Enlarge / Portrait of Beethoven by Joseph Karl Stieler, 1820. Toxocology analysis of the composer's locks of hair showed high levels of lead. (credit: Beethoven-Haus Bonn)

Last year, researchers sequenced the genome of famed composer Ludwig van Beethoven for the first time, based on authenticated locks of hair. The same team has now analyzed two of the locks for toxic substances and found extremely high levels of lead, as well as arsenic and mercury, according to a recent letter published in the journal Clinical Chemistry.

“It definitely shows Beethoven was exposed to high concentrations of lead,” Paul Janetto, co-author and director of the Mayo Clinic's Department of Laboratory Medicine and Pathology, told The New York Times. “These are the highest values in hair I’ve ever seen. We get samples from around the world, and these values are an order of magnitude higher.” That said, the authors concluded that the lead exposure was not sufficient to actually kill the composer, although Beethoven very likely did suffer adverse health effects because of it.

As previously reported, Beethoven was plagued throughout his life by myriad health problems. The composer began losing his hearing in his mid- to late 20s, experiencing tinnitus and the loss of high-tone frequencies in particular. He claimed the onset began with a fit in 1798 induced by a quarrel with a singer. By his mid-40s, he was functionally deaf and unable to perform public concerts, although he could still compose music.

Enlarge / The Colorado River toad, also known as the Sonoran Desert Toad. (credit: Mark Newman)

It is becoming increasingly accepted that classic psychedelics like LSD, psilocybin, ayahuasca, and mescaline can act as antidepressants and anti-anxiety treatments in addition to causing hallucinations. They act by binding to a serotonin receptor. But there are 14 known types of serotonin receptors, and most of the research into these compounds has focused on only one of them—the one these molecules like, called 5-HT2A. (5-HT, short for 5-hydroxytryptamine, is the chemical name for serotonin.)

The Colorado River toad (Incilius alvarius), also known as the Sonoran Desert toad, secretes a psychedelic compound that likes to bind to a different serotonin receptor subtype called 5-HT1A. And that difference may be the key to developing an entirely distinct class of antidepressants.

Uncovering novel biology

Like other psychedelics, the one the toad produces decreases depression and anxiety and induces meaningful and spiritually significant experiences. It has been used clinically to treat vets with post-traumatic stress disorder and is being developed as a treatment for other neurological disorders and drug abuse. 5-HT1A is a validated therapeutic target, as approved drugs, including the antidepressant Viibryd and the anti-anxiety med Buspar, bind to it. But little is known about how psychedelics engage with this receptor and which effects it mediates, so Daniel Wacker’s lab decided to look into it.

Enlarge / Xorides praecatorius is a parasitoid wasp. (credit: TorriPhoto via Getty)

If you puncture the ovary of a wasp called Microplitis demolitor, viruses squirt out in vast quantities, shimmering like iridescent blue toothpaste. “It’s very beautiful, and just amazing that there’s so much virus made in there,” says Gaelen Burke, an entomologist at the University of Georgia.

M. demolitor  is a parasite that lays its eggs in caterpillars, and the particles in its ovaries are “domesticated” viruses that have been tuned to persist harmlessly in wasps and serve their purposes. The virus particles are injected into the caterpillar through the wasp’s stinger, along with the wasp’s own eggs. The viruses then dump their contents into the caterpillar’s cells, delivering genes that are unlike those in a normal virus. Those genes suppress the caterpillar’s immune system and control its development, turning it into a harmless nursery for the wasp’s young.

The insect world is full of species of parasitic wasps that spend their infancy eating other insects alive. And for reasons that scientists don’t fully understand, they have repeatedly adopted and tamed wild, disease-causing viruses and turned them into biological weapons. Half a dozen examples already are described, and new research hints at many more.

Enlarge / Prediction of the structure of a coronavirus Spike protein from a virus that causes the common cold. (credit: Google DeepMind)

Most of the activities that go on inside cells—the activities that keep us living, breathing, thinking animals—are handled by proteins. They allow cells to communicate with each other, run a cell's basic metabolism, and help convert the information stored in DNA into even more proteins. And all of that depends on the ability of the protein's string of amino acids to fold up into a complicated yet specific three-dimensional shape that enables it to function.

Up until this decade, understanding that 3D shape meant purifying the protein and subjecting it to a time- and labor-intensive process to determine its structure. But that changed with the work of DeepMind, one of Google's AI divisions, which released Alpha Fold in 2021, and a similar academic effort shortly afterward. The software wasn't perfect; it struggled with larger proteins and didn't offer high-confidence solutions for every protein. But many of its predictions turned out to be remarkably accurate.

Even so, these structures only told half of the story. To function, almost every protein has to interact with something else—other proteins, DNA, chemicals, membranes, and more. And, while the initial version of AlphaFold could handle some protein-protein interactions, the rest remained black boxes. Today, DeepMind is announcing the availability of version 3 of AlphaFold, which has seen parts of its underlying engine either heavily modified or replaced entirely. Thanks to these changes, the software now handles various additional protein interactions and modifications.