A ball python, like most pythons, sits coiled in its enclosure in a lab at the University of Colorado Boulder, unhurried and unconcerned. It’s been 28 days since it last ate. This is not an issue. Burmese pythons, which are closely related to ball pythons, can go 12 to 18 months without eating in the wild. During this time, they do not waste away or develop the metabolic chaos that a human would experience on any similar fast.
They just wait until they eat, and when they do, something remarkable occurs within them. Their hearts enlarge by twenty-five percent. They experience a 4,000-fold increase in metabolism. Their organs start to change. After digestion is finished, everything adjusts, and the waiting process starts over. For twenty years, Professor Leslie Leinwand has observed this process. Recently, she discovered something unexpected in the blood.
| Category | Detail |
|---|---|
| Key Molecule Discovered | pTOS (para-tyramine-O-sulfate) — a metabolite that spikes 1,000-fold in python blood after eating |
| Lead Research Institutions | University of Colorado Boulder, Stanford Medicine, Baylor University |
| Senior Authors | Prof. Leslie Leinwand (CU Boulder) and Dr. Jonathan Long (Stanford School of Medicine) |
| Published In | Nature Metabolism — March 19, 2026 |
| Python Species Studied | Ball pythons and Burmese pythons — fed once every 28 days in the lab |
| Mouse Trial Results | Obese mice given pTOS lost 9% of body weight over 28 days; ate significantly less than control mice |
| Side Effects Observed | None — no gastrointestinal problems, muscle loss, or energy expenditure changes |
| How pTOS Works | Acts on the hypothalamus (brain’s appetite center) — different mechanism from GLP-1 drugs |
| Source of pTOS | Produced by gut bacteria through breakdown of tyrosine (amino acid in dietary protein) |
| Human Presence | pTOS found in human urine at low levels; rises modestly after meals in most people |
| Commercial Venture | Arkana Therapeutics — startup formed by Leinwand, Long, and CU Boulder colleagues |
| Reference | Stanford Medicine News — Python Research |
Within hours of the snake eating, the molecule, known as para-tyramine-O-sulfate, or pTOS, spikes more than a thousandfold in python blood. Even by itself, that figure is powerful. When researchers administered concentrated doses of pTOS to obese lab mice, the mice stopped eating, which made the study scientifically intriguing. Significantly, but not completely. Compared to the control animals, they had lost 9% of their body weight after 28 days.
They displayed no symptoms of gastrointestinal distress, no loss of muscle, and no alterations in movement or energy expenditure. Rather than through the stomach-slowing mechanism that makes GLP-1 medications like Ozempic and Wegovy effective for some patients and challenging for others, the weight loss seemed to come solely from eating less, mediated by activity in the hypothalamus, the part of the brain that controls appetite.
Leinwand’s lab at CU Boulder, Dr. Jonathan Long’s team at Stanford School of Medicine, and researchers at Baylor University collaborated to publish the findings in Nature Metabolism on March 19. It came at a time when the market for weight-loss medications is both incredibly successful and genuinely unfinished. GLP-1 drugs have led to population-scale weight loss that is dramatic, consistent, and medically significant—results that clinical medicine had never seen before. However, the dropout rates are actual.
According to studies, up to half of patients who begin GLP-1 therapy discontinue it within a year due to side effects, expense, or the practical difficulties of receiving weekly injections for an indefinite period of time. Alternatives, or complementary strategies with distinct mechanisms and tolerance profiles, are clearly needed in clinical settings. It is evident in the billions of dollars spent on research as well as in the silent annoyance of both patients and medical professionals.
The Python story’s lineage is what makes it interesting and serves as a helpful reminder of how drug development actually operates. The active ingredient in Ozempic and Wegovy, semaglutide, is not derived from human biology. It was created after a hormone known as exendin-4 was found in the saliva of the Gila monster, a poisonous lizard indigenous to the American Southwest. That hormone was so similar to a human gut peptide that it served as the model for a whole class of drugs that are currently taken by millions of people worldwide. Anticoagulants and blood pressure medications have already been added to the pharmacopoeia by snake venom. A thorough examination reveals that the animal kingdom is conducting metabolic experiments that human physiology hasn’t tried, and sometimes the findings translate.
When outlining his lab’s methodology, Long made it clear that studying only mice and humans would limit the scope of what biology is capable of if the objective is to comprehend metabolism. A metabolic extreme is represented by pythons. They consume nearly all of their body weight in a single meal, go through a period of fasting that would be physiologically disastrous for humans, and come out of it with intact muscle mass, healthy hearts, and no obvious long-term harm. Their biochemistry is handling that shift in a way that science is just now starting to understand. Researchers are currently methodically investigating the 208 metabolites that markedly increased in python blood following feeding, with pTOS being the first to generate a clinically intriguing signal in animal models.
The story becomes more complex—that is, more honest—when it comes to the human aspect of pTOS. Low amounts of the molecule are found in human urine, and most people’s levels do slightly increase after meals—by two to five times in five of the six datasets the researchers looked at. This indicates that the molecule may not be completely alien to human physiology, which is encouraging. However, “present in humans” is not the same as “safe and effective as a drug.” One person in those datasets had a more than 25-fold increase in pTOS after a meal, which was getting close to Python territory.
However, the researchers were unable to determine from the available data whether this person felt fuller or ate less as a result. A metabolite database’s correlation does not constitute a clinical trial. Both Leinwand and Long agree that more research is needed before pTOS could be a viable therapeutic option for humans, and that many promising molecules that performed well in animal models but poorly in human patients have been identified along the way from obese mice to human patients.
Nevertheless, Leinwand, Long, and their CU Boulder colleagues have established a startup named Arkana Therapeutics to pursue commercializing what they’re learning from pythons. This is a significant indication of how seriously the research team takes this direction. Generally speaking, academic researchers don’t create businesses based on findings they deem marginal.
Given that nausea, constipation, and stomach pain are among the most frequently reported reasons for discontinuing GLP-1 therapy, the lack of gastrointestinal side effects in the mouse trials is especially appealing. If pTOS performs well in additional testing, it may eventually fill a different treatment niche for patients who require appetite suppression but cannot tolerate the stomach-related side effects of current medications, or it may be used in combination with GLP-1 medications. It’s also quite possible that it doesn’t go that far. There are many intriguing early discoveries in drug development that eventually ran into problems.
Observing the development of this specific line of research gives one the impression that the story of obesity medications is still in its early stages; semaglutide and tirzepatide are significant but not definitive, and the next generation of treatments will come from less obvious sources. It turns out that one of those experiments is being conducted by a snake that is quietly waiting 28 days between meals in a laboratory in Boulder. The lessons it imparts to viewers are genuinely fascinating. Only time and a lot more research will be able to determine whether what it’s teaching them becomes medicine.
