Pure Pedantry

I was struck by this story on NPR about so-called “stem cell tourists.” Stem cell tourists are parents taking their children to China for injections of stem cells in hopes of curing a wide variety of diseases. I want to convey at least in some small way what an insanely bad idea this is:

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.

Listen to the whole thing. They have an interview with the guy who started the company.

While I don’t doubt that these parents are at their wits end trying to help their child, this is a dangerous and untested way to do it.

They are injecting these stem cells (from cord blood) either into the blood or into the CSF with no mechanism for specifying how they will become the desired cell type. The company advertises this as a sort of one-size-fits-all therapy to cure whatever ails you (from Lancet coverage):

The procedure is the same for all diseases: intravenous and/or intrathecal injections of stem cells, followed by daily infusions of growth factors. Chin describes this as “one treatment fits all”. Unusually, patients get to decide how the cells are given, which depends on their willingness to endure painful spinal puncture, and how many times the procedure is done, which depends on their budget.

That claim is just plain hookum for two reasons.

First, there is not a shred of evidence to suggest that you can just inject stem cells, and they will become whatever the hell you want. Stem cells differentiate in a certain proscribed millieu based on the presence of certain growth factors and signals from neighboring cells. Specifically in the case of the girl with optic nerve hypoplasia, you want these stem cells to become neurons and the appropriate supporting cells. There is no research to suggest that stem cells derived from cord blood are capable of doing this. We have no idea what growth factors would be necessary to make them make this transition.

Second, I would love to believe there is some magic cure for everything that ails you, but medicine doesn’t work that way. Specific medical conditions have specific pathophysiologies that require specific interventions to cure them. Specifically in the case of ONH, we don’t really know what causes it. In addition to the failure of the optic nerve to grow, patients with ONH often have a variety of pituitary hormone disturbances. (More on ONH here.) Because we don’t know what causes this disease, we should only intervene when there is considerable evidence from animals that what we are doing works. There is no such evidence in this case.

Now this company claims that people are getting good results, and the parents of the child described above report that their child is seeing better:

Dr. Sean Hu, the 40-year-old chairman of Beike Biotechnology, is a medical doctor-turned-entrepreneur with a doctorate in biochemistry from a Swedish university.

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. And no one knows for sure what the possible risks might be.

There are several reasons to be skeptical of claims of improvement in these cases. With respect to the child with optic nerve hypoplasia, ONH does spontaneously improve in some cases as the child gets older regardless of what you intervene or not. This point is made on an off-radio interview with Dr. Mark Borchert (scroll to the bottom), head of the vision center at Children’s Hospital Los Angeles:

What happens in children who are getting an experimental treatment?

We currently know that regardless of whether or not they are treated, at least 50 percent of children get some improvement up until five years of age. We don’t know whether they can improve beyond that.

It is totally possible that the incremental improvements the parents observed have nothing to do with the experimental treatment, but they don’t do the experiment that is the only way that we could be sure whether the treatment is effective. This is my second reason to be skeptical: none of the studies reported by this company have controls or are published in peer-reviewed journals. When you don’t have a control group, you have no idea whether the improvement was do to a placebo effect. (And as was reiterated by a meta-analysis of antidepressant medications published last month, placebo effects can be quite large.) Any peer-review of their findings would demand that they provide controls, but they haven’t done that.

Why all the fuss though? So what if it is a placebo? At least it is making the parents feel better.

While we don’t know enough about the side effects of injecting stem cells into a person, we can reasonably expect some — a number of the serious. Not the least is that in animal studies injecting stem cells into the animal can cause cancer. Stem cells are undifferentiated cells not that different from the cells that cause cancer, and it is a highly risky proposition to just put them in someone’s body. (The relationship between stem cells and cancer is reviewed here.)

(As an aside, this is still a concern in spite of the fact that these stem cell transplants do not appear to be autologous [meaning that they come from the same person]. An autologous transplant would not be recognized as foreign by the immune system. Thus, an autologous transplant would be much more likely to cause cancer because of more limited immune surveillance. However, Beike technology can’t have it both ways. You either acknowledge that immune cells are killing your transplanted cells — rendering your treatment a sham — or you acknowledge that you transplant poses a reasonable risk of cancer.)

Besides the medical risk on for the recipients, these people are lying to the parents when they suggest they have the slightest reason to believe that these injections help. Surely, these patients may improve, but there is no reason to believe that these injections made that so. Taking into account the considerable cost and this company’s exploitation of people’s ignorance, this company is doing something deeply ethically wrong.

Parents should not be subjecting their kids to this treatment, and China needs to exercise some scientific oversight over this company. Stem cells do show tremendous promise in curing numerous different diseases — ONH may well be one of them — but it shouldn’t be used until we understand how to apply the technology better. Exaggerated claims of the effectiveness of stem cells will only draw the entire field into disrepute, and it may hurt a lot of people in the process.

(Ed. I made some grammar and spelling corrections after posting this.)

Comments

  1. #1 Ken Clark
    March 19, 2008

    Like the saying goes, you have to take a test to get a drivers license, any couple with functional organs can be parents *sigh*

  2. #2 Doug
    March 19, 2008

    Funny. The Related Ad associated with your post is for a bit of woo called StemEnhance, which claims to be a “natural botanical extract that supports wellness by helping your body maintain healthy stem cell physiology”.

    I don’t expect much from China’s regulation of woo if we cannot even regulate our own very successful woo.

  3. #3 Caledonian
    March 19, 2008

    If the child develops cancer in the next, oh let’s say five years, will the parents consider the possibility that their injections were harmful?

    [Gypsy Fortuneteller Robotic Head]: “Hey, do you want false hope or not?”
    [Stephen J. Fry]: “Only if you don’t have any real hope.”

  4. #4 Paul
    March 20, 2008

    The issue of stem cell injections in China made the news here in the UK last year
    http://news.bbc.co.uk/1/hi/uk/6720453.stm

    There was also a documentary which discovered that not only were their no publications supporting the treatment but that the physicians and surgeons involved didn’t even seem to be undertaking the kind of assessments that would be necessary to find out if the treatment was having an effect (positive or negative).

  5. #5 spindizzy
    March 20, 2008

    I agree that this procedure is unlikely to work, could possibly have adverse effects, and needs proper scientific investigation rather than snake-oil salemanship.

    However, we cannot rule out the possibly of positive effects. The field is surely young enough for the orthodoxy to be challenged.

    In any case, the parents in question have chosen a long shot because they think it’s worth it. Even if you are an expert in your field, you do not have the right to dictate how other people care for their children.

    The smarter you are, the greater the temptation to behave like an autocrat. Resist it!

  6. #6 ian
    March 20, 2008

    Are you suggesting we should stem this sell?!

  7. #7 Richard Eis
    March 20, 2008

    and this is different to “energies”, chakras and quantum cures because…..

    Let’s face it this really is just the next “fashion” isn’t it.

    It wouldn’t surprise me if the “doctors” are just pretending to inject stuff then sending the parents on their merry way.

  8. #8 nottomention
    March 20, 2008

    God forbid their otherwise healthy child be, gasp, blind! Ask the new governor of New York, or Stevie Wonder, how they feel about this. I mean, it’s great when there is something wrong and you can fix it, but isn’t this a bit retrograde when it comes to people with disabilities? The money those parents are spending could be used instead to give their child a wonderful education at a specialized institution geared to people with visual disabilities. I’m sorry but not everyone with a disability is ‘broken’ and I sure they are putting a big psychological trip on their daughter about being blind, whether or not they intend it.

  9. #9 Karen Ventii
    March 20, 2008

    This NPR story has been quite a hot topic around the water cooler & coffee machines at work. Thanks for blogging about this!

  10. #10 Stagyar zil Doggo
    March 21, 2008

    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. #11 John
    April 8, 2008

    Please get educated on how stemcells work. There is no much published yet. however, if you lose your sight or your kid/grand kid loses it. Do you want to have the option of stem cells treatment? Or are you just doctors that will be out of work if China takes advantage of this procedure?

    Think about it. Do you believe Jesus made the blind see? …. Go ahead and explain me that… I do believe.

  12. #12 Jon
    May 8, 2008

    Hey guys, the NPR story was completely a set up. They came in with their angle and did not want to hear anything else. They gave five minutes to the US scientist Bruce Dobkin who has everything to lose by this treatment coming out and they gave Dr. Hu about 2 minutes and cut up everything he said. The patients were not happy with them and one that was interviewed demanded that their interview not be aired because they felt they were very rough and were mistreating them. I know it sounds strange because people believe NPR is unbiased but I thought the Wall Street Journal was biased against China until they came in. You can see that all of the patients in the story felt they had improvements. Not sure how every patient out of the thousands treated could be imagining it. And all of the 15 children that were treated all suddenly just by chance started to have their vision improve. John is completely right..

    If they had not cut off Dr. Hu’s statement on how it works, you would have heard that the stem cells are giving off growth factors and proteins which help dying cells to reinvigorate themselves and also to help the body repair itself. They do not need to differentiate into other cells because their work is done by emitting growth factors soon after the injections.

    The intersting part is that NPR was able to get the quote off the front of the web page (www.beikebiotech.com) which says “Tomorrow’s Treatments Today” but somehow managed to not scroll down a little further to explain how it works.

    Biotech and science is a very dirty business because it is very lucrative. China is putting a lot of money into the research as it is a key national objective just like India. The amount of money that is being invested is not alone going to make China the leader in this area but the less complicated regulatory structure and cost of labor may very well.

    - Jon

  13. #13 nick
    May 27, 2008

    been there done it any questions just ask.

  14. #14 Graeme Moore
    January 3, 2009

    Jake….you and your US colleagues are just jealous and Anti Chinese. Its that simple dude. And you dont have a sick child or family member. So what about you get off your high horse and just get on with your studies. The last thing I need is a “med student” masquerading as a subject matter expert on STEM CELL research and therapies. You sound sweet, write cute, but its all gas. I do have a child with severe myclonic epilepsy of infancy and I will be looking into this seriously if I dont see the west lifting a finger to catch up and offer something for my kid.

  15. #15 Melissa
    January 7, 2009

    Well put Graeme Moore.

  16. #16 Jena Teague
    January 30, 2011

    Wow,
    Hi its me jena teague the girl that actually told npr yes we will do the interview,when the others wld not for fear of people like u guys!!! When I did for one simple reason for people to become aware that this is happning and there is another option besides nothing which is what our doctors here provide!!! So I find it so intresting everyone’s comments on here esspicaly the one who is running there mouth without having a clue as to what they are talking about befor they start. The one who says (god forbid the other wise healthy child be gasp blind!!!) Oh my how I have so much to tell you for one maybe your parents should have spent a little extra money with you and sent you to a Special school maybe that way you would know to think befor you open your mouth!!! my child is not only blind but she has cerebal palsy and many other brain conditions wonder what the governer of new york would feel like if she knew her daughter could not crawl or walk or only said a couple of words or if she could not hold her head up or heavean forbid what if stevei wonder was this way well i guess he would not be stevie wonder(wow imagine that),so now dont you feel like the stupid one or maybe not because it sounds like you dont have any feelings!! Let me tell you something sara palin I envey her!!! Her child can walk talk eat u know everything people take for granted people like you!!! Stevie wonder what an amazing man who is only blind what an amazing artist lucky man also and if he could hear your comment he would think you were not very bright but if he could meet my daughter even though he canot see would open his mouth use his brain they way everyone can and say that she is the brightest thing he has ever saw!!! For the people that actually had a brain and made comments THANK YOU!!! The one person who said please get educated on how stem cell work,THANK YOU and there other comment Do you belive jesus made the blind see’ I do!! you are so right these people probebly have never even read the bible. So GOD help them!!! Befor we went to china my daughter couldn’t even hold her head up could not get in a jumparo and jump or roll over what a child at that age should be doing befor we left she was doing all of those she gained a little light perception and yes GOD is good and as long as you have faith that he knows what he is doing no matter the gain or not the gain of something i know he has a plan!!! Stem cell does work I watched a little boy while we were there in china that was fom here in the united stated go from completly blind to not even being legally blind while we were there you have no idea how amazing this was and his parents and I still keep each other updated and he is doing great and so is laylah my baby!!! You know in Bosten now and many other of our states here in the united states are doing clinical trials for umbillical cord stem cell for lots of things now and having amazing results like treating cerebal palsy and making the patients walk and be able to funtion it is so amazing guess some of you spoke to soon!!!! By the way embryotic stem cell are the only one that has the ability to turn into tumors and cancer not adult stem cells u people are amaxing you dont have a clue!!! GOD SPEED!!!
    PLEASE IF U WLD LIKE TO ASK ME ANY QUESTIONS DO SO!!!
    P.S I dont have time for spell check or any look over to see what I maybe spelled wrong but hey just gives you smart people who know everything something to comment about!!!