Digitalis to Digitoxin

By Joanna Wolstenholme

The foxglove, it seems, is more than just a pretty flower. Now a wide stream drug – with the trade name of digoxin – used to treat congestive heart failure, it has been used in folk medicine since at least 1596.

481px-Digitalis_purpurea_Koehler_drawing

Digitalis purpurea, or purple foxglove

Traditional herbals – compendiums of folk knowledge, accumulated and added to over the years and generations – are a mine of knowledge for possible new drug sources. William Withering, a forward thinking gentleman [s1] of the 18th century, understood this in a time when many dismissed such folk knowledge as witchcraft. He took a claim from John Gerard’s 1596 Herball that ‘Fox gloue boiled in water and wine…. Openeth also the stopping of the liver, spleene and milt and other inward parts’. This claim for the effects of the foxglove on the internal organs caught the curiosity of Withering, and he investigated further to find that foxglove was an effective cure for dropsy, a swelling of the limb and torso; a disease we now know is due to the inadequate pumping of the heart.

This use for foxglove was brought to the light after Withering’s conversations with a wise old woman in Shropshire, who had a family recipe for the cure of dropsy. Withering’s knowledge of herbs and the human body (he had training both as a doctor and a botanist, only truly becoming interested in botany after being asked to collect flowers for his sweetheart to paint) allowed him to isolate foxglove from the 20 odd herbs in the lady’s magic potion. He humbly commented later that it was ‘not very difficult for one conversant in such subjects, to perceive, that the active herb could be no other than foxglove’.

Withering went on to prescribe infusions of the leaves, and ground dried leaf powder, as a cure for dropsy. Modern reanalysis of the data that Withering recorded of his patients shows that he had a 65-80% success rate – good even by today’s standards. Powdered foxglove – now sold as Digitoxin, but still extracted from countless hundreds of foxgloves – is still prescribed to treat congestive heart failure, an underlying case of dropsy.

Stories such as these surely tell us that we cannot simply dismiss knowledge held in ancient herbals as nonsense, or witchcraft. Whilst those recording these cures may not have known how they work at the molecular level, nor conducted double blind trials, but they recorded potions and infusions that they knew to be successful. What worked then, in an age of ignorance of what caused terrifying ailments, will work now, in an age where we have the ability to extract the active compounds, and even synthesise analogues with fewer side effects.

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Mathematical Patterns in Plants: Fibonacci and The Golden Ratio

By Ellie Archer

Spiral patterns abound in nature, manifesting themselves in plant petals, sunflower heads and pine cones. Remarkably, the maths behind these patterns all stems from one simple number: the golden ratio.

What is the golden ratio? Mathematically, it is the number ϕ such that ϕ = 1 + ϕ-1, approximately equal to 1.61803. Visually, if we draw a rectangle with sides in the ratio 1:ϕ, we obtain what is deemed to be the “perfect” rectangle (indeed Da Vinci used these rectangles to paint the perfect proportions for the Mona Lisa’s face). We can then construct a sequence of golden rectangles, as in the picture, inside of which we may inscribe the Fibonacci spiral, and it is precisely this spiral that we see exhibited so frequently in the natural world.

 

fibonacci

The Fibonacci Spiral (Image credit: people.rit.edu)

Perhaps the most classic example in nature is that of seed arrangement in a sunflower head. The seeds spiral out from the centre, and the problem is how to arrange the seeds to make the most efficient use of the space available. If you spiral too tightly, the seeds get squashed too close together and do not have sufficient space to mature. If you spiral too slowly, a lot of the space available isn’t utilised. It transpires that the most efficient path to take is a Fibonacci spiral.

Why is this? Imagine we are tracing a spiral by forming a seed, then rotating through a certain angle, then forming a new seed, and repeating. Suppose we make a quarter turn between forming each seed. We just end up with four straight lines of seeds, branching out from the centre in a cross shape. A similar thing occurs if we take any simple fraction (such as 5/7 or 1/31, giving seven or 31 branches respectively). Perhaps if we take an irrational number, say π, things may be better. But in actual fact π is very close to 22/7, so again we get seven branches, this time with very slight spiral behaviour.

ϕ is special because it is pretty much as far from a simple fraction as it could be.  Repeatedly applying the relation ϕ = 1 + ϕ-1, we can write it as the following infinite fraction:

This means that rotating through a fraction ϕ of a full turn avoids building up branches with empty space in between. Instead we get a pattern as shown in the sunflower, which is in fact a lot of Fibonacci spirals.

sunflower

Fibonacci spirals in sunflowers (Image credit: brilliantbotany.com)

The golden ratio is deeply connected to the Fibonacci sequence (0, 1, 1, 2, 3, 5, 8, 13, 21, …, where each term is formed by adding the previous two). Though the Fibonacci numbers were initially studied in relation to mating patterns in rabbits, it turns out that the ratio between two successive Fibonacci numbers is very close to ϕ, and indeed gets arbitrarily close as we take larger Fibonacci numbers. This means that the total number of spirals we see is usually a Fibonacci number, and if we count spirals going in opposite directions, we get two consecutive Fibonacci numbers, as shown in the pine cone below.

Pine

Fibonacci spirals in a pine cone. We count 13 and 8 spirals in each direction, both Fibonacci numbers. (Image credit: http://www.maths.surrey.ac.uk/hosted-sites/R.Knott/Fibonacci/fibnat.html)

There are countless examples of this in the plant world. Not only does this explain why three-leafed clovers are far more abundant than their four-leafed counterparts, but next time you see a daisy, take a look: chances are it’ll have 21 petals!

Anything you can do, plants can do better!

By Stephanie French

The other week I bumped into a friend of mine in Sainsbury’s. We were chatting away as usual when he asked me: “are plants alive?”. I thought to myself that this was just another example of how under-appreciated the Plantae kingdom is, and yes, of course, most people do know that plants are alive, but many perceive them to be boring, simple lower-life organisms.

Credit: Atanu Saha

Credit: Atanu Saha

However, this is far from the truth; land plants actually evolved after animals, and in some ways are more complex. For example, while animals can move away from poor environments, plants are forced to cope with whatever nature throws their way. They may not appear to change very much in different weather conditions, but within plants hundreds of dynamic signalling events are occurring from the cellular to the whole-plant level allowing the plant to survive in extreme environments. For example, during high light-stress, plants can move chlorophyll within their cells to more “shaded” areas, rapidly move their leaves, develop surface reflectants (pubescence), and dissipate excess heat using the xanthophylls cycle…the list goes on. Plants, unlike animals, are actually acclimating throughout their entire life cycle.

Further complexity of the plant cell can be seen just by looking down a microscope, or thinking back to the classic ‘animal cell vs plant cell’ picture present in nearly all high school biology text-books. Plants contain more organelles including, of course, chloroplasts! And, sure, animal cells can differentiate to form more complex-looking cells such as nerve cells, but plant cells can do that too (e.g. sieve-tube elements). Also, although not generally realised by most people, plants can form organs like animals too – leaves and flowers etc. are indeed organs. Do you know any animals that have chloroplasts? I think not (ok actually there are actually three but they steal the chloroplasts from plants)

And if you thought your love life was complex, for plants it is (probably) even more so. As angiosperms (flowering plants) can produce multiple stamens (male-parts) and carpels (female-parts) there is so much more potential for variation. A single flower can be male or female or hermaphrodite. On the whole plant, all flowers may be the same sex or there may be a combination of male, female or hermaphrodite flowers. Plants even have a complex mechanism called self-incompatibility, to prevent inbreeding.

When sex does occur, it is twice as good as in the animal kingdom. Double fertilization occurs whereby one sperm cell penetrates the egg cell while another penetrates a different cell called the central cell. Both these cells develop within the seed, the former forming the embryo and the later forming the endosperm, which provides nutrients to the developing plant.

In fact plants are so complex and diverse that they even confused Charles Darwin! He frequently referred to angiosperms as an ‘abominable mystery’, as he could not figure out what the most ancestral flowering plants looked like or why they diverged so rapidly. This is still disputed over by many scientists! One theory is that by using other organisms to carry their gametes, angiosperms were able exploit many niches and diverge in a short space of time.

These are just a few of the many reasons why plants deserve so much more respect than they currently receive. So much research is focussed on animals, with the possibility that it may enable future drug discoveries, which of course is great. However, plants have the potential to increase crop productivity and provide the world with renewable energy, so research on plants is equally, if not more, important.

Harmful algal blooms; the monster in the shallows

By Alex Steeples

Many of us will have been there, sat on a sunny beach unable to go into the sea, due to the presence of a polite sign warning you of toxic algae. To many this seems illogical; what harm can some floating green specks or tangle of sea weedy mush do? Especially when there are great white sharks and box jellyfish lurking in the deep.

Harmful algal bloom (HAB) is a non-specific term used to refer to any sudden increase in the amount of algae that is deemed to be detrimental to the environment. This harm can be either through the production of harmful toxins, primarily neurotoxins such as brevetoxin and domoic acid; or through the large increase in algal biomass reducing water oxygen content and affecting the food web.

HABs occur due to a sudden increase in the nutrient content of the water, which allows for rapid growth. These increases, particularly in nitrogen and phosphorous, are often associated with specific seasonal changes, meaning many areas suffer from repeated periodic algal blooms.

Neurotoxin producing algal species such as Karenia brevis, primarily show their effects through the killing of large quantities of fish, which later wash up on shore. Higher mammals may also be killed, or suffer severe illness, if they ingest toxins via a vector such as fish or sea grass. The consumption of contaminated fish was associated with death of over 100 bottlenose dolphins off the coast of Florida in 2004. In the case of humans, whilst fatalities are rare, shellfish poisoning often occurs. This results from the ingestion of shellfish, primarily mussels and clams, which accumulate the toxin.

Although HABs have a wide ranging ecological impact, they also have important socio-economic effects. HABs can cause the closure of fisheries, and sea side resorts for the duration of the bloom, leading to loss of income and, in some cases, livelihood.

So next time you see that sign warning you of algae, pay attention. After all, not all dangers lurk in the deep.

There’s plenty more CO2 in the sea

By Charlie Whittaker

Life in water isn’t all plain sailing, particularly if you’re photosynthetic. As well as the problem that you’re wet all the time, it actually poses pretty big problems for a cell’s CO2 uptake (something essential for photosynthesis). Most CO2 in water is dissolved, and in the form HCO3-. As well as this, stuff in general diffuses far more slowly in water than air, all in all causing a massive problem for the organisms that need it.

Ninghui Shi

Credit Ninghui Shi

In response to these challenges, aquatic organisms have evolved a wide array of means of stuffing themselves with as much CO2 as possible. These are known as Carbon Concentrating Mechanisms (CCMs for short) and are found in a huge number of different algal species, as well as the critters that gave rise to the chloroplasts, the cyanobacteria. In algae, the CCM relies upon the usage of a subcellular structure called the pyrenoid. All of the Rubisco (the enzyme that uses the CO2) aggregates in a specific part of the chloroplast, and CO2 delivered, in doing so generating awesomely high local concentrations. Cynaobacteria on the other hand use Carboxysomes, which are protein covered boxes chock full of Rubisco.

Either way, they’re pretty neat, and enable these guys to generate over 50% of the world’s primary productivity, despite the unfavourable conditions!

Stop trimming the fat! Fat algae fuel the future

By Sophie Harrington

A recent breakthrough at the Scripps Institution of Oceanography has provided a way to increase the production of valuable fat molecules in algal biofuel production. These lipid oils are necessary for fuel production. However, they are only produced by algae in nutrient starved conditions. Previously, this had limited algal growth and, as such, prevented significant lipid accumulation.

Credit Steve Jurveston

Credit Steve Jurveston

Dr. Emily Trentacost and her team were able to genetically target lipases, the molecules responsible for fat breakdown, and limit their activity. As a result, algae grown in high nutrient conditions began producing significant quantities of lipids. Algal growth no longer has to be compromised to obtain the fats needed for biofuels.

Not only does this development lower the cost of biofuel production, but techniques used in the process have now been adapted to increase the speed of biofuel production. While it’s still a long way before algal biofuels are competitive in price to gasoline, this breakthrough is only one in a line of recent discoveries that are improving their yield and cost effectiveness. It seems like the sky might be the limit for algal biofuels!

Plants and Folklore: Coco de Mer

By Nathan Smith

A lush palm forest sits untouched by mankind. Huge leaves spread out to gather the sun’s rays and through the forest … swims a shark? This is the case of the Coco de Mer and the legend that surrounded it.

The Coco De Mer is a unique plant. The sole member of its genus, it is found naturally only in the Seychelles. Its seeds are the heaviest in the plant kingdom, weighing up to 17.6 kg. If and when a Coco de Mer fruit falls into the sea, it sinks to the bottom. After a while, the husk drops off and the internal parts of the nut decay. The resultant gases that form inside the nut cause the bare nut to float to the surface.

Those who witnessed the nut rise up out of the ocean reasoned (semi-logically) that it must grow on underwater trees located at the bottom of the ocean. Furthermore, many believed (a lot less logically) that these underwater trees to be the home of a fearsome bird-like creature that could hunt elephants and tigers.

In 1768, the origin of the nuts  was finally traced to the Seychelles by the expedition of Chevalier Marion Dufresne. His second in command, Jean Duchemin, returned a year later and exported such a quantity of nuts as to flood the market and quash much of their extraordinary reputation.