Increasing Critical Questions Amid Mexican Mitochondrial Replacement Therapy Experiment

Mitchondrial Replacement Therapy (MRT) – sometimes referred to with its headline name "Three Parent Babies" – is an innovative, in humans yet unproven, reproductive genetic technology, by which it is hoped that a more effective avoidance of having children with severe mitochondrial hereditary disease (as a rule extremely severe, untreatable and lethal). MRT is controversial both as assisted reproductive technologies are controversial, primarily among certain religious groups, and because it is the first example of hereditary genetic modification of human beings – so-called germline genetic modification – that has been seriously contemplated. A nice summary of the scientific and ethical complexities involved can be found here.  The last couple of years, ethical, legal and scientific debate about whether or not human trials of this experimental technique should be allowed has surged, and special legal provisions have been created for this purpose in the U.K., as well as some US states. However, the leading reproductive researchers in the UK and US just stepping up to make an opportunity out of this new legal room were quickly overtaken by the less prominent colleague of Dr. John Zhang, from a US private fertility clinic, who almost a year ago reported a human MRT experiment conducted at a Mexican clinic in order to duck US regulatory oversight.

Already from the start, ethical and regulatory questionmarks have surrounded this experiment. First, objections have been raised about the ethics of Dr. Zhang to create MRT embryos in the US to then be moved to foreign soil in order to circumvent US regulatory frameworks and scientific guidelines for MRT. Second, while Dr. Zhang had described why Mexico was chosen as the country to host the experiment by claiming that “there are no rules” regarding MRT there, subsequent legal analysis by my bioethics scholarly colleagues César Palacios Gonzalez and María de Jesús Medina Arellano has revealed that the experiment very likely breached a number of Mexican legal statutes related to research and reproductive medicine. A popular presentation of this finding can be accessed here.

In the meantime, the US Food and Drug Administration, yes, the mighty FDA, has apparently been silently probing the matter with regard to Dr. Zangh's relationship to US federal law. For just a few days ago, Mary A. Malarkey, Director of the FDA's Office of Compliance and Biologics Quality, sent a briskly phrased (to say the least) official letter to Dr. Zhang, enumerating a number of US federal legal violations allegedly involved in the Mexico MRT adventure. I have uploaded the letter to to Google and made it available for anyone to view and share, here. Among the allegations made in this letter are the following:

0. ... you are using MRT to form a genetically modified embryo, which is subject to FDA’s regulations with respect to human cells, tissues, or cellular or tissue based products (HCT/Ps) under 21 CFR Part 1271, issued under authority of section 361 of the Public Health Service Act (PHS Act [42 U.S.C. 264]). HCT/Ps that do not meet all of the criteria in 21 CFR 1271.10(a) and do not qualify for any exceptions in section 1271.15, are subject to additional regulation, including appropriate premarket review.

   The genetically modified embryo that you formed using MRT does not meet all the criteria in 21 CFR 1271.10(a) and does not qualify for any exceptions. /... /

   [The HCT/P is] also regulated as a drug as defined under section 201(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. 321(g)], and a biological product as defined in section 351(i) of the PHS Act [42 U.S.C. 262(i). Specifically, your processing constitutes more than minimal manipulation of cells or nonstructural tissues, as defined in 21 CFR 1271(f)(2)

   To lawfully market a drug that is also a biologic, a valid biologics license must be in effect [42 U.S.C. 262(a)]. Such licenses are issued only after a demonstration of safety, purity, and potency. While in the development stage, such biological drugs may be distributed for clinical use in humans only if the sponsor has an IND application in effect as specified by FDA regulations (21 U.S.C. 355(i); 42 U.S.C. 262(a)(3); 21 CFR Part 312). The MRT-produced HCT/P is not the subject of an approved biologics license application (BLA) nor is there an IND in effect. / ... /
   
   

   Nor is exportation permitted unless it meets the requirements of an applicable export exemption.

    / ... / your export at issue here did not meet the requirements of any of these export exemptions. / ... /

   The Director signs off by noting:
   
   
   

   This letter is not intended to be an all-inclusive list of violations. It is your responsibility to ensure full compliance with the FD&C Act and the PHS Act and their implementing regulations. 
   
   We request that you notify this office, in writing, of the steps you have taken or will take to address the violation noted above and to prevent recurrence.

   
   While I am cautiously positive to having well-regulated legal room for MRT trials, I have to say I found Dr. Zhang's maverick action very ill-conceived from the start. While the experiment has been subsequently reported scientifically, it is not part of any controlled and planned experimental series that could contribute to the formation of a solid body of scientific evidence to either substantiate or rebut the hypothesis that MRT is a viable medical procedure. Nor was it done in response to any sort of dire medical need, but solely as an attempt to overcome efficiency problems in IVF, thereby lacking any of the ethical justification usually cited as the main reason to allow for human MRT trials. Moreover, as there was no research ethical review, no check has been applied to the consent procedure, making it very likely that the couple who were the patients have been exposed to what is known as the therapeutic misconception. Therefore, the experiment brings to mind  the sorry tale of what has become of the once red-hot scientific field of stem cell therapy, nowadays mostly ruined and disreputed by gung-ho experimenters and unchecked, semi-fraudulent commercial operations preying on vulnerable people's desperation in a hunt for money and personal glory. If germ-line gene therapy is to be allowed and able to develop out of MRT experiments, it has to proceed within a very rigid and tight oversight, both scientifically and ethically. Stunts like the one of Dr. Zhang constitute a threat to that. Therefore, I'm very pleased to see FDA yank whatever legal leash it has as hard as it can, and I hope the scientific community will do the same. As a first step, a retraction of the article in Reproductive Biomedicine Online due to false statements regarding ethical and legal status of the reported trial may be in order?
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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?

Old AJOB Rut re. Prenatal Dex Picks up New Steam as Undisclosed Double Loyalties and Dependencies of Now Editor Skip Nelson are Suggested

Amended 2014-04-18: see bottom of this post!

I'm sure several readers remember a long series of posts across 2011-12, connected to a series of internal troubles in the management of the American Journal of Bioethics. One of the roots of all that mess was a controversy that eventually led to the resignation of Hilde Lindemann from the AJOB editorial board in protests of its managerial operations, followed by other weighty ones later by, e.g. Udo Schuklenk and John Lantos. Eventually, after much external pressure, following a less than elegantly handled stepping over to private business by then editor-in-chief, Glenn McGee (later to become CEO of the now defunct stem cell banking, cosmetics and therapeutic business RNL Europe), the drop-out of the AJOB operation of both him and his wife Summer Johnson McGee, who had initially been appointed to advance to co-editor with the new EiC appointed to succeed McGee.

The last post with any substance out of this mess was this one, and the entire series is found here.

The affair leading to the resignation of Lindemann connected to a critical scrutiny, and eventual letter to the FDA, signed by a large number of bioethicists, regarding some unresearched, non-evidence based, experimental off-label prenatal drug treatment at the Mount Sinai hospital with regard to congenital adrenal hyperplasia. This led to a long series of complicated controversies involving AJOB, later leading up to the developments summarised above, and one of those concerned the possible conflict of interests of several centrally placed AJOB managerial figures. Among those involved was Robert “Skip” Nelson, now editor-in-chief of the AJOB Empirical Bioethics journal, at the time ethicist linked to the FDA (he still is, as a matter of fact), who sent a letter to the Office for Human Research Protections on the Prenatal Dex case, as it came to be known, clearing the accused doctor of having broken any FDA regulations. Now it is reported that, apparently, Nelson at the same time had close and live ties, to AJOB and the people in the management who were deeply involved in one side of the controversy. That is, it is argued in a recent post by Alice Dreger and Ellen K Feder (who belong clearly to the other side, it must be added), one of the prime expert sources had hidden loyalties and dependencies that remained undisclosed and is now holding a gallant EiC title in the AJOB family of journals.

The whole story and argument is told much better than I ever could by Alice Dreger and Ellen K. Feder themselves at the superb Canadian Impact Ethics blog.

Amendment:
Skip Nelson contacted me personally after posting the first version of this report, and made clear that he finds nothing new in what is described by Dreger and Feder, that no payments to him from AJOB have ever been involved in his service as EiC, that he performs this job as part of his FDA assignment, and that what he claimed in his letter to the OHRP regarding Prenatal Dex remains true (Dreger's and Feder's view on that is set out here). Nelson also told me that he has no plan to respond publicly to Dreger and Feder. This post has been amended in the light of that in a few places above.

US Approval of the GMO Salmon "Frankenfish" - Reasons for Continuous Caution Remain in the Absence of Added Value

Today, New Scientist reports about what looks like a landmark event in the USA and (due to the role of the US for the world economy, trade and global regulation affecting trade) global handling of the possibility of using genetically modified animals for food production. Other reports can be found here, here, here, here. The FDA, in a statement released on December 27, has cleared a particular brand of GM Salmon – dubbed the "Frankenfish" by my US bioethics colleague Art Caplan in a comment that is nevertheless cautiously positive of the development, at least from a food safety point of view – modified to internally produce more growth hormone and thus grow to full size faster on less feeding or larger size with maintained feeding levels. To forestall possible negative environmental impact, it has also been engineered to carry a sex-chromosome abnormality, rendering it sterile, and the production will take place in closed off settings, especially in its initial phases, where it will take place in tanks isolated from the natural environment. All of these things are expanded on in the NS piece and the links it provides. The proposal by the FDA will be open for public comment for 60 days.

Concerning the use of genetically modified organisms for food production, there are basically four issues to address: Is it good for anything, what is its benefits? How safe is it to eat and produce (in the same way as we would ask of any other crops or cattle)? How environmentally safe is it? Are the two safety levels mentioned sufficient to warrant production in light of the benefits? Art Caplan comments on the food safety side of the issue, something that has traditionally attracted lots of attention in the media. It is also angle often played by opponents of GMO for food, since immediate safety to consumers (and sometimes workers) is something that appeals very directly to people's sentiments and may thereby affect their moral and political views. However, the GMO industry likes the food safety side of the discussion very much as well, since – as a matter of fact – when assessed on the basis of actual evidence, GM food stands up pretty well compared to many more "traditionally" produced food. This is the point that Art is making and precisely for this reasons, I agree that food safety is not what the discussion should focus on with regard to GM food. However, this is far, far from deciding the issue, since there remains the environmental risk aspects of not the eating, but the actual production of the food. This has always and continue to be the overwhelming reason for a high degree of caution, skepticism and restraint in the GM food area.

In a very recent (and, I would say, seminal) book by David B. Resnik, Environmental Health Ethics, that I just finished reading and am about to review for the journal Public Health Ethics, this is the main conclusion to embrace, although it is held out that GM food may bring some rather particular food safety issues when the genetic modification concerns the production or resistance to toxic agents. Nevertheless, Resnik ends up supporting the notion of a regulated and supervised introduction of GM food, where a number of factors must be considered to decide an issue like that of the "Frankenfish" Salmon production. In my own thinking around the GM food issue – foremost in my book The Price of Precaution and the Ethics of Risk (in particular in chapter 6) – I reached a similar, yet slightly more specific, conclusion. One thing that Resnik lists among the factors to ponder is that of the value of the final product, however, there is not much of specific discussion of what the actual value of actual GM foods is (rather than what it may be). My own analysis, in contrast, takes this into account and ends up, because of this, in the position that, in fact, most actual GM food prospects are very difficult to justify in view of the environmental risks. This since most GM food provides no benefit whatsoever that cannot be had in other ways, besides a better profit margin for the producer.

So where do we end up regarding the GM salmon in light of this. Well, first of all, it should be underscored that the project has indeed put some impressive environmental safeguards in place. The environmental concerns with regard to GM food production are basically two, genetic leakage over species borders and (because of genetic leakage or other reason) ecological hazard, and these are indeed addressed by the sterility of the "Frankenfish" as well as the external measures, such as initial growth in isolated tanks. However, as we know, nature is a very complex system that we still understand only partially (to put is mildly), and there will of course be risks, uncertainties and things we currently don't know about remaining. The crucial question, therefore, is the last one formulated above, whether or not the added value of this particular product makes it worth allowing the introduction in view of the risks and uncertainties, given the safeguards described. It is here, that I become less optimistic than the FDA, Caplan and (possibly) Resnik. While there may certainly be envisioned a use of GMO technology to provide humanity with significant benefits to justify large scale introduction (under oversight) of GM food with safeguards of the sort described, the "Frankenfish" salmon, just as the "roundup ready" crops, does seem to provide benefit, first, merely of a monetary kind and, secondly, only to the producer. This is, in the GM salmon case, no different than the use of growth hormone or antibiotic feeding supplement in industrial farming. Therefore, I can see no added value of this product and thus it cannot justify its environmental risks, however small.

Burzynski Clinic Sued by Patient for Fraud, Neglience and Whatnot

So, at last, something seems to be happening that is somewhat along the lines I called for in my last post on the ugly operations of the Burzynski Clinic. It is now reported that a patient that has been victimised financially as well as medically by the Burzynski confidence scam is suing for "punitive damages for negligence, negligent misrepresentation, fraud, deceptive trade and conspiracy". Hopefully she will win the case and hopefully this will put the Burzynski operation out of business.

However, this operation is in fact a business model for the callous and greedy in the world of private health care business. So, even if the suit would manage to put the Burzynski Clinic down, the phenomenon remains possible as long as the FDA accepts and permits clinical trials on the conditions exemplified by the Burzynski scam. The case for FDA to change its policy therefore stands unmoved.

My best of luck to the claimant, Ms. Quinlan!

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.