Youyou Tu – A Woman Who Made A Breakthrough In Malaria Treatment

The first women ever to win a Nobel prize in any discipline for China, a brilliant mind, and a crucial discovery in which would ultimately lead to lives saved and a brighter future where we can stand up to Malaria and fight it off. Youyou Tu was born in Zhejiang Ningbo, “a city on the east coast of China with a rich culture and over seven thousand years of history” as stated in an autobiography from Tu, on the 30th of December 1930 to a rather large family consisting of her four brothers and two well-educated parents, with her father working in a bank whilst her mother took the task of looking after Tu and her four brothers. Before making her way through the ranks and entering university, Tu had a great experience with school due to her family’s history of really valuing education, which means she was given many great opportunities to enter the top-quality schools in her area.

The first school in which she would attend was the private Ningbo Chongde Primary School from 1936 to 1941 and following that the private Ningbo Maoxi Primary School from 1941 to 1943, her middle school of choice would be the private Ningbo Qizheng Middle School from 1943 to 1945. All these schools before University are well regarded and set up Tu with a great background before entering the next level of education, which some might say is rather underwhelming. Tu has a somewhat inexperienced background regarding her formal education in which she only accomplished a bachelor’s from the School of Pharmacy at Beijing Medical University in 1955, as well as completing a course from 1959 to 1962 which was centred around traditional Chinese medicine. Tu had the drive to learn about medicines and discover new ones that could help benefit patients, for this reason, she chose pharmacy. This does mean Tu does not have her doctorate degree or a membership into the Chinese Academy of Sciences, this “led some Chinese scientists to disregard her experience, and to claim the credit should instead go to her team or others”, showing that Tu’s excellent work is mostly recognised outside of China.

Straight out of college, Tu quickly go on to sharpen her already excellent knowledge and improved her medical skills in the Institute of Chinese Materia Medica, where they focused on professional training, research and developing Chinese medicines further. During her time here, “she worked on research projects such as finding a treatment for Schistosomiasis, a disease caused by Schistosoma type parasitic flatworms”, ultimately preparing her for a full-time training program to improve her knowledge on traditional Chinese Medicines even more. All of Tu’s hard work and self-development through University and her job where she was placed with the highest level of both pressure and responsibility, lead her down the path to which was her greatest discoveries of both artemisinin and dihydroartemisinin, which both aided to helping treat malaria. Tu would have to put her family aside as she had to leave both her two young daughters (aged four and one) with her parents. Returning to see them after three years they couldn’t even recognise her. As unfortunate as it might have been, Tu had to put all her time into this research, for malaria is a very scary disease and sacrifices had to be made.

To begin with, malaria is a dangerous disease caused by protozoa parasites in the Plasmodium genus. P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi, are the five species of Plasmodium that can infect humans. Mosquitos are the main transporters of these Plasmodium’s, where after injected by the female mosquito, are sent to the humans’ liver, infecting hypnozoites (liver cells). These infected cells will proceed to split and multiply into dangerous merozoites, the merozoites will then attack the red blood cells and reproduce to cause symptomatic malaria. Having malaria brings many harmful and unwanted symptoms such as fevers with cold, hot, and sweating stages, headaches, diarrhea, and abdominal pain. P. falciparum is most deadly Plasmodium and its reproduction can take place not only in liver cells but also capillaries in internal organs “In untreated severe malaria, the progression can lead to coma or death”. Malaria is a world-wide disease in which in the year 2015 alone, there were approximately 438 thousand deaths. So, just how does Tu’s brilliant discovery of both artemisinin and dihydroartemisinin contribute to treating patients with this deadly disease? During the Vietnam war, where both China and North Vietnam worked together, the deadly P. Falciparum was a big danger to soldiers from both countries, leading to a ‘secret’ Chinese program in 1967 with the main goal to search for new antimalarials, which included more than 500 scientists working in 50 laboratories. This secret program went under the name ‘Project 523’.

Youyou Tu led a department specialising in traditional herbal medicine. It was in 1971 that Tu’s colleagues and herself discovered the antimalarial properties of Artemisia annua, isolating it a year later and naming is ‘artemisinin’, Tu actually found a lot of her data from repeatedly reading relevant paragraphs from the old literature where data of the use of ‘Qinghao’ was recorder as relieving malaria symptoms, where she found interesting information such as certain extraction methods that use heat could actually aid in destroying artemisinin in its process, this pushed Tu to develop a cold extraction technique instead, using an ether that proved to be more of a success. This amazing discovery from Tu and her colleagues occurred during China’s Cultural Revolution, which led to Tu and her colleagues having to test the drug on themselves initially, for the reason to prove the drugs overall safety, and lack of unwanted side effects. Later this was tested on malaria patients which further went on to support both the efficacy and safety of the artemisinin. Patients were put into three groups, taking in different doses of the drugs, ” We closely monitored the patients’ body temperature and change in the numbers of parasites in the blood specimen” Tu states in her biography. All patients ultimately recovered from their fever symptoms and there was no sign of malaria prior to these trials. Artemisinin proved to be a great leap in treating malaria for it has the unique benefit of killing Plasmodium at an earlier than usual stage, relative to other drugs, it has a short half-life (meaning that the drug is quickly removed from the body) and proving to be effective against chloroquine sensitive and resistant Plasmodium.

The other drug Youyou Tu is credited for discovering, dihydroartemisinin, is approximately ten times more potent than artemisinin, proving more rapid action along with less toxicity. Considering how great this drug is, it might be a surprise to many that it was slow to make itself known to most parts around the globe. This, of course, is due to many factors such as Project 523 being a secret project, and a lack of English from the scientists involved. Much due worldwide attention was finally brought to artemisinin through the World Health Organization (WHO), the World Bank, and United Nations Development Program (UNDP). These organizations would ‘hold the fourth Malarial Chemotherapy Science Working Group meeting in Beijing in 1981’. Throughout this meeting, artemisinin would have several presentations showing its clinical application including Tu’s own report ‘Studies on the Chemistry of Qinghaosu’.

Positive responses led to thousands of infected malaria patients being successfully treated with artemisinin. Over decades millions of patients have now been treated and even today, malaria is still the most commonly treated with artemisinin-based combination therapy (ACT). ACT is when the fast-acting artemisinin is combined with a slower acting antimalarial, the reason being for this combination therapy is due to resistance towards artemisinin trying to be deterred as much as possible. This is a big change in clinical practice for resistance has been a common problem with regards to antimalarial drugs, for example ‘Previous compounds used to treat malaria, such as chloroquine and sulphones or combined sulphonamides and pyrimethamine, have ceased to be effective due to growing resistance”. This resistance to antimalarials is what makes artemisinin so important, as well as why it is crucial to try stop any resistance growing towards it.

So, thanks to Youyou Tu the fight against malaria is looking as strong as it ever has and the drugs she discovered have truly innovated the industry and advanced them with an antimalarial that is extremely effective. Some may be surprised when they hear that artemisinin might also be effective against many other organisms (Schistosoma, Chlonorchis Sinensis) and even more surprising, there have been studies that suggest artemisinin has anticancer properties! Considering the benefits of this drug it is no wonder that it has inspired research through the integration of diversified disciplines after all this drug that stemmed from traditional Chinese medicine has gone so far. Research also continues into artemisinin itself to help further our knowledge on its action mechanisms, and delay resistance.