Tomas Lindahl and the Surprising Instability of DNA

Today we know that each and every day, our DNA is damaged by UV light, free radicals or carcinogenic substances. And even without such external attacks, DNA can undergo many changes, for instance during replication. But in the 1960s, with the discovery of DNA’s double helix structure only one decade earlier, DNA was viewed as something inherently stable.

 

Tomas Lindahl during the Nobel Prize press conference in Stockholm in December 2015. Photo: Holger Motzkau, CC BY-SA 3.0

Tomas Lindahl during the Nobel Prize press conference in Stockholm in December 2015. Lindahl has worked in the UK for several decades and is emeritus director of Cancer Research UK at Clare Hall Laboratory in Hertfordshire. Photo: Holger Motzkau, CC BY-SA 3.0

In 1969, Tomas Lindahl set out to tackle a question that seemed so far-fetched at the time that he didn’t even apply for a grant. Instead, to study the stability or instability of DNA exerimentally, he used money he had been awarded beforehand.

Already as a postdoctoral researcher in Princeton, Tomas Lindahl had found that tranfer RNA, or tRNA, could be quite unstable under certain conditions. This finding ran against the current belief that DNA should be extremely stable. Since RNA is usually single-stranded, some reduced stability would be expected. But still Tomas Lindahl couldn’t get the question of the inherent stability or instability of DNA out of his mind.

In the US, he had been the first to describe the previously unknown enzymes DNA ligase and DNA exonuclease, both important for repairing DNA breaks. But at the time, “we did not have the techniques available to attempt to prove their roles in intracellular recombination events,” Tomas Lindahl writes in his autobiography for Nobelprize.org.

Back in Stockholm and with his own small lab, he now began to look for signs of DNA decomposition in a neutral aqueous solution. He decided to start out with some pilot experiments, “and if the results did not seem promising – quietly bury the project,” Lindahl describes these early steps in his Nobel Lecture. But the results were indeed promising, and so he carried on with “a series of time-consuming experiments to attempt to quantify and characterise the very slow degradation of DNA solutions under physiological conditions”.

With the help of chromatography, he found that some base residues were lost from DNA. Also, the remaining DNA bases had changed, “the most important of these is the deamination of cytosine residues to uracil”. This change is described in the graph below, deamination meaning ‘loss of an aminogroup’.

When Lindahl started to quantify these observed changes, he found the startling number of thousands of DNA changes per day in any mammalian cell: a number that should have made the development of life on earth as we know it impossible. The compelling conclusion was that there were powerful DNA repair mechanisms at work round the clock.

 

Base excision repair

 

Step by step, Lindahl was able to describe the pathway of a repair mechanism that became kown as ‘base excision repair’. Several enzymes need to work together to find, to excise, and finally to replace a damaged nucleotide. Cytosine, one of the four building blocks of DNA, easily loses one aminogroup, as mentioned above, the result is a base called uracil. But uracil cannot bind with guanine, the other half of the GC base pair. Now, an enzyme called glycosylase detects this problem and excises uracil. Next, the enzyme DNA polymerase fills the gap with cytosine, and finally the strand is sealed by DNA ligase. By finding this pathway, Lindahl’s research came full circle: he could now prove the role of the enzyme he had first described as a postdoc years earlier.

In 2015, the Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar ‘for mechanistic studies of DNA repair’. Aziz Sancar has described ‘nucleotide excision repair’, the mechanism that cells use to repair UV damage to DNA, and Paul Modrich has demonstrated how cells correct errors that occur when DNA is replicated during cell division. This repair mechanism is called ‘mismatch repair’.

This means that base excision repair is only one repair pathway among many, albeit an important one. And not all pathways have been discovered yet. Correspondingly, there are many different enzymes involved in the various repair pathways. And each and every enzyme is an interesting starting point for cancer drug research, because inhibiting one of these enzymes also means suppressing DNA repair. As Lindahl himself likes to point out: these repair pathways can be seen as a ‘double-edged sword’, because normal cells use them all the time to remain healthy, but cancer cells use them as well to stay alive and cancerous.

 

Angelina Jolie at the launch of the UK initiative on preventing sexual violence in conflict, May 2012. One year later, she made public that she is the carrier of a BRCA mutation and that she underwent a double mastectomy and later an ovariectomy to reduce her cancer risk. BRCA genes are responsible for DNA repair, their mutations can lead to a very high cancer risk. Photo: Foreign and Commonwealth Office, Open Government Licence v1.0 (OGL)

Angelina Jolie at the launch of the UK initiative on preventing sexual violence in conflict, in May 2012. One year later, she made public that she is the carrier of a BRCA mutation: BRCA genes are responsible for DNA repair, and their mutations can lead to a sharply increased cancer risk. Photo: Foreign and Commonwealth Office, Open Government Licence v1.0 (OGL)

As a result of this research, novel ‘targeted therapies’ now aim to affect the repair pathways that some cancer cells rely on, hopefully leaving healthy cells unaffected. One drug that is mentioned in the scientific material of the Royal Swedish Academy of Sciences is the cancer drug Olaparib: it’s a PARP inhibitor, inhibiting a polymerase named PARP (poly ADP ribose polymerase), one of the many enzymes of DNA repair. It is approved for use against cancers in patients with BRCA1 or BRCA2 mutations.

Female carriers of these mutations are five times more likely to develop breast cancer and up to thirty times more likely to develop ovarian cancer. These mutations, which are more frequent in certain popluation groups like for instance Ashkenazi jews, became widely known when Hollywood actress Angelina Jolie explained publicly that she was a BRCA1 carrier and that she had a double mastectomy and ovariectomy to hopefully prevent her getting cancer. After she made this step public, there has been a marked increase in women seeking tests for their BRCA status – an important step for making an informed decision about medical procedures.

In his 2015 Nobel Lecture, Tomas Lindahl concluded that many more small molecules than are currently known can probably damage DNA, meaning “that there are more DNA repair enzymes waiting to be discovered”. And each and every one can be viewed as a new hope for cancer patients. Lindahl’s vision for the future is that cancer will become a disease of old age, like type 2 diabetes: you need to take some medication against it, but you can live with it and enjoy a good quality of life.

This summer, Tomas Lindahl will visit the Lindau Nobel Laureate Meetings for the first time. We’re looking forward to welcoming him in Lindau and to hearing his lecture on DNA repair.

 

The Helix Bridge  is a pedestrian bridge linking Marina Centre with Marina South in Singapore. Its design is based on the double helix model of DNA. This can be seen best at night, when pairs of the coloured letters G and C, as well as A and T, are lit up in red and green. They represent cytosine, guanine, adenine and thymine, the four bases of DNA. Photo: joyt/iStock.com

The Helix Bridge is a pedestrian bridge in Singapore linking Marina Centre with Marina South. Its design is based on the double helix model of DNA. This can be best seen at night, when pairs of the coloured letters G and C, as well as A and T, are lit up in red and green. They represent cytosine, guanine, adenine and thymine, the four bases of DNA. Photo: joyt/iStock.com

 

Tomas Lindahl, Entdecker der DNA-Reparatur

Heute wissen wir, dass unsere DNA jeden Tag durch UV-Strahlung, freie Radikale und andere schädliche Substanzen beschädigt wird. Und selbst ohne äußere Einflüsse unterliegt das Erbgut in unseren Zellen ständigen Veränderungen, beispielsweise während der Zellteilung. Doch in den 1960er Jahren dachte man, die DNA-Doppelhelix sei extrem stabil – ihre Struktur war erst ein Jahrzehnt zuvor entdeckt worden.

 

Tomas Lindahl bei der Nobelpressekonferenz in Stockholm im Dezember 2015. Er arbeitete viele Jahrzehnte in Großbritannien und jetzt emeritierter Direktor von Cancer Research UK/Clare Hall Laboratory. Foto: Holger Motzkau, CC BY-SA 3.0

Tomas Lindahl bei der Nobelpreis-Pressekonferenz in Stockholm im Dezember 2015. Er forschte viele Jahrzehnte in Großbritannien und ist jetzt emeritierter Direktor von Cancer Research UK/Clare Hall Laboratory. Foto: Holger Motzkau, CC BY-SA 3.0

Im Jahr 1969 machte sich Tomas Lindahl nun daran, die Stabilität oder Instabilität der menschlichen DNA experimentell zu erforschen. Diese Fragestellung galt damals als derartig abwegig, dass er sich nicht traute, Forschungsgelder hierfür zu beantragen. Stattdessen verwendete er andere Gelder, die bereits bewilligt waren.

Schon als Postdoc in den USA hatte er festgestellt, dass tRNA unter bestimmten Bedingungen erstaunlich instabil sein kann. Das widersprach zwar der herrschenden Vorstellung, dass DNA sehr stabil ist, doch da RNA in der Regel einsträngig vorkommt, könnte der fehlende Strang eine Erklärung hierfür liefern. Seine Kollegen vermuteten sogar, er hätte die Probe mit seinen Fingern verunreinigt und so unwissentlich die Ergebnisse verfälscht. Trotz aller Zweifel konnte Lindahl diese Entdeckung nicht vergessen, ebenso wenig die Frage, ob DNA nun stabil ist oder nicht.

In den USA hatte er als Erster die bis dahin unbekannten Enzyme DNA-Ligase und DNA-Exonuclease beschrieben, beide sind wichtige Komponenten der DNA-Reparatur. Doch damals „hatten wir nicht die Technik, die wir gebraucht hätten, um zu versuchen, ihre genaue Rolle in den Vorgängen im Zellinnern zu entschlüsseln“, schreibt Tomas Lindahl in seiner Autobiografie auf Nobelprize.org.

Zurück in Stockholm begann Lindahl nun ernsthaft mit der Suche nach DNA-Abbauprozessen, er hatte mittlerweile sein eigenes kleines Labor. Zunächst führte er ein paar Vorversuche durch, und „wenn diese nicht aussagekräftig gewesen wären, dann hätte ich das Projekt sang- und klanglos beerdigt“, erklärt er in seiner Nobel Lecture in Stockholm Ende 2015. Diese Versuche stellten sich jedoch als sehr vielversprechend heraus, daher plante er als nächstes eine aufwändige Versuchsreihe „um die langsame Zersetzung von DNA unter physiologischen Bedingungen zu charakterisieren und zu quantifizieren“.

Er stellte fest, dass tatsächlich einige Bausteine der DNA-Basen sich in seinen Proben von der DNA lösten. Als Konsequenz davon veränderten sich auch die verbliebenen Basen; „die wichtigste Veränderung stellt hierbei die Desaminierung von Cytosin zu Urasil dar“. Dieser Prozess wird in der Grafik unten beschrieben. ‘Desaminierung’ beschreibt den Verlust einer Aminogruppe.

Als sich Lindahl nun daran machte, die gefundenen Veränderungen zu quantifizieren, stellte er fest, dass es in jeder Säugetierzelle jeden Tag tausende DNA-Veränderungen gibt – eine Größenordnung, die die Entwicklung von Leben auf der Erde eigentlich hätte verhindern müssen. Die zwingende Schlussfolgerung war: Es muss ausgefeilte DNA-Reparaturmechanismen geben, die rund um die Uhr Fehler aufstöbern und beseitigen.

 

Base excision repair

 

Schritt für Schritt gelang es Lindahl nun, den DNA-Reparaturweg zu beschreiben, der heute als Basen-Exzisionsreparatur (base excision repair) bekannt ist. Damit das Finden, Entfernen und Ersetzen von beschädigten Nukleotiden funktionieren, müssen viele verschiedene Enzyme zusammenarbeiten. Wie bereits erwähnt, neigt das Nukleotid Cytosin dazu, eine Aminogruppe zu verlieren, das Ergebnis ist eine Base namens Uracil. Nur leider kann Uracil mit dem gegenüberliegenden Guanin keine Wasserstoffbrücken bilden. Das Enzym DNA-Glykolase entdeckt diesen Defekt und entfernt das Uracil. Weitere Enzyme beseitigen die letzten Basenreste. Das Enzym DNA-Polymerase füllt nun die Lücke mit Cytosin und DNA-Ligase verschließt am Ende den Strang: Endlich konnte Lindahl die Funktion jenes Enzyms beschreiben, das er Jahre zuvor entdeckt hatte.

Im Jahr 2015 erhielten Tomas Lindahl, Paul Modrich und Aziz Sancar den Chemienobelpreis für ihre Studien zur DNA-Reparatur. Während sich Lindahl vor allem mit dem Austausch einzelner Basen befasste, untersuchte Sancar den Austausch von größeren DNA-Abschnitten von bis zu 30 Basenpaaren. Nötig wird dieser Austausch vor allem bei typischen UV-Schäden. Modrich wiederum studierte den Prozess der Zellteilung, hierbei vor allem Basenfehlpaarungen und wie diese repariert werden können (mismatch repair).

Die von Lindahl entschlüsselte ‘Basen-Exzisionsreparatur’ ist also nicht der einzige DNA-Reparaturweg: Er ist einer unter vielen, wenn auch ein sehr wichtiger. Und wir dürfen auch nicht vergessen, dass noch nicht alle Reparaturwege bekannt sind. Wenn es also zahlreiche Reparaturwege gibt, dann benötigen diese eine noch unbekannte Anzahl von Enzymen, damit sie funktionieren. Und jedes dieser Enzyme stellt wiederum einen vielversprechenden Ansatzpunkt für neue Krebstherapien dar, denn wer die Bildung eines dieser Enzyme unterdrücken kann, der unterdrückt damit oft auch die DNA-Reparatur. Da Krebszellen ebenfalls auf solche Reparaturwege angewiesen sind, kann dies als Ansatzpunkt zur Entwicklung neuer Medikamente genutzt werden, die weniger Nebenwirkungen haben, das ist zumindest die Hoffnung. Tomas Lindahl selbst bezeichnet die DNA-Reparatur als ein ‘zweischneidiges Schwert’: Einerseits brauchen gesunde Zellen diese Reparaturwege um gesund zu bleiben, andererseits benutzen Krebszelle dieselben Mechanismen, um weiterhin Schaden anrichten zu können.

 

Schauspielerin Angelina Jolie im Mai 2012. Ein Jahr später machte sie ihre Entscheidung öffentlich, sich aufgrund einer BRCA-Mutation mehreren Operationen zu unterziehen, um ihr Krebsrisiko zu senken. Foreign and Commonwealth Office, Open Government Licence v1.0 (OGL)

Schauspielerin Angelina Jolie im Mai 2012. Ein Jahr später machte sie ihre Entscheidung öffentlich, sich aufgrund einer BRCA-Mutation mehreren Operationen zu unterziehen um ihr Krebsrisiko zu senken. Foto: Foreign and Commonwealth Office, Open Government Licence v1.0 (OGL)

Auf Grundlage dieser Forschung werden nun konkrete Krebsmedikamente entwickelt, die möglichst die Reparatur von Krebszellen verhindern und gleichzeitig gesunde Zellen so wenig wie nötig belasten sollen. Ein solches Medikament wird in dem wissenschaftlichen Begleitmaterial der Königlichen Schwedischen Akademie der Wissenschaften genannt: Olaparib, ein sogenannter PARP-Inhibitor, der ein bestimmtes Enzym der DNA-Reparatur hemmt. Es ist zugelassen zur Behandlung von Eierstockkrebs, wenn eine der beiden Genmutationen BRCA1 oder BRCA2 vorliegt.

Frauen mit einer dieser Mutationen haben im Durchschnitt ein fünffach erhöhtes Brustkrebsrisiko und ein bis zu 30-fach erhöhtes Risiko an Eierstockkrebs zu erkranken. Die BRCA-Mutationen wurden weltweit bekannt, als die berühmte Hollywood-Schauspielerin Angelina Jolie im Jahr 2013 öffentlich machte, dass sie selbst Trägerin der Mutation BRCA1 ist und sich deshalb präventiv das Brustgewebe und später auch die Eierstöcke entfernen ließ. Nach dieser öffentlichen Erklärung stieg weltweit die Nachfrage nach solchen Tests, mit denen vor allem Frauen aus Risikogruppen oder -familien Klarheit über ihren Genstatus bekommen können.

In seiner Nobel Lecture erklärte Tomas Lindahl, dass es wahrscheinlich viele kleine Moleküle gibt, die unsere DNA schädigen können, die aber noch gar nicht als dafür bekannt sind. „Deshalb gibt es auch noch zahlreiche DNA-Reparaturwege, die darauf warten entdeckt zu werden.“ Und jeder einzelne neu entdeckte Reparaturprozess kann als neue Chance für Krebspatienten gesehen werden. Lindahls Hoffnung für die Zukunft ist, dass Krebs „eine Alterskrankheit wird, ähnlich wie Typ-2-Diabetes“: Man muss Medikamente dagegen nehmen, aber man kann mit der Erkrankung leben und sich dabei einer hohen Lebensqualität erfreuen.

Diesen Sommer wird Tomas Lindahl zum ersten Mal die Lindauer Nobelpreisträgertagung besuchen. Wir freuen uns sehr darauf, ihn in Lindau begrüßen zu dürfen, und freuen uns auf seinen Vortrag über DNA-Reparatur.

 

Die Helix-Brücke in Singapur. Ihr Design wurde von der DNA-Doppelhelix inspiriert. Das sieht man besonders gut bei Nacht, wenn die vier Buchstaben G, C, A und T in verschiedenen Farben leuchten. Sie stehen für Cytosin, Guanin, Adenin und Thymin, die vier Grundbausteine der DNA. Foto: joyt/iStock.com

Das Design der Helix-Brücke in Singapur wurde von der DNA-Doppelhelix inspiriert. Das sieht man besonders gut bei Nacht, wenn die vier Buchstaben G, C, A und T in verschiedenen Farben leuchten. Sie stehen für Cytosin, Guanin, Adenin und Thymin, die vier Grundbausteine der DNA. Foto: joyt/iStock.com

Nobel Laureate Oliver Smithies passed away

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

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

 

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

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

 

Smithies with his wife Prof. Nobuyo Maeda at the

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

 

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

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

 

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

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

 

 

Ten Astonishing Facts About Longevity

Constant rise in life expectancy after 1840: in early years, the most gains were achieved by reducing child mortality. In the mid-19th century, infectious diseases  were fought with vaccines, in the 20th century with antibiotics. Source: US National Institute on Aging, data from the Human Mortality Database

Constant rise in life expectancy after 1840: In early years, the most gains were achieved by reducing child mortality. In the mid-19th century, infectious diseases were fought with vaccines, and in the 20th century with the help of antibiotics. Source: US National Institute on Aging, data from the Human Mortality Database

In developed countries, life expectancy is still increasing linearly at a rate of about three months per year for women, and at a slightly lower rate for men. And also developing countries have witnessed considerable increases since the mid-20th century, albeit with setbacks like the HIV epidemic in Africa.
This trend has been evident since the mid-19th century – and it has sparked a longstanding scientific debate: Will this trend continue indefinitely into the future? Or is there a biological limit to human life? The latest contribution to this debate is a statistical study from the Albert Einstein College of Medicine in New York.

 

1. Most increases not in oldest age group

In this study, Jan Vijg, a Dutch-American geneticist, and his team analysed data from the Human Mortality Database that spans 38 countries and is run by American and German researchers. Since life expectancy increase is still strong, the researchers needed other theories and data if they are searching for indicators of a future slowdown. Their theory was: If there is no upper lifespan limit, the age group with the biggest increase in survival should get older continually. But contrary to this assumption, the largest increase in survival rates has plateaued around the age of 99 in 1980, and has only increased very slightly since. They interpred this plateau effect as an early sign of slowdown.

 

2. Supercentenarians rarely older than 115

To further test their theories, Dr. Vijg’s team also used data from the International Database on Longevity from the Max Planck Institute for Demographic Research in Rostock, Germany. Watch out! Now the ages of lucky individuals are analysed, whereas before, increases in age groups were studied. Jan Vijg’s team found that the maximum age reached by individuals plateaued at 115 years in the mid-1990s, with very few, yet famous, exceptions. The researchers see this as another sign of slowdown. “It seems highly likely we have reached our ceiling,” says Jan Vijg. “From now on, this is it. Humans will never get older than 115.”

 

3. Japan is different

Interestingly enough, the longevity database used by the Vijg team was assembled at the Max Planck Institute for Demographic Research, that is also one of the main contributers to the Human Mortality Database. But James Vaupel, founding director of this institute, doesn’t share Dr. Vijg’s interpretation. One of his objections is that in Japan, the age group enjoying the fastest growth is still getting older; this holds true for a few other developed countries as well. As James Vaupel wrote in an earlier paper, together with Jim Oeppen: Experts asserting that “life expectancy is approaching a ceiling … have repeatedly been proven wrong.”

 

Every third baby born in Britain today has a good chance of celebrating its 100th birthday, according to the Office for National Statistics ONS. Photo: iStock.com/David Freund

Every third baby born in Britain today has a good chance of celebrating its 100th birthday, according to the Office for National Statistics ONS. Photo: iStock.com/David Freund

4. Highest life expectancy, lowest birthrate

Japan has the highest life expectancy in the world and thus is of special interest to demographers: currently 86.8 years for women and 80.5 years for men. Japan also has one of the lowest birthrates. A web population clock from Tokyo University predicts that the last Japanese child will be born in the year 3,776 if this latter trend is not reversed – meaning that the Japanese will die out about one hundred years later. Some estimates suggest that by the year 2050, up to one million centenarians will live in Japan.

 

5. Can ageing be reversed?

In all other species, lifespans can be increased by genetic interventions, certain proteins or dietary changes. Several teams at James Vaupel’s institute in Rostock conduct research on these topics with different model animals, as well as many other research teams worldwide. So why should humans be an exception? “There is no time bomb that explodes at a certain age,” says Linda Partridge, director at the Max Planck Intitute for Biology of Ageing in Cologne, Germany, who is also specialising in strategies to influence ageing processes. In recent years, ageing in mice could be reversed with telomerase, and similar experiments were conducted successfully with human cells.

 

6. Animals that never age

There are some animals that don’t age. The biologist and mathematician Prof. Annette Baudisch for instance studied species like this, for instance robins and the freshwater polyp Hydra vulgaris, i.e. their mortality rate doesn’t increase with age, and they retain similar levels of health throughout their lives. Unfortunately, humans don’t belong in this group, the same holds true for most lab animals. But these surprising species may have some traits that could point to strategies against ageing as we know it in humans; human ageing comprises many factors: the slowdown of biological processes, the shrinking of organs, the deposit of lipofuscin, the accumulation of genetic mutations, etc.

 

Rita Levi Montalcini was an Italian neurobiologist who was awarded the 1986 Nobel Prize in Physiology or Medicine for her discovery of nerve growth factor, together with Stanley Cohen. She celebrated her 103rd birthday in 2012 and died the same year. Photo: Peter Badge

Rita Levi Montalcini was an Italian neurobiologist who received the 1986 Nobel Prize in Physiology or Medicine for her discovery of nerve growth factor, together with Stanley Cohen. She celebrated her 103rd birthday in April 2012. Photo: Peter Badge

7. Game changer: advances in medicine

Several researchers argue that Jan Vijg’s team didn’t take the medical advances of the future into account, that might target the afore mentioned ageing processes, as well many deadly diseases. “The result in this paper is absolutely correct, but it says nothing about the potential of future medicine, only the performance of today’s and yesterday’s medicine,” says biomedical gerontologist Aubrey de Grey of the SENS Research Foundation in Mountain View, California. Conversely, potentially negative trends like the global obesity epidemic, with the side effects of soaring type 2 diabetes and nonalcoholic fatty liver disease numbers, are also not taken into account.

 

8. New trends lower life expectancy

Even today, the increase in life expectancy is being reversed in developed countries for certain groups. As Nobel Laureate Angus Deaton and Prof. Anne Case showed, white middle-aged Americans without college degrees are dying younger than in the past. For all other ethnic groups, life expectancy is still rising in the US, but for this group it’s falling. The researchers could also explain how prescription drug abuse, alcohol and suicide shortens the lives of too many middle-aged Americans.

 

9. Centenarians are exceptions, not examples

Centenarians seem to be quite an exceptional group, as a recent German study showed, again: One third of the patients over 100 years of age didn’t show any signs of dementia, three quarters were not depressed, almost a quarter didn’t take any drugs on a regular basis, and an astounding 65 percent hadn’t been admitted to hospital in the last twelve months. If this group is so healthy, gerontological research might learn a lot from them – but because they’re so special, maybe they’re not the best group to predict everyone’s ageing process.

 

10. Longer life due to Nobel prize

Winning the Nobel prize adds one or two years of life expectancy. The British economists Matthew Rablen and Andrew Oswald wrote: “It has been known for centuries that the rich and famous have longer lives than the poor and ordinary,” but the causality behind that remained unclear. That’s why they looked for cases where a sudden rise in status occured, and biographical data were also available: they found Nobel Laureates. And really: the positive status shock of winning a Nobel prize adds one or two years compared to researchers of the same age and from the same country who were merely nominated for this prestigious prize.

 

Only time and future studies will tell if humanity has already reached an ‘age ceiling’ – or not. But if we consider quality of life together with the quantity of years, it becomes evident that adding years doesn’t automatically mean more healthy years. On the contrary, additional years often mean more years of disease. This is why Jan Vijg wrote in his study that we should pay more attention to our  ‘health span’ instead of concentrating solely on our lifespan.

 

Exercise is a vital ingredient both to longevity and to healthy ageing. Others are: normal weight, a diet rich in fibres and low in sugar and red meat - and meeting people, having fun and playing games to ward off dementia. Photo: iStock.com/Horsche

Exercise is a vital ingredient both to longevity and to healthy ageing. Others are: normal weight, a diet rich in fibres and low in sugar and red meat – and meeting people, having fun and playing games to ward off dementia. Photo: iStock.com/Horsche

Langlebigkeit: zehn erstaunliche Aspekte

Steigende Lebenserwartung seit 1840: anfangs sank vor allem die Kindersterblichkeit, ab Ende des 19. Jahrhunderts wurden Infektionen mit Impfungen bekämpft, im 20. Jahrhundert mit Antibiotika. Quelle: US National Institute on Aging, mit Daten von der Human Mortality Database

Steigende Lebenserwartung seit 1840: Anfangs sank vor allem die Kindersterblichkeit, ab Ende des 19. Jahrhunderts wurden Infektionskrankheiten mit Impfungen bekämpft, im 20. Jahrhundert mit Antibiotika. Quelle: US National Institute on Aging, mit Daten von der Human Mortality Database

In den entwickelten Ländern steigt die durchschnittliche Lebenserwartung weiterhin unbeirrt um drei Monate pro Jahr für Frauen, etwas langsamer für Männer. Auch die Entwicklungsländer konnten seit der Mitte des 20. Jahrhunderts deutliche Anstiege verzeichnen, aber es gab auch Rückschläge wie die HIV-Epidemie in Afrika.
Diesen Trend der linear steigenden Lebenserwartung existiert in Europa und den USA seit dem mittleren 19. Jahrhundert, und er hat eine langlebige wissenschaftliche Debatte ausgelöst: Wird es endlos so weitergehen? Oder gibt es eine natürliche Obergrenze für menschliches Leben? Der neueste Beitrag zu diesen Fragen stammt aus dem Albert Einstein College of Medicine in New York.

 

1. Älteste Gruppe wächst nicht mehr
In dieser Studie analysiert der amerikanisch-niederländische Genetiker Jan Vijg die Daten der ‘Human Mortality Database’, einer Datenbank mit Sterbedaten aus 38 Ländern, die von deutschen und amerikanischen Forschern gemeinsam betrieben wird. Da die durchschnittliche Lebenserwartung weiterhin ansteigt, benötigten die Forscher eine andere These, um einer möglichen künftigen Abremsung auf die Schliche zu kommen. Sie sagten sich: Wenn es keine absolute Obergrenze gäbe, dann müsste eigentlich die Gruppe mit dem größten Zuwachs immer älter werden. Das stimmt aber nicht. Stattdessen stellten sie fest, dass diese Gruppe seit ungefähr 1980 bei 99 Jahren stagniert, seitdem ist deren Alter nur minimal gestiegen. Diesen Plateau-Effekt interpretieren sie als einen ersten Hinweis auf eine Verlangsamung des Anstiegs.

 

2. Hochbetagte selten älter als 115
Um weitere Effekte in diese Richtung zu finden, untersuchte Jan Vijg und seine Mitarbeiter als nächstes die Daten der Langlebigkeits-Datenbank (International Database on Longevity), die vom Max-Planck-Institut für demografische Forschung in Rostock betrieben wird. Achtung: Jetzt geht es um das Alter einzelner Individuum, im vorigen Punkt ging es um Altersgruppen. Das Vijg-Team fand heraus, dass seit den 1990er Jahren kaum jemand älter als 115 Jahre wurde, mit wenigen Ausnahmen. Das maximale Alter steigt also kaum noch – ein weiterer Hinweis auf eine Verlangsamung. “Es erscheint mir sehr wahrscheinlich, dass wir eine ‘Decke’ erreicht haben”, kommentiert Vijg. “Wir müssen konstatieren: Das war’s. Die Menschen werden nicht mehr älter werden als 115.”

 

3. In Japan laufen die Uhren anders
Die Langlebigkeits-Datenbank, auf deren Daten sich das Team von Vijg bezieht, wurde vom Max-Planck-Institut für demografische Forschung eingerichtet, das auch die ‘Human Mortality Database’ mit betreibt. Gründungsdirektor James Vaupel teilt allerdings die Interpretation seiner Kollegen aus New York nicht. Einer seiner Einwände lautet: In Japan, einem sehr wichtigen Land für Demografen, wird die Altergruppe mit der höchsten Wachstumsrate weiterhin immer älter, ebenso in einzelnen europäischen Ländern. In einem früheren Artikel schrieb Direktor Vaupel zusammen mit Jim Oeppen: Vorhersagen, dass “die steigende Lebenserwartung an eine Decke stößt… wurden bereits vielfach gemacht und widerlegt.”

 

Jedes dritte Baby, das heute in Großbritannien zur Welt kommt, wird voraussichtlich seinen 100. Geburtstag feiern können, mein die britische Nationale Statistikbehörde. Foto:  iStock.com/David Freund

Jedes dritte Baby, das heute in Großbritannien zur Welt kommt, wird voraussichtlich seinen 100. Geburtstag feiern können, laut der britischen Nationale Statistikbehörde ONS. Foto: iStock.com/David Freund

4. Höchste Lebenserwartung, niedrigste Geburtenrate
Wegen der höchsten Lebenserwartung weltweit kann Japan als Lieblingsland der Demografen bezeichnet werden: Gegenwärtig beträgt sie 86,8 Jahre für Frauen und 80,5 Jahre für Männer. Gleichzeitig weist Japan eine der niedrigsten Geburtenraten der Welt auf, zusammen mit Südkorea, Deutschland, Italien, Spanien und Griechenland. Die Zahlen einer Art Bevölkerungs-Uhr, kürzlich auf einer Website der Universität Tokyo installiert, ergeben, dass voraussichtlich im Jahr 3776 das letzte japanische Kind geboren werden wird, wenn kein Trend sich umkehrt – und spätestens hundert Jahre später werden die Japaner komplett aussterben. Manche Hochrechnungen ergeben auch, dass in Japan bereits 2050 über eine Million Hundertjährige leben könnten.

 

5. Kann Altern rückgängig gemacht werden?
In allen Tiermodellen kann die Lebensspanne verlängert werden, sei es durch genetische Veränderungen, durch Nahrungsumstellung oder bestimmte Proteine. Viele Forscherteams weltweit arbeiten mit unterschiedlichen Spezies an dieser Frage, so auch mehrere Gruppen an Vaupels Institut in Rostock. Warum sollten Menschen bei diesem Thema die absolute Ausnahme sein? “Es gibt keine Zeitbombe, die in einem bestimmten Alter losgeht”, kommentiert Direktorin Linda Partridge vom Max-Planck-Institut für Biologie des Alterns die Ergebnisse ihrer New Yorker Kollegen. Auch sie hat sich auf Alterungsprozesse spezialisiert und darauf, wie man diese aufhalten oder rückgängig machen kann. In den letzten Jahren gab es tatsächlich ein paar spektakuläre Versuche, bei denen das Altern von Mäusen und von menschlichen Zellkulturen mit Telomerase rückgängig gemacht werden konnte.

 

6. Tiere, die nicht altern
Manche Spezies altern nicht, das heißt, ihre Sterblichkeit steigt mit zunehmendem Alter nicht an und sie erfreuen sich gleichbleibender Gesundheit. Prof. Annette Baudisch studierte solche Tiere, zum Beispiel Rotkelchen oder den Süßwasserpolyp Hydra vulgaris. Leider gehören wir Menschen nicht in diese Gruppe, auch den meisten Labortieren ist das nicht vergönnt. Doch diese ungewöhnlichen Tiere könnten manche Eigenschaften haben, die Wege zeigen, wie man das menschliche Altern bekämpfen kann, das sich aus vielen verschiedenen Faktoren zusammensetzt: verlangsamte biologische Prozesse, schrumpfende Organe, Ablagerung von Alterspigment, angesammelte Gendefekte, usw.

 

Rita Levi Montalcini war eine italienische Neurobiologin. Sie erhielt den Medizinnobelpreis 1986 für die Entdeckung des Nervenwachstumsfaktors, zusammen mit Stanley Cohen. Im April 2012 feierte sie ihren 103. Geburtstag. Foto: Peter Badge

Rita Levi Montalcini war eine italienische Neurobiologin. Sie erhielt den Medizinnobelpreis 1986 für die Entdeckung des Nervenwachstumsfaktors, zusammen mit Stanley Cohen. Im April 2012 feierte sie ihren 103. Geburtstag. Foto: Peter Badge

7. Medizinischer Fortschritt
Mehrere Forscher haben kritisch angemerkt, dass das Team um Jan Vijg künftige Fortschritte in der Medizin nicht eingerechnet hätte, die sich auch gegen die genannten Alterungsprozesse richten könnten, sowie die Behandlung heute tödlicher Krankheiten stark verbessern werden. “Die Ergebnisse dieser Studie sind absolut korrekt, sie besagt allerdings nichts über die Medizin der Zukunft, sie bewertet nur die Fähigkeiten der heutigen und gestrigen Medizin”, erklärt Aubrey de Grey, ein Gerontologe von der SENS Research Foundation in Mountain View, Kalifornien. Umgekehrt sind aber potentiell negative Trends auch nicht eingerechnet, wie die weltweit um sich greifende Epidemie der Fettleibigkeit, die einen steilen Anstieg von Diabetes-Fällen nach sich zieht, ebenso die neue Erkrankung Nicht-alkoholische Fettleber, die bald die häufigste Ursache für Lebertransplantationen in den USA sein wird.

 

8. Unerwartet sinkende Lebenserwartung
Schon heute gibt es bei bestimmten Bevölkerungsgruppen in der entwickelten Welt einen Rückgang der Lebenserwartung. Wirtschaftsnobelpreisträger Angus Deaton konnte zusammen mit Prof. Anne Case zeigen, dass weiße Amerikaner mittleren Alters ohne höhere Bildung heute früher sterben als in vergangenen Jahren. Alle anderen US-amerikanischen Bevölkerungsgruppen erfreuen sich nach wie vor einer steigenden Lebenserwartung, nur für diese Gruppe hat sich der Trend umgekehrt. Die Forscher fanden heraus, dass vor allem Alkohol-, Drogen- und Medikamentenmissbrauch, sowie Selbstmorde für diese erschreckende Trendumkehr verantwortlich sind.

 

9. Hundertjährige sind Ausnahmen
Eine neue Studie der AOK Nordost zeigte mal wieder, dass Hundertjährige eine ganz besondere Gruppe sind: Ein Drittel der untersuchten Patienten über 100 zeigte keinerlei Anzeichen von Demenz, drei Viertel waren überhaupt nicht depressiv, knapp ein Viertel nahm nicht regelmäßig Medikamente, und erstaunliche 65 Prozent hatte im Studienjahr 2015 keinen Tag im Krankenhaus verbracht. Gerontologen können sicher viel von dieser ungewöhnlichen Gruppe lernen – aber sie eignet sich nicht unbedingt, um den allgemeinen Alterungsprozess zu beschreiben.

 

10. Länger leben mit Nobelpreis
Wer einen Nobelpreis erhält, bekommt gleichzeitig bis zu zwei Jahre Lebenszeit hinzu. Die beiden britischen Ökonomen Matthew Rablen und Andrew Oswald wollten der Frage nachgehen, warum weltweit die Reichen und Berühmten länger leben als die Armen und Unbekannten. Das Phänomen ist zwar seit Jahrhunderten bekannt, aber die ursächliche Erklärung ist nur unzureichend erforscht. Also suchten sie eine Gruppe, die schlagartig eine große Portion ‘Status’ erhält – und fanden die Nobelpreisträger. Tatsächlich bedeutet der prestigeträchtige Preis, dass die Empfänger durch den ‘positiven Status-Schock’ bis zu zwei Lebensjahre dazugewinnen, sogar verglichen mit Forschern gleichen Alters aus dem gleichen Land, die ebenfalls für einen Nobelpreis nominiert waren.

 

Nur die Zukunft und künftige Studien werden klären können, ob die Menschheit tatsächlich schon die ‘Decke’ der Lebenserwartung erreicht hat oder nicht. Wenn man jedoch nicht nur die Menge an Jahren betrachtet, sondern auch die Lebensqualität, wird schnell klar, dass zusätzliche Jahre nicht immer auch gesunde Jahre sind. Ganz im Gegenteil: Mehr Lebensjahre bedeuten häufig auch mehr Krankheitsjahre. Deshalb schließt Jan Vijg seine Studie auch mit dem Hinweise auf die ‘Gesundheitsspanne’, Englisch ‘health span’, auf die wir uns künftig konzentrieren sollten, anstatt immer nur auf die quantitative Lebensspanne zu achten.

 

Bewegung und Sport sind unverzichtbar, wenn man gesund alt werden möchte. Ferner ist es wichtig, sein Gewicht zu halten, wenig Zucker und rotes Fleisch, dafür aber viele Ballaststoffe zu essen, wie sie in Rohkost, Obst, Gemüse und Vollkornprodukten enthalten sind. Und man sollte häufig andere Menschen treffen, Spaß haben und Spiele Speilen - um eine beginnende Demenz im Zaum zu halten. Foto: iStock.com/Horsche

Bewegung und Sport sind unverzichtbar, wenn man gesund alt werden möchte. Ferner ist es wichtig, das Gewicht zu halten, wenig Zucker und rotes Fleisch, dafür aber viele Ballaststoffe zu essen. Und man sollte regelmäßig andere Menschen treffen, mit ihnen Spaß haben und Spiele spielen – auch, um einer Demenz vorzubeugen. Foto: iStock.com/Horsche

Op-Ed: Science must be Brazil’s Bridge to the Future

The Nobel Prize is the highest scientific award since its creation in 1901 and its recipients must have attained life-long, ground-breaking, achievements in their respective area. To this rule there is no exception: Hard and continuous work is the key to success. But this is certainly not all, since, for somebody to perform at a Nobel-Prize winning level, there must be a given number of prerequisites to be fulfiled, some intellectual, others material. Here I would like to address exactly this issue: what are the prerequistes for high-level and -impact research at the “Nobel level”?

My personal interest in this question lies in the fact that I am Brazilian and I have always wondered why Brazil, or other developing countries for that matter, have not received (any) Nobel Prizes in sciences yet. This is a really complex question to answer and any attempts will be obviously partial, but I would like to give it a try. For this, let us consider the two kinds of prerequisites I mentioned in the particular context of Brazil, about which I can speak with more propriety.

 

Rio's newly finished Museu do Amanhã (Museum of Tomorrow) is certainly a right step in creating public awareness for science. Still, its construction relied heavily on private sponsors. Photo: iStock.com/rmnunes

Rio’s newly finished Museu do Amanhã (Museum of Tomorrow) is certainly a right step in creating public awareness for science. Still, its construction relied heavily on private sponsors. Photo: iStock.com/rmnunes

Asking my Brazilian PhD supervisor and some of his colleagues about what it takes to reach top-level research, the answer was unanimous: a School (yes, with capital ‘s’). Competent scientists are not spontaneously generated, but require good and close advising from senior researchers whose experience was also gained in a similar way, as well as an encouraging working environment, where new ideas can blossom. These are necessary conditions to create a School, i.e., provide solid education for the young students centered around the urging scientific questions of their time – but also with a look at the humanistic side of science by developing more critical citizens. This is a very slow and delicate project which requires a lot of personal involvement and dedication, as well as some basic infra-structure.

 

Nobel Laureate Abdus Salam in 1987. Photo: Molendijk, Bart / Anefo (CC BY-SA 3.0 NL).

Nobel Laureate Abdus Salam in 1987. Photo: Molendijk, Bart / Anefo (CC BY-SA 3.0 NL).

For the sake of concreteness, let us take the International Centre for Theoretical Physics (ICTP) in Trieste, Italy, which was founded in 1964 by the Pakistani Nobel Laureate Abdus Salam. Its mission was to foster and support science in the developing world and, for this, Salam and others worked in the direction of gathering top scientists to support and supervise young scientists from “third world” countries. They built effectively a School – from which my Brazilian advisor (J.A. Helayël-Neto) profited very much. This included not only technical knowledge, but also the general feeling of how to conduct a research group which benefits from diversity, thus creating a flourishing ambiance that enabled the then students to develop state-of-the-art research and gather the necessary experience to return to their home countries and found their own research groups, carrying the values passed by their mentors in Trieste (this is the case in our group at CBPF).

The human factor in creating a School is clearly very important and it is certainly a decisive aspect in the “production” of Nobel Prizes, but it is not the only one. Under-paid researchers in under-equipped institutions will very likely perform poorly. Governments are therefore also fundamental parts in the making of high-level research. That this is true can be seen by the amount of money invested by Germany in research and science (almost 15 billion euros in 2013 representing an increase of 70% with respect to 2000) and the number of research centers, e.g. Max Planck Institutes (more than 80 in various areas) [1] – no wonder they have more than a hundred Nobel Prizes! Similar situations are found in other scientifically leading countries, such as the USA, Austria, France and the UK, just to mention a few. How is this to be contrasted with Brazil?

It must be noted in the first place that science is a motor for societal and economic development. The industrial revolution, for example, was only possible through the development of the vapour motor by James Watt, which was clearly based on top knowledge of thermodynamics. The transistor and digital revolutions are similarly based on fundamental physics, e.g. quantum mechanics. The USA and western Europe are leading industrial powers since the early days of industrialization and the interplay between investments in science, research and education and the resulting (economical) development is very clear. Where do Brazil, or more generally Latin America, and Africa come into play? Well, they were mostly colonies since the XVI century and most of the capital available in Europe for the industrial revolution came directly or indirectly from the exploitation of mineral and human resources from their colonial possessions [2].

This was a huge off-set: Latin America and Africa were not colonies for population (occupation) like the USA or Canada, but exploitation colonies, so the colonial powers had absolutely no interest in developing the land in terms of education, infra-structure, let alone science. In this sense, the culture of education – yes, this is a culture – and science in general in Latin America is a very young and quite fragile one. Despite all the economical progress in the recent years, traditionally, Brazil (and I imagine that the situation is similar in other latin-american countries) does not have a solid and consistent approach to education at the governmental level. This can be easily seen by the continuous ups-and-downs from the budgets dedicated to education and culture (EC, for short), science, technology and innovation (STI), which are very often the first areas to suffer cuts in difficult times. To cite a concrete example, the Brazilian interim president has recently merged the STI Ministry with the Communication Ministry – a clear sign that STI are not being treated with due respect and priority.

 

Science is a motor of economical development but the future of itsf unding in Brazil looks rather bleak currently. Photo: iStock.com/rmnunes

Science is a motor of economical development but the future of its funding in Brazil looks rather bleak currently. Photo: iStock.com/Gervanio

In the last two decades Brazil experienced an increase in investments in STI, in particular in the 2000’s, whereby many universities and education centers were created in various locations throughout the country. This meant not only a larger coverage of the higher education landscape, but also a large number of newly created positions for professors and researchers. During those years the existing universities also received better funding and paychecks arrived on time. This is not to say that the situation was good, it was only comparatively better than in the previous years: basic education was still way behind international standards, the existing infrastructures were maintained, but hardly improved, etc. Compared to what was coming, these years would be remembered as almost perfect.

During her last electoral campaign, Dilma Roussef, who is now under investigation in a more than suspicious impeachment process – some would call it a coup d’état [3], promised that education and science would be her priorities: Her campaign slogan read “Brazil, an educating country” (Brasil, pátria educadora). However, after getting elected, the first area to be penalized with budget cuts was science and education: Some funding agencies had their budgets cut by more than 50%. Research institutes, like mine (CBPF), saw themselves forced to rationalize toillet paper, printers and essentially freeze any subsidy to funding events or buying new equipment or basic material. The same people who helped her get elected were the very first to suffer from the spontaneous and unannounced cuts. This was a low blow, but it could have been anticipated, since the true priorities had not actually changed.

 

On the last day of #LiNo16 the future of science and education was the topic of a panel discussion. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings.

On the last day of #LiNo16 the future of science and education was the topic of a panel discussion. Photo: Ch. Flemming/Lindau Nobel Laureate Meetings.

During the 66th Lindau Nobel Laureate Meeting it was discussed the role of education in the making of a better future and fairer society. Though highly interesting, the debate did not come to new solutions, but merely reinforced the well-known formula: Science is key to a better world. To put it in the words of Nobel Laureat Brian Schmidt, it is necessary to have political and social stability, as well as a 20 year (planning) horizon, to reach visible improvement in a society. These points synthesize the essence of what is currently missing in the approach of governments in Latin America: A solid compromise to long-term investments in education. The usual 4-year horizon with which politicians work is the fruit of a not so naïve short-sightedness which results in a never ending cycle, where inequality and poverty are simply never consistently addressed. How can a School (of thought, research, education, etc) be established on such shifting grounds?

The role of science is to push human society forward and this is not only the task of lonely scientists, but rather a greater goal that has to be dilligently sought for by the people as a whole. Governments in developing countries need to break the secular traditions and start investing heavily in basic education and science – this is the only way to escape from poverty and underdevelopment.

Valuing the teachers is therefore a key ingredient in improving education: “teachers are the most important people in the world, pay them well!”, said Nobel Laureate Dan Schechtman at Lindau 2016.

Maybe, after some decades, if we follow the wise advise of Nobel Laureates – hopefully the politicians will pay attention – we will see that long-term investments and support indeed pay off and a Nobel Prize in sciences will no longer be out of reach for Latin America or Africa, thus crowning those who took the long and difficult path towards a better society.

 


My special thanks to Maria Elidaiana, José A. Helayël-Neto, Sebastião Alves, Yuri Müller and Célio Marques, all from the Brazilian Centre for Research in Physics (CBPF, Rio de Janeiro) for their collaboration in the writing of this piece.

[1] http://www.nature.com/news/germany-hits-science-high-1.13762

[2] “The open veins of Latin America”, Eduardo Galeano, Madrid 1980.

[3] The New York Times: http://www.nytimes.com/2016/05/24/world/americas/brazil-dilma-rousseff-impeachment-petrobras.html?_r=0

Geniuses are getting older

Lawrence Bragg was barely 25 when he was awarded the Nobel Prize in Physics in 1915. The research for which he received the award – his work on analyzing crystal structures using x-rays – had been completed two years earlier when he was only 23. With this achievement he confirmed a famous observation by Albert Einstein:

A person who has not made his great contribution to science before the age of 30 will never do so.

The great physicist himself is also proof of this: Einstein developed the special theory of relativity and completed his work on the photoelectrical effect, for which he was awarded the Nobel Prize in 1921, before he turned 30.

But are all scientific breakthroughs really made by young researchers? Benjamin Jones and Bruce Weinberg from the National Bureau of Economic Research in Cambridge have studied this question (“Age dynamics in scientific creativity”, PNAS 108/47, 2011). Their analysis is based on the work of Nobel Laureates in the categories of Physics, Chemistry and Medicine or Physiology between 1901 and 2008. They determined the age at which the scientists carried out their award-winning research and confirmed that while Einstein did not pluck his statement about ‘young geniuses’ out of thin air, his observation was only valid in the past.

The average age of physicists who were awarded the Nobel Prize in later years was 37.2. The corresponding age for chemists is 40.2 and 39.9 for medical researchers. Clear differences can be observed when the very early Laureates (who made their discoveries before 1905) are compared with the later ones (whose research was carried out after 1985). In medicine, the average age of scientists when they made major discoveries in the earlier period is 37.6, and 45 in the later period. At 36.1 and 46.3 years respectively, the gap is even bigger in chemistry. The biggest gap can be observed in physics: the earlier Laureates in this discipline made their discoveries at an average age of 36.9 years while their later counterparts were 50.3 year of age on average.

Since the turn of the millennium, only 19 percent of the award-winning discoveries were made by physicists under the age of 40; this age group had previously accounted for 60 percent of such discoveries. In chemistry, no scientist under the age of 40 has been awarded Nobel Prize in the 21st century (66 percent of the chemistry laureates before the year 2000 were under 40).

 

Nobel Laureate Peter Doherty giving advice to young scientist Julia Nepper at the 65th Lindau Nobel Laureate Meeting.

Nobel Laureate Peter Doherty giving advice to young scientist Julia Nepper at the 65th Lindau Nobel Laureate Meeting.

At present, it is only possible to speculate about this shift in the age at which scientists achieve such breakthroughs. It is probably due to the fact that scientists simply have a lot more to learn now than before. Thanks to the development of quantum mechanics, physics underwent a complete revolution in the first half of the 20th century. A large number of young scientists, in particular, were involved in this development, for example Albert Einstein, Paul Dirac and Werner Heisenberg. The young scientists were, perhaps, at an advantage here precisely because quantum mechanics was so different from the physics previously taught and researched. Whether or not these young scientists had studied the “old” science in detail was of little or no importance. They were able to get involved directly in the new physics and make major contributions without such preliminary knowledge.

The image of the brilliant young scientist who makes important discoveries is less and less valid today,

explains Bruce Weinberg, summarising the findings of the study. Today, scientists are awarded the Nobel Prize for research they carried out at an average age of 48.

Therefore, all of the young scientists who will soon gather in Lindau again to discuss their research with the Nobel laureates still have plenty of time to make their mark. Those who are in a hurry to do so should concentrate on theoretical research, however, because as Jones and Weinberg also discovered: on average, theorists achieve their major breakthroughs 4.4 years earlier than experimental scientists.