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For Mezzanine’s 20th anniversary, the band have encoded the album in strands of synthetic DNA. One spray can contains around one million copies.

Massive Attack’s Mezzanine was the first album to be streamed for free online when it was released 20 years ago, and the dark, paranoid beats and sparse samples have infused music ever since. To celebrate its 20th anniversary, the pioneering Bristol dance act offers another world debut: the re-issued Mezzanine is the first album ever to be released encoded as strands of synthetic DNA.

This week, Massive Attack are announcing a limited-edition spray can containing approximately one million DNA copies of the album. Each copy of the album is translated into a total of 920,000 DNA fragments and then stored in tiny glass beads – a process that takes over two months. There will also be an art print by band member and artist Robert Del Naja, ink-jet-printed using ink containing Mezzanine DNA.

“The four DNA bases adenine, cytosine, guanine and thymine are coded into binary digital audio,” Del Naja says. “If you were to spray, scrape it off the wall and have it analysed in the correct conditions, you’d be able to play the album back – as soon the right player becomes available.”

The band worked with scientists at TurboBeads, a commercial spin-off from Swiss science, engineering and mathematics university ETH Zurich, to adapt technology pioneered by maverick US biotechnologist Craig Venter when he created a synthetic chromosome of a bacteria species in the laboratory, with four “watermarks” written into its DNA.

Robert Grass, professor at ETH Zurich’s Functional Materials Laboratory, and his colleague Reinhard Heckel used similar chemical techniques to translate Mezzanine’s digital audio into genetic code. “We store digital information in a sequence of zeros and ones, but biology stores genetic information using the four building blocks of DNA,” Grass explains. “We compressed Mezzanine’s digital audio then coded it as DNA molecules by converting the binary 0s and 1s into a quaternary code – with adenine representing 00, cytosine representing 01, guanine representing 10 and thymine representing 11. The resulting DNA resembles natural DNA in every way, although it contains no useful genetic information.”

The idea of storing information on DNA has been around since Mikhail Neiman, a Soviet physicist, published his works in the journal Radiotekhnika in 1964-65, but the first successful execution was in 2012, when Harvard biologist George Church encoded one of his books in DNA. Using an inkjet printer, Church embedded short fragments of chemically-synthesized DNA onto the surface of a tiny glass chip, converting data into DNA’s four-letter alphabet. Each DNA fragment contains a digital “barcode” that records its location so that they can theoretically be rearranged back in order.

Initial costs to code digital into DNA are relatively high – $650,000 for 20mb of data. Once the transfer is complete, Grass says, you can make millions of copies more or less for free. At the moment, the MinION from Oxford Nanopore is the only portable real-time device for DNA and RNA sequencing. The Nanopore sequencer is about the size of a USB stick and costs around £75,000. The MinION would take roughly a week and a powerful computer to ‘play’ Mezzanine, but Grass expects faster devices soon.

“The storage potential of DNA is huge,” del Naja says. Indeed, one milligram of the molecule could store the complete text of every book in the Library of Congress and have room to spare. “If you think about DNA versus the ridiculous amounts of server farms that have got to be cooled 24/7 all around the world, this looks like a much better solution going forward. It allows us to archive music for hundreds to thousands of years.”

The band has always pushed technology to its limits, he explains, from the days “when we were just playing a sound system at parties and pushing volume as high as it could go,” Del Naja recalls. “Since then all of our music has been based on sampling and looping.”

Massive Attack worked with Andrew Melchior at technology consultancy 3rd Space Agency – the man who helped Björk convert her performance of “Stonemilker” into virtual reality for her 2015 MOMA show. Melchior expects a future synthetic DNA culture bank along the lines of the Svalbard Global Seed Vault, which is storing seeds against possible doomsday scenarios.

“The advantage with DNA is that our civilisation could crash into dust and rebuild itself using entirely different technology, meaning they couldn’t access our computers or disks,” Melchior explains. “Since every human carries DNA, we can expect any future civilisation to work out how to play back DNA-stored information. Which means the first thing a future civilisation would learn about us might be Mezzanine.”

Thanks to Kebmodee for bringing this to the It’s Interesting community.

https://www.wired.co.uk/article/massive-attack-mezzanine-dna-album

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By Moises Velasquez-Manoff

The man was 23 when the delusions came on. He became convinced that his thoughts were leaking out of his head and that other people could hear them. When he watched television, he thought the actors were signaling him, trying to communicate. He became irritable and anxious and couldn’t sleep.

Dr. Tsuyoshi Miyaoka, a psychiatrist treating him at the Shimane University School of Medicine in Japan, eventually diagnosed paranoid schizophrenia. He then prescribed a series of antipsychotic drugs. None helped. The man’s symptoms were, in medical parlance, “treatment resistant.”

A year later, the man’s condition worsened. He developed fatigue, fever and shortness of breath, and it turned out he had a cancer of the blood called acute myeloid leukemia. He’d need a bone-marrow transplant to survive. After the procedure came the miracle. The man’s delusions and paranoia almost completely disappeared. His schizophrenia seemingly vanished.

Years later, “he is completely off all medication and shows no psychiatric symptoms,” Dr. Miyaoka told me in an email. Somehow the transplant cured the man’s schizophrenia.

A bone-marrow transplant essentially reboots the immune system. Chemotherapy kills off your old white blood cells, and new ones sprout from the donor’s transplanted blood stem cells. It’s unwise to extrapolate too much from a single case study, and it’s possible it was the drugs the man took as part of the transplant procedure that helped him. But his recovery suggests that his immune system was somehow driving his psychiatric symptoms.

At first glance, the idea seems bizarre — what does the immune system have to do with the brain? — but it jibes with a growing body of literature suggesting that the immune system is involved in psychiatric disorders from depression to bipolar disorder.

The theory has a long, if somewhat overlooked, history. In the late 19th century, physicians noticed that when infections tore through psychiatric wards, the resulting fevers seemed to cause an improvement in some mentally ill and even catatonic patients.

Inspired by these observations, the Austrian physician Julius Wagner-Jauregg developed a method of deliberate infection of psychiatric patients with malaria to induce fever. Some of his patients died from the treatment, but many others recovered. He won a Nobel Prize in 1927.

One much more recent case study relates how a woman’s psychotic symptoms — she had schizoaffective disorder, which combines symptoms of schizophrenia and a mood disorder such as depression — were gone after a severe infection with high fever.

Modern doctors have also observed that people who suffer from certain autoimmune diseases, like lupus, can develop what looks like psychiatric illness. These symptoms probably result from the immune system attacking the central nervous system or from a more generalized inflammation that affects how the brain works.

Indeed, in the past 15 years or so, a new field has emerged called autoimmune neurology. Some two dozen autoimmune diseases of the brain and nervous system have been described. The best known is probably anti-NMDA-receptor encephalitis, made famous by Susannah Cahalan’s memoir “Brain on Fire.” These disorders can resemble bipolar disorder, epilepsy, even dementia — and that’s often how they’re diagnosed initially. But when promptly treated with powerful immune-suppressing therapies, what looks like dementia often reverses. Psychosis evaporates. Epilepsy stops. Patients who just a decade ago might have been institutionalized, or even died, get better and go home.

Admittedly, these diseases are exceedingly rare, but their existence suggests there could be other immune disorders of the brain and nervous system we don’t know about yet.

Dr. Robert Yolken, a professor of developmental neurovirology at Johns Hopkins, estimates that about a third of schizophrenia patients show some evidence of immune disturbance. “The role of immune activation in serious psychiatric disorders is probably the most interesting new thing to know about these disorders,” he told me.

Studies on the role of genes in schizophrenia also suggest immune involvement, a finding that, for Dr. Yolken, helps to resolve an old puzzle. People with schizophrenia tend not to have many children. So how have the genes that increase the risk of schizophrenia, assuming they exist, persisted in populations over time? One possibility is that we retain genes that might increase the risk of schizophrenia because those genes helped humans fight off pathogens in the past. Some psychiatric illness may be an inadvertent consequence, in part, of having an aggressive immune system.

Which brings us back to Dr. Miyaoka’s patient. There are other possible explanations for his recovery. Dr. Andrew McKeon, a neurologist at the Mayo Clinic in Rochester, Minn., a center of autoimmune neurology, points out that he could have suffered from a condition called paraneoplastic syndrome. That’s when a cancer patient’s immune system attacks a tumor — in this case, the leukemia — but because some molecule in the central nervous system happens to resemble one on the tumor, the immune system also attacks the brain, causing psychiatric or neurological problems. This condition was important historically because it pushed researchers to consider the immune system as a cause of neurological and psychiatric symptoms. Eventually they discovered that the immune system alone, unprompted by malignancy, could cause psychiatric symptoms.

Another case study from the Netherlands highlights this still-mysterious relationship. In this study, on which Dr. Yolken is a co-author, a man with leukemia received a bone-marrow transplant from a schizophrenic brother. He beat the cancer but developed schizophrenia. Once he had the same immune system, he developed similar psychiatric symptoms.

The bigger question is this: If so many syndromes can produce schizophrenia-like symptoms, should we examine more closely the entity we call schizophrenia?

Some psychiatrists long ago posited that many “schizophrenias” existed — different paths that led to what looked like one disorder. Perhaps one of those paths is autoinflammatory or autoimmune.

If this idea pans out, what can we do about it? Bone marrow transplant is an extreme and risky intervention, and even if the theoretical basis were completely sound — which it’s not yet — it’s unlikely to become a widespread treatment for psychiatric disorders. Dr. Yolken says that for now, doctors treating leukemia patients who also have psychiatric illnesses should monitor their psychiatric progress after transplantation, so that we can learn more.

And there may be other, softer interventions. A decade ago, Dr. Miyaoka accidentally discovered one. He treated two schizophrenia patients who were both institutionalized, and practically catatonic, with minocycline, an old antibiotic usually used for acne. Both completely normalized on the antibiotic. When Dr. Miyaoka stopped it, their psychosis returned. So he prescribed the patients a low dose on a continuing basis and discharged them.

Minocycline has since been studied by others. Larger trials suggest that it’s an effective add-on treatment for schizophrenia. Some have argued that it works because it tamps down inflammation in the brain. But it’s also possible that it affects the microbiome — the community of microbes in the human body — and thus changes how the immune system works.

Dr. Yolken and colleagues recently explored this idea with a different tool: probiotics, microbes thought to improve immune function. He focused on patients with mania, which has a relatively clear immunological signal. During manic episodes, many patients have elevated levels of cytokines, molecules secreted by immune cells. He had 33 mania patients who’d previously been hospitalized take a probiotic prophylactically. Over 24 weeks, patients who took the probiotic (along with their usual medications) were 75 percent less likely to be admitted to the hospital for manic attacks compared with patients who didn’t.

The study is preliminary, but it suggests that targeting immune function may improve mental health outcomes and that tinkering with the microbiome might be a practical, cost-effective way to do this.

Watershed moments occasionally come along in medical history when previously intractable or even deadly conditions suddenly become treatable or preventable. They are sometimes accompanied by a shift in how scientists understand the disorders in question.

We now seem to have reached such a threshold with certain rare autoimmune diseases of the brain. Not long ago, they could be a death sentence or warrant institutionalization. Now, with aggressive treatment directed at the immune system, patients can recover. Does this group encompass a larger chunk of psychiatric disorders? No one knows the answer yet, but it’s an exciting time to watch the question play out.

When Amanda Kitts’s car was hit head-on by a Ford F-350 truck in 2006, her arm was damaged beyond repair. “It looked like minced meat,” Kitts, now 50, recalls. She was immediately rushed to the hospital, where doctors amputated what remained of her mangled limb.

While still in the hospital, Kitts discovered that researchers at the Rehabilitation Institute of Chicago (now the Shirley Ryan AbilityLab) were investigating a new technique called targeted muscle reinnervation, which would enable people to control motorized prosthetics with their minds. The procedure, which involves surgically rewiring residual nerves from an amputated limb into a nearby muscle, allows movement-related electrical signals—sent from the brain to the innervated muscles—to move a prosthetic device.

Kitts immediately enrolled in the study and had the reinnervation surgery around a year after her accident. With her new prosthetic, Kitts regained a functional limb that she could use with her thoughts alone. But something important was missing. “I was able to move a prosthetic just by thinking about it, but I still couldn’t tell if I was holding or letting go of something,” Kitts says. “Sometimes my muscle might contract, and whatever I was holding would drop—so I found myself [often] looking at my arm when I was using it.”

What Kitts’s prosthetic limb failed to provide was a sense of kinesthesia—the awareness of where one’s body parts are and how they are moving. (Kinesthesia is a form of proprioception with a more specific focus on motion than on position.) Taken for granted by most people, kinesthesia is what allows us to unconsciously grab a coffee mug off a desk or to rapidly catch a falling object before it hits the ground. “It’s how we make such nice, elegant, coordinated movements, but you don’t necessarily think about it when it happens,” explains Paul Marasco, a neuroscientist at the Cleveland Clinic in Ohio. “There’s constant and rapid communication that goes on between the muscles and the brain.” The brain sends the intent to move the muscle, the muscle moves, and the awareness of that movement is fed back to the brain.

Prosthetic technology has advanced significantly in recent years, but proprioception is one thing that many of these modern devices still cannot reproduce, Marasco says. And it’s clear that this is something that people find important, he adds, because many individuals with upper-limb amputations still prefer old-school body-powered hook prosthetics. Despite being low tech—the devices work using a bicycle brake–like cable system that’s powered by the body’s own movements—they provide an inherent sense of proprioception.

To restore this sense for amputees who use the more modern prosthetics, Marasco and his colleagues decided to create a device based on what’s known as the kinesthetic illusion: the strange phenomenon in which vibrating a person’s muscle gives her the false sense of movement. A buzz to the triceps will make you think your arm is flexing, while stimulating the biceps will make you feel that it’s extending. The best illustration of this effect is the so-called Pinocchio illusion: holding your nose while someone applies a vibrating device to your bicep will confuse your brain into thinking your nose is growing.

“Your brain doesn’t like conflict,” Marasco explains. So if it thinks “my arm’s moving and I’m holding onto my nose, that must mean my nose is extending.”

To test the device, the team applied vibrations to the reinnervated muscles on six amputee participants’ chests or upper arms and asked them to indicate how they felt their hands were moving. Each amputee reported feeling various hand, wrist, and elbow motions, or “percepts,” in their missing limbs. Kitts, who had met Marasco while taking part in the studies he was involved in at the institute in Chicago, was one of the subjects in the experiment. “The first time I felt the sense of movement was remarkable,” she says.

In total, the experimenters documented 22 different percepts from their participants. “It’s hard to get this sense reliably, so I was encouraged to see the capability of several different subjects to get a reasonable sense of hand position from this illusion,” says Dustin Tyler, a biomedical engineer at Case Western Reserve University who was not involved in the work. He adds that while this is a new, noninvasive approach to proprioception, he and others are also working on devices that restore this sense by stimulating nerves directly with implanted devices.

Marasco and his colleagues then melded the vibration with the movement-controlled prostheses, so that when participants decided to move their artificial limbs, a vibrating stimulus was applied to the muscles to provide them with proprioceptive feedback. When the subjects conducted various movement-related tasks with this new system, their performance significantly improve.

“This was an extremely thorough set of experiments,” says Marcia O’Malley, a biomedical engineer at Rice University who did not take part in that study. “I think it is really promising.”

Although the mechanisms behind the illusion largely remain a mystery, Marasco says, the vibrations may be activating specific muscle receptors that provide the body with a sense of movement. Interestingly, he and his colleagues have found that the “sweet spot” vibration frequency for movement perception is nearly identical in humans and rats—about 90 Hz.

For Kitts, a system that provides proprioceptive feedback means being able to use her prosthetic without constantly watching it—and feeling it instead. “It’s whole new level of having a real part of your body,” she says.

https://www.the-scientist.com/notebook/vibrations-restore-sense-of-movement-in-prosthetics-64691

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Whiile human genetic mutations are involved in a small number of Parkinson’s disease (PD) cases, the vast majority of cases are of unknown environmental causes, prompting enormous interest in identifying environmental risk factors involved. The link between Helicobacter pylori (H. pylori) and gastric ulcers has been known for several decades, but new evidence suggests that this harmful bacterium may play a role in PD as well. A new review in the Journal of Parkinson’s Disease summarizes the current literature regarding the link between H. pylori and PD and explores the possible mechanisms behind the association.

In a comprehensive review of prior studies, investigators uncovered four key findings:

People with PD are 1.5-3-fold more likely to be infected with H. pylori than people without PD.
H. pylori-infected PD patients display worse motor functions than H. pylori-negative PD patients.
Eradication of H. pylori improved motor function in PD patients over PD patients whose H. pylori was not eradicated.
Eradication of H. pylori improved levodopa absorption in PD patients compared to PD patients whose H. pylori was not eradicated.
“This is an in-depth and comprehensive review that summarizes all the major papers in the medical literature on Parkinson’s disease and H. pylori, the common stomach bacterium that causes gastritis, ulcers and stomach cancer,” explained lead investigator David J. McGee, PhD, Associate Professor, Department of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, Shreveport, LA, USA. “Our conclusion is that there is a strong enough link between the H. pylori and Parkinson’s disease that additional studies are warranted to determine the possible causal relationship.”

Investigators also analyzed existing studies to try and find possible testable pathways between the bacterial infection and Parkinson’s to lay the groundwork for future research. They found four main possible explanations for the association:

Bacterial toxins produced by H. pylori may damage neurons.

The infection triggers a massive inflammatory response that causes damage to the brain.

H. pylori may disrupt the normal gut microbial flora.

The bacteria might interfere with the absorption properties of levodopa, the medication commonly used to treat the symptoms of Parkinson’s disease.

The onset of PD is often preceded by gastrointestinal dysfunction, suggesting that the condition might originate in the gut and spread to the brain along the brain-gut axis. In the review, investigators note that this has been documented in rats.

Screening PD patients for the presence of H. pylori and subsequent treatment if positive with anti-H. pylori triple drug therapy, may contribute to improved levodopa absorption and ultimately improvement of PD symptoms, potentially leading to a longer life span in patients with PD.

“Evidence for a strong association among H. pylori chronic infection, peptic ulceration and exacerbation of PD symptoms is accumulating,” concluded Dr. McGee.

“However, the hypotheses that H. pylori infection is a predisposing factor, disease progression modifier, or even a direct cause of PD remain largely unexplored. This gut pathology may be multifactorial, involving H. pylori, intestinal microflora, inflammation, misfolding of alpha-synuclein in the gut and brain, cholesterol and other metabolites, and potential neurotoxins from bacteria or dietary sources. Eradication of H. pylori or return of the gut microflora to the proper balance in PD patients may ameliorate gut symptoms, L-dopa malabsorption, and motor dysfunction.”

https://scienmag.com/eradicating-helicobacter-pylori-infections-may-be-a-key-treatment-for-parkinsons-disease/

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by IRIS KULBATSKI

Consuming a mixture of sugar syrup and glyphosate, the active ingredient in Monsanto’s Roundup herbicide, alters honey bees’ microbiomes, and these changes increased mortality among insects exposed to pathogenic bacteria, according to a study published yesterday (September 24) in PNAS.

Glyphosate is the most commonly used herbicide worldwide. It acts by blocking a key plant enzyme used in the production of amino acids. Researchers are divided on whether the chemical is safe to animals at the levels it is usually used as a herbicide. However, some bacteria are known to produce this enzyme, and the new study demonstrates what some researchers have suspected: glyphosate may harm animals indirectly by killing their resident microbes.

Nancy Moran of the University of Texas at Austin and colleagues found that glyphosate consumption can lower the levels of the common bee symbiont Snodgrassella alvi by up to five times in the guts of honey bees, and high levels of the herbicide thwarted growth of S. alvi in vitro. Moreover, bees were more susceptible to infection by Serratia marcescens, a bacterium commonly present at low levels in beehives, after drinking the glyphosate–sugar water cocktail: only 12 percent of the insects survived, compared with 47 percent of infected bees that had not been fed glyphosate.

Given these findings, more research is warranted to determine whether the proposed mechanism of honey bee morbidity contributes significantly to issues of colony collapse and overall rates of honey bee decline worldwide, University of Illinois bee geneticist Gene Robinson tells Science.

Moreover, the current study raises the possibility that glyphosate may alter the gut microbiome of other animals, including humans, Moran tells Science.

https://www.the-scientist.com/news-opinion/herbicide-may-harm-microbiome-of-bees-64860?utm_campaign=TS_DAILY%20NEWSLETTER_2018&utm_source=hs_email&utm_medium=email&utm_content=66214269&_hsenc=p2ANqtz–RVJMklVdDEAWS-ddB7O5kVzSQTWCLWqUOnn8jMfmpot3jBytURnj14l3Nx2fPlFTeNO-ZlmSqqln8Wjtd9SqOUpzqTQ&_hsmi=66214269

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by SUKANYA CHARUCHANDRA

It wasn’t until the latter half of the 13th century that human dissections became acceptable in Italy. Previously, both the Roman Empire and Islamic law had prevented the dissection of humans and its depiction. While the Greek surgeon Galen’s anatomical drawings from the second century had been preserved and studied until the Renaissance, they were largely based on dissections of animals, such as apes.

In the mid-16th century, however, famed Flemish anatomist Andreas Vesalius dissected the bodies of executed criminals—not an uncommon practice in that period—while studying in Paris. He realized that Galen had been “misled” by apes, whose anatomy was not exactly like that of humans.

“The challenge of anatomy is rendering the 3-D experience of opening bodies onto a 2-D page,” writes Hannah Marcus, a science historian at Harvard University, in an email to The Scientist. Lack of refrigeration also presented a challenge. In overcoming those hurdles to produce the first realistic depictions of internal human biology, Vesalius’s De Humani Corporis Fabrica, published in Basel, Switzerland, in 1543, galvanized the study of anatomy.

Meanwhile, Spanish-born Juan Valverde de Amusco was learning anatomy under the guidance of Roman surgeon Realdo Colombo, and possibly of Vesalius himself, at the University of Padua in Italy. Valverde observed and participated in many dissections under Colombo’s guidance, and pored over old books on the subject. He later moved to Rome and was welcomed into the home of Spanish Cardinal Juan Álvarez de Toledo.

In 1555, Valverde served as a doctor at the foremost contemporaneous Roman hospital, Santo Spirito, where many luminaries of anatomy worked during that period, including Bartolomeo Eustachi, under whom Valverde studied for a time. The following year, Valverde crafted the Spanish-language anatomical text Historia de la Composicion del Cuerpo Humano, or Account of the Composition of the Human Body. In seven parts, the book covered topics such as “bone and cartilage,” “ligaments and bandaging,” and “instruments of sensation and external motion.” Largely copied from the 1543 and 1555 editions of Vesalius’s tome, it included 15 new illustrations in four copper plates. Valverde’s book also included more than 60 corrections to Vesalius’s text, which enhanced the contemporary understanding of the intracranial passage of carotid arteries, the extraocular muscles, the stapes bone of the middle ear, and how blood moves through the septum. Historians attribute the few original illustrations to Spanish-born Gaspar Becerra.

“Vesalius was angry about Amusco’s work and accused him of plagiarism,” Marcus writes. In 1564, Vesalius wrote in his book Anatomicarum Gabrielis Fallopii Observationum Examen that “Valverde who never put his hand to a dissection and is ignorant of medicine as well as of the primary disciplines, undertook to expound our art in the Spanish language only for the sake of shameful profit.” Valverde conceded his borrowing, explaining that Vesalius’s drawings were so thorough that “it would look like envy or malignity not to take advantage of them.”

Valverde simplified Vesalius’s Latin text considerably, however, as he considered it difficult to understand. His more concise (and thus cheaper) text had more than a dozen editions published in Italian, Latin, Dutch, and Greek, in addition to Spanish, and facilitated the spread of scientific ideas and Vesalius’s modern anatomy throughout Europe and the Spanish Americas.

https://www.the-scientist.com/foundations/homo-sapiens-exposed–1556-64679

by Alison Abbott

It had been hiding in plain sight. The original letter — long thought lost — in which Galileo Galilei first set down his arguments against the church’s doctrine that the Sun orbits the Earth has been discovered in a misdated library catalogue in London. Its unearthing and analysis expose critical new details about the saga that led to the astronomer’s condemnation for heresy in 1633.

The seven-page letter, written to a friend on 21 December 1613 and signed “G.G.”, provides the strongest evidence yet that, at the start of his battle with the religious authorities, Galileo actively engaged in damage control and tried to spread a toned-down version of his claims.

Many copies of the letter were made, and two differing versions exist — one that was sent to the Inquisition in Rome and another with less inflammatory language. But because the original letter was assumed to be lost, it wasn’t clear whether incensed clergymen had doctored the letter to strengthen their case for heresy — something Galileo complained about to friends — or whether Galileo wrote the strong version, then decided to soften his own words.

Galileo did the editing, it seems. The newly unearthed letter is dotted with scorings-out and amendments — and handwriting analysis suggests that Galileo wrote it. He shared a copy of this softened version with a friend, claiming it was his original, and urged him to send it to the Vatican.

The letter has been in the Royal Society’s possession for at least 250 years, but escaped the notice of historians. It was rediscovered in the library there by Salvatore Ricciardo, a postdoctoral science historian at the University of Bergamo in Italy, who visited on 2 August for a different purpose, and then browsed the online catalogue.

“I thought, ‘I can’t believe that I have discovered the letter that virtually all Galileo scholars thought to be hopelessly lost,’” says Ricciardo. “It seemed even more incredible because the letter was not in an obscure library, but in the Royal Society library.”

Ricciardo, together with his supervisor Franco Giudice at the University of Bergamo and science historian Michele Camerota of the University of Cagliari, describe the letter’s details and implications in an article in press at the Royal Society journal Notes and Records. Some science historians declined to comment on the finding before they had scrutinized the article. But Allan Chapman, a science historian at the University of Oxford, UK, and president of the Society for the History of Astronomy, says “it’s so valuable — it will allow new insights into this critical period”.

Mixed messages
Galileo wrote the 1613 letter to Benedetto Castelli, a mathematician at the University of Pisa in Italy. In it, Galileo set out for the first time his arguments that scientific research should be free from theological doctrine (see ‘The Galileo affair’).

He argued that the scant references in the Bible to astronomical events should not be taken literally, because scribes had simplified these descriptions so that they could be understood by common people. Religious authorities who argued otherwise, he wrote, didn’t have the competence to judge. Most crucially, he reasoned that the heliocentric model of Earth orbiting the Sun, proposed by Polish astronomer Nicolaus Copernicus 70 years earlier, is not actually incompatible with the Bible.

Galileo, who by then was living in Florence, wrote thousands of letters, many of which are scientific treatises. Copies of the most significant were immediately made by different readers and widely circulated.

His letter to Castelli caused a storm.

Of the two versions known to survive, one is now held in the Vatican Secret Archives. This version was sent to the Inquisition in Rome on 7 February 1615, by a Dominican friar named Niccolò Lorini. Historians know that Castelli then returned Galileo’s 1613 letter to him, and that on 16 February 1615 Galileo wrote to his friend Piero Dini, a cleric in Rome, suggesting that the version Lorini had sent to the Inquisition might have been doctored. Galileo enclosed with that letter a less inflammatory version of the document, which he said was the correct one, and asked Dini to pass it on to Vatican theologians.

His letter to Dini complains of the “wickedness and ignorance” of his enemies, and lays out his concern that the Inquisition “may be in part deceived by this fraud which is going around under the cloak of zeal and charity”.

At least a dozen copies of the version Galileo sent to Dini are now held in different collections.

The existence of the two versions created confusion among scholars over which corresponded to Galileo’s original.

Beneath its scratchings-out and amendments, the signed copy discovered by Ricciardo shows Galileo’s original wording — and it is the same as in the Lorini copy. The changes are telling. In one case, Galileo referred to certain propositions in the Bible as “false if one goes by the literal meaning of the words”. He crossed through the word “false”, and replaced it with “look different from the truth”. In another section, he changed his reference to the Scriptures “concealing” its most basic dogmas, to the weaker “veiling”.

This suggests that Galileo moderated his own text, says Giudice. To be certain that the letter really was written in Galileo’s hand, the three researchers compared individual words in it with similar words in other works written by Galileo around the same time.

Chance discovery
Ricciardo uncovered the document when he was spending a month this summer touring British libraries to study any handwritten comments that readers might have left on Galileo’s printed works. When his one day at the Royal Society was finished, he idly flicked through the online catalogue looking for anything to do with Castelli, whose writings he had recently finished editing.

One entry jumped out at him — a letter that Galileo wrote to Castelli. According to the catalogue, it was dated 21 October 1613. When Ricciardo examined it, his heart leapt. It appeared to include Galileo’s own signature, “G.G.”; was actually dated 21 December 1613; and contained many crossings out. He immediately realized the letter’s potential importance and asked for permission to photograph all seven pages.

“Strange as it might seem, it has gone unnoticed for centuries, as if it were transparent,” says Giudice. The misdating might be one reason that the letter has been overlooked by Galileo scholars, says Giudice. The letter was included in an 1840 Royal Society catalogue — but was also misdated there, as 21 December 1618.Another reason might be that the Royal Society is not the go-to place in the United Kingdom for this type of historical document, whose more natural home would have been the British Library.

The historians are now trying to trace how long the letter has been in the Royal Society library, and how it arrived there. They know that it has been there since at least the mid-eighteenth century, and they have found hints in old catalogues that it might even have been there a century or more earlier. The researchers speculate that it might have arrived at the society thanks to close connections between the Royal Society and the Academy of Experiments in Florence, which was founded in 1657 by Galileo’s students but fizzled out within a decade or so.

For now, the researchers are stunned by their find. “Galileo’s letter to Castelli is one of the first secular manifestos about the freedom of science — it’s the first time in my life I have been involved in such a thrilling discovery,” says Giudice.

TIMELINE: THE GALILEO AFFAIR
1543 Polish astronomer Nicolaus Copernicus publishes his book On the Revolutions of the Heavenly Spheres, which proposes that the planets orbit the Sun.

1600 The Inquisition in Rome convicts Dominican friar and mathematician Giordano Bruno of heresy on multiple counts, including supporting and extending the Copernican model. Bruno is burnt at the stake.

1610 Galileo publishes his book The Starry Messenger (Sidereus nuncius), describing discoveries made with his newly built telescope that provide evidence for the Copernican model.

1613 Galileo writes a letter to his friend Benedetto Castelli, arguing against the doctrine of the Roman Catholic Church in matters of astronomy. Copies of this letter are circulated.

1615 Dominican friar Niccolò Lorini forwards a copy of the letter to the inquisition in Rome. Galileo asks a friend to forward what he claims to be a copy of his original letter to Rome; this version is less inflammatory than Lorini’s.

1616 Galileo is warned to abandon his support of the Copernican model. Books supporting the Copernican model are banned. On the Revolutions of the Heavenly Spheres is withdrawn from circulation pending correction to clarify that it is only a theory.

1632 Galileo publishes Dialogue Concerning the Two Chief World Systems, in which he lays out the various evidence for and against the Church’s Ptolemaic model of the Solar System, and the Copernican model. The Inquisition summons Galileo to Rome to stand trial.

1633 Galileo is convicted on “vehement suspicion of heresy” and the book is banned. He is issued with a prison sentence, later commuted to house arrest, under which lived the last nine years of his life.

Nature 561, 441-442 (2018)

https://www.nature.com/articles/d41586-018-06769-4