The Miraculous Fever-Tree: Malaria, Medicine and the Cure that Changed the World

DEDICATION

For Dan, for the best of gifts and so much else besidesAnd for my father who, without quinine,would have died as a boy

CONTENTS

Cover

Title Page

Dedication

Maps

Early-Eighteenth-Century South America

Central Africa

World Distribution of Malaria

Introduction: The Tree of Fevers

1 Sickness Prevails – Africa

2 The Tree Required – Rome

3 The Tree Discovered – Peru

4 The Quarrel – England

5 The Quest – South America

6 To War and to Explore – From Holland to West Africa

7 To Explore and to War – From America to Panama

8 The Seed – South America

9 The Science – India, England and Italy

10 The Last Forest – Congo

Notes on Sources

Further Reading

Index

Acknowledgements

About the Author

Praise

Copyright

About the Publisher

INTRODUCTION The Tree of Fevers

‘Cinchona revolutionised the art of medicine as profoundly as gunpowder had the art of war.’

BERNARDO RAMAZZINI, physician to the Duke of Modena, Opera omnia, medica et physica (1717)

Francesco Torti’s ‘Tree of Fevers’ may be nearly three hundred years old, but it swells on the page as though it rose from the ground this very spring. At the crown, its trunk branches like an earthly anemone, and its arms grow thick and dark. On the left side of the engraving, the tree bark hums with sap and leaves grow at intervals in thick bunches of green. The branches on the right, by contrast, are denuded and leafless. Tissue-white, they curl upwards as if in supplication to the Almighty.

Torti, who once saved his own life by taking a dose of powdered Peruvian quinine bark to cure an intermittent fever, as malaria was once called, believed that there were two kinds of fever: those, represented by the leafy branches on the left side of his tree, that respond to treatment with the bark; and those, like the dead willowy kind, that do not.

But Torti took his inspiration from another tree, one that he had never seen, and one that for centuries would remain an enigma. The magnificent Cinchona calisaya, the red-barked Andean tree that produces quinine, is one of ninety varieties of cinchona, a relative of the madder family, which also includes coffee and gardenias. Some cinchonas have large leaves, some small; some smooth, some roughly corrugated. But the leaves on the older trees of the true red bark – the cascarilla roja that grows eighty feet high – are fiery red. The colour offsets the lilac-like flowers that grow in delicate white clusters, and which are followed by a dry fruit that splits, at the onset of winter, to release narrow winged seeds so tiny and fine that they run to as many as 100,000 to the ounce. Joseph de Jussieu, the first European to set eyes on the cinchona, thirty years after Torti’s engraving of 1712, believed that Cinchona calisaya was the most beautiful tree he had ever seen.

For Torti and de Jussieu, intermittent fever or malaria was a disease of the Old World. No one knew for certain where it came from or what caused it. But everywhere the Old World expanded its boundaries – pushed ever on by commerce, religion and war – malaria followed. And the price it exacted was beyond imagining. ‘Malarial fever,’ wrote Sir Ronald Ross, the Englishman who in 1902 was awarded the Nobel Prize for Medicine for proving that malaria is transmitted by mosquitoes, ‘is important not only because of the misery it inflicts upon mankind, but also because of the serious opposition it has always given to the march of civilisation … No wild deserts, no savage races, no geographical difficulties have proved so inimical to civilisation as this disease.’

Within the foul-tasting, bitter red bark of the cinchona tree is an alkaloid that prevents and treats malaria. The Peruvian bark, which was first brought to Europe in 1631 or thereabouts, was looked upon as a miracle. But its discovery was also a riddle. Cinchona was a tree of the New World. It grew where the rain was plentiful in the foothills of the high Andes, where malaria had never existed. How did anyone guess that among all the trees in South America, it was the bark of the cinchona that would cure malaria? How was it that a seed so small it is almost invisible could grow into a tree, one eighteenth-century source wrote, that was as crucial to the art of medicine as gunpowder had been to the art of war?

This book is the story of the riddle of quinine, the miraculous fever-tree which transformed medicine – and history.

1 Sickness Prevails – Africa

‘Malaria treatment. This is comprised in three words: quinine, quinine, quinine.’

SIR WILLIAM OSLER, Regius Professor of Medicine, Oxford, 1909–17

‘If you ever thought that one man was too small to make a difference, try being shut up in a room with a mosquito.’

THE DALAI LAMA, 1977

My grandparents had been married for many years when they left Europe for Africa in 1928, though not to each other.

My Parisian grandmother, Giselle Bunau-Varilla, had had at least two husbands, if not three. My Neapolitan grandfather, Mario Rocco, was being sought by Interpol for trying to kidnap his only child. His first wife, a tall, thin Norwegian with wide cheekbones and a finely arched brow, had been labouring for years to expunge him from her life. She wanted, above all, to change their daughter’s identity from Rosetta Rocco, a Catholic, to Susanna Ibsen, a Protestant – and to be rid of her husband forever.

The Neapolitan solution was to remove the child by force and go into hiding, a plan that ultimately failed, though not before it had annoyed the authorities and landed my grandfather in a great deal of trouble.

As an antidote, a year-long safari in the Congo seemed a welcome distraction to all concerned. Yet as the moment of departure drew near, both my grandparents were filled with the excitement of the unknown. Their journey turned from being an all-too welcome respite from their domestic travails to a grand, passionate tropical adventure.

A few hours before New Year 1929, they boarded the sleeper train in Paris that was bound for Marseilles. My grandmother, as always, could be counted on to remain calm even while eloping to Africa with someone else’s husband. My grandfather, who had jet-black hair with a deep white streak that swept back from his forehead, only felt his fine sense of the dramatic swell as he put Paris behind him. ‘Don’t even tell my in-laws what continent I shall be in,’ he wrote to his family from the train.

In Marseilles they boarded the SS Usambara, a passenger ship of the Deutsch Öst Afrika line that would bear them across the Mediterranean to Port Said, through the Suez Canal, and down the East African coast to Mombasa. From there, the plan was to travel by train and on foot across Africa’s thick equatorial waistline to the heart of the continent. They thought they would be away for at least a year. Longer, perhaps.

My grandparents were accompanied by a sizeable quantity of luggage. To equip themselves for a hunting trip that would take them as far west as the Ituri forest on the banks of the Congo river, they had paid a visit to Brussels, to the emporium of Monsieur Gaston Bennet, a specialist colonial outfitter who sold ready-prepared safari kits with everything a traveller might need for a journey of three, six or even nine months.

Monsieur Bennet’s inventory sounds much like the necessities that H. Rider Haggard’s hero Alan Quartermain packed when he set off in search of King Solomon’s Mines. For their extra-long hunting trip, he sold my grandparents four heavy-calibre rifles, including a double-barrelled Gibbs .500 which my grandfather Mario, with manly Neapolitan excitement, described in his diary as ‘una vera arma’ – a real weapon – and a .408 Winchester for my grandmother Giselle, who hoped to shoot an elephant. Eight months later she killed a lone male; its tusks soared high above her head when it lay dead on its side. She allowed herself to be photographed alongside the beast, leaning heavily on the barrel of her rifle as if it were a staff. But the truth is that she felt a little sick at what she had done. Killing the elephant unnerved her. She was five months pregnant at the time, which may have made her especially sensitive. She never shot an animal again.

As well as the rifles, my grandparents were outfitted with two pairs of shotguns, a twelve-bore and a lady’s twenty-bore; five hundred kilos of ammunition in watertight boxes; six trunks of tropical clothing; twelve cases of brandy; eight of books; a typewriter; a gramophone with my grandfather’s favourite record, ‘My Cutie’s Due at Two-to-Two Today’; coloured beads for gifts; and enough sketchpads, pastels and modelling clay to last them a whole year—my grandfather was a painter and my grandmother a sculptress. Their effects were packed into tin trunks weighing not more than twenty-five kilos each, the maximum that would be carried by an African porter. Giselle stood barely an inch over five feet and always wore a turban, which had the effect of both hiding her incipient baldness and making her seem taller than she really was. When my grandparents reached the Ituri forest she unpacked her clay and set about modelling a local Tutsi chief who towered nearly two feet above her. He watched her as she worked, his face impassive. He said nothing, but his children danced around and called her ‘Potipot’, she who works with clay.

In addition to the safety precautions of heavy Damascus-barrelled guns and several changes of boots, Monsieur Bennet packed my grandparents a sizeable medicine chest that was manufactured from black metal and lined with marbled endpapers to absorb any moisture and keep its contents safe from ants. In it he placed gauze bandages and sutures, several bottles of Dr Collis Brown’s Elixir, a concoction made of morphine, cannabis and treacle that had been invented in 1856 and was recommended for treating diarrhoea, boric acid for the eyes, carbolic acid against lion and leopard scratches, Epsom salts and castor oil for constipation, and a brown goo called Castellani’s Paint to fight skin fungi. There were also twenty-four sets of steel syringes and needles, each packed in a small metal box with a tight lid for easy boiling, the best method of sterilisation in the bush. No medicine chest bound for Africa was complete without a supply of purple crystals of permanganate of potash, for washing raw vegetables and cleaning out snakebite wounds. With it came a snakebite pencil which you used to cut a Y-shaped incision, so you could lift the skin immediately surrounding the bite and pack it with permanganate.

Snakes are highly sensitive to vibration, and most of them will slither away when they detect you approaching. Mosquitoes, on the other hand, do not. Among the most important items in Monsieur Bennet’s medicine chest was packet after packet of powdered sulphate of quinine, to guard against malaria. Alan Quartermain packed an ounce of quinine and one or two small surgical instruments into his bag for the final assault on King Solomon’s Mines. He would not have left home without it. ‘This was our total equipment, a small one indeed for such a venture,’ he wrote. ‘Try as we would we could not see our way to reducing it. There was nothing but what was absolutely necessary.’

From Mombasa Mario and Giselle headed west towards their first stop, Voi, a railway junction halfway between Mombasa and Nairobi. The land was flat and scrubby, with occasionally a mound of hills rising in a greeny-purple haze in the far distance. They saw Masai herders with thin, high-boned cattle that were oblivious to the sun’s heat. Dried-out umbrella thorns provided the only shade, and a patchy shade at that. Shortly after Voi they made a detour south across the border with Tanganyika to try to get a better view of Mount Kilimanjaro, Africa’s highest peak. They passed the spot where General von Lettow-Vorbeck, the German soldier-adventurer, had routed a British regiment fourteen years previously. By 1917 the British had begun to fight back, and von Lettow was in trouble. Supplies were running short. Recurring bouts of malaria had reduced many of the soldiers, von Lettow among them, to yellow, shrunken skeletons. Unable to obtain any imported quinine tablets, von Lettow’s officers began making it themselves from the powdered bark of cinchona trees that they found growing locally. The cinchona had been planted in the early 1900s, by Tanganyika’s German colonial masters. Von Lettow’s soldiers couldn’t make tablets, though, so they stirred the ground-up bark into their coffee. It was a horrible brew which the troops called ‘Lettow-schnaps’, but it worked.

Although they had lived in Europe their whole lives, both my grandparents already had some experience of malaria before they left for Africa. In 1886 my great-grandfather, Philippe Bunau-Varilla, became the Chief Engineer of the Panama Canal, a scheme that had been dreamed up by Ferdinand de Lesseps shortly after he had finished his canal at Suez. By the time France’s Panama project collapsed in 1889, twenty-two thousand men had died of yellow fever and malaria.

No one made it a requirement that those who went to Panama should take regular doses of quinine. This is astonishing, for quinine was already well known by then – Jules Verne wrote about it in his novel L’Île mystérieuse in 1874; later Chekhov would call his favourite dog Quinine (being a doctor, he called his other dog Bromide). The problem was that quinine was difficult to obtain, as supplies from the 1860s on were intermittent. Worse still for the project’s managers, it was expensive: while the American Civil War was at its height, much of what was available was shipped north to protect the Union soldiers who were taking over more and more of the Confederate land where malaria had long been a scourge, and that trade still ran strong after the war ended. The officials of the French Compagnie Universelle du Canal Interocéanique calculated that it was cheaper to let its workers die than to spend a lot of money trying to cure them with costly medicines. Even a prophylactic dose, which would surely have saved them much money over the long run, was, they calculated, beyond their budget. The Americans, who took over the canal’s building works in 1903, were of the opposite view, and forced their workers to take a regular prophylactic dose of quinine or face mandatory punishment. In less than a year, the US Army’s soldier-engineers managed to stamp out virtually every trace of malaria. But that is getting ahead of the story.

My grandfather, for his part, was born in Naples but spent much of his childhood staying with an aunt who lived in the hills of Maremma. To many, this part of Tuscany was known as ‘la Maremmamara’ – bitter Maremma – because of how malaria had forced people to abandon the land in the eighteenth and nineteenth centuries. Another aunt lived in the Roman Campagna, where malaria had existed since Roman times, and from which it was not wholly stamped out until the 1930s, when Mussolini embarked on draining the Pontine marshes at the mouth of the Tiber, thus ridding western Italy of the pools of stagnant water in which the malaria-carrying mosquitoes bred.

In truth, the whole of southern Italy in summer was a hellhole of malaria. Travelling through the region in 1847 on his way to Sicily, Edward Lear, the artist and poet whose children’s verse usually speaks lovingly of the oddities across the seas, noted in an unusually serious vein that malaria turned the population yellow and shrivelled many to living skeletons. ‘After May,’ he wrote in a letter to his brother in the spring of that year, ‘the whole of this wide and fertile tract … is not habitable, and in July and August to sleep [i.e. to die] there is almost certainly the consequence of fever.’

George Gissing, who made the same journey nearly sixty years later, wrote in his Calabrian classic By the Ionian Sea of the amiable Dr Sculco, who advised him to ‘get to bed and take my quinine in dosi forti. [Was I not] aware that the country is in great part pestilential [because of] la febbre?’ Of course, Gissing, Lear and the other foreign writers who journeyed to the south of Italy could always leave if things got too bad. For the innkeeper in Giovanni Verga’s nineteenth-century short story ‘Malaria’ there was no such option. First came the railway, which took away the brisk business he’d enjoyed from the carriage trade. Then it was the malaria that struck, bearing away each of his four wives in turn, earning him the nickname ‘Wifekiller’. When none of the village girls would consent to become his fifth bride, he said to himself, ‘Next time I’ll be taking a wife who’s immune to the malaria. I won’t go through all this again.’ But it was not to be.

‘The fact is,’ wrote Verga, ‘that malaria enters your bones with the bread that you eat and whenever you open your mouth to speak … The malaria fells the townspeople in the deserted streets, it pins them down in the doorway of houses whose plaster is peeling in the sun, as they shudder from the fever, wrapped up in their overcoats, and with all the blankets from their beds round their shoulders.’

Massimo Taparelli, the writer and statesman who, as Marchese d’Azeglio, served as Prime Minister of Italy under King Victor-Emmanuel II, often mentioned the disease in his diaries. ‘While we were staying at Castel Gandolfo [the Pope’s summer home],’ he wrote on one occasion in 1860, ‘I used to go down to the plain to shoot. But instead of birds I got the terrible marsh fever, the ancient scourge of Latium …

‘No one can have any idea of the iciness of the cold phase or the burning heat of the hot attack of these painful fevers. Quinine is certainly the most beneficent discovery for the Roman Campagna. There may be no steam there, no newspapers, no other modern inventions but at least they have quinine, and that’s worth all the rest put together.’

When my grandfather was growing up, everyone in southern Italy regularly took quinine in the summer, when the danger of catching malaria was at its worst.

My grandfather saw his African safari as just the start of a grand adventure that would take him and my grandmother around the world. ‘From here, we shall travel on, to Dar es Salaam, to Beira and then around the Cape to Rio de Janeiro,’ he wrote to his mother as they arrived in Africa in February 1929. They never left. Later that year my grandmother, who had already lost her first baby in childbirth, became pregnant again. Already thirty-seven, she wanted to take no risks a second time. The couple returned to Nairobi to await her confinement.

While she was in hospital, Mario took off in a small plane to look for a friend they had made during their months in the Congo. Before the end of the day he ran out of fuel and crash-landed by the shores of Lake Naivasha, about seventy-five miles from Nairobi on the shady floor of the Rift Valley. A grizzled Englishman, who introduced himself as Harvey, hailed him when he climbed, unhurt, from the wreckage. Mr Harvey took him back to his house, a bungalow with a mottled thatch roof, where after several stiff drinks and a lot of talk he offered to sell Mario his property. Hurrying back to Nairobi to tell Giselle, Mario stopped at the telegraph office to send a cable to his father-in-law, who would be putting up the purchase price.

That telegram was sent more than seventy years ago, and I have it here before me as I write. Its blue folds are as soft as a baby’s cheek, and the pages quite floppy with being taken out and put away so many times. It is addressed, in brief telegraph-speak, to ‘Bunovarila, 1 Grande Chaumiere, Paris’. And it says: ‘Purchased shamba Naivasha 3000 acress [sic] three miles lake front. 5000 pounds. 2000 cash, balance three years. Best bargain. Cable if you want me home to fix everything or cable approval.’

By the time Mario and Giselle decided to stay in Africa on the farm by the shores of Lake Naivasha, the supply of little packets of quinine sulphate they had brought with them in 1929 had long since been used up. Neither of them had caught malaria in the Congo; only heatstroke. But in 1936 Mario came down with a bad attack as he returned from a trip to Lake Victoria, a notorious malarial spot even today. In 1940, just after the start of the Second World War, he had another attack while he was in a British internment camp in Nairobi.

As an Italian, Mario had been arrested as soon as war broke out in September 1939. Giselle, a French national, was allowed to remain on the farm, where she turned her attention from sculpture to raising pigs, as well as to my father and his two sisters. She stayed in touch with her family in Paris, and though the seaborne post was slow, it did its work. Once a month, sometimes more often, a postal vessel docked at Mombasa and a few days later my grandmother received a delivery of letters, newspapers and parcels from Europe, which contained among other things regular supplies of quinine for all the family. And, if she was lucky, there might also be a letter from my grandfather.

I found those letters in an old shoebox the morning after Mario died in 1976. For more than a quarter of a century he had kept them under his bed. Lonely, frustrated and often sick in the internment camp, he longed for home. His letters were restricted by the camp authorities to a single sheet of paper, and over time he perfected the tiniest, neatest handwriting you ever saw, so that he could write first in one direction and then at right angles over the page, stretching out for as long as he could the connection with his family. ‘I dreamed last night that you were sitting by my bed,’ he wrote to Giselle in the winter of 1943 after a bad attack of malaria. By then he had been interned for nearly four years. ‘Nothing would heal me more quickly than to feel your hand upon my cheek.’

Through the war years Mario fell ill several times with malaria. ‘I don’t know what is worse; the fever or the shivering,’ he wrote. ‘There is no quinine. Cold water is the best we can hope for.’ Beyond the heartache and the loneliness there was a cold reality about malaria in Africa that is as relevant now as it was then. With access to efficient anti-malarial drugs, Giselle and her children remained healthy. Mario, who like so many Africans today did not have the medicines he needed, did not.