Research on flies and insects is buzzing

Mon, Jul 23, 2012, 01:00

As many of the basic processes in flies are seen in humans – and flies are remarkably resistant to infections – their study and that of other insects has the potential for enormous societal and commercial benefit

IN 2008, US vice-presidential candidate Sarah Palin famously stuck it to science when she was giving out about “earmark” funding from Congress for basic research: “Sometimes these dollars, they go to projects having little or nothing to do with the public good. Things like fruit fly research in Paris, France. I kid you not.”

But despite Ms Palins misgivings, flies can be important lab models.

Like Drosophila melanogaster, a tiny fly that has made a big contribution to our understanding of genetics and how tissues develop – many of the basic processes in flies are also seen in humans.

And if scrutinising insects still sounds like something that should be banished to the farthest corner of campus, how about this: asking the question “why do insects not get sick?” burst open our understanding of the human immune system, an area that has the potential for enormous societal and commercial benefit.

Earlier this month, immunologist and 2011 Nobel Laureate Prof Jules Hoffmann was in Dublin for Euroscience Open Forum (ESOF) 2012, and he spoke about making that basic discovery through experiments that involved grasshoppers and flies.

“Insects are remarkably resistant to infections and we wanted to look at mechanisms that account for resistance,” he told a symposium at the Trinity Biomedical Sciences Institute. “We did not think of any application, it was a blissful time, you had the curiosity and you did your work.”

It eventually led Hoffmann and colleagues to discover a process in the immune system involving proteins called Tolls. That revolutionised our understanding of not only how insects ward off disease but also how the Toll system is involved in human defences.

And while that basic understanding of the immune system is important in its own right, it is also starting to generate more commercial and clinical potential, explains Luke O’Neill, professor of biochemistry at Trinity College Dublin and academic director of the TBSI.

“We are going from fundamental discoveries in the fly towards new medicines,” he says. “There are multibillion markets for vaccine adjuvants that act via the Toll pathways, and there’s also the prospect of new treatments for many diseases.”

O’Neill and colleagues at Trinity were funded by Science Foundation Ireland in the early 2000s to look at Tolls, and that led to the foundation of Opsona Therapeutics, which is developing molecules to block the receptors for Tolls and affect the immune system in a targeted way.

The company has so far raised a total of $45 million to date and is on the road to raising another $43 million, according to O’Neill.

Ultimately he sees controlling Tolls as an approach in tackling auto-immune diseases (such as rheumatoid arthritis), cancer and possibly even malaria. And this month Opsona starts phase two clinical trials of a Toll-blocking compound that seeks to help overcome rejection after kidney transplants.

“Opsona would never have gotten off the ground without Hoffmann’s discovery,” says O’Neill.

Another area in biomedicine where fundamental discoveries have opened the way to applications include cholesterol – working out its biochemistry in the body led to the development of blockbuster statins, explains O’Neill.

And in particle physics, work at CERN led to the world wide web and has had applications in medical imaging technology and even cancer treatment.

Of course we can cite examples where fundamental research led to a specific commercial or societal outcome, but it’s difficult to predict in advance when that’s going to happen, admits O’Neill. “The essence of basic frontier research is that you don’t know what way it is going to go. But if we don’t fund it, where are the breakthroughs going to come from?” he asks. “There’s a huge unmet need in cancers and pathologies like Alzheimer’s and the only way to make progress is to understand the disease at a fundamental level. That involves basic research.”

While O’Neill is an advocate of fundamental research, which can provide the meat for innovation and which also trains scientists who may then move to industry, he points out there’s still the need for more applied science too.

“Let’s say we do make a fundamental discovery and we don’t commercialise and someone else does, that would be terrible,” he says.“It’s like in football – you would be stupid to have a whole load of backs on your team, you need wingers and forwards as well.”

Prof Peter Doherty, who was awarded the Nobel Prize in 1996 for his work on the immune response, was also in Dublin for ESOF. He sees the value of fundamental research and the challenges.

“There’s no easy path,” he says. “You have to try and facilitate things so that discoveries can be turned into products and something of value. On the other hand, it’s very hard to legislate for it and you have got to be prepared to spend the money on the basic science. And you have got to back your best people.”

Doherty, who is based at the University of Melbourne and the St Jude Children’s Research Hospital in Memphis, says governments can play a role in helping to build scientific centres that mix disciplines in research. “You need to bring a lot of people together who are doing different things but have some sort of commonality and interest,” he says. “If you don’t have good institutions you can’t have good science.”

And he cautions not to get out of the traps too early on commercialisation when translating discoveries from the lab to the clinic. “You have to do the basic science, you have to do the hard yard.”

We are going from fundamental discoveries in the fly towards new medicines

You have to try and facilitate things so that discoveries can be turned into products and something of value