Zap Your Brain with Transcranial Magnetic Stimulation

Have you ever wanted to stimulate some part of your brain, only to be thwarted by that pesky skull ensconcing it? Don’t want to drill holes and implant electrodes? Well lucky it’s the 21st century so now you don’t have to. Let’s take a dive into the weird science of transcranial magnetic stimulation.

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The Neuroscience of Juggling

Over the past few years a slew of news outlets have been singing the cognitive benefits of learning to juggle. If one is to believe the hype, this ancient circus activity will increase your brain powermake your brain bigger (permanently, no less), and may even prevent Alzheimer’s disease. Dang.

Can there be any truth to these heady claims, or is it another case of the media committing that most egregious of sins: distorting science for the sake of a catchy headline? Here we plunge into the literature and investigate what has actually been shown experimentally.  Continue reading

How to Improve your Crappy Memory – With Evidence!

It’s a fact universally acknowledged that physical fitness can be trained, and that this is a healthy and clever thing to do. What is less often considered is that mental fitness can also be trained. And luckily for us, we live in an age when we have the science to point us in the right direction!

Before we dive into the following techniques, it’s worth pointing out that learning is really just the process of acquiring memories. As such, some of these tricks will address the acquisition phase of memory (learning), and others will address the retention phase (remembering). Learning a physical skill involves a similar neurological process to learning information, so that might come up too.

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Pixar’s Inside Out: children’s films, moral psychology and neurospirituality

My mum likes to remind me how, as a little kid, I cried in the movie Bambi when Bambi’s mother gets killed by the hunter. Looking back, it feels like it may have been one of my most salient developmental moments. Bambi was a kid just like me, a massive mummy’s boy just like me, and I probably didn’t have much of a concept of death up until that point. Maybe Bambi was the very first time I realised that loved ones don’t stay with us forever.

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Shortly thereafter The Lion King came out, and because of my brother’s massive obsession, I was dragged to see it at the cinema three times. It’s hard to mount a compelling defence for staying home alone when you don’t even have armpit hair to back you up. For all my protesting though, the movie touched me deeply. I hated the dastardly Scar. I probably cried every single time I had to watch young Simba hopefully nudging the lifeless body of his father. (I recently re-watched The Lion King for the first time in over a decade, and I still cried when Mufasa died. Whatever. It’s sad!)

Seeing animals lose parents is distressing, and so is seeing evil triumph over good. These are very simple moral messages that anyone can relate to, even prepubescent kids. We’ll return to this point shortly.

Fast forward to 2015, and the latest children’s blockbuster is Pixar’s Inside Out. If you haven’t yet seen it yet, bookmark this page and go watch it ASAP. It received a rating of 98% on Rotten Tomatoes, plus it’s Pixar so you already knew it would be good. Also, spoilers be coming.

The film follows the development of an American girl named Riley from birth until the age of 11. That sounds kind of dull, and it possibly would be if it weren’t for the twist: Riley is only a surrogate protagonist. The real action takes place inside her brain, where a bunch of anthropomorphised emotions – Joy, Sadness, Fear, Disgust and Anger – caper and banter and ultimately control all of Riley’s thoughts via a “cognition” control panel.

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The gang at the control panel: Anger, Envy, Joy, Fear and Sadness

The film colourfully explores other aspects of Ripley’s cognition such as memory formation and loss, abstract reasoning and dreaming. The narrative is delightfully engaging, but the most significant aspect of Inside Out is an implicit message it carries which is both surprisingly scientifically accurate and spiritually profound, as well as representing a major advancement in the broad moral history of children’s films. Before we get to what it is –

The broad moral history of children’s films

There are many ways in which humans are socialised and morally wired during their developmental years. Obvious influences include school, parents and religious teachings. However, it’s possible to overlook the significant role played by stories, including those told in TV shows and movies. Humans are powerfully predisposed to respond to stories. This is why they are heavily exploited in marketing and may account for why one death can be a tragedy when a million is just a statistic. The stories told in movies, and their moral messages, may truly affect people’s long-term world views.

For example, I grew up on a diet of Bambi, Captain Planet and Pokemon. These days I’m a vegetarian environmentalist with a weird compulsion for collecting sets of things. Coincidence, or something more significant?

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Could they be any less subliminal?

If it’s true that children’s films can have a meaningful impact on moral development—and admittedly this is extremely difficult to demonstrate experimentally—then we might have more cause for optimism about the upcoming generation than we realise.

The popular children’s films of the past few decades (almost of them Disney) are extremely diverse in the situations and moral issues they address. Compare Sleeping Beauty with Peter Pan, The Little Mermaid with Aladdin, etc). For all their diversity though, a few underlying themes stand out to me as pretty much constant:

  1. There is a clear delineation between good and evil characters. There is never any doubt that Captain Hook, Ursula the Sea Witch and Jafar are baddies. They look evil and everything they do is evil. A motive isn’t necessarily needed for being a baddie; some characters just are that way.
  2. Old timey gender roles. This one is a bit obvious since movies are products of their times, but it bears consideration nonetheless. A heterosexual romance is almost always involved, it’s generally a male protagonist who saves the day, and it’s always happily and monogamously ever after.

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Along with a slew of other moral values such as individualism and self-reliance, these are the messages that the previous generations grew up hearing. And, these are the generations now controlling governments and institutions the world over: governments that base foreign policies on a concept of evil baddies, and institutions that fail to see the justice in marriage equality.

Something happened in the past decade though to take children’s film morality in a radically new direction, and that something is largely Pixar. Check out the following major releases:

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The issues explored in these films are so much more complex than those of 20th century Disney, it’s hard to overstate it. Compared to narratives based on good defeating evil and old timey gender roles, consider the messages these films might be sending:

WALL-E

Humans run the risk of rendering Earth uninhabitable, mindless consumption strips people of their humanity, artificially intelligence machines may one day possess every bit as much humanity as humans do—or conversely, they might enslave us through an innocuous mistake in their programming (see: the paper-clip maximiser and Wait But Why’s The AI Revolution)

Up

Even in the best case scenario of marriage and happily ever after, there will still be hardships such as miscarriages and death, if you’re not careful it’s possible to go your whole life neglecting to ever pursue your dreams, old people can also do interesting things, scientists tend to get tiresomely hung up on their life’s work

Frozen

Even loving healthy relationships can deteriorate because of personal burdens, there is such thing as moral ambiguity! (people can have reasons and experiences that lead them to destructive behaviour), there are also charismatic sociopaths to watch out for who can seem benign at first, girls can save the day just fine without the help of a prince

And now along comes Inside Out, taking things to a whole new level again by exploring one of the deepest moral and existential issues there is: neurospirituality.

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The neurospirituality of Inside Out

If you’ve never heard of neurospirituality before, it’s essentially an ever-expanding intersection of agreement between the radically unrelated fields of neuroscience and spirituality. It considers the neuroscientific basis of spiritual experiences such as meditation and contemplation of the Self. The term neurospirituality seems to have been coined in this 2005 journal article, which predictably and annoyingly is hidden behind a pay wall (but that’s a conversation for another day).

It turns out that neuroscience and spirituality are by no means as incompatible as one might assume. Both seek to understand human consciousness—that voice in our head that we call our “Self”. One discipline does it externally and experimentally, while the other does it internally and experientially. To find out what the neurospiritual view of Self is, there may be no easier and more enjoyable way than by watching Inside Out.

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Long-term memory: damn daunting when you see the scope of it

The film repeatedly cuts back and forth between Riley in the physical world, where she plays and interacts like any normal child, and the inside of her brain, where we see that her every thought and emotion is actually triggered by some anthropomorphised emotion pulling a lever or fiddling with a memory. All the emotions and other characters inside her brain have unique personalities and interests which frequently conflict and undermine each other.

Early in Riley’s life, Joy manages to hold sway over the other emotions and Riley’s infancy is consequently mostly happy. As Riley matures and things start to go wrong in the physical world though, emotions like Sadness and Anger wrest more time for themselves at the control panel of her consciousness. This directly directs Riley’s feelings and behaviours. In addition to all this, dream monsters and imaginary childhood friends get up to trouble in other parts on her brain, and mischievous maintenance workers in her long-term memory repeatedly trigger an annoying ad jingle, setting Riley to humming the jingle in the real world.

Let’s consider these plot devices from both the neuroscientific and spiritual angles.

The neuroscientific angle

The science in Inside Out is excellent, and was achieved by Pixar following in the footsteps of Interstellar and conferring with actual scientists in storyboarding the film. This is a practice we will hopefully see a lot more of in the near future.

Every day of Riley’s life, hundreds of memories form. When she goes to sleep at night, these memories are siphoned away and either stored in her labyrinthine long-term memory or discarded into a pit of forgetting. This accurately reflects the critical role that sleep plays in memory consolidation. Even memories that make it to Riley’s long-term memory aren’t safe indefinitely, as old ones that she stops caring about gradually fade to grey and get dumped, just as in a real brain. In one giggle-inducing moment, several containers of facts and opinions get knocked over and jumbled together, something we probably all do more often than we care to admit.

An interesting decision was to depict Riley’s emotions as gendered: Joy is female, Fear is male etc. While the producers surely couldn’t have known this at the time, a landmark brain imaging study just published found that “human brains are comprised of unique ‘mosaics’ of features, some more common in females compared with males, some more common in males compared with females.” I.e. most people’s brains really are mishmashes of typically male and female parts, regardless of their biological sex. Whichever part of the brain is responsible for fear (and it may not be the amygdala after all), it’s now completely plausible that an 11 year-old girl could have a ‘male’ Fear character.

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Not all the brain’s workings in Inside Out are depicted entirely accurately. Perhaps most misleading is the portrayal of memories as self-contained and immutable¹, rather than conceptually linked and constantly being rewritten. But Inside Out fundamentally aims to be a fun children’s movie, and by that metric the science is superb.

For all its cute and clever explorations of cognitive processes, Inside Out‘s most profound message is this: there is no single ‘Self’ controlling Riley’s consciousness. There is no ‘Riley’ inside her own head, no character that could be described as her will or volition. Riley’s mind is a plurality. Thoughts, feelings and memories pop up because one of the characters in her brain decided unilaterally to make it happen. And this is exactly how neuroscience thinks the brain works.

Do you feel like a unified Self? If so, you might like to read about some experiments that have been conducted in patients with the two hemispheres of their brain severed, so-called “split-brain” patients. In these subjects, it appears that the two halves of their brain can process information independently, have separate desires, and even reach moral judgements differently. If this is how the brain works, which one is the real ‘you’? Or consider this Nature article, which concludes that “different mental processes are mediated by different brain regions, and there is nothing to suggest the existence of any central controller”. All of our minds are pluralities with no core Self to be found.

While this may seem an uncomfortable concept, what does spirituality have to say about the matter?

The spiritual angle

According to spiritual teachings stretching back 2500 years to the time of Buddha, the Self (that thing in your mind that feels like ‘you’) is an illusion. It is actually a stream of spontaneously arising thoughts and feelings that your mind clumps together and erroneously interprets as a unified persisting identity.

While the growing accessibility of scientific ideas to the general public has been a wonderful advancement for humanity, one distasteful side-effect has been New Agey spiritualists co-opting and misrepresenting these ideas. In the case of neurospirituality though it’s the other way around: science is co-opting a spiritual concept, or at least happily supporting it.

One of the three core tenets of Buddhism is No-Self, a believe which, as we’ve just seen, has been supported by the latest neuroscientific findings. As noted by Quartz, “Some scientific researchers have recently started to reference and draw on the Eastern religion [Buddism] in their work—and have come to accept theories that were first posited by Buddhist monks thousands of years ago.”

Think about that. Way before a single living human being had any clue that heliocentricity or DNA or neurons or sporks could be things—back before anyone even knew that the freaking planet was round—Buddha was relaxing under a tree pointing out a neuroscientific truth that it’s taken us until now to confirm.

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“No biggie, you’re welcome.”

(Interestingly, the other core tenets of Buddhism are Impermanence, which agrees eerily well with quantum mechanics and Suffering, perhaps better translated as “lack of lasting satisfactoriness”, which recapitulates the observed psychological phenomenon of the hedonic treadmill. Either Buddha landed some crazy lucky guesses, or there really must be something to meditation huh?)

So, with children’s cinema kicking off in 1937 with Snow White, which features a cheery outlook on what would today be deemed sexual assault, almost 80 years later we’ve arrived at Inside Out, which explores the profoundest neuroscientific and spiritual insights yet achieved by humankind.

The social significance

While this may be well and good, an obvious question is: will children even be able to understand it? The concept of an absence of Self is, after all, supremely unintuitive and difficult even for highly educated adults to grasp. Will children be able to draw the connection between Riley’s haphazardly emergent consciousness and their own?

One of the psychologists who advised the creators of Inside Out gives a touching example of just such a case:

“I got an email from a mom who took her highly functioning autistic boy to the movie, and seeing the movie was the first time that this young guy had insight into his emotional difficulty. He said: “Mom, I know I have anger, fear, and disgust, but I really struggle with sadness and joy—I don’t know where they are.” And she said it was their breakthrough moment.”

It would be fascinating to find out how many children interpreted the film so literally or found similar personal relevance in it. If you too have a child who has seen Inside Out, please leave a comment below about their response.

Finally, what would the ramifications be of a society that broadly understood and accepted the truth of No Self? Well, a lack of Self is very closely related to concepts such as determinism and there being no such thing as free will, so we may see an upsurge in these beliefs. While many people find such ideas superficially scary, public figures such as Daniel Dennett and Sam Harris have argued elegantly for why they needn’t be: Even if you were always destined to do every single thing that you do done, it still feels as though you’re in control. You can still act, plan, exercise compassion, learn etc. There’s no reason to resort to apathy or fatalism.

One likely policy shift in such a society would regard the criminal justice system. A lack of free will removes any rational justification for shaming or punishment, at least on moral grounds². The justice system could form policies based of pure pragmatism: how can we most effectively deter crime? Given the predispositions of this or that criminal cognitively, is rehabilitation and reintegrate into society possible? If so, how can it most effectively be achieved?

*       *       *

One children’s film won’t single-handedly launch a spiritual and cultural revolution. But shifts in values and world views can and do gradually occur with the changing moral zeitgeist. And with such excellent influences as WALL-E, Up, Frozen and Inside Out becoming increasingly commonplace (especially amongst little humans who are still compiling their moral frameworks), it’s hard not to get a tiny bit excited for the future of civilisation.

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¹In Inside Out the main emotion associated with a memory can change, but the details of the event seem to be kept constant

²This doesn’t mean punishments wouldn’t still be used, but that the rationalisation would be different, and likely also the execution. Punishment would only be seen as justified or useful insofar as it influenced future behaviours.

All Your Favourite Drugs Exist Thanks To… Insects?

Well, maybe not your *favourite* drugs, depending what you’re into. But it’s true: the existence of many of the most popular drugs on the planet can be traced directly back to insects.

This includes nicotine, cocaine, possibly cannabis (with a fuzzy asterisk), and of course the most widely used psychoactive substance in the world: caffeine.

Coffee is the second most highly traded commodity globally, losing out only to crude oil. 500 billion cups are consumed every year – an average of 70 cups for every man, woman and child. As a species we’re junkies for it.

Pretty much everyone everywhere.

So why are psychoactive compounds, A.K.A. drugs, so appealing? The answer lies in how they work. Once inside our bodies, psychoactives slip mischievously inside our brains and start fiddling around with the control panel. Different psychoactives fiddle in different ways, but something the popular ones all have in common is that they tend to crank up the happiness dial.

Many of these popular drugs, from caffeine to cocaine, were invented by plants. But why did they do this? Plants don’t have happiness knobs to be twiddled by drugs, and they’re definitely not just out to give us humans kicks. And how do insects come into the picture?

To properly understand this tale, we’ll have to travel 450 million years back in time, trace the progression of a brutal conflict that has claimed more lives than the entire history of human warfare, and finish by shrinking down to gaze at the very foundations of consciousness itself.

Hold on tight, it’s going to be a bumpy ride.

In the Beginning…

The majestic Planet Earth, 450 million years ago in the late Ordovician period:

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Well, something like this. Maybe.

The first multicellular organisms to blob up onto land were sluggish low-lying plants that looked pretty much like modern day mosses and liverworts. And for a while, that’s all there was.

For those stunted critters, this brave new rocky world above the roiling sea must have seemed an idyllic paradise. Vast stretches of land awaited colonisation, the air was heady with CO2, and there wasn’t a predator to speak of. Alas, it wasn’t to last.

When we hear the word “herbivore”, we usually think of sizable mammals like cows and rabbits and giraffes. But plants have a far more ancient, insidious, and destructive foe. More than 200 million years before evolution wobbled out its first half-arsed proto-rat, there were insects.

By raw numbers, insects are the most successful branch of life of all time, boasting an estimated 6-10 million species. Four “super-radiations” have been particularly virile: beetles, moths, wasps and flies. These types of insect alone make up the majority of animal life on Earth.

Back in the Ordovician though, it was a different story. Much like early plants, the first insects were actually kind of crappy.

They were probably scavengers or predators, feeding on decaying organic matter and each other. They also weren’t particularly mobile. It would take evolution 70 million years to puzzle out how to build wings, so these early pioneers were stuck with crawling and walking to get around.

It wasn’t long though before something clicked, and the early insects turned their prehistoric compound eyes to the untapped treasure lying at their (numerous) feet: a delicious, stationary and completely undefended food source.

The Never-Ending War

Those first few centuries must have been a gustatory massacre: hordes of rampaging insects feasting on the soft succulent vegetation.

But plants fought back. They diversified, developing intricate vein-like vascular tissue that allowed them to grow larger and migrate inland. Insects followed, and responded by evolving Sap Suckers, fiendish vampires who could stab into the plants and drink their very fluids. This one keeps its enormous proboscis tucked back under its body:

Plants began secreting waxy coatings to make their leaves slippery and harder to penetrate. Marauding proto-aphids toppled hundreds of times their body height to the ground.

Insect forms multiplied, and one lineage decided to get into the mining business, adapting their bodies to best burrow into leaves, submerging themselves in a giddy world of pure deliciousness. Plants retaliated, developing machinery to sacrifice infected leaves and toss them scornfully to the ground, curled and brown.

The battle was well and truly under way.

Plants reinforced their critical systems – stems and seeds – with tough fibres that gradually evolved into woody bark and shells. Insects found ways to keep pace by strengthening their mandibles. Worse yet for plants, a strain of Leaf Miners mutated themselves into a grotesque new foe: Plant Borers. These creatures were able to burrow not just into leaves but directly into stems, roots and even the precious seeds.

Life force battled hard against life force. Ecosystems diversified and increased in complexity as military innovation piled up upon military innovation. Bizarre alien forests rolled across the Earth as the Ordovician Period faded into the Silurian, which in turn faded into the Devonian. And all the while, inexorably, the death toll crept higher.

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A Devonian forest, courtesy of http://www.fossilmuseum.net

About 406 million years ago, insects finally mastered flight. Having wings transformed their world from essentially flatland into a rich 3-dimensional environment of endless possibilities. Migration and innovation boomed, and with it insects differentiated into a dizzying array of never-before seen forms.

During the next 60 million years most modern orders of species came into existence. Early winged arthropods included crickets and the elegant predatory dragonflies. And soon enough, there were beetles.

Beetles are so endlessly varied that they alone account for 30% of all animal species in existence. As the evolutionary biologist J.B.S. Haldane summed it up:

“The Creator, if He exists, has an inordinate fondness for beetles.”

Shortly afterwards, beetles were joined by wasps, moths and flies, and the four super-radiations were loosed upon the world – a beautiful insect evolutionary tree can be found here. It seemed that insect domination over plants was assured.

In a final twist of the plot, in this harsh prehistoric world when all seemed lost, plants stumbled upon a way to turn the tide of the war. They would transform insects’ greatest strength – mobility – into their greatest weakness. Plants invented chemical warfare.

Insects aren’t just gifted with movement; they are dependent upon it to do anything – to find food, to escape predators or to reproduce. Movement requires the coordinated use of multiple systems: powerful flight muscles, machinery for vision, advanced aerial navigation equipment. And all of these systems are plugged directly into a brain.

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Behold: Flybrain

Plants began producing toxic compounds called allelochemicals to attack insect brains. Any insect eating a plant would have to eat its allelochemicals too. These toxins would then seep into its brain and start messing with the delicate movement systems. Insects would either have a seizure and die from energy depletion, or become paralysed and be eaten by predators.

What do these deadly allelochemicals looks like? Examples include nicotine, caffeine and cocaine.

As always in evolutionary wars, insects responded, this time by developing resistances. But the cost was great. Many species were forced to become specialists, living on only a narrow range of plants whose poisons they could tolerate. Some probably failed to adapt altogether.

Insects and plants dug into the trenches, so to speak, and gradually, over a long period, the conflict settled into a kind of equilibrium. The two ancient enemies constantly refined their poisons and resistances, their weapons and armour, but neither ever again gained a real upper hand over the other. Eventually some plants and insects even set aside their differences and, with their powers combined, forged one of nature’s all-time greatest collaborations: flowering plants and pollinators.

And what about us mammals? Millions of years passed in this period of plant-insect equilibrium; amphibians arose; reptiles arose; and finally, some time in the early Triassic, the very first mammals peeled away from reptiles to launch our own evolutionary journey of diversification and warfare. We sure were latecomers to the party though. By this point, insects and plants had been at each other for 200 million years.

Now, to finally answer the mystery about drugs, it’s time to go…

Inside the Mind Itself

To understand how brains work, it’s surprisingly useful to look at how computers are built. Computers are essentially big networks of logic gates connected by wires. If you’re not familiar with them, logic gates take in two signals and use them to output one signal. The signals can be either ‘on or ‘off‘, and different types of logic gate behave differently.

An OR logic gate outputs on when either input is on.
Think: “I’ll go out with my friends if either mum or dad says I’m allowed to.”

An AND logic gate outputs on when both its inputs are on.
Think: “I’ll only clean my room if both mum and dad make me.”

With enough logic gates strung together, computers are able to carry out the endless complex operations that we tell them to.

Brains work is a remarkably similar way, using neurons instead of wires. There are two major differences though:

  • Neurons aren’t limited to just two inputs, and instead can receive signals from up to hundreds of other neurons
  • Neurons communicate on and off signals using neurotransmitters, tiny molecules that substitute for electricity

So really, a brain is just a (mind-bogglingly complex) tangle of neurons that form an astronomical number of logic gates. These logic gates are endlessly being bombarded with neurotransmitters carrying on and off signals. Logic gates rapidly read these inputs, process them into their own on or off signal, and fire it onwards, from neuron to neuron, logic gate to logic gate, racing and rippling and splitting and looping around, all in a vast never-ending neurotransmitter Yin-Yang sea of Dos and Don’ts, of ons and offs.

And through this process, we control every minuscule aspect of our existences: breathing, feeling, moving and consciousness itself.

Plant allelochemicals, A.K.A. psychoactive drugs, work by mimicking insect neurotransmitters. They screw up the fine Yin-Yang balance of signalling, either by sending an unregulated blast of ON, or freezing the system with a wave of OFF. Enough allelochemical and the insect dies from either seizure or paralysis.

Humans are very distant cousins of insects, around 500 million years distant, and we use many of the same neurotransmitters. However, with so much time apart, our brains have obviously evolved down separate paths, and our logic gates are made somewhat differently. Because of our shared ancestry with insects, plant drugs designed to attack insects can still affect us, but only in a weak and wobbly kind of way. If allelochemicals are like a bolt of lightning to insects, we get a warm shower of sparks.

Also unlike insects, we have the unintended benefit of having evolved pleasure centres in our brains. It is one of nature’s great chemical coincidences that, just as no one predicted that aspartame would be sweet, or that angina medication would cause whopping erections, plants never imagined that their anti-insect drugs would be great at turning up the happiness dials of distant future humans.

So next time you’re enjoying your morning cup of java, maybe spare a thought for the countless poor insects who gave their lives in order that we may have our buzz.

Sources

Chocolate, Cannabis and Chemistry of the Brain

About two decades ago, a team of scientists at the San Diego Neuroscience Institute found themselves in the enviable situation of having spare grant money lying around. During a particularly dull lab meeting, one of the scientists – who was fantasising about chocolate instead of paying attention* – drifted into a wacky line of thought:

Why was chocolate so damn addictive? Could it possibly be because it contains psychoactive compounds? Compounds like maybe… tetrahydrocannabinol (THC), the active ingredient in cannabis?

 

The daydreamer put the question to the group, and after a brief debate the scientists all agreed that they had to find out. They grabbed the grant money and popped down the street to buy some chocolate.

They ground it up to analyse its chemical structure†, and what they learned was quite amazing: the chocolate contained tiny amounts of anandamide. Anandamide is a compound produced naturally by your brain, and it has a very similar structure as THC in cannabis. In fact, it has the same effect on your brain. Anandamide is your brain’s way of getting itself high, if just a tiny little bit.

 

They published their findings in Nature. In typically sciencey language:

“Cannabinoid drugs [such as anandamide and THC] are known to heighten sensitivity and produce euphoria. A possible side effect of elevated brain anandamide levels could be to intensify the sensory properties of chocolate thought to be essential to craving.”

In other words, eating chocolate might give you a little case of the munchies.

 

A note on the munchies, courtesy of Urban Dictionary:

“Contrary to popular belief, when you have the munchies you are generally NOT HUNGRY. It’s more like… eating feels really really good. Imagine everything tasting like the best-tasting thing you ever ate in your life.”

Does that sound suspiciously like chocolate to you?

Notably, the researchers found no anandamide in white chocolate. And in a way, this isn’t surprising. Has anyone ever craved white chocolate? No, of course not.

While the discovery was intriguing, it wasn’t clear whether chocolate contains enough anandamide to affect people’s brains in any meaningful way. A group of scientists based in Naples, Italy came in to tackle the question. Their plan: they were going to get a bunch of mice high.

I approve of this plan.

 

They reasoned that they could feed the mice different amounts of anandamide, and find the smallest dose needed to noticeably change their behaviour. They would then compare this dose to how much anandamide was in chocolate. If chocolate contained at least as much, it was probably affecting the brain. Being Italians, as a control treatment they used… olive oil. Seriously. Olive oil.

While some of the mice probably quite enjoyed the experiment, the result came out negative – there was nowhere near enough anandamide in chocolate to affect their behaviour. They published the findings in Nature:

“Our results show that the amounts of anandamide… are several orders of magnitude below those required, if administered by mouth, to reach the blood and cause observable ‘central’ effects.”

The Californian scientists wrote back a snarky response, criticising the Italians’ methodology and pointing out that of course chocolate didn’t get you high. Any psychoactive effects it might have would be subtle and subjective.

At its peak, this chocolate-cannabinoid question burst into the courtroom. A man had been accused of smoking and dealing marijuana after showing positive in a urine test. His lawyer had heard about the recent research, and decided to try it out as a defence. He argued that his client had eaten a huge amount of chocolate just prior to taking the urine test, and it was actually the anandamide from the chocolate that had made him fail. The judge, uncertain how to proceed, called in the scientists.

They synthesised pure anandamide, mixed it with urine, and then checked whether the concoction could trigger a positive result on a standard test. It couldn’t, and the man was convicted.

And this is where the story might have ended. Following the case, everyone seemed to lose interest in the chocolate-cannabinoid question. No further research was done, and the idea was forgotten.

Until, that is, a new group of Italian scientists entered the scene in the late ‘00s. By this time it was known that both THC and anandamide work by turning on a brain protein called CB1. CB1 then triggers a bunch of changes in your brain that create all the fun effects of cannabinoids. CB1 is also somehow involved in people’s motivation to eat “highly palatable” foods – anything sugary, fatty and delicious. In your brain it looks a bit like this:

Anandamide-THC-neuron

 

The Italian scientists had a colony of rats that they were raising on a diet of water and standard rat chow. It was healthy and filling, but not especially palatable.

To see what would happen, the scientists started offering the rats a highly palatable chocolate drink. It turns out that rats are just like humans and love chocolate – they started sipping it all the time. Now the rats were hooked on the chocolate, the scientists gave some of them a drug that turned off CB1 in their brains. This meant that cannabinoids like THC and anandamide wouldn’t affect them any more.

What happened? The rats without functioning CB1 lost interest in the chocolate drink. They still ate whenever they were hungry and maintained their weight, but they no longer seemed to care what they ate. Bland rat chow was just as good as chocolate. They had lost their ability to appreciate deliciousness.

 

*               *               *

 

To this day it’s still unknown whether there’s enough anandamide in chocolate to turn on CB1 in our brains at all. It’s clear though that this pathway is critical to our enjoyment of food. Without cannabinoids such as anandamide or THC turning on CB1 in our brains, we wouldn’t crave that delicious cheesy pizza or that caramel swirl ice cream. In line with this, drugs that block CB1 are currently being investigated as a possible tool for weight loss.

If, on the other hand, you’re someone who likes to supplement their brain with the occasional bit of THC, next time you’re enjoying that delicious junk food, you’ll know which protein to thank.

 

marley choc

 

Sources:
  • Brain cannabinoids in chocolate; Di Tomaso, E; Beltramo, M; Piomelli, D; Nature August 22, 1996, Vol. 382 Issue 6593, p677
  • Trick or treat from food endocannabinoids? Di Marzo, V; Sepe, N; Petrocellis, L; Berger, A; Crozier, G; Fride, E; Mechoulam, R; Nature, UK; Vol. 396 (6712), 1998, 636.
  • Cannabinoid mimics in chocolate utilized as an argument in court; Tytgat, J; Van Boven, M; Daenens, P; International Journal of Legal Medicine; 20000509, Vol. 113 Issue: 3 p137-139, 3p, 2000
  • Suppression by the cannabinoid CB1 receptor antagonist, rimonabant, of the reinforcing and motivational properties of a chocolate-flavoured beverage in rats; Maccioni, P; Pes, D; Carai, MA; Gessa, GL; Colombo G; BEHAVIOURAL PHARMACOLOGY; MAY, 2008, 19 3, p197-p209, 13p.

*This sentence is a complete fantasy with no basis in fact

†The chocolate also contained two related compounds which act to stabilise anandamide and prolong its effects. These other compounds were synthesised and included along with anandamide in the legal case.

GMOs Pt 4: Is the Apocalypse Nigh?

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Disclaimer: Trading Atoms has no interests, financial or otherwise, in any biotechnology or related company.

Genetically modified (GM) crops are playing an increasingly significant role in global agriculture, and quite literally changing the face of our planet. Unfortunately, science has a rich history of inadvertently messing things up, which raises a question: should we be concerned about GM crops too? There are five major worries that people commonly hold regarding the technology:

  1. GM food is dangerous for human health
  2. GM crops lead to increased pesticide use
  3. Farmers are exploited by biotech companies
  4. Genes from GM plants might spread into the wild
  5. Triffids?!

If you’ve already read up on What Genetic Modification Is and What the Heck is Out There, you have all the background needed for us to turn up our coat collars, dive boldly in and see where the evidence leads on these questions.

 

Chemicals and critters

We’ve mentioned previously that of the millions of hectares of different GM crops out there, just two types of modification account for almost all of them: herbicide tolerance and insect resistance. It’s worth understanding these in a bit more detail before addressing the five major worries.

Herbicide tolerance is a modification that allows plants to survive a synthetic chemical called glyphosateGlyphosate was created by Monsanto in the 1970s and brought to market as “Roundup”. After their patent expired in 2000, glyphosate use expanded greatly, soon becoming the most widely used herbicide in the world. It has been described as a “one in a 100-year discovery that is as important for reliable global food production as penicillin is for battling diseases.” This weighty claim is worth taking seriously.

Glyphosate interferes with a protein called EPSPS which is critical for growth. This protein is only found in plants and bacteria, meaning glyphosate has minimal toxicity toward humans and other animals. It is also cheap, has a relatively short half-life in the environment, and has replaced the use of several more toxic and persistent herbicides.

“Roundup Ready” plants, developed by Monsanto, contain a modified copy of the EPSPS gene which lets them grow even in the presence of glyphosate. This means that farmers can spray glyphosate on their Roundup Ready crop, and only weeds and competing plants will be killed. This represents a vast simplification of pest management strategies.

Fun fact: the modified EPSPS gene was isolated from a bacterium found growing in a glyphosate manufacturing waste stream.

 

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Micrograph of a colony of bacillus thuringiensis

The other major crop modification, insect tolerance, is achieved by giving plants a gene to make “Bt”. Bt is a naturally occurring protein that gets its name from its creator: Bacillus thuringiensis, a common soil bacterium. A simple overview of the Bt system is provided by the European Commission.

When Bt is ingested by an insect, it is activated by the alkaline environment of the insect’s stomach and becomes toxic. It interferes with the insect’s digestive tract, eventually causing the insect to starve to death. Because humans and other vertebrates have acidic stomachs, any Bt ingested remains in its non-active form, and is therefore not toxic. A review from the European Food Safety Authority (see p. 8) reached this same conclusion of Bt non-toxicity in mammals. Furthermore, Bt is only harmful to insects that ingest it, meaning that beneficial insects like honeybees, which don’t eat crop plants, are left unscathed.

Bt has been used as an insecticide since the ’60s, when it was approved in Germany as a spray. Because Bt is a naturally-occurring product, it is also commonly used on organic farms as a spray – there’s a good chance your organic kale was grown with the help of Bt. Genetically modified Bt crops let farmers skip the spraying step, instead making the protein automatically inside their cells, where it will only harm any insects which eat the plant.

Now we’ve covered the two main GM technologies, let’s tackle the five major worries!

 

1. Is GM food dangerous for human health?

It turns out that this question has the clearest answer of all: GM food is in no way dangerous to human health. Follow this link for more information and references about the safety of GM food than you could possibly care to read. In short though:

“There are nearly 2000 peer-reviewed reports in the scientific literature which document the general safety and nutritional wholesomeness of GM foods and feeds.”

 

A selection of the many scientific and medical organisations that have publicly supported this assessment:

14-12-01 The science of genetically modified food

For a GM crop to be certified as safe for human consumption by organisations like the FDA, it must display “nutritional equivalence” to its non-GM counterpart. Remember, the fundamental change in a GM plant is that it has a few extra genes sprinkled amongst tens of thousands of genes, making one extra protein amongst tens of thousands. This means that nutritional equivalence is not surprising.

The main risk of introduced proteins is that they could cause an allergic reaction. Accordingly, allergenicity testing is a strict requirement for any proposed GM crop. This testing is effective, and to date, “no biotech proteins in foods have been documented to cause allergic reactions.” Interestingly, GM technology can actually be used to go the other way, remove existing allergens from food.

If you have any lingering doubts about the health safety of GM food, hopefully this 29-year study of over 100 billion GM-fed animals will satisfy them.

 

2 & 3. Do GM crops lead to increased pesticide use, and are farmers exploited by biotech companies?

We’ve seen that Roundup Ready crops can survive copious spraying of glyphosate. Could this encourage farmers to apply the chemical recklessly? If so this is a worry, as the more glyphosate that is used, the more pressure there is on weeds to develop resistance, necessitating the use of ever greater quantities of glyphosate. As for exploitation of farmers, claims along the following lines are well-known: “Roundup Ready crops do not increase the yield or profits of farmers, [and so] only serve to benefit Monsanto.”

To address these two issues, we turn to the latest and most comprehensive peer-reviewed meta-analysis of the economic impacts of GM crops, published in 2014 in the journal PLOS ONE.

The authors screened over 20,000 agronomic studies, narrowing down to a set of 147 which met stringent criteria for inclusion. They analysed a range of factors, including yield, pesticide use and farmer profits. Here are their results when comparing GM crops to conventional ones. *** indicates high statistical significance (at the 0.01 level):

journal.pone.0111629.g002

So they found that, on average, GM crops increase yield by 21.6%, decrease pesticide used by 36.9%, and increase farmer profits by a whopping 68.2%. There is no significant effect on total production cost. As the authors explain, although GM seeds are more expensive than conventional ones, this cost is offset by savings in pesticide use and manual pest control.

These results may come as a surprise; however, the story changes when we separate out herbicide tolerant (Roundup Ready) and insect resistant (Bt) crops. Analysed on their own, Roundup Ready crops only increase yield by about 9% (compared to 25% for Bt crops), and while both types of modification increase farmer profit by around 68% on average, this figure is extremely variable for Roundup Ready crops. It seems that they are sometimes great for profits (150% increases or more), but other times they actually hurt profits badly (-24% or worse). Also notably, the decrease seen on the graph in pesticide use is due entirely to Bt crops (which use 42% less than conventional crops). Roundup Ready crops seem to need just as much pesticide as conventional crops.

The take-home message is that not all GMOs are created equally. Overall, genetic modification has been a great boon to farmer profits and played a role in decreasing pesticide use, but it will be necessary to evaluate each new modification on its own merits.

 

4. Can genes from GM plants spread into the wild?

Is it possible that GM crops could escape into the environment and run rampant much like an introduced species, or perhaps breed with weeds/wild relatives to create a so-called “superweed“?

First, the scary news: breeding of crop plants with wild ones occurs constantly. Rapeseed can mate with turnip rape, genes from cultivated maize can cross to wild maize, and sugar beet can form hybrids with garden beet. This process happens for both GM crops and crops bred over time for selected traits.

Furthermore, it turns out that glyphosate-resistant weeds have already emerged, with half of all U.S. farms now struggling to control these pests. While this is a serious issue for food security and highlights the danger of relying on a single pest-control mechanism, the resistance is not due to GM genes escaping. Rather, it has evolved independently in the weeds. Such evolution is ubiquitous and inevitable, and the same process underlies multidrug-resistant bacteria, insects overcoming every insecticide ever made (including Bt), and why effective cancer drugs are extremely difficult to develop.

Short of some game-changing technological breakthrough, humans will always be locked into these evolutionary battles against pests and diseases.

Regardless, do we need to be concerned about the spread of GM genes? It depends on the modification, but the answer will often be “not really.” To understand why, let’s consider a critical Darwinian question:

“Will the extra protein(s) give the GM plant an advantage over wild ones?”

It costs a plant resources to make proteins, so if those proteins don’t do something to give the plant a leg up over its competitors, the plant won’t spread. Glyphosate doesn’t exist in nature, so building glyphosate-resistance proteins is just dead weight.

On the other hand, there are modifications, such as faster growth or insect resistance, that could conceivably give a GM plant an advantage over competitors – Bt is a good candidate. In these cases, management strategies such as seed sterility, buffer zones, and altered flowering timing are critical for ecological safety.

There are no known instances of GM plants spreading genes into the environment – although interbreeding with non-GM crops is another issue (maybe for a future article) maybe for a future article. At this point the risk seems manageable Once again though, genetic modifications will have to be scrutinised on a case-by-case basis.

 

5. Triffids?!

 

Biological traits like mobility and intelligence are super complicated to even understand, let alone engineer. We’re probably safe on this front for a long while yet.

 

Do we actually need GM crops?

We’ve seen that, thankfully, a lot of the criticisms and worries around GM crops don’t stand up to scrutiny. It’s clear that, overall, GM crops have increased yield and farmer profits, decreased pesticide use, and are safe for human consumption. Nonetheless, it may be worth considering whether we really need GM crops. There will always be unknown risks involved in tampering with complex systems such as global agriculture, and these unknowns may exceed the known benefits.

One of the strongest arguments in favour of GM food rests on the projected global population for the coming century, which is set to increase significantly. Agriculture already covers about a third of the world’s landmass, and short of further deforestation, there simply isn’t more space to devote to it. This means that if we are to feed a growing population, yield per hectare will have to increase. It will be difficult to achieve these increases without (and possibly even with) turning to GM technology – especially in the face of climate change.

Another argument is one of humanitarianism and international development. Contrary to common perception, 90% of GM crop farmers live in developing countries, largely China and India, and till small resource-poor farms. We have seen that GM crops typically lead to increased yields and profits for farmers. Anecdotally (see link above), this extra income often goes to financing things like improved access to health care and education.

Maybe the apocalypse isn’t quite so nigh as we may have feared.

Want to learn more? Two reputable and well-researched websites are the Genetic Literacy Project, and the European Union’s GMOcompass.

GMOs Pt 3: What the Heck is Out There?

Disclaimer: Trading Atoms has no interests, financial or otherwise, in any biotechnology or related company.

Welcome to the third part of this mini-series on Genetically Modified Organisms (GMOs), where we’ll take a more detailed look at what the heck is out there in the environment. If you’ve just tuned in, you might like to first read up on what exactly genetic modification is, and maybe how to make your very own GMO.

Let’s start with some context by taking a starry-eyed look back over 10 of the most significant developments in GMO technology that have led up to today.

A Montage of Genetic Modification

1953: Watson, Crick and Franklin discover the structure of DNA.

1973: Boyer and Cohen create the world’s first ever GMO when they modify the bacteria E. coli to express an antibiotic-resistance gene. In the process they unintentionally foreshadow a serious problem soon to hit the world: the evolution of antibiotic-resistant bacteria in hospitals.

1974: Jaenisch and Mintz create the first GM animal. They injected a primate virus into mouse embryos, then transplanted the embryos into surrogate mothers. The mice grew up normally except that they contained the viral DNA.

1978: Genentech, the world’s first genetic engineering company is founded, and engineers E. coli that can produce human insulin. Diabetics and livestock everywhere rejoice.

1980: The U.S. Supreme Court rules 5 to 4 in General Electric’s favour that “A live, human-made micro-organism is patentable subject matter”. In so doing, it sets the entire course of GMO history to come. GE immediately patents a bacteria engineered to eat crude oil.

1983: The first modified plant is created, again by adding an antibiotic resistance gene. Can you guess the species? (Hint: it was the ’80s). Yep, of course it was tobacco.

1987: The first field release of a GMO takes place – a “Frostban” bacteria designed to protect crops from frost. Activists attack and attempt to sabotage the trial site the night before. It’s said that history repeats.

1994: Calgene produces the first commercial genetically modified (GM) crop plant, the Flavr Savr tomato. This tomato doesn’t produce a natural protein that degrades cell walls, meaning it stays ripe for longer. The Flavr Savr experiences a tumultuous commercial life of initial success, then by a decline at the hands of consumer distrust, and finally discontinuation by 1997.

1995: The commercial GMO market explodes, with the development of potato, cotton and maize strains that can resist insects.

In the ensuing two decades, two particular classes of modification have come to dominate the GM plant market: insect resistance (via insertion of the “Bt” toxin gene), and resistance to the herbicide “glyphosate” (marketed as Roundup). Glyphosate resistance now dominates the GM market to such a degree that it is present in a whopping ~90% of all transgenic crops, making it the Big Cheese of commercial GMOs. We’ll talk about this as well as Bt in the next instalment.

How many GMOs are out there?

To date, all GMOs approved for human consumption have been plants. A common source of confusion regarding this claim is recombinant bovine growth hormone (rBGH), which is injected into dairy cattle to increase milk production. rBGH is produced by genetically modified bacteria, in much the same way as human insulin. Injecting rBGH into cattle doesn’t cause them to become genetically modified. It is however a form of doping, one which is demonstrably harmful for their health and wellbeing. Human growth hormone has been abused by athletes since the ’80s.

So, why haven’t GM animals been commercialised (except for certain novelty uses)? There are a few possible reasons. Plant products make up the bulk of the average person’s diet, and consequently plants account for the majority of the value of the agricultural sector. Aside from this economic incentive, plants are arguably easier to modify and cultivate than animals.

Nonetheless, there’s also a clear legislative bias at play against commercialising GM animals. This may reflect an unproven notion that there’s less risk of GM plants escaping and spreading. A more reasonable argument might be that because plants lack sentience, there’s no risk of them suffering because of a modification. The main reason for the bias may not be so rational though.

Since animals are our closest evolutionary ancestors, we typically hold them in a more reverential and even “sacred” light than plants. You can probably imagine a mutant two-trunked pine tree without being too bothered, but a two-headed rat feels a lot more uncanny valley.

Whatever the reason, at this point in history, crop plants are the undisputed stars of GM technology, so we’ll refocus our radar in the direction of agriculture.

 Delicious Data About Agriculture

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Agriculture covers a full third of the Earth’s land area, and as of 2013, GM crops made up about 3.5% of the total. That corresponds to more than 1.7 million square kilometers, or an area greater than the entire landmass of Iran. Given this, it’s probably fair to say the prevalence of GMOs is not insignificant.

Legal regulations and social attitudes towards GMOs vary widely between countries, which means that these crops aren’t just scattered around the globe randomly. A particularly rich source of information on GM crops is the report Global Status of Commercialized Biotech/GM Crops: 2012, commissioned by the pro-GM group ISAAA (The International Service for the Acquisition of Agri-biotech Applications). Despite their partisanship on the issue the data seem solid, and the report is worth a read if you’re interested in details about a particular country’s GMO activities.

Which nations are the biggest adopters of GMOs? There were only 28 countries growing GM crops as of 2012, though these countries are home to 60% of the world’s population. Uptake is overwhelmingly focused in North and South America. Interestingly, and largely owing to Europe having the strictest GMO regulations in the world, there are only eight industrialised countries growing GM crops, meaning the rest are developing nations.

Most GM-growing nations are currently focusing on cotton, maize and soybean. GM food crops are predominately used as livestock feed rather than for human consumption, and as mentioned earlier, most GM crops are herbicide resistant and/or insect resistant. This is changing though, with an increasing proportion of “second generation” strains entering the market, which have these traits stacked with others, such as enhanced nutrition or drought tolerance. The USA and China are cultivating GM versions of several other food crops, including things like papaya, sugarbeet and sweet pepper.

While the USA has the greatest land area devoted to GM crops of any nation, as well as the highest number of GM species, GM land is mostly devoted to just a few staple crops, for which an extremely high proportion grown are GM varieties. For the “big three” of cotton, maize and soybean, over 90% of farms are now growing GM varieties. In Canada, a record high of 97.5% of canola crops are GM.

The increasing uptake of GM crops is an interesting story. Despite the USA easily dominating the pack in this modern day space race, the vast majority of remaining GM crops – and 90% of GM farmers – are located in the developing world. Developing nations are also taking up GM technology at a greater rate. As you can see in the chart below, industrialised nations have already lost the majority share of the market.

How do we explain the huge differences in GMO legislation and uptake rates between countries, particularly Europe and the USA? It’s worth first reminding ourselves that, by many metrics, the USA is just a weird outlier, so this may be a very difficult question to answer.

Nonetheless, one possible explanation is labelling requirements (though the causality is hard to tease apart). In the late ’90s, a strong opposition movement to GMOs grew in Europe, and it succeeded in mandating strict labelling of any GM products. Supermarkets responded with a wave of panic, banning products containing any GM ingredients out of fear of losing customers. In a very short time, the entire European GM industry was dead. Conversely, see North America on the graph below (click for larger version). It has no labelling requirements.

Without labelling of GM products, there is less consumer concern and less avoidance of them, meaning the economic incentive for farmers is to grow GM crops rather than less efficient conventional ones. Is this a bad situation for the USA? This debate is currently raging in several US states, with recent or upcoming votes on GMO labelling. All we will say here is that when public concern is coupled with scientific misunderstanding, the outcome can be quite harmful.

Unravelling Some Sticky Side-Issues

Neil deGrasse Tyson was recently lambasted for defending GM technology by claiming it is not all that different from the domestic selection that humans have been exerting on plants and animals for thousands of years. As he pointed out when he later clarified his statement, there is a big sticky mess of related issues tangled up with GMOs, and it was these that his attackers mostly took issue, not the science itself. It’s worth dissecting out a couple of these confounding topics before closing the book on current GMO status.

The sticky mess includes things like: corporate exploitation of small farmers, monocultures, and the merits of “organic” farming (a term that every organic chemist will tell you is meaningless as they sigh into their erlenmeyer flask).

1. Corporate exploitation and patenting. Tales are rampant of farmers in developing countries being forced into unfair annual contracts for GM seeds, or of organic farmers losing their organic licence then being sued because their crops have been contaminated by a GM strain. Such situations rightly invoke our moral outrage. However, according to the excellently researched and independent Genetic Literacy Project, these stories simply aren’t true. Some are myths while others have the facts twisted. Even if these tales were true though, lawsuits and rigid contracts are issues of equitable IP legislation, not of science. The same problem applies to the pharmaceutical industry, with potentially life-saving medications being fiercely protected by patents and kept artificially expensive.

2. Monocultures. A common claim is that GM crops are always “monocultures”, meaning genetically identical plants are grown en masse. The risk here is that if a virus or pest evolves which one plant is susceptible to, all would be susceptible, leading to rapid losses of huge numbers of plants. As it turns out though, when a GM plant is developed, the trait is typically bred across into many cultivars in order to increase the genetic diversity and minimise this risk. That said, growing only one type of crop in an area does harm soil quality and biodiversity and so should be avoided where possible. Most GM crops, excepting pesticide resistant ones, can be grown in mixed plots with no barriers.

3. Organic food. The main point to stress here is that GM crops are not the opposite of “organic” crops. While organic farming excludes the use of GMOs on ideological grounds, it is primarily an alternative to conventional large-scale agriculture. You could grow a patch of GM alfalfa using entirely organic farming practices if you wanted to. Despite this, GMOs and organics are often pitted against each other in the context of food production and security.

Whatever merits organic farming may have, superior food production is sadly not one of them. A 2012 meta-analysis published in that most weighty of scientific journals, Nature, found that organic farming typically produces 34% lower yields when compared to conventionally farmed crops in comparable conditions. This entertaining and well-researched video explores the pros and cons around organic food and dispels some common myths.

If you’ve made it this far, congratulations! You should now be clued up on exactly what genetic modification means, where GMOs come from, their history, and what the heck is out there at the moment. This means it’s time to face the upcoming last part in the series: GMOs Pt 4: Is the Apocalypse Nigh?

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GMOs Pt 2: How to Make Your Very Own!

Disclaimer: Trading Atoms has no interests, financial or otherwise, in any biotechnology or related company.

In Part 1 of this series we delved into the realm of genetics and looked at just what constitutes a genetically modified organism (GMO). We said the essential difference is that a GMO usually produces one or more extra proteins that don’t exist in the original species. These extra proteins were added to create some kind of desired trait, such as pesticide resistance in wheat. In the coming instalments we’ll look at the prevalence of GMOs and whether we should be terrified, but before all that dry reality, it’s time to make our very own!

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The fabled Umbuku lizard.

 

Step 1: Pick your species and desired trait

Back in the idealistic days of my childhood, I had a vision for what my life’s work would be: I would be the one to engineer the world’s very first actual Pokemon! It would probably look something like this.

However, as the years rolled by I gradually came to accept the harsh truth: I would never achieve my dream. The problem was that Pokemon tended to violate the laws of physics. And that was before even considering the technical limitations to genetic engineering. So with this lesson of genetic hubris in mind, what kinds of creatures could we build?

Until quite recently, the limited tools at our disposal for manipulating DNA meant that the best we could aim for was the addition or subtraction of maybe a few genes.

This is no longer the case. With the creation of the first self-replicating synthetic bacterial cell, and the development of new, extremely versatile genetic tools, DNA can be snipped and chopped and changed in pretty much any way we want. Luckily this hasn’t yet lead to an influx of dystopian creations – say, a weaponised psychedelic wasp, or my personal favourite in GM scaremongering:

But if the sky’s the limit when it comes to DNA manipulation, why haven’t we seen this kind of stuff? Let’s assume that scientists are bound by absolutely no ethical qualms or regulatory oversights, and would be keenly interested in adding a digestive tract and muscular system to the common carrot.

The reason, it turns out, is that the way embryos develop is really, really complicated. To make something as complex as a limb, thousands of different genes have to be turned on and off in precisely the right moments in the right cellular locations and at the right levels. Embryonic development is a splendidly complex genetic symphony. Just look how confusing and boring the development of a fruit fly is!

 

 

And that’s a highly simplified explanation, only looking at the very first cell. As you can imagine, the process gets exponentially more complex as different types of cells and tissues begin developing and talking to one another. It quickly reaches the point where a detailed understanding is nearly impossible. The complete story though, if we do ever one day manage to unravel it, looks to be quite beautiful:

So, now that our wildest dreams have been crushed for the foreseeable future, what are we left with?

Well we can still do a lot of pretty interesting things, provided it only involves fiddling with simple and well-understood systems. Generally speaking, this means we’re still limited to changing one or a few genes at a time. While no one is going to be adding wings to lions any time soon, some noteworthy innovations have still been made.

  • One of the earliest breakthroughs, taking place as early as 1978 and providing a major boon for type 1 diabetics, was the insertion of the human insulin gene into E. coli. Before this time, insulin could only be harvested from the pancreatic glands of slaughtered pigs and cattle – not a cheap or pleasant process for anybody. These days, E. coli bacteria happily grow away in vats churning out the stuff.
  • With climate change increasingly impacting upon the yield and yearly predictability of agricultural harvests, drought-resistant wheat may soon prove an important tool in the fight for food security, not to mention farmers’ livelihoods. The wheat is being developed right now.
  • The first genetically modified animal proposed for human consumption is the AquAdvantage salmon. It possesses an extra growth hormone gene that came from a related species of salmon. This extra growth hormone causes it to reach full size in about half the time of a conventional salmon.

 

While all these developments are clearly useful and quite interesting, none of them are very visually exciting. So, without any further delay, let’s see if we can make a cat that glows in the dark. If all goes to plan, here’s what our GlowKitty might look like:

 

 

 

Step 2: Figure out how to obtain your trait

Fiddling with an entire biochemical pathway is Hard, but luckily for us, the modification needed to make a GlowKitty is actually quite simple – we only have to add a single gene. This gene will make a protein called Green Fluorescent Protein (GFP), which looks a bit like a microscopic barrel. The barrel works by absorbing high-energy blue light and re-releasing it as green light. As long as the gene is turned on in enough of the kitty’s cells, we should get a good healthy glow. Note: the gene that makes GFP is also named GFP. This can be a little confusing, but it’s standard practice in the world of genetics.

But where do we get this handy gene from? GFP originally comes from a handsome bioluminescent jellyfish which lives off the coast of North-Western America. Its name is Aequorea victoria, the Crystal Jelly.

As an aside, GFP has probably been played with more than any other gene in history. If you hadn’t heard of it before, you can find it cited in thousands upon thousands of papers. The extremely handy thing about GFP is that you can stick it onto another protein that you’re interested in. Usually, trying to look at a protein in a cell is like trying to spot a black plane in the night sky. Adding GFP is like installing a navigation light.

So, back to the project at hand. We’ve picked our species (cat), decided what trait we want to give it (glow in the dark), and we know we can get the trait by adding a single jellyfish gene (GFP). Time to move on to…

 

 

Step 3: Clone the gene

When Hollywood does genetics, it likes to delve into the spicy issue of cloning things. Things like dinosaurspeople, maybe alien-people (Caution: there may be a spoiler or two in there for anyone living under a particularly stable rock).

There’s also a smaller-scale, less sexy type of cloning you can do: simply copying a piece of DNA. It still counts as cloning! You’re replicating a biological sample aren’t you? It turns out that this kind of cloning is way easier than creating a whole living creature. In fact, it’s an extremely common and straightforward lab procedure, and cloning GFP will be our next step in making GlowKitty.

The process used is called Polymerase Chain Reaction (PCR). If you’re not familiar with PCR, it’s a bit too detailed to explain properly here. Basically though, it involves mixing DNA with enzymes and repeatedly heating and cooling the mixture to help the enzymes copy the DNA. This video provides a pretty good insight into what goes down in the lab whenever somebody does PCR:

 

 

PCR is an amazingly versatile technique. As the song scientific video explains, it’s central to a whole bunch of DNA-related techniques, from paternity testing to detecting mutations and forensic investigations.

Now we’ve covered the theory, you should get out your PCR machine, turn it on and have it idling at about 90-100ºC. If you don’t have a PCR machine, you can substitute in an oven, a bowl of ice and a pair of tongs. Then just follow these easy steps:

  1. Prepare some DNA containing the jellyfish GFP gene.
  2. Add a dash of DNA-copying enzymes (known as “polymerases”). These can be harvested from bacteria, or really any living creature. Make sure to use only trusted species, as cheaper options can result in mutations. Pyrococcus furiosus makes a product that you can count on for peace of mind.
  3. Season with loose DNA bases, salts and primers.
  4. Cook for about two hours, cycling between hot and cool.

Et voila! If all has gone to plan, you should now have several billion copies of your GFP gene.

 

Step 4: Put the gene into your species

We hit an immediately problem here: we can’t just inject the GFP gene into an adult cat. If we did so it would only end up in a few cells, and we want our cat to be glowing all over. We’d also like it to one day be able to have GlowKitties of its own, so we need the gene to be in its sex cells too.

The only option we have is to get the GFP gene into a single-celled embryo. This way, the GFP will join the rest of the cat’s DNA, and when the embryo grows and divides, the GFP gene will get copied into every cell too. So, go out and get your hands on some cat embryos.

There are a range of approaches we could try in order to get our gene in there. Injecting it into embryos with a tiny needle is pretty tedious and finicky, but it does seem to work quite well for a lot of species. We could also try chemicals. There are compounds that punch holes in the outer “skin” of cells, allowing our gene to slip in. The problem is that, unsurprisingly, this tends to seriously weaken the embryos. There are other types of chemicals that wrap DNA up in a ball of fat, allowing it to slip right through the embryo’s skin like a ghost through walls. Unfortunately, these chemicals also tend to be a bit toxic.

Or, there is this:

Yes, that is literally a gene gun. Or if you like, “biolistic particle delivery system”. It fires tiny balls of some kind of heavy metal, often tungsten or gold, which are coated with DNA, right into cells. It works pretty well for plants and animal tissues, where there are a bunch cells together to take the impact. However, as you can imagine, blasting a defenceless little cat embryo with balls of tungsten is like cannonballing a ship. Not good.

As with most things, evolution itself has devised a more elegant solution than anything us humans have been able to come up with. Viruses and certain bacteria have spent billions of years mastering the art of slipping inside living cells. Luckily for us, it’s not too hard to harness these clever critters to do our bidding. We simply have to take out their genetic material and replace it with the GFP gene, and we’ve made the perfect little Trojan horse.

Whichever technique you end up choosing, hopefully you’re successful and get the gene in there.

 

Step 5: The agonising screening process

After all this rigmarole, we might still only be halfway to having our GlowKitty! It’s time to carry out a bunch of screens and checks, not to mention then raising our embryo to an adult cat.

Most life forms have state-of-the-art defence systems to stop new genes from sneaking into their DNA – after all, that’s the kind of nefarious thing that a virus might try to pull. These defences can also make it quite hard for us to get DNA to stay in an embryo. Depending on what technique was used, we might have to screen hundreds or even thousands of embryos to find one that has taken up the gene. This process can be pretty exhausting, especially in something as complex as a cat. Sooner or later though, we should have our glorious eureka moment.

The GFP gene will have picked a spot somewhere along the cat’s DNA to bury in and join the family. Again depending on what technique was used, the spot was probably picked completely randomly. If we’re lucky, it will have picked a boring patch of DNA that wasn’t doing anything. If we’re unlucky though, it might have dived right into one of the cat’s genes and messed it up. There’s also the chance that two or three copies of GFP have jumped in, all at different spots. We definitely need to investigate this, and we do so by reading the DNA code on either side of the GFP gene.

We can compare these DNA sequences to the cat genome to see where the GFP has buried in. If there are no cat genes in these areas, we can be happy that the GFP hasn’t screwed up anything and push ahead. Otherwise, it’s back to the screening process to find a different glowing embryo.

As the cat develops, we’ll have to monitor that the gene is making enough GFP – but not too much – that it’s making it in the right tissues, and that nothing else unexpected has gone wrong. With a bit of luck though, the cat will grow to term happy and healthy and glowing green.

If you’ve made it up to here: Congratulations. You have obtained your GlowKitty.

 

https://i2.wp.com/i.kinja-img.com/gawker-media/image/upload/s--bKtNQ7cq--/18lq421ptf7j0jpg.jpg

scienceinseconds.com

The Twist

If you had your finger on the pulse back in 2011, you may know that GlowKitty already exists!

The story is that U.S. researchers wanted to study the cat version of HIV (called “Feline Immunodeficiency Virus”, FIV). They did this by adding a resistance gene again FIV, and joined it to GFP to act as a beacon. They followed the same process that we have, choosing a virus to get the genes into cat embryos. These cats can now glow in the dark, and won’t get AIDS as easily.

If you’re the type to be upset by this kind of manipulation of animals, I’ve got some bad news for you: GlowKitty is by no means a unique development. For what it’s worth though, glowing in the dark is not thought to cause any pain or emotional distress, and GlowKitties can lead essentially normal lives, probably oblivious to their sciencey superpowers.

*               *              *

Stay tuned for GMOs Pt 3: What the Heck is Out There? We’ll be investigating the prevalence and types of modified creatures that have most come to populate the planet.

GMOs Pt 1: Just What is Genetic Modification?

Disclaimer: Trading Atoms has no interests, financial or otherwise, in any biotechnology or related company.

The development of Genetically Modified Organisms (GMOs) is clearly one of the more controversial issues of our time, with a wellspring of strongly held opinions issuing forth, particularly from the political left. With such widespread distrust and uncertainty amongst concerned citizens, the topic is well and truly ripe for some informed discussion. Riper than a GM Flavr Savr tomato, some might even suggest.

In this first instalment on GMOs, we’ll be going through the basics of just what genetic modification means. Stay tuned for Part 2 where we’ll walk you through a simple guide on how to make your very own GMO, then in Part 3 we’ll address the more sobering question of whether the technology is even safe, and possibly have you regretting that spider-shark you’ve unleashed upon the world.

A Quick Review of Genetics

As you would surely have heard at some time, all living creatures have DNA (deoxyribonucleic acid) in them. If you’d like to get a bit spiritual-sciencey (as we sometimes do), you can legitimately think of DNA as the mystical life force that vibrates through and connects all living creatures on the planet. It is the real-world midichlorians. This particular molecule is present in every single life form, from the elegantly simple bacteria, to the towering trees, to the most majestic of animals.

Capture

Pretty much everything you need to remember about DNA is contained in the following three sentences. DNA is an incredibly long spiral ladder, with four types of rung. These rungs are organised into genes. Each gene is a blueprint to make a certain protein.

When the word ‘protein’ gets mentioned, most people think of that new diet they’re trying, or how sigh, they really should be making better use of that gym membership. While it’s true that muscles are largely made up of two particular types of proteins, there are many, many more types. It’s actually best to think of proteins as tiny machines that swim around in your cells, controlling every single thing you ever do. They are like the little cogs whirring away driving the immense living robot that is your body.

So to recap:

DNA –> is organised into –> Genes –> are blueprints for –> Proteins –> are tiny machines that control everything you do

A protein-machine grabbing onto pink DNA

A protein-machine grabbing onto pink DNA

How Many Genes are There?

Humans are intricately complex beings, with a huge array of different cell types and processes going on. Before the Human Genome Project, scientists speculated about how many different types of genes and proteins we must have to sustain all this complexity. Guesses ranged from over 6 million genes back in the ’60s, down to 100,000 genes by the National Institute of Health in 1990, to a post-genome estimate of 22,000. Recent evidence suggests the number is probably actually around 19,000 to 20,000.

Whatever the exact figure, it’s still very large, especially considering that those sweet guns you’ve been working on are mostly made up of just two proteins. Out of the thousands of others, only a small handful are well understood, and many remain outright mysterious.

How many Genes are there in Other Branches of Life?
kerrydarlington.co.uk

kerrydarlington.co.uk

Bearing in mind that it’s very hard to say exactly how many genes any species has, geneticists have found some interesting results:

Humans – 20,000

Dog/cat – 19,000/20,000

Mouse – 25,000

E. coli4,200

T. vaginalis60,000

HIV – 9    (Note: RNA not DNA)

Brewing yeast – 6,000

Fruit fly – 14,000

Frog – 20,000-21,000

Rice – 46,000-55,000

Wheat – 94,000-96,000

So if you thought that humans were a superior species genetically, think again. While we do have very impressive brains, our gene sets are not so different from a whole bunch of everyday animals. If you’ve ever been unlucky enough to suffer a bout of vaginitis, you may have Trichomonas vaginalis to thank – a single-celled parasite with three times as many genes as you.

Plants in particular can have staggeringly large gene sets. This is often the result of accidental DNA duplications that occur during evolution, which are then chosen by selective breeding (more on that below).

This discussion of gene sets is actually quite facetious, because what has become clear over time is that the number of genes doesn’t really matter. Merely witness the devastation that HIV is able to wreak with its measly nine genes. The important thing to remember is that most species have thousands of genes, and we generally have very little idea what they do.

What Is Genetic Modification?

Time to get serious. Here’s the legal definition:

“Any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology.”

This is basically saying that an organism is considered to be a GMO if it has had its DNA changed by scientists. There are a few possible kinds of changes:

  • inserting a gene from another species
  • editing (mutating) an existing gene
  • deleting an existing gene
  • changing how much protein a particular gene makes (regulatory changes)

Overwhelmingly, the GMOs created to date have had one or a few genes added to them from other species to create new functionality. A few examples of this include:

Contrary to the raft of hysterical images circulating online about GM food in particular, GMOs are NOT injected with mysterious chemicals, they do not gain explosive or radioactive properties, and they do not spontaneously develop circulatory systems.

Rather:

GMOs have a tiny difference in the proteins they make

To illustrate this point, let’s say that scientists make a drought-resistant strain of wheat by adding two genes.

The gene sets of the two strains would look like this:

  • Original wheat: 95,000 genes, making 95,000 proteins
  • GM wheat: 95,002 genes, making 95,002 proteins

Your body doesn’t know what any of the original 95,000 proteins are, and we’re not specially adapted to be able to deal with them. Rather, imagine a conveyor belt manned by thousands of eager unsupervised 5-year olds, with intricate Lego creations travelling along it. It’s going to be an orgy of joyful destruction.

Our digestive systems are much like this. Whatever shape or function a protein has, this becomes irrelevant once it enters the stomach. Gastric juices and enzymes will tear apart everything. The two extra wheat proteins will be broken down just like all the others.

It is possible that, while still in the wheat, the drought resistance proteins could make a chemical that is relevant to human health, such as bacteria that produce insulin. For this reason not all GMOs are equal, and the functions of introduced proteins have to be well understood. In most cases though, the only difference between GMOs and “wild” strains will be one or two extra proteins. We’ll explore health risks of GMOs further in Part 3.

What isn’t Genetic Modification?

An organism can be considered GM if even a single rung in its DNA ladder is changed – even if that rung does absolutely nothing. Let’s return to our legal definition:

“Any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology.”

The important clause is “through the use of modern biotechnology.” What this means is that the DNA has to be altered in a specific fashion for it to count as genetic modification. Otherwise – bizarrely – any changes are considered natural.

There are several ways that DNA can be altered without the use of modern biotechnology. As we shall see, these “non-GM” methods generally result in far more significant and unpredictable changes.

carrotmuseum.co.uk

carrotmuseum.co.uk

The oldest way that humans have been modifying DNA is through the 10,000 year-old practice of selective breeding. An example of this is cultivating crops with duplicated sets of genes. These plants typically have larger fruit and tens of thousands of newly evolving genes. Humans have also both accidentally and intentionally created hybrid species, throwing together thousands of unfamiliar genes from two species. Modern staple crops, like maize, wheat, rice and fruit trees, are all human-created mutants which differ wildly from their natural ancestors.

A far more rapid process is that of random mutagenesis. If adding one gene using biotechnology was like carefully painting a single dot on a piece of canvas, random mutagenesis is Jackson Pollock. It involves splattering random and sometimes catastrophic changes all throughout a species’ DNA, potentially affecting hundreds of genes at once. This can be achieved chemically with a substance like EMS, but another method frequently used by farmers, “radiation breeding”, simply involves shining a little X-ray or gamma radiation on seeds before planting them. China has even sent seeds to space to give them a nice gamma ray bath.

Predictably enough, random mutagenesis is massively destructive to most of the seeds exposed. However, sometimes a few will mutate in just the right way to gain new functionality such as faster growth or better yield, and these are what farmers are after.

Unlike GM strains created with modern biotechnology – which have to be extensively characterised and regulated – randomly mutagenised seeds are rarely (if ever) characterised, let alone disclosed to consumers as being mutants. Almost no country except Canada has any regulatory restrictions or requirements around the practice, nor does random mutagenesis violate any country’s organic standards.

Thinking about this for a second, we reach an absurd yet true conclusion. It’s completely possible that:

a) A specific mutation could be created in a lab using modern biotechnology. Meanwhile at a farm, completely by chance, the same mutation could be created using random mutagenesis. The resulting two organisms would be identical, but only one of them would ever be characterised, labelled or regulated.
b) An organic company that was fervently against “GMOs” could employ random mutagenesis in their crops. In fact, have you ever bought an organic Rio red grapefruit?

The practice of radiation breeding is on the rise, and possibly far more prevalent than anyone realises. Furthermore, there are solid arguments that conventional GMOs pose less threat than randomly mutagenised seeds. As a result, the current regulatory situation is, to put it politely, extremely strange.

The development of GMOs is an important issue for us to collectively address as we move into the future. Until the science is understood by people like you and me, no informed policy decisions can be made, and we’ll be stuck with the kinds of illogical regulations that currently exist. So if you’ve made it this far, congratulations! You’re a part of the solution, and next time you hear the term “GMO” you can think, “Aha. That means a protein has probably been added.”

Interested for more? Read on with GMOs Pt 2: How to Make Your Very Own!