Pythons—A Model to Study Human Heart Disease? By Max Sherman Many of my previous articles for RAPS have featured a host of disparate animals that are or could be used in medicine or in medical research, including leeches, maggots, rats, spiders, whipworms, Gila monsters and zebrafish. Now, there is new evidence to include Burmese pythons on this distinguished list. This snake species may be used to develop drugs to treat human heart disease.1 In anticipation of this event, it would be prudent to know more about Burmese pythons, their diet, their unusual digestive processes, why they were selected as a research tool and their possible therapeutic use. Description Burmese pythons (Python molarus bivittatus) are one of the six largest kinds of snakes in the world. They can weigh up to 200 pounds and can grow to great lengths. The largest pythons are always female, they can grow to be 13 to approximately 18 feet long while the typically smaller males grow to a maximum of 8 to 17 feet.2 According to one report, the record maximum length is 5.74 m (18 ft 10 in).3 Burmese pythons are dark colored with many brown blotches bordered in black down the back. The attractiveness of their skin pattern contributes to their popularity with reptile keepers and the leather industry. They are native to a large variation of tropical and subtropical areas of Southern and Southeast Asia.4 Pythons are constrictors, therefore they do not have fangs and are nonvenomous. Their back curving teeth are used to seize and hold their prey. Pythons have two lungs, one more than most snakes. This species lacks eyelids but it does have a thin epidermal membrane covering the eyes to protect them. Pythons have small heat pits, or holes, in their upper lip that allow them to detect heat radiating from any animal nearby. They are able to smell with the aid of the “Jacobson’s organ” in the roof the mouth. They dart their tongues in and out of their mouths to obtain gases in the air.5 This gas detection method allows the python to catch its prey in light regulatoryfocus.org June 2012 1 or dark conditions. Pythons do not have to eat very often, and for this reason they have proven invaluable in research. Diet Pythons are known for their enormous appetites. Like all snakes, they are carnivorous. In a single meal, they can devour animals as big as they are. There was a recent report about a 16-foot Burmese python devouring a 76-pound deer.6 (Pythons are able to swallow their prey because of their hinged jaws, which separate to allow an intake of an object four to five times as wide as their heads.) An autopsy showed the python had of girth of 44 inches after eating the deer, found still fully intact inside the python’s belly.7 The digestive process for such large prey has made the python a model species for digestive physiology.8 Truly remarkable is what happens inside the python as it digests its food. Within a day, the internal organs can double in size and the metabolic rate, insulin production and lipid levels rise extraordinarily.9 The entire digestive system undergoes a massive remodeling, with rapid hypertrophy of the intestines, production of stomach acid, and a 40% increase in mass of the heart ventricles to fuel the digestive process.10 The python’s organs return to normal size in a few days and metabolism slows. The snake can then fast for months or even a year without losing muscle mass or showing ill effects.11 Research Tools Using a snake to study heart disease is not as rare as one might think. The entire history of biology illustrates the importance of selecting suitable species as models. Examples include the contributions made by squid axons, pigeon breast muscle, salamander kidneys and fruit flies.12 The flies have taught scientists a great deal about the development of human embryos. Roundworms and mollusks have been used to learn the basis of neural organization and memory.13 Each of the species models distinguished themselves by exaggerated structures or responses, or by experimental convenience with respect to the phenomenon under study. Once biologists unravel the model species, they can devise experiments for doing so in humans.14 The field that had been in need of a model species was vertebrate regulatory biology. Scientists were searching for a species to advance an understanding about organ growth (the heart) and atrophy or signal pathways for hormone release. Of particular interest are models, unlike rats and humans, that are adapted to consuming large meals at long, erratic intervals. Some experimentally tractable candidates have been tested, including 18 species of frogs, lizards, turtles and snakes. (Other candidates could have included lions, wolves, whales or Komodo dragons, but they were rejected for obvious reasons.) Maximum voluntary meal size and post-feeding increases in metabolic rate, enzyme and transporter activities and organ masses have been measured.15 The most promising candidates turned out to be snakes. Their typical feeding intervals are one to two months, but may exceed one year.16,17 The eventual choice was the Burmese python, a popular pet available from commercial breeders. Possible Therapeutic Use Using the previous work cited above, researchers at the University of Colorado sought answers to the biology behind the snake’s expanding heart and how it possibly correlates with human health. Of particular interest was the method by which a gorging python expands its heart by enlarging existing cells and not by creating new ones.18 Chief Scientific Officer Leslie Leinwand and her research team found the amount of triglycerides—the main constituent of natural fats and oils—in the blood of Burmese pythons one day after eating increased by a factor of more than 50. Despite the massive amount of fatty acids in the bloodstream, there was no evidence of fat deposition in the heart. Moreover, there was an increase in the activity of a key enzyme (superoxide dismutase) known to protect the heart from damage.19 According to one of the scientists involved in the study, “A combination of fatty acids can induce beneficial heart growth in living organisms.” She further stated that the molecular mechanisms behind the process might lead to new therapies to improve heart disease conditions in humans.20 One or the more regulatoryfocus.org June 2012 2 relevant discoveries was that a combination of fatty acids promoted physiological heart growth when injected into other pythons or in mice.21 Final Thoughts In addition to their contributions to research, pythons have a long history as pets. For anyone who contemplates purchasing a Burmese python, it is wise to ensure that the animal has clear, firm skin, a rounded body shape, a clear vent (the posterior opening for urinary and fecal excretion) and clear eyes. It should be one that actively flicks its tongue when handled. On the other hand, a prospective buyer should remember that the snake may grow to more than 15 feet long, weigh up to 200 pounds and have bowel and bladder habits like a horse. It may live more than 25 years, and a snake owner must provide mice, rats and eventually rabbits to feed it.22 Additionally, pythons are wild animals, unpredictable and dangerous. After weighing the benefits versus the risks, it may be wise to limit pet selection to an aquarium inhabited by zebrafish. References 1. Altman LK. “Snake’s feat may inspire heart drugs.” New York Times, 27 October 2011. 2. WhoZoo (http://whozoo.org/students/stamoo/pythonhtml.html (accessed 11 June 2012) 3. Barker DG et al: The corrected length of two well known giant pythons and the establishment of a new maximum length record for Burmese pythons, Python bivittatus. Bull Chicago Herp Soc 2012;47(1):1-6. 4. Kiberstis PA. “Snake oil revisited.” Sci Signal 2011; 4:ec307. 5.Ibid. 6. Op cit 3. 7. ABC News (http://abcnews.go.com/blogs/headlines/2011/10/16-foot-long-burmese-python-devours-76) accessed 21 April 2012. 8. Op cit 4. 9. Op cit 1. 10. Op cit 4. 11. Op cit 1. 12. Secor SM and Diamond J. “A vertebrate model of extreme physiological regulation.” Nature 1998; 395:659-662. 13. Wilson EO. The Social Conquest of Earth. WW Norton Publishers, New York, 2012 14. Op cit 12. 15.Ibid. 16. Secor SM and Nagy KA. “Bioenergetic correlates of foraging mode for the snakes Crotalus cerastes and Masticicophis flagellum.” Ecology 1994; 75:1600-14. 17. Pope CH. The Giant Snakes. Knopf Publishers, New York, 1961. 18. Op cit 1. 19. Riquelme CA et al. “Fatty acids identified in the Burmese python promote beneficial cardiac growth.” Science 2011; 334:528-31 20. University of Colorado Boulder (http://cimb.colorado.edu/news/pythons-provide-clues-to-human-heart-health). Accessed 1 April 2012. 21. Op cit 19. 22. Melissa Kaplan’s Help Care Collection (www.anapsid.org/burm.html). Accessed 1 April 2012. © 2012 by the Regulatory Affairs Professionals Society. All rights reserved. regulatoryfocus.org June 2012 3
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