Scurvy History

Scurvy History
A decoction of spruce or pine needles was known in
Sweden to cure scurvy at least as early as the sixteenth
century, and North American Indians demonstrated
a similar elixir to the French explorer Jacques Cartier
in 1535. Ships’ crews of the East India Company had
been using lemon juice to combat scurvy from 1601
onward at the instigation of Sir James Lancaster.
However, this knowledge was not publicised and
scurvy was still the scourge of sailors enduring long
sea voyages. In 1734, Bachstrom stated his belief that
‘this evil is solely owing to a total abstinence from
fresh vegetable food, and greens; which is alone the
primary cause of the disease’.

The fi rst recorded experiment on the cause and
cure of scurvy in humans was performed in 1747 on
board H.M.S. Salisbury by the Scottish naval physician
James Lind. Twelve sailors with scurvy were divided
into six pairs and each pair was given a different
daily concoction in addition to a common diet. Two
fortunate patients were each given two oranges and
one lemon every day; only these two recovered, thus
demonstrating the effi cacy of oranges and lemons. In
Lind’s A Treatise of the Scurvy published in 1757, Lind
stated that ‘greens or fresh vegetables, with ripe fruits,
are the best remedies’ and ‘the diffi culty of obtaining
them at sea, together with a long continuance in the
moist sea air’ are the true causes of scurvy at sea. Although
he was mistaken as to the bad effects of salt
water and salt air, Lind’s powers of observation led
him to discover the true cause of scurvy and many of
the factors infl uencing its occurrence.
Captain James Cook maintained a healthy crew by
stopping frequently to take on fresh fruit and vegetables
during his 1772–1775 voyages around the world.
4 Vitamins: their role in the human body
The Royal Navy, on the other hand, refused to accept
Lind’s fi ndings and countless sailors succumbed to
scurvy for several years to follow.
Lind devoted his energies to securing a regular issue
of lemon juice in the Royal Navy, but it was not until
1795 that success was fi nally achieved. The argument
for issuing lemon juice was reinforced by a report
in the previous year of a 23-week voyage, during
which each seaman received two-thirds of an ounce
of lemon juice daily: the crew remained entirely free
from scurvy. The scheduled allowance for the sailors
in the Navy was fi xed at 1 ounce of lemon juice (often
called ‘lime juice’) after two weeks at sea. The consequences
of the new regulations were startling and by
the beginning of the nineteenth century scurvy in the
British Navy had disappeared.

The modern era of research into scurvy, leading to
the discovery of vitamin C, began in 1907 when Holst
and Frölich reported from Christiana (now Oslo)
that the disease could be produced experimentally in
guinea pigs. It was Holst and Frölich’s original intention
to fi nd a suitable mammalian species for studying
beriberi, following Eijkman’s experiments with
chickens. When the guinea pigs were fed a specially
prepared cereal-based diet, the animals developed not
the expected signs of beriberi, but rather the characteristic
signs of scurvy, namely loss of body weight,
loosening of teeth, haemorrhages in all parts of the
body, and severe bone lesions. Supplementation of the
basal cereal diet with fresh vegetables and fruit had a
protective and curative action. This important discovery
led Chick and Hume in 1919 to develop a bioassay,
using the guinea pig, for testing antiscorbutic activity
in biological materials. The decision by Holst and
Frölich to use guinea pigs was fortuitous as we now
know that the more usual laboratory rodents (rats
and mice) are not rendered scorbutic when deprived
of dietary vitamin C.

From 1910, Zilva and his associates at the Lister
Institute in London were engaged in studying the
chemical nature of the antiscorbutic factor. Two
great obstacles to progress were the instability of the
vitamin and the diffi culty of guiding the required
chemical steps by biological assays. Assay periods were
13 weeks, later shortened to 8 weeks. By 1927, Zilva
had obtained syrupy concentrates of the antiscorbutic
substance from the juice of lemons and shown them
to possess strong reducing properties. The reducing
power appeared to be associated with the antiscorbutic
activity, and yet freshly oxidized solutions still
retained their activity. This apparent anomaly was
resolved by Tillmans who correctly deduced that the
antiscorbutic factor was responsible for the reducing
properties of the lemon juice concentrates, and that
both oxidized and reduced forms of the reducing substance
possessed antiscorbutic activity. Drummond’s
proposal to name the antiscorbutic factor ‘vitamin C’
was accepted in 1922.

In September 1931, C. G. King and W. A. Waugh
at the University of Pittsburgh obtained a crystalline
product from lemon juice that exhibited antiscorbutic
activity. They prepared to publish their fi ndings,
but press reports then appeared that Rygh at
the University of Oslo had identifi ed vitamin C as
methylnornarcotine. King and Waugh deferred their
manuscript until they tested Rygh’s claim and found
it to be spurious.

Meanwhile, Albert Szent-Györgyi was investigating
redox systems in plants and animals for his Ph.D.
degree at Cambridge University, England. In 1927 he
isolated from the adrenal cortex of oxen, and also from
cabbage and paprika, a crystalline, optically active,
acidic substance with the empirical formula C6H8O6.
This substance was a strong reducing agent and gave
colour tests characteristic of sugars, therefore Szent-
Györgyi designated it as a ‘hexuronic acid’. Later, in
his native country Hungary, Szent-Györgyi suspected
that hexuronic acid might be vitamin C, but he did not
have the practical experience in his laboratory to test it
with the guinea pig assay. Then fate intervened. Joseph
Svirbely, who had only recently left King’s laboratory
in Pittsburgh, turned up at Szent-Györgyi’s laboratory
in Szeged to offer his services. Szent-Györgyi
asked Svirbely to test hexuronic acid for vitamin C
activity and after one month the result was evident:
hexuronic acid was indeed vitamin C. Szent-Györgyi
and Svirbely’s note in Nature, April 1932, appeared
two weeks after King and Waugh’s deferred paper in
Science (neither of these publications carried a date
of receipt). A sample of hexuronic acid prepared
from adrenal glands by E. C. Kendall using new and
very different procedures was found to be identical to
King’s vitamin C preparation from lemons.