Ozempic and "Useless Science"

In the late 1970s, scientists were trying to identify the gene carrying the instructions for making the hormone glucagon, which was discovered half a century earlier and noted for its ability to cause a rise in blood glucose, a “glucose agonist”, hence its name. By studying the Brockmann bodies of American anglerfish, P. Kay Lund and Richard Goodman did eventually find the gene that makes glucagon, and were surprised to find out that this gene also makes two other peptides showing “striking homology with glucagon and other peptides of the glucagon family”. They were named glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). Ah, the creativity of our dear scientist friends never ceases to amaze me… So, research on GLP-1 and GLP-2 began. It turned out that GLP-1 promotes insulin secretion and satiety, reducing feelings of hunger and lowering blood sugar, exactly the characteristics that could make it a promising treatment for type 2 diabetes. However, there was just one critical hurdle: GLP-1 is broken down almost as fast as it is secreted, meaning it does not stick around long enough in the body to induce its effects. How could we overcome this problem?

The Gila monster is a large venomous lizard native to the Southwestern United States and the northwestern Mexican state of Sonora. Vibrant, eccentric and sluggish by nature, the Gila monster rarely eats, meaning it needs a way to maintain its metabolism during prolonged periods of fasting. Research uncovered that the saliva of the Gila monster contains exendin-4, a structural analogue of human GLP-1, but with a much longer half-life. Yet, no one took much notice, until a synthetic version of exendin-4, exenatide, was manufactured by a drug company and approved by the Food and Drug Administration for the treatment of diabetes in 2005. This was the precursor of semaglutide, the active ingredient in the diabetes turned weight loss medications Ozempic and Wegovy which took the world by storm and were heralded as miracle drugs. Like children playing with legos, chemists tweaked exendin-4 to make new drugs that last ever longer in the body. Semaglutide, for instance, lasts 144-168 hours, a drastic improvement from the mere minutes of GLP-1 and the 2.4 hours achieved by exendin-4. This means people can take fewer doses and see the same results, an extraordinary 10% reduction in body weight over the course of a year. With the health risks and stigma that obesity carries, these drugs have undoubtedly changed the lives of many people around the world for the better,  albeit coming with side effects that should not be ignored.

Anglerfish guts, Gila monster spit and a miracle weight loss drug, these seemingly random and unrelated things are emblematic of the conflict between pure and applied research. Should science be for the sake of gaining knowledge or are resources better allocated with the aim of developing useful products? For cash-strapped governments who prefer short-term returns that can lend them an edge during the next election cycle, the answer has almost always been clear. This is why Richard Nixon would much rather splash money at NASA to put a man on the moon, and  fund cancer research to cure history’s most insidious disease. Yet, this story proves precisely the opposite, that basic research allows us to build up a comprehensive understanding of the world, and down the road, may lead to an answer we do not even have the question for yet. When research conducted by scientists at Bell Labs into semiconductors led to the invention of transistors in the late 1940s, who would have thought that they would lead to a technological revolution, heralding the digital age? When John von Neumann, the Hungarian-American mathematician and physicist, developed a strange machine that could solve logical problems, who could have predicted that he was laying the foundation for the architecture found in almost every computer today? When the German scientists Otto Hahn and Fritz Strassmann discovered nuclear fission, which was subsequently used to create the nuclear bomb during the Manhattan project, who would have believed that the world was just a button away from total self-annihilation? Louis Pasteur, the renowned French chemist and microbiologist, once wrote, “There is no such thing as a special category of science called applied science; there is science and its applications, which are related to one another as the fruit is related to the tree that has borne it.” How can we savour the fruit, whether sweet or bitter, if we haven’t planted the tree?

Credits

Thank you for reading. This article is inspired by the video “Why Useless Knowledge Can Be So Useful?” on the YouTube channel “Be Smart”. It closely follows the video’s layout, and also includes information from other sources I referenced and my own opinions and interpretations.

References

1. Why Useless Knowledge Can Be So Useful

2. R. Paul Robertson. (July 2023). Brief overview: glucagon history and physiology. Journal of Endocrinology, 258(2). https://doi.org/10.1530/JOE-22-0224

3. P. K. Lund et al. (1982). Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem. Proc. Natl. Acad. Sci. U.S.A, 79(2), 345-349. https://doi.org/10.1073/pnas.79.2.345

4. Bogert, Charles M., Rafael Martin del Campo. (1956). The Gila Monster and its allies: the relationships, habits, and behavior of the lizards of the Family Helodermatidae. New York: Bulletin of the American Museum of Natural History.

5. Deane, A. M., Chapman, M. J., & Horowitz, M. (2010). The therapeutic potential of a venomous lizard: the use of glucagon-like peptide-1 analogues in the critically ill. Critical care (London, England), 14(5), 1004. https://doi.org/10.1186/cc9281

6. Donna H. Ryan et al. (2024). Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nature Medicine. https://doi.org/10.1038/s41591-024-02996-7

7. Quote by Louis Pasteur: “There is no such thing as a special category of...”

Image Credit: https://www.meritpharm.com/product/ozempic-semaglutide-prefilled-injection-pen-2mg-1-pen-non-returnable/