Sex might be fun but it’s not without risks. As your partner exposes themselves to you, they also expose you to whatever bacteria, viruses or parasites they might be carrying. But some animals have a way around that. Ekaterina Litvinova has found that when male mice get a whiff of female odours, their immune systems prepare their airways for attack, increasing their resistance to flu viruses.
Litvinova worked with a group of mice that were exposed to bedding that had previously been soiled by females in the sexually receptive parts of their cycle. She compared them to a second more monastic group that were isolated from female contact.
Male mice use smells to track down females who are ready to mate. They’ll follow markings of faeces and urine and when they actually find the female, they’ll continue sniffing her nose and genitals. Each of these nasal encounters could be a source of infection. She then pitted both groups against a flu virus. Influenza doesn’t affect wild populations of house mice, so the virus in this case is acting as more of an indicator of the animals’ defences, rather than a representative of a real threat.
Both groups of mice lost a bit of weight, but at certain doses of virus, those that had been exposed to female aromas kept more of their grams on. They also fared better in the long run – just 20% of them died, compared to 46% of those that had only smelled male odours.
The Not Exactly Pocket Science experiment continues after the vast majority of people who commented liked the pilot post. I’m really enjoying this, for quite unexpected reasons. It’s forcing me to flex writing muscles that usually don’t get much of a workout. Writing short pieces means being far more economical with language and detail than usual. It means packing in as much information as possible while still keeping things readable. And it means blitz-reading papers and writing quickly without losing any accuracy.
One quick note before the good stuff: last time, a few people suggested that I put each NEPS item in a separate post, but the majority preferred multiple items per post. For now, I’m keeping it that way because otherwise, the longer pieces would be diluted by the smaller ones. We’ll see how that works for the foreseeable future.
Rising DAMPs – when enslaved bacteria turn our bodies against themselves
Our immune systems provide excellent defence against marauding hordes of bacteria, viruses and parasites, using sentinel proteins to detect the telltale molecules of intruders. But these defences can be our downfall if they recognise our own bodies as enemies.
All of our cells contain small energy-supplying structures called mitochondria. They’re descendents of ancient bacteria that were engulfed and domesticated by our ancestor cells. They’ve come a long way but they still retain enough of a bacterial flavour to confuse our immune system, should they break free of their cellular homes. An injury, for example, can set them free. If cells shatter, fragments of mitochondria are released into the bloodstream including their own DNA and amino acids that are typical of bacteria. Qin Zhang showed that trauma patients have far higher levels of such molecules in their blood than unharmed people. Our white blood cells have sentinel proteins that latch onto these molecules and their presence (incorrectly) says that a bacterial invasion is underway.
This discovery solves a medical mystery. People who suffer from severe injuries sometimes undergo a dramatic and potentially fatal reaction called “systemic inflammatory response syndrome” or SIRS, where inflammation courses through the whole body and organs start shutting down. This looks a lot like sepsis, an equally dramatic response to an infection. However, crushing injuries and burns can cause SIRS without any accompanying infections. Now we know why – SIRS is caused by the freed fragments of former bacteria setting off a false alarm in the body. The technical term for these enemies within is “damage-associated molecular patterns” or DAMPs.
More from Heidi Ledford at Nature News
Reference: Nature DOI:10.1038/nature08780
Different gut bacteria lead to mice to overeat
On Wednesday, I wrote about the hidden legions residing up your bum – bacteria and other microbes, living in their millions and outnumbering your cells by ten to one. These communities wield a big influence over our health, depending on who their members are. Matam Vijay-Kumar found that different species colonise the guts of mice with weakened immune systems, and this shifted membership is linked to metabolic syndrome, a group of obesity-related symptoms that increase the risk of heart disease and type 2 diabetes.
Vijay-Kumar’s mice lacked the vital immune gene TLR5, which defends the gut against infections. Their bowels had 116 species of bacteria that were either far more or less common than usual. They also overate, became fat, developed high blood pressure and became resistant to insulin – classic signs of metabolic syndrome. When Vijay-Kumar transplanted the gut menagerie from the mutant mice to normal ones, whose own bacteria had been massacred with antibiotics, the recipients also developed signs of metabolic syndrome. It was clear evidence that the bacteria were causing the symptoms and not the other way round.
Vijay-Kumar thinks that without the influence of TLR5, the mice don’t know what to make of their unusual gut residents. They react by releasing chemicals that trigger a mild but persistent inflammation. These same signals encourage the mice to eat more, and they make local cells resistant to the effects of insulin. Other aspects of the metabolic syndrome soon follow. The details still need to be confirmed but for now, studies like this show us how foolish it is to regard obesity as a simple matter of failing willpower. It might all come down to overeating and inactivity, but there are many subtle reasons why an individual might eat too much. The microscopic community within our guts are one of them.
Reference: Science DOI:10.1126/science.1179721
The stretchy iron-clad beards of mussels
For humans, beards are for catching food, looking like a druid, and getting tenure. But other animals have beards with far more practical purposes – mussels literally have beards of iron that they use as anchors. The beard, or byssus, is a collection of 50-100 sticky threads. Each is no thicker than a human hair but they’re so good at fastening the mussels to wave-swept rocks that scientists are using them as the inspiration for glue. So they should. The byssus is a marvel of bioengineering – hard enough to hold the mussel in place, but also stretchy enough so that they can extend without breaking.
The mussel secretes each thread with its foot, first laying down a protein-based core and then covering it in a thick protective layer that’s much harder. When Matthew Harrington looked at the strands under a microscope, he saw that the outer layer is a composite structure of tiny granules amid a looser matrix. The granules consist of iron and a protein called mfp-1, heavily linked to one other – this makes the byssus hard. The matrix is a looser collection of the same material, where mfp-is 1 heavily coiled but easy to straighten – this lets the byssus stretch. The granules have a bit of give to them but at higher strains, they hold firm while the matrix continues extending. If cracks start to form, the granules stop them from spreading.
It’s unclear how the mussel creates such a complicated pattern, but Harrington suggests that it could be deceptively simple – changing a single amino acid in the mfp-1 protein allows it to cross-link more heavily with iron. That’s the difference between the tighter granular bundles, and the looser ones they sit among.
Reference: Science DOI:10.1126/science.1181044
Cause of dinosaur extinction
Sixty-five million years ago, the vast majority of dinosaurs were wiped out. Now, a new paper reveals the true cause of their demise – legions of zombies armed with chaingu… wait… oh. Right. An asteroid. You knew that.
More from Mark Henderson at the Times
Reference: Science DOI:10.1126/science.1177265
Today, a new paper published in Nature adds another chapter to the story of FOXP2, a gene with important roles in speech and language. The FOXP2 story is a fascinating tale that I covered in New Scientist last year. It’s one of the pieces I’m proudest of so I’m reprinting it here with kind permission from Roger Highfield, and with edits incorporating new discoveries since the time of writing.
The FOXP2 Story (2009 edition)
Imagine an orchestra full of eager musicians which, thanks to an incompetent conductor, produces nothing more than an unrelieved cacophony. You’re starting to appreciate the problem faced by a British family known as KE. About half of its members have severe difficulties with language. They have trouble with grammar, writing and comprehension, but above all they find it hard to coordinate the complex sequences of face and mouth movements necessary for fluid speech.
Thanks to a single genetic mutation, the conductor cannot conduct, and the result is linguistic chaos. In 2001, geneticists looking for the root of the problem tracked it down to a mutation in a gene they named FOXP2. Normally, FOXP2 coordinates the expression of other genes, but in affected members of the KE family, it was broken.
It had long been suspected that language has some basis in genetics, but this was the first time that a specific gene had been implicated in a speech and language disorder. Overeager journalists quickly dubbed FOXP2 “the language gene” or the “grammar gene”. Noting that complex language is a characteristically human trait, some even speculated that FOXP2 might account for our unique position in the animal kingdom. Scientists were less gushing but equally excited – the discovery sparked a frenzy of research aiming to uncover the gene’s role.
Several years on, and it is clear that talk of a “language gene” was premature and simplistic. Nevertheless, FOXP2 tells an intriguing story. “When we were first looking for the gene, people were saying that it would be specific to humans since it was involved in language,” recalls Simon Fisher at the University of Oxford, who was part of the team that identified FOXP2 in the KE family. In fact, the gene evolved before the dinosaurs and is still found in many animals today: species from birds to bats to bees have their own versions, many of which are remarkably similar to ours. “It gives us a really important lesson,” says Fisher. “Speech and language didn’t just pop up out of nowhere. They’re built on very highly conserved and evolutionarily ancient pathways.”
Two amino acids, two hundred thousand years
The first team to compare FOXP2 in different species was led by Wolfgang Enard from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. In 2001, they looked at the protein that FOXP2 codes for, called FOXP2, and found that our version differs from those of chimpanzees, gorillas and rhesus macaques by two amino acids out of a total of 715, and from that of mice by three. This means that the human version of FOXP2 evolved recently and rapidly: only one amino acid changed in the 130 million years since the mouse lineage split from that of primates, but we have picked up two further differences since we diverged from chimps, and this seems to have happened only with the evolution of our own species at most 200,000 years ago.
The similarity between the human protein FOXP2 and that of other mammals puts it among the top 5 per cent of the most conserved of all our proteins. What’s more, different human populations show virtually no variation in their FOXP2 gene sequences. Last year, Enard’s colleague Svante Pääbo made the discovery that Neanderthals also had an identical gene, prompting questions over their linguistic abilities (see “Neanderthal echoes below).
“People sometimes think that the mutated FOXP2 in the KE family is a throwback to the chimpanzee version, but that’s not the case,” says Fisher. The KEs have the characteristically human form of the gene. Their mutation affects a part of the FOXP2 protein that interacts with DNA, which explains why it has trouble orchestrating the activity of other genes.
There must have been some evolutionary advantage associated with the human form of FOXP2, otherwise the two mutations would not have spread so quickly and comprehensively through the population. What this advantage was, and how it may have related to the rise of language, is more difficult to say. Nevertheless, clues are starting to emerge as we get a better picture of what FOXP2 does – not just in humans but in other animals too.
During development, the gene is expressed in the lungs, oesophagus and heart, but what interests language researchers is its role in the brain. Here there is remarkable similarity across species: from humans to finches to crocodiles, FOXP2 is active in the same regions. With no shortage of animal models to work with, several teams have chosen songbirds due to the similarities between their songs and human language: both build complex sequences from basic components such as syllables and riffs, and both forms of vocalisation are learned through imitation and practice during critical windows of development.
All bird species have very similar versions of FOXP2. In the zebra finch, its protein is 98 per cent identical to ours, differing by just eight amino acids. It is particularly active in a part of the basal ganglia dubbed “area X”, which is involved in song learning. Constance Scharff at the Max Planck Institute for Molecular Genetics in Berlin, Germany, reported that finches’ levels of FOXP2 expression in area X are highest during early life, which is when most of their song learning takes place. In canaries, which learn songs throughout their lives, levels of the protein shoot up annually and peak during the late summer months, which happens to be when they remodel their songs.
So what would happen to a bird’s songs if levels of the FOXP2 protein in its area X were to plummet during a crucial learning window? Scharff found out by injecting young finches with a tailored piece of RNA that inhibited the expression of the FOXP2 gene. The birds had difficulties in developing new tunes and their songs became garbled: they contained the same component “syllables” as the tunes of their tutors, but with syllables rearranged, left out, repeated incorrectly or sung at the wrong pitch.
The cacophony produced by these finches bears uncanny similarities to the distorted speech of the afflicted KE family members, making it tempting to pigeonhole FOXP2 as a vocal learning gene – influencing the ability to learn new communication sounds by imitating others. But that is no more accurate than calling it a “language gene”. For a start, songbird FOXP2 has no characteristic differences to the gene in non-songbirds. What’s more, among other species that show vocal learning, such as whales, dolphins and elephants, there are no characteristic patterns of mutation in their FOXP2 that they all share.
Instead, consensus is emerging that FOXP2 probably plays a more fundamental role in the brain. Its presence in the basal ganglia and cerebellums of different animals provides a clue as to what that role might be. Both regions help to produce precise sequences of muscle movements. Not only that, they are also able to integrate information coming in from the senses with motor commands sent from other parts of the brain. Such basic sensory-motor coordination would be vital for both birdsong and human speech. So could this be the key to understanding FOXP2?
New work by Fisher and his colleagues supports this idea. In 2008, his team engineered mice to carry the same FOXP2 mutation that affects the KE family, rendering the protein useless. Mice with two copies of the dysfunctional FOXP2 had shortened lives, characterised by motor disorders, growth problems and small cerebellums. Mice with one normal copy of FOXP2 and one faulty copy (as is the case in the affected members of the KE family) seemed outwardly healthy and capable of vocalisation, but had subtle defects.
For example, they found it difficult to acquire new motor skills such as learning to run faster on a tilted running wheel. An examination of their brains revealed the problem. The synapses connecting neurons within the cerebellum, and those in a part of the basal ganglia called the striatum in particular, were severely flawed. The signals that crossed these synapses failed to develop the long-term changes that are crucial for memory and learning. The opposite happened when the team engineered mice to produce a version of FOXP2 with the two characteristically human mutations. Their basal ganglia had neurons with longer outgrowths (dendrites) that were better able to strengthen or weaken the connections between them.
A battery of over 300 physical and mental tests showed that the altered mice were generally healthy. While they couldn’t speak like their cartoon equals, their central nervous system developed in different ways, and they showed changes in parts of the brain where FOXP2 is usually expressed (switched on) in humans.
Their squeaks were also subtly transformed. When mouse babies are moved away from their nest, they make ultrasonic distress calls that are too high for us to hear, but that their mothers pick up loudly and clearly. The altered Foxp2 gene subtly changed the structure of these alarm calls. We won’t know what this means until we get a better understanding of the similarities between mouse calls and human speech.
For now, the two groups of engineered mice tentatively support the idea that human-specific changes to FOXP2 affect aspects of speech, and strongly support the idea that they affect aspects of learning. “This shows, for the first time, that the [human-specific] amino-acid changes do indeed have functional effects, and that they are particularly relevant to the brain,” explains Fisher. “FOXP2 may have some deeply conserved role in neural circuits involved in learning and producing complex patterns of movement.” He suspects that mutant versions of FOXP2 disrupt these circuits and cause different problems in different species.
Pääbo agrees. “Language defects may be where problems with motor coordination show up most clearly in humans, since articulation is the most complex set of movements we make in our daily life,” he says. These circuits could underpin the origins of human speech, creating a biological platform for the evolution of both vocal learning in animals and spoken language in humans.
Holy diversity, Batman
The link between FOXP2 and sensory-motor coordination is bolstered further by research in bats. Sequencing the gene in 13 species of bats, Shuyi Zhang and colleagues from the East China Normal University in Shanghai discovered that it shows incredible diversity. Why would bats have such variable forms of FOXP2 when it is normally so unwavering in other species?
Zhang suspects that the answer lies in echolocation. He notes that the different versions seem to correspond with different systems of sonar navigation used by the various bat species. Although other mammals that use echolocation, such as whales and dolphins, do not have special versions of FOXP2, he points out that since they emit their sonar through their foreheads, these navigation systems have fewer moving parts. Furthermore, they need far less sensory-motor coordination than flying bats, which vocalise their ultrasonic pulses and adjust their flight every few milliseconds, based on their interpretation of the echoes they receive.
These bats suggest that FOXP2 is no more specific to basic communication than it is to language, and findings from other species tell a similar tale. Nevertheless, the discovery that this is an ancient gene that has assumed a variety of roles does nothing to diminish the importance of its latest incarnation in humans.
Since its discovery, no other gene has been convincingly implicated in overt language disorders. FOXP2 remains our only solid lead into the genetics of language. “It’s a molecular window into those kinds of pathways – but just one of a whole range of different genes that might be involved,” says Fisher. “It’s a starting point for us, but it’s not the whole story.” He has already used FOXP2 to hunt down other key players in language.
The executive’s minions
FOXP2 is a transcription factor, which activates some genes while suppressing others. Identifying its targets, particularly in the human brain, is the next obvious step. Working with Daniel Geschwind at the University of California, Los Angeles, Fisher has been trying to do just that, and their preliminary results indicate just what a massive job lies ahead. On their first foray alone, the team looked at about 5000 different genes and found that FOXP2 potentially regulates hundreds of these.
Some of these target genes control brain development in embryos and its continuing function in adults. Some affect the structural pattern of the developing brain and the growth of neurons. Others are involved in chemical signalling and the long-term changes in neural connections that enable to learning and adaptive behaviour. Some of the targets are of particular interest, including 47 genes that are expressed differently in human and chimpanzee brains, and a slightly overlapping set of 14 targets that have evolved particularly rapidly in humans.
Most intriguingly, Fisher says, “we have evidence that some FOXP2 targets are also implicated in language impairment.” Last year, Sonja Vernes in his group showed that FOXP2 switches off CNTNAP2, a gene involved in not one but two language disorders – specific language impairment (SLI) and autism. Both affect children, and both involve difficulties in picking up spoken language skills. The protein encoded by CNTNAP2 is deployed by nerve cells in the developing brain. It affects the connections between these cells and is particularly abundant in neural circuits that are involved in language.
Verne’s discovery is a sign that the true promise of FOXP2’s discovery is being fulfilled – the gene itself has been overly hyped, but its true worth lies in opening a door for more research into genes involved in language. It was the valuable clue that threw the case wide open. CNTNAP2 may be the first language disorder culprit revealed through FOXP2 and it’s unlikely to be the last.
Most recently, Dan Geschwind compared the network of genes that are targeted by FOXP2 in both chimps and humans. He found that the two human-specific amino acids within this executive protein have radically altered the set of genetic minions that it controls.
The genes that are directed by human FOXP2 are a varied cast of players that influence the development of the head and face, parts of the brain involved in motor skills, the growth of cartilage and connective tissues, and the development of the nervous system. All those roles fit with the idea that our version of FOXP2 has been a lynchpin in evolving the neural circuits and physical structures that are important for speech and language.
The FOXP2 story is far from complete, and every new discovery raises fresh questions just as it answers old ones. Already, this gene has already taught us important lessons about evolution and our place in the natural world. It shows that our much vaunted linguistic skills are more the result of genetic redeployment than out-and-out innovation. It seems that a quest to understand how we stand apart from other animals is instead leading to a deeper appreciation of what unites us.
Box – Neanderthal echoes
The unique human version of the FOXP2 gives us a surprising link with one extinct species. Last year, Svante Pääbo’s group at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, extracted DNA from the bones of two Neanderthals, one of the first instances of geneticists exploring ancient skeletons for specific genes. They found that Neanderthal FOXP2 carries the same two mutations as those carried by us – mutations accrued since our lineage split from chimps between 6 and 5 million years ago.
Pääbo admits that he “struggled” to interpret the finding: the Neanderthal DNA suggests that the modern human’s version of FOXP2 arose much earlier than previously thought. Comparisons of gene sequences of modern humans with other living species had put the origins of human FOXP2 between 200,000 and 100,000 years ago, which matches archaeological estimates for the emergence of spoken language. However, Neanderthals split with humans around 400,000 years ago, so the discovery that they share our version of FOXP2 pushes the date of its emergence back at least that far.
“We believe there were two things that happened in the evolution of human FOXP2,” says Pääbo. “The two amino acid changes – which happened before the Neanderthal-human split – and some other change which we don’t know about that caused the selective sweep more recently.” In other words, the characteristic mutations that we see in human FOXP2 may indeed be more ancient than expected, but the mutated gene only became widespread and uniform later in human history. While many have interpreted Pääbo’s findings as evidence that Neanderthals could talk, he is more cautious. “There’s no reason to assume that they weren’t capable of spoken language, but there must be many other genes involved in speech that we yet don’t know about in Neanderthals.”
People infected with the bird flu virus – influenza A subtype H5N1 – go through the usual symptoms of fever, aching muscles and cough. The virus is so virulent that 60% of infected humans have died. But according to a study in mice, the infection could also take a more inconspicuous toll on the brain, causing the sorts of damage that could increase the risk of diseases like Parkinson’s and Alzheimer’s many years after the virus has been cleared.
The link between influenza and Parkinson’s disease is hardly old but certainly controversial. Previous studies have found no traces of flu genetic material in Parkinson’s patients, but one of the strongest pieces of evidence for a link comes from analysing an outbreak of von Economo disease following the 1918 flu pandemic.
To date, 433 people have been infected with H5N1, and a few cases have shown problems with their nervous system, running the gamut from inflammation of the brain to coma. For the survivors, it’s too early to say if their brief time with the virus could lead to neurological problems later on in life. Instead, Haeman Jang from St Jude’s Children’s Research Hospital turned to mice for answers.
He clearly showed that the H5N1 virus can infect mouse neurons within a few days, where it causes certain proteins to gather in the sorts of clumps that are so strongly associated with neurodegenerative disease. It kills off important cells, triggers symptoms reminiscent of Parkinson’s like tremors, and even stimulates an over-the-top immune response that lasted for months after the original infection was cleared.
Jang thinks that this long-lasting immune response may be how the virus leads to a higher risk of chronic diseases long after it has left its host. It’s a hit-and-run strategy, where the initial infection paves the way for something else to come along later on in life and make a “second hit”. According to this model, the flu virus doesn’t directly cause Parkinson’s or related diseases, but it primes the neurons for other things that do. This could also explain why scientists have been unable to detect influenza RNA in Parkinson’s patients.
Itching is an unpleasant sensation that drives us to scratch reflexively in an effort to remove harmful substances from our body. It’s also how I get most of my physical activity for the day. Not being able to scratch an itch is intensely frustrating and many scientists have long described itch as the milder cousin of pain.
But a team of scientists from Washington University’s Pain Center (I wonder if they have problems with recruitment) have discovered a group of neurons in the spines of mice that are specific to itch but not to pain. Remove them, and mice hardly ever scratch when they’re exposed to itchy chemicals, even though they can still feel pain as well as any normal mouse.
The discovery settles a long-standing debate about whether itch and pain are governed by separate neural systems. It confirms the so-called “labelled line” theory, which says that both sensations depend on different groups of nerve cells.
Two years ago, Yan-Gang Sun and Zhong-Qiu Zhao discovered an itch-specific gene called GRPR that is activated in a small group of neurons in the spinal cords of mice. Without a working copy of this gene, mice became immune to itching but they still responded normally to heat, pressure, inflammation and the noxious flavour of mustard. The duo even managed to stop mice from scratching by injecting them with a chemical that blocks GRPR.
But neurons that activate an itch-specific gene aren’t necessarily restricted to conveying the sensations of itching – they could also be involved in pain. To test that idea, Sun and Zhao injected mice with a nerve poison called bombesin-saporin, which specifically kills neurons that use GRPR. Without these neurons, the mice resisted a wide variety of substances that cause normal mice to scratch furiously, even though their movements were generally unaffected. Just compare the two mice in the video below – both have been injected with an itching agent but the one on the left lacks any working GRPR neurons.
However, even bereft of GRPR neurons, the mice felt pain just as any other mouse would, reacting normally to heat, pressure and noxious chemicals like mustard oil and capsaicin, the active component of chillies. Clearly, these neurons are specific to itch.
It’s 1964, and a group of Canadian scientists had sailed across the Pacific to Easter Island in order to study the health of the isolated local population. Working below the gaze of the island’s famous statues, they collected a variety of soil samples and other biological material, unaware that one of these would yield an unexpected treasure. It contained a bacterium that secreted a new antibiotic, one that proved to be a potent anti-fungal chemical. The compound was named rapamycin after the traditional name of its island source – Rapa Nui.
Skip forward 35 years and rapamycin has made a stunning journey from the soil of a Pacific island to the besides of the world’s hospitals. Its ability to suppress the immune system means that it’s given to transplant patients to stop them from rejecting their organs and its ability to stop cells from dividing has formed the basis of potential anti-cancer drugs. But the chemical has an even more interesting ability and one that has only just been discovered – it can extend lifespan, at least in mice.
David Harrison, Randy Strong and Richard Miller, leading a team of 13 American scientists, have found that capsules of rapamycin can extend the lifespans of mice that eat them by 9-14%. That’s especially amazing given that the mice were already 20-months-old at the time of feeding, the equivalent in mouse years of a 60-year-old human.
There will undoubtedly be headlines that proclaim the discovery of the fountain of youth or some such, but it is absolutely critical to say up front that this is not a drug that people should be taking to extend their lives. Rapamycin has a host of side effects including, as previously mentioned, the ability to suppress the immune system. Harrison says, “It may do more harm than good, as we know neither optimal doses nor schedules of when to start for anti-ageing effects.” So the new discovery doesn’t put an anti-ageing pill within our grasp. It’s far better to see it as a gateway for understanding more about the basic biology of ageing, and for designing other chemicals that can provide the same benefits without the unwanted risky side effects.
Nonetheless, it’s still very exciting, especially since the nutrition market is already awash with supplements that claim to slow the ageing process but which have little evidence to back their claims. Likewise, scientists have tested a number of different chemicals but the few positive effects have typically been small or restricted to a specific strain of mouse. Rapamycin is different – as Harrison himself explains, “no other intervention has been this effective when starting so late in life on such a diverse population.”
When Walt Disney created Mickey Mouse in 1928, he understood the draw that anthropomorphic mice would have. But even Walt’s imagination might have struggled to foresee the events that have just taken place in a German genetics laboratory. There, a group of scientists led by Wolfgang Enard have “humanising” a gene in mice to study its potential relevance for human evolution.
The gene in question is the fascinating FOXP2, which I have written extensively about before, particularly in a feature for New Scientist. FOXP2 was initially identified as the gene behind an inherited disorder that affected language and grammar skills. Subsequently hailed as a “language gene”, it proved to be anything but. The gene, and its encoded protein, is incredibly conserved among animals, even among those without sophisticated communication skills. The chimp version differs from our own by just two amino acids; the mouse adds a single change on top of that.
The two amino acids that have cropped up since our split from chimps are unique to us and there’s plenty of evidence that they’re the result of intense natural selection. There has always been the tantalising possibility that these changes were crucial for the evolution of our speech and language skills but until now, no one really understood their purpose. No human has ever been found with mutations at these crucial positions. Obviously, genetically manipulating humans or chimps is out of the question, but the fact that the mouse version is so similar gave Enard a unique opportunity.
He tweaked the mouse Foxp2 so that it produced a protein with the two human-specific amino acids. The resulting mice couldn’t speak like their cartoon equals, but their calls were subtly altered, their central nervous system developed in different ways, and they showed changes in parts of the brain where FOXP2 is usually expressed (switched on) in humans. Simon Fisher, who first discovered the important role of FOXP2 and contributed to the study, says, “This shows, for the first time, that the [human-specific] amino-acid changes do indeed have functional effects, and that they are particularly relevant to the brain.”