The Stock Center
It was realized as early as the 1920's that one could make hybrids between the different species of Xiphophorus. These hybrids were normally viable and could produce subsequent generations of offspring. In some cases, one simply had to place one Xiphophorus species next to another in an aquarium, and they would reproduce. In many situations, the resulting hybrid fish would show traits from both parent species, and were intermediate in appearance. For example, several dominant pigment patterns derived from two fish strains would appear within F1 hybrids giving them characteristics of both species. In other cases, the hybrid fish were quite different from either parent, such as when fish developed beautiful red or yellow colors. In such situations, pigment patterns were derived from one of the species and became enhanced in the hybrid offspring. Scientists in Germany and the United States also discovered that hybrid fish sometimes also developed melanoma, one of deadliest skin cancers. These melanomas were derived from improperly regulated melanistic pigment patterns. Scientists immediately began to study Xiphophorus hybrids, since they realized that they had discovered an animal model that could be useful in the study of cancer.
Today, we continue the work that was begun by the scientists in the 1920's and pursued by other researchers for the last 70 years. Our work focuses on studying melanoma and other cancers that form in hybrid fish.
Why do we need genetic stock centers?
Genetic stock centers are priceless resources in scientific research. Genetic experiments often require that special strains of genetically-identical animals or plants are used. Among vertebrate stock centers (like XGSC), genetically-identical animals most often are produced by inbreeding for many generations between brothers and sisters; in each generation, about one-half of the genetic differences between the parents are lost, increasing genetic identity among siblings with each inbred generation. The high degree of genetic identity in model organisms is scientifically important for a couple of reasons:
- Reproducible Results: Genetic differences can cause differences in biology that could change the results of an experiment. If different labs are using organisms that they *think* are the same, but in fact have critical differences, they may not be able to reproduce results from each other's labs (reproducibility is an important component of scientific research). Genetic stock centers carefully track the ancestry of each organism maintained at the center, and purposely breed individuals to control and enhance genetic identity among different lines.
- Clearer Connection Between Gene and Characteristic: By limiting the amount of variation in an experimental model system, scientists are much better able to see biological differences that result from specific genetic differences, allowing them to connect genes with function and/or disease much more quickly.
Xiphophorus as the Gordon-Kosswig melanoma model: the start of the XGSC
In the 1920s, the American biologist Dr. Myron Gordon and German biologists Haussler and Kosswig independently discovered that inter-species hybrids of a particular strain of the platyfish, Xiphophorus maculatus, and the swordtail, Xiphophorus hellerii, developed cancers virtually identical to malignant melanomas in man (reviewed here). They traced the origin of these tumors to pigment cells of a platyfish color pattern consisting of black spots on the dorsal fin. Genetic studies demonstrated that melanomas developed only in hybrids that had replaced both copies of a platyfish regulatory gene with swordtail forms that could not control proliferation of the platyfish pigment cells (reviewed here). This animal model was one of the first to prove that some cancers were inherited diseases; after 65 years, these fish are still used in cancer research in the United States, Germany, Canada and Japan.
Dr. Gordon realized that to precisely identify the genes responsible for development of cancer, scientists would require genetically identical platyfish and swordtails for research. Therefore, in 1939, he established the Xiphophorus Genetic Stock Center, housed at the American Museum of Natural History and the New York Aquarium until 1993, when transfer of the stock center to Texas State University-San Marcos was completed. Since its inception more than 70 years ago, the stock center has been directed by first, Dr. Gordon and Dr. Klaus D. Kallman in New York, and currently by Dr. Ronald Walter at Texas State University.
A genetic cross between two Xiphophorus species that leads to the development of melanomas.
The importance of the XGSC in conservation of both inbred model organisms and threatened/endangered wild species
Several of the original genetic strains of platyfish and swordtails developed by Dr. Gordon in the 1930s are still available today; they are virtual genetic clones, the products in some cases of more than 100 generations of brother-to-sister matings. The XGSC is one of the oldest live-animal resource centers in the world. It surprises even many scientists that one of the oldest and best-defined groups of model organisms are livebearing fishes of the genus Xiphophorus, the platyfishes and swordtails familiar to the tropical fish hobbyist.
When Dr. Gordon began his genetic studies and field work in Mexico and Central America, only a half-dozen species of Xiphophorus fishes were known to science. Today some 26 species have been described; representatives of all but two are maintained at the stock center. Ongoing field studies continue to discover new species, and are critical to the preservation of the increasingly valuable genetic resources of the genus. No fewer than eight species are confined to extremely small geographic areas and are threatened by human habitat destruction; several species have already been listed as endangered, and another was thought to be extinct until recently. By providing fish to the international scientific community for study, the Xiphophorus Genetic Stock Center reduces collecting pressure on wild populations, and may ultimately preserve the only living representatives of some species. As the science of conservation genetics has evolved, so have the breeding strategies of the stock center, away from generation of new inbred strains to maintenance of maximal natural variability in newly originated genetic stocks.
Services of the Stock Center
The Xiphophorus Genetic Stock Center provides fish from more than 70 genetic strains to scientists and aquarists around the world. Scientists in more than 30 laboratories in the United States, Canada, Mexico, Japan and Germany work on Xiphophorus genetics and depend on strains available from the stock center. In addition to supplying strains and consultation on husbandry and genetic questions, the stock center makes custom hybrids for a variety of projects, producing hundreds of such fish each year at very affordable costs. Unlike most mammals, where fertile hybrids between species are difficult or often impossible to produce, Xiphophorus hybrids are almost always fertile and are extremely valuable for their genetic variability and their very specific susceptibilities for many different cancers. Extensive use of these hybrids for gene mapping has made the Xiphophorus gene map the fifth-largest among vertebrates, exceeded only by maps of man, mouse, rat and cow in numbers of genes assigned.
The beauty of many Xiphophorus strains has attracted tropical fish fanciers for decades. The demand among cognoscenti for extraordinary fish like X. montezumae, with a sword longer than its body, far exceeds the production capabilities of the stock center, but surplus fish are made available to aquarists when possible. The present stock center facilities hold some 1,200 aquaria, balanced between 900 tanks for genetic stock perpetuation and 300 for hybrids for research projects. While this number may seem large, each new species or newly identified genetic strain necessitates some redesign of the overall management plan.
Quality control at the stock center must be impeccable to maintain integrity of the large numbers of genetic strains (even fish manage to escape, and a "jumper" can mean disaster). Most strains have been purposely bred to carry diagnostic morphological traits such as red and black pigment patterns. Each strain possesses a unique genetic "signature" which can be checked for assurance of stock purity. Individual broods are never mixed, and males and females are separated prior to sexual maturity. All parents of broods are preserved for later reference in the event of later questions. All these precautions take a great deal of time, but have been essential in maintaining stock integrity sometimes more than 50 years.
The Future of the Stock Center
Though Xiphophorus fishes are among the best studied vertebrates genetically, largely because of availability of well characterized genetic stocks, maintenance of large numbers of genetic stocks requires constant effort and substantial funding. Texas State University is providing excellent facilities and support for the stock center, but state funds for this institution are inadequate to ensure maintenance of the center. Federal grants have helped support the stock center through purchase of fish for research, but an increasing share of the budget must be generated from tax-exempt donations. Operating a genetic stock center is a continuing program; lack of funding for a year would result in the loss of more than six decades of carefully controlled breeding. For security of these priceless genetic resources, the goal of the center is to raise $3 million of endowed funds to support stock center maintenance for many years into the future. This endowment would support all day-to-day operations and provide funds for gradual expansion to include newly discovered species and construction and maintenance of new strains. Only liberation from year-to-year funding crises can assure continued availability of these fascinating fish to scientists and aquarists of the future.