Venom

As much as I like Venom and his buddy Eddie Brock, this blurb isn't about this dynamic duo but rather about biological venom and the benefits it has for mankind as nature never disappoints if one looks hard enough
to learn why.

lIllustration by Armando Veve

There are two opposite paths to achievement in science. The first is straightforward: Identify a problem and set about solving it. The second is rather unscientific-sounding and perhaps more faith-based: Study in obscurity and hope serendipity strikes.

For one researcher, the start point was the Gila Monster.

Gila Monster | Evolutionary splitting of the genus Heloderma into species (Reiserer et al)[6]

Gila monsters — sluggish, thick-tailed ground dwellers — are native to southern Arizona and northern Mexico. They have blunt noses and bumpy black skin with tan, pink or orange squiggles. They spend 95 percent of their lives underground. Like their cousins to the south, Mexican beaded lizards, they are one of the very few lizard species that produces venom, which they excrete from mouth glands into grooves in their serrated teeth.

Something's afoot.

One of the scientists there, an endocrinologist named John Eng, was impressed by Raufman’s work with the Gila monster. He was especially intrigued by its glacial metabolism — the lizard can survive on fewer than a handful of meals per year. Eng and Raufman paired up, screened the venom again and found molecules Raufman had not observed before. They called these molecules exendin-3 and -4.

Eng recognized the exendins as a potential diabetes therapy. He had patients with the condition who needed to calibrate their insulin injections carefully to avoid both hyper- and hypoglycemia. Exendin-4, on the other hand, resembled a human hormone called GLP-1, which works as a natural insulin manager in people without diabetes. When we eat, the small intestine releases GLP-1, prompting the pancreas to produce more insulin only when blood-sugar levels get too high. The molecule also slows digestion and makes us feel full. Scientists suspected that injections of GLP-1 would be a much easier and safer diabetes treatment than insulin, except for one crucial problem: The hormone lasts only a few minutes in the bloodstream before it breaks down. But the Gila monster analogue, Eng and Raufman were surprised to note, lasts for hours.

Fast forward a few years ...

Under the brand name Byetta, exenatide was approved by the Food and Drug Administration for the treatment of Type 2 diabetes in 2005.

Patients who took Byetta and other exendin- and GLP-1-inspired drugs also experienced substantial weight loss, trials revealed, but pharmaceutical companies were slow to realize how useful that side effect could be. Once they did, and had improved their formulations, the consequences transformed society: Ozempic and Wegovy, followed by Mounjaro and Zepbound, became blockbuster drugs for treating diabetes and spurring weight loss. What’s more, many of them appear to have additional beneficial impacts that researchers are only beginning to understand. Some seem to be protective against kidney and heart disease and may reduce inflammation in the brain that is linked to the development of Parkinson’s and Alzheimer’s. You might say that the Gila monster — this shy, subterranean reptile — harbored a blueprint all along for medicines that may be among the most consequential health advances of our time.

Venom delivery systems have been around for a very long time. :)

Venom is generally considered distinct from poison. Whereas poison is passive — a substance, like a laundry-detergent pod or berries from a black nightshade plant, that can be lethal if ingested — venom must be actively administered by an animal, often via fangs, teeth or barbs, usually to capture prey or defend against predators. Nature has engineered this capacity surprisingly often. There are at least 1,250 species of venomous catfish alone, each with its own venom formula. Venomous creatures include insects, spiders, corals, mollusks, snakes, lizards and a few mammals (platypuses, shrews). Many of them, such as marine species, are difficult to observe in their natural habitats, and so we know next to nothing about how and why they use their toxins.

Cone snails, may have the most sophisticated venom in the world.

In closing ...

But in the venoms of creatures that researchers have been able to examine more closely, two features stand out that hint at their significant medical potential. They are incredibly potent and fast-acting — necessary qualities if they are to aid the survival prospects of the creatures deploying them. They can be produced in advance and stored for long periods at ambient temperatures (in the animals’ glands). They are composed of hundreds — or sometimes thousands — of molecules that often serve multiple purposes, making venoms “essentially ecological Swiss Army Knives,” as a 2019 review in the journal Toxins put it. And a majority of those molecules are peptides and proteins honed over millions of years to target other animals in the host’s ecosystem, including plenty of creatures whose biology overlaps that of humans.

Read the long NYTimes piece in its entirety. You'll learn a lot. I know I have. :)