science & societyEMBO reports VOL 5 | NO 12 | 2004 ©2004 EUROPEAN MOLECULAR BIOLOGY ORGANIZATIONanalysis1122to raise the attractiveness of Europe todraw scientists from other parts of theworld; and to raise the overall level ofresearch investment in Europe. An ERCthat is just a funding mechanism might notbe able to achieve this. It was Iain Mattaj,present Scientific Director and the desig-nated Director General of the EuropeanMolecular Biology Laboratory (EMBL) inHeidelberg, Germany, who askedwhether an ERC should fulfil a furtherrole: that of formulating a Europeanresearch strategy?At present, there is clearly no suchstrategy. Science policy is formulated inBerlin, London, Paris, and other capitals,and to some extent at the EC, but none ofthese take a truly international outlook onbasic research, on the career and jobprospects of scientists across Europe, onthe role and function of large Europeanresearch infrastructure and facilities (suchas EMBL, the European Laboratory forParticle Physics (CERN) and the EuropeanSpace Agency), and on how to removehurdles to the mobility of researchers. Thesuccessful creation of an ERC mightprompt European scientists to push foreven greater change, as they realize thatthey can make a difference. As JoséMariano Gago, Chair of the ISE and a for-mer minister of research and technologyin Portugal, summarized, “Science policyhas entered a new state,” which is increas-ingly driven by the scientists themselves.Catherine Dargemont, President ofSauvons La Recherche (Let’s SaveResearch), the organization that forcedthe French Government to take back itsannounced cuts to science and researchearlier this year, reassured the audiencethat if there is a will, there is a way: “Asscientists we should not underestimateour capacity to influence our politicians.”Holger Breithauptdoi:10.1038/sj.embor.7400306In 1989, David Strachan from theLondon School of Hygiene and TropicalMedicine, UK, proposed an intriguingexplanation for the sudden rise in hayfever and allergic diseases in developedcountries during the previous fewdecades. His theory, later nicknamed the‘hygiene hypothesis’, linked allergies tohygiene and household size. Based onobservations that children in large fami-lies were less likely to develop hay feverthan those with fewer siblings, Strachandeclared that “declining family size,improved household amenities and higherstandards of personal cleanliness” had alldecreased the number of infections thatchildren contracted, which might haveled to more allergic diseases (Strachan,1989). Before long, his hypothesisbecame synonymous with the belief thatthe trend towards better hygiene andcleanliness was the main cause for the rel-atively recent emergence of asthma, hayfever and other allergies. At that time, immunological researchseemed to support the idea that a naiveimmune system—that is, one that was notpermanently challenged by infectious orparasitic organisms—was likely to over-react to more benign objects in the envi-ronment. Work over the past 15 years,however, has revealed that the real pic-ture is much more complicated. Recentresearch indicates that the risk of develop-ing allergies is not necessarily caused by alack of bugs and parasites in the environ-ment per se, but rather by a lack of certainorganisms that have, over the course ofevolution, trained our immune system bemore tolerant. This suggests that the timehas come to rethink, and rename, thehygiene hypothesis.When researchers first tried tounderstand the link betweeninfectious and allergic diseases,it seemed logical to focus on one particularcomponent of the immune system: T-helper(Th) cells. Th1 cells normally fight bacterialor viral infections, but also have a role inautoimmune disease. By contrast, Th2 cellsdeal with parasitic infections and mediateallergic reactions. Allergy researchers ini-tially believed that reduced exposure tomicroorganisms failed to prime the Th1response, which then led to overcompensat-ing Th2 activity and resulted in allergies.However, “at exactly the same time, a small-er number of people working in the field ofautoimmunity, where diseases are of coursemostly mediated by Th1 lymphocytes, wereproducing the reverse hypothesis,” saidGraham Rook, a professor at the Centre forInfectious Diseases and International Healthat the Royal Free and University MedicalSchool in London, UK. “They were actuallysaying there’s not enough Th2 activityaround now, we need more Th2 to down-regulate the Th1 that’s causing multiple scle-rosis, type 1 diabetes, and Crohn’s disease.”In fact, while allergy specialists had beenpreoccupied with explaining the suddenrise of asthma and allergic disorders, theprevalence of autoimmune diseases, such asmultiple sclerosis, type 1 diabetes andinflammatory bowel disorders, had risenjust as dramatically.This, in turn, put paid to the theory thatTh2 cells were directly responsible andprompted researchers to look elsewhere.“What one needs is a hypothesis that canexplain a simultaneous increase in Th2-mediated diseases, Th1-mediated diseasesand also inflammatory bowel disease,which is mostly Th1-mediated but possiblyShould auldacquaintance be forgot…The ‘hygiene hypothesis’is less about cleanliness, and more about thechanges that humans have made to their lifestyle… the time has come to rethink,and rename, the hygienehypothesisIt is still not clear what the legalsetting for an ERC will be—whether as an executive agency ofthe EC … with a governing boardof representatives from nationalgovernments, or as a new trulyEuropean institutionscience & society©2004 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION EMBO reports VOL 5 | NO 12 | 2004analysis1123ulcerative colitis with a smidgen of Th2 aswell,” explained Rook. “And of coursethere’s also an increase in food allergy,which is rather a different issue from othersorts of allergy. These things are allincreasing. What they have in common isthat there are targets that the immune sys-tem should not be attacking, and those tar-gets are self, gut content and trivialamounts of the neighbour’s cat waftingpast in the breeze.”Instead of focusing on the Th cellsthemselves, researchers turned to regula-tory T-cells and their role in controllingTh1, Th2 and unwanted immune responses.“What is exciting now is that if you look atpeople with these various [allergic andautoimmune] diseases, it’s becoming quiteobvious that they do indeed have deficitsin regulatory
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