Make history, not vitamin C

(This post was previously hosted on my old blog at http://blogs.nature.com/eva and is published in print in The Best Science Writing Online 2012)

“Does the Flap of a Butterfly’s Wings in Brazil Set Off a Tornado in Texas?”
- Edward Lorenz

This is a story about a tiny molecular shift affecting war, politics, disease, agriculture and international corporations. Like all good stories, it also contains a healthy dose of biochemistry and genetics, some pirates and a few rodents of unusual size. The very start – the event that set everything in motion – is a genetic mutation that happened millions of years ago, but we’ll get to that. First, let’s meet the pirates.

The pirates in this story are Dutch pirates, and they were active near the end of the 16th century. During this time, the Netherlands were occupied by Spain, and after a period of repression, the Northern (protestant) provinces started to fight off the Spanish. They were most successful on water. From 1568 onward, several ships received government permission to attack and plunder Spanish ships. These “watergeuzen” dominated on sea, but in 1572 they captured the city of Brielle, marking a turning point in the Eighty Year’s War.

Meanwhile, a large part of the income for the Spanish side of the war came from trade with the East Indies. The European supply of pepper was solely provided by Portuguese fleets, and the trading post in Lisbon was no longer easily accessible to the Dutch while they were at war with Spain. Pepper was extremely valuable in those days, and the Portuguese kept their routes secret to make sure nobody else would cash in on the spice. But eventually, Dutch ships found a route to the East Indies. They sailed south, all the way around Africa, and returned with enough spices to finally make some money.

VOC ship off the coast of South Africa

Finding a trade route to the East Indies led to the formation of the East India Company (VOC) in 1602 – the first multinational corporation, and the first company to sell stocks. The company did more than buy and sell spices, though. For several years, it had a monopoly on colonial activities in Asia, and it had the power to take prisoners and establish colonies. During its existence, the VOC boosted the economy of the Netherlands to the top of the world. This period of economic growth is referred to as the “Golden Century” in Dutch history.

Money may not buy happiness, but the sudden wealth of the country certainly formed the perfect environment to nurture artistic endeavours and encourage major scientific progress. These were the century and country in which Rembrandt painted the Night Watch and Antonie Van Leeuwenhoek developed the microscopes with which he first observed single celled-organisms. The effects of the VOC trade have shaped entire fields of art and science, all because a few ships found a route to the East Indies in a time of economic need.

There was just one problem with the VOC trade route to the East Indies: It was quite long.

Scientific progress notwithstanding, there was no suitable way to keep the crew’s food, especially fresh fruit and vegetables, from going bad before they were even halfway there. This was a problem, because without fresh fruit, the crew was prone to scurvy. Scurvy was the scourge of sea travellers since the 15th century, when ships started to sail across oceans and stayed away from home – and fruit – for too long. Starting with some spots on the skin, scurvy can progress to bleeding from mucous membranes, ulcers, seeping wounds, loss of teeth, and eventually death. 15th century explorers could lose up to 80% of their crew to scurvy. The solution was known and simple: eat lots of fresh fruit.

Scurvy is caused by a lack of ascorbic acid – better known as vitamin C. Our bodies use this vitamin for many metabolic processes, such as producing collagen or repairing tissue damage. Without vitamin C, we essentially slowly start to fall apart – skin breaks open, wounds won’t heal, teeth fall out.

But we humans are one of the few animals that need to eat fruit and vegetables to keep our vitamin C levels up. Most animals are quite capable of synthesising their own vitamin C. Most, but not all. We share our need for fruit and veggies with other primates, including closely related apes, but also monkeys and tarsiers. Our inability to synthesize vitamin C is the result of a mutation that occurred more than forty million years ago in our shared primate ancestor, affecting the gene that encodes the L-gulonolactone oxidase (GULO) enzyme. Normally, this enzyme catalyses a crucial step in the formation of vitamin C. But in humans and related primates the genetic mutation produces a broken enzyme. It doesn’t work, and we can’t make our own vitamin C anymore. Luckily, it’s quite easy to compensate for the lack of GULO by simply taking in vitamin C via our diets, but this also meant that there was no selective pressure for a functional GULO, and us primates have been living with a broken version ever since.

The relative ease by which animals can compensate for no longer producing their own vitamin C is illustrated by the fact that the mutation that disabled our GULO enzyme millions of years ago was not the only mutation in the animal kingdom to shut down vitamin C biosynthesis. It happened at least three other times: bats, guinea pigs, and sparrows also have defective GULO enzymes and get vitamin C via their diets. The mutation in the guinea pig’s ancestor happened more recently than ours – possibly “only” about 20 million years ago, but that is still far enough back to also have affected another member of the caviidae family: The capybara also needs a steady diet of vitamin C to keep a hold on its title of largest living rodent on earth. Especially in captivity these R.O.U.S. (rodents of unusual size) are, like the sailors and pirates of yore, at risk of scurvy unless they eat enough fresh vegetables.

 

Speaking of fresh vegetables – how were the VOC crew going to manage the journey to the East Indies, which took longer than the expiration date on their perishables? The ideal solution was to restock along the way, but the continent of Africa was not exactly a farmers market where you can just get some more fruit and veg when you need it. Well then, they would just have to make a farmers market. The VOC took several Dutch farmers, and settled them in South Africa to grow more food for the ships passing by along their trade route. The restocked ships could then sail on with a scurvy-free crew.

 


The VOC’s Commander of the Cape, Jan van Riebeeck, founding the first Dutch colony in South Africa on April 6, 1652.


If the VOC crew had been able to make their own vitamin C, like most animals do, they wouldn’t have had to bring farmers to South Africa. That move, guided by a mutation that happened millions of years ago, entirely shaped the more recent history of South Africa. How? Here’s a hint: The Dutch word for farmer is “boer”.

The Boer population of South Africa were the direct descendants of the farmers relocated there to supply the VOC ships with the fruit and vegetables for their voyage to and from the East Indies. After the VOC was disbanded and British colonials settled in South Africa, the Boer population moved away from the Cape. Conflicts between the Boers and the British Empire, most notably the Second Anglo-Boer War at the end of the 19th century, directly led to the formation of the Union of South Africa in 1910, which was the predecessor of the current-day Republic of South Africa.

So there you have it. In a scene set by pirates, and with R.O.U.S. lurking in the background, an entire country, with all its political and cultural complications, was formed as a result of a method to distribute fruit and vegetables to the crew of 17th and 18th century trade ships to compensate for a genetic mutation that makes humans incapable of synthesising their own vitamin C.

Our broken GULO enzyme may not have been able to make vitamin C for millions of years, but it’s made history all right.

10 thoughts on “Make history, not vitamin C”

  1. This post took forever to research. While I knew the basics, I had to look up a lot of details.

    I’ll try to find all the references for this, especially the 40 million years estimate (it’s based on the estimate of how old tarsiers are), and some of the historic facts (e.g. 80% of ships’ crews lost to scurvy). Most of it, though, came from Wikipedia, which has a lot of info on South Africa and the VOC.

    The Golden Century info was the only thing I just knew, but even then I had to double-check when Van Leeuwenhoek and Rembrandt were actually alive. I’m sooooo bad at history. This was a huge challenge!

  2. I couldn’t remember how to log in :-( It’s been a while.

    I loved the reference to R.O.U.S. More seriously, though, are we still transcribing <i>GULO</i> RNA, and if so, why and in what tissues? "But in humans and related primates the genetic mutation produces a broken enzyme. It doesn’t work, and we can’t make our own vitamin C anymore."

    Great post, Eva. An obvious submission to The Open Laboratory…

     

  3. I forgot, but I think at least one of the mutations (maybe ours) is an early STOP (partial transcript maybe?). The birds/bats/cavies/primates were all different, and can’t remember which is which. Can look it up when I do the references.

  4. It would be interesting to learn just how GULO expression is broken,  If it is as simple as a splicing mutation, taking a steric-blocking antisense oligo might restore GULO expression.  I’m afraid that technology came too late for the VOC though.  Fascinating post, Eva!

  5. It’s probably mutated in multiple places by now, since we haven’t used it for millions of years, though.

  6. Excellent post! Bravo!

    As an aside, whenever an American or Australian calls me a limey or pommie, respectively, in a disparaging way, I say "yeah, we cured scurvy. We suck."

  7. Not just that, Cath, but Brits discovered the sublime combination of little green citrus, quinine laced soda and gin, that evile juniperic cortex solvent.  Anywhere I go where the British empire has extended, I can count on finding that refreshing concoction AND jigger my odds of contracting malaria.  So, King Georce sucked but the G&Ts and the Beatles alleviated the pain.  On the whole I’m glad we’re neighbors.  Sorry about Rupert.

  8. Doubt there’s enough quinine in tonic water to keep you from getting malaria, Jon – though I dare say it’s presence helped with the advertising.

    Juniper-flavoured spirit, aka gin, is, of course, another of those things where the Dutch might be making a claim to being the inventors…

     

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