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Are These Crime Drama Clues Fact or Fiction?

Steven Avery, featured in the Netflix documentary Making a Murderer, served 18 years in prison for rape, then was exonerated by DNA. He was convicted of murder in 2007, based partly on DNA evidence.
Steven Avery, featured in the Netflix documentary Making a Murderer, served 18 years in prison for rape before being exonerated by DNA in 2003. In 2007, he was convicted of murder, based partly on DNA evidence.

I’m often just as surprised by what forensic scientists can’t do as by what they can. In the Netflix documentary Making a Murderer, for instance, the question of whether police planted the main character’s blood at a crime scene comes down to whether or not the FBI can detect a common laboratory chemical called EDTA in a bloodstain.

On a TV crime show, this would be a snap. The test would take about five minutes and would involve inserting a swab into a magic detector box that beeps and spits out an analysis of every substance known to humankind.

In real life, there’s no common and accepted test in forensic labs for EDTA even today, nine years after the FBI tested blood for the Steven Avery trial featured in Making a Murderer. In that case, the FBI resurrected a test they had last used in the 1995 O.J. Simpson trial, and testified that the blood in question did not contain EDTA and therefore was not planted using EDTA-preserved blood from an evidence vial. (Avery was convicted.)

Questions about the test’s power and reliability have dogged the case ever since. There’s even an in-depth Reddit thread where fans of the Netflix show are trying to sort out the science.

Having worked in chemistry labs, it surprised me at first that this analysis would be difficult or controversial. After all, a quick search of the scientific literature turns up methods for detecting low levels of EDTA in everything from natural waters to beverages.

Steven Averys
Steven Avery’s attorneys Jerome Buting (shown) and Dean Strang struggled to dispute chemical evidence introduced mid-trial that undermined the idea that police had planted blood evidence.

But the key here is that we’re talking about forensic science, not beverage chemistry. Beverage chemistry, in this case, is much more exacting. Was there really no EDTA in the blood swabbed from victim Teresa Halbach’s vehicle, or was the chemical simply too diluted or degraded to be detected with the FBI’s method? Could the test have missed a small amount of EDTA? It would be hard to say without further experiments that replicate crime scene conditions, experiments that essentially put the test to the test.

The reality is that forensic science today is a strange mix of the high-tech and the outdated, so questions about evidence like those in Avery’s case are not uncommon. Methods that we take for granted, like measuring a particular chemical, or lifting a fingerprint off a gun and matching it to a suspect, can be difficult—and far from foolproof. On the other hand, some of the real science happening now sounds like something dreamed up by Hollywood script writers, such as new methods aiming to reconstruct what a person’s face looks like using only their DNA.

Making a Murderer, whether it sways your opinion on Steven Avery or not, has done a service by getting people interested in something as arcane as EDTA tests, and by showing why real-life crimes are not solved nearly so neatly as fictional ones.

I see the messiness of forensic science all the time, because I scan its journals and often come across new studies that make me think either “you mean we couldn’t already do that?” or “I had no idea that was possible.” I’ve gathered a few recent examples for a quiz.

How well can you separate CSI fact from fiction? Here are a few crime-solving scenarios I’ve cooked up; see if you can tell which use real methods based on new forensic research. You’ll find the answers below.

  1. A skeleton is found buried in a shallow grave. The body’s soft tissues have completely decomposed, so only the teeth and bones remain. A forensic anthropologist examines the bones and reports that they come from a female who was five foot six inches tall, and obese. Could she really tell the person was overweight?
  2. The body of a white male in his 50s turns up on a nature trail, scavenged by animals. The victim’s bones show a number of puncture wounds consistent with animal bites, but x-rays reveal fine lines of different density in the bone around some of the punctures. An expert says these lines show that the wounds were made about 10 years before death. Is it possible to tell the approximate age of these wounds from x-rays?
  3. A woman is found dead in her home, bludgeoned to death. A bloody frying pan lies on the floor next to her. Her husband is the main suspect. Fingerprints on the pan’s handle are too smudged to make a definitive ID, but an analyst says she can still rule out the husband: All of the fingerprints on the pan came from a woman, the expert says. Is it possible to tell if the fingerprints were from a male or female?
  4. A woman is sexually assaulted and identifies her male attacker in a lineup. The suspect’s DNA matches DNA found on her body. It looks like an easy case for the prosecutor—until the suspect reveals that he has an identical twin. Neither twin admits to the crime. Is it possible to tell which twin’s DNA was found at the crime scene?
  5. A witness sees a man in a stocking mask rob and shoot a man outside his home. A stocking is found near the house, and a hair-analysis expert testifies that 13 hairs in the mask are all human head hairs from an African-American. A microscopic analysis matches the characteristics of one hair to a particular African-American suspect. The prosecutor tells the jury that the chances are one in ten million that this could be someone else’s hair. Can hairs be matched to an individual this accurately?


Answers Below


  1. Yes. Biologists have long known that greater body mass changes the weight-bearing bones of the legs and spine, and a new study shows that even bones that aren’t supporting most of the body’s weight, such as arm bones, have greater bone mass and are stronger in obese people. So even in a skeleton missing its legs, our forensic anthropologist might be able to tell that the person was obese.
  2. No. This one is from an actual episode of Bones (The Secret in the Siege, Season 8, Episode 24, reviewed here by real-life bioarchaeologist Kristina Killgrove). In the episode, Dr. Temperance Brennan uses Harris lines to determine the age of bone injuries in two victims. Harris lines are real, but they form only in growing bones, so are useful only in determining childhood injuries or illness.
  3. Yes. A study published in November showed that the level of amino acids in sweat is about twice as high in women’s fingerprints as in men’s. Of course, as with all the new methods, this one could face challenges as evidence in a U.S. court of law, where the Daubert standard allows judges to decide whether scientific evidence is admissible based on factors including its degree of acceptance by the scientific community.
  4. Yes, if you do it right. Standard DNA tests don’t distinguish between twins, who are born with nearly identical DNA, but it’s possible to do a more sophisticated test to catch post-birth mutations and epigenetic differences, which you can think of as genetic “add-ons” that don’t affect the DNA sequence itself. One new test distinguishes between twins by looking for small differences in the melting temperature of their DNA that are caused by such epigenetic modifications.
  5. No. The field of hair analysis has come under heavy scrutiny, especially after a review by the U.S. Justice Department revealed major flaws in 257 out of 268 hair analyses from the FBI. The case described here is the real-life case of Santae Tribble, convicted in 1978 of murder. In 2012, DNA tests showed that none of the hairs matched Tribble—and one was from a dog.
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A Personalised Mini-Stomach, Grown in a Dish

In a lab at Cincinnati Children’s Hospital Medical Center, a series of small blobs sit in a Petri dish. They’re white, hollow, and the size of small peas.

They are stomachs.

More precisely, they are lab-grown model stomachs. Graduate student Kyle McCracken worked out how to make them by coaxing stem cells into producing stomach tissue—a feat that no one had yet managed. The results look like simple baubles, but the growing cells somehow organise themselves into the classic architecture of an actual stomach. They make the right layers, folds, and pockets, and they switch on the usual genes. “They’re not mixed bags of cells,” says Jim Wells, who led the study. “They look shockingly like mini-stomachs.”

These creations, known as gastric organoids, are more representative of our actual organs than cultured stomach cells, which lack any three-dimensional structure, or lab mice, which don’t suffer from stomach diseases in the same way as us. They’re not going to help you digest your meals, but they do open the door to experiments that couldn’t be done before.

For example, we know that diseases like ulcers and stomach cancer are mostly caused by a bacterium called Helicobacter pylori. This spiralling microbe has been humanity’s companion since our origins in Africa, and used to infect the majority of people. It colonises us during childhood and stays with us for decades, and even helps us to regulate the acids in our stomachs. But it can also cause disease, typically later in life.

Many scientists have studied H.pylori and how it affects the stomach for decades. Some have even won Nobel prizes for their efforts. But the moments when the microbe colonises a young stomach—those very first handshakes between host and bacterium—are still a mystery, and one that Wells hopes the organoids can solve. “Now we can say: Bacteria, meet stomach,” says Wells. “Then, what happens?”

The gastric organoids are the latest in a growing line of ‘organs-in-a-dish’. Other scientists have used stem cells to grow versions of many other organs, including eyes, guts, kidneys, and even brains. But growing stomachs proved to be exceptionally challenging, because the team didn’t have a clear map to follow.

Through decades of work, researchers have thoroughly charted the genes and molecules that turn stem cells into different organs, and followed these steps to direct the development of the equivalent organoids. But the stomach is the Ringo of viscera—it doesn’t get a lot of attention compared to starrier neighbours like the liver or pancreas. “We just didn’t have a good blueprint for how the stomach forms,” says Wells. They had to work that out for themselves.

For example, McCracken showed that two genes, WNT3A and FGF4, work together to convince a ball of stem cells to create a gut tube—a primitive tube that eventually becomes the entire digestive system. The gut tube divides into three sections and the stomach develops from the first of these—the foregut. To make that, the team had to block a gene called BMP that defines the later sections. In similar ways, McCracken had to identify genes and chemicals that tell the developing organoids to make a complex lining, full of glands that secrete digestive juices and cells that release appetite-controlling hormones.

For the moment, the organoids are still immature. They’re like the stomach of a third-trimester foetus, so they lack some of the features that adult organs have. They also represent just one part of the stomach—the antrum, which connects it to the intestine. The team are now working on developing the other part—the acid-secreting fundus.

But as they stand, the organoids can already be used for experiments. Team member Yana Zavros found that they react to H.pylori much like actual stomachs would. The bacteria stick to their linings and trigger the growth of more cells, but only if they carried a gene called CagA. This gene makes a protein that H.pylori can injects into its host’s cells to exert its influence over them. It’s an interaction gene, and strains with CagA are more likely to cause stomach cancer and to protect against oesophageal cancer. The organoids could help scientists to study both of these effects.

They can also be personalised. Wells’ team can take your cells, revert them to stem cells, and create a miniature version of your stomach in a dish.

There’s a lot of potential there. You could see how different strains of H.pylori affect people from different parts of the world, for example. We know this match between host and microbes is important. In some regions, people have much higher rates of stomach cancer because they carry H.pylori strains that don’t share their ancestry. With organoids, perhaps scientists can work out why that is, or whether your particular strains are going to cause trouble in your particular stomach.

Reference: McCracken, Cata, Crawford, Sinagoga, Schumacher, Rockich, Tsai, Mayhew, Spence, Zavros & Wells. 2014. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature http://dx.doi.org/10.1038/nature13863

More on organoids:The Cerebral Organoid, a Lab-Grown Model Brain

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How Did You Get Five Fingers?

Your arms and toes began as tiny buds that sprouted from your sides when you were just a four-week-old embryo. By six weeks, these limb buds had grown longer and five rods of cartilage had appeared in their flattened tips. By week seven, the cells between the rods had died away, sculpting five small fingers or toes from once-solid masses of flesh.

Now, a team of scientists led by James Sharpe from the Centre for Genomic Regulation in Barcelona has discovered that these events are orchestrated by three molecules. They mark out zones in the embryonic hand where fingers will grow, and the spaces in between that are destined to die. Without this trinity, pianos and keyboards wouldn’t exist, jazz hands would be jazz palms, and giving someone the finger would be impossible.

These three molecules work in a way first envisioned by legendary English mathematician and code-breaker Alan Turing. Back in 1952, Turing proposed a simple mathematical model in which two molecules could create patterns by spreading through tissues and interacting with each other. For example, the first molecule might activate the second, while the second blocks the first. Neither receives any guidance about where to go; through their dance, they spontaneously organise themselves into spots or stripes.

Since then, many scientists have found that these Turing mechanisms actually exist. They’re responsible for a cheetah’s spots and an zebrafish’s stripes. For 30 years, people have also suggested that they could sculpt our hands and feet, but no one had found the exact molecules involved.

Sharpe knew that these molecules would need to show a striped pattern—they’d either be active in the bits that become the fingers or the areas in between. Sox9 seemed like the most promising candidate. It is activated in a striped pattern from a very early stage of development. It controls the activity of other genes and if you get rid of it, its underlings lose their neat periodic patterns.

By comparing cells where Sox9 is active or inactive, Jelena Raspopovic and Luciano Marcon found two other groups of genes—Bmp and Wnt—also formed striped patterns. Bmp rises and falls in step with Sox9 and both are active in the digits. Wnt is out of phase; it’s active in the gaps. The three molecules also affect each other: Bmp activates Sox9 while Wnt blocks it; and Sox9 blocks both of its partners.

Sox9, Wnt and Bmp interact in a developing limb. The arrows mean that one molecule is activating another. The T-shaped line means that one is blocking another.
Sox9, Wnt and Bmp interact in a developing limb. The arrows mean that one molecule is activating another. The T-shaped line means that one is blocking another. From Zuniga & Zeller, 2014. Credit: AAAS.

It looked like these were the molecules the team was searching for—not a pair, as Turing suggested, but a trinity. To confirm this, they created a simulation of a growing limb bud and showed that Sox9, Bmp and Wnt can organise themselves into a pattern of five stripes, by activating and blocking each other.

The team also used their simulation to predict what would happen if they removed each of the partners from the dance. If they took out Bmp, Sox9 activity also died away and the fingers didn’t form at all; instead, the virtual limb bud continued growing as a shapeless lump. If they took out Wnt, Sox9 became active everywhere and the spaces between the fingers disappeared. If they blocked Bmp and Wnt together, these effects partly cancelled each other out but the number of fingers decreased.

The team then checked these predictions by applying drugs that block Wnt and Bmp to isolated limb buds growing in Petri dishes. In every case, the reality matched the predictions.

There’s still a lot to discover, though. For example, I’ve used Bmp and Wnt as shorthands here—in reality, each represents a class of several molecules, and the team still needs to work out which specific member is part of the Turing trinity.

They also want to identify molecules that affect the trinity. One of these might be FGF, a protein that’s more concentrated at the fingertips than at the base of the hand. Sharpe thinks that it changes the relationships between the Turing trinity to widen the Wnt canyons between the Sox9/Bmp peaks. It effectively increases the wavelength of the fingers as you move to the tip of the hand. It might explain why your fingers are slightly splayed, rather than strictly parallel.

There’s also the most obvious question: why do we have five fingers and toes?

On one level, the answer depends on simple physical traits like how quickly the Turing molecules spread through the hand, how strongly the interact with each other, and how fast the limb bud grows. If the molecules diffuse more quickly, the gap between the fingers would be larger and you’d get fewer digits. If the limb bud grows 20 percent bigger and everything else stays the same, you suddenly have room for an extra digit—this is why around 1 in 500 people are born with an extra finger or toe.

These cases, known as polydactyly, show that there’s a lot of flexibility built into the Turing system. Change the parameters slightly, and you can change the numbers of fingers and toes. So why has evolution set these parameters so they almost always make five? It’s clearly possible to make more. Some people are born with more. Ernest Hemingway used to own a six-toed cat, whose descendants still live in the writer’s Florida home. And the first tetrapods (four-legged animals) to invade the land had anywhere up to eight toes per foot.

But the common ancestor of all mammals, birds, reptiles and amphibians had five, and we have stuck with that number. Many groups have lost digits, but five is still the basic number. A horse has a single toe on each foot but if you look at an early horse embryo, its limb buds have five little stripes of Sox9, just like ours.

Some might say that we never need more than five fingers, but that’s not true either. Pandas have adapted a wrist bone into a pseudo-thumb to help them grasp bamboo; they effectively have six fingers. Others think that it’s too hard to change the number of digits because the pertinent genes (like Sox9) control the development of other body parts. Mutations that give you more fingers might also screw up your heart or spine. But Sharpe doesn’t like this answer either. “It implies that the animal body plan is fairly locked, and obviously evolution happens,” he says.

So, why five? No one really knows. “It’s the ultimate meta-problem on top of everything,” says Sharpe. “I often say that if we understood why five, we’d probably understand everything.”

References: Raspopovic, Marcon, Russo & Sharpe. 2014. Bmp-Sox9-Wnt Turing network modulated by morphogen gradients. Science http://dx.doi.org/10.1126/science.1252960

More on Turing patterns

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Why Naked Mole Rats Don’t Get Cancer

The problem with writing about the naked mole rat is the long list of bizarre traits that you don’t have space to talk about. For this post, let’s  forget that they look like a wrinkled finger with teeth. Put aside their inability to feel pain in their skin, their tolerance for chokingly low oxygen levels, their bizarrely rubbish sperm or their poor temperature control. Don’t even think about how they live in ant-like colonies, complete with queens and workers. Ignore their ability to live for more than 30 years—an exceptional lifespan for a rodent of their size.

Instead, let’s talk about the cancer angle.

They don’t get it.

No one has ever seen a naked mole rat with a tumour. Scientists have raised large colonies of these rodents and watched them for many years. They’ve never seen an individual spontaneously develop cancer.

Now, Xiao Tian, Jorge Azpurua and Christopher Hine from University of Rochester have discovered one of the secrets behind this exceptional resistance. The team were trying to grow skin cells from naked mole rats in laboratory flasks, when they noticed something weird. The liquid that the cells were growing in would get viscous and syrupy within a few days.

This was because the cells secreted a sugar called hyaluronan, which was thickening the liquid. Hyaluronan is common in the skin, cartilage and other connective tissues of mammals. Like mortar in a wall, it’s one of many molecules that fill the spaces between cells and provide them with support. The naked mole rat makes an exceptionally large version of the sugar that’s over five times bigger than ours. And it has a lot of it.

There are two innovations behind the naked mole rat’s hyaluronan-fest—ineffective versions of the enzymes that digest hyaluronan, and altered versions of the protein that makes it. This hyaluronan-maker, known as HAS2, is made of 552 amino acids. The naked mole rat has altered just two of these, which are always the same in other mammals. These tiny changes were enough to allow it to make a monster hyaluronan.

Andrei Seluanov, who led the study, suspects that the larger hyaluronan physically cages potential cancer cells, preventing them from breaking free and growing into tumours. But it also allows cells to stop each other from growing if they become too crowded. This is called ‘contact inhibition’—it’s why healthy cells form a flat layer if they’re grown in a dish but cancerous ones pile on top of each other.

Based on an earlier study, Seluanov’s team suspected that naked mole rat cells are protected against cancer because they’re especially sensitive to contact inhibition. Now, they’ve shown that large hyaluronan is responsible. The rodents’ cells are very receptive to the sugar; as they get close, hyaluronan sticks to their surface and triggers a genetic programme that stops them from growing.

As a final test of their ideas, the team switched on a couple of cancer genes in naked mole rat cells and transplanted them into mice. Normally, nothing would happen—the cells are that resistant to cancer. But when the team also interfered with hyaluronan, either by stopping its production or boosting its destruction, the naked mole rat cells finally did the unthinkable—they formed tumours.

Seluanov thinks that hyaluronan is probably the naked mole rat’s “primary anti-cancer mechanism”. After all, disrupting it makes the rodent’s cells as cancer-prone as those of a mouse. Not so fast, cautions Rochelle Buffenstein from the University of Texas Health Science Center, who discovered the naked mole rats’ cancer resistance. “This is now the third study to provide a potential mechanism,” she says. “Clearly there are multiple anti-cancer defenses employed in the naked mole rat.” Others might include mass suicide of overgrowing cells, and a tolerance for DNA-damaging oxygen molecules.

So why did this animal evolve its super-sized hyaluronan? The answer might have nothing to do with cancer.  Seluanov says that the large sugars are slightly elastic and surround themselves with water molecules—two properties that make the naked mole rat’s skin very loose and stretchy. This allows it to move through tight underground tunnels without ripping its flanks as it rubs against dirt, rocks or tubers. Perhaps the large hyaluronans evolved as an adaptation for underground life, and a cancer-free existence was just a neat bonus!

Does this discovery mean anything for humans? It’s tempting to think that hyaluronan holds the secret to stopping cancer, but we have to tread carefully. In the early days of hyaluronan research, scientists were confused by the fact that the molecule seemed to both prevent and cause cancer (the Daily Mail would have loved it).

Since then, we’ve discovered that the sugar’s size is responsible for its dual nature. Bryan Toole from the Medical University of South Carolina, who studies hyaluronan, says that high concentrations of the large versions can stop cells from turning cancerous, while smaller versions can actually promote cancer. In a similar way, the large forms tamp down inflammation while the small ones exacerbate it, which may relevant to cancer since inflammation is tied to several tumours. “It’s not clear how the cell distinguishes between the two,” adds Seluanov. That’s something the team still needs to find out.

Reference: Tian, Azpurua, Hine, Vaidya, Myakishev-Rempel, Ablaeva, Mao, Nevo, Gorbunova & Seluanov. 2013. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature http://dx.doi.org/10.1038/nature12234

For more on the naked mole rat, check out Dan Engber’s award-winning piece at Slate.

Correction: An earlier version of this piece suggested that hyaluronan is a protein, which it isn’t. Your friendly neighbourhood science writer regrets the error.

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One Protein Shows Elephants and Moles Had Aquatic Ancestors

Whales, seals and manatees are so at home in the water that it’s easy to believe their recent ancestors were also aquatic. That conclusion is harder to sell for lumbering elephants, burrowing moles or bumbling spiny echidnas. And yet, new evidence from Scott Mirceta at the University of Liverpool suggests that all of these groups recently descended from ancestors that spent a lot of time in the water.

Mirceta’s conclusion is based on a single protein called myoglobin, and it shows just how much one molecule can tell us about the evolution of an entire group of creatures.

Myoglobin is an oxygen-storing and iron-carrying protein found in the muscles of all mammals. It gives meat its red colour. Animals that live in the water tend to have more myoglobin than those that live on land, and those that dive regularly, like sperm whales or elephant seals, have the highest concentrations of all. With every inhalation, the myoglobin bonanza in their muscles traps a huge amount of oxygen, allowing them to carry out a lot of activity before needing another influx. So, if you know how much myoglobin an animal has, you can work out how long it can hold its breath.

Sperm whales are among the best mammals at breath-holding, and can stay underwater for 90 minutes at a time. Sure enough, their muscles are rife with myoglobin, and their version of this molecule is one of the best studied of all proteins. In 1959, English biochemist John Kendrew worked out its structure, down to the position of every atom—the first time anyone had done that. He earned a Nobel prize for this breakthrough three years later.

Myoglobin. By Azatoth.
Myoglobin. By Azatoth.

Fifty years on, and myoglobin is still yielding new secrets. For example, Mirceta’s team found that diving mammals don’t just have more of the stuff—their myoglobins also have more positively charged surfaces. This means that the individual molecules repel each other more strongly. Thanks to this charge, deep-divers can pack their myoglobin into ever higher concentrations without it clumping together uselessly.

The team found highly charged version of myoglobin in the muscles of many aquatic mammals, including seals and walruses, whales and dolphins, beavers and muskrats. Other partially aquatic species, like American water shrews and star-nosed moles, have myoglobins with less charge than those full-time swimmers but still more than land-living species.

Of course, mountaineers and burrowers also need a lot of oxygen, but the team found that their myoglobins lack the positive charges of diving mammals. It seems that a positively charged myoglobin is a clear sign of a diving lifestyle.

That’s huge news.

Muscles don’t fossilise, so you can’t measure how much myoglobin an extinct animal had. But you can work out how charged its myoglobin was. A protein’s charge depends on which amino acids it contains. By working back from the myoglobins of modern mammals, the team could reconstruct the amino acids of their ancestors’ proteins, and deduce how positively charged they were. And from that, they could work out how much myoglobin these long-extinct species had, whether they were divers, and even how long they could hold their breaths.

“This is really cool,” says Jennifer Burns from the University of Alaska, who studies marine mammals. “The evolutionary history of marine mammals has been worked out from hard parts but while body shape and size hinted at diving behaviour, it couldn’t elucidate diving capacity. This combination of approaches is a unique and important advancement in the field.”

The team team applied their methods to a family tree that included 130 living mammal species. Some of the conclusions were unsurprising.

The whales gradually developed highly charged myoglobins between 54 and 36 million years ago. Early members like wolf-sized Pakicetus weren’t particularly specialised for life in the water, and couldn’t even hold their breath for 2 minutes. Later species like the huge Basilosaurus had strongly charged myoglobin and were fully adapted to life in the water, but even this giant could only hold its breath for 17 minutes. This suggests that more recent species like sperm whales and beaked whales evolved to exploit extremely deep sources of food that their ancestors could never reach.

Other results were more surprising. The team found that echidnas and moles both descend from ancestors with charged myoglobins. These species might spend their time burrowing today, but they hail from a line of swimmers. The same was true for dedicated landlubbers like elephants and hyraxes—small mammals that look like guinea pigs but are actually close relatives of elephants.

“At first, we thought: There goes that theory!” says Michael Berenbrink from the University of Liverpool, who led the study. But on closer inspection, he found that the conclusions weren’t as far-fetched as they seemed. “We looked up echidnas and found a recent paper that proposed, based on fossils, that echidnas had an amphibious past,” he says. Other palaeontologists had also suggested that elephants and moles had aquatic ancestors. Myoglobin was just reiterating the story that the bones were starting to tell.

African elephant crossing the Zambezi river. Credit: Hans Hillewaert.
African elephant crossing the Zambezi river. Credit: Hans Hillewaert.

Still, Berenbrink says, “We always wanted to look at loopholes.” Among living aquatic mammals, the manatees and dugongs have myoglobins with little positive charge. But that’s probably because they have little need for oxygen-hogging muscles. They’re sluggish animals with no need to dive, since the plants they eat grow in shallow waters.

The team concluded that 65 million years ago, when most dinosaurs were going extinct, the common ancestor of elephants, hyraxes and manatees was swimming around, using muscles powered by highly charged myoglobin. If they’re right, it’s a wonderful conclusion. We don’t have any bones for this ancestor and we can only speculate what it looked like, but we can say with confidence that it was partially aquatic.

Berenbrink is quick to point out that his team’s impressive study depended on a huge amount of work by other scientists. They relied on an accurate family tree that showed how mammals are related, which could only be constructed thanks to a lot of sequencing and fossil-hunting. They used measurements of the diving times, myoglobin levels, and oxygen capacities of different mammals, which physiologists have amassed over decades. “We just added a new dimension to the mix,” says Berenbrink. “On its own, we couldn’t do much with myoglobin.”

Reference: Mirceta, Signore, Burns, Cossins, Campbell & Berenbrink. 2013. Evolution of Mammalian Diving Capacity Traced by Myoglobin Net Surface Charge. Science http://dx.doi.org/10.1126/science.1234192

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Spreading corrupted proteins cause Parkinson’s signs in mice

This post contains material from an older one, updated based on new discoveries.

There are many things you don’t want gathering in large numbers, including locusts, rioters, and brain proteins. Our nerve cells contain many proteins that typically live in solitude, but occasionally gather in their thousands to form large insoluble clumps. These clumps can be disastrous. They can wreck neurons, preventing them from firing normally and eventually killing them.

Such clumps are the hallmarks of many brain diseases. The neurons of Alzheimer’s patients are riddled with tangles of a protein called tau. Those of Parkinson’s patients contain bundles, or fibrils, of another protein called alpha-synuclein. The fibrils gather into even larger clumps called Lewy bodies.

Now, Virginia Lee from the University of Pennsylvania School of Medicine has confirmed that the alpha-synuclein fibrils can spread through the brains of mice. As they spread, they corrupt local proteins and gather them into fresh Lewy bodies, behaving like gangs that travel from town to town, inciting locals into forming their own angry mobs. And as these mobs spread through the mouse brains, they reproduce two of the classic features of Parkinson’s disease: the death of neurons that produce dopamine, and movement problems.

This is the clearest evidence yet that alpha-synuclein can behave like prions, the proteins that cause mad cow disease, scrapie and Creutzfeld-Jacob disease (CJD). Prions are also misshapen proteins that convert the shape of normal peers. But there is a crucial distinction: prions are infectious. They don’t just spread from cell to cell, but from individual to individual. As far as we know, alpha-synuclein can’t do that.


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A network of molecules, building each other at the dawn of life

Every time one of the cells in your body divides, it has to double its quota of DNA so that each daughter cell gets a complete set. DNA is a replicator—a molecule that can be accurately duplicated, admittedly with some help from proteins. DNA has been doing this for billions of years, well before there were humans, before animals existed, and probably before the first cells evolved.

But what came before DNA? Probably RNA, a related molecule. Certain types of RNA can store genetic information, just like DNA. And much like proteins, they can fold into three-dimensional shapes to speed up chemical reactions, among other functions—these are called ribozymes.

The dominant theory is that an “RNA world” preceded the origin of life. It’s possible that the Earth’s first true replicators were RNA molecules that could fold up to speed up their own replication. They copied themselves. They did so imperfectly, creating daughter molecules with slightly different sequences. Some of them copied themselves more efficiently, and left more descendants than their peers. Gradually, the entire population evolved towards ever more efficient replication.

But there’s a problem with this story. The RNA molecule we’re talking about would have been long and folded into a complex ribozyme. But the ribozymes that scientists can make today are simple, and made from very short pieces of RNA. You can imagine a simple molecule gradually growing and evolving into a more complex one, but that idea has problems too. Mathematical models predict that this burgeoning replicator would be unable to copy itself accurately enough, and would start accumulating errors. After a while, it would face an “error catastrophe”, where the build-up of mistakes crippled it.

But what if there wasn’t just one RNA replicator copying itself? What if, instead, there was a whole network of them? This idea was originally floated in 1971 by Nobel-winning chemist Manfred Eigen. “He came to the conclusion that an individual replicator couldn’t persist for very long, and came up with the idea of a hypercycle,” says Niles Lehman from Portland State University. That is, molecule A helps B to copy itself. B helps C, C helps D and so on, eventually looping back to A.

Eigen predicted the existence of hypercycles using mathematics. Now, Lehman has created something similar in a test tube. It’s a contrived set-up, and it doesn’t confirm that such networks were genuinely involved in the origin of life, but it shows that they can form, and that they become more complex over time. As James Attwater and Philipp Holliger from the University of Cambridge write in an accompanying piece, the study makes “a persuasive case for the benefits of cooperation even at this nascent stage of life. The first genes may not have been so selfish, after all.”


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Painkilling chemicals with no side effects found in black mamba venom

The black mamba has a fearful reputation, and it’s easy to see why. It can move at around 12.5 miles (20 kilometres) per hour, making it one of the world’s fastest snakes, if not the fastest. Its body can reach 4.5 metres in length, and it can lift a third of that off the ground. That would give you an almost eye-level view of the disturbingly black mouth from which it gets its name. And inside that mouth, two short fangs deliver one of the most potent and fast-acting venoms of any land snake.

Combined with its reputation for aggression (at least when cornered) and you’ve got a big, intimidating, deadly, ornery serpent that can probably outrun you. It’s not the most obvious place to go looking for painkillers.

But among the cocktail of chemicals in the black mamba’s venom, Sylvie Diochot and Anne Baron from the CNRS have found a new class of molecules that can relieve pain as effectively as morphine, and without any toxic side effects. They’ve named them mambalgins.


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Transformer protein changes from nunchucks to flower

Your body is full of little pieces of origami. They’re proteins – the molecular machines that keep your cells ticking over. Each is a long sequence of amino acids that folds into a complicated three-dimensional shape. The classical view is that the shape is fixed, and set by the protein’s sequence.

But Bjorn Burmann from Ohio State University has found a bacterial protein that can refold into two radically different shapes, each with very different roles. While there are some other proteins that can change shape, none can do so to such a dramatic degree, and many that do cause disastrous brain diseases.

I’ve written about the study for The Scientist, so head over there for the details.

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As oxygen filled the world, life’s universal clock began to tick

The Earth’s earliest days were largely free of oxygen. Then, around 2.5 billion years ago, primitive bacteria started to flood the atmosphere with this vital gas. They produced it in the process of harnessing the sun’s energy to make their own nutrients, just as plants do today. The building oxygen levels reddened the planet, as black iron minerals oxidised into rusty hues. They also killed off most of the world’s microbes, which were unable to cope with this new destructive gas. And in the survivors of this planetary upheaval, life’s first clock began to tick and tock.

Today, all life on Earth runs on internal clocks. These ‘circadian rhythms’ are the reason we feel sleepy at night, and why our hormones, temperature and hunger levels rise and fall with a 24-hour cycle. They’re molecular metronomes that keep the events inside our bodies ticking in time with the world around us.

Until now, it seemed that the major branches of the tree of life each had their own timekeeping systems, evolved independently of the others. But Akhilesh Reddy and John O’Neill from the University of Cambridge have disproved that idea, by finding a universal clock that ticks in all kingdoms of life. “It’s exciting because it shows that circadian rhythms are likely as primitive as life on Earth,” says Erik Herzog from Washington University.


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Synthetic XNA molecules can evolve and store genetic information, just like DNA

Out of all the possible molecules in the world, just two form the basis of life’s grand variety: DNA and RNA. They alone can store and pass on genetic information. Within their repetitive twists, these polymers encode the stuff of every whale, ant, flower, tree and bacterium.

But even though DNA and RNA play these roles exclusively, they’re not the only molecules that can. Vitor Pinheiro from the MRC Laboratory of Molecular Biology has developed six alternative polymers called XNAs that can also store genetic information and evolve through natural selection. None of them are found in nature. They are part of a dawning era of “synthetic genetics”, which expands the chemistry of life in new uncharted directions.


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Scientists transform scar tissue into beating heart muscle

In an act of transformation worthy of any magician, scientists have converted scar tissue in the hearts of living mice into beating heart cells. If the same trick works in humans (and we’re still several years away from a trial), it could lead us to a long-sought prize of medicine – a way to mend a broken heart.

Our hearts are made of several different types of cell. These include muscle cells called cardiomyocytes, which contract together to give hearts their beats, and connective cells called cardiac fibroblasts, which provide support. The fibroblasts make up half of a heart, but they become even more common after a heart attack. If hearts are injured, they replace lost cardiomyocytes with scar tissue, consisting of fibroblasts. In the short-term, this provides support for damaged tissue. In the long-term, it weakens the heart and increases the risk of even further problems.

Hearts can’t reverse this scarring. Despite their vital nature, they are terrible at healing themselves. But Deepak Srivastava from the Gladstone Institute of Cardiovascular Disease can persuade them to do so with the right chemical cocktail. In 2010, he showed that just three genes – Gata4, Mef2c and Tbx5 (or GMT)– could transform fibroblasts into new cardiomyocytes.

This only worked in cells growing in a laboratory dish, but it was a start. Srivastava’s team have now taken the next step. By injecting living mice with GMT, they turned some of the rodents’ fibroblasts into cardiomyocytes. Since hearts are already loaded with fibroblasts, Srivastava’s technique simply conscripts them into muscle duty. Best of all, the technique worked even better in the animals than in isolated cells. No transplants. No surgeries. No stem cells. Just add three genes, and watch sick hearts turn into healthier ones.


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OpenLab: The Renaissance Man, and how to become a scientist over and over again

I originally wrote this feature about the amazing Erez Lieberman Aiden back in June. It’s been one of the most popular posts on Not Exactly Rocket Science over the past year, and it was recently nominated for inclusion in the latest edition of Open Lab, the anthology of the world’s best science blogging. For that reason, I’m giving it another airing.


Erez Lieberman Aiden is a talkative witty fellow, who will bend your ear on any number of intellectual topics. Just don’t ask him what he does. “This is actually the most difficult question that I run into on a regular basis,” he says. “I really don’t have anything for that.”

It is easy to understand why. Aiden is a scientist, yes, but while most of his peers stay within a specific field – say, neuroscience or genetics – Aiden crosses them with almost casual abandon. His research has taken him across molecular biology, linguistics, physics, engineering and mathematics. He was the man behind last year’s “culturomics” study, where he looked at the evolution of human culture through the lens of four per cent of all the books ever published. Before that, he solved the three-dimensional structure of the human genome, studied the mathematics of verbs, and invented an insole called the iShoe that can diagnose balance problems in elderly people. “I guess I just view myself as a scientist,” he says.

His approach stands in stark contrast to the standard scientific career: find an area of interest and become increasingly knowledgeable about it. Instead of branching out from a central speciality, Aiden is interested in ‘interdisciplinary’ problems that cross the boundaries of different disciplines. His approach is nomadic. He moves about, searching for ideas that will pique his curiosity, extend his horizons, and hopefully make a big impact. “I don’t view myself as a practitioner of a particular skill or method,” he tells me. “I’m constantly looking at what’s the most interesting problem that I could possibly work on. I really try to figure out what sort of scientist I need to be in order to solve the problem I’m interested in solving.”

It’s a philosophy that has paid dividends. At just 31 years of age, Aiden has a joint lab at MIT and Harvard. In 2010, he won the prestigious $30,000 MIT-Lemenson prize, awarded to people who show “exceptional innovation and a portfolio of inventiveness”. He has seven publications to his name, six of which appeared the world’s top two journals – Nature and Science. His friend and colleague Jean-Baptiste Michel says, “He’s truly one of a kind. I just wonder about what discipline he will get a Nobel Prize in!”


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How coral snakes cause excruciating pain

Everyone has felt pain, and many experience it daily. But for such a universal sensation, it is still a mysterious one. We are only starting to understand the molecules that produce a painful sensation. Nature, however, is well ahead of us. Many animals are armed with chemicals that hijack the nervous systems of their targets, producing feelings of intense pain. They are unknowing neuroscientists, and by studying their weapons, we can better understand how pain manifests in our bodies.

Take the Texas coral snake. This brightly coloured serpent, clad in warning hues of red, black and yellow, usually shies away from confrontation. When it’s threatened, it defends itself with venom that can cause excruciating and unremitting pain.


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Extending healthy life by getting rid of retired cells

As we get older, many of the cells in our bodies go into retirement. Throughout our lives, they divided time and again, all in the face of radiation bombardments and chemical attacks. Slowly but surely, their DNA builds up damage to that threatens to turn them into tumours. Some repair the damage; others give up the ghost. But some cells opt for a third strategy – they shut down. No longer growing or dividing, they enter a state called senescence.

But they aren’t idle. Senescent cells still secrete chemicals into the body, and some scientists have suggested that they’re responsible for many of the health problems that accompany old age. And the strongest evidence for this claim comes from a new study by Darren Baker from the Mayo Clinic College of Medicine.

Baker has developed a way of killing all of a mouse’s senescent cells by feeding them with a specific drug. When he did that in middle age, he gave the mice many more healthy years. He delayed the arrival of cataracts in their eyes, put off the weakening of their muscles, and held back the loss of their body fat. He even managed to reverse some of these problems by removing senescent cells from mice that had already grown old. There is a lot of work to do before these results could be applied to humans, but for now, Baker has shown that senescent cells are important players in the ageing process.