Secretin Rises from the Grave!
September 30th, 2008
From time to time, I receive comments like:
"Why are you so opposed to studying ‘alternative’ therapies that have a low probability of working? If the study shows the therapy doesn’t work, people will stop using it."
Oh, if that were only true!
Let’s take – for example – the use of secretin as a therapy for autism. This has been repeatedly shown to be ineffective (no better than placebo), yet it keeps rising from the grave like some unquiet corpse.
Although it’s a bit early for Halloween, Stephen M. Edelson (PhD) of the Autism Research Institute has once again raised the "secretin-cure-autism" hypothesis from the dead. It is now roaming the "alternative" autism therapy community, munching on the brains of the "reality challenged". You can read it yourself in the ARI newsletter, Autism Research Review International (volume 22, number 2, pages 3 and 6).
In his editorial, Dr. Edelson starts with an abbreviated (and redacted) timeline of the secretin "controversy" (he says "controversy", I say "debacle"). He then goes on to explain why his unscientific parent survey of treatment effectiveness is a significantly better measure of the effectiveness of secretin than the over twenty studies that have been done to date. Among his "reasons" are:
[1] The largest studies (including the Repligen Corporation’s Phase 3 study) used human secretin instead of porcine secretin. Porcine secretin, you see, was what was used in the earlier, smaller, less well-designed studies that showed some effect. More about this later.
[2] The studies didn’t focus on the children with gastrointestinal problems – specifically chronic diarrhea and chronic constipation – which (again, in the few studies that showed an effect) were the children who showed the most effect.
Secretin Timeline
For those who are new to the scene, let me give you a capsule summary of the rise, fall, and (at least for a while) death of the "secretin-cures-autism" hypothesis. You’ll notice that many of the details I cover are not included in Dr. Edelson’s timeline. Case reports and studies showing that secretin is an effective treatment for autism are in red , studies that show that secretin is no better than placebo are in blue .
A few definitions that might come in handy:
Double-blind : Neither the subjects (or their parents) nor the researchers knew which treatment the subjects were receiving until after the final evaluations were recorded. This keeps the patients/parents and researchers from unconsciously "shading" their interpretation of the results based on their knowledge of which subjects are getting the drug.
Randomized : The subjects were assigned to the treatment (secretin) or placebo group at random. This helps to prevent a certain "type" of patient from being assigned to the drug or placebo groups. Without randomization, "sicker" children might be assigned to the drug group (or, conversely, they might be shunted over to the placebo group to keep from "screwing up" the results).
Crossover study : In a crossover study, the subjects are assigned to one of two (or more) groups. One group receives the study drug (secretin, in this case) and the other group receives the placebo. After a suitable "washout" period to allow the effects of the drug (if any) to dissipate, the group that initially received the drug gets a placebo and the group that initially received the placebo gets the drug. This allows the subjects to act as their own "controls" (sort of – there are some problems with this assumption).
1996
1996 – Parker Beck undergoes an upper GI endoscopy at the University of Maryland hospital. During this procedure he receives – as is typical – an injection of secretin to stimulate pancreatic secretion so that the gastroenterologist can confirm that the pancreatic duct is open (patent) without having to inject X-ray contrast, which carries the risk of causing pancreatitis.
A few days later, Parker – who was autistic – began to talk for the first time. [Note: at least one source – written by Bernie Rimland – states that Victoria Beck (Parker’s mother) had to INSIST on the secretin injection. This seems unlikely, since secretin is a routine part of upper GI endoscopy AND because she would have had no reason to insist on secretin, as it had never before been associated with improvement in autism.]
According to Ms. Beck – documented in numerous interviews – Parker remained verbal with improved social interaction even though he received only a single dose of secretin until a approximately year later.
1997
1997 (approx) – Parker Beck begins receiving repeated secretin injections.
December 1997 – Repligen Corporation stock trading at $0.78 on volumes of 65,600 shares.
1998
A case report of three (3) autistic children who received secretin as part of endoscopy and showed improvement.
May 19th, 1998 – Victoria Beck and Dr. Karoly Horvath file a patent (#6,020,310) on the use of secretin for the treatment of autism and for the use of secretin levels in the diagnosis of autism. This patent was later sold to the Repligen Corporation.
September 1998 – Repligen Corporation stock selling at $1.31 a share with volumes of about 41,000 shares.
October 1998 – Victoria Beck – Parker Beck’s mother – appears on both "Dateline" and "Good Morning America" to reveal to the world how secretin cured her child.
October 16, 1998 – Ferring Pharmaceuticals - the only manufacturer of secretin at the time – sells its last vial of secretin. The company had decided earlier to stop manufacturing secretin due to the low demand, a decision which should go down in economic texts as an example of epic bad timing.
November 1998 – Repligen stock trading at $1.69 on volumes of 37,000 shares.
1999
January 13, 1999 – Victoria Beck and Bernie Rimland file a patent (#6,197,746) on methods of administering secretin for treating autism that includes (besides injection):
"Other methods and compositions for administering the effective amount of secretin include other transdermal carrier substances, such as gels, lotions, or patches; oral carriers, such as tablets, capsules, or lozenges; inhalation through the nose or mouth (e.g., as an aerosol); suppository forms of secretin and secretin compositions; and using acoustic waves to cause the secretin to penetrate the skin."
This patent was later sold to the Repligen Corporation
March 1999 – Bernie Rimland publishes an "update" on secretin in the ARI newsletter . In it, he mentions how Victoria Beck patented the use of secretin for the treatment of autism and how she fought off attempts by the "university medical school doctors" to try to patent it.
He fails to mention that he is also a holder of a patent on the use of secretin for autism (see above). Dr. Rimland mentions in passing that the Becks sold their patent to Repligen Corporation and donated the proceeds and royalties to ARI, which at that time was owned and operated by Bernie Rimland.
March 1999 – Repligen stock trading at $3.06 on volumes of over 200,000 shares.
1999 – Victoria Beck’s book, "Confronting Autism: The Aurora on the Dark Side of Venus: A Practical Guide to Hope, Knowledge, and Empowerment" is published.
A study of 56 children with autism. Randomized, double-blind placebo controlled, single dose. No effect seen from secretin.
2000
February 2000 – Repligen stock trading at $13.13 per share on volumes of 1.3 million shares.
A study of 56 autistic children. Open label (both researchers and parents knew what the child was getting), single injection. A second double-blind placebo-controlled study was done with 17 children who had responded the most in the first study and 8 new subjects who got an additional injection of secretin or placebo with crossover at four weeks.
"Results of both inquiries indicate that although treatment with secretin was reported to cause transient changes in speech and behavior in some children, overall it produced few clinically meaningful changes when compared to children given placebo injections."
A study of 95 autistic children. Placebo-controlled, randomized, double blind – single injection of either secretin or placebo. "No significant differences in language or autistic behaviour measures were observed at the 3-week follow-up between the groups."
2001
March 5, 2001 – Victoria Beck and Bernie Rimland file a patent (#6,790,825) for "Method of using secretin and compositions made therefrom for the treatment of autism and other neurological, behavioral and immunological disorders". This patent was later sold to the Repligen Corporation.
April 2001 – The Repligen Corporation, which makes recombinant human secretin, completes a Phase 2 study of secretin in autistic children.
May 2001 – Coniglio et al. A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin as treatment for children with autism. J Pediatr . 2001 May;138(5):649-55.
A study of 60 children with autism. Placebo-controlled, randomized, double-blind – single dose of either secretin or placebo.
"A single dose of intravenous secretin does not appear to have significant effects on either parents’ perception of autistic behaviors or language skills at 6 weeks after injection. Transient, marginally significant improvements in autistic behaviors may occur in some children."
A study of 64 autistic children. Randomized, placebo-controlled, double-blind – each child received either two doses of porcine secretin or two doses of placebo. "No evidence is provided for the efficacy of repeated doses of porcine secretin in the treatment of children with autism."
“Secretin hormone given daily in transdermal cream was associated with marked and sustained developmental progress in an aphasic two-and-a-half year old child diagnosed with autism.”
A study of 12 autistic children. Randomized, placebo-controlled, double-blind – single dose crossover study. Outcome measures included gastrointestinal problems.
"Statistically significant differences were observed on measures of positive affect and activity level following secretin infusion. In general, the autistic children did not demonstrate the improvements described in the initial retrospective report."
October 2001 – Dr. Walter Herlihy of Repligen Corporation (the company trying to get FDA approval to label its recombinant human secretin for the treatment of autism) gave a presentation at the "Defeat Autism Now!" conference in San Diego, CA.
In this presentation, he reported that the Phase 2 trials [Note: Phase 2 trials are intended to show that the proposed treatment is safe in the intended patient population] did not show a statistically significant difference (in safety or efficacy) between secretin and placebo. He argued that the criteria for statistical significance were "arbitrary" and that secretin had shown more effect on younger children with gastrointestinal problems like chronic diarrhea and constipation.
A study of 56 autistic children. Randomized, double-blind, placebo-controlled – crossover study of one injection of either placebo or secretin followed in four weeks by the opposite treatment.
"There was no evidence for efficacy of secretin in this randomized, placebo-controlled, double-blind trial."
2002
April 2002 – Repligen Corporation starts a Phase 3 trial of secretin in autistic children. Based on preliminary (and statistically non-significant) results from their Phase 2 trial, they focus the trial on children ages 32 – 59 months (2 ½ - 5 years) and looked specifically at gastrointestinal problems – primarily chronic diarrhea and chronic constipation.
April 5, 2002 - Repligen obtained FDA approval to market its brand of synthetic porcine secretin (SecreFlo TM) for use in pancreatic assessment.
A study of 6 autistic children. Randomized, placebo-controlled, double-blind crossover study. Each child received six injections – three placebo and three secretin – in random order every four weeks. "In this placebo-controlled study, multiple doses of secretin did not produce any symptomatic improvement."
A study of 19 autistic children, 5 with "chronic diarrhea". Randomized, placebo-controlled, double-blind crossover study – single injection of either secretin or placebo followed by the opposite treatment at three weeks.
Analysis of the entire group showed no statistically significant effect. Limiting analysis to the five (5) children with chronic diarrhea (but not the two with chronic constipation) gave statistically significant results.
A study of 85 autistic children. Randomized, placebo-controlled, double-blind – single dose. The children were divided into trios matched by age and communication level – one child from each trio received porcine secretin; one received synthetic (human) secretin and one received placebo.
"No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately ."
December 20, 2002 – Victoria Beck and Dr. Karoly Horvath file a patent (#7,091,182) for "Method for assisting in differential diagnosis and treatment of autistic syndromes" which is described as "comprising the administration of a therapeutically effective, preferably intravenous, dose of secretin to an individual with autistic syndrome" and "an analysis of an individual’s blood and/or intestinal tissue for the presence of secretin and comparison of the level of secretin to known norms". This patent was later sold to the Repligen Corporation.
A study of 42 autistic children. Randomized, placeb-controlled, double-blind – crossover study. Each child received either placebo or secretin and then the opposite treatment at six weeks. "There were no significant differences in the mean scores on any measure of language, behavior, or autism symptom severity after treatment with secretin compared to treatment with placebo."
2003
A study of 62 autistic children. Randomized, placebo-controlled, double-blind – crossover study. "Five children showed clinical improvement in standard scores: two after HSS [human synthetic secretin] and three after placebo. There were no significant changes in gastrointestinal symptoms after HSS or saline placebo."
From Part II:
"At the conclusion of the study, parents were asked to guess their child’s group assignment. Twenty seven families guessed their child’s group assignment correctly and 27 guessed incorrectly."
September 2003 – Repligen stock trading at $7.47 a share on volumes of about 400,000 shares. Its cash value is estimated at about $1 per share.
December 2003 – Repligen stock trading at $4.37 a share on volumes of 740,000 shares.
2004
January 5, 2004 – Repligen announces that there were no significant differences between the treatment and placebo groups in its Phase 3 study of secretin for autism. This study – although Dr. Edelson seems unaware of the fact – focused on younger children and also looking at chronic gastrointestinal problems.
January 2004 – Repligen stock trading at $3.33 on volumes of over 2 million shares.
Early 2004 (exact date difficult to determine) – Dr. Rimland sends a letter to Walter Herlihy of the Repligen Corporation essentially denouncing their decision to declare that secretin was no more effective than placebo.
July 2004 – Repligen stock bottoms out at $1.62 a share on volumes of 200,000 shares.
2005
A study of 15 autistic children. Randomized, placeb-controlled, double-blind – crossover study. Transdermal secretin or placebo was applied daily to the backs of children for four weeks. After a six-week "washout" period, the groups switched treatments.
"Overall, there were no statistically significant differences in speech, sociability, sensory, and health scores for treatment versus placebo periods. In addition, there were no differences in such scores for children with a history of diarrhea."
November 2005 – Repligen Corporation starts a Phase 2 trial of secretin for the treatment of schizophrenia.
Present
September 25, 2008 – Repligen stock trading at $4.89 on volumes of 45,000 shares. The company has a little over 31 million shares outstanding.
Human vs Porcine Secretin:
Between 1998 and today, over 20 studies have been done (and published) to determine the effect of secretin on autism. At least nine (9) used porcine secretin and at least four (4) used human secretin. For the others, the methods section didn’t specify or was unclear (initially, only porcine secretin was available, so there was no need to specify). The results of the Repligen Phase 3 study have never been published.
Only three secretin studies (with a total of 23 subjects – really only 9 if you consider that Kern et al found a positive effect only among the 5 children with chronic diarrhea) found any effect on autism. At least twelve other studies – with a total of 609 children enrolled – showed that secretin had no effect in the treatment of autism. Despite this, Dr. Edelson is convinced that secretin "works" for autism. He attributes the discrepancy to the "fact" that the largest studies (by Repligen) used synthetic (recombinant) human secretin instead of the porcine secretin used in the earlier studies.
Well, he’s wrong on a couple of counts.
To begin with, many of the larger studies used porcine secretin – one even compared it to both synthetic (recombinant) human secretin and placebo (all three were equally effective).
Secondly, the difference between human and porcine secretin is only two amino acids out of twenty-seven. Only dogs have a secretin molecule that’s closer to ours than the porcine secretin. In addition, the two substitutions – aspartate for glutamate and serine for glycine – would have minimal effect on the function or structure of the protein. Aspartate and glutamate both have carboxylic acid side chains and serine’s higher affinity for water – compared to glycine – would be masked by the fact that it’s situated right next to aspartate, which is very hydrophilic.
In fact, if Dr. Edelson had bothered to check, he would have found that porcine and human secretin were found to be functionally interchangeable. Of course, he could have guessed that from the fact that porcine secretin was used in humans for years to produce the same effect as human secretin. Think about the "good old days" when diabetic people used porcine or bovine insulin. The few amino acid differences didn’t change the function of the insulin, although they did lead to a few people developing antibodies to bovine insulin.
On more thing to ponder before you go off to read Dr. Edelson’s editorial. There are only two manufacturers making secretin these days (in the US, anyway):
Manufacturers of human secretin:
ChiRhoClin – ChiRhoStim (human secretin - $415 per 16 mcg/160 U vial)
Manufacturers of porcine secretin:
Repligen – SecreFlo (porcine secretin - $425 per 16 mcg/160 U vial)
Both products are recombinant – meaning that they are made by bacteria or yeast that contain the gene for human or porcine secretin. Since there is no conceivable reason why Repligen shouldn’t use its "house brand" of human secretin (RG1068) for pancreatic imaging, I wonder if they are positioning themselves for a "replay" of the "secretin-cures-autism madness of a few years ago. Unlike Ferring in 1998, Repligen would be in good position to profit from a resurgent interest in PORCINE secretin.
The Gastrointestinal Issue:
Dr. Edelson is also convinced that his survey of parental impressions is correct about the effectiveness of secretin because the Kern et al (July 2002) study showed that (porcine) secretin was significantly more effective in children with autism AND chronic diarrhea.
Let’s examine this claim, shall we?
The Kern et al study looked at 19 autistic children and was a double-blind, randomized crossover study of a single dose of porcine secretin. Of the 19 children in the study, five (5) had chronic diarrhea. These five (5) children apparently showed more improvement that the others (in whom secretin was no better than placebo).
That’s right – Dr. Edelson is basing his defense of secretin on the results seen in five (5) autistic children with chronic diarrhea (five out of nineteen in the Kern et al study).
Just a few months after the Kern et al study came out, Unis et al published their study of porcine (that’s right – porcine ) and recombinant human secretin in autism. They had eighty-five (85) autistic children in their study (one third received porcine secretin) and concluded:
"No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed."
"This held true when children with and without gastrointestinal problems were examined separately."
So, a larger study (to be fair, only about 28 received porcine secretin) found no difference, even when looking at children with gastrointestinal problems.
And what about Dr. Edelson’s parent survey?
The parent survey that Dr. Edelson keeps referring to is posted on the ARI website. Parents fill it out and mail, fax or e-mail the form back to ARI. There is no attempt to get a representative sample of parents of autistic children and the "data" are inclusive to the beginning of the survey, several years ago. Here’s what visitor’s to the ARI website see when they look at the survey’s assessment of secretin (dated February 2008):
Intravenous secretin (468) Got worse: 7%; Got better: 44%; No change 49%
Transdermal secretin (196) Got worse 10%; Got better: 37%; No change 54%
To "help" the parents in their assessment of the various treatment options listed, the survey gives a ratio of the number of children who "got better" to the number who "got worse" - this completely ignores the children who had "no change", which is often a large number. Now, Dr. Edelson’s better:worse ratio makes secretin look like a magic bullet, with a better:worse ratio of 6.3 for intravenous secretin and 3.6 for transdermal secretin.
However, if we look at "better" vs "not better" (i.e. either no change or got worse), the numbers don’t look so rosy: 0.8 for intravenous and 0.6 for transdermal secretin.
As luck would have it, I happen to have saved ARI’s survey results from last year:
IV secretin (422) Got worse: 7%; Got better 45%; No change 48%
TD secretin (176) Got worse 10%; Got better 37%; No change 53%
If we use these numbers to "dissect" that past year’s activity, the survey reports from Feb 2007 and Feb 2008 show that, in the course of a year, ARI received reports that after treatment with IV secretin:
3 children got worse
3 children got better
39 children showed no change
This is about what you’d expect from a treatment that doesn’t work.
What I find particularly disappointing is that Dr. Edelson has a PhD in psychology and should know that his survey results are meaningless. He should also know how to read the scientific literature and interpret the data. There are all of these things that he should know , and yet he acts as though he was unaware of them.
I’ll let you draw your own conclusions about why Dr. Edelson is trying to breathe life back into this dead hypothesis. As for the validity of his arguments, I think Dean Yeager in Ghostbusters (I) said it best:
"Your theories are the worst kind of popular tripe, your methods are sloppy and your conclusions are highly questionable."
Prometheus
ADDENDUM:
I forgot to mention that Dr. Edelson, at the conclusion of his editorial on secretin, puts out a call for researchers willing to do a study of porcine secretin in autistic children with chronic GI problems. He offers ARI funding, but I doubt that he realizes how expensive such a study would be.
I’d be willing to act as Principle Investigator for such a research project, even though I doubt that negative results would get people to stop injecting (or rubbing) autistic kids with secretin. This passed from a scientific issue to a religious one years ago. Still, there’s nothing I love more than a futile effort in a lost cause.
I happened to mention this idea to the head of the university IRB (the body that approves and monitors human research) and asked her to give me an unofficial opinion on the study. I gave her the available published research and a brief outline of a study design. Her response, which appeared in my e-mail this morning, was that the IRB would not likely approve such a study for the following reasons:
[1] The published research indicates that there is no reason to suspect that secretin would be helpful in the treatment of autism (minimal to zero chance of benefit).
[2] There is a small, but non-zero, risk of harm.
[3] The study population is an "at risk" group (minor and disabled); they cannot give informed consent AND their parents are likely to be willing to accept risks that parents of "typical" children would not.
[4] The proposed research is unlikely to significantly increase the scientific knowledge on the subject. As a result, the risk to the subjects, although it is very small, would exceed the benefit of the knowledge gained.
Filed under: Autism Policy, Autism Practitioners, Myths About Science, Uncategorized | 17 Comments »
How they do the voodoo that they do so well - Part 2
September 19th, 2008
End Games:
Eventually, even the most successful, charismatic “alternative” practitioner will have a patient who doesn’t improve enough to satisfy the parents. Not only are these parents a real drag on the “alternative” practitioner’s ego, there is the very real chance that they might start to talk about how “the Emperor has no clothes”. For those situations, there are a number of strategies that are typically used.
Did you follow my instructions to the letter?:
One of the oldest dodges in the “alternative” medicine “biz” is to prescribe a regimen of treatment that is too complicated for most patients to follow. If they get better (by chance), then it was due to the “treatment” – if they don’t get better….well, they didn’t follow all of the instructions exactly, did they?
Much the same is happening in “alternative” autism therapy. One of the first chelation regimens promoted for treating autism required that the parents give their children a dose every four hours around the clock for two weeks. This meant waking the child up in the middle of the night – every night – for two weeks and getting them to drink a foul-smelling liquid.
The parents were cautioned that missing a single dose – or being late by more than two hours – meant risking having more mercury deposited in the brain. This – needless to say – was absolute nonsense. But no parent who failed to see the promised results could honestly say that they had given every dose on time.
Likewise, a parent who returns to the “alternative” practitioner and complains that the promised “recovery” has not happened will have to answer the same question: “Did you follow all of my instructions?”
Too little, too late…:
Another common retort of the “alternative” practitioner when faced with failure is to complain that the patient was brought to them too late. “If you had only come to me earlier.”, they will say. “The treatment is more effective on younger children.”
A variant of this excuse is to blame the parents for not being willing – or able – to do more therapies. “If you had been willing to try ABC and XYZ as well, he would be better by now.” This is the reason – consciously or unconsciously – that “alternative” practitioners will propose so many possible “therapies” at the start; the parents can’t possible do them all, which gives an easy “out” if (when?) the results aren’t as promised.
And if that doesn’t work…:
Since there are new “alternative” therapies coming out every week, the parents who aren’t happy with the progress of their autistic child can always be shunted onto another treatment “track”. “Chelation and mega-vitamin therapy not working? Try HBOT!”; “HBOT a bust? Try Valtrex for persistent measles virus!” [note: Valtrex/valacyclovir has absolutely no effect on the measles virus – it can’t, since it targets an enzyme the measles virus doesn’t have]
If shunting to different therapies doesn’t work, the “alternative” practitioner can always shunt the patient to an entirely different practitioner. This will almost always be another “alternative” practitioner, as a “real” doctor might say nasty things about the treatments the child has been subjected to – “alternative” practitioners rarely say nasty things about each other (see: “Glass houses, throwing stones and”).
There are none so blind…:
A particularly brazen tactic I have heard some parents discuss is for the “alternative” practitioner to contradict the parents and insist that the autistic child actually has improved. You’d think this would be a violation of the “parents know the most about their child” dogma, but it just shows how “flexible” that piece of dogma really is.
In this scenario, the practitioner confronts the parents who complain about the “lack of improvement” by saying something like, “Oh, but he/she has improved! You don’t see it because you are with him/her every day, but it’s readily apparent to everybody else!” Sadly, many parents probably buy this line, simply because is has the ring of truth. After all – as I’ve discussed above – autistic children do improve, even if you do nothing to/for them. If the parents think back, they’ll have noticed some improvement - especially if their “alternative” practitioner insists that they do.
Of course, it would be equally valid for the practitioner to pull out the medical record and show the parents the growth chart (they do keep a growth chart, don’t they?). They could show the parents the chart and say, “See, he was 95 cm tall when I saw him at three years and now he’s six and he’s already 110 cm tall! That’s real, measurable progress and all due to my treatments!”
[note: for those who don’t have a growth chart on their refrigerator door, those heights correspond to the 50th percentile at three years and below the 25th percentile at six years]
The scary thing is that at least some of the practitioners who have argued with parents over a lack of improvement truly believe that the child really has made significant improvements as a direct result of their “therapies”.
Heads I win; Tails you lose:
One of the best parts about being an “alternative” medical practitioner must be the ability to just make it up as you go along. For example, if a patient shows improvement after trying the “alternative” therapy, it was the therapy that made them better – score! If they get worse…..it’s the “toxins” coming out – score! It’s a win-win world – at least for the practitioner. There are a lot of variations on this theme, but they all share a common feature: no matter what is happening to the patient, it’s a sign that the therapy is working.
Like a lot of the pseudoscience in “alternative” medicine, this one has a grain (64.8 mg) of truth (fact) at its core.
Back in the early days of antibiotic therapy, doctors noted that people being treated for syphilis would often suffer from fever, chills, muscle aches, headaches and worsening skin lesions (in secondary syphilis) immediately after starting the antibiotics.
Two of these doctors – Dr. Jarisch and Dr. Herxheimer – discussed these reactions in papers they published,
[Jarisch A. Therepeutische Versuche bei Syphilis. Wien Med Wochenschr (1895) 45: 721–42. ; Herxheimer K, Krause D. Ueber eine bei Syphilitischen vorkommende Quecksilberreaktion. Deutsch Med Wochenschr (1902) 28: 895–7. ]
leading to the phenomenon being called the “Jarisch-Herxheimer reaction” (sometimes shortened to the “Herxheimer Reaction” or, worse yet, “herx”). Readers familiar with German will note that the article by Dr. Herxheimer is discussing a reaction seen after treating syphilis with mercury. This might account for number of “alternative” practitioners who claim to see a “Herxheimer reaction” while chelating for mercury, but I doubt that many of them have actually read the paper.
The Jarisch-Herxheimer reaction is also seen during treatment of Borrelia infections (Lyme disease and tick-borne relapsing fever), Coxiella infections (Q-fever), typhoid fever (Salmonella enterica serovar Typhi) and trichinellosis (a parasitic worm). It is caused by the rapid release of endotoxins from the bacteria (or parasitic worms) when they die from the antibiotic.
[Note: this reaction is due to inflammatory cytokines secreted in reaction to the sudden release of endotoxins, so "boosting" the immune system would only make the reaction worse.]
Anyway, it’s important to note that the Jarisch-Herxheimer reaction has not been noted during treatment of fungal infections (which would include “yeast”), despite the myriad references to “Herxheimer reaction” or “herxing” (shudder!) during “alternative” treatments of “yeast”.
Also, the symptoms of the Jarisch-Herxheimer reaction are similar to a bad “cold” or influenza-like illness (apart from the worsening of syphilitic skin lesions). It does not include the many fanciful symptoms that are often attributed to it by enthusiastic but poorly-educated “alternative” practitioners (and their fans).
Of course, a simple way around the limitations of the Jarisch-Herxheimer reaction is to simply avoid the term. Many “alternative” practitioners simply attribute any untoward symptoms (or lack of improvement) to “the toxins coming out”. Thus, if an autistic child shows a worsening in their behaviors after starting an “alternative” therapy, it’s “the toxins coming out”. If they develop a rash, lose their appetite, turn sickly yellow, suffer vomiting and diarrhea or collapse into a stupor….it’s “the toxins coming out”.
It’s a great system – if the patient gets better, it’s a sign that the “therapy” is working; if the patient doesn’t get better (or even gets worse), it’s a sign that the therapy is working.
Heads I win; tails you lose.
When in Doubt, Blame the Yeast:
[Note: "yeast" is placed in inverted commas because the term is usually used by "alternative" practitioners to mean Candida albicans – a specific fungus. However, the term "yeast" actually does not refer to a specific organism or even a genus. "Yeast" are simply single-celled fungi – it is a growth type, not a phylogenetic description.]
“Yeast” seems to be a popular scapegoat for “alternative” practitioners, although some hedge their bets by blaming “dysbiosis”, which has the same effect without tying them to a specific organism (or group of organisms). The obvious advantage to “yeast” is that they are ubiquitous – every body surface has some amount of fungal colonization or contamination, including the surface we refer to as our gastrointestinal tract. If you culture a stool sample, you can pretty much bet on growing “yeast” unless you do something to prevent it. “Real” doctors diagnose yeast overgrowth in the gastrointestinal tract (which does happen, but rarely) by microscopically examining the stool, looking for large numbers of fungal cells - not by trying to get “yeast” to grow out of a stool sample.
My favorite “yeast” quote comes from an audiotape of a DAN! “conference” made in – I believe – 2000. On it, a DAN! founding father (I’ll let him remain anonymous) makes the following statements:
“I test every autistic child for yeast. If I don’t find any yeast, I treat them for it, anyway.”
As silly as that may sound, he is just putting into words what many “alternative” practitioners express through their actions: yeast is always present (even if we can’t find it) and it is always a problem.
Reading through the material put out by various “alternative” practitioners, as well as the parents’ reports of their conversations with “alternative” practitioners, it becomes clear that “yeast” is also widely used to “explain” why therapies don’t work. Thus we hear:
“The [therapy] can’t work until we clear up the yeast (or “dysbiosis”).”
“He/she gets worse after [whatever] because it stirs up the yeast.”
“The [symptom] happens because the [therapy] makes the yeast worse.”
“The [therapy] was working until [event] caused his/her yeast to flare up.”
The list is endless, but the examples above should give you the idea. The bottom line is that - at least in “alternative” medicine - anything can be blamed on “the yeast” (or “dysbiosis”). This is because there are no agreed-upon signs and symptoms of “dysbiosis” or “yeast overgrowth”, as these terms are generally used by “alternative” practitioners. Any sign, any symptom can - in the eyes of the “alternative” practitioner - be a sign of “yeast”. And since there is thus no limit to what you can blame on “the yeast”, it has become a universal scapegoat.
Discussion:
I’ve probably omitted a number of gambits used by “alternative” practitioners, so feel free to bring up your “favorites” and we can discuss them in the comment section.
I also want to take this chance to reiterate my hopelessly naive belief that the majority of “alternative” practitioners are truly convinced that they are doing a valuable service to autistic children and their parents. I feel that most of them are honest (but mistaken) and sincere (but gullible) in their belief that their “therapies” are helping “recover” autistic children.
Which leads us to a topic that I have been pondering for some time:
The Semantics of “Recovery”:
I’ve noticed that the “alternative” autism therapy “community” has begun to settle on the term “recovered” to describe autistic children whose signs and symptoms of autism have either moderated or resolved. For the most part, this may be no more than people following a “fad” in the language they use to describe their children. It may also be a reaction to skeptics mocking their claims of a “cure”.
However, whatever the reason, the word “recovered” carries some implied meanings that are worth considering.
I’m ”well” again:
In the most obvious meaning of this usage of “recovered”, it implies that someone was previously “well”, became “sick” and is now “well” (or “better”) again. This is the meaning we use when we say that someone has “recovered” from “the flu” or has “recovered” from surgery. The deeper implication - as it pertains to describing autistic children - is that these children were previously “not autistic”, became autistic for some reason and now are “not autistic” (or “better”) again.
This ignores (perhaps deliberately) the very real possibility that these children were autistic from birth, and therefore can’t be said (even if they are “not autistic” now) to have “recovered”. You cannot “recover” to a condition you never before experienced. If someone is born missing a heart valve and they receive an artificial valve, you cannot say that their heart has “recovered” - it has been “fixed” or some other similar term, but it can’t have “recovered” because it never had that valve to start with.
At some level - possibly unconsciously - the people describing their autistic children as “recovered” are denying the possibility that their children were born with autism. For those people, the autism is something that was imposed upon their previously “well” (or “normal”) child.
I’m back:
Another meaning of “recover” that may be applicable here is in the sense of getting back something that was lost. People “recover” lost property, lost dignity and lost children. This meaning also plays into the mind-set of autism as something that was “done to” a previously normal and healthy child. Many parents of autistic children - particularly those involved in the “biomedical” treatment of autism - have long talked about “getting back” their children.
In both of these meanings, using the word “recovered” makes it linguistically impossible to include the idea that an autistic child may have been “that way” from (or before) birth. “Recovered” implies that the child was “healthy” and was then made autistic.
The implication that autism was imposed on a previously “normal” child leaves open the possibility that someone is to blame. And if someone is to blame, then there is “someone” to be angry at and someone to potentially pick up the tab for the treatments and special schools and special diet…. you get the picture. On the other hand, if autism is an integral part of the child at birth, then there is no focus for the anger and nobody to pay the bills.
Inside the “Shell”:
For years, I have heard parents talk about trying to “break through the shell” and find the child they know is “trapped” inside “the Hell of autism” (or other such phrases). At some point, I realized that “trapped” child they were talking about was the fantasy child that all parents-to-be create before the real child is born.
Eventually, all parents have to give up that fantasy child and live with the child they actually have. Few children live up to all of the aspects of their parents’ fantasy child; those who do may be the worse off for having done so. For some parents - especially those with disabled children - it is very difficult to reconcile the differences between the child they thought they would have (some say “deserved” to have) and their actual child. Some parents, sad to say, never let go of the fantasy child - and some of them will ignore, neglect or even abuse their actual child because it does not meet their expectations.
I am concerned that some of the parents who doggedly pursue “alternative” treatments for their autistic children are - consciously or unconsciously - willingly and knowingly risking harm to their actual child in the hopes of finally getting their fantasy child. They - again, consciously or unconsciously - do not value the child they have because they see it as “just a shell” that is keeping them from having the child they expected to have. What would those people do differently if they knew - or even suspected - that the child they see before them is not a “shell” and that there is no “normal” child “trapped” inside?
What would they do differently if they thought that there was no “lost child” to “recover”?
That’s what makes words so powerful.
Prometheus
Filed under: Autism Practitioners, Autism Science, Autism Treatments, Critical Thinking | 20 Comments »
How they do the voodoo that they do so well - Part 1
September 10th, 2008
You’ve probably heard the story. A child is diagnosed with autism and the desperate (yes, I said “desperate”) parents search for answers. The “mainstream” doctors tell them that there is little that they can do (note: ”mainstream” doctors almost never say, “There’s nothing that can be done.”). Not satisfied with that answer (and what parent would be satisfied?), the parents try “alternative” practitioners.
And sure enough, the “alternative” practitioner has just the answers the parents are looking for. He or she can help them “recover” their child.
Or can they?
Over the years, I’ve shown how many of the “therapies” that claim to “cure” or “recover” autistic children haven’t been shown to work. But how do the practitioners keep the parents “on the hook”, even when the treatments aren’t working? That’s the topic of today’s lecture.
Before I get started, I need to make one thing perfectly clear. Despite being a hard-bitten cynic, I am convinced that most of the “alternative” practitioners truly believe that what they are doing is helping their patients. There are, of course, a minority that are consciously trying to deceive their patients (or their parents), but I believe that the majority are convinced that their treatments actually work.
Once again, being honest is no protection against being wrong.
So, with that disclaimer, what are some of the techniques that the “alternative” practitioners use to keep parents satisfied even when the treatments don’t work?
[Note: the same techniques are used by most "alternative" practitioners, but I will approach them from the perspective of the parents of an autistic child.]
Opening gambits:
I am the one:
Excessive humility is not a failing among most “alternative” practitioners. Most are more than willing to tell you how their diagnostic and treatment techniques are far superior to those of anyone else. They are also usually willing discuss the failings of their colleagues – at least, those that are “mainstream” physicians – at great length. And the parents, having heard the cautious and tentative words of “mainstream” doctors – “This might help.”, “It’s hard to predict what your child’s progress will be.”, “Some children do better with this.” – are usually captivated by a practitioner who says, “I can cure your child.”
So, if parents want to hear “I can help your child!”, why do the “mainstream” doctors “hedge” so much? Well, mostly it’s because they’re telling the truth. And not just the “truth” of what they “believe” is true – it’s the truth of what the data support.
Data on the eventual outcome of autistic children is not terribly abundant, but several studies have shown that the initial degree of disability - seen at the time of diagnosis or early on in the child’s development - is not a good predictor of eventual functional level. Studies have also shown that there are no treatments - even “mainstream” treatments – that work on all or even most autistic children. “Mainstream” doctors – the good ones, anyway - don’t talk of “cure” or “recovery”, they talk of managing specific problems, of helping the child become as functional and independent as possible. They do this because it is unethical to lie to patients (or their parents), even if it makes them “feel better”.
Feel the anger, Luke!:
It’s a sad fact of human nature that most people – all people, in some circumstances – will more readily believe a pleasant lie than an unpleasant truth. If you believe in the Kubler-Ross stages of grief, denial and anger are the first two stages in dealing with a loss – and finding that they have an autistic child is a loss to most parents. A practitioner who feeds into that denial and anger is more likely to be believed than one who tries to get the parents past that and into acceptance. It’s just the way we humans are.
Interestingly, many of the more militant so-called “autism advocacy” groups also feed on the denial and anger of parents. And – strangely enough - those that do are also the most active in promoting “alternative” autism therapies. It is a synergistic relationship. Keeping the parents “stuck” in their denial and anger profits the “alternative” practitioners and swells the ranks of the militant “advocacy” groups.
Anger is a very “empowering” emotion that can help people keep from feeling other “negative” emotions – like loss, grief, sadness and guilt. I mention guilt because much of the “alternative” autism field – and “alternative” medicine in general – is about shifting blame and avoiding guilt. Parents of autistic children (and children with other disabilities) almost always end up – at some point – wondering if they are to blame for their child’s disability. “Should I have eaten only pesticide-free organic food when I was pregnant?” “Should I have removed my amalgam fillings?” “Was it my genetics (or my spouse’s genetics)?” “What about that antibiotic I took – did it cause the autism?”
By shifting the “blame” for autism to a clearly external source – such as vaccines or pesticides or plasticizers – the practitioner (and advocacy group) can relieve the parents of the guilt they may be feeling. This may seem like a good thing, since the parents really aren’t to blame (as far as the data can tell), but it doesn’t deal with the guilt or resolve it, it just shifts the guilt one square away. Someone is guilty, it’s just not the parents….except that it still is.
The problem with shifting the blame is that it merely changes the target, not the “game”. Now, instead of blaming themselves (or the other parent), they can blame “the government” (a perrenial favorite for blame-shifting), doctors, pharmaceutical companies, “toxins” in the environment, “non-green” vacines - the list is endless. Unfortunately, since blame and guilt are “still in the game”, they can always be shifted back. That’s the chief flaw in the “blame game”: if your new target for blame doesn’t work out - the data shows that the MMR vaccine isn’t to blame, for instance - then you need a new target.
Or you can simply ignore that part of reality that conflicts with your ability to blame the old target - you can convince yourself that the studies were flawed or even fraudulent. As King Lear says, “Oh, that way madness lies; let me shun that.“ Good advice. The more of reality that you have to ignore, the harder it gets to have open discussions with people who are not “in” on your way of seeing (or, more appropriately, not seeing) the world.
The advantage of the “blame game”, from the perspective of “alternative” practitioners and militant advocacy groups is that it “locks in” the parents. Since the parents have to ignore more and more “inconvenient truths” about their world, it is easier for them to associate mostly with people who have the same “world non-view”. It can also be used as a tool to keep the parents in line. If the parents don’t do what they’re told – give this supplement, do this treatment, buy this device, support this rally, etc. – they are guilty of not doing “all they can do to recover their child”. In other words, if the parents don’t play the game, they get their guilt back - with interest.
On the other hand, if the parents had been allowed to deal with and resolve their feelings of guilt – perhaps with a supportive practitioner who told them that there was nobody to blame – they wouldn’t be as vulnerable to “guilt-tripping”.
Middlegames:
Time is on my side (with apologies to The Rolling Stones):
To understand how time works to the advantage of “alternative” practitioners, you have to understand something about the nature of autism. As I have said innumerable times, autism is a syndrome of developmental delay – not developmental stasis. Kids with autism continue to make progress, although it is slower than their typical peers. And like their typical peers, their development comes in spurts.
Thus, if you wait long enough, any autistic child will get “better”.
There are people who insist that their autistic child “didn’t make any progress” until “alternative” therapy XYZ. They are either not remembering correctly or their child doesn’t have autism. I’ll say it once more – autism is a syndrome of developmental delay, not developmental stasis.
I have noticed that more and more the “alternative” practitioners and many of the more militant “autism advocacy” groups are claiming that autistic children will not develop beyond some very early level without some sort of “intervention”. Even though this is not true – and has been known to be untrue since “autism” was first described – it does make it easier for the “alternative” practitioners to claim that their “interventions” were the cause of any progress made by the children under their care.
Thus, the criteria for judging an “alternative” autism therapy to be effective has been moved from “more improvement than placebo” (the standard for real medicine) to “any improvement at all – even if it’s unrelated to the therapy”. That makes it so much easier for the “alternative” practitioners (and their cheerleaders) to claim “success”. Whether or not their therapies “work” is irrelevant, as long as they “feel” that they do.
However, reality being what it is, some of the more observant parents (and even practitioners) have noticed that it sometimes takes longer for one child to show “improvement” than others. This is usually dealt with in one of two ways: either by adding more “therapies” (see: “A Shotgun Wedding” below) or by of saying “It takes some children longer than others.” – with or without a pseudoscientific explanation (e.g. “Your child has a serious gut dysbiosis.”) or parental guilt-tripping (e.g. “If we only you had come to me when he was younger…”). As they accumulate more experience with a particular “alternative therapy”, a gullible but observant “alternative” practitioner will often conclude that the amount of time it takes for the “therapy” to “work” is extremely variable. They will usually encourage parents to “wait it out” and to “give it a chance”. [note: A less gullible practitioner would also at least entertain the idea that the therapy might not "work" at all. Sadly, few "alternative" autism practitioners do.]
Folks who have been watching the “alternative” autism therapy scene for a while will have noticed this trend. When chelation first came out as an “alternative” treatment for autism, the practitioners using it were claiming that autistic children were “getting better” in a matter of weeks. Then it was months. Then a year. Then two. Now, it’s three years.
Think about it – if an autistic child doesn’t show some improvement in three years, they need a thorough work-up, not just more chelation.
And it’s not just the practitioners telling parents that “you need to give it more time”. If you visit any of the myriad “alternative” autism therapy groups on the Internet, you’ll read parents telling other parents to “just stick with it” and “don’t quit before the miracle”.
In this way, parents are kept “on the hook” long enough for a spontaneous improvement in their child’s condition to happen. They are then encouraged – by their peers and the practitioners – to attribute that improvement to the therapy (or therapies) they were using at the time.
One effect of this is that parents are often puzzled about how various “alternative” therapies “stop working”. In fact, the therapies haven’t “stopped working” – they never worked in the first place. A spontaneous improvement was seen and erroneously attributed to a therapy, and then the improvement stopped – as it always does.
Even in typical children, periods of advancement are followed by a period of little or no progress. A child learns to walk and then spends weeks or months “consolidating” that skill before moving on to the next milestone. If an autistic child is started on a therapy just before one of these spontaneous periods of advancement, it would be the rare parent who didn’t credit it with causing the improvement.
By extending the window of time that parents will attribute improvement to a treatment, the technique of telling them to “give it time to work” merely increases the chance that parents will mistakenly believe that it is the treatment that caused the (spontaneous) improvement.
In fact, you only have to look at the hundreds of therapies that are said to “work” for autism. Everything from ABA to Valtrex to HBOT has its cadre of loyal believers who are convinced that it has “recovered” their children.
One of these treatments –secretin – was once said to work “with the first dose” in up to 70% of autistic children. Then (surprise!) its supporters said that it took several weeks of treatment. Then months…..you get the idea.
Eventually, the science caught up with the hype and we found out that secretin was no more effective than salt water (saline) injections. Sadly, there are still people who believe that secretin “recovered” their children and there are still practitioners who prescribe it. In fact, the “Autism Research Institute” recently came out with yet another smoke-and-mirrors, hand-waving, pay-no-attention-to-the-man-behind-the-curtain “explanations” of why secretin seemed to work so well in initial (uncontrolled) trials yet failed so miserably when it was actually tested (more about that in another post).
A Shotgun Wedding:
In “mainstream” medicine, “shotgun therapy” is considered bad form, if not bad medical practice. “Shotgun therapy” is the practice of starting a number of treatments at the same time in the hope that one of them will work. The preferred approach is to use one treatment at a time, stopping those that do not work and adding others as needed to deal with problems that persist.
If too many treatments are started at the same time, it is often impossible to tell which one(s) is (are) working, thus obligating the patient to either keep going with all the therapies or start a long process of trial and error. Contrary to popular “alternative” belief, most “mainstream” doctors want to have their patients on as few therapies as practical.
For “alternative” practitioners, however, the “shotgun” is their favorite tool.
There are some “alternative” practitioners who avoid the “shotgun”, but most seem unable to put it down. It is an all-too-common story from parents visiting an “alternative” practitioner – they are overwhelmed with the number of therapies recommended. Some “alternative” practitioners seem to take the position that all the therapies are equally effective (or equally ineffective) and leave it up to the parents to choose which ones to try. Others have their own favorite group of therapies and use them on every patient, regardless of their complaint or diagnosis (which begs the question of how “individualized” these therapies are).
From my conversations with parents, it seems that the practitioners give them little or no guidance, telling them things like:
“Parents know more about their children than any doctor.”
“The parents are the best lab test.”
“I’ve learned everything I know about autism from parents”
These all sound so….empowering. Who could disagree with that?
The problem is that professionals – including medical professionals – are supposed to give their clients – their patients – their professional opinion about the best course of action. Of course, there are times when there is no clear best course and all choices are equally good or equally poor. But every time? The “alternative” practitioners who abdicate that responsibility have reduced themselves to the role of a self-help video.
But…..one advantage of that approach is that the parents cannot turn around at some later time and accuse the practitioners of making the wrong choice or giving bad advice – the practitioner has made no choices and given no advice. By forcing the parents to play the role of medical professional, the “alternative” practitioner makes THEM responsible for any failure. Of course, the “alternative” practitioner is always willing to take credit for any successes.
Insurance? We Don’t Take No Stinking Insurance!:
The “alternative” practitioners usually frame this issue in a way that makes them out to be the Brave Maverick Doctor fighting against the mindless minions of orthodoxy. “No, my treatments aren’t covered by insurance – the insurance companies are in the pocket of ‘Big Pharma’ and the AMA.”
In truth, most insurance companies will pay for an examination and evaluation by any licensed physician – and many licensed non-physician practitioners. However, they don’t pay as much as some of the “alternative” practitioners charge. An initial (”new patient”) visit with our pediatrician costs $150 and is scheduled for one hour. A one-hour “initial consultation” with one “alternative” practitioner (who has not completed any specialty training) is $800. Insurance companies won’t pay that much, so there is little incentive for this “alternative” practitioner to bother with insurance, not as long as they have a waiting list for appointments.
Not taking insurance also sidesteps one of the most effective monitoring programs in medicine. State medical boards have been largely emasculated by laws passed to benefit “alternative” practitioners, so the only effective check on physicians who use substandard, unproven or dangerous therapies are the insurance companies (including Medicare and Medicaid), which have fairly effective quality control programs.
Another kind of insurance – one that most patients don’t think to ask about – is malpractice insurance. Some of the “alternative” practitioners can’t even get malpractice insurance because they don’t have a license to practice medicine; others simply choose not to carry it. Being uninsured not only saves the practitioner money on insurance premiums, but it also actually reduces their risk of being sued. Few tort lawyers will take a case on contingency if the practitioner isn’t insured.
Pay no attention to the man behind the curtain:
Many “alternative” practitioners encourage their patients (or their parents) to ignore any “skepticism” they may hear about the treatments. The practitioners’ explanations vary slightly, but generally revolve around the theme that the “mainstream” medical community and/or “Big Pharma” either refuse to acknowledge the “truth” or – more ominously – know the truth but are covering it up to protect their profits or to prevent lawsuits and embarrassment.
This serves to prevent any information about the efficacy, safety or even plausibility of the treatment from interfering with the relationship between the “alternative” practitioner and their prey…I mean, their patients.
The practitioners are aided and abetted by the more militant “autism advocacy” groups, many of which openly accuse doctors, pharmaceutical companies and government agencies of conspiring to “cover up” the “real” cause of autism. Although believing in this level of conspiracy is nearly diagnostic of psychopathology, it also helps them (the practitioners and militant “autism advocacy” groups) keep the parents isolated from other sources of information. After all, if they can convince the parents that doctors (except, of course, for the “Brave Maverick Doctors”) and governmental agencies are part of a conspiracy of deception, then the only remaining source of information is…. the “alternative” practitioners and the militant “autism advocacy” groups.
Well, that’s enough for today. Next up - Endgames and Discussion.
Prometheus
Filed under: Autism Practitioners, Autism Science, Autism Treatments | 29 Comments »