1. Birth defects in Northern California Goats, Dogs and Humans Might be Related Amanda Risler Liana Wiegel Eli Yoder

2. Birth Defects in Boy Severe bone deformities in his arms and hands, including a partial absence of forearm bones (radial aplasia) and absent thumbs Severe bone deformities in his arms and hands, including a partial absence of forearm bones (radial aplasia) and absent thumbs Histories and genetic analyses of his parents indicated that the probable cause was environmental Histories and genetic analyses of his parents indicated that the probable cause was environmental Mother feared that somehow exposure to herbicide spraying was responsible Mother feared that somehow exposure to herbicide spraying was responsible Mother drank goat milk from local goats regularly throughout pregnancy Mother drank goat milk from local goats regularly throughout pregnancy

3. Birth Defects in Goats and Puppies Goats giving birth to kids that are stillborn or have deformed legs Goats giving birth to kids that are stillborn or have deformed legs Puppies born to a dog fed the goat's milk during pregnancy were likewise deformed Puppies born to a dog fed the goat's milk during pregnancy were likewise deformed Survey of nearby areas where the goats had regularly browsed at the time of the mother's early pregnancy showed Lupinus latifolius Survey of nearby areas where the goats had regularly browsed at the time of the mother's early pregnancy showed Lupinus latifolius

4. Problem Are the birth defects of the boy, kids and puppies related? Are the birth defects of the boy, kids and puppies related? Are the defects related to "crooked calf disease"? Are the defects related to "crooked calf disease"? Hypothesis – Defects of the boy, kids and puppies are directly related to crooked calf disease Hypothesis – Defects of the boy, kids and puppies are directly related to crooked calf disease

5. Lupine-induced Disease “Crooked calf disease” “Crooked calf disease” Characterized by bone abnormalities in the forelimbs and, to a lesser extent, spine and skull (scoliosis and cleft palate) Characterized by bone abnormalities in the forelimbs and, to a lesser extent, spine and skull (scoliosis and cleft palate) Attributed to ingestion of a specific lupine alkaloid (anagyrine) Attributed to ingestion of a specific lupine alkaloid (anagyrine) Exposure during the second or third month of pregnancy Exposure during the second or third month of pregnancy

6. Losses from Crooked Calf Disease In 1997 4,000+ calves from about 12,000 cows either died or were destroyed in Adams county, Washington because of birth defects In 1997 4,000+ calves from about 12,000 cows either died or were destroyed in Adams county, Washington because of birth defects Resulted in a $1.7 million direct loss and over $5 million in indirect losses in Adams county Resulted in a $1.7 million direct loss and over $5 million in indirect losses in Adams county Lupine-induced losses also occurred in Utah, Montana, Nevada and Oregon Lupine-induced losses also occurred in Utah, Montana, Nevada and Oregon

7. Lupine Species 19 Lupine species are potentially teratogenic due to their concentrations in anagyrine and piperidine alkaloids 19 Lupine species are potentially teratogenic due to their concentrations in anagyrine and piperidine alkaloids Alkaloid concentration varies in the plant (most to least concentration) Alkaloid concentration varies in the plant (most to least concentration) –Seed, flower, young leaf material, mature leaf Concentration of anagyrine over 1.44 g/kg is generally teratogenic Concentration of anagyrine over 1.44 g/kg is generally teratogenic –Lupinus latifolius has anagyrine 6.04-11.43 g/kg

8. Cause of Birth Defects Experimental studies indicate that these alkaloids exert their effect by producing a sedating effect on the fetus that depresses normal fetal movements in utero Experimental studies indicate that these alkaloids exert their effect by producing a sedating effect on the fetus that depresses normal fetal movements in utero May be in an abnormal position when its movements become depressed from the sedative effect of the ingested alkaloid and it remains “fixed” in that abnormal position while it still continues to grow May be in an abnormal position when its movements become depressed from the sedative effect of the ingested alkaloid and it remains “fixed” in that abnormal position while it still continues to grow

9. Anagyrine in Milk Experimental studies show when lactating goats are fed lupine seeds, anagyrine and other alkaloids were detected almost immediately in the milk by gas chromatography/mass spectrometry Experimental studies show when lactating goats are fed lupine seeds, anagyrine and other alkaloids were detected almost immediately in the milk by gas chromatography/mass spectrometry Control milk sample taken immediately before feeding lupine did not contain any of these alkaloids Control milk sample taken immediately before feeding lupine did not contain any of these alkaloids

10. Anagyrine Toxicity in Humans Anagyrine- containing milk cannot be fed experimentally to human mothers Anagyrine- containing milk cannot be fed experimentally to human mothers High potency of the teratogen during a short period early in pregnancy may not be analytically detection before any defects can be recognized High potency of the teratogen during a short period early in pregnancy may not be analytically detection before any defects can be recognized Case study correlation of specific deformities with the incidence of toxic plant species or dietary peculiarities might have positive leads Case study correlation of specific deformities with the incidence of toxic plant species or dietary peculiarities might have positive leads Adequate proof may be long in coming Adequate proof may be long in coming