The story began, like so many in biotechnology, with an upbeat press release: Up to 100 patients with a progressive form of blindness would be treated with cells extracted from their own body fat, in a clinical research trial.
“We are excited to determine whether cellular therapy can offer new hope to this patient population,” the lead researcher on the trial, Shareen Greenbaum of the Hollywood Eye Institute in Cooper City, Florida, said in the release.
The trial also seemed to have an impressive ethical stamp of approval. “The study has been reviewed and approved by the Institutional Review Board (IRB) of the International Cellular Medicine Society (ICMS),” the press release, issued in December 2013, noted.
But by June 2015, the story had turned into a tragedy. As BuzzFeed News reported last week, three elderly women whose eyesight was still reasonably good became legally blind after cells from their body fat were injected into their eyeballs. One, a retired college professor from Missouri called Elizabeth Noble, can no longer tell night from day.
The Florida company behind the study, formerly known as Bioheart and now called US Stem Cell, now denies that the trial ever started. But a 2016 court filing in a suit brought by another of the women who was blinded, a Florida retiree called Patsy Bade, suggests otherwise.
The ethical review board, meanwhile, has distanced itself from the trial, saying that it only approved plans to treat patients who were already legally blind — and then only in one eye at a time.
Inquiries by BuzzFeed News reveal that the original ethical approval raised troubling questions from the start. The ICMS lobbies for doctors’ right to practice stem cell medicine free from federal oversight. “No other group has done more to protect a physician’s right to practice stem cell and regenerative medicine,” its website claims. ICMS council members and advisers must affirm that stem cells are “exempt from any US Food and Drug Administration regulations” — as long as the cells are injected back into the same patient they came from, and have not been grown in laboratory cultures.
What’s more, the ICMS ethical board that approved the trial included one doctor whose medical license had been placed on probation for failing to meet the “applicable standard of care” in his own medical practice, plus another who had earlier been convicted of violating federal law by breaching a patient’s medical privacy.
Those doctors refused to comment on the trial’s approval and their own qualifications to serve as ethical reviewers. After inquiries from BuzzFeed News, the ICMS posted a statement on its website, stating that did not approve the specific treatment that led to the three women losing their sight. But its executive director, Reed Davis, refused to answer questions.
“The statement posted on the ICMS website is the extent of our comment on this matter,” Davis told BuzzFeed News by email. “Furthermore, I am respectfully requesting that you cease contacting and harassing members of the IRB.”
The FDA maintains that stem cells should be treated as experimental drugs, requiring extensive scientific testing before they can be approved for regular clinical use, if they have been subjected to anything more than “minimal manipulation.” In draft guidance published in December 2014, the agency suggested that cells extracted from a patient’s own body fat, like those used to treat the three women who were blinded in Florida, would fall into the more-than-minimally-manipulated category.
But for years, rebel doctors have fought against the FDA’s authority. The battle lines were drawn in 2008, after the FDA told a Colorado doctor called Christopher Centeno to stop marketing a stem cell therapy called Regenexx, used to treat arthritis and joint injuries. It took until 2012 before the agency prevailed, when a federal court ruled that the treatment was a drug, requiring FDA approval.
The ICMS was forged in the heat of that legal dispute. Centeno was also the medical director of a nonprofit called the Spinal Injury Foundation, which by 2010 had been reconstituted as the ICMS. It lobbied for stem cell therapies to be treated as the “practice of medicine,” rather than drugs, and established an Institutional Review Board to approve clinical studies.
But the ICMS IRB was chastised by the FDA in June 2012 for approving a stem cell clinical trial that the agency had shut down three years before. That letter documented a series of problems with the IRB’s procedures, including granting approval without the required quorum of members being present.
The retina of a patient with macular degeneration, in which fatty deposits (center right) form in the region used for detailed vision.
National Eye Institute, NIH
In late 2013, the ICMS IRB reviewed the Florida trial, intended to test the ability of stem cells from fat to treat an eye disease called Age-Related Macular Degeneration, which slowly robs people of the sharp central vision they rely on to read and drive. By then, Centeno had parted ways with the organization. “I have not been involved with the ICMS in many years and have no part in the approval of this protocol, nor would I have approved it had I been part of the organization,” he told BuzzFeed News by email.
The ICMS IRB that reviewed the Florida clinical trial consisted mostly of doctors who themselves practice unproven stem cell therapies. Its chair was David Harshfield, who works at the Arkansas Institute of Regenerative Medicine in Little Rock, and who has trained other doctors to set up their own stem cell practices. A 2015 press release about a workshop in Puerto Rico says that he would “teach doctors how to use and successfully market” stem cell therapies.
Harshfield did not respond to phone calls and emails from BuzzFeed News.
The IRB also included another Arkansas doctor, Jay Holland, who in 2009 pled guilty to violating federal law on medical privacy. Then at the St. Vincent Infirmary Medical Center in Little Rock, Holland watched a report about a local TV news reporter who had been found beaten and bloody in her bed. (She later died from her injuries.) Filled with curiosity, Holland illegally accessed the reporter’s medical records from his home computer. He was sentenced to one year’s probation, and fined $5,000.
In a promotional video, Jay Holland describes using blood plasma, stem cells, and lasers to treat chronic wounds. His collaborator, Carl Keller, is a “community member” of the ICMS IRB.
Another member of the ICMS IRB was Dean Reeves, a doctor in Roeland Park, Kansas. In April 2012, his medical license was put on probation by the Kansas State Board of Healing Arts, which regulates doctors in the state, because of problems with his use of “prolotherapy” — an alternative medical practice in which doctors inject patients’ joints with fluid, which is supposed to promote healing. The board faulted him for issues including failing to properly use medical imaging to guide his injections, failing to combine the treatment with physical therapy, and failing to document important aspects of the procedures, including his use of sedation.
Both Holland and Reeves hung up when BuzzFeed News asked them about their troubled disciplinary histories. “We won’t continue this conversation. We need to say goodbye,” said Reeves — whose disciplinary difficulties continue to this day. In September 2016, Reeves wrote to the Kansas board, requesting that his probation be terminated. But in November, the board initiated fresh proceedings against him, alleging further departures from appropriate care in Reeve’s treatment of 15 patients.
“It’s very easy to find physicians who do not have a troubled disciplinary history,” Leigh Turner, a bioethicist at the University of Minnesota who last year published a survey of clinics offering unproven stem-cell therapies, told BuzzFeed News. “These are individuals that undercut the integrity and credibility of the IRB.”
Turner also argued that the ICMS has “obvious conflicts of interest” when acting as an independent ethical reviewer for stem-cell studies that have not been submitted to the FDA for approval, given its opposition to the agency’s regulatory role.
The ICMS and Kristin Comella, chief science officer for US Stem Cell, once had a professional relationship. In 2012, before her company submitted the macular degeneration trial for approval to the society’s IRB, she was a prominent speaker and one of the “conference faculty” at a scientific meeting in Florida organized by the ICMS.
Today, things are rather different. Comella and Becker Public Relations, which represents US Stem Cell, did not respond to emails and phone calls from BuzzFeed News. But last week, Comella told the New York Times that an independent review board approved the plan to treat patients in both eyes at once.
That was flatly contradicted by the statement posted online by the ICMS, which stated: “Throughout the protocol, the treated eye is consistently referred to in the singular and the protocol does not contemplate, much less condone, bilateral treatment. If the protocol had mentioned bilateral treatments, it would not have received approval from the ICMS IRB.”
On one point, however, the ICMS and US Stem Cell are still on the same page: The trial, they both claim, never enrolled any patients.
Yet in repeated filings to the Securities and Exchange Commission, most recently in its annual report for the year ending December 31, 2015 — more than two years after the original press release announcing the clinical trial — US Stem Cell wrote: “We have also initiated several Institutional Review Board studies in 2013 using adipose derived stem cells for various indications including dry macular degeneration.”
A July 2016 court filing by Patsy Bade, after she had settled with US Stem Cell but before her settlement with Greenbaum, alleges that the trial did start enrolling patients. It indicates that Greenbaum was convinced by Comella — they met at the gym where Comella was an aerobics instructor, according to the court document — to become the trial’s lead researcher. Greenbaum was allegedly trained by Comella in how to harvest and use stem cells from fat, with the $7,500 cost being deferred in exchange for Greenbaum agreeing to work on the clinical trial.
The court filing indicates that Greenbaum treated “approximately six” patients as part of the clinical trial, before she started to have misgivings about its legitimacy.
In Spring 2015, according to the court filing, Greenbaum told Comella that she could no longer participate. But she allegedly still conducted an initial examination of the three women who were subsequently blinded, before Comella and a registered nurse conducted the procedure.
Greenbaum has since settled with Bade, in an agreement that prevents all of the parties from discussing the case. She did not respond to calls and emails from BuzzFeed News.
Whether or not the trial actually enrolled any patients, Turner argues that there is a serious problem.
“The company seems to have made the determination that this was clinical research,” he said. “Why were the patients being treated if they weren't being giving cells as part of study?”