Experiments on formulated diets

In the meantime, research was under way into what
constituted a physiologically complete diet. Lunin,
a pupil of the Swiss biochemist Bunge, fi rst showed
in 1882 that laboratory animals failed to thrive when
kept on an artifi cial diet comprising the then known
constituents of food (fat, protein, carbohydrate, mineral
salts and water) in purifi ed form. Taking a similar
approach of using isolated purifi ed food ingredients,
Pekelharing formulated a baked product containing
only casein, albumin, rice fl our, lard and a mixture of
all the salts which ought to be found in food. When
this product, plus water to drink, was provided as
food for mice, the mice failed to grow and died. When
other mice were provided with the same meal, but
with milk to drink instead of water, they kept in good
health. Pekelharing concluded in 1905 that ‘There is
an unknown substance in milk, which, even in very
small quantities, is of paramount importance to
nutrition. If this substance is absent, the organism
loses the power properly to assimilate the well-known
principal parts of food, the appetite is lost and, with
apparent abundance, the animals die of want. Undoubtedly,
this substance not only occurs in milk, but
in all sorts of foodstuffs, both of vegetable and animal
origin.’ Stepp from 1909 to 1913 provided mice with
a natural complete foodstuff (milk and bread) from
which he had removed certain constituents by means
of alcohol-ether extraction. He discovered thereby
that milk and other foods contained some unknown
alcohol-soluble dietary factor indispensable for life.
As no-one had yet succeeded in isolating the factor,
there was no proof of its existence and many doubts
were raised concerning the validity of Pekelharing’s
conclusions. One school of thought was that the animals
failed because of the mere monotony of the diet,
or its lack of palatability, or to the absence of fl avouring
substances. Others thought that the cause was to
be found in insuffi cient consumption or failure of
absorption.

That a monotonous and unaccustomed food may
be used successfully over long periods of time without
ill-effects was proved by the experiments of Falta and
Noeggerath, published in 1905. They maintained rats
successfully for six months or more on monotonous
diets of milk, milk powder or lean horsemeat.
We now turn to the work of Sir Frederick Hopkins
in England. He fed young rats on an artifi cial food
mixture containing caseinogen, starch, cane sugar,
lard and inorganic salts. When these constituents
were given in their crude condition, they were apparently
adequate to maintain life and a certain amount
of growth. When, however, they were subjected to
careful purifi cation, growth invariably ceased within
a comparatively short time, and the rats died. By carefully
determining the total energy consumption of his
test rats, Hopkins was able to show that this failure was
not due to an insuffi cient food intake. They ceased, in
fact, to grow at a time when they were consuming food
in more than suffi cient quantity to maintain normal
growth. Cessation of growth took place before any
failure in appetite. Any effects upon the appetite must
therefore have been secondary to a more direct effect
upon growth processes. In his classic paper (Hopkins,
1912), Hopkins suggested the term ‘accessory factors’
for the missing nutrients, postulating that their necessity
is a consequence of physiological evolution. Hopkins’
work was the fi rst to attract general attention to
the existence of the hitherto unrecognized growthpromoting
substances.

Casimir Funk, a Polish biochemist working at the
Lister Institute in London, set out to isolate the antiberiberi
factor from rice polishings and obtained
a biologically active, crystalline substance with the
chemical properties of an amine. Funk believed that
he had isolated the pure factor, but it was later realized
that he had not. In 1912 Funk published a review of
the existing knowledge of the diseases caused by nutritional
errors (Funk, 1912). He proposed that beriberi,
scurvy, pellagra and possibly rickets were caused
by the absence from the diet of ‘special substances
Historical events leading to the establishment of vitamins 7
which are of the nature of organic bases, which we will
call vitamines’. His new word ‘vitamine’ was derived
from vita (meaning life in Latin) and amine. Funk
postulated the existence of an anti-beriberi vitamine,
an anti-scurvy vitamine, probably an anti-pellagra vitamine
and possibly an anti-rickets vitamine. Later, in
1922, Funk wrote, ‘I must admit that when I chose the
name vitamine I was well aware that these substances
might later prove not to be of an amine nature. However,
it was necessary for me to choose a name that
would sound well and serve as a catch-word.’
The year 1912 was a landmark in the history of vitamins
and heralded a new era in vitamin research. Hopkins’
celebrated paper and Funk’s review, published a
few months earlier, attracted world-wide attention
and, fi nally, a general acceptance of the existence of
vitamins. In his review Funk commented, ‘There is
perhaps no other subject in medicine where so many
contradictions and inexact statements were made,
which, instead of advancing the research, retarded it
by leading investigators in a wrong direction.’
The importance of the pioneering experiments of
Eijkman and of Hopkins was fi nally recognized by the
award to them jointly of the Nobel Prize for Physiology
or Medicine in 1929.