Last month, we brought you the story of the retraction of a paper by Nobutu Yamamoto and colleagues about “a protein being used — unapproved by health agencies — to treat diseases including cancer and autism.”
A second paper by the group, about using the protein to treat HIV, has been retracted. Here’s the notice for “Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF),” from the Journal of Medical Virology:
The above article, published online on 21 Nov 2008 Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between Dr. Ari Zuckerman, Editor-in-Chief, Journal of Medical Virology and Wiley Periodicals, Inc. due to irregularities in the documentation for institutional review board approval.
We’ve noticed that retractions for IRB documentation problems are often a bit like jailing Al Capone on tax evasion: They’re the easiest charges to prove, but they’re likely the least of a study’s problems. And the excerpt of an email from the journal to Fabio Franchi, who brought the issues to the editors’ attention, suggest that’s the case here:
I do hope you can appreciate that some of the issues you raise are beyond the purview of Wiley and COPE [Committee on Publication Ethics]. You will note that in consultation with Dr. [Arie] Zuckerman [, who edits the journal,] we are retracting the article due to unverifiable IRB documentation; we leave to you and others conversations regarding Dr. Yamamoto’s scientific research.
Here’s the abstract of the paper, which has been cited 16 times, according to Thomson Scientific’s Web of Knowledge:
Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of HIV-infected patients was lost or reduced because Gc protein is deglycosylated by alpha-N-acetylgalactosaminidase (Nagalase) secreted from HIV-infected cells. Therefore, macrophages of HIV-infected patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Since Nagalase is the intrinsic component of the envelope protein gp120, serum Nagalase activity is the sum of enzyme activities carried by both HIV virions and envelope proteins. These Nagalase carriers were already complexed with anti-HIV immunoglobulin G (IgG) but retained Nagalase activity that is required for infectivity. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage activating factor (termed GcMAF), which produces no side effects in humans. Macrophages activated by administration of 100 ng GcMAF develop a large amount of Fc-receptors as well as an enormous variation of receptors that recognize IgG-bound and unbound HIV virions. Since latently HIV-infected cells are unstable and constantly release HIV virions, the activated macrophages rapidly intercept the released HIV virions to prevent reinfection resulting in exhaustion of infected cells. After less than 18 weekly administrations of 100 ng GcMAF for nonanemic patients, they exhibited low serum Nagalase activities equivalent to healthy controls, indicating eradication of HIV-infection, which was also confirmed by no infectious center formation by provirus inducing agent-treated patient PBMCs. No recurrence occurred and their healthy CD + cell counts were maintained for 7 years.
Increasing access to papers through Open Access will increase scrutiny, as argued by Stephen Curry in his post on who governs science.
http://www.theguardian.com/science/occams-corner/2014/aug/15/who-governs-science
That leaves the question as to who should catch fraud, the subject of a recent post by neuroskeptic
http://blogs.discovermagazine.com/neuroskeptic/2011/11/02/who-should-catch-fraud/#.U-8foSgz3jR
Leaving it to individuals is problematic, as neuroskeptic, points out.
As stated above, going for one problem is analogous to putting Al Capone in jail for tax evasion – it is indeed correct, but there are other issues that need to be dealt with too.
The only solution I can see, which I posted on recently (http://ferniglab.wordpress.com/2014/08/16/policing-the-police/) is for individuals not to have to work alone, so comment, post, including (especially) at PubPeer frequently, politely, and volubly, This appears to cause stirrings and more action than if we put up and shut up.
I wish you were right! However PubPeer has just came under siege. It recently received its first legal threat, and – an interesting coincidence – unregistered commenters even started arguing against the practice of highlighting gel image problems especially in older papers: https://pubpeer.com/topics/1/A9C1A3DBF6649CC62871AA7DC87B17#fb13270
BB, this is a very interesting, important and somewhat negative development, I feel (but one that was bound to happen sooner or later). Can any more details be provided about the legal threats, and if those threats are being made against PubPeer or against a person who has made comments about a paper. It is very important because what academic critics might simply be considering critical analysis and critique of the errors and faults of a paper, the victims (aka, the authors of the faulty paper) would definitely try to project it as libel. I think this is the tragedy of the academic critics and anonymous movement that is genuinely trying to correct the literature and expose, or reveal, the errors and problems: they are demonized. I do not want to comment too strongly about gel images, but in some ways, I feel that there is some logic, or truth, in revealing errors with considerably older papers, especially that used methods that, at the time were considered to be “advanced”, or with methods that were still experimental or that would have evolved and improved over time. This makes criticism tricky because we sometimes critique with a current prism in mind when in fact we need to take a step back and observe what was the experimental reality in the age when that paper was published or when that research was conducted. Independent, any more detailed information or thoughts about what you have written would be a valuable learning point.
The retracted J Medical Virology paper is still listed on the GCMAF.eu website here: https://www.gcmaf.eu/gcmaf-science/published-patient-trials/
The website also, amusingly, includes a page called “Beware of Blogs”.