Respectful Insolence

There’s no doubt about it: Stem cells are hot.

Yes indeed, they’re not only hot, but they’re hip, they’re happenin‘, they’re right now, baby. Scientists are falling all over themselves with excitement at the potential applications that could potentially come from stem cell technology. True, no validated therapies for embryonic stem cells have yet made it into clinical practice, and the challenges that need to be overcome before that can happen are arguably greater than what was believed in the heady days a few years ago, before President Bush declared his ill-advised restriction on embryonic stem cell research to only a few preexisting cell lines. Even so, that stem cell research has not yet lived up to its hype does not diminish its potential to deliver powerful new treatments for a wide variety of injuries and illnesses, including spinal cord injury, diabetes, heart muscle damage after myocardial infarction, cancer, and many others. What makes stem cells so promising is that they are at least pluripotent and possibly totipotent, with the ability to differentiate into any tissue if we can only figure out the methodology to induce that differentiation.

Unfortunately, it is these characteristics that make them almost custom made for woo-meisters, hucksters, scammers, and snake oil peddlers of all types, and China appears to be Ground Zero for this, as a story in NPR showed me yesterday, with the continuation of the story this morning. The story, which I happened to come across while flipping channels on my way to work, was about “stem cell tourism.” In essence, various stem cell therapies are being offered in countries that have–shall we say?–somewhat less rigorous regulations than the U.S. or European nations, countries that have the scientific know-how but where, when it comes to medicine, it’s the Wild West.

Countries like China.


Specifically, this story was about one stem cell “entrepreneur” in China offering dubious stem cell “therapies” to desperate Westerners with $23,000 a pop to spend, Westerners like Jena Teague and Terry Williams:

Jena Teague and her husband Terry Williams are among these new visitors. They traveled to China to seek stem-cell treatment for their blind, 7-month-old baby daughter, Laylah. She was born with optic nerve hypoplasia, or ONH — when the optic nerves fail to develop properly in the womb. Conventional medicine offers no treatment and no cure.

But Teague came across a Web site about stem-cell treatments offered by Beike Biotechnology in China and decided to try it — against advice from specialists at home in Georgia.

“None of the specialists had heard of the stem cells, of what they’re doing here. They didn’t believe it would work. They told me not to expect anything to happen out of it,” Teague says.

Nonetheless, the family traveled to the eastern Chinese city of Hangzhou, where Beike is based. They are spending $23,000 for Laylah to have infusions of stem cells harvested from umbilical cords — not the more controversial embryonic stem cells. In the U.S., cord blood stem cells are used for treating blood diseases, but are not used for treating other conditions, such as Laylah’s vision problem.

That deluded, unscientific, or unscrupulous practitioners would be offering stem cells as a panacea should be no surprise. I’ve said before many times that, if there’s one aspect that defines true quackery more definitively than almost any other, it’s the use of one treatment to treat in essence every disease. Think Hulda Clark, who blames intestinal flukes for AIDS, cancer, and even boldly declares the “zapper” that she uses to “treat” these parasites as the “cure for all disease.” Think Robert O. Young, who claims that excess “acidity” is the root of all disease and that “alkalinization” is the cure, even for cancer. Ditto chelation therapy, which is claimed to be good for cardiovascular disease, autism, and a wide variety of chronic disorders and diseases. You get the idea. It’s the same for stem cells, where, as described in The Lancet, the treatment is always the same: intravenous or intrathecal injections followed by the administration of various growth hormone cocktails.

Of course, stem cells do actually have the potential to treat many diseases in which the regeneration of differentiated tissue could correct the pathophysiology causing the disease, and indeed some of the hype in the early days of stem cell research flirted uncomfortably with sounding like one of these woo-meisters in that claims for stem cells were made that made them sound miraculous: The crippled will walk, cancer will be cured, the blind will see–those sorts of claims. It’s no wonder that the public could easily become confused or come to view stem cells as some sort of panacea. Adding to the confusion is that some of these claims might be partially or even all true–eventually. However, we are nowhere near there yet and do not yet know for what conditions stem cell-mediated therapy will or will not be useful.

That doesn’t stop stem cell “entrepreneurs” though. I wrote about this once before, where in Russia a brisk business of “stem cell” injections to eliminate wrinkles in the aging rich are being peddled at $20,000 a pop. (What is it about the $20,000 price point for this form of woo?) That is the sort of treatment that is ripe for quackery.

There are all sorts of reasons to be very suspicious of this treatment offered by Beike, under the direction of its founder, Dr. Sean Hu. For one thing, ONH is a disease with a variable course, and, according to Dr. Mark Borchert, head of the vision center at Children’s Hospital Los Angeles, it is not unusual for children with ONH to have marked improvement in their vision:

Most children do not have a miraculous improvement. A child will not go from light perception to 20/40 vision or driving vision or reading vision. That would be extremely unusual. However, it is extremely common for children to go from no light perception or bare light perception to being able to see very large objects, such as automobiles, or being able to navigate around a room without a cane or a dog.

In other words, any intervention that is claimed to be an effective treatment for the vision loss in ONH must be tested in a well-designed randomized, double-blind controlled trial of standard interventions versus standard interventions plus the new therapy. In a way, ONH is like autism in that the severity and course can be quite variable, making it difficult to identify effective treatments as effective and easy for the unscrupulous, misguided, or scientifically unsophisticated to conclude based on improvements in some patients that an ineffective therapy is effective.

There are other reasons to be suspicious as well. First, what is being used is not embryonic stem cells but cord blood stem cells. The protocol appears to involve an infusion of the cells followed by growth factor inejctions. Perhaps the biggest problem is that there is no evidence that cord blood stem cells can form neurons. In addition, there is no scientific background or evidence to lead us to expect that an intravenous injection of stem cells will lead them to “home” in on the optic nerve in these patients and form new neurons. It is true that stem cells can hone in on damaged myocardium after an MI, even in the case of acute injury the majority injected go elsewhere, as Dr. Amit Patel at the University of Pittsburgh Medical Center described:

“An intravenous injection of cells – euch,” says Evan Snyder, the director of the Stem Cells and Regeneration Program at the Burnham Institute in La Jolla, Calif. One problem, Snyder notes, is that you can’t control where cells go once you put them in the bloodstream. Given the propensity of stem cells to aggregate around a site of injury, moreover, there’s no reason the injected cells couldn’t all end up migrating to a cut on your finger. At $35,000 a shot, that would amount to an extraordinarily expensive Band-Aid.

And that’s the benign case. Among others, Dr. Amit Patel, of the University of Pittsburgh Medical Center, worries about darker possibilities. Because there’s no way to control where the stem cells go once they’re injected, they may end up causing more problems than they cure. Mice bred to have stomach ulcers, for instance, were shown to have a higher incidence of cancer formation at the site of the sores, because stem cells aggregate at those lesions. Adding more stem cells might increase that risk. Likewise, Patel points out, a patient could have a small, undetected tumor growing in the liver or a lung, in which case the injection of stem cells might actually accelerate the cancer.

“Even when I do direct injections to the heart, the majority of the cells don’t stay there,” Patel says. “Once the cells are in your bloodstream, who knows where they’re going to land.”

In other words, in real usage, stem cells are hard to control and may have possible side effects that could be quite serious. Indeed, among the Russians getting injected with stem cells to stave off aging, it’s been reported that some have developed skin tumors. But there’s more to the plausibility problem than this. Not only has it never been reported that cord blood stem cells can form functional neurons, but even if they could they’d have to develop into specialized neurons responsible for vision. Moreover, the time course of some of the reported improvements is much too fast to make any biological sense. As Bruce Dobkin is director of the neurologic rehabilitation and research program at the University of California, Los Angeles puts it, “it is extreme nonsense to think that cells can be incorporated into the complex nervous system and do so much, when we cannot even get cells in mice and rats to do very much.”

But you never know. Perhaps Dr. Hu is on to something. It’s unlikely, but not entirely possible. Perhaps he has some highly compelling evidence to support his claims for Beike’s stem cell treatment. It could happen. It didn’t though:

Less than three years ago, he set up Beike. Since then, 3,000 patients — most of them from China — have received Beike’s stem-cell treatments for a wide range of conditions. He says 70 percent have seen improvements, but he admits he can’t explain why.

“In the clinical areas, we know there are improvements. We don’t know the mechanism behind it,” Hu says.

That raises many concerns. Any improvement could be due to the placebo effect — or other factors besides the stem-cell therapy — and may not lead to longer-term functional gains. No rigorous, controlled clinical trials were carried out before the treatment was offered to patients. No research has yet been published in established peer-review journals overseas.

No rigorous controlled trials of Dr. Hu’s stem cell therapy? Color me shocked, shocked, I say! Instead, all we have are testimonials, just like the case for most “alternative” medicine therapies. We have very little in the way of any sort of objective measurements before and after, with the vast majority of reports being subjective. There is no clinical trial, much less any well-designed randomized trial. There isn’t even a well-designed observational study reported, and none of Dr. Hu’s results, as far as I can tell, have been published in the peer-reviewed literature. There’s no compelling reason to believe that Dr. Hu’s therapy is anything more than a very expensive and elaborate placebo.

Is Dr. Hu concerned about the ethics of what he is doing? Not really. He gives the same answer beloved of quacks everywhere when asked:

“I can say I changed the life of these patients. Now they get their vision back. They went from completely blind, now they can see stuff. You think that’s ethical or nonethical?” he asks.

I’m sure readers will recognize this as a variant of “I’m doing too much good to be bothered with doing clinical trials to show that my therapy works.” Dr. Hu is so certain that his treatment is curing the blind that he sees no need to actually show that it does anything more than placebo or that the improvements seen in his patients are anything more than confirmation bias and regression to the mean. No, what is really unethical is to subject patients to unvalidated therapies that have the potential to have real side effects–at $20,000 a pop. What is really unethical is advertising such unvalidated and unproven therapy as a means to treat children, who are not able to give informed consent for a medical procedure and whose parents are desperate to do anything that will give them hope. What’s really unethical is claiming that this scientifically implausible stem cell therapy works for the diseases in question when there is not yet any good evidence that it does. Perhaps Dr. Hu really and truly thinks he’s doing good, but that doesn’t absolve him from having to back up his therapies wit science or excuse him for charging exhorbitant prices for what is in essence an experimental therapy.

Sadly, stem cell therapy is not yet ready for prime time. I wish it were, but, as often happens, biology is more complex than we can ever imagine, and there remain significant problems to be worked out and hurdles to be jumped before we can use cord blood stem cells (or other kinds of stem cell) to treat disease, much less cure chronic, presently intractable ones.

Comments

  1. #2 Ivan
    March 20, 2008

    same blog, different personality responding.

    How can physicians inform those who may be less able to understand things like what you, Orac, have written……about the very real harm-potential of woo?

    I can follow your writing to an extent……what about those who can’t?

    I think fighting and defeating sensationalism about “wow” claims of cure and treatment…..are uphill battles. Certainly not unwinnable, but uphill nonetheless, because of the mind’s reaction to sensationalism……which depends a lot (I think, I could be wrong) on one’s level of education…

    You and others have won half the battle, which is writing about this stuff and debunking it in the first place. The other half is going “viral” with this information in accessible forms so that many more people are exposed to the truth about this kind of quackery as you have been describing for the 4th entry in a row (I’m learning quite a lot. I’d never heard about a lot of this stuff prior to reading your blog)…..

    Autistic people who want others to understand them and not be concerned with curing them have a very similar problem…..getting our information out there so many people can read, hear, understand………..etc…..our viewpoints.

    There’s a lot of woo in autism treatments as well…….you’ve mentioned some of it…..chelation…..etc.

    Best of luck with educating whoever will be educated……on the ills of woo.

    Ivan of athenivanidx
    (Athena, Ivan, The Integral)

  2. #3 qetzal
    March 20, 2008

    There’s no compelling reason to believe that Dr. Hu’s therapy is anything more than a very expensive and elaborate placebo.

    Actually, I’d say there’s very good reason to suspect it’s less than placebo. A true placebo such as a sugar pill would have virtually zero direct risk. Not so in this case.

    Injecting these cells almost certainly can’t work, for all the reasons discussed. But they can certainly have unwanted side effects. Even if we discount the tumor risks as hypothetical, they certainly expose these infants to risk of infection and risk of immune reactions.

    No, I don’t think these can be considered placebos at all.

  3. #4 qetzal
    March 20, 2008

    There’s no compelling reason to believe that Dr. Hu’s therapy is anything more than a very expensive and elaborate placebo.

    Actually, I’d say there’s very good reason to suspect it’s less than placebo. A true placebo such as a sugar pill would have virtually zero direct risk. Not so in this case.

    Injecting these cells almost certainly can’t work, for all the reasons discussed. But they can certainly have unwanted side effects. Even if we discount the tumor risks as hypothetical, they certainly expose these infants to risk of infection and risk of immune reactions.

    No, I don’t think these can be considered placebos at all.

  4. #5 Liesele
    March 20, 2008

    I’m particularly concerned about the use of this in treating children with ONH. Septo-optic dysplasia/optic nerve hypoplasia is a birth defect highly correlated with endocrine diseases as well, and I would be very worried that somehow the stimulation from either the stem cells or the hgh could trigger diabetes mellitus, thyroid disease, or some other very negative effect. If they find in mice with lesions that stem cell injection leads to tumor growth around the lesions, I would suspect that in these children there could also be a greater risk of tumors in the thyroid, pancreas, or anywhere else there is likely to be related damaged tissue.

  5. #6 jypsy
    March 20, 2008

    Here’s a case where, after trying “Behavioral Therapies – including Applied Behaviour Analsysis (ABA) and Picture Exchange System (PECS) – vision exercises to improve eye contact, speech therapy, vitamin and chelation therapy, and hyperbaric oxygen therapy.” the parents turned to Chinese Stem Cell Therapy to cure their child’s autism.

    Poor kid, I wonder what’s next…

  6. #7 c coe
    March 21, 2008

    re medical tourism—a relative in usa just received stem cell treatment for cancer at manila clinic. lots of odd things about it, and unanswered questions, but the relative did it anyway feeling it a legitimate (if very expensive) option. I obviously have many worries about the safety, & other doubts and continue to try to research this place/drs to ease my mind that this treatment is legitimate medical effort and not the usual scam. Not too much luck. how do you research these things other than fruitlessly googling and going through PubMed for hints? Bad situation

  7. #8 jypsy
    March 21, 2008

    Here’s a case where, after trying “Behavioral Therapies – including Applied Behaviour Analsysis (ABA) and Picture Exchange System (PECS) – vision exercises to improve eye contact, speech therapy, vitamin and chelation therapy, and hyperbaric oxygen therapy.” the parents turned to Chinese Stem Cell Therapy to cure their child’s autism.

    Poor kid, I wonder what’s next…

  8. #9 Coin
    March 21, 2008

    First, what is being used is not embryonic stem cells but cord blood stem cells.

    For some reason I found this bit a relief. When I saw this story in the news elsewhere (although I’m not entirely sure whether the story I saw was discussing the same case) I somehow reached the assumption that these were embryonic stem cells. The irony of embryonic stem cells just being wasted on random injection treatments while legitimate researchers are still having trouble getting them would have just been painful.

    But there’s more to the plausibility problem than this. Not only has it never been reported that cord blood stem cells can form functional neurons, but even if they could they’d have to develop into specialized neurons responsible for vision.

    I’m imagining a scenario here where they inject stem cells into some guy hoping for them to form vision neurons and cure his blindness, and by lucky coincidence they do decide to form into neurons, but they land in the wrong place or something and thus grow instead into a supersized olfactory bulb. So he still can’t see, but has like a superhuman sense of smell.

    Given powers far beyond those of any human, but ironically slowly dying of the brain tumor that stemmed from that same pluripotent cell injection that gave him his gift, he uses his newfound powers… to fight crime.

  9. #10 Coin
    March 21, 2008

    First, what is being used is not embryonic stem cells but cord blood stem cells.

    For some reason I found this bit a relief. When I saw this story in the news elsewhere (although I’m not entirely sure whether the story I saw was discussing the same case) I somehow reached the assumption that these were embryonic stem cells. The irony of embryonic stem cells just being wasted on random injection treatments while legitimate researchers are still having trouble getting them would have just been painful.

    But there’s more to the plausibility problem than this. Not only has it never been reported that cord blood stem cells can form functional neurons, but even if they could they’d have to develop into specialized neurons responsible for vision.

    I’m imagining a scenario here where they inject stem cells into some guy hoping for them to form vision neurons and cure his blindness, and by lucky coincidence they do decide to form into neurons, but they land in the wrong place or something and thus grow instead into a supersized olfactory bulb. So he still can’t see, but has like a superhuman sense of smell.

    Given powers far beyond those of any human, but ironically slowly dying of the brain tumor that stemmed from that same pluripotent cell injection that gave him his gift, he uses his newfound powers… to fight crime.

  10. #11 Stagyar zil Doggo
    March 21, 2008

    Following is a re-post of a comment I made over at Pure Pedantry:

    It appears that Stem Cell based therapies, including most of the (soon to be here) first generation, ‘actually effective’ therapies, will carry significant cancer risk. In fact, this is likely to be the case for any cells that are subjected to incompletely understood genetic manipulation before being (re-)introduced into the body. It will be a number of years more before we are able to eliminate this risk. In the interim, it would be desirable to add some kind of a “kill switch” to all such artificially manipulated cells inserted into a patient’s body as part of a treatment regimen. Heritable/genetic susceptibility to a specific chemical agent which leaves normal human tissue unharmed appears to be one obvious way to go. This agent would then be the highly effective, zero side effect drug to be taken in the event of such stem-cell related cancers. Do you know if anyone is already working on this?

  11. #12 Patchouli
    March 27, 2008

    No matter what type of research you support, either embryonic stem cell or non-embryonic stem cell based, if the funds are not available to conduct the research, then nothing is accomplished. With the war costing the country trillions of dollars and research funding being drastically cut year after year causing promising scientists to flee the field, there will be no progress to treat or cure diseases. As a stem cell researcher, I see the effect the Bush administration has done to the field. Yes, we are still making great discoveries, but not nearly at the rate we could if funding wasn’t such an issue for everyone, especially brilliant, young scientists.

  12. #13 Jon
    May 8, 2008

    I can not find any scientist who will tell me that umbilical cord stem cells will cause cancer. If there were serious immune reaction, don’t you think you would have heard about it after the treatment of thousands of Chinese patients and hundreds of Americans. Look the drugs in the US approved by the FDA, I am guessing you have heard more about problems from them.

    In terms of effectiveness, please read the following and see if you really believe that the scientists quote are correct and that all of these children are just spontaneously getting vision improvement.

    http://ozarksfirst.com/media_player.php?media_id=20247 (please watch the second half)
    http://www.nbc-2.com/articles/readarticle.asp?articleid=14343&z=3&p=&
    http://www.fortmilltimes.com/124/story/138669.html
    http://www.ky3.com/news/specialreports/18345884.html?

    Patient blogs (gives you a feel for the treatment and also mentions some doctor checkups to verify the results)
    http://stemcellschina.com/blog/justinl/
    http://www.blessherwithsight.com/China_Blog.php
    http://www.nomoredarkness.com/
    http://stemcellschina.com/blog/laylah/
    http://stemcellschina.com/blog/carl/ (Older patient with optic nerve problems not ONH)
    http://www.hopeforandrew.org/Diary.html?
    http://www.tresmiracle.com/web/do/site/journal?ID=325514
    http://stemcellschina.com/blog/lydia/