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