From reptiles to remedies: How python blood is inspiring an Ozempic alternative

Most mammals need to consume small, frequent meals to maintain their metabolism. Pythons, however, are classic “sit-and-wait” ambush predators adapted to extreme feast-and-famine cycles. Adult Burmese and ball pythons can routinely fast for months, and sometimes more than a year, between large meals. During these prolonged fasts, their standard metabolic rate drops significantly, reducing energy expenditure during the long intervals between meals. A single meal can weigh anywhere from 50 per cent to more than 100 per cent of a python’s own body weight.

Once digestion is complete—typically seven to 14 days after feeding—a python undergoes a rapid, coordinated process known as postprandial organ regression and metabolic down regulation. As part of this process, the lining of the small intestine undergoes widespread programmed cell death and shedding. Heart mass decreases by approximately 28-40 per cent, while cardiac output, heart rate and systemic blood pressure fall sharply. Metabolic rate also plummets 30- to 44-fold from its peak during digestion.

Recently, researchers at the University of Colorado discovered an appetite-suppressing compound in python blood. The team studied Burmese and ball pythons and found that 208 metabolites (a metabolite is any small molecule produced, used or broken down during metabolism) increased significantly after the pythons ate. One molecule, para-tyramine-O-sulfate (pTOS), soared 1,000-fold.

Further studies showed that when high doses of pTOS were given to obese and lean mice, the compound acted on the hypothalamus, the brain’s appetite-regulating centre, prompting weight loss without causing major gastrointestinal problems, muscle loss or a decline in energy levels. The researchers claim that drugs based on pTOS could potentially offer an alternative to the current drugs based on GLP-1 (glucagon-like peptide-1, the gut hormone that helps regulate blood sugar and appetite after a meal).

Blockbuster GLP-1 drugs such as Wegovy and Ozempic also belong to a class first inspired by a reptile. The Gila monster, a venomous lizard native to North America that can survive for months without food, produces a venom or saliva peptide similar to human GLP-1, the gut hormone that helps regulate blood sugar and appetite after a meal. Drugs like Wegovy and Ozempic are synthetic analogues of human GLP-1, engineered to last longer and thereby suppress appetite more effectively.

While human GLP-1 is produced in the gut, pTOS—the compound found in python blood—is also present in human urine, albeit at low levels.

University of Colorado researchers are now working on commercialising some of the lessons they have learned from pythons. At the same time, they are studying other, rarer metabolites, with the long-term goal of developing synthetic analogues that could one day become human therapies. These therapeutic goals reportedly extend beyond weight loss to potentially reversing conditions such as age-related muscle loss. The researchers reportedly believe that the unique physiology of pythons—marked by massive cycles of physiological change in response to food intake—could provide insights into developing treatments for conditions such as sarcopenia (the gradual loss of muscle mass, strength and function that occurs as people age).

The remarkable biological adaptations found in different animals have inspired the discovery of many life-saving drugs. Nevertheless, animal and human physiology can differ significantly. When developing new classes of drugs based on the biological “superpowers” of other species, it is therefore important to consider the complex physiological transformations that occur naturally in those animals, as well as the potential side effects that may arise when these mechanisms are replicated or modified for use in humans.