NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
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THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VII, II
suffer from ' Hypervitaminosis ', i.e., a surfeit of vitamins, the symptoms of which
are worse and more to be dreaded than ' Avitaminosis ' or a deficiency of vitamins.
It was known for a long time that there were certain diseases caused by a
lack of some nutrient in our food. There is something in the food the absence of
which causes us disease. This vitamin deficiency has been traced to certain
very common diseases. It sometimes takes the form of beri-beri, which is very
common in India, particularly among the populations who use rice as their staple
food. Beri-beri is caused by the lack of a certain type of vitamin. Rickets
is also caused by the absence of a particular vitamin. We have a common disease
known as scurvy which is a skin disease, and which is found to be caused by the
absence of the particular vitamin C. There is a curious resemblance of vitamins
to the hormones and the enzymes in the physiological activity when occurring
in minute traces, but the vitamins differ from the latter, inasmuch as they can-
not apparently be synthesized by the body and have to be obtained from some
outside source. Thus there is an element of change in the matter of supplying
the essential vitamins in our foods which explained the occurrence of such diseases
as mentioned above, affecting the human race brought up on highly artificial diets,
although the primitive man, with his simple habits and tastes and healthy instincts
for natural food, had no difficulty in obtaining all the essential vitamins in his
food.
It was Hopkins who first laid the foundation of quantitative nutrition work
just before the war, so that really the subject of nutrition is hardly 25 years old.
The employment of this method of animal feeding experiment in a strictly quanti-
tative sense has revealed the existence of quite a number of hitherto unrecog-
nised members of the different types of vitamins and led to our present know-
ledge of the subject. This work has been taken up by other workers in different
parts of the world. The same method is adopted in India in the Coonoor Nutri-
tion Institute.
'There are a few other workers in India, not very many, carrying nutrition
work. Either rats, guinea pigs, or pigeons which are available in large numbers
are found suitable animals for experimentation. Striking progress has been
made possible only by the international co-operative efforts of teams of workers
qualified in such diverse subjects as medicine, physiology, organic chemistry,
physical chemistry and even statistics.
The six vitamins regarding the chemical identity of which there remains little
or no doubt at present, have been named A, B 1, B 2 , C, D and E. I will tell you
briefly the sources of each and the method of concentration and also the manner
in which they are tested, both chemically and biologically.
Vitamin A is found in all kinds of calorial matter, in fruits and also in milk
and butter and in certain oils obtained from fishes like cod, halibut or other sea-
fish. It has been found that sea-water-fish liver contains a fairly large amount
DEVELOPMENTS IN THE CHEMISTRY OF VITAMINS
135
of vitamin A. The vegetable sources are plantains, bananas, tomatoes, carrots,
spinach, apricots, etc. Apricots are considered recently by American workers
to be the best and the richest source of vitamin A.
In a concentrated form vitamin A is prepared chiefly from cod-liver oil. Here
we have national patriotism. An amusing example of this is afforded by the
rival claims of Professors Drummond and Hilditch who, on behalf of the British
Empire Marketing Board, had emphasised the unrivalled medicinal value of the
cod-liver oil produced in Scotland and New-foundland, whilst the Norwegian
workers claimed their cod-liver oil to be superior and to possess twice the potency
of the New-foundland oil. However, it is gratifying to learn that the Indian fish-
liver oils particularly that from " Vetki", a fish quite common in the Madras
market, are much superior to the cod-liver oil in this respect.
An Indian chemist, Guha of Calcutta, published results of his work on vita-
min A, by the expedient of measuring the intensity of the blue colour developed
by mixing the liver oils with antimony trichloride in chloroform solution under
standard conditions. I wish you can find out the concentration of vitamin A
in the particular substance. The method that he used was very simple and can
be carried out by any person without any training. The liver of the fish was taken
out, thoroughly ground with sodium sulphate or hydro-sodium sulphate and
this powdered dried substance was weighed and extracted rapidly with ether.
It dissolved in antimony. The substance was dried and it was spontaneously
evaporated under an electric fan leaving a deep yellow oil. He took 4 c.c. of oil
and dissolved it in 4 c.c. of chloroform and treated this with the solution of anti
mony, left for 30 seconds and in this way he obtained the following results :—
Vetki (Lates Calcaufer)
.
.
.
.
.
Rohit (Labeo
Rohita)
.
.
.
.
.
Mrigae (Cirrhive Mrigala)
.
.
.
.
Katla (Cutla)
.
.
.
.
.
.
Hilsha (Chigia Itisha) . . . .
Cod
.
.
.
.
.
.
.
.
Halibut
.
.
.
.
.
.
.
(Jour. of Med., Chir. Sec., 1933—P. 364-365).
284 Carr. No. units.
227
174
109
59
5
614
Do.
Do.
Do.
Do.
Do.
Do.
I have been asked by a worker in Bengal whether the ghee which we make
by clarification of butter does contain the whole of the vitamin which was present
in the butter in spite of our having boiled it at high temperature on the oven
for the preparation of ghee, but this gentleman was of opinion that the vitamin
present in the butter is lost in the preparation of ghee from butter. Of course,
I do not know how far his experiment is reliable, but it is interesting to know
more about it, particularly because it concerns all of us, who depend upon ghee
as a very important constituent of our food.
I
136
THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VII, II
Prolonged vitamin A deficiency produces diseases of the nervous system chiefly
of the mucous membranes and lastly, by no means the least, it causes the person
who is suffering from this deficiency to be readily attacked by infectious diseases.
Vitamin B is always found on the outer surface chiefly in seeds, cereals, grains,
pulses, etc. It is found in the embryo of the seed and not on the whole of the
seed. In the case of rice it is the main bulk which we eat, but the embryo is a
very small part and this embryo is simply lost during the milling and polishing
operations. If you want polished or milled rice, it is mostly deprived of the
embryos and it is vitamin-free and there lies the danger of populations depend-
ing on this rice as their food, suffering from deficiency diseases caused by the
lack of vitamin B 1 , chiefly beri-beri. Vitamin B 1 is found in eggs, particularly
in the embryo tissues, also in fish livers, fruits, chiefly figs, grapes and lastly it is
found in that wonderful substance called " yeast ". Yeast is now the chief source
of this vitamin. Vitamin B 1 has been, prepared in a pure condition from yeast.
There have been schools of workers on vitamin B 1 throughout the world. All
these workers prepared almost simultaneously crystalline B 1 hydrochloride. It
was really wonderful how each arrived at the same result almost at the same time.
The biological assay of vitamin B 1 deficiency was established recently, by
the electro-cardiographic method of Harris of determining the heart beats of
rats suffering from vitamin B 1 deficiency and the careful study of the conditions
under which they develop. This method has proved invaluable in identifying
the crystalline vitamin B 1 hydrochloride, synthesized by Williams a few months
ago with the natural vitamins, the method of measuring the resistance of the capil-
lary walls of the skin in vitamin C deficiency by observing the minimum pressure
required to produce haemorrhages in the skin under standard conditions, the
calcification or " lime test " of McCollum, based on X-ray examination of the
bones of puppies, etc. Although these appear to be rather complex and difficult
to carry out, the experimental technique has been perfected to such an extent in
individual laboratories as to make these well-defined quantitative tests of great
accuracy serve to detect and estimate the nearest traces of particular vitamin
occurring in different food-stuffs.
The most interesting fact we have recently concerning vitamin B 2 , the growth-
promoting factor, is its identification with certain organic compounds which
are called flavines. These are nitrogenous organic matter which have been found
to be characterised by the yellow colour. I may tell you that ghee-yellow con-
tains flavine. It will be surprising to know how ghee contains flavine. It
does. Flavine prepared from various sources were tested and they all agreed
in one characteristic, namely the yellow colour. Ghee-white has been found
to give vitamin B 2 .
DEVELOPMENTS IN THE CHEMISTRY OF VITAMINS
137
Vitamin C has been found chiefly in fruits, among which are oranges, grapes,
lemons. Seeds contain none, unless they germinate. Eggs likewise contain none.
There is a special variety of vegetable in Hungary known technically as ' Vitapric '.
This is the richest source of vitamin C.
The application of the spectroscope in the study of vitamins has met with
phenomenal success, most of the vitamins being found to give very characteristic
absorption bands in the ultra-violet region of the spectrum, the intensity and
persistence are found to correspond quantitatively to the amounts of vitamins
present.
II. STRUCTURAL FORMULAE OF THE VITAMINS A AND B
Although the vitamin problem might justly be regarded as bio-chemical in
its inception, the interest had widened considerably in the course of the last three
years and it would be more appropriate now to treat them as problems of out-
standing interest for the organic chemist.
With regard to vitamin A, two distinct lines of attack had been most fruit-
ful of results, viz., the examination of the oils derived from the livers of fish, chiefly
cod and halibut, and the exhaustive study of certain vegetable pigments named
" Carotenoids " or Lipochromes, which had been extracted from such common
vegetables as carrots, tomatoes, maize, etc. While the concentration of the un¬
saponifiable matter of the liver oils constituting nearly one per cent of the original
oil and containing all the vitamin activity, by crystallisation, precipitation of
impurities like sterols and fractional distillation in a high vacuum led, on the one
hand, to the isolation of a fairly pure specimen of this vitamin, the intensive
study of the pigment of carrots resulted on the other in the isolation of an orange
red crystalline substance which was found to have the action of vitamin A when
fed to animals. Although this red colouring matter, which had been named
" Carotene " and the purest form of vitamin A were similar in their biological
action and also in many of their chemical properties such as destruction by oxida-
tion and ozonisation and the development of a blue colour with antimony tri-
chloride, the recognition that they were different bodies was not long to follow,
the discrepancies being finally explained by the brilliant work of Moore, who
during the years 1929-31, demonstrated conclusively that carotene was converted
into vitamin A in the animal body ; it thus became clear that carotene was an
immediate precursor of vitamin A and that plants could synthesise only carotene
but not vitamin A while the animal organisms converted the carotene into vita-
min A chiefly in the liver. The experimental work on the carotenoids and of
Karrer's preparation of pure vitamin A from halibut liver oil have opened a new
method of purification of compounds of these types which had been named " chro-
matographic analysis " and which had proved to be of the greatest value in these
researches. The method, technique of which had been perfected by Kuhn, Zech-
meister and others, was shown to be, in principle, essentially that of capillary
138
THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VII, II
analysis, being based on the fact that the adsorbability of a number of allied sub-
stances on any one adsorbent is frequently susceptible of very fine differentiation
enabling a separation between them being made which was impossible by other
methods. This chromatographic adsorption analysis is now the most delicate
method at the disposal of the chemist for work in this field, the purification of
vitamin A by Karrer and also by Heilbron and others having been accomplished
with its aid.
" Perhydro-vitamin A " was synthesised in the laboratory of Karrer in Zurich
and this could be identified with that obtained from the natural vitamin by re-
duction. (This part of the lecture was illustrated fully with lantern slides).
The original vitamin B 1 curative to beri-beri, variously known as "Aneurin",
" Torulin ", " Oryzanian ", etc., has been the subject of much research by
Jansen and Van Veen in Java, Ohdake in Japan, Windaus in Germany, Peters
in England and Williams in America, who had all prepared in their laboratories
the pure vitamin in crystalline form at about the same time hardly a year ago.
A rough idea of the difficulties of experimental work with this vitamin which had
been prepared by diverse workers from rice, bran, rice polishings, yeast, etc., would
be realised from the figures given recently by Peters in a paper wherein he showed
that 4½ tons of yeast had to be worked up to get about 3 grms. of this vitamin
under the most favourable conditions. The previous work of Windaus made us
understand the oxidation products of this vitamin and how the precipitation
properties and the adsorption curves of the vitamin resembled closely those of his¬
tidine and cytosine respectively. Further careful investigations by Williams
and his co-workers of the Department of Physiological Chemistry, Teacher's
College, Columbia University, New York, during the last year culminated in the
synthesis of vitamin B 1 hydrochloride three months ago. (The various degra-
dation products of the vitamin and the syntheses were illustrated with slides).
Biologically evidence is growing that vitamin B 1 is concerned in some oxida-
tive mechanism in carbohydrate metabolism, an attractive hypothesis being that
it played the role of a co-enzyme in an oxidative enzyme system, e.g., a dehydro-
genase. Highly interesting work on these lines is carried out by Peters and his
collaborators of the Oxford School who had succeeded in demonstrating the accu-
mulation of abnormal amounts of lactic acid and pyruvic acid in the brains of
pigeons suffering from polyneuritis (deprivation of vitamin B 1 ) and they corre-
late them with the lowered oxygen consumption of the brain tissues of these birds.
Future years would reveal many other important aspects of the action of these
vitamins and I hope, now that their structures have been determined, that che-
mists would be able to make them available to medicine and biology.
140
THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VII, II
composition except that it is found to be equally susceptible to inactivation by
visible light. This component is now being designated as vitamin B 6 , the old
name vitamin B 2 being reserved for the growth-promoting factor alone. As a
result of recent experiments on the distribution of vitamin B 6 , it has been found to
be present in considerable amounts in fish muscle (herring, salmon and haddock)
and attempts are now being made to prepare it in a pure condition from these
sources.
VITAMIN C
The determination of the structure of vitamin C and ultimate synthesis con-
stituted another outstanding chemical triumph in recent years. One of the charac-
teristics of vitamin C is that of curing a very well-known disease known as scurvy.
This disease is chiefly found among soldiers, prisoners and sailors, particularly
among soldiers who are actually in a camp and who mostly depend on tinned ra-
tions, prisoners who are often given somewhat starch food materials and sailors
who also depend on the food materials which they carry in the vessel. The pe-
culiar characteristic of this disease is the degeneration of the capillary walls of the
skin. The generous supply of orange and lemon juice and of fresh vegetables has
been known to cure this disease.
It has been recognised that the anti-scorbutic principle is concentrated in fruit-
juices. The chemical investigation of vitamin C began only, four years ago when
several workers in different parts of the world independently and almost simul-
taneously recognised that the sugar acid isolated in 1928 by the Hungarian
investigator Prof. A. Szent-Gyorgyi from the adrenal cortex of oxen which he
called ' Hexuronic acid ' and the anti-scorbutic principle known as vitamin C
were really one and the same. The progress made from this time onwards in the
chemical examination of this material has been amazingly rapid, beginning with
the discovery of methods of easy preparation of the substance in quantity from
a number of sources such as orange and lemon juice and particularly from Paprica
or Hungarian red pepper fruits, and ending with the determination of its chemical
constitution by Haworth, Hirst and others in co-operation with Szent-Gyorgyi
in England, followed finally by the syntheses of the vitamin nearly three years
ago by the two schools of research, one led by Haworth in England and the other
by Reichstein in Switzerland. Vitamin C has now been named by general agree-
ment " Ascorbic acid " and the contents of this acid of some fruit preparations
are given below :—
Ascorbic acid contents of some fruit preparations mg. per grm.
Vitapric . . . . . . . . . .
Paprica (whole fruit) . . . . . . . . .
Lemon juice . . . . . . . . . . . .
Spinach flower . . . . . . . . . .
Tomato . . . . . . . . . . . .
Guava (whole fruit) . . . . . . . . .
4.5
1.8
1.78
1.16
1.09
1.04
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THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VII, II
In conclusion, I hope I have made it clear in the discourses which I have been
giving during the past week that a great body of accurate knowledge about food
and nutrition has been gained recently through the co-operative labours of che-
mists and biologists. What only a few years ago were mysterious and intangible
growth-promoting, anti-scorbutic or anti-rachitic properties in good food-stuffs
caused by certain unidentified and probably unidentifiable bodies called vitamin
and given vague descriptive letters like A, B, C, etc., had now been proved by the
chemist to be definite organic substances the structural formulae of which had
been determined and which, in at least three instances, had been synthesized
in the laboratory. The consequences of these discoveries could not fail to be of
far-reaching importance. Nutrition and food are the first weapons of preventive
medicine and the clinician of the future would be enabled to prescribe an exact
dose consisting of a given number of International Units of the standardised
synthetic vitamins for curing or preventing disease and place the science of nutri-
tion, which was hardly a science upto now, on a scientific and logical basis.
Nutrition should be regarded as one of the most important subjects in the present
day. It is possible for instance by treatment of population with these vitamins
not only to cure existing diseases but also to protect them from the ravages of
dreadful diseases like haemophilia, pyorrhoea, nephritis, or some of the diseases
like scurvy, rickets and so on.
ABSTRACTS
The Chemotherapy of Dirofilaria immitis. HERBERT G. JOHNSTONE. (Amer.
J. Trop. Med., 16, 207-224, 1936).
STUDIES on the chemotherapy of Dirofilaria immitis were undertaken by
Johnstone with the hope of eventually finding some specific remedy for the treatment
of the various types of human filariasis. In an interesting résumé the author points
out that various drugs have been extensively used over a period of years for the treat-
ment of human filariasis with disappointing results. Numerous chemotherapeutic
agents have been advocated, and upon administration have shown promise during
the initial trials only to be discarded following a more widespread application.
No satisfactory treatment for heartworm was known until a group of Japanese
workers reported some success with certain antimony compounds. Itagaki and
Makin [1927] used intravenous injections of sodium antimony tartarate which caused the
disappearance of microfilariæ from the peripheral blood of seventeen dogs. However,
living adult worms were found after death of the dogs tested. Wada [1927] treated
seven dogs with the average dose of 0.011 grm. of neostibnal per kg. administered
subcutaneously for ten to twenty times. Microfilariæ disappeared from the peripheral
circulation in all the dogs treated and in one of the animals a dead worm was found.
Intravenous injections of carbon tetrachloride and solutions of neutroflavine have
also been tried with negative microfilaricidal action.
Philipp [1931] was the first to report good results with Fouadin, a proprietary anti-
mony compound, in the treatment of heartworm disease. Underwood and Wright
[1932] reported favourably on the use of Fouadin in four infested dogs. They found
that best results were obtained when treatment was pushed to the limit of tolerance
in order to obtain a maximum concentration of the drug as soon as possible. Popesco
[1933] treated fourteen dogs with Fouadin with excellent results. The first injection
varied from 2—5 c.c., and the course varied from four to eight injections over a period
of five to fourteen days with a total of 10.5—43.5 c.c. There was a reduction in the
number of microfilariæ but no reference to the effect of the drug on the adult worms
was made. In an important paper Wright and Underwood [1934] reported that
Fouadin is comparatively safe to use if certain restrictions are observed resulting in
the disappearance of the microfilariæ and the eventual destruction of some or all of the
adult worms in the heart and pulmonary artery. The drug is contra-indicated in cases
of organic heart disease or pathologic conditions of liver or kidney. Destruction of a
large number of worms all at once may cause embolic pneumonia or an acute toxemia.
Recently Cheu and Khaw [1935] claimed that " Concentrated Fouadin ", a solution
containing eleven per cent sodium-antimony III pyrocatechin-disulphonate of sodium
and calcium, was four or five times therapeutically more potent in its effects than
( 145 )