y the time Peter Seeberger Colloids and Interfaces in Potsdam- Sugars, especially those that form long, arrives at the campus of the Golm. Some of his staff, however, are branched chains and cover cells like a Freie Universität - still located in Berlin, at a university-af- fluffy fur coat, are Seeberger’s domain. shortly before ten filiated institute where the 75-member Attached to proteins and lipid mole- o’clock, he has already ac- team has been working for the past six cules that anchor them to cell mem- B complished a few things – perhaps the years. But Seeberger’s Berlin office is al- branes, they are a means for cells to in- most pleasant ones on his agenda. He ready empty, apart from a standard teract with their environment – with has taken his daughter to elementary desk-and-chair set, making our conver- friend and foe alike. Bacteria and virus- school, played with his son for an hour, sation echo around the room. Better to es also carry complex sugars on their and then driven the three-year-old to the retreat to a bench outside to enjoy the surfaces and use them to attach to hu- university daycare center. These are pleasant sun of another hot July day. man cells. things the 49-year-old would like to do Peter Seeberger, dressed casually in Seeberger has developed a synthe- more often than just once a week. But his a polo shirt and jeans, has just launched sizer to automatically produce these job leaves him little room for maneuver. his fifth company. Vaxxilon, founded sugar chains, which are also known as Currently, Peter Seeberger also has by the and the glycans (see MAXPLANCKRESEARCH 3/2013, to commute between two sites: His Bio- Swiss-based company Actelion Ltd. in p. 54). His team is particularly interest- molecular Systems Department was re- Berlin-Adlershof, will develop and mar- ed in the glycans found on the surfac- cently finally able to move into the ex- ket sugar-based vaccines to prevent bac- es of parasites and bacteria that cause

tension of the Max Planck Institute of terial infections. tropical diseases like malaria, leishman- Photo: David Ausserhofer

62 MaxPlanckResearch 4 | 15 MATERIAL & TECHNOLOGY_Personal Portrait

A Scientist with a Sweet Tooth

Basic scientist, entrepreneur, citizen and family man: what Peter Seeberger, Director at the Max Planck Institute of Colloids and Interfaces in Potsdam, manages to cram into one lifetime would take others three. One of his goals is to prevent diseases that afflict particularly people in developing countries – and his weapon of choice is sugar.

TEXT CATARINA PIETSCHMANN

iasis and a particular form of encepha- can be transported to the most remote enough to implement all the ideas litis. The aim is to develop novel vac- villages in Africa and Asia unrefrigerat- flowing out of his brain. cines based on these glycans. ed. With conventional vaccines, the re- But these two things are only a brief frigeration chain accounts for half the distraction, because Seeberger has a gift SEEBERGER IS ABLE TO INSTILL immunization costs. that few possess and that can’t be ENTHUSIASM IN OTHERS Vaxxilon, however, will focus pri- learned: He can quickly put listeners marily on hospital-acquired infections. under his spell and instill enthusiasm Sugars alone are not very effective as “We can find investors for these much for his ideas. His candid manner cer- vaccines. They need an adjuvant, an more easily than for poverty-associated tainly helps him win people over. He immunostimulator to enhance its ac- diseases,” says Seeberger, who speaks speaks plainly and invites his conver- tivity. A novel adjuvant has been devel- from experience. More on that later. sation partners to do the same. He is oped that – unlike conventional carrier When the Max Planck Director also aware that he sometimes comes proteins – is not a heat-sensitive pro- speaks, his soft Franconian accent is across as arrogant – but the longer you tein, but a stable glycolipid, a com- unmistakable. His years spent in the listen to him, the more you realize: it’s pound consisting of a fatty acid and US, Switzerland and even multicultur- not about himself but about his re- sugar. Immunization with such a com- al Berlin have done nothing to temper search. pletely synthetic vaccine is less likely to it. And Peter Seeberger also speaks ex- Seeberger was born in Nuremberg trigger allergic reactions and is also tremely fast, as though he doesn’t want and grew up in a caring home. His fa- much cheaper, because the substance to waste time talking so as to leave ther was trained as an auto mechanic;

4 | 15 MaxPlanckResearch 63 his mother worked in an office. And al- though he was the first in his family to attend a university, he never shed his no-nonsense roots. As a boy, Peter wanted to become a garbage man, and later, a librarian. Starting in fifth grade, his goal was to become a mathematics professor. Seeberger laughs. “Well, that almost happened.” He found learning easy, and his chemistry teacher at his high school in Fürth had no trouble sparking his interest in atoms and mol- ecules. But sports, especially team handball, was often more important than his lessons. The game helped shape his character. “Handball is a team sport, and that is also fundamentally true of a research group.” He didn’t really apply himself un- til the final two years of high school, when there was a promise of a schol- arship for gifted students. With his high school grades, he could have studied dentistry, but after completing his military service, Peter Seeberger en- rolled to study chemistry and econom- ics at Erlangen University. “In an ide- al world, I would have become an archeologist, but the job prospects were pretty miserable.”

PRODUCING CARBOHYDRATES AUTOMATICALLY?

After six semesters – by which time he had nearly completed all of his degree requirements – he won a Fulbright scholarship on the strength of his grades and, with his BSc diploma in his pocket, traveled to Boulder, Colorado for a year as an exchange student. It soon became apparent that the univer- sity was an incubator for outstanding biochemists. But he had studied only chemistry. “I didn’t have a clue!” he says. For the first time in his life, he wasn’t among the best in his class, but at the bottom, instead. And no wonder – all the classes were in English, which he had pretty much neglected in school, thinking: I’ll never need it. Af- ter all, I live in Bavaria.

Custom-made sugar: Peter Seeberger developed a synthesizer that facilitates the manufacture of a wide variety of specified carbohydrates.

64 MaxPlanckResearch 4 | 15 Photo: David Ausserhofer; graphic: Peter Seeberger/MPI of Colloids and Interfaces In short:thefirstyearinBoulderwasre- to gotheoperaatMet. the samesituation.Andhe made time wasin this period.Afterall,everyone and manyafriendshipwas forgedin calls. Theteamusedtogoout together, here- ways hadabitoffunafterwards,” sometimes 18-hourdays.“Butweal- plex carbohydrates.Heworked16-, ter, whereSeeberger synthesizedcom- doc attheSloanKetteringCancerCen- York. HeacceptedSeebergerasapost- tion ofSamuelDanishefskyinNew matically, whynotcarbohydrates? and peptidescanbemanufacturedauto- five years,hekeptaskinghimself:ifDNA ed withpeptidesandnucleicacidsfor different reasons.Whileheexperiment- turn hisattentiontosugarsforentirely Seeberger wasofcoursemotivatedto 1980. Althoughhehasasweettooth, had inventedtheDNAsynthesizerin Caruthers,who ofMarvin the laboratory ate inbiochemistry. Sohecontinuedin vited tostayonandstudyforadoctor- mester atthetopofhisclass,hewasin- hike. Whenhecompletedhissecondse- ing, hewenttothemountainsskiand books hard.Inthebreaksbetweenstudy- ally tough.Seebergerhadtohitthe isrepeated. cycle the isremoved, tPG the as soon As attached. be can link grou chain another protecting where atemporary carries molecule attached The (LG). group aleaving of site the at precisely molecule sugar another combine molecule this coupling, the During reactions. chemical from them shielding thus groups, hydroxyl the of most mask (PGs) linker. Protect achemical of means by carrier apolystyrene to islinked molecule Asugar step: by step chain asugar Building Sugar synthesiswasthespecializa- Polystyrene P o Seeberger actuallywantedtoteachin SHOCK AFTER13 YEARS IN THE US SWITZERLAND –ACULTURE three andahalfyears. sis. Hewasofferedtenureafterjust S bers to35,andpublishedarticlesin research groupfromitsinitial 4mem- he becameaprofessor. Hebuiltuphis moved toBoston.Hewasonly30when stitute ofTechnology came,Seeberger invitation fromtheMassachusettsIn- as assistantprofessoratMIT?Whenthe plans forhim:Whynottakeupapost , butDanishefskyhadother disappointment. Thetwo sides were inMunich. Butthissoonproveda try nent professorshipinorganic chemis- thrilled toreceiveanofferfor anemi- seemed easierinGermany, sohewas oncile workwithfamilylife. Things his colleaguesatMITmanagedtorec- point, realizedwithdismaythatfewof who wantedtohaveafamilyatsome You’re neverthereanyway!”Seeberger, ed inthereproach:“There’s nopoint. non-existent. Relationshipsculminat- er, andhis private lifewasasgood His workdaysdidn’t becomeanyshort- CIENCE Linker aboutautomaticsugarsynthe- protecting group Removal of the Coupling MATERIAL & TECHNOLOGY_Personal Portrait er thoughtatthetime.But astheold way I’llleavehereisfeetfirst,” Seeberg- And lifeinZurich?Adream! “Theonly work atETHwentexceedingly well. flyer cardwasrarelyoutof use.The ton, SanDiegoandback–the frequent insouthernCalifornia.Zurich,Bos- ry ceuticals, aswellasecondlaborato- Boston theyearbefore,AncoraPharma- a realcultureshock,hesays. in 2003.After13yearstheUS,itwas berger, now 36,movedtoSwitzerland ter thantheoneinMunich,andSee- atETHwentmuchbet- the interview entirely differentleague.Nevertheless, Planck.” Butthatseemedtobeinan The onlyhopewouldthenbeMax have beenabletoreturnEurope. ing Munich,Iwouldprobablynever also turneddownZurichafterreject- a fewmonthslater. “IknewthatifI his CV. TheinvitationfromETHcame Seebach askedSeebergertosendhim for threehoursoneSaturdaymorning, MIT. Afterthe twodiscussedchemistry bach fromETHZurichheldalectureat German organicchemistDieterSee- er turneddownthepost. unable toagreeonterms,andSeeberg- He hadsetuphisfirststart-upin A shorttimelater, therenowned 4 | MaxPlanckResearch 15MaxPlanckResearch ing groups groups ing Linker p (tPG) p (tPG) s with s with 65 MATERIAL & TECHNOLOGY_Personal Portrait

Artemisinic acid

Extraction waste Artemisia annua R = methyl ß-artemether

R = ethyl ß-arteether

Dihydroartemisinic Artemisinin Dihydroartemisinin Genetically acid α-artesunate modified yeast

A new approach to a malaria drug: Until recently, artemisinin was obtained only from sweet MPI process wormwood (Artemisia annua). In the process, however, the artemisinic acid and dihydroarte- Already practiced misinic acid were discarded as waste products. Peter Seeberger’s group developed an efficient Technically feasible method to synthesize artemisinin and the currently used active agents (blue) from these sub- Active agents currently in use stances, which can also be produced in genetically modified yeast.

saying goes: if you want to make God later, they met again in Berlin – where shop.” That’s also a disadvantage. “You laugh, tell him about your plans … Beate Koksch had since moved. “It took have to be careful not to neglect your In 2004, the Society of German a while for us to get together.” But the personal life.” When they argue, it’s Chemists invited Seeberger to Leipzig. chemistry between them was simply about all the traveling that goes with For the first time he had to present a lec- too good – even professionally! So See- the job. “Coordinating it is incredibly ture in German. “Sure I could still speak berger added the German capital to his difficult.” Otherwise, everything is well German! But I had only ever thought flight plan. When their daughter was organized. Once the children are in about sugars in English. I didn’t know born in late 2006, it became clear that bed, each goes to their respective office which terms to translate and which not. their professional situation would have and answers e-mails, writes articles or To be safe, he translated every word, and to be adjusted. deals with other matters until midnight the audience was very amused. “That A year later the Max Planck Society or even later. Saturdays and Sundays are was incredibly embarrassing!” asked Seeberger to become Director at reserved for the family. the Max Planck Institute for Medical HAVING THE SAME PROFESSION Research in Heidelberg. However, for COMPOSITE MATERIALS FROM HAS ITS UPS AND DOWNS several reasons, Berlin was the better CELLULOSE AND CHITIN? option for him. “The Max Planck Soci- But the remarkable thing about this ety was extremely accommodating and Seeberger didn’t plan his career; it just event was something altogether differ- appointed me to a post at the institute happened – thanks to jobs that were ent. Before Seeberger set foot in the au- in Potsdam.” And because the Max usually brought to his attention. “Mov- ditorium, a few meetings had been ar- Planck Institute there was already too ing away from a location was always a ranged with colleagues, including Beate small and needed a new building, Peter difficult decision,” he says in retro- Koksch. They chatted animatedly. She Seeberger pursued research from 2009 spect. “You never know what lies ahead. had just received two job offers and on the Freie Universität campus in But each time I was able to expand my asked his opinion: the US or Berlin? Dahlem, just a few hundred yards from field of research.” Whereas Boston was “Without thinking, I said: Berlin! It’s his wife’s research group. still about sugar chemistry pure and much better!” Talk about arrogant, Is it good or bad for a couple to have simple, biology and animal experi- thought Koksch. the same profession? “Both,” says See- ments for vaccines were added in Zur- When Seeberger received the Otto berger. “We understand exactly what ich. In Berlin he perfected automated

Klung Weberbank Prize a few months the other is doing and can always talk synthesis, which another startup, Gly- Graphic: Peter Seeberger/MPI of Colloids and Interfaces

66 MaxPlanckResearch 4 | 15 Photos: David Ausserhofer chemical research. of part essential –an paper on reactions new sketches scientist the hisdesk, At Interfaces. and Colloids of Institute Planck Max the at building new the into moved recently only group Seeberger’s Peter of members Many office: New nevertheless workonaninterdisciplin- teamsthatcan small complementary isn’t organizedhierarchically butin er’s research, agroupisneededthat hard Lipowsky. ter Fratzl,MarkusAntoniettiandRein- with hisPotsdam-basedcolleaguesPe- years.” Projectsarealreadyunderway great potentialthereinthenext20 research fieldtobeexplored.“Isee terials, Seebergercontinues.Another combined toformnewcompositema- know.” Chitinandcellulosemightbe gle up?Dotheyfold?We simplydon’t throw themonasurface?Dotheytan- gle sugarpolymersbehavewhenwe What forces areatwork? “Howdosin- are carbohydratemoleculesbranched? from scratchraisesnewquestions:Why to reconstructthesenaturalmaterials thusiastically. Theoptionofbeingable structural aspects,”Seebergersaysen- form ofcelluloseandchitin. versatile structuralmaterialsinthe molecules thatareusedinnatureas saccharides topolysaccharides–giant links, thejumpwasmadefromoligo- ty ofbuildingchainsupto50sugar fresh impetus.Thankstothepossibili- berger’s sugars,havegivenhiswork fromSee- es is,atfirstglance,afarcry research intobiomaterials andinterfac- them lessexpensive. to simplifytheirmanufactureandmake synthesis methodsforsomedrugsthere building blocks.Healsodevelopedflow ly since2013,completewithsugar coUniverse, hasbeenmarketingglobal- To coverthebroadrangeofSeeberg- His colleaguesinPotsdam,whose “I hadneverpreviouslyconsidered ary basis. “Basically, I hire people who stance, has made the field of biological- he could well imagine being more ac- can do something that I can’t.” Besides ly relevant sugars accessible to science. tive in developing countries. For the chemists and biochemists, they include After genomes and proteomes, now past 11 years he has been involved in medical doctors, parasitologists, engi- also glycomes have become a subject of the Swiss Tesfa-Ilg Foundation, which neers and, most recently, a crystallog- vigorous basic research. Seeberger’s in- he was instrumental in setting up. The rapher for structural analyses. The team fluence is also evident from what has foundation built a plant in Ethiopia in includes 18 nationalities, and that is as become of his people: 47 of his more which 300 women now produce insec- it should be, Seeberger emphasizes. than 200 alumni are professors today, ticide-impregnated mosquito nets. “I’m completely intolerant of intoler- and most of them continue to push the Where does the urge come from to ance. And anyone who doesn’t accept boundaries of sugar chemistry with devote himself – professionally and pri- that has to go.” their ideas. Next year, for his 50th vately – more to the problems of devel- Does he ever think about what he birthday, they will gather from all cor- oping countries than those of industri- will do when he retires? Rarely. One ners of the world at a symposium in alized countries? “I’ve always traveled thing is certain, however. He doesn’t Harnack House. a lot, even as a child with my parents, want to be one of those who can’t and I saw very early on that not every- stop, who after retirement flies off to IT’S ABOUT IMPROVING one has it as good as we do.” conferences or haunts institutes, giv- THE WORLD He doesn’t see himself as a do- ing their successors advice. “At some gooder, but his aim is “at the end of point you have to stop, no matter how Of course Seeberger will continue to the day to make the world a slightly hard it may be.” follow their work after retiring. But better place.” And he can’t stand it In any case, he can already look from a distance, because he believes when bureaucratic obstacles and fi- back on an impressive career. His devel- that there should be a life after one’s ca- nancial interests of corporations make

opment of synthesis machines, for in- reer. Assuming he is still in good health, it difficult to produce drugs and vac- Photo: David Ausserhofer

68 MaxPlanckResearch 4 | 15 MATERIAL & TECHNOLOGY_Personal Portrait

That’s not the whole story by any means: Around 75 people work in Peters Seeberger’s group at the Max Planck Institute of Colloids and Interfaces and the Freie Universität Berlin. Less than half of them are gathered here in the new premises in Potsdam.

cines for poverty-associated diseases with a 400 million dollar financial in- regard. “Because they put their ideas such as malaria and HIV more quickly jection from the Bill & Melinda Gates into practice and developed things that and less expensively. Patience isn’t his Foundation? “In my opinion, that’s improved people’s lives. That’s what I strong suit, he says. only a small step in the right direction, want to do.” Seeberger’s research always “On the one hand you see people because the efficacy of RTS,S in young seems application related, but that was dying of diseases that should no longer children is below 10 percent.” never planned, he emphasizes. It just exist, because they can’t get the drugs, From 2001 to 2008 Seeberger teamed happened. “I’m interested in basic re- or they get only counterfeit drugs,” he up with a company to develop a sugar- search. But it’s very satisfying if it leads says, his anger clearly audible. “For one based malaria vaccine. In animal exper- to more than a paper or two.” After all, thing, the drugs could be manufactured iments it had an initial 75 percent re- most money for research comes from cheaply. But in the process of creating sponse rate and nearly 100 percent after taxpayers, and they should see that the value, a lot of people earn a lot of mon- further development work. But the results are useful. ey, and in the end the drugs are so ex- project was put on ice before the first What does he plan to do in the sec- pensive that patients in developing study with humans. The expected prof- ond half of his career up to the age of countries are unable to afford them!” it was too low, it was said. He was in dis- 67? “My aim is for us to establish sug- cussions with the Bill & Melinda Gates ars everywhere: in medicine, nutrition A SUGAR-BASED VACCINE Foundation at the time. “But I had to and material sciences. There’s still a lot BEFORE RETIREMENT learn that the best technology doesn’t to do.” Before he retires, he would like always get the money. Contacts and po- to have at least one sugar-based vaccine To remedy this situation, Seeberger has litical and commercial aspects are also approved. And it would be nice if his offered pharmaceutical companies his very important.” Because of a secrecy name were one day associated with the patent for the flow synthesis of artemis- clause, Seeberger was not allowed to term sugar synthesis as firmly as the inin free of charge – with the proviso talk about the vaccine or even contin- name Emil Fischer a century before. that they supply the malaria drug cheap- ue to research it for a long time. At least Seeberger laughs. “Okay, I’m not entire- ly. The response? None whatsoever. his team is now working on the sub- ly free of vanity,” he says. But you have But thanks to a healthy portion of stance again. to set the bar high. “Science is like stubbornness and pragmatism, Seeberg- Given his personal ambitions, it’s sports: you should never be satisfied, er isn’t easily discouraged. “I draw en- no surprise that he holds the German because more is always possible! And ergy from resistance,” he says grinning. inventors of the 19th century in high I’m never satisfied.” There must be another way! In 2013 he set up ArtemiFlow GmbH, which devel-

oped the method to market maturity. And now an alumnus is implementing the artemisinin project with a compa- GLOSSARY ny in Vietnam. “Malaria is under con- trol in the country itself, but drugs for Glycans are carbohydrates that consist of a sometimes branched chain of various simple sugars, such as glucose and fructose. Glycans perform various functions in biology. other developing countries can be in- They not only supply energy but also have a supportive function in plants in the form of expensively manufactured there.” cellulose or hemicellulose and enable cells to communicate with their surroundings. Won’t artemisinin soon be superflu- Glycome: The term was inspired by the words genome and proteome. It denotes the ous, since GlaxoSmithKline plans to ap- entirety of all simple and compound sugars in an organism. ply for approval of the malaria vaccine RTS,S, which the company developed

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