Is it right to use stem cell therapies on patients with life-threatening or debilitating diseases for which there are a few cures, or none at all? Is it ethical? Is it illegal?
Those questions are at the heart of a brewing bioethics scandal implicating the Houston, Texas start-up biotech company, Celltex Therapeutics Corp., which is involved in Texas Gov. Rick Perry’s unregulated adult stem-cell operation last year.
In the latest development, a University of Minnesota bioethicist filed a complaint with the U.S. Food and Drug Administration saying that by marketing unlicensed stem cell therapies, Celltex wasn’t complying with federal laws on stem cells and putting patients in grave danger. The complaint was filed on Feb. 21 but only reported in the press in mid-March.
Officially, Celltex’s main business is banking people’s stem cells for future reinjection in the event of disease or injury. But although the company hasn’t admitted it, there is growing evidence that it also markets stem cell treatments that haven’t been cleared by the FDA.
“It appears their business plan involves injecting or infusing on a for-profit, commercial basis non-FDA-approved adult stem cells into paying customers,” bioethicist Dr. Leigh Turner writes in an eight-page letter sent to the FDA on Feb. 21. “This plan conflicts with FDA regulations governing human stem cells.”
An associate professor at both the Center for Bioethics in the University of Minnesota’s School of Public Health, and its College of Pharmacy, Dr. Turner has written extensively on bioethics and related issues like medical tourism, the illegal transnational industry of body organs and national healthcare systems.
The FDA hasn’t made a public statement, but Dr. Turner told the Houston Chronicle that an agency official informed him the matter is being taken seriously and an investigator has been assigned to look into the issue.
Complicating the matter is the fact that Celltex is associated with Texas Gov. Rick Perry, who has touted his recovery from back pain after being injected last year with stem cells by a doctor linked to the company.
While pursuing the Republican presidential nomination last year, Gov. Perry revealed that he had stem cells taken from fat in his body, grown in a lab, and then injected into his back in operation to address back pain. The procedure was done by Dr. Stanley Jones, a Houston orthopedic surgeon associated with Celltex.
Medical experts have since criticized the treatment, pointing out that untested stem cell therapies carry a host of potential risks — ranging from blood clots to infection and even possibly cancer in the long run.
Meanwhile, Gov. Perry has endorsed stem cell therapies like the one he had undergone and has even said he will back laws to support the operation of companies like Celltex to operate in Texas.
A former Dupont executive and chairman of the Board of Regents at Texas A&M University, Celltex’s owner David Eller is a major donor to Perry’s political campaigns.
Eller has said that his company doesn’t conduct medical treatments, but stores and processes stem cells for doctors who will use them for stem cell therapies.
Last year Celltex paid US$30 million to license technology from RNL Bio, another stem cell company that courted controversy two years ago when patients in China and Japan died after receiving treatments of stem cells it produced. RNL Bio has offices in the U.S. and South Korea.
“Have CellTex and RNL Bio provided to the FDA data concerning safety and efficacy of their adult stem cell procedures?” asks Turner in his letter — first reported by the Minneapolis Star Tribune.
Selling hope, not science
“I think there’s a role here for the FDA to ensure that people are receiving safe and effective treatments,” Dr. Turner tells the Associated Press. “I think a lot of these stem cell therapies seem like 21st century quackery.”
Described as precursor cells or “building blocks” of the body, stem cells can develop into blood, brain, bones and all other body organs. Because of this, they have the potential to regenerate damaged and diseased organs — and revolutionize the future of medicine.
Stem cells offer the hope of being a renewable source of replacement cells and tissues to treat many painful, debilitating or fatal diseases or conditions for which few or no treatments exist.
Because stem cells are biologics — or therapies involving living cells rather than chemicals — medical experts say the FDA should allow these “minimal manipulation” therapies to be conducted without its oversight.
But because many of the diseases for which stem cells hold the most promise are debilitating and disabling — like Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injuries, burns, heart disease, diabetes and arthritis — people who suffer these conditions are made vulnerable to unscrupulous providers of stem cell treatments.
This is why the FDA does regulate stem cell therapies. To ensure the safety of patients undergoing these treatments, the federal agency requires institutions and companies to turn their stem cell therapies and treatments studies into clinical investigations that it will first review and authorize, then study and monitor until completion.
In fact, the FDA maintains an advisory on its site warning Americans to make sure that any stem cell treatment they are considering has been approved or is an authorized clinical investigation. It also warns consumers from going overseas to seek stem cell treatments in countries where regulations are lax.
In its advisory, the drug regulator makes it very clear that it hasn’t approved any stem-cell treatment for routine clinical use. The only stem cell product it has approved is Hemacord — a cord blood-derived product made by the New York Blood Center and used to treat patients with disorders affecting their blood-forming systems, the FDA says.
What’s more, the agency has recently stepped up enforcement of unregulated adult stem cell activity and has even cracked down on some companies that are marketing the therapies. Working with the justice department, the FDA has accused a number of companies of misleading patients with false advertising putting people in danger.
But according to the Houston Chronicle, it’s unclear whether the FDA would look into Gov. Perry’s procedure because he seems fully informed — and unharmed by it.
Texas medical policy to go through final approval on April
So far, Celltex has claimed that it’s fully behind the federal plan to turn all stem cell treatments into clinical trials. But at the same time, it’s been supplying stem cells to doctors who have undoubtedly used them in unauthorized treatments. In some cases, the company has even paid doctors to use its stem cells in treatments.
The procedure Gov. Perry underwent highlights the gray areas for the FDA: the agency oversees medical products but isn’t authorized to regulate the practice of medicine. This is one reason why illegal stem cell therapies abound, even in the U.S. — a number of doctors have been extracting adult stem cells from patients’ fat and reinjecting them into patients for skin-smoothing facelifts, joint-strengthening and other experimental treatments. This has gone on for years — and the FDA can’t take action against these treatments because they don’t involve commercial medical products or devices that fall within the agency’s mandate.
Thus, health experts have been pushing the FDA to consider as a medical product the stem cells that are cultured in labs and fused with other substances to modify the cells. So far, the FDA has brought an injunction barring a Colorado company from growing marrow-derived stem cells in this way and court proceedings in this case are underway.
Meanwhile, the Texas Medical Board is now considering a new policy that would oblige providers of stem cells or other experimental drugs to use these only after approval by independent review committees. These bodies will put the treatments under trials to ensure patient safety. The policy comes up for final approval in April.
According to Celltex’s CEO, the company is now registered with such a review committee.
Uncovering Celltex lies
Dr. Turner’s letter lays out eight concerns about Celltex, including:
• Are the stem cells it processes safe and effective?
• Stem cells being administered by Celltex come from its founding partner, RNL Bio, which is implicated in the deaths of patients from trials in Asia.
• Company marketing emphasizes cures but doesn’t provide information about risks.
• There’s a growing amount of unregulated stem-cell therapy already involving the company.
Calling Dr. Turner’s allegations “false,” a lawyer for Celltex wrote the FDA and argued that the company ensures banked cells are genetically identical to the original and free of contaminants.
The lawyer also wrote to the University of Minnesota, asking the university to muzzle Dr. Turner and remove his letter to the FDA from the Internet. The university’s general counsel, Mark Rotenberg, has responded, saying U&M was taking the letter seriously. But he also out: “it’s important to remember that our faculty is protected by the Regents Policy on Academic Freedom and Responsibility. This safeguards the freedom to write on matters of public concern without institutional discipline or restraint — with the responsibility to make it clear that when one is speaking on matters of public interest, one isn’t speaking for the institution.”
Eller has admitted that Celltex has stored the stem cells of more than 100 people so far. He estimated doctors have reinjected cells in 40 to 50 of them.
So far, Dr. Turner remains undeterred. “Celltex charges over US$20,000 for its role in providing stem cells,” he said told the Houston Chronicle. “It’s not clear that what people are receiving is safe, efficacious and administered with the knowledge and approval of the FDA. It seems to me that the FDA should investigate.”
“Because we know so little about mesenchymal stem cells and whether they are indeed effective for treating any condition, I’d be very wary of how they are being infused into patients. And certainly, (I’d be) concerned if practitioners are charging patients for medical procedures that haven’t been proven to work and could in fact be harmful,” says Dr. George Daley, director of the Stem Cell Transplantation Program at Harvard Medical School, who helped the International Society for Stem Cell Research to draft its guidelines.
After the deaths of patients in China and Japen following stem cell treatments from Celltex’s South Korean partner, RNL Bio, the International Cellular Medicine Society initiated a probe into the deaths, as well as an evaluation of RNL’s ethical and clinical practices.
The evaluation was conducted by bioethicist Dr. Glenn McGee, who recommended changes in both practices and adherence to ethical standards at RNL.
But about a month ago, Dr. Turner noticed that Dr. McGee — who was then the editor, and even founder, of the American Journal of Bioethics (AJOB), the field’s most-cited journal — took a job as Celltex’s first president for ethics and strategic initiatives.
On Feb. 14, Dr. Turner posted about his discovery at his blog, Health in the Global Village. Other ethicists cried foul after followed his links.
Dr. John Lantos, director of the Children’s Mercy Bioethics Center in Kansas City, Missouri, and a past president of the American Society for Bioethics and Humanities says, “Imagine if the Editor of the New England Journal of Medicine took a job as Vice President at Merck, and the Mass Medical Society asked him to stay on as Editor, opining that the conflicts of interest would be manageable. One might rightly wonder, ‘What are these people smoking?’”
Following four weeks of outrage from the scientific community, Dr. McGee stepped down from his corporate post on Feb. 28.
According to an investigative article by Nature magazine — the most-cited interdisciplinary journal — Celltex supplies adult stem cells to Texas doctors who offer unproven treatments to patients. The company is also involved in these treatments, the journal goes on to show.
According to one doctor interviewed by Nature, the treatments are part of a company-run clinical study. Celltex patients up to US$25,000 for a treatment course, the doctor reveals, and the company pays him US$500 a time to inject the cells into patients.
One Celltex patient has also been blogging about the stem-cell treatments she has been receiving from the company for multiple sclerosis, Nature reporter David Cyranoski says. The woman, Debbie Bertrand has been blogging about her experiences with a five-injection treatment with cells prepared at Celltex.
Photographs of herself alongside Dr. Jones, the Houston surgeon who injected stem cells into Gov. Perry’s back, a Celltex nurse named Jennifer Novak, RNL Bio CEO Jeong Chan Ra, and a neurologist who works for the United Neurology clinic in Houston, Jamshid Lotfi, are found on her blog: http://debbiebertrand.blogspot.com.
One photo is captioned: “My cells are being processed in here for my next infusion!!!” A third shows Bertrand, Lotfi and a physician called Matthew Daneshmand, who is, according to the caption, injecting Bertrand’s stem cells into an intravenous drip, ready for the infusion.
Nature has been unable to contact the woman blogger, but Cyranoski was able to speak with Dr. Jamshid Lofti, the Houston neurologist who injected the cells into the woman. Dr. Lofti admitted that the injections had been made — and that both he and Celltex had charged the patient for them. He admits that he gets US$500 per injection and that Celltex charges the patient US$7,000 per 200 million cells.
Dr. Lotfi also admits to Nature that he administered cells processed by Celltex to “five or six” people — including Bertrand — who have multiple sclerosis and “four or five” who have Parkinson’s disease. All in all, he says, he’s injected Celltex stem cells into more than 20 people.
Patients sign up for treatment by contacting Celltex nurse Novak, Dr. Lofti explains. Then the cells are prepared by removing about five grams of fat — containing roughly 100,000 mesenchymal stem cells –from the patient’s abdomen.
These are then cultured over a three-week period until they reach about 800 million cells, and patients get at least three injections of 200 million cells each, the doctor explains. But the cells don’t take effect until about a few months later, he says.
While he claims that most of his patients feel better after the treatment, the surgeon does admit that there’s no scientific evidence that the cells are effective.
“The scientific mind isn’t convinced by anecdotal evidence,” he acknowledges in an interview with the journal Scientific American. “You need a controlled, double-blind study. But for many treatments, that’s not possible. It would take years, and some patients don’t have years.”
“The worst-case scenario is that it won’t work,” he admits. “But it could be a panacea, from cosmetics to cancer.” He also tells the Scientific American that Celltex is conducting a trial in which patients “will be their own control.” “If you can compare before and after and show improvement, there’s no need for a placebo,” he explains. “How can you charge people, and then give them a placebo?”
But Dr. Arnold Kriegstein, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco, says “the very nature of Celltex’s business plan, which involves charging patients considerable fees for so-called treatments for diseases and disorders for which there’s no good clinical evidence of efficacy, crosses an ethical line.”
The prestigious magazine Slate has also been dragged into the controversy, after it retracted a commentary bioethicist Dr. Carl Elliott had written Feb. 17 on the McGee/Celltex controversy.
Slate’s editor David Plotz explains: “Because of shortcomings in the editorial process, the article didn’t meet Slate’s standards for verification and fairness and shouldn’t have been published. We withdraw the article and apologize to Dr. Glenn McGee.”
But according to the Minnesota Post, what Plotz didn’t mention was that Slate had received a letter from lawyers representing Dr. McGee, which included this statement: “[W]e will file appropriate papers if the article isn’t formally retracted by close of business Tuesday, February 28, 2012.”
“I think one of the reasons that Slate could be bullied so easily is that they didn’t know enough about stem cell tourism or bioethics or McGee’s history to know how much of his threat was bluster and how much had a basis in fact,” Dr. Elliott speculates in a talk with William Heisel, a former Los Angeles Times investigative reporter who is now the communications officers at the Institute for Health Metrics and Evaluation.
“I spent two hours on the phone trying to persuade them not to give in to a bully, but it did no good,” Dr. Elliot says.
Dr. Elliott has since written broadly about the incident in his weekly online column for the Chronicle of Higher Education. He also wrote a detailed, point-by-point rebuttal of the charges that Celltex made regarding his Slate article.
“I have received a handful of retraction demands over the years. Never has a newspaper or website where I worked looked at a letter like the one Slate received and pulled the piece. I have had to write clarifications and corrections over the years. That’s part of the process.”
“But when an outlet as respected as Slate caves in to pressure from a politically connected company it will undoubtedly make other writers pull back when considering a commentary on or investigation of a difficult subject — especially freelance writers who could be left to hang while the lawyers gather.”