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Authors: Napoleon's Buttons: How 17 Molecules Changed History

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COOK: HUNDREDS-SCURVY: NIL
James Cook of the British Royal Navy was the first ship's captain to ensure that his crews remained scurvy free. Cook is sometimes associated with the discovery of antiscorbutics, as scurvy-curing foods are called, but his true achievement lay in the fact that he insisted on maintaining high levels of diet and hygiene aboard all his vessels. The result of his meticulous standards was an extraordinarily good level of health and a low mortality rate among his crew. Cook entered the navy at the relatively late age of twenty-seven, but his previous nine years of experience sailing as a merchant seaman mate in the North Sea and the Baltic, his intelligence, and his innate seamanship combined to ensure his rapid promotion within the naval ranks. His first experience with scurvy came aboard the
Pembroke,
in 1758, on his initial voyage across the Atlantic Ocean to Canada to challenge the French hold on the St. Lawrence River. Cook was alarmed by the devastation this common affliction caused and appalled that the deaths of so many crew, the dangerous reduction of working efficiency, and even actual loss of ships were generally accepted as inevitable.
His experience exploring and mapping around Nova Scotia, the Gulf of St. Lawrence, and Newfoundland and his accurate observations of the eclipse of the sun greatly impressed the Royal Society, a body founded in 1645 with the aim of “improving natural knowledge.” He was granted command of the ship
Endeavour
and instructed to explore and chart the southern oceans, to investigate new plants and animals, and to make astronomical observations of the transit of planets across the sun.
Less known but nonetheless compelling reasons for this voyage and for Cook's subsequent later voyages were political. Taking possession in the name of Britain of already discovered lands; claiming of new lands still to be discovered, including Terra Australis Incognita, the great southern continent; and the hopes of finding a Northwest Passage were all on the minds of the admiralty. That Cook was able to complete so many of these objectives depended to a large degree on ascorbic acid.
Consider the scenario on June 10, 1770, when the
Endeavour
ran aground on coral of the Great Barrier Reef just south of present-day Cooktown, in northern Queensland, Australia. It was a near catastrophe. The ship had struck at high water; a resulting hole in the hull necessitated drastic measures. In order to lighten the ship, the entire crew heaved overboard everything that could be spared. For twenty-three hours straight they manned the pumps as seawater leaked inexorably into the hold, hauling desperately on cables and anchor in an attempt to plug the hole by fothering, a temporary method of mending a hole by drawing a heavy sail under the hull. Incredible effort, superb seamanship, and good fortune prevailed. The ship eventually slid off the reef and was beached for repairs. It had been a very close call—one that an exhausted, scurvy-inflicted crew could not have summoned the energy to answer.
A healthy, well-functioning crew was essential for Cook to accomplish what he did on his voyages. This fact was recognized by the Royal Society when it awarded him its highest honor, the Copley gold medal, not for his navigational feats but for his demonstration that scurvy was not an inevitable companion on long ocean voyages. Cook's methods were simple. He insisted on maintaining cleanliness throughout the ship, especially in the tight confines of the seamen's quarters. All hands were required to wash their clothes regularly, to air and dry their bedding when the weather permitted, to fumigate between decks, and in general to live up to the meaning of the term
shipshape.
When it was not possible to obtain the fresh fruit and vegetables he thought necessary for a balanced diet, he required that his men eat the sauerkraut he had included in the ship's provisions. Cook touched land at every possible opportunity to replenish stores and gather local grasses (celery grass, scurvy grass) or plants from which he brewed teas.
This diet was not at all popular with the crew, accustomed as they were to the standard seamen's fare and reluctant to try anything new. But Cook was adamant. He and his officers also adhered to this diet, and it was by his example, authority, and determination that his regimen was followed. There is no record that Cook had anyone flogged for refusing to eat sauerkraut or celery grass, but the crew knew the captain would not hesitate to prescribe the lash for opposing his rules. Cook also made use of a more subtle approach. He records that a “Sour Kroutt” prepared from local plants was initially made available only to the officers; within a week the lower ranks were clamoring for their share.
Success no doubt helped convince Cook's crew that their captain's strange obsession with what they ate was worthwhile. Cook never lost a single man to scurvy. On his first voyage of almost three years, one-third of his crew died after contracting malaria or dysentery in Batavia (now Jakarta) in the Dutch East Indies (now Indonesia). On his second voyage from 1772 to 1775, he lost one member of his crew to illness—but not to scurvy. Yet on that trip the crew of his companion vessel was badly affected by the problem. The commander, Tobias Furneaux, was severely reprimanded and instructed yet again by Cook on the need for preparation and administration of antiscorbutics. Thanks to vitamin C, the ascorbic acid molecule, Cook was able to compile an impressive list of accomplishments: the discovery of the Hawaiian Islands and the Great Barrier Reef, the first circumnavigation of New Zealand, the first charting of the coast of the Pacific Northwest, and first crossing of the Antarctic Circle.
A SMALL MOLECULE IN A BIG ROLE
What is this small compound that had such a big effect on the map of the world? The word
vitamin
comes from a contraction of two words,
vital
(necessary) and
amine
(a nitrogen-containing organic compound—it was originally thought that all vitamins contained at least one nitrogen atom). The C in vitamin C indicates that it was the third vitamin ever identified.
Structure of ascorbic acid (or vitamin C)
This system of naming has numerous flaws. The B vitamins and vitamin H are the only ones that actually do contain nitrogen. The original B vitamin was later discovered to consist of more than one compound, hence vitamin B
1
, vitamin B
2
, etc. Also, several supposedly different vitamins were found to be the same compound, and thus there is no vitamin F or vitamin G.
Among mammals, only primates, guinea pigs, and the Indian fruit bat require vitamin C in their diet. In all other vertebrates—the family dog or cat, for example—ascorbic acid is made in the liver from the simple sugar glucose by a series of four reactions, each catalyzed by an enzyme. Thus for these animals ascorbic acid is not a dietary necessity. Presumably, somewhere along the evolutionary path humans lost the ability to synthesize ascorbic acid from glucose, apparently by losing the genetic material that enabled us to make
gulonolactone oxidase,
the enzyme necessary for the final step in this sequence.
A similar set of reactions, in a somewhat different order, is the basis for the modern synthetic method (also from glucose) for the industrial preparation of ascorbic acid. The first step is an oxidation reaction, meaning that oxygen is added to a molecule, or hydrogen is removed, or possibly both. In the reverse process, known as reduction, either oxygen is removed from a molecule, or hydrogen is added, or again possibly both.
The second step involves reduction at the opposite end of the glucose molecule from that of the first reaction, forming a compound known as
gulonic acid.
The next part of the sequence, the third step, involves gulonic acid forming a cyclic or ring molecule in the form of a
lactone.
A final oxidation step then produces the double bond of the ascorbic acid molecule. It is the enzyme for this fourth and last step that humans are missing.
The initial attempts to isolate and identify the chemical structure of vitamin C were unsuccessful. One of the major problems is that although ascorbic acid is present in reasonable amounts in citrus juices, separating it from the many other sugars and sugarlike substances that are also present in these juices is very difficult. It's not surprising, therefore, that the isolation of the first pure sample of ascorbic acid was not from plants but from an animal source.
In 1928, Albert Szent-Györgyi, a Hungarian doctor and biochemist working at Cambridge University in England, extracted less than a gram of crystalline material from bovine adrenal cortex, the inner fatty part of a pair of endocrine glands situated near a cow's kidneys. Present at only about 0.03 percent by weight in his source, the compound was not initially recognized as vitamin C. Szent-Györgyi thought he had isolated a new sugarlike hormone and suggested the name
ignose,
the
ose
part being the ending used for names of sugars (like
glucose
and
fructose
) and the
ig
part signifying that he was ignorant of the substance's structure. When Szent-Györgyi's second suggestion for a name,
God-nose,
was also rejected by the editor of the
Biochemical Journal
(who obviously did not share his sense of humor), he settled for the more sedate name
hexuronic acid.
Szent-Györgyi's sample had been pure enough for accurate chemical analysis to show six carbon atoms in the formula, C
6
H
8
O
6
, hence the
hex
of hexuronic acid. Four years later it was shown that hexuronic acid and vitamin C were, as Szent-Györgyi had come to suspect, one and the same.
The next step in understanding ascorbic acid was to determine its structure, a task that today's technology could accomplish relatively easily using very small amounts but was nearly impossible in the absence of large quantities in the 1930s. Once again Szent-Györgyi was in luck. He discovered that Hungarian paprika was particularly rich in vitamin C and, more important, was particularly lacking in other sugars that had made the compound's isolation in fruit juice such a problem. After only one week's work he had separated over a kilogram of pure vitamin C crystals, more than sufficient for his collaborator, Norman Haworth, professor of chemistry at the University of Birmingham, to begin the successful determination of the structure of what Szent-Györgyi and Haworth had now termed
ascorbic acid.
In 1937 the importance of this molecule was recognized by the scientific community. Szent-Györgyi was awarded the Nobel Prize for medicine for his work on vitamin C, and Haworth the Nobel Prize for chemistry.
Despite more than sixty years of further work, we are still not completely sure of all the roles that ascorbic acid plays in the body. It is vital for the production of collagen, the most abundant protein in the animal kingdom, found in connective tissues that bind and support other tissues. Lack of collagen, of course, explains some of the early symptoms of scurvy: the swelling of limbs, softening of gums, and loosening of teeth. As little as ten milligrams a day of ascorbic acid is said to be sufficient to keep the symptoms of scurvy at bay, although at that level sub-clinical scurvy (vitamin C deficiency at the cellular level but no gross symptoms) probably exists. Research in areas as varied as immunology, oncology, neurology, endocrinology, and nutrition is still discovering the involvement of ascorbic acid in many biochemical pathways.
BOOK: Penny le Couteur & Jay Burreson
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