proteomics

What we can learn from scientific analysis of Renaissance recipes

artifact conservation, culture, history, proteomics, renaissance medicine, Science / Kris Guyer / March 3, 2026

“a key change in how people constructed knowledge”

Multispectral imaging, proteomics, historical texts yield new insights into 16th-century medical manuals.

Credit: The John Rylands Research Institute and Library, The University of Manchester

Forget “eye of newt and toe of frog/wool of bat and tongue of dog.” People in the 16th century were more akin to DIY scientists than Macbeth’s three witches when it came to concocting home remedies for everything from hair loss and toothache, to kidney stones and fungal infections. Medical manuals targeted to the layperson were hugely popular at the time, according to Stefan Hanss, an early modern historian at the University of Manchester in the UK. “Reader-practitioners” would tinker with the various recipes, tweaking them as needed and making personalized notes in the margins. And they left telltale protein traces behind as they did so.

Hanss is part of an interdisciplinary team of archaeologists, chemists, historians, conservators, and materials scientists who have analyzed trace proteins from the fingerprints of Renaissance people rifling through the pages of medical manuals. The team reported their findings in a paper published in The American Historical Review. It’s the first time researchers have used proteomics to analyze Renaissance recipes, enhanced further by in-depth archival research to place the scientific results in the proper historical context.

“We have so many recipes of that time, [including] cosmetic, medical, and culinary recipes, as well as handwritten recipes passed down for generations,” Hanss told Ars. “It’s really a key element of Renaissance culture, and [the manuscripts] are all covered with scribbled marginalia of [past] users. Experimentation was everywhere. It’s not only about book-learned knowledge but hands-on practical knowledge. It’s a key change in the way people constructed knowledge at that time.”

As previously reported, a number of analytical techniques have emerged over the last few decades to create historical molecular records of the culture in which various artworks were created. For instance, studying the microbial species that congregate on works of art may lead to new ways to slow down the deterioration of priceless aging art. Case in point: Scientists analyzed the microbes found on seven of Leonardo da Vinci’s drawings in 2020 using a third-generation sequencing method known as Nanopore, which uses protein nanopores embedded in a polymer membrane for sequencing. They combined the Nanopore sequencing with a whole-genome-amplification protocol and found that each drawing had its own unique microbiome.

Mass spectrometry-based proteomics is a relative newcomer to the field and is capable of providing a thorough and very detailed characterization of any protein residues present in a given sample, as well as any accumulated damage. The technique is so sensitive that less sample material is needed compared to other methods. And unlike, say, gas chromatography-mass spectrometry, it’s also capable of characterizing all proteins present in a sample (regardless of the complexity of the mixture), rather than being narrowly targeted to predefined proteins. In 2023, scientists used this approach to discover that beer byproducts were popular canvas primers for artists of the Danish Golden Age. Hanss et al. are extending this methodology to Renaissance medical manuals.

A thriving DIY medical marketplace

This latest study has its roots in an event Hanss organized a few years ago called “Microscopic Records,” which brought together experts in various scientific fields and early modern historians. One of the master classes on offer focused on proteomics. Hanss was intrigued when he learned that researchers had extracted proteins from the lower-right and left corners (i.e., where contact occurs when one turns a page) of archived manuscripts in Milan. “I thought, we must have a conversation about doing this for Renaissance recipes,” said Hanss. “We know there was experimentation, but we couldn’t really trace it. This is really the first time that we’ve sampled and identified and contextualized biochemical traces of materials.”

Hanss et al. focused on two 1531 German medical manuals published by 16th-century physician Bartholomäus Vogtherr: How to Cure and Expel All Afflictions and Illnesses of the Human Body and A Useful and Essential Little Book of Medicine for the Common Man. The two tomes are bound together into a single volume and are part of the collection of the John Rylands Research Institute and Library at Manchester. The recipes included domestic remedies for brain disease, infertility, skin disorders, hair loss, wounds, and various other severe illnesses, written in the vernacular and targeted at the common populace.

It was a relatively new genre at the time, per the authors, a kind of everyday DIY science, since the manuals encouraged at-home hands-on experimentation. In 16th-century Augsburg (a printing hub), “experimentation was everywhere,” and the city boasted a thriving medical marketplace. It’s clear that people used the Rylands copies of Vogtherr’s manuals for their own experiments because the margins are filled with scribbled notes and comments dating back to that period.

The first step was to take high-resolution photographs and then run the pages through multispectral imaging (including infrared and UV wavelengths), which helped them recover the most faded, previously illegible handwriting, such as on the inside cover. One scribbled note turned out to be instructions to use a mixture of viola and scorpion oil as a treatment for ulcers. Then they sampled various pages from the manuals for the proteomics analysis, focusing on areas where Renaissance users would be most likely to rest their writing hand or leave fingerprints. That’s also why they avoided the bindings, which are far more likely to be handled by modern-day conservators.

While proteomics cannot establish the dates of specific samples, the team was able to distinguish between contemporary and old peptides based on degree of degradation (such as oxidation). The quantity of peptides detected was also a clue. In fact, the team ended up excluding one of the samples from the final paper because there was such a significantly higher number of peptide results (2,258) than expected, compared to all the other samples (which ranged from 40 to 210 peptides). And for these two particular manuals, “They were in use for more than a hundred years and we know the [users’] names,” said Hanss. “We could make an informed interpretation based on other recipes at the time, and letters exchanged between [Renaissance] medical practitioners.”

The handwritten marginalia are a fascinating window into how people experimented with and tweaked various Renaissance domestic remedies. For those suffering from urinary stones, for instance, a “reader-practitioner” commented that during painful flare-ups, “parsley powdered or soaked in wine” could be effective. There are references to the benefits of broadleaf plantain juice (administered anally), and eating scarlet hawthorn leaves.

The proteomics results confirmed, among other things, the presence of many popular ingredients used in the recipes, such as beech, watercress, and rosemary traces found next to hair loss remedies—commonly attributed to an “overheated brain—along with cabbage and radish oil, chicory, lizards, and, um, human feces. (Just how badly do you want to grow back that thinning hair?) The manuscripts also include recipes for blonde hair dyes. The analysis revealed traces of plants with particularly striking yellow flowers on those pages. “That is a common theme in cosmetic and medical discourse at the time,” said Hanss. “The idea was to look for resemblances between the remedies and what you wish to achieve in terms of the treatment.”

One of the most remarkable results, per Hanss et al., was the recovery of collagen peptides from hippopotamus teeth or bone, pointing to the global circulation of more exotic ingredients in the 16th century. Hippo teeth were said to cure kidney stones and “take away toothache,” and were even used to make dentures.

Hanss et al. also found that several of the proteins they found had antimicrobial functions, such as dermcidin (derived from human sweat glands), which kills E. coli and yeast infections like thrush. The samples also yielded insight into how Renaissance people’s bodies responded to the remedies. Traces of immunoglobulin, lipocalin, and lysozyme are indicators of an active immune response, for instance.

Hanss is so pleased with these initial results that he hopes to launch a large-scale project to extend this interdisciplinary approach to other collections of medical manuals. He also hopes to further improve the dating methodology. “The ingredients for success are there,” said Hanss. “It’s not only that we found new answers to old questions, but we are now in a position to ask completely new questions.”

The American Historical Review, 2025. DOI: 10.1093/ahr/rhaf405 (About DOIs).

Jennifer is a senior writer at Ars Technica with a particular focus on where science meets culture, covering everything from physics and related interdisciplinary topics to her favorite films and TV series. Jennifer lives in Baltimore with her spouse, physicist Sean M. Carroll, and their two cats, Ariel and Caliban.

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The controversial “Dragon Man” skull was a Denisovan

ancient DNA, ancient proteins, anthropology, Archaeology, Denisovans, hominins, Neanderthals, paleoanthropology, paleoproteomics, proteomics, Science, skeletons and skeleton accessories, skulls / Tim Belzer / June 18, 2025

It’s a Denisovan? Always has been.

After years of mystery, we now know what at least one Denisovan looked like.

A 146,000-year-old skull from Harbin, China, belongs to a Denisovan, according to a recent study of proteins preserved inside the ancient bone. The paleoanthropologists who studied the Harbin skull in 2021 declared it a new (to us) species, Homo longi. But the Harbin skull still contains enough of its original proteins to tell a different story: A few of them matched specific proteins from Denisovan bones and teeth, as encoded in Denisovan DNA.

So Homo longi was a Denisovan all along, and thanks to the remarkably well-preserved skull, we finally know what the enigmatic Denisovans actually looked like.

Two early-human skulls against a black background. — Credit: Ni et al. 2021

The Harbin skull (left) and the Dali skull (right).

Unmasking Dragon Man

Paleoanthropologist Qiang Ji, of the Chinese Academy of Sciences, and colleagues tried to sequence ancient DNA from several samples of the Harbin skull’s bone and its one remaining tooth, but they had no luck. Proteins tend to be hardier molecules than DNA, though, and in samples from the skull’s temporal bone (the ones on the sides of the head, just behind the cheekbones), the researchers struck pay dirt.

They found fragments of a total of 95 proteins. Four of these had variations that were distinct to the Denisovan lineage, and the Harbin skull matched Denisovans on three of them. That’s enough to confidently say that the Harbin skull had belonged to a Denisovan. So for the past few years, we’ve had images of an almost uncannily well-preserved Denisovan skull—which is a pretty big deal, especially when you consider its complicated history.

While the world is now aware of it, until 2021, only one person had known what the skull looked like since its discovery in the 1930s. It was unearthed in Harbin, in northeast China, during the Japanese occupation of the area. Not wanting it to be seized by the occupying government, the person who found the skull immediately hid it, and he kept it hidden for most of the rest of his life.

He eventually turned it over to scientists in 2018, who published their analysis in 2021. That analysis placed the Harbin skull, along with a number of other fossils from China, in a distinct lineage within our genus, Homo, making them our species’ closest fossil relatives. They called this alleged new species Homo longi, or “Dragon Man.”

The decision to classify Homo longi as a new species was largely due to the skull’s unique combination of features (which we’ll discuss below). But it was a controversial decision, partly because paleoanthropologists don’t entirely agree about whether we should even call Neanderthals a distinct species. If the line between Neanderthals and our species is that blurry, many in the field have questioned whether Homo longi could be considered a distinct species, when it’s even closer to us than the Neanderthals.

Meanwhile, the 2021 paper also left room for debate on whether the skull might actually have belonged to a Denisovan rather than a distinct new species. Its authors acknowledge that one of the fossils they label as Homo longi had already been identified as a Denisovan based on its protein sequences. They also point out that the Harbin skull has rather large molars, which seem to be a common feature in Denisovans.

The paper’s authors argued that their Homo longi should be a separate branch of the hominin lineage, more closely related to us than to Denisovans or Neanderthals. But if the Harbin skull looked so much like Denisovan fossils and so little like fossils from our species, the alleged relationship begins to look pretty dubious. In the end, the 2021 paper’s authors dodged the issue by saying that “new genetic material will test the relationship of these populations to each other and to the Denisovans.”

Which turned out to be exactly what happened.

A ghost lineage comes to life

Denisovans are the ghost in our family tree. For scientists, a “ghost lineage” is one that’s known mostly from genetic evidence, not fossils; like a ghost, it has a presence we can sense but no physical form we can touch. With the extremely well-preserved Harbin skull identified as a Denisovan, though, we’re finally able to look our “ghost” cousins in the face.

Paleogeneticists have recovered Denisovan DNA from tiny fragments of bone and teeth, and even from the soil of a cave floor. Genomics researchers have found segments of Denisovan DNA woven into the genomes of some modern humans, revealing just how close our two species once were. But the handful of Denisovan fossils paleoanthropologists have unearthed are mostly small fragments—a finger bone here, a tooth there, a jawbone someplace else—that don’t reveal much about how Denisovans lived or what they looked like.

We know they existed and that they were something slightly different from Homo sapiens or Neanderthals. We even know when and where they lived and a surprising amount about their genetics, and we have some very strong hints about how they interacted with our species and with Neanderthals. But we didn’t really know what they looked like, and we couldn’t hope to identify their fossils without turning to DNA or protein sequences.

Until now.

Neanderthals and Denisovans probably enjoyed the view from Denisova Cave, too. Credit: loronet / Flickr

The face of a Denisovan

So what did a Denisovan look like? Harbin 1 has a wide, flattish face with small cheekbones, big eye sockets, and a heavy brow. Its upper jaw juts forward just a little, and it had big, robust molars. The cranium itself is longer and less dome-like than ours, but it’s roomy enough for a big brain (about 1,420 millimeters).

Some of those traits, like the large molars and the long, low cranium, resemble those of earlier hominin species such as Homo erectus or Homo heidelbergensis. Others, like a relatively flat face, set beneath the cranium instead of sticking out in front of it, look more like us. (Early hominins, like Australopithecus afarensis, don’t really have foreheads because their skulls are arranged so their brains are right behind their faces instead of partly above them, like ours.)

In other words, Harbin’s features are what paleoanthropologists call a mosaic, with some traits that look like they come from older lineages and some that seem more modern. Mosaics are common in the hominin family tree.

But for all the detail it reveals about the Denisovans, Harbin is still just one skull from one individual. Imagine trying to reconstruct all the diversity of human faces from just one skull. We have to assume that Densiovans—a species that spanned a huge swath of our planet, from Siberia to Taiwan, and a wide range of environments, from high-altitude plateaus in Tibet to subtropical forests—were also a pretty diverse species.

It’s also worth remembering that the Harbin skull is exactly that: a skull. It can’t tell us much about how tall its former user was, how they were built, or how they moved or worked during their life. We can’t even say for sure whether Harbin is osteologically or genetically male or female. In other words, some of the mystery of the Denisovans still endures.

What’s next?

In the 2021 papers, the researchers noted that the Harbin skull also bears a resemblance to a 200,000- to 260,000-year-old skull found in Dali County in northwestern China, a roughly 300,000-year-old skull found in Hualong Cave in eastern China, and a 260,000-year-old skull from Jinniushi (sometimes spelled Jinniushan) Cave in China. And some fossils from Taiwan and northern China have molars that look an awful lot like those in that Tibetan jawbone.

“These hominins potentially also belong to Denisovan populations,” write Ji and colleagues. That means we might already have a better sample of Denisovan diversity than this one skull suggests.

And, like the Harbin skull, the bones and teeth of those other fossils may hold ancient DNA or proteins that could help confirm that intriguing possibility.

Science, 2023 DOI: 10.1126/science.adu9677 (About DOIs).

Kiona is a freelance science journalist and resident archaeology nerd at Ars Technica.

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