Q&A with Carl Elliott

Carl Elliott, a bioethicist at the University of Minnesota and author of such works as White Coat, Black Hat and a recent article on Slate that, shall we say, burned bright, hot and fast, interviewed me and posted our conversation on the Brainstorm blog at The Chronicle of Higher Education. Carl is known for his courageous and influential work on serious issues in medical ethics, so it was a great honor for me to have this opportunity to talk about about the history of this blog and issues in the predatory marketing of stem cells. 

More than minimally manipulative

While the Celltex travesty was unfolding down in Texas, the International Cellular Medicine Society (ICMS), a marketing-savvy group of proponents of the deregulation of stem cell injections, announced the appointment of plastic surgeon Ricardo Rodriguez as its new president. Dr. Rodriguez, whose advertised procedures include BOTOX, breast augmentation (warning: link may be NSFW), and the B'more butt-lift, will be the third leader of this organization, which has shown a frankly astonishing ability to project its simplistic, stem cell business-building messages (and those of its previous leaders, sports medicine doctor Christopher J. Centeno, and chiropractor/epidemiologist Michael D. Freeman) in major media and across the internet. 


But what exactly is the ICMS about, how did it burst so suddenly onto the stem cell scene, who are its leaders, and what motivates them to promote expensive, wild-eyed stem cell schemes without independent oversight or evidence of safety and efficacy? The tale is long and very, very twisted, so I'm afraid I'm going to need to ask a bit more of your time than usual to explain why I think the ICMS is not all that, and much more than, it seems.

Let's go back to the roots. If you ever find yourself in Salem, Oregon, try heading south of city center to a downscale neighborhood near the municipal airport and Stone Quarry Lake. Drive a few hundred meters down 22^nd St, to where the sidewalk ends just east of McGrath’s Fish House and Prestige Auto Repair, and you will find the global headquarters of the ICMS: a post office box at 2667 22nd St SE, Salem, OR 97302. If you need directions, the ICMS graciously provides them on its Facebook page, although I generally prefer Google Maps to Bing, if only for the pictures...

The bleeding edge of stem cell therapy...

... on the banks of Stone Quarry Lake.

The Salem P.O. box is a convenient place for ICMS executive director, Salem-based David Audley, to pick up the mail, and just one hour by car from Oregon Health Sciences University in Portland, where former ICMS president, Michael D. Freeman (2009-2012), teaches forensic epidemiology. Freeman, originally a chiropractor, is himself no stranger to Salem - the ICMS mailbox is less than 10 miles from the clinic where, in 1991, he and four other chiropractors (including Freeman's father) were accused by the state of fraud and racketeering for using a doohickey known as a Toftness Device (but as the court documents note, also referred to as a "radionics detector" or "Freeman device"). The online Museum of Quackery points out that these *ahem* diagnostic tools were rigged together from PVC tubes and couplings. The defendants asserted that the device they used in their practices was, however, substantially different from the TFD, as it included "rubbing plates" and anyway, had been approved by the Oregon Board of Chiropractic Examiners - so there! In any case, the case was dropped even though the chiropractors did not deny using these devices, giving Freeman a defendant's-seat view of the amazing healing power of wriggly legal maneuvers. More recently, he seems to be putting this knowledge to frequent use as an expert witness in various cases, including testifying for the defense in the Casey Anthony trial, and giving a non-self-reflective lecture on "Exposing, defusing and debunking junk science" in Los Angeles this January.

Hat tip, Eugene Register-Guard.

I don't know what led Freeman out of chiropractic and into the arms of epidemiology, expert testimony, and his longtime partnership with Chris Centeno, owner of Regenerative Sciences (of Regenexx™ and USA v Regenerative Sciences fame), but PubMed shows their first co-authored publication to be from 2004 ("Waddell's signs revisited?"). This co-authored comment in Spine (sorry, paywall) and their next six papers have nothing to do with stem cells, but rather various forms of spinal injury, with a focus on whiplash. For the past few years I thought this was anomalous, and not particularly worth commenting on. 

But then last month I stumbled across some real expert testimony, by orthopedic surgeon George Muschler, in the FDA vs Regenerative Sciences case (via a link in this story on HuffPo). At 107 pages (48 pf which are Muschler's CV, and several of which have been redacted), this is not for the short of time. But for anyone interested in seeing what an actual scientifically-minded M.D. makes of the published claims in support of Centeno's Regenexx™ stem cell product, it is definitely worth a read. My one-word summary would be: scathing. For the curious, I have excerpted a few choice passages below:

Based on these observations, while I have no reason to question the motive of Dr. Centeno et al. to provide service to patients, I am concerned at this point that continued progress along the direction that has currently been established may be degenerating into an undisciplined and unfocused and even groping and wishful fishing expedition. The process that has been established does not appear to be subject to adequate oversight at the level of the IRB. From the personal level, this has the risk of exposing hopeful patients to a broad range of unnecessary and unproductive clinical therapy attempts under the banner of a “research investigation” that is, in fact, incapable, by design, of detecting the very treatment effect that RS purportedly hopes to demonstrate. On the medical level, I am concerned that the studies, as proposed, are being conducted using a culture expanded cell product that has not yet been adequately characterized. Furthermore, product specifications for quality assessment have not been defined, specific release criteria are not articulated, and the product has not been subjected to a rigorous assessment of safety that satisfies contemporary practice standards. [Muschler declaration, p. 31]

 and..

According to the paper [referring to (Centeno CJ et al., Safety and ComplicationsReporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells usingAutologous Platelet Lysate Technique, Current Stem Cell Research & Therapy, 2010;5:81-93)], four of the six authors (Centeno, Schultz, Cheever, and Robinson) have equity ownership in RS. Centeno 2010 article at 81. Another author (Marasco) has equity ownership in NeoStem, a company to which RS has reportedly licensed the Regenexx procedure in Asia. http://www.regenexx.com/2009/05/regenexx-in-china/ (November 22, 2010). Thus, all but one of the authors in this report have direct financial conflicts. Of particular note, Dr. Centeno and Dr. Schultz served as the only two reviewers charged with screening follow- up MRI scans for evidence of abnormal growth or tumor formation. Centeno 2010 article at 82. They also served as the only two adjudicators of patient complaints. Id. at 83. [Muschler declaration, p. 38]   

and furthermore...

Although bearing more on the ethical context of these studies than their scientific context, the IRB overview of these studies warrants brief discussion. The IRB that took responsibility for review, approval, and oversight of the studies authored by Dr. Centeno is identified as the Spinal Injury Foundation IRB. In the case of the Centeno 2010 article, the paper states that treatment of the “Group 1” patients was approved by the Spinal Injury Foundation IRB. Centeno 2010 article at 81. No mention is made of any IRB approval of treatment of the Group 2 patients discussed in that study. 

From records provided to me, it appears that Dr. Centeno has an unusually close relationship to the Spinal Injury Foundation IRB: Dr. Centeno was the registered agent and Medical Director of the Spinal Injury Foundation. See 2009 EIR Attachments 6-7 (Kreuzer Dec. Exhibits 19-20). It should be noted that Dr. Centeno apparently recused himself from voting on the IRB’s approval of the studies. It is not clear if he was also excluded from the review and discussion of these protocols and/or if the voting records of IRB members were secret, so as to minimize potentially biased influence of a professionally and financially conflicted member. It should also be noted that John Schultz, M.D., and Michael Freeman, Ph.D., who are listed as co- authors on some of Dr. Centeno’s publications regarding the RS cultured cell product, were also members of the SIF Board of Directors.

It is of potential significance that, according to the current (November 22, 2010) Spinal Injury Foundation website (http://www.spinalinjuryfoundation.org/), the Spinal Injury Foundation is now operating under a different name, International Cellular Medicine Society, which is located in Oregon. Among the nine points in the ICMS mission statement is the goal: “To establish that when A-ASCs are minimally culture expanded, are not biologic drugs but rather human tissue.” http://www.cellmedicinesociety.org/physicians/join (accessed November 22, 2010). Dr. Centeno also serves in a leadership role in ICMS, specifically as the Medical Director. http://www.cellmedicinesociety.org/home/boards-and-councils/board-of-directors (accessed November 22, 2010). [Muschler declaration, p. 40]

The TL;DR summary: Centeno and Freeman were leaders of a separate, now-defunct organization (Spinal Injury Foundation) prior to becoming the first and second president of the ICMS, and said organization was tasked with, among other things, providing the institutional review of a body of research behind Centeno's Regenexx™ product line that one expert noted as being at risk of "degenerating into an undisciplined and unfocused and even groping and wishful fishing expedition." Freeman responded to the FDA's expert declarations here, and Regenerative Sciences posted a chronology here.

Freeman and Centeno: the early years

At this point in the story, I have to give credit to an anonymous friend of the blog who pointed out that the Spinal Injury Foundation itself evolved from a different website, Whiplash 101, a resource used to, among other things, direct patients to apply for a one-hour consultation with Centeno for $350. Centeno also founded an (also now-defunct) online Journal of Whiplash and Related Disorders, for which he and Freeman, unsurprisingly, served as co-editors-in-chief. 

http://web.archive.org/web/20050210122622/http://whiplash101.com/

Centeno and Freeman's Spinal Injury Foundation ramped up its marketing game even as they were careening off toward the stem cell fringe, running awareness days and other fundraisers including, in 2007, the novel concept of rewarding anyone who donated $1495 to this whiplash organization with a chance to drive a Lamborghini, Ferrari, Bentley, or other speedmobile around a race track in the Rockies. The promotional page for the event included the cautionary text: "If you can't find a car you like, consider psychiatric help or high-dose antidepressants."  

Snap your neck for whiplash!

It was in around 2005 that Centeno showed visible symptoms of the stem cell itch (his first n=1 stem cell paper was published the following year). We know this because 2005 was the year he sold the Colorado professional corporation known as "Christopher J. Centeno, M.D., P.C."  to Florida-based company PainCare Holdings for $3,250,000 in cash and 1,132,931 PainCare shares valued at $3,750,000. What Centeno (the person) specifically did not sell, however, was intellectual property surrounding a certain stem cell process he had cooked up while running the Spinal Injury Foundation, and Whiplash 101, and his busy clinic, and the whiplash journal, without (as far as the literature reveals) any previous published indication of interest, ability, or experience in stem cell research and development. Another stem cell miracle!

Stem Cell Intellectual Property .  (i) Any and all activities and work product of Sellers regarding regenerating damaged or degenerated tissue, including, but not limited to, the development and sale of a turnkey solution for the isolation, processing and expansion of autologous stem cells for such regenerating damaged or degenerated tissue and the pursuit of any and all business opportunities available as a result of such activities; (ii) any and all work and work product of Sellers related to the isolation, processing and expansion of autologous stem cells; and (iii) any and all work and work product of Sellers related to the isolation, “processing” (as hereinafter defined), expansion and “storage” (as hereinafter defined) of autologous stem cells and/or storage of stem cells, Mensenchymal stem cells, chrondrocytes, or other unnamed progenitor cells, including but not limited to the development of short and long term stem cell storage plans.  “Storage” means the freezing or otherwise storing stem cells in a suspended activity state for later use.  “Processing” means includes but not limited to manipulation, expansion, isolation, purification, and/or differentiation of autologous stem cells or any stem cell line. [from PainCare - CJC Asset Purchase Agreement]

The PainCare deal turned rancid after that company was accused of overstating its revenues, and became subject to multiple class action suits. Centeno was able to regain his eponymous assets for a small fraction of the original selling price.

Not long after this settlement, Centeno and Freeman were cobbling together the first version of the ICMS, known as the American Stem Cell Therapy Association (ASCTA) at www.stemcelldocs.org. This group, whose founding members included Freeman, Centeno, and Centeno's partner John Schultz, as well as, o-ho!, Centeno's fellow University of South Florida alum Zannos G. Grekos (someone readers of this blog should certainly recognize), espoused the same basic set of values that characterizes the ICMS, including an emphasis on the de-regulation of autologous stem cell products, and a strange insistence that dark forces stand in the way of stem cell progress (with enthusiastic support from the bleachers at Stem Cell Pioneers, and its own, now apparently static, patient info portal, safestemcells.org). 

Over the years, the ICMS has embraced a galaxy of stem cell proprietors, the likes of Korea's own Booger-cloning Ra Jeong Chan [wayback], and Jorge Tuma [wayback] and Augusto Brazzini [wayback] of Peru on various councils, although you won't find much trace of them on the current version of the site. But even after making the transition to an "international" society, the group has maintained some oddly America-centric positions, including the oath it requires prospective board and council members to take prior to entering service (secret decoder ring not included):

Advisory Board and Council Members must affirm that minimally culture expanded stem cells are 1). Part of the practice of medicine and used as part of a physician practice in one state and through the state practice of medicine, 2). Do not constitute the creation of a new biologic drug or product that would fall under any part of FDA regulation on new drugs or biologics and 3). Exempt from any US Food and Drug Administration regulations.

Note that this vow makes no mention of the substantively similar provisions for the regulation of human cell and tissue products in the EU, UK, Canada, and other countries, which seems strange for a group that labels itself "international." 


Whatever the case, the ICMS' general strategy seems to me to have consisted from Day One of: 1) the promotion of treatments based on human cells that have not been subjected to rigorous scientific study or independent oversight; 2) the encouragement of healthcare providers to challenge and indeed violate existing laws established for the protection of patients; and 3) the invocation of baseless conspiracy theories and legal attacks when such practices are criticized and prosecuted (which I call the "tout, flout, and pout" model). 

In a remarkably short time, the ICMS whipped itself into the semblance of a credible organization, complete with various guidelines for budding stem cell entrepreneurs, an Offshore Clinics Report (which if nothing else serves as an excellent scorecard for what clinics have signed up with ICMS), another patient portal (Stem Cell Watch), a newsletter, a Treatment Registry for which patients were charged $350 to store their own treatment information, which at 750 registered patients and counting means at least another $262,500 for this NPO (and as I noted in an earlier post, the inclusion of RNL Bio in the ICMS Treatment Registry at $50 per patient on the provider side would potentially have cost that company $400,000+), and a Clinic Accreditation Program for clinics willing to pay the society for a fig leaf to plaster on their website (more on this below). Without apparent irony, the organization also recently announced a deal with an insurance company to provide malpractice insurance for their members (many of whom have built businesses around putative stem cell injections supported by guesswork, anecdote, slapdash research, and "expert" hand waving). This, in my view, may prove to be one of the most valuable member service ICMS has introduced to date, and I'm sure it will see plenty of use....

Short of "stem cell" cred? We've got you covered.

The accreditation program, however, is their marketing master stroke, as it lends a veneer of authenticity and a web-friendly banner to otherwise incredible stem cell-flavored medical claims made by enrollees. The first outfit accredited by the ICMS is the Regenerative Medicine Institute of Tijuana, Mexico. The ICMS process, which was originally announced as taking a rigorous 18 months, took less than a year (the RMI application for accreditation was announced on March 15, 2011, and the ICMS approval announced on February 24, 2012). In the more recent release, ICMS executive director and marketing whiz David Audley praised the clinic, saying, "The safety profile has been excellent. We have tracked patients over at least two follow ups and a minimum of six months and not seen a single cell-related adverse event." 

This is remarkable, as only four months earlier the ICMS announced an investigation of the death of a patient treated at the same clinic, and then just two weeks later announced the expected finding that its paying customer was not to blame, based on what appears to be only partial evidence (e.g., no autopsy), interviews, and testimony. No mention is made of the identities of the three physicians who conducted the investigation on the ICMS' behalf, or of the ethicality of subjecting a a frail ('"the patient was told by his family physician that he was very weak and that another infection would most likely be fatal") 74-year-old man with lung disease to an uncontrolled, for-profit medical experiment in Mexico.

The RMI, which is operated by the Angeles Health International medical tourism network and connected to the website www.stemcellmx.com, is itself worthy of another long and detailed post, particularly given its close relationships with Bioheart and Stemedica, two US-based companies with registered clinical trials (here, here), and its extraordinarily long and diverse list of ungrounded treatment claims. By this, I mean Parkinson's disease, and Alzheimer's disease, and traumatic brain injury. And stroke and cerebral palsy and multiple sclerosis. And heart failure! And don't forget macular degeneration and glaucoma and diabetic retinopathy. And diabetes and kidney failure to boot! 


The ICMS has accepted other applications as well. Take World Stem Cells, LLC, for instance. Located in Cancun, Mexico, this clinic flies the ICMS badge of shame right on the top page of its website, and applied for accreditation last May, which if the RMI experience is any indicator, means the results of the "18-month" review are already overdue. I don't feel like typing the long list of World Stem Cells' treatment claims in its entirety, so please feel free to click away below. 

http://worldstemcells.com/stem-cell-therapy-conditions.html

Ever the businessman, Chris Centeno has been keeping busy after being replaced by Freeman as head of the ICMS, and unceremoniously dumping his previous NPOs and the whiplash journal he launched. In 2010, he tried unsuccessfully to sue the FDA (revealing in the process that by June of that year his company, Regenerative Sciences, had already performed 43 unapproved treatments earning $236,500 and banked 242 patients' cells at $5,000 - $8,000 a pop; i.e., $1.2 to 1.9 million in revenue), and is now locked in a legal fight over an injunction the FDA sought against his company Regenexx. He has licensed his cultured cell product (Regenexx-C) to partners in Argentina and China, and set up a stem cell treatment subsidiary in the Cayman Islands. He is also a planning committee member and speaker for this year's one-day ICMS-sponsored session in Hollywood, FL, held in conjunction with the annual meeting of the Age Management Medicine Group, alongside other such alt-med luminaries as Jeffry S. Life (alternative medicine is, anyway, familiar turf for Centeno). 

Yes, that Jeffry S. Life.

So forgive me for my skepticism. Having watched the crass casuistry, hucksterism and vampire squid ethology that have characterized the organization so far, I can't help but think the real meaning of "ICMS" is International Cellular Marketing Service. It is too soon to say whether things will change under their new leadership, and best of luck to Dr. Rodriguez and the latest generation of ICMS leaders in setting the group on a course to science-based medicine. But given the proven profit potential of many other companies selling variations on the stem cell miracle cure, and the growing demand for weaselly workarounds to independent pre-marketing safety and efficacy requirements of the sort the ICMS has specialized in to date, I wouldn't bet my life on it. 


And neither, my valued reader, should you.

High times in stem cell land

For much of the past decade, Beike Biotechnology, a private company based Shenzhen, China was one of the most prominent stem cell profit centers on earth. In its early years Beike founder, Hu Xiang (a.k.a Sean Hu) teamed up with an American professional named Jon Hakim (a.k.a John Harris), who had just extricated himself from a company called Transplants International whose business model involved the trafficking of human organs from freshly executed Chinese prisoners (a kidney was $40,000, while a liver could be had for $60K). “I see this is clearly something that I do not want to be part of,” he told a reporter from the Daily Telegraph in 2005 who had uncovered the appalling operation. Hakim next set up the website China Stem Cell News, which became a one-stop shop for glowing patient testimonials that were used extensively by China-based stem cell marketers to flog their untested and unregulated wares.

After BBC made an investigation of Beike Biotech, in which they confronted Hakim about his past, he effectively disappeared from view (I couldn’t find him anyway) and may have left the company (he had been Chief Operating Officer). But with thousands of foreign patients paying $26,500 each in ante to join the stem cell crapshoot, it was only a matter of time before greed rushed in to fill the void.

Scott Alexander Moffett (who usually goes by Alex; I know, I’ve met him) teamed up with Beike fresh out of a string of apparently successful herbal and ayurvedic medicine businesses in south and southeast Asia (visit his public LinkedIn page for a list of companies he has headed). He became the new head of Beike Biotech’s holding company, Beike Holdings and embarked on an impressive campaign to diversify their business outside of China. In the two and half years he was there, he helped build a network of affiliates and subsidiaries that spanned from Romania to Saudi Arabia to India to Malaysia and Indonesia.

Alex and me (first and second from left), with Jeannie Fontana and Grant Albrecht at the World Stem Cell Summit 2009. Watch the video here

But when Hu abruptly sold his company in late 2010 (after presumably clearing over $100 million in revenues through treatment of 9,000+ foreign and Chinese patients), Moffett followed soon after, buying out the holding company and launching his own new venture, a Bangkok-based “Vanuatu corporation” called Siricell (apparently meaning “The wealth of the cell” in Sanskrit/English), which has the improbable mission of targeting “age related disease management and to assist in the extension of life until the Singularity Nexus expands the scope and capacities of our work in these areas.” For those of you who don’t read science fiction, the “Singularity” is a proposed future point at which technological development makes it possible to extend human lifespan radically or perhaps even indefinitely. Whether that is achieved through unforeseeable and unlikely advances in medicine, or by uploading a digitized simulacrum of one’s neural network into a computer, I for one will not be holding my breath for it to arrive. (But good luck to all the True Believers!)

And there are many true believers indeed, represented enthusiastically by the SENS (Strategies for Engineered Negligible Senescence) Foundation, an anti-aging research group headed by Aubrey de Grey, with backing from such impressive backers as PayPal co-founder and Ron Paul’s favorite sugardaddy Peter Thiel and “Internet entrepreneur” Jason Hope. (If you had hundreds of millions of dollars, as these two do, you might try to live forever too.) Interestingly, the SENS Foundation is listed on the Siricell website as a member of the advisory board.

Moffett himself is no stranger to out-of-the-box thinking. He did spend nearly 20 years, after all, at the helm of various companies in the "ayurceutics" and herbal medicine space (during which tenure he was applauded for introducing sapayul oil, cat's claw, and kava kava, among others, to the armamentarium). And, as with his most Singular stem cells, and apparently drum machine technology (see Linn Moffet Electronics) as well, his expertise was self-taught (see Education). Although to be fair, he did spend quite some time in his youth on the luxurious compound of the Fellowship of Friends, an esoteric group in Northern California established by an elementary school teacher in the early 70s to keep the teachings of Gurdjieff and Ouspensky alive. By some definitions of alive, at least. Moffett previously listed this on his Education history, but now only this screenshot remains.

And what good friends they are!

What Moffett makes no mention of at all in his profile, however, is the time he spent testifying before a grand jury in a remarkable drug-smuggling case involving a whole cast of interesting characters, including one Steven Marshank, who was arrested and charged for his involvement in an attempt to smuggle 35 tons of marijuana into the US (referred to in court documents as the “Hartog Load”)in the late 80s. Luckily for Marshank, his defense attorney, Ronald Minkin, had been cooperating with authorities in a most conflicted and unethical way, which allowed Marshank to assert, successfully, that his Fifth and Sixth Amendment rights had been violated, and the case was thrown out. It isn't reported what happened to that 70,000 lbs of weed.

Also luckily for Marshank, one Scott Alexander Moffett, who had testified to a grand jury in the case, had “retracted any statements he made previously concerning Marshank, stating that he had given false information to the government under pressure and in the hopes of receiving a lighter sentence for a drug conviction” (see Ref 13). The pair walked free. Their LinkedIn pages tell us that between 1983 and 1987, Marshank and Moffett were the co-founders and CEOs of Premier Herbs, “A Los Angeles based herbal ingredients import and distribution company focusing on introduction of South American traditional medicines.” Noted without comment.

And now, here in 2012, we find Moffett and Marshank together again, with Moffett the Founder, Chairman and CEO and “Visionary Entrepreneur” Marshank the Director of International Development. Rounding out the crew is Narin "Jimmy" Apiraichuk, the youthful former VP of Theravitae, the Bangkok-based stem cell profit center set up by Don Margolis. Marshank claimed via LinkedIn that, “SiriCell now has subsidiaries in India, Hong Kong, Thailand, Malaysia, Philippines and the Britisch [sic] Virgin Islands. In 2011 we will be opening subsidiaries in Panama and Egypt.”

I remain unconvinced that Moffett and Marshank have stumbled upon the fountain of youth, but they may have found the golden fleece. When medicine goes unmonitored, it allows some highly irregular characters to set up shop and indeed to thrive. Libertarians, free-marketeers, and ICMS fans - beware. You might just get what you're wishing for.

New revelations in Grekos case

The Naples News has published dramatic new developments in the case surrounding Zannos Grekos, who has been accused by the Florida state medical board of injecting an elderly and very ill patient with stem cells in his Bonita Springs, FL clinic, despite an emergency restriction specifically prohibiting this activity that was placed on his medical license last year. In the March 19 article, the newspaper reveals that a second Lee County physician, Konstantine K. Yankopolus of Fort Myers, has also had an emergency restriction placed on his license for assisting Grekos in a botched stem cell bamboozle that ended up killing the 77-year-old man, who had serious lung disease. Yankopolus told an NBC news reporter that he considered his action in assisting Grekos in the procedure to be "humanitarian." I have not been able to find how much the patient was charged for this particular unscientific treatment, but Regenocyte has typically charged $65,000. 

Yankopolus unrepentant

Even more interestingly, according to the article, the medical board has alleged that Yankopolus "entered a false progress note in (the patient's) chart falsely indicating that no stem cell preparation was infused." This is not the first time that such allegations have been made following a death by lethal injection at the Grekos clinic. Earlier this year, the widower of a woman who died days after Grekos attempted to treat neurological symptoms with an improbable bolus of something (we really don't know what he is injecting) into her carotid artery, raised doubts about the authenticity of a signature on an informed consent form that Grekos produced as evidence. No decisions have been reached in either case, but I would forgive anyone who told me they saw a pattern of criminal negligence and cavalier hubris unfolding here.

Celltex lawyers up

The Celltex/Glenn McGee/AJoB/RNL Bio/ICMS fiasco has snowballed into a much bigger story than I ever expected it would back when I first blogged about it in January. This is largely thanks to the efforts of Carl Elliott and Leigh Turner, both of whom are faculty members of the Center for Bioethics at the University of Minnesota. Elliott published a detailed article of the situation in Slate, with explanations of why the relationship between Glenn McGee (who was listed as editor in chief of the American Journal of Bioethics for at least part of the time that he was serving as president of ethics and strategic initiatives at Celltex) raised legitimate conflict of interest concerns. I for one share in Elliott's views, but Slate retracted the story following allegations of factual error and defamatory content by David Eller, the millionaire who serves as Celltex CEO (to which Elliott sent a rebuttal), and later by a law firm hired by McGee (which I also blogged about here).

Threatening academics with litigation since 2012.

More recently, a different law firm, representing Celltex, has sent a letter to the office of the president of the University of Minnesota making similar complaints about a letter that Ellliott's colleague Turner had sent to the FDA raising concerns about Celltex's activities. This has been covered extensively elsewhere, so I encourage readers interested in the details to read Turner's letter to the FDA, the complaint from the Celltex attorney, and a number of accounts of the legal threats that have been published elsewhere (Pharmalot has the most extensive writeup; others can be found here, here, and here). For the record, I think that both Elliott and Turner should be commended and supported by their university and the community at large for their courageous critiques. 


Celltex's carping over Turner's use the word "administer" in particular seems to be a dodge around larger problems alluded to by Turner and exposed in the excellent investigative work of David Cyranoski at Nature, who found that Celltex not only supplies cells to at least one local physician for unapproved uses, but in fact pays him a $500 commission for each use. (To my knowledge, there have been no threats of legal action against Nature for this or other articles it has published about the Celltex affair, suggesting this apparently litigious company accepts them as factual and true). So, rather than resorting to legalistic suppressive fire, it seems to me the company should be open about what it does with the cells it banks and processes, what it tells patients they can be used for, how they are described and delivered to physicians, and how it perceives its regulatory position with respect to current U.S. laws governing, inter alia, the banking and provision for clinical use of human cells and tissues. 


And just as Celltex could do right by making a full disclosure of its practices, now that McGee has quit the company, the editor-in-chief role at AJoB, his position at the Center for Practical Bioethics, and his position on the board of directors at the ICMS, he could certainly use his inside knowledge to help clear the air and make a valuable contribution to understanding the factors at play in this contentious case by providing verifiable documentary evidence detailing:

• The official positions of RNL staff members and others he spoke with in developing his findings (i.e., whether he had unfettered access)
• The nature of questions he asked and data he examined  during the course of his investigation, and the nature of the responses on the part of RNL Bio representatives (i.e., whether he performed due diligence).
• Specifically, whether he questioned the company regarding the justification for performing thousands of clinical interventions (many of which were for nebulous "anti-aging treatments" that were not supported by scientific evidence and outside the context of regulated clinical trials , and if so, the nature of their responses. 
• Whether he had access to full English translations or bilingual versions of regulatory, procedural and informed consent documents, and other important primary data (many of which presumably were originally in Korean).
• Whether he consulted any outside, independent experts not linked to the RNL Bio case or ICMS in developing his recommendations.
• Whether he is aware of the reasons for RNL Bio's non-compliance with the various ICMS recommendations; specifically, whether RNL refused to pay the "the negotiated, onetime, per patient procedure fee of $50" required by ICMS for participation in its Complications Treatment Registry program. (Presumably this would have cost RNL Bio $400,000 or more to register the 8,000+ patients it is reported to have treated.)   
• Whether he or members of his family subsequently received direct or indirect income or other financial considerations as representatives of the Center for Practical Bioethics (an NPO with which McGee and his wife were both affiliated at the time of his investigation) to conduct comprehensive ethics training, and if so, at what amount(s), for subsequent consulting or other services. 

As with much of the ugly, unscrupulous business of stem cell marketing in the absence of regulation or evidence, the whole Celltex affair smells bad, and no amount of waving briefs and threats of injunctions in people's faces will make that go away. Hopefully the U Minn administration and the FDA will recognize the stench of corruption, and not give in to strong-arm legal defenses of otherwise indefensible practices. And we should all look forward to McGee living up to his promise to provide "timely, lengthy, pointed comments on the matter."

Grekos kills again

Image source: Mugshots dot com

A friend of the blog just forwarded me a link to a CNN report on the latest grim development in the Zannos Grekos case, in which the Florida state medical board has now imposed an emergency suspension of his license after yet another patient died in his care. The Naples News further reports that the county sheriff is launching a criminal investigation into his (mal)practice. This time, an elderly patient is reported to have died during an illegal, expensive and unscientific procedure for pulmonary hypertension that Grekos advertises as involving processed stem cells he has named "regenocytes."  The emergency action by the medical board follows their emergency restriction of his license last March, after a different elderly patient died within days after receiving a lethal injection of a purported stem cell concentrate at his hands. Before getting the stem cell itch, Grekos had previously killed another patient back in 1997*, through simple neglect. 

Don Margolis, griefer extraordinaire and Grekos' business mentor, is going to have to start shopping for a new member for his advisory board. 

"Regenocyte Adult Stem Cell Therapy is safe, highly effective and presents minimal risk!" 

The identity of the deceased patient is being kept confidential for now, but the Lee County sheriff stated that he had traveled to Bonita Springs, where Grekos' practice was located. I have no doubt that he was very sick already, and it is too soon to determine whether the cause of death was an embolism caused by whatever Grekos injected, or some other complication relating to the anesthesia, surgical stress, or plain old incompetence. 

But what is clear is that doctors who beguile the trusting with simplistic pseudoscience, who jeopardize and impoverish their patients in pursuit of easy cash, and who excuse their refusal to proceed cautiously and scientifically as a right protected in the practice of medicine, are no different from the quacksalvers of yore. These are not bold pioneers - we need to recognize them for the base and craven swindlers they are.  


*Note: a previous version of the post indicated that this death had taken place in 2001.
==================================================
UPDATE (March 19, 2012): The Naples News has reported that Zannos Grekos' latest attorney is asserting that the most recent patient death connected to Regenocyte was not from a stem cell injection, as the patient had only received a liopsuction (presumably to harvest what Grekos advertises as stem cells), and that the procedure was performed by a different physician at the clinic. It will be interesting to see what the Florida medical board and local law enforcement authorities make of these claims. The victim's sister, however, is clear about who is to blame, saying about Grekos, "This guy needs to be stopped."

March update - allergy testing

Sorry I haven't written .... well not really ... I haven't written because I'm just feeling good and there's nothing to add.

Oh, I got allergy testing done. Remember how I ate at Bonefish Grill and had a crusted trout, so thought that since it was Bang Bang shrimp night that I got sick from shrimp contamination? Uh, surprise surprise. It wasn't the shrimp ...... it was the pecan crust on the trout! I'm allergic to pecans, peanuts (I knew), and sunflower seeds, but not shellfish.

I got a blood test done to confirm and don't have those results yet.

Still taking:

1 drop Lugol's iodine
Blood Builder, 1 tablet
magnesium
5HTP at bedtime
Armour Thyroid
Vitamin D3

Sometimes take:

Vitamin C
other antioxidants (resveratrol, or something else)

Update: My blood test came back as mildly allergic to clams, oysters, squid, and scallops.

Slate retracts, Nature reports, McGee resigns

I was disturbed to learn yesterday that Slate has made an editorial retraction of the article "The Celltex Affair" by Carl Elliott, and issued an apology to Glenn McGee, a bioethicist who has been criticized by me and many others for his professional involvement with the troubled Texas stem cell company and RNL Bio licensee, CellTex, at a time when he was also editor-in-chief of the American Journal of Bioethics. The retraction was apparently prompted by allegations of factual error and defamation made initially by David Eller (Celltex CEO), to which Carl Elliot responded, and later by a law firm representing McGee. The excellent blog Retraction Watch has provided a nice summary of the recent developments, and Leigh Turner has posted a thoroughgoing chronicle of the events and issues that surround this case up to the day before Slate's sudden retraction. (Turner's article was published on Feb. 28, while the retraction is dated Feb. 29).


With the intensive scrutiny and crying foul over the past month, I don't know if I have a lot to add to the commentary. I do note that my blog is mentioned in the letters from Eller and DeShazo and Nesbitt, McGee's lawyers, with particular reference to a correction I made to one point in my original post on the ICMS Potemkin investigation of RNL Bio, which had stated the McGee had participated in and authored the report of an investigation of RNL's provision of cells for use in unproven treatments overseas. He emailed me stating that he was not the author of this particular report, but that he wrote a different report specifically on the company's ethical practices. I noted this both in the original post and in the more recent one on his joining CellTex, and apologized for the mistake. 


It is clearly vital to get all the facts straight, and I am happy to correct any factual errors discovered in my writing, but equally clearly many of the other disturbing facts of the case remain uncontested, and I have to wonder why Slate would decide to retract such an important story, particularly given Elliot's rebuttal, which I found to be reasonable and compelling. Perhaps Eller's decade-long libel suit against Forbes and journalist William Barrett was more compelling evidence still of the potential cost of engaging millionaires in the courts.


I should further comment on one point in Eller's accusation, which claims "Fact: Dr. McGee has no knowledge as to whether Dr. Ra served on boards" (referring to the participation of RNL Bio CEO Ra Jeong Chan on the Laboratory Advisory Board of the International Cellular Medicine Society in fall of the year when the patient deaths in Japan and China occurred. In fact, I did email Dr McGee on September 10, 2010 at his bioethics.org address prior to writing my first blog post, as I thought at the time that he might be unaware of some important aspects of the ICMS organization. 


McGee did not acknowledge or respond to this email, so I cannot say whether he actually read it, but even if he failed to familiarize himself as a director with the members of other boards, he had clear opportunity to do so just by opening his inbox. I therefore do not think this particular defense is valid, and more generally feel Elliot is owed an apology from the editor of Slate for making a retraction when a correction or clarification on several minor points would have sufficed. This is particularly true as the basis for defamation seems to rely largely on intent, and neither Eller nor the McGee lawyers seem to have done anything to show any alleged error was made intentionally on Elliott's part. 


Things get even more interesting now that Nature journalist David Cyranoski has published a nifty bit of investigative journalism on March 1, with an accompanying editorial, that lays out how CellTex delivers processed adipose cells to a local physician and pays him a commission to inject them into patients with diseases like multiple sclerosis. What's worse, the Texas Medical Board, a group of 17 political appointees less than half of whom have an MD, has drafted new regulations that appear to suggest that Texas views FDA oversight over the clinical use of investigational agents (such as stem cells) as optional. The feds may tend to disagree, as they showed last year in arresting Fredda Branyon, Vincent Dammai, Alberto Ramon, and Frank Morales for similar practices (although it was allogeneic cord blood in that case, rather than processed autologous adipose cells). 


McGee, who did not agree to be interviewed for the March 1 Nature article, abruptly announced his resignation, effective Feb. 28, from CellTex, just three months after joining the company. He also previously stepped down as editor in chief of the American Journal of Bioethics, and says via twitter he is preparing "lengthy, pointed comments on the whole matter." 


Given all the many villains and clowns in this big-money drama, we can only hope that McGee opts to redeem himself through full disclosure.