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SCIENCE SUMMIT The 64th Lindau Nobel Laureate Meeting devoted to Physiology and Medicine More than 600 young scientists came to Lindau to meet 37 Nobel laureates

CAREER Women to Women: Science and Family FOTOLIA / SUPHAKIT WONGSANIT

INFLAMMATION The Stress of Ageing

FOTOLIA / FLASHPICS

CANCER RESEARCH J. Michael Bishop and the Discovery of the first CHRISTIAN FLEMMING / LINDAU NOBEL LAUREATE MEETINGS FOTOLIA / JUAN GÄRTNER Human Oncogene EDITORIAL IMPRESSUM

Chefredakteur: Prof. Dr. Carsten Könneker (v.i.S.d.P.) Dear readers, Redaktionsleiter: Dr. Daniel Lingenhöhl Redaktion: Antje Findeklee, Jan Dönges, Dr. Jan Osterkamp where else can aspiring young scientists Ständige Mitarbeiter: Lars Fischer Art Director Digital: Marc Grove meet the best researchers of the world Layout: Oliver Gabriel Schlussredaktion: Christina Meyberg (Ltg.), casually, and discuss their research, or their Sigrid Spies, Katharina Werle Bildredaktion: Alice Krüßmann (Ltg.), Anke Lingg, Gabriela Rabe work – or pressing global problems? Or Verlag: Spektrum der Wissenschaft Verlagsgesellschaft mbH, Slevogtstraße 3–5, 69126 Heidelberg, Tel. 06221 9126-600, simply discuss soccer? Probably the best Fax 06221 9126-751; Amtsgericht Mannheim, HRB 338114, UStd-Id-Nr. DE147514638 occasion is the annual Lindau Nobel Laure- Geschäftsleitung: Markus Bossle, Thomas Bleck Marketing und Vertrieb: Annette Baumbusch (Ltg.) Leser- und Bestellservice: Helga Emmerich, Sabine Häusser, ate Meeting in the lovely Bavarian town of Ute Park, Tel. 06221 9126-743, E-Mail: [email protected]

Lindau on Lake Constance. Die Spektrum der Wissenschaft Verlagsgesellschaft mbH ist Kooperati- onspartner des Nationalen Instituts für Wissenschaftskommunikation Daniel Lingenhöhl> GmbH (NaWik). Das NaWik ist ein Institut der Klaus Tschira Stiftung Redaktionsleiter Spektrum – Die Woche GmbH und des Karlsruher Instituts für Technologie. Wissenschaftlicher. Direktor des NaWik ist Spektrum-Chefredakteur Dr. Carsten Könneker. E-Mail: [email protected] Each year, a number of journalists and Twitter: @lingenhoehl bloggers are invited to these meetings. Bezugspreise: Einzelausgabe € 1,49. Im Abonnement jährlich: € 39,95; ermäßigt € 30,00. They cover the Lindau event from a subject- Alle Preise verstehen sich inkl. Umsatzsteuer.

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2 INHALT

CAREER 14 CANCER RESEARCH Women to Women:> J. Michael Bishop and the Science and Family 08 Discovery of the first Human RAVEN Oncogene ISTOCKPHOTO / JUAN GAERTNER KATHLEEN

INFLAMMATION DATA-DRIVEN SCIENCE 17 25 The Stress> Big Data – not a big deal,> of Ageing just another tool CHRISTIAN FLEMMING / LINDAU NOBEL LAUREATE MEETINGS FOTOLIA / CARSTEN REISINGER

05 DEMOGRAPHY 28 SCIENCE PLACES 42 BACTERIAL INFECTIONS The Future Belongs to Women Virtual Visit at the Institut On Man and Microbes –> Scientists and CEOs Pasteur in Paris Barry Marshall

07 WHO WAS THERE? 31 SCIENCE COMMUNICATION 45 MEDICAL RESEARCH Laureates at the 64th Lindau Randy Schekman: Honest Physician-Scientists:> Nobel Laureate Meeting Exchange of Knowledge An Endangered Species?

11 CANCER RESEARCH 36 VIRUS RESEARCH 51 SYNTHETIC BIOLOGY Research for the Dogs –> Could A Cow Virus Cause> Synthetic Genes, Synthetic Cells Young Scientist profiles Colon Cancer? – Synthetic Life

22 IMMUNE SYSTEM 39 INFECTIOUS DISEASES 55 FANDOM Why Don’t Grasshoppers> From Mice and Fruit Flies Towards Autographs vs. #NobelSelfie Catch Colds? Novel Infection Treatment 3 The Lindau Nobel Laureate Meetings Since 1951, Nobel Laureates and young scientists from all around the globe come together at Lindau to discuss science and society. The Lindau Nobel Laureate Meetings foster the Exhibitions Nobel Portraits Annual Meetings cross-cultural and inter-generational exchange Sketches of Science Medicine | Chemistry | Physics | Economics of knowledge and help to create new networks Discoveries for the future. All articles in this edition have all been Mediatheque published in the Lindau Blog. Are you interested Lectures Background in more posts on global science issues, the latest Nobel Labs 360° scientific developments, intriguing personal Penzias Painting Public Lectures stories and the interplay between science and MINT-Education society? Thinking about taking part in the Webinars discussion or contributing yourself? Visit the Events Lindau Blog and become a guest blogger. Weblog Social Media Art Catalogues www.lindau-nobel.org Stakeholder Initiatives Educational Books Teaching Spirit Innovation Forum Publications blog.lindau-nobel.org Alumni

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4 DEMOGRAPHY The Future Belongs to Women Scientists and CEOs Christine Gorman Christine Gorman about Hans Rosling’s impressive Presentation at the Opening of the 64th Lindau Nobel Laureate Meeting.

Hans Rosling talks about future population

CHRISTIAN FLEMMING NOBEL LAUREATE / LINDAU MEETINGS 5 or the first time in its 64-year influenced by preconceived ideas of what whenever we talk about the next 50 to 100 history, a prestigious, invita- the world is like. years of life on earth. »If you score worse tion-only meeting of young sci- Hans Rosling, the always entertaining than random, then the problem is not lack entists and Nobel Laureates is and informative professor of international of knowledge«, Rosling told the audience. made up of more women than health at the Karolinska Institute in Swe- It is about why the perception of the world Fmen. Between 3,000 and 4,000 graduate den, posed four questions of the audience. divided between »developed« and »devel- and post-graduate students in science ap- Thanks to the interactive clickers available oping« countries refuses to budge from so plied to attend the Lindau Nobel Laureate to all participants, we quickly discovered many perceptive people’s fundamental Meeting, held every year in a picturesque that less than 10% of the dignitaries, scien- understanding of the world. Bavarian town near the southern tip of tists and budding scientists knew that 80 Who do you think scores better than the Lake Constance in Germany. »This year, for percent of all children around the world chimpanzees when Rosling’s performs this the first time, more young women than are vaccinated against measles (most pop quiz? The CEOs of international com- men have qualified« for the coveted 600 guessed either 20 percent or 50 percent) or panies. < spots, Countess Bettina Bernadotte told that the number of children that will be participants at the opening ceremony in born in the coming decades is actually not You can read more about Rosling’s quizzes in Lindau, Germany. expected to grow significantly beyond the this BBC News article. But that was probably not the most sur- number that are currently born. (It’s the prising thing most people learned this af- number of adults that is going to shoot up, ternoon. More surprising was that even boosting world population to 9 billion by this highly educated group did not do so 2050, up from 7 billion now.) A greater Sie suchen eine well on a pop quiz about some basic facts number of participants came up with the Mathematikerin about global health. Before you make any correct answer for the other two questions, für ein Interview? snide remarks, realize that their answers but the gap between perception and reality were in line with those given by citizens of was greatest for measles vaccination and the U.S.,U.K. and Sweden as well as some of projected number of children. Rosling’s fellow professors. In fact, the only The point, as Rosling explained, was not group that scored better were a bunch of to embarrass a bunch of scientists, but to chimpanzees at a Swedish zoo, who, be- help them to realize some of the very www.academia-net.de cause they answered randomly, were not strong cognitive biases that still hold sway

6 Laureates at the 64th Lindau Nobel Laureate Meeting

Top row from left: Johann Deisenhofer, Peter Agre, Ada Yonath, Arieh Warshel, Martin Chalfie, Thomas Steitz, Tim Hunt, Hartmut Michel, Brian P. Schmidt,> Barry J. Marshall, Randy W. Schekman, Hamilton O. Smith

Bottom row from left: Roger Y. Tsien, Aaron Ciechanover, Ferid Murad, Elizabeth Blackburn, Oliver Smithies, Countess Bettina Bernadotte af Wisborg, Martin J. Evans,> Erwin Neher, Edmond H. Fischer, Bert Sakmann, Kurt Wüthrich, Harald zur Hausen

7 CANCER RESEARCH J. Michael Bishop and the Discovery of the first Human Oncogene Stephanie Hanel At the Lindau Nobel Laureate Meeting for the first time: John Michael Bishop, who revealed how retroviral cancer genes develop on a molecular level.

GAERTNER / JUAN ISTOCKPHOTO 8 n the late 1970s, J. Michael Bishop man oncogene: c-Src. During his extensive and Harold Elliot Varmus met and research, Bishop not only studied onco- created one of these rare work genes, but also their predecessors, the so groups where the results are so called proto-oncogenes. In Bishop’s own much more than the sum of its words: »Src is a wayward version of a nor- Iparts. Both researchers’ work has changed mal cellular gene (which we would now call our view on cancer fundamentally. They a proto-oncogene), pirated into retroviral were able to transfer the experimental genome by recombination (in a sequence works of scientists like Deborah Spector of events known as transduction), and con- and Dominique Stehelin in the realm of verted to a cancer gene by mutation.« animal virology to human medicine, or Varmus has studied tumorgenesis and more precisely: to the field of cancer- re breast cancer tumors, has concentrated on search. viral replication, especially on the HI- and What seemed like a revolutionary the hepatitis b virus, and became director change of perspective on cancer back then of the National Cancer Institute in 2010. is part of today’s general knowledge. Can- Besides being an excellent scientist, cer genes are not necessarily foreign in- Bishop has another talent, too: for instance, truders, but important cell genes that can he’s a very good scientific writer. Maybe re- wreak havoc under certain circumstances – sulting from his self-professed love of read- from friend to foe, so to speak. ing? He says himself that he loves books –

PETER BADGE Bishop’s main areas of interest are ret- only science fiction and crime are not his John Michael Bishop attended this year’s roviridae and oncogenes. Retroviridae are favourites – and he enjoys writing. Anoth- Lindau Nobel Laureate Meeting. Watch J. able to introduce genes into the DNA of er of his passions is music, a legacy from Michael Bishop´s lecture in the Lindau host cells. If this happens, normal cell his past: Born in 1936 as the son of a Lu- Mediatheque. growth, division or differentiation can re- theran minister in Pennsylvania, he spent sult in the creation of cancer genes, or on- his childhood with piano, organ and vocal cogenes. The latter can become part of the lessons, far away from metropolitan life or host’s own DNA. In the early 1980s, Bishop scientific research. In fact, nothing hinted and Varmus discovered the very first hu- at a career in life science. In the course of

9 his career, he experienced many surpris- Fireworks over Lake Constance ing changes and variations – changes of topics, locations and colleagues. In retro- spect, he likes to thank the many people he met along the way: Some had offered help- ful and unconventional advice on how to advance his research and career – with a truly exceptional outcome, as we know. J. Michael Bishop, winner of the 1989 Nobel Prize in Physiology or Medicine to- gether with Harold Elliot Varmus, attended the Lindau Nobel Laureate Meeting for the first time this year. He gave a lecture on »Forging a Genetic Paradigm for Cancer«, read an abstract of his lecture here. He also participated in a panel discussion on the topic »Large Data and Hypothesis – Driven Science in the Era of Post-Genomic Biolo- gy«. < NOBEL LAUREATELINDAU MEETING

10 ISTOCKPHOTO / ADAM WALICZEK Research for the Dogs – Dogs play acrucialrole inhumancancerresearch. Kathleen Raven Young Scientist profiles RESEARCH CANCER 11 ore young scientists Comparative oncology gained a foothold – and physicians should or should we say »paw«-hold – in the US a know this, says Floryne few years ago; Europe still needs to catch O. Buishand, a Young up, Buishand said. Scientist at the 64th »The dogs’ owners allow their pets to MLindau Nobel Laureate Meeting. With her participate in the research because they DVM, Buishand is a small animal surgery want to help – they are enthusiastic about resident at the faculty of veterinary medi- it«, she said. A clinical trial testing an agent cine at Utrecht University in The Nether- in dogs can run between one and three lands and also on a PhD track. At the Meet- years, whereas human clinical trials stretch ing, she wishes to make »comparative on- between 10-15 years, Buishand pointed out. cology« a buzzword among her peers (She Comparative oncology research could help. quickly adds that she listens to researchers If results from canine trials were integrat- during coffee breaks and has already gained ed into human trials, »then we could speed significant cross-disciplinary insight on up the whole process,« she said. various subjects). Buishand is technically already an »award-winning« scientist. In 2009, she RAVEN

But back to the dogs. won a prestigious research award from

KATHLEEN For research on stem cells and endocrine Cornell University in New York. An observ- Young Scientist Floryne O. Buishand, pancreatic cancer, »we are using dogs as an er would not know this from her humble The Netherlands animal model for humans,« Buishand ex- attitude. »From the moment you arrive plained. »Dogs have spontaneous tumors, here, you are just breathing in the inspira- which are better than what mice develop. tion«, she said, referring to the Congress. Mice are often immune-deficient,« she »The conference is so far exceeding my ex- said, referring to dogs who develop tumors pectations.« naturally versus mice injected with cancer Meanwhile, another Young Scientist, in the lab. Buishand’s clinical work focuses Remco Molenaar, MSc, of the University of on surgical oncology. She works with pet Amsterdam, The Netherlands, said the Lin- dogs suffering from pancreatic tumors. dau meeting has re-energized his efforts to

12 look at scientific problems in new – and There’s much more work to be done, and even unpopular – ways. Like many of the Molenaar hopes to have results from cellu- Nobel Laureates in Physiology or Medicine, lar experiments in by summer’s end. Molenaar has faced intense criticism of his When Barry Marshall (Nobel Prize, Phys- unique research ideas. Earlier this year, iology/Medicine 2005) gave his talk on He- Molenaar co-authored an article entitled licobacter pylori earlier in the week, Mol- »The driver and passenger effects of isoc- enaar said the following message resound- itrate dehydrogenase 1 and 2 mutations in ed most with him: Do not immediately be- oncogenesis and survival prolongation,« lieve anyone who wants to prove you wrong. in the journal Biochimica et Biophysica When Molenaar heads back to his lab after Acta. Lindau, he hopes to infect his fellow peers »This was a perspective paper,« Mol- with excitement about research. < enaar explained. He explained that muta- RAVEN

tions in isocitrate dehydrogenase 1 and 2

KATHLEEN (IDH1 and IDH2) occur in the development Young Scientist Remco Molenaar, of different types of cancer, including, for The Netherlands example, acute myeloid leukemia and chondrosarcoma. In brain tumor patients, at least, patients with the mutation live on average three years after diagnosis. Pa- tients without the mutation live only about one year, Molenaar said. »We have the hy- pothesis that the mutation causes cellular defense mechanisms to kick on, thereby causing the tumor cells to be more stressed, and more susceptible to treatments like chemotherapy, he said. »The mutation could lower the death threshold needed to kill the cells,« Molenaar said.

13 CAREER Women to Women: Science and Family Kathleen Raven The key to the early child-rearing years is to be> well-organized with a laser-like focus.

A group of Young Scientists RAVEN

KATHLEEN 14 irsty Renfree Short is not sur- Johnston, director, Sydney Harbour Re- critics said. With these stories on their prised. She shrugged her search Program, Sydney Institute of Ma- minds, the panelists then turned to possi- shoulders at the fact that fe- rine Science; Brian Schmidt (Nobel Laure- ble solutions to fixing this leaky pipeline. male young researchers out- ate, Physics 2011), The Australian National Over at Slate.com, AAAS Mass Media Fel- number their male counter- University; and Elizabeth Blackburn (No- low Jane Hu also covered »the leaky pipe- Kparts at the 64th Lindau Nobel Laureate bel Laureate, Physiology or Medicine 2009) line problem« in a story titled Old Boys’ Meeting, marking a first-time event in the University of California, San Francisco. Lab, which covers discouraging statistics. storied Congress’ history. »Women out- In her opening remarks, Suzanne Cory According to the story, 52 percent of US bi- number men in grad school, so, why not?« recalled the scarcity of female speakers at ology Ph.D.s are women, but that number the University of Queensland, Australia, the earliest scientific conferences she- at decreases to 39 percent of postdocs before postdoctoral student and Lindau Young tended. »I expected everything to be total- shriveling to only 18 percent of tenured Scientist said. Short, along with five other ly transformed by now, and it’s not«, she professors. female Young Scientists, stood round a tiny said. The panelists nodded their heads in table before the start of the Science Break- agreement. The three women chose sci- Avoid the drop-off in interest fast on 30 June sponsored by the state of ence as their career path at a time when Girls and boys seem equally engaged in bi- Australia. »What I want to know is why are even the thought of such pursuits seemed ological and other sciences until about year there so many female researchers at the preposterous to most. A common theme 6 of schooling, Brian Schmidt observed. graduate-school level, but not high up in soon emerged from their stories. From the Blackburn and Cory, having both attended leadership?« asked Tracy Norman, a doc- start, each female scientist adopted one at- the same all-girls high school in Australia, toral candidate at the Georgia Institute of titude: I’ll show them. Blackburn recalled a agreed with the observation. This drop-off Technology, USA. Your correspondent fol- school teacher’s reaction to her career could be partly explained by social pres- lowed up the statement with a question goals. »Why would a nice girl like you want sures – conscious and unconscious – young about family. Did the women plan to have to go into science?« she said, repeating the women face in the junior and high school children? Three raised their hand in the af- teacher’s words. Blackburn pursed her lips years. »Women may get intimidated about firmative. The other three? Undecided. shut at the time, she said, but doubled how to go on with their interests«, Black- Adam Spencer, a self-described celebri- down with even more determination. John- burn said. The solution could be to ensure ty mathematician, moderated the talk with ston described the deep skepticism she that science clubs and activities for women Suzanne Cory, immediate past president, faced after declaring her passion for sci- especially remain well-funded and sup- Australian Academy of Science; Emma ence. »You should study law instead«, her ported through years 6-12, Schmidt said. At

15 every stage in academics, women need con- Raising children requires first and fore- person who jumps into the deep end needs fidence, Cory agreed. To the mostly female most a partner who is willing to make sac- to be rescued«, he said, to audience laugh- audience, Cory said: »You are at a crucial rifices as well, the panelists said. When ter. He encouraged mentoring of both gen- age now. Don’t drop off.« Adam Spencer asked if female scientists ders and better awareness of the situation. should consider taking an extended break Structural changes need to occur in aca- The impact factor of family of two or three years, the answer was a re- demia and the industry, he said. One of One of the hazards of modern science and sounding »No.« »Science is really a these could be extending the tenure clock academia is the intense focus on tracking, fast-moving world«, Cory said. »If you get for female researchers who choose to start Schmidt said. Citations, papers, symposi- out, even for three years, it becomes very a family early in their career, Schmidt said. ums or patents can all be considered part difficult to get back in. And you lose Another option is to create childcare pro- of the formula. But this formula overlooks self-confidence, connections with your grams akin to what Princeton University the fact that a single great paper can have peers and knowledge.« The women agreed offers, Blackburn said. When parents at up to three times the impact of an average that the key to the early child-rearing years that institution suddenly have a sick child paper, Schmidt said. »We need to single out is to be well-organized with a laser-like fo- who cannot attend daycare, the university really great papers and provide those re- cus. Blackburn gave up dinners out and so- provides a fully vetted babysitter immedi- searchers with resources«, he said. After all, cializing. »My life was research and fami- ately. Above all, the panelists agreed, wom- those who worry about the impact factor ly«, she said. en must step forward at every turn in their are »bottom feeders«, Blackburn said, to careers and say, »I am the person for this laughter from the audience. She went on to Take a chance on women job. Choose me.« < emphasize that women need to look at rais- Toward the end of the talk, Cory gave the ing children, if they choose to do so, as a analogy of the young boy who dives into temporary impact on and overall scientific the deep end of the pool without thinking career that may span 40 or more years. »It’s and just learns to swim. The young girl, by only 18 or so years of your life«, Blackburn contrast, stays in the shallow end until she said, as chuckles erupted again. But a fami- is certain that she will stay afloat, then ly and a successful career are not exclusive moves deeper. To the women scientists, of the other, all women agreed. »Putting Cory said: »You’ve got to jump into the off children until much later is not biologi- deep end.« Schmidt disagreed a little. »I cally the smartest thing«, Blackburn said. would say that there are cases when the

16 INFLAMMATION The Stress of Ageing Jalees Rehman Aging, most researchers assume, is mainly a cellular phenomenon. But what changes in cells to make the body frail?

FOTOLIA / CARSTEN REISINGER 17 ow do I knock off thirty Thanks, but no thanks. Faust does not years from my age? Faust, like manual labor and is quite happy with the protagonist in Johann his current lifestyle, so he instead opts for Wolfgang von Goethe’s fa- plan B – a magic youth potion. mous play, poses this Nearly two centuries after Goethe’s Hquestion to Mephistopheles in the chapter Faust was first performed, our quest for re- Hexenküche (Witches’ kitchen). Mephis- versing the aging process continues. The topheles provides some pretty good ad- magic potion which reverses aging contin- vice – considering that he is the devil and ues to be as elusive as ever, but aging re- this fictitious exchange takes place in the search has made substantial progress dur- dark Middle Ages: ing the past few decades. One biological definition of aging is the gradual decline in Begib dich gleich hinaus aufs Feld, function observed over time. Humans ex- Fang an zu hacken und zu graben perience this age-related decline at a whole Erhalte dich und deinen Sinn body or organ level such as memory loss or

In einem ganz beschränkten Kreise, weakening of muscle strength, but aging CHRISTIAN FLEMMING NOBEL LAUREATE / LINDAU MEETINGS Ernähre dich mit ungemischter Speise, also takes place in individual cells. Cellular Nobel Laureate Elizabeth Blackburn Leb mit dem Vieh als Vieh, und acht es aging or cellular senescence describes a in Lindau 2014 nicht für Raub, form of »exhaustion« to the point where Den Acker, den du erntest, cells can no longer divide and a disruption selbst zu düngen; of normal cellular activity. A substantial amount of scientific data suggests that the Here is the paraphrased essence of the dev- aging of individual cells plays a central role il’s advice: Seek out a life of moderation, in the general decline of function in our stop being lazy, exercise regularly by muscle function, blood flow or metabo- ploughing the field and avoid unhealthy lism which occurs when we grow older. But foods! How does the great scholar and sci- understanding cellular aging will not only entist Faust respond to these common- unlock some of the mysteries of »healthy« sense suggestions? aging, it may also help us understand and

18 TIZIANO OF VECELLIO: MAN, AGES THREE CA / PUBLIC 1512 DOMAIN prevent certain age-associated diseases of the newly formed chromosomes, small Painting by Tiziano Vecellio: such as heart disease or cancer. chunks of DNA are trimmed off at the end Three Ages of Man One of the central mechanisms respon- of the chromosomes. By having protective sible for the aging of cells is the shortening telomere caps, the shortening process only of telomeres. Telomeres are repetitive DNA affects the telomeres and not the essential sequences at the ends of chromosomes gene-encoding parts of the chromosome. which act as protective caps. Every time a When cells in a tissue are damaged then cell divides, its chromosomes undergo a their neighboring cells or reservoirs of re- doubling process so that the two daughter generative stem cells and progenitor cells cells receive equal amounts of DNA. Dur- have to step in, divide to replace the dam- ing the DNA replication and the separation aged cells. Having long telomeres would al-

19 low these regenerative neighbors to keep sense that having long telomeres would be the healthy regenerative potential of the on dividing and restoring the tissue, where- a good thing but it is nice to have real-world body. To reduce the risk of cancer we need as short-telomere cells would have to give data collected from thousands of humans an ideal level of telomerase, with not a up early on because their protective tel- confirming that this is indeed the case. A whole lot of room for error. This clarifies omere caps would dwindle. Regenerative prospective study collected blood samples that »telomerase shots« are not the magi- cells such as stem cells are frequently called and measured the mean telomere length cal anti-aging potion that Faust and so upon to divide and this is why it is a good of white blood cells in 787 participants and many other humans have sought through- thing that these regenerative cells tend to followed them for 10 years to see who out history. contain high levels of an enzyme called tel- would develop cancer. Telomere length Why is that telomere lengths are such omerase which helps prevent the shorten- was inversely correlated with likelihood of good predictors of longevity, but too much ing of the telomeres. Telomerase thus acts developing cancer and dying from cancer. telomerase can be bad for you? The answer as an anti-aging enzyme. The roles of tel- The individuals in the shortest telomere is probably that telomere lengths meas- omeres and telomerase in cellular aging group were three times more likely to de- ured in the white blood cells reflect a broad were first uncovered in the 1980s and 1990s velop cancer than the longest telomere range of factors, such as our genetic make- by the pioneers Elizabeth Blackburn, Carol group within the ten year observation pe- up but also the history of a cell. Some of us Greider and Jack Szostak, who all shared riod! A similar correlation between long may be lucky because we are genetically the 2009 Nobel Prize in Physiology or Med- telomeres and less disease also exists for endowed with a slightly higher telomerase icine for »the discovery of how chromo- cardiovascular disease. Dr. Blackburn was activity or longer telomeres, but the envi- somes are protected by telomeres and the quick to point out that these correlations ronment also plays a major role in regulat- enzyme telomerase«. do not necessarily mean that there is a di- ing telomeres. If our cells are exposed to a At the 64th Lindau Nobel Laureate meet- rect cause and effect relationship. In fact, lot of stress and injury – even at a young ing, Elizabeth Blackburn reviewed the his- increasing telomerase levels ought to age – then they are forced to divide more tory of how she and her colleagues identi- lengthen telomeres but in the case of can- often and shorten their telomeres. The tel- fied the role of telomeres and telomerase cer, too much telomerase can be just as bad omere length measurements which pre- in the cellular aging process, but also pre- as too little telomerase. Too much telomer- dict health and longevity are snapshots sented newer data of how measuring the ase can help confer immortality onto can- taken at a certain point in time and cannot length of telomeres in a blood sample can cer cells and actually increase the likeli- distinguish between inherited traits which predict one’s propensity for longevity and hood of cancer, whereas too little telomer- confer the gift of longer telomeres to some health. It makes intuitive and theoretical ase can also increase cancer by depleting and the lack of environmental stressors

20 which may have allowed cells to maintain age. This means that the body of a person in cious cycle: Once cells begin aging, they long telomeres. their 30s or 40s exposed to high levels of in- themselves release inflammatory proteins What are the stressors which can affect flammation or oxidative stress may already which in turn can activate aging in neigh- cellular aging and shortening of telomeres? numerous cells showing signs of aging. boring cells, thus setting a self-reinforcing Blackburn listed a few of them such as stress How do these stressors lead to prema- cascade of aging in motion. hormones, oxidative stress and inflamma- ture aging? Shortening of telomeres could Where does this interaction of tel- tory stress. All of these stressors cause stress be one answer. If cells are chronically in- omere-dependent and telomere-inde- on a molecular level, which means they can flamed due to autoimmune diseases or in- pendent aging pathways as well as the in- damage proteins and other essential com- flammation-associated diseases such as fluence of known (and many unknown) ponents of a cell. Oxidative stress, the ex- obesity and atherosclerosis then they have stressors leave us? The molecular under- cess production of reactive oxygen species to be continuously replaced by cell divi- standing of cellular aging is progressing oxidizes proteins, disrupting their struc- sion which shortens telomeres. However, steadily, but the complexity of cellular ag- ture and function to the extent that oxi- telomere shortening is not the only route ing and the even more complex question dized proteins become either useless or to cell aging. Aging research groups have of how organs such as the brain and heart even harmful. Inflammatory stress refers to uncovered multiple additional pathways age requires a lot more work. There will be excessive inflammation which transcends which can accelerate the premature aging no single molecular switch which can re- the normal inflammatory response of cells of cells without necessarily requiring the verse or halt aging and triple our lifespan, from which they can recover. Prolonged in- shortening of telomeres. Inflammation or but most aging researchers do not see this flammation, for example, can cause cells to oxidative stress can activate certain aging as their goal. Understanding specific aging activate a cell-death program. Recent stud- pathways such as the aging regulator pathways, as well as the genes and stress- ies in mice have shown that activation of in- p16INK4a. Our own work has shown that ors which activate them, will allow us to flammation pathways in the brain can sup- an inflammatory cytokine can convert prevent and treat age-related diseases as press cognitive function, muscle strength highly regenerative blood vessel progeni- well as one day be able to provide person- and overall longevity. Blackburn also point- tor cells into aged cells which no longer alized advice to individuals on how to ed out that stressors are often interconnect- replicate by activating p16INK4a, and that maximize their »healthspan«. For now, we ed. Prolonged elevation of stress hormones this occurs without affecting telomere can stick to some of the broad lifestyle in- or prolonged inflammation can increase length. Judith Campisi from the Buck Insti- terventions which were recommended by oxidative stress. The higher the level of these tute of Aging as well as several other re- Mephistopheles: exercise and a healthy stressors, the more prematurely cells will searchers have uncovered an important vi- diet. <

21 CC0

IMMUNE SYSTEM / REALWORKHARD / PIYABAY Why Don’t Grasshoppers Catch Colds? Christine Gorman Insects seem to be extraordinarily resistant to infections. This mystery hasn’t been solved so far.

22 ile this under things you never mon ancestors date so far back in time that hearts. Now assuming you have read this thought to ask: Why are grass- they are among the first animals ever to far in the story, you may be asking your- hoppers and other insects re- have lived on the planet. self, why would anybody care so much sistant to so many different in- Indeed, Hoffmann concluded from the about grasshoppers? Perhaps you have fections? evidence found in his and other labs that never heard about the grasshopper swarms FJules Hoffmann asked himself that ques- innate immunity must have evolved with that ate everything in their path in the tion nearly fifty years ago and in the pro- the rise of multi-cellular organisms 1 bil- American Midwest in the 1930s or that cess of trying to figure out the answer, he lion years ago. sometimes rain havoc on the farmlands of eventually won a share of the 2011 Nobel Chad, Mali, Nigeria and other parts of west- Prize in Physiology or Medicine. His re- It started with grasshoppers ern Africa? search also helped to determine what A quick peek at Hoffmann’s biography Figuring out what makes grasshoppers makes the base layer of the immune sys- shows that he started studying grasshop- so resistant to infection could well have a tem – commonly called innate immunity – pers when he joined the laboratory of practical benefit for agriculture, Hoffmann work so well. Pierre Joly at the French National Research took care to point out in his Lindau lecture. (The other part of the immune system, Agency (CNRS) in the 1960s. Joly performed But, I certainly got the sense, listening to in vertebrates at least, is known as adaptive lots of transplants between grasshoppers him, that he was also riveted by the intel- immunity; that’s the part that is responsi- in the course of his studies and marveled lectual challenge. ble for creating antibodies.) that they never succumbed to bacterial in- In 1978, Hoffmann became head of his Speaking to a packed audience at the fections as a result. own laboratory and by the 1990s, he had 64th Lindau Nobel Meeting in Lindau, Ger- Naturally, the experiments were per- changed the focus of his lab’s research from many, Hoffmann, chose to take the long formed under sterile conditions, but even studying grasshoppers to studying fruit view–the very long view–with the young so, you would have expected at least some flies (Drosophila melanogaster). The move, scientists and fellow Nobelists in the con- grasshoppers to develop surgical infec- he said, came in large measure because the ference hall. tions as a result. genes of fruit flies are easier to study. (One The same genetic building blocks that Hoffmann dedicated his PhD to study- species of grasshopper, for example, has a give rise to the immune system found in ing this unexplained mystery in greater genome that is 100 times larger in size than the insects he has studied over the years detail and found that he could destroy the that of Drosophila melanogaster and six are also found in sea urchins and sea anem- grasshoppers’ ability to stave off infection times greater than that of humans.) Fruit ones, Hoffmann said—species whose com- by irradiating some tissue around their flies, like grasshoppers and other insects

23 are also highly resistant to infection with longer, they probably would have needed to Alles, was Sie bacteria (both gram-positive and gram-neg- evolve something else to layer on top of it. wissen müssen. ative bacteria) and fungi. Which is exactly what, in fact, a shark- In 1996, Hoffmann and his colleagues like ancestor of ours did about 460 million Auf Ihrem Bildschirm published their work showing that a previ- years ago (give or take a few million). Most ously discovered protein named Toll, which of the time, humans and other vertebrates plays a role in development, also plays a do just fine with their innate immunity. fundamental role in maintaining the fruit But sometimes our innate immunity gets fly’s nearly impregnable defenses against overwhelmed by the onslaught of infec- infection. His lab later determined that an- tion or of toxins. And that’s when adaptive other protein, known as IMD, was at the immunity comes into play. Well, it’s not ac- center of a second immune system path- tually so cut-and-dried as that makes it way found in insects. sound – but that’s definitely a story for an- Later work by Bruce Beutler (who shared other time. < the Nobel Prize with Hoffmann and Ralph Steinman in 2011) showed a similar pro- tein, dubbed a Toll-like receptor plays a key role in the innate immune systems of mice and people. DAS SPEKTRUM (And in case you were wondering about DER WISSENSCHAFT viruses, fruit flies defend against viral in- fections with a process called RNA interfer- DIGITALABO ence, which Hoffmann, mentioned, but Wissenschaftler berichten über die aktuellen Erkenntnisse said he really didn’t have time to tell that ihrer Fachgebiete. story.) Jahrespreis (12 * im Jahr) € 60,–; It turns out that insects really only need ermäßigt (auf Nachweis) € 48,– the innate immune system to survive and thrive—perhaps because they live for such HIER ABONNIEREN a short period of time. If they lived any

24

DATA-DRIVEN SCIENCE Big Data – not a big deal, just another tool Mohit Kumar Jolly »Big Data«, however fancy it might appear, is just another tool that can be useful to find some associations. CHRISTIAN FLEMMING NOBEL LAUREATE / LINDAU MEETINGS

Panel Discussion: Large Data and Hypothesis-Driven Science in the Era of Post-Genomic Biology Bruce A. Beutler, J. Michael Bishop, Moderator Stefan H.E. Kaufmann, Brian Schmidt and Jules A. Hofmann (from left) 25 ig Data, a buzz word these days do clinical trials. Then, as expected, you’ll get driver oncogene (the gene that is absolutely in biological research, promises drug resistance. Then you again go back se- essential for causing tumors). Beutler men- to collect and analyze the large quence the genome of the patient, and this tioned: »The big data approach is opposite to datasets (genomics, proteomics, cycle continues.«Bishop shared two specific mine. I am a reductionist. I start my study metabolomics etc.) to predict examples where the predicted associations with a phenotype, and try to identify what Bsome novel associations between genes and were completely misleading: »In the google causes it.« On being asked about his views diseases. »But these are just associations, and flu-tracking study, they almost made us be- about big data, he said »I do not think we unless we go back in the laboratory and es- lieve that they would be able to predict the should argue among tools. Tools should be tablish causal connection, it’s hardly of any spread of flu in different areas. We had high chosen according to the problem one’s trying use. You can really get fooled badly by the big hopes, but it all failed; later they realized that to address, not because everyone else uses data«, said J. Michael Bishop. »There was no the metric they used for analysis was too it.« Thus, two messages came out very clearly big data earlier, we still used to do good sci- squishy.« More importantly, a recent big data about the big data approach in biology - ence«, opined Jules A. Hoffmann. »Big data is study predicted an association between cho- (i) It can only give associations, not causal con- just another tool – not the only one certainly. lesterol levels and a pulmonary disease. The nections or mechanisms. Use it when you need it. You need not learn it patients were treated with cholesterol inhib- (ii) It can at maximum be an extra tool to yourself«, mentioned Brian P. Schmidt. To- iting drugs, and the clinical trials failed mis- complement the canonical reductionist gether with Bruce A. Beutler the Nobel Laure- erably. Schmidt, Nobel Laureate in Physics, approach, not replace it. ates debated about the role of big data at a unlike the three other Laureates on the panel Therefore, what can be considered as a bridge panel discussion in Lindau. They discussed (all of them in Physiology), mentioned that between ‘big data analysis’ and canonical their expectations as well as apprehensions he had been using the big-data approach rig- ‘small scale analysis’ is ‘meso scale analysis’ about the ‘big data’ approach. Schmidt men- orously for a long time. »But in physics, we based on physical sciences where we study tioned that big data is one tool that can pro- use really stringent statistical tests before the set of interactions between a finite num- pose some hypothesis that can be used to concluding anything – I do not see that kind ber of molecular players involved to under- drive research. Bishop added to it, saying that of stringency in big data biological studies. stand how those interactions explain the big data analysis and (reductionist) experi- Also, biological systems have its own unique emergent phenotypes. This approach has al- ments in the laboratory often form a vicious framework.« Bishop agreed with the same, ready been in use in simplier organisms (eg. cycle: »Let’s say you identify an oncogene us- saying that analyses with big data in tumor bacterium) for some time to elucidate their ing big data, then you go and verify that in biology often gives a list of potential onco- operating principles, and is entering cancer the lab. If you’re lucky, you design a drug, and genes, but that is not sufficient to identify the research too. <

26 There are enormous problems in the world. Maybe science is our only hope. It is very important to have young students!

– Edmond H. Fischer, Nobel Laureate, Physiology/Medicine 1996

Supported by Since 1951, young scientists and Nobel Laureates discuss ideas and solutions for the future at the Lindau Nobel Laureate Meetings.

60 years of science dialogue: mediatheque.lindau-nobel.org SCIENCE PLACES Virtual Visit at the Institut Pasteur in Paris

Stephanie Hanel NobelLabs 360° – in the lab Meet »Scientist Activist« Françoise Barré-Sinoussi. of Françoise Barré-Sinoussi

HTTP://NOBELLABS.LINDAU-NOBEL.ORG/PS_BARRESINOUSSI/INDEX.HTML AUS SCREENSHOT

28 ith the help of the No- panoramas, but include several short vide- fections« at the prestigious Institut Pas- belLabs 360°, we are os and other interactive elements. Looking teur in Paris. She was honoured by the No- able to visit the labs of nosily around the lab is highly welcome! bel Committee for the discovery of the Nobel Laureates and The newest Nobel Lab is the research HI-virus causing Aids. can almost look over unit of Françoise Barré-Sinoussi, recipient Normally, it would be a great honour to Wtheir shoulders as they, together with their of the 2008 Nobel Prize in Physiology or be taken on a lab tour at Institut Pasteur. teams, perform their daily tasks. The mul- Medicine. The French virologist heads the But with the Nobel Labs, everyone can join timedia presentations not only show 360° department »Regulation of Retroviral In- in. The tour starts on the rooftop terrace,

NobelLabs 360° – in the lab of Françoise Barré-Sinoussi

HTTP://NOBELLABS.LINDAU-NOBEL.ORG/PS_BARRESINOUSSI/INDEX.HTML AUS SCREENSHOT 29 Alles über Ihre from where the Safe Lab, the cytometry ways the result of team work. In order to grauen Zellen. lab and the Western Blotting labs can be understand complex systems, you always visited. My advice: take your time to look need a large team contributing findings Auf ihrem Bildschirm. around, then start one of the interview from different angles. But at the same time, videos. In one of these, Beatrice Jaquelin, you need charismatic researchers to ex- an engineer in the Safe Lab, tells us about plain to the world the relevance of this re- her work under strict security measures search effort. There is a current debate go- and amidst the noise of all the necessary ing on whether the concept of giving re- machines. The researcher Hicham El Costa search awards to single researchers is still explains how the Western Blot lab studies up-to-date. Shouldn‘t prizes and awards go HIV-transmissions from mother to child. to the teams, groups or institutes that con- Interspersed are messages from their com- ducted most of the actual work? In the for- mitted boss: she supplies background in- mat Nobel Labs, scientific achievements formation on key questions of their re- are presented as what they are: the com- search, for instance: how come that Green bined efforts of a strong team. Monkeys can be carriers of HIV without At the 64th Lindau Nobel Laureate Meet- getting ill? Barré-Sinoussi also says »We ing, Françoise Barré-Sinoussi gave a lecture can do better!«, meaning that greater in- on the topic »On the Road Toward an HIV ternational efforts are necessary to study Cure«. Visiting her lab is an excellent prepa- DAS GEHIRN UND GEIST HIV and to reduce infection rates. She is ration to understand her work – and it is DIGITALABO not only a researcher, but she is also an easier to leave her lab behind knowing that Alles über die Erforschung von AIDS activist and has been the president we will soon be able to watch a video from Ich und Bewusstsein, Intelligenz, of IAS, the International Aids Society, since her latest lecture here. < Emotionen und Sprache. 2012. By now, she has the inofficial title of Jahrespreis (12 * im Jahr) € 60,–; a »scientist activist«, which see seems to ermäßigt (auf Nachweis) € 48,– enjoy. Nobel Labs 360° is a non-profit educational project by The format Nobel Labs also reveals: now- the Lindau Nobel Laureate Meetings, performed by HIER ABONNIEREN adays, relevant scientific findings are- al German photographer Volker Steger.

30

SCIENCE COMMUNICATION Randy Schekman: Honest

CHRISTIAN FLEMMING NOBEL LAUREATE / LINDAU MEETINGS Exchange of Knowledge Beatrice Lugger Randy Schekman believes scientists can explain> their science in an understandable and honest way.> An Interview.

31 his morning in Lindau a Schekman: Yes, sure, that of course helps. bunch of journalists had the I think scientist should be made to explain pleasure to interview Randy themselves clearly to other people. There- Schekman, Nobel Laureate in fore every paper that we publish on eLife Physiology and Medicine in – Schekman is editor in chief of this Open T2013 together with James Rothman and Access journal – has something that we call Thomas C. Südhof for their »ground-break- an eLife digest that is written for a broader ing work on cell membrane vesicle traffick- audience. Broader in a sense of written for ing«. Schekman is not only well known for someone who has a basic understanding of his research, but especially for his engage- life sciences. So we try to remove the tech- ment in the open access movement. nical language that would be just for spe- During this interview Schekman point- cialists.

ed out, that scientists themselves should communicate in a better understandable Q: Who is in charge of these

way. Also during recruitment processes special digests? AUSTEN KAT some short essays written without techni- Randy Schekman in Lindau cal details could be of help, Schekman rec- Schekman: This is mainly an editorial ommends. People today get access to sci- thing. Although I think scientist can do it, entific articles, whether they are specialists unfortunately a number of scholars sim- themselves, researchers in another field or ply can’t be bothered. It is difficult to get interested in science at all. There is not them to write it in a way that could gener- ‘only’ the special scientific community but ally be understood so we have to pay peo- a broader audience. ple to help copy at that. We have actual a physicist in our staff, who writes these. Q: When the general public is interested in reading the original papers and the de- Q: So there is a communication tails of science doesn’t that mean, there is specialist and scientists communicate at least a need for abstracts, written in a the same way they do in a scientific language, understandable for lay people? paper?

32 Der ganzen Kosmos. Schekman: I think it is a scientist’s respon- scholars craft an impact statement of may- sibility to learn how to communicate effec- be 250 words. Then the committee can cre- Auf Ihrem Bildschirm. tively with a broader public. This also has a ate a short list of candidates and then look positive effect on science itself. When I give into the papers and letters of recommen- a talk I know that most of the people in the dation and refine judgments. It should be audience are not specialists in my topic. So written in a way a broader group of other unless I want to talk to the two people in scholars can read and say ‘Oh, wow, he dis- the front row, who are my competitors, I covered that’. ‘I didn’t know that, but that have to make myself clear. Teaching under- sounds really important’. graduate students for many years has helped me. They expected these lectures to Q: Present yourself in the best way? be made clear and understandable. Schekman: Well, we are relying to the hon- Q: Are communication skills something esty of the individual to fairly represent that should even be part of recruitment themselvs. Not only in this context stu- processes? dents have to be educated about the impor- tance of the ethics of sciences. We need the Schekman: That could well be a criterion. honest exchange of knowledge. So students DAS STERNE Unfortunately it is not. But it could be. have to be educated in the proper values UND WELTRAUM When hundreds of people apply for a job, via scholarship and the penalties for break- DIGITALABO you can’t read hundreds of papers. For a ing those rules, which are really severe. < Erfahren Sie alles über Astronomie better recruitment process I suggest to ask und Raumfahrt – direkt aus each scholar to prepare a narrative, an im- Thank you, Randy Schekman. den Forschungslaboren der Welt. pact statement, about their most impor- Jahrespreis (12 * im Jahr) € 60,–; tant work. Scientists are used to this when ermäßigt (auf Nachweis) € 48,– we describe ourselves for a fellowship or a job and other applications. But I would like HIER ABONNIEREN to make it more formal, I would like to have

33 AIDS RESEARCH The HIV-Pandemic and Scientific Persistence – Barré-Sinoussi Yasin Emanee »Never give up and never stop believing that you will and can make a difference.«

Anti-Retroviral Treatment center of Gauhati Medical College in Guwahati, India

ENAMEE YASIN 34 rancoise Barré-Sinoussi, Nobel greatest turning point in his life. Many a Laureate in Physiology or Medi- times, I have personally escorted the vic- cine 2008, says at the Lindau tim to the psychiatry ward for a consulta- Meeting she had never im- tion before we start treatment.« agined this pandemic when she HIV thus is a multifaceted problem com- Finitially started working on the virus in the plicated by cultural and emotional dimen- early 1980s. The Nobel scientist shares this sions, and warranting a similarly unique experience with patient counselors and strategy for its elimination. Whereas on one physicians all around the globe. I have vis- end we are on the edge of understanding ited D. Gogoi, a patient counselor at the An- the scientific complications underlying the

ti-Retroviral Treatment center of Gauhati mystery of the Berlin Patient, we have the ENAMEE YASIN Medical College in Guwahati, Assam, India vast range of behavioral interventions that Indisches Aufkärungsposter before my trip to Europe and the Lindau we need to devise on political and social Meeting. his centre works under the Na- principles that would help us get ahead of must be above everything. Diseases do not tional Aids Control Programme (NACO) of the virus. Barre-Sinoussi was apt to point know borders, and so we cannot afford to India. Gogoi sits in a desk surrounded by out the same on multiple occasions (and in fight them as individual groups. TheLindau colorful posters on how AIDS (Acquired her plenary session) along with the need for Nobel Laureate Meeting 2014 is already Immune Deficiency Syndrome) spreads scientific activism to inspire the next gener- proving a great inspiration for science on and how it can be stopped. ations, something she considers continuing that theme. With people from across the She tells me, reminiscing her 20 years of even after her imminent retirement. Asked, globe discussing novel strategies to diag- service in that position, »We are doing our what is the one suggestion that she wants to nose and know diseases, planning collabo- best; our control programs and treatment give to young scientists starting out their rations, discussing how others’ research can protocols are good, but the epidemic has research careers, Barré-Sinoussi answered be helpful to their own and much more, I not grown weaker. Sometimes when I feel pointedly: »Persistence. Never give up and look forth to the remaining days of the that maybe the patient load is finally going never stop believing that you will and can meeting with inspiring and beautiful forays to decrease, there is always this one patient make a difference. There is no finish line. into the sea of science. < who has been recently diagnosed with the Even when we come up with a cure for HIV, malady, perhaps young and energetic, for that will still mean we can use HIV as a tool More about the laureates’ reflections of the disease whom the news of this will become the for studying other diseases.« Thus science problem and its solution strategies here and here.

35 VIRUS RESEARCH Could A Cow Virus Cause Colon Cancer? Christine Gorman There is a well-known connection between red meat and colon cancer. Nobel laureate Harald zur Hausen thinks the culprit might be a virus.

DREAMSTIME CRETU / DAN 36 he remote possibility that I erably with a generous helping of ketchup And why should anyone pay attention might develop mad cow dis- and relish). But that was before I heard Har- to what Harald Zur Hausen thinks? Well, he ease as a result has never ald zur Hausen hypothesize that a cow vi- won a Nobel Prize in 2008 for proving that stopped me from diving into rus might be responsible for most cases of most cases of cervical cancer are caused by a nice juicy hamburger (pref- colon cancer. a few strains of Human Papilloma Virus T (HPV). Nor is HPV the only viral cause of cancer. Chronic infection with certain hep- atitis viruses, for example, is a major cause of liver cancer. Zur Hausen provided some intriguing factoids to support his idea at the 64th Lin- dau Nobel Laureate Meeting in Lindau, Germany. But he certainly does not have a smoking gun (nor did he claim to). Still, he could not resist tweaking the »cancer is genetic misregulation« crowd, including perhaps J. Michael Bishop, who gave a talk the day before, entitled »Forg- ing a Genetic Paradigm for Cancer.« »The common idea is that human can- cers occur because of an imbalance be- tween proto-oncogenes and tumor sup- pressor genes,« zur Hausen told the audi- ence of 600 young scientists who had won a competition among 3000 to 4000 appli-

Harald zur Hausen during his

CHRISTIAN FLEMMING NOBEL LAUREATE / LINDAU MEETINGS talk in Lindau 2014

37 cants for the honor of attending the meet- problem for one kind of cooked meat, but a viral culprit. »But I don’t want to talk too ing. »That viral infections can cause cancer not another? much about the identity of these virus or is a great disturbance to this beautiful pic- Then zur Hausen relayed the curious virus isolates because it’s under active in- ture.« fact that the country of Mongolia has very vestigation,« he said. Of course, zur Hausen concedes that low colon cancer rates, but it also has high- At this point, the bovine virus-colon genes play a role—even in cervical and liv- est meat consumption per capita of any cancer link is clearly more speculation than er cancer. But those tumors will not take country in the world. Perhaps the fact that science, but zur Hausen wasn’t done yet. hold for the most part without the viral in- Mongols eat mostly yak, mutton goat, As his talk was winding up, the Nobel fection having occurred in the first place. canned meat and horsemeat has some- laureate added yet another wrinkle to his thing to do with the apparent mystery. mix of provocative hypotheses. Breast can- A viral cause for colon cancer? Colon cancer incidence is relatively low cer, he noted, is one of the few cancers in Zur Hausen’s intriguing line of evidence in India (where vegetarianism is quite which immune suppression results in a consists mostly of provocative questions prominent), some Arabic countries (where DECREASE in its incidence. that take on the received wisdom—ques- goat is more common) and Bolivia as well, There are plenty of potential reasons tions that he is more than willing to follow zur Hausen said. The Bolivian situation is a why that might be the case—but one possi- with further investigation of the sort that bit complicated by the fact that so many of bility is that breast cancer, too, might have a will eventually prove his hypothesis right the beef cattle there appear to be mixes viral component. And sure enough when or wrong. from different species. zur Hausen compared breast cancer and co- For example, the received wisdom is The evidence suggests to zur Hausen lon rates in Bolivia, Mongolia and India, he that the connection between red meat and that the risk factor for colon cancer in red found they tracked each other—not abso- an increased risk of colon cancer has some- meat has to do with the Bos taurus species lutely identically—but in a very similar way. thing to do with the number of heterocy- of beef—the most common around the His best guess is that if there is viral clic amines that form during the cooking planet. Perhaps, he posits, there an undis- agent responsible for breast cancer, that it of red meat. covered virus that is causally involved in may be related to but not the same as the And yet, zur Hausen reported, »fried, human colorectal cancer with respect to one for colon cancer grilled or smoked fish or chicken actually raw or undercooked red meat (beef espe- Oh dear, another reason (besides in- have the same or higher concentration of cially). creased risk for heart disease and food poi- heterocyclic amines as red meat.« In other So far, his lab has found 18 different ge- soning) to avoid hamburgers, especially if words, why would heterocyclic amines be a netic sequences that might be evidence of they’re medium rare. <

38 INFECTIOUS DISEASES From Mice and Fruit > Flies Towards Novel > Infection Treatment Susanne Dambeck Susanne Dambeck on the Research of immunologists Bruce Beutler and Jules Hoffman who are both at Lindau for the first time.

FOTOLIA / AAALI 39 ver since the discovery of the his closest friends and colleagues, rousing role of pathogens more than a most of them from sleep. hundred years ago, researchers Beutler won the Nobel Prize for his asked: but how does the body breakthrough on the innate immune sys- identify pathogens in order to tem, more precisely: on toll-like receptors. Ecombat them? Bruce Beutler and Jules He discovered that one toll-like receptor, Hoffman both made important discover- TLR4, was responsible for the identification ies on the workings of the immune system. of bacteria on a molecular level. Mice with- This year, both will attend the Lindau No- out functioning TLR4 were unable to beat bel Laureate Meeting for the first time. bacterial infections. Beutler is a doctor by On October 3rd in 2011 at 2:30 a.m., training, but always was a scientist at heart. Bruce Beutler was lying wide awake in his Already as a teenager he had worked in his apartment in San Diego. He was still on father’s lab: Ernest Beutler was a renowned Hong Kong time, where he had received pioneer in modern hematology. His par- the Shaw Prize in Life Sciences. He also ents had fled with him from Germany in MOTZKAU knew that the Laureates for the 2011 Nobel 1935. Young Bruce was just as gifted as his

HOLGER Prize in Physiology and Medicine would be father: He finished high school at age 16 Jules A. Hoffmann won the 2011 Nobel announced that day – in Stockholm, nine and graduated from college at 18. He went Prize in Physiology and Medicine, together time zones ahead of him. Bleary-eyed, he to medical school at the University of Chi- with Bruce Beutler looked at his cell phone: there was one new cago, just like his father – but the pull of email, with just two words in the subject the lab was stronger. line: Nobel Prize. Too excited to read more Jules Hoffmann was awarded the Nobel than the introductory congratulations, he Prize together with Beutler: he had de- ran downstairs and called a colleague: scribed the role of the toll-gene for the in- »Bets, I think I won the Nobel Prize!« Con- nate immune system of fruit flies. The firmation was difficult, there being too third recipient, Ralph M. Steinman, who much traffic on the Nobelprize.org- web had coined the term »dendritic cells« in site. Once the good news was confirmed, the 1970s, died three days before the prize Beutler called his his sons, his mother, and was announced of pancreatic cancer. Since

40 the Nobel Committee hadn’t been aware of his death, he is still considered a Nobel Sie suchen eine Laureate; normally, the prize is not award- ed posthumously. Hoffmann is a Luxem- Medizinerin bourg-born French biologist who has spent als Rednerin für his career working with the model organ- ism drosophila melanogaster, or fruit fly. Ihren nächsten He had studied and worked in Strasbourg, and now is the research director of the Na- Kongress? tional Center of Scientific Research (CNRS) there. Today, toll-genes and toll-like receptors are known to exist in mammals, insects and even plants. In fruit flies, they play a crucial role in embryonic development, as MOTZKAU well as in the immune system. Ten human

HOLGER TLRs are known, mice have three addition- Bruce Beutler won the 2011 Nobel Prize in al TLRs. With their presence in the den- Physiology and Medicine, together with Jules dritic cells, they are also considered to Hoffmann form an important link between the in- nate and the adaptive immune system. Many drug development efforts have tar- geted these receptors and have for in- stance developed treatment strategies against autoimmune diseases like rheu- Das Rechercheportal für herausragende Wissenschaftlerinnen matoid arthritis. Labs around the world are working on novel strategies to modu- late the immune responses to bacterial or www.academia-net.de viral infections. <

41 BACTERIAL INFECTIONS On Man and Microbes –

CHRISTIAN FLEMMING NOBEL LAUREATE / LINDAU MEETINGS Barry Marshall Hanno Charisius The bacterium Helicobacter pylori causes stomach ulcers. But it may have a helpful side, too.

Barry Marshall in Lindau 2014 42 n the summer of 1984, the Australi- was that gastric ulcers were mostly a psy- Indeed, H. pylori is one of humanity’s an scientist Neil Noakes took some chosomatic affliction caused by too much old friends and companions: the germ has bacteria from a petri dish, mixed stress. Accordingly, patients were treated been with us for at least 50,000 years, and them with lukewarm beef extract – with tranquillizers, anti-depressants, psy- probably longer. Roughly fifty percent of the normal nutrient solution for chotherapy or antacids. Instead the young all humans carry it around in their stom- Ibacteria in the lab – and filled a little more doctor Marshall treated them all with anti- achs. Interestingly, the percentage of in- than one cup into a beaker. Then he hand- biotics, and his results were impressive. fected people has been decreasing since ed this mix to his colleague, the gastroen- From his clinical practice, he developed the the 1950s, with richer countries having terologist Barry Marshall, who downed it theory that the spiral-shaped Helicobacter much lower rates than the rest of the world. without complaining. bacterium causes gastritis, painful stom- In the US, less than 25 percent of adults and Three days later, Marshall felt nauseat- ach ulcers and even stomach cancer. Be- only about 5 percent of all school children ed and his mother told him he had bad cause he had had no suitable test animals are infected. Marshall says that better hy- breath. Next he started vomiting. But he at hand, he used his own body for the de- giene and clean drinking water are respon- still waited a few days before taking the an- scribed experiment. sible for the bacteria’s eviction. tibiotics that were supposed to kill the bac- From this moment on, the only good Doctors claim that Helicobacter is re- teria in his stomach. A gastroscopy not Helicobacter was a dead one. Loads of anti- sponsible for three out of four stomach ul- only clarified his diagnosis, but ultimately biotics were used to combat this germ. cers, two thirds of all gastric tumors and resulted in his winning the Nobel Prize in Some experts even wanted to eradicate practically all duodenal tumors; the duo- Physiology and Medicine about twenty Helicobacter as a precautionary measure. denum is the part of the small intestine years later. And Marshall received the Nobel Prize in that comes directly after the stomach. So With his famous self-experiment, Mar- 2005, together with his former co-worker its extermination should be a good thing – shall was able to demonstrate that Helico- Robin Warren. In the meantime, even Mar- shouldn’t it? bacter pylori bacteria can cause acute gas- shall has become more sympathetic when But at the same time as the germ was re- tritis which in turn may cause ulcers. He he talks about the germ that made him fa- treating, other health problems occurred. had asked neither an ethics commission mous – almost as if it where an old friend. Since the 1950s, the number of patients nor his wife for permission to conduct this During his lecture at the 64th Lindau No- with allergies, asthma or autoimmune dis- experiment. His colleagues thought him bel Laureate Meeting, he points out that eases has sky-rocketed. Children without completely insane to take a risk like that. this single-cell organism might even help Helicobacter in their stomachs are more Back in the 1980s, the prevailing theory to fight some diseases. likely to suffer from skin allergies or hay fe-

43 ver. The bacteria also seem to provide a cer- nism during human history: when groups But he expects adults to profit only little tain protection against coeliac conditions, of Homo sapiens left Africa in prehistoric from his results. Contact with these mi- also known as wheat gluten intolerance. times, these bacteria prevented them from crobes seems to be crucial in the first few The bacteria might even manipulate our developing severe allergies against all new years of life during the development of the appetite: the New York based doctor Mar- plants they encountered on their long jour- immune system. tin Blaser assumes a connection between ney. If they had stayed in Africa and only But the thought to give bacteria to new- its eradication and the growing obesity eaten plants and animals from their im- borns that might later cause cancer makes problem worldwide. mediate vicinity, no slow down switch for most people feel uneasy. Another idea will Blaser was in fact one of the first scien- the immune system would have been nec- probably be more easily accepted: We can tist who noticed that the germ is not only essary. »One theory says that only with the only provide the components of the bacte- causing harm. He first thought about its help of these bacteria, we humans were ria that are needed to keep the immune positive aspects when he saw data on pa- able to adapt to a varied diet«, Marshall ex- system in check, Marshall said. This tients with stomach ulcers, who seldom plains. shouldn’t cause inflammation but could suffered from heart burn or esophageal So now, instead of fighting his favorite still help to curb our immune system. Mol- cancer. On the other hand, people without germs, Marshall focuses on studying the ecules on the bacterium’s surface would be Helicobacter in their system don’t develop effects of reinfections of humans. But not possible candidates for this job. many ulcers, but are much more likely to with a gulp from some meat extract, as he Although Marshall talks more in a have heart burn and reflux problems, did in the past. There are many different H. friendly way about his former opponent sometimes even resulting in cancer. pylori variants that vary greatly in aggres- now, in one situation he remains uncom- Nowadays, even Barry Marshall sees the siveness. Only the more harmless should promising: »If the bacterium causes trou- germ’ two faces – the dangerous and the be used for experiments like that, says Mar- ble, it has to go.« As long as it makes no helpful. Many studies suggest that H. py- shall, who already secured patents in that problems, it may stay. But there are very lori is an important training partner for area of interest. effective antibiotics to get rid of it. our immune system: it seems to be able to Whether reinfection really offers a cer- Besides Helicobacter pylori, more than contain the immune response. If the bacte- tain protection against allergies is current- 1,000 other types of bacteria live on and in ria are missing, our immune system ly tested on mice in several research groups. the human body, resulting in a total num- over-reacts when confronted with pollen, But even humans are swallowing these ber of about 100 trillion bacteria. So there wheat gluten or peanuts. Marshall thinks germs again in the name of science, Mar- should be no lack in substitute training that this connection was a vital mecha- shall is currently planning clinical studies. partners for our immune system. <

44 MEDICAL RESEARCH Physician-Scientists:> An Endangered Species? Jalees Rehman Can excellent scientists be excellent physicians at the same time?

»Portrait of Dr. Paul Gachet« –

1890 / PUBLIC GACHET, DOMAIN GOGH: DR.VINCENT VAN PAUL Painting by Vincent van Gogh

45 would like to ask you about a trip to had asked me a question which directly able to convince him. I remember this an- Thailand.« This is not the kind of pertained to my research. My laboratory’s ecdote so well is because in my career as a question I expected from a patient in focus was studying the release of growth physician-scientist, the two worlds of sci- » my cardiology clinic at the Veterans factors from stem cells and whether they ence and clinical medicine rarely overlap Administration hospital in Indianap- could help improve cardiovascular func- and this was one of the few exceptions. Iolis. Especially since this patient lived in tion. But my excitement was short-lived Most of my time is spent in my stem cell rural Indiana and did not strike me as the and gradually gave way to horror when the biology laboratory, studying basic mecha- adventurous type. patient explained the details of the plan. A nisms of stem cell metabolism and molec- »A trip to Thailand?«, I mumbled, »Well, private clinic in Thailand was marketing ular signaling pathways. Roughly twenty ummm … I am sure … ummm … I guess the bone marrow cell injections to treat heart percent of my time is devoted to patient trip will be ok. Just take your heart medica- patients with advanced heart disease. The care, treating patients with known cardio- tions regularly, avoid getting dehydrated patient would have to use nearly all his life vascular disease in clinics, inpatient wards and I hope you have a great vacation there. savings to travel to Thailand and stay at and coronary care units. I am just a cardiologist and if you want to this clinic, have his bone marrow extracted As scientists, we want to move beyond know more about the country you ought and processed, and then re-injected back the current boundaries of knowledge, ex- to talk to a travel agent.« into his heart in order to cure his heart dis- plore creative ideas and test hypotheses. I realized that I didn’t even know wheth- ease. As physicians, we rely on empathy to com- er travel agents still existed in the inter- Much to the chagrin of the other pa- municate with the patient and his or her webclickopedia world, so I hastily added tients in the waiting room, I spent the next family, we apply established guidelines of »Or just use a travel website. With photos. half hour summarizing the current litera- what treatments to use and our patient’s Lots of photos. And videos. Lots of videos.« ture on cardiovascular cell therapies for comfort takes precedence over satisfying Now it was the patient’s turn to look con- the patient. I explained that most bone our intellectual curiosity. The mystique of fused. marrow cells were not stem cells and that the physician-scientist suggests that those »Doctor, I didn’t want to ask you about there was no solid evidence that he would of us who actively work in both worlds are the country. I wanted to know whether you benefit from the injections. He was about able to synergize our experiences from sci- thought it was a good idea for me to travel to undergo a high-risk procedure with entific work and clinical practice. Being a there to receive stem cell injections for my questionable benefits and lose a substan- scientist indeed has some impact on my heart.« I was thrilled because for the first tial amount of money. I pleaded with him clinical work, because it makes me evaluate time in my work as a cardiologist, a patient to avoid such a procedure, and was finally clinical data on a patient and published pa-

46 pers more critically. My clinical work helps Dr. J. Michael Bishop me to identify areas of research which in the long-run may be most relevant to pa- tient care. But these rather broad forms of crosstalk have little bearing on my day-to- day work, which characterized by mode-switching, vacillating back and forth between my two roles. Dr. J. Michael Bishop, who received the Nobel Prize in 1989 with Dr. Harold Var- mus for their work on retroviral cancer genes (oncogenes), spoke at panel dicus- sion at the 64th Lindau Nobel Laureate Meeting about the career paths of physi- cian-scientists in the United States. Narrat- ing his own background, he said that after he completed medical school, he began his clinical postgraduate training but then ex- clusively focused on his research. Dr. Bish- CHRISTIAN FLEMMING NOBEL LAUREATE / LINDAU MEETINGS op elaborated how physician-scientists in why it is so difficult to remain active as a JR: You embody the physician-scientist the United States are often given ample op- scientist and a clinician. role, by actively managing neuro-oncol- portunities and support to train in both To learn more about physician-scientist ogy patients at the university hospital in medicine and science, but many eventual- careers in Germany, I also spoke to Dr. Heidelberg as well as heading your own ly drop out from the dual career path and Christiane Opitz who heads a cancer me- tumor metabolism research group at the decide to actively pursue only one or the tabolism group at the German Cancer Re- German Cancer Research Center other. The demands of both professions search Center, DKFZ, in Heidelberg and is (Deutsches Krebsforschungszentrum or and the financial pressures of having to an active clinician. She was a Lindau at- DKFZ in Heidelberg). Is there a lot of bring in clinical revenue as well as research tendee as a young scientist in 2011 and this crosstalk between these two roles? Does grants are among the major reasons for year has returned as a discussant. treating patients have a significant influ-

47 ence on your work as a scientist? Does But I also know that even if we were lucky Physicians and scientists have always your work as cancer cell biologist affect enough to uncover a new mechanism, it conducted »translational research«, but it how you evaluate and treat patients? is very difficult to predict if and when it has now become a very popular buzzword. would contribute to a new treatment. This For that reason, I am a bit concerned when CO: In my experience, my being a physi- is why my scientific work is primarily driv- too much focus and funding is shifted to- cian influences me on a personal level and en by scientific curiosity and guided by the wards application-oriented science at the my character but not so much my work as experimental results, whereas the long- expense of basic science, because then we a scientist. Of course I am more aware of term hope for new therapies is part of the might lose the basis for future scientific patients’ needs when I design scientific ex- bigger picture. breakthroughs. We need a healthy balance periments but there is not a lot of crosstalk of both. between me as a physician and me as a sci- JR: Is it possible that medical thinking entist. I treat patients with malignant brain doesn’t only help science but can also be JR: Does the medical training of a physi- tumors which is a fatal disease, despite problematic for science? cian draw them towards application-ori- chemotherapy and radiation therapy. We ented translational science and perhaps unfortunately have very little to offer these CO: I think in general there is increasing fo- limit their ability to address the more patients. So as a physician, I see my role as cus on translational science from bench- fundamental mechanistic questions? being there for the patients, taking time to to-bedside, the aim to develop new treat- talk to them, provide comfort, counseling ments. This application-oriented approach CO: In general, I would say it is true that their families because we do not have any may bear the risk of not adequately valu- people who were trained purely as scien- definitive therapies. This is very different ing basic science. We definitely need trans- tists are more interested in addressing ba- from my research where my aim is to study lational science, because we want patients sic mechanisms and people who were basic mechanisms of tumor metabolism. to benefit from our work in the basic scienc- trained as physicians are more interested There are many days when I am forced to es. On the other hand, it is very important in understanding applications such as tell a patient that his or her tumor has re- to engage in basic science research because therapies, therapeutic targets and resist- lapsed and that we have no more treat- that is where – often by serendipity – the ance to therapies. They are exceptions, of ments to offer. Of course these experienc- real breakthroughs occur. When we con- course, and it is ultimately dependent on es do motivate me to study brain tumor duct basic science experiments, we do not the individual. I have met physicians who metabolism with the hope that one day my think about applications. Instead, we pri- are very interested in basic sciences. I also work might help develop a new treatment. marily explore biological mechanisms. know researchers who were trained in the

48 basic sciences but have now become inter- haps we used to roam the earth in large programs, does it compromise our clinical ested in therapeutic applications. numbers and have now become rather rare. skills to a point where we may not make I am not sure this is an accurate portrayal. the best decisions for our patients? JR: When physicians decide to engage in It is true that current financial pressures at We are often forced to sacrifice our week- basic science, do you think they have to research funding agencies and academic ends, the hours we sleep and the time we perhaps partially »unlearn« their natu- institutions are placing increased demands spend with our families or loved ones so ral tendency of framing their scientific on physician-scientists and make it harder that we can cope with the demands of the experiments in terms of therapeutic ap- to actively pursue both lines of work. How- two professions. This is probably also valid plications because of their exposure to ever, independent of these more recent fi- for other dual professions. Physician-sci- clinical problems? nancial pressures, it has always been ex- entists are a rare breed, but so are physi- tremely challenging to concomitantly cian-novelists, banker-poets or philoso- CO: We obviously need application-orient- work in two professions and be good at pher-scientists who try to remain actively ed science, too. It is important to encour- what you do. Dr. Bishop decided to forsake engaged in both of their professions. age physicians who want to pursue transla- a clinical career and only focus on his mo- There will always be a rare population of tional research in the quest of new thera- lecular research because he was passionate physician-scientists who are willing to take pies, but we should not regard that as about the research. His tremendous suc- on the challenge. They need all the availa- superior to basic science. As a physician cess as a scientist shows that this was prob- ble help from academic institutions and who is primarily working in the basic ably a good decision. research organizations to ensure that they sciences, I make a conscious effort to focus As physician-scientists, we are plagued have the research funds, infrastructure and on mechanisms instead of pre-defined by gnawing self-doubts about the quality optimized work schedules which allow therapeutic goals. of our work. Can we be excellent scientists them to pursue this extremely demanding and excellent physicians at the same time? dual career path. It should not come as a Looking to the future Even if, for example, the number of days surprise that, despite the best support Dr. Opitz’s description of how challenging we see patients are reduced to a minimum, structure, a substantial proportion of phy- it is to navigate between her clinical work can we stay up-to-date in two professions sician-scientists will at some point feel in neuro-oncology and her research mir- in which a huge amount of new knowledge overwhelmed by the demands and person- rors my own experience. I have often heard is produced and published on a daily basis? al sacrifices and opt for one or the other ca- that the physician-scientist is becoming an And even though the reduction in clinical reer. Even though they may choose drop »endangered species«, implying that per- time allows us to develop great research out, the small pool of physician-scientists

49 will likely be replenished by a fresh batch of younger colleagues, attracted by the prospect of concomitantly working in and bridging these two worlds. Instead of lamenting the purported de- mise of physician-scientists, we should also think about alternate ways to improve the dialogue and synergy between cutting-edge science and clinical medicine. A physician can practice science-based medicine with- out having to actively work as a scientist in a science laboratory. A scientist can be in- spired or informed by clinical needs of pa- tients without having to become a practic- ing physician. Creating routine formalized exchange opportunities such fellowships or sabbaticals which allow scientists and clinicians to spend defined periods of time in each other’s work environments may be much more feasible approach to help bridge the gap and engender mutual un- derstanding or respect. <

After a long Lindau day: Evening at the conference venue

50 NOBEL LAUREATE / LINDAU MEETINGS ROLF SCHULTES

SYNTHETIC BIOLOGY Synthetic Genes, Synthetic Cells – Synthetic Life Hanno Charisius Nature needed about one billion years to create the simplest single-cell organisms that swam around in the primordial soup. Now, scientists are eager to create synthetic life – but better and faster.

Hamilton O. Smith 2014 at Lindau 51 amilton Smith (Nobel lot of ‘genetic waste’ has accumulated that »a genome that is very understandable – Prize in Chemistry 1978 might have been useful at some point, but we are searching for the genetic kernels of with Werner Arber and was rendered useless by mutations. Some life«. In sorting out the genes, Smith uses Daniel Nathans) started genetic fragments were in fact smuggled three gene categories. The genes he analy- his lecture at the 64th No- into the genome by viruses, others were ses are either Hbel Laureate Meeting in Lindau with a created by accidental duplications of ge- quote from Richard Feynman (Nobel Prize netic segments. Numerous molecular • essential for life in Physics 1965): mechanisms lead to many genetic varia- • not essential, but knocking them tions – rendering evolution possible in the out leads to slower cell growth first place. But over time, many of these • non-essential »What I cannot create, genes and segments have become useless. I do not understand.« Currently Smith tries to tidy up the ge- Smith also assumes that all genes from the nome of Mycoplasma mycoides, a microbe last group can be switched off without neg- Feynman had probably meant physical normally living in the digestive tract of ru- ative impacts on the microbes. Concerning models, whereas Smith referred to living minants. Originally Smith and his team the middle category, the researchers have organisms. In his laboratory at the J. Craig wanted to use the genome of Mycoplasma to carefully weigh all options. When all is Venter Institute, he tries to create synthet- genitalium, the bacterium with the small- done, the result should be a bacterium that ic cells: »I hope that if we create that, we est known genome – it needs only 475 genes can still multiply rapidly, at least in labora- will understand.« to live. Smith estimates that about 100 of tory conditions that offer plenty of nour- Nowadays, the entire human genome these are non-essential. But since M. my- ishment, constant temperatures, but no has been decoded. But how a live human coides has a much higher cell division rate, competitors. The researchers’ goal is a fifty being develops from DNA molecules, a hu- although its genome is twice as large, ex- percent genome reduction in a happily man being that can breath, eat, walk, study, periments with M. mycoides proved to be thriving microbe that divides at least once love, receive Nobel Prizes and award them – more effective. During this ‘minimal cell in 100 minutes. nobody really understands yet. Even for project’, the researchers switch off one gene During his Lindau lecture, Smith called single-cell organisms, this isn’t crystal after another and study the effects on the the genetic waste »spaghetti code«, a pro- clear. Even the simplest bacteria exhibit microbes. (And the slower the microbes grammer term used to describe some genes without apparent function, that are grow, the longer the researchers have to messy program code that was written, for not essential for life. During evolution, a wait for their results.) Smith’s final goal is instance, by too many programmers and

52 The genome before … … and after the modifications OF H. SMITH’S 2014 LINDAU SCREENSHOT LECTURE AT has become completely chaotic, although enzymes), controlled by said software. As researchers might succeed: four years ago, it still functions. The tidying up of a code soon as a cell receives a new genetic pro- Smith’s team caused a sensation by bring- like this is called »refactoring« if the pro- gram, it starts to put this program to use. ing bacteria to life with a completely syn- gram’s function remains the same. And In order to test their own synthetic pro- thetic genome designed on their comput- that is exactly what Smith and his team are grams, Smith and his team replaced the ers. Nowadays automated synthesising doing with the genetic code of a bacteri- bacterium’s DNA with synthetic DNA con- machines that can create any DNA form um: Its genome is reduced to the absolute taining their basic program. To date, the the four original bases, or with Smith’s minimum requirements of life, to the old ‘hardware’ has not adopted the new words: »simply a piece of software written »core machinery of life«, as Smith puts it. program ‘update’. In computer speak, trou- in a four-letter code.« But the researchers Smith likes using computer terms to de- bleshooting and maintenance are called did not invent a new bacterium, they cop- scribe his work. He compares the genome »debugging«: Smith and his team will be ied the M. mycoides genome with a few var- of any organism with its software, the rest busy with debugging for some time. But iations to later identify their creation in is hardware (the cytoplasm, proteins and recent successful projects suggests that the the living cell. They transplanted this syn-

53 thetic genome into bacteria that are close- several Nobel Prizes. A few examples: Ar- ing in a research moratorium about cer- ly related to M. mycoides – the new genome thur Kornberg won the 1959 Nobel Prize, tain gene regions and combinations effec- took over and controlled the cells, as together with Severo Ochoa, for discover- tive for several years. Finally in 1986, Kary planned. Because this experiment con- ing »the mechanisms in the biological syn- Mullis was honoured for his discovery of a firmed the software metaphor so nicely, it thesis of DNA«, especially the role of poly- technique to amplify DNA sequences in became an important stepping-stone to- merase in DNA duplication. James Watson the lab, making the resulting improved wards creating synthetic life. This novel and Francis Crick won the 1962 prize for PCR (polymerase chain reaction) the cen- discipline is called synthetic biology, its their famous description of the DNA dou- tral method in molecular biology. goal is the creation of organisms with new ble helix. And Smith, Arber and Nathans Without these findings, Smith and his biological functions that don’t already ex- received the 1978 prize for discovering type team would not be able to pursue their goal ist in nature. Until recently, biotechnolo- II restriction enzymes, enzymes that are to create synthetic life. They not only want gists could only make small changes in ge- able to cut the DNA at specific nucleotide to understand – they also want to apply nomes, like switching off certain genes or sequences very precisely. Two years later, their knowledge. The novel microorgan- inserting new genes, to give plants, bacte- Paul Berg, Walter Gilbert and Frederick isms they are trying to create are supposed ria or animals new functions. Often the re- Sanger won the prestigious prize: Gilbert to produce everything from drugs and bio- sulting bacteria produce some protein that and Sanger had developed a new DNA se- fuel to chemicals. The researcher’s imagi- is needed for drug development or produc- quencing method. Today’s hundreds of ge- nation has no limits, only the present-day tion. But things get more difficult when an- nome studies published every month were knowledge. »We can chemically design any other substance besides proteins is the tar- made possible only by these sequencing DNA sequence«, Smith explains, »but we get. The 2006 transplantation of an entire methods, as well as by the subsequent price cannot yet design a gene at the computer metabolic pathway caused quite a stir. The slump in genome analysis in recent years. with a specific enzymatic activity. We can resulting yeast cells were able to produce ar- Berg was one of the first researchers to best modify existing protein designs.« Na- temisinic acid, that can be converted into an combine genes from different organisms, ture’s programs can be copied and modi- anti-malaria drug. Thus the transplantation and is considered one of the founding fa- fied, but no synthetic formula for life has of an entire genome was the next logical thers of genetic engineering. He was also yet been found or invented. But computer step, although the novel synthetic organ- one of its first critics: He co-initiated the programmers learn by copying existing ism doesn’t produce anything useful yet. Asilomar in 1975, where scientists shaped programs until they truly understand how All of these developments were only voluntary guidelines concerning the safety the stuff works. Then they can start to get made possible by past discoveries worth of recombination DNA technology, result- creative. <

54 FANDOM Autographs vs. #NobelSelfie Vincenzo Hiemer Meeting Participants Renata Gomes and Adam Spencer had a Nobel Laureate Fan Competition. Find out who won!

Adam Spencer snapping a selfie with Ada Yonath SPENCER

ADAM 55 or people attending a Lindau Nobel Laureate Meeting for the first time it is often a surprise how approachable and fun-lov- ing the Laureates actually are. FBut once the surprise has set, the big hunt Renata Gomes showing for autographs and pictures begins. her hunting trophy. Young Scientist Renata Gomes had the idea to transform her meeting bag into a wearable autograph card and started to col- lect signatures from this year’s Nobel Lau- reates. When we heard about this we post- ed a photo of her and Martin Chalfie on Facebook to encourage her on the quest of collecting as many laureate autographs as possible. Australians are widely known for being easygoing – Sidney University’s science am- bassador and self-proclaimed geek Adam Spencer however felt the fire of competi- tion inside of him when he heard about Re-

nata’s autograph hunt. He had already start- CHRISTIAN NOBEL FLEMMING/LINDAU LAUREATE MEETINGS ed a #lnlm14 Twitter craze with a series of Selfies with Nobel Laureates and now want- get over 20 autographs on her bag making https://twitter.com/adambspencer. There- ed to know who the better ‘hunter’ was. it the most scientific and fashionable auto- fore we hereby declare Adam Spencer the The Lindau Blog Team decided to host graph card of the year. winner of the competition! Congratula- this fierce battle of Nobel fandom for the Adam Spencer on the other hand suc- tions, Adam! Renata fought bravely but in whole community to enjoy. So let the bat- cesfully got over 30 selfies with Nobel Lau- the end Adam showed his killer instinct tle begin! In the end Renata managed to reates. To see them all go to his Twitter: and scored the victory. <

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