Sleuths Read Old Booby-Trapped Letters Without Opening Them

On July 31, 1697, Jacques Sennacques sent a letter to his cousin—one Pierre Le Pers, a French merchant living in the Hague—begging him, for the love of Pete (that’s paraphrased), to send him a death certificate for his relative, Daniel Le Pers. In a 17th century version of the dreaded “as per my previous email,” Sennacques wrote: “I am writing to you a second time in order to remind you of the pains that I took on your behalf.” Basically, you owe me a favor, and I’ve come to collect.

Sennacques put down his pen and intricately folded the letter, turning it into its own envelope. Today, historians call this technique “letterlocking.” In Sennacques’ time, people had come up with a galaxy of different ways to fold their letters—some so characteristic, in fact, that they acted as a kind of signature for the sender. They weren’t doing this because they wanted to save money on envelopes, mind you, but because they wanted privacy. By folding the paper and tucking corners, they could arrange it in such a way that to open the correspondence, the reader had to rip it in certain places. If the intended recipient opened the letter and found it already torn, they’d know a snoop had gotten inside. Whole bits of paper might rip off, so if they opened the letter and didn’t feel or hear any tearing, yet a chunk still fell out, they’d know they weren’t the first person to read its contents.

It was the early modern period’s version of one of those seals that voids a device’s warranty if you break it. Unlike the self-destructing messages from Mission Impossible, you could still read a torn letter, and if you were familiar with the technique of the person who sent it to you, you might even know tricks to avoid tearing it in the first place. Yet the letterlocking set booby traps that exposed spies.

Unfortunately for all parties involved, Sennacques’ second letter never made it to his merchant cousin. Instead, it ended up in a trunk, known as the Brienne Collection, which contains 2,600 letters sent between 1689 and 1706 from across Europe to the Hague. Sennacques’ letter is one of hundreds that remain unopened, folded tightly in on itself.

How, then, do we know that the man was losing patience with his cousin? Writing today in the journal Nature Communications, researchers describe how they used an advanced 3D imaging technique—originally designed to map the mineral content of teeth—to scan four old letters from the Brienne Collection to unfold them virtually, no tearing required. “The letters in his trunk are so poignant, they tell such important stories about family and loss and love and religion,” says King’s College London literary historian Daniel Starza Smith, a coauthor of the paper. “But also, what letterlocking is doing is giving us a language to talk about sorts of technologies of human communication security and secrecy and discretion and privacy.”

folding paper

One of the letters being unfolded virtually

Photograph: Unlocking History Research Group

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Could Fruit Flies Help Match Patients With Cancer Treatments?

“I’m about two months away from finding out if there are other drugs and combinations that could actually save my life,” says Silverman, who has been taking a targeted therapy based on the detection of a mutation in the PIK3CA gene. It’s not clear if that drug is diminishing the lung lesions. “If they could stop what’s going on in my lung, my life is saved—or at least prolonged,” he says of Vivan Therapeutics.

The basic science underlying Vivan Therapeutics dates back to 1918, when Mary Stark, a little-known scientist in biologist Thomas Hunt Morgan’s famous Fly Room at Columbia University, identified tumors in Drosophila larvae and experimented with transplanting pieces of them into healthy larvae. Over the decades, the lowly fruit fly became an exquisite model of human disease. (Morgan received a Nobel Prize for his Drosophila work in 1933.) The fruit fly reveals attributes and treatments for disorders ranging from amyotrophic lateral sclerosis to aging, from epilepsy to eye disease—the source of enough discoveries to fill a book titled First in Fly. (The author, Harvard geneticist Stephanie Mohr, also contributes to an ongoing blog called Drosophila Models of Human Disease.)

When the Drosophila melanogaster genome was sequenced in 2000 (three years before the human genome), new possibilities arose for probing the genetic origins of disease. Developmental biologist Ross Cagan was studying the mechanisms of cancer in fruit flies, but in 2010 he turned the question around: Could the flies reveal cancer-killing drugs, even if the science wasn’t fully worked out?

He created the drug testing process in his lab at Mount Sinai Medical Center in New York City that has since been licensed by Vivan Therapeutics. “We’re exploring which drugs work, attacking the cancer network with a therapeutic network,” says Cagan, who recently moved his work to the University of Glasgow in Scotland.

First, scientists analyze the patient’s tumor, comparing its exome with the whole exome sequencing of the patient’s blood to identify the tumor’s protein-coding alterations. They select the changes most likely to drive the growth or proliferation of the tumor, based on their function or location. (A single tumor can contain hundreds of genetic alterations, but typically only five to 15 of them drive its growth.)

“There are many, many tumors that are not caused by one mutation. Or one mutation is compounded with two or three others that allow the cancer to grow, proliferate, and stay alive,” says Marshall Posner, a Mount Sinai oncologist specializing in head and neck cancer who has conducted fly research with Cagan but is not affiliated with the company.

Scientists next inject strands of synthetic bacterial DNA into fruit fly larvae to integrate the mutations into the genome. The location is precise; a colorectal cancer will be expressed in the fly’s gut, for example. Then they calibrate larvae development by altering the temperature of their environment, so the tumor is timed to kill the larvae in seven days. (Larvae typically metamorphose into flies in 10 to 11 days.)

Then these fruit fly “avatars” must propagate. Vivan Therapeutics uses about a half million fly larvae to test about 2,000 drugs and drug combinations, encompassing a version of most FDA-approved drugs that are currently in use, says the company’s chief scientific officer, Nahuel Villegas. For example, an anti-inflammatory or anti-hypertensive drug might have unexpected cancer-fighting properties when used with a tumor suppressor.

The larvae live in tubes in groups of 35—half with the tumor, half without to serve as the control group—feeding on drug-laced food. The healthy larvae have been tweaked with genetic alterations that make them shorter and fatter, so they can be distinguished from those carrying tumors. After seven days, their survival rates are compared. Every drug is tested on at least 300 larvae, and promising drug combinations are retested. The top candidates are ranked based on the survival rates, but ultimately the selection takes into account the human patient’s clinical history and their oncologist’s judgment. For example, a patient with an underlying cardiac problem might steer clear of a drug associated with cardiac concerns, Villegas says.

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Million-Year-Old DNA Rewrites Mammoths’ Evolutionary Tree

Ancient DNA has revolutionized how we understand human evolution, revealing how populations moved and interacted and introducing us to relatives like the Denisovans, a “ghost lineage” that we wouldn’t realize existed if it weren’t for discovering their DNA. But humans aren’t the only ones who have left DNA behind in their bones, and the same analyses that worked for humans can work for any other group of species.

Today, the mammoths take their turn in the spotlight, helped by what appears to be the oldest DNA ever sequenced. DNA from three ancient molars, one likely to be over a million years old, has revealed that there is a ghost lineage of mammoths that interbred with distant relatives to produce the North American mammoth population.

Mammoths share something with humans: Like us, they started as an African population but spread across much of the planet. Having spread out much earlier, mammoth populations spent enough time separated from each other to form different species. After branching off from elephants, the mammoths first split into what are called southern and steppe species. Later still, adaptations to ice age climates produced the woolly mammoth and its close relative, the North American mammoth, called the Columbian mammoth. All of those species, however, are extinct, and the only living relatives are the elephants.

We have obtained DNA from two of these species, the woolly and Columbian mammoths. These revealed both a number of adaptations to cold climates and a small degree of interbreeding, as woolly mammoths made their way into North America and contributed a small amount (about 10 percent) to the genome of the Columbia population.

The new work focused on mammoth teeth found in Siberia, where conditions have favored both the preservation of remains and the preservation of the DNA they contain. The teeth come from layers of material that appear to have been deposited at the start of the most recent glacial period, which is when the ancestors of the woolly mammoth population should have been present in the area.

We don’t have precise dates for any of the teeth, as they appear to be too old for carbon dating. Instead, dates have been inferred using a combination of the species present in the deposits and the known timing of flips in the orientation of Earth’s magnetic field. In addition, the shape of the teeth provides some hints about what species they group with and some further indication of when they were deposited. In all, one tooth is likely to be at least 500,000 years old, another about a million years old, and a third somewhat older still.

Previously, the oldest DNA obtained from animal remains is roughly the age of the youngest of these samples. But the researchers were able to recover some elephant-like DNA from each of the molars, although it was badly fragmented, and many individual bases were damaged. Researchers were able to isolate the full mitochondrial genome for each of the three teeth, as each cell contains many copies of this genome in each of its mitochondria. Only fragments of the nuclear genome could be obtained, however—at most, about 10 percent of one genome, and at worst under 2 percent. (Less than 2 percent is still tens of millions of individual bases.)

Using the differences between the mammoth and elephant DNA and assuming a constant rate of mutation, the research team was able to derive independent dates for when each of the animals that left a tooth must have lived. Based on the mitochondria genome, the dates were 1.6 million, 1.3 million, and 900,000 years ago. For the two that had enough nuclear genome to analyze, the dates were 1.3 million and 600,000 years ago. The DNA-based dates for these two lined up nicely with each other and the date of the material they were found in. The oldest sample might be older than the deposit it’s in, and thus it might have been moved after death.

While these dates are fairly uncertain, they pretty clearly place two of the samples as the oldest DNA ever obtained from animals. And it would mean that these mammoths were living in Siberia shortly after ice-age conditions prevailed, although before there was a clear woolly mammoth lineage. They’d also predate the known appearance of mammoths in North America.

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The Brain’s ‘Background Noise’ May Be Meaningful After All

At a sleep research symposium in January 2020, Janna Lendner presented findings that hint at a way to look at people’s brain activity for signs of the boundary between wakefulness and unconsciousness. For patients who are comatose or under anesthesia, it can be all-important that physicians make that distinction correctly. Doing so is trickier than it might sound, however, because when someone is in the dreaming state of rapid-eye movement (REM) sleep, their brain produces the same familiar, smoothly oscillating brain waves as when they are awake.

Lendner argued, though, that the answer isn’t in the regular brain waves, but rather in an aspect of neural activity that scientists might normally ignore: the erratic background noise.

Some researchers seemed incredulous. “They said, ‘So, you’re telling me that there’s, like, information in the noise?’” said Lendner, an anesthesiology resident at the University Medical Center in Tübingen, Germany, who recently completed a postdoc at the University of California, Berkeley. “I said, ‘Yes. Someone’s noise is another one’s signal.’”

Lendner is one of a growing number of neuroscientists energized by the idea that noise in the brain’s electrical activity could hold new clues to its inner workings. What was once seen as the neurological equivalent of annoying television static may have profound implications for how scientists study the brain.

Skeptics used to tell the neuroscientist Bradley Voytek that there was nothing worth studying in these noisy features of brain activity. But his own studies of changes in electrical noise as people age, as well as previous literature on statistical trends in irregular brain activity, convinced him that they were missing something. So he spent years working on a way to help scientists rethink their data.

“It’s insufficient to go up in front of a group of scientists and say, ‘Hey, I think we’ve been doing things wrong,’” said Voytek, an associate professor of cognitive science and data science at the University of California, San Diego. “You’ve got to give them a new tool to do things” differently or better.

Bradley Voytek
Bradley Voytek, an associate professor of cognitive science and data science at the University of California, San Diego, helped to draw attention to the significance of aperiodic activity in the brain by developing software to study it.Photograph: Jessica Voytek

In collaboration with neuroscientists at UC San Diego and Berkeley, Voytek developed software that isolates regular oscillations—like alpha waves, which are studied heavily in both sleeping and waking subjects—hiding in the aperiodic parts of brain activity. This gives neuroscientists a new tool to dissect both the regular waves and the aperiodic activity in order to disentangle their roles in behavior, cognition and disease.

The phenomenon that Voytek and other scientists are investigating in a variety of ways goes by many names. Some call it “the 1/f slope” or “scale-free activity”; Voytek has pushed to rebrand it “the aperiodic signal” or “aperiodic activity.”

It’s not just a quirk of the brain. The patterns that Lendner, Voytek and others look for are related to a phenomenon that scientists started noticing in complex systems throughout the natural world and technology in 1925. The statistical structure crops up mysteriously in so many different contexts that some scientists even think it represents an undiscovered law of nature.

Although published studies have looked at arrhythmic brain activity for more than 20 years, no one has been able to establish what it really means. Now, however, scientists have better tools for isolating aperiodic signals in new experiments and looking more deeply older data, too. Thanks to Voytek’s algorithm and other methods, a flurry of studies published in the last few years have run with the idea that aperiodic activity contain hidden treasures that may advance the study of aging, sleep, childhood development and more.

What Is Aperiodic Activity?

Our bodies groove to the familiar rhythms of heartbeats and breaths—persistent cycles essential to survival. But there are equally vital drumbeats in the brain that don’t seem to have a pattern, and they may contain new clues to the underpinnings of behavior and cognition.

When a neuron sends a chemical called glutamate to another neuron, it makes the recipient more likely to fire; this scenario is called excitation. Conversely, if a neuron spits out the neurotransmitter gamma-aminobutyric acid, or GABA, the recipient neuron becomes less likely to fire; that’s inhibition. Too much of either has consequences: Excitation gone haywire leads to seizures, while inhibition characterizes sleep and, in more extreme cases, coma.

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Can Hamburger Buns Save Your Pipes from Freezing?

So, imagine this steel container is instead the water line going into your house. (Unless you collect rainwater or make water from hydrogen and oxygen, you probably have one.) If it gets too cold, the water can freeze and literally burst your pipe. That’s bad. Now for some questions and answers.

Why Doesn’t This Happen More Often in the South?

Residential water lines are almost always underground—and that’s a good thing. Although air temperatures can vary drastically from summer to winter, the ground temperature is much more constant. In the southern states, this ground temperature isn’t very likely to get below freezing—so water in the pipes will also be above freezing (and stay liquid).

But there are some exceptions. In some places with warm climates, not all parts of a water pipe system will be underground, and will pass through regions of air. (Heck, I have water pipes in my attic, and I live in a warmer location). Although there is a small temperature difference between cold water (let’s say 1 degree Celsius) and warm ice (0 C), there is a huge energy difference. It takes quite a bit of energy to change water from its solid phase to a liquid. We call this the latent heat of fusion. For water, this has a value of 344 joules per gram. That might be difficult to comprehend, so how about an example?

Suppose you have a liter of ice (with a mass of about 1,000 grams). If you want to take this ice at 0 C and turn it into water at 1 C, it would take 344,000 joules of energy (plus a tiny bit more energy to raise the temperature of water). How much energy is that? Well, let’s say you have a smartphone with a 3,000-mAh battery (milliamp-hours). This is equivalent to 41,000 joules. So, it might have enough energy to run your phone for a full day, but you would need eight or nine of these phones to melt all that ice.

It’s actually a good thing. It means that you can use melting ice to cool off your drinks—and you don’t actually need that much ice. That also means that you need to remove quite a bit of thermal energy from your pipes to get them to freeze. One cold night probably isn’t going to be enough to make your pipes burst.

Does It Help to Leave a Faucet Running?

Yes. OK, imagine you’re inside of a water pipe. (Yes, you are super tiny now.) If the water is stationary, you might be stuck in a part of the pipe that is exposed to cold air. You could actually freeze, and then you would have to break the pipe. But now suppose it’s running water, caused by a faucet that is slightly dripping. You are still a tiny person inside of a pipe, but now you are also moving. You pass through the section of cold pipe and you get cold—but you don’t freeze. Instead, you just move on to other parts of the house.

Oh, but more water from the main underground line is coming into that cold part of the pipe. Would it freeze? It’s not as likely. Remember, the water pipe is at ground temperature, which is almost certainly not below freezing. So, the incoming water isn’t super cold, and hopefully it won’t freeze.

What About Insulation?

Insulation helps. If you wrap some foam insulation around any exposed pipes, it does the same thing as your cooler or insulated drink cup. The insulation decreases the rate that energy is transferred from the hot thing to the cold thing through a thermal interaction. If you put a cold drink out on a table, energy is transferred into the drink to cause it to increase in temperature. Putting the drink in a cooler, on the other hand, increases the insulation and decreases the rate of energy transfer so that it takes longer for the drink to warm up.

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Nature Makes Wood. Could a Lab Make It Better?

For all the ways that humans have toyed with nature, how we grow and extract materials from the forest and fields remains fundamentally unchanged. To get lumber, for example, we plant a tree, let it grow, and chop it down. Wood and other plant-based materials may be renewable resources, but obtaining usable forms typically requires lots of transportation, milling, and processing.

Now, a group of MIT researchers hopes to drastically trim these inefficiencies. The researchers grew wood-like plant tissue in the lab, which, if scaled up, could perhaps one day lead to the development of lab-grown wood, fiber, and other biomaterials aimed at reducing the environmental footprint of forestry and agriculture. Their work is described in a recent Journal of Cleaner Production paper.

“The hope is that, if this becomes a developed process for producing plant materials, you could alleviate some of [the] pressures on our agricultural lands. And with those reduced pressures, hopefully we can allow more spaces to remain wild and more forests to remain in place,” says Ashley Beckwith, the study’s lead author and a mechanical engineering PhD candidate at MIT.

Beckwith’s earlier research examined using 3D-printed microfluidics for biomedical applications like analyzing tumor fragments. But after she spent time working on and learning about organic farms, she became interested in more efficiently using agricultural and natural resources.

Lab-grown plant material wouldn’t depend on climate, pesticides, or arable land for cultivation. And producing only the useful portions of plants would eliminate discarded bark, leaves, and other excess matter, the researchers note. “The higher-level idea is about producing goods where it’s needed, when it’s needed,” says Luis Fernando Velásquez-García, a study coauthor and principal research scientist at MIT’s Microsystems Technology Laboratories. “Right now, we have this model where we produce goods in very few locations, and then we spread them.”

Growing plant tissues in the lab starts with cells, not seeds. The researchers extracted live cells from the leaves of young Zinnia elegans, a species chosen because it grows quickly and has been well studied in regard to cell differentiation, the process by which cells change from one type to another. Placed in a nutrient broth culture, the cells reproduced before being transferred to a gel for further development. “The cells are suspended within this gel scaffold, and, over time, they grow and develop to fill out the scaffold volume and also transform into the cell types we’re interested in,” Beckwith says. This scaffold contains nutrients and hormones to sustain cell growth, meaning the plant-based material develops passively—no sunlight or soil necessary.

Yet a concoction of plant cells and gel won’t turn into anything very useful without some tinkering. So the researchers tested how manipulating the gel medium’s hormone concentrations, pH, and initial cell density, among other variables, influenced development and could affect the properties of the resulting plant tissues. “The plant cells have the capability to become different cells if you give them the cues for that,” says Velásquez-García. “You can persuade the cells to do one or another thing, and then they get the properties that you want.”

To achieve a wood-like material, the researchers had to prompt the plant cells to differentiate into vascular cell types, which transport water and minerals and make up woody tissue. As the cells developed, they formed a thickened secondary cell wall reinforced with lignin—a polymer lending firmness—becoming more rigid. Using fluorescence microscopy to analyze the cultures, the researchers could observe which cells were becoming lignified (or turning into wood) and also evaluate their enlargement and elongation.

Once it was time to print them, heating and then 3D bioprinting the gel allowed the resulting material to take almost any shape after it cooled and solidified. The dark green tissue that the research team produced is pretty firm, but it wouldn’t be structurally strong enough for most construction purposes. For now, the thin, rectangular printed structures are only several centimeters long and are undergoing mechanical testing and characterization, Beckwith says, although printing larger versions is feasible. (Oh, and the researchers couldn’t resist some fun, printing dog bone- and tree-shaped structures, too.)

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How to Calculate the String Angle of a Kite vs. a Balloon

What? This looks just like the forces for the balloon? OK, it does look similar—but there is a big difference. For the balloon, there is that upward-pushing buoyancy force, and it’s just one value. It doesn’t change when the wind speed increases. For the kite, the upward pushing force is the lift, and it DOES depend on the wind speed. So it’s not the same. Just consider the case when there is zero wind. The drag force will be zero, which means the lift is zero. The kite won’t fly—it just falls down and it’s sad.

Again, I get two force equations that I can use to eliminate the unknown value of T. With that, I get the following expression for the angle of the kite (θk). Actually, I put a subscript k on a bunch of stuff so you could see it’s different than the values for the balloon. Oh, air still has the same density for both objects.

Illustration: Rhett Allain

OK, I’m about to make a plot of the flying angle for both the balloon and a kite at different wind speeds. But before I do that, let’s think about the minimum speed to fly this kite. In order to lift off the ground, the lift force must be at least equal to the weight of the kite. I can then solve this for the wind speed. Anything lower than this and you won’t have a flying kite.

Illustration: Rhett Allain
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Scientists Find Strange Critters Under a Half Mile of Ice

But because the researchers couldn’t collect specimens, they can’t yet say what exactly these sponges and other critters could be eating. Some sponges filter organic detritus from the water, whereas others are carnivorous, feasting on tiny animals. “That would be sort of your headline of the year,” says Christopher Mah, a marine biologist at the Smithsonian, who wasn’t involved in the research. “Killer Sponges, Living in the Dark, Cold Recesses of Antarctica, Where No Life Can Survive.”

And Griffiths and his team also can’t yet say if mobile creatures like fish and crustaceans also live around the rock—the camera didn’t glimpse any—so it’s not clear if the sessile animals face some kind of predation. “Are they all eating the same food source?” asks Griffiths. “Or are some of them kind of getting nutrients from each other? Or are there more mobile animals around somehow providing food for this community?” These are all questions only another expedition can answer.

It does appear that sedimentation around the rock isn’t very heavy, meaning the animals aren’t in danger of being buried. “It’s kind of a Goldilocks-type thing going on,” says Griffiths of the rock’s apparently fortuitous location, “where it’s got just enough food coming in, and it’s got nothing that wants to eat them—as far as we can tell—and it’s not getting buried by too much sediment.” (In the sediment surrounding the rock, the researchers also noticed ripples that are typically formed by currents, thus bolstering the theory that food is being carried here from afar.)

It’s also not clear how these stationary animals got there in the first place. “Was it something very local, where they kind of hopped from local boulder to local boulder?” asks Griffiths. Alternatively, perhaps their parents lived on a rock hundreds of miles away—where the ice shelf ends and more typical marine ecosystems begin—and released their sperm and eggs to travel in the currents.

Because Griffiths and his colleagues don’t have specimens, they also can’t say how old these animals are. Antarctic sponges have been known to live for thousands of years, so it’s possible that this is a truly ancient ecosystem. Perhaps the rock was seeded with life long ago, but currents have also refreshed it with additional life over the millennia.

The researchers also can’t say whether this rock is an aberration, or if such ecosystems are actually common under the ice. Maybe the geologists didn’t just get extremely lucky when they dropped their camera onto the rock—maybe these animal communities are a regular feature of the seafloor beneath Antarctica’s ice shelves. There’d certainly be a lot of room for such ecosystems: These floating ice shelves stretch for 560,000 square miles. Yet, through previous boreholes, scientists have only explored an area underneath them equal to the size of a tennis court. So it may well be that they’re out there in numbers, and we just haven’t found them yet.

And we may be running out of time to do so. This rock may be locked away under a half mile of ice, but that ice is increasingly imperiled on a warming planet. “There is a potential that some of these big ice shelves in the future could collapse,” says Griffiths, “and we could lose a unique ecosystem.”


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What Happens When You Swap a Human Gene With a Neanderthal’s?

What are the key differences between modern humans and our closest relatives, the Neanderthals and Denisovans? For the Neanderthals, there doesn’t seem to be any sort of obvious difference. They used sophisticated tools, made art, and established themselves in some very harsh environments. But, as far as we can tell, their overall population was never particularly high. When modern humans arrived on the scene in Eurasia, our numbers grew larger, we spread even further, and the Neanderthals and Denisovans ended up displaced and eventually extinct.

With our ability to obtain ancient DNA, we’ve now gotten a look at the genomes of both Neanderthals and Denisovans, which allows us to ask a more specific question: Could some of our differences be due to genetics?

The three species are close relatives, so the number of differences in our proteins are relatively small. But a large international research team has identified one and engineered it back into stem cells obtained from modern humans. And the researchers found that neural tissue made of these cells has notable differences from the same tissue grown with the modern human version of this gene.

As the first step in their work, the researchers had to decide on a gene to target. As we mentioned above, the genomes of all three species are extremely similar. And the similarity only goes up when you look at those parts of the genome that encode proteins. An added complication is that some of the versions of genes found in Neanderthals are still found in a fraction of the modern human population. What the researchers wanted to do is find a gene where both Neanderthals and Denisovans had one version and nearly all modern humans had another.

Out of tens of thousands of genes, they found only 61 that passed this test. The one they chose to focus on was called NOVA1. Despite the explosive-sounding name, NOVA1 was simply named after having originally been found associated with cancer: Neuro-oncological ventral antigen 1. A look through the vertebrate family tree shows that Neanderthals and Denisovans share a version of NOVA1 with everything from other primates to chickens, meaning that it was present in the ancestor that mammals shared with dinosaurs.

Yet almost all humans have a different version of the gene (in a search of a quarter-million genomes in a database, the researchers were only able to identify three instances of the Neanderthal version). The difference is subtle—swapping in a closely related amino acid at a single location in the gene—but it is a difference. (For those who care, it’s isoleucine to valine.)

But NOVA1 is the sort of gene where small changes can potentially have a big impact. The RNAs that are used to make proteins are initially made of a mixture of useful parts separated by useless spacers that need to be spliced out. For some genes, the different parts can be spliced together in more than one way, allowing distinct forms of a protein to be made from the same starting RNA. NOVA1 regulates the splicing process and can determine which form of multiple genes gets made in cells where it’s active. For NOVA1, the cells where it’s active include many parts of the nervous system.

If that last paragraph was somewhat confusing, the short version is this: NOVA1 can change the types of proteins made in nerve cells. And, since behavior is one area where modern humans may have been different from Neanderthals, it’s an intriguing target of these sorts of studies.

Obviously, there are ethical issues with trying to see what the Neanderthal version would do in actual humans. But some technologies developed over the past decade or so now allow us to approach the question in a very different way. First the researchers were able to take cells from two different people and convert them into stem cells, capable of developing into any cell in the body. Then they used Crispr gene-editing technology to convert the human version of the gene into the Neanderthal version. (Or, if you’re less charitable, you could call it the chicken version.)

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Don’t Tell Einstein, but Black Holes Might Have ‘Hair’

Identical twins have nothing on black holes. Twins may grow from the same genetic blueprints, but they can differ in a thousand ways—from temperament to hairstyle. Black holes, according to Albert Einstein’s theory of gravity, can have just three characteristics—mass, spin and charge. If those values are the same for any two black holes, it is impossible to discern one twin from the other. Black holes, they say, have no hair.

“In classical general relativity, they would be exactly identical,” said Paul Chesler, a theoretical physicist at Harvard University. “You can’t tell the difference.”

Yet scientists have begun to wonder if the “no-hair theorem” is strictly true. In 2012, a mathematician named Stefanos Aretakis—then at the University of Cambridge and now at the University of Toronto—suggested that some black holes might have instabilities on their event horizons. These instabilities would effectively give some regions of a black hole’s horizon a stronger gravitational pull than others. That would make otherwise identical black holes distinguishable.

However, his equations only showed that this was possible for so-called extremal black holes—ones that have a maximum value possible for either their mass, spin, or charge. And as far as we know, “these black holes cannot exist, at least exactly, in nature,” said Chesler.

But what if you had a near-extremal black hole, one that approached these extreme values but didn’t quite reach them? Such a black hole should be able to exist, at least in theory. Could it have detectable violations of the no-hair theorem?

A paper published late last month shows that it could. Moreover, this hair could be detected by gravitational wave observatories.

“Aretakis basically suggested there was some information that was left on the horizon,” said Gaurav Khanna, a physicist at the University of Massachusetts and the University of Rhode Island and one of the coauthors. “Our paper opens up the possibility of measuring this hair.”

In particular, the scientists suggest that remnants either of the black hole’s formation or of later disturbances, such as matter falling into the black hole, could create gravitational instabilities on or near the event horizon of a near-extremal black hole. “We would expect that the gravitational signal we would see would be quite different from ordinary black holes that are not extremal,” said Khanna.

If black holes do have hair—thus retaining some information about their past—this could have implications for the famous black hole information paradox put forward by the late physicist Stephen Hawking, said Lia Medeiros, an astrophysicist at the Institute for Advanced Study in Princeton, New Jersey. That paradox distills the fundamental conflict between general relativity and quantum mechanics, the two great pillars of 20th-century physics. “If you violate one of the assumptions [of the information paradox], you might be able to solve the paradox itself,” said Medeiros. “One of the assumptions is the no-hair theorem.”

The ramifications of that could be broad. “If we can prove the actual space-time of the black hole outside of the black hole is different from what we expect, then I think that is going to have really huge implications for general relativity,” said Medeiros, who coauthored a paper in October that addressed whether the observed geometry of black holes is consistent with predictions.

Perhaps the most exciting aspect of this latest paper, however, is that it could provide a way to merge observations of black holes with fundamental physics. Detecting hair on black holes—perhaps the most extreme astrophysical laboratories in the universe—could allow us to probe ideas such as string theory and quantum gravity in a way that has never been possible before.

“One of the big issues with string theory and quantum gravity is that it’s really hard to test those predictions,” said Medeiros. “So if you have anything that’s even remotely testable, that’s amazing.”

There are major hurdles, however. It’s not certain that near-extremal black holes exist. (The best simulations at the moment typically produce black holes that are 30 percent away from being extremal, said Chesler.) And even if they do, it’s not clear if gravitational wave detectors would be sensitive enough to spot these instabilities from the hair.

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