The international exchange of Drosophila melanogaster strains

Summary Drosophila melanogaster has been a model organism for experimental research for more than a century and the knowledge and associated genetic technologies that have accumulated make it extremely important to contemporary biomedical research. A large international community of highly collaborative scientists investigate a remarkable diversity of biological problems using genetically characterised strains of Drosophila and frequently exchange these strains across borders. Despite its importance to the study of fundamental biological processes and human disease-related cellular mechanisms and the fact that it presents minimal health, agricultural or environmental risks, Drosophila can be difficult to import. The authors argue that streamlined regulations and practices would benefit biomedical research by lowering costs and increasing efficiencies.


Introduction
For over a century, scientists have been using the fly Drosophila melanogaster to investigate biological processes. It is probably safe to say that more is known about the genes, genome and genetic regulation of cellular, developmental, physiological and behavioural processes in Drosophila than in any other multicellular organism. The genetic 41_1_06_Cook&Parks -pre-print 2/21 approaches and technologies available for Drosophila experimentation are extraordinarily advanced and have led to profound contributions to human health. This role of Drosophila as a "research system" makes it different from most other insects described in this volume: it is not a disease vector, a significant agricultural pest or a biocontrol agent…and it is hard to envision Drosophila as a significant addition to the diet of anyone. It attracts the attention of scientists solely as a vehicle for discovery.
As directors of a major repository of Drosophila strains, the authors will try to give a glimpse into the significance of Drosophila research, an idea of the scale of international exchange of Drosophila strains, and suggestions for promoting international collaborations by improving import regulations and practices.

The importance of Drosophila to biological research
In the wild, Drosophila melanogaster is attracted to a wide variety of foods and is among the first animals to find damaged fruit and lay eggs on it. Early development is extremely fast (roughly 5 days) and the young leave the fruit quickly to metamorphose into adults-as one might expect for an insect that relies on fleeting resources. This combination of adaptability and fast development preadapted Drosophila to life as a human commensal (or, less flatteringly, a "garbage species"), an organism like the rat that has associated with humans who unwittingly provide it food and habitat. Drosophila has spread with human migrations and trade from its origin in southern Africa and it is now found everywhere that people live (1,2).
In the early 1900s, Thomas Hunt Morgan of Columbia University was the first scientist to take advantage of the flexibility and fast growth of

Drosophila stock resources and international exchange
More than 188,000 scientific papers have been published with  pathogen of human or agricultural concern. Likewise, it is nearly impossible for lab cultures to be contaminated with a microbe of concern. Nearly all experiments are conducted with stocks whose origins can be traced to flies brought into lab in the early to mid-1900s.
Most fly geneticists will spend their entire careers never having worked concern-even though their distribution has been tightly controlled.
These facts lead to the conclusion that Drosophila melanogaster is an innocuous organism reared under clean conditions that carries transgenes that do not increase risks in the strains that would be moved.
It should, consequently, be one of the easiest research animals to exchange between countries and, in the opinion of the authors, every country should encourage its importation to further scientific progress.
Box 1 discusses other Drosophila species. losses come from delivery delays associated with import regulations and practices. The BDSC takes regulatory compliance seriously, but satisfying import officials in every country often seems like an unattainable goal. Here the authors will make a few points about importation that will, admittedly, reflect their frustration.

Import practices should reflect the identity of the animal and how it was raised
A major improvement would be for practices to make sense for the animals being imported. Import rules seem to be predicated on all animals being treated the same and therefore requiring similar paperwork and inspections. Consequently, the BDSC often completes paperwork for Drosophila that makes no sense.
One illogical 'one-size-fits-all' imperative is the insistence by some

Permits should be long lasting
In many countries, a specific import permit is required for each shipment. This is a burden when many projects require multiple shipments and the strains are uniform with respect to regulations.
Permits for multiple shipments would save everyone time and effort.

Fees should be appropriate
Application and inspection fees can be expensive. Until the EU changed its regulations, scientists were often paying hundreds of euros in veterinary fees per box of flies (for which repositories could be charging as little as €3). Fees should cover actual costs for justifiable expenses.

Import rules should be articulated clearly
The BDSC has seen from its interactions with import officials that there can be considerable uncertainty about applying regulations to Drosophila. Import officials often find it difficult to advise scientists on importing flies instead of mammals, and shipments are treated inconsistently in many, if not most countries. The authors hope the articles in this volume will spur regulatory agencies to clarify internal practices regarding insect importation.
In general, repositories do not have the personnel resources to keep up with the import practices of all the countries they serve and to supply scientists with up-to-date information. Users are often surprised when they learn repositories cannot provide all the paperwork necessary for importation and they must acquire permits themselves. Ideally, scientists would figure out what kinds of preapproval and documentation they need for their countries and pass along that information to repositories and their colleagues, but requirements are 41_1_06_Cook&Parks -pre-print 11/21 usually complicated and often require lengthy registration and application processes, and it is rare to find a scientist who has mastered the intricacies well enough to provide definitive explanations. There is an immense need for instructions on exactly how to import insects into most countries. This lack of explicit guidance has led to an enormous amount of misinformation among scientists, and it is often hard to convince them that their workarounds do not comply with regulations of their own countries.
The BDSC has a standing offer to work with scientists and import officials to assemble instructions for importing Drosophila into other countries and to post them on its website in the same way it has provided guidance on U.S. importation (15). It is, nevertheless, difficult to interest busy scientists in the task and nearly impossible for the BDSC to interact with government officials in other countries without a domestic intermediary. It would be much better for regulatory agencies themselves to provide clear guidance for importing insects specifically.     41_1_06_Cook&Parks -pre-print 20/21