Python biology research offers potential new treatments for human disease

Researchers at the University of Colorado Boulder and Stanford Medicine are investigating the physiological extremes of pythons to uncover potential clues for treating human disease. By studying how these snakes manage dramatic metabolic shifts, scientists aim to address conditions ranging from heart disease and muscle atrophy to obesity.

Python physiology and cardiac remodeling

Pythons are capable of fasting for extended periods, sometimes lasting months or up to a year, while maintaining muscle tone. When they consume a large meal — which can approach 100% of their body weight — they undergo rapid physiological changes. According to researchers, these snakes can increase their metabolism from 10 to 40 times following a feeding. To support this energy demand, the python's heart can increase in size by 50% or more, while cells that do not normally divide, such as insulin-producing beta cells in the pancreas, also increase in number.

This cycle of organ growth and subsequent return to a resting state draws comparisons to heart growth in humans. However, unlike human hearts, which can stiffen or develop scarring due to high blood pressure or heart attacks, pythons appear to avoid these negative consequences, with their hearts returning to their previous size after digestion is complete. Leslie Leinwand, a geneticist and the executive science officer of CU Boulder’s BioFrontiers Institute, first began researching this translational potential two decades ago. Her team is working to identify the biological signals that govern this cardiac remodeling, with the long-term goal of developing therapies to stop or reverse problematic heart growth in people.

The pTOS molecule and appetite regulation

In addition to cardiac research, scientists have identified a metabolite that spikes significantly in pythons after a meal. This molecule, called pTOS, was found to increase more than a thousandfold in the blood of Burmese and ball pythons post-feeding. A paper published in the journal Nature Metabolism describes how this metabolite is a byproduct of the breakdown of tyrosine, an amino acid present in dietary protein, by bacteria in the gut.

When administered to obese laboratory mice, pTOS acted as an appetite suppressant, causing the animals to eat significantly less and lose 9% of their body weight after 28 days. Jonathan Long, a senior author of the study and associate professor of pathology at Stanford Medicine, noted that the molecule activates neurons in the hypothalamus to regulate feeding behaviors. Unlike common GLP-1 medications like Ozempic, the researchers found that pTOS does not work by reducing the rate of stomach emptying or changing hormone levels known to regulate feeding. Human datasets indicate that while most people experience a two- to fivefold increase in pTOS after a meal, it remains difficult to isolate from other metabolic changes; however, researchers noted one individual in a dataset who reached python-level concentrations.

Future directions in biological research

The study of pythons highlights a broader scientific interest in utilizing extreme animal adaptations to inform human health. Scientists argue that while mammals have a relatively narrow physiological range, studying species that have evolved under extreme conditions can identify molecules or metabolic pathways that might also affect human metabolism. Researchers have formed a company, Arkana Therapeutics, to develop these discoveries into potential drugs and treatments.

Current investigations are ongoing regarding how these findings might translate to therapies for patients, such as using snake-derived molecules to stimulate cell division in patients with defective beta cell function or to facilitate organ remodeling in those with liver disease. As noted by Ashley Zehnder, CEO of Fauna Bio, identifying these bioactive molecules relies on understanding animals that have been "evolutionarily perfected." Despite the challenges of maintaining such species in a lab environment, researchers believe this approach could broaden the palette for drug discovery and contribute to new therapies for age-related muscle loss and other human health challenges.