The War Against Disease. Food Factors

The germ theory dominated the minds of most physicians through the last third of the nineteenth century but there were a few who resisted it. The German pathologist, Virchow, was the most eminent of these. He preferred to think of disease as being caused by some irritation from within, rather than some agent from without. He was also a man of strong social consciousness who spent some decades in Berlin city politics and in the national legislature. He pushed through important improvements in such matters as a purified water supply and an efficient sewage system. Pettenkofer was another of this type and he and Virchow were among the founders of modem notions of public hygiene (the study of the prevention of disease in the community).

Such improvements interfered with the easy transmission of disease (whether Virchow believed in germs or not) and were probably as instrumental in putting an end to the epidemics that had, until the mid-nineteenth century, plagued Europe, as was the more direct concern with germs themselves.

If Hippocrates' interest in cleanliness retained its force in the days of germ-consciousness, that was to be expected. Perhaps more surprising was the fact that Hippocrates' advice as to a good and varied diet also retained its force, and not only for the sake of general well-being, but as a specific method of preventing specific diseases. Poor diet as a cause of disease seemed to many, during the germ-conscious generation from 1870 to 1900, to be an outmoded notion, and yet there was strong evidence to show that it was not at all outmoded.

Thus, in the early days of the Age of Exploration, men spent long months on board ship, living only on food items that could keep over those periods, since refrigeration was unknown. In those days, scurvy was the dreaded disease of seamen. A Scottish physician, James Lind (1716-94), took note of the fact that scurvy accompanied monotonous diet not only on shipboard, but in besieged cities and in prisons. Could a missing dietary item be the cause of the disease then?

In 1747, Lind tried different food items on scurvy-ridden sailors and found that citrus fruits worked amazingly well in effecting relief. Slowly, this device was adopted. Captain James Cook (1728-79), the great English explorer, fed citrus fruit to his men on his Pacific voyages in the 1770s and lost only one man to scurvy. In 1795, the British Navy, under the pressures of a desperate war with France, began compulsory feeding of lime juice to sailors, and scurvy was wiped out on British ships.

However, such empirical progress is slow in the absence of the necessary advances in basic science. Through the nineteenth century, the major discoveries in nutrition concerned the importance of protein and, in particular, the fact that some proteins were "complete" and could support life when present in the diet, while others, like gelatin, were "incomplete" and could not.

An explanation for this difference among proteins came only when the nature of the protein molecule was better understood. In 1820, the complex molecule of gelatin was broken down by treatment with acid and a simple molecule, named "glycine," was isolated. Glycine belonged to a class of compounds called "amino acids."

At first it was assumed that glycine was the building block of proteins, as the simple sugar, glucose, was the building block of starch. However, as the nineteenth century progressed, this theory turned out to be inadequate. Other simple molecules were obtained out of various proteins. All were of the class, amino acid, but they differed in detail. Protein molecules were not built out of one, but out of a number of amino acids. By 1900, a dozen different amino-acid building blocks were known.

It was quite possible, then, that proteins might differ in the relative proportions of the different amino acids they contained. A particular protein might even be lacking altogether in one or more particular amino acids and those amino acids might be essential to life.

The first to show that this was indeed so was an English biochemist, Frederick Gowland Hopkins (1861-1947). In 1900, he had discovered a new amino acid, tryptophan, and had developed a chemical test that would indicate its presence. Zein, a protein isolated from corn, did not respond to that test and therefore lacked tryptophan. Zein was an incomplete protein and would not support life where it was the sole protein in the diet. If, however, a bit of tryptophan was added to zein, the life of the experimental animals was prolonged.

Similar experiments conducted during the early decades of the twentieth century made it quite clear that some amino acids could be formed by the mammalian body from substances usually available in the tissues. A few, however, could not so be manufactured and had to be present, intact, in the diet. It was the absence of one or more of these "essential amino acids" that made some proteins incomplete and brought on sickness and eventual death.

Thus was introduced the concept of a "food factor": any compound that could not be made in the body, and that had to be present in the diet, intact, if life was to be maintained. To be sure, amino acids were not serious medical problems, however interesting they might be to nutritionists. An amino acid deficiency was generally brought on by artificial and deliberately lopsided diets. A natural diet, even a poor one, usually supplied enough of each amino acid.

If a disease such as scurvy could be cured by lime juice, it was reasonable to suppose that the lime juice was supplying a missing food factor. It was not likely however that the food factor was an amino acid. In fact, all the constituents of lime juice known to the nineteenth-century biologist would not, taken singly or together, cure scurvy. The food factor involved must therefore be a substance that was necessary only in trace quantities and one that might well be quite different, chemically, from the usual components of food.

Actually, the mystery was not as hard to solve as it might seem. Even as the concept of the essential amino acid was worked out, other more subtle food factors, required only in traces, were also being discovered, and, as it happened, not through a study of scurvy.