Saturday, June 16, 2012

Biomedical traditional Chinese medicine (BTCM)

Artemisia annua. Source: Jorge Ferreira.
In this post I want to suggest some connections between Chinese herbal medicine and biomedicine, and highlight the existence of a hybrid discipline that one might call 'biomedical traditional Chinese medicine' (BTCM, I think more narrow in my meaning than Elisabeth Hsu's 'Chinese medicine and pharmacotherapy', but please c.f.).

Let's begin with the conventional arguments on Chinese herbal medicine and its relationship to science. The first is East vs. West - polar opposites. The cultural critique of this dichotomy follows, i.e., the idea that both East and West are essentialist constructs, faulty to the core, one, by analogy to Edward Said, the product of Orientalism (one might call its opposite 'Occidentalism', pace Chen Xiaomei). Scholars such as Sean Hsiang-lin Lei and Vincanne Adams move around the edges of this subject.

Another line of commentary, developed out of the work of Kim Taylor and Elisabeth Hsu, runs along historiographical tracks laid down by Eric Hobsbawm, namely, that Chinese Traditional Medicine (TCM) was 'invented' in Maoist China and therefore is not 'traditional' at all. This revelation is taken several steps further in the writing of the polemicist Edzard Ernst, who condemns TCM as a sham and draws a parallel to the Nazis' fixation  with homeopathy in the 1930s.

All great analyses produced by others who know far more than me - and represented rather briefly and crudely in the above summary (and apologies for that). I want to take a different approach . What I am interested in describing is the modern interpenetration of ('Western') biomedicine and Chinese herbal medicine to the extent that the two have become indistinguishable components of a new form of biomedicine we see today.

Hsu makes a point about the indivisibility of the 'two medicines' in a material sense, describing how Chinese medical cures sold in East Africa combine ostensibly Western preparations such as paracetamol with ostensibly Chinese cures based around herbs - in the same pill (here, pay wall). This represents a material form of alternative modernity.

What of this interpenetration, cast in institutional and scientific terms, beyond the materiality of the cure itself? After all, modern biomedical research is not about cures per se, but the evocation of future medical utility in the basic biological sciences.

Let's tackle this problem in two parts. In the first, I want to map out what contemporary biomedical TCM (BTCM) might be. Characteristics thus established, I will then describe how it might have arisen in conjunction with contemporary biomedicine.
Biomedical Traditional Chinese Medicine (BTCM)
Let us consider the ways in which BTCM is promoted, studied and described, using as our starting point a Nature supplement dedicated to the subject. (The WHO has more recently published a similar piece, available here.)

The first point is the tendency in this new discipline to describe 'modern medicine' as highly reductionist. Thus we learn that 'modern medicine, imported [into China] from the West, consists of chemically purified compounds that have been discovered through scientific investigation and tested in controlled clinical trials' and that 'for decades, European and US regulatory agencies held the view that a drug must be either a highly purified or synthetic agent.'

The Nature commentary probably sounds a little simplistic for anyone with a passing acquaintance with medical history - a history in which American, European and Chinese scientists reveal themselves to be (actually) rather sophisticated thinkers about the nature of health, medicines and healing. The point is that we have a biomedical straw-man (of weirdly simplistic orthodoxy) against which the more sophisticated forces of BTCM can react.

The second hallmark of BTCM is technological boosterism - in other words, that herbal medicine is a 'treasure house' of (now) lucrative cures waiting to be uncovered (to subvert Chairman Mao's comment on the matter, but not in the sense he meant it).

What is BTCM, as a laboratory practice? In an interesting article on South Korean research on herbal medicines, Jongyoung Kim described how herbal screening work was boring, creativity-sapping and ultimately soul-destroying. Junior investigators had to plow through organic extractions and bio-assays on different herbs, producing identikit data and dull, identikit papers.

This picture of labor practice will hardly surprise anyone who has visited a biomedical laboratory recently. It is the kind of repetitive work that requires no brain input and therefore can (when funds and technology allow) be readily outsourced or automated, or both.

There is a synergy between the practices of BTCM and those most biomedical/neo-liberal constructs, 'systems biology' and 'personalized medicine' - but let's leave that for another day.
The co-construction of herbal medicine and biomedical science?
In any discussion on BTCM, attention invariably alights on qinghaosu/artemisinin as proof of concept. The drug, a sequiterpene lactone, was extracted from a herb traditionally used in Chinese medicine to treat fever. The special significance of the drug may not be that it works as a biomedicine (anti-malarial drugs are, after all, ten-a-penny), but because it articulates a larger project of biomedical reform, a story in which China plays a central part.

Typically, the artemisinin story is told along the lines of conventional pharmacognosy. Accordingly, credit for the work of discovering the drug falls to Tu Youyou, the Chinese scientist who isolated the active principle. However, this telling of the story - of pharmacognosy sui generis - misses out the broader significance of the drug in framing the post-1980 construction of BTCM - and the parallel story of its interpenetration with biomedicine.

It's worth noting in passing the coincidence between the contemporary globalization of Chinese medicine and equivalent changes in the practice of biological research (re-configured as 'biomedicine') that occured in the late 1970s and afterwards.This is probably nothing more than a coincidence.

Two points. The first as follows. Even casual acquaintance with the story of artemisinin reveals the importance of intellectual property issues in negotiations between the Chinese government on one side, and the World Health Organization on the other. The Chinese, by their own admission, were obsessed with safeguarding the intellectual property around what was actually a rather run-of-the-mill medical discovery.

Indeed, the post-1980 history of the drug was shaped by disputes over who owned what and who had the right to make the drug. Looking back, this seems all perfectly understandable, but in the context of the time, it is rather curious. Here was what amounted to government-backed research, conducted in academic centers, being pushed into a commercial context.

Of course, as it turned out, there was no way for the Chinese scientists to protect their IP, simply because such a legal concept did not exist in China in the years when the discovery was made (private property of any sort being anathema in a Communist regime). The important thing is that the Chinese wanted to protect their IP, even if such a move was deemed legally impossible.

What is interesting is that this is a time when, even in America, the various instruments of contemporary biomedical IP, such as routine patenting of unproven or non-commercial discoveries, the use of material transfer agreements, etc., were still in their infancy. Thus, I want to suggest that the evolving connections between academic research and intellectual property were made in important ways through the medium of artemisinin - ways of which we have zero understanding.

A second point. Chinese qinghaosu factories, which were designed to make the drug, notably the Guilin and Kunming plants, were deemed to be producing below GMP standards and therefore the drugs they made were not suitable to export, according to inspectors from the US Food and Drug Administration. By September 1982, Chinese manufacture for export had been effectively thwarted. But the point for the Chinese, at least in the only account we have of the process, was to learn how to implement GMP standards in Chinese pharmaceutical factories (see the Project 523 account, Zhang, et al., pp. 78-79).

The willing transfer of knowledge from American experts to China is a familiar scenario from that era - but a possibly critical role of artemisinin in the reform of the Chinese pharmaceutical trade needs to be investigated. In other words, what was the role of artemisinin in the broader story of the Chinese drug trade?

I want to suggest that, while also a medicine derived from traditional practices, artemisinin was one of the means by which the Chinese pharmaceutical trade modernized (and perhaps, also, American standards were revised and qualified). In this case, the supposed opposites of herbal medicine and biomedicine were constitutionally inseparable.
The pharmaceutical industry as a herbal hybrid?
Source: Dartford Town Archive
Synthetics were not the be-all-and-end-all of the modern drug trade, even in the West. Investigation (and production) of herbal medicines was in fact stock-in-trade of at least the British pharmaceutical industry. Wellcome, for example, operated a materia medica farm at Dartford in Kent in the 1930s, where the company grew foxgloves for the production of the heart drug digitalis (see the picture above - and note the factory in the background).

We can take the story into the post-WWII period, to the 1950s - the chemical conglomerate Fisons set up a plantation in Nicaragua to grow Ipecacuanha root (source of emetine) [see: 'The End of a Chapter', a printed history of Whiffen and Sons, Ltd., by Rupert S. Law, B/WHF/245, 1972].

My point here is that these fragments of a yet-to-be-written history show that herbal extracts continued to have commercial value in the pharmaceutical industry in the mid-twentieth century. Furthermore, while herbal medicines probably declined in value as a source of revenue for firms after the 1950s (it was cheaper to make drugs from coal tar and petroleum, rather than exotic herbs), the trade did not give up on them entirely.

Two achievements of post-WWII commercial research attributable in part to herbal medicines were the development of 'The Pill' by the firm Syntex (story told here); and lesser-known, Fisons' work on the anti-asthmatic drug sodium cromoglycate, or Intal.

As this intriguing film shows (above), in the 1960s, a scientist called Roger Altounyan initiated research on khella tea, a traditional middle-eastern herbal remedy for spasm. By experimenting on himself, he found that khella derivatives were anti-allergenic (they stopped his asthma attacks from developing).

The fact that Fisons would commit to such a long-term development project on the drug - eight years - implies that herbal medicines were taken seriously within the management of the company.
Roche and artemisinin
That brings me back to artemisinin, which like Intal, must be one of the major triumphs of post-war  pharmacognosy. In a study of herbal medicine research at the London School of Hygeine and Tropical Medicine, Taylor and Berridge make the point that researchers at the school were always receptive to herbal drugs - and indeed, when qinghaosu was announced to the world in 1979, the school commenced research on the drug without any qualms. In other words, herbal medicines were not a conceptual leap for the leading academic experts of the time.

In this final section I want to flesh out the artemisinin story by examining the work of the Swiss drug maker, Roche.

The Roche Far East Research Foundation, an organization that operated between 1970 and 1999 (in 1987 it seems to have been re-christened the 'Roche Asian Research Foundation'), is a little-known player in the emergence of qinghaosu. Working out what this organization actually did is rather difficult  - Swiss drug company Roche's official history says nothing of it. Accordingly, I have gathered the following data through Google. Based in Hong Kong; its registered address was a mysterious post office box (no. 98595) in Tsim Sha Tsui - there is also reference to an office at 1332 Prince's Building (a tower block on Hong Kong Island); notable staff and collaborators included Dr. Keith Arnold, Dr. R. Laserre and Dr. T. Harinasuta.

Publications associated with the institution give us clues as to its work: apparently lacking its own laboratory facilities, it funded and organized conferences, helped Asian scientists publish their work in English-language journals and provided grants for scientific research and medical training in countries like Thailand, Indonesia, Singapore, Burma and China. Areas of interest included, at a minimum, infectious diseasemental health and 'psychotropic drugs'.

We can deduce that the foundation's aim was to tap medical expertise in Asia, look around for ideas, and  perform a hearts and minds function among governments, academics and medical doctors. It was effectively an intelligence-gathering organization, appropriately based in Hong Kong, which, as a British colony adjacent to Communist China, served as a wider intelligence hub throughout the Cold War.

The big coup for the foundation, if one can call it that, occurred in 1979, when Keith Arnold found out about qinghaosu. How he actually obtained this information, we can only speculate, but the significance of it was that Roche established a relationship with a Chinese researcher, Li Guoqiao, at the Malaria Research Unit, Guangzhou College of Traditional Chinese Medicine (just across the border from Hong Kong, in Mainland China).

The extent to which these contacts benefited Roche financially is hard to gauge (anti-malarial drugs are not major profit centers), but the company certainly made some of the early running when G. Schmid and W. Hofheinz of the company's pharmaceutical research department in Basel succeeded in the first total synthesis of the drug, publishing their work in 1983 (here, pay wall). Roche also secured a contract as principal maker of the drug for the World Health Organization (WHO).

What is interesting is the way Roche moved the drug from a bit player in the anti-malarial game to the leading treatment for the disease, often in combination with another Roche product, mefloquine. Indeed, did Roche actively push the use of qinghaosu in Thailand and Vietnam? Certainly, the Roche Far East Foundation's already-established network of academic collaborators, notably Professors Nick White and François Nosten in Thailand are closely implicated in the story. In Vietnam, Keith Arnold directly recruited Professor Tran Tinh Hien to the program of study and promotion of the drug.

To move one step further, the apparent opposition of the WHO to the artemisinin program, typically read as an ideological bias against 'the East' or herbal medicine, might also be seen as an uneasiness about Roche's commercial projects. Ultimately, it seems to have been academic collaborators, not Roche directly, who conducted extensive clinical trials on qinghaosu, and vociferously argued for its use. The WHO eventually dropped its opposition and embraced the drug.

What I think we can say is that in the 1980s and 90s, 'biomedical' drug companies like Roche seem to have been receptive to the idea of herbal drugs - and were prepared to develop them and promote their use.
We know practically nothing about the actual relationship between 'traditional' knowledge and biological science in the production of drugs - but the cursory grab-bag of factoids I have assembled here suggests a rich history in which the two forms of knowledge have been thoroughly co-constructed.

To talk in terms of binary opposition is clearly fallacious and probably always was. If anything, science's supposed hostility to traditional knowledge is a manufacture of very recent vintage and has more to do with the epistemic practices of contemporary biomedicine (inflected as they are by the US Food & Drug Administration's very particular scientific culture as the key regulator of innovation in the pharmaceutical trade) - rather than some essentialist conflict over the 'truth' of traditional knowledge.

BTCM appears to thrive as a scientific practice in China and elsewhere.

Monday, February 15, 2010

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

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:


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).

Wednesday, August 13, 2008

Changshan 常山

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.

Tuesday, July 22, 2008

Who should get the Nobel Prize?

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

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

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?

Sunday, July 13, 2008

Qinghaosu heads West

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.

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.