25 Sep 1997: NIH Project to Characterize Pfiesteria Toxins and Explore Their Potential Danger to Humans
National Institute of Environmental Health Sciences Director Kenneth Olden, Ph.D., said today that two laboratory extracts derived from the Pfiesteria organism have shown the ability, in one case, to cause skin lesions characteristic of recent coastal fish kills and, in the other, to affect the nervous system. Olden, appearing at a Congressional hearing, announced a $400,000 "add on" research program to further isolate and chemically characterize the toxins in these Pfiesteria extracts so that their potential danger to humans can be determined.
Daniel G. Baden, Ph.D., director of the NIEHS Marine and Freshwater Biomedical Sciences Center at the University of Miami, will be the principal investigator, with work also being conducted at the University of Maryland School of Medicine and the John Hopkins University School of Medicine, both in Baltimore. Olden said university-located NIEHS centers had been established beginning in 1973 and had been at the forefront of research on toxins from marine and freshwater microorganisms as well as other environmental health-related issues. Dr. Baden has successfully worked on the isolation of some Ciguatoxins, which are the most widespread of the toxins that sometimes make human fish consumers ill, as well as Brevetoxin and Saxitoxin, both of which derive from red tides.
Dr. Olden told a House Human Resources subcommittee chaired by Rep. Christopher Shays, R-Conn., that there appear to be at least two distinct toxins of Pfiesteria piscicida:
- a fat-soluble called "Nogatoxin," isolated by colleague Kathleen Rein from extracts provided by North Carolina State University investigator Edward Noga. "Nogatoxin" causes lesions on fish like the "blistering of the epidermis" that Dr. Noga noted in first describing the Pfiesteria fish kills in North Carolina in 1991.
- a water-soluble toxin that appears to poison the nervous system (and which may be responsible for temporary memory loss in people exposed accidentally in labs and in the field). NC State investigator JoAnne Burkholder reported this progress August 26 at a marine toxins workshop at NIEHS.
Pfiesteria is a microscopic organism that has been implicated in fish kills in North Carolina and Maryland and, more recently, Delaware and Virginia. It has become a focus of a great deal of public concern as watermen report skin blisters and short-term memory loss, possibly from exposure to Pfiesteria-infested waters.
Dr. Olden said there had been "a major bottleneck to progress in Pfiesteria research - the isolation and characterization of the toxins implicated in Pfiesteria fish kills and human health effects." He said, "there is an urgent need to purify the toxins in sufficient quantities to allow for structural analysis, determination of dose-response relationships, human health effects, and development of laboratory tests and animal models. Using a multifaceted approach to increase the pace with which these toxins are being isolated, NIEHS/NIH is providing a $400,000 supplement to the Marine and Freshwater Biomedical Science Center at the University of Miami," which will collaborate with public health officials and physicians and scientists at the Maryland and Hopkins schools of medicine.
"The plans," Dr. Olden continued, "are to study the oral toxicity of these toxins in a mouse model and the respiratory toxicity in a sheep asthma model. Researchers also plan to collect preliminary information on risk factors and critical exposure levels for health effects associated with human environmental exposures and the duration of symptoms associated with exposure."
This new award augments an ongoing research program to purify and study Pfiesteria toxins. NIEHS also has its own intramural researchers in the National Toxicology Program working with Dr. Burkholder of NC State and with scientists at the National Oceanic and Atmospheric Administration's National Marine Fisheries Service in Charleston, S.C.
NIEHS, which is an institute of the National Institutes of Health but located in Research Triangle Park, N.C. has other marine and freshwater research centers at Oregon State University, the University of Wisconsin-Milwaukee, and the Yale-associated Mount Desert Island Biological Laboratory in Maine, as well as at Duke University Marine Biomedical Center. NIEHS has also awarded funds to the Duke center to define neurotoxic effects of Pfiesteria.
Co-investigators with Dr. Baden on the new award are Kathleen S. Rein, Ph.D., Gregory Bossart, Ph.D., both of the university, and William Abraham, M.D. of Mount Sinai Medical Center. The principal investigator at the University of Maryland School of Medicine would be Glenn Morris, M.D., working with Lynn Grattan, Ph.D, and David Oldach, M.D. and Hopkins' Trish Perl, M.D., and Patricia Charach, M.D.
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