The Future is No Clockwork Orange

By Nathan Smith

Imagine a life without citrus. No glass of orange juice in the morning. No slice of lemon for your iced tea. No having to segregate the green jelly babies because no one honestly likes them and you don’t understand why they continue to be produced. It would be a very different world indeed, but perhaps one we need to start considering.

Credit Father.Jack

Down with the green jelly babies… (Credit Father.Jack)

The threat to our favourite sources of Vitamin C comes from the double-pronged assault of the bacterial diseases citrus canker and huanglongbing (or citrus greening disease), which are currently having a massive impact on the citrus industry. To make matters worse there are few signs of resistance among the plants. This is mainly because the majority of citrus fruits aren’t natural species, they’re cultivars which are the result of varying inter-specific crosses. A few examples are the sweet orange, which is the result of a cross between a male mandarin and a female pomelo; and the grapefruit which is the result of a cross between a male sweet orange and a female pomelo.

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The invincible kumquat (Credit Acongagua)

A study by a group from Pakistan tested how various citrus cultivars responded to the citrus canker disease and found that some are more susceptible (like Valencia Oranges) than others (like Pigmented Oranges). While two cultivars were identified as highly resistant, Tahiti Lime and Kozan Sweet Oranges, all the cultivars showed some levels of disease. Unfortunately this indicates that all would eventually succumb to the ravages of citrus canker. That is, all except for the kumquats!  Both cultivars of kumquat tested (Meiwa and Naghmi) lacked the canker-caused lesions that unfairly graced the other plants. This may be because kumquats are only citrus fruits in the loosest sense. Unlike most of these other fruits, which belong to the Citrus genus or are products of genetic crosses within the genus, kumquats belong to the genus Fortunella. This makes them distinctly different to oranges and lemons genetically and means they may be a non-host for citrus canker and perhaps by extension for other diseases plaguing citrus; though reports of a huanglongbing-type disease in Kumquats in Taiwan suggests otherwise.

Even so resistance to citrus canker is promising. Humanity may learn to adapt and a future without oranges certainly seems brighter with the potential for Kumquat Flavoured Jelly Babies. At the very least they might taste better than the green ones.

 

 

Global health calls on an old foe to help fight Ebola

by Charlie Whittaker

Since March this year, at least 5,800 people across the countries of Guinea, Liberia, Nigeria, Senegal and Sierra Leone have contracted Ebola. Of those infected, more than 2,800 have died. As well as being the largest outbreak on record, this particular incident is worrying because of its potential scale- in August, the WHO hoped to have it contained within 9 months (and with 20,000 infected) but recent research by American epidemiologists suggests that the process of containment could take up to 18 months, with 100,000s of people infected before the outbreak is brought under control.

Ebola is the common name for Ebola Haemorrhagic Fever, caused by the similarly named ebolavirus. Spread through direct contact with bodily fluids such as blood or vomit, symptoms tend to manifest after a 1-2 week incubation period. Fever, muscle pain, vomiting and declining organ function are all symptoms, usually followed by significant internal and external bleeding.

The disease has a startlingly high mortality rate; this varies from outbreak to outbreak, but is usually put at somewhere between 50 and 90%. Pressingly, there is currently no available specific treatment for the disease, with care usually limited to oral rehydration therapy and intravenous fluids. This lack of effective treatment coupled with the naturally high mortality rate means any outbreak has the potential to claim many lives, and is therefore a serious concern for both the countries involved and the wider international community.

Recent efforts by the American government have seen an experimental vaccine fast tracked and delivered to 2 infected aid workers without the usual rounds of clinical trials. ZMapp contains neutralising humanised antibodies that recognise and bind specifically to ebolavirus particles, rendering them harmless.

Given the potential scale and immediacy required of doses of vaccine, a problem is presented in terms of the means of production. Many thousands of doses are required, often at very short notice. In order to circumvent this potential issue, researchers have been investigating the potential for the use of plants as “bioreactors” to grow and produce these antibodies.

The principle behind this approach involves the inoculation and subsequent infection of a particular strain of tobacco, Nicotiana benthamiana (a close relative of the cigarette supplying cousin Nicotiana tabaccum) with a virus from the group of plant viruses called the Geminiviridae. These have single stranded circular DNA genomes, and although responsible for significant crop losses worldwide, here they have been co-opted for human benefit.

Nicotiana benthamiana  Image Credit: Charles Andres

Nicotiana benthamiana
Image Credit: Charles Andres

Their genomes are exceedingly pliable, and extra sections of DNA can be inserted in without compromising infectivity. In this case, DNA sections encoding the humanised antibodies making up the ZMapp treatment were inserted, and the subsequent genome produced then transfected into the plant. Once inside the plant, the existing viral features of the genome ensure replication and propagation of the entire vector, including the antibody, leading to production of high levels of antibody. These antibodies can then be purified and extracted from the plant, and refined in order to provide doses of the vaccine.

The advantages of production and accumulation of antibodies from plant-based bioreactors are numerous. Firstly, the particular viruses in question, the Geminiviridae, are able to replicate extensively within the plant, resulting in high yields. In addition, costs of production are lower as the maintenance of growing conditions is relatively inexpensive. Finally, generating the Ebola antibodies in plants minimises the risk of cross contamination with other mammalian viruses.

All in all then, could this be a timely and effective source of the treatment for this deadly disease? ZMapp has been fast-tracked in this instance, but must first still pass a battery of clinical trials to ensure its efficacy and safety, and questions still remain over the accessibility of it as a healthcare option for the poorest worldwide, for whom it is perhaps most urgently needed. Perhaps more solidly impressive is the global attention gained for the use of plants as bioreactors, and for their ability no act as relatively inexpensive and high yielding sources of various pharmaceutical goods. This makes them potentially able to lower the current cost of production to levels that would make these pharmaceutical products more universally affordable.

Tulips and TBV: The Curse of Beauty

By Nathan Smith

Think of a word to describe disease. Any number of negative adjectives may come to mind: painful, sorrowful, terrifying. But can a disease be beautiful?  Enter Tulip Breaking Virus (TBV), a disease of (unsurprisingly) tulips that causes colour-breaking in the plant’s flower. Colour-breaking is where the flower of the tulip displays more than one colour; for tulips, in a world free from disease, come only in solid colours.

Absalom tulip (Image Credit jpwbee)

Absalom tulip (Image Credit jpwbee)

In fact, TBV is one of five plant viruses that cause tulips to break this restriction, creating patterned petals in infinite combinations of streaks, stripes, feathers and flames. The cause of such wondrous symptoms is the irregular distribution of anthocyanin within the plant cells. Within TBV two strains are recognised, a severe and a moderate form. The severe form causes lack of anthocyanin leading to light breaking and the moderate form causing dark breaking due to excess anthocyanin.

The virus is historically important as being the cause of tulip mania, a period in Dutch history where tulip bulbs sold for increasingly high amounts. It was the rare bulbs affected by TBV that sold for the most, and at one point 12 acres of land were offered for one bulb of Semper Augustus, believed to be one of only two bulbs in existence at the time!

Infected tulips display other, less aesthetically pleasing symptoms too. Leaves become mottled and the bulb becomes increasingly stunted until it lacks the energy to flower and the bulb withers away or breaks apart. The unique beauty of these flowers is temporary, and after a brief flash of radiance their delicate splendour is lost to the annals of history. This is true for some of the most famous varieties, such as Semper Augustus or Viceroy, of which a single bulb sold for more than ten times the average craftsman’s annual earnings during the tulip mania.

Semper Augustus

Semper Augustus

Today, infected tulips still exist such as Absalon, which flowers a chocolate background with rich yellow swirls and has existed since at least 1780. However, to prevent spread of the virus many countries, including the UK, have placed a ban on the sale of “broken bulbs”.  For those still desperate to get their hands on patterned tulips, stable variants do exist that are the result of breeding and not of viral infection, such as Rem’s Sensation, though to many they do not match the spellbinding beauty of a flower doomed to die.

Three in the bed make for a hot relationship

By Nathan Smith

A plant, a fungus, and a virus live together in an environment inhospitable to each partner on their own. This isn’t an absurdist sitcom that’s been written whilst high in the garden, but a genuine biological phenomenon.

The plant, a type of grass known as Panic Grass (Dichanthelium lanuginosum), can grow at temperatures of up to 65C (for a point of comparison, the lethal temperature for humans is about 40C). It is found growing in Yellowstone National Park but only when it has a fungal symbiont Curvularia protuberata and this in turn is ‘infected’ with Curvularia thermal tolerance virus (CThTV).

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Too close for comfort? Not for Panic Grass, found near geysers in Yellowstone National Park in the United States

The ecological love-triangle was shown to be necessary for the plant-partner’s survival. This was done by infecting the plant with a ‘cured’ fungus (one that lacks the virus) and comparing it to a plant with both fungus and virus and a plant with no symbionts. The plants were then treated to growing conditions of 65C for 10hrs and 37C for 14hrs. At the end of the treatment, only plants with both partners remained healthy. Furthermore, all plants with both symbionts remained alive whereas the majority of the plants with only the fungus or nothing at all died before the experiment was completed.

However, panic grass isn’t that important or useful to us. It’s not eaten, nor is it cultured to produce fibre or biofuels. So is there any point to this knowledge? Well, the tri-kingdom system can be translated into more economically important crops. It has been shown that the fungal symbiont can colonise the roots of tomato plants and provide protection against higher temperatures, though not to the same extent as is provided to panic grass. It also suggests that the adaption to this system is widespread in nature, as panic grass and tomatoes diverged relatively early in the evolution of plants.

This certainly is hot stuff!