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Tu Yu published a speech entitled "Artemisinin - A Gift for Chinese Medicine to the World"

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(China Traditional Chinese Medicine News reporter sent from Stockholm) "'Chinese medicine is a great treasure house, we should work hard to find and improve it.' Artemisinin was discovered from this treasure house. Through the antimalarial artemisinin The research experience, I deeply feel that both Chinese and Western medicine have their own strengths. The two are organically combined and complement each other. When they have greater development potential and good development prospects." Local time December 7 at 14:15, in Sweden Carolynska College, a researcher at the Chinese Academy of Traditional Chinese Medicine, gave a speech entitled "Artemisinin - a gift from Chinese medicine to the world". In the speech, she reviewed the discovery process of artemisinin and said that the interdisciplinary study provided preparation for the success of the research. The literature enlightenment played a key role. Traditional Chinese medicine is a rich treasure. Through inheritance and development, excavation and improvement must be There will be discoveries and innovations that will benefit mankind.


Tu Yu expressed his gratitude to all members of the team of Chinese Academy of Traditional Chinese Medicine who participated in the “523 Anti-malaria Research” and the “523 Project” units throughout the country, bearing in mind their active investment and outstanding contributions in the research, discovery and application of artemisinin.


>>>>The following is the full text of the speech

Dear Sir, Dear Winners, Ladies and Gentlemen,

Today, I am extremely honored to give a lecture at Karolinska Institute. The title of my report is: Artemisinin - a gift from Chinese medicine to the world.


Before the report, I would first like to thank the Nobel Prize jury, the Nobel Prize Foundation awarded me the 2015 Physiology or Medicine Award. This is not only a personal honor, but also a recognition and encouragement to all Chinese scientists. In just a few days, I deeply felt the enthusiasm of the Swedish people, and I would like to express my gratitude.


Thanks to William C. Campbell and Satoshi?mura for their wonderful reports. What I am going to say now is that 40 years ago, in a tough environment, Chinese scientists worked hard to find a new anti-malarial drug from Chinese medicine.


The discovery process of artemisinin may have been seen in many reports. Here, I will only make a brief introduction. This is a brief summary of the work of the anti-malaria drug research team of the Institute of Traditional Chinese Medicine. The blue background marks the work done by the team of the hospital, and the white background marks the work done by other collaborative teams across the country. The blue-to-white transition to the white background indicates that both the hospital and the collaborating unit participate in the work.


The Chinese Medicine Research Institute team began research on anti-malarial Chinese medicine in 1969. After a lot of repeated screening work, the focus of work in 1971 was on the traditional Chinese medicine Artemisia annua. After many failures, in September 1971, the extraction method was redesigned, and the sample was prepared by low temperature extraction, refluxing with diethyl ether or cold soaking, and then removing the acidic portion with an alkali solution. On October 4, 1971, a neutral extract of Artemisia annua L., a sample of No. 191#, was orally administered at a dose of 1.0 g/kg body weight for 3 consecutive days. The evaluation of the efficacy of rat malaria showed that the inhibition rate reached 100%. . The monkey malaria experiment from December of the same year to January of the following year also resulted in a 100% inhibition rate. The breakthrough of antimalarial efficacy of the neutral extract of Artemisia annua L. is the key to the discovery of artemisinin. From August to October 1972, we conducted a clinical study on the neutral extract of Artemisia annua L., and all 30 patients with falciparum malaria and vivax malaria were markedly effective. In November of the same year, the crystal of the antimalarial effective monomer compound was successfully isolated from this site, and was named "artemisinin".


In December 1972, the chemical structure of artemisinin was explored. The molecular formula of the compound was determined by elemental analysis, spectrometry, mass spectrometry and optical rotation analysis. The molecular formula was C15H22O5 with a molecular weight of 282. It is clarified that artemisinin is a nitrogen-free sesquiterpenoid.


On April 27, 1973, the analytical chemistry laboratory of the Institute of Materia Medica of the Chinese Academy of Medical Sciences further reviewed the molecular formula and other related data. Since 1974, the Shanghai Institute of Organic Chemistry and the Institute of Biophysics of the Chinese Academy of Sciences have been working on the collaborative research of artemisinin structure. The structure of artemisinin was finally determined by X-ray diffraction. It was confirmed that artemisinin is a novel sesquiterpene lactone containing a peroxy group. The three-dimensional structure was published in the scientific bulletin of China in 1977 and was included in the chemical abstracts.


Since 1973, derivatives have been prepared for the study of functional groups in the artemisinin structure. The dihydroartemisinin was invented by sodium borohydride reduction reaction to confirm the presence of a carbonyl group in the artemisinin structure. Studies on structure-activity relationship: It is clear that the peroxy group in the artemisinin structure is an antimalarial active group, and the malaria titer of some dihydroartemisinin hydroxyl derivatives is also improved.


Here, the molecular structure of artemisinin and its derivatives dihydroartemisinin, artemether, artesunate and artemisinin are shown. Until now, other types of artemisinin derivatives have not been reported for clinical use.


In 1986, artemisinin was awarded a new drug certificate by the Ministry of Health. In 1992, he obtained the new drug certificate for dihydroartemisinin. The clinical efficacy of the drug is 10 times higher than that of artemisinin, which further embodies the characteristics of artemisinin drugs that are "efficient, quick-acting, and low-toxic".


In 1981, the World Health Organization, the World Bank, and the United Nations Development and Planning Agency jointly held the fourth meeting of the Malaria Chemotherapy Scientific Working Group in Beijing. A series of reports on artemisinin and its clinical application triggered a warm response. My report is "Chemical Research of Artemisinin". In the 1980s, thousands of Chinese malaria patients were treated with artemisinin and its derivatives.


After listening to this introduction, you may think that this is just an ordinary drug discovery process. However, the process of excavating artemisinin from the traditional Chinese medicine Artemisia annua L., which has been used for more than 2,000 years in China, was quite difficult.


Clear goals and adherence to beliefs are prerequisites for success. In 1969, the Institute of Chinese Materia Medica of the Chinese Academy of Medical Sciences participated in the national "523" anti-malaria research project. The study of the leaders of the scholastics decided that I was instructed to set up the "523" project team to undertake research and development of anti-malarial Chinese medicine. This project was a key military project at the time. For a young scientific researcher, I have the opportunity to accept such a heavy responsibility. I have realized the trust that the country has placed in me. I feel that the responsibility is great and the task is arduous. I am determined not to disgrace my mission, work hard, and do my best to complete the task!


Disciplinary interdisciplinary preparations for research findings. This is a photo of me just arrived at the Institute of Traditional Chinese Medicine. On the left is the famous pharmacist building. He guides me to identify the medicine. From 1959 to 1962, I took a course in Western medicine learning Chinese medicine and systematically studied Chinese medicine. The chemist Louis ̇ Paste said that "the opportunity to be prepared for people." The old saying goes: Everything in the past is a prelude. However, the overture is a preparation. When the anti-malaria project gave me the opportunity, the prelude in Western learning provided me with good preparation for artemisinin research.


Information collection and accurate analysis are the basis for the success of research findings. After accepting the task, I collected and compiled traditional Chinese medicine classics, visited famous Chinese medicine practitioners and collected their prescriptions and Chinese medicines for malaria prevention, and also read a large number of folk medicines. On the basis of more than 2000 internal and external prescriptions including plants, animals, minerals, etc., a series of malaria single prescriptions based on 640 kinds of traditional Chinese medicines was prepared. It is the collection and analysis of this information that has laid the foundation for the discovery of artemisinin, and it is also the place where the research on new Chinese medicine is different from the development of common botanical drugs.


Key literature implications. When I faced the research dilemma, I revisited the ancient books of Chinese medicine and further thought about the Eastern Jin Dynasty (AD 3-4th century) Ge Hong's "Elbow Reserve Emergency" about "Agriculture Artemisia, holding two water stains, twisting juice, serving "The interception of malaria." This reminds me that the extraction process may need to avoid high temperatures, thus switching to a low boiling point solvent extraction method.


Regarding the application of Artemisia annua L., it was first seen in the "Fifty-two Diseases" of the Mawangdui No. 3 Han Tomb, and the subsequent "Shen Nong's Herbal Classics", "Replenishment of the Thunder and the Cannons", "Compendium of Materia Medica" and other books have Artemisia annua The record of treatment. However, although there are many ancient books, there is no clear classification of plants of Artemisia annua. In the same year, the varieties of Artemisia annua were confusing, the Pharmacopoeia contained two varieties, and four other confusing varieties were also used. Subsequent in-depth research found that only Artemisia annua L. contains artemisinin, which is effective against malaria. This objectively increases the difficulty of discovering artemisinin. In addition, the content of artemisinin in the original plant is not high, as well as the influence of the medicinal part, the place of origin, the harvesting season and the purification process. The success of the neutral extract of Artemisia annua L. is indeed hard to come by. Chinese traditional Chinese medicine is a rich treasure, and it is worthwhile for us to think more and discover and improve.


In the face of difficulties, we need to persevere. In the 1970s, China's scientific research conditions were relatively poor. In order to supply enough effective parts of Artemisia annua L. for clinical use, we used water tanks as extraction containers. Due to the lack of ventilation and exposure to large amounts of organic solvents, the health of some researchers has been affected. In order to get on the clinic as soon as possible, based on the animal safety evaluation, I and the research team members themselves take effective site extracts to ensure the safety of clinical patients. When the clinical trial effect of artemisinin tablets is not satisfactory, after hard work and persistence, the reasons for further investigation are finally found to be the problem of disintegration. The use of artemisinin monomer capsules in time confirmed the antimalarial efficacy of artemisinin.


Teamwork, selfless cooperation accelerates the discovery of scientific discoveries into effective drugs. On March 8, 1972, the National 523 Office held a professional meeting on antimalarial drugs in Nanjing. On behalf of the Chinese medicine, I reported the results of the extract of Artemisia annua L. No. 191 against malaria and monkey malaria, which was greatly concerned by the meeting. On November 17, the same year, at the national conference held in Beijing, I reported the results of 30 clinically significant results. Since then, the prelude to the national collaboration on the antimalaria research of Artemisia annua has been opened.


Today, I would like to express my heartfelt gratitude to all members of the team of the Chinese Academy of Sciences who worked on 523 anti-malarial research in the past, bearing in mind their active input and outstanding contributions in the research, discovery and application of artemisinin. Thanks to the cooperation of the 523 project units across the country, including the Shandong Institute of Chinese Medicine, the Yunnan Institute of Materia Medica, the Institute of Biophysics of the Chinese Academy of Sciences, the Shanghai Institute of Chinese Academy of Sciences, the Guangzhou University of Chinese Medicine, and the Academy of Military Medical Sciences. I sincerely congratulate the collaborating unit. The multifaceted results we have achieved and the dedicated service to malaria patients. I would like to express my sincere respect to the unremitting efforts of the National 523 Office in organizing anti-malaria projects. Without the team spirit of selfless cooperation, we cannot contribute artemisinin to the world in the short term.


Malaria remains a serious challenge to world public health. WHO Director-General Margaret Chan has had such an assessment when it comes to controlling malaria. We are deeply impressed by the achievements being made globally in reducing malaria cases and deaths. Nonetheless, according to statistics, 3.3 billion people in 97 countries and regions are still suffering from malaria, and 1.2 billion of them live in high-risk areas, and the prevalence of these areas is likely to be higher than 1/1000. Statistics show that in 2013, there were approximately 198 million malaria patients worldwide, and the number of deaths caused by malaria was about 580,000, of which 78% were children under 5 years of age. Ninety percent of malaria deaths occur in the hardest hit areas of Africa. 70% of African malaria patients are treated with Artemisinin-based Combination Therapies (ACTs). However, the number of malaria patients who are not treated with ACTs is still between 560 and 69 million.


Plasmodium resistance to artemisinin and other antimalarials. In the Greater Mekong region, including Cambodia, Laos, Myanmar, Thailand, and Vietnam, Plasmodium falciparum has developed resistance to artemisinin. In many parts of the Cambodia-Thai border, Plasmodium falciparum has developed resistance to most antimalarial drugs. Please see the distribution of artemisinin resistance reported this year. Red and black indicate local resistance to Plasmodium falciparum. It can be seen that not only resistance in the Greater Mekong River Basin, but also resistance in a few areas in Africa. These situations are serious warnings.


The World Health Organization's 2011 global plan to curb artemisinin resistance. The plan was introduced to protect the effectiveness of ACTs for falciparum malaria. Given that the resistance of artemisinin has been confirmed in the Greater Mekong River Basin, the potential threat of proliferation is also being investigated. More than 100 experts involved in the program believe that the chances of containing or eliminating drug resistance are very limited before artemisinin resistance is transmitted to highly infected areas. The task of curbing the resistance of artemisinin is imminent. To protect the effectiveness of ACTs for falciparum malaria, I sincerely hope that global antimalarial workers will seriously implement the WHO global plan to curb artemisinin resistance.


Before I finish, I want to talk about Chinese medicine again. "Chinese medicine is a great treasure house, and we should work hard to find and improve it." Artemisinin was discovered from this treasure house. Through the research experience of antimalarial artemisinin, we deeply feel that Chinese and Western medicines have their own strengths. The two are organically combined and complement each other. When they have greater development potential and good development prospects. Nature provides us with a lot of plant resources, and pharmaceutical researchers can develop new drugs from it. Traditional Chinese medicine has begun to cultivate a hundred grasses from Shennong, and accumulated a lot of clinical experience in the development of thousands of years. The medicinal value of natural resources has been sorted out. Through inheritance and development, and excavation and improvement, we will certainly discover and innovate, thus benefiting mankind.


Finally, I would like to share with you a famous poem written in the Tang Dynasty in China, written by Wang Zhijun, “Deng Yuquelou”: the day is full of mountains, the Yellow River flows into the sea, and you want to go to the top of the building. Please take the opportunity to take it to the next level, to appreciate the charm of Chinese culture and discover the treasures contained in traditional Chinese medicine!


I sincerely thank all the colleagues, colleagues and friends who have contributed to the discovery, research and application of artemisinin! I am deeply grateful to my family for their constant understanding and support!


Sincerely thank you all for coming to the conference!

thank you all!