CRISPR/Cas9 and its Natural Inspiration

Jayde Martin highlights the role of evolution in developing the genome editing tool

What’s natural about genetic engineering? That’s the first question I hear you ask. I would like to argue that it is, indeed, nothing short oforganic. CRISPR/Cas9 is a unique technology that enables geneticists and medical researchers to edit parts ofthe genome by removing, adding or altering sections ofthe DNA sequence. Significantly, its inspirational origin is based on that ofa type ofmutational change – a natural development consequently, this type of genome editing can be classed as ‘natural’. CRISPR/Cas9 is modelled offan entirely organic process in bacteria: scientists have learnt to utilise the adaptive immune response of Staphylococcus aureus to a viral infection, as a genetic modification template. This is important to help the human species overcome predisposed genetic conditions that could lead to rapid degenerative decline and early death. Here, we have a case ofa scientific technique derived from a natural process, to further manage and expand human life expectancy. For this alone, I would like to state that genetic engineering is, in fact, natural.

The immune response ofa bacterium, such as S. aureus, to a viral infection is the result ofprokaryotic evolution. The bacteria create two RNA strands, one ofwhich mirrors the DNA sequence ofthe virus in question. These two RNA strands then form a complex with Cas9, which is essentially a nuclease, the cut and paste enzyme of the biological world. Cas9 takes a section ofthe viral DNA, severs it, and then matches the RNA to the viral DNA. It essentially robs the virus ofits original DNA, without which the virus cannot replicate. Cas9 and its mischievous RNA strands have a 20 set base pair to match the viral DNA–many ofthese Cas9 enzymes will take different sections of the virus to fully incapacitate it, by snatching strands ofits entire DNA sequence. So how does this relate to the manipulation and mutation ofthe human genome? Instead of20 base pairs ofRNA that matches virus DNA, Cas9 can be used to target 20 base pairs ofthe human genome, replicate it, and cut. Controlling what and where CRISPR/Cas9 cuts is how we exploit this natural process as a tool for our own means–just like we did with fire and the invention ofthe wheel.

The prevailing fear of changing our genes is arguably outdated, so the important question to pose is: why does our control over it scare us? Yes, there are fears ofneo-eugenicism (an ideology concerned with improving a species, through influencing or encouraging reproduction with parents that have desirable genetic traits). However, through awareness and consideration of disability studies, identity politics, and even the study ofpost-colonialism, we, as the next generation ofresearchers, can avoid the mistakes ofthe past. It is time to change the way in which we perceive genetic engineering. Shedding the image that dystopian science fiction has painted it to be, I believe we can make it something different. We can inclusively adapt genetic engineering to our advantage: its potential application in genetic therapies is promising for carriers of genetic disorders, such as phenylketonuria, cystic fibrosis and sickle cell syndrome. Instead ofthe messy idea oferadicating ‘disease’, we can develop a genetically-diverse spectrum ofindividuals, and reinstate the right to a full and longer life in individuals who would otherwise succumb to genetic disorders. Genetic modification should always be considered alongside identity politics and ethics. But instead of blindly fearing advances in biotechnology, we should opt to utilise it sensibly to improve the quality of living–after all, it is ofa naturally occurring process!

Branching Out to Nature

Marion Cromb uncovers the logic behind the branching patterns of trees


Have you ever noticed that on trees small twigs tend to stick out from thick branches at right angles, but branches of the same size split from each other at smaller angles? This is not a feature that is unique to arboreal branching, and in fact can be understood with a model for the human vascular system: Cecil D. Murray’s physiological principle of least work. Work is the energy transported by a force, so this principle is about finding the configuration that expends the least energy. In other words; nature is lazy. Just as the arteries Murray studied transport blood throughout the body, we can model tree branches as a transportation network for water. Moving fluid along a narrow tube encounters larger frictional resistance (and thus takes more work) than moving fluid the same distance along a wide tube. So, to move from one point to another, taking a direct route in a small channel can be a lot less efficient than taking a longer, less direct route along a large channel then a short perpendicular hop in a narrow channel.

If two equal sized branches fork off the trunk on opposite sides, they do not deflect the trunk and emerge at the same angle. If just one branch emerges from the trunk, this will deflect the trunk, often considerably. Depending on the relative diameter of the trunk, branches come off at an angle between 70° and 90° to the original trunk, and the trunk is deflected between 0° and 90°. To have a network that fills the available space efficiently (e.g. to collect the most sunlight), it is necessary to minimise the length of inefficient narrower channels (that can fill gaps between larger channels) whilst minimising the overall material used. This results in the branches that ‘feed’ the biggest areas being the thickest. Leonardo da Vinci observed that as a rule of thumb, the cross-sectional area of a branch is equal to the sum of the areas of the branches it splits into.

Of course, the trees themselves have not predetermined a high efficiency network to grow into, but grow in a modular fashion, obeying the same simple rules of cell division in the meristem at every stage of growth. But despite this fixed process trees don’t turn out as completely uniformly repeating structures because environmental factors come into play, for example competition for resources such as sunlight, and twigs snapping off in the wind. Those trees with growth rules that combine with these external factors to create efficient branching networks are those that evolution favours and that we see thriving today. Branching is a result of very different mechanisms in many different physical phenomena: Lichtenberg figures, lightning and river systems to name a few. These branched networks all have similar properties and statistics to purely mathematical networks generated by random numbers, hinting that effective branching patterns are more dependent on the geometry of space itself than the processes behind them.

In the Palm of Monoculture

Chyi Chung investigates the place of oil palm monoculture in nature

I grew up in Malaysian Borneo. I remember the long drives to the airport on the outskirts oftown. I remember where the urban sprawl relents to a sea ofprickly green, dominating the car window for the rest ofthe journey. I remember admiring row upon row ofshort, stunted trees with fans for leaves, seemingly reaching beyond the horizon. Having moved away, the oil palm trees are my first sight ofwelcome out ofthe plane window. From this bird’s eye vantage, their monoculture is an impressive mark ofagricultural science in nature. Oil palm (E. guineensis) is native to an area between modern-day Gambia and Angola. It was introduced as a cash crop to South-East Asia by British and Dutch colonialists in the 20th century. A productive perennial crop, it yields up to 3.6 tonnes ofoil annually from the stones ofits kernels—seven times of what soy and rapeseed can achieve per hectare ofland. It exists as a semi-solid state at room temperature (a property associated with more expensive animal fat), hence allowing fractionation for different uses. In 2014, WWF found that halfofthe packaged goods from British supermarkets contain palm oil, an unsurprising statistic considering its versatile applications, ranging from chocolate bars and biscuits, to detergents and cosmetics. The global palm oil market stands at 48 million tonnes; 85% ofwhich comes from Indonesia and Malaysia, the two countries that share Borneo with oilrich, land-locked Brunei. The world’s peatland forests, concentrated in Southeast Asia, harbour masses ofcarbon dioxide. From 1990 to 2010, peat forest cover in the region fell from 77% to 36%, coinciding with the rise of oil palm plantations. To clear land, slash-and-burn is often callously adopted out of ease, despite its illegality.

In 2015, El Niño drove warmer waters ofthe Western Pacific along the equator eastward to accumulate in the coastlines ofSouth-East Asia. El Niño is the term dedicated to a climate cycle beginning in the Pacific Ocean which can have consequences across the globe. This warming effect merely added fuel to the forest fires raging across Kalimantan (Indonesian Borneo) and the neighbouring Sumatra Island, resulting in thick haze smothering the region. In the worst affected areas, residents lived in a sepia-tinted world, where Pollutant Standard Index rose to six-fold above hazardous levels. Water bombs were dropped to cleanse the air by inducing rain. Under international pressure, the Indonesian government imposed a ban on cultivating oil palm on peat, but lifted it within a year, belying their environmental responsibility over commercial interests. The world is ravenous for palm oil, with demands expected to double by 2050. A push for a better industry resulted in the Roundtable on Sustainable Palm Oil forming in 2004, which works on a certification system like Fair Trade’s.

But detractors are quick to highlight that the skew in its committee—a third being goods manufacturers with oil producers making up less than a fifth—may just be a smokescreen for multi-national companies to hide behind. From heavy timber logging in the early 1900s to the current palm oil boom, the Bornean rainforest has been shrinking to its core, along with its delicate ecology. Animals indigenous to the island include the pygmy elephant [1], sun bear [2], and orang-utan [3]; all three are at least vulnerable, with the critically endangered orang-utan adopted as mascot for anti-deforestation campaigns. A 2008 ecological study by E.B Fitzherbert, shows that an oil palm plantation only sustains 15% ofits natural forest diversity, in which lies the fallibility ofmonoculture (single crop cultivation). From the Great Irish Famine to the decline ofthe South American rubber trade, leafblights and other diseases have obliterated whole populations ofmonoculture crops in the past. For example, recently, there have been concerns about the susceptibility ofthe Cavendish banana to a new strain ofPanama Disease. Agriculture sustains our ever-growing human population, but monoculture is a short-term solution. Polyculture and different alternatives ofcommodities should be encouraged. Only then can science imposed on nature become more in line with science in nature.

Magnetoreception: Nature’s Invisible Map

Bruce Saleeb-Mousa explores an extraordinary way animals are able to navigate

The ease with which we navigate towns, cities, continents and oceans is owed to our ability to manipulate the laws ofphysics and engineer tools and gadgets that help us reach our destinations. Ofcourse, it wasn’t always this way. Those before us faced the frequent, painstaking task ofplotting a course and constantly getting lost. This is because, as humans, we rely heavily on visual aids and memory to help us navigate, whether it be landmarks or the night sky. The major problem with this, being that, over large distances, landmarks may become indistinguishable, our memory may not serve us well, or simply our navigating techniques may be inadequate. Fortunately for many critters across the animal kingdom, this is not a problem—they can use the Earth’s magnetic field to navigate land and sea. This field is generated by the Earth’s liquid outer core. It has characteristics akin to that ofa huge bar magnet placed at the Earth’s centre, oriented at around 11 degrees to the rotational axis. The strength ofthe field ranges from around 25 microtesla at the equator, to around 60 microtesla at the poles.

In comparison, a standard fridge magnet is around a hundred times larger at about 5 millitesla—so Earth’s field is pretty weak. Thus, in order to navigate using the variation in this field, the method ofsensing must be able to resolve small changes ofup to ~35 microtesla. Navigation using the geomagnetic field has been established experimentally for certain animals [1]. Behavioural patterns in migratory birds, for example, suggest that they use magnetic sense to find their way south in autumn, and north in spring. The underlying mechanism involved in magnetoreception, however, is not fully understood. Three main processes may play a part: mechanical reception, where a magnetic field exerts a torque on a ferromagnetic material (the reason why a compass needle rotates); electromagnetic induction, where a change in magnetic field through a conductive material induces a voltage; or chemical reception, where variations in magnetic fields cause changes in the spin states ofcertain molecules. Of these three, most evidence seems to support a chemical reception mechanism [2]. There is debate as to whether humans are able to sense magnetic fields [3]. Theories based on the mechanical reception mechanism suggest that tiny compass-like needles made ofa material called magnetite sit in animal receptor cells, and that these can trigger nerve endings. The same material can be found in humans—unfortunately our ability to manipulate or even sense this seems to have been lost.

[2]SCHULTEN K, ETAL., Z. PHYS. CHEM, VOL 111, PP. 1-5.
[3]HAND E, DOI:10.1126/SCIENCE.AAF5804

Seahorses: Riding on Myths

Chyi Chung reports on the mysterious and misunderstood seahorse.

Poseidon, god of the sea, rides upon his chariot of hippocampi, fantastical creatures that possess the head and torso of a horse but the belly and tail of a fish. Their name mirrors their physique: a portmanteau of horse (hippos) and sea monster (campus) in Ancient Greek. Aptly so, hippocampus has been adopted as the genus of their real-life inspiration. Continue reading “Seahorses: Riding on Myths”

Return of the Leeches

Philippa Jefferies draws out the truth behind the leech’s comeback in modern medicine.

Usually, when someone mentions leeches and bloodletting, images of medieval physicians forcing leeches on their patients for any ailment are the first to jump to mind. Whilst it is common knowledge now that this is probably not the best way to relieve every symptom, leeches aren’t without their uses in modern medicine. In 2004, the FDA approved the sale of leeches for medical use in the USA and they are vital in many surgeries – particularly skin grafts and reconstructive surgery.
Continue reading “Return of the Leeches”

Osman Kent: An Improbable Journey

Interview and article by Phillipa Jefferies, Joanna Chustecki and Sara Jebril With thanks to the EPS Community and Alumni Relations Office.

On Wednesday 8th March Osman Kent, computer science and electronic engineering alumnus, returned to the University of Birmingham to inspire a whole new generation of technologists and entrepreneurs. He was cited by Business Insider magazine as one of the top 15 technologists in the world in 2012. However, as he discusses in his EPS distinguished lecture, it hasn’t always been plain sailing.
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Chemtrails: Is the Government Trying to Poison Us?

Bethany Rothwell takes to the sky and assesses the supposed impact of jet plane ‘chemtrails’.

It’s a gorgeous sunny day. You hear a plane passing overhead, look up at the sky and what do you think about? The pretty patterns of white streaking across the blue sky? Plans for your next summer holiday? Or the government’s ruse to shower us with psychologically-manipulating or weather-modifying chemical agents?
Continue reading “Chemtrails: Is the Government Trying to Poison Us?”

Cordelia Fine: Delusions of Gender

Marion Cromb reviews the book that reveals the neurosexism all around us.

Gender stereotypes are extremely pervasive, but is there any truth to them? In ‘Delusions of Gender’, psychologist Cordelia Fine picks apart the notion that different behaviours of the sexes are somehow innate. With a comprehensive review of the scientific literature (over 80 pages of references!), Fine wittily debunks the essentialist notions found in pop science books with titles such as ‘Men are from Mars, Women are from Venus’ and ‘Why Men Don’t Listen and Women Can’t Read Maps’. Continue reading “Cordelia Fine: Delusions of Gender”