Sunday, February 18, 2018

The metastases of Quackery, and vice versa

This post was earlier cross-posted at Leonid Schneider's site, hence the unfrivolous tone. The version there includes Leonid's frame-story.

A recent post by our host mentioned the impressive research productivity of Professor Wen Jiang at Cardiff University -- over 500 papers! -- and how this piqued the interest of the pseudonymous data-integrity vigilante, Clare Francis.

Of course high productivity is easier if one organises one's own conferences. When the proceedings of the 2015 China-UK Cancer Conference were published in Anticancer Research, 18 of the 31 papers cited Prof. Jiang as a co-author.¹ And one cannot afford to be fastidious in one's choice of journals and publishers. Prof. Jiang publishes in the ambitiously-titled World Journal of Oncology, from the predatory stable of "Elmer Press", I am not making this up (he is also the journal's Editor-in-Chief).²
Predatory stable: Diomedes devoured by Mares
Francis' inquiries led to a formal investigation into the re-use, re-labelling and manipulation of visual data within that research output. It has also alerted us to the presence of Fried Divine Comedy, entomophagic fungi, and general weirdness, all being stovepiped through Cardiff University, in concentrations that exceeded all expectations. The central theme is Traditional Chinese Medicine (TCM).

Now TCM has not received good press lately, what with the impending extinction of a Pacific dolphin species as collateral damage from oceanic strip-mining for a magical fish bladder, while Himalayan habitats are stripped bare to feed the demand for the fruiting bodies of a caterpillar-parasitising fungus (the Ophiocordyceps sinensis fruiting bodies look vaguely phallic, which means by the principles of sympathetic magic that they must cure impotence). Let us hope that the related New Zealand species, O. robertsii, does not come to the attention of industrialised Chinese quackery.

Strangely enough, the current generation of Chinese leaders have adopted a policy of recognising, regulating and promoting TCM -- presenting it for local consumption as an emblem of nationalist pride, and internationally as a flag-bearer for cultural supremacy. This is as weird as if India's rulers embraced the magical mediaeval scammocopoeia of Ayurveda for political advantage, no wait. Whatever next? Will the conservative kleptocrats of Western democracies follow the same route of Renaissance revivalism, and make it patriotic to self-medicate with trichobezoar, narwhal horn, and moss scraped from a skull beneath a gibbet by midnight? But there is big money in TCM, so perhaps not so strange after all.

Here we are concerned with Yiling Pharmaceuticals, founded in 1992 by Wu Yiling ("a tutor of doctoral students") to re-package TCM medicaments in modernised delivery vehicles, and sell them to gullible numpties around the world. His scam was successful enough to make him the world's 1107th-equal richest person in 2013, according to Forbes.
Yiling pharma sticks to the principle of taking TCM academic development to impetus industrialization, taking technology as the forerunner, market as the guide, and built operational “Five in One” mode as integrating scientific research, clinical practices, production, marketing and teaching together. Yiling products involve TCM, health care products, western formulations and TCM slices etc. It owns the modern product line for capsule, soft capsule, tablet, granule, liquid injection,etc. By now, Yiling products have been exported to South Korea, Vietnam, England, Canada, Netherlands, Singapore, Russia and so on
Even in its modern retconned recension, TCM is not concerned with the isolation of single active elements: practitioners prefer to emphasise the harmonious, symphonic blending of ingredients. So items recur... much as a mediaeval herbalist might put dried mice and skull-scraped moss in every single prescription. For instance: "Yangzheng Xiaoji" or YZXJ requires 16 components, largely vegetal in nature, though Eupolyphaga sinensis is a species of wingless cockroach -- dried and pulverised -- while "Endothelium corneum gigeriae galli" translates as "chicken gizzard lining" [alternatively translated as "Wall of Sand bag" elsewhere in Prof. Jiang's oeuvre]. Fortunately the definition of "herb" is sufficiently elastic as to include the fungi Poria cocos and Ganoderma lucidum.

Most of those components are re-used in "ShenLingLan extract" a.k.a. SLDM:
Fourteen individual herbs (including Astragalus, Ligustrum lucidum, Ginseng, Ganoderma lucidum, Curcuma, Gynostemma, Atractylodes (fried), Poria, Cordyceps sinensis, Xu changqing, Eupolyphaga, Panax, diffusa, Scutellaria barbata, Divine Comedy (fried)).
Here "fourteen" = 15 if one bothers to count... they like Ginseng so much, they include it twice. "Individual herbs" includes our fungal friend C. sinensis, while fried "Divine Comedy" is itself an ill-defined combination of multiple herbs, probably not Dante's poem, though anything is possible.

We know all this because Yiling researchers lodged a patent application in May 2012, standardising the composition of YZXJ, staking out a claim for its use in all manner of angiogenic conditions (notably cancer), and detailing how to process those 16 components. The patent includes details of a dissolved extract, DME25, with results of in-vitro studies purporting to show that the unknown blend of chemicals in that extract reduces the motility of cancer cells. Which is good news if you are ever pursued by one.

The traditional Chinese medicine composition comprises traditional Chinese medicine ingredients such as radix astragali and ligustrum lucidum. The traditional Chinese medicine composition is capable of benefiting qi and nourishing yin, invigorating spleen and tonifying kidney, and removing stasis and relaxing vein; and the applications of the traditional Chinese medicine composition are right focused on pathomechanism. It is confirmed by experiments that the traditional Chinese medicine composition is capable of inhibiting angiogenesis effectively, and can be used for treating malignant tumor, rheumatoid arthritis, diabetic retinopathy and unstable arterial plaque in clinic.
The translation is not perfect, but it's free, thanks Team Google!

What brings this document to our attention is a pair of papers, submitted a few months later to the International Journal of Oncology² and to Anticancer Research.¹ The authors were a team of researchers at Cardiff University led by Prof. Wen Jiang.

An adroit use of Passive Voice allowed the Cardiff authors to foster the impression that they extracted DME25 from powdered YXZJ and named it themselves, rather than obtaining a ready-mixed form from Yiling Pharma. Ah, Passive Voice, is there anything that it can't do can't be done by it? Though the papers and the patent do not entirely converge on such details as the wavelength of light used to calibrate the concentration.

Test drug pretreatment
For the convenience of the experiment, the present invention is a drug (Shijiazhuang Yiling Pharmaceutical Co., Ltd.) as follows pretreatment: Drug capsule contents present invention 400mg, added DMSOlml, rotating wheel at room temperature 20 rev / min, 12 hours, speed 14000 rpm centrifuged for 30 min, the supernatant was added balanced salt solution, filtered, the degree of absorption of 405nm metering, diluting the extract to the optical absorption of 0.25, this is called DME25, aliquots as standardized extracts, spare.

For completeness, "Application of electric cell substrate impedance sensing in evaluation of traditional medicine on the cellular functions of gastric and colorectal cancer cells" is yet another 2012 account from Cardiff (a chapter in a book edited and co-authored by Professor Jiang). It misprints the optical density, and the calibration frequency has shifted all the way to 490 nm., blue-green light instead of violet. Copy-pasting is hard! *

Curiouser still, the papers report the same in-vitro experiments as the Patent, and are illustrated with the same Figures... despite the absence of overlap between the lists of authorship and Inventors.

So who performed the actual research? If Yiling employees deserve the credit, we must conclude that the Cardiff staff signed their names to plagiarised results and stovepiped them into the literature. Conversely, if we credit the Cardiff staff, then their funding providers are supporting a prosperous Chinese company.
We wish to thank the Albert Hung Foundation and Cancer Research Wales for supporting the study
The Authors would like to thank support from the Albert Hung Foundation and Cancer Research Wales.
You will be pleased to know that the collaboration continued, with further papers on DME25, all agreeing on its inhibitory effects on cancer cells, though disagreeing on the mechanism of this inhibition (heat-shock protein 27? Focal adhesion kinase? Growth-factor antagonism? Sonic Hedgehog? All of the above?).

Authorship on these later papers now includes Yong Cao, Cong Wei and Yiling Wu. Their institutional affiliation is to Yiling Medical Research Institute, which sounds innocuous -- a respectable high-minded academic institution -- but in fact is just the manufacturer's marketing wing**. So the pretense of separation between Cardiff and Yiling Pharma has been dropped, and questions like "Who did the work?" are no longer an issue. In fact Yiling Wu there is the company owner, going among his people incognito in the manner of a caliph from an Arabian Nights story.***

Another point on which these papers agree is that "The authors declare that they have no competing interest". I guess this is true, as long as "loyalty to the company whose products are examined" is the authors' only interest.

The background to all these shenanigans is the Cardiff China Medical Research Collaborative. This is hosted at Cardiff University and appears to consist of Professor Jiang. Its functions include the promotion of the yearly China-UK Cancer Conference. The exact date of its establishment is not clear. An early press release heralding "Cardiff - Peking Universities Cancer Breakthrough" was picked up by the BBC, and is a load of self-congratulatory cobblers -- packed with tropes of "ancient wisdom of the East", more full of shit than a 10-pound pigeon.

This is the crucial aspect of the Collaborative:
An award-winning medical and cancer research group working in collaboration with our partners in China - Peking University, Capital Medical University, Sun Yat-sen University and Yiling.

So it's a formal partnership with a TCM manufacturer, meaning that quackery and charlatanism are not just a peripheral aspect of the Collaborative, they are a central goal. The heads of Cardiff University really need to explain why they are in bed with scammers (albeit state-sanctioned ones); and why their staff and students are working on the behest of an industrial-scale fraudster in China, using research grants provided by Welsh funding bodies to advertise his worthless witchdoctory.

Jiang assures us (through Cardiff Uni's website) that 'Professor' Yiling Wu is "a highly accomplished scientist, medic, academician, entrepreneur and politician in China", which sounds better than "unqualified son of a herbalist".

But wait, there's more! Prof. Jiang's colleagues have more recently focused on giving Cardiff University's imprimatur of legitimacy to another item from Yiling Pharma's range of magic-based products. This being ShenLingLan, the herbal decoction mentioned above with the indeterminate number of ingredients (some of them genuinely herbal!), notably including "...panax, diffusa...". The authors are insistent on this list, repeating it verbatim in Owen et al. (2017A), Owen et al. (2017B)³ and a conference poster. If you are generously minded (like me), you have wondered if the "... panax, diffusa..." was a typo for "Panax diffusa' -- but there is no such species.

All is clarified by an earlier Yiling Pharma patent, filed in 2002, with ShenLingLan as the subject.

The present invention provides one medicine composition for raising body's immunity and invigorating spleen and kidney based on the Chinese medicine theory of strengthening body's resistance to eliminate evil. The medicine composition has 15 kinds of Chinese medicinal materials including astragalus root, privet seed, ginseng, glossy ganoderma, gynostemma pentaphylla, etc

An increase immune function pharmaceutical composition consisting ratio (weight / weight) include astragalus [...] Ligustrum [...] ginseng [...] Ganoderma [...] Curcuma [...] Gynostemma [...] Atractylodes (fried) [...] Poria [...] cordyceps [...] Xu Changqing [...] Eupolyphaga [...] March [...] diffusa [...] banzhilian [...] The Divine Comedy (fried)

Translating terms one-by-one from the Patent, we learn that 三七 = sānqī = Panax notoginseng; 白花蛇舌草 = Hedyotis diffusa. One can only suppose that English-speaking members of the Cardiff-Yiling collaboration were not in a position to question the quality of the translation.
1. Anticancer Research (Ed. J.G. Delinasios) also publishes Proceedings from the International Conferences of Anticancer Research, organised by the International Institute of Anticancer Research (i.e. J.G. Delinasios). In that capacity it has contributed materially to the gaiety of nations, with such Ignobel-Prize contenders as "Are the centrioles sensory centres in living cells?" [spoiler alert: No]

ACR has also provided a convenient vehicle for the promotional activities of the Saisei-Mirai cancer-quackery clinics, who advertise their scams by publishing success-story anecdotes there; and for Marco Ruggerio's tireless efforts to legitimise and advertise his various derivatives of GcMAF.

Prof Jiang's contributions there are dominated by his presentations to the various China-UK Cancer Conferences, but not limited to them.

2. Other observers have noted that Prof Jiang also likes to publish in journals from Spandidos Publications ("114 publications were found"), where he is also Editor a Member of the Editorial Academy.

It goes without saying that Spandidos Publications also organise conferences; also they hand out awards for attending them, although Cardiff University no longer boast so prominently about the Outstanding Achievement trophy received by Prof. Jiang.

* A 2015 paper goes back to 450 nm, as the calibration wavelength, and is quite emphatic about it:
The extract was diluted in a balanced salt solution (BSS) and standardised by quantifying the optical density of the preparation using a spectrophotometer at 450 nm wavelength (Biotek, Wolf Laboratory). A master preparation which gave 0.25 OD at 450 nm was stored as the master stock and so named as DME25 for the subsequent experiments.
** As well as a product manufactory and a Research Institute, the Yiling Group has acquired its own hospital, AND a Yiling Health-themed hotel, AND a Yiling International Travel Agency to bring the suckers from all around the world. Their general style is modeled on those cancer-clinics / stem-cell garages / v14gra dispensaries in Tijuana.

*** A more recent DME25 patent filed by Wu Yiling and Wei Cong on behalf of Yiling Pharma claims priority for the use of the mystic decoction in preventing peritoneal metastases from cancer. Their work subsequently found its way into a presentation to the 2014 Meeting of the American Association for Cancer Research. It is not clear what the Cardiff co-authors of that presentation added to the data in the Patent, other than protective camouflage.

3. Publisher for Owen et al. (2017B) is "Noble Research", which turns out to be a Mancunian dude by the name of Sreeman Etamsetti.
OUTTAKES: Prof. Jiang's Spandidos Participation Trophy appears again in the Self-Congratulations webpage at the Cardiff Collaborative site, but YZXJ is the real focus there:
The herbal formula had previously been shown to be beneficial to cancer patients
The claims for clinical benefits from the cockroach-fungus combination largely boil down to a pair of publications in the Chinese Journal of Difficult and Complicated Cases, one testing it on gastric dysplasia and the other on hepatic carcinoma, the two conditions having so much in common.

This Chin J. Diff. Compl. Case sounds like a Riddled invention, but it is a thing. There is some involvement with state agencies for the Promotion of TCM and the Encouragement of Positive Results, although the details of publisher and editor are such that it might better be characterised as the Yiling Pharma in-house magazine.

These two papers feature in the References of every publication from Prof. Jiang's group. It is not clear how closely they have read them.

As well as this idiosyncratic interpretation of 'gastric dysplasia', Prof. Jiang has managed to confuse the "hepatic carcinoma" from the second reference with "lung cancer", in at least two publications and one Beeb interview.

We cannot recommend Cardiff Cut-price Organ Transplants.


H. Rumbold, Master Barber said...

I was going to reference the Cardiff Giant but find that it's Cardiff, New York.

Emma said...

Oh, god. This was painful.

HERE'S AN AMUSING PERSONAL ANECDOTE: I have a 14-year-old dog with hypothyroidism, a severe meat/protein allergy, mild arthritis, and some weird kind of dog alopecia. For these disorders, she takes thyroid hormones, a twice-weekly steroid, a chondroitin supplement, and an omega-3 supplement (we also feed her a specialty kibble based on hydrolyzed protein, and give her a monthly bath & haircut to facilitate airflow). She goes twice a year, barring other problems, to the vet for a checkup and bloodwork. She's doing great, and has been for several years. During her last visit, one of the practice's newest vet recruits gave her some kind of damned fucking TCM pill that cost $75 for 30 pills, and when I looked it up it claimed to cleanse the yin out of her liver. How I wish that were a semi-racist exaggeration on my part! The vet wasn't going to take it back, until I got medieval on the phone. Lesson learned: Dad doesn't get to take the dog to the vet by himself anymore.

HERE'S ANOTHER ONE: Like most of the people in my family, I suffer from various autoimmune diseases. I used to go online to talk about these problems and trade lifestyle advice with other sufferers — until recently, when people began to accuse me of lacking initiative because I refuse to suck down unregulated TCM tinctures. I have seen people driven out of digital communities over their lack of enthusiasm for alternative medicine. Acupuncture or GTFO. Also, one time I saw a lady with autistic kids tell another lady with autistic kids that she (Lady #2) was "as good as killing" her children by giving them cheese.

These stories you post are funny and interesting, but they also represent a creeping cultural phenomenon that has real consequences for non-academics. Why there aren't anti-quackery journalists at major newspapers eludes me. This is getting dangerous.

Okay, I'm done. Sorry.

Smut Clyde said...

I like the word "tincture" - it's not just for heraldry! - and should use it more often.

Emma said...