This is a follow-up to the previous article, about a misconduct investigation at the Cardiff University in UK into the published works of cancer researcher Wen Jiang, professor of Surgery and Tumour Biology, Fellow of Royal Society of Medicine and chair of Cardiff China Medical Research Collaborative. The following guest post by my regular contributor Smut Clyde now delves deep into the peculiar approach with which Professor Jiang intends to cure cancer: namely by peddling herbal (and not so herbal) medicinal powders, manufactured by a Chinese company Yiling Pharmaceuticals. Jiang sees there no conflict of interest, even in presenting the patented concoctions of Yiling as his own research in Cardiff. It is not exactly the case that Jiang was hiding his connections to Yiling, outside of his conflict of interest declarations, that is. His own Cardiff University initiated the collaboration with the Chinese company in 2013 and proudly announced the engagement to the British Parliament in 2014. In 2015, Yiling helped Jiang and Cardiff University to organise The China–United Kingdom International Cancer Conference, attended by the First Minister of Wales and the Vice-Chancellor of the Cardiff University.

Jiang’s cancer-fighting magic ingredients are ginseng and other herbs, plus a cockroach, a parasitic fungus and bits of chicken gizzard, all sold by Yiling. Sometimes it includes Divine Comedy (don’t ask). Yiling’s potion named “Yangzheng Xiaoji” was certified by Cardiff University in an Impact statement as a metastasis inhibitor, which “has been shown to be beneficial to patients with certain solid tumours when used alone…“. The sole basis for this bold claim from respected British university was a 2009 paper by Yiling in an obscure Chinese journal, which incidentally is edited and published by Yiling.

Update: scroll down for relevant Cardiff University press release.

The metastasis of Quackery, and also vice versa, by Smut Clyde

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. 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”, he is also the journal’s Editor-in-Chief.

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 business idea was successful enough to make him the world’s 1107^th-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”. 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 Oncology and to Anticancer Research. 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 pretence 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 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.

“Prof Jiang, the director of the Cardiff University- Peking University Joint Cancer Institute at Cardiff, explained: “Traditional Chinese medicine where compounds are extracted from natural products or herbs have been practised for centuries in China, Korea, Japan and other countries in Asia.

“Although a few successes, most of the traditional remedies are short of scientific explanation which has inevitably led to scepticism – especially amongst traditionalists in the West”.

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 quack company in China, using research grants provided by Welsh funding bodies to advertise this worthless witchdoctory.

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) 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. There is Panax ginseng though, and there is also Damiana (Turnera diffusa), which is used as a herbal aphrodisiac.

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)”

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.

* 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.

*** 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.

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Update 28.03.2018. Two days ago, I received a reply to my FOIA inquiry from Cardiff University’s Assurance Adviser Alison Preece. My questions are in bold.

1. Please declare the amount of remuneration, direct or indirect, including advisory activities, which Prof Wen Jiang received from Yiling Pharma since 2012. 

The University neither confirms nor denies whether records are held in relation to direct or indirect payments made to members of its staff. To confirm one way or the other whether records are held would confirm whether a payment had been made. The remuneration of individual members of staff is considered personal data and it would not be in the reasonable expectation of members of staff that such information is disclosed into the public domain. To do so would risk damage and distress to individuals and would damage the relationship of trust between employer and employee. As such to confirm or deny that information was held would likely be considered unfair to individuals and thus in breach of the first principle of the Data Protection Act concerning fairness. Therefore the exemption under S40 (5)(b)(i) is engaged.

2. Please declare the financial flows between Cardiff University and Yiling Pharma since 2012.

In the period 2014-16 the Yiling Pharmaceuticals Company Limited donated £300,000 to Cardiff University to support cancer research in the School of Medicine. The donation was used to fund a number of scholarships which allowed early career researchers and doctors, from China, to undertake cancer research within the School.

Further information on financial payments between Cardiff University and Yiling Pharmaceuticals is exempt from disclosure under Section 43(2) of the Freedom of Information Act 2000. This exemption may be applied where to release information would, or would be likely to, damage the commercial interests of the University or any third party.

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Update 24.04.2018. The Cardiff University now issued a press release, where this very article was fingered for raising false allegations:

Allegations relating to research misconduct – 19/04/2018

“In recent months a number of allegations have emerged on social media and blog posts about research conducted by Professor Wen G. Jiang, notably on https://forbetterscience.com/2018/02/14/fried-divine-comedy-featuring-anti-cancer-cockroach-and-phallic-fungus/#more-23091

Some of these allegations, relating to research misconduct, were formally submitted to Cardiff University by an anonymous whistleblower.

Cases of research misconduct are rare at Cardiff University. However, when allegations are made they are considered in accordance with the University’s Procedure for Dealing with Allegations of Misconduct in Academic Research.

The University’s procedure is in line with guidance issued by the UK Research Integrity Office, to which the University subscribes.

The University has conducted a formal investigation into the allegations.

In all it reviewed allegations relating to 19 publications and has not upheld the allegations of misconduct.

Cardiff University reviews the research quality of all its academic staff as part of performance development reviews and ongoing preparations for the next national Research Excellence Framework (REF). Professor Jiang has been assessed by independent review as having research outputs of a standard eligible for submission to the next REF.

Questions have also been raised about the relationship between the Yiling Pharmaceutical Company Limited and Cardiff University

Yiling Pharmaceutical Company is one of China’s high-tech pharmaceutical companies, devoted to research and development, manufacture and marketing of new medicines. Its products are listed in China’s National Formulary and Health Insurance list.

Its research work has focused on the health benefits of the traditional Chinese medicine preparation Yangzheng Xiaoji and on the development and advancement of new treatments for cancer and infectious diseases, with a particular focus on Chinese medicine.

The Cardiff University – Yiling Group Joint Medical Research Centre was established in 2013 through a gift from Yiling Pharmaceutical Company to Cardiff University. This followed a due diligence report, completed in October 2013, which found no issues of concern.

Under the terms of the gift agreement, Yiling Pharmaceutical Company agreed to donate £300,000 over three years (November 2013 to July 2016) to support a number of scientific researchers, known as “Yiling Scholars”,  through provision of a stipend, research and publication costs, to undertake research projects in cancer molecular pathology at Cardiff University.

Yiling Scholars, who were selected by Peking Cancer Hospital and Capital Medical University, were early career medical doctors and scientists. Yiling Pharmaceutical Company did not play any role in scholar selection, nor were any scholars employees of the company. The use of the gift from Yiling Pharmaceutical to Cardiff University was determined by the University, not the company.

Research conducted at Cardiff University under Professor Jiang’s direction has been concerned with understanding the molecular pathological mechanisms of cancer and metastasis. A minority of studies have examined the efficacy of traditional Chinese medicine preparations and potential mechanisms of action.

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