On the surface it seems easy. Overseas stem cell “clinics” peddling unproven treatments to desperate and dying patients, charging tens of thousands of dollars for the privilege of being injected with mysterious concoctions of cells meant to cure almost every ailment: What’s not to hate? But for many patients, the issue is more complex than it may at first seem. To them, the fact that a treatment has not been thoroughly tested and approved by the U.S. Food and Drug Administration is a minor detail, with hope trouncing logic in a world where mainstream medicine can sometimes neither cure nor alleviate suffering. The result is a booming international business that is growing every year, thanks in large part to the Internet and the savvy marketers who prey on patients’ fears.

“What we’re hearing on these websites promoting these unproven treatments is that regulatory agencies like the Food and Drug Administration and the pharmaceutical industry don’t want you to get better,” says Douglas Sipp, the manager of scientific communications at RIKEN Center for Developmental Biology in Kobe, Japan, and an international expert on the marketing of such treatments around the world. “And this resonates with people who are, in many cases, seriously ill, and who are frustrated by the perceived lack of progress in established medicine.”

With people who are so sick, comes the opportunity and risk of exploitation, says Ezekiel Emanuel, MD, PhD, director of the National Institute of Health’s Department of Bioethics and special advisor for health policy in the White House’s Office of Management and Budget. “These overseas clinics are charging a very vulnerable population a lot of money for treatments that are unproven and are operating with no oversight and no monitoring,” says Emanuel.

And in fact, there’s really no way to know exactly what patients are receiving as part of their “treatment.”

This tension between patients who believe they have the right to undergo any procedure  they hope will help them and the government agencies and scientists who wish to bar practitioners from providing unproven treatments is not going to be easily resolved, in part because “right” answers in cases like these are hard to come by. What seems clear-cut on paper — experimental treatments shouldn’t be marketed for large amounts of money to desperate patients — can be upended in the presence of a person with a life-threatening illness whose personal risk-versus-benefit equation is so different from your own.

“It’s a much more complex set of decisions than you might imagine,” says Stanford bioethicist Christopher Scott, who directs Stanford’s Program on Stem Cells in Society. “Our devotion to clinical trials doesn’t acknowledge that, for the most part, enrolling in a trial is an act of altruism. Early phase trials are designed to test safety, not to benefit participants.”

In contrast, stem cells appear the stuff of magic and miracles; their existence taps into a deeply held awe about the nature of what it means to be human. The advances that they could bring about for medicine are mind-boggling, and we’re now seemingly on the cusp of promises delivered. But, in this arena, every legitimate advance carries with it an unavoidable cost.

“When we report something good about stem cells, it gets picked up in the media, or in a blog that patients read,” says Jeanne Loring, PhD, director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, Calif. “It gives them more ammunition to say that the FDA is stupid for denying access to treatments that seem like they should work.”

Indeed, the fact that there are a number of ongoing clinical trials testing the ability of embryonic and adult stem cells to treat a variety of human diseases appears to validate the use of these treatments. And the proponents of untested treatments can be very persuasive and appear to have good credentials. Sifting fact from fiction can be difficult even for trained scientists, in part because the claims proponents make often hover just on the edge of believability: Your body uses stem cells to heal itself (yes); stem cells can be purified from blood and other tissues (yes); these stem cells, when injected back into the body, can heal wounds or repair damaged tissue (er, sometimes?).

Most laypeople would not spot the flaw in the preceding argument — namely that, in contrast to the embryonic stem cells or laboratory-generated induced pluripotent stem cells often featured in the media, most stem cells found in the body (called “adult” stem cells) are highly tissue-specific. A bone stem cell can’t churn out replacement neurons, and a blood stem cell can’t make new skin. This tendency of so-called stem cell clinics to tip over the edge into the realm of speculation and circumstantial evidence has no place in commercialized treatments, say observers.

Furthermore, a lack of follow-up and the absence of standardized guidelines for these procedures make it impossible to meaningfully assess the outcome of patients who receive purported embryonic or adult stem cell treatments. Recent reports of at least four deaths associated with such procedures overseas have fanned the flames of opposition to such clinics. And, because there’s no way to tell what patients of these clinics are actually receiving, they are subsequently disqualified from participating in any legitimate clinical trials in this country.

“Tens of thousands of patients are being mistreated,” says Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and immediate past president of the International Society for Stem Cell Research, or ISSCR. “In some, the treatments will disqualify them from receiving therapies that we know are at least somewhat effective. Also, failures of these unproven treatments will undoubtedly affect the public and private support of legitimate stem cell science.”

‘It’s a much more complex set of decisions than you might imagine. Our devotion to clinical trials doesn’t acknowledge that, for the most part, enrolling in a trial is an act of altruism.’

“Harm is being done at a lot of levels,” agrees Loring. “But on the list of things that offend me, the false hope they offer to patients is at the top.”

But the hope is cleverly packaged. “These clinics never promise a patient will be healed,” says Sipp. “They’ll say things like, ‘most patients experience an improvement.’ And, when you’ve spent a lot of your own money, or money that was given to you by friends or relatives, the incentive to report that the treatment helped is very strong. There’s a lot of room for the placebo effect.”

Thanks in part to efforts of organizations like the ISSCR, the phenomenon of what’s been termed stem cell tourism has gained attention during the past year. (Sipp, who is an ISSCR member, discourages the use of this phrase because it trivializes the patient experience and because travel is not always required.) In response, Costa Rica recently shut down a popular clinic called the Institute of Cellular Medicine that claimed to have treated at least 700 patients during the past five years. The company still operates in Panama under the name Stem Cell Institute. In March 2010, India launched a review of stem cell medicine in that country, and the Chinese Ministry of Health in 2009 vowed to tighten regulation of stem cell therapies. Yet the number of providers continues to grow.

“It’s a worldwide industry,” says Sipp, who estimates there are about 300 clinics that offer what they claim to be stem-cell-based treatments for everything from autism to diabetes, from ALS to cancer. “And recently we’ve been seeing a growing complement of places in the United States that either refer people to nearby international clinics in Mexico or the Dominican Republic for the treatment, or even perform procedures domestically.”

By tracking the number of patients some of the bigger clinics state they have treated, Sipp has concluded that tens of thousands of people may have received unproven stem cell treatments worldwide during the past decade, which indicates a market size approaching $1 billion.

In June 2010, the ISSCR launched a website called “A Closer Look at Stem Cell Treatments” devoted to public education about stem cells and medicine. The website encourages people to submit names of suspect clinics for investigation by the ISSCR, but because the organization won’t evaluate the safety or efficacy of any treatment — only whether the clinic is supervised by an official regulatory agency such as the Food and Drug Administration or the European Medicines Agency and whether a medical ethics committee was involved to protect patients’ rights — its usefulness to patients may be limited.

Although ISSCR representatives say there are several ongoing investigations as of January 2011, no results have yet been posted.

It’s no surprise, really, that Americans in particular would bristle at being denied access to what may seem to be the most promising clinical advance in generations. We have freedom of speech, freedom to bear arms, freedom to worship as we please and the freedom to choose how to educate our children. Why can’t we also choose our own medical treatment? After all, the outcome of such a choice is intensely personal in its repercussions. We live or we die. We get better or we don’t. What’s it to anyone else?

“I do think there are still, when you are dying, better or worse ways to die,” responds Emanuel. “There is this phenomenon of preying on people who would otherwise be very competent and rigorous in a moment when they are weak and not necessarily having them get all the information they need. You can certainly be made sicker or worse off by some of these treatments.”

“It’s clear that a patient can’t make an informed choice if he or she is not truly informed,” says Stanford’s Scott. “That’s an ethical problem. In this situation, we have individuals making choices based on who they’ve talked to and anecdotal information they have gathered. But on the other hand, when I talk to the people I know in this situation, I’m surprised to realize that they usually have a pretty good understanding of the science and the regulatory issues that impact their disease.”

Regardless of how well-informed a patient is, clinicians and stem cell experts agree that there is really no way to stop someone from choosing to undergo an unproven treatment.

“I respect people’s choices,” says Loring, who has counseled several prospective patients. (Some have gone on against her advice to receive unproven treatments. Others have decided against it.) “The best I can do is to offer the information that people need in order to go into treatment with their eyes open. After that, other than physically restraining them, I can’t stop them.”

Loring’s gone to greater lengths than most to get the information to people who need it. She’s recorded a video for the California Institute for Regenerative Medicine warning against the use of unproven stem cell treatments, and she’s offered to screen the composition of any sample of “stem cells” sent to her by a patient. No one has done so.

“One patient was going to, but he didn’t because he was afraid he would be denied treatment by the clinic if he asked for a sample of the cells he was going to be injected with,” says Loring. Patients are reluctant to put their hope under the microscope, even when their lives are on the line.

And so the argument rages on. Recent recalls have amply shown that successful clinical trials don’t absolutely guarantee a drug will work as expected. Conversely, the fact that a particular treatment hasn’t been thoroughly tested doesn’t automatically mean that it won’t benefit at least some patients.

‘They are very logical. But they don’t show evidence that their treatment works; they just say it should. It’s hard to argue when there are no facts involved.’

“This is a new field,” says Weissman. “We are learning what kinds of stem cells can regenerate which kinds of failing organs. But we always remember that our first goal is to do no harm. That’s why we begin our tests in animals before moving into early phase clinical trials in humans, and at every stage we verify the solidity and reproducibility of the science and that the investigators have no potential commercial or personal conflicts of interest that could influence the outcome of the trials. Any attempt to commercialize unproven treatments in the absence of independent or regulatory oversight endangers not only the lives of those who receive the treatments, but also the entire field of regenerative medicine.”

The precarious nature of a field balanced on the edge of a scientific frontier is illustrated by the fate of gene therapy. In the early ’90s the technique, which relies on cells engineered to express genes that are missing or faulty, was viewed as a promising treatment for a variety of diseases. But the 1999 death of 18-year-old Jesse Gelsinger after his inclusion in a gene therapy trial led by the University of Pennsylvania set the field back immeasurably, says Weissman. [See a Q&A with Gelsinger’s father]

Without appropriate regulation and enforcement to stop the global marketing of unproven stem cell treatments, he and others fear a similar outcome for stem cell science. But it will take work to teach patients what’s truly at stake. And in the meantime the clinics themselves perpetuate the confusion to their advantage with arguments that on the surface seem eminently reasonable.

“They are very logical,” says Loring. “If it weren’t for the fact that I’m a really educated scientist, it would all make sense to me. But they don’t show evidence that their treatment works; they just say it should. It’s really hard to argue when there are no facts involved.”

“A plurality of anecdotes does not constitute evidence,” says Sipp. “Just because people swear up and down that something works doesn’t make it true.”

 

E-mail Krista Conger