The quest for better pain relief keeps many of the world's best chemists busy, made urgent by the spreading opioid crisis. A possible solution has been found in the mud by a boat ramp, although the long development phase has at least 10 years to run.
Professor Rob Capon of the University of Queensland is part of a program screening the natural world for chemicals that may prove useful to humanity. Sixteen years ago, he found a molecule called bilorphin that looked like nothing we had seen before in a sample of mud from the Huon Valley estuary in Tasmania.
The molecule turned out to be the product of a species of Penicillium fungus, the genus that famously gave us the first oral antibiotic.
Many molecules are chiral, meaning they can have a left- or right-handed structure. However, for reasons that remain mysterious, almost all amino acids found in nature are left-handed. The molecule Capon found, however, is made of four amino acids, joined by peptides, two left- and two right-handed.
Inevitably such a molecule aroused interest, and Capon’s team noticed similarities between this molecule and one of the human body’s natural endorphins, which plug into the brain’s opiate receptors.
Professor Macdonald Christie of the University of Sydney took the analysis further. "The structure we found has never been seen before," Christie said in a statement. Indeed, it is the first time we have found something that acts on opiate receptors from microbes.
The researchers noticed similarities between the Penicillium molecule and those being tested as possible pain relievers that avoid the side effects of opioids, a project that has drawn hundreds of millions of dollars. They set about first modifying the molecule to increase its potency, and then producing a new version, which they have named bilactorphin in the Proceedings of the National Academy of Sciences, that can be taken orally.
Opioids are so deadly because the dose required to prevent pain is close to the dosage that depresses breathing to the point where the brain can’t get enough oxygen. In animal studies, it appears bilactorphin provides pain relief without significantly affecting respiration. Moreover, Christie told IFLScience, it appears possible it will also not have the same addictive effects as existing opioids, although this part is less certain.
Bilactorphin’s safety and effectiveness will take at least a decade to prove, probably including further modifications to the molecule. Nevertheless, the potential is enormous in the face of the seemingly unstoppable nature of the opioid crisis.
Even if bilactorphin turns out to be addictive, while not repressing breathing, Christie thinks it may have niche roles, offering pain relief to the elderly or others with compromised breathing. However, he acknowledges such a drug might struggle to get FDA approval.
Christie told IFLScience he doesn’t think the Penicillium species has been found outside the Huon Valley, adding: “I’m not sure if anyone has looked anywhere else.” The Valley is famous for its natural beauty and has been the site of a long-running struggle over proposals to build a woodchip mill, which would see the destruction of much of the area’s ancient forests. Whether alterations of the Huon River’s catchment area would affect the fungus is unknown. Precious as the information it revealed may be, we do not need the fungus itself to make medications. Christie told IFLScience it would be far cheaper to synthesize bilactorphin than to farm the low-yielding fungus.