The Miraculous Fever-Tree

by Fiammetta Rocco

  They were there to celebrate the three-hundredth anniversary of the first recognised use of cinchona, 1630 being the date that the Countess of the legend was said to have been cured with a dose of quinine. Many of those attending had travelled halfway across America. Others had come from Scotland, and even as far afield as Indonesia.

  Among them were George and Frederic Rosengarten from Philadelphia, descendants of the Rosengarten who had supplied Dr Sappington with the quinine he used to make his fever-pills before the American Civil War. In the intervening years their company had become America’s biggest quinine manufacturer, and had recently merged with another large pharmaceutical company, Merck & Co.

  Present also was Dr M. Kerbosch, the director of the Dutch government’s cinchona estate at Pengalengan in Java. Dr Kerbosch had taken a four-month sabbatical to journey around the world with his wife, taking in the celebrations in St Louis on the way. Dr A.R. van Linge, an elderly Dutchman who ran a company called Nederlandsche Kininefabriek, was also there. He was more accustomed to working long hours in the small Amsterdam office from which he controlled the marketing and sale of all the cinchona produced in Java, and the manufacturer of 95 per cent of the world’s quinine, than to gatherings of this sort. Dr van Linge was a shy man, and felt rather nervous about the prospect of addressing three hundred delegates at a banquet. It was, he told them, the first time he had ever given a speech in public.

  The trustees and board of the St Louis Botanical Garden were, for their part, anxious for the visitors to appreciate that their garden held pride of place among botanists in America, with as fine a collection of plants and a history as any more venerable botanical garden elsewhere. As part of the show they put on a display of giant chrysanthemums with huge rounded heads of rust and yellow, for which St Louis was well known, and which had been specially forced in heated greenhouses so that they would have attained their rotund perfection on the day. The visitors were shown over every inch of the garden’s 1600 acres of plants and trees, in particular its world-famous collection of orchids, which had been gathered from all over the world.

  The climax was a magnificent banquet at the Jefferson Hotel. The guests, most of them unused to wearing formal evening wear, gathered a little self-consciously in twos and threes. But they soon relaxed, falling into conversation with their neighbours about the tree that had drawn them together. After dinner, George Moore, Director of the St Louis Botanical Garden and the host of the evening, pushed back his chair and stood up. ‘We are met here today to glorify a plant product,’ he began. And glorify it they did. Casting their minds back over the journey that cinchona had taken over the past three centuries, each of the speakers told a different chapter of the cinchona story.

  They spoke of the Jesuit priests who had carried the bark to Europe in their saddlebags, of the great medical and theological disputes that set Christian against Christian when the bark began to be distributed, of the changes that its very existence had forced upon the closed and dusty world of Renaissance medicine, of the damage done to the trees that grew in the Andes, and of the ambitious schemes put forward by Sir Clements Markham and the directors of Kew Gardens to grow cinchona in India, so that Britain’s burgeoning colonies could have a plentiful and cheap supply of the only drug that was known to cure the fever. As the speeches moved on towards the end of the nineteenth century, the focus shifted away from botany and into the realms of chemistry, pharmacy and, inevitably, industry, as the harvest of quinine moved from field to factory. Whatever their particular speciality, the quinine delegates who gathered in St Louis on that perfect autumn evening had every reason to be pleased with what they and their predecessors had achieved.

  It was the British Army’s Macedonian campaign during the First World War that had finally proved, even to the most sceptical commander, how important it was that soldiers who were expected to fight in areas close to where mosquitoes bred in summer should be treated with a malaria prophylaxis if they were to remain healthy.

  The British Army’s medical expertise in 1914 had come a long way since the Walcheren expedition of a century earlier. Yet, despite the fact that Major ‘Mosquito’ Ross, by now a colonel, took part in the Greek campaign, there was still much the authorities didn’t know about mosquitoes. Of the four species of Anopheles mosquito that are known to spread malaria in Macedonia, only two were considered at all dangerous: Anopheles maculipennis, which thrives at sea level, and was to be found in the Struma and Vardar valleys and west of Salonika, in the deltas of the Vardar and Galiko rivers; and Anopheles superpictus, which breeds at higher altitudes. At the start of the war, Britain and France were reluctant to send troops to the Balkans, preferring to let the Serbs fight the forces of Austria-Hungary alone. But when Bulgaria threatened to attack Serbia in September 1915, the Allies had no choice but to enter the conflict. They decided to establish a new base at Salonika, from which they hoped to block the German advance into northern Greece.

  Unlike the British generals at Walcheren and their American counterparts at Vicksburg, the commanders of the Franco-British expeditionary force were well aware of the threat of malaria. As a result they delayed their arrival until October 1915, when it would be too cold for the mosquitoes to breed. Army camps and field hospitals were set up in the hills above Lake Langaza, and the soldiers began to advance up the Struma and Vardar valleys. The cold did not last, though it was not until early the following summer that the Allies realised their delay had been futile, and that their men were prey to both types of malaria-bearing mosquitoes. The numbers admitted to hospital quickly reached proportions not seen since Walcheren: 4500 in July 1916, 7500 in August, nine thousand by September. The following year proved even worse, with thirty thousand cases in September and October alone.

  Colonel Ross was drafted in to formulate a plan of action. He proposed brigades that would drain the marshes, clean up streams and eradicate mosquito larvae. Nothing seemed to work. By the end of 1917, a further seventy thousand soldiers were suffering from malaria. The field hospitals were overwhelmed, and as it had done at Walcheren, the army began sending the worst cases back to Britain for treatment. By October 1918, when the end of the war was just a month away, there had been 162,000 admissions out of a force of 160,000 men. Some men had fallen sick with malaria twice, or even three times, each time being readmitted to hospital. Yet, despite these huge numbers, only 821 men died from malaria during the whole campaign. Troops who caught malaria were promptly treated with quinine, and were not permitted to stop taking it until they appeared to have been cured. As part of German reparations after the war, the Treaty of Versailles forced Germany in Annex VI to hand over to the Allies a quarter of its production of salts of quinine.

  The First World War had made quinine many fresh converts. By 1918 demand for the drug had vastly increased, and the world price of quinine, though far lower than it had been in the 1860s, had more than doubled. Such prices, though, were unsustainable. In peacetime, the military would no longer be a major purchaser, and there was bound to be a reduction in price once the war was over.

  In 1918 the quinine producers in Java signed an agreement with the three remaining factories in Holland, as well as the plant in Bandoeng in Indonesia, that would help guarantee a decent price for planters while also ensuring adequate supplies. To the Europeans, the agreement, which was known as the Second Quinine Convention (a similar arrangement had been in place before the war), had been undertaken in the interests of stabilising the market for all concerned. However, it met with considerable opposition in America, where it was regarded as a restrictive monopoly. Despite that, most of the foreign visitors to the St Louis meeting in 1930 were confident that in the long term the Americans would come around to the European point of view that a stable, controlled market was in the interests of producers and consumers alike.

  What they could not know, of course, was that in less than a decade a new war would break out that would involve intense fighting all over the tropics, in the course of whic
h hundreds of thousands of soldiers would fall sick with malaria. Although many of them were treated quite successfully with the drug, the Second World War would come close to destroying the quinine industry altogether.

  When Great Britain and France declared war on Germany just two days after Hitler’s invasion of Poland in September 1939, the potential threat of malaria was far from the minds of the Allied leaders. Yet in the six years that followed, European, African, Asian and American soldiers would fight over more tropical and malarious terrain than in any previous conflict. From Senegal to Singapore and beyond, soldiers on all sides would fall prey to malaria in numbers not seen since the British had established garrisons that virtually guaranteed death within a year on the West African coast more than a century earlier. Along a broad equatorial belt, tropical seasonal rain, warm temperatures, year-round humidity, pools of water stagnating in tank tracks and coconut shells that allowed mosquitoes to breed with impunity, together with a heavily infected local population on which they could feed, would create perfect conditions for an epidemic of the deadly Plasmodium falciparum or the recurring Plasmodium vivax.

  General William Slim, whose British, Indian and African soldiers of the 14th Army were responsible for repelling the Japanese invasion of Arakan in 1944 and for the reconquest of Burma the following year, reckoned malaria was his biggest problem after supplies – more of a danger even than combat. In 1943, over 60 per cent of his men succumbed to the disease; among the forward troops the figure was far higher. More than half of those who caught malaria would fall ill with it several times within the year.

  Some of the senior French and British medical authorities had witnessed at first hand the Macedonian campaign of a quarter of a century earlier; the younger ones had read about it. The most far-sighted realised that an efficient method of treating the sick was essential. Yet that did not stop many of the Allied generals from growing impatient with attempts to ensure well-ordered medical assistance in the field. As one senior American commander at Guadalcanal in 1942 barked: ‘We are here to kill Japs, and to hell with mosquitoes.’

  Despite that, military doctors knew that whatever success they might have in killing mosquitoes – and eradicating them in numbers that would make a real difference was unlikely – one thing was certain. Troops – whether French soldiers in West Africa, British in Singapore and then in Sicily, Germans in the eastern Mediterranean, Japanese in China or Australians and Americans in the south-west Pacific – would die in their thousands without adequate supplies of quinine.

  The quinine situation had changed radically, however, since the balmy autumn evening when quinine growers and manufacturers had gathered in Missouri in 1930, confident that their industry had achieved a maturity which meant it could not be threatened. When the German army invaded Holland on 10 May 1940, reaching Amsterdam just days later, it quickly set about securing essential machinery and supplies. The quinine from Java that was stored in warehouses in the city was requisitioned and sent to Berlin. There was nothing for the directors of the Kinabureau, the Amsterdam-based agency that managed the Dutch quinine industry, to do but to hand control of the plantations in Java over to their managers in Bandoeng, and hope for the best. Less than two years later, though, Java itself fell to the invading Japanese army. At a stroke, virtually the entire world supply of quinine was now in enemy hands.

  The Japanese were careful to keep their German allies well supplied. In 1995 the wreck of Japanese Imperial Navy submarine I-52 was found almost intact seventeen thousand feet down on the seabed in the mid-Atlantic. It had been designed not as an attack submarine, but as a cargo vessel capable of carrying hundreds of tons of war materiel. The submarine would travel underwater by day and cruise on the surface at night while recharging its batteries, thus avoiding Allied detection.

  The sub had left its base at Kure, not far from Hiroshima, in March 1944, carrying two tons of gold, 228 tons of molybdenum, tungsten and tin, and fourteen experts from the industrial company Mitsubishi. They were to meet some German counterparts in occupied France in order to exchange desperately needed German technology for a supply of raw materials that the Nazis were equally anxious to obtain. On its way to the French coast, the submarine made only one stop, in Singapore, where it refuelled and loaded fifty-four tons of raw rubber and three tons of quinine before heading towards the Indian Ocean. I-52 rendezvoused with a German submarine in the mid-Atlantic on 23 June, and picked up a German pilot who would guide it into port at Lorient in the Bay of Biscay. Within hours of the rendezvous, though, the American escort carrier USS Bogue had picked up a signal from the submarine and despatched a torpedo bomber to attack and sink it.

  Malaria, though a nuisance, was something European troops were familiar with. For the Americans, who had rarely fought abroad, the experience would be quite different. At the start of the Second World War, only twenty-four doctors who were both fit for military service and possessed some sort of training in tropical medicine could be found in the whole of the United States. As a result, thousands of young American soldiers would die when they were sent to fight the Japanese in the South Pacific in 1942.

  They had their first taste of the dangers that lay ahead in Bataan. Three days after their attack on Pearl Harbor in December 1941, the Japanese were again on the offensive against American troops, this time in the Philippines, which America had controlled since 1898. Brave, numerous and ruthless, the Japanese soon overpowered the American garrison, and General Douglas MacArthur, the commander of the South Pacific forces, ordered a swift withdrawal across the bay of Manila to the 450-square-mile Bataan peninsula. Mountainous and covered in thick jungle, Bataan was well suited to a defensive battle; but medically it proved a nightmare, with too many people to care for and too few skilled doctors and nurses to look after them, a landscape that made evacuations difficult, and, worst of all, an epidemic of mosquito-borne falciparum malaria which would affect virtually all the 100,000 soldiers and civilians who found themselves squeezed onto the peninsula.

  Quinine was in short supply. In January 1942 the prophylactic dose of ten grains a day had to be halved, and a few months later any pretence of trying to prevent the disease was abandoned, and the remaining drug saved to treat those who were sick in hospital.

  The Japanese, who were waging war in the tropics for the first time, found themselves in an equally difficult situation. Their leaders had planned for the Philippines campaign to be fought according to a rigid timetable, and although the Japanese troops on Bataan should theoretically have had access to all the quinine they needed, in fact there was only enough of the drug to last them a month. By February 1942, three months after the campaign began, just three thousand of the original fighting force of fifteen thousand Japanese soldiers were still fit, the remainder having succumbed to malaria, dysentery and beriberi. A Japanese interpreter later told American prisoners that in some units of the 14th Army the unfit rate had reached 90 per cent, with many deaths, and that Sternberg General Hospital in Manila was packed with sick Japanese soldiers from Bataan.

  Whatever casualties the Japanese suffered, they could replace their sick men with fresh, well-trained troops who had fought in Malaya. For the Americans there was no such option, and many of the soldiers who had been evacuated from Bataan before it fell in April 1942 found themselves launched four months later into a ferocious attack on the island of Guadalcanal, in the Solomon archipelago, where the Japanese were building an airfield from which they planned to block the sea lanes between America and Australia.

  The loss of the Philippines marked the last mass surrender by American forces to the Japanese, but it took a long time, and heavy losses, before the tide of war turned decisively in the Americans’ favour. Guadalcanal was the start.

  ‘Guadalcanal,’ an official history remarks, ‘was not a picturesque South Pacific island paradise.’ Hot and humid, its coastal lowlands and mountain valleys were loathed by all who fought there. Surprised by the unexpected American attack in August 1942, many
of the Japanese soldiers fled the airstrip they were building, leaving behind meals that had been cooked but not eaten, and hot mugs of tea still waiting to be drunk. The Americans’ supply system was plagued by confusion and inadequacy: some Marines arrived on the island unfed, as their transport had run out of all food but soup. Had it not been for the large quantities of enemy rice that fell into their hands, many American soldiers would have gone hungry.

  Even those who started out well found it hard to stay fit. The heat was unbearable. A short march left men ‘staggering, gasping from the sheer airlessness and almost senseless from exhaustion’. There were too few salt tablets available to the men, who were sweating profusely, and any fresh food they had quickly spoiled in the heat. Dysentery, fungal infections and skin diseases were rife. Everyone was dirty and wet, and raw, open sores soon broke out between the toes, in the groin and between the buttocks. That was before the malaria started.

  Just as had happened at Walcheren, the disease broke out in the third week of August. Its progress in the 1st Marine Division was rapid: nine hundred cases before the end of the month, 1724 the next, 2630 in October. By mid-December the division had counted more than 8500 hospital admissions for malaria alone. Ninety per cent of its men caught the disease, most of them falciparum cases, and many fell sick with it more than once.

  The experiences of Bataan and Guadalcanal persuaded the American government that malaria had to be fought in a number of different ways. In the long term, synthetic chemical drugs that were already being developed would be used with increasing regularity. Mosquito-eradication campaigns, especially after the insecticide DDT became more available, would also be more common. In the meantime, the country needed all the quinine it could lay its hands on.

  In January 1943, five months after the invasion of Guadalcanal, Donald Nelson, President of the American War Production Board, recommended that a national pool of quinine stocks be established to ensure that the military had all the febrifuge it needed. The pool would be the direct responsibility of the American Pharmaceutical Association, which was told that ‘each donation will be a direct contribution to winning the war’. It was exactly the sort of patriotic, all-shoulders-to-the-wheel effort at which Americans excel, and the project’s goal was set at collecting 100,000 ounces of quinine.