Birth of Method

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On the fifteenth of June, 1744, the storm-battered 60-gun centurion approached the coast of England. The battleship of his Majesty’s Royal Navy was the only surviving vessel of a squadron of eight ships that had set sail four years earlier under Commodore Jorge Anson on a circumnavigation of the world. Of the 1955 sailors who sailed, only about 500 returned home. It was not the attacks of the natives, the fighting with the hostile Spanish fleet, or the fierce storms that were to blame. More than 1,300 sailors were taken by scurvy – a mysterious disease that for centuries killed those who went on a long sea voyage. The surviving members of the expedition wrote:

Soon after we passed the Straits of Le Mer, scurvy made itself felt. Our long sojourn at sea, fatigue, and many disappointments led to the spread of scurvy to such an extent that by the end of April there were very few people on Board unaffected by the disease. This month alone, 43 people died aboard the Centurion.

Manifestations of the disease became apparent as the squadron rounded the southern tip of America. The sailors attributed the inexplicable disease to the fact that they had advanced too far South, and expected that the disease would recede when, after rounding Cape horn, they began to move North again. But the hopes were not realized: in may, twice as many people died from scurvy. And by the middle of the next month, on the Centurion alone, the disease had taken more than 200 sailors, and the captains of the ships could no longer muster the right number of men fit for duty.

This disease, which often overtakes those who have gone on a long voyage, is by far the strangest and most inexplicable of all that afflicts the human body. Its symptoms are numerous and fickle, but there are those that occur more often than others. These are large discolored spots on the entire surface of the body, swollen legs, rotting gums and, above all, incredible fatigue of the whole body, especially after any, even the most insignificant load. This fatigue is replaced by a tendency to faint at the slightest effort or even movement… the Disease is often accompanied by a strange dejection of spirit, trembling, and a tendency to the most terrible fears. Any event that deprived our people of hope gave the disease strength: killed those who were in its last stages, and chained to hammocks those who still had the strength to serve…

There is no end to the list of signs of this disease. It also often causes putrid fever, pleurisy, jaundice, severe rheumatic pains, sometimes long constipation, and usually the following difficulty of breathing – the most deadly symptom. In other cases the whole body, and especially the legs, was covered with hideous sores, the bones rotted, and the flesh became a spongy mass, and there was no escape.

Now we know that scurvy is caused by a lack of ascorbic acid, which we also call vitamin C. Vitamins are substances that the body can not produce on its own and must receive for normal functioning from the outside, for example with food. The main source of vitamin C is fresh vegetables, herbs and fruits. Especially a lot of it is contained in citrus.

Most plants and animals are able to synthesize ascorbic acid, but some animals, such as bats, Guinea pigs, capybaras and some species of monkeys [33], including us, have lost this ability. This could have been the result of a random mutation that did not become fatal because the food provided enough vitamin C from the outside. Thus, the mutation was passed on to descendants and remained in our genes.

Ascorbic acid is vital because it is involved in the synthesis of collagen, the most common protein in the body. From a quarter to a third of all protein in our body is collagen [34]. Connective tissue is built from it: skin, bones, cartilage, ligaments and vessel walls. It is thanks to collagen that organs retain their shape. When a person receives insufficient amounts of vitamin C with food, the body synthesizes” wrong”, insufficiently strong collagen. Then the frame on which the body rests weakens. Due to the lack of reliable collagen support, body tissues literally disintegrate, which leads to symptoms of scurvy: spots appear on the skin, and it ulcerates, gums swell and begin to bleed, teeth fall out. Often the first symptoms are described in the Chronicles of George Anson’s journey weakness, lethargy, change of mood. Cease to heal wounds, and reopen previously healed. The Chronicles of the Centurion’s circumnavigation of the world describe a case in which a patient’s wounds, received many years ago, were opened.

On this occasion there was a case worthy of mention, when one of the scurvy sufferers on Board the Centurion, who had been wounded 50 [sic] years before at the battle of the Boyne, soon cured and in good health all these years, the wounds opened anew and looked as if they had never been treated. And, more surprisingly, the callus of a once-broken bone, long formed, had disintegrated, and the fracture looked as if the bone had never fused.

In the absence of treatment, which consists in taking vitamin C, a painful death is inevitable. The fragility of the walls of capillaries and vessels causes spontaneous bleeding, and the patient inevitably dies from blood loss or concomitant infection.

Many of our men, though chained to hammocks, still looked quite well, ate and drank well, were full of energy, spoke in a loud and cheerful voice; but when they were moved a little, even if only from one end of the ship to the other, even in hammocks, they immediately gave up the Ghost. Others, believing in their apparent strength, decided to leave the hammocks and died before they could get on deck. There were times when those who could walk and work suddenly fell dead when they tried to do something with special effort.

Scurvy has been known to mankind for a long time. The disease often overtook those who were forced for a long time to abandon the usual diet in travel or military campaigns. It is mentioned in the Bible [35], in the works of the ancient Roman historian Pliny the Elder and in descriptions of the Crusades [36]. With the beginning of the era Of great discoveries, scurvy became a real disaster for those who went on a long voyage. Columbus, Magellan, Vasco da Gama, Francis Drake-all these famous sailors lost dozens and hundreds of people because of an incomprehensible and terrible disease. It is believed that in just the XVI–XVIII century scurvy claimed the lives of about two million sailors.

Not knowing about the existence of vitamins, people could not correctly explain the causes of the disease until the late XIX-early XX century. It was rarely associated with nutrition. Although it was, of course, in the products of which consisted of the diet of the sailor. Vegetables, greens and fruits were not taken on Board – they were too quickly spoiled in the open sea. Therefore, what could remain relatively edible for a long time was purchased: biscuits, salted meat, dried pears and grain. During the long voyage, these, and so imperfect in the opinion of the modern nutritionist, products rotted, moldy and began to swarm with worms and larvae. George Anson’s ship’s surgeon wrote that ” the biscuits were so worm-eaten that they turned to dust.” Another ship’s surgeon described the diet of sailors of the time as ” rotting beef, rotten pork, moldy biscuits and flour.” Had it not been for the occasional stopover for fresh food, including fruit and vegetables, probably no long journey would have ended with even a small portion of the crew returning home.

During George Anson’s four-year circumnavigation of the world, a significant portion of the crew died. Anson had to abandon ships because there were not enough men to operate them. Of the eight ships of the squadron, only the flagship centurion survived and returned home. Fortunately, near Jakarta, the crew was lucky enough to capture a Spanish Galleon with a large cargo of silver, so that the return to England was a triumph, not a defeat. The campaign full of dramatic events became a topic of conversation for a long time. And the role of scurvy, which almost led to his failure, attracted the attention of many doctors to the disease. Among them was a young ship’s surgeon, James Lind, who was destined to be the hero of one of the most important and controversial subjects in the history of medicine.

James Lind was born in 1716 in Edinburgh, into a family of merchants, well-to-do, but with no special connections or prominent position in society. Probably influenced by his uncle, a doctor, James chose a medical career. From the age of fifteen he began to learn this science, becoming an apprentice surgeon. The professions of surgeon and physician were still very different: surgeons, whose work was less prestigious than that of physician and less paid, did what they had done in Pare’s time-amputating limbs, treating wounds, and setting bones.

A few years later, James began to master the theory of medicine at the University of Edinburgh. We can fairly imagine how he was taught the causes and treatment of scurvy. Humoral theory was still the basis of physiology, but under the influence of developing chemistry, more and more attention was paid to what happens to humors under the influence of various factors, how they deteriorate in this case. Special authority enjoyed the work of the Dutch doctor Hermann Burgave, who, supplementing the humoral theory with the achievements of modern physics and chemistry, described the body as a hydraulic system. Burgave attributed the disease to mechanical disturbances in its operation – changes in pressure in the pipes and blockages – or chemical changes in the fluids flowing in the system. For example, he considered the cause of scurvy to be a blockage of the spleen. It was assumed that because of the swollen spleen, black bile does not find a way out of the body and, accumulating, causes disease.

Further development of the ideas burhave gave rise to the putrefactive theory, which has long adhered to Lind himself. It said that poor diet, bad sea air and other hardships of sea service lead to disruption of digestion of food, which latches and begins to rot in the body. Not much has changed in the past from the time of Ancient Egypt and Ancient Greece two thousand years, isn’t it?

However, compared with another Dutch doctor, Severinus Eglenus, who wrote that scurvy was sent to us from above for the sins of the world, Burgave and his ideas were incredibly progressive.

Recommendations for the treatment of scurvy followed logically from these theories. The idea of leaching undigested food led to attempts to use different acids: the most popular was vitriol elixir, a flavored solution of sulfuric acid. For many decades, on the orders of the Admiralty [37], they were supplied with sailing ships. Acetic acid, various remedies for improving appetite and correcting impaired digestion, as well as laxatives for “clearing blockages”were used just as persistently and unsuccessfully.

At the age of thirty-one, Lind passed his examination and was employed as surgeon to the fourth-class ship, [38] the Salisbury, of the Straits Fleet. [39] Lind had boarded the Salisbury as an experienced physician; his studies at the University had been interrupted by the war with Spain, during which he had served as assistant surgeon to the ship. He read a great deal, knew Latin, Greek, German, and French, and was certainly interested in medicine beyond the treatment of wounds and amputation of limbs – the usual trade of surgeons. And of course, he was intrigued by the mystery of the main killer of sailors – scurvy.

In April 1747, the Straits Fleet began patrolling The English channel. Despite the fact that the ships of the fleet did not depart far from the coast, a meager diet within a few weeks led to the inevitable. 400 of the 4,000 sailors in the fleet, including a large part of the crew of the Salisbury, showed signs of scurvy, and on may 20, 1747, James Lind did what forever inscribed his name in the history of medicine.

Lind selected twelve sailors with the most similar symptoms, divided them into six groups of two patients each, placed them side by side, and provided them with the same care and nutrition. The same except for one single component – treatment, the test of which was the purpose of the experiment. The first group was given a quart [40] of cider daily; the second, twenty-five drops of vitriol elixir for rinsing the mouth and three times a day inside; the third, two spoonfuls of vinegar; the fourth, half a pint [41] of sea water; the fifth Lind gave two oranges and one lemon a day, and the sixth took a complex medicine recommended by the hospital doctor and made of garlic, mustard seeds, horseradish, Peruvian balsam and myrrh. In addition to these twelve men, Lind observed several other patients, of whom we only know that they received no treatment other than a mild laxative.

Within a few days the difference became apparent. The quickest and most noticeable effect was produced by oranges and lemons. One of those lucky enough to get the citruses had recovered enough by the end of the sixth day to return to duty. The health of the second allowed him to take care of the other patients. The next most effective after oranges was cider. Apple cider may contain small amounts of vitamin C. it is too small for a quick and complete recovery, but enough for Lind to note some improvement. Rinsing the mouth with vitriol elixir reduced inflammation in the mouth, but did not affect the rest of the symptoms of scurvy. And the condition of those who drank sea water, took vinegar and a complex medicine of the hospital doctor, did not improve at all and did not differ from the condition of those who did not receive treatment. The difference in the condition of the patients in the different groups was so obvious that Lind could not but infer the unconditional efficacy of lemons and oranges.

A few years later came the first edition of James Lynde’s Treatise on scurvy, dedicated to Commodore George Anson. The treatise contains everything already written about the disease by other authors, as well as Linda’s own thoughts on the causes, prevention and treatment of the disease. The experiment aboard the Salisbury is also described. Despite the completely wrong understanding of the causes of the disease, Lind noted the obvious-citrus fruits were the most effective means.

If you assume that this publication once and for all changed the treatment of the disease and saved the lives of hundreds of thousands of sailors, you are mistaken: after the publication of the “Treatise on scurvy” nothing happened at all. The Admiralty has not added fresh citrus to the diet of sailors, the use of useless drugs has not stopped. Both during the seven Years ‘ war, which began three years later, and during the American war of independence, which began twenty years later, the losses of the British Navy from scurvy far exceeded those from combat.

Why didn’t Linda’s work solve the problem once and for all?

First, it contradicted the theories and methods of treatment advocated by far more influential doctors. For example, the king’s personal physician, and later President of the Royal society [42] John Pringle was fascinated by the problem of rot. Previously, he conducted experiments in which he showed that fermentation, in particular the presence of yeast, slows down the decay of meat [43]. It is not difficult to guess that it was experiments with fermenting barley wort [44], and not with citrus, that received his full and unconditional support. It persisted even after negative results [45] until barley malt became the main remedy for scurvy, tons purchased by the Admiralty. How could the President of the Royal society, John Pringle, admit that he was wrong and accept the rightness of Lind, who occupied a much more modest position in society? In addition, he sympathized with the Jacobites [46], which in itself was a sufficient reason for dislike on the part of loyal to the current government medical officials.

Secondly, in the absence of peer-reviewed medical journals, scientific conferences, databases of scientific articles and other modern communication tools, Lind’s “Treatise on scurvy” went largely unnoticed. In the middle of the XVIII century, the publication of important results did not mean that at least a narrow circle of experts interested in the topic would know about them. The story of the young doctor William stark shows how little attention Linda’s work attracted. Stark studied scurvy by conducting dietary experiments on himself. He kept detailed records, from which we know that at first stark tried to live only on bread and water, and then added one by one various products-fat, milk, beef, olive oil, pudding. In time, he expected to reach the vegetables and fruits, but did not have time: eight months later, stark died of scurvy. There is no mention of Linda in his notes. If stark had known about his experiments, fruits and vegetables would surely have appeared on the menu much earlier.

Third, from the Admiralty’s point of view, lemons and oranges were the worst possible solution. In the UK, they were not only expensive, but also difficult to access, especially during the war with their main supplier – Spain. Besides, they took up a lot of space in the cramped holds and were not stored for too long. Vinegar, vitriol elixir, sauerkraut [47], barley wort – anything was preferable to expensive and quickly perishable fruit. Especially sea water. Lind is not the only one who hoped to cure scurvy with it – it is not easy to give up the hope of scooping up a bucket of life-saving medicine free of charge from the side of any ship.

Alas, the progress of science rarely resembles the straight forward movement as it is usually described. One experiment, no matter how convincing, is not enough to change the dominant scientific point of view-it depends on a variety of social, communication, political and economic factors.

Lind soon retired from the Navy, passed another exam, and began working as a therapist, opening a private practice. A few years later, he was offered the leadership of Haslar, the largest and most modern hospital of his time. There he continued to work on the problem of scurvy. Realizing that he would never convince the Admiralty of the need to purchase citrus, he developed a special concentrate that was supposed to contain the medicinal properties of their juice in a small volume. Alas, Lind did not know that in the process of manufacturing the concentrate lost up to half, and when stored another 90% of the active substance. At the same time, Lind recommended it in such small doses that the concentrate was completely ineffective, as his tests demonstrated. The Admiralty refused to purchase.

Lind never again resorted to the experimental method he had devised and brilliantly applied, and he took it for granted that the concentrate retained all the properties of fresh juice – for it was no different in taste or appearance. Although Lind himself once wrote that he believed “it is absolutely impossible that a cure for scurvy will be found on the basis of a theory not based on experience,” he allowed himself to make the same mistake that his opponents made. It’s always harder to notice your mistakes.

The longer Lind seeks treatment for scurvy, the more confused she becomes. In the last edition of the” Treatise ” he, in addition to citrus, starting from old erroneous theories and relying on abstract reasoning, recommends laxatives, diuretics, milk and even-a curtsey to Pringle’s ideas-fermented beverages. In the same edition of the Treatise he writes:

The afterword is my last contribution to this work, which I probably cannot continue without going into the realm of conjecture and uncertainty. Perhaps from the examination of several thousand patients, the careful study of all the published books, and the extensive correspondence with different parts of the world, through which the knowledge of all the significant cases of this disease was collected, better results and more reliable treatment were to be expected. Although some scattered facts and observations give hope for greater success, experience always demonstrates the fallacy of any achievements of the medical art.

Lind’s pessimism was in vain. Even during the experiment aboard the Salisbury, he was a step away from winning. But it took another half-century and tens of thousands of lives to take that step.

In 1789, sir Gilbert blaine, baronet, took the post of chief medical officer of the Navy. It was he who brought what James Lind had begun to an end. A year after Linda’s death, lemon juice became a mandatory part of the diet of British sailors. Through his social position, connections, and persuasive experiments, blaine was able to prove to the Admiralty that the high cost of lemon juice was justified by its undeniable effectiveness. Soon scurvy for the Royal Navy of great Britain remained in history. Thanks to this, in 1805, during the battle of Trafalgar, he completely defeated the weakened scurvy fleet of Napoleon Bonaparte. Gradually, lemon juice was replaced by lime juice, which grew in the British colonies. Therefore, foreign sailors began to call the British limeys [49]. But the British wore this, initially offensive, nickname with pride. And they had every reason to do so: the British Navy was the first to defeat the deadly disease.

The eradication of scurvy in the Royal Navy did not mean final victory. Not only in the navies of other countries, but in the merchant Navy of great Britain, her colonies and prisons, she continued to claim thousands of lives every year. Thirty years after the victory over scurvy in the Royal Navy, a special Commission established in connection with the epidemic of scurvy in the prison of British Dorchester, concluded that the disease is not related to food, so there is no need to change the diet of prisoners. In a situation where scientific truth is blurred, it is always tempting to assign truth to what promises the greatest financial benefit.

The road to understanding the causes and symptoms of scurvy was even longer than the search for a cure. The nineteenth century gave rise to many new theories: in the age of electricity, the disease was explained by nervous disorders, in the era of rapid development of Microbiology-toxic secretions of bacteria. It was not until 1907 that Alex Holst and Theodore Froelich, while studying beriberi [50] in Guinea pigs, suddenly discovered symptoms of scurvy in animals, and then that symptoms disappear after eating fresh vegetables and their extracts. The emergence of laboratory animals, on which can be was simulate disease and treatment, allowed quite quickly move in research, and already in 1932 team Hungarian scientist albert St. Gyorgy was able point to L-hexuronovuyu acid and prove, that she and is those substance, which cures and prevents scurvy. In 1933, it was synthesized in the laboratory, thereby confirming its chemical structure. The acid was named ascorbic from the Latin name of scurvy-scorbutus. For this and other works, albert St. Gyorgy was awarded the Nobel prize.

In the second half of the XX century, vitamin C again for a while was in the spotlight. This time the pendulum swung in the opposite direction, and taking large doses of ascorbic acid was promoted by some scientists as a way to treat almost any disease and even the key to longevity. However, this is another story.

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