The Cures: Malaria - The Countess of Chinchon and Tu YouYou
Malaria has plagued mankind for millennia. It is, in fact, one of the oldest diseases known to man. Evidence of malaria has been found in various historical artefacts to indicate its existence from as early as the stone age Neolithic era. Through migration and colonisation, malaria made its way from the tropical continents to Europe and America. Malaria has had a role in changing the course of history – it contributed to the fall of the Roman Empire in 476AD and was the leading obstacle to African colonisation as it killed many European arrivals for more than 300 years. Malaria has influenced how populations grow and develop, how wars are fought, and to a greater extent, how human evolve.
Despite its long history, the first known treatment against malaria only appeared in the 17th century. Before, treatments focused on symptoms rather than the real cause of the disease. This first treatment was a compound called quinine, taken from the bark of a native South American tree called Cinchona tree. Realising the power of quinine, the British and Dutch scientists explored various parts of the world in search of these trees and ways to bring them back. In the mid-19th century, the Dutch discovered a grafting technique that allowed them to grow these trees in Java, Indonesia. They soon dominated the quinine production, contributing to 80% of the world supply. However, this monopoly and growing resistance to quinine forced other countries to try to develop other treatments.
The discovery of quinine was a romanticised tale. It was first documented in 1663 by a Genoan physician who met merchants recently returned from Peru. The tale talks of Lady Ana de Osorio, the Countess of Chinchon, who was the vicereine of Lima when she fell ill with malaria. When acquaintances heard about this malady, one wrote to her suggesting a remedy from local tree bark. The remedy worked miracles, and the Countess immediately ordered that this bark was shared with the locals. Upon her return to Spain a few years later, she took a supply of this precious bark to share its healing power with the Spanish medical community. The Countess’ generosity was forever remembered by the Chinchon people and the many lives she helped save by introducing this medicine to Europe. This tale was repeated for over a century and immortalised in 1735 when Swedish botanist Linnaeus officially named this magical tree Cinchona. Unfortunately, this story has been debunked in the 21st century. While Lady Ana did exist, she was never a countess (she died before her husband became the Count of Chinchon), she never lived in Peru (the Count did, however, move there with his second wife), and unfortunately, that means the origin of this first malaria treatment remains a mystery.
Malaria is a life-threatening tropical disease caused by parasites that are transmitted through the bites of female Anopheles mosquitoes. The parasites responsible are called Plasmodium, and there are 5 known species that can cause malaria in human. Through mosquito bites, parasites enter human bloodstream and travel to the liver. The infection seeks refuge inside the liver to develop for some time before re-entering the bloodstream. The parasites reside in the red blood cells, digesting haemoglobin (the protein responsible for carrying oxygen) to enable the parasites’ survival and multiplication. The infected blood cells eventually burst, releasing more parasites into the bloodstream. The burst-and-release occurs every 48-72 hours, showing up as symptoms such as fever and chills. If the disease is left to progress, the bursts end up depleting the body of blood cells and disrupting the flow of blood to various organs. The first symptoms of malaria – high fever, headaches, muscle pains, vomiting and diarrhoea – usually appear after a week or longer after the parasites rested in the liver. Failure to seek medical attention might lead to serious conditions such as anaemia or multi-organ failure.
Awareness and prevention are key to tackle malaria as the disease-carrying mosquitoes are only found in tropical countries. World Health Organization reported that in 2017 half of the world’s population was at risk of contracting malaria. The majority of cases and deaths occur in Africa, South-East Asia, Eastern Mediterranean, Western Pacific, and the Americas with different areas harbouring different types of Plasmodium parasites. Bite prevention is crucial — bites can be avoided by using repellent, covering your limbs, and using an insecticide-treated mosquito net at nights. As these mosquitoes lay their eggs in water, the risk of infection is highest during the rainy season.
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Antimalaria tablets work to both prevent and treat this disease. When travelling to specific areas with a high number of cases, taking antimalarial tablets might be necessary. These tablets can reduce the risk of contracting the disease by about 90%. The best way to treat malaria is to seek medical treatment immediately. When properly diagnosed and treated, malaria patients are expected to recover fully. The best available treatment is currently artemisinin-based combination therapy (ACT). ACT combines an artemisinin-based drug with a partner drug. While artemisinin-based drugs are highly efficient in treating malaria on their own, combination therapy is now highly recommended as single drug therapies have in the past created drug resistance.
Artemisinin was discovered in 1971 by the Chinese scientist Tu YouYou who was working on a secret government project, Project 523. Project 523 aimed to find a drug to combat malaria by researching traditional herbal medicines. The project would’ve been highly controversial if it had gone public as the Cultural Revolution going on at the time saw intellectuals and academics as elitists and enemies of the nation. However, China desperately needed to support its ally, North Vietnam. At the time North Vietnam was fighting South Vietnam and its US ally at a malaria-infested region. They needed to quickly find a new treatment as the malaria parasites had developed resistance to chloroquine, the main drug at the time. The scientists involved in the project had outdated technologies and less training compared to their Western counterparts, but the unusual socialist approach worked well in developing artemisinin as an antimalarial drug. The government mobilised multidisciplinary experts and even employed unskilled workers to help with clinical trials.
Project 523 scientists started with a list of 2000 candidate recipes. They later screened over a hundred herbal extracts, finding a promising contender in Qinghao, a herbal anti-fever medicine. Qinghao comes from a plant called sweet wormwood, which has been used as a traditional Chinese medicine for more than 1500 years. Tu noticed that Qinghao sometimes work well in the laboratory. Tu later found a recipe: “Take a handful of Qinghao, soak in two litres of water, strain the liquid, and drink” in a textbook by Ge Hong from 340 AD. She wondered if low temperature was the key — they had been collecting the extracts with heat in the laboratory and this might have damaged the active ingredient. Considering this theory, Tu redesigned the extraction method and in 1971 successfully cleared the parasites in test animals with the new extract.
To expedite the project, Tu and two colleagues even volunteered as subjects to test the toxicity of this extract. The first clinical trial was done between August and October 1972 in which all 21 patients affected by 3 different Plasmodium parasites recovered completely. Subsequently, the extract was purified even further and was named Qinghaosu (artemisinin). The discovery was shared with other teams in Project 523 but remained a secret until 1978, when a national article was published. The first English report came out in 1979, and since then Artemisinin was researched and used worldwide.
As Project 523 was initially a secret military project, many details were omitted when artemisinin’s ability to treat malaria was shared with the rest of the world. The Cultural Revolution at that time meant the Chinese government was not interested in publicising the individual scientists and their contributions. This meant Tu did not receive the recognition she deserved both in China and internationally. However, in 2011 she was awarded the Lasker~DeBakey Clinical Medical Research Award and in 2015 the Nobel Prize in Physiology or Medicine. While she was immediately given an award by the Chinese government in 1979, there was little effort to publicise her great work until the 1990s.
Tu YouYou was born in 1930 to loving parents who encouraged her curiosity and desire to study. She received a four-year training in School of Pharmacy at the Beijing Medical College between 1951 and 1955. Upon graduating she was assigned to work at the Institute of Materia Medica, Academy of Traditional Chinese Medicine, where in the first 30 months she was trained in traditional herbal medicine. She has worked in the institute continuously since 1955. After she was awarded various international awards, the Chinese government proudly celebrated though with some self-reflection. She was nicknamed the Three-Without Scientists: she had no postgraduate degree (at that time China awarded no such degree), had no overseas education, and was refused membership to Chinese Academy of Sciences. The fact that she was acknowledged worldwide by the best scientists has given the government a lot to think about.
Billions have fallen ill or died from malaria, but lucky for us, there are many treatments now available to treat this disease. The long history of this disease cannot be condensed without omitting details, but it was time for the world the story of these two women. Countess Chinchon and Tu YouYou were hailed heroines for finding cures and sharing them with the world. However, a deep look into history has proven that Countess Chinchon was wrongly credited for the discovery. The romantic tale didn’t stand up to scrutiny. On the opposite, while after decades of secrecy, Tu YouYou finally got the recognition she deserved. To give credit where it is due is necessary, even if the truth isn't
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References and further reading:
Carter R and Mendis KN. Evolutionary and Historical Aspects of the Burden of Malaria. Clinical Microbiology Reviews Oct 2002, 15 (4) 564-594
Lasker~DeBakey Clinical Medical Research Award 2011 information page.
McKenna P. Nobel Prize goes to modest woman who beat malaria for China. New Scientist 9 November 2011.
Neill US. From branch to bedside: Youyou Tu is awarded the 2011 Lasker~DeBakey Clinical Medical Research Award for discovering artemisinin as a treatment for malaria. J Clin Invest. 2011 Oct 3; 121(10): 3768–3773.
Pain S. The Countess and The Cure. New Scientist 15 September 2001.
Panosian C, Gelband H, editors. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance. 2004 Washington (DC): National Academies Press (US).
Shu X-Z and Miller LH. The discovery of artemisinin and Nobel Prize in Physiology or Medicine. Sci China Life Sci 2015 Nov: 58 (11): 1175-1179.
Woodrow CJ, Haynes RK, Krishna S. Artemisinins. Postgraduate Medical Journal 2005;81:71-78.
Zhang J.-F. A Detailed Chronological Record of Project 523 and the Discovery and Development of Qinghaosu (Artemisinin.) 2005 Yang Cheng Evening News Publishing Company.
Zou L. Chinese Scientist Wins Nobel Prize in Medicine; China Hails the Laureate with Reflection. People’s Daily Online. 5 October 2015.