On 18 August 1961, the Santa Cruz Sentinel reported (1) that thousands of "crazed seabirds" were diving into lamp posts, buildings, cars, and streets to their death on the shores of North Monterey Bay, California. The birds appeared to be confused and disoriented, exhibited seizure activity, and flew at terrified residents. Eight people were bitten, but none suffered a related illness. Alfred Hitchcock contacted the newspaper for details. As the story is told, the Hollywood movie producer used the incident as research material for the classic 1963 thriller The Birds. About 30 years later it was established that the culprit of this extreme event was an algal bloom of Pseudo-nitzchia, select species of which produce domoic acid (DA). (2) DA is a potent neurotoxin that bioaccumulates in filter-feeding shellfish and subsequently enters the food web. DA has been responsible for multiple mass illness and mortality events of shore birds (3) and marine (4-6) and coastal-dwelling mammals, (7) particularly on the U.S. Pacific Coast. These events provided opportunities to capture the naturally occurring physical, physiological, neurologic, cardiac, and behavioral impacts of DA exposure, as well as advance understanding of delayed effects, reexposures, and rehabilitation possibilities. (8,9) Laboratory studies of zebrafish, shellfish, marine mammals, and mice further expanded the capacity for hypothesis testing relevant to protecting public health. (10-12) Nonhuman primate studies, such as that presented by Petroff et al. (8) in this issue of Environmental Health Perspectives, represent a unique opportunity to improve understanding of an important contemporary issue: the neural mechanisms underlying chronic exposure to presumably safe levels of DA.
The potential risk of domoic acid to human health was first discovered in Montreal, Canada, in 1987. People who consumed mussels harvested from the Prince Edward Island region with high levels of DA suffered the acute onset of severe gastrointestinal and neurologic symptoms, which in some cases included seizures, coma, and even death. (13,14) Many survivors were left with a permanent anterograde memory disorder, amnesic shellfish poisoning (ASP). Autopsy findings of patients with ASP and early nonhuman primate studies identified damage to the hippocampus as central to seizures and memory problems associated with DA neurotoxicity. (14,15) In the aftermath of this outbreak, extensive research using shellfish, rodent, and nonhuman primate models helped establish current regulatory limits of 20 ppm, ostensibly preventing new cases of ASP. (16-19)
However, the evidence collected over the past decade--which came from epidemiological cohort studies of at-risk Native American communities, (20-22) surveys of recreational and subsistence razor clam harvesters, (23) and risk assessments, (24) combined with zebrafish (25) and rodent, (26,27) models--indicates that repeated, chronic exposure to DA at presumably safe levels (<20ppm) may have neurotoxic effects impacting many people. Studies of coastal Native American communities with repetitive, low-level exposure for up to 8 y identified the hallmark memory problems associated with ASP in attenuated form. (20,21) Similarly, problems with spatial memory were found in...