J Nat Toxins 1999 Feb;8(1):63-80
USDA-ARS Poisonous Plant Research Laboratory, Logan, UT 84341, USA.
Research on teratogenic plants started at the USDA-Agricultural Research Service-Poisonous Plant Research Laboratory in the mid 1950s when Dr. Wayne Binns, Director of the laboratory, was asked to investigate the cause of a cyclopian facial/skeletal birth defect in lambs. Dr. Lynn F. James joined the staff shortly after. These two people worked as a team wherein most planning was done jointly with Binns supervising most of the laboratory work and James the field studies. It was determined that when pregnant ewes grazed Veratrum californicum on day 14 of gestation a significant number of lambs had the cyclopic defect. Skeletal and cleft palate birth defects in calves was associated with pregnant cows grazing certain lupine species during 40-70 days of gestation. Shortly thereafter research work was initiated on locoweed which caused abortions, wasting, right heart failure, skeletal birth defects, and fetal right heart failure. Dr. Richard F. Keeler, a chemist who joined the staff in the early 1960s, isolated and characterized the teratogens in V. californicum as the steroidal alkaloids cyclopamine, jervine, and cycloposine. He also described the teratogen in lupines as the quinolizidine alkaloid anagyrine and the piperidine alkaloid ammodendrine. Drs. Russell Molyneux and James identified the toxin in locoweed as the indolizidine alkaloid swainsonine. In 1974 the editor of Nutrition Today (Vols. 9 and 4) wrote "The idea that birth defects occurring in humans may be in some way related to diet is not widely held ..." Dr. Lynn James pointed out in this issue that such defects in animals can be produced with absolute predictability and regularity by foods ordinarily beneficial to livestock. Management strategies have been developed to prevent or minimize the economic impact of the cyclopian lamb and the crooked calf condition on livestock producers and well on the way to doing the same with locoweed. It is of interest to note that livestock research on Veratrum, lupines and locoweed and toxins therefrom are now significant research tools for specific human health problems.
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