Response to Anti-Vaccination Parent

Ginger Taylor, the parent of a six-year-old son with autism, wrote a lengthy response to my previous post, "The Disappointment of Hearing 'Your Results Don't Matter.'" Ms. Taylor sounds like a woman who is truly dedicated to her son's successful development. However, I still find a number of Ms. Taylor's contentions to be unfounded. I am responding to her comments, albeit with a bit of hesitation. I am not an expert on the subject of autism, and do not wish to misrepresent the scientific community. If there are any mistakes, they are solely my own. Here goes:

You seem to have made an assumption here, that certainly would be a reasonable one if Paul Offit and his compadres are your main source of information on biomedical intervention for autism. And that seems to be that just because Jenny McCarthy didn't present the kind of evidence you are looking for to prove the efficacy of the treatments she used when she was on Oprah, and just because Offit says there is none, that they don't exist.

Perhaps it's true that there is better evidence than that which Jenny McCarthy presents("My science is Evan, and he's at home. That's my science¹"). However, I honestly haven't seen such evidence. I've read a lot of anecdotal accounts of "miraculous" recoveries, "immediate" personality changes following administration of the MMR vaccine, and emotional appeals to the public's sense of outrage, but nothing that comports to the standards of science. Advocacy groups, such as Autism Speaks, the Autism Research Institute, and Generation Rescue, all feature many studies of very poor quality, and I can only assume that what they present is the "best evidence they've got."

I am the mother of a 6 year old that regressed into autism following his 18 month vaccinations and have gotten him about halfway back with the evidence based interventions that Offit has derided.

How do you know that you haven't gotten him "back" (I assume you don't mean "cured") simply due to good parenting? Effective behavior modification techniques? A good social environment? There is no way to know if your child improved due to any specific intervention. Don't sell yourself so short. I'm sure that your son's success has a lot more to do with the time and devotion you dedicate to him than to anything that anybody's selling you. There is a long history of blaming autism on "bad mothering²."Parents should feel pride in their children's progress, rather than (unfounded) guilt due to a feeling that they've exposed their children to something harmful.

Offit is not a good source on autism treatment (he does not even treat children with autism, he is an infectious disease specialist), and his vast conflicts of interest should be raising huge red flags for you.

-He is a vaccine patent holder who won't say exactly how many millions he made from RotaTeq, but says it was like "winning the lottery".

-He was reprimanded by Congress for his ethical breaches and conflicts of interest when as a member of the ACIP failed to abstain, but rather voted to put RotaShield on the CDC schedule, effectively creating a market for his own vaccine by insuring that it would go directly into doctors offices nationally the day after it was approved.

-RotaTeq is arguably the least important vaccine on the schedule for children to receive as Rota virus represents a minimal health threat to American children. (CDC's web site recommends that it be treated with rest and Pedialite). If Jenny's message that kids are getting "Too Many, Too Soon" is taken seriously and adopted, and the vaccine schedule is paired down, certainly RotaTeq will be the first to go as it has been confirmed that it causes Kawasaki's disease and fatal Intussusception.

-He has been publicly and repeatedly corrected for spreading misinformation and inaccurate statements about the cases in the vaccine injury compensation program, most notably this past year in both the Wall Street Journal and the NEMJ.

-He is currently being sued for libel by at least one person he wrote about in the book.

-Although he is quoted at least weekly claiming that vaccines have no relationship to autism, he almost never discloses that he is a vaccine patent holder and has major conflicts of interest. CBS News even did a piece on his failure to disclose (Along with AAP and Every Child By Two. And it turns out Amanda Peet is even being paid by Wyeth for her vaccine promotional spots).

-He routinely makes outlandish and irresponsible remarks such as his famous, "theoretically a baby can receive 100,000 vaccines at once safely" absurdity (I wrote to him the first time I saw this in print and was sure it was a misquote, and asked for a corrected quote from him. He replied that it was a correct quote and "that is probably a conservative number".)

(To be frank, we can't under stand why anyone takes him seriously, and suspect that it is his mere bravado that has prevented people from cluing in to the fact that he is not responsible physician.)

So given all the potential for bias here, don't you think that it might be wise to take a hard look at the other side and make sure that the information he is giving you is reliable and complete?

Perhaps Offit is a mean, greedy man, who enjoys slandering people, and who is simply trying to make more money from his Rotavirus vaccine. I don't know him personally, so I have no specific objections to these claims. The problem is, I don't care about Offit's personality or accomplishments or lack thereof. My only concern is whether or not the statements about autism that he states in his book are factual. Luckily, if I'm suspicious about potential conflicts of interest, I can investigate all of his claims independently, as Offit has provided 32 1/2 exhaustive pages of footnotes in his book, all of which refer me to all of the relevant papers and transcripts. If you can show me a place in his book where Offit

1) Falsifies information from these references AND
2) Such falsification is so damning that it undercuts his basic argument (i.e. invalidates the heap of evidence that he provides in the other 246 pages in his book),

then I would certainly take this objection seriously. But none of the arguments presented above satisfy either of those conditions, as they only address why Offit might want to falsify information, not whether or not he actually did so.

(Parenthetically, please know that intussusception occurs spontaneously in approximately 1 out of 2,000 healthy young infants and children per year. The fact that Rotateq may cause intussusception (bowel obstruction) in 1 out of 12,000 patients must be weighed against the fact that the vaccine is generally administered in developing countries, where approximately 475,000–580,000 children die from rotavirus infection each year, according to the WHO. All treatments (and human actions) have costs. You must compare these costs to the corresponding benefits).

Because it is not like you have just one mom, Jenny McCarthy, standing up in public and claiming that she recovered her son from autism using these methods, the same year that her book came out, 2007, the Autism Research Institute documented more than 1,100 cases of kids loosing their autism diagnosis following biomed.

The plural of anecdote might not be data, but is a hell of a clue that any honest, earnest, evidence based loving clinician would be remiss not to examine, to put it politely. Criminal might be a better characterization.

Unfortunately, the studies propagated by the Autism Research Institute do not nearly satisfy the conditions of evidence based medicine. Let's look at one oft-cited ARI-sponsored article: "Effect of pioglitazone treatment on behavioral symptoms in autistic children⁴" in Journal of Neuroinflammation, written with co-contributors Stephen Edelson and James Adams of ARI.

Even after a cursory reading of this article, I find that the study included only 25 children, with no indication about whether the research subjects were recruited randomly or from a population that already subscribes to the researchers' theories. Most importantly, the study featured no control group. Scientific Method 101 says that you can't test a hypothesis without having a control. P values were not reported, so there is no way of determining whether the findings were statistically significant or simply occurred due to random chance. In fact, the authors themselves only conclude only that there should be "further testing," a viewpoint that they presumably shared even before writing the article.

Some people outright deny that the scientific method is a meaningful means of testing alternative medicine. In certain ways, I find the "research" of the ARI to be more pernicious. Their work has the cloak of science, and would seem quite convincing to someone who has no background in basic study design. I probably just prefer the people who outright claim that the scientific method is irrelevant, because at least they're being honest about their beliefs.

I know that you believe that it is "criminal" not to further investigate the claims of people who believe in the vaccine/autism link, because of the shear number of complainants. However, these claims have been investigated (Ten studies to show MMR doesn't cause autism. Six that show thimerosal doesn't cause autism, etc.) ⁵ More importantly, even if there hadn't been so many studies, I reject the notion that "any honest, earnest, evidence based loving clinician would be remiss not to examine" this issue, simply because many people believe in it. I will not "investigate" the claims of HIV denialists. Mass hysteria is a common historical phenomenon. If you are interested in reading an account of hundreds of people who were (erroneously) so convinced that they had been infected by a virus, that they actually began to experience symptoms of nausea and vomiting, please refer to Desenclos, J.C., Gardner, H., & Horan, M. (1992). "Mass Sociogenic Illness in a Youth Center." Revue D'Epidemiologie et de Sant, Publique, 40, 201-208.

Even if i had not reviewed some of the relevant literature, one hint to me that these vaccination claims are baseless would be the fact that the proposed pathophysiology constantly changes, while the culprit remains the same. Originally, it was proposed that the virulence of MMR stems from an infection caused by harmful proteins from the attenuated measles virus that reach the brain⁶. Others then said that MMR induced autism via an "autoimmune phenomenon⁷." Then others started to relate autism to thimerosal, saying it was due to mercury neurotoxicity, or perhaps thimerosal's binding to testosterone, which leads to hyperandrogenism⁸. Today, many activists acknowledge (or at least don't deny) that the vaccines are generally safe, but say that they just should not be administered to kids below a certain age, or that too many vaccines should not be administered during a short period of time (i.e. "Too Many, Too Soon"). The proposed mechanism and subsequent recommendations constantly shift and adapt with new evidence, but never actually disappear.

"her case is scientifically irrelevant, so long as it was not added to long list of comparable patients of a similar demographic."

So ask yourself, if Offit and CDC and AAP and the vaccine industry are so keen on insuring vaccines don't cause autism, and why have then not take Evan and those 1,100 kids, put them in a long list and compare them to patients of a similar demographic? (Why is there no study comparing kids with an autism diagnosis who undergo biomed with those who don't to see how functional they are at age 10 or so?) Jenny has repeatedly called CDC and asked them to examine her son and all the kids like her son, yet they have never contacted her or ARI or any of the parents who have before and after videos all over the internet showing their recovery stories.

Does that lack of curiosity raise any red flags for you?

Do you think that if one medical practice (much less several dozen) announced they had 1,100 cases of people who recovered from HIV/AIDS, all with evaluations, test results, medical records and videos to prove it, that CDC et all would collectively yawn, quote Brinner, claim it is not data and never even pick up the phone to see if an actual cure had been found? Even for just some cases of HIV/AIDS?

Not in a million years.

(...and if that ever happened, San Francisco would burned to the ground by protesters).

So why is it that with all the claims of vaccine regression and subsequent recovery, are you satisfied with the "no association, no know cause or cure" line from the very people, Offit, HHS, CDC, AAP et al, who would be held responsible and be out of their collective posteriors for causing the autism epidemic if it turned did out to be the vaccines?

Especially when they are not showing up in our community to evaluate our claims and examine our kids?

Especially when they are doing everything possible to prevent REAL vaccine research from being done. Like just three days ago when the Federal members of the IACC voting NOT to study vaccine causation" with the funding from the Combating Autism Act (in opposition to the community members, autism parents, who wanted the research done), one of the regional intents of which was to study the possible association between vaccines and autism.

Ask yourself, why won't health authorities do a simple study comparing vaccinated and unvaccinated children, to look for overall health out comes and see if kids vaccinated according to the CDC schedule have more autism, ADD, asthma, diabetes, arthritus and other neurological and immune disorders?

Why does a Congresswoman have to propose a bill to force NIH to do the study? Shouldn't they want to do it? Certainly there are more and more unvaccinated kids out there to study, and if in fact Offits claim that there is absolutely no association is true, then it can only improve vaccination rates to put a study out that can make the claim with authority.

And why... when no such study exists, can anyone make the claim that vaccines don't cause autism? Vaccines as a whole have never been studied, merely a few different aspects of the vaccine program. And they have been studied quite poorly in many cases.

I do not know why you believe the vaccination-autism claim has not been and is not being investigated. The NIH currently has four studies being performed on the subject, in addition to the many studies that already have been performed in a number of different countries. Many thousands of records have been analyzed, with every study concluding that there is no link between autism and MMR or autism and thimerosal. Japan, when it discontinued the use of MMR, did not see any subsequent decrease incidence of autism diagnoses.⁹ Additional studies might be initiated when the six “Centers for Excellence in Autism Research" are created with money from the Children's Health Act of 2000. Millions and millions of dollars have been and will be spent to investigate this unfounded assertion. This money could be better spent on studies that would investigate credible "leads" about the causes of autism (such as the excellent work of the Autism Genome Project).¹⁰

If you feel that these studies are still insufficient, all I can say is that there is only so much money we can use to chase after every proposed claim. If we performed studies to investigate each person's purported "cancer cure," we'd be left with non-useful confirmations of what we already know (i.e. that virtually all of these claims are bunk). Such studies have enormous opportunity costs, as they take away potential funding from plausible hypotheses that stem from prior research and well-reasoned pathophysiological mechanisms, rather than from conjecture. For example, it is a waste of money to study whether or not diluted duck liver cures the flu, (as homeopaths contend)¹¹. At least eating duck liver is harmless. Non-vaccination has led to numerous preventable deaths in developed countries in the 21st century.

I erred when I said, "her case is scientifically irrelevant, so long as it was not added to long list of comparable patients of a similar demographic," because I implied that it would make sense to now add Evan's case to a scientific study. A good study would be double-blind randomized, controlled, trial including a random sample of kids with autism, rather than a cherry-picked selection of kids whose parents oppose vaccines, or whose parents who have already used alternative "treatments." Certain information can be obtained from a cohort study (a study where random children with certain conditions who have or have not had certain exposures are simply "followed" to determine outcomes), but these more necessarily require repeated investigation others, as they introduce a greater number of potential sources of error than randomized control trials.

Numerous randomized controlled trials have been conducted on kids with autism to test "natural," "biological" materials. These include the gluten-free casein-free “special diet" (which has only shown to cause bone density loss),¹² ”dimethylglycine¹³, and (hot off the presses, published just last week!) human immunoglobulin therapy ¹⁴. Needless to say, none of these treatments have proven to be effective. An NIH-sponsored study is underway to study the effects of cod liver oil, Vitamin B6, and Magnesium on kids with autism ¹⁵ (These vitamins are currently repackaged and sold -with a trumped up price- as "Super Nu Thera," to parents of autistic children).

You assert that the testimony of thousands of parents satisfied with "biomed" treatment should be more discomfiting to clinicians. However, thousands of parents swore by "facilitated communication," as well as by secretin, and those thousands of parents were proven to have been influenced by the placebo effect (I am not blaming parents. Nearly everyone, including myself, are at least somewhat influenced by the placebo effect). At least 15 studies were performed to test secretin therapy, a treatment once heavily promoted by the Autism Research Institute.¹⁶ All randomized controlled trials demonstrated that the hormone caused no improvement in autism symptoms, in comparison to the placebo.

Some studies simply cannot be performed, because the proposed intervention is already known to be potentially lethal. For example, chelation therapy can be dangerous, even for someone in an acute condition who is already known to be suffering from heavy metal poisoning. When used on healthy children with autism, who have no measurable increase of "heavy metal toxicity," we put children at risk for the fate of Abubakar Tariq Nadama. Indeed, the NIH extensively planned to perform a randomized controlled trial of chelation therapy, and called it off only when the initial animal testing demonstrated that the treatment caused extensive brain damage in rats.

As for the challenge of how we can "make the claim that vaccines don't cause autism?," my answer is we cannot make this claim, just as no one can make any claim with 100% certainty. We use science-based medicine to diminish our levels of uncertainty, until they become extraordinarily low. The fact that we can not, in any study, conclude that the "null hypothesis (in this case, that vaccines don't cause autism) is accepted," does not mean that it makes any sense to favor the alternative hypothesis (i.e. that vaccines do cause autism). For example, let's say someone made a claim that "Xenu...was the dictator of the "Galactic Confederacy" who, 75 million years ago, brought billions of his people to Earth in DC-8-like spacecraft, stacked them around volcanoes and killed them using hydrogen bombs¹⁷." My null hypothesis would be that this event didn't happen. However, I can never affirm this null hypothesis with 100% certainty, just as I can never state "vaccination doesn't cause autism" with 100% certainty.

So... at the conclusion of my long winded comment, I would like to call your attention to Bryan Jepson's book, "Changing the Course of Autism: A Scientific Approach to Parents and Physicians". I would like to encourage you to read it and then look back at Offit's book and see if he actually is taking apart the case for biomedical research or just going after the easy targets like McCarthy, while ignoring the actual biomedical approach to autism and the science to back it up.

You owe it to your future patients to have actually teased out the truth on this for yourself rather than just swallowing what those who quite obviously and transparently protecting professions and individual careers tell you the truth is.

Upon your recommendation, I read parts of Jepson's book. To buttress his arguments, Jepson heavily cites the work of Dr. Andrew Wakefield. Many of Wakefield's co-writers testified in court [CORRECTION 1.29.09: It was not a court trial but an omnibous proceeding for the Vaccine Injury Compensation Program, for which Wakefield was not on trial. I confused this with the British General Medical Council, which is holding a hearing to examine charges of professional misconduct] that he had falsified data, and 10/13 authors retracted their names from portions of Wakefield's most significant study, stating "We wish to make it clear that in this paper no causal link was established between the MMR vaccine and autism, as the data were insufficient." One witness at Wakefield's trial, Nicholas Chadwick, was the research assistant who had actually carried out the tests for the Wakefield's 1998 Lancet paper. He testified in court that, despite the fact that he informed Dr. Wakefield of the negative PCR test results, Dr. Wakefield reported positive findings in his paper.¹⁸ There were a number of such testimonies, despite the fact that Wakefield gave $30,000-$180,000 to expert witnesses who testified on his behalf¹⁹.

(Parenthetically, Wakefield is also under investigation for subjecting children to unnecessary and risky tests, such as lumbar punctures and colon biopsies, which would be inappropriate for any study, so long as these procedures were not medically indicated. An associate affiliated with the study ended up perforating a child's colon in a number of places.²⁰ Some of the actions that Mr. Wakefield is accused of performing, such as handing out cash to children who attended his son's birthday party, and then collecting their blood as samples, are downright bizarre. He failed to use a random sample of children in his studies, using mostly clients of a trial lawyer, Richard Barr, from whom Wakefield had received, on his own admission, at least $50,000²¹).

In other words, I do not find Jepson's book, which heavily references Wakefield's papers (as well as the work of the Geiers, who also performed poor research), to be particularly reliable.

You clearly, clearly want to make the right decisions for your patients. What if the right decision for some of your patients was not to vaccinate them according to the current CDC schedule (clearly it was the wrong decision for Hannah Poling, Madison Hiatt and the thousands of others who have received a billion of dollars from the Vaccine Injury Compensation Fund)? And the right decision for some of your patients with ASD was exactly what Jenny McCarthy did for her son? And what if you never looked into it because Offit etc told you not to bother?

In terms of the Vaccine Court, the fact that those girls got money from the Vaccine Compensation Fund is not particularly relevant, because the cases are not judged based on scientific evidence. A team of lawyers (called "special masters") with no medical background, rather than a judge, jury, scientists, or medical professionals, preside over the cases. The court's guidelines state that “special masters are not bound by formal rules of evidence” and that both sides should “be creative” in presenting their arguments “quickly and less expensively²².”

The court had no way of verifying whether or not Hannah Poling's autism (caused by an underlying mitochondrial disorder) was indeed aggravated by vaccination. Even Poling's doctor, John Shoffner, an expert in mitochondrial disease, was "genuinely puzzled" by the verdict. As far as I'm concerned, the findings of this court have little to do with science.

Bottom line, if you don't look all sides on this and make your own decision (rather than just joining the Orac insult-o-rama), then you risk taking on their crime of injuring children and withholding needed treatment if 'my side' is right.

I urge you, while you are still very early in your career, to take this subject very seriously and listen to autism parents and see if their concerns, questions and challenges are actually being answered by those you are taking your advice from currently. Are they really dealing with them, or just setting up straw men and knocking them down?
I (and many other parents) would be happy to talk to you about what we have learned and experienced and why we believe as we do, should you earnestly want to investigate autism causes and treatments on your own.

As I wrote on my other post, learning about the experiences of my patients and their families will be crucial for my providing good care, but is not relevant to science-based medicine (excepting in the use of case studies, which have limited value, and which are generally only used to develop hypotheses).

I know that "look at all sides on this" sounds neutral and unbiased, and that I should not "risk taking on their crime of injuring children and withholding needed treatment if 'my side' is right." The problem is that I am confident that I would cause more harm if I spent time to "look at all sides on this" and continued to pore over everyone's counterpoint for these debunked claims. I can spend a lot of time investigating whether or not HAART causes AIDS, or whether oleander defeats cancer, and any other medical claim ever proposed. Nobody can independently investigate every contention. However, doing so would detract from learning to read EKGs or chest X-rays, or performing other tasks that are crucial to avoiding future medical errors and providing excellent patient care.

Every one needs a gestalt about which resources to trust, and on what basis to accept information. A method may occasionally fail, but one chooses it because, compared to all other strategies for acquring information, it provides the greatest accuracy for the most important issues, with the greatest efficiency. To me, trusting a random website would be quick, but unreliable. Doing my own experiments on every issue might be reliable, but extremely inefficient. The best method available for clinicians to acquire scientific information is to use books and journals edited by people whom we know subscribe to a similar epistemoligical approach (i.e. commitment to the scientific method), and whom we know are held accountable for their claims, by the scrutiny of peer review. Will people sometimes falsify data or make errors? Yes. However, after a while, repeatability of experiments stops bad or mistaken research in its tracks.

I figure you might think that this is just a battle of "my favorite studies" versus "your favorite studies," and that the abundance of conflicting papers means that we can't know who is correct (which would theoretically render scientific research to be quite useless, on the whole). While controversy and uneven results can indeed be frustrating, I must say that this isn't a matter of my preferentially selecting studies that would help my case. The scientific method requires "appropriate design and analytic methods...critical to achieve meaningful results." Such methods include "definition of exposures and outcomes, validation of developmental diagnoses, provision of sample size calculations and/or discussion of study power, and statistical methods including techniques to control for potential confounding." One study compared a number of epidemiological cohort studies that investigated a possible vaccination-autism correlation, and found that only the study by the Geiers, (which was also the only study that reported a correlation between vaccination and autism) fulfilled zero out of eight epidemiological criteria. There are a lot of seductive "studies," that we may hope to rely upon, but we can still distinguish the good from the bad, especially with the power of repeatability.

Good luck, Ms. Taylor, and I hope your son's development continues to be successful. I have a family member with an autism-spectrum disorder, and I have observed firsthand the amazing dedication and love that parents put in to careing for these wonderful kids.

Footnotes:

1. Jenny McCarthy on Oprah. Interview by Oprah Winfrey, Oprah Winfrey Show, NBC, September 18, 2007. Source from Offit, Paul A. Autism's False Prophets (Columbia: New York, 2008).
2. Bettelheim, Bernard. The Empty Fortress: Infantile Autism and the Birth of the Self (New York: Free Press, 1972). Source from Offit.
3. Offit. 110-111.
4. Boris, Martin and Claudia C. Kaiser, et. al. "Effect of pioglitazone treatment on behavioral symptoms in autistic children." Journal of Neuroinflammation 2007, 4:3. http://www.jneuroinflammation.com/content/4/1/3
5. Please see the pages-long list of studies in Offit 256-7 and 266-7.
6. Letter from Dr. Wakefield to journalist Brian Deer. 12.2.04. http://briandeer.com/mmr/wakefield-st-statement.htm
7. Waisbren, Burton A. "It is time to face up to the problems of MMR vaccination and its possible relationship to Autism." http://www.waisbrenclinic.com/mmr-autism.html
8. Geier, David A. and Mark R. Geier. "The Biochemical Basis and Treatment of Autism: Interactions between 3 Mercury, Transsulfuration, and Androgens." Autoimmunity Reviews. Retracted by publisher before publication. Available at http://briandeer.com/wakefield/geier-mark.pdf
9. Honda, Hideo and Yasuo Shimizu. "No effect of MMR withdrawal on the incidence of autism: a total population study" Journal of Child Psychology and Psychiatry. 46:6. 572-579. http://www3.interscience.wiley.com/cgi-bin/fulltext/118735419/HTMLSTART Source from Offit.
10. The Autism Genome Project (AGP) Consortium. "Mapping autism risk loci using genetic linkage and chromosomal rearrangements." Nature Genetics. Published online: 18 February 2007, doi:10.1038/ng1985.
11. Vickers AJ, Smith C. "Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-like syndromes.", Cochrane Database Syst Rev. 2006, Issue 3. Art. No.: CD001957.
12. "Autism in Celiac Disease: Failure to Validate the Hypothesis that a Link Might Exist." Biological Psychiatry. 42(1997):72-75. See other sources in Offit 270.
13. 5. Bolman, William N., John A Richmond. "A Double-Blind, Placebo-Controlled, Crossover Pilot Trial of Low Dose Dimethylglycine in Patients with Autistic Disorder," Journal of Autism and Developmental Disorders 29:3 (1999) 191-194
14. 7. Handen, Benjamin L. and Raun D. Melmed. "A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder," Journal of Autism and Developmental Disorders
DOI 10.1007/s10803-008-0687-y. http://www.springerlink.com/content/r741394286415x84/
15. "Treating Oxidative Stress and the Metabolic Pathology of Autism" Arkansas Children's Hospital Research Institute. ClinicalTrials.gov Identifier: NCT00572741.
In recruitment stage.
16. A.D. Sandler, K.A. Sutton, et. al. "Lack of Benefit of a Single Dose of Synthetic Human Secretin in the Treatment of Autism and Pervasive Developmental Disorder," New England Journal of Medicine 341 (1999):1801-6. See other studies mentioned in Offit 251-2.
17. Wikipedia article on the Scientology figure, "Xenu." http://en.wikipedia.org/wiki/Xenu
18. United States Court of Federal Claims. Docket Number 98-916Vftp://autism.uscfc.uscourts.gov/autism/transcripts/day10.pdf
19. Full Legal Services Commission Report obtained by Brian Deer via Freedom of Information Act. Available at http://briandeer.com/wakefield/legal-aid.htm
20. R. Ellis, "₤500,000 Payout for Autistic Boy Left Fighting for Life After Being Used as an MMR Guinea Pig." Daily Mail. December 8, 2007. Source from Offit.
21. MP3 audio available at http://briandeer.com/mmr/wakefield-archive.htm and sources cited in Offit page 258.
22. "Guidlines for Practice Under the National Vaccine Injury Compensation Fund." The Office of Special Masters. United States Court of Federal Claims. Available at http://www.docstoc.com/docs/831292/Guidelines-for-Practice-Under-the-National-Vaccine-Injury-Compensation-Program Source obtained from Grant, Andrew. "Inside the 'Vaccine Court.'" Scienceline. http://scienceline.org/2008/07/25/policy-grant-autismvaccinecourt/

The Disapointment of Hearing "Your Results Don't Matter"

I am not categorically opposed to "alternative medicine," provided that each accepted treatment is properly tested in an ethical and scientifically sound manner (but I just call using acidic Vitamin A to treat acute promyelocytic leukemia plain old "medicine"). However, friends will sometimes advocate for a particular alternative therapy, be it a tincture, muscle manipulation technique, or adjunct cancer treatment, with the the promotion "My relative tried it and she had great results." To which I usually just respond with, "Cool, Thanks."

I respect the intelligence of my friends, and thus usually speak up and engage them in conversation, when I find something they say to be questionable. However, I keep mum when facing a statement about a close one's personal recovery. There is simply no polite way to say "The experience of your relative does not matter."

I am certainly happy if a friend's loved one recovered successfully from his or her illness. But the fact of his recovery has a less than minuscule effect on my views concerning the value of the treatment. I have no idea if the recovery was because of the treatment, despite the treatment, or for some completely unrelated reason. I say a "less than minuscule", rather than a non-existent effect on my confidence in the medication, because the anecdote does teach me "At least one person was able to recover from his illness while (but not necessarily as a consequence of) using this treatment (Treatment A)." The practical effect of this knowledge would be that, were I placed in a hypothetical situation, in which I had to quickly save someone by choosing between said Treatment A or Unknown Treatment B, I would probably preferentially grab Treatment A. I don't anticipate facing such a "deserted island"-like scenario in my lifetime, so I can safely say that I would be no more or less likely to use Treatment A in practice.

I wonder if the harshness of the objection is what makes some people resistant to evidence-based-medicine. What we are basically saying that no matter how much someone suffered, and no matter the magnitude of her eventual breakthrough, her case is scientifically irrelevant, so long as it was not added to long list of comparable patients of a similar demographic. People want to feel like their experiences matter. Nobody wants to simply be a statistic.

The problem is that treating people as individuals, and caring deeply about the welfare of one patient, both requisite components of empathy-based-patient care, are not pertinent components of evidence-based medicine. It is when we take the good intentions of the former, and impose them upon the cold calculations of the latter (or vice-versa), is when we start to provide medical care that is less efficacious, and less empathic, respectively. Empathy requires a dogged commitment to the patient and his relatives, science involves an exacting focus on anonymous people whose names will never be disclosed. Perhaps it is this intense desire to celebrate the personal, rather than the abstract, that drives us to make crucial cognitive mistakes.

While I am angry that Jenny McCarthy's "advocacy" work may harm many children, her biases seem to stem from natural human feelings that arise to deal with uncertainty, to maintain control over our environment, and, most of all, to find personal meaning in our experiences.
I am currently reading Paul Offit's wonderful book, "Autism's False Prophet's," which transcribes Jenny McCarthy's statements on Oprah, including this response to a question:

"My science is Evan, and he's at home. That's my science." [Loud, thunderous applause].

I honestly am not mocking Ms. McCarthy when I say that I wish I could point to the difficult experiences of loved one's illnesses and call them "my science." But no matter my sympathy of the motivations, it is irrational, nonetheless. And it could potentially cause enormous harm.

Paul Offit also presents the transcription of a doctor name Dr. Geier, who testified against vaccinations in court, and who had been peddling his own untested autism medication called "Lupron." Dr. Geier said,

"We presented a new idea on how to treat autism and how to treat mercury poisoning, because these kids aren't autistic, they're mercury poisoned. Although I'm not happy with trying it on children without further research, these people are desperate and there have been some remarkable responses."

"Remarkable responses," "Try it: He had good results," "My family is my science": All of these are erroneous statements that are damaging to health care. One must develop the humility necessary to accept the limited applicability of one's experiences and observations. This is a difficult bias to overcome. But to do so is necessary, because, as Roger Brinner brilliantly quipped, "The plural of anecdote is not data."

Adding Worse Doctors, Getting Better Medicine?

Edwin Leap worries that, if doctors no longer earn a decent profit, the best and brightest will find no good incentive to enter the healing profession.

He writes:

Physicians have to be paid well in order to continue to practice medicine. It wasn’t always this way. Because, there was a time in modern medicine when the rewards of the practice of medicine were considered higher than mere cash. Why did early physicians expose themselves to epidemics and death? Why did they go to battlefields and learn surgery? Why did they labor with the miserable and poor? Because they sensed the value of human-kind. They were taught, and believed, that every life was valuable in God’s eyes, and that if they ignored their calling, and ignored suffering, they would face God’s wrath. They also believed that if they did right, if they endured under hardship, if they died of the diseases they fought against, they would be rewarded by their Creator.

We are too modern for all that, now, aren’t we? We don’t need mumbo-jumbo, irrational, anti-scientific theories about human worth. We’re post-moderns! We will do right, because it’s good for mankind and good for society and because our reward will be…well, it will be science and knowledge…I mean, it will be the survival of all the fittest for the collective good of mankind in a few eons…it will be…a good review from my boss and a nice retirement with a boat…it will be a vacation and a car and….well, some money will do nicely, if you please.

Reject transcendence if you will. But if you do, prepare large boxes of cash. Because doctors without a sense of temporal and eternal purpose will have to be rewarded financially in order to stay in a long, arduous educational system, in order to work all hours, in order to expose themselves to risks physical, emotional and legal and in order to come back day after day to a job that is sometimes amazing but often quite tedious and frequently quite maddening.

Given that it may make more sense, from a purely economic perspective to become a UPS driver than a doctor, and that the average GPA of pre-medical school matriculants is still about a 3.7, the risk of a sudden doctor dry-up is rather low. I am not sure if it is due to a continuous devotion to "transcendence," but Pre-meds are still undergoing Fear Factor level feats to contest for every last available medical school chair in the country. When all else fails, many pack their bags for four sunny years in Grenada.

The unaccepted applicants are, all things considered, less-qualified on average. Some unaccepted applicants bombed their MCATs, some got a C in Orgo Sophomore Year, some had a stain on their tie during their interviews, and some were simply "more average" all around.

Would these potential physicians be worse doctors than the current matriculants, assuming economic conditions lured the smartest college students to law, business, or package delivery? Perhaps. However, the brutal admissions process doesn't measure some of the most crucial skills necessary to become a doctor: Good patient rapport, observation skills, manual dexterity, superhuman ability to function without any sleep, a healthy self-esteem that can endure frequent criticism, and the motivation to keep up with the latest in science-based medicine (a criterion that automatically excludes many working spinal surgeons). There is no reason to believe that Team A possess these skills to a much greater extent than Team B.

Let's say, however, that the currently shut-out applicants would actually become inferior doctors. Maybe they'd miss a few more crucial diagnoses, screw up a few more procedures, or show up to work with that stained tie, every single day. . The fact is that the stuff they do right might outweigh the probability that they would make a few more mistakes. In other words, while medical errors are an enormous problem, many people do not even have the opportunity to be at risk of being victims of medical errors. They do not have doctors, period, and have no chance to be diagnosed and treated, altogether. If you see the slow-growing elephantiasis and massive tumors being sported in our ED's waiting room, you'd see what I mean.

Imagine a mediocre doctor who goes into a small town with no primary care physicians. The doctor misses a few diagnoses, but also recognizes a whole bunch, all of which would have been undetected otherwise. He administers a lot of STD tests, and performs tons of vaccinations. All things considered, I'd say it's a win.

In other words, we shouldn't only focus on the quality of doctors. Even the best doctors can only see so many patients. Those physicians should be doing the trickiest procedures, managing the most complex clinical cases, and addressing actual emergencies. But let's allow nurse practitioners, physician's assistants, and less-stellar doctors to take care of everyone and everything else. Because poor people without any medical care could really benefit from a lot more "good enough."


HT: Kevin, M.D.

Radiolab on Choice

Today I listened to a podcast of "Radiolab," the WNYC show hosted by Jad Abumrad, the voice and inflection clone of that other NPRish guy who does "This American Life (Does that voice trainer do some standard laryngoplasty on everyone?) The experimental music and sound effects alone provide a worthy opponent to TV, despite the inability to exploit one of our senses. The topic of the day was "Choices" and the potential psychological perils of its abundance.

People, like myself, who read lots of "happiness studies books" (which is distinct from reading self-help books. Not that there's anything wrong with that...) will recognize some of the usual players who are interviewed, most notably, Barry Schwartz, a professor of psychology at Harvard who wrote "The Paradox of Choice." Schwartz studies how the abundance of available options in developed countries commonly leads to self-doubt, regret, paralysis in decision-making, and an overall feeling of dysthymia. Schwartz believes that government should act to limit people's choices, by paring down, say, the hundreds of peanut butter options at Whole Foods.

Predictably enough, as a libertarian, I disagree with Barry Schwartz's prescriptions, if not his assessments. Even if, theoretically, government were justified in restricting choices without consent, and even if in practice did a decent a job ridding the public of some unnecessary choices, we'd still all have to cope with overwhelming options sooner or later. Schwartz, in his book, even provides strategies for doing so. Since Schwartz presumably doesn't believe in censorship, I'd still have millions of books listed on Amazon to devour. With some benevolent meddler paring down my reading list, I'd still mull over whether to read altogether to move on to cooking dinner instead (using a pared down list of recipes). In other words, people simply have to learn strategies of prioritization. Uncle Sam's wagging finger in the peanut butter aisle would simply help me avoid setting up the an internal Grand Supermarket Shopping Prioritization Strategy Task Force, a necessary step for learning to move on and get stuff done.

Abumrad interviews Oliver Sacks, who outlines his strategy to avoid deliberating on too many time-wasting decisions. He says, "I make a willful choice. Certain things I care about a lot and I worry over, and then there's a whole swath of my life that I just don't even choose." Every week, his housekeeper buys one half-gallon of soy milk, one half-gallon of prune juice, seven apples, seven pears, and several tins of sardines. She will then cook up a gallon of orange jello and a vat of tabbouleh, to be consumed for dinner each night, along with the sardines.

Sacks is so normalized to his menu, that he "never gets bored" with his food. Presumably, his main hedonic pleasure is music. To maximize time invested in such pursuits, he simply ignores other potential sources of joy, such as variety in food. Repetition, however, is not the same as denial: every day, he keeps exactly a dollar in his pocket, to buy a piece of 72% cacao chocolate at the chocolatier on his way home.

Later in the program, Abumrad highlights human irrationality in decision-making, through the concept of "risk aversion," or how our fear losing something overpowers our perceived joy of winning that same item. Mimicking a previously performed psychological study, the djs wandered around outside, offering random bystanders opportunities to play "heads or tails." The djs started out offering one dollar for the strangers' dollar (a proposition rejected by all), but then offered increasingly high amounts of money to match the bystander's dollar. Most people didn't accept the match until the djs reached about two dollars. On the show, the djs then speculate as to why, for most people, loss is twice as "painful" as gain.

Risk aversion is real, but I don't see how it is always irrational. For one, the dj's dollar is not worth the same amount as my dollar. My dollar is already in my pocket. His dollar has to sacrifice some pennies to pay for my trust that this stranger is good for the money, and this isn't just one big scam.

One guy, cited that he "was just not a gambler," and, for reasons other than religion, wouldn't even play if the odds were 100 to 1. Perhaps his view of gambling as different from other economic transactions is irrational (I avoid casinos, not because it's "gambling," but simply because I know my odds of winning are poor. I viewed my regrettable purchase of that "As Seen on TV" Super Slicer as simply a gamble with better odds). However, if the man is a conscientious objector to coin tosses, is that necessarily irrational? Perhaps, due to family history, he knows he may be susceptible to a gambling problem (thus making an irrational decision that is only rational, because it is used to combat an irrational compulsion). Maybe he just wants to die bragging that he never gambled. The problem with these studies, I find, is that the researchers just don't give their subjects enough credit.

Even if there were no doubts about the integrity of the djs, nor any personal opposition to gambling, a more serious error is to assume that a potential dollar won is worth the same as the dollar the person already has. In fact, I suspect Sir Oliver Sacks himself might have refused to play the game of chance. A hundred to one odds might allow the chance to purchase the fanciest products displayed in the supermarket. But he could also lose the opportunity to buy a piece of 72% cacao chocolate on the way home from work.

Update 1/7/09: The very day I wrote this post, I randomly came across this at the "Overcoming Bias" blog. I suppose the Baader-Meinhoff phenomenon is my personal bias of the hour.

Is "Parasites the Correct Word" Continued.

Commenting on my post, "Is 'Parasites' the Correct Word?,'" the Probe writes:

As for the question whether parasites is the correct word, a semantic analysis as yours does not consider the feelings of those who take the risks, albeit miniscule, and vaccinated their children. Thus, parasite sounds good, and freeloader or leech sounds even better.

You said: "Vaccination is the boy scout of medicine...". I just love this line. Always ready to help. Of course, sometimes the scout and the little old lady get mowed down by a speeding drunk, but, the scout was prepared.

I agree that my analysis might concentrate excessively on semantics over substance, but I think logically characterizing the lapses of non-vaccinators is important. I am wholly convinced that vaccination is one of the most important milestones in medical history, and a major cause for modern human flourishing. However, any time we force someone to do something against his will, there are both ethical and practical consequences. So we must distingish between people who benefit from other's actions from people who directly cause harm, from people who fail to prevent harm, etc.

In other words, I might prefer allowing people to benefit, via herd immunity, from my vaccinating my own children, despite the mild risks imposed on my family, over the inevitable law suits, growing conspiracy theories and other problems that stem from requiring the kooks to vaccinate their kids. For one example of the dangers of a backlash, read this note that I received from someone upset about some pro-vaccination comment I made on YouTube:

I'm assuming that you don't have a child who was injured by a vaccine then. Vaccines are toxins intentionally injected into babies and children FOR MONETARY GAIN OF PHARMACEUTICAL COMPANIES. The CDC knows exactly the harm caused by these vaccines. It's a scam - just like health insurance, cesarean sections caused by induction, and many other facts of American life. Vaccines aren't proven to work anyway. Vaccinate your own kids if you like, but mine are staying AWAY from those toxins!

If we force this person to vaccinate his kids, everything from the kid's future failures in school to his inability to make friends will be immediately blamed on vaccination (In this case, I'd blame the parent...). I'd rather the conspiracy theorist be forced to scramble to find something else to vilify.

Thank you, Probe, for reading my blog. For now, anyone who makes thoughtful comments will get personal responses.

Can't Escape Bacteria

For some people, the whole world's a stage. For me, the stage is apparently just a world of medical disorders. Today, I was listening to the soundtrack of "Rent," in which Mimi sings about her S+M work at the "Cat Scratch Club." Then I realized: Was Jonathan Larson making a reference to Cat Scratch Fever? Cat Scratch Fever often manifests as Bacillary Epitheliod Angiomatosis, an infection featuring red papules, due to proliferation of small, round, blood vessels. It is caused by the Bartonella Henseli bacteria, which usually enters the body after the host is scratched by a feline. However, it is also a very common Clinical Category "B" symptom for HIV. Was Jonathan Larson making a medical allusion about his character, Mimi, the HIV-positive exotic dancer?

Is "Parasites" the Correct Word?

Following my post on Amanda Peet's calling parents who don't vaccinate their kids "parasites," I've pondered about the technical applicability of the term.
In ecology, there are three basic categories of symbiosis, or dependant ineractions with members of another species. The definitions, according to the MadSci Network, are as follows:

PARASITISM:
(+/-) Where one organism benefits (the parasite) and the other is
negatively affected (the host). Fleas on a dog are a great demonstration of Parasitism at work.

COMMENSALISM:
(+/--)Where one organism benefits and the other neither benefits nor is
negatively affected. An example is barnacles on a whale - the barnacle gets
a place to live and relative safety, and the whale seems unaffected.

MUTUALISM:
(+/+)Where one or more organisms benefit from the partnership occuring
between them. Clown fish in anemonies and photosynthetic zooxanthallae
algae in corals are both examples of an "intimate" relationship occuring
between two species.

Technically, these terms apply only to interactions among different species, not within a single species, but the term "parasite" is often used colloquially to refer to fellow humans.

However, according to these definitions, Peet should have accused non-vaccinators of being "commensalists." Such people don't generally harm others, yet enjoy the benefits of herd immunity, or the fact that infectious microbes have little chance to spread when there is such a small number of potential human hosts. And if you, like me, understand that vaccines pose virtually no harm, then the only "benefit" extracted is the ability to avoid an extra trip or two to the doctor, and to spare a kid from a shot.

There are circumstances, however, in which refusing vaccination can cause considerable harm to others. Inoculations do not work on immunosuppressed people, because the process requires a functioning immune system. Caccinations work by introducing a "fake" microbe that has similar protein markers to an actual pathogen, but is really a benign imposter. This leads your immune system to copy many lymphocytes (B and T white blood cells) that can recognize and attack any pathogen with the specific protein marker.

Why can't your body just do this to fight the real pathogens when they really attack? They do, but the difference between beating a virulent pathogen and falling prey to it is simply a matter of timing.
Having once been introduced to what the immune system "thinks" is the pathogen, the body creates "Memory" B and T cells. The process of recognition, proliferation, and attack by the immune system would normally take about two weeks, which would often be too late. By having the memory B and T cells immediately always ready on standby, your body can now beat the polio, measles, or other virus before it gets very far. Vaccination is the boy scout of medicine: it does nothing directly to fight or kill any bacteria or virus. It simply allows your body to "be prepared" for the future.

Because the success of a vaccination is dependent on the body's ability to respond to the vaccine and create functional "memory lymphocytes," people with poorly-functioning immune systems (whether due to a congenital deficiency, uncontrolled HIV, certain leukemias, etc.) are non-responsive (or much less responsive) to vaccination. In other words, their white blood cells will be "underenthused," when meeting the "antigen," or specific protein marker, presented by the vaccine for the first time, and their bodies will not create the memory cells ready to respond quickly to the actual attack.

Thus, theoretically, if a non-vaccinated child exposes a pathogen to an immunosuppressed child, then this can no longer be considered "commensalism." The non-vaccinated child (well, his parents) caused others unecessary harm. I do not know how common this possibility is; it may have a very low incidence, and therefore have little practical relevance. If, however, many parents suddenly decided not to vaccinate their children, the incidence would surely increase, could cause major harm to immunocompromised people.

Would this be considered parasitism? The non-vaccinators injured others because of their decision. Then again, they didn't actually injure the same people from whom they extracted benefit. In fact, the non-vaccinators presumably contracted and suffered from the illness, and did not benefit from herd immunity, altogether. However, they still affected others. A world of inusfficient communal vaccination is most dangerous to those for which vaccination is not an option.

Should we force people to vaccinate their children?
On the one hand, I don't believe in forcing people to do much of anything. Also, because of herd immunity, not every one actually requires vaccination, provided that the non-vaccinated children are roughly randomly distributed in the population, and don't live in vulnerable pockets.

On the other hand, while adults can do what they want, parents are required to provide minimum care for their children (not just caring as an emotion, which I'm sure people like Jenny McCarthy possess. Intentions don't always count). Additionally, as explained above, non-vaccinated children are in a position to potentially harm others. Perhaps we should consider this a "tort" issue. That way, parents could do what they want, but must understand that they are responsible (i.e. can be sued) if this decision negatively impacts others.
Even this presents its own complications. Unlike a "slip and fall" or medical malpractice, it is very difficult to determine who directly caused an immunosuppressed person to contract an illness. It could be anyone with whom she came into contact. Additionally, this contention raises the question: Do immunosuppressed have any personal responsibility to avoid place in she might contract a dangerous illness?

I suppose the only good strategy to avoid these problems is to maintain good education and PR about the benefits of vaccination.

I think some of these benefits are plainly apparent through the following charts:

TEN PRINCIPAL CAUSES OF DEATH IN MASSACHUSETTS - 1900
1. CARDIOVASCULAR-RENAL DISEASES
2. INFLUENZA & PNEUMONIA
3. TUBERCULOSIS
4. GASTROENTERITIS
5. MALIGNANT NEOPLASMS
6. DIPHTHERIA
7. TYPHOID & PARATYPHOID
8. MEASLES
9. WHOOPING COUGH
10. SYPHILIS

TEN PRINCIPAL CAUSES OF DEATH IN United States - 2005
1. HEART DISEASES
2. CANCER
3. CEREBROVASCULAR DISEASES
4. CHRONIC LOWER RESPIRATORY DISEASES
5. ACCIDENTS (UNINTENTIONAL INJURIES)
6. DIABETES MELLITUS
7. ALZHEIMER’S DISEASE
8. INFLUENZA & PNEUMONIA
9. NEPHRITIS, NEPHROTIC SYN. & NEPHROSIS
10. SEPTICEMIA
Sources:
1900 Massachusetts data was obtained from one of my pathology lecture notes handouts. I can ask my instructor for the specific source, for anyone who is interested. 2005 U.S. Mortality Data taken from National Center for Health Statistics, Centers for Disease Control and
Prevention, 2008.