Highly Problematic Stance on Fake "Antivaxx" Authorship By the Indian Journal of Medical Ethics

It is a recognised challenge of my research field, bioethics, to include and empower researchers and institutions from low- and midlle-resource settings. Since a few years, the leading journal of Bioethics, runs the side journal Developing World Bioethics to address this issue, and over the past few years a number of journals have appeared, based at institutions outside of the most affluent parts of the world with a natural focus on bioethical issue of relevance to such settings, as well as global health related issues. One of these is the Indian Journal of Medical Ethics, that has quickly been rising in the ranks and attracting respect for its consistent work.

However, very recently the IJME has been dragged into potential scandal. First, the editor, Amar Jesani, decided to publish an article by a fake author, claiming fake credentials and affiliations, of an obvious antivaxx junk article of the sort that antivaxxers – just like tobacco-industry sponsored scientists used to do regarding the dangers of smoking – are constantly trying to peddle to various journals to create an image of "scientific controversy" around the use of vaccines to fight infectious disease and build public health. The fakes were all very easy to detect, and already the fact that the "author" was not using the email-domain of, and has no profile at the webpages of, the institution (Karolinska Institutet) to which he claimed affiliation should have rung immediate alarm-bells. But then, when this is pointed out, and the journal is alerted to this research fraud, the editor Amar Jesani decides not to retract the article! Instead, the editor appears to have decided to trust the author's obviously bogus explanations for his (?) fraud, and to attempt to counter a, to my mind, quite sound statement on the matter from the Karolinska Institutet president, Ole-Petter Ottersen.

The bogus explanations and Jesani's expression of sympathy with them, and Ottersen's stringent response, is to be found here. This very surprising and ill-conceived action of Jesani is potentially extremely damaging for the IJME, and in effect risks to soil the reputation of the entire field of bioethics. The fake author's attempt at justifying the fraud is that he/she has to be anonymous to protect him-/herself from persecution for unpopular views. This, of course, is not even worth the scrap of paper it was scribbled on. The real role of the fraud is to block any investigation into conflicts of interests (the antivaxx movement is nowadays a flourishing industry of quackery), other activities of the author that would undermine confidence in the article's content, and the fact the author lied to the editor, and offered the explanation only in retrospect when the scam had been uncovered should, of course, mean that the editor should have no trust in what the author is claiming. This is a proven fraudster, and should be treated as such. Just as authors lying about ethics approval should have their papers taken out, authors who lie about other things of relevance to the evaluation and assessment of the research have their papers removed. As Ottersen says in his second blog post: an editor of an ethics journal should know this. The editorial board of the journal should immediately and strongly recommend its editor, who has obviously let his personal prestige lead him astray in this matter, to revise his position and act according to the high publication ethical standards expected of a bioethics journal that aspires to be well regarded.

Let me, lastly, comment on the possible need for author anonymity for research articles. The afterconstructed reason brough forward by the fake author and that Jesani surprisingly buys, is the idea that is often practices within news reporting. Where, eg., a newspaper may protect sources by keeping them confidential. However, that also means that whatever story is built on this, needs to present suffient additional public evidence, that is open for scrutiny, in order to compensate for the loss of control following source anonymity. This has not taken place in the case of the fraudulent article. Also, the whole spinn about author/source confidentiality is obviously a lie in the present case: Had the author had any such plan, he/she would have honestly and openly contacted the IJME editor about it, and Jesani could have pondered - bringing in the editorial board - the issue. Had they decided to approve such a request, this would have brought with it extraordinarily strong obligations to check the author credibility, CoI, etc. This is not what occurred, however. What occurred is that a con-man defrauded the journal, and the journal editor then decides, against any common sense, to trust said con-man. Unbelievable!

****

Independent Science Journalist Who Exposes Research Fraud, Ethics Breaches & Corruption Threatened by Lawsuits: Here's How You Can support Him!

As I have been reporting before, no holds barred independent German science journalist Leonid Schneider, who runs the blog For Better Science to expose and call out science fraud, ethics breaches and general scientific hype and institutional corruption, particularly in the life and medical sciences, has recently been hit by civil lawsuits to silence his reporting. Besides the couple of Thorsten and Heike Walles, another exposed former Paolo Macchiarini associate and likely co-fraudster and ethics villain, Philipp Jungebluth, is now also suing Schneider for libel. In both cases, court injunction have already been made threatening Schneider with massive monetary fines or prison time, and he is now facing the substantive economic cost of defending himself in two separate proceedings and, if the court so decides, pay the fines and the legal costs of the plaintiffs. Note that what Schneider has been reporting is only already publicly available and proven facts, so he is not in any way slandering these people, but rather providing an important information service to universities, hospitals, research funders, and potential patients (and possible guinea pigs) of the dear doctors. Of course, the whole thing is a so-called SLAPP operation, to shut Schneider up by scaring him with the financial consequences of continuing his reporting.

To help Schneider manage through this challenge, you may first of all sign this letter of support of his reporting. If you're in such a position, you may also engage Schneider professionally. But he has also set up this crowd funding page, to help everyone who dislike science fraudsters and unethical researchers, as well as the practice of silencing important public reporting by abusing civil law, to pitch in financially. I've become a monthly "patron", but there are many options and you may chose your contribution freely, with more generous amounts providing you with a steady stream of Schneider's homemade satirical science cartoons, such as this one:

Forget the "Editing" Hype: Human Genome Action Painting Attempted in China

Recently, there's been a lot of hype around what's been referred to as genome editing. What it's all about is that there's a new bioetechnological strategy for effecting genetic modification in organisms, called CRISPR/Cas9, that has shown promise in facilitating more precise and specific changes of a genome more effectively than before. This is an important advance for laboratory biology research, as the effecting of specific genetic changes in the genome of organisms and study of how these "behave" in response to various stimuli, in different environments, and reproductively over generations is a basic way of advancing knowledge of basic biological mechanisms. However, as usual, there has also been some lack of temperance among those who immediately want to move the new promising lab-tool into practical "in vivo" applications, sparking calls for a global moratorium on practical application, akin to that famously adopted in 1974 at the Asilomar Conference to apply to the then novel recombinant DNA technology. In addition, there has been especially forceful calls to abstain from "editing" a human genetic germ line. The reasoning is an apparently sound precautionary argument to the effect that before practical applications are attempted, sufficient understanding of the technology, its potentials and limits, possible consequences and suitable security protocols, need to be attained and put into place.

At the same time, when new technologies are hyped like this, my bioethics alarm bells start ringing loudly for a number of reasons. We know from a long series of hyped new technologies that, while they may indeed over time prove to be advances compared to what has been previously available (though by far not always), the promises of new "clean", "precise" tool that will effect all that we aim for without any side-effects or mistakes is usually as credible as the promises of precision warfare foreboding the 2003 Iraq invasion – or worse. What one mustn't forget is that there are almost always substantial vested interests around, that have high stakes in having the tech they personally hold patents for, or stock in start-up companies that do, or have stakes in institutes or universities that do, and so on, appear in much better light that there is actual evidence to support. And, in this respect, CRISPR-Cas9 is no different. This is a basic reason to primarily interpret any positive claim about the technology outside of the bona fide peer reviewed scientific literature as part of a marketing campaign aimed at upping the the price of licensing fees, credit rating of the patent holder, attraction for external financial investors, and (if it is a start-up company) stock price pending a coming introduction into a stock exchange or a emission of new shares. Other agents with similar vested interests include those who have already invested in the product somehow, or those who want to peddle quack junk to people under the guise of novel science, much in the spirit the infamous stem cell clinics that continue to jack money out of the hands of conned, often desperate, people.

So, for me, it was no surprise when the reality of the "editing" showed its true face when a group of Chinese researcher recently applied it to human in vitro embryos (modified, so that they could never have resulted in a living human baby, but also never implanted to effect a pregnancy). What we learn from this study is that if there's any honesty among gene modification scientists, the "editing" misnomer should be dropped immediately:

The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”
His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome.

What we seem to be looking at in the reality outside of the hype is some sort of human genome action painting, where now and then a drop of the right colour lands in the right place, several other drops land where we absolutely do not want them to, but most of the result is just general heap of pint randomly applied by these the Jackson Pollocks of human genetics.

Moratorium? No shit?!!

This is Huge: Serious Research Misconduct in Almost 3/4 of FDA Inspected Clinical Trials – Hidden by Both Inspecting Agency and Researchers

First I had problems taking it in: Almost 75% of US clinical trials inspected over a period of 15 years by the Food and Drug Agency, responsible for upholding regulation in this area, display serious misconduct of various kinds. It can't be that bad, I asked myself; if it was, I would have heard something about it before – research ethics in medicine being one of my areas of expertise! Except that I wouldn't, since neither the FDA nor the researchers in question have reported these stunning findings to the outside world. That is, until Charles Seife, an MD but also a journalist, decided to have a look at FDA documents of some of the made inspections between 1998 and 2013. What he found is reported in a recent article in the journal JAMA Internal Medicine, where out of originally 600 trials, 101 where identified where the FDA had found strong reason of issuing complaint, and among these:

Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.

 Seife concludes:

The FDA has legal as well as ethical responsibilities regarding the scientific misconduct it finds during its inspections. When the agency withholds the identity of a clinical trial affected by scientific misconduct, it does so because it considers the identity to be confidential commercial information, which it feels bound to protect. However, failing to notify the medical or scientific communities about allegations of serious research misconduct in clinical trials is incompatible with the FDA’s mission to protect the public health /... /

To better serve the public health, the FDA should make unredacted information about its findings of research misconduct more readily available. The agency should make sure that any substantial evidence of misconduct is available to editors and readers of the scientific literature /.../

... most of the burden for ensuring the integrity of the research in the peer-reviewed literature falls to the authors of the articles submitted to peer-reviewed journals. Currently, there is no formal requirement for authors seeking to publish clinical trial data to disclose any adverse findings noted during FDA inspections. Journals should require that any such findings be disclosed.

The nail on the head if there ever was one, and Seife is backed by an editorial, signed by three strong voices from the Yale and UCSF medical schools. FDA is liable to serious criticism for not proactively informing the scientific and medical communities, as well as the general public, of these matters. Journals which not immediately effect the standard indicated by Seife would deserve equally serious criticism. But the worst of all is the fact that such journal policies would be needed in the first place. 

The by far heaviest burden of criticism befalls those researchers, many of which have not only committed scientific fraud and serious ethical breaches, but have all in addition consciously choosen to actively surpress highly relevant information about the quality of the studies they have conducted. Not only is this relevant for the publication screening at journals to safeguard the quality of scientific publications. It is even more relevant for the assessment of the results reported in publications for the purpose of, e.g., licencing or decisions on clinical use, or public funding. These researchers have sold their scientific credibility and honour to whatever bidder (in the vast majority of cases, one suspects the pharmaceutical company funding the study) have incited them to keep mum. People doing such things have no place in either the academic or the medical community.

Seife has a popular report of the significance of his study in Slate, here.

This is, as far as I can see, a major research ethics and regulatory scandal, and it might just be hiding an even larger one. For, given the frequency of serious misconduct now revealed, one may very well ask what would be found if FDA was to cast its inspection net wider and inspect even more trials. And what would be the outcome of similar procedures in, e.g., Europe or Asia?

Update: Facebook Experiments Lacked Support in User Agreement and May Have Included Minors

I posted yesterday about the ethical and possibly legal ramifications of the already infamous emotional manipulation experiment where researchers tweaked Facebook user feeds and studied ensuing user behaviour. The post yesterday gave links to a number of useful accounts and analyses, but I did also mention my own doubt that the research, including the subsequent publication of the findings, was covered by the Facebook user agreement. Today, Kashmir Hill at Forbes reveals that this is exactly what was the case. Not only did the user agreement not include "research", however, apparently Facebook realised what this meant for the defensibility of the study and retrospectively added "research" to the agreed to activities by users after the study's data collection in January 2012. In addition, it is also revealed that the study inclusion criteria did not exclude minors, and since Facebook allow users down to the age of 13, this means that the researchers may very well have been children without their or their parents' consent.

Both of these revelations are, of course, of substantial importance for the research ethical assessment of the study. Not least is the combination rather damaging not only for Facebook and its study leader Adam Kramer, but also for the non-Facebook employed researchers Jamie Guillory and Jeffrey Hancock. This since it may be assumed that the research ethical assessment that was allegedly performed at their universities, Cornell and the University of California, rested, at least partly, on the presumption of consent being implied by the Facebook user agreement. Moreover, this point is especially sensitive because of the possible enrollment of children, as research ethics standards, regardless of area, is especially adamant on rigorous consent procedures and protection mechanisms for children, as it is for other vulnerable groups, and mandatory involvement of their parents or guardians in one way or another, especially when they are below 15 years of age. Possibly, dirt may therefore spill over also on the journal PNAS's responsible editor Susan T. Fiske of Princeton University, whose responsibility it was to ensure the ethical soundness of the article before publication.

That's ethics. But, of course, today's revelation also means that there may be basis for substantial legal complaints. Not least, since Facebook and the involved universities are based in the USA – the heaven of civil lawsuits for astronomical amounts of money – it seems far from improbable that users who where included in the study may join in a class-action suit against (primarily) Facebook and the involved universities. Whether or not there would be grounds for administrative of criminal legal action is more difficult to assess, as I lack knowledge of sufficient details of the relevant sections of US law.

Facebook Emotional Manipulation Experiment: A Collection of Readings

I will not make a real post of my own re the already infamous experiments (initially claimed to be military funded, but that, it seems, was a hoax), where Facebook allowed behavioural researchers to manipulate the allocation of status updates in personal feeds, to study the resulting emotional communicative behaviour of users. My own brief take is that, whatever else may be said on the matter, this is definitely not covered by the user agreement I've signed when joining Facebook. For while I did agree to Facebook testing out all sort of things to improve their service, I did certainly not agree to be a subject in a scientific research experiment, the result of which is published in a scientific journal. I also think that the study may harbour some substantive both methodological and research ethical difficulties, spilling over to not only Facebook, but also the prestigeous PNAS journal's editors, who seem to have taken proof of research ethical review rather lightly... But don't take my word for it, here are four selected sources, not all echoing my views exactly, which may help you make up your mind.

The first one simply set up what the whole thing is about in broad terms, providing a few useful links. The second discusses the scientific quality of the study, which is also important from a research ethics standpoint. The third is an account by a usually brilliant bioethics and research ethics law scholar, discussing the legal ramifications of the study, as well as details regarding what has and should have happened in procedural terms. The fourth is a purely research ethical account by a trusted bioethics colleague of mine. Enjoy!

1. Meyer, R: Everything We Know About Facebook's Secret Mood Manipulation Experiment, from The Atlantic.

2. Grohol, JM: Emotional Contagion on Facebook? More Like Bad Research Methods, from PsychCentral.

3. Meyer, MN: Everything You Need to Know About Facebook’s Controversial Emotion Experiment, from Wired.

4. Hunter, D: Consent and Ethics in Facebook’s Emotional Manipulation Study, from The Conversation.

Cross Post: More psychiatric research misconduct at the U? A Fox 9 television report on Dan Markingson and another abused research subject at U of Minnesota Psychiatry

Cross-posting this from the Fear and Loathing in Bioethics blog. It connects to several of my earlier posts, the last of which is here, on the appalling research ethical scandal connecting to University of Minnesota Psychiatry. And once you thought you heard it all, more comes to light through this Fox 9 documentary:

KMSP-TV

When having watched it, you might want to sign this petition to the Minnesota governor for an independent investigation of the University of Minnesota pertaining these matters.

Threats, Libel, Calls for FDA & Government Action – and a Petition to the Governor: Research Ethics Morass at the University of Minnesota Psychiatry Continues

The sad and disgraceful story about the appalling unwillingness of the University of Minnesota to in any way investigate closer what several pieces of evidence suggest may very well be a major research ethics scandal in its psychiatry department continues. The scandal involves drug trials connected to several major Pharma companies, such as Astra-Zeneca, but for once it is not them who appear to be doing the bad deed – it is the university itself.

Former reports on this by myself are here, and here. The reporting of University of Minnesota bioethicist Carl Elliott is assembled here – an overview of the basic background story about apparently mishandled psychiatric drug trials linked to at least one death by suicide is here. In the Scientific American, blogger and clinical trial specialist Dr. Judy Stone is also reporting and commenting on the case, here.

So, what's new?

Well, first of all, not only does the University of Minnesota clearly bend its own rules inside out to avoid what would otherwise be the obvious line of action: investigate, clarify and report with full disclosure and transparency. It has, it now appears, sunk so low as to use its own General Counsel – one Mark Rotenberg, who just happens to be identical to the lawyer who has been attempting to whitewash this story and motivate the avoidance of investigations – to in so many words try to threat Elliott with possibly disciplinary actions for pressing on for an inquiry. Yes, that's right, a university threatens one of its academic employees – a bioethics professor at that – for simply insisting on that the truth be sought out and revealed. In short: for doing his job well.

In fact, not only that – the University of Minnesota President, Eric Kaler has chosen this well-timed moment to hint that research ethics regulation at the University, not least with regard to academia-industry collaboration in psychiatry may be "excessively burdensome" and expressing a "low tolerance of risk" and that "we’re afraid a misdeed of two decades ago will reappear again" – the latter obviously referring to past very serious misconduct cases (described in the post linked to above) in, where do you think? – yes indeed, the department of psychiatry. Nice.

Second, the University has finally tried to respond to the claim of Elliott that several patient consent and other forms seem to exist in duplicate but not differing – for instance, not all are signed! – versions, apparently originating from different times. This is covered in Elliott's former postings linked to above, as well as Dr. Stone's astute analysis in the Scientific American. The formerly mentioned General Counsel, Mark Rotenberg, responds on behalf of the university in an article in the Star Tribune to this is, again in so many words: Hey, you probably faked those yourself – or the families of the victims did!! That is, he doesn't mention any particular party and uses the word "authenticity", but in context the content is clear. Being a European, even though I am a Scandinavian and thus possibly with some kinship to the mysterious Minnesota ways of academia, I may be misinformed of some legal peculiarities: but isn't it at least a little bit legally troublesome to accuse other people of illegal actions (forgery of official legal documentation is a criminal act in Minnesota and the USA, isn't it?) without any shred of evidence?

Elliott's own response is the obvious and only sensible one (besides suing the guy for libel, that is): if you say so, help me to find out! Substantiate your claim! Open the files! Disclose the evidence! That is, run the investigation that should have been run ages ago, but that you and those you serve have denied and forestalled!

Third, Elliott has now officially written to both the Office of Civil Rights of the U.S. Department of Health and Human Services and to the Office of Compliance of the FDA to call for investigations of related parts of this troubling story. The letters you can see and download below.

   Letter to HHS Civil Rights About Possible HIPAA Violations by   MarkingsonCase

 

   Request  that FDA Office of Scientific Investigation to investigate "evaluation to consent" forms... by   MarkingsonCase

And Elliott is not the only one acting. A close friend and the mother of Dan Markingson, the young man whose death by suicide is clearly linked to one of the deeply suspicious psychiatry research trials involved in this potential scandal, is petitioning the Minnesota Governor to investigate the University of Minnesota for its refusal to act and investigate. You can read the statement and, if you want to, sign it yourself here.

There will be more, I'm sure......

Continuing stinks out of University of Minnesota Psychiatry: If it looks like it, smells like it and sounds like it, at least it deserves an inquiry...

This is just to point interested readers to what looks more and more as a multi-layered bona fide research ethics scandal at the psychaitry department of the University of Minnesota, involving at least one death and possible falsified patient documents in order to fake proof of consent. My US colleague Carl Elliott has been covering this mess for a long time, patiently trying to have the university's own research intergrity administration take hold of the case, and work it as they should. However, instead of doing what a university in this situation is supposed to do – namely acting in a prudent and transparent way to undo any unsubstantiated suspicions – it continuously acts to sweep whatever crap it is they feel they need to hide under a dirty, old mat of hollow and increasingly unsound or even obviously invalid bureaucracy blabber.

Is it as simple and disgraceful as one commentator at Carl's blog suggest, that:

...the University of Minnesota will never look into these issues because they are scared too death of what they might find, or actually might have already found. /..../ The University at this point has no option but to stay the course of denial, for to give in and admit fault would open the flood gates...

??

Read more here.

Updates on this case will follow as they appear by way of Carl.

Comment in Nature on Proposal to Slack Ethical Requirements on Gene Therapy Research

So, if anyone's interested, I just posted a comment in Nature's online edition on a proposal from gene therapy research specialist Fulvio Mavilio to slack the research ethical requirements for clinically introducing gene therapy. A few typos managed to find their way in, but I don't think the message is muddled by that.

Overselling Science, Halting Progress, Killing Opportunities: Gene Therapy, Cloning, Stem Cell Medicine & Synthetic Biology

Here's a note, slightly provoked by a pretty ridiculous piece posted at the webpage of the Institute for Ethics and Emerging Technologies. In this piece, a self-proclaimed, so-called "positive futurist" named Dick Pelletier delivers a sales-pitch for the program of synthetic biology much as envisioned by Craig Venter when holding his regular presentations aimed at potential funders, investors and customers in order to raise the value of his services, products and patents. Right off the bat, I want to underscore that what I mean to be saying here is not against Venter's scientific aims or, for that matter, his visions of what his science might eventually be good for. Not at all. What I want to point to, however, is the sort of overselling of scientific areas which are, frankly, in rather early stages of development that is going on in Pelletier's piece and that Venter himself is a bit guilty of as well, but that does not in any way limit itself to this particular field. Rather, I will here use similar patterns from the areas of human genome and associated gene therapy research, research on cloning and stem cell medicine to illustrate what this sort of overselling actually achieves, and why people and organisations (such as the IEET) seriously committed to using science and technology for the good should be wary of of this type of rhetoric.

So, what is it that Pelletier says? Well, a lot of unsubstantiated stuff, mostly, besides a lot about what synthetic biology "might" or "may" lead to, such as all of that which Craig Venter said when presenting his institute's breakthrough a while back. Very nice. I can see why Venter wants to attract investors and raise the share price of the company holding his patents, as well as the prices of the latter, and I suppose that Pelletier has some personal reasons, unknown to me, to help him doing that. What boggles my mind, however is the lack of complications, risks and the pretty optimistic (or is it infantile?) time-scale applied:

...they will produce a complete cellular system by 2015. Once this happens [...] Darwinian evolution will take over. This knowledge will help scientists understand how humans evolved in the past, and provide guidance towards a future human evolution driven, not by nature, but by tomorrow’s synthetic life technologies. We will see tiny self-reproducing factories, disease-killing machines, and exotic creations performing many useful functions.

 Nice. Getting help from something that certifiably works to understand nature better with the help of some technological innovation. Sound scientific strategy, right? But, who would have thought that....

....by 2020, synthetic life creations could eliminate, or make manageable, nearly all human sicknesses, including most of today’s dreaded age-related diseases.
 

Hmmm? And that is not the end, for in fact....

...by 2030 or before, human-made life forms could provide everyone with an affordable, ageless and forever healthy body fashioned from newly-created ‘designer genes.’

Right. Fantastic. Here's my life savings, then - no questions asked.

Not a word about risk, failure, misuse, limitations or the wicked ways of the world that most likely will see to it that this, just as any other piece of technology, no matter how well it works, will certainly not provide "everyone" with anything worth having. In particular if guys like Pelletier (as well as Venter) continues to cry wolf long, long before there is anything even close to worth having in those areas where imminent delivery is ambitiously promised. Perhaps this is what it means to be a positive futurist? Well, in that case we don't really need them do we? We already have them, just they are known under other names (take your pick) when calling us up at the least suitable hours, or filling our email inboxes, with one senseless business scam after another.

Ok, ok, so calm down. So far, this is just another of these naïve grown-up school boys and useful idiots letting some steam off. Admittedly, there is also a wider organisation with academic ambitions that for some reason is publishing the rant, which is perhaps a bit more of a reason to get worked up. But, hey, that's nothing new, is it? So what is the problem? To get to that, I need to widen the lens a bit, in order to describe how this is just one of many examples of how – indeed! – exciting and promising scientific and technology areas are ridiculously oversold, to the possible financial gain of a few of the involved experts, but to the detriment of those people that could in fact have reaped substantial benefits from the field, had it not been for the fact that once that stage is near, everyone with a buck to spare to make it happen has lost interest and, frankly, faith. So here's my cases:

1. Gene therapy. This baby has in fact been pitched as being right around the corner since the 1950's (and through the 60's and 70's), believe it or not (just pick up some of the scientific articles in the field and look for the little motivator sentence at the end). It is a wonder that James Watson was able to reuse it to attract funding for the HUGO project (although he had to switch to the wider concept of genomics half-way, when the prospect revealed itself to be much less practical than what had been thought at the outset). However, now when at last some of the first really promising clinical applications are indeed surfacing, investors have lost interest and so would I, had I been in their midst. The example of a fully developed, initially tested and very promising gene therapy for cancer sitting in the freezer due to lack of funding to do the larger sort of trials needed to have good evidence for safety and effectiveness is telling. I mean, who would believe anyone claiming to have a "promising" gene therapy that just needs some testing when that song and dance has been performed a million times before with the same depressing aftermath?

2. Cloning. Well, this story is in fact a part of that of gene therapy, as well as the next one of stem cell medicine. Here, the overselling has been mainly in the form apparent mavericks claiming to be planing very shortly or to actually have done human cloning, as well as to claim human cloning to be a help for a large number of problems that may engage people. I won't supply any link here, since this is fraud and tinfoil-hat territory, but if you're curious, just google "human cloning" and surf away. In any case, human cloning comes in two basic varieties. One is what is also known as "therapeutic cloning" or, better, somatic cell nuclear transfer, as used in a process to produce pluripotent embryonic stem cells. Another one is what is sometimes referred to as "reproductive cloning", meaning that SCNT is used to produce a human embryo, which is then transferred into a woman's uterus and allowed to be carried to term. This latter technique is interesting mostly as the most realistic prospect for having a gene therapy procedure that could in fact work for some of the major and most serious genetic diseases. However, the prospect of having anyone allow that to happen, even less to provide funding for it has been substantially crippled by the actions of the mentioned mavericks. In effect, while gene therapy for mitochondrial genetic disease might slip through the net raised in response to the proof of the apparently obvious irresponsibility of scientists provided by said mavericks, the dream of of this sort of powerful gene therapy has otherwise been effectively bumped off.  

 3. Stem cell medicine. This is a very much alive area, and in recent years there has been a stream of news about fraudulent or highly questionable operations (other examples are here and here, and these are just a few, among the ones popping up through a simple search). Hurrying to promise this or that on the basis of a scientific basis that is still pretty frail and full of gaps, and clinical experience is effectively nil. All of these operations, of course, grossly oversell the potential of whatever stem-cell based service they are offering and, of course, they do that to attract paying customers and investors. A step away from that regarding fraudulent behaviour, but still related when it comes to vested interests playing a part, we have the recent European case of the failed attempt to have embryonic stem cell lines patented. While the reasoning of the court may be discussed, it is clear to me that the case for a patent at this early stage will have to contain pretty obvious misleading parts, lest the condition of usefulness present in all patent laws would be difficult to meet. Furthermore, said sort of overselling would have had to continue when making use of the patent. Stem cell scientists and supporters enraged over the ruling were all pretty open about that the idea of the patent was to sell it to big pharma in order to have them fund clinical development, research, large trials, and so on. Well, that's fine, but would at this early stage seem to imply promising said corporate actors enough to have them open the purse. So, one may justifiably wonder what was indeed happening in the case of professor Brüstle, who was denied a patent by the European Court of Justice – was it just a loss of clinical prospect or was it his personal financial exit strategy that disappeared in a cloud of mist, or was it a bit of both? Probably the last, so we may be certain that he would have just as good a reason to oversell as in the other cases I have mentioned, had he instead been allowed his patent. And I'm pretty sure that this would have backfired, just as the other examples I have been given above, all while the rights of the patents would have blocked the scientific progress that might one day have made the sales-pitch honest and fair. Or, it that would have proven to be overly pessimistic, to discourage any potential funder or investor, just as in the case of gene therapy.

And backfire it will also in the synthetic biology case if people like Pelletier continue to rant and do Craig Venter's marketting work for him, albeit the latter – I'm sure – will laugh all the way to the bank.

Time for Pressure on Media Promoting and FDA Facilitating the Burzynski Clinic Quack-Scam

The criticism of the close to fraudulent cancer treatment scam operated by the Burzynski Clinic that I have covered in some earlier posts (here, here), due to its attempt to silence public criticism through legal threats and general bullying and harassment, needs to shift focus. We know that what the clinic does is a confidence scam of a classic type: The necessary confidence-part is secured by conveying an impression of offering a "last hope" experimental treatment to desperate cancer patients and their close ones (while what one is actually offering is a procedure that has been experimental for three decades and not been shown to have any sort of effect in spite of all these years of research devoted to that end). The actual scam is the appallingly high price charged for the FDA-approved chemotherapy treatment that has to accompany the experimental one, lest the clinic would be clearly guilty of severe malpractice. But, as I said, this is now well-known and need not be further supported, besides mentioning some additional details that have surfaced lately, such as the disastrous track-record of the Burzynski clinic's clinical trials and the piquant fact that those who want to make donations to support the clinic's research are asked to wire the money directly not to the clinic or its attached research center, but to the dear Dr. Burzynski himself, and the fact that said Dr. Burzynski is under investigation for rather serious misconduct by the Texas Medical Board.


But let's not once again lose ourselves in what we already know, but ask the question: what makes the scam possible? One, of course, is the combination of the quite understandable desperation of anyone who has been struck by the information that one or one of one's close ones has incurable, terminal cancer – this is the source of there being a prey for the Burzynski vulture-strategy. Second, equally obvious, the complete  ruthlessness of the clinic itself and , at least, its leadership and its medical and management staff. But the fact is that that the clinic is extended ample help and support from two directions that are not equally obvious or expected.


One of these is "old" mass media. What started the whole story this round was an article in the UK newspaper The Observer, promoting a charity call for financial support of a family that wanted to take their sick child into the Burzynski program, but couldn't afford it (no wonder!). It was blog posts (primarily this one and this one) reacting to the fact that an otherwise respectable newspaper in this way made itself into a mindless megaphone of a quack-scam that attracted the wrath of the Burzynski Clinic, eventually leading to the ensuing threats and harassment. Later, it has been discovered, that the very BBC choose to publish a more or less similar item. Quite recently, The Evening Standard (also the UK) made a rather similar publication, wording its article carefully to make the facts about the Burzynski treatment look dubious and inconsequential by placing the word 'unproven' last in the article and surrounding it with square quote-marks (thus implicitly conveying the message: 'that's the establishment using fancy words to hide the fact that they don't care about seriously ill children'). Representatives of all publishers have defended the publication of their articles (here, here and here), but seem not to understand what they have been doing – which is making themselves into marketing tools of the confidence scam of the Burzynski Clinic for the prospect of attracting a few more readers. They all refer to a "human interest" reason for publication, but this falls apart as soon as one sees through the shallow, shiny coating that makes the Burzynski Clinic remind of a respectable health care institution at first glance. This is simply bad news-evaluation, poor research and bad publication judgement. Unless, of course, there are deals under the table that would at least make the publication make short-sighted financial sense. In either case, I fully concur with Josephine Jones' conclusion that the publications are immoral.


The other source of support comes from the U.S. Food and Drug Administration, FDA. This was a theme of the criticism that was pursued by Oxford University neurolopsychology professor and popular author Dorothy Bishop early on and which I mentioned in my first post on Burzynski. With all the threats and harassment against bloggers, however, it sadly disappeared as a major theme in the discussion. For, this is a fact: one thing that makes the Burzynski Clinic scam possible to run within the limits of the law is the fact that FDA has been continuously granting the clinic permission to run clinical trials for several decades. This despite the set-up of the scam operation, where these trials are systematically exploited to press enormous amounts of money off of desperate and vulnerable people. There are three very good reasons for why this should make the FDA retract all trial permissions. 

First, one may plausibly argue that what the Burzynski Clinic does is to use the hugely elevated charge for regular chemotherapy to cover the costs of the clinical trials, which means that what people are in fact paying for is to be allowed to participate in experiments with unproven procedures. But this goes against all minimally decent research ethical standards. When a patient participates in a clinical trial, it is the the patient who is doing the clinic running the trial a service, not the other way around. If anyone should be payed anything, it is the patient who should receive and the clinic that should give.


Second, the confidence scam is by itself reason enough to withdraw permissions. Someone may try to argue that, for a private health care institution, it is not wrong or unreasonable to cover costs of research by distributing them in the form of a price increase on offered services (that's a bit like viewing research as a part of the overhead). However, in the case of the Burzynski Clinic, this argument is unavailable for two reasons. One, the clinic offers but two services: regular chemotherapy on its own, or chemotherapy plus the experimental procedure, and it is the price of the latter that is elevated. Two, the clinic's marketing shows that in reality the research and the regular clinical practice cannot be separated. The Burzynski Clinic has but one service on offer: regular and approved chemotherapy with add-on of an experimental procedure. From whatever side one looks, this is a clinical trial, and that is what the clinic charges for.


Third, the track-record of both the past research of the clinic and the scientific publication of Dr. Burzynski himself is, in combination, a rather serious reason for doubting both the scientific basis for viewing the research as defensible in the first place, and the competence of the Burzynski Clinic team to conduct it. Add to this the investigation of the Texas medical Board mentioned above, and you can add reason to doubt the scientific, medical and ethical integrity of the research leader.


If the FDA was to decide to review the entirety of this complex of reasons, I'm quite sure that they would indeed find cause to revoke the permissions for conducting clinical trials granted to the Burzynski Clinic. And if not that, so at least reasons for changing some of its regulation so that a decision to revoke could indeed be supported. In effect, there are very good reasons to pressure the FDA on this point. Not being a US citizen, I myself do not feel well placed to figure out the best strategy for doing that in an effective manner (petitions? open letters? formal complaints?....), but if someone better placed takes an initiative, I would be more than happy to get on the wagon!

Lame Response from the Burzynski Clinic

Yesterday, the Burzynski Clinic issued a press release in response to the massive twitter (1, 2) blog and eventually old media coverage of how an alleged representative of the clinic bullied and threatened bloggers exposing the highly unethical practices of the clinic (see my former post). What the clinic does is to charge huge sums of money for people to access what is described on the clinic's website as "tomorrow's cancer treatment today" (duh!), which basically consists of state of the art treatment of chemo-/radiation-therapy (available at much cheaper cost at other clinics) plus Dr. Burzynski's own little discovery, antineoplaston, that has remained in the phase II of clinical trial, where the aim is to demonstrate any sort of benign effect, for several decades with zero results. One very limited version of the treatment (for Brainstem Glioma, a very malign and inoperable form of cancer) has been approved by the FDA for studies in phase III, going beyond this limit – planned to start this year according to the clinic's website. This approval has been issued under a special so-called orphan drug statute, meaning that the FDA considers there to be an extra important reason to allow research due to the rareness and severity of the disease combined with the fact that there is no existing very efficient treatment. There are no details on the arms of the trial, but one may assume that since there is some efficiency of chemo- and radiotherapy also regarding Gliomas, the setup will be such therapies by themselves compared to the same plus Burzynski's own invention. Any other arrangement would be a scandal.

In any case, the deeply unethical and very close to fraudulent practice of conveying to devastated people hit by the tragic information that they or one of their loved ones suffer from incurable cancer that they can access some sort of miracle cure if only they empty their savings accounts in the greedy lap of the Burzynski Clinic has to stop. It is highly problematic already in a phase II trial, but it is completely unacceptable and against all research ethical standards in a phase III trial. In fact, if anyone should be paying anyone anything it is the Burzynski clinic that should pay trial participants for their service to lend out their already heavily burdened bodies and minds to help investigate a procedure that as yet has shown no clinical effect whatsoever. And if FDA regulation allows such practice in phase III, it has to change, effected immediately, since it is a loophole for manipulating and conning seriously ill and very vulnerable people.

Of course, as always in science, caution should be exercised in predicting results of forthcoming studies. Basically, we'll see what the phase III trial eventually shows. But if this summary of the history of research on Dr. Burzynski's research is to be believed, there is not much cause for optimism. But, hey, I haven't said anything about the press release yet, so let's go there.

The most important message of the press release is that the clinic clearly distances itself from the content of the messages sent to bloggers by Marc Stephens and stating that said Stephens is not a representative of the clinic, but....:

So, Stephens was indeed hired by the clinic to do the job that he did, he just did it so bad it is even fascinating. To see this, we go to the next stage of the message when the clinic starts to address how it will now proceed in relation to said bloggers with regard to said dissemination of allegedly false information:

Of these, points A and B are inconsequential for the matter at hand (although it may be noted that point A is a lie, search for ANTINEOPLASTON A 10 here and see for yourself). They don't affect at all to what extent the Burzynski clinic is manipulating vulnerable people to pay out hundreds of thousands of US dollars for a treatment they could have received much cheaper elsewhere and with an add on with no proven effect. Tastelessly enough, in the press release is included a report on how a single, named patient who is in one of these phase II trials is doing. I will not name her, and I find it rather inappropriate of the clinic to do so. In any case, the statement that she is improving because of Dr. Burzynski's antineoplaston treatment lacks all foundation, since antineoplaston has not yet been demonstrated to have any effect. The patient's promising form is thus most probably the effect of the radio-/chemo-therapy administered in addition to the antineoplaston addition. In any case, a phase II trial cannot prove otherwise, no matter how many patients are included.

So, what about point C, then? This indeed is of some relevance, since scientific publication is the sign that a researcher has made progress in a way that is condoned by independent scientific specialists in the area. Well, after 2006, the list provided in the press release states 1-3 articles a year up to 2010 (when there is one). None for 2011, apparently. But anyway, that's pretty OK, isn't it? Well, actually not, according to this look into what sort of publications these are. In short, the publication record of Dr. Burzynski's research isn't worth zilch. Prior to 2007 it is either published in journals with no impact factor at all (meaning not even considered serious enough a scientific journal to be worthy a rank in terms of importance), or a ridiculously low one for a medical journal (meaning that virtually no one pays attention to what is published there). This, in turn, implies that stuff sent to these journals is stuff that no one of the more influential and better journals deems worthy of publication. It may be added, that if there had indeed been some result of a new cancer therapy, that would be material for the most high esteem journals in the world. In addition, these journals turn out to be either fronts for pseudo-science or the works of happy local amateurs.

From 2007, however, there are articles listed from the quite respectable  journal Neuro-Oncology. But..... wait a minute, I may just as well directly quote Jen McCreight, whose analysis I am using:

Burzynski has not published a single paper in this journal. Every single citation is an abstract from a presentation made at a conference. For those of you not in academia, we like to hold conferences where people can present their research and network. However, you’re allowed to present preliminary results that haven’t been published yet. Any scientist can submit abstracts in order to speak at conferences, and if that single paragraph sounds interesting, you get to give a talk. It’s pretty much impossible to judge how legitimate research is from an abstract (or presentation) alone, and some conferences are not competitive at all when it comes to who gets to speak – they have plenty of spaces to accept all presenters. Journals often act as archives for conferences they’re affiliated with, and will list those abstracts.

This means that none of Burzynski’s research from this journal has actually been peer-reviewed by the journal. The fact that he never actually published this data says a lot. Seriously – if you legitimately found something that helped cure cancer, prestigious journals would be tripping over themselves to have you publish in them. The fact that you can’t publish your research anywhere except in the occasional bottom-of-the-barrel shady journal means your research is terrible.

 McCreight in addition rounds off with the observation that there have been several attempts to replicate the promising results of antineoplaston reported by Burzynski, but all have failed.

So, there we are. After 2006-2007, Dr. Burzynski has made numerous presentations at scientific conferences reporting promising results, but no one seems to be able to replicate these. These presentations have indeed been abstracted in the journal Neuro Oncology. However, after some articles in scientifically completely insignificant journals, after 2007 there are no scientific articles reporting Dr. Burzynski's research in print.

In effect, due to the list of publications provided by the press release, the scientific standing of the Burzynski Clinic now actually looks even less impressive than before. In effect, the call for the clinic to immediately shut down its preposterous financial scam has been strengthened. And so has the case for FDA to urgently revise any regulation making such scams possible.