We evaluated the effects of past and future trends in temperature and discharge in the Fraser River on the migratory performance of the early Stuart population of sockeye salmon Oncorhynchus nerka. Fish of lower condition exhibited disproportionately higher mortality during the spawning run, elucidating a critical link between energetic condition and a fish's ability to reach the spawning grounds. We simulated spawning migrations by accounting for energetic demands for an average individual in the population from the time of entry into the Fraser River estuary to arrival on the spawning grounds (about 1,200 km upstream) and estimated energy expenditures for the average migrant during 1950-2001. The model output indicates relatively high interannual variability in migration energy use and a marked increase in energy demands in recent years related to unusually high discharges (e.g., 1997) and warmer than average water temperature (e.g., 1998). We examined how global climate change might effect discharge, water temperature, and the energy used by sockeye salmon during their spawning migration. Expected future reductions in peak flows during freshets markedly reduced transit time to the spawning ground, representing a substantial energy [Article] savings that compensated for the effect of the increased metabolic rate resulting from exposure to warmer river temperatures. We suggest that such watershed-scale compensatory mechanisms may be critical to the long-term sustainability of Pacific salmon, given expected changes in climate. However, such compensation will probably only be applicable to some stocks and may be limited under extremely high temperatures where nonenergetic factors such as disease and stress may play a more dominant role in defining mortality. Our results further indicate that a long-term decline in the mean mass of adult sockeye salmon completing their marine residency could erode their migratory fitness during the river migration and hence jeopardize the sustainability of sockeye salmon and the fishery that targets them. 656 RAND ET AL.

Since 1995, several stocks of Fraser River sockeye salmon (Oncorhynchus nerka) have begun upriver spawning migrations significantly earlier than previously observed. In some years, the timing of peak migration has shifted more than 6 weeks. Coincident with this early migration are high levels of en route and pre‐spawning mortality, occasionally exceeding 90%. These phenomena pose risks to the perpetuation of these fisheries resources. At present, although there are many competing hypotheses (e.g., energetics, osmoregulatory dysfunction, oceanic conditions, parasites) that may account for early migration and high mortality, there are no definitive answers, nor any causal evidence that link these issues. With poor predictive ability in the face of uncertainty, fisheries managers have been unable to effectively allocate harvest quotas, while ensuring that sufficient fish are able to not only reach the spawning sites, but also successfully reproduce. If trends in mortality rates continue, several important sockeye salmon fisheries and stocks could collapse. Indeed, one sockeye stock has already been emergency listed as endangered under Canadian legislation.

Toxicology can no longer be used only as a science that reacts to problems but must be more proactive in predicting potential human safety issues with new drug candidates. Success in this area must be based on an understanding of the mechanisms of toxicity. This review summarizes and extends some of the concepts of an American Chemical Society ProSpectives meeting on the title subject held in June 2006. One important area is the discernment of the exact nature of the most common problems in drug toxicity. Knowledge of chemical structure alerts and relevant biological pathways are important. Biological activation to reactive products and off-target pharmacology are considered to be major contexts of drug toxicity, although defining exactly what the contributions are is not trivial. Some newer approaches to screening for both have been developed. A goal in predictive toxicology is the use of in vitro methods and database development to make predictions concerning potential modes of toxicity and to stratify drug candidates for further development. Such predictions are desirable for several economic and other reasons but are certainly not routine yet. However, progress has been made using several approaches. Some examples of the application of studies of wide-scale biological responses are now available, with incorporation into development paradigms.

Adult sockeye salmon (Oncorhynchus nerka) acquire infections with the myxosporean kidney parasite Parvicapsula minibicornis during their spawning migration in the Fraser River, British Columbia. Controlled infections with this parasite in wild sockeye salmon had no significant impact on plasma ionic status, metabolic rates, and initial maximum prolonged swimming performance (Ucrit) for fish ranked as either strongly, weakly, or noninfected by polymerase chain reaction analysis of kidney tissue. However, strongly infected fish had significantly lower second Ucrit and recovery ratio (8%) values, indicating decreased ability to recover from exercise. As the present study shows that the severity of infection is affected by time and temperature, the accumulated thermal units (ATU) of exposure in this study were compared with those experienced by naturally migrating sockeye salmon. A parallel telemetry study revealed that early-timed sockeye experienced significantly more ATU (741.4 ± 29.4 °C) than normally migrating salmon (436.0 ± 20.0 °C) prior to spawning because of a significantly longer holding period in the lake system. The present data are discussed in the context of a threshold of >450 °C ATU for severe infection that would first manifest in early-timed fish in the upper reaches of the Fraser River and certainly on the spawning grounds.