constraints are important because young people cannot borrow enough against their future human capital and thus suffer from lower consumption when they are in school.

In a second paper, Rong finds that reducing income inequality between low and median income households improves economic growth. But reducing income inequality through taxation between median and high-income households reduces economic growth.

 

Angela De Martiis and other young economists during the 6th Lindau Meeting on Economic Sciences,  Picture/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Angela De Martiis and other young economists during the 6th Lindau Meeting on Economic Sciences, Picture/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

 

When investigating economic inequalities, there are many reasons to explore inequality within cities or states, especially if we consider that individuals move across space. Thus, the disparity of a particular area is also a reflection of the skills of these individuals as potential workers. From a labour economist perspective, Sarah Bana, an American Ph.D. candidate at the University of California, Santa Barbara, is interested in understanding the returns to skills and the role that skills play in earnings inequality in the US labour market.

One of her current research papers looks at displaced workers, those who lose their jobs as a result of a firm or plant closing. Analysing comprehensive occupational employment data, the results of her research suggest that vulnerable displaced workers’ difficulties in the labour market are a function of their skills and less related to the goods and services they were previously producing. This is due to the fact that the same set of tasks can be applied in the production of various goods and services, but there appears to be little scope for workers from shrinking occupations to find work with similar earnings, which may help to explain the large earnings losses.

As a researcher in labour economics, Sarah thinks of an individual’s work as their contribution to their family, community and society. But this may be hard for those workers who are displaced in worse labour market conditions.

Several studies investigate the effects of the global financial crisis on the labour market. The data from the displaced workers survey from 1984 to 2014 clearly show a sharp increase in the rate of job loss. Besides the effects on the labour market, the long-lasting impacts of the financial crisis on the economy and wider society have questioned the adequacy of the traditional tools in explaining periods of financial distress as well as the adequacy of the existing policy response.

At the same time, the financial crisis has shown that complex interconnections among financial institutions represent a mechanism for the propagation of financial distress and they are nowadays recognised as one of the key elements of potential financial instability or systemic risk.

This is one of the crucial issues that the young Italian economist Chiara Perillo, Ph.D. candidate at the University of Zurich, is investigating. In particular, she is exploring the implications of the unconventional monetary policies (such as quantitative easing) in the euro area by combining financial network analysis with econometric methods. Using the time evolution of loans granted from euro area banks to different institutional sectors operating in the euro area, her results show that since the beginning of quantitative easing there has been an increase in bank lending, but mostly addressed to the banking system itself.

Another element that drew my attention while getting to know the young women economists was their diverse backgrounds, another powerful tool for academic research in the diversity of thinking. Being Russian by origin and doing research based in Germany, Maria Kristalova, Ph.D. candidate at the University of Bremen, investigates the impact of the mutual sanctions between the EU and Russia, followed by the escalation of the Ukraine conflict in 2014. Her results show a division pattern of all EU-27 countries in two groups: the West European countries that recovered from the sanctions shock, and the East European and Baltic countries, which are still suffering with negative consequences.

Angela De Martiis (right) and Maria Kristalova during the 6th Lindau Meeting on Economic Sciences

Angela De Martiis with Maria Kristalova, Picture: Courtesy of Angela De Martiis

According to Maria, this topic is of crucial importance for gaining a better understanding of the costs of political decisions that might affect the aspired convergence of Europe. In a second research topic, Maria also looks at long-run co-evolution of innovation activities and public funding in German regions. The results show strong empirical evidence of its existence.

Another issue of crucial importance, one of the most controversial, is climate change. According to Jennifer Uju Okonkwo, a young Nigerian economist based at the University of Kiel, regardless of what sceptics think, research shows evidence that the climatic system is changing and this change has several negative consequences, such as rising sea levels, coastal flooding, droughts, global warming and changes in precipitation. Hence, there is a dire need to understand optimal ways to adapt to the changing climate. Her research thus aims at finding cost-effective strategies to manage climate change that could be beneficial to developing countries with limited adaptation funds.

When investigating the issue of climate change, we immediately come across divergent views and an asymmetry in information, thus generating inefficiencies in addressing and solving such a phenomenon. As a young Iranian economist working on applied microeconomic theory at Warwick University, Zeinab Aboutalebi is investigating the role of information asymmetry.

Her research is dedicated to tracing inefficiencies created through the strategic interaction among economic actors. The role of information asymmetry is crucial in shaping the resulting consequences and in reducing the inefficiencies using, for example, different incentive schemes, designing incentive mechanisms, delegation or persuasion techniques.

Zeinab is currently working on feedback in experimentation and how the goodwill of a principal to not discourage an agent, while providing him/her feedback about the result of the experiment, could cause large inefficiencies and uninformative communication between the principal and the agent. Information asymmetry and the lack of informative communication are thus the building blocks of most of today’s big phenomena.

From climate change, to inequality, displaced workers, sanctions, growth, monetary policy and information asymmetry, it was a pleasure to make this journey into the lives and research interests of seven young women economists – to discuss new research ideas, exchange views and laugh while talking about science and about a world that is a fascinating place still to be discovered with a pinch of serendipity and a lot of determination. Thank you for sharing your passion!

Only as Strong as the Weakest Link: Global Food Supply Chains

This article appeared in a shorter form in the German newspaper Handelsblatt on August 24, 2017.

A ‘Marshall Plan for Africa’ – 300 million Euro in total. This is Angela Merkel’s bold development promise ahead of the Federal election. Germany has also placed Africa at the heart of its G20 presidency. So the future chancellor, whoever it is, needs a solid development strategy. This strategy should put farmers’ needs first and leverage the scientific expertise of companies, like Mars, that are networked throughout Africa through their supply chains.

As Bill Gates has said, “if you care about the poorest, you care about agriculture.” This is why I am joining the best economists in the world at the Lindau Nobel Laureate Meetings in Germany 22—26 August. We are convening an event to discuss economic inequality, agriculture and the role of businesses.

 

I was discussing economic inequality at the 6th Lindau Meeting on Economic Sciences with economists Romesh Vaitilingam, Eric Maskin (Nobel Laureate) and Devaki Ghose.

I was discussing economic inequality at the 6th Lindau Meeting on Economic Sciences with economists Romesh Vaitilingam, Eric Maskin (Nobel Laureate) and Devaki Ghose.

 

Why is this such an important issue? Over 475 million of the world’s 570 million farms are smaller than two hectares. Even though these smallholder farms produce over 80% of the world’s food, 80% of the global population deemed “chronically hungry” are farmers. This is the 80-80 paradox.

Agricultural supply chains in food-insecure regions like Africa need an upgrade — but this won’t happen without a concerted and long-term effort. Look at China, where they managed the ‘structural transformation’ from a mostly farming to a mostly industrial economy well. From 1952 to 2004, the structure of China’s economy shifted, from agriculture providing half the country’s GDP to providing only 14% in 2004. During this transition, the non-farm rural sector boomed – services, transport, processing, etc. The rural non-farm sector went from providing almost none of the GDP to more than one-third. Importantly, the Chinese government sent engineers and scientists into the countryside to transfer knowledge and technology to farmers and encourage non-farm business growth. Knowledge sharing combined with better infrastructure linkages between small farmers, processing facilities and retailing companies lies at the core of China’s success.  

Yet, while we can take inspiration from China, replicating the transformation process of a highly regulated, state-managed economy is not feasible elsewhere. Many governments do not have the capacity to effect these changes. I believe multinational corporations can fill this void. Companies need to be part of the international development strategy and leverage their unique position at the apex of global supply chains to share technical skills and cutting-edge innovation.

Indeed, this is already starting to happen. For example, the staple food crops grown by African smallholder farmers are finally getting attention. Traditionally, crops suited to Western climatic conditions, like potato, wheat and corn, have received all the scientific investment. Their yield, for example, has increased by a factor of five or six since the 1930s. The yield of traditionally African crops, on the other hand, is much the same as it was 100 years ago.

 

The average yield of maize and wheat has tripled since 1961 whereas the yield of millet, a crop traditionally grown in areas of Africa and India, has only increased by 50 percent

The average yield of maize and wheat has tripled since 1961 whereas the yield of millet, a crop traditionally grown in areas of Africa and India, has only increased by 50 percent.

 

Through a lack of R&D, finger millet, Bambara groundnut, teff and other staple African crops are still vulnerable to disease, pests and drought. The resulting low yields mean that African farmers have too little food to feed their families. It is no wonder that 80% of the global population deemed “chronically hungry” are farmers.

When we saw that this was happening, a group of uncommon collaborators came together for one of the most ambitious projects in the history of plant science. Mars, NEPAD, Illumina, BGI, WWF, the UN Food and Agriculture Organization, the World Agroforestry Centre and others partnered to sequence 101 African orphan crop genomes to accelerate breeding programs and improve food security for the farmers who depend on these crops. The genomes are being made available to the public so that plant breeders everywhere can breed new cultivars of the African crops with higher yields and more resistance to disease, pests and climate change. Better crops create jobs and can stimulate the rural non-farm sector in Africa. African seed companies will spring up to distribute the new cultivars to farmers; transport companies will bring surplus to markets; processors will take on the role of making food ready for the consumer, and so on.

 

Taro is a traditional crop in areas of Africa and one of the 101 crops whose genomes we are sequencing to improve nutrition, yield and resistance to drought, diseases and pests. Picture/Credit: karimitsu/iStock.com

Taro is a traditional crop in areas of Africa and one of the 101 crops whose genomes we are sequencing to improve nutrition, yield and resistance to drought, diseases and pests. Picture/Credit: karimitsu/iStock.com

 

We welcome the German government’s initiative to boost development aid to Africa, but to maximize the impact of taxpayers’ money, we need more inclusive private-public partnerships to play their role and bring the Marshall Plan for Africa to life. An inclusive approach is the only way to address one of the travesties of our age: people who grow food that don’t have enough to eat.

Choosing the Right Mentor is Most Important, Says Lindau Alumna

Interview with Lindau Alumna Floryne Buishand

This interview is part of a series of interviews of the “Women in Research” blog that features young female scientists participating in the Lindau Nobel Laureate Meetings, 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 Floryne and get inspired.

 

Floryne Buishand, 30, from the Netherlands, is a postdoctoral researcher at the National Cancer Institute/NIH, Bethesda, USA, studies genomic changes associated with endocrine cancers with the ultimate goal of identifying novel diagnostic and prognostic markers, as well as novel therapeutic targets. One of her special interests is the field of veterinary comparative oncology: the study of naturally occurring cancers in pet dogs provides a suitable model for the advancement of the understanding, diagnosis and management of cancer in humans. Floryne participated in the 64th Lindau Nobel Laureate Meeting.

 

Floryne Buishand

What inspired you to pursue a career in science?

My background is in veterinary medicine. When I started at vet school, I was convinced that I would become a small animal veterinarian in private practice, because this had always been my dream. However, during college I was selected to participate in the Honors Program of Utrecht’s Faculty of Veterinary Medicine. This program is an additional year on top of the normal curriculum, and it is 100% research focused. During that year I got inspired to pursue a career in translational science. I realised that solely practicing veterinary medicine would eventually become too much of a routine for me; however, research would always stay challenging. The combination of clinic and research was very appealing to me, because on the one hand I could immediately contribute to curing small animals by practicing, and on the other hand I could contribute to potential future anti-cancer therapies through my research. Also, it would allow me to formulate fundamental research questions based on clinically relevant problems, take these to the lab, and eventually translate the research findings back to the clinic. Since I was fortunate enough to get good results from my Honors Program research, after obtaining my DVM degree, I was able to continue this research project as a Ph.D. candidate. I obtained a grant from The Netherlands Organization for Health Research and Development, and this allowed me to perform my Ph.D. research alongside my clinical residency in small animal surgery.

 

Who are your role models?

Obviously, I’m thankful to my parents. Without their support I wouldn’t have been in the position that I am in now.

On a professional level, I have many role models. To name a few that I have met personally, I’d like to start with late Prof. Wim Misdorp, who was one of the founding fathers of veterinary comparative oncology. He was the first veterinarian to receive a grant in comparative cancer pathology at the Dutch Cancer Institute and the Queen Wilhemina Cancer Foundation, which resulted in his Ph.D. thesis in 1964 “Malignant mammary tumors in the dog and the cat compared with the same in women”. During his impressive career he has established collaborations between human hospitals and veterinary practices and he was the first to get a dual professorship at Utrecht’s Faculty of Veterinary Medicine, both in the Pathology Department as well as in the Small Animal Medicine Department. Standing with one leg in the pathology lab and with one leg in the clinic, he was able to further integrate these two disciplines. Other role models are Profs. Douglas McGregor and David Fraser, who have established the Veterinary Leadership Program at Cornell University. This unique summer research experience combines faculty-guided research with student-directed learning through participation in modules, workshops and group discussion that encourage responsible leadership, critical thinking and the development of teamwork skills. Over the last 28 years, Douglas McGregor and David Fraser have inspired many veterinary medicine students, including myself, facilitating career counselling and promoting the professional development of programme alumni as independent scientists and public health professionals.

Finally, thinking of strong women in science, I consider late Nobel Laureate Rita Levi-Montalcini as a role model. She was awarded the 1986 Nobel Prize in Physiology or Medicine for the discovery of Nerve Growth Factor. At the time of her death, aged 103, she was the oldest living Nobel Laureate. Besides her outstanding research accomplishments, she also served in Italy’s Senate as Senator for Life and she has a foundation to support African women with potential for scientific accomplishment. I like her quote: “Above all, don’t fear difficult moments. The best comes from them.”

 

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

During the final phase of my Ph.D., I realised that it would be important to gain research experience abroad, in order to build a successful scientific career. I always had NCI/NIH at the back of my mind, since I had visited NIH once in 2009, as part of a workshop of the Veterinary Leadership Program.

When I participated in the 2014 Lindau Nobel Laureate Meeting, I met Prof. Jens Habermann from Lübeck University. We shared similar research interests, so he invited me to give a lecture in Lübeck in 2015. It turned out that he had performed his postdoc at NCI and when he learned that I was looking to do a postdoc abroad, he connected me with Dr. Thomas Ried, his former postdoc supervisor at NCI. I applied for a Rubicon grant from the Dutch Organization for Scientific Research, and luckily this grant was honoured to me. That allowed me to start my postdoc at the Ried lab in 2016. Later this year I will start a new challenge at NCI as postdoc in the lab of Dr. Electron Kebebew.

 

Promotie Floryne Buishand (2)

 

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

Each project is different and has its own charm. Something that I very much enjoyed was one of the final projects during my Ph.D. In this project, we identified CD90 as a putative cancer stem cell marker in pancreatic endocrine cancer. Using a zebrafish embryo xenograft model we also demonstrated that anti-CD90 monoclonal antibodies decreased the viability and metastatic potential of insulinoma cells, suggesting that anti-CD90 monoclonals form a potential novel adjutant therapeutic modality. Obviously, this therapy is still far from the clinic. However, with my clinical background I also tremendously enjoy projects that are closer to the clinic. Therefore, I enjoyed my recent rotation at NCI’s Cancer Therapy Evaluation Program (CTEP) very much, too. During my time at CTEP, I reviewed letters of intent for clinical trials and clinical trial protocols, and made improvement recommendations. It was very satisfying to realise that many people could already benefit from these clinical trials within 1-3 years, and even more people in the future if these drugs make it through Phase III trials.

 

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

It’s not my personality to feel immensely proud of what I do, or maybe this moment is yet to come. However, I’d like to rephrase: if that moment comes, I would be proud of the team work and not of my work alone, since science is ultimately a team effort. I tend to be my own devil’s advocate, always critically reviewing my work, looking for ways to improve. Although, I don’t feel pride, I can be very happy about work-related things. The happiest moment was during my Ph.D. defence. It was wonderful to end a period of hard work with a ceremonial defence in the midst of family, friends and colleagues.

 

Floryne Buishand (2)

 

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

On a regular day I get up at 6 am, eat breakfast and go to the gym. I have started going to the gym every morning – weekends and holidays included – after I arrived in the U.S., and I haven’t missed a single day since. It’s a great way for me to wake-up and get energised for a productive day. I bike to NIH and normally start around 8 am. In the lab I am able to immediately start with my experiments, since I plan them ahead of time. I try to get as many experiments running in parallel in the morning. During protocol waiting steps I send emails, search papers or write manuscripts or grant proposals. However, if I really have to focus on writing, I’d rather do that at home, where I can focus better. If I am not having lunch with co-workers, I eat lunch in 5 min at my desk; it’s a habit that still persists from the time I was on clinics. I could probably make more time for lunch, but I like to keep going. During the afternoon I am finishing my experiments. The time I actually finish depends on the things I am working on that day, but usually I don’t have to work late on experiments. When I am finished I go home, make dinner or go out for dinner to meet friends. Bethesda is well known for its many restaurants, and I have made it my goal to eat at every one of them – I am getting there. After dinner I usually work a little more on emails, manuscripts or grants, and often my husband and I finish the day watching a good series. It’s too bad that we have to wait until 2019 for the final GoT season…

 

What are you seeking to accomplish in your career?

My short term goals for my postdoc are to identify novel diagnostic and prognostic markers, as well as novel therapeutic targets, leading to several high impact first authored publications. Also, I am aiming to establish an endocrine cancer comparative oncology consortium. Clinicians and investigators in the fields of veterinary and human endocrine oncology, clinical trials, pathology, and drug development will be joined in this consortium, in order to improve knowledge, development of, and access to naturally occurring canine endocrine tumours, as a model for human disease. Canine and human comparisons represent an unprecedented opportunity to complement conventional endocrine tumour research paradigms, addressing a devastating group of cancers for which innovative diagnostic and treatment strategies are clearly needed. A clinical trial testing an agent in dogs can run between one and three years, whereas human clinical trials stretch between 10-15 years. Comparative oncology research could help by integrating results from canine trials into human trials, thereby speeding up the whole drug development process.

In the long term, I would like to keep contributing to the improvement of current cancer treatment modalities, either by running my own lab, or by coordinating a clinical therapeutics development program, like the work that is being performed at NCI’s Cancer Therapy Evaluation Program.

 

Floryne Buishand

 

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

Back in The Netherlands, I used to play the piano a lot. I have been playing since I was five years old and although I did get the chance at the conservatory to pursue a career as a professional pianist, this has never been my dream. It’s great as a hobby, and I do miss having a piano here in the U.S. Furthermore, I love to be active: besides going to the gym, I am playing tennis and I love to hike, especially in the National Parks. So far, I have visited ~35 of them, and I am looking forward to add two more during our upcoming road trip through Colorado, South Dakota, Wyoming Utah and Arizona.

 

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

Historically, gender stereotypes in science have impeded supportive environments for women faculty. Stereotypes not only affect the social interactions and external evaluations of a stereotyped individual, but can also affect that individual’s performance. Social science research suggests that women’s perceptions of their environments are influenced by stereotype threat: the anxiety faced when confronted with situations in which one may be evaluated using a negative stereotype. For instance, it has been demonstrated that women perform worse on math tests when reminded of their gender, like older adults perform worse on memory tests when reminded of their age. So first of all, women should try to prevent that stereotype threat influences their perception of the environment. Since gender stereotypes should not be an issue, I would give women the same advice as men: the most important thing that someone interested in science should think very carefully about is who they will choose as a mentor. A mentor will have a big impact on the future career of a young scientist, both through an inspirational experience and through the practical benefits of vocational planning. Training decisions should only be made after discussing scientific interests and objectives with trusted advisors and individuals currently in training. Individuals contemplating graduate training should be advised to seek relevant information concerning prospective mentors, including a prospective mentor’s training record, his or her academic progression and productivity, the journals in which he or she has published, and peer regard as reflected in the frequency with which his or her published papers are cited in the scientific literature.

 

Promotie Floryne Buishand

 

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

CRISPR/Cas9 is a hot genome editing tool that was first reported in 2010 as a programmable system for creating DNA cuts at desired locations in prokaryotes. Since then, the system has been adapted enabling its use in eukaryotic cells. So far, CRISPR/Cas9 has been successfully used in vitro and ex vivo for editing, regulating and targeting genomes. The next step would be to use CRISP/Cas9 in vivo, because it could be the next breakthrough in cancer treatment. All cancers harbour multiple mutations that cause uncontrolled cell proliferation. With CRISPR/Cas9 these mutations could be corrected directly in cancer patients. However, before CRISPR/Cas9 makes it to the clinics, obviously some challenges still need to be solved, like off-target effects and efficiency and specificity of in vivo CRISPR/Cas9 delivery methods.

 

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

During the last two decades, women have already made substantial progress in several science, technology, engineering and mathematics fields. Female assistant professors are now at or above parity in psychological science and in most social sciences, and they are approaching parity in biological sciences. However, women remain less numerous at senior ranks in all fields. For example, females make up more than half of biomedical science undergraduate (58%) and postgraduate (53%) degrees but only 18% of full professors in the biomedical science. Apparently, women leave science at the transition from a mentored to an independent stage of their careers. These transition points along this career path offer a target to prevent the loss of highly trained women scientists.

One strategy to keep women on board is to provide specific “women in science fellowships”. At NCI the Sallie Rosen Kaplan postdoctoral fellowship for women in cancer research, provides additional mentoring opportunities, seminars, and workshops designed to strengthen leadership skills over a one-year period, which should enable female postdoctoral fellows to feel better equipped to transition to independent research careers.

Other strategies that could stimulate women to stay in science are a) various forms of flexibility with federal-grant funding designed to accommodate women with young children keeping these women in the game; b) increasing the value of teaching, service, and administrative experience in the tenure/promotion evaluation process; c) providing on-campus childcare centres; d) supporting requests from partners for shared tenure lines that enable couples to better balance work and personal/caretaking roles; e) stopping the tenure clock for one year per child due to childbearing demands; f) providing fully-paid leave for giving birth for tenure track women for one semester; g) providing equal opportunity for women and men to lead committees and research groups.

Looking Ahead to Economics in 2020

Young economists and laureate Oliver Hart during the 6th Lindau Meeting on Economic Sciences.

Nobel Laureate Oliver Hart and young economists during the 6th Lindau Meeting on Economic Sciences. Photo/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

 

The last four triennial Lindau Meetings on Economic Sciences have managed to come at significant moments for the global economy and the debate over how it should be run.

In 2008, there were emerging signs that the ‘Great Moderation’ of the previous decade had come to an end. But most people expected that the turbulence would be confined to the subprime mortgages of the United States.

 

Joseph Stiglitz in 2011 during the 4th Lindau Meeting on Economic Sciences. Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

Joseph Stiglitz in 2011 during the 4th Lindau Meeting on Economic Sciences, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

Three years later and the economics profession was in the dock for failing to give any warning of what had turned out to be a global financial crisis and subsequently, a ‘Great Recession’ that cast millions into unemployment and left the major western economic powers reeling. Lindau 2011 was a focus of media attention as laureates such as Joseph Stiglitz lambasted his colleagues.

At this year’s meetings, the atmosphere was calmer with few signs of an imminent external crisis. Yet given the tenth anniversary of the onset of the global financial crisis, much of the media attention was on the defence of the European Central Bank’s quantitative easing programme by its president Mario Draghi, who gave the opening keynote speech.

Participating journalists were also intrigued by comments by German Federal Minister Peter Altmaier on Brexit and by laureate Chris Pissarides demanding that Germany reduce her current account surplus to bring a better balance to the eurozone and relief to countries such as Greece.

 

Christopher Pissarides during his lecture at the 6th Lindau Meeting on Economic Sciences, Picture/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Christopher Pissarides during his lecture at the 6th Lindau Meeting on Economic Sciences, Picture/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

But at the same time, the Nobel Laureates and young economists at the Lindau Meeting were engaged in discussing a huge amount of new economic research that is going on at universities around the world that may well lead to new theories on how to make people wealthier, healthier and happier.

A total of 85 young economists made presentations on their research to a panel of laureates. These included: an experiment to achieving a collective agreement on which transactions using the cryptocurrency Bitcoin are valid and which are invalid by Demelza Hays of the University of Lichtenstein; the potential for education investment in China to combat child labour by Tang Can of Renmin University; and the work by Cindy Lopez-Bento of Maastricht University on knowledge spillovers from subsidised R&D – to name just three.

Assuming that the world economy continues on its path of consistent – albeit weak – growth, then the next Lindau Meeting on Economic Sciences in 2020 may be the first for 12 years where the focus will be far more on looking forwards than backwards.

How can economics tackle the growing problem of inequality? What can be done to boost levels of productivity that are essential for growth in per capita income and wealth? What does economics have to say about high levels of poverty and ill health in developing countries? All these issues were discussed at Lindau with two science breakfasts on productivity and inequality.

But hopefully in three years time these issues will be the ones grabbing the media limelight.

Young Economists Comment on the ‘Post-Truth’ Era

The economic consensus on such matters as the benefits of trade, technology and global integration has taken a political battering recently. We asked young economists of #LiNoEcon about their perspectives on what is often referred to as a ‘post-truth’ era, and what they think economists could or should do to combat it.

 

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, GermanyI think it is hubris to think that the economic consensus has ever played a role in influencing the man on the street. While the effects of trade nationalism may be catastrophic in economic dimensions I feel that in other research disciplines (e.g., climate research) the stakes are much higher. Consequently, we should stay resilient, persistent and join our fellow researchers from other fields speaking up in the name of truth.

        Chris Flath from Germany

 

 

 

 

 

 

        Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings           

 

 

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, GermanyEconomists and other academic researchers are often wary of over representing their findings, which does not make it easy to communicate the complexities of these problems to the public.

Sarah Quincy from the US

 

 

 

 

 

 

 

 

 
 

 

           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

 

 

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, GermanyI think that this fact is mainly the outcome of the financial crisis and, more importantly, of the growing inequality in our societies.

        Dimitris Papadimitriou from Greece

 

 

 

 

 

 

 

 

 

 

 
 
Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings           

 

 

HelenaPolitical instability worldwide associated with migration flows and the financial crisis of 2008 (and thus rising income inequality) might be responsible for the development of extreme political and economic attitudes across society, especially in Europe.

Helena Chytilova from the Czech Republic

 

 

 

 

 

 

 

 
 
 
           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

 

 

6th Lindau MeetingI don’t think that this ‘post-truth’ phenomenon is a reaction against truth or science, but against ideology-based opinions disguised as facts.

        Pedro Degiovanni from Argentina

 

 

 

 

 

 

 

 

 

 

 

           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings           

 

 

6th Lindau Meeting on Economic SciencesCommunicate, communicate, communicate. We need to better explain our work and results, and actively engage in a discussion with the greater public.

Sofie R. Waltl from Austria

 

 

 
 

 

 

 

 

 

 

 
 
           Photo/Credit: Christian Flemming/Lindau Nobel Laureate Meetings           

 

 

6th Lindau MeetingI believe we as economists need to do a much better job of communicating ideas, basic economic concepts and research findings in a manner conducive to being easily understood by lay persons.

        Farooq Pasha from Pakistan

 

 

 

 

 

 

 

 

 

 

 

           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings          

 

 

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, GermanyThe tackling of anti-intellectualism should follow from building a consensus that is capable of better foreseeing the consequences of the policies justified by it. Additionally, economists would be in a much better position to address anti-intellectualism if we embraced natural sciences, and built the profession as a natural offspring of other major disciplines.

Benjamin Leiva from the US

 

 

 

 

 

 

 

 

           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings           

 

 

 

6th Lindau MeetingIn my opinion, the dissemination of information is the best way to combat the ‘post-truth’ mentality. Economists and researcher in various fields of study should try to connect their work with people; the debate should come out of closed circles, be more interactive and open to the dialogue in various areas of society using simple and easily accessible communication tools.

        Giovanna Zeny from Brazil

 

 

 

 

 

 

 

 
           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings           

 

 

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, GermanyWhile I believe it is important to speak in terms everyone can understand when explaining economic ideas, economists should not simplify so much as to say ‘trade is always good’ when we know that trade creates winners and losers.

Andrew Jonelis from the US

 

 
 

 

 
 
 
 
 
 
 
 
           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings           

 

 

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, GermanyOur policies should have in mind the poorest, neediest, and least educated citizens in our societies. We need a Europe that takes care first of all of those citizens who do not travel abroad and do not speak any other idiom than their native language. Once we’ll have that Europe, we will be dramatically closer to a truly united Europe.

        Alessandro del Ponte from Italy

 

 

 

 

 

 

 

 

 

           Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings           

Blockchain Technology: ‘Proof-Of-Work’ Versus ‘Proof-Of-Stake’

Bitcoins. Photo/Credit: skodonnell/iStock.com

Bitcoins. Photo/Credit: skodonnell/iStock.com

 

Cryptocurrencies like Bitcoin and the blockchain technology that underpins them are gradually becoming household words. Although peer-reviewed research is only just beginning to develop on the topic, the cryptocurrency ecosystem is growing at an exponential rate. Everyday, new businesses, investors and researchers enter this dynamic space.

At the University of Liechtenstein, I have been working on an experimental blockchain project with Professor Dr Martin Angerer and Jonas Gehrlein, MSc from the University of Bern. Our research on blockchain technology has been an educational, demanding and exciting journey.

The terms ‘blockchain technology’ and ‘distributed ledger technology’ refer to a variety of different technologies that attempt to solve different problems. Cryptocurrencies and blockchain technology emerged after the 2007/08 global financial crisis. The most popular example of these technologies is Bitcoin.

Bitcoin is a decentralised and open-source digital currency that stores transactional data in a distributed database that is maintained by computers all around the world. The creator of Bitcoin, who is still unknown but goes by the pseudonym Satoshi Nakamoto, wanted to provide a decentralised, private and secure means of transferring value online that did not rely on trusting sovereign entities, central banks or financial intermediaries.

A major discussion in the cryptocurrency realm relates to the optimal algorithm for achieving a collective agreement on which transactions are valid and which are invalid within a distributed network. Currently, the two most popular methods are known as ‘proof-of-work’ and ‘proof-of-stake’.

Bitcoin’s proof-of-work algorithm uses large quantities of energy and hardware equipment, which have been estimated to cost approximately $400 million per year. Proof-of-stake is a newer invention that has not been rigorously tested in the market.

When my colleagues and I began our research project, we wanted to investigate the differences between these two consensus mechanisms in a laboratory environment. Our motivation was simple: if both systems achieve the same outcome but one system (proof-of-work) incurs a negative externality on the environment, then why are people still using it?

Despite the seeming superiority of proof-of-stake, market participants prefer proof-of-work. Using market capitalisation as a proxy for demand, the highest market capitalisation coins all rely on proof-of-work. But proof-of-stake is gaining popularity: Ethereum, the second largest market capitalisation coin, is expected to switch from proof-of-work to proof-of-stake during the next year.

Our research uses game theory and behavioural economics to study the strengths and weaknesses of these two competing systems in a lab environment with students.

Our first step was to boil down the complex nature of these consensus mechanisms into abstract concepts that could be easily modelled in a lab. We spent months reviewing the research literature and brainstorming possible set-ups for the experiment.

The lab setup for proof-of-work was relatively straightforward. We planned to draw from the public goods literature on network externalities. Students would be given the option to use a medium of exchange that incurred an internal personal cost or a medium of exchange that incurred an external cost for the environment.

Essentially, this represented the current fiat system versus the energy-guzzling Bitcoin. At this point, we were very excited about the direction of our research and about the contribution that it could make to the fields of economics and information science.

Unfortunately, our research hit an insurmountable obstacle when we tried to model proof-of-stake: we could not find a way to do it easily in a lab. We discussed potential drawbacks of the proof-of-stake system such as 51% attacks, deflationary spirals and uncertainty stemming from ambiguity. But we came to the conclusion that Bitcoin’s proof-of-work suffered from the same drawbacks, albeit to a lesser degree.

During my own reflection on the differences between proof-of-work and proof-of-stake, I came to the conclusion that these systems resemble our transition from a gold standard to a fiat standard. Like gold, Bitcoin uses electricity and capital equipment to mine new coins. The probability of randomly being chosen to create a block and receive a reward is equal to each miner’s amount of mining power divided by the total amount of mining power on the network.

On the other hand, proof-of-stake allows the users with the largest holdings to create coins out of thin air. In a proof-of-stake system, the probability of receiving a reward is equal to the fraction of coins held by the user divided by the total number of coins in circulation.

Following this logic, proof-of-stake would appear to be superior to proof-of-work because economic theory argues that the fiat system is superior to the gold standard due to deflationary spirals caused by hoarding. (Note, however, that my late uncle, the American economist Larry Sechrest, argued in his 1993 book, Free Banking: Theory, History, and a Laissez-Faire Model that the problems associated with the gold standard actually stemmed from regulation and not from the scarcity of gold.)

To date, my reflections have not helped us find a suitable set-up for the lab experiment: we have been unable to find a major setback of the proof-of-stake consensus mechanism. The only problem that I could find was quite philosophical in nature and too complicated to be easily modelled in a lab.

The twentieth-century Austrian logician, Kurt Gödel, argued that no system can prove its own correctness from within itself. In reference to proof-of-work and proof-of-stake, the former appears to solve Gödel’s incompleteness theorem while the latter relies on external truth to achieve consensus.

In a proof-of-work system, anyone can join the system and immediately determine the correct history of transactions in the blockchain because the correct chain is the longest chain by default. In comparison, proof-of-stake has not developed a method for ensuring that every computer in the network comes to the same conclusion on the correct history of transactions from within the system.

Instead, proof-of-stake relies on an external third party or host of third parties to establish agreement on the history of transactions. In plain terms: proof-of-stake establishes truth by appealing to an external anchor while proof-of-work establishes proof from within. Although the introduction of counterparties may not be a problem in every case, the original goal of the blockchain technology was to create consensus without intermediaries.

In the end, we could not find a suitable way to model proof-of-stake in a lab with humans. In our own analysis of this problem, we realised that there was a fundamental problem with the premise of our study: we were trying to model a lab experiment with humans based on a technology that was designed to minimise human interaction.

Although we have encountered this major setback in our study, we have learned a tremendous amount about blockchain technology and about our own strengths and weaknesses as researchers. Instead of giving up, we are going in a new direction with our blockchain research. After all, the journey for pioneers is never paved.