Lethal Poison = Life-Saving Drug?

Modern pharmacology is full of paradoxes. One of them is using poison as a remedy. Over hundreds of million years, evolution pushed animal venoms to be precise biological weapons: built to kill, paralyze, destroy the living tissue in their prey (Utkin, 2015). Weird people, once again, used it to cure themselves. The very traits that make these toxins deadly–specific identification of cellular receptors, structural stability– render them as most perfect drug candidates. The venomomics, emerging field of integrative disciple fusion(genomics, transcriptomics, and mass spectrometry-based proteomics), is now actively used to revolutionize human therapeutics (Calvete, 2017).

Historically, many ancient healers used venoms as a medicine, but for a long period of time (until now) it was viewed as an alternative medicine. As a matter of fact, the Greek word “pharmakon”, from which modern pharmacology, pharmacy, etc. derives, means both remedy and poison. The overall process of collecting poison for medicine was a painstaking and long process  that required milking thousands of wild specimens to yield tiny droplets of crude liquid (Freuville et al., 2024). Traditional bio-guided fractionation frequently proved itself to be scarce in samples and complex to chemically identify. Modern venomomics, however, reads genetic blueprints of venom glands through RNA sequencing, not requiring a whole ecosystem for a drop of essence (Romano et al., 2023). By coupling transcriptomic sequence data with bioinformatic algorithms and chemical synthesis, scientists can computationally identify novel bio-active peptides, synthesize them in the laboratory, and screen their therapeutic potential without capturing a single animal (Calvete, 2017).

The products of this revolutionized bio-prospecting are already helping millions of people, all in the most affordable ways. If you ever heard or taken “captopril” (like me) – blood-pressure stabilizing medication– just know that it is derived from the venom of Brazilian pit viper Bothrops jararaca, proving that a lethal hypotensive agent could be safely re-engineered into a blockbuster drug (King, 2011). Despite cutting-edge technologies that are used in creating captopril, its retail price  in the US ranges from $37 to $100 and even lower with the prescription discount programs. Following this milestone, “exenatide” for type 2 diabetes management is made from Gila monster saliva, while non-opioid analgesic that alleviates severe chronic pain signals in spinal cord is yielded from marine cone snail toxins (Freuville et al., 2024). Unique disulfide-rich molecular scaffolds are the reason for the venom peptides’ efficacy. As peptides often destruct from the human enzymes, those scaffolds prevent that, guiding them to hit ion channels precisely (King, 2011).

Yet the most exciting part is yet to come. Researchers actively use AI and machine learning to accelerate the screening of massive venom libraries. To that end, some treatments for complex autoimmune disorders, neurodegenerative decay, and drug-resistant cancers are promised to be uncovered in the next few years (Romano et al., 2023). Biomedical scientists are designing biomolecules that could cross the brain-blood barriers with ease, as they are deciphering the mystery of toxins’ evolutionary engineering optimizations that use the same required patterns (King, 2011). The biggest medical paradox is the key for affordable and revolutionary medicine and venomomics is the greatest instant of it. Nature's most exquisite defense mechanisms turned from lethal biological weapons into life-saving remedies for millions. 

References:

• Calvete, J. J. (2017). Venomics: integrative venom proteomics and beyond. Biochemical Journal, 474(5), 611–634. https://doi.org/10.1042/bcj20160577 Cited by: 253

• Freuville, L., Matthys, C., Quinton, L., & Gillet, J.-P. (2024). Venom-derived peptides for breaking through the glass ceiling of drug development. Frontiers in Chemistry, 12, Article 1465459. https://doi.org/10.3389/fchem.2024.1465459 Cited by: 35

• King, G. F. (2011). Venoms as a platform for human drugs: Translating toxins into therapeutics. Expert Opinion on Biological Therapy, 11(11), 1469–1484. https://doi.org/10.1517/14712598.2011.621940 Cited by: 729

• Romano, J. D., Li, H., Napolitano, T., Realubit, R., Karan, C., Holford, M., & Tatonetti, N. P. (2023). Discovering venom-derived drug candidates using differential gene expression. Toxins, 15(7), Article 451. https://doi.org/10.3390/toxins15070451 Cited by: 8

• Utkin, Y. N. (2015). Animal venom studies: Current benefits and future developments. World Journal of Biological Chemistry, 6(2), 28–33. https://doi.org/10.4331/wjbc.v6.i2.28 Cited by: 256