Malaria, linked to the fate of the country.

Today we talk about malaria, especially to show you
those unknown information.

Malaria, a disease infected by mosquito bites, the patient will sometimes shiver, sometimes fever, red blood cells will be destroyed, anemia, spleen will enlarge, severe will be fatal
.
The fact that we have very few malaria patients around us now does not mean that it will not break out again, especially since malaria has become resistant to many drugs in recent years
.

This time, we introduce the history of malaria diagnosis and treatment from the aspects of traditional Chinese medicine and Western medicine, so that everyone can more objectively understand the key events
of those years.

1.
How was malaria treated in ancient China?

China has had malaria
since ancient times.

Why is it called malaria? The pre-Qin and Han dynasties were the era of the formation of Chinese characters, when the disease was very harmful, "malaria" is the abbreviation of "", and "" is a huiyi character, you see a boil character head, inside is an abuse character, and the abuse word from , like a tiger's foot to catch people, the original Italian text is cruel, so it was named malaria
.
It's a very brutal disease, a terrible disease
.

The earliest period of discovery of the name of malaria is probably 400 BC ago (Spring and Autumn Warring States Period), and there is information that there was malaria in the earlier Yin Shang period, considering that we are not archaeohistorical, do not need to be too entangled in the specific period, we roughly know: Yin Shang, Spring and Autumn Warring States period (more than 2000-3000 years ago) we have malaria in China
.

For example, there is such a record in the Spring and Autumn "Zuo Chuan": In the seventh year of Lu Xianggong, "Zixi made the thief kill the Duke of Xixi at night, and went to the princes with malaria"
.
That is to say, in the Spring and Autumn Period, a cadre of a state organ in the Lu state sent someone to kill his leader, and he pretended that the leader died of malaria, and under the guise of this, he reported
to his brother country at that time.

This time, malaria carried a pot
.
But at least we know that malaria was already there
.

(1) Qin and Han dynasties

We jump straight to the Han Dynasty
.

The Inner Canon of the Yellow Emperor is the first of the four classic medical books of traditional medicine in China, and according to current scholars, it should have been written during the Western Han Dynasty (202 BC-8 AD), so far around
2100 years.
The book "The Inner Canon of the Yellow Emperor" also has an understanding of malaria, and it is relatively comprehensive, creatively classified, and invented the method
of using acupuncture to treat malaria.

The "Yellow Emperor's Internal Canon" devotes a large part to the introduction of "malaria theory" and "malaria", which shows the high importance attached to malaria at that time
.
I reviewed the many diseases recorded during the pre-Qin and Han dynasties, and there was really no other disease that received as much attention from doctors as malaria, and malaria was already well studied at that time
.

The book mentions: The origin of malaria is also the first hair, the lack of stretch, the cold jaw, the pain in the lumbar spine, the cold is hot inside and outside, the headache is broken, and the thirst for cold drinks
.

This passage points out the main symptoms of malaria, which is not far
from the current understanding.
Especially if the headache is about to break this, anyone who has had malaria knows that that kind of headache really has to hit the
wall.
In addition, the book gives an approximate indication of the time of inter-day malaria onset and recurrence
.
It is said that malaria has two outbreaks of malaria, there are many daily outbreaks of malaria, there is cold malaria that is cold before heat, there is warm malaria that is hot before cold, and there is malaria that is hot but not cold
.

In terms of treatment, the theory of stinging malaria says: when it occurs first, it is like eating and stabbing it, one thorn is weak, then it is pricked, and three thorns are gone
.
As for whether the effect is really this good, we can't verify
it now.

There is also a book, called "Fifty-two Sick Formulas" (written before 168 BC), a simple medical book unearthed in 1973 in Mawangdui, Changsha, which also records malaria and its treatment
.

At the end of the Eastern Han Dynasty, the medical saint Zhang Zhongjing (about 150-215 AD) was endemic with plague, and because of this, he wrote "Typhoid Miscellaneous Diseases", malaria is also an infectious disease, infectious diseases used to be called plague, the book records: malaria veins from the string, the number of strings is hot, the strings are late, the strings are cold, the strings are tight and poor, the strings are late, the strings can be warm, the strings are tight but not small, sweating acupuncture also
.
Those who float big can spit it out, and those who number the strings can also be furious, and stop with food news
.

This is Zhang Zhongjing's discussion of malaria, in addition, in Zhang Zhongjing's medical prescription, he has taken the traditional Chinese medicine Changshan as the first choice for the treatment of malaria
.
Changshan is one of the protagonists of
our article today.
We'll talk about
that later.
Below are several Changshan recipes in Zhang Zhongjing's book, the first to treat malaria
.

The Shu lacquer mentioned in Zhang Zhongjing's book refers to the fine leaves
of the traditional Chinese medicine Changshan.
His prescription for treating malaria is called Shu Qi San, and there are three ingredients, namely: Shu Qi San, mica, and keel
.
According to the information I can find, mica and keel have sedative effects
.
Later generations analyzed, why Zhang Zhongjing will have three drugs to treat malaria, the real drug for malaria is Shu Qi (there are quite a few studies before and after liberation, more on that later), but Shu Qi has obvious digestive side effects, causing vomiting in many people, so it is compatible with sedatives to stop vomiting
.
This is the same
as the pharmacological research of later generations and now.

In fact, when I see Zhang Zhongjing's formula, there will still be shock, around 1950, many domestic pharmacologists and some pharmacologists in the United States have shown that Changshan's antimalarial effect is better than quinine (a malaria specific drug in the 19th century and early 20th century), but it has obvious vomiting side effects
.
Of course, Zhang Zhongjing also found it, so he added mica and keel to reduce the effect of vomiting, without rich experience, rich knowledge of pharmacology and medicinal properties, it is impossible to have such a formula
.

Zhang Zhongjing is indeed a cow man
.

As for how good Zhang Zhongjing's prescription is in treating malaria, it is impossible to calculate, but from the research of the Republic of China and the early liberation, the effect of this formula is good
.

Some people said that China has been fighting malaria for thousands of years, hundreds of remedies, but none of them are effective, and many people die every time there is a malaria epidemic, which is miserable
.
This claim must be untenable, and I don't know where it came from
.
"The Biography of Tu Youyou" does write: Tu Youyou and others spent 3 months to collect more than 2,000 prescription drugs, including internal, external, plant, animal, mineral drugs, and selected and edited the "Malaria Single Secret Formula" of 640 prescription drugs, their research process was not smooth, and they did not have to screen out better drugs than quinine and chloroquine (artemisinin had not yet been developed at that time), but this does not mean that these prescriptions are not curative, because there was no lack of relevant research in China around 1930-1960.
It proves that many prescriptions have certain therapeutic value, especially the traditional Chinese medicine Changshan
.

(2) Jin, Sui and Tang dynasties

In the Eastern Jin Dynasty, Ge Hong's (283-363 AD) "Elbow Reserve Emergency Formula" recorded dozens of prescriptions for malaria treatment, the most famous of which must be the one Tu Youyou's team said: Artemisia annua one hand, Artemisia annua one hand, stained with two liters of water, strangled juice, and obeyed
.

Ge Hong was an alchemist, but at that time, many people's identities were multiple, and it was undeniable that he was also a doctor
.
It's just that we also have to look at these ancients from a developmental perspective, although Ge Hong is the first documented doctor to propose the use of Artemisia annua to treat malaria, but the content of his book is also mixed with fish and dragons, and there are many obvious superstitions, so Tu Youyou said that traditional medicine is a treasure trove, but this treasure house cannot be used directly, it has to be tapped
.

It was also from Ge Hong that the use of Artemisia annua in traditional medicine to treat malaria has also increased
.

Artemisia annua is the big protagonist
of our article today.
Artemisia became the protagonist because of Tu Youyou
.
Before Tu Youyou's team came up with artemisinin, Artemisia annua was not valued by traditional medicine, and Changshan and Shu Qi were the protagonists
at that time.
Ge Hong recorded dozens of remedies for malaria, 14 of which used Changshan and only one used Artemisia annua, which shows that the protagonists of malaria treatment in the Qin, Han and Eastern Jin Dynasties were still Changshan and Shu Qi, not Artemisia
annua.

And at that time, doctors had recognized that malaria was an epidemic and infectious disease, but limited to technical reasons, it was impossible to know that malaria was caused by malaria parasites (the French discovered malaria parasites under a microscope in 1880), but believed that it was related to external wind chill and related to geography
.

Chao Yuanfang (550-630 AD) of the Sui Dynasty wrote in his "Treatise on the Origin of Diseases" edited by him: This disease (malaria) was born in Lingnan, with the miasma of the mountains, and its appearance was cold and hot.

The miasma Chao Yuanfang is talking about here refers to what we now call falciparum malaria (one of the most serious kinds of malaria).

Chao Yuanfang recognizes that malaria is an infectious disease, and believes that Lingnan here is more, and more fierce (there is falciparum malaria), the cause is miasma and poisonous gas, and it is more in the clear water of mountains and streams, this understanding must not be right at present, malaria is not caused by poisonous gas, but by malaria parasites, but what Chao Yuanfang summarizes is not for nothing, at least it knows that the disease is caused by foreign substances (he thinks it is poisonous gas, it is actually malaria parasites), and he thinks that there are more clear water by the stream in the deep mountains, which is correct, Because there are the most mosquitoes, mosquitoes carry malaria parasites, bite people, and natural people will become ill.

I think it's
remarkable that Chao Yuanfang was able to observe and sort out this objective fact.

In the Tang Dynasty, the medical scientist Wang Tao's "Secrets of the Outer Platform" (written in 752 AD) wrote: At the beginning of this disease, there was not much difference from Tianxing, but also headache and bone pain, cold hands and feet, dry mouth, nose and tongue, good drinking water, hair, strong desire to rebel in the waist, and red urine
.
However, first cold and then hot, the onset is sometimes, can not be examined, and the day of the onset is accurate
.

At that time, medical scientists had a complicated understanding of malaria, and there were quite many symptoms of malaria, which was dazzling, which also showed the high degree of attention to malaria at that time
.
It may be that malaria also has a broad and narrow sense, and there are many classifications, such as orthoplasma, warm malaria, cold malaria, wet malaria, miasma malaria, labor malaria, malaria mother, and so on
.
The process of dialectical treatment is more complicated, we will not go into detail here, we focus on the malaria interception drugs at that time, the so-called malaria interception, the meaning is probably similar to the meaning of killing malaria parasites now, but there was no malaria parasite at that time, so the specific meaning is definitely different
.

Sun Simiao (541-682 AD, age disputed) of the Tang Dynasty wrote in "Preparation for Emergencies": To cure malaria, those who do not ask about new jiu, verbena juice five combinations, wine three combinations, divided into three servings
.
Verbena does have the effect of cutting malaria, but it is basically rarely used now, because the actual effect is better than many Changshan and artemisinin.

(3) Song, Yuan, Ming, and Qing dynasties

In the Song Dynasty, there was a medical book "Yang's Family Tibetan Fang" that recorded that the seven treasures of malaria were the representative of malaria, and Changshan was still used in Fangzhong, as well as betel nut and so on
.

The Ming Dynasty Li Shizhen (1518-1597 AD)'s "Compendium of Materia Medica" also records the Qibao Sanfang: cure all malaria, or cold first and then hot, or cold and cold, or cold and hot, or hot and cold, or one a day, or two or three times a day, or even days, or every day, or once in three or four days, unstable ghosts and food and food, those who do not accept water and soil, and mountain miasma like malaria, can be cured
.
Changshan 1 money.
.
.
.
.
Half of the drinks.
.
.
.
.
Fry twice.
.
.
.
.
It works
.

Although Changshan has the effect of treating malaria, due to its toxicity, Li Shizhen listed it as a lower product and listed it in the Department of
Poisonous Herbs.

As we said above, starting from Zhang Zhongjing, Changshan is an important drug for the treatment of malaria, but Changshan has a disadvantage, easy to lead to vomiting, many people can not stand it, successive generations of doctors are also thinking of a way, how to ensure its antimalarial effect, but also to reduce adverse reactions, here dosage and processing methods, matching, etc.
, are related to side effects vomiting, indicating that people at that time have mastered this effective experience
.

Li Shicai (1588-1655), a famous medical scientist in the late Ming and early Qing dynasties, also had a lot of experience in treating malaria, and he mentioned in his medical case: Changshan intercepts malaria like a god, robs phlegm to cure malaria, and there is no other medicine to compare.
.
.
I don't know that Changshan vomits, but if you use it more, you will vomit
when you use it with licorice.
If the wine is soaked thoroughly, but with a little, every miracle is seen, and it is not spit out
.

There are still many historical materials I will not post one by one, write so much, in order to illustrate that in ancient times, traditional medicine treatment of malaria, traditional Chinese medicine Changshan is the key protagonist, according to the records of ancient doctors, Changshan antimalarial efficacy is outstanding, but it is not good
to cause vomiting.
Beginning in 1967, when Tu Youyou's team was researching antimalarial drugs, they also focused on Changshan at first, but Tu Youyou said that they could not overcome Changshan's vomiting side effects, so they gave up, and later set their sights on Artemisia, which is the Artemisia annua written by Gehong of the Eastern Jin Dynasty
.

There are also people in modern times who say that although there are many prescriptions for treating malaria in ancient traditional medicine, they are useless, which is very disrespectful to the facts, and we have relevant data to prove
it later.

We have been talking about Changshan for so long, so what does Changshan look like? Everyone must be very curious
.

In the past, scholars believed that Changshan was the root of the rutaceae plant, and after the field investigation of Guan Guangdi (1904-1952, Nanjing, Jiangsu), a Chinese pharmacocist, in 1942 he published an article saying that the Changshan recorded in the "Compendium of Materia Medica" is actually a saxifrage plant, which is a subshrub rich in Sichuan, because it resembles chicken bones, so it is also known as chicken bone Changshan
.
But there are many varieties of this medicine, including Bai Changshan, Huang Changshan, Tuchangshan and so on
.

Look, it looks like this:

(Image from China Plant Network)

In this case, Changshan is usually referred to in medicinal terms, referring to its roots, while Shu Qi refers to its fine leaves
.

In ancient China, Changshan played a big role
in the fight against malaria.

Many people say that traditional medicine is ineffective in treating malaria, and one example is malaria of the Kangxi Emperor during the Qing Dynasty
.
According to historical records, in 1693, at the age of 39, the Kangxi Emperor contracted malaria, and the doctors of the dynasty were helpless, and finally cured the malaria
by relying on the bark of the Westerners' cinchona tree (which was later extracted from this bark).
This incident should be true, because the French missionary Fan Guoliang also recorded it in his "Yanjing Opening Strategy"
.

Kangxi cold fever (malaria), the imperial doctor is helpless, presumably the imperial doctor is familiar with ancient medical books, will not know Changshan, Artemisia annua and other drugs, but at that time the treatment effect was indeed not good, the reason, it is difficult to analyze now, but it cannot be said that traditional medicine is ineffective
against malaria.
But at the same time, it can be seen that cinchona cream (made from the bark) is indeed a good treatment for malaria!

(4) Can Changshan cure malaria?

Whether the Kangxi Emperor used Changshan or not, we can't figure it out
.

Let's objectively evaluate the antimalarial effect
of Changshan.
After all, it has been more than 2,000 years since Zhang Zhongjing began to use Changshan, and this medicine has been used for more than
two thousand years.

Artemisinin developed by Tu Youyou's team is the main result of the "523 Plan" started by the state in 1967, when the state organized a large number of talents to concentrate on research on antimalarial drugs, for two reasons, one is that the United States and Vietnam were at war, the tropical rainforest in that part of Vietnam, mosquitoes were particularly numerous, malaria was very rampant at that time, and the attrition due to malaria was much more than the war injury, from this point of view, who can control malaria, who can grasp the initiative
in war 。 At that time, we and the Soviet Union secretly supported Vietnam, so the chairman and prime minister gave instructions to develop antimalarial drugs, and the meeting was held on May 23, so it was called Project
523.

In fact, there are already antimalarial drugs, such as quinine, chloroquine, when the malaria parasite resistance was already very serious, these drugs are not very effective, and new and more effective antimalarial drugs are urgently needed
.
The United States and China are working hard at the same time, and later it turns out that the Americans did not come up with good medicine, but our country got artemisinin
.
Until now, artemisinin and its derivatives have been a key drug for the treatment of malaria.

But in fact, before the 523 plan, before artemisinin came out, there was also a lot of malaria in our country, so medical scientists and pharmacists at that time were studying malaria treatment drugs
.

Changshan is one of
the most popular drugs.
After Tu Youyou and they received the 523 task, the drug they focused on at first was also the traditional Chinese medicine Changshan, and then they thought that they could not overcome the side effects of Changshan, so they turned to Artemisia.

Why was everyone interested in Tokoyama at that time? Because the malaria drug at that time was quinine, and during the Anti-Japanese War, the price of quinine and A'an equal drugs rose ridiculously, and the source was interrupted, when Japan also occupied the cinchona production area (Southeast Asia, especially the Indonesian island of Java), mastering more than 90% of the world's source of quinine, and it was
more difficult for us to import quinine.
China desperately needs its own antimalarial drugs
.
In order to solve the problem of domestic antimalarial drugs, many medical scientists and pharmacists who returned from studying in the West at that time began to study
Changshan ingredients.

The name of Changshan is like thunder, so many ancient books and traditional medicine scholars who introduce malaria treatment are praising Changshan, so it is reasonable
for everyone to study Changshan first.
And the prescription containing Changshan is effective in treating malaria, so can Changshan himself fight malaria?

In 1941, it was unknown whether Changshan alone could fight malaria
.

The first to contribute were Zhao Chengxi, Jiang Daqu, Feng Zhidong and others, who did research
on the chemical composition of Changshan.
Later, Zhang Changshao (1906-1967), Hu Chengru and others also made some achievements
in its pharmacology.
This can be regarded as using Western medical technology at that time to understand traditional Chinese medicine
.

It soon became clear that Tokoyama alone was effective
in treating malaria.
The Nationalist government at that time also supported this research and brought in experts from various fields, including Guan Guangdi (1904-1952, pharmacognosophist), Jiang Dawei (chemistry), Hu Chengru (pharmacology), Chen Fangzhi (clinician), etc
.

In 1943, Zhang Changshao was the first scholar to publish a paper on the treatment of malaria in traditional Chinese medicine Changshan ("Research on Domestic Antimalarial Drug Changshan", published in the Chinese Medical Journal
.
In the summer of 1942, they directly gave 13 malaria patients oral administration of Changshan, and found that Changshan defervesced at a similar rate as quinine, and the antimalarial effect was slightly slower than quinine
.

Since the French extracted quinine in 1820, quinine has been the gold standard for treating malaria for more than 100 years, and the cinchona cream that cured Kangxi was later quinine
.
More on that
later.

Zhang Changshao also did a lot of research, they extracted and crystallized 4 molecules from Changshan, two alkaloids, only Changshan alkali B has the effect
of treating malaria.
Their animal studies showed that Changshan could treat malaria, and its active ingredient was dozens of times
more effective than quinine.

In 1947, Zhao Chengga (gu), Zhang Changshao, Fu Yongfeng, Gao Yisheng and others published an article in China's "Science" magazine (English), identifying the molecule of Changshan alkali that has the effect of treating malaria as C16H19O3N3, which is soluble in water
.

In 1948, they published an article in the journal JACS, an important journal in the international chemical community, on the redefinition
of the molecular formula of Changshan alkali.
In the same year, Merck in the United States also reported on the alkaloids
they isolated from the traditional Chinese medicine Changshan in JACS.

Subsequent reports found that some alpines were 100 times more effective in treating malaria than quinine, and other bases were equivalent to quinine
.

Hu Chengru's research also found that after malaria patients took Changshan, the fever was reduced on 2-3 days, the malaria parasites in the peripheral blood were eliminated on the 4-5 days, and the malaria parasites in the bone marrow were all eliminated
on the 7-8 days.

Before this, there were also prescriptions for the treatment of malaria in the military camps of the National Government, and the main drug was also Changshan, and it was reported that tablets were first made at that time, and then injections were made to try 207 patients at the National Central Political School at that time, and 198 cases
were cured.
After treatment, 66 cases of three-day abuse, 36 cases of vicious abuse, and 1 case of four-day abuse were treated, all of which were effective
.
Therefore, they determined that Changshan was no less effective in curing malaria than quinine
.

The antimalarial miracle drug used since Zhang Zhongjing was finally scientifically verified at that time, and it did have antimalarial efficacy
.

Since Changshan's antimalarial effect is so bullish, is it going to soar into the sky? ?

As a result, everyone also knows that the most famous antimalarial drug is not Changshan, but artemisinin.

Why?

Because Changshan's side effects have been shown, it is easy to cause patients to vomit
violently.
Such a good drug, and the side effects are so prominent, it really makes people anxious
.
Researchers have done a lot to see if they can reduce or eliminate side effects
while retaining antimalarial efficacy.
Unfortunately, the results show that when the antimalarial effect is strong, the emetic effect is also strong
.
And when the emetic effect becomes weaker, the antimalarial effect is also very weak
.
As for the reason, it was not clear at the time, and it has not been clear
until now.
If one day we figure out the reason, such as knowing that the mechanism of antimalarial action and emetic effect is overlapping, then Changshan will never come out (from the perspective of modern medicine), but if we can find that the antimalarial effect and the emetic effect are separated, then there must be a way to take its essence and remove its waste, but the time has not come
.

But the above is the view
of modern medicine.

How does traditional medicine deal with the side effects of Changshan? Traditional medicine also knows that Changshan will produce emetic effects, so since Zhang Zhongjing, no one has used Changshan alone to treat malaria, all in combination with other drugs, such as Zhang Zhongjing's Shu Qizhan, which contains mica and keel, and the data records that they can be sedative and may cover up vomiting symptoms
.

In 1954, the General Association of the Chinese Medical Association held a symposium on academic exchanges between Chinese and Western medicine, and the content of the meeting was compiled into text and published in the "Chinese Journal of Pharmacy" of that year, and I roughly sorted out: the meeting first was Professor Lou Zhicen (1920-1995, a famous pharmacognosyist, Tu Youyou's teacher) issued a systematic report
on Changshan's medicine 。 Then there was Jiang Daqu (1905-1987, famous natural medicinal chemist) on the chemical aspects of Changshan, ancient book records, etc.
, he believed that Changshan with licorice or seven treasure scatter can make vomiting, but the reason is not clear, and he believes that as long as the manufacturing method, the right coordination, and the appropriate dosage, it will not vomit or less vomiting, and can cure malaria
.

Then some pharmacologists spoke, and everyone confirmed the efficacy
of Changshan in treating malaria.
Finally, Li Zhensanfu (son of the famous Chinese medicine practitioner Li Dingming, Li Zhensan was also a famous Chinese medicine practitioner at that time) spoke, he explained that the reason why Changshan in Chinese medicine does not vomit is because there are keels (sedation), oysters and licorice (can make acid), etc.
, emphasizing that Changshan
should be used together, not alone.

As a junior, it is quite interesting for me to look back at the written records of tens or hundreds of years ago, and sometimes quite shocking
.
The envoys of traditional medicine are actually similar
to the contraindications of drug matching in our modern medicine.
For example, if you use anti-inflammatory analgesics, afraid of causing gastric ulcers, you will use some drugs that inhibit stomach acid at the same time, Western medicine, Chinese medicine is also the same
.

In 1956, researchers from Chongqing First Hospital of Traditional Chinese Medicine published a paper saying that they treated 15 cases of vivax malaria and 9 cases of vicious abuse within 2 years, all of which were treated by Changshan, but in order to prevent vomiting, they added half summer
.
As a result, the effect was quite good, 24 patients recovered and were discharged from the hospital, and only one case vomited
.
However, due to the age, the reliability of this research data at that time is difficult to verify
.

But in general, the antimalarial effect of Changshan should be confirmed, at that time, in addition to Chinese use Changshan, foreigners also used Changshan, especially the United States, because Japan controlled the source of quinine, and the United States also needed to develop new antimalarial drugs
.

But at that time, Western medicine talked about single-drug use, at least quinine at that time was a single drug, this antimalarial drug extracted from the bark of the cinchona tree, was the special drug at that time, the gold standard
.
Quinine is a single agent with a definite
effect.
We wanted to find an alternative to quinine, and of course we wanted to use
it alone.

It's a pity that Changshan can't do single-drug use
.

So in 1967, when the chairman and prime minister ordered the 523 Plan, people left Changshan
behind.
In fact, the focus at the beginning was still here in Changshan, including Tu Youyou's research group, who was still Changshan dominated
when they screened drugs in the first round.
At that time, Tu Youyou's key task was to solve the side effects of Changshan alkali vomiting, which was recorded
in "The Legend of Tu Youyou".
But Tu Youyou tried a lot, but failed to succeed, so she had to give up
.

This led to the later artemisinin.

2.
How do Western countries treat malaria?

In Western medicine, the greatest contribution was the birth of quinine
.
Quinine was extracted by the French in 1820
.
Before this, Westerners took a long detour
.

Westerners have known malaria for thousands of years, and Hippocrates BC (460-370 BC) can already divide malaria into three types: alternate-day fever, daily fever, and three-day fever
.

(1) The appearance of quinine

At that time, there were many drugs for malaria in the West, but none of them were effective
.
There were four major outbreaks of malaria in ancient Roman history, when a secret recipe invented by an imperial physician, Andromachus (37-68 AD), had 57 flavors of medicine, among which was poisonous snake meat
.

Dioscorides (40-90 AD) was a pharmacologist who wrote the Medicinal Journal, and he advocated the use of fleas
in the treatment of malaria.
In his pharmaceutical works, there are also animal medicines, plant medicines, and mineral medicines, which are similar
to the "Shennong Materia Medica" compiled during the Western Han Dynasty.

By the time of Galen, Galen (129-199 AD) was about the same time as Zhang Zhongjing (150-215 AD) at the end of the Eastern Han Dynasty, and each of them was the best doctor
in the East and the West.
But objectively speaking, Zhang Zhongjing's achievements were greater than Galen's, Zhang Zhongjing proposed Shu Qishan to treat malaria at that time, while Galen still advocated bloodletting therapy and diarrheal therapy to treat malaria
.

Western bloodletting was created by Hippocrates in ancient Greece and further popularized by Galen
.
Bloodletting therapy was not only available in the West, but also in the East at that time, and traditional Chinese medicine also had bloodletting therapy, but the two were different
.
Western bloodletting therapy is to separate the veins, this way of bleeding is like unscrewing a faucet, the blood comes out, countless people have lost their lives, and it is said that the president of Washington (1732-1799) also died of excessive blood loss due to bloodletting therapy
.

Traditional Chinese medicine bloodletting therapy is to pierce the skin with a three-sided needle, generally targeting capillaries, bleeding will not be too much, rarely heard of traditional Chinese bloodletting therapy leading to excessive blood loss shock death
.

The ancient Roman Empire was later defeated and lost for many reasons, including malaria in the army
.
As we mentioned above, even in the 1970s, when the United States fought with Vietnam, there were still serious attritions due to malaria epidemics, not to mention the era when ancient Rome only had bloodletting therapy
.

The word malaria is derived from the Western medieval Italian: mala aria--- bad air
.
This view is somewhat similar to the traditional medicine in China that miasma causes malaria, right? This shows that human intelligence is connected, or it is the result of
communication.

In medieval Europe, due to the high status of the church, it oppressed the exploration of science and medicine, so until the 16th century, the level of science and technology and medicine in the West did not make much progress, basically standing still
.

How afraid were Westerners of malaria back then? Take a look at the following sets of data:

In 1569, Portugal sent an expedition to the Zambezi River valley, and most of the crew died of malaria
.
In 1777-1779, during the William Bolts expedition to Deguara Bay in Africa, 87%
of his crew died of malaria.
Later studies showed that the malaria mortality rate of the British Royal Navy who served in West Africa from 1817 to 1836 was as high as 66.
8%.

Westerners are also in dire need of drugs
that can treat malaria.

As early as the 15th century, the Italian Columbus discovered the New World, that is, the Americas
.
Soon people discovered a tree in South America in the New World, whose bark boiled into soup can cure malaria! It was first discovered by a Catholic missionary, who said in his report in 1663: In Loxa there is a strange tree, called a cold and hot tree, the bark of the tree is like cinnamon, take the bark into powder, soak it in water to make a drink, then malaria can be cured
.

At that time, Western cargo ships pulled back many things from South America, among which was this bark
.
It is called cinchona bark
.
But at that time Western medical scientists did not believe in this thing, did not admit it, did not use it
.
Only folk use it
.

In 1653, another doctor wrote a book called "The Hypocritical Antipyretic Pill of the Americas," saying that the new herbs of the Americas were not only ineffective, but also dangerous
.
The only formal treatment for malaria is bloodletting and laxative, which Galen advocated 1500 years ago
.

Although the official and imperial doctors did not recognize it, Catholic missionaries continued to use this imported herb to treat diseases despite the opposition of the medical community, and made countless
profits.

In 1666, the famous English physician Thomas Sydenham published the book "Malaria Treatment Act", he strongly opposed the use of cinchona bark to treat malaria, and British medical scientists at the time echoed his statement
.
He never tried one or two patients, and was completely philosophical and arbitrarily considered cinchona bark useless
.

It is an objective fact that the spread of cinchona in the West was opposed by Western traditional medical beliefs and the church, so the bark
of the cinchona tree was not widely used throughout 17th-century Europe.
Even King Charles II refused to treat his son
suffering from malaria with cinchona.

But in 1667, the Englishman Robert Tlabor cured the malaria of Louis XIV of France with cinchona bark, and was appointed as a pharmacist by King Charles II of England, and then the bark of the cinchona tree in South America was included in the official British pharmacopoeia
for the first time.

At the same time, in order to determine the composition of the cinchona bark, the plant exploration
of cinchona began in Europe.
It was not until 1816 that the Portuguese naval surgeon Dr.
Gomez first extracted the active ingredient of the bark and called it weak cinchona.

In 1820, two French chemists believed that there was a plant alkaloid similar to morphine and strychnine in the bark of the cinchona tree, and isolated two alkaloids of cinchona, quinine and cinchonine
.
In 1852, the French microbiologist Pasteur (1822-1895) proved that quinine is a levorotator
.
By 1854, the Germans had determined the molecular formula
for quinine.

For more than a hundred years, quinine has been the definitive drug
for malaria.

From the perspective of timeline, the reason why the West has made these advances is inseparable from their industrial development at that time, industry, science and technology, and technology have developed, and medical capabilities and theories have also improved
accordingly.
The separation of quinine in 1820 was a product
of the Industrial Revolution.

A specific drug for malaria has been found, so why is there malaria?

(2) What causes malaria?

Before this, the understanding of the West and the East was similar, malaria caused by miasma and bad air, but Westerners pried open the door to the field of microbiology in the 19th century, especially the French microbiology leader Pasteur (1822-1895) and the German Koch (1843-1910) made great contributions, they are pioneers in the field of microbiology, well-deserved
.

Around 1870, Pasteur and Koch's discoveries led to the belief that the cause of many diseases was
bacterial.
People have also found a lot of evidence that bacteria cause diseases, such as tuberculosis is caused by a bacillus, and plague is also caused by a bacillus
.

What about malaria?

In 1880, French physician Charles Louis Alphonse Laveran (long name) discovered the parasite while working in a military hospital while looking under a microscope at the blood smear of a patient who had just died of malaria! He named it Plasmodium, but the discovery was not taken seriously
at the time.
It wasn't until 1884 that it was believed that malaria was indeed caused by malaria parasites, not bacteria
.

In the following years, the researchers observed more information
.
By 1890, malaria was known to be caused by protozoan parasites that invaded and multiplied in red blood cells, and there were three parasites with specific periodicity and other characteristics that could correspond to vivax, malignant abuse, and four-day malaria
.

Without modern industry, scientific and technological progress, no microscope, no microbiology concept, it would be impossible to find malaria parasites, then we will remain in the era
of miasma and bad air causing malaria.
Of course, the absence of malaria parasites does not prevent people from finding specific drugs, such as the bark of cinchona in South America, such as Changshan in traditional Chinese medicine, cinchona is obviously better because it has fewer
side effects.

(3) Drug replacement

When did quinine enter China?

It is probably recorded at the end of the 17th century, around the time when the Kangxi Emperor contracted malaria
.
By 1765, quinine (cinchona) was also included in the
Compendium of Materia Medica.

Quinine has been on fire for a long time, at the end of the 19th century and the beginning of the 20th century, quinine is the best treatment of malaria, it has killing effect on the erythrocyte trophozoites of various malaria parasites, can control clinical symptoms
.
Even after World War II (1939-1945), quinine remained the antimalarial drug of choice
.

But as quinine became more widely used, resistance to malaria parasites gradually emerged
.
In the past, the treatment effect was very good, but then the effect is not very effective
.
People have had to seek new antimalarial drugs
.

The next drug to appear is chloroquine
.

Chloroquine first appeared in 1934 and was first synthesized
by Bayer in Germany.
The Germans had to come up with chloroquine because they were stimulated during World War I (1914-1918), when cinchona trees were in Southeast Asia and controlled by the British, and as soon as the war began, Germany's supply of quinine was cut off, so the Germans had to reassemble the drug
.

This brings us chloroquine
.

Chloroquine has improved efficacy and safety compared to quinine , so it has been replaced by quinine for the treatment
of malaria since 1940.
But resistance soon returned, and by around 1970, chloroquine's effectiveness had declined
significantly.

The period of the U.
S.
war with Vietnam (1961-1975) coincided with a period
when malaria faced no new drugs available.

The world continues to develop new drugs, the United States needs it, Vietnam needs it, and China needs it
.
Vietnam came to us, so we had the 523 plan
mentioned by the chairman and prime minister at the beginning of the article.

The 523 project mobilized a very large number of manpower and material resources, and Tu Youyou's team was only a small part of it, fortunately, they found artemisinin
.

During this period, the United States also screened hundreds of thousands of chemicals, but did not find particularly good antimalarial drugs
.
And Tu Youyou, they found Artemisia annua
from ancient books.
It was eventually isolated and purified from the plant Artemisia annua, a Chinese invention
that won the Nobel Prize in 2015.

As mentioned earlier, Tu Youyou (1930 to present) initially focused on the traditional Chinese medicine Changshan, but they could not overcome the side effects of Changshan, so they had to find other alternatives, and then Artemisia annua faced the eyes
.

The process of screening drugs was very difficult, Tu Youyou was only 39 years old when she received the task, and she should not have taken on this big task, but during the Cultural Revolution, many highly qualified seniors were pulled to criticize and even die, so Tu Youyou was in
danger.

From receiving the task in 1969 to the end of 1971, more than 2 years, Tu Youyou's antimalarial results of their Artemisia annua ether neutral extract came out, and the substance inhibited malaria parasites by 100%.

At that moment, the whole laboratory boiled
.

Then came various experiments, including animal tests, human trials (Tu Youyou tested them themselves), and clinical trials
.

In 1973, they conducted clinical trials of artemisininin, but the first appearance was unfavorable and the effect was not good
.
It was later found that there was a problem with the degree of drug disintegration, which affected the absorption
of the drug.
Tu Youyou and they decided to put artemisinin monomers directly into capsules
.
Finally, all 3 cases treated with artemisinin capsules were cured
.

In 1976, they published the results
of artemisinin research under the name of the Artemisinin Structure Research Collaboration.

In addition, in 1975, the research group modified the structure of artemisinin and obtained dihydroartemisinin, which was significantly enhanced and the efficacy was increased by 10 times
.
Later, artesunate, artemether, etc
.
were synthesized on the basis of artemisinin.

Since 2000, some 240 million people in the African region have benefited from artemisinin combination therapy each year, and some 1.
5 million people have avoided malaria deaths as a result of this treatment, and this Nobel Prize is well deserved
.
Of course, as Tu Youyou herself said, this award was not for her alone, but for all Chinese researchers at that time
.
For such a huge project, the power of one person is small, and the strength of the collective is the greatest
.
But it is undeniable that Tu Youyou has taken a step ahead in this field, and she is a pioneer
.

The advent of artemisinin has reborn malaria patients who have been resistant to drugs
.
And because of the problem of side effects, the encounter between Chinese medicine Changshan and artemisinin was lost
.
Is there a possibility that in the days to come, Changshan will emerge from the cocoon? Especially when artemisinin is also gradually facing drug resistance, we still need new drugs
.

3.
Write at the end

I looked at the infectious disease diagnosis data released by our National Center for Disease Control and Prevention in recent years, malaria has not broken out in our place for a long time, in recent years it has been about 1,000 cases every year, and in 2021 it was only more than 700 cases, and the deaths were in single digits, less than 1% of the mortality rate
.

But given that malaria has been going on for thousands of years (since records have been), it's a very old disease that may come back to ravaging at some point, so we still need to be vigilant
.

In the whole field of malaria, before the birth of modern medicine, traditional medicine was superior to Western countries
in treating malaria.
But quinine was indeed introduced by Western countries, and chloroquine was also synthesized in Western countries, which we have to admit
.
In terms of doing the antimalarial research of traditional Chinese medicine Changshan, the Americans were also doing it at that time, and we were also doing it, and our research was deeper than the Americans, and the Americans often cited the results of
Zhang Changshao and others at that time.
Finally, during the search for alternatives to quinine and chloroquine, artemisinin was also developed by us, which is also ahead of Western countries
.

Modern medicine was initiated by Western countries first, and we accept it, but it does not mean that we will always lag behind
.
With the improvement of our country's comprehensive strength and the development of science and technology and medical level, more and more modern medical achievements will be born in our land in the future, and by that time the so-called Western medicine will be renamed Eastern medicine? No, it's still called modern medicine
.

Modern medicine has done irreplaceable work in treating malaria, but has traditional medicine not helped at all? Before reading so many historical texts, many people may think that traditional medicine does not help to treat malaria, but after reading so many documents, who can erase the contribution of traditional medicine in history
.

That must be unobjective
.