A paper about a protein being used — unapproved by health agencies — to treat diseases including cancer and autism has been retracted.
Here’s the notice from the International Journal of Cancer about a 2007 paper purporting to show that the substance, GcMAF, is useful against breast cancer:
This article has been retracted at the request of
Editor-in-Chief
‘Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF)’ by Yamamoto, N., Suyama, H., Yamamoto, N. and Ushijima, N.
The International Journal of Cancer, published online on 12 October 2007 in Wiley Online Library and in Volume 122, Issue 2, pp 461–467, has been retracted by agreement between the journal Editor-in-Chief Peter Lichter and Wiley Periodicals, Inc. due to irregularities in the documentation for institutional review board approval.
Reference: Yamamoto, N., Suyama, H., Yamamoto, N. and Ushijima, N. (2008) ‘Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF)’ Int. J. Cancer, 122: 461–467. doi: 10.1002/ijc.23107
Here’s the abstract for the paper, which has been cited 34 times, according to Thomson Scientific’s Web of Knowledge:
Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of breast cancer patients was lost or reduced because Gc protein was deglycosylated by serum a-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Patient serum Nagalase activity is proportional to tumor burden. The deglycosylated Gc protein cannot be converted to MAF, resulting in no macrophage activation and immunosuppression. Stepwise incubation of purified Gc protein with immobilized b-galactosidase and sialidase generated probably the most potent macrophage activating factor (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages treated in vitro with GcMAF (100 pg/ml) are highly tumoricidal to mammary adenocarcinomas. Efficacy of GcMAF for treatment of metastatic breast cancer was investigated with 16 nonanemic patients who received weekly administration of GcMAF (100 ng). As GcMAF therapy progresses, the MAF precursor activity of patient Gc protein increased with a concomitant decrease in serum Nagalase. Because of proportionality of serum Nagalase activity to tumor burden, the time course progress of GcMAF therapy was assessed by serum Nagalase activity as a prognostic index. These patients had the initial Nagalase activities ranging from 2.32 to 6.28 nmole/min/mg protein. After about 16–22 administrations (approximately 3.5–5 months) of GcMAF, these patients had insignificantly low serum enzyme levels equivalent to healthy control enzyme levels, ranging from 0.38 to 0.63 nmole/min/mg protein, indicating eradication of the tumors. This therapeutic procedure resulted in no recurrence for more than 4 years.
The corresponding author, Nobutu Yamamoto, did not respond to a request for comment. However, the Anticancer Fund, which has been pushing journals to correct the record on GcMAF, laid out for Retraction Watch the problems it saw with this paper:
This paper and 2 other papers from the same group report results of the use of GcMAF to treat cancer patients. Later in 2009 this group published another article reporting their results treating HIV using again GcMAF. GcMAF is supposed to be a naturally occurring protein capable of activating macrophages. It is claimed that an enzyme called Nagalase would deglycosilate GcMAF, impeding macrophages’ activation. With all this background the authors of this series of articles claim they created a GcMAF resistant to Nagalase. The authors reported treatment success by measuring Nagalase in serum, stating, in the cancer-related articles, that it is produced by cancer cells. In the HIV-related article they claim Nagalase is a viral component.
After several patients asked our organization, the Anticancer Fund, about GcMAF as a cancer treatment, we decided to look for the evidence supporting its use in cancer. The IJC article reports the use ofGcMAF in 16 breast cancer patients. All patients had previously mastectomy or lumpectomy and all but one received radiotherapy or chemotherapy, prior to the initiation of the treatment with GcMAF.
- The authors do not give any information on the staging of these patients. However, they determined that these patients had metastatic disease, based on an elevated level of serum Nagalase. Elevated Nagalase level is not a criterion to define metastatic disease in the TNM classification of cancer, 7th edition. There is therefore no proof that the patients had residual disease after the standard treatment they received.
- According to the information presented in Table 1, no patient received both radiotherapy and chemotherapy, which is rather unusual in the management of breast cancer patients. Especially, two patients who had lumpectomy did not receive radiotherapy which is recommended after lumpectomy.
- Our organization tried to contact Yamamoto’s co-authors. We found out that Hirofumi Suyama, a co-author affiliated to the Nagasaki Immunotherapy Research Group in Japan, passed away in 2009. Pr. Hirofumi Suyamawas a professor of Forensic Medicine at the Nagasaki University who retired in 1987 and did not publish papers from 1991 until 2007, when he co-authored several papers together with Nobuto Yamamoto. The co-authors affiliated to the Socrates Institute for Therapeutic Immunology in Philadelphia, organization from which Yamamoto appears to be director, are untraceable.
- The Nagasaki and the Hyogo Immunotherapy Research Groupst hat gave IRB approvals for these trials do not exist anywhere except in the papers from Nobuto Yamamoto. Moreover, three people listed in the approval documents denied being part of those groups or having ever participated in Yamamoto’s work.
- The purported sponsors of this trial denied having supported clinical research on GcMAF. They supported Yamamoto’s preclinical work, in the 90s. The US Public Health Service from 1992-1994 and the Elsa E. Pardee Foundation only in 1998. When he was associated to other institutions rather than the Socrates Institute for Therapeutic Immunology.
- We also found that Yamamoto forged the name of Pr. Charles E. Benson from the University of Pennsylvania, when he presented further results of GcMAF to treat some types of cancer and HIV to FOCIS meetings.
The most worrisome problem is that this article and others published in other peer-reviewed journals is used by some GcMAF manufacturers to support their claims and sell it illegally to patients. Plus these people are reporting their outcomes treating cancer, HIV, Chronic Fatigue Syndrome, Autism and other ailments, using invalid endpoints such as Nagalase; to promote the illegal marketing of GcMAF.
We have serious concerns at many levels concerning the development of this research and we have an obligation to find answers for the sake of desperate patients using this therapy.
GcMAF has also caught the attention of Jeffrey Beall, who wonders, “Would You Take a Cancer Cure Proven Effective in a Predatory Journal?” Here are some of the claims being made by GcMAF.eu, which sells the substance:
The results from all the diseases we list are astonishing, but in late stage cancer the clinics achieve an average of 25% tumour reduction per week. (We get that reduction with pancreatic cancer too.) These results are peer reviewed and published in prestigious scientific journals…
CFS/ME [Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]: Full recoveries in 70% of cases
An early-stage trial — not designed to test whether GcMAF actually works, just whether it is safe — is now underway.
Interesting story! Especially older people appear to become the victoms of illegally sold, not really approved chemicals, nutrition supplements and similar. It appears difficult to tell those victims that there are no miracle compounds like this.
This was an interesting reading as I could see more then 20 papers on this topic in Pubmed.
Since you have mentioned Jeffrey Beall, consider this: An article published in International Journal of Cancer in 2007 is retracted from the journal in July 2014 due to “irregularities in the documentation for institutional review board approval.” This paper has already been cited 34 times.
The question is, didn’t the Editor-in-Chief, members of the Editorial Board and the reviewers inquire about and examine the “institutional review board approval” in 2007? Is this a failure of the review process of a journal published by none other than Wiley Periodicals – a failure which Bohannon so eloquently presented about open access journals in his sting?
The story is interesting because it shows how failed traditional peer review can have a real-life impact in society because it was unable to deal with a basic issue of medical papers: institutional review board approval. On Beall’s blog, reference is made to three papers on GcMAF published “in the American Journal of Immunology a journal published by Science Publications, a publisher on my list.” I have requested Jeffrey to please indicate all of the attributes, qualitative and quantitative, that led this publisher to be listed as predatory. I think it is important to not simply take Beall’s opinon and classification at face value, or to have blind faith in Bohannon’s sting, either. So, if Beall states that publisher X, Y or Z is predatory, we should not just swallow this claim blindly. Instead, as scientists, we should demand of Beall to please explain the exact criteria that led to this publisher to be considered as predatory and why, for example, it would be more predatry than, as Paul Frank correctly points out, Wiley, one of science’s BIG 5 publishers NOT listed on Beall’s list. At a broader scale, this now causes some doubt about the veracity of statements in biomedical journals regarding patient approval, institutional review board approval, animal treatent approval, ethics approval, etc. We often read such statements in medical papers, but, upon submission of a paper to a journal, do the authors have to also submit a formal signed document by the university as proof of such approvals? If not, then what’s to say that such statements are not true (i.e., false)? Just because an MD writes in a paper that they obtained approval from patients, ethics boards, etc. doesn’t necessarily make it true. If any of the medical scientists who publish in medical journals have more details about this documentation, more details would be welcome here. I suspect that this could be an important issue that is being grossly overlooked.
I agree, this is what my concern is. I have followed Beall’s blog from the day he made his first post.
From late November 2013 till mid July 2014 he has added 129 publishers to his list but he has given explanation for about 10. What about the rest of the publishers? I have also commented on many of his posts. Till date non of those comments has been published.
Paul Frank, you will see an in-depth analysis of my critiques of the weaknesses of the Beall blog here at RW:
http://retractionwatch.com/2014/01/20/jeffrey-beall-scores-a-retraction/
That said, one has to distinguish fact from importance. Somewhat like the Bohannon sting. On one hand, we have to carefully scrutinize the methodology, because there is clear fault there. But we cannot ignore the underlying message that is carried, because there is truth, too. I guess you and I are able to see the dividing line, but what about most non-native English speakers, or those scientists who are fairly naive about publishing-related issues? They will swallow the whole lot at face value. That is why critics are essential, about Beall, about Bohannon, about PLoS, about Nature, about Potti, about me, about everything that revolves around science. To keep all these elements in check.
Consider this:
“Open access movement removes the voice of the reader, the consumer of scholarly research. The subscription model provides a valuable community validation function, because when readers or subscribers are unhappy with a journal because of low research quality, poor editorial standards and the like, they cancel their subscription.” – Jeffrey Beall (http://content.yudu.com/A2z1pz/RIAUGSEPT14/resources/4.htm)
On the top of this page is the story of a retraction by International Journal of Cancer, which evidently shows that there was a deficiency in the review process. How many libraries are gong to cancel subscription of International Journal of Cancer? This site is called “retration watch”. Based on the reports on this website, how many subscriptions will be cancelled, especially in today’s world of bundling of journals for subscription?
Here are some quotes from Beall’s paper: “The Open
Access Movement is Not Really about Open Access” (http://triplec.at/index.php/tripleC/article/view/525/514)
The open-access movement is really about anti-corporatism. OA advocates want to make collective everything and eliminate private business, except for small businesses owned by the disadvantaged. They don’t like the idea of profit, even though many have a large portfolio of mutual funds in their retirement accounts that invest in for-profit companies.
The open-access movement is a negative movement rather than a positive one. It is more a movement against something than it is a movement for something.
But a close analysis of the discourse of the OA advocates reveals that the real goal of the open access movement is to kill off the for-profit publishers and make scholarly publishing a cooperative and socialistic enterprise. It’s a negative movement.
The traditional publishing model, where publishers lived or died on subscriptions, encouraged quality and innovation. Publishers always had to keep their subscribers happy or they would cancel. (IS HE TALKING ABOUT COMISSIONS?)
Building on this idea, I do find that the open-access movement is a Euro-dominant one, a neo-colonial attempt to cast scholarly communication policy according to the aspirations of a cliquish minority of European collectivists.
Some tenured open-access advocates are pressuring young scholars away from submitting their work to traditional journals, sacrificing them to the open-access movement.
The open-access movement was born of political correctness, the dogma that unites and drives higher education.
Paul Frank, valuable insight, indeed. May I suggest that we conter all critiques about Beall on the page at RW I list above. If your comments are being erased, as dozens of mine were by Beall, then it is time to express your views elsewhere, i.e., here at RW. Beall is a key personality in the scholarly OA movement. That we cannot deny. And he is doing something unique that nobody else has the courage to do. So, let credit be given where credit is due. BUT, his blog has serious problems. So, do as I did, post your comment and, whil ein moderation (“Commen tin moderation” appears on your screen), take a screenshot (fn + prt sc). Save it. If it does not get posted (please use sensible language of course), then bring that injustice to RW, where a fair – but moderated – voice is allowed.
Thank you for your comments. I absolutely agree that what Beall is doing is essential to preserve the integrity of scientific discovery and reporting. What I don’t agree with is i) he is the qualified person to do it, and ii) his methods. I don’t know his motives. My very first comment on this page was first made on Beall’s blog. When it was not published there, I posted it here on retraction watch.
I agree to your suggestion. We can post a comment there and if it is not posted, post it here. The problem with you and me is not uncommon – http://scholarlyoadisq.wordpress.com/about/
Yamamoto’s Socrates Institute for Therapeutic Immunology in Philadelphia appears to be as small as an organization can get. According to a site that follows charities: http://non-profit-organizations.findthebest.com/l/411111/Socrates-Institute-For-Therapeutic-Immunology
“Socrates Institute For Therapeutic Immunology reported $0 in assets as of 2013 year-end, making it one of the smallest organizations.
The 2013 reported income for Socrates Institute For Therapeutic Immunology was $0, making it one of the lowest-earning organizations.”
Haven’t you noticed, there’s no money in cures.
In most countries, including the US, the government pays a very large proportion of health care costs. They are very interested in cures. They are also interested in evidence, as otherwise, they will be spending money on things that only enrich quacks. A drug/preparation that treats cancers (disorders of cell replication), viruses, developmental disorders, etc., is very likely not to treat any of these, and needs particular scrutiny.
Autism is not a disease.
I see that Yamamoto published two other papers about the wondrous panaceal qualities of GcMAF. Are they next in line for retractions?
GcMAF.eu is essentially Marco Ruggiero. Back in January, Ruggiero was third author on a paper in “Frontiers in Human Neuroscience”. First author was Jeff Bradstreet, who tells families of autistic children he will ‘cure’ them with chelation, “magnetic resonance therapy”, stem cells, and now he’s moving on to GcMAF. The paper claims to have found a reliable brain-anatomy test for autism. Perhaps closer scrutiny of the paper is in order?
well this is a bit strange… http://www.naturalnews.com/050553_Dr_Bradstreet_GcMAF_cancer_therapy.html
More on the propagators of GcMAF here – clearly out of their depth!
http://blueprintnation.blogspot.com/2015/07/gcmaf-and-people-pushing-untested-drug.html?m=1
I ended up here after attempting to edit a Wikipedia article on GcMAF that has become a favorite target of Anticancer Fund supporters who think it appropriate to editorialize the article rather than just let it be about the chemistry of the molecule.
I’m NOT a scientist, but I can follow this debate about retractions well enough to see that the pursuit of these retractions is not about the science as much as it is about citation “irregularities,” which sounds like more the concern of bureaucrats than intellectually curious scientists. The Anticancer Fund should quit wasting donations vetting citations and actually test the products since that is allegedly their concern.
This conversation has now broadened way past exposing GcMAF and has ventured into the realm of questioning the state of editorial integrity, in general. And this seems to be lacking in not a few scientific publications, at least according to Beall, the self-appointed watcher of the watchers. And now here we all are questioning Beall, the watcher of the watchers. How far back will this regress go before you watchers watching watchers will finally see what market-oriented economists (specifically Menger and Bohm von Bawerk) figured out centuries ago:
The market is smarter than the experts and can watch itself.
It doesn’t require committees, review boards, regulatory agencies, or any other team of experts to make products safe and effective; it just takes time, even when we’re talking about something technically complex like a drug. The market has been safely delivering technically complex products in the realm of physics and electronics (namely computers, cars, aircraft, etc.) for decades without the assistance of agencies and legislation.
Interestingly, GcMAF is now old news at this point. Marco Ruggiero and others evolved GcMAF years ago by joining it to oleic acid, vitamin D, and chondroitin sulfate in a new formulation called Goleic. But guess what? Goleic is now old news too and was modified, also years ago, leaving behind the human-protein part when they realized all the other included components could activate macrophages, independently of this protein by using just the chondroitin sulfate portion as the carrier. This new product was called Rerum.
The motivation for jettisoning GcMAF didn’t come out of the blue though. It originated from users complaining about an immune response provoked by Goleic’s human-protein carrier. Well, necessity is the mother of invention, so Rerum was born well ahead of the latest regulatory pronouncement on the dated GcMAF issued by the MHRA, after successfully prosecuting David Noakes in November of 2018 for manufacturing the “drug” GcMAF without a license.
But the story doesn’t end here. It gets worse… for the so-called watchers like Anticancer Fund, who are still preening about irregularities in peer-reviewed publications containing GcMAF articles while Rerum (two iterations beyond GcMAF) has proliferated after been made incredibly affordable through the efforts of a housewife who simply wanted to make Rerum more available to parents of autistic children like herself who could not afford either Rugiero’s Rerum or the Big Pharma’s drugs.
Rugiero and company, however, were not so patent-centric like pharmaceutical companies as to waste their time stopping this mother from doing this: She simply contacted a manufacturer, presented them with the list of ingredients for Rerum, and then made the same stuff for 350-times less. Now she’s selling it to others since it worked so well for her son. Maybe it works for them, maybe it doesn’t, but the cost is affordable and no one who’s tried it seems interested to raise a stink about it.
I think Rugiero didn’t concern himself with Rerum being knocked off since by the time this happened, he had already developed a new product, Rerum’s next iteration. And I think now, he is beyond that too. Are you beginning to see how this is supposed to work?…………McFly? Hello? Economics drives the science towards safer, better products, without the government’s “help.”
This is what naturally happens when you don’t have intervention to slowing development, adding expense, and creating barriers of entry for safer alternatives. The market outs the best and kills the worst — a hard pill to swallow for regulatory advocates who think the market needs their help to make this happen and don’t realize their efforts to do so tend to produce the opposite effect in spite of their adherence to evidence-based, scientifically vouchsafed procedures. How else do you explain chemotherapy’s continued use after decades of abysmal single-digit 5-year survival rates.
Rerum (two iterations beyond GcMAF) has proliferated after been made incredibly affordable through the efforts of a housewife who simply wanted to make Rerum more available to parents of autistic children like herself who could not afford either Rugiero’s Rerum or the Big Pharma’s drugs.
I know of three different knock-off versions of Ruggiero’s “Rerum”… there was “Omnia”, made and sold by Trevor Banks (previously from the GcMAF industry); “ReViVe” from Candice Lee-Bradstreet; and “KK Condroitin”, from Kerry Rivera, best known as an exponent of bleach enemas as a treatment for autism.
https://4.bp.blogspot.com/-o2A8t7ctPwI/WpHkQ6TkZ2I/AAAAAAAAXV0/Wez69vFLckgqTnV3p_PBI4-uWJIZ6DJzgCLcBGAs/s1600/prices.png
The housewife you mentioned, is she an addition to this list?
Well, how about autism? No comments on it. Must be at least one miracle there. If you see a pile of horsesh-, look for the pony.