Qinghaosu Project

Further progress along the road to integrating Chinese and Western medicine...

2010-02-15T23:59:00.000-08:00

Here's a paper from January 1979 reporting on the qinghaosu discovery. It was published in the Journal of New Medicine and Pharmacology. The headline reads:

在中西醫結合道路上乘勝前進－記青蒿素治疔瘧疾科研成果鑒定會

In other words:

Further progress along the road to integrating Chinese and Western medicine － Report of a meeting to appraise scientific research on qinghaosu as a cure for malaria

In fact this is an editorial introducing a series of articles on qinghaosu. It's the earliest mention I can find of qinghaosu as a cure for malaria (as I've discussed before, the 1977 paper doesn't mention the malaria part).

Changshan 常山

2008-08-13T16:38:00.000-07:00

Haven't posted here for ages, too busy watching the Olympics.

Well, here's an article that's been in the pipeline for ages but finally came out this month, on 8 August no less. It's about Dichroa febrifuga, or changshan 常山.

The article's DOI is: 10.1016/j.endeavour.2008.07.001. I'm afraid you'll need a subscription to read it in full.

Who should get the Nobel Prize?

2008-07-22T00:57:00.000-07:00

I thought I'd wrap up today's discussion with this provocative question, which I'll discuss in more detail in later posts.

My citation would be: For their analytical work leading to the discovery of artemisinin.

Based on the record of published scientific works, two Chinese scientists should get the prize. They are: Tu Youyou 屠呦呦 and Zhou Weishan 周維善.

But, as a Nobel can go to three people, I'd give the final third of the prize to Milutin Stefanovic. He may not have known the chemical could cure malaria, but he beat the Chinese to the printing press.

There's a precedent for this: Jerome Horwitz gets the credit for developing the anti-HIV drug AZT, even though he synthesized the chemical long before HIV came on the scene. Like Stefanovic, he could never have dreamed his chemical would later help millions of people.

Now let's pull these conclusions apart again and see where we get...

Chinese scientists and Western journals

2008-07-22T00:48:00.000-07:00

Why didn't the Chinese scientists publish the first qinghaosu report in a Western journal?

Well, Western journals aren't the be all and end all, but I think the reason here must be that to publish in a foreign journal in the 1970s would have been viewed as treason. Anyone who did it would have been labeled a capitalist-roader or some such and dealt with very harshly.

So it wasn't until March 1982 that Tu Youyou 屠呦呦 published a report on the discovery in a foreign (German) journal, Planta Medica.

Now, of course, there's no such reticence and Chinese scientists are positively encouraged to publish in high-impact foreign journals. Shows how times have changed.

Publishing delays

2008-07-22T00:18:00.000-07:00

Back to the Kremlinology...if the Chinese discovered qinghaosu in 1972, why didn't they publish anything until 1977?

The usual explanation is that this was the time of Chairman Mao's reign of terror, so there was no place to publish because the scientific journals had been closed down. In historical research, of course, just because things happen at the same time doesn't make one the cause of the other.

Go in a little closer and it gets more interesting. While the reason not to publish must surely have been the reign of terror, the reason they eventually did publish seems to have been good old academic rivalry. It's nice to know that survived in spite of everything.

According to Zhang Jianfang's account, the Chinese saw the suggestive footnote in Milutin Stefanovic's 1975 paper, and rushed to the presses.

If we fast forward a bit, the other question that bugs me is the long lead times between the early papers being sent to the journals and the papers actually getting published:

1. Structure and reactions of arteannuin. Submitted: 3 April 1978. Published May 1979.
2. Crystal structure and absolute configuration of qinghaosu. Submitted: 9 May 1978. Published: March 1980

Perhaps there was a long backlog of papers because the journals had been closed down for a bit? The editor might therefore have worked through, methodically publishing submissions in chronological order, according to when they had been received.

Scrupulously fair no doubt, but surely any journal editor worth his or her salt would have realized the qinghaosu papers were dynamite, and rushed them to the presses?

Qinghaosu heads West

2008-07-13T16:25:00.000-07:00

I'm going to fast forward to the early 1980s and the first reports about qinghaosu published in Western scientific journals. For the moment I'm ignoring the large numbers of scientific papers published in Chinese journals that came out at the same time, which you can easily find by searching PubMed (don't worry, I'll return to these later).

To begin, here are some highlights:

March 1982
Tu Youyou 屠呦呦 is the first Chinese scientist to publish a qinghaosu article in a Western scientific journal.
Tu You-you, Ni Mu-yun, Zhong Yu-rong, Li Lan-na, Cui Shu-lian, Zhang Mu-qun, Wang Xiu-zhen, Ji Zheng and Liang Xiao-tian. (1982) Studies on the constituents of Artemisia annua Part II*. Planta Medica 44:143-145.
(*Part I is Structure and reactions of arteannuin, published May 1979.)

13 March 1982
Veteran malariologist Leonard Bruce-Chwatt publishes a short letter describing qinghaosu.
Bruce-Chwatt, L.J. (1982) Qinghaosu: a new antimalarial. British Medical Journal (Clinical Research Edition) 284:767-768.

7 August 1982
Keith Arnold is the first Western scientist to publish a primary research paper on qinghaosu (in collaboration with Li Guoqiao 李國橋).
Jiang, J.B., Li, G.Q., Guo, X.B., Kong, Y.C. and Arnold, K. (1982) Antimalarial activity of mefloquine and qinghaosu. Lancet 2:285-288.

1983
Publication of two papers from a collaboration between Gu Haoming 顧浩明 (Shanghai Institute of Materia Medica); Li Zelin 李澤琳 (Institute of Chinese Materia Medica, Beijing); and David Warhurst and Wallace Peters (London School of Hygiene and Tropical Medicine).
Gu, H.M., Warhurst, D.C. and Peters, W. (1983) Rapid action of qinghaosu and related drugs on incorporation of [3H]isoleucine by Plasmodium falciparum in vitro. Biochemical Pharmacology 32:2463-2466.
Li, Z.L., Gu, H.M., Warhurst, D.C. and Peters, W. (1983) Effects of qinghaosu and related compounds on incorporation of [G-3H] hypoxanthine by Plasmodium falciparum in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 77:522-523.

July 1984
The first entirely Western study of qinghaosu, conducted by Daniel Klayman at the Walter Reed Army Institute of Research in the USA.
Klayman, D.L., Lin, A.J., Acton, N., Scovill, J.P., Hoch, J.M., Milhous, W.K., Theoharides, A.D. and Dobek, A.S. (1984) Isolation of artemisinin (qinghaosu) from Artemisia annua growing in the United States. Journal of Natural Products 47:715-717.

31 May 1985
Daniel Klayman finally brings the discovery out of the shadows and into the scientific mainstream when he publishes his famous qinghaosu review in Science.
Klayman, D.L. (1985) Qinghaosu (artemisinin): an antimalarial drug from China. Science 228:1049-1055.

Citations in the early scientific papers

2008-06-27T18:13:00.000-07:00

Now we are in the realms of Kremlinology, but lets proceed anyway to analyse the citations in the early Chinese papers.

What puzzles me is the inconsistency of citation in the following papers (papers that I've already mentioned on this blog):

1. Structure and reactions of arteannuin, published May 1979
2. Antimalaria studies on qinghaosu, published December 1979
3. Crystal structure and absolute configuration of qinghaosu, pubished March 1980

What's curious is that the 1980 paper doesn't cite the 1979 papers (see picture for list of references in the 1980 paper), nor does the December 1979 paper cite the May 1979 paper. Most obviously, why doesn't the 1980 paper cite the May 1979 paper, as both are on similar topics?

What could be the explanation for these inconsistencies? It seems to me there are two possibilities.

First possibility: the authors of the 1980 paper - and we don't know their names because the paper went out under an anonymous byline of the Institute of Biophysics - didn't know about Tu Youyou 屠呦呦 and Zhou Weishan 周維善 and the other authors of the May 1979 paper.

Second possibility: we are in much darker waters, where the authors of the 1980 paper did know about Tu and Zhou but deliberately avoided citing them.

Either way, it would tend to suggest that, far from being a highly coordinated project (as it is often thought to have been), it was a bit disorganized, with different (rival?) groups publishing their results pretty much independently.

青蒿情黃花香

2008-06-27T17:50:00.000-07:00

A very interesting blog called 青蒿情黃花香, in other words, "Qinghao - news and views on the yellow flower", referred to me. (For those who don't know, Artemisia annua sports rather pretty yellow blooms.)

It's nice to know a Chinese person is reading my blog, and what's more, is interested in the history of qinghaosu and what people outside China think about the discovery.

青蒿情黃花香 says that my blog is "a mixture of fact and speculation", so lets get on with the facts and speculation...

Li Shizhen 李時珍

2008-06-09T00:23:00.000-07:00

My final stop on this tour of references in the 1979 Chinese Medical Journal paper is Li Shizhen 李時珍, author of the famous Ben Cao Gang Mu. He lived in Qizhou 蘄州, about 60 miles from Wuhan. I visited the town last year to see the Li Shizhen museum.

Qizhou is very much China B, to use China-watcher Nicholas Bequelin's terminology. The old town was razed to the ground by Red Guards during the Cultural Revolution - and what replaced it isn't pretty. The streets aren't paved and there's rubbish everywhere.

There's a run-down looking Li Shizhen hospital built in a pastiche Ming dynasty style. When new, it must have been quite something. But when I visited it was deserted and very grubby. It was a travesty of what a hospital should be - all the more ironic given the Li Shizhen connection. Next door there was an overgrown football stadium that hosted a forlorn medicinal herb market.

On a dismal December day it was extraordinarily depressing even for a casual day-tripper like me.

There obviously had been some investment once, but it had dried up. These days I doubt China's metropolitan central government is going to lift a finger to help. But I think the companies making money out of artemisinin should be able to chip in a dollar or two to help the town of Qizhou.

There is always beauty, no matter how bleak. Around the town there are reed-lined lakes. Men and women wade around in the water grubbing for lotus roots that they boil with pork to make a wholesome stew. Their feet must be frozen in the icy water and their hands swollen and chapped, but I tasted some of the stew in what seemed to be the town's only functioning restaurant and it tasted good.

I digress: there is large museum dedicated to the town's most famous son, Li Shizhen. It was built on the outskirts in the 1980s.

Ge Hong and Mount Luofu 羅浮山

2008-05-31T01:37:00.000-07:00

The story goes that in the year 331, Ge Hong retired to Mount Luofu 羅浮山 where he lived until his death.

In my ongoing quest to track down every place even remotely connected with qinghaosu, I made a stop at Mount Luofu last year.

It's a couple of hours drive from Guangzhou 廣州, deep in the countryside. When I visited there was a temple, a few souvenir stalls, a fairground-style shooting range - and a stand of Artemisia annua.

The artemisinin maker Artepharm has even sponsored a few plaques and information boards that record Ge Hong's legendary connection with the drug. They are clustered around the A. annua plants.

I took this photo when I visited. The banner reads: 青蒿抗瘧尋源羅浮山. This means
something like: Mount Luofu - the birthplace of antimalarial qinghao.

In 2007, a Chinese journalist wrote an article about Mount Luofu, Ge Hong and artemisinin that is misleading, flippant and, frankly, insulting to the millions who die from malaria every year, so I hesitate to point you in that direction, but you can read it on the Reuters web site.

Zhou Hou Bei Ji Fang 肘後備急方

2008-05-22T15:20:00.000-07:00

This is Ge Hong's book, Zhou Hou Bei Ji Fang 肘後備急方. The title is usually translated as Handy Therapies for Emergencies.

I reproduce the critical page from my edition of the book, published by Tianjin Science and Technology Press 天津科學技術出版社. Unfortunately I don't think this book has ever been translated into English.

The page starts:

Volume three.
Number 16. Prescriptions for treating various types of nüe with chill and fever.
Prescriptions to treat nüe disease.

Then we get a list of about 20 or so prescriptions. Prescription number two reads, in Elisabeth Hsu's translation:

Another recipe. Take a bunch of qing hao and two sheng of water for soaking it, wring it out to obtain the juice and ingest it in its entirety.

In the first instance, I think there are two points worth making.

First, the recipes are to treat nüe 瘧. In modern Chinese this character simply means malaria, but in Ge Hong's time, it must have been a less precise term. That said, the mention of chill and fever pins it down more precisely as these are typical malaria symptoms we know today.

The second point is more trivial: according to Elisabeth Hsu, two sheng was about 400 mL - about a cup of water - not one litre as is usually stated.

I followed Ge Hong's recipe using a handful of fresh Artemisia annua leaves from a plant I grew in my back garden. Squeezing, or wringing out, the leaves in the water produced a pale green-coloured liquid that had a very subtle herbal flavour (a bit like camphor, but not unpleasant). But it was so weak I can't believe it would have any effect against a serious malaria infection.

Ge Hong 葛洪

2008-05-19T18:23:00.000-07:00

My next stop is Ge Hong 葛洪, or reference number three in the Chinese Medical Journal paper.

While the Ma Wang Dui manuscript is merely a historical curiosity, this reference is said to be directly related to the discovery.

I've scanned an excerpt from an article in the magazine China Reconstructs - now known as China Today - that was published in August 1979 and throws a little light on this part of the story.

The sweet wormwood mentioned must be qinghao. In other words: Artemisia annua.

In those days China Reconstructs was the main English-language organ of the Chinese Communist Party, and it was edited by a Western journalist called Israel Epstein who had defected to China in the 1950s and was actually a Chinese citizen.

Incidentally, the paragraph excerpted here comes from an article written by Ximen Lusha. It doesn't sound like a Chinese name, but Hubert Wang from the English Department at China Today told me that Ximen Lusha was a Chinese woman. I don't have the characters for her name, so it's really difficult to find out anything about her, or even if she's still alive. I wonder if there's anyone out there on the Web who could tell us more?

Medical manuscripts from Ma Wang Dui 馬王堆

2008-05-19T17:15:00.000-07:00

I just stumbled across Donald Harper's translation of the medical manuscripts, so here is his rendering of the entry on qinghao. It doesn't make for pretty reading:

Female Hemorrhoid

Recipe for (female hemorrhoids) that are one cun inside the anus, are shaped like a cow louse, burst and ooze blood when defecating, and face upward when not defecating.

Take five dou of urine. Use it to boil two large handfuls of qinghao, seven fuyu (golden carp) the size of a hand, a six cun piece of smithed gui (cinnamon), and two nodules of dried jiang (ginger).

Let it bubble ten times. Remove (the liquid) and put it in a water jar. Bury (the jar) under a sitting mat, make an opening in it, and fumigate the hemorrhoids. Stop when the medicine becomes cold. Fumigate thrice a day...

Ma Wang Dui 馬王堆

2008-05-18T23:47:00.000-07:00

Well, time for a detour into the ancient past, and reference number one in the Chinese Medical Journal paper. This refers to the medical manuscripts excavated from Ma Wang Dui 馬王堆 at Changsha 長沙 in southern China.

I used to have a copy of the manuscripts, or rather Donald Harper's English translation in his book Early Chinese Medical Literature, but I seem to have lost it somewhere.

If I remember rightly, there was a lot of discussion about herbs that could improve a man's sexual performance, and the best sexual positions for "approaching the inner chamber". All in all it was a rather racy read for something that's nearly two thousand years old.

But the point here is that it mentions a herb called qinghao 青蒿, not as a sex aid, but to treat hemorrhoids - the manuscript advises the reader to expose his bum over a steaming concoction of the herb.

It's the first mention of qinghao in history, and a rather undignified one at that. But the herb is said to have been Artemisia annua. A stretch of the imagination perhaps, but not completely implausible.

Curious about the tomb itself, I visited 長沙. The first must-see is the Hunan Provincial Museum, which houses the artefacts from the tomb.

The second, more obscure, tourist attraction is of course the site of the tomb itself, ironically in the grounds of a hospital. Here's a picture I took of the hospital's entrance. The sign reads: 湖南省老年醫院, 湖南省馬王堆療醫院. In other words: Hunan Geriatric Hospital, Hunan Ma Wang Dui Hospital.

The Chinese discovered the tomb in 1971 during construction of underground wards, although having now been to the hospital myself, there weren't any underground wards that I could see.

The name Ma Wang Dui literally means King Ma's Mound, but actually the tomb contained a Chinese nobleman, his wife and son and a thousand-and-one perfectly preserved artefacts. They were all sealed in giant wooden coffins that protected them from the elements.

Among the artefacts, which included musical instruments, clothes, statues and furniture, the archeologists found manuscripts written in black ink on strips of bamboo and on sheets of silk, and that is where the characters 青蒿 appear for the first time.

Discussion of the 1979 paper in the Chinese Medical Journal

2008-05-18T15:54:00.000-07:00

Here I'm continuing my discussion of the famous 1979 Chinese Medical Journal paper, in particular the references on the paper.

The first thing that strikes me: although the paper is entirely in English, the authors decided to keep the reference list in Chinese. To my mind, a very strange decision as the paper's intended audience, the international scientific community, can't (as a general rule) read Chinese.

The second thing to note is that references 1-8 are 1950s reprints of old Chinese medical books, or materia medica.

At the time, Chairman Mao made a big show of promoting Chinese medicine, so Chinese publishers made a big effort to revive the old books by reprinting them. This, by the way, is an interesting story in itself, and it's been documented by the historian Kim Taylor in her book Chinese Medicine in Early Communist China, 1945-63.

References 1-8 give me an excuse to wander off into an incense-filled world of temples, scholars and Daoists, but before I do that, I want to tackle the more prosaic issues brought up by references 9-10.

The question here is: why don't the authors cite the 1979 article by 屠呦呦 and 周維善? Could it be they were not aware of this article - or did they deliberately avoid citing it?

Reference 9 is, of course, the 1977 paper in 科學通報.

Reference 10 I think must refer to a paper submitted to the journal Scientia Sinica 中國科學 on 9 May 1978 and published in English in March 1980. I reproduce the original title and abstract of that paper here, but I'll discuss it at a later date because I'm trying to keep a roughly chronological order to these blog entries, at least in the first instance.

The Chinese Medical Journal paper, 1979

2008-05-18T01:05:00.000-07:00

This must be about the most famous artemisinin paper ever. It really brought the artemisinin discovery to the world's attention, not least because it was written in English.

Professor Nick White, who pioneered the clinical use of artemisinin in Thailand, waxes lyrical about when he first saw the paper.

The Chinese published it in the December 1979 issue of the Chinese Medical Journal - again under an anonymous authorship, so we have no idea who wrote it.

I'm not going to reproduce the paper here; what interests me most are the paper's references, published in Chinese. So before I get on with any more discussion, I want to post up a translation.

1. Ma Wang Dui Han Tomb Study Group. Ma Wang Dui Han Tomb Excavation Medical Book Translation [Explanation?] (2nd). Wu Shi Er Bing Fang [Fifty-two Prescriptions]. Report 9:42, 1975.

2. Wei Dynasty. Wu Pu. Shen Nong Ben Cao Jing [The Divine Farmer's Materia Medica]. Volume 3. Page 103. Shang Wu Publisher, 1955.

3. Jin Dynasty. Ge Hong. Zhou Hou Bei Ji Fang [Handy Therapies for Emergencies]. Volume 3. Page 44. Ren Min Wei Sheng Publisher, 1956.

4. Sheng Ji Zong Lu [General Record Commissioned by Sagely Benefaction]. Volume 36. Page 724. Ren Min Wei Sheng Publisher, 1962.

5. Yuan Dynasty. Zhu Zhen Xiang. Dan Xi Xin Fa [The Heart and Essence of Dan-Xi's Methods of Treatment?]. Volume 4. Page 47. Shanghai Science and Technology Publisher, [1955?].

6. Ming Dynasty. Zhu Su. Pu Ji Fang [Prescriptions for Universal Benefaction]. Volume 197. Page 2755. Ren Min Wei Sheng Publisher, 1955.

7. Ming Dynasty. Li Shizhen. Ben Cao Gang Mu [The Great Pharmacopoeia]. Volume 15. Page 13. Shang Wu Book Publisher, 1955.

8. Qing Dynasty. Wu Ju Tong. Wen Bing Tiao Bian [Systematic Discourse on Warm Diseases?]. Volume 2. Page 169. Chinese Medicine [Publisher?], 1955.

9. Coordinating Group for Research on the Structure of Qinghaosu. A new type of sesquiterpene lactone - qinghaosu. Ke Xue Tong Bao 22:142, 1977.

10. China Science Biophysics Institute, Qinghao Structure Group. Absolute crystal structure of qinghaosu. Waiting to be published.

A Detailed Chronological Record of Project 523 and the Discovery and Development of Qinghaosu (Artemisinin)

2008-05-08T17:36:00.000-07:00

I've been meaning to post this up for some time, so it's a bit out of date. This is the book published in 2006 that gives a historical overview of the artemisinin discovery, from the Chinese perspective.

Here's the citation:
張劍方. 遲到的報告五二三項目與青蒿素研發紀實. 羊城晚報出版社, 2006.
Zhang Jianfang. A Detailed Chronological Record of Project 523 and the Discovery and Development of Qinghaosu (Artemisinin). Yangcheng Evening News Publisher, 2006.

Zhang Jianfang, who edited the volume, directed the artermisinin project back in the 1960s, and the book is a good start on mapping the details of the discovery. But I think it's vital the Chinese make even greater efforts to record the oral history of the discovery - and do it now, rather than waiting. If I understand it right, one of the leading project workers from the 1960s/70s, Professor Zhou Keding 周克鼎, sadly died of old age a few months ago.

Another unfortunate problem is that the book isn't available online, and of course it's in Chinese. There is an English translation, but a Chinese publisher apparently backed out of printing it because he couldn't read English and worried the translation might say something that would upset the censor.

Dr Keith Arnold - the first Western scientist to hear about artemisinin when he visited Guangzhou in 1979 - kindly gave me the unpublished English version of the first two chapters back in 2007, but as far as I know the full translation hasn't yet found a publisher. Arnold's wife, Dr Muoi Arnold, did the translation.

There was talk at the time of posting the English version online, but I don't think this has happened. The British Medical Journal commissioned me to write an article on the book, but in the end they didn't publish it, so the story sank without trace.

For those wanting to know more, the only online information I can find on the book is the publisher's site, Yangcheng Evening News. I do wonder if you can order the book from Chinese Amazon, or similar (I haven't checked because I already own a copy).

Artemisinin, 1979

2008-05-06T03:02:00.000-07:00

This is the big year - 1979 - when the Chinese announce their artemisinin discovery in detail, two years after the first brief report. And it starts in May 1979, exactly 29 years ago this month, with a paper in the journal Hua Xue Xue Bao 化學學報. It's quite a long paper, 10+ pages, so I only reproduce the first page.

There's a lot to discuss here, but I first want to point out that the authors submitted the article to the journal on 3 April 1978, a full year before it was actually published.

For the first time we have some actual Chinese names. They are: Liu Jing-ming, Ni Mu-yun, Fan Ju-fen and Tu You-you, at the Institute of Chinese Materia Medica, Academy of Chinese Traditional Medicine, Peking; and Wu Zhao-hua, Wu Yu-lin and Chou Wei-shan, at the Institute of Organic Chemistry, Academia Sinica, Shanghai. Here I'm using the original English transliterations that accompanied the paper back in 1979 (it was before the widespread use of pinyin).

So we can clearly say who the key players were. According to the standard format, where the leaders of the research go last in the lists of authors, they are: Tu You-you 屠呦呦 and Chou Wei-shan 周維善. Mark those names well, because it gets more complicated. I'm going to discuss these complications in later posts.

Into China in search of Artemisinin 青蒿素

2008-05-04T18:33:00.000-07:00

We finally reach China, after beginning our journey in Belgrade. This is the first scientific article to report on Chinese artemisinin research. It appeared in the journal Ke Xue Tong Bao 科學通報 in 1977. According to a footnote printed at the bottom of the article itself, it was received at the journal on 20 February 1976.

It's a one page article and I reproduce a picture of the page here. The title reads: "A new type of sesquiterpene lactone - qinghaosu". The body texts starts with the words: "We isolated a type of crystal from Artemisia annua. It was given the name qinghaosu." Then we get a mass of technical details about melting points and infrared, proton and C-13 spectra, that, frankly, would only be comprehensible to a physical chemist and certainly aren't comprehensible to me.

But I think a few things are still worth noting. First, the Chinese refer to the molecule as qinghaosu 青蒿素. They abandon Stefanovic's "arteannuin A" terminology, and they also don't cite Stefanovic, or anyone else, because the paper lacks references.

Second, the paper goes out under an anoymous authorship, namely: "Coordinating Group for Research on the Structure of Qinghaosu". There's no information whatsoever about who might be part of this group, or even how many members there are.

Third, unlike Stefanovic, I think the Chinese get the chemical structure correct. I would, however, appreciate the views of a proper organic chemist on this conclusion.

But there is something more. Unbelievably, they don't mention malaria! Essentially, they avoid telling us just about the most interesting feature of the molecule: that it can cure malaria. This is such a curious omission that it raises all sorts of interesting questions that I will discuss in future posts.

Milutin Stefanovic and Artemisinin 青蒿素

2008-05-03T03:23:00.000-07:00

The next artemisinin reference I've found came out in 1975. In a short note submitted to the journal Phytochemistry on 6 February 1975 and published later that year, Stefanovic mentions a chemical he calls "arteannuin A". The note itself is, unfortunately, not about arteannuin A, but another, unrelated, chemical found in Artemisia annua.

But what's interesting is the reference attached to the arteannuin A, which I've scanned here. The first part cites the New Delhi abstract. The second part is more tantalizing: "full experimental data will be published soon." Alas, Stefanovic never published that data. In my view, a mistake of historic proportions because of course "arteannuin A" is artemisinin.

Artemisinin 青蒿素

2008-05-02T18:58:00.000-07:00

The blockbuster antimalarial drug artemisinin is one of my favourite topics because, as many of you will know, it was discovered in China in the 1970s. Well that's the story anyway.

The thing is there's so little documentation, and a lot of things that get said about the discovery turn out to be untrue, or at least not strictly true. So I've made an effort to find the original scientific papers on the drug so that we can begin to disentangle fact from fiction. I'm going to be posting these up over the next few months, as a first step towards putting the jigsaw together.

The first one is a real bombshell. The drug was not discovered in China at all, but by a Yugoslav chemist called Milutin Stefanovic. His name has been in the frame for a few years, but no one seems to have bothered chasing him up, so that's what I did. He's now a very old man in his 80s who lives in retirement in Belgrade, and unfortunately I couldn't speak to him in person.

But a former student of his, Bogdan Solaja, who is now a Professor of Chemistry at the University of Belgrade, kindly sent me an original scientific abstract, published in 1972, which I think confirms that Stefanovic discovered the drug before the Chinese. Stefanovic didn't know it could cure malaria, and I think he probably studied it because of Soviet claims about the antibacterial properties of a herb called Artemisia annua. A. annua contains artemisinin in quite large amounts.

But that's not the point here, so I give you a scanned version of the original abstract, presented at the Eighth International Symposium on the Chemistry of Natural Products, held in New Delhi, India, 6-12 February 1972.

Stefanovic got the chemical structure a little wrong, but in my opinion he's describing artemisinin. How this relates to the Chinese discovery of the drug, well that's something I'll be discussing over the coming months.