Why the concept of a “paleo” diet is virtually impossible in our modern day world

One of the most popular diet trends at the moment is known as the “paleo” diet. Paleo; stands for Paleolithic; an era 3.3 million years ago, a time of cavemen who had just managed to start using tools made from stone. The diet intends to include only foods that these prehistoric humans may have ate, such as meat, fish, fruits and vegetables, but completely rules out any groups of food that are domesticated such as grains, dairy products and legumes. The whole general idea is that we were not evolved to eat these foods and so they cause havoc with our metabolism and so should be a no-go.

There are several other key flaws in the whole concept. 

Number 1: it’s not just grains we have cultivated, human kind has had an impact on virtually every naturally growing edible plant on this planet 

If you walk into any supermarket, fruit and veg shop, even one which is “organic”, it is highly likely you will see rows of perfectly formed, brightly coloured and unblemished fruits and veg, bursting with juice and flavour. You think they naturally grew like that? Even before our ability to genetically modify our produce, human kind selectively bred fruits and veg for years to alter the taste, texture and size. For example, look at the watermelon painted by an Italian artist of the 17th Century, Giovanni Stanchi and contrast this with the modern day watermelon. That is the difference that 400 years has played – so what can 3.3 million years do?  

Left: water melon from the 17th century
Right: Modern day watermelon

Modern day apples have been domesticated from wild crabapples from Ancient China. They were originally named crabapples as crabbe was the old English meaning bitter and have been grown and developed, over roughly 4000 years, into over 35 different types of sweet, succulent and juicy modern day apples, with varying sugar and acid contents to alter taste. 

Left: Crabapple: the original apple
Right: Modern day apples

There are countless more examples, but to make the point, the nutrition obtained from eating modern day fruit would be very different from what the hunter gatherers were getting 3.3 million years ago. 

Number 2: we have also been selectively breeding animals for higher produce for over 10000 years

Pigs, cows, chickens and sheep… some of the favourites of the dinner table. Millenia of domestication, selective breeding and arranged mating has given us species which provide us  with plentiful meat supply, tender chicken breasts and succulent, juicy steaks. 

Modern day selective breeding is highly efficient, and the turkeys in the pictures are the product of selective breeding of the last 50 years. Development of technology and science has allowed us to link distinct phenotypes such as weight or the ratio of lean tissue to fat mass with specific genes or groups of genes, further increasing the efficiency of our manipulations. Now, on average, only the top 1-2 % top yielding “producers” of our herds, flocks and broods are picked to reproduce and only those genes and traits are passed down to the next generation. However, a less strategic and well-informed, but similar, type of selective behaviour has  been occurring for over 10, 000 years. The oldest evidence of meat domestication was found in China where fossilised remains of a bird species closely related to modern day chickens has been discovered. Since that time, we have been breeding animals to give us more, more, more. It doesn’t matter if the meat source is “organic” or “free range”, these eye catching ideas do not change the fact that the heritage of this meat is, fundamentally, unnatural.

Image result for genetically modified cattle
Genetically modified cattle: the gene Myostatin has been completed removed. Myostatin normally inhibits muscle growth, keeping the body in balance. Without its inhibiting actions, cattle grow to enormous, unethical sizes.
Tempting?

A stone age diet would, also, undoubtably have included meat sources most people would never dream of consuming now such as insects, rodents and reptiles. I don’t see many paleo guidelines offering recipes for tasty spiders or snakes instead of steak or pork chops. Are we to believe that the animals that human kind have moulded into shape and sculpted to perfection over the years provide us with the same nutrition that hunter gathers would have obtained from their catches in the stone age? 

Number 3: We are continuing to evolve and adapt

Evolution has continued, relentlessly, since the stone age. We are now able to process, digest and obtain nutrients from a range of foods that were key to the survival of some of our species. 

An example is lactose, found in diary products such as milk, cheese and yoghurt. Now the paleo diet rules these out, claiming they are unnatural, but these have been staples in parts of the world with a domesticated dairy industry for around 10,000 years, and in these countries astonishing adaptations took place to facilitate populations to be able to digest and extract nutrients from dairy products: an obvious indication of the survival advantage that these substances could offer us. 

Image result for lactose tolerance map
World map of lactose intolerance: this correlates strongly with cultures with strong reliance of dairy domestication

All babies are lactose tolerant – they produce lactase – an enzyme which breaks down lactose into its counterparts, allowing all babies to thrive on mother’s milk. As we grow older, it used to be that we switched off the lactase gene, meaning that the lactose accumulated in our GI tract, was fermented by bacteria instead. This fermentation process produces accumulation of gas: the reason why lactose intolerance causes bloating, wind and stomach pain. Now, in just 400 generations, a strong selection pressure caused the spread of a single nucleotide base change. This single nucleotide base is not actually in the gene sequence but is thought to play a role in the switching of the gene from “on” in young children to “off” in adults. This change has reached 77 % of Northern Europeans in an extremely short time frame (in evolutionary terms) suggesting that it offered positive survival benefits, and increasing the likelihood of surviving to mate. 

Now I am not denying that a diet without highly-processed food is healthy and that eating plenty of fruit, veg and whole foods has a whole array of health benefits. I am just pointing out that a diet, such as paleo, with extremely rigid rules about what qualifies as “natural” and “designed for us” is completely undermined by our years of manipulating the natural world to suit us. We have sculpted our environment and, in turn, been sculpted by the cultures we have created. It’s worked wonders for our survival as a species, and we should not demonise our ability to make wonderful new foods, some of which can offer many nutritional benefits. 

Why does binge drinking give you the munchies?

If you were to describe your typical night out binge drinking experience, 9 times out of 10 it will conclude with the grand finalé: the unashamedly wild and predatory ambushing of the chosen fast food joint. Whether it be a big mac with nugs, a greasy kebab or a killer dominoes pizza, the avid determination to devour something as salty, greasy and carb heavy as possible is overwhelming and often inevitable after a night on the lash. It just tastes so good. In a recent survey on YouGov, people reported consuming an additional 6300 extra calories on top of what they would normally consume after a heavy night out. A recent meta analysis showed that the average fresher gains 3.4 kg during freshers year1, probably the most boozy year of their lives. But why is this? 

So that end-of-night feast has become more than a routine, it’s now an ingrained ritual. You and your mates have made it a habit. Societal norms like this can have drastic impacts on our decisions and people give in to peer pressure more easily when intoxicated. It is a well-known concept that alcohol consumption causes people to loose their inhibitions. It’s why you can make that crude joke you’d have never made sober, why you may dance with your boss at a work night out or go in for a kiss with the person you’ve had the hots for for ages. But the combination of societal norms, peer pressure, loss of self-control and increase in impulsive behaviour is not all that contributes to the over-eating phenomenon. It’s recently been shown that alcohol is able to cleverly manipulate the brain into “starvation mode”. This causes the undeniable cravings, the cravings which, physiologically, do not make sense. After a night of heavy drinking it is virtually impossible to be in a calorie deficit; alcohol is nearly as calorie dense as fat per gram. 

fMRI scans showing that alcohol induces overactivity in brain regions involved in the olfactory response to food aromas

This is not just a subjective phenomenon, it has been documented in many a scientific study. For example, a study in 35 non-obese women, which injected either alcohol or salt water directly into the blood stream, showed that those given alcohol ate significantly more calories at a buffet meal afterwards, regardless of the food choices they made. To understand how alcohol has this effect, we need to look at the mechanisms controlling hunger and food intake, a process which is normally balanced by a region of the brain called the hypothalamus. Within the hypothalamus, a group of neurones, AgrP neurones, sit which, when activated signal a ravenous hunger. When they imaged the brains of these women using fMRI scanning, they showed that this area of the brain was significantly more overactive when they were exposed to delicious food odours compared to when they were exposed to odours of non-food items2

The hypothalamus plays an important role in regulating appetite

Mice also shown this alcohol-induced overeating pattern, suggesting this is an evolutionary conserved biological phenomenon. Brain slices can be taken from these mice, and these can be used to study the complex mechanisms at play. These brain slices retain the architecture of the neurones as they would be naturally in the mouse brain, and so it is possible to inject substances into the ArgP neurones specifically. Very sensitive dyes, that only are fluorescent when a neurone is activated, have been used to show that ethanol causes hyper-activity of these neurones. This group of scientists then decided to use advanced genetic engineering techniques to completely abolish the neuronal activity of these AgrP neurones in live mice models. In these mice, alcohol no longer produced its over-eating effect3

Fluorescently labelled AgrP neurones in brain slices taken from genetically modified mice

There is also evidence to suggest that alcohol has an effect on peripheral signals determining hunger cues. Adipose tissue is actually one of the largest endocrine organs in the body- secreting hormones in the bloodstream. One of these hormones is leptin, the blood concentrations of which are directly proportional to the mass of adipose tissue on the body. Leptin acts to signal to the brain that there is plenty of energy stored as fat. As leptin levels begin to fall, the body interprets this as the body loosing its fatty energy supplies. It enters into a starvation mode to try and replenish these lost stores, stimulating hunger cues and promoting appetite. Studies have shown that alcohol consumption effectively stops leptin secretion from adipose tissue, causing it to accumulate in the adipose tissue and decreasing the levels in the blood4. Another factor contributing to the ravenous hunger.  

Leptin deficient mice get morbidly obese: they have no leptin so the body acts as though it is starving even when it’s got plenty of adipose tissue stores

So is there anything you can do to try to prevent the maccies trip? Alcohol can also cause you to become hypoglycaemic (low blood sugar), especially if you haven’t eaten anything before a binge-drinking episode. This is due to a decreased ability of the liver to break down glycogen into glucose and regulate blood sugar and also because of a hyper-responsiveness to insulin. Drops in blood sugar are detected and this is reported back to the hypothalamus, also increasing appetite. So, if you eat a balanced meal before the big night out you’ll be less likely to pig out after. But, who says you shouldn’t treat yourself to the post-booze burger? It’s not like you do it every night, right? 

(1) Vadeboncoeur, Claudia, Nicholas Townsend, and Charlie Foster. “A meta-analysis of weight gain in first year university students: is freshman 15 a myth?.” BMC obesity 2.1 (2015): 22.

(2) Eiler, William JA, et al. “The aperitif effect: alcohol’s effects on the brain’s response to food aromas in women.” Obesity 23.7 (2015): 1386-1393.

(3) Cains, S. et al. Agrp neuron activity is required for alcohol-induced overeating. Nat. Commun. 8, 14014 doi: 10.1038/ncomms14014 (2017).

(4) Otaka, Michiro, et al. “Effect of alcohol consumption on leptin level in serum, adipose tissue, and gastric mucosa.” Digestive diseases and sciences 52.11 (2007): 3066-3069.

“Addictive personalities”: can your genes get you hooked?

Being a student, I’ve seen for myself: most of us go out, have a good time, have more than a few drinks and maybe the more adventurous (or foolish) dabble in some of the harder substances. All in all, most of us will wake up the next morning, extremely hungover, but not obviously harmed and definitely without overwhelming urges to recover with another pint of wine. However, for a select few people, the tendency to become addicted to elicit substances is considerably higher. These nights, which seem like harmless fun and just part of the package of being young and a student, can lead on to devastating and unforeseen consequences.

The idea of an “addictive personality” is not a new concept and studies have demonstrated that an individual’s genetic material, in combination with environmental factors experienced throughout their life, can directly influence how likely they are to become “hooked”. Here – I’m going to begin to explain how a change of just a few DNA bases out of 3 billion can increase the likelihood of someone developing characteristics of an addict and why these select few have such a high relapse rate in recovery (70-80 % of recovering addicts relapse within a year!)

Synapses in the brain communicate using neurotransmitters such as dopamine

Dopamine, is a neurotransmitter in the brain, which is vital for survival. Not only is it involved in complex circuits which allow us to maintain precise and coordinated control of our physical movements, but it is also the main chemical released in the “rewards pathway” in the brain. Through evolution, it has been necessary for us to be motivated to seek food, water and sex to survive and make sure the population is sustained. This innocent urge to live is has shaped the dopamine pathway which has made us love, crave and seek necessities which are key to flourishing as a species. It stimulates us to seek rewarding substances by creating a feeling of anticipation and then aids in the feeling of pleasure when we have obtained them – that’s why we all eat too much chocolate and why some people have the tendency to look a little like a sexual predator on nights out.

Rats will self-administer drugs to the point of death

The neurones which secrete dopamine originate in midbrain nuclei and have project to a part of the brain called the nucleus accumbens. This is named the mesolimbic pathway and is the dominant one potentiated by addictive substances. By this, I don’t just mean drugs of abuse but all sorts of addictions such as gambling, sugar, nicotine, alcohol, sex – you name it- they all cause a dopamine surge. It has been difficult to study this pathway in humans but since the 1950s it has been known that if you provide rats with a lever which, when pressed, electrically stimulates the mesolimbic pathway, they will continue to press the lever over 6000 times per hour! They become so distracted and involved in self-stimulating that they forget to drink and eat and eventually die from lack of water and food. This reiterates the power of the pathway and helps explain why drug addicts continue to self-administer even when they know that it is causing them severe harm and even when they have the desire to give up. Dopamine-containing neurones also project to the cortex- the region of the brain used for strategic planning and voluntary actions. If you think about how many movements and stages need to be carried out in order to obtain drugs – calling the dealer, waiting in artic conditions to meet him, hurrying a mile down the road to get cash out – it is no surprise that higher regions of the brain are involved.

There are 100 trillion synapses (connections) in the human brain, which can have one or more different neurotransmitter signals. This makes the brain the most complex structure known to man

In the brain of an addict, the carefully designed and regulated neurocircuits are not in balance. Over time, connections between neurones can be strengthened – a process known as long term potentiation and this is how we form memories. The strengthening of certain connections means that an addict has a more powerful drive to complete the actions needed to be done to obtain the rewarding substance. Additionally, the associated memories are strong – meaning certain seemingly innocent cues can prompt neuronal firing and “cravings”. If you show a cocaine addict an image of someone else snorting a line and image their brain, there is significantly more hyperactivity observed in the brain regions involved in the dopamine pathway than in a healthy control. This activity is thought to initiate cravings and a desire to complete the task themselves. In addition to this, the reward value of other, naturally rewarding activities, such as spending time with family and friends, are decreased. Rationality goes out the window as the input descending from the prefrontal cortex, which is normally the main source of self-control and the reason why most people would say no, is diminished.

So how do mutations in certain genes, coupled with environmental factors, lead to disruptions and discrepancies in this dopamine pathway?

How can these cause some people to become addicts and go through endless cycles of recovery and relapse? Most people who have used elicit substances are lucky enough to be able to leave it all behind them and go on to obtain successful careers, get married, have kids, go on package holidays and pay off their mortgage. What is it, in the genetic make up, which helps code for these differences? The answer, in part, is down to a protein which codes for a subtype of dopamine receptor: DRD2. These are expressed in the membranes of neurones throughout the brain. When dopamine binds to DRD2 it acts as an inhibitory signal, dampening down activity of these neurones via complex cascades of signalling proteins and chemicals.

We have 23 pairs of homologous chromosomes, one from each parent, and each carrying a single copy of each gene

DRD2 gene has two variants (alleles): A1 and A2. Each person obtains one allele from each of their parents and so the potential combinations are A1/A1, A1/A2 or A2/A2. Randomised studies performed on Caucasian populations have demonstrated a significant correlation between alcoholics and the A1 allele of the DRD2 gene. Although this linkage has been debated widely for
many years, it has now been suggested that this A1 allele is also implemented in addiction to other substances such as cocaine, nicotine, heroin, marijuana, amphetamines and even carbohydrate cravings. Looking at patients recovering from heroin addiction and dependence – those which held one or two copies of A1 consumed TWICE as much heroin as those patients with two A2 alleles and were 4 times more likely to relapse. But hope is not lost, many people who possess the A1 allele have recovered from alcoholism, lost weight or quit smoking. There are so many other environmental, biochemical and genetic factors at play that this definitely cannot be used as an excuse to keep chugging the cigarettes and eating excessive numbers of chocolate digestives.

So how do these alleles have such influences on behaviour?

PET scans showing decreases DRD2 expression in obese, cocaine addicted and alcoholic individuals compared to a healthy control. Red = DRD2

By labelling DRD2 in the brain radioactively, it has been shown that patients with the A1 allele actually have reduced expression of DRD2. This agreed with results from post-mortems which showed reduced DRD2 in A1 patients, in key brain regions involved in dopamine pathways. It has been shown for years, with brain imaging studies that people addicted to psychostimulatory substances e.g. cocaine, have reduced DRD2 receptor density, but it was heavily debated whether this was a cause or a consequence of their addictive behaviour and actions. More and more evidence is being accumulated that these patients actually started off with fewer DRD2 receptors – they were predisposed to become addicted. Whereas somebody with a healthy density of DRD2 neurones gets a fulfilling amount of hedonic sensations from natural rewards such as palatable foods and good sex, those with fewer DRD2 need to actively seek more potent rewards and reinforce them regularly to get the same effects.

DRD2 receptors become internalised into the cells after chronic drug abuse

The continuous stimulation of the dopamine pathway as they become chronically addicted then causes receptors to be internalised and down-regulated to stop the cell being over-excited to death. This results in even less DRD2 receptors available leading to a never-ending cycle of relapse, addictive behaviour and plummeting DRD2 levels. The role of DRD2 can also help to explain why stressful situations can lead to reinforcement of the addicted behaviour. When you are stressed, the actual numbers and density of DRD2 receptors in the striatum (a region essential for dopamine release) are reduced via other pathways probably induced by prolonged cortisol release. Shockingly, this decrease in DRD2 expression is correlated to social status and poverty.

Although brief, this may give a little insight into why some people are more prone to become addicted. There are real neuroanatomical and neurochemical differences caused by both nature and nurture. The more we find out about the differences, the more likely we are to design drugs and develop therapies to help alleviate the difficulties faced by those suffering from addiction. Moral of the story – don’t be quick to judge those who are “hooked” – stresses, genetics, life style choices and chemicals in the brain are all involved in why they continue to pursue their habits the extent they do.

References

Bressan, Rodrigo A., and Jose A. Crippa. “The role of dopamine in reward and pleasure behaviour– review of data from preclinical research.” Acta Psychiatrica Scandinavica 111.s427 (2005): 14-21.

Clarke, Toni-Kim, et al. “The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction.” Annals of human genetics 78.1 (2014): 33-39.

Compton, Peggy A., et al. “The D2 dopamine receptor gene, addiction, and personality: clinical correlates in cocaine abusers.” Biological psychiatry 39.4 (1996): 302-304.

Comings, D. E., et al. “The dopamine D2 receptor (DRD2) as a major gene in obesity and height.”Biochemical medicine and metabolic biology 50.2 (1993): 176-185.

Fattore, Liana, and Marco Diana. “Drug addiction: an affective-cognitive disorder in need of a cure.” Neuroscience & Biobehavioral Reviews 65 (2016): 341-361.

Fattore, Liana, et al. “Role of opioid receptors in the reinstatement of opioid-seeking behaviour: an overview.” Opioid Receptors. Humana Press, New York, NY (2015): 281-293.

Koob, George F., and Michel Le Moal. “Drug addiction, dysregulation of reward, and allostasis.”Neuropsychopharmacology 24.2 (2001): 97.

National Institute of Drug Abuse, 2014, Drugs and the Brain. Found at: https://www.drugabuse.gov/pubs/teaching/largegifs/slide-9.gif

Shuttershock: Artificial Synapse Bridges the Gap to Brain to Artificial Computers. Found at: https:// singularityhub.com

Talkin’ the talk: better than walkin’ the walk?

Have you ever stood back and tried to imagine a world without language? A world, not just without spoken speech, but without written text and also without that little voice in your head which is constantly thinking in words. Have you ever tried to make a conscious effort to try and turn off that voice in your head when you cannot sleep, or are stressing about something? Or tried to give someone the “silent treatment” when they’ve pissed you off? Or glanced at written text in your native language and tried NOT to start reading it? Many people find these basic tasks much more challenging than they would originally seem for one key reason- the immense strength of the innate disposition humankind have, to learn and interact using language. Key brain areas essential for these language functions are ingrained to be active from day 1. Incredibly, a human embryo can distinguish vowel sounds in utero. Even individuals who are born death use equivalent brain regions for sign language communication. 

Language is one of the only qualities that is truly unique to humankind. No other animals have the ability to communicate in such an expressive and articulate manner. Although dogs and monkeys may understand simple words such as “sit” or “walkies”, there is a long jump between that and the sorts of communication we are capable of. Even if a meaning of a word is known, the complexity of our language means that we have to be able to adapt the meaning depending on the context. In fact, this may be the one thing which enabled us a thrive to dominate so many other species. Not only can we communicate to work together to catch prey or warn others of predators, we can also chat, debate and gossip about concepts which are completely imaginary and man-made entities such as religion, separate provinces, royalty or the economy. 

But what is it that makes us, firstly, able to perform the intricate and complex task of communication and secondly, what gives us the such strong urge right from the day we were born to want to learn and use this skill?

To try and understand this, first we need to delve into how the brain comprehends, processes and articulates language. 

The Chatty Left Hemisphere

Pierre Broca was a leading figure in the field of linguistics, performing a series on examinations on stroke victims who had suffered damage to particular brain areas, altering their ability to articulate fluent sentences. He cottoned the famous phrase “on parle avec l’hemisphere gauche”- one speaks with their left hemisphere: and this is true in 97% of people (interestingly, the remaining 3% are far, far more likely to be left handed). He identified “Broca’s area” in 1861, of the left brain hemisphere, an area seeming highly responsible for the coordinating all the required micro-movements needed to form fluent language. Stroke patients with damage to this area were able to understand speech but found it extraordinary difficult to respond, often only managing a few disjointed words- this condition was termed Broca’s aphasia. However, the brain has a remarkable ability to adapt, and dedicated practise over time was able to restore at least some language function in these patients. 

Language function is predominantly in the left side of the brain in a healthy individual (left pictures) but can recover after damage to these areas (right) in perinatal stroke victims

The 1960s was a time when, if you suffered with severe epilepsy, a commonplace and often devastating surgery, severing connections between your left and right hemispheres, would be performed, supposedly helping to stop the “flow of the fit” between both sides of the brain. Roger Sperry performed a series of famous studies on such epileptic patients who lacked the connections between the right and left brain hemispheres. Patients were blindfolded and presented with an array of distinct household objects, which they were asked to blindly feel with their left and right hands separately.  Sensory inputs from the right hand flow up the arm, across to the opposite side of the spinal cord, and run into the left side of the brain. The objects felt with the right hand, therefore, could be eloquently identified and named with ease e.g. a ball. However, when feeling with the left hand, the inputs from which would be received by the right brain, the descriptions were either completely absent or were mostly indirect, disjointed associations e.g. “round thing”. 

Roger Sperry’s simplified model of brain lateralisation, created from experiments with “Split Brain” epileptic patients, 1968

More recent work has demonstrated that the entire language system is an extremely complex network of multiple brain regions which is different for each individual. The idea that it was solely lateralised to the left hemisphere of the brain, was primitive, but a solid model to start. However, these basic principles suggest a common innate pattern is genetically encoded for and laid out in development, but is plastic and adaptable depending on environmental conditions. So what is it about our unique development that has built our brains with such elaborate tools and building blocks needed to develop this advanced and useful skill?

The language gene – FoxP2

It was Hurst in 1990, who first described a family known as the “KE family” – a family with an inherited language disorder. This family appeared to be affected by a genetic mutation which could be passed, dominantly, from parent to child and resulted in severe speech and language problems, with children unable to pick up and produce language. This was coupled with low performance IQ, developmental delay and brain abnormalities. 

The pattern of effected individuals in the KE family: a family suffering from an inherited speech disorder

Later, it was discovered, via genome studies, that this gene was the FoxP2 gene. When this gene is active, it is able to bind to the DNA and ultimately dampen down expression of over 100 different genes in key brain regions involved in the motor coordination of creating language. In the long sequence code for this gene, it was just a one letter change that caused catastrophic effects on the childhood ability to produce and understand language. The single change renders the FoxP2 protein unable to bind DNA efficiently and this has knock-on effects on the 100 other genes also influenced by FoxP2. The fMRI brain imaging of these studies showed that the lateralisation of language function had disappeared and whereas in an unaffected individual, Broca’s area clearly and independently lit up in response to a mental verb task, the affected individuals had multiple and disordered over-activity. 

The lateralisation of the language system in healthy (left) is disrupted in members of the KE family suffering with the inherited speech disorder (right)

FoxP2 in other animals

Mouse pups will make ultrasonic vocalisations when removed from their mother

What is remarkable about this properties of this gene is that it is strikingly conserved throughout many other species – yet, it is minuscule differences between species render them relatively inarticulate. For example, the mouse FoxP2 has 3 DNA bases different from the human FoxP2. But if you make a genetically modified mouse, in which the mouse FoxP2 has been replaced with the healthy human isoform, these mice have significantly increased number and plasticity of neural connections in key vocalisation areas of the brain. The ultrasonic vocalisations, for example the cries pups make in response to being removed from their mother, also increase in frequency. But, if you put the KE family’s damaged gene into mice it causes motor impairment and severe alternations in ultrasonic vocalisations, damaging pup-mother relationships. 

When did language start? 

Depiction of a Neanderthal

In 2007, the “modern speech gene” was found in the Neanderthal’s genome. Whether Neanderthal’s had mastered the art of language is a hotly debated topic. Considering modern day humans have about 1-4 % Neanderthal DNA, it would suggest they were capable of at least some, if primitive, type of lingual interaction. Issues with extraction of such ancient DNA and the fact that language is so multi-factorial means that the fact they possessed the humanised form of the gene does not prove they had language as we know it. However, it definitely makes the concept a viable option.

It is highly likely that FoxP2 is just the tip of the iceberg, especially when you consider that there are more than 7000 languages around the world, each with its own set of rules, rhythms and rhymes. This really allows you to marvel at how amazingly complex, but also how flexible, the language system is in your brain, with all the intricate components wired together and interlaced just so to allow you to gossip, chat, fret, argue, debate and get heard but also to listen, learn, read and develop. 

Magic mushrooms – medicinal as well as mystical?

Maybe when you think of magic mushrooms, you may picture a stereotypical scene consisting of a haggle of “flower-power” hippies sat round a camp fire, away with the fairies. What is typically thought of as a bit of fun for the more adventurous and promiscuous in society, is now being seriously studied for the treatment of crippling mental health disorders. The full potential of the mind-boggling power of these naturally occurring fungi to increase spirituality, connectivity, creativity and to reinstate a sense of purpose and meaning is beginning to be realized and may shortly be unleashed as a legal and viable therapy for a monopoly of different disorders. 

Prehistoric cave paintings depicting magic mushrooms at Salva Pascuala, Spain. Credit: Juan Francisco Ruiz López

Humankind across the world have co-evolved with magic mushrooms, with prehistoric cave paintings depicting these fabulous fungi dated back to over 10,000 years ago in North Africa, but also evidence of their use in ancient tribes of Spain, South America and Central America. Despite this extensive history, the civilized Western world only was introduced to mushrooms in 1957, when Life magazine published an article, “Seeking the Magic Mushroom”, an enrapturing depiction of the experience of Robert Wasson had when participating in a spiritual ritual traditional of the Mazatec people, the indigenous people of Mexico. 

Magic mushrooms, alongside other compounds such as LSD were grouped into a new category of drugs, those that were “mind-manifesting”. In 1956, these were named “psychedelics” by grouping the two Greek words “psyche” (mind or soul) and “delos” (to manifest). The active component of magic mushrooms, a substance known as psilocybin was identified by Albert Hoffmann, the same man who had previously described the psychoactive properties of LSD. The psychedelics all function by acting at receptors in the brain that are activated by the “happy chemical” – serotonin.  The powerful ability of psychedelics to refashion states of consciousness and to enhance the sensation of meaning was unlike the effects of any other drug previously described in modern medicine. Scientists and doctors, alike, were quick to realize their therapeutic potential for mental health disorders and “psychoactive therapy” was commonplace the 1960s, offering hope to tens of thousands of patients. 

Women protesting the Vietnam War, Washington DC, 1968. Credit: AP/State Department

If the research that began in the 1960s was permitted to bloom, who knows where we would be now in the field of psychedelics as medicines? However, President Nixon had other ideas. Not only were psychedelics contributing to the rising anti-Vietnam war movement, they were instrumental in women’s rights, anti-racism and anti-violence movements. Nixon signed the Controlled Substances Act in 1970, and psychedelics loaded into the barrel of Schedule I drugs, along with amphetamines, opioids and narcotics. The irrational, unjust and discriminating “War of Drugs” began. As Ehrlichman, Nixon’s public health policy adviser stated:

President Nixon, 1972

“We knew we couldn’t make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did.”

Mental health statistics, House of Commons, 2014

Consequently, and maybe devastatingly for the prognosis of those suffering with mental health disorders, all research and medicinal use of psychedelics was put on hold for 30 years. In the meantime, mental health disorders, such as depression and anxiety, poised an ever-increasing burden on society. Rates escalated consistently to reach current levels; 1 in 4 people suffering with a mental health disorder at some point in their lives. SSRIs remain the first-line drugs, but they are ineffective, with only 40% of those suffering with major depressive episodes ever achieving remission from their symptoms, as well as possessing strong side effects and a prolonged time-lapse before improvements are made. It is obvious that alternative therapies must be sort after.

Credit: OceanBreezeRecovery.org

Luckily, research into psychedelics began to be rekindled in the late 1990s and have been shown to be effective, when used in clinics alongside counselling, to treat addictions, OCD and anxieties commonly observed in critically ill cancer patients. Recent trials, at Imperial College have demonstrated strong evidence to suggest the utility of just a single dose to treat patients suffering with major depression, that had previously been untreatable. Although these are very primitive studies, all but one of the participants had a significantly reduced depression score 5 weeks after the single administration. 

But how does psilocybin elicit such anti-depressive effects? 

The ability of psilocybin, when administered in this supportive clinical setting, to enhance a sense of purpose and to elicit a spiritually significant experience is staggering, with up to 86% of patients describing it as one of the most meaningful experiences of their lives in a magnitude of studies. This enhancement of consciousness, addition of multiple mystical dimensions and amplification of perception contrasts drastically with the way that traditional anti-depressants seem to flatten the experience of the world, masking the underlying pain. Could psilocybin be a way of forcing patients to come face-to-face with their inner demons and the root of the pain, allowing them to target the underlying problem, rather than hiding it behind a fog which will inevitably clear one day? This was achieved by just a single dose – and the lasting enlightening effects have been described as an “after-glow”. 

The Imperial college research group also performed brain imaging, using fMRI scanners, which are able to identify the regions of the brain which are most active, by looking at the blood flow. They observed drastic differences after treatment with psilocybin in many regions of the brain. For example, the amygdala. The amygdala is sometimes termed the emotion centre of the brain, as a reflection of how its activation is involved in sensations of intense emotion, such as stress responses, fear and anxiety. The amygdala is commonly over-activated in depressive patients but its chronic high activity was significantly decreased after pscilocybin treatments. Maybe this is the start of an era where we can draw the dots between the seemingly separate worlds of spirituality and science. 

The effects of a single dose pf pscilocibin on blood flow to brain regions – does this link to the intensity of the experience? Credit: Robin Carhart-Harris et al. 2017

But what about the use of pscilocibin for those who do not suffer mental health disorders? 

Modern day society is a world in which we do not struggle to survive as we are constantly comfortable, fed and watered. The apparent ease of our lives is not reflected by a matched ease in our brains, however. We consistently set ourselves unachievable goals, strive to meet societal and live in an increasingly socially isolated fashion. The ever-dwindling belief in spiritual entities contributes to the lack of true meaning in our lives we all sometimes feel. Microdosing: that is, taking fractions of the dose required for hallucinations, has been shown to increase creativity, empathy and sense of purpose in healthy individuals, reducing self-criticism and focusing the mind on the amazing external inputs we receive on a day to day basis, but now all take for granted. Are you ever amazed by the absolute raw excitement and anticipation young children have when encountering the world? We lose this as we mature into adults, but maybe microdosing can bring back some of the true child-like joy and appreciation of the world around us. 

Due to the 30 year brake that was put on this research, these findings are still in their infancy. The diversity of the conditions that psilocybin has been used to improve is impressive. As it is ever-increasingly becoming clear that our mental and physical health is entwined in complex and intimate ways, this raises the question of whether psilocybin could offer hope for other health conditions, previously viewed as disparate from our brains, such as allergies or chronic pain? Maybe, or maybe not, but for mental health, a field of medicine in which the research seems to have been stagnant for so long, there may be a ray of hope on the horizon. 

References

Anderson, Thomas, et al. “Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers.” Psychopharmacology 236.2 (2019): 731-740.

Carhart-Harris, Robin L., et al. “Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.” Scientific reports 7.1 (2017): 13187.

Carhart-Harris, Robin L., and Guy M. Goodwin. “The therapeutic potential of psychedelic drugs: past, present, and future.” Neuropsychopharmacology 42.11 (2017): 2105.

Fabulous fibre: a rock “salad” foundation for your diet

 We’ve all heard it countless times before: eat your 5 a day, swap the whites for the browns, fill your cupboards with whole-grains and, whilst we’ve at it, why not swap the crisps for a handful of nuts? But, despite the relentless tips put out in the media or splurged all over your newsfeed, less than 10% of the UK adult population reached the recommended 30 g/day fibre intake in 20161. Considering that not getting adequate amounts of fibre increases overall mortality by a whopping 20-30%, I would say this is a pretty big deal. Study after study have highlighted the role high fibre diets have in preventing cardiovascular disease, stroke, coronary heart disease, Type II diabetes and colorectal cancer2. Fibre is unquestionably a key component of a healthy human diet and low fibre intake observed nationwide could be potentially contributing to the massive metabolic disease crisis.

But how does this fabulous fibrous lifeline work? 

Fibres feed our friend – the gut microbiota

Each and every one of us has a massive biodiverse ecosystem thriving in our intestines – the gut microbiota. To put the diversity and expanse of the gut microbiota into some context; each human has approximately 23 thousand genes, whereas the typical gut microbiota found in just one human being contains a whopping 3 million genes.

Real live imaging of the gut microbiota – Tolhini et al., 2017

Of course, these genes are not without effect, and contribute to our health enormously – in particular, our metabolism, physical fitness and energy levels. Discrepancies in the gut microbiota profile have been correlated with many disease states, including mental health, neurodegenerative disorders, inflammatory disorders and obesity3.  

Fibre is made up of complex rope-like structures that are bound together in a meshwork. Our lowly human digestive system is unable to break down this highly-resistant structure alone using traditional enzymes that are produced endogenously in humans. Instead, we need to call upon the help of the gut microbiota to provide the machinery needed to digest fibre-rich foods. As a by-product of these break-down reactions, small metabolites known as short chain fatty acids (SCFAs) are produced. These SCFAs consist of acetate, propionate and butyrate, all of which have a range of actions that positively impact physiology. The desirable action of SCFAs is highly dependent on the complex interplay between the gut microbiota composition and the diet. A healthy, diverse gut microbiota, which provides you with SCFAs in plentiful supply, needs you to provide it with fibre so it can continue to thrive. If you don’t provide it with the fuel it needs, it will start breaking down the protective mucus layer of your gut, leading to inflammatory diseases such as IBS. You get what you give in this world. 

So, SCFAs, what’s the big deal? 

The gut is the key sight of SCFA biogenesis, so the neighbouring cells lining the gut have immediate access to this supply. This exposure helps the gut cells weld themselves together more tightly, reducing the “leakiness” of the gut and stopping you absorbing unwanted toxins, inflammatory mediators and even excess nutrition. However, SCFAs also enter the blood circulation, spreading them throughout the perimeters of the body and allowing them to impart a whole magnitude of benefits.

How do SCFAs benefit your body? 

Number 1: SCFAs actually change which genes are expressed

Although each and every cell in your body, excluding gonad (sex) cells, contain exactly the same genetic code, they appear different and perform divergent and specialised functions. This is only possible because each cell type can “choose” which genes to express and which to silence. However, this is not a static process, and fluctuations in the signals from the surrounding environment can alter the expression levels of genes- this is known as epigenetics. One of the mechanisms by which this happens is by proteins named HDACs. They remove small carbon based groups (acetyl groups) from the histone proteins associated with DNA. The DNA in our cells is coiled, folded and tied up with histone proteins in a complex mesh, but adding or taking away acetyl groups gives an element of control of how tightly associated the strands are, and subsequently affect the likelihood of whether the gene will be switched on or off. 

Image of a human colon, S. Sculler 2019

It has been shown that butyrate, and, to an extent, propionate, can enter cells and inhibit HDACs, stopping them from removing the acetyl groups. This ultimately changes expression of many genes, some of which are key to governing metabolism. For example, in the colon butyrate alters the expression of genes involves in transport of fats, fatty acid metabolism, energy metabolism and proteins involved oxidative stress, a condition often associated with inflammation and metabolic disease2.  Additionally, butyrate increases the expression of a gene known as pyy, which codes for a peptide hormone secreted by the gut in response to a meal. PYY enters the circulation and can also modulate signals to the brain via the vagal nerve, promoting satiety and inhibiting appetite4.

Number 2: SCFAs can act as messengers, producing many signal responses

In addition to direct modulation of gene expression, SCFAs are actually able to signal via other mechanisms. Proteins; FFAR2 and FFAR3; on the surface of certain cells are receptive to SCFAs, and elicit signalling cascades when associating with them. In gut endocrine cells, these signalling cascades lead to the release of PYY, GLP-1 and other satiating gut hormones that act in key brain areas to inhibit appetite4,5. These hormones also slow the gut motility, allowing the feeling of fullness to be prolonged. FFAR3 is expressed throughout your sympathetic nervous system – the one which governs the “fight or flight” response requiring a high metabolic output (preparing your body to run from a lion or fight with a bear) – and thus, acts to balance energy expenditure and increase insulin sensitivity6. FFAR2 is expressed in adipose tissue, and, when activated, encourages the usage of fat instead of glucose as the fuel to power your body6. These effects promote a lean phenotype and protect against diabetes. 

So where can you find this fibre-rich goodness? 

Although “carbs” have been bad-mouthed relentlessly in society, fibre is a form of carbohydrate. Bread, pasta, rice and chips are the typical foods you may think of immediately when considering carbs. However, carbs are also found in fruits, nuts and vegetables. Even the wood making up tree trunks is predominantly cellulose – a carb. Next time you hear someone stating grandly they are “cutting out carbs” it may be useful to inform them that includes broccoli, celery and basically any type of vegetable or salad. However, be wary, many highly-processed foods claim to be rich in fibre, but are also very high in refined sugars and have had many beneficial components of the original grain stripped away. To get the recommended amount of fibre a day, you would have to eat 13 pieces of Hovis’s “wholemeal” brown bread – maybe not such a wise idea. On the other hand, getting your 5 a day is a healthier (and more pleasant) method of ensuring you hit your fibre targets. Really, you should aim to consume the natural whole grains, vegetables, nuts and fruits we evolved as a species to survive as this also provides you with many essential vitamins, minerals, antioxidants and polyphenols.

1. Roberts, Caireen, et al. “National Diet and Nutrition Survey: results from years 7 and 8 (combined) of the Rolling Programme (2014/2015–2015/2016).” (2018). 

2. Reynolds, Andrew, et al. “Carbohydrate quality and human health: a series of systematic reviews and meta-analyses.” The Lancet 393.10170 (2019): 434-445. 

3. Anderson, James W., Belinda M. Smith, and Nancy J. Gustafson. “Health benefits and practical aspects of high-fiber diets.” The American journal of clinical nutrition 59.5 (1994): 1242S-1247S.

4.. Shreiner, Andrew B., John Y. Kao, and Vincent B. Young. “The gut microbiome in health and in disease.” Current opinion in gastroenterology 31.1 (2015): 69.

5.. Larraufie, Pierre, et al. “SCFAs strongly stimulate PYY production in human enteroendocrine cells.” Scientific reports 8.1 (2018): 74.

6.. Tolhurst, Gwen, et al. “Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein–coupled receptor FFAR2.” Diabetes 61.2 (2012): 364-371.

7. Kimura, Ikuo, et al. “Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41).” Proceedings of the national academy of sciences 108.19 (2011): 8030-8035.

8.. Ge, Hongfei, et al. “Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids.” Endocrinology 149.9 (2008): 4519-4526.