Big discovery from little flies
Who could have anticipated that looking at fruit flies would produce such significant results ? Tom Kennedy reports on how fundamental research led to a major discovery on how the body defends itself against disease .
Is fundamental science important ? High profile scientist Luke O ’ Neill certainly thinks so and at last year ’ s European Science Open Forum ( ESOF ) event in Dublin he stressed that “ you cannot underestimate the importance of basic science .”
Luke , based in Trinity College Dublin , has earned an international reputation for his work on immunology , an important field because it helps us to understand how the body can defend itself against all kinds of diseases . Understandably this is also the sort of research that attracts funding because there is always a high probability that results can be turned into commercial products .
Immunology is one of the strengths of Irish science , yet , as Luke observed , this level of performance could never have been planned in advance . All of the current success , he said , can be tracked back to the type of research that most people might dismiss as having little or no practical value . For something like forty years Jules A Hoffmann worked on fruit flies , those little Drosophilia insects that like to congregate around over-ripe fruit . “ Hoffmann ,” said Luke , “ is a real hero to us all ,” and the reason for this is that he made a fundamental discovery that sparked off an explosion of interest in how animals defend themselves against invading micro-organisms . Luke remarked that it was because of this fundamental discovery that he became an immunologist . “ My work was inspired by Hoffmann , ” he said . What was so important about this discovery is that it revealed the existence of a key trigger that sets off the fly ’ s initial defences against infection . While the discovery that fruit flies have the ability to withstand an assault might not have the impact of prime-time news , the significance became more obvious when it was found
that the same trigger is universal . All animals , including humans , depend on this trigger , known as Toll , to set off our innate immune system . Without it we would be overwhelmed by invading bacteria and fungi .
In recognition for this enormously significant discovery Jules Hoffmann was awarded a Nobel Prize for Medicine in 2011 . Hoffmann shared this award with two other scientists , Bruce A Beutler and Ralph M Steinman because they had also made closely related discoveries on how the immune system actually works . As Hoffmann made clear , when speaking at the ESOF event in Dublin , collaboration between many different scientists has always been a feature of this research , and during his years of research on fruit flies he often relied on the genetic , biochemistry or other expertise of others to fill in the gaps that would , in effect put the jig-saw of a complex chain of reactions together into one coherent system .
Jules , who grew up on the border between Luxembourg and France , said that his own interest in insects began because of his father , a teacher of biology , who enjoyed collecting and identifying
SCIENCE SPIN Issue 58 Page 13
“ You cannot underestimate the importance of basic science .”
Jules A Hoffmann and Bruce Beutler
the various species in the surrounding countryside . It fascinated him that insects make up most of the species on the planet , and it was a natural progression for him to study Zoology at Strasbourg University . For his PhD he worked under Professor Pierre Joly who had a special interest in grasshoppers , particularly the troublesome Locusta migratoria . These are the locusts that swarm into enormous clouds , causing starvation because they devour everything in their path .
Jules Hoffmann was struck by a remark that his supervising professor made one day . “ In all his studies ,” said Jules , “ he had never encountered an opportunistic microbial infestation in these insects in spite of the fact that he had not taken any precautions to prevent this .”
“ This was a defining moment in my life ,” said Jules . He began to look for reasons why these insects had such a good defence , painstakingly examining every step in what was then known about their immune system . It was known that engulfing micro-organisms in a process known as phagocytosis was involved , but techniques and analytical equipment at that time were not as advanced as they are now . Blood from many thousands of blow flies was collected in an unsuccessful attempt
to identify components , known as peptides , that might be involved in alerting the defensive cells to go in for the kill .
Even so , Jules Hoffmann persisted , going from one species of insect to the next , before concentrating on fruit flies . His aim was to identify the peptide trigger that set off the immune reaction and to link this to the genetic code responsible for producing it . Many