Drosophila melanogaster, more commonly known as the fruit fly or vinegar fly, has been used as a model for biological research for over 100 years (explained in our first movie below). To date, Drosophila is the conceptually best understood animal organism in science, ideal also to be used as a teaching tool in schools to convey fundamental concepts of biology (explained in this blog). Five Nobel Prizes in “Physiology or Medicine” were given to researchers who made their groundbreaking discoveries in Drosophila (LINK; therein: “Select Animal/Drosophila”), and many aspects of modern medicine are based on foundations laid through fly research (explained in our second movie below). But how can such a small, invertebrate organism teach us anything about human biology?
So far 5 Nobel Prizes for “Physiology or Medicine” were awarded to 7 scientists performing the essential work in Drosophila.
What flies have taught us
As is explained in the first film below, Drosophila research at the beginning of last century has seeded the field of Genetics and laid essential foundations for modern biology, and work in flies has given us essential understanding across a wide spectrum of fundamental biology since then. Flies have taught us how genes are organised on chromosomes and the rules of inheritance, numerous mechanisms of how gene activity is regulated, the nature of mutations and danger of radiation. They have given us the first genes for information processing in nerve cells and learning, an understanding of the biological 24 hr clock that organises our daily schedules and causes jet lag, principles of embryonic development including the formation and fundamental organisations of the nervous system, key mechanisms of the immune system, rules of gene pool dynamics in large populations (population genetics), as well as the first artificially generated animal species (Drosophila synthetica) demonstrating how evolution works. Moreover, work in flies is advancing our understanding of the importance of nutrition for biological performance and longevity, and the fundamental biology of stem cells and cancer (cell division, cell communication). Drosophila is even helping us to understand how certain genetic defects can lead to a range of diseases including brain disorders (e.g. Alzheimer’s and Parkinson’s disease), and many aspects of modern medicine are based on foundations laid through fly research. For more information on how fly can be used and how it contributes to the process of scientific discovery, read examples provided by these lay articles, the “Organs” tab and this NINDS blog.
The 1st key: cost-effective & efficient
The 1st key lies in the pragmatic advantages of Drosophila which allow rapid progress and fuel therefore widespread use of flies in biological research:
- Research in flies is highly cost-effective, affordable even for scientists on a budget. They are easy and cheap to breed in great numbers, and the equivalent of the population of London can be kept on a handful of laboratory trays. These tiny organisms are therefore ideal for large-scale or high-throughput experiments, as an important prerequisite to gain deeper conceptual understanding of biological processes.
- Fruit flies have a short life span (two months) and generation cycle (10 days): they become grandparents in as little as 3 weeks. Therefore, family trees over many generations are quickly drawn, and research progresses much faster than in more complex animals. Where experiments in flies usually take weeks or a few months, they last many months or years in a mouse.
- In this context, it is important to point out that there are very few legal restrictions for experiments with flies, and experiments can be started straight off the drawing board.
- Drosophila ideal for genetic analyses, because it has only 4 chromosomes, it can be easily handles in great numbers, and its short life cycle makes it easy to draw a family over many generations.
- For example, numerous genetically identical progeny can be easily produced. This means that the influence of individual genetic backgrounds, which can have enormous impact on biological processes (see personalised medicine), can be excluded as a factor of uncertainty during experimentation.
- it allows the performance of genetic screens, i.e. unbiased searches for genes that regulate or mediate biological processes of interest (termed forward genetics). Such screens, and the subsequent systematic study of the resulting genes in flies, have been important motors in modern biosciences, leading to thorough conceptual understanding of biological processes in far shorter time than can be achieved in larger animals (second movie below).
- Drosophila is so small that whole embryos or whole fly organs or brains can be analysed in one go at high resolution under the microscope or even reconstructed in 3D (see first movie below showing embryonic development live from two angles, or second movie with 7 parallel cellular labels in one animal). Microscopic data are therefore easy to obtain and interpret – for example when studying the impact of a gene mutation on embryonic development. Surprisingly, the small size of fly embryos (0.5 mm long!) does not deter scientist from other kinds of experiments, and feasible strategies were developed to dissect these tiny specimens for taking out organs, manipulating or labelling specific cells, or performing sophisticated physiological measurements.
- The fly genome is less complex than in higher organisms, thus making it easier to disentangle and understand fundamental principles or gene functions, i.e. to understand the organisation and working of genes as well as their roles within biological processes. Such understanding presents a valuable template for work in higher animals (see 3rd key below).
Flies develop fast and are highly amenable to genetics and other experimentation – ideal to study genes, biological processes and even mechanisms of disease.
“You get 10 times more biology for a dollar invested in flies than you get in mice” [LINK] – and knowledge of fundamental biology is the lifeblood for translational research into the causes and the treatment of disease.
The 2nd key: knowledge & infrastructure
The 2nd key lies in the long history of Drosophila research. Flies were introduced as genetic model organisms by T.H. Morgan over 100 years ago (LINK1, LINK2), and have stayed at the forefront of biological research since. Once knowledge and know-how starts building up, this tends to accelerate subsequent developments. This has led to a continuous and unprecedented build-up of…
- knowledge about fly biology which is uniquely profound,
- cutting-edge, highly refined, powerful (and constantly improved) research strategies and technologies for Drosophila, and
- an ample portfolio of fly-specific resources and infrastructure.
For example, virtually every gene of Drosophila is amenable to experimental manipulation with genetic tools that can usually be readily ordered from stock centres. If combined with the highly sophisticated and efficient research strategies available, the ample pre-existing knowledge of relevant biological contexts facilitating interpretation of results, and the speed and cost-effectiveness of fly research (see key 1) enormous progress can often be achieved in impressively short time periods.
The 3rd key: similarity
Genes link us together
The 3rd key lies in our shared evolutionary roots and history. Thus, many of our organs still share fundamental principles of their organisation and function (see details here). Consequently, the genes and fundamental biological processes underpinning health and disease in humans are often very similar to those that can be studied in Drosophila, and it has been estimated that “…about 75% of known human disease genes have a recognisable match in the genome of fruit flies” (Reiter et al., 2001, Genome Res 11, 1114ff). Therefore, flies are often used as “test tubes” to pioneer research on a gene or biological process of interest, followed by work aiming to determine whether the new understanding obtained in Drosophila is applicable in mice or even humans. For an example, see this school article.
This said, flies are of course NOT mini humans. For example, work on Alzheimer’s disease in flies cannot be used to study “personality loss”, a very human aspect of this disorder. But what Drosophila DOES PROVIDE are very powerful means to unravel the fundamental biological mechanisms of nerve cell decay. Since understanding this decay will be crucial for designing possible Alzheimer’s cures, it poses exciting opportunities for fly research to make crucial contributions (see further explanations & examples here). The list of cases where work in flies has inspired or significantly accelerated advances in mammalian or human research is impressive.
…work on Drosophila
has helped to generate conceptual understanding and unravel fundamental mechanisms in many areas of biology, including classical genetics, developmental biology, physiology, nutrition, nervous system development/function, stem cell biology, behavioural sciences (e.g. learning, sleep, aggression) – and flies are frequently used to study mechanisms underlying human diseases including cancer
). In this way, Drosophila
will remain an important pillar in the process of scientific discovery for the foreseeable future, providing a powerful means to drive discovery and new developments that can then instruct research in higher animals and humans.
See our educational movies