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We’ve written a lot about anti-vaccine zealotry on this blog, as Steve and I take a particular interest in this particular form of dangerous pseudoscience for a number of reasons. One reason, of course, is that the activities of antivaccine groups like Generation Rescue and its spokesmodel since 2007 (Jenny McCarthy, a frequent topic on this blog) have started to frighten parents about vaccines enough that vaccination rates are falling well below that required for herd immunity in some parts of the country. Indeed, McCarthy, at the behest of her handlers in Generation Rescue, serves up a regular “toxic” brew of misinformation and nonsense about vaccines, most recently in a video that was the subject of a post by Val Jones about her unbelievably pseudoscience-laden blather. Truly, it has to be seen to be believed. Meanwhile, Generation Rescue has sent McCarthy on a media propaganda tour for her latest antivaccine pro-quackery book and set up a misinformation-laden propaganda site called Fourteen Studies (blogged about by Steve Novella, Mark Crislip, and, of course, yours truly) in which they attack well-designed studies that have failed to confirm their pet idea that somehow, some way, vaccines must be the cause of autism. And, when their pseudoscience is criticized, the antivaccine movement has a tendency to launch vicious ad hominem attacks, as they recently did against Steve Novella and have done multiple times in the past against me.

However, there is one other consequence of the antivaccine movement, however, and it is at least as important as the public health implications of the potential dimunition of herd immunity caused by the fear mongering of groups like Generation Rescue. That consequence is the cottage industry of “biomedical” treatments to which desperate parents subject their children. Gluten-free diets, chelation therapy (which has caused deaths), hyperbaric oxygen chambers (a recent story described a child getting severely burned when one of these caught fire), autistic children have been subjected to it all. But of all the biomedical woo to which autistic children have been subjected, one form of woo stands out as being particularly heinous. Indeed, I agree with our fearless leader Steve in characterizing it as an “atrocity.”

I’m referring to Mark and David Geier’s favored “treatment” for autistic children, namely a drug called Lupron.



THE LUPRON PROTOCOL

I first became interested in Mark and David Geier around four years ago, around the same time I first became aware of and interested in the antivaccine movement.Dr. Mark Geier is a physician but has no expertise in pediatrics, endocrinology, vaccines, or autism. His son only has a bachelor’s degree in biology; yet he assists his father in his “research” and in essence helps him treat patients, despite his lack of medical training. Together, they are the Batman and Robin of autism woo (the 1960s camp version, not the updated Dark Knight version) going into battle against autism, which–surprise! surprise!–they blame on vaccines. But not just any vaccines. Oh, no. Batman and Robin–excuse me, Mark and David–were there at ground zero of the formation of the mercury militia. Together, they were at the forefront of promoting the now scientifically discredited concept that mercury in the thimerosal preservative that was in childhood vaccines until the end of 2001 causes autism and published many dubious papers arguing that mercury in vaccines caused autism.

Not that the Geiers didn’t put their own personal spin on things. Not at all. In fact, around four years ago, they conjured up a “hypothesis” (my fingers seized up as I typed that, not wanting to dignify their idiotic idea with such a scientific term) that testosterone somehow bound to mercury, making it harder to chelate. They even claimed that testosterone binds to mercury, leading to a complex that can’t pass the blood-brain barrier and keeps mercury in the body, a complex that the quackery known as chelation therapy won’t chelate (more on that later). They claimed that autistic children were really undergoing premature puberty and had too much testosterone, which was binding to mercury and somehow enhancing its toxicity. So what was their solution?

In essence, chemical castration using a powerful anti-sex hormone drug called Lupron.

The Geiers even called it their “Lupron protocol,” and a disturbing number of parents not only fell for this disturbing abuse of autistic children, but they even paid big bucks for it. Even after the revelations of what the Geiers did, I could never figure out, though, since 2006, more than three years ago, is just how. How did they manage to keep subjecting children to a treatment with science so bad that it doesn’t even qualify as junk science? And why didn’t the mainstream media ever notice, even though a small cadre of skeptical bloggers wrote about it repeatedly?

I don’t know, but I do know that finally a major newspaper noticed the Geiers, who operate a makeshift laboratory in the basement of Dr. Geier’s house, complete with a tissue culture hood. Yesterday, the Chicago Tribune ran companion stories entitled ‘Miracle drug’ called junk science and Physician team’s crusade shows cracks.

All I can say is that it’s about time.

I first learned about the Geiers’ Lupron protocol (to my horror) back in Februrary 2006, when I first read blogger Kathleen Seidel’s account of their activities. Somehow, some way, the Geiers have managed to inject autistic children with a powerful drug that suppresses sex hormone production for over three years now. How did this all get started? First, let me explain what Lupron is.

Lupron is the trade name for a drug called leuprolide acetate, a synthetic analog of a hormone known as gonadotropin releasing hormone (GnRH, a.k.a. LH-RH). After causing an initial stimulation of gonadotropin receptors by binding to them, chronic administration of Lupron inhibits gonadotropin secretion, specifically leutenizing hormone (LH) and follicle stimulating hormone (FSH). The end result is the inhibition of the synthesis of steroid hormones in the testes in men and in the ovaries in women. In men, testosterone and androgen levels fall to castrate levels, and in women estrogens are reduced to postmenopausal levels.

This is a drug that doesn’t have very many uses. Perhaps the most common use is in men with metastatic prostate cancer, because prostate cancer is an androgen-dependent tumor. Back when I was a surgical resident, such patients were treated with surgical castration. These days, they are usually put on Lupron or a similar GnRH agonist, and this treatment works quite well to suppress the growth of prostate cancer for a while. Such tumors will inevitably develop androgen-independent growth and become resistant to hormonal suppression with Lupron, but in the meantime chemical castration with Lupron can provide excellent palliation. Another use for Lupron is in women with estrogen-dependent conditions, such as endometriosis and uterine fibroids. One troubling side effect of its use in women is the onset of menopausal symptoms, often quite severe, a problem that sometimes causes women to stop taking it. The other major use of Lupron is during cycles of in vitro fertilization, in which it is used to suppress ovarian function completely in order to allow complete control of hormone levels and ovarian follicle development through the use of hormone injections. Without Lupron or similar drugs, it is very difficult to get multiple ovarian follicles to develop and mature at the same time, allowing the harvest of many eggs.

But we’re not talking about adults here. We’re talking about children. Are there any medically accepted uses of Lupron in children? Yes, but only one: Precocious puberty. Precocious puberty is defined as the onset of secondary sexual characteristics before 8 years old in girls and 9 years old in boys. It can be the result of tumors, central nervous system injury, or congenital anomalies. The package insert for Lupron emphasizes that children should not be treated with Lupron unless they meet the following criteria:

Onset of secondary sexual characteristics before age 8 in females and age 9 in males. The clinical diagnosis must be confirmed by a pubertal response to GnRH (adequate secretion of LH in response to a challenge with injected GnRH) and bone age advanced at least one year beyond chronological age. Baseline evaluation has to include: Height and weight measurements; sex steroid levels; adrenal steroid level to rule out congenital adrenal hyperplasia; beta-chorionic gonadotropin (beta-HCG) to rule out a beta-HCG-secreting tumor; pelvic and adrenal ultrasound to rule out a steroid-secreting tumor; and a CT of the head to rule out an intracranial tumor.

Also, precocious puberty is a rare condition. Autism is not. Not that that that stops the Geiers. In any case, in my book, if you’re going to give a potent drug like Lupron to children, a drug that can almost completely shut down the synthesis of both male and female steroid hormones, you’d better have damned good evidence that it’s likely to help to make it worth the risk.

So did the Geiers have good evidence three or four years ago, when they first started pumping autistic children full of Lupron? Take a guess. As pointed out by Kathleen Seidel, the Geiers seemed quite excited about manipulating testosterone levels and were recruiting children for a “clinical trial,” having presented their concept in 2005 at the Autism One conference in Chicago. Prior to that, they had published their idea in a medical journal known as Medical Hypotheses, giving it the patina of respectability. The problem is, Medical Hypotheses is a fringe journal that is not well respected. For one thing, it’s not peer-reviewed. The other reason that it exists to publish “radical” ideas that “conflict with current theory and practice.” Such a speculative journal may serve a useful purpose in the publishing world, but citing speculative articles published in it is not exactly good evidence for anything, other than that

Not surprisingly, the paper was a mess, full of unsupported speculation. Its first flaw was apparent right from the beginning. First, the Geiers implicitly assumed that mercury is the cause of autism and that chelation is the cure. As evidence, they cited the usual suspects, such as the Hornig “rain mouse” study; the Redwood et al study using a model to predict the hair level of mercury due to vaccines (while ignoring the Pichichero et al, which actually measured the levels and showed that mercury levels in infants given thimerosal-containing vaccines according to a standard schedule had blood levels well within what is considered safe); papers studying cultured cells treated with ridiculously high concentrations of thimerosal, concentrations unattainable in humans; and the infamous Boyd Haley study that showed lower levels of mercury in the hair of autistic babies compared to normals, leading him to speculate without evidence that autistics do not secrete mercury as well, leading it to accumulate in the brain. They also cited the Bradstreet article that looked at mercury levels excreted in response to a “challenge” with the chelating agent DMSA and supposedly found that autistic children secrete more mercury than nonautistic children. The problem was, Bradstreet used a nonstandard method of normalizing their mercury concentrations in the urine, didn’t measure total mercury excretion, not to mention that they didn’t match the ages of their groups very well. Worse, their data was so full of scatter that it’s hard to tell how they made any conclusions. (Not surprisingly, this article was published in the Journal of American Physicians and Surgeons, a really crappy journal that’s chock full of antivaccination rhetoric, antifluoridation articles, and an article defending Alan Yurko, an antivaccination activist who was tried for shaking a baby to death but got off by claiming it was the result of vaccines causing encephalitis. Many of the rest of the articles cited had been written by the Geiers themselves, and they ignored important studies that cast serious doubt on any link between mercury and autism. Worse, through it all, the Geiers stated as fact that chelation therapy is effective, when there is in fact no credible evidence suggesting that it is.

As I’ve mentioned before, however, the new twist that the Geiers placed on their mercury madness is the concept that testosterone somehow increases the toxicity of mercury. The way the Geiers came to this concept is rather roundabout. First they cite a paper suggesting that there are increased markers of increased oxidative stress in autistic patients. (To me this begs the question of why there was so much focus on mercury rather than abnormalities in oxidative metabolism in autism. Since then, there has been a lot of such work that has been used to justify all manner of antioxidants and other dietary manipulations. But I digress.) They also presented a paper in which the investigators treated cultured neuroblastoma and glioblastoma tumor cells with high concentrations of thimerosal and show that pretreatment with glutathione (an antioxidant) is protective against thimerosal toxicity. However, the authors themselves state:

Acute high dose exposures to Thimerosal (mmol/L) in cultured cells were used to study mechanistic aspects of Thimerosal toxicity and not intended to mimic exposures of developing brain cells in vivo to Thimerosal in vaccines (nmol/kg).

Little details like that never stopped the Geiers from representing the study as strong “evidence” that defects in oxidative metabolism potentiate thimerosal toxicity as a cause of autism. At best the study shows that very high concentrations of thimerosal are toxic to brain cancer cells and that glutathione can protect these cells.

So how did the Geiers link oxidative metabolism defects observed in some autistics, testosterone, and mercury? Well, if you’re the Geiers, it’s easy. You wave your hands and point out that one of the one enzyme (hydroxysteroid transferase) that modifies a testosterone precursor DHEA to DHEA-S (a sulfate group added) requires glutathione and is inhibited by mercury. Of course the Geiers cite a 30-year old paper and don’t even use the name of the enzyme that I find in the more recent literature, namely DHEA sulfotransferase. In any case, DHEA is the main precursor to androgens like testosterone, and DHEA sulfotransferase adds a sulfate group to it, “shuttling” DHEA away from the pathway to make testosterone by turning it into DHEA-S. DHEA-S is thought to be a “storage” form of DHEA, and DHEA and DHEA-S are freely interconverable. If something prevents DHEA from being converted to DHEA-S, there’s more precursor for testosterone synthesis. Elevated DHEA and DHEA-S levels have been implicated in polycystic ovary syndrome.

This all sounds well and good, but there was no good evidence then that any of this, at least as explained by the Geiers, has anything to do with the pathogenesis of autism, nor is there any evidence now that it does. The abnormalities in oxidative metabolism observed in some autistics may be a cause of autism or they may simply be a consequence of other genetic abnormalities that are responsible for autism. It is not yet possible to know their significance with the current state of our data, but that hasn’t stopped the Geiers from mining this rich vein for pesudoscientific justifications for their Lupron protocol over the last four years.

But if you really want to know how risibly bad the Geiers’ understanding of biochemistry is, consider the “testosterone sheet” nonsense they laid down three years ago, when they were quoted as saying that mercury binds to testosterone and forms “sheets” in the brain, leading to a complex that can’t pass the blood-brain barrier and keeps mercury in the body. This is indeed nonsense on many levels. Besides the fact that there is no persuasive evidence that mercury causes autism in the first place, there is even less evidence that testosterone in any way prevents the elimination of mercury from the body. I can’t help but note that the claim that testosterone binds mercury and prevents it from being excreted was not in the Medical Hypotheses paper, suggesting that it was too far out even for that far out journal. Instead, the Geiers included large figures showing complex pathways of steroid biosynthesis and wildly speculated that the combination of testosterone and decreased glutathione might inhibit the activity of DHEA sulfotransferase. Thus even if mercury were the cause of autism, there would be no biochemical justification for the shotgun approach of using Lupron to suppress steroid hormone synthesis in boys. Remember, Lupron doesn’t just suppress testosterone production; it suppresses both the androgenic and estrogenic pathways.

The Geiers have also liked to cite a paper they published in Hormone Research. The Chicago Tribune article quite nicely pointed out what garbage it was:

To support their theory that a link exists between testosterone, mercury and autism, the Geiers often cite their own paper published in the journal Hormone Research. Their report describes symptoms and lab results for 16 autistic children ages 3 to 10 and finds nearly all have high testosterone. Experts who read the paper said it is deeply flawed and its conclusions are baseless. The blood tests the Geiers use as proof of excessive testosterone don’t show that at all, and other data they cite mean nothing, said Paul Kaplowitz, chief of endocrinology at Children’s National Medical Center in Washington, D.C., and an expert on precocious puberty. They also leave out test results that could help show whether the children are in early puberty, he added. Looking at the tests, Kaplowitz said he asks himself: “Is Dr. Geier just misinformed and he hasn’t studied endocrinology, or is he trying to mislead?”

Another deconstruction of the paper can be found here.

Once again, if you’re going to propose doing something as radical as shutting down steroid hormone synthesis in children, you’d better have damned good evidence to justify it, and the Geiers didn’t then and don’t now. The best piece of clinical evidence that suppressing testosterone might help autistic boys they can muster is a case report in which a 24-year old autistic man exhibiting severe frequent inappropriate sexual behavior who frequently masturbated in public and became sexually aroused around young children was placed on Lupron. Surprise, surprise! His inappropriate sexual behavior decreased markedly. Chemical castration will do that. This case report said nothing about what treating children with Lupron would do. (It also raised some seriously touchy ethical questions.)

It isn’t that there hasn’t been at least some evidence suggesting that abnormal testosterone levels might have something to do autism. Certainly, the high proponderance of males with autism alone could suggest such a linkage. There’s just one problem. Nearly all of the evidence supporting such this link has correlated high levels of prenatal exposure of the fetus to testosterone with autism and autism spectrum disorders. The main proponent of this hypothesis is Simon Baron-Cohen, who has published several papers finding correlations between elevated fetal testosterone and empathy, decreased quality of social relations, gender-typed play, and autism. This has led to Baron-Cohen’s concept that autism is due to an “extreme male brain.” This is a controversial concept in the autism research community, and I can see why. Personally, I found the evidence supporting this concept to be a somwhat shaky after reading several papers describing it. Even so, the concept is probably worth further study. Of course, none of Baron-Cohen’s data provides any real support for the Geiers’ concept that lowering testosterone will help autistics. Nearly all of the evidence implicating testosterone in autism pathogenesis come from correlations with prenatal testosterone levels and markers for high prenatal levels of testosterone. Presumably, treating children several years after birthwould be too late; the brain has already been largely shaped by the prenatal testosterone.

THE CHICAGO TRIBUNE NOTICES THE GEIERS

I had first got wind through some of my online sources that the Tribune might be doing a story on the Geiers a couple of weeks ago. I was skeptical, but apparently the inciting event was the yearly autism quackfest known as Autism One held in Chicago every Memorial Day week. Mark and David Geier be spoke there this year, as they have most years in the recent past. For those not familiar with Autism One, it’s best described as an autism Quackapalooza. Chelation, hyperbaric oxygen, “biomedical” interventions, gluten-free diets, every form of autism woo and quackery that you can imagine is there, all under one roof. But, above, all there is the antivaccine movement. As long as it’s antivaccine, it’s all good, and every luminary of the antivaccine movement, including most of the crew of Age of Autism will be there, probably Tweeting and blogging away. Heck, Jenny McCarthy herself was the keynote speaker in 2009, just as she was in 2008.

Moreover, quackfest that Autism One is, the organizers don’t in the least like skeptics or those who don’t buy into the claim that vaccines cause autism to be there. They don’t like it at all. Indeed, one such skeptical blogger, despite remaining polite but firm in his questions, was expelled last year on a trumped up excuse. Indeed, the irony of the timing, so hot on the heels of Ben Stein’s anti-evolution documentary Expelled!, was not lost on those of us who have corresponded with this particular blogger. This time around, not surprisingly Autism One organizers took measures to prevent skeptics from infiltrating and most especially to prevent anyone not associated with Autism One from videotaping or recording, but what are they going to do if the Trib decides to send reporters?

Be that as it may, I like the chorus of strongly condemning quotes from real scientists studying autism:

Four of the world’s top pediatric endocrinologists told the Tribune that the Lupron protocol is baseless, supported only by junk science. More than two dozen prominent endocrinologists dismissed the treatment earlier this year in a paper published online by the journal Pediatrics. Simon Baron-Cohen, a professor of developmental psychopathology at the University of Cambridge in England and director of the Autism Research Center in Cambridge, said it is irresponsible to treat autistic children with Lupron. “The idea of using it with vulnerable children with autism, who do not have a life-threatening disease and pose no danger to anyone, without a careful trial to determine the unwanted side effects or indeed any benefits, fills me with horror,” he said. Experts in childhood hormones warn that Lupron can disrupt normal development, interfering with natural puberty and potentially putting children’s heart and bones at risk. The treatment also means subjecting children to daily injections, including painful shots deep into muscle every other week.

And:

Specialists in autism, hormones and pharmacology who are familiar with the Geiers’ protocol said it cannot work as they suggest. “In terms of science, there is nothing suggesting the most basic elements of what they are talking about,” said Tom Owley, director of the Neurodevelopmental Pharmacology Clinic at the University of Illinois at Chicago and a specialist in the treatment of autistic children with medicine. “That there are high levels of mercury in autism — not proven! That they have precocious puberty — not proven!”

I shared Dr. Baron-Cohen’s horror three years ago. So did Kathleen Seidel. So did a number of other bloggers. I didn’t really know, though, just how much money this protocol sucks out of desperate and gullible parents. I knew Lupron is an expensive drug and that insurance won’t pay for it for autism. That’s exactly why, as Kathleen put it, the Geiers found a way to label virtually every child they used the drug on as having “precocious puberty,” even though by definition any girl older than 8 or boy older than 9 cannot have precocious puberty. That doesn’t stop the Geiers from this:

To treat an autistic child, the Geiers order $12,000 in lab tests, more than 50 in all. Some measure hormone levels. If at least one testosterone-related level falls outside the lab’s reference range, the Geiers consider beginning injections of Lupron. The daily dose is 10 times the amount American doctors use to treat precocious puberty. By lowering testosterone, the Geiers said, the drug eliminates unwanted testosterone-related behaviors, such as aggression and masturbation. They recommend starting kids on Lupron as young as possible and say some may need the drug through the age of puberty and into adulthood. The cost of the Lupron therapy is $5,000 to $6,000 a month, which health plans cover, Mark Geier said. However, two families told the Tribune that they had trouble getting insurance to pay for the treatment.

This is big bucks. Seriously big bucks. It’s also possibly insurance fraud, because the Geiers claim precocious puberty but in fact are using Lupron to treat autism. Indeed, the way the Geiers do their testing is all but guaranteed to produce in most children the “desired” diagnosis. The reason has to do with multiple lab values. The “normal” range of lab values, by definition, is designed so that 95% of “normal” patients will fall within that range. That means, for any “normal” child and any single given laboratory test, there is by random chance alone a 5% chance that his or her lab value will fall outside the “normal” range. 5% of 50 tests would mean that the average child would be likely to have 2.5 (or, given that these are whole numbers) between 2-3 lab values that fall outside the normal range. And–presto!–that will mean that they have “precocious puberty” and need the Geiers’ Lupron protocol. It’s all bogus (word choice intentional)

In fact, it’s so bad that the antivaccine propaganda blog Age of Autism actually–to my shock!–allowed a post that was critical of the Lupron protocol:

It is of great concern that studies on testosterone and autism are being misinterpreted, leading to the use of therapies aimed at disturbing steroid hormone production in individuals with autism. Currently, many autistic children may be being treated, without proof of safety and scientific and medical evidence of benefit, with a view to reducing their hormonal secretion of testosterone (Lupron Therapy, Spironolactone). The rationale behind advocating these therapies appears to be based on a misunderstanding of autistic behaviours and without systematic laboratory evidence of abnormal testosterone levels.

Word to Mark and David Geier: When the antivaccine cranks at Age of Autism starts attacking you (even if they don’t do it by name and they draft an outsider to write the post), your credibility is seriously shot. So how do the Geiers defend themselves against all these scientists criticizing them? You guessed it! A panoply of the usual excuses used by purveyors of pseudoscience:

Don’t knock it till you’ve tried it: Mark Geier responded that these are “opinions by people who don’t know what they are talking about,” saying the pediatric endocrinologists interviewed by the Tribune don’t treat autistic children and have not tried the Lupron treatment.

Mark Geier responded that these are “opinions by people who don’t know what they are talking about,” saying the pediatric endocrinologists interviewed by the Tribune don’t treat autistic children and have not tried the Lupron treatment. Misrepresenting the work of real scientists: David Geier said prominent scientists support their work and gave as an example Baron-Cohen, the autism expert who told the Tribune that the Geiers’ Lupron treatment filled him with horror.

David Geier said prominent scientists support their work and gave as an example Baron-Cohen, the autism expert who told the Tribune that the Geiers’ Lupron treatment filled him with horror. Conspiracy theories: The Geiers also say mainstream medicine condemns them because of their vocal stance that pediatricians, health officials and drug companies are covering up the link between vaccines and autism. “Nobody likes a whistle-blower,” Mark Geier said in an interview.

The Geiers also say mainstream medicine condemns them because of their vocal stance that pediatricians, health officials and drug companies are covering up the link between vaccines and autism. “Nobody likes a whistle-blower,” Mark Geier said in an interview. The pharma gambit: The Geiers are not dissuaded by the criticism. Mark Geier said the courts are biased against him and that the medical establishment is more concerned about preserving drug companies’ profits than about protecting children. “There’s no question this will turn out to be true,” Mark Geier said in an interview, referring to the vaccine-autism connection.

And, most despicable of all, the Geiers demonize the very autistic teens upon whom they are plying their quackery:

“With masturbating there is a degree of normal, and then there is autism. Parents will say: ‘He will hump pillows, he will hump your leg,’ ” David Geier told doctors at Eisenstein’s office. He made similar statements on the same visit to about 60 parents of autistic children. In an autistic teenager, high testosterone will lead to dangerous aggression, Mark Geier said, mentioning an autistic Ohio teen accused of killing his mother. “They are incredibly strong. They can hurt you,” he said. “You have to respect that these kids are on massive testosterone.” Autistic children with high testosterone are heading down an ominous path, the Geiers said, and likely will end up hooked on psychiatric drugs, institutionalized or jailed.

This is nonsense. Even worse, it’s pernicious nonsense. Unfortunately, it’s exactly the same sort of pernicious nonsense they’ve been pushing since four years ago, when they published their “case report” of the autistic child whose inappropriate sexual behavior abated after he was dosed with Lupron.

Of course, the parents of Geiers’ patients are largely self-selected to believe the woo and have a serious incentive, after sinking thousands of dollars into it, to believe it’s working. And they do provide testomonials, a couple of which were included in the Trib story. It wouldn’t even surprise me if some of them are true. If you shut down a child or teen’s testosterone production, they will likely become more docile and have a decreased sex drive. That doesn’t mean the drug is doing anything at all for the teen’s autistic symptoms or to improve their neurocognitive functioning. Indeed, it could be doing great harm to the child. While Lupron may not be too risky for prepubertal children, giving it to teens can “put puberty on hold,” as one scientist put it, calling it “chemical castration”:

Said Kaplowitz: “You can lower sex drive, yes, but are you going to do that for every autistic [teenage] boy, do a medical castration? … For a year? For their lives?” Neither Eisenstein nor the Geiers dispute that what they are doing amounts to chemical castration. Speaking about one teen he put on the drug, Mark Geier said: “I wasn’t worried about whether he would have children when he is 25 years old. If you want to call it a nasty name, call it chemical castration. If you want to call it something nice, say you are lowering testosterone.”

Karl Rove would be proud of Dr. Geier.

In a companion article, another aspect of the Lupron protocol is deconstructed:

Abbott Laboratories, which sells Lupron in the U.S., once applied for a patent with the Geiers through a now-defunct joint venture with another drug company, yet never pursued work with them. A spokeswoman for the North Chicago-based company said there was no scientific evidence to justify further research.

When a pharmaceutical company decides it isn’t interested in pursuing a potentially lucrative new indication for one of its drugs, you know you’re deep into pseudoscience. I will say, though, that Abbott Laboratories should be ashamed of itself. Until now, it has been winking and nodding at the use its product is being put to, even though its scientists know there is no scientific justification for it. Of course, the Geiers had already tried to patent their Lupron protocol once, because, of course, they’re doing this all out of the goodness of their hearts.

Not:

The Geiers’ first Lupron patient, a Virginia boy with severe autism who is now 13, started the treatment about four years ago. Since then, the Geiers have opened eight clinics in six states, including one in Springfield and their arrangement with Eisenstein, which he described as a “franchise” of sorts. “We plan to open everywhere,” Mark Geier said in February at Eisenstein’s office. “I am going to treat as many as I can.” Some of the Geiers’ clinics are headed by doctors; a psychiatrist runs the Springfield clinic. But that is not always the case. The clinic in Indianapolis is run by an X-ray technologist who has an autistic child. In Washington state, the head is a health advocate and documentary filmmaker.

I can’t help but ask: How do the Geiers get away with it? These people whom they’ve hired to run their other clinics are not physicians. They are clearly practicing medicine without a license!

WHAT THE TRIBUNE MISSED

There were only two deficiencies in these articles. The first one almost goes without saying in stories of this type. There was too much of the usual “tell both sides” journalistic construction, in which testimonials were given far more weight than they deserved and the Geiers were extensively quoted. I’ve given up expecting anything other than that from journalists. The other deficiency is that there was no mention of how the Geiers played fast and loose with human research protections in order to ply their quackery. There was no report at all of this in the Trib’s article.

What do I mean? In essence, the Geiers formed their own Institutional Review Board (IRB) to review their own studies and thereby get around federal regulations over human subjects research. The IRB is usually reported as being from an entity formed by the Geiers listed as The Institute for Chronic Illnesses. As Kathleen Seidel first reported, it’s an elusive institute whose address is the same as that of Dr. Mark Geier’s home residence. (It also has a lovely tennis court.) But, elusive or not, The Institute for Chronic Illnesses does have its own IRB, and that IRB is actually registered with the federal government. Leave it to Kathleen’s tenacity to track down through a Freedom of Information Act request some information on this particular IRB. What she found is very disturbing indeed.

In order for you to understand why what Kathleen discovered is so disturbing, a word is in order about just what an IRB is and does (or should be and is supposed to do). I’ve written about the international treaties and U.S. law regulating human subjects before, but not in detail about what IRBs are and do. After the horrors of Nazi medical experimentation and the abuses during the Tuskegee syphilis study right here in the good ol’ USA, it was clear that rules were needed to protect human research subjects from such abuses. A historic document in the development of such rules in the U.S. was the Belmont Report on Ethical Principles and Guidelines for the Protection of Human Subjects of Research finalized on April 18, 1979. This report identifies three essential and fundamental ethical principles for human subject research (respect for persons, beneficence, and justice) that form the basis of all Department of Health and Human Services human subject protection regulations to this day. It is essential reading for anyone doing human subject research in this country. In 1991, these regulations were codified into what is now known as The Common Rule. All institutions doing federally funded research are required to adhere to The Common Rule. Moreover, some states, such as Maryland (where the Geiers have their businesses) require that all human research, regardless of funding source, must conform to the Common Rule.

A key aspect of The Common Rule is the IRB. The IRB is in essence a committee that oversees all human subject research for an institution and makes sure that the studies are ethical in design and that they conform to all federal regulations. Basically, IRBs are charged with weighing the risks and benefits of proposed human subject research and making sure that (1) the risks are minimized and that the risk:benefit ratio is very favorable; (2) to minimize any pain or suffering that might come about because of the experimental therapy; and (3) to make sure that researchers obtain truly informed consent. Once a study is in progress, regular reports must be made to the IRB, which can shut down any study in its institution if it has concerns about patient welfare. Indeed, the IRB at my particular institution is like a bulldog; it’s utterly ruthless in how it deals with researchers. The same is the case at most institutions that receive significant federal funding, and these are the criteria for approving a study:

(a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied: (1) Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes. (2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility. (3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons. (4) Informed consent will be sought from each prospective subject or the subject’s legally authorized representative, in accordance with, and to the extent required by 46.116. (5) Informed consent will be appropriately documented, in accordance with, and to the extent required by 46.117. (6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects. (7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. (b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

It sounds pretty clear-cut. And, from discussing studies with members of different IRBs, I know that good IRBs take the above guidelines very seriously, almost always erring on the side of being more protective of human subjects. (If you’re interested in learning more about federal human subject research guidelines, check out this course.) Now here’s where it gets even more interesting. The membership of an IRB must be at least five persons according to these guidelines:

a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects. (b) Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution’s consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession. (c) Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.

Well, guess who was on the IRB of the Institute for Chronic Illnesses at the time of their seminal “studies” on testosterone and autism (and, as far as I know, are still on the ICI IRB)? If you’ve clicked on the link to Kathleen’s article you already know, but for those who haven’t done so yet (or who don’t believe in clicking on links), now’s a good time to do so:

Mark Geier, Chair

Affiliated Scientist; MD, PhD; Genetics David Geier

Affiliated Scientist; BA; Biochemistry Lisa Sykes

Unaffiliated Non-Scientist; MA; Clergy (Rev. Sykes is a Richmond, Virginia Methodist minister, anti-thimerosal activist, and mother of a participant in Dr. Geier’s study. The clinical data for Patient #1 in the Hormone Research article is identical to data from her son’s medical records, which were displayed at the 2005 and 2006 Autism One conferences.) Kelly Kerns

Unaffiliated Scientist; RDH; Dentistry (Mrs. Kerns is a Lenexa, Kansas dental hygienist, anti-thimerosal activist, and petitioner in vaccine injury complaints for each of her three autistic children.) John Young

Unaffiliated Scientist; MD; OB-GYN, Genetics (Dr. Young is Dr. Geier’s business partner in Genetic Consultants of Maryland and Genetic Consultants of Virginia; he, Dr. Geier and various business entities were codefendants in a 1994 medical malpractice lawsuit.) Anne Geier

Affiliated Scientist; BS; Educator (Mrs. Geier is wife of Dr. Mark Geier and mother of David Geier. She is a ranking member of the U.S. Tennis Association.) Clifford Shoemaker

Affiliated Non-Scientist; JD; Legal (Mr. Shoemaker is a vaccine injury lawyer, a member of the Vaccine Injury Alliance, and a member of the Omnibus Autism Proceeding Petitioners’ Steering Committee. Dr. Geier has testified on behalf of his clients in Price v. Wyeth et al, Platt v. HHS, Jenkins v. HHS, Lewis v. HHS, Raj vs. HHS, Jefferies v. HHS, and other cases.)

Notice how conveniently every single member of this IRB was either one of the Geiers, an anti-thimerosal activist, a Geier associate, or a lawyer suing on behalf of “vaccine-injured” clients. Anyone want to make a bet about how closely they adhere to the guidelines for human research listed above? It almost doesn’t matter anyway because, as Kathleen pointed out, besides the fact that none of the members of this IRB has any expertise in endocrinology, Mark and David Geier would not be eligible to debate or vote on their own protocols anyway; having them on the IRB is utterly unethical and almost certainly illegal. Ditto Anne Geier, who wouldn’t be eligible to vote because of her relationship to Mark and David, and Lisa Sykes, who wouldn’t be eligible to vote if her child is to be a subject in the research protocol being reviewed. And does anyone really think that any of the other members of this particular IRB has research subject protection as his or her overriding concern?

But it didn’t end there. If the FOIA information that Kathleen has obtained is complete, then it looks as though the research reported under the auspices of this IRB was done before the IRB of The Institute for Chronic Illnesses was even registered with the federal government. It is hard not to strongly suspect that the Geiers were told by someone while submitting their paper that human subjects research had to be approved by an IRB and that no reputable journal would publish such research without a statement to the effect that the research encompassed in the manuscript had been approved by an IRB.

CONCLUSION

After having watched with frustration for over three years how the Geiers have managed not only to continue to subject autistic children to, in essence, chemical castration and have large numbers of parents sufficiently desperate or sufficiently believing in “alternative” medicine that they are willing to pay the Geiers big bucks to submit their children to their “protocol,” I am gratified that the Chicago Tribune did this investigation and wrote this study. True, the reporters didn’t uncover the chicanery the Geiers have been demonstrating for years with the dubious IRB, and I can’t help but be a bit disturbed at this because, as a clinical researcher, I try very hard to hew to the rules and law governing human subjects research and conduct such research ethically.

The Geiers’ saga, in fact, demonstrates a number of things. First, there is the utter lack of medical ethics that would allow them to inject autistic children with a powerful anti-androgen and anti-estrogen drug based on a concept as easy to demonstrate to be without scientific foundation as mercury being bound up in “testosterone sheets.” But more importantly, there is the issue of how on earth our laws and regulations could be so lax that the Geiers could get around them by creating a dubious “Institute,” creating an equally dubious IRB, and then stacking that IRB with true believers and cronies, among them the principal investigator of all of the Geiers’ “studies,” Dr. Mark Geier himself.

The price of antivaccine lunacy is steep and getting steeper. In addition to decreasing herd immunity and endangering those who do not subscribe to their toxic mix of paranoid conspiracy theories and pseudoscience, antivaccine zealots like the Geiers have managed to make a mockery of our system of human subjects protection. Above, all, however, autistic children pay the price for the current antivaccine madness sweeping through our country.

I just hope that the media will increasingly notice. Shining the light of day on this quackery and egregious flouting of human subjects protections is the only chance these children have to be spared from such atrocities.