From at least December 15, 2011 to February 9, 2012, Glenn McGee served as Editor-in-Chief of The American Journal of Bioethics (AJOB) while also working as an executive at Celltex Therapeutics Corporation (CellTex). On February 9, 2012, several individuals began tweeting about McGee’s conflict-of-interest and demanding that he resign from AJOB. The next day, members of AJOB’s Editorial Board were informed that McGee was stepping down as journal editor.
Following Glenn McGee’s exit from AJOB, the appointment of Summer Johnson McGee as one of the next two Co-Editors-in-Chief of the journal provoked a controversy among bioethicists. Largely (though not entirely) neglected in the dispute concerning Glenn McGee’s conflict-of-interest and his subsequent replacement by his wife is any sustained effort to examine Celltex, the company Glenn McGee joined while still editor of AJOB. For example, David Magnus, the other journal co-editor, blithely describes Celltex as a “stem cell company”, as though it is much like any other life sciences firm, while failing to acknowledge what it is about this company that makes Glenn McGee’s decision to take a position there so disturbing. Conflicts-of-interest are sometimes examined in abstract terms, paying little attention to how particular features of companies can make them more or less problematic employers for bioethicists. Here, I turn away from the abstract and toward the particular, examining what can be learned about Celltex.
In brief, Celltex takes adult stem cells obtained from human adipose tissue (what most of us call “fat”) and then processes and banks these cells. The stem cells are later injected and infused into individuals who are ill, injured, or interested in using stem cells for cosmetic purposes. Celltex’s corporate partner is RNL Bio, a South Korean company known for cloning dogs, preparing stem cells that are administered to customers in China, Japan, and Mexico, and selling expensive cosmetics such as “Dr. Jucre’s Million Stem Cell Magic Concentrate.” Together, the two companies operate The Celltex RNL Bio Stem Cell Processing Facility in Sugar Land, Texas. The ribbon-cutting ceremony for the facility occurred December 15, 2011. CellTex’s senior management team includes Chairman and Chief Executive Officer David G. Eller, Vice President and Chief Medical Officer Dr. Stanley Jones, President, Ethics Research Division, Dr. Glenn McGee, and Vice President, Donna Lee.
Celltex brings to the partnership approximately thirty investors from the oil-and-gas industry. In turn, RNL Bio provides Celltex with technical expertise in processing and banking stem cells. According to the Technology Licensing and Purchase Agreement between Celltex (called BioLife Stem Cell Corporation at the time the agreement was signed) and RNL Bio, Celltex licenses from RNL Bio “patent rights to certain adult stem cell Technology.” In particular, Celltex licenses from RNL Bio, “the right to develop, market, manufacture, make, use, sell, license and sub-license certain stem cell technologies which are applied to humans and animals.” Celltex paid RNL Bio $30 million to license RNL Bio’s stem cell technology. Depending upon how much money Celltex earns from banking stem cells and providing stem cells to customers, it could in total pay RNL Bio an additional $270 million in licensing fees.
The list of stem cell-related interventions RNL Bio licenses to Celltex includes: “Fat derived autologous stem cell extraction and culture; Fat derived autologous stem cell banking, Fat derived autologous stem cell treatment, Fat derived allogenic stem cell treatment (HLA typing), Placenta derived autologous stem cell extraction and culture, placenta derived autologous stem cell banking, placenta derived autologous stem cell treatment, Placenta derived allogenic stem cell treatment (HLA typing),” and stem cells for cosmetic purposes. In short, while Celltex specializes in banking and providing adult stem cells, its business plan includes extracting, banking, and administering other sources of stem cells. Celltex’s licensing agreement states that RNL Bio “will, as quickly as possible, assist Licensee in beginning the treatment of patients.” Planned operating capacity at the start of business operations is described as “at least 250 patients per month.”
Celltex’s website is password-protected. It is therefore difficult to know exactly how Celltex promotes itself to customers. However, Celltex’s fee schedule provides insight into Celltex’s marketing strategy. For $1750 the company provides “a batch culture and transport of a minimum of 50 million autologous mesenchymal stem cells.” For $50,000 the company provides the lifetime banking option of “blood analysis, fat tissue collect and transport, stem cell extraction, culturing, preparation, lifetime cryopreservation, and unlimited transport of cultured cells for a minimum of 2 billion autologous mesenchymal stem cells.”
Stem cell research has considerable promise and in future it is possible that medical interventions based upon different types of stem cells will be used to treat numerous illnesses and injuries. Acknowledging that stem cell research might eventually lead to safe and effective medical therapies, there are many reasons to be concerned about Celltex’s business activities. By far the most pressing legal, ethical, and medical issue is that stem cells prepared by Celltex apparently are being infused and injected into Celltex customers even though Celltex has no clinically proven, FDA-approved adult stem cell interventions to market. Such activity appears to contravene FDA regulations governing administration of adult human stem cells.
In July 2011, Dr. Stanley Jones, Celltex’s Vice President and Chief Medical Officer, administered to Texas Governor Rick Perry adult stem cells taken from Perry’s own fat tissue. The stem cells Jones injected into Perry were reportedly prepared at the Celltex RNL stem cell facility. Governor Perry is CellTex’s most famous recipient of stem cells but he is not the only person to receive stem cells processed and banked by Celltex. To the contrary, it appears that Celltex, without first conducting clinical trials or obtaining FDA approval, is both banking stem cells and providing individuals with stem cells that are then injected or infused into them. Precisely how stem cells reach Celltex’s clients is unclear. It seems that stem cells are prepared at the Celltex stem cell bank and then transported to nearby clinics. There, physicians and other health care providers administer the stem cells to clients. In a blog post, one Celltex client mentions that her cells are being processed prior to her next infusion. This same customer mentions “meeting people who are also having treatments—some I had talked with by phone because their relatives or friends wanted them to know about the option of stem cells.” She also describes observing additional Celltex customers getting ready to have stem cells administered. “I had my 5th infusion today and am now the recipient of a total of 1 billion new stem cells. While I was having my treatment, we were able to visit with three other people who were there to meet with the doctor and make preparations to begin the process.” This patient’s blog contains photos of the clinic where she received infusions, Celltex employees, and the health care providers involved in administering stem cells to her.
The legal, ethical, and scientifically legitimate way to bring adult stem cells into the realm of mainstream medical practice is to first conduct clinical trials approved by the Food and Drug Administration (FDA) and assess safety and efficacy. Adult stem cells need to be tested in the context of properly designed clinical trials because it is important to determine whether adult stem cells have any effect beyond the placebo effect. No matter how many individuals are enthusiastic about the promise of adult stem cells—and Celltex’s partner, RNL Bio, has a history of using patient testimonials as a marketing device—rigorous clinical trials are required to confirm that adult stem cells used for a particular purpose work better than placebos and do not cause harm.
Celltex’s apparent decision to provide adult stem cells to clients is disturbing because at least two patients who received adult stem cells from RNL Bio died after having stem cells administered to them. One RNL Bio customer died in Japan and a second client died in China after receiving stem cells prepared by RNL Bio. There are reports of other individuals stating that they were harmed by the adult stem cells they received. For example, former customers claiming they had been injured by the stem cells they received disrupted a RNL Bio news conference in South Korea. Whether the stem cells provided to these individuals caused death or injury is unknown and needs to be investigated. The South Korean Food and Drug Administration reportedly initiated an investigation of the two deaths but there is no publicly accessible English-language report of its findings. Another organization, The International Cellular Medicine Society, also investigated these two deaths but the statements it produced fail to provide comprehensive analysis of ethical and clinical issues related to the deaths. Given these prior deaths and the inadequate manner in which they were investigated, there is reason to question whether clients of Celltex and RNL Bio are receiving safe and effective interventions.
RNL Bio reportedly has administered stem cells to 10,000 clients. However, studies published by RNL Bio researchers are based upon small sample sizes rather than hundreds or thousands of research participants. For example, in one study, adult stem cells were administered to ten individuals suffering from various medical problems. The study sample included research subjects with autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis, and rheumatoid arthritis. The study did not use randomized controlled trial methodology or blinding in an attempt to reduce study bias. It also does not seem to have gone through IRB review. In a second study stem cells were administered to eight individuals with spinal cord injury. These publications appear to be representative of articles published by RNL Bio researchers. The studies are uncontrolled case studies. They do not randomize research participants to a novel intervention versus the existing standard of care. There is no attempt to control for researcher bias. Sample sizes are too small to reach meaningful conclusions. These studies provide no reassurance that RNL Bio has products ready for FDA approval and commercial sale. If these publications reflect the quality of scientific research undergirding Celltex’s stem cell technology, there is reason to suspect that Celltex is far from having adult stem cell interventions ready for commercialization and routine clinical use.
Celltex depends upon RNL Bio for scientific expertise and experience conducting adult stem cell research. And yet, despite reportedly putting adult stem cells into thousands of customers, RNL Bio does not have stem cell-based interventions approved by either the US FDA or the South Korean FDA. To date, it appears that RNL Bio has initiated clinical trials that either failed to generate significant findings or were halted by the South Korean Food and Drug Administration. Reports of morbidity and mortality in individuals receiving stem cells provided by RNL Bio combined with limited evidence concerning safety and efficacy of RNL Bio’s “stem cell technology” generate serious concerns about Celltex’s apparent willingness to market and sell infusions and injections of adult stem cells. Also cause for concern is a report stating that Celltex representatives emphasize the safety of adult stem cells. It is possible that clients of Celltex are receiving inadequate information about risks associated with having clinically unproven stem cells administered to them.
Safety and efficacy of Celltex’s adult stem cell injections and infusions are unknown. Adult stem cells marketed by Celltex might play a role in treating illnesses and injuries, cause harm, or have no discernable effect upon health and illness. It is conceivable that individuals with multiple sclerosis and other serious health problems are paying for stem cells that provide no clinical benefits or expose them to unnecessary risks. Celltex has a legal, ethical, scientific, and clinical duty to establish safety and efficacy of its products, demonstrate that it is providing clinically proven medical interventions, and obtain FDA approval before selling stem cells to customers. With a bioethicist in a senior executive position, Celltex’s management team must be aware of the company’s moral responsibilities to the recipients of the stem cells it provides and its legal obligation to obtain FDA approval prior to initiating clinical trials and selling stem cells to clients.
When, whether, and how the FDA will respond to Celltex’s business operation is uncertain. An investigation by the FDA appears warranted because available evidence suggests that Celltex’s clients are receiving clinically unproven, non-FDA-approved adult stem cells that fall within the regulatory authority of the FDA. If the FDA begins asking questions about Celltex’s business operation the company might respond by claiming that the FDA has no legal authority over the adult stem cells that it processes, banks, and administers to clients. The FDA’s current legal action against Regenerative Sciences Incorporated, another company that markets adult stem cells and administered stem cells to clients without first seeking and obtaining approval from the FDA, suggests that the FDA would respond to such a claim by asserting its authority to regulate administration of adult stem cells into humans. The process could begin (as happened with Regenerative Sciences) with the FDA sending Celltex a warning letter stating that the company must comply with FDA regulations. If it appeared that customers of Celltex continued obtaining accessing to stem cells the FDA might then go to court and seek an injunction. However, if the FDA concludes that customers of Celltex are at risk of harm, it is conceivable that the FDA could act in a more forceful manner. With the bioethicist Glenn McGee employed at Celltex as a senior corporate executive, if the FDA chooses to initiate legal action against Celltex’s management team the field of bioethics might witness the next phase of an unusual career arc that began in the halls of academe, proceeded to the corporate boardroom, and could reach the courtroom. And with Glenn McGee’s spouse, Summer Johnson McGee, his replacement as Editor-in-Chief of The American Journal of Bioethics, one bioethics journal will have front-row seats should FDA officials initiate legal proceedings against Celltex. I think it reasonable to predict that if such an event occurs, at least some members of AJOB’s Editorial Board will wish that the journal to which their names are attached had not been allowed to drift quite so close to the action.
February 28, 2012