Why Is So Much Research Done on One Species? An Accident That Became a Standard

Comparing results between experiments requires that the animals be comparable, and animals from a wild population differ from each other enormously in genetics, in prior exposure to disease and in early experience, which introduces variation that swamps the effect being studied. Breeding animals to be genetically near-identical removes most of that, so a difference between treated and untreated groups can be attributed to the treatment rather than to the animals. Standardised strains also let a result obtained in one laboratory be compared against one obtained elsewhere, which is the foundation of an accumulating literature. That reasoning is sound, and every consequence of it follows from taking uniformity as the priority.

The history is more contingent than the standardisation suggests:

• •Laboratory rats descend largely from albino animals bred for fighting and fancy
• •A colony at the Wistar Institute from 1906 supplied a foundational strain
• •Laboratory mice descend substantially from animals bred by hobbyists
• •Abbie Lathrop, a Massachusetts mouse fancier, supplied many founding animals
• •Inbred strains were created deliberately from the 1900s onwards
• •A handful of strains now account for the great majority of work

The uniformity that makes results comparable also makes them narrow, and that trade has been examined critically. A result established in one inbred strain may not hold in another strain of the same species, which has been demonstrated repeatedly for behaviour, drug response and disease susceptibility. Animals are housed in conditions that are clean, constant and unlike anything natural, which affects immune function, stress and metabolism measurably, and a proposal to house animals at temperatures they find comfortable rather than convenient has changed results in several studies. Males have historically been used far more than females on the grounds that females introduce variation, which is now recognised as having produced a literature with systematic gaps.

Research concentrates on a small number of species across the whole of biology, and each was chosen for practical reasons that are worth knowing. A small roundworm has exactly the same number of cells in every individual, is transparent, and had its entire cell lineage mapped, which made it the organism in which programmed cell death was discovered. A fruit fly breeds in days and has been used for genetics for over a century. A soil bacterium and a yeast supply the foundation of molecular biology. A small flowering plant with a short generation and a compact genome does the same for plant science. A zebrafish has transparent embryos that develop outside the mother. In each case the choice was convenience, and everything known about them reflects it.

Several pressures have altered how this work is done. Regulation in most countries now requires that any procedure be justified against three principles, namely replacing animals where possible, reducing the numbers used, and refining procedures to lessen suffering, and ethical review is required before work begins. Requirements to include both sexes have been imposed by major funders. Reporting standards demand that strain, sex, housing and handling be stated, since they affect results. Alternatives including cell cultures, tissue grown in three dimensions, organ models on chips and computational prediction have replaced animal work in several areas, most notably in early toxicity testing, and regulators in several countries have begun accepting them formally.

Genetically near-identical animals remove variation that would otherwise swamp the effect being studied and allow results to be compared between laboratories, which is why a handful of strains dominate. Those strains descend substantially from animals bred by hobbyists and fanciers. Uniformity narrows what the results cover, since findings frequently do not transfer between strains, and the historical preference for males left systematic gaps.