After Tu youyou made headlines in China | by Jeffrey


On June 14, an international symposium was held at the Kaiyuan Hotel in Beijing.

The seminar, “Artemisinin and Global Malaria Prevention and Elimination: History and the Future.” was organized by Peking University’s School of Public Health.

The meeting was high in the specification, and Tu Youyou, Director of the WHO Malaria Division and Nobel Laureate, was invited.

Tu youyou herself did not attend, and only in the 20-minute opening address, which was attended by three experts, was delivered in a video format. Wang Jigang, a member of Tu youyou research team and a unique expert at the Institute of Traditional Chinese Medicine of the Chinese Academy of Traditional Chinese Medicine, attended the meeting. Among them, “The Challenge of Artemisinin Resistance” emerged as one of three thematic reports, and the reporter was not a member of the Tu Youyou team. Drug resistance research is a severe problem in the area of artemisinin antimalarial.

Since the 1990s, Western experts have been hoping to slow the large-scale use of artemisinin, citing the possibility of drug resistance or drug resistance.

Two days later, the Tu Youyou team was linked to “significant progress in artemisinin resistance.”

On the evening of June 16, Xinhua news agency issued a statement saying, “The Tu youyou team is announcing a breakthrough in scientific research tomorrow.”

On the morning of June 17th, the mystery was solved: In response to the problem of resistance to resistance in some parts of the world in recent years, Tu Youyou and his team made breakthroughs in the study of antimalarial mechanism, “drug resistance causes” and “adjusting treatment methods”, and recently proposed practical treatment options to deal with the “artemisinin resistance” problem. In the interview, published by Xinhua News Agency, the 89-year-old Tu Youyou said word for word:

The problem of so-called “artemisinin resistance” can be solved if the drug use is appropriately extended, or if the drug resistance has been developed in artemisinin combination therapy.

For a time, the praise from public opinion like a tsunami, the capital market gave more direct feedback: as of the close, 9 artemisinin concept stocks all rose, including Yuheng Pharmaceuticals and Kun Pharmaceutical Group all day in the day in the ups and downs.

However, then the event took a turn. Shortly after the Xinhua interview was released, at noon on June 17th, a researcher within Tu Youyou’s team said they had invested heavily in the study, and some of the ideas were being put into practice but were still in their early stages. The final outcome is based on clinical data.

“It is a basic common sense that none of the basic experimental data is clinically convincing.”He said it would take time for the research to take shape.

Also according to the news report, Tu Youyou’s unit, the Chinese Academy of Traditional Chinese Medicine, the relevant person in charge of the Institute of Chinese Medicine, said that Tu Youyou team’s current research results are “progress” rather than a breakthrough.

The person said the number of discussions generated by the report had left them unexpected and might then give the public a more accurate briefing or explanation.

Back in December 2015, Tu Youyou publicly stated at a Nobel Press Conference in Sweden that once artemisinin develops resistance, it will take another decade to research new drugs.

At the time, it was only two months since she received the Nobel Prize for artemisinin.

In recent years, in Cambodia, Thailand, Myanmar, Viet Nam and other countries in the Greater Mekong Subregion, the three-day cycle of artemisinin-based treatment for malaria-infected people has shown signs of slow removal and resistance to artemisinin.

“Artemisinin can treat all malaria types, it works particularly quickly, and it works within minutes of injection. Gao Qi, a professor at the Institute of Parasitic Diseases Prevention and Control in Jiangsu Province, points out that it is true that artemisinin’s sensitivity to malaria parasites is declining.

Over the past three days, more than 90 percent of the insects can be killed, and half-life drugs kill the remaining insects. Now, within three days, artemisinin could not kill more than 90 percent of the insects, or even less than half.

The more scientific approach is that the early insect clearing efficiency of artemisinin is declining. Malaria remains one of the world’s leading causes of death, with one child dying every two minutes and more than 200 million new cases reported each year, according to the newly released World Malaria Report 2018, which “reduces malaria infection rates and mortality rates by 40 percent by 2020.”

Milestones are almost impossible to achieve. Artemisinin is the most effective drug worldwide to fight malaria. Its pharmacological pathway is that when the malaria parasite destroys red blood cells in the human body, it releases extremely high concentrations of hemoglobin, which activates artemisinin, binds it to hundreds of proteins in the plastic system, and ultimately kills the parasite.

Moreover, artemisinin has very little toxic side effect son-in-use for normal cells, which makes it the preferred antimalarial combination therapy drug 40 years after its introduction. But 40-year treatment cycle is enough to allow the malaria parasite to recognize the killer’s path and make tactical adjustments accordingly. Artemisinin has a fatal weakness — short half-life, in layman’s terms, is physical strength can not, can play, but can play for a long time.

Studies show that artemisinin in the human body half-life is only 1 hour to 2 hours, and the earliest clinical use of artemisinin combination therapy treatment is only three days, which means that artemisinin efficient insecticidal window only 4 hours to 8 hours. In response to this fate, the malaria parasite changed its life cycle, that is, to fight the “delay war.” When the malaria parasite detects the presence of artemisinin, they temporarily go into hibernation, slowing the metabolic rate and reducing the release of hemoglobin. For artemisinin, there is no target of hemoglobin, and there is no way to attack the malaria parasite. It was not until artemisinin had failed that the malaria parasite began to kill red blood cells.

This is known as “artemisinin resistance.”

Gao Qi pointed out that some cases of artemisinin resistance if treated with high doses of artemisinin needles, can still be cured.

The current public reports of resistance to artemisinin are not, in fact, resistance to artemisinin itself, but resistance based on one or two artemisinin-based derivatives. According to media reports, when using artemisinin-based drugs in patients early on, the initial method of use is a one-sided (artemisinin-only) dose for three days. But the effect is not good, about 50% of patients within a month of treatment, there will be repeated.

Later exploration extended to five days and seven days, found that the effect of artemisinin alone for seven days is better, the cure rate can reach 95% to 98%.

But artemisinin works very quickly, the average patient with two or three days later, the fever back. It is difficult for patients to continue to use artemisinin for up to seven days without a fever. Therefore, although the effect of seven-day therapy is good, the patient’s compliance is not good.

Therefore, the domestic use of improved compound preparation. Artemisinin-based compound drugs do have several drug resistance.

But there are two conditions for this resistance: one is caused by insufficient artemisinin content in it, and the other is that the other is resistant to drugs, which are not the same.

For the first drug resistance, Tu Youyou and her team proposed the first solution to increase the amount of medication appropriately, “Artemisinin is currently eaten once a day, so we consider eating twice a day.” Originally with three days of medicine, now add to use five days, with seven days.

Wang Jigang, a member of the Tu Youyou research team and a special expert at the Institute of Traditional Chinese Medicine of the Chinese Academy of Traditional Chinese Medicine, said.

For the second type of drug resistance, the second option proposed by the Tu youyou team is the replacement of complementary drugs.

But Gao Qi believes that the media claims of artemisinin to treat malaria, three-day therapy increased to five or seven days.This statement is inaccurate.

“Our country has been using seven-day therapies for more than 20 years since the 1980s. Later, the patient could not accept seven days, so it became three days. Now I’ve found out there’s a problem for three days. But the solution can’t simply go back to five or seven days. That is to say, the current anti-drug mechanism research is still at the theoretical level, to say that the guidance of practice and drug use still need a long way. ”

Research on complementary drugs that have developed resistance to drug resistance in the replacement of artemisinin combination therapy is also ongoing. It has not been determined which drug to replace.

The Tu youyou team’s research on artemisinin resistance is generally at an early stage.

An industry expert, who did not want to be named, pointed out that the Tu youyou team’s “major discovery” has been exaggerated by the media:“There has been a lot of research on the mechanism of resistance to artemisinin, and more research is needed to confirm the possible mechanism, the key mechanism or the only mechanism, a different type of auxiliary drug is not the fundamental solution.”

In an interview published by Xinhua News Agency on June 17th, it also revealed that traditional Chinese medicine research works, written by Tu Youyou team member and researcher Liao Fulong, a researcher at the Chinese Academy of Traditional Chinese Medicine, and other experts, are expected to be included for the first time in the upcoming re-release of the international authoritative medical textbook Oxford Medical Textbook (sixth edition).

The news, three years ago Tu Youyou won the Nobel Prize after the “artemisinin Chinese and Western medicine dispute” topic, was mentioned again. The Chinese medicine school, which has the upper hand in this incident, firmly believes that artemisinin was discovered under the guidance of Chinese medicine theory.

On the basis that Tu Youyou herself had said in his speech at the Nobel Awards ceremony that “Chinese medicine is a great treasure trove that should be explored and improved”, adding that individual domestic media at that time also defined artemisinin as Chinese medicine when they were reported, which has created a great deal of momentum for the Chinese medicine school.

The latest voice came from Cox, editor-in-chief of Oxford Medical Textbook, who pushed for the inclusion of Chinese medicine in the textbook, “the Chinese medicine chapter is both important and deep, all of which is the result of the outstanding efforts of Chinese scientists.”

Opponents are on the side of modern Western medicine, which is more evidence-based. In their view, artemisinin is not a Chinese medicine, but a single, well-structured chemical extracted from plants, and aspirin, Tamiflu is no different. What’s more, Chinese medicine pays attention to frying, artemisinin in more than 60 degrees will be due to structural damage failure, and choose to use ether to extract artemisinin, is based on modern pharmacology of drug discovery, and Chinese medicine has nothing to do.

In terms of illustration, they seem to be more at the bottom of their strength. First of all, the China Drug Administration, to give artemisinin is the chemical drug quasi-size, also known as western medicine.

Second, at the launch of the Nobel Prize, at least three members of the Nobel Committee made it clear that “we did not award the prize to traditional medicine, we gave it to researchers inspired by traditional medicine to create new drugs.”

In fact, even if artemisinin is inspired by traditional medicine (i.e., Chinese medicine), it is somewhat unreasonable.

Artemisinin research began in the Vietnam War when the warring sides died of malaria far more than they died at war, and malaria-stricken Vietnam turned to China for help in developing antimalarial drugs. Because China itself also has a need to treat malaria, in 1967, the National Leading Group on Malaria Control was established in Beijing, mobilizing more than 500 researchers from dozens of units to screen more than 40,000 compounds and herbs over a five-year period through human-sea tactics.

Artemisinin was discovered on 4 October 1971 by Youyou. In the process, a drug book called “Elbow Reserve Emergency” has become the core controversy of today’s debate over whether artemisinin originated in Chinese medicine. Elbow Reserve Emergency Side is written by Ge Hong, an East Jin refiner, to collect folk bias as the purpose.

According to Tu Youyou herself, she saw the book “artemisinin a grip, water two liters of stains, winch juice, to serve” a sentence, suddenly realized that could not heat artemisinin, only then thought to use ether to extract artemisinin.

A person in favor of modern medicine told Eight o’clock Health News that the above-mentioned expression of “sudden insight” reflects a certain chance of discovering the efficacy of artemisinin. At that time, he said, Tu Youyou systematically collected the medical texts of past generations, sought out the practical experience of folk Chinese medicine, and summarized more than 640 kinds of herbs, including artemisinin. But at the same time, American pharmacologists screened a sample of more than 200,000 plants.

“This directly determines that we pre-empted the Creation of artemisinin, if Chinese medicine has contributed, it is reflected here.”

A number of pharmaceutical experts believe that artemisinin is no longer belong Chinese medicine.It is based on the natural pharmaceutical method, this component is independently proposed a process, is essentially based on the theory of Western medicine research and development formed, is chemical synthesis, refining the purification process.

This process is common in Western medicine, such as the earliest aspirin.

The restoration process of restoring artemisinin confirms this. The discovery of artemisinin is actually a relay-style process. Zhang Jianfang published the “late report — China 523 project 59th-anniversary edition” written, Yu Yagang summarized and excavated the effective work of artemisinin and artemisinin hydrolysis extract, Tu Youyou first found the effective artemisinin extract, Zhong Yurong extracted artemisinin crystals,

Luo Zeyuan was the first to get an anti-abuse monomer from the chrysanthemum yellow flower artemisinin, li Guoqiao was the first to verify the effectiveness of artemisinin.

Eight o’clock Health News once interviewed Luo Zeyuan, a researcher at the Institute of traditional Chinese medicine in Sichuan Province, she recalled that in 1972, the head of the “523 Office” in Yunnan Province learned that the Beijing Institute of Traditional Chinese Medicine artemisinin extract has a good antimalarial effect, and then suggested to the researchers, Can similar active substances be found from the close-edge plants of the Artemisinin genus in Yunnan.

In the Spring Festival of 1973, Luo Zeyuan, who accompanied her daughter to Yunnan University, discovered an unknown artemisinin plant (later identified as a large-headed variant of the yellow flower artemisinin). With experience, she prepared several extracts, in which the ether extraction site showed significant anti-rat malaria activity.

Through further research, she found that the composition of “bitter artemisinin -Crystal 3” has a strong anti-rat malaria activity, thus becoming the first scientist to get antimalarial monomers from the chrysanthemum jaundice artemisinin. In September 1974, Li Guoqiao, a professor at the Institute of Tropical Medicine of Guangzhou University of Traditional Chinese Medicine, participated in a clinical trial of artemisinin. Previously, jaundice has been shown to be effective against malaria in animals. The effectiveness of artemisinin was found in 3 patients.

Between October and December of the same year, they treated 18 patients, all of whom were quickly and clinically cured.

“More and more Chinese medicine is based on natural pharmaceutical chemistry, extracting ingredients from plants and animals, but compared with Western medicine, the experimental aspects of doing less, and the Western scientific argument is still fundamentally different.”A former deputy director of the pharmacy department of Beijing Sanjia Hospital told Eight o’clock Health News.

A plant medicine rich in hundreds of ingredients. Whether it is a large dose of a single ingredient to produce an effect, or a variety of ingredients superimposed to produce an effect, can not be distinguished, from the origin of medicinal herbs to the way of frying, may affect the efficacy of the drug. What is lacking in the study of Chinese medicine is a clear evaluation system.

Taking the anti-flu drug Tamiflu as an example, in the development process of this drug, Western scientists first based on the influenza pathogen, designed the ideal model of the molecular structure of the effective drug, and then chemical synthesis by model.

In the synthesis process, chemists found the need to use “reckless oxalic acid”, and thus took the initiative to find “reckless oxalic acid” content of very high octagonal fennel to refine.

The above-mentioned experts believe that the Western system of Chinese medicine is a direction in which Chinese medicine gets out of its predicament.

It is worth noting that on March 12 this year, the Chinese Medicine Evidence-Based Medical Center was established in Beijing, the world’s first evidence-based medical center in the field of Chinese medicine.Related people said that for world medicine, this is a win-win situation.

The establishment of evidence-based centers represents the stage of Chinese medicine moving away from blind drug search and towards experimental research using certain criteria.

“This should also be the mainstream of research and development of new drugs in China, rather than the waste of financial and human resources in the hope of a miracle.” The above-mentioned people said.


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