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  • Writer's pictureDale DeBakcsy

Ancient Secrets, Modern Methods: Nobel Laureate Tu Youyou, Malaria, and the Discovery of Artemisinin

In 1955, the World Health Organization had what, on the surface, seemed a splendid idea: Let’s Get Rid of Malaria. Just four years earlier, the United States, after a concentrated anti-malarial programming that involved the spraying of 4.5 million houses with 1939’s Miracle Insecticide DDT, had declared malaria definitively eradicated – why not use similar methods on a global scale to defeat the disease once and for all?


Why not indeed.


The WHO gave it their best shot, coordinating, with varying degrees of success, efforts to spray malaria-carrying mosquitoes into extinction alongside more everyday mosquito abatement programmes. It went well at first, but the uneven application of the methods, the migrations caused by war, and the existence of countries which refused treatment altogether resulted in something fearful: the rise of a strain of malaria parasite, plasmodium falciparum, which was entirely resistant to the quinine medications that were humanity’s only real effective defence against the disease.


The impact was not long in making itself felt: in the jungles of south-east Asia, where American and Vietnamese troops slogged through mosquito-ridden jungles, the number of malaria cases began a precipitous climb. The Americans lunged forward in a mad search for a cure that combed through over 200,000 potential drugs, with no luck, while in China a woman who combined the rigour of Western pharmacological training with an awareness of the traditions of Chinese medicine discovered after many trials and many more tribulations the plant that could stand up to the parasite.


Tu Youyou’s (b. 1930) life spans China’s greatest convulsions and acts of tragic self-definition. Born in the brief respite between Chiang Kai-Shek’s consolidation of North and Central China in 1927 and the invasion by the Japanese in 1937, Tu as the only girl in a family of boys might have expected domesticity as her lot in life, but in fact was sent to a series of private schools by her parents to get the very best education available. Speaking of this time in her Nobel memoirs, she mentions every school she attended, but curiously, and perhaps portentously, makes no mention of the impact on her life of the 1937 invasion by the Japanese of her home town.


Besides the technical details of her schooling, we know little of Tu’s early years until she contracted tuberculosis at the age of 16. It knocked her out of school for two years and gave her a compass with which to steer her life: she would devote herself to the study of medicine. Recovering at last in 1948, she made up for lost time, finished high school by 1951, and was on her way to Peking University to major in pharmacognosy – the study of medicinal drugs derived from natural sources such as plants. Here she picked up crucial training in how different plants responded to different extraction techniques that would form a central part of her great discovery two decades later. She also learned, from a Western perspective, how drugs operate on the body, which gave her new insights into the world and assumptions of traditional Chinese medicine.


In 1955, the Chinese Ministry of Health opened up a new academy, the Academy of Traditional Chinese Medicine (ATCM), and it was here that Tu found her first work directly out of university, and where she would do the work that saved millions of lives and made herself the first Chinese woman ever to win a Nobel Prize. In an effort to improve the state of medicine in China, the government heavily encouraged cross-communication between Western-educated doctors and practitioners of traditional Chinese medicine, each contributing their best insights to foster the development and improvement of the other.


After spending her first professional years analysing the properties of traditional cures for flatworms, Tu was sent on a three-year intensive course in traditional Chinese medicine in 1959, emerging at precisely the point when the need for new anti-malarial drugs was most profoundly felt. In 1964, Ho Chi Minh asked Mao Zedong to devote resources to the finding of a new cure for malaria, resulting in 1967 in the secret creation of Project 523. It was the red-hot beginning of the Cultural Revolution, a time when scientists were suspected of being fundamentally bourgeois and anti-Communist. In the decade that followed, over a million accused ‘bourgeois sympathisers’ died while as many as 10 million more academics, researchers and members of the intelligentsia were assigned to manual labour in remote parts of the country.



Tu, at the age of just 39, was given charge of the ATCM’s effort to find an anti-malarial drug, a position of great visibility and importance with corresponding pressures to perform. Her husband had been sent away to the countryside as part of the governmental programme to compel urbanites to develop rural skills, and she had to give her 4-year-old daughter to her parents, and place her 1-year-old daughter in the custody of a family who ran a daycare centre, in order to attend to her new work. When she finally got to visit her older daughter three years later, the child did not recognise her.


But there was plenty of work to fill the void – Tu compiled a list of 2,000 possible malaria remedies culled from the last couple of millennia of Chinese medical writings, and her team set to work to prepare and test the most promising. Artemisia annua, or sweet wormwood, was found all over the historical records and yet in testing the only thing consistent was the inconsistency of its efficacy. It was in danger of being abandoned altogether when Tu had her crucial insight: combining her knowledge of extraction methods with her close reading of the original texts with her insight into variables that can impact drug potency, she came to the conclusion that the extraction process for Artemisia annua was fundamentally flawed. Traditionally, plants were boiled in water to extract the compounds that had medicinal properties, but Tu believed the high temperature was adversely affecting the ability of the compound to function, and opted for a method using ethyl ether which required a much lower temperature.


The change in method made all the difference. In animal trials, the new drug showed a 100 per cent efficacy and, in order to overcome doubts about its impact on the human respiratory and circulatory systems, Tu volunteered to be the first human to take the drug. Working around the clock in close quarters that adversely affected the health of her team, samples of the drug we now know as artemisinin were prepared for test trials while Tu carried out the analysis to discover its chemical nature.


In the process of those analytical studies, she managed to synthesise a second drug, dihydroartemisinin, almost entirely by accident in 1973, and in trials she discovered it was ten times more effective against malaria than artemisinin. After almost interminable rounds of interdepartmental meetings, administrative flowchart adjustments, and trial review, the existence and structure of artemisinin were formally announced in 1979, a decade after Tu first was charged with finding a new cure for malaria.


The discovery of artemisinin was a major breakthrough that saved millions of lives, but its discoverer languished in almost perfect obscurity until she won the Lasker Prize in 2011 and the Nobel Prize in 2015, becoming the first Chinese scientist to win a Nobel in Medicine, and the first woman in China to win a Nobel in any field. For a hint as to why the years 1979 to 2011 represent such a void in the historical record, we can look to Tu Youyou and the Discovery of Artemisinin (2017) by Yi Rao, Daqing Zhang and Runhong Li. The book purports to be primarily about Tu, but in fact she is scarcely present in its pages, the majority being given over to minute descriptions of committee structures and an overarching emphasis on the bureaucratic flow of communication that dominated Project 523. This focus on the bureaucracy of Chinese science in the 1960s and 1970s at the expense of the individuals within is both fascinating to behold and characteristic of a philosophy of the heroism of collective effort, but also results inevitably in the diminution of any relevant individuals like Tu.


Photo by Bengt Nyman

Her youth had been spent in times of war and revolution, sometimes in sickness but always in study. Her most productive years saw her separated from her family so that she could carry on work that ultimately saved millions of lives. Her autumn brought her official honours in China and creeping obscurity in the rest of the world until finally, at the age of 85, she was vaulted into prominence as an example of what Chinese medical science could accomplish when properly directed. Through her, two massive traditions looked at each other for a moment and found common cause, and eventual triumph. As she heads to her ninetieth year, Tu continues to advocate for stretching that moment into an era, one of discovery and understanding as history and modernity trade their insights and push their shared world forward.


FURTHER READING:


The book by Yi, Daqing and Runhong mentioned above is, as I said, fascinating as a glimpse into the bureaucratic focus on Chinese medical research in the midst of the Cultural Revolution, but is absolute rubbish as a book about Tu Youyou. There is nothing about her life before artemisinin, nothing about it after, and about the time in between the mixture is about 97 per cent mind-numbingly dull flow charts about administrative reporting responsibilities between government agencies and 3 per cent repetitions of the same couple of research facts about Tu’s process. As a biography of a woman scientist, it is probably the worst I have ever read. So save your money and check out her Nobel memoir, which you can find on the Nobel Prize’s website.


And if you want to read more stories about astounding women in medicine, you can grab a copy of my History of Women in Medicine and Medical Research, available on Amazon or from Pen & Sword Books.



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