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A Short History of Nutritional Science: Part 1 (1785–1885)

Department of Nutritional Sciences, University of California, Berkeley, CA 97420-3104

¹To whom correspondence should be addressed. E-mail: kcarp{at}uclink.berkeley.edu

	ABSTRACT

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
Preface

This is the first of four invited articles planned to provide a short introduction to the history of our science and a possible text for courses in the subject. Given the space limitations, I have concentrated on work most directly related to discovering nutritional needs and the qualities of foods in supplying them. Our science has greatly relied on developments in analytical chemistry and general physiology, but there are already histories that cover these subjects.

It would have been possible to give brief references to more names and papers, but it would, I believe, have made for more tedious reading. I have preferred to select topics that were breaking new ground, and seemed to inspire other work. No two authors would make the same choices in this situation.

I have also tried to portray the problems as they were seen by workers at the time, and to follow a chronological course, without referring prematurely to modern explanations of phenomena. In most instances the original historical reference to a paper is given, but it is often supplemented with a more easily available review of the subject that also contains additional references. Where a quotation comes from a book or a long article, the Editors have given special permission for the exact page(s) on which it occurs to be listed.

Take, for example, the finding with important implications that was reported to the French Academy of Sciences in 1785 by Claude Berthollet. He had found that the vapor that came from decomposing animal matter was ammonia, and that this gas was composed of three volumes of hydrogen and one volume of nitrogen, or around 17% hydrogen and 83% nitrogen by weight, for which the modern values are 17.75 and 82.25%, respectively (1 ). This was impressive work and one wonders how many of today’s researchers would be able to repeat this finding, especially if they could use only the equipment available at the time.

Others confirmed the presence of nitrogen in animal matter and its absence from sugars, starch and fats. It had been realized for some time that wheat flour contained a fraction (that we know as gluten) that seemed to have the properties of animal matter, including the evolution of alkaline vapor when a sample was allowed to rot. It had been a matter of debate as to whether this was what made wheat such a good food, and whether the more newly introduced potatoes, which seemed to contain nothing comparable to gluten, could be considered to be an adequate substitute for wheat (2 ).

Many of the chemists involved in the "Chemical revolution" in France, including its most famous member Antoine Lavoisier, also had an interest in metabolism. In collaboration with his assistant Armand Seguin, he measured human respiratory output of carbonic acid (that we now know as carbon dioxide), both at rest and when lifting weights, and showed how it increased with activity (3 ,4 ) (Fig. 1 ). This, in itself, was an important advance because it had previously been supposed that the sole purpose of respiration was the cooling of the heart, and that the bodily balance of adults required that the weight of ingested material that was not recovered in stools or urine must have been lost through "insensible perspiration."

View larger version (134K): [in this window] [in a new window]   FIGURE 1 Schematic drawing by Mme. Lavoisier of her husband measuring the carbonic acid output of his collaborator Armand Seguin, while she noted down the results. (Wellcome Institute, London)

Lavoisier had returned to further studies on respiration when he was arrested in 1793 during the Reign of Terror and kept in prison. On the day of his trial in 1794 he pleaded for a short stay of execution that would allow him to do one more experiment, but the judge is believed to have replied that the Republic had no need of "savants," and he was guillotined the same afternoon.

In addition to the scientific progress during the time of the French revolution, there also seemed to be a new spirit at work, a feeling that it was a time to begin again with none of the old assumptions being taken for granted. The period certainly marked a new beginning for nutritional science, and the chemical revolution had provided the necessary tools for its development. A young French pioneer commented that: "Nutrition has often been the subject of conjectures and ingenious hypotheses but our actual knowledge is so insufficient that their only use is to try to satisfy our imagination. If we could arrive at some more exact facts they could well have applications in medicine."

The writer was François Magendie, who had grown up in revolutionary Paris and practiced as a surgeon before changing to physiology (7 ). His first work in the field was reported to the Academy of Sciences in 1816, and addressed directly the question as to whether animals could use atmospheric nitrogen to "animalize" ingested foods of low nitrogen content. There was, of course, a plentiful supply of nitrogen in the air, and some chemists had suggested that this kind of combination must occur during an animal’s digestion of plant foods so as to give the ingesta the characteristics that would allow them to be incorporated into the animal’s own tissues either for growth or replacement of worn-out materials.

Magendie’s famous experiment was a very simple one, so simple that one wonders at its never having been tried before. It was to take a single food that was accepted as being nutritious, even though it did not contain nitrogen, and to feed it to dogs, a species that would eat both plant and animal foods. Sugar was the food that he tested with his first dog. It continued to eat well for about 2 wk, but then began to lose weight and to develop a corneal ulcer. After a month it died. He repeated the experiment, and then tried using olive oil, gum or butter as the sole foods for his dogs, in each case with the same result, except that no ulceration was seen in the dog receiving olive oil (8 ).

His conclusions were that none of these foods was "preeminently nutritive" (which I take to mean "providing all the dogs’ needs"), even though they were well absorbed, and, second, that at least the majority of the nitrogen in a dog’s tissue must come from the food that it has consumed. With hindsight, we can see the gap in his reasoning; there may have been other deficiencies in the foods tested apart from nitrogenous material, and he had no positive control, such as "sugar plus albumin or gluten." In his 1816 paper he had written: "Everyone knows that dogs can live very well on bread alone," but later, when he actually put this to the test he found that "a dog does not live above fifty days." His final conclusion, still echoed in present-day dietary guidelines, was that "diversity and multiplicity of aliments is an important rule of hygiene; which is, moreover, indicated to us by our instincts" (9 ).

At this time there was a controversy as to whether gelatin, obtained by boiling bones, and which was nitrogen-rich, could be used as an economical substitute for meat in French hospitals. Magendie was asked by the Academy of Sciences to carry out further trials to investigate the question. After 10 y of research, which yielded apparently paradoxical results, he had to report that: "As so often in research, unexpected results had contradicted every reasonable expectation." It was clear that gelatin was not a complete food for dogs, but neither was meat after it had been extracted with water. He suggested that chemists investigate what essential material it was that was leached out of meat: "It could perhaps be iron or other salts, fatty material or lactic acid" (10 ). In fact, there was to be a gap of another 75 y before this type of question began to be re-explored in the United States by E. V. McCollum, using the young rat as a more convenient model.

An important, unmentioned assumption behind Magendie’s work was that an animal species could be used as a model for humans; in other words, that our bodies were essentially of the same general character as those of animals. This may have arisen, at least in part, as a result of an interest in France for studies in comparative anatomy.

Another active investigator in France in the 1830s, with a quite different background from that of Magendie, was also studying the source of an animal’s nitrogen-rich tissues. This was Jean Baptiste Boussingault, who had learned his chemistry in a school for mining engineers. After a period of adventurous geological exploration in South America, he returned, married a farm owner’s daughter and put his mind to agricultural science. He obtained a position at the Sorbonne in Paris, where he collaborated with J. B. Dumas, one of the leading French chemists, and divided his year between Paris and the farm (11 ).

Working first with plant crops, he was able to show that leguminous plants, but not cereal grains, were able to utilize atmospheric nitrogen during growth. He then turned to cows and horses, whose common feeds had the reputation of being exceptionally low in nitrogen. His approach was first to find the level of feeding that kept his animals at constant weight, and then for 3 d to record the animal’s feed, excreta and, in the case of the cow, its milk, and also to analyze all these for their nitrogen content. With the horse, receiving altogether some 8.5 kg hay and oats per 24 h, the daily nitrogen intake was 139 g, and the nitrogen recovered in urine and dung came to only 116 g. The cow, fed on hay and potatoes, had a daily intake of 201 g nitrogen and the recovered output, including 46 g from milk, was only 175 g (Table 1 ). He concluded that the animals’ feed provided sufficient nitrogen to meet their needs and that there was no need to hypothesize that they had to obtain nitrogen from the atmosphere (12 ,13 ).

	Why the concentration on nitrogen?

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
Even before carrying out his balance experiments with herbivores, Boussingault had proposed that the relative nutritional values of plant foods could be assessed from their contents of nitrogen (14 ). His justification for this went roughly as follows: "Magendie has shown that foods that do not contain nitrogen cannot continue to support life, therefore the nutritional value of a vegetable substance resides principally in the gluten and vegetable albumin that it contains." Investigators at this time certainly knew that animal bodies also contained minerals that they must have obtained from their food. Even earlier, two workers had written that: "Beans are so nourishing because they contain starch, an animal matter, phosphate, lime, magnesia, potash and iron. They yield at once the aliments and the materials proper to form and color the blood and to nourish the bones" (15 ). Perhaps in response to such criticism, Boussingault explained, "I am far from regarding nitrogenous materials alone as sufficient for the nutrition of animals; but it is a fact that where nitrogenous materials are present at high levels in vegetables they are generally accompanied by the other organic and inorganic substances which are also needed for nutrition" (16 ). It is clear from the context that the "organic substances" to which he is referring are starches and not any hypothetical trace nutrients.

Was there any reason at this period for investigators to suspect that other nutrients might also be needed to constitute a complete diet? One might think that the problem of scurvy appearing among sailors and the evidence for the value of fruits and green foods in the prevention of the disease, would have suggested it. However, even James Lind, famous for his controlled clinical trial of different potential antiscorbutics, believed that they were active in countering the bad effects of sea air, and were not required by people living on land any more than quinine would be of any value for people not living in a malarious area (17 ,18 ). Also, it was clear that dogs, the animals being used by the French workers, thrived without such supplementary food items.

	Synthesis only by plants

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
In light of the results considered above, Boussingault’s colleague, the chemist Dumas, concluded that the plant kingdom alone was capable of synthesizing the kinds of nitrogenous compounds abundant in animal tissues. Then, from the observation that the overall reactions of animals were characterized by oxidation, he made the further generalization that the animal kingdom was only capable of oxidizing the materials that it obtained from its plant food (19 ).

The leading German organic chemist of the time, Justus Liebig, now comes into the picture. He too had become interested in the subject of "animal chemistry," and wrote that Dumas must be wrong because it was well known that pigs would fatten when fed on potatoes that were rich in starch, but contained only a negligible level of fat. This meant that animals must be able to convert carbohydrates to fat even though the conversion required "reduction" rather than oxidation.

This was a challenge to the French workers who had been the undisputed authorities in the field, and Boussingault put the matter to the test in another pioneering study. He killed and analyzed the carcass of a young pig, while feeding a littermate of the same starting weight on measured amounts of feed for an additional 3 mo. Carcass analysis of the second pig showed that it contained an additional 13.6 kg fat, whereas the feed it had eaten had only contained 6.8 kg (20 ).

This careful work had therefore shown that the French school was in the wrong on this point. Boussingault and Dumas both retired from working with animals, and Liebig became the new authority, even though he had never actually carried out a feeding trial. He continued to push his ideas on physiology and nutrition. Most of these were gradually shown to have been completely wrong, but at least they stimulated others to do research, putting them to the test.

	The atomic theory

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
While the work described above was in progress there was another important advance in chemistry that would be put to use in subsequent nutritional studies. John Dalton, a poor and largely self-educated schoolmaster in the north of England, had an important idea. This was that all elements are made up of indivisible particles, or "atoms," and that for each element every atom is identical. Chemical combination occurs when two or more different atoms form a firm union (21 ). These ideas were supported by the proportions of different elements in any compound being fixed and by the different compounds between the same two elements being in simple ratios by weight. Thus the gas we call "carbon dioxide" has exactly twice the weight of oxygen (per unit weight of carbon) that is present in the other gas called "carbon monoxide." Finally, gases were found to combine in simple relations by volume. Thus 3 volumes of hydrogen combine with 1 volume of nitrogen to form exactly 2 volumes of ammonia gas (22 ). From this it also follows that equal volumes of different gases contain the same numbers of molecules, once one accepts that many elements, such as hydrogen, oxygen and nitrogen, have two atoms combined together to form a single molecule.

For some years there was controversy as to whether carbon and oxygen each had one-half of the atomic weights that are now assigned to them, although it is easy to correct molecular formulas obtained in that period. Thus Prout, in England, subjected urea to improved methods of analysis, and obtained a molecular formula of C₂H₄N₂O₂, which agrees with the modern formula of CH₄N₂O when we double the atomic weights for C and O (23 ). In the following decade, Friedrich Wöhler in Germany found that he had obtained urea by heating silver cyanate with ammonium chloride. He wrote excitedly to his former professor: "I can make urea without the use of kidneys." Admittedly, urea was only an excretion product, but the synthesis was one small step in demonstrating that an organic compound produced in living systems could also be produced in the laboratory without the aid of any "vital force."

Wöhler, in collaboration with Liebig, also developed an important concept in organic chemistry. This was the idea of a common radical that would combine with other reagents, but still retain its own nature and be recoverable by further reactions. The first example was the "benzoyl" radical. Starting with benzaldehyde, one could oxidize it to benzoic acid or form a chlorinated derivative, and so on, and then reproduce the original benzaldehyde by appropriate reduction (24 ).

	The composition of "animal substance"

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
Up until then it had been recognized that so-called "animal substances" came in different forms that were named albumin, fibrin, casein and so forth, and that they differed in solubility and other physical properties, but all contained 16% of nitrogen. In 1839, it was suggested by a Dutch worker, Gerrit Mulder, that these substances were all compounds of a common radical combined with different proportions of phosphorus, sulfur or both; and the hypothetical radical was named "protein," from a Greek term implying that it was the primary material of the animal kingdom. He further proposed, using the symbol "Pr" for the radical, that egg albumin could be expressed as "Pr₁₀ · SP" and serum albumin as "Pr₁₀ · S₂P," and that the radical itself had the molecular formula "C₄₀H₆₂N₁₀O₁₂" (25 ).

Liebig received these ideas enthusiastically, and reported that the comparable materials that he had isolated from plant tissues also had exactly 4 atoms of carbon to 1 atom of nitrogen. He went further and suggested that, although it was only plants that could make the "protein" radical, animals had the power to add or subtract the added elements, thus converting albumin to fibrin, etc. (26 ). Dumas and Cahours, working in Paris, wrote that they too had found a 4:1 ratio of C:N in both casein and serum albumin. However, "legumin" extracted from peas and beans, and which Liebig had called "vegetable casein," had only a 3.25:1 ratio. This was a problem because there was reason to believe that legume crops had a high nutritive value, although legumin clearly could not be converted into albumin just by addition or subtraction of sulfur and/or phosphorus (27 ).

Liebig too was beginning to regret having adopted Mulder’s ideas. Workers in his laboratory had been unable to obtain the "protein radical" by removing the sulfur from egg albumin in the way described by Mulder; nor could they find the expected proportions of sulfur and phosphorus in different materials. Mulder was enraged by the tone of the criticism from Liebig, who was now denying what he himself had previously asserted. In any case, the concept of a protein radical now disappeared from the literature and the term "Protein" gradually began to be applied to all the materials previously described as "animal substance."

	Protein the only true nutrient

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
Meanwhile, Liebig had published a widely read book entitled Animal Chemistry or Organic Chemistry in its Application to Physiology and Pathology. In it he argued that, because his analyses of muscles failed to show the presence of any fat or carbohydrate, the energy needed for their contraction must come from an explosive breakdown of the protein molecules themselves, resulting in the production and excretion of urea. Protein was therefore the only true nutrient, providing both the machinery of the body and the fuel for its work (28 ).

If that was true, what role was left for the other constituents of the diet, and why did carbonic acid production increase so greatly during exercise? Liebig’s explanation was that increased respiration was needed to keep the heart and other tissues from overheating. However, this unfortunately led to more oxygen gaining access to the tissues, which could cause oxidative damage and loss of protein tissue. It was the function of the fats and carbohydrates to mop up this excess by being themselves preferentially oxidized.

Liebig’s book was at first generally regarded as a giant intellectual synthesis, and many people were converted to his ideas. For example, when the Professor of Medicine at Edinburgh University was called in to investigate a serious and unexpected outbreak of scurvy in a Scottish prison, his immediate conclusion was that it must be the result of an inadequate intake of protein (29 ). However, his calculations indicated that the average daily protein intake was an ample 135 g. But only 15 g of this quantity were from animal sources and 102 g were from gluten. He suggested that the power of the body to convert gluten to animal protein was limited, and that the level of milk in the diet should be increased so as to raise the intake of animal protein. Another Scottish physician replied that the value of lemon juice in the prevention of scurvy was well established and could not possibly be attributed to its protein content, given that a curative dose contained only a negligible amount of nitrogen (30 ).

Another difficulty in believing that muscular work required the breakdown of protein was that the traditional diet of laborers was of lower protein content that that of the less active rich. Edward Smith, a British physician and physiologist who was interested in the welfare of prisoners, and was concerned at the stressfulness of their having to work on a treadmill, measured their urea excretion in the 24 h during and after their 8 h of work, and again on their subsequent rest days, and found no difference (31 ) (Fig. 2 ). This was, of course, quite contrary to what Liebig would have predicted on the basis that the energy expended all came from the breakdown of protein that resulted in the production of urea.

View larger version (177K): [in this window] [in a new window]   FIGURE 2 Picture of the treadwheel in a London prison of the type used by Edward Smith to compare urea excretion on "work" and "rest" days, and to measure his own increase in carbon dioxide output when climbing a known distance on the treads. Both sets of measurements were used to advance knowledge of the fuels used by muscles and their efficiency (British Register, 1823).

	The conservation of energy

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

A critical experiment was then designed by two Swiss scientists, the physiologist Adolf Fick and the chemist Johannes Wislicenus, to test Liebig’s belief that protein constituted the sole muscle fuel. They traveled to the base of a mountain in Switzerland with a path to the top that was fairly easy to climb and a hotel at the top. They ate a very low nitrogen diet before and during their experiment, and collected their urine during and for 6 h after their climb (34 ). Analysis of the urine samples showed that they had excreted, on average, a quantity of nitrogen equivalent in nitrogen content to 35.0 g protein, using the usual "N x 6.25" conversion factor. They calculated, as best they could, the energy that could have been obtained from the combustion of this quantity of protein, but had values only for the combustion of carbon and hydrogen as such, that yielded a high value of 6.73 kcal/g protein. Even with this value they calculated that the energy obtainable was less than the work that they had done against gravity in their climbing.

In the same period, Edward Frankland, Fick’s brother-in-law in England, was developing a technique for measuring directly the heat of combustion of foods and of urea. For protein, with an allowance for the gross energy remaining in the excreted urea, he obtained a metabolizable energy value of 4.37 kcal/g. Using this factor, the energy obtained from the average quantity of protein metabolized (i.e., 35 g) was 153 kcal. With the mechanical equivalent of heat being taken as 423 "kg · m against gravity" per kcal, the mechanical work obtainable from 153 kcal was 64,700 kg · m.

In the climb the two men had risen 1956 m against the force of gravity and, with an average weight of 71 kg, had done an absolute minimum of 138,900 kg · m of work per head (Table 2 ). Because this was more than twice the energy that could have come from their breakdown of body protein, even assuming 100% efficiency of the muscles and neglecting the work of the heart and so forth, much of the fuel consumed must have come from other sources, presumably fat and/or carbohydrate (35 ). Frankland drew the analogy of a muscle to a steam engine in which the engine did not consume itself when working, but remained intact while using an entirely different fuel.

	Digestion

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
During the period under consideration, very little original work that related to nutrition was carried out in the United States. However, two names are remembered from this time. John Young, a medical student who died tragically at 21 from tuberculosis, described in 1803 in his M.D. thesis numerous experiments on digestion. He had found that regurgitated stomach contents did not undergo acetous fermentation, which was contrary to the current opinion. He also followed the fate of bagged samples of foods that he subjected to gastric digestion in frogs, snakes and birds, and showed that animals that were normally carnivorous could at least dissolve plant foods, and vice versa (37 ).

Some 20 y later, a U.S. Army surgeon, William Beaumont, had the opportunity to become a pioneering physiologist. At a remote trading post a young man was accidentally shot in the stomach and the wound left a permanent fistula through which food samples could be introduced and removed. Because the victim was destitute, Beaumont took him into his house and used him as a subject intermittently for almost 10 y. He observed that gastric juice, which always contained hydrochloric acid, was secreted only in response to eating. He also saw that oily food was only slowly digested, but that it was speeded by "minuteness of division" (38 ).

At that time the stomach was thought of as the major site of digestion. However, in the 1850s, Claude Bernard discovered that the secretions into the small intestine from the pancreas, together with the emulsifying effect of the bile, were of the greatest importance for the digestion of fat into glycerol and free fatty acids, and its absorption (39 ). This and the later discoveries of the proteolytic activity in the small intestine, to be discussed in Part 2, made the study of purely gastric digestion seem less important.

	Scurvy and other diseases

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
In 1842 George Budd, Professor of Medicine at King’s College, London, gave a memorable lecture titled "Disorders resulting from defective nutriment," from which these are some of his opening comments: "There is no subject of more interest to the physiologist or of more practical importance to the physician ... than the disorders resulting from defective nourishment. ... These disorders are, no doubt, frequently presented to us by the destitute poor in our large towns; but ... from our not being acquainted with all the circumstances in which they arise, their real cause escapes us. It is only—as in ships, garrisons, prisons and asylums—when large numbers of men ... become affected with one disease, that our attention is fixed upon it, and that we can succeed in discovering its cause by considering what is peculiar in their circumstances" (40 ).

There is one exception to the generalization at the beginning of the chapter that no systematic work relevant to nutrition had been carried out before 1785, and this must now be described. It is the pioneering controlled clinical trial of the various therapies recommended for the disease of scurvy, which was carried out in 1746 by James Lind on sailors at sea. Lind was, at that time, a 30-y-old ship’s surgeon in the British navy, with no academic education, but with a special interest in the problem of scurvy. He took 12 sailors, all with a similar severity of the disease, divided them into pairs and, for 2 wk, gave each pair one of the many treatments that had been recommended for the condition. His trial is described in more detail elsewhere, but the salient point for modern readers is that the pair receiving lemons and oranges were almost recovered after only 6 d, whereas those receiving either dilute sulfuric acid or vinegar had shown no improvement after 2 wk (41 ,42 ).

The importance of Lind’s trial has often been described as showing that citrus fruit was a cure, or preventive, for scurvy. This had, in fact, been known already for some 200 y but could not always be made use of. Neither oranges and lemons nor fruit juice could be stored on long voyages before the days of refrigeration because they went moldy. Because of this, the College of Physicians in London had reasoned that other acids could act as substitutes, given that it was thought that scurvy was a "putrid" disease, and animal tissues that went putrid became alkaline. It seemed therefore to follow that citrus juice acted as it did as a result of its acidity, and that other more stable acids like sulfuric acid (diluted before use!) or vinegar could be used equally well. As a consequence, ships’ surgeons were issued with sulfuric acid for many years without its actual value having been put to a critical test.

In 1753, after Lind had qualified as a university-trained physician, he wrote in his treatise on scurvy: "The Channel fleet for many years was supplied with vitriol [sulfuric acid]. Yet it often had a thousand men miserably over-run with the disease. ... Of theory in physic [medicine] ... it is indeed absolutely necessary yet, by carrying it too far, it may be doubted whether it has done more good or hurt in the world" (43 ).

If other acids could not replace lemon juice, and if lemons or their juice were too unstable for carriage on long voyages, what could be done? Lind himself suggested that the juice could be slowly concentrated in shallow bowls over boiling water until they had condensed to a thick syrup, or "rob" as he called it. This was tried but found to be of little value in practice. A more effective product, and one welcome to sailors, was to preserve the juice with a proportion of rum or brandy. Another approach was to extract citric acid from the juice and to issue that to ships. Unfortunately, many writers, assuming that citric acid was the active factor, would refer to "administering the citric acid," even when they were actually giving lemon juice. In some instances this is clear, but in others not. Finally, after many years of uncertainty it was agreed that true pure citric acid was not antiscorbutic (44 ).

Lind had believed that the true value of citrus fruit was that it had "a saponaceous, attenuating and resolving virtue" [or "detergent action"] that helped to free perspiration pores in the skin that had become clogged in sea air so that poisons accumulated without being able to escape. He believed that the disease did not occur on land, so that land dwellers did not therefore require an antiscorbutic as sailors did. But this was not the case. It was clear by 1843 that there had, from time to time, been at least 20 outbreaks of scurvy in British prisons. The condition seen in the prisoners was exactly the same as that seen at sea. The only common factor that could be found to explain these outbreaks was that, for some time previous to the outbreaks, potatoes had been omitted from the diet; and when these were added back to the diets, the disease disappeared (45 ).

The importance of potatoes as antiscorbutics was confirmed in the period from 1845 to 1848, when successive European potato harvests failed because of fungal attack. In Ireland, where potatoes had become the major source of energy for much of the population, there was disastrous starvation on top of the expected scurvy. In England, where more grain was grown and there was no overall shortage of energy, the major effect was again a series of outbreaks of scurvy, this time in the general population as well as in prisons. The serious outbreak in a Scottish prison has already been discussed in relation to the belief of a disciple of Liebig that protein was "the only true nutrient" and therefore, if a diet was inadequate in quality, the deficiency must be in the supply of protein. In practice, green vegetables were found to be effective alternative antiscorbutics when neither potatoes nor fruit were available.

Land scurvy would continue to be a problem whenever food supplies were limited by supply problems. Thus it occurred among prospectors during the California gold rush, soldiers during the Crimean War, prisoners in the American Civil War and ordinary civilians during the Siege of Paris in 1871 (46 ). In every case, the problems were resolved when either fresh vegetables or fruit juice became available again.

	Arctic scurvy

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
As the nineteenth century progressed, ship travel became faster, so that long voyages without the opportunity of collecting fresh food at ports of call became rarer, as did sea scurvy. However, arctic exploration proved to be the exception to this generalization. In 1875 the British navy mounted an expedition that would attempt to get farther north than had been achieved by earlier explorers. The navy was confident that scurvy would not be a problem. In the Napoleonic wars they had been able to blockade French ports and to remain at sea for long periods as a result of the well-organized supply of lemons from Sicily. Now the authorities had changed to using limes from the West Indies, believing that, because they were more acidic, they would also be even better antiscorbutics. The juice was bottled in England, preserved with spirits.

The two ships sailed in May 1875 with 122 on board, wintered in the ice at 82°N and sent out sledging expeditions in the following spring. By June there had been 60 cases of scurvy with four deaths and the ships returned home. This was considered to have been a major scandal and a thorough inquiry was begun. Everyone on board had received daily rations that included 4 oz of "preserved vegetables," 1 oz of pickles and 1 oz of lime juice. One critic argued that Liebig had made physiology a new science and that the doctrine of antiscorbutics had been given a death blow. Others urged that attention should be given to how the Eskimos managed to remain healthy in the far North without the use of fruit or fresh vegetables (47 ). As we will see in the following chapter, this problem led to the adoption of new theories that were to mislead explorers for a considerable time, and to provide an example of knowledge apparently going backward for at least 20 y.

Another problem encountered on long voyages, sometimes in conjunction with scurvy, was night blindness. Some ship’s surgeons considered it be an early sign of developing scurvy, and both conditions were found to respond to the addition of fresh green vegetables to the diet. However, most believed it to be a separate disease because the two conditions did not always appear together, and sufferers from night blindness frequently went on to develop ulcers on their corneas (48 ).

There are several reports by physicians of their successful treatment of the condition with fish or cod liver oil early in the nineteenth century (49 ,50 ). It was also a very old folk treatment for the eye problems to give patients cooked liver from any of a variety of animals. This was put to the test in the 1850s on a round-the-world voyage organized by the Austrian navy. On the last long leg of the voyage, from the Cape of Good Hope to Gibraltar, 60 of the 350 on board developed night blindness. The ship’s surgeon, who had been asked to carry out the test if an opportunity presented itself, obtained ox liver at Gibraltar, gave it to all 60 and reported that the result was "a true miracle" (51 ). Nevertheless, he was attacked in the medical press "for his frivolous conclusion that it was a nutritional disease, which could only be regarded as self-aggrandizement by someone ignorant of the literature on the subject."

In 1863 P. Bitot, a French physician whose name has been given to the white spots on the cornea that he recognized as being associated with night blindness, made no mention of being able to cure his patients with any food supplement, and described the condition as being "purely vital or nervous" in nature (52 ).

In 1881 a British physician reported that the condition responded well in patients being dosed with cod liver oil and suggested that they were possibly "suffering from some want of tone or nutrition" (53 ). However, this was still not the generally established conclusion. In 1884 a German physician who had seen the condition at an orphanage where he had medical responsibilities concluded that it must be the result of an infection, given that the children were receiving a good diet (54 ).

	Goiter and cretinism

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 
Goiter, seen as a swelling in the front of the neck, had been recognized as existing in some specific areas for millennia. In the same areas there was also a smaller proportion of babies born with cretinism, characterized by stunting and low mentality. For sufferers from goiter it had been a long-standing folk treatment to give them dried seaweed and sponges, or the ash prepared by burning them. In 1812 the element iodine was discovered in this kind of ash, and French chemists suggested that it be used for the treatment of goiter. However, it was frequently found to be toxic in the doses given and the treatment was largely abandoned (55 ). At the end of the period covered by this presentation, Hirsch, in a wide-ranging scholarly review, wrote that the iodine-deficiency theory was "a short-lived opinion ... endemic goiter and cretinism have to be reckoned among the infective diseases" (56 ).

We have seen in the examples of Arctic scurvy, night blindness and goiter, the growing belief that more and more diseases were going to be explained in terms of either direct infection with microorganisms or indirectly by the power of these organisms to produce toxins. Undoubtedly, the development of the germ theory of disease made an enormous contribution to reducing human suffering but, at least for a period, some well-established facts regarding other diseases were to be treated as no more than old wives’ tales. To take a further quotation from George Budd: "Large numbers of men ... have been kept on a diet insufficient in quantity and variety ... diseases of strange kind have appeared—the cause has been recognized, and the remedy applied ... but the lesson has been forgotten—and at a short interval of time, and in a different place, a knowledge of the imperious necessity of nourishment more abundant or more varied is again dearly bought by the experience of wholesale sickness" (57 ).

Manuscript received 18 December 2002. Revision accepted 27 December 2002.

	LITERATURE CITED

TOP ABSTRACT Why the concentration on... Synthesis only by plants The atomic theory The composition of "animal... Protein the only true... The conservation of energy Digestion Scurvy and other diseases Arctic scurvy Goiter and cretinism LITERATURE CITED

 

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