Could a fly save your life?

Dr Mariam Orme, Post-Doctoral Training Fellow in the Cell Death and Inflammation Team.

The answer to this seemingly absurd question is, quite definitely, yes. Now, I don’t mean that a fly is going to give you mouth-to-mouth or save you from a burning building. But if you ever have to take pharmaceutical drugs for a health condition such as cancer, it is quite possible that those drugs will have been developed with the help of research conducted using fruit flies – those same small flies that swarm around your compost heap in the summer.

Scientists all over the world use fruit flies for their work, which generally falls into the category of ‘basic research’. This means research that is primarily curiosity-driven: trying to find out more about how the world works for the sake of increasing mankind’s knowledge. That’s in contrast to the two other broad types of research: applied research, which is aimed at solving specific problems, and translational research, which links basic and applied research.

In recent times, there has been a shift away from basic science: governments and funding bodies, who provide the money for research, are leaning more towards funding applied and translational research, and less towards basic research. On the surface, this makes sense: particularly in these times of austerity, why not concentrate the available money on research that is specifically aimed at finding more effective treatments for cancer, for example? But this is a short-sighted view. Applied and translational research stands on the shoulders of basic science: without the knowledge generated by basic research, there would be no foundation for applied and translational research. When Benjamin Franklin flew his kite in an electrical storm in that famous experiment of 1752, he didn’t have in mind the myriad uses we have for electricity in today’s world… he was merely curious.

So, back to the flies: how can they help us find treatments for cancer? Fruit flies have been used as a research model for understanding human biology since the beginning of the 20th century, when a few pioneering scientists realised the huge potential of flies as a cheap and convenient research tool. One of these scientists, Thomas Hunt Morgan, won the 1933 Nobel Prize for Physiology or Medicine for his studies using flies to discover that heritable material (what we now call genes) is carried on structures called chromosomes in every cell. Thomas Hunt Morgan was the first, but by no means the last, scientist to have their work on fruit flies recognized with that highest of accolades.

There are of course many differences between flies and humans – not least the fact that flies have wings and six legs! But in terms of basic biological processes, flies (and indeed all animals) are very similar to humans. So if we can find out how a fundamental biological process works in a fly, the chances are it works pretty much the same way in humans. Flies are relatively cheap to keep and breed; they have a short life-cycle which means that experiments can be done much more quickly than with closer relatives of humans such as mice; and over the years scientists have developed all sorts ways of manipulating flies genetically, to facilitate clever experiments. Another advantage of flies is that they are ‘simplified’ models of humans: often humans have several different versions of a gene, whereas in the fly there will usually just be a single gene, making it much easier to unravel what the function of that gene is. All these characteristics combine to make the fly a very attractive starting point for finding out about biological processes in humans.

That ‘interest-driven’ basic science can lead to tangible benefits for humans can be seen from a new class of targeted anti-cancer drug called ‘SMAC mimetics’. Studies on fruit flies about 15 years ago identified proteins that, when released in a cell, cause the cell to die. This prompted a successful hunt for the equivalent protein in humans, which they named SMAC… and as the name suggests, this new class of SMAC mimetic drugs has been designed to mimic SMAC and thereby kill cancer cells. These drugs, which are being developed by several pharmaceutical companies, have in some cases progressed to phase II clinical trials and are looking very promising as effective therapies with fewer side-effects than traditional anti-cancer drugs.

Flies can also be used for applied research. For example, researchers in New York have developed a fly model for multiple endocrine neoplasia type 2 (MEN2) - a group of medical disorders that cause tumours in endocrine tissues such as the thyroid gland. What these researchers did was to ‘express’, or turn on, cancer-causing versions of the gene responsible for most cases of MEN2. Importantly, they did this only in the eye, giving rise to flies that are otherwise healthy, but have an easily visible ‘rough’ malformed eye. Having developed this model, the researchers fed a drug called vandetanib to these flies and found that it reverts their eyes to a more normal appearance – suggesting that this drug might be a good treatment for MEN2. Less than ten years later, vandetanib is in phase III clinical trials and is showing great potential to be the first ever chemotherapeutic drug for MEN2. More recently, this research team has extended their approach to screen a panel of known drugs, to try and identify even more effective therapies for MEN2.

It’s not just cancer research that flies can assist us with.  Research on fruit flies has helped shed light on numerous human diseases including diabetes, Parkinson’s disease, growth defects, Alzheimer’s disease, cardiovascular disease, epilepsy, asthma… the list is growing, but we must continue to fund basic research in order to keep it that way. Basic research may not be focused on providing new therapies for disease, but you never know how crucial the new knowledge it uncovers could prove in the future.

So the next time you see a fruit fly buzzing annoyingly around your pint of beer, give a thought to the great work its cousins are doing in research labs all around the world!

Image: Fruit fly (Drosophila melanogaster, male), by Max Westby / Creative Commons BY-NC-SA