About four months ago, the skeptical blogosphere was abuzz about a tragic story. The story was that of a Belgian man named Rom Houben, who had been unfortunate enough to have been in a motor vehicle collision and suffered serious brain injury. That brain injury left him in a comatose state, which had been diagnosed as a persistent vegetative state. What brought him worldwide prominence was a claim by neurologist Steven Laureys that he was not in a persistent vegetative state at all, but was rather fully conscious and "locked in," meaning that he could see, hear, and feel everything but could not move any part of his body. Unfortunately, part of the methodology by which Dr. Laureys came to this conclusion was through the woo known as facilitated communication. It was recently definitively shown (once again) that Houben was not communicating through facilitated communication, but the concept of being "locked in" both fascinates and horrifies me. I have a hard time imagining a worse fate, and stories of the locked-in hold a special fascination for me.
That's why I was disturbed to find out about a woman in Toronto named Alda Byers who is definitely locked in and has resulted in yet another round of bad reporting, which renders the tragedy even more hard to take. The case of Alda Byers involves what is likely (but not certainly) quackery coupled with a number of thorny ethical issues that are hinted at, but barely touched upon, in a story by Michele Mandel entitled Trapped in her own body, docs won't help: Woman denied stem cell treatment that offered hope. The title alone was painful to read because it paints the doctors who won't help Byers pursue stem cell woo as being heartless and blocking her from her last chance at a cure from her horrific state.
The story begins:
Freedom flickered so elusively close, with a joyous new wiggle of her toes, with the thrilling turning of her head.For Alda Byers, imprisoned by a rare, paralyzing brain stem stroke, a controversial stem-cell treatment in Mexico last fall seemed to deliver on its promise of improvement.
But now all her progress has come to an abrupt end and her family believes it's Canadian medical reticence that is standing in her way.
The pretty 52-year-old remains trapped in her hospital bed at West Park, her world confined by walls brightly decorated with loving cards and dozens upon dozens of photos of her family, friends and beloved dog.
Yes, the article itself, in the name of "human interest," has let us know that the Canadian medical establishment is apparently too uncaring to help the Byers family achieve its ends and save the unfortunate Mrs. Byers from her fate. The article even continues with a real, live, honest-to-goodness testimonial:
With the help of hundreds of friends, they held two fundraisers and put together the thousands of dollars they needed to get her a stem-cell transplant last September in Cancun.
At first, the results were astounding.
She could suddenly move her neck from side to side. She could open her mouth and form an "O". She could wiggle her toes and fingers. She could laugh and even breathe on her own for short spells. For someone who couldn't move at all, it was a breathtaking promise of what lay ahead.
Soon after arriving back at West Park, with Byers happily demonstrating her new tricks for all her visitors, they received a follow-up e-mail from her Mexican doctor: to continue the stem cells' work, she'd need to take a cocktail of drugs for the next six-to-eight weeks.
They never anticipated any problem with a Toronto doctor writing the prescription. The three drugs -- erythropoeitin, filgastrim and somatotropin -- are not rare or experimental. The first two are generally used for anemia, renal failure and chemotherapy, the third has been used in children and athletes as a growth hormone.
Even though these are drugs that are approved and available and even though doctors can prescribe drugs off label, apparently the family has had difficulty finding a doctor willing to prescribe the drugs requested. This is not surprising, given that these are powerful drugs with serious potential side effects, particularly the first two. Indeed, one wonders why the clinic in Mexico peddling this stem cell woo would consider erythropoietin, which stimulates red blood cell production, and filgastrim, which stimulates white blood cell production, to be essential to its protocol. These are not generally substances that would stimulate the growth of new neurons from stem cells; any effect that they might have on stem cells would be to promote differentiation into hematopoietic cells. In the absence of evidence demonstrating the efficacy of whatever "stem cell" protocol the Mexican clinic had prescribed and absent a demonstration that this protocol required these drugs, the Canadian physicians approached to prescribe them were right to be wary and reluctant.
When I first saw this story, I did a little Googling to learn about Byers' story. I found out that the specific clinic to which her family took her last summer was that of Calvin Cao from Stem Cell Therapy International Inc., in Tijuana. It's a highly dubious-appearing clinic whose website contains several the hallmarks of quackery, specifically claims of efficacy for many, many conditions, including diabetes, cirrhosis, and neurological conditions, among the more common diseases. Amazingly, SCTI also claims efficacy of its particular stem cell woo for adhesions of the abdominal cavity after surgery and the "rejuvination" (spelling error copied from the website) of women after menopause, both applications I haven't heard before for stem cells. The latter of these is described using word salad devoid of any real science behind it:
We developed the regimen of biological preparation introductions, its characteristics and necessary dosage. As opposed to the treatment of androgenous disorders, in this case we used 10-12 week preparations with XX genotypes. Before carrying out treatment with preparations, a profound study of somatic and gynecologic anamnesis in view of contra-indications to hormonal therapy, mammography and bio-chemical examination, ultrasound of organs of the small pelvis on the 5-7th days of the menstrual cycle are made.
From what I can figure out, SCTI seems to be using some sort of cell-based bioidentical hormone therapy, but it's hard to tell from the word salad science on its website. Regardless, apparently its woo is not limited merely to stem cell woo.
Not surprisingly, I could not find on its website a single instance of peer-reviewed research directly supporting the efficacy of the "biological preparations" administered by SCTI. The website cites thousands of articles apparently culled from PubMed searches on certain keywords, but it doesn't provide, as far as I can find, a single example of a well-designed clinical trial published in a peer-reviewed journal demonstrating that their methodology has a measurable therapeutic effect on the conditions for which SCTI claims efficacy for its methods. They make the excuse that the real reports that allegedly show the efficacy for their methods are all in Russian and German and not indexed in MEDLINE and further brag that "an estimated 20 million patients worldwide received in the U.S.S.R. developed live human placental tissue implantations with various kinds of trophoblastic cells." Given the amount of Russian stem cell quackery out there, I'm not sure I'd be bragging that this is the primary evidence of efficacy for SCTI's preparations if I were Mr. Cao.
Also nowhere on the SCTI website could I find evidence that any of its preparations actually contain real human stem cells, pluripotent cells that can be induced to differentiate into many, if not any, organ. In fact, I'd be highly suspicious of their preparations and that they can even make stem cells suitable for attempts at stem cell therapy. The website lists a lot of "applications" for their stem cells, but don't include a link to a single scientific paper supporting these claims. There is no detailed outcome data to show that they have results better than what could be expected using the standard of care, much less high quality data from randomized clinical trials demonstrating efficacy of their stem cell preparations. In brief, SCTI shows all the hallmarks of peddling pseudoscience to the Byers, all for $50,000 for six daily injections of "stem cells," a sum that ballooned to $150,000 when all other expenses, including a private plane for transportation, were added in.
Regardless of one's opinion of the SCTI clinic (and I have made my opinion of the extreme dubiousness of any of its claims known), the question remains of what to do with Mrs. Byers now that she has returned and her husband is claiming significant improvement. First, we must remember that there appears to be no objective evidence of concrete improvement other than the word of Byers and her husband. We have no detailed neurological examinations documented before and after the treatment, for example. While it is possible that the improvement claimed are real and due to the "stem cell therapy," it is also unlikely. We have no idea whether some of these movements were possible before the treatment and the perceived improvement the result of expectation effect and confirmation bias or whether there was a real improvement. Again, there is no reported objective documentation of these improvements, and there needs to be. I can understand Mr. Byers' frustration here:
It's like hitting your head against the wall," says Byers, 60, waving a thick file of e-mails from physicians turning them down.
"Everybody wants case studies," he complains. "But somebody with a brain stem stroke is one in a million and how many of them have undergone stem cell treatment? None."
On the other hand, this is a bit of a straw man. I'd bet that most of those doctors who want case studies would understand that locked in syndrome is (mercifully) rare and would be willing to accept evidence from case studies of stroke victims who suffered less devastating neurological damage than locked-in syndrome or victims of spinal cord injury. For example, if a stroke victim with a complete hemiparesis of one side of their body were to demonstrate documentable, objective improvement in the affected side after the stem cell therapy, that would be a legitimate case study that might convince me there was something going on worthy of further study. If a patient with a complete transection of his spinal cord and complete paralysis below the waist for three years suddenly could move his feet after stem cell therapy by SCTI, that would be suggestive evidence that might convince me that it's worth continuing with the SCTI stem cell therapy in Mrs. Byers' case, given that her current condition is so horrific and there is currently nothing medicine can do to ameliorate or reverse it. I can find no such case studies with any objective documentation of improvement in neurological function beyond what could be expected in the natural course of their condition in patients with severe neurological injury like stroke or spinal cord transection.
In the case of Mrs. Byers, there are at least two major ethical considerations at play, along with the problem of pitting science-based medicine versus stem cell hucksters selling what is likely to be false hope. First, there is the ethical precept of "First, do no harm." Prescribing drugs like erythropoietin has a real risk of doing harm. Also impacting the case is the ethical precept against performing experimentation on humans without sound science and extensive preclinical data to prove a reasonable degree of plausibility. In this, the stem cell therapy offered by SCTI fails utterly, given how little evidence appears to support it. Even worse, SCTI charges $50,000 per round of treatments for what is at best a highly experimental treatment not ready for prime time and at worst pure quackery. Without strong evidence for the efficacy of such a treatment, it is in general unethical to charge so much money for it, and it pains me to see these stem cell clinics taking advantage of patients as sad and desperate as Alva Byers.
I could understand it if a physician, hearing Mr. Byers' plea, decided that Alva's condition was so terrible that he might as well grant their wishes and prescribe the drugs SCTI requested. I might disagree, but I could understand someone who says, in essence, that Mrs. Byers' current condition is a fate worse than death and, even if there really hasn't been any evidence of objective improvement due to the alleged stem cell therapy, there's nothing to lose by giving her the three drug cocktail that's supposed to keep the stem cell treatment going. What I can neither understand nor forgive are companies like SCTI peddling unproven and likely ineffective varieties of "stem cell" therapy to desperate patients like Mrs. Byers, all in order to separate them from their money.
Nor can I forgive reporting as irresponsible and supportive of companies like SCTI victimizing patients like Mrs. Byers as demonstrated by Michele Mandel. Such reporting serves no purpose other than to encourage other desperate patients to seek out companies like SCTI and be separated from their money as well.
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Michele Mandel's columns are always filled with stuff like this. Last winter it was the evils of the Flu Vaccine.
http://www.torontosun.com/news/columnists/michele_mandel/2010/02/06/127…
Wow. Just, wow. What bad journalism. I didn't go to journalism school, and even I can tell it's bad. That reporter thrives on this BS, doesn't she?
First off I would like to say that I actually like Michele and she has written many columns that I have found of very good human interest and I believe that her intentions are primarily good and I dont think it would be fair to criticize her for the article. That Being Said, I read this article on the weekend and when it mentioned that the Therapy was thought to be quackery the first thing I thought of was "I wonder what Orac would say about this" so I forwarded this to him yesterday. Maybe he had already seen it and had planned to post about it, either way I must thank him for making this post, It has given me much more insight then I had previously.
Although I had suspected Woo, part of was hoping that it wasn't, My heart goes out to the family. I hope that if a Dr does give them the medication that she is watched carefully and that any improvements or non-improvements will be well documented and investigated to confirm if the treatment actually did anything or not.
It seem like an easy OUT for the Clinic, tell the patient that they need X drugs knowing full well that they won't get them from their local Doctor, thus when the patient doesn't get better they have an excuse.
Ken #1:
I had read that article and I even questioned her on what exactly the point of it was. But it was not an article of the Evil's of the flu shot. She actually doesn't even take a stance on either in the article and she doesn't make any claims about what Vaccines do. The article is about GBS which is valid, she even reports that the cases of GBS were at that point even less then what would be expected. It was a Human interest story and I believe the main issue in it was if this persons GBS was a result of the Vaccine or not and to point out the Government's un-willingness to put the cause of her GBS on the vaccine.
I didn't think it was one of her best articles and it was difficult to understand the point she was trying to get across, but it was not your typical anti-vaccine type of article.
@3, RodM
Just because her columns are normally of good quality does not give her a free pass on the ones that are not. I also find it telling that this is not her first credulous, one-sided woo-friendly article. Perhaps she is normally a fine reporter, but it seems that when her stories touch on science and medicine, the quality drops because she is venturing outside her area of expertise.
For science journalism to improve, poorly-written articles and lazy reporting must be called out. In two articles on medical matters, Mandel did not speak with a single doctor; perhaps she would have gotten a more complete picture of the situation if she had.
This is more of a logistical/EBM based question.
You write (and correctly so), that, "[i]f a patient with a complete transection of his spinal cord and complete paralysis below the waist for three years suddenly could move his feet after stem cell therapy by SCTI, that would be suggestive evidence that might convince me that it's worth continuing with the SCTI stem cell therapy in Mrs. Byers' case".
But at what point does this FIRST trial happen. Doesn't someone have to be the 'brave maverick doctor' that initiates this treatment?
Lycanthrope #5
I am not trying to give her a free pass but she is a human interest Columnist and don't think she should be put in the same boat as Science Journalists.
That being said I do agree that even in the role that she is in it would be better if she did research a bit more. A More objective article would have been in line with the idea that she is already in shut a dire situation that there would be nothing to lose prescribing the drugs.
I mainly just think that in this case the criticism should be focused on the topic and less on the columnist.
How do you separate what was written from the person who wrote it?
Pablo
Good Point, I guess where I am coming from is that I don't expect as much from Human Interest columnist as I would an Investigative reporter or even a science blogger.
Of Course then one could argue that if she is leaving her expertise then maybe she shouldn't be reporting on it.
Not at all. (Significant simplification follows.) Prior to that first trial, the treatment should be tested in animals. Assuming the animal testing is properly done, correctly reported, and successful, it is proper to move on to clinical trials. At that point, trying it in humans is not the act of a 'brave maverick doctor', but a typical clinical trial.
Trying it in humans without that foundation isn't being a 'brave maverick doctor', it's unjustified and unethical human experimentation which no competent IRB would allow. I'd suspect it would probably be grounds for loss of licensure.
'Brave maverick doctor' is more properly described as 'doctor who takes shortcuts around the proper processes in place to ensure that treatments are safe and effective, thereby endangering his patients'.
Sadly, it's to be expected - mindless media hype has turned stem cells into the the new "Dr. Shonky's Snake Oil". The ignorant and desperate lap it up and any real discoveries are drowned in a sea of woo. Got a headache? Use stem cells! Girlfriend left you? Use stem cells! Genitals too small? Use stem cells! They make everything better! Now in peppermint flavour!
Out of curiosity, with these dodgy clinics injecting "genuine stem cells" into patients (God only know how pure it is, or even if there are any real stem cells let alone where they got them), how bad would be the immune/rejection response be (not counting the cancer danger)?
Question @ 5:
Of course, but it does suggest another question:
If no doctor has yet initiated this treatment under controlled circumstances, what the hell is this clinic in Mexico doing giving it to all of these patients? How come they haven't been able to publish a single case report, despite using this treatment often enough that they know what cocktail of drugs will allegedly maintain the treatment?
Really, there are only two possibilities:
1) They know how to cure some of the most devastating conditions mankind can face -- but don't give a rip van winkle about sharing this secret with anyone else, as it might cut into their profits, or are simply too lazy to even document the fact that it worked on even one of their patients.
2) They're full of shit, and comfortable in the fact that not enough people will notice.
The latter seems a great deal more likely.
From the article:
This attitude always bothers me. It's like doctors should be at the beck and call of their patients, and that anything a patient requests they should be given. When the patient doesn't get what they want, they blame doctors for being greedy or being more concerned about covering their butts. I hear this often in my mommy circles and the media has no problem playing it up either.
A writer could do the human interest story from the other side as well. Present the case of a doctor who has gone into medicine for the purpose of helping people, has taken an oath to do no harm, and then is faced with the unpleasant choice between giving the patient what they ask for - thus making them happy, or doing what they know to be right and providing appropriate treatment. Doctors not only have the responsibility to provide the best treatment possible, they also have to manage the emotional consequences of working in a field where they often have to give patients bad news. This angle is rarely ever touched on in MSM.
Instead, you see things like this from the article:
You know, because all those other doctors who turned her down were simply insensitive assholes.
You know, about halfway through Orac's article, I seriously went back just to check to make sure that the woman's name wasn't Peggy.
Because that is all I could think. "Oooo, those doctors at those other places were mean to me. But at Cancer Treatment Centers of America..."
Don't forget, they are not the first to do it. There are thousands of studies in German and Russian to support their work, they're just saving us from the horrors of google translate by not listing them.
Lost in all of this is something Orac points out -- namely, that there's serious doubt as to whether Calvin Cao actually is using stem cells in his treatments.
We're talking about something that is at best an unproven experimental therapy. Yet Cao's charged the Byers over $150,000 for it? He should have done it for free as part of a clinical trial.
After more Thinking about this, how do we explain/convince the family in a situation like this?
The Family clearly believes that the treatment did something and I doubt they could ever be convinced otherwise, but how do you try to explain it to them?
Would it not be better in a situation where a person seeks out questionable medical treatment that the established Medical community Ie. their own Dr. work with them through it, if not to verify a working treatment but to help debunk it?
Having an infant with a current idiopathic anemia, I've been into the hematology stuff for a little while now.
Hemopoietic stem cells will just make blood.
Now it's good that they would have specialized stem cells down a path - undifferentiated stem cells just form teratomas if they are injected and somehow survive the immune system (don't look up teratomas, or if you do, don't look at the pictures; I'm warning you) - but there's nothing along the line of hematopoiesis that I can at all imagine would help this woman. Does she need neutrophils? Macrophages? Platelets?
Anything that sort of therapy could do, transfusions could do just as well, if not better, given that transfusions are pretty predictable and these 'hemopoietic stem cells' are not, at least not outside of bone marrow transplant procedures.
Of course, they have come up with some amazing bullcrap about their 'hemopoietic stem cells'. Contrasted to the normal scientific understanding of them, they have decided to mix in some false equivocation. From their Biological Preparations page:
Yes, but you're injecting hemopoietic stem cells, not nerve cells.
Not true. Embryonic stem cells have this sort of totipotency. Specialized stem cells have a much more limited bank of tissues into which they can turn, but they are more useful for specific purposes and where there are pre-existing organs.
They do not, to my knowledge, 'de-differentiate' back up the potency tree.
They truly expect us to believe that a bone marrow precursor cell is going to turn into freaking neurons!?
Yes, but you're not injecting embryonic stem cells, are you? At least you had better goddamned well not be; otherwise you had best be hoping you don't encounter an immune-suppressed patient that will allow those to grow. See teratomas, above.
I'll bet they are! So this whole treatment is not even as good as placebo?
Goddamned jerks.
You gotta love this site. While Orac has a lot of insight, along comes comments by folks like Ritchie, people who really know what's going on with these specific treatments, and the problems that arise.
When the wife was taking path in vet school, she was always showing me pictures of teratomas. Apparently, she thought they were cool.
This really is an awful situation.
I just imagine myself being "locked in" and unable to point out the glaring scientific deficits as my woo-tastic family get suckered by Tijuana clinic woo.
Terrifying.
I don't suppose the problem comes up much, but how do "locked in" patients give informed consent for treatment? Do nothing for no, do nothing twice for yes? This looks like an ethical dilemma.
Hooray! I'm so glad Orac commented on this article! I read it yesterday and immediately my woo alarms started sounding. It's sad that a journalist is painting the Canadian medical establishment in such a negative light to the undiscerning general population, most of whom have no scientific background and whose only knowledge of scientific research comes from poorly-written articles such as this.
Please tell me I'm not the only one who goes straight to Google when I read something like this?
No. No, you are not.
I'm sure that says something about us, but I'm not sure I want to know what.
Scott @ 20: I believe to get a diagnosis of "locked in syndrome", you have to have some method of communication. Otherwise, they just call you "minimally conscious". It may be along the lines of "blink once for yes, blink twice for no".
@Cali
That's a relief. I'd hate to think they couldn't communicate at all. Even Jan in The Brain that Wouldn't Die had that much.
@Calli and Scott: yes, it usually is something as subtle as "blink 1x for yes, 2x fast for no" or "look left for yes (eyeball movement, not head turning, of course) and look right for no". But it IS usually a very subtle movement.
Scott -- not to freak you out too much, but there's really no way of knowing if there are people who cannot even blink or twitch their eyes and who are actually aware of what's going on around them. You don't get diagnosed with locked-in syndrome unless they can communicate with you in some way and prove you're aware of the world around you. If you are aware but can't communicate at all . . . then you go undiagnosed, and confined to your own private hell. Many with locked-in go undiagnosed for a time before someone notices whatever tiny movement they are capable of and manages to distinguish it from the random twitches a totally unconscious person might make.
It would be an amazing research result if it could be determined that hemopoietic stem cells could turn into nerve cells. Researchers would want to know all about the mechanism behind it; perhaps it could even be reformulated into an in-situ therapy and developed so that nearby tissues, even if just stem cells of a different variety, could be turned into neurons or whatever else we like.
One of the 'hot' research items these days is generating fate maps. That's where we try to figure out what progenitor cells turn into what other cells. We don't necessarily have all the products, proteins and genes that cause the cell development to happen in those directions, but that is an active component of the likes of evo-devo research.
We have the full fate map of C. elegans, but it is a particularly small and simple critter. It gets a lot harder - and quickly so - for bigger creatures.
Fate maps resemble phylogenetic trees in a way, though instead of semi-arbitrary levels of creature classification, we have - as far as we know so far - increasingly specialized cells. Salipante and Horwitz's Phylogenetic Fate Mapping paper from 2006 is a particularly cool look at trying to generate fate maps with phylogenetic techniques; they actually looked at common change areas (apparently, tracts of GGGGGGG in the genome change length with division a lot) and used those to attempt to figure out a fate map of mouse liver tissue.
I would be surprised if we didn't eventually find some spots where cells actually de-specialize before re-specializing somewhere later, but my guess would be that it is pretty rare.
So either these guys are amazingly far ahead of the research curve, or they have found something which would make for amazing research, or they're full of shit.
I concur rather highly with Calli's post at #12 :)
I hate to say this, but if I ended up in this situation, I'd try near any voodoo that might work. Particularly, since I am an American and the religious right in the United States has already decided that my preferred method of handling this situation (being taken out back and shot like Old Yeller style, but without the endless crying) is immoral and that they know best.
Off topic: the Texas Freedom Network, which is bravely fighting the effort to introduce creationism, anti-Thomas Jeffersonism, and all sorts of right-wing nuttery into Texas school text books, has just made a grievous error:They have just invited Arianna Huffington! Noooo.... (via PZ Myers)
One might ask, that for $150k they could spring for the post "op" meds?
But then they wouldn't be able to blame the insensitive medical establishment for their "failure".
Word salad science indeed, the first page of the website is crammed full of howlers.
re: Teratomas
The very first image I got (you know we all do it!) was a knitted teratoma. Awesome!
I suffered a brain stem stroke in 1999 left me locked-in. You may want to read my blog http://kesuresh.blogspot.com/.
People need to be careful with these alternative medicines. My late husband was locked in. Within a year, he gained an ability to smile and move his head a bit. He was able to blink within the first few weeks after the stroke. Weeks later it was discovered he could move his right middle finger. Those were tremendous movements â faint, but lifesavers, because he was able to communicate through these two movements. While regaining his full mobility were never part of his story, people always spent time praying he could walk again. The reality was that the eye blinks and the finger movement were huge!
@RodM, often, the main / primary doc has tried to reason w/ patients, but to no avail. Also, even human interest columnists are quoted as "authorities" in the promotional literature - for the marketers, a positive newspaper article is a positive newspaper article, no matter who wrote it. That's why *all* columnists have a responsibility to handle such cases carefully.
Stacy: Those would be huge! The difference between zero communication and any communication is incredible. I'm sure Hawking would agree on that count.
The thing that makes me really sad about the Alda Byers story is that those little tiny improvements they talk about... almost guaranteed that they were not a result of the dubious therapy in Tijuana, but because she had that therapy, any natural improvement is going to be interpreted as due to the therapy.
...and they're out $150,000 for their trouble. That's criminal.
If I were a physician to someone asking for this "therapy", I would refuse based on my reluctance to aid and abet an act of fraud. This, of course, is in addition to the harm caused by giving false hope and possible harm from the drugs themselves. This is not innocuous stuff.
K Suresh, I love your blog. I've added it to my bookmarks. Live long & prosper - and Nils Carborundum lligitimi!