Vitamins’ Old, Old Edge

December 9, 2013

By CARL ZIMMER

In 1602, a Spanish fleet was sailing up the Pacific coast of Mexico when the crew became deathly

ill. “The first symptom is pain in the whole body that makes it sensitive to touch,” wrote Antonio de

la Ascensión, a priest on the expedition. “Purple spots begin to cover the body, especially from the

waist down; then the gums become so swollen that the teeth cannot be brought together, and they

can only drink, and finally they die all of a sudden, while talking.”

The crew was suffering from scurvy, a disease that was then both bitterly familiar and deeply

mysterious. No one knew why it struck sailors or how to cure it. But on that 1602 voyage,

Ascensión witnessed what he considered a miracle. While the crew was ashore burying the dead,

one sick sailor picked up a cactus fruit to eat. He started to feel better, and his crewmates followed

his example.

“They all began to eat them and bring them back on board so that, after another two weeks, they

were all healed,” the priest wrote.

Over the next two centuries, it gradually became clear that scurvy was caused by a lack of fruits and

vegetables on long-distance voyages. In the late 1700s, the British Navy started supplying its ships

with millions of gallons of lemon juice, eradicating scurvy. But it wasn’t until 1928 that the

Hungarian biochemist Albert Szent-Gyorgyi discovered the ingredient that cured scurvy: vitamin

C.

Szent-Gyorgyi’s experiments were part of a wave of early-20th-century research that pulled back

the curtain on vitamins. Scientists discovered that the human body required minuscule amounts of

13 organic molecules. A deficiency of any of the vitamins led to different diseases — a lack of

vitamin A to blindness, vitamin B12 to severe anemia, vitamin D to rickets.

Today, a huge amount of research goes into understanding vitamins, but most of it is focused on

how much of them people need to stay healthy. This work does not address a basic question,

though: How did we end up so dependent on these peculiar little molecules?

Recent research is providing new answers. It appears that vitamins were essential to life from its

earliest stages some four billion years ago. Early life-forms could make their own vitamins, but

some species — including ours — later lost that ability. Species began to depend on each other for

vitamins, creating a complex flow of molecules that scientists have named “vitamin traffic.”

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A Universal Chemistry

Every vitamin is made by living cells — either our own, or in other species. Vitamin D is produced

in our skin, for example, when sunlight strikes a precursor of cholesterol. A lemon tree makes

vitamin C out of glucose. Making a vitamin is often an enormously baroque process. In some

species, it takes 22 different proteins to craft a vitamin B12 molecule.

While a protein may be made up of thousands of atoms, a vitamin may be made up of just a few

dozen. And yet, despite their small size, vitamins expand our chemical versatility. A vitamin

cooperates with proteins to help them carry out reactions they couldn’t manage on their own.

Vitamin B1, for example, helps proteins pull carbon dioxide from molecules.

Vitamins carry out these chemical reactions not just in our own bodies but in all living things. “If

you talk about bacteria, fungi, plants, humans — everybody needs them,” said Harold B. White III,

a biochemist at the University of Delaware.

This universal chemistry is likely the result of evolution. Scientists generally agree that life on earth

today evolved from a chemically simpler form perhaps four billion years ago. Those primordial

organisms relied on a single-stranded variant of DNA, called RNA. Back then, RNA did double

duty, carrying genes, the way DNA does today, and catalyzing chemical reactions, as proteins do

now.

Dr. White was one of the first scientists to think seriously about this primordial “RNA world.” In

1975, he proposed that vitamins helped RNA molecules carry out their chemical reactions. While

proteins took over those reactions, they still rely on the same vitamins. “There’s no way we’re going

to get rid of them now,” he said.

When Dr. White offered up his theory, other scientists were skeptical. “People were saying, ‘How

are you going to test it?’ ” he recalled. “I said, ‘I can’t.’ I didn’t see any way to do that work at the

time.”

It took nearly four decades for technology to catch up. Dipankar Sen, a biochemist at Simon Fraser

University in British Columbia, set out in 2007 to test Dr. White’s idea.

After six years of tinkering and testing, Dr. Sen and a graduate student, Paul Cernak, found an

RNA molecule that could use vitamin B1 to pull carbon dioxide from another molecule. That is

what proteins use B1 for today, just as Dr. White had predicted. Dr. Cernak and Dr. Sen described

their experiment in Nature Chemistry.

The Ability We Lost

Once the ability to make vitamins evolved, some species became especially good at making them.

Plants, for example, evolved into vitamin C factories, packing their leaves and fruits with the


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molecule. At first, vitamin C probably defended plants against stress — a function it carries out in

other species, including us. But over time, the vitamin took on new jobs in plants, like helping

control the development of fruit.

It took hundreds of millions of years for plants to become such proficient vitamin C manufacturers,

but vitamin production can change in far less time. Our own ancestors needed just thousands of

years to alter their production of vitamin D. When humans left equatorial Africa and spread to

higher latitudes, the sun was lower in the sky and supplied less ultraviolet light. By evolving lighter

skin, Europeans and Asians were able to continue making a healthy supply of vitamin D.

Aside from vitamins D and K, we humans can’t make any of the vitamins we need to stay healthy.

In some cases, our ancestors could make them, but lost that ability. Our mammalian ancestors 100

million years ago never got scurvy, for example, because they could make their own vitamin C.

Many vertebrates can make vitamin C, and use an identical set of genes to do so. “We should be

able to make it, too, since we have all the genes,” said Rebecca Stevens of the French National

Institute for Agricultural Research.

Unlike a frog or a kangaroo, however, we have crippling mutations in one of those genes, known as

GULO. Unable to make the GULO protein, we cannot produce vitamin C.

“It’s not just us — it goes back a long time,” said Guy Drouin, a molecular evolutionary biologist at

the University of Ottawa. He and other researchers have found that apes and monkeys, our closest

primate relatives, have disabled GULO genes, with many of the same mutations. Dr. Drouin has

concluded that the common ancestor we share with those other primates lost the ability to make

vitamin C around 60 million years ago.

It Wasn’t Just Us

Primates are not the only animals with a damaged GULO gene, however, and that’s why scientists

were able to discover vitamin C in the first place. Dr. Szent-Gyorgyi made his breakthrough thanks

to a discovery that guinea pigs, unlike other rodents, get scurvy. It turns out that their GULO gene

is disabled by a different set of mutations from the ones we carry.

As it did in primates and guinea pigs, the GULO gene became disabled in a few other lineages, like

bats and songbirds. Scientists have found that animals tend to lose vitamin C after a switch to a

diet rich in it. Our primate ancestors, for example, started eating fruit and leaves that supplied

them with far more vitamin C than they needed.

“It may seem counterintuitive that you would lose a gene that enables you to be independent,” said

Katherine E. Helliwell of the University of Cambridge, co-author of an August review about

vitamin decay in Trends in Genetics. “But if you’re always surrounded by a vitamin for a long


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period of time, then you don’t need to use the gene.”

Now that scientists can scan genomes of thousands of species, they’re discovering many more cases

in which vitamin genes have either decayed or disappeared altogether. Sergio Sanudo-Wilhelmy of

the University of Southern California and his colleagues recently surveyed the genomes of 400 of

the most abundant species of bacteria in the oceans. As they report in a paper to be published in

the Annual Review of Marine Science, 24 percent of the bacteria lack genes to make B1, and 63

percent can’t make B12.

These recent studies are especially surprising because bacteria have long been considered

self-sufficient when it comes to vitamins. Now scientists need to figure out why many species of

bacteria in the ocean aren’t dead from a microbial version of scurvy.

“Somebody’s making it for the good of the community, but we don’t know who,” Dr. Sanudo-

Wilhelmy said.

Only recently have scientists made measurements of vitamins in the sea. They are finding some

places that are abundant with them and others that are vitamin deserts. It is possible that the

difference influences not just bacteria and algae, but the animals that feed on them.

Vitamins flow in complex routes, not just in the ocean, but on land. We humans can’t make our

own supply of vitamin B12, for example, so we need to get it from food. One way is to eat meat like

beef, which contains B12. It turns out that the cows and other animals that we consume don’t make

B12 in their own cells. Instead, the bacteria in their guts manufacture it for them.

We are also home to thousands of species of bacteria, which synthesize vitamins as they eat our

food. Does that mean we depend on our internal vitamin traffic? “It’s still theoretical,” said Douwe

van Sinderen, a microbiologist at University College Cork in Ireland. “But evidence is building that

bacteria can provide some vitamins that we need.”

If that’s so, we may need to think of our bodies as self-contained oceans of vitamin traffic — a

continuation of the traffic that has occurred on earth for four billion years.


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