The operation is delicate. The liver and ovaries must be removed with great care and the skin must be removed in a very special way developed 2300 years ago so as not to contaminate the rest of the animal’s meat. That’s why not everyone can do it. After just three full years of study and a very complex examination that includes theoretical tests and at the same time exhausting the result of your own study, a cook can prepare the most poisonous fish in the world.

Now we learned how to easily synthesize that poison. Something that will be key to the next generation of painkillers.

fugue. Known as ‘pufferfish’ among us, fugu is considered a delicacy in Japan and the United States; Consumption is prohibited in Europe, however taken into account, and for good reason: it is an extremely venomous animal, the second most venomous vertebrate species in the world (after the venomous golden frog). The explanation is simple (and also extremely complex): tetrodotoxin.

One of the world’s most dangerous toxins. Tetrodotoxin is one of the most potent neurotoxins known. Traditionally, it was believed to be something unique to puffer fish. However, in recent years it has been found in a wide variety of species, from octopuses to toads to salamanders. So we discovered that it wasn’t something those animals produced.

It was something biosynthesized by certain bacteria that infected the species; something that accumulates in the bodies of their hosts and finally plays a key role in defending them against predators with one of these evolutionary tricks.

beyond the fish. The interesting thing about it is that the toxin has many uses beyond fish. It has been tested for the treatment of diseases such as cancer or migraine and has been very carefully studied in recent years to learn about the biosynthesis and ecology of next generation pain relievers.

Focusing on its current practical uses, tetrodotoxin has become an indispensable tool in neurological research as it selectively blocks sodium channels and therefore can be used to silence electrical signals in certain neuronal circuits.

A biosynthetic puzzle. The problem is that the tetrodotoxin molecule has a complex structure made up of interconnected oxygen-rich rings, which frankly is a huge challenge to synthesize. It was first obtained in 1972, but the method of achieving it was so complex that it was not worth doing. Now researchers led by David Konrad have found a relatively simple way to synthesize the toxin from a glucose derivative.

We’re not talking about a revolution, that’s true. It is a 22-step process with a total yield of 11% from the starting materials. However, it is a giant leap forward in our ability to understand and manufacture some of the most complex molecules in nature. One step will open new avenues to modern medicine.

picture | Brian Yuracites