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Snake Oil Cures for Damaged Hearts

In early 2006 Leinwand ordered 20 baby pythons from a reptile supplier and set up a colony in an empty laboratory downstairs from hers. For the first experiment, she drew blood from a couple of snakes, fed them a big rodent meal, then took another sample. The post-meal blood looked like a cardiologists worst nightmare. The blood became so filled with fat that it was almost milky, Leinwand recalls. In humans, fat in the bloodstream tends to produce fatty deposits on arterial walls and in the heart itself. Yet when Leinwand inspected the snakes hearts, she could not find any accumulating fat deposits. She realized that whatever chemical was strengthening the heart was also preventing the buildup of fat. She still had no idea how the pythons did it or whether the process would work in other animals, but she was determined to find out. Part of the issue was settled when Cecilia Riquelme, a postdoc in Leinwands lab, drew blood from recently fed pythons and applied it to a dish of living rat heart cells. Within two days the cells had grown significantly and were filled with helpful proteins and enzymes. Riquelmes simple experiment suggested that mammals, perhaps including humans, could benefit from the heart-bolstering chemical machinery of pythons.

Leinwand was emboldened to identify that machinery in python blood. It was no easy task: Blood contains thousands of compounds, and any combination of 2 or 20 could have held the secret to heart health. So she isolated compounds in pre-meal blood samples and looked to see if their concentrations shot up after feeding. Whenever she found a candidate, she injected it into mice, hoping their hearts would grow. After two years and dozens of dead ends, Leinwand finally found a compound that strengthened mouse hearts. She tried it on unfed pythons too, and it triggered the same effect, as if they had consumed a giant meal. The crucial recipe was a mixture of myristic acid, palmitic acid, and palmitoleic acid, all of which were isolated from the milky part of the blood that Leinwand had observed in her first experiment. Ironically, a trio of fatty compounds held the key to strengthening the heart, which in turn prevented other fats from clogging up the works. Leinwandsresults appeared in Science last October. Python Therapy Now Leinwand wants to observe python bloods effect on at-risk test subjects. Over the next several months she will breed mice with high blood pressure and inject them with the key fatty acids. She hopes the trial will show that a

python-inspired pill could treat heart failure by reversing damage and adding heart muscle. Leinwand is also injecting healthy mice to see if python blood can prevent symptoms of heart failure before they start. Although human drug trials are several years away, Leinwand has cofounded a company to fund her research. Her colleagues hope this work will keep her occupied for a long while. Everyone has made me promise not to bring another exotic animal into the lab, she says. They think one is enough.

Exotic Medicine Pythons are not the only exotic animals whose body fluids have inspired serious drug research. A variety of outlandish reptiles, arachnids, and mammals also have the potential to overturn their frightening reputations and help fight disease.

Gila monsters These nearly two-foot-long lizards use their poisonous bite to prey on small animals in the
southwestern United States. But scientists figured out how to harness the monsters venom, and in 2005 the Gilainspired drug Byetta was approved as a treatment for type 2 diabetes. Tarantulas Scientists at the University of Buffalo discovered a compound in tarantula saliva that could disable the faulty mechanism that destroys healthy muscle in some people with muscular dystrophy. The researchers are now raising money to start a small-scale clinical trial. Vampire Bats The saliva of these blood-consuming predators contains an anticoagulant, dubbed draculin by the researchers who found it, that can dissolve blood clots. A new drug based on that chemical, currently in human trials, could give doctors more time to treat people who have just suffered a stroke. Mary Beth Griggs

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