Wednesday, July 02, 2008

Nobel Laureate: Sir Frederick Hopkins


The Nobel Prize in Physiology or Medicine 1929.
"for his discovery of the growth-stimulating vitamins"

Sir Frederick Gowland Hopkins (1861 - 1947) received the Nobel Prize in Physiology or Medicine for his seminal contributions to the discovery of vitamins. Hopkins identified essential components in milk that were absolutely required for growth and development in rats. Only a few drops of milk per day were sufficient.

The essential vitamins in milk can be separated into two different components. The lipid-soluble component consists of vitamins A and D [Monday's Molecule #78].

Hopkins is often credited with being the discoverer of vitamins but he disclaims this honor, pointing out in his Nobel Lecture that essential nutrients had been recognized by many others before him. He shared the Nobel Prize with Christiaan Eijkman. Altogether, there have been seven Nobel Prizes awarded for work on vitamins.

Hopkins became Professor of Biochemistry at Cambridge University in 1914. I think he was the very first Professor of Biochemistry at Cambridge.

The presentation speech was delivered by Professor G. Liljestrand, member of the Staff of Professors of the Royal Caroline Institute, on December 10, 1929

Nobel Laureates
Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

That the fruits of civilization are not solely beneficial is shown by, inter alia, the history of the art of medicine. Not a few illnesses and diseases follow close on the heels of, and are more or less directly caused by, civilization. This is the case with the widespread disease beriberi, first described more than 1,300 years ago from that ancient seat of civilization, China. In modern times, however, it was not until towards the end of the 17th and the beginning of the 18th century that the disease attracted more general attention. Subsequently it has, on different occasions and with varying degrees of violence, made its appearance in all five continents, but more particularly its haunts have been in Eastern and South-Eastern Asia. At times the disease has been a serious scourge there. Thus in 1871 and 1879, Tokio was visited by widespread epidemics, and during the Russo-Japanese War it is said that not less than one-sixth of the Japanese army was struck down.

Beriberi shows itself in paralysis accompanied by disturbances in the sensibility and atrophy of the muscles, besides symptoms from the heart and blood vessels, inter alia, tiredness and oedema. Decided lesions have been shown in the peripheral nerves which seem to explain the manifestations of the disease. Mortality has varied considerably, from one or two per cent to 80 per cent in certain epidemics.

A number of circumstances indicated a connection between food and beriberi: for example, it was suggested that the cause might be traced to bad rice or insufficiency in the food of proteins or fat.

The severe ravages of beriberi in the Dutch Indies led the Dutch Government to appoint a special commission to study the disease on the spot. At the time, bacteriology was in its hey-day, and it was then but natural that bacteria should be sought as the cause of the disease, and indeed it was thought that success had been attained. The researches were continued in Java by one of the commission's coadjutors, the Dutch doctor Christiaan Eijkman. As has so often been the case during the development of science, a chance observation proved to be of decisive importance. Eijkman observed a peculiar sickness among the hens belonging to the laboratory. They were attacked by an upward-moving paralysis, they began to walk unsteadily, found difficulty in perching, and later lay down on their sides. The issue of the disease was fatal unless they were specially treated. It has been said that the secret of success is to be prepared for one's opportunity when it presents itself, and indubitably Eijkman was prepared in an eminent degree. With his attention focussed on beriberi, he immediately found a striking similarity between that disease and the sickness that had attacked the hens. He also observed changes in numerous nerves similar to those met with in the case of beriberi. In common with beriberi, this ailment of the hens was to be described as a polyneuritis. In vain, however, did Eijkman try to establish micro-organisms as the cause of the disease.

On the other hand, he succeeded in establishing the fact that the condition of the hens was connected with a change in their food, in that for some time before they were attacked they had been given boiled polished rice instead of the usual raw husked rice. Direct experiments proved incontestably that the polyneuritis of the hens was caused by the consumption of rice that by so-called «polishing» had been deprived of the outer husk. Eijkman found that the same disease presented itself when the hens were fed exclusively on a number of other starch-rich products, such as sago and tapioca. He also proved that the disease could be checked by the addition to the food of rice bran, that is to say, the parts of the rice that had been removed by polishing, and he found that the protective constituent of the bran was soluble in water and alcohol.

Eijkman's work led Vorderman to carry out investigations on prisoners in the Dutch Indies (where the prisoner's food was prepared in different ways according to the varying customs of the inhabitants), with a view to discovering whether beriberi in man was connected with the nature of the rice food they consumed. It proved that in the prisons where the inmates were fed on polished rice, beriberi was about 300 times as prevalent as in the prisons where unpolished rice was used.

When making investigations to explain the results reached, Eijkman considered that protein or salt hunger could not be the cause of the disease. But he indicated that the protective property of the rice bran might possibly be connected with the introduction of some particular protein or some special salt. At the time it might have been readily imagined that the polyneuritis in the hens and beriberi were due to some poison, and Eijkman set this up as a working hypothesis, though his attempts to establish the poison were in vain. In his view, however, such a poison was formed, but it was rendered innocuous by the protective substance in the bran. It was only Eijkman's successor in Java, Grijns, who made it clear that the substance in question was used directly in the body, and that our usual food, in addition to the previously known constituents, must contain certain other substances, if health is to be preserved. Funk introduced the designation vitamins for these substances, and since then the particular substance that serves as a protection against polyneuritis has been called the «antineuritic» vitamin.

It might have been expected that Eijkman's discovery would lead to an immediate and decided decline in beriberi - perhaps to the disappearance of the disease. But this was by no means the case, and not even in the Dutch Indies, where Eijkman and Grijns had worked, were the results particularly brilliant. The reasons for this were several: the reluctance of the inhabitants to substitute the less appetizing unpolished for polished rice, the opinion that polyneuritis in birds was not a similar condition to beriberi in man, and an inadequate appreciation of Eijkman's work. As a result of numerous experiments by different investigators on animals and human beings, who offered themselves for experimental work, it has gradually become clear that beriberi is a disease for the appearance of which lack of the vitamin found in rice bran - but also other circumstances - is of decisive importance. These experiences, in addition to successful experiments made in various places on the basis of Eijkman's observations, especially in British India, have gradually led to a general adoption of Eijkman's views. The successful attempts to combat beriberi which are now proceeding are the fruits of Eijkman's labours.

It was the analysis of the nature of the food used in cases of polyneuritis in hens that led Eijkman to his discovery. As a rule, analysis and synthesis complete each other, and indeed the employment of both these avenues of approach has been of decisive importance also for the development of the science of vitamins.

Although a number of experiments carried out about 50 years ago supported the assumption that, if our food is to have its full value, it must contain something more than the long-known basic constituents - proteins, fat, carbohydrates, water, and salts - yet it is not until our own days that complete certainty has been reached. One line of development has been sketched above. But numerous investigations have also been carried out by different experimentors with a view to testing the value of foods composed exclusively of the above-mentioned constituents in pure form. Sometimes it has proved to be a matter of some difficulty to get young animals to grow on such foods. One explanation put forward for this was the monotony of the food, and another was that the excessive purity resulted in the absence of certain substances giving the food taste which are necessary for appetite, and which must be present if the food is to be taken in sufficient amount. From other quarters, however, it was reported that even from the pure constituents, a food had been successfully produced which led to growth in the young organism.

When Hopkins joined the numbers of those who were trying to find a solution to this problem, he had the advantage of a far-reaching experience within similar fields of research, for he had done a great deal of detailed work on the presentation in pure form of certain proteins, and in connection therewith he had discovered the amino acid tryptophane as an element in certain proteins. As early as 1906 he had carried out careful feeding experiments on mice with different proteins, and by means of regular weighings it was observed whether the food was sufficient or not. It appeared from these experiments that the animal organism cannot itself build up tryptophane - proteins which do not contain it are not sufficient for the needs of the body. The simple methods employed by Hopkins came to play an important role later on.

When Hopkins continued his experiments, he fed young rats on a basic diet which, in addition to the necessary salts, contained a carefully purified mixture of lard, starch, and casein, i.e. the protein that is most abundantly found in milk. After some time the animals ceased to grow, which showed the insufficiency of this basic food in itself. By various experiments, however, Hopkins demonstrated that it was only necessary to add a very small daily amount of milk - two to three cubic centimeters for each animal - for growth to recommence. This amount of milk only corresponded to one or two per cent of the energy-content of the food, so that in this respect the addition of milk was insignificant. It was indeed found that incompletely purified casein, e.g. the ordinary casein of commerce, owing to the slight quantities of active substances present, was sufficient, with the other basic food, to maintain growth, even though it was considerably delayed. It was evident, as Hopkins was able to show more explicitly, that here was to some extent the explanation of the older and conflicting results.

Hopkins showed that there was a sufficiency of food consumed without the added milk, but it could be fully utilized by the body only when the growth-promoting influence of the milk was present. This effect was found not to be connected with any of the known constituent parts of milk. It was found also with yeast and the green parts of plants.

Hopkins communicated certain of his main results - but in an extremely brief form - as early as in 1906, and he returned to the subject in 1909 in a series of lectures, but it was not until three years later that his work was published in its entirety. By then Stepp had given accounts of experiments which, though they certainly seem less capable of one definite interpretation than those of Hopkins, yet point in the same direction, and the ground was also in other respects prepared, so that Hopkins' work was a great incentive to continued experiments in the young science of vitamins. Chiefly by American investigations it was shown that there are at least two vitamins necessary for growth, one soluble in fat, the other in water. It is still an open question whether the latter is identical with the antineuritic vitamin.

Just as at one time the newly acquired knowledge of bacteria as causes of illness opened the door to an entirely new province of research of extraordinary importance, so now the discovery of vitamins - even though to a lesser degree - has opened up new vistas to medicine, and we have advanced nearer to the understanding of numerous obscure maladies. Under the influence of Eijkman's discovery, Holst, with Frölich, exposed the nature and character of scurvy. Above all by the efforts of Hopkins' pupil Mellanby, it was found that rachitis was an illness due to lack of certain substances, and others have shown similar conditions for a large number of other maladies, the last one being pellagra, the similarity in principle of which to beriberi was already indicated by Eijkman in his classic work.

At the same time, extensive and important contributions have been made to the question of the nature of the physiological processes which are affected by vitamins.

Thus the discovery of vitamins, which is this year rewarded with the Nobel Prize, implies an advance of extraordinary significance, but there is still much of importance to be discovered that can at present be but dimly discerned or suspected.

Your Excellency, Baron Sweerts de Landas Wyborgh, Sir Frederick Gowland Hopkins. Many years have passed, since Eijkman found the antineuritic principle in food, but the great importance of this work has been appreciated but slowly. Today, however, the outstanding significance of the discovery is universally acknowledged not only for our understanding and our attempt to combat beriberi, but also because it has indicated a way of investigating and controlling many other deficiency diseases.

You, Sir Frederick, have demonstrated the physiological necessity of the vitamins for normal metabolism and growth, thus very considerably extending our knowledge of the importance of vitamins for life processes as a whole.

The discoveries of the antineuritic and the growth-promoting vitamins, for which the Caroline Institute has awarded the Nobel Prize in Physiology or Medicine this year, are foundation stones of the science of vitamins. Great as has been the progress in this field, yet we may still hope to reap rich harvests in the future.

On behalf of the Caroline Institute I express its hearty congratulations to the prizemen, and I beg Your Excellency to convey to your famous countryman its felicitations. With these words I have the great honour of asking you to accept the Nobel Prize for Physiology or Medicine from the hands of His Majesty the King.

[Photo Credit: Wikipedia]

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