Letter to Neuroendocrinology Letters · May 1, 03:15 PM


Significant Misrepresentations
Mark Geier, David Geier & the Evolution of the Lupron Protocol
(Part Fourteen) • Related articles
Concerns About the “Institute for Chronic Illnesses” & Its Research on Autistic Children

1 May 2007

To the Editorial Board of Neuroendocrinology Letters:

I am writing to call your attention to numerous irregularities in the research described in, A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders, by Dr. Mark Geier and Mr. David Geier (Neuroendocrinology Letters, December 27, 2006, pp. 833-8). In my opinion, these irregularities warrant consideration of retraction of the paper in its entirety. My concerns include:

A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders is the fifth in a series of published reports of ongoing research on autistic children purportedly sponsored by the “Institute for/of Chronic Illnesses,” with ethical review purportedly conducted by its in-house Institutional Review Board (IRB). The issues I raise, therefore, demand the personal attention and judgment not only of Neuroendocrinology Letters‘ Editorial Board, but also of the Editorial Boards of other scientific journals that have published Dr. and Mr. Geier’s recent papers. These papers include:

Geier DA, Geier MR. A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders. Hormone Research, July 5, 2006.
Geier DA, Geier MR. A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States. Neuroendocrinology Letters, August 27, 2006.
Geier DA, Geier MR. A prospective assessment of porphyrins in autistic disorders: a potential marker for heavy metal exposure. Neurotoxicity Research, August 10, 2006.
Geier DA, Geier MR. The biochemical basis and treatment of autism: Interactions between mercury, transsulfuration, and androgens. Autoimmunity Reviews, in-press uncorrected proof published online 27 October 2006; subsequently retracted with minimal explanation by the journal.
Geier DA, Geier MR. A case series of children with apparent mercury toxic encephalopathies manifesting with clinical symptoms of regressive autistic disorders. Journal of Toxicology & Environmental Health, May 15, 2007.

I am therefore copying this letter to the editors and Editorial Board members of Hormone Research and its publisher, S. Karger A.G.; Neurotoxicity Research and F.P. Graham Publishing; Autoimmunity Reviews and its publisher, Elsevier; the Journal of Toxicology & Environmental Health and its publisher, Taylor and Francis; the International Council of Medical Journal Editors, the National Library of Medicine, the Committee on Publication Ethics, the International Association of Scientific, Technical & Medical Publishers, the University of Pennsylvania Center for Bioethics, and Citizens for Responsible Care and Research (CIRCARE).

In order to properly critique Dr. and Mr. Geier’s paper, one must understand the context in which the “Lupron Protocol” has arisen. This letter is therefore considerably longer than the article that inspired it. Many of the observations that follow will be very similar to those in Significant Misrepresentations: Mark Geier, David Geier and the Evolution of the Lupron Protocol, a series of essays and letters that I have written over the past year.

Undeclared conflicts of interest

In their conflict of interest statement Dr. and Mr. Geier acknowledge their status as consultants in cases before the National Vaccine Injury Compensation Program (NVICP) and in civil litigation (p. 833). However, they do not disclose how many of their research subjects are or have been parties to these cases.

The mother of Patient #1 in Dr. and Mr. Geier’s study, Rev. Lisa Sykes, has made public presentations and given interviews about her son’s participation in their research, and also serves on the Institutional Review Board alleged to have approved it. Her child is the subject of the $20,000,000 product liability lawsuit, Lisa Sykes et al. v. Glaxo Smith-Kline et al. (Case 2:06-cv-01111-LS, U.S. District Court for the Eastern District of Pennsylvania), in which most claims against the defendants were recently dismissed. (The plaintiffs have appealed the decision.)

In the product liability lawsuit, Doe v. Ortho-Clinical Diagnostics (Case 1:03-cv-00669-JAB-WWD, U.S. District Court for the Middle District of North Carolina), Dr. Geier’s expert testimony was rejected by the court as unreliable, and all claims against the defendants were subsequently dismissed with prejudice. The mother of the child at the center of this case has identified him as one of Dr. and Mr. Geier’s research subjects.

I am the mother in this article [Suit lacks evidence linking mercury, autism] and I would be glad to answer any questions anybody may have about this case. (North Carolina, July 8, 2006)
[The same mother, ten days later] My son has been on the Lupron treatment for over a month now along with the DMSA. (North Carolina, July 18, 2006)

It would be particularly appropriate to determine how many other subjects in Dr. and Mr. Geier’s study are plaintiffs in vaccine-injury litigation given that their public presentations have been hosted by organizations that promote the identification of autism as vaccine injury, and champion the legal agenda of vaccine-injury plaintiffs (for example, Autism One, Autism Research Institute/Defeat Autism Now! (DAN!) and the National Autism Association).

Another research subject is the son of Dr. Geier’s office manager. From his August 2006 presentation to the U.S. Autism and Asperger Association:

My office manager has an Asperger’s who’s fourteen… We did his testing, and he had the pattern, and of course, his testosterone is much higher because he’s partway in puberty. We treated him… (Dr. Mark Geier, August 2006)

Dr. and Mr. Geier acknowledge having a “patent pending for the treatment of autistic disorders” (p. 833). In fact, their portfolio includes not one but two patent applications – one filed with the U.S. Patent and Trademark Office (USPTO), the other with the World Intellectual Property Organization (WIPO). Both pertain to the specific evaluation and treatment regimen described in this paper; the international application was filed in partnership with TAP Pharmaceuticals, manufacturer of Lupron. The authors’ economic interest in promoting the use of Lupron as an autism treatment, and their relationship with TAP Pharmaceuticals, constitutes the undeclared subtext for their capitalized display of the brand name “LUPRON®” sixteen times over six pages. This represents a record for product promotion in a supposedly scientific report by Dr. and Mr. Geier; The biochemical basis and treatment of autism: Interactions between mercury, transsulfuration, and androgens takes second place, with fourteen repetitions of “LUPRON®” over seven pages.

Inadequate disclosure of investigator affiliations and qualifications

Dr. and Mr. Geier acknowledge sponsorship by “The Institute of Chronic Illnesses” (alternately “The Institute for Chronic Illnesses”) in Silver Spring, Maryland (p. 838). David Geier is identified as Vice-President of the Institute; his father, Mark R. Geier, is identified as President of “The Genetic Centers of America, U.S.A.” (p. 833). The latter title refers to Dr. Geier’s private medical practice, which he conducts from his home and at offices in Maryland and Virginia; he is not licensed to practice medicine in any other state. In the article byline, Dr. Geier fails to disclose that he is also founder and President of the Institute of which his son is Vice-President. In the contact information, Dr. Geier’s academic degrees – an M.D. and Ph.D. – are specified; however, David Geier’s are not. By withholding this information, the authors create an inaccurate impression of Mr. Geier’s professional qualifications and independence. Partial disclosure serves to obscure the fact that the young Mr. Geier serves in a position created for him by his father; that the grandiosely-named “Institute” is a legal entity incorporated in 2005, its headquarters the Geier family’s suburban Maryland home; and that although this Institute ostensibly sponsors medical research, its Vice-President’s most advanced academic degree is a B.A. in Biology. The University of Maryland-Baltimore County advises degree candidates that their B.A. curriculum in Biology “is not appropriate for students who want to pursue a career in laboratory science, or who plan to go on to graduate, medical, or dental school.”

Papers published by Dr. and Mr. Geier prior to 2006 identify Dr. Geier as President of Genetic Centers of America, and Mr. Geier as President of MedCon, Inc. The Maryland Department of Assessments and Taxation record for this firm indicates that MedCon, Inc. is an active business established in August 1999, the year David Geier graduated from high school. However, his status as principal of this firm remains undisclosed in A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders, and is mentioned in only one published paper submitted by Dr. and Mr. Geier to a scientific journal after mid-2005.

Three papers by Dr. and Mr. Geier published in 2006 identify David Geier as a graduate student in the Department of Biochemistry of The George Washington University (GWU), inaccurately implying that their research was reviewed and/or sponsored in part by that institution:

An assessment of downward trends in neurodevelopmental disorders in the United States following removal of Thimerosal from childhood vaccines. Medical Science Monitor, June 2006
Early Downward Trends in Neurodevelopmental Disorders Following Removal of Thimerosal-Containing Vaccines. Journal of American Physicians and Surgeons, Spring 2006
An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States. Journal of Toxicology & Environmental Health, June 2006

The first paper in which they reported results from their Lupron study, A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders (Hormone Research, July 2006), originally omitted any reference to David Geier’s status as a graduate student; his affiliation statement – “Department of Biochemistry, George Washington University” – inaccurately implied that he was a member of the faculty. In May 2006, after the paper’s online publication by Hormone Research, I contacted the Department of Biochemistry and Molecular Biology at GWU to inquire about David Geier’s status there. The department chairman informed me that Mr. Geier had enrolled in the graduate biochemistry program in 2003, took two courses in that department during the 2003-2004 school year and none thereafter, and took the last of three public health courses during the Spring 2005 semester. He stated that David Geier had never served on the GWU faculty; that he was no longer enrolled in courses in his department; that neither the Institute for Chronic Illnesses or its IRB were in any way associated with GWU; and that none of the research described in the Hormone Research article was sponsored by GWU or conducted in the GWU laboratories. He described the affiliation statement in the Hormone Research article as “fallacious,” and stated that it conveyed a “significant misrepresentation” of Mr. Geier’s credentials in the field of biochemistry. Hormone Research temporarily withdrew the paper from their website, and republished it two months later, with “MedCon, Inc.” replacing “Department of Biochemistry, George Washington University” in David Geier’s institutional affiliation statement.

The revised version of the Hormone Research paper also contains a “Potential Conflict of Interest and Affiliation Statement” that had not appeared in the original version:

Dr. Mark Geier is not affiliated with MedCon, Inc. David Geier is the President of MedCon. MedCon does not have a financial interest in relation to autism and puberty. Neither Dr. Mark Geier nor David Geier has any conflict of interest regarding anything related to this paper.

In spite of this denial, a conflict of interest existed at that time with respect to the subject of the paper – Dr. and Mr. Geier’s pending application to patent the medical diagnostic process described in it. This was acknowledged by Dr. Geier in a comment he submitted to Wikipedia:

[O]ur patent has nothing to do with testosterone sheets and everything to do with what we published in Hormone Research. (Dr. Mark Geier, August 3, 2006)

Inadequate ethical review

Dr. and Mr. Geier cite approval of their study by “The IRB of the Institute for Chronic Illnesses (Office for Human Research Protections, U.S. Department of Health and Human Services IRB number: IRB00005375)” (p. 834). After encountering the first such reference to this Institute in Hormone Research, I discovered that although its IRB was registered with the Office of Human Research Protections (OHRP), the Institute had no telephone listing, no address other than the Geier home, no Maryland business or charitable organization registration, and no 501©(3) tax exemption. (In mid-2006, tax exemption was granted to the Institute, registered at attorney Clifford Shoemaker’s Vienna, Virginia address.) Neither the Maryland Board of Physicians, the Maryland State Medical Society, nor the Maryland Department of Health and Mental Hygiene had any knowledge of the Institute. According to documents which I subsequently obtained from OHRP, Dr. Geier originally submitted the IRB registration in February 2006; it was added to the OHRP database in March 2006. Registration of an IRB is a prerequisite to approval of a Federal Wide Assurance (FWA), the certification of the IRB’s ability and commitment to enforce compliance with the Common Rule (45 CFR Part 46), the federal regulations governing the protection of human research subjects. Such certification is mandatory for all IRB’s supervising federally-funded research involving human subjects, or research otherwise subject to federal oversight. Since Dr. and Mr. Geier do not receive federal funding, they are not obligated to obtain a Federal Wide Assurance, and they have never applied for or obtained one. The Maryland Code (Title 13, Section 20) and the laws of a number of other U.S. states, however, require that all research involving human subjects conform to the Common Rule, regardless of the investigators’ source of funding.

The membership of The IRB of the Institute for Chronic Illnesses consists of:

Mark Geier
David Geier
Anne Geier (Mrs. Mark Geier)
Lisa Sykes, Virginia Methodist minister, political ally, vaccine-injury plaintiff, co-author of a book with Dr. and Mr. Geier, mother of their first autistic research subject
Kelly Kerns, Kansas dental hygienist, political ally, plaintiff in three pending vaccine-injury cases
John Young, M.D., Dr. Geier’s business partner, codefendant in a 1994 malpractice lawsuit, Defeat Autism Now! practitioner
Clifford Shoemaker, vaccine-injury lawyer, associate of Dr. Geier, Omnibus Autism Proceeding Petitioners’ Steering Committee member.

Under the U.S. Common Rule (45 CFR Part 46), the IRB of the Institute for Chronic Illnesses could not have voted to approve Dr. and Mr. Geier’s research. If all conflicted members recused themselves as required, it would be impossible to achieve a quorum. Every member is either a member of the Geier family, a client, political or business associate of Dr. and Mr. Geier, or parent of a research subject. Dr. John Young’s reference to Lupron injections on his DAN! Practitioner listing places him as a co-investigator in the Dr. and Mr. Geier’s study.

In my opinion, it is unlikely that any member of the IRB of the Institute for Chronic Illnesses possesses the necessary experience and expertise, professional competence and understanding of applicable law and regulations to adequately supervise research in pediatric endocrinology, toxicology or pharmacology. According to his November 2004 .html” target=”_new”>Easter v. Aventis Pasteur (Case No. 5:03-cv-141, U.S. District Court for the Eastern District of Texas, Texarkana Division), Dr. Geier has no advanced training or professional certification in the fields of pharmacology, pharmacokinetics, toxicology, toxicokinetics, or the diagnosis and treatment of autistic children. He is board-certified in genetic counseling and no other specialty. The American Board of Medical Specialties database confirms that Dr. Young is certified by the American Board of Obstetrics and Gynecology and no other certifying board.

Although Dr. and Mr. Geier began conducting pharmaceutical experimentation on autistic children in November 2004, the Institute that supposedly reviewed and approved their study was not incorporated until September 2005, almost a year later. Its IRB was registered in March 2006 – fourteen months after their first research subject was administered his first injection of Lupron.

In light of this IRB’s apparent inability to comply with the U.S. Common Rule (45 CFR Part 46), the references in this paper to OHRP, HHS and the IRB registration number are superfluous and misleading and should have been deleted prior to publication. In my opinion, the study could also not be approved under the Declaration of Helsinki (Part B, Section 13), which requires review by an ethics committee independent of the sponsor and the investigator. Dr. and Mr. Geier’s failure to fully disclose the ethical guidelines under which their research was reviewed and approved appears to be inconsistent with the Uniform Requirements for Manuscripts Submitted to Biomedical Journals of the International Committee of Medical Journal Editors, as well as Neuroendocrinology Letters‘ own editorial policy.

Inadequate disclosure of funding sources

Dr. and Mr. Geier indicate that their research was “funded in part by the non-profit Institute for Chronic Illnesses through a grant from the Brenen Hornstein Autism Research and Education (BHARE) Foundation“ (p. 838), which now hosts a freely-available copy of A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders on its website. BHARE’s Board of Directors includes the uncle of one of Dr. and Mr. Geier’s research subjects. The child’s father has publicly discussed the fact that the costs of their investigational lab work and drugs have been almost entirely shouldered by private insurance companies, Medicaid, and the parents of research subjects, to whom the tests they order and the drugs they prescribe are represented as medically necessary.

Medi-Cal (California’s Medicaid) has been helpful picking up the portion of both the labs and the lupron that the private insurance won’t cover, co-pays, etc. I didn’t know it at the time and paid co-pays for over 1½ years. Labcorp and mail in pharmacies aren’t good about Medicaid as secondary insurance, so you have to be persistent and get a hold of someone who knows what they’re talking about, to get them to bill the remaining portion to Medicaid instead of billing you. (California, December 21, 2006)

The promise of insurance reimbursement is a significant inducement to participation in Dr. and Mr. Geier’s study.

If you wish for your child to be considered for our protocol, please call Eli at 301-989-0548 to make an appointment for an initial one hour consult with us. The consult will take a full hour and we will go over your child’s case in great detail. This can be done either over the phone or in person if you come to our offices in Rockville (near Washington, D.C.) or Owings Mills (near Baltimore) Maryland. After the consult we will order a series of laboratory tests, both blood and urine to be done on your child. These are done at a LabCorp office near you home and the cost of these is almost always completely covered by health insurance. (Attributed to Dr. Mark Geier, December 8, 2006)
I have Dr. Geier’s Phone #. I have talked to him. He is a vaccinologist and has done tons of research! He asked me if we wanted to be a part of his research w/ Dr. Mary Megson on the connection of high testosterone (percousious puberty) and how Mercury binds to it. He explains it very well. He is the only doctor who was given permission to view the CDC’s vaccination files! I am currently getting blood tests to prove High testosterone. The Lupron injections are scary to me. It will stop the production of [testosterone] for a time in order to chelate the mercury, taking no longer than a year. This can only be done before puberty. This lupron is covered by insurance! Chelation is not. I am using CaEDTA (Detoxamin) which does not require a script. Hope this helps! (Location unknown, April 15, 2005)
[the same mother, 1½ months later] My son is 9 and 5’ 1”. His bone age was 12.9. Get an Endocrinologist to do the tests to prove precocious puberty. Get the rx. for Lupron. and get your reg. pediatrician to perform the monthly shots. Then thru your Dan doctor do the chelating . I learned this thru experience. You have to piece this together myself, but it is possible. This way the insurance pays for the Lupron and follow-up blood testing. Don’t even mention you are doing the chelating. Trust me. Your Dan Dr. will do the other needed testing. (Location unknown, June 5, 2005)
We have seen Dr. Mark Geier and his son David who have ran a gamut of test on our son! One being the testosterone! Our son’s testosterone level was at the range of a 14 to 17 year old young man! Our son is only 5 years old! We have started this week on Lupron injections that will lower the testosterone levels and then we are starting tomorrow oral DMSA to help with detoxifying all these metals that are in him! […] We are excited about this… our son has been considered to have precocious puberty with these high levels and the BC/BS are paying for majority of the drug but the copay! Otherwise it would cost us approximately $7000 for the total script amount!!!! (Indiana, March 2, 2006)
[W]e will be using oral DMSA & Lupron through Dr. Geier. Both precocious puberty & mercury intoxication are ICD-9 coded diagnoses. Insurance has no choice, we’re covered. (Tennessee, April 23, 2006)
We have not gotten any bills for our phone conferences. They bill to your insurance and do not ask for anything up front, which is nice. They used reputable labs like Labcorp or Quest. So far our insurance has paid for the labs, but Labcorp has to accept the reasonable and customary since they are a preferred provider. The Lupron is very expensive but if your child has precocious puberty they should pay. It depends on your insurance I suppose. (Ohio, December 20, 2006)
We are using the Geier Treatment protocol, and we have 4 kids on the protocol, and have not yet paid for anything but a small copay. Insurance pays the doctor, labs, and meds. If your kids are younger than 18 and also have state insurance – medicaid, a lot of ASD kids do, then you probably won’t even have the small copay. I have 2 18 and older, and 2 younger. The 2 older, they copay is $3 for each med they get (which is 2) a month. (Kansas, March 28, 2007)

Inadequate substantiation of debatable claims

In the introduction to A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders, Dr. and Mr. Geier state that “researchers have reported that exposure to mercury can cause… dysfunctions similar to traits defining or associated with autistic disorders, and that these similarities extend to neuroanatomy, neurotransmitters, and biochemistry [2-4, 14]” (p. 834). The majority of the “researchers” they cite (Sallie Bernard, Heidi Roger, Lyn Redwood, Albert Enayati, and Mark Blaxill) are the parent-founders of SafeMinds, an advocacy organization whose stated mission is to “to encourage and support efforts to conduct medical research that provides credible findings to support that the mercury/autism hypothesis is true.” Co-founder Lyn Redwood is a plaintiff in vaccine-injury litigation. The organization has expended considerable energy and funds on efforts to influence legislation and public opinion in support of vaccine-injury plaintiffs, including making large payments to political lobbyists (such as BC&A Associates, paid $113,805 in 2004) and public relations firms (such as Venture Communications, paid $77,000 in 2005). Two of the SafeMinds references were published in Medical Hypotheses, a vanity journal which eschews peer review. No matter how noble its founders’ intentions might be, their public pronouncements indicate a determination to validate pre-existing conclusions about autism causation and prevail in litigation; they do not reflect an impartial attitude towards scientific evidence.

Dr. and Mr. Geier quote from E.M. Faustman et al’s Mechanisms Underlying Children’s Susceptibility to Environmental Toxicants (Environmental Health Perspectives, March 2000), regarding “potential implications” of the influence of mercury on neuronal development (p. 834). Faustman’s article is a review containing no original data; the speculative passage extracted by Dr. and Mr. Geier features its only reference to autism. In similar fashion, they cite Joachim Mutter et al’s Mercury and autism: accelerating evidence? (Neuroendocrinology Letters, October 2005), a review article and opinion piece offering no original data to support its authors’ many speculations about mercury and autism causation. One of its authors – Prof. Boyd Haley of the University of Kentucky – serves with Dr. Geier as an expert witness to plaintiffs in vaccine-injury litigation.

Dr. and Mr. Geier claim that autistic individuals have a high prevalence of premature puberty, and that they have increased levels of androgens relative to controls (p. 834). Of the three papers cited to support these assertions, only one – Sylvie Tordjman et al’s letter to the editor, Androgenic Activity in Autism (American Journal of Psychiatry, November 1997) – contains original data; the other two – Baron-Cohen et al’s Sex differences in the brain: implications for explaining autism (Science, November 4, 2005) and Dr. and Mr. Geier’s A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders (Hormone Research, July 2006) – cite Tordjman, but offer no additional original data. Closer examination of Tordjman’s study reveals that although three of the nine autistic subjects had unusually high concentrations of plasma testosterone, only one was of pre-pubertal age. This tiny study fails to demonstrate either a high incidence of precocious puberty or consistently high androgen levels in an autistic population large enough to be statistically meaningful, and provides an insufficient basis for generalizing about or conducting pharmaceutical experimentation on autistic people.

Inappropriately obscured self-citation

Dr. and Mr. Geier state that,

“It has previously been suggested as a medical hypothesis that some ASDs may result from interactions between the methionine cycle transsulfuration and androgen pathways following exposure to mercury. [10] It was suggested that children experiencing such a condition would have an elevated body-burden of heavy metals and have increased androgens. Based upon this knowledge, treatment modalities were suggested to attempt to dually lower the body-burden of heavy metals and decrease androgen levels in children with ASDs, in the hopes that addressing the steroid hormone pathways, in addition to treatments that successful lower heavy metal body burdens, would work synergistically to improve clinical outcomes [10].” (p. 834; emphasis added)

References [9] and [10] are articles written by Dr. and Mr. Geier themselves. Reference [9], The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity (Medical Hypotheses, January 2005) was submitted for publication during the same month as Dr. and Mr. Geier’s original USPTO patent application; in it, they summarized the hypotheses and treatment proposals described in the application, but did not disclose the application as a potential conflict of interest. Reference [10], A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders (Hormone Research, July 2006), contains their analysis of the results of various blood tests from sixteen children who underwent eligibility assessment for the “Lupron Protocol” study.

By using the passive voice to refer to their own hypotheses, suggestions and observations, Dr. and Mr. Geier obscure the fact that they are the only people who have ever proposed, developed, implemented or evaluated an autism treatment regimen premised upon the unsubstantiated assumption that mercury and androgens synergistically contribute to the development of autism, and that autistic individuals might therefore benefit from reproductive hormone suppression in conjunction with chelation. The fluidity with which they equate their own speculation with “knowledge” is particularly breathtaking when one examines their recruitment procedures and the evaluation and pharmaceutical “treatment modality” they promote.

Nonstandard use of standard terminology

Dr. and Mr. Geier state that the purpose of their “clinical trial” is “to employ a combined anti-androgen and anti-heavy metal treatment in consecutive series of children with ASDs that presented to the Genetic Centers of America, and to evaluate its effect on clinical behaviors,” and correctly characterize their study as “experimental” (p. 834). Although they discuss chelation in their paper, they use the word “chelation” only twice. Chelation has recently gained popularity as an autism treatment due to aggressive promotion by entrepreneurs who assert that autism is a consequence of iatrogenic mercury toxicity. The risks posed to children by chelation were tragically demonstrated in August 2005, when a five-year-old autistic boy died in a Pennsylvania doctor’s office while undergoing the procedure. In its alternate guise as a treatment for heart disease and general “detoxification,” chelation has been associated with a worrisome number of deaths. A recent Cornell study also suggests the risk of long-term decline in cognitive function in individuals undergoing chelation. By employing “anti-heavy metal therapy” – an awkward neologism found nowhere else in the scientific literature – as a euphemism for the more recognizable “chelation,” Dr. and Mr. Geier deflect attention from the procedure’s risky and controversial nature.

Dr. and Mr. Geier state that upon intake and at the end of the study period, “a clinical examination was undertaken for each patient to evaluate clinical symptoms/behaviors of hyperandrogenemia such as early growth spurt, early secondary sexual changes, body and facial hair, and aggressive behaviors” (p. 836). They do not disclose who performed these examinations, where they were performed, or whether the individuals conducting the examinations possess any expertise in endocrinology – a matter of particular interest given Dr. Geier’s lack of board-certification in that field, and Mr. Geier’s lack of medical credentials.

Dr. and Mr. Geier’s references to “hyperandrogenemia” represent an idiosyncratic use of a term that properly describes a state of androgen excess in women characterized by obesity, amenorrhea, hirsutism or alopecia, hypertension, hyperlipidemia and glucose intolerance. In A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders, they use the term “hyperandrogenicity” to describe the same condition. However, in their patent applications and in numerous public presentations and radio interviews conducted in 2005 and early 2006, Dr. and Mr. Geier claimed that their subjects – and indeed, the great majority of autistic children – were suffering not from “hyperandrogenemia” or “hyperandrogenicity,” but from central precocious puberty (CPP) – the only pediatric indication for which Lupron is FDA approved. They defended their unorthodox pharmaceutical regimen by claiming that it represents “mainstream” therapy for CPP.

And just a last comment so that nobody misunderstands. We believe this therapy will work for most children who are mercury-toxic, whether or not – girls or boys – whether or not they are really in precocious puberty or not. We chose to work with precocious puberty because that puts us in mainline medicine. You can’t criticize using Lupron for precocious puberty; we believe it’ll work for most people. We believe that measuring testosterone is interesting, but since the test doesn’t work, it really doesn’t give you a level, and the girls that have autism in several studies have shown to have high testosterone as well, and high precocious puberty levels and we think, we haven’t done a girl yet, but we’re planning to do some girls as well. (Dr. Mark Geier, Autism One conference, May 27, 2005)

However, their idiosyncratic definition of CPP – whereby the condition could be diagnosed in telephone consultations, solely on the basis of “elevated results” from any one of thirty-three laboratory tests – was decidedly non-mainstream.

Sex steroid levels can be used to determine and diagnose whether a child is suffering from precocious puberty. (Mark and David Geier, U.S. Patent Application 20060058241, September 13, 2005)
What we look for are markers of high androgens. This is a list of the kinds of things that we’re testing. And really, to try to treat patients, we’re looking for one of those, at least one, preferably more of those to be abnormal, with the autism. (David Geier, Autism One Conference, May 26, 2006)
As far as that list, you don’t have to have all of those, those are the sort of what – the areas we’re looking at, as I said, we’re looking at one or more of those usually is what we’re looking at, for at least a candidate, so it’s not that restrictive. (David Geier, Autism One Conference, May 26, 2006)
I’m doing the protocol. Tell your hubby that my son did not have hair or a very brown scrotum and he was rx’ed. (Location unknown, June 5, 2005)

Parents have reported conversations in which Dr. and Mr. Geier frankly disclosed their purpose in diagnosing autistic children with CPP.

[T]he labs, according to the Geiers are ONLY an attempt to determine CPP and get insurance coverage for Lupron Depot. (Kentucky, June 4, 2005)
I spoke with Dr. Mark Geier briefly, recently. Testosterone can be measured with blood SSH & LH levels. I don’t know how expensive this is. He did say, however, that abnormal enough levels would qualify your child for the dx of “precocious puberty” (premature puberty) which should make the treatment covered by most insurance policies. Apparently, the key is to use the appropriate testosterone reference ranges (i.e. for the sex and age groups in question). (Kansas, February 4, 2005)

In her presentation at the 2005 Autism One conference, Rev. Lisa Sykes stated that her son had been administered Lupron since November 2004 pursuant to a diagnosis of CPP. In his presentation at the 2006 Autism One conference, David Geier described administration of Lupron to the same child pursuant to a diagnosis of “hyperandrogenicity.” In A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders, Dr. and Mr. Geier state that they diagnosed all of their subjects with “hyperandrogenemia.” However, they do not discuss their original practice of diagnosing research subjects with CPP, their retroactive modification of diagnoses or their rationale for making those modifications.

By creating their own diagnostic criteria for established diagnostic categories, Dr. and Mr. Geier create the inaccurate impression that they are engaged in generally accepted medical practice. By using “less restrictive” diagnostic criteria for central precocious puberty, Dr. and Mr. Geier enable the acquisition of Lupron for experimental purposes at the expense of their research subjects’ insurance providers. However, by publicly describing their process of diagnosing central precocious puberty before audiences that include medical doctors, they also expose themselves to scrutiny by individuals capable of recognizing the difference between a serious endocrine disorder requiring treatment with powerful pharmaceuticals, and non-pathological variations in children’s hormonal metabolism and sexual maturation.

One of the conversations circulating during the [May 2006 Autism One] conference was among doctors who are VERY concerned about the Geier’s misrepresentation of the safety of lupron. I sat in on a roundtable discussion where the Geiers and other panelists were discussing what is new in autism. Dr. Geier very irresponsibly repeated several times that lupron is “very safe”, it MAY chelate, it MAY raise secretin levels, it MAY blah, blah, blah. I was stunned at the amount of speculation he attributed to lupron, never addressing the documented adverse events. They attempted to dominate the entire first session with a sales pitch that had me and others squirming the entire time. Another doctor on the panel finally spoke up and addressed the dangers that taking lupron poses, as well as the lack of science supporting the protocol, and asked that the discussion head in another direction. (Washington, June 3, 2006)
I am also more than a bit concerned about using such a powerful drug based on the premise that testosterone is the cause of autism in males or that testosterone and mercury somehow bind. There seems to be no end to the danger that some seem to put children based on theories that may or may not be true and theoretical treatments that cost a fortune. (Dr. Lawrence Leichtman, Virginia, June 3, 2006)

By shifting to a “novel” use of diagnoses not generally associated with children, Dr. and Mr. Geier avoid the necessity of defending insupportable diagnoses of central precocious puberty, and obscure the decidedly off-label nature of their use of Lupron in conjunction with chelation.

Apparent disregard for U.S. federal regulations for research on Investigational New Drugs

Dr. and Mr. Geier state that they sought to evaluate the effects of the “Lupron protocol” on “clinical behaviors.” Behavior modification represents a new indication for all of the drugs employed in the “Lupron Protocol,” rendering Dr. and Mr. Geier’s research subject to FDA regulations for research conducted under Investigational New Drug (IND) applications (as set forth at 21 CFR 312). However, the FDA Bioresearch Monitoring Information System (updated to April 4, 2007) includes no entries for either Dr. or Mr. Geier or their IRB, indicating that they lack an IND.

Failure to completely and accurately describe the study and subjects

Dr. and Mr. Geier describe their endeavor as an “open-label clinical trial,” and their subject pool as “11 consecutive children with previously diagnosed… regressive ASDs that presented to the Genetic Centers of America from November 2004 through January 2006” (p. 834). Research recruitment efforts commenced immediately after they filed their application to patent the “Lupron Protocol,” in the same month that Dr. Geier testified to his lack of any experience in the diagnosis and treatment of autistic children. According to a newsgroup post made by the father of one patient/subject, by August 2005 Dr. and Mr. Geier’s Lupron study had attracted about a dozen subjects.

We just started the protocol. As of a few days ago, there were about 12 kids on it. (California, August 2, 2005)

Unless the rate of recruitment increased dramatically between August 2005 and January 2006, one can be reasonably certain that there is significant overlap between the subject pool in A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders – 16 previously diagnosed autistic children “that presented from November 2004 to November 2005 to the Genetic Centers of America” – and the subject pool described in A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders – 11 previously diagnosed autistic children “that presented to the Genetic Centers of America from November 2004 through January 2006.” In A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders Dr. and Mr. Geier refer to “two children excluded from the study that deviated from the treatment protocol” (p. 834), suggesting that the subject pool is a subset of the subject pool for the earlier study. Their detached reference to their June 2006 paper in Hormone Research inaccurately implies that it involved a different “consecutive series of children with ASDs” than the “consecutive children” discussed in their December 2006 paper in Neuroendocrinology Letters.

In at least one instance, overlap of subjects is demonstrable. In several public presentations and interviews, Rev. Lisa Sykes has offered emotional testimonials about the efficacy of the “Lupron Protocol,” discussing and displaying her son’s medical records and educational evaluations. These data surface in the description of “Child X” in the patent applications, in the entries for “Patient 1” in A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders, and in Table 4 of A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders. Although Rev. Sykes’ son and other subjects described in A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders have been administered Lupron and other drugs since their entry into Dr. and Mr. Geier’s study, that paper omitted any reference to the study’s pharmaceutical component.

Failure to identify co-investigators

Dr. and Mr. Geier offer a summary of the personal characteristics of their research subjects in Table 1 (p. 835). Although they do not specify the exact location of the “Genetic Centers” where these children “presented,” the table indicates that the children are located in Maryland, Virginia, Delaware, Massachusetts, New Jersey, Indiana, Kansas, and California. They fail to specify how many research subjects they have examined and evaluated physically, or how many subjects they have enrolled subsequent to long-distance telephone consultations with parents. The previously-cited solicitation attributed to Dr. Geier and newsgroup messages posted by parents of research subjects indicate that the latter scenario is common.

[Are you doing this through your Dan Dr.?]
Yes, through a DAN Dr. in conjunction with the Geiers. (California, August 3, 2005)
My son just finished his tests for the Geiers and we are waiting for results. Dr. Geier uses a special lab that will reference D[…]‘s level with boys his own age. We live in NH so it is possible to be a patient of the Geiers’ Just a lot of phone consultations. (New Hampshire, February 5, 2006)
The Geiers can have him tested long distance. […] we had a few consultations over the phone, ordered a huge battery of tests at Labcorp (who works with insurance) and discovered M[…]‘s needs. She’s on the protocol, and we didn’t have to fly to Maryland. (Illinois, April 5, 2006)
I am doing it with my dan doc, whose son also an aspie is also under Dr G’s care and a few weeks ahead of us in his treatment. So I am in very good company. Its going to cost the average family less than 1 hour of OT for a months supply of the chelation + lupron. Dr G will do it with your Dan and a phone consult. They’ll want your charts that you have from your son’s birth and order up 33+ tests, much of which will be paid by insurance. (North Carolina, April 27, 2006)
Q: What are your thoughts on treatment of high levels of testosterone? A: The testosterone is a theory put out there by the Geiers. It’s premature. The lupron therapy – I’ve used in a couple of kids. (Dr. James Neubrander, New Jersey, May 2, 2006)
My son sees Dr. [Anne] Hines. She is a wonderful and very caring and understanding doctor. She also works very closely with the Geirs on the new treatments. (North Carolina, May 31, 2006)
We have started the Lupron treatment with the Geiers and Dr. [Mary] Megson. Dr. Geier has a Lupron Protocol with IM shots every 2 weeks and a daily subcutaneous shot. Dr. Megson on the other recommends once a month. (Virginia, December 10, 2006)
The finding of low DHEA-Sulfate, high testosterone for age and gender, and low FSH appears to be a common finding in autism. The Geiers found it in 15 consecutive patients and I have seen it in the handfull of autistic patients I have tested. In addition, low glutathione, low methionine, low cysteine, low cystathionine, and other transulfuration products have been found consistently. These seem to be the most consistent biological findings in autism regardless of age, severity, or gender. My opinion is that these findings appear to be highly significant and may form a basis for diagnosing and treating autistic children and adults. (Dr. Kenneth Sokolski, Irvine, California, December 11, 2006)
We recently did the testosterone test with Dr. [Lynne] Mielke and my son’s was very high – 26. The range is 0-10. Dr. Mielke said that according to my son’s age – 5 years – it should have been closer to zero! (California, December 19, 2006)
I’ve had two conferences with Dr. Geier. Tomorrow Dr. [Phillip] DeMio and I are going to talk about her labs. The Geier’s said they were “alarming” but I was not surprised at that response. (Ohio, December 20, 2006)
I have 20 yr old daughter on protocol, 16 yr and 15 yr son on protocol. I also have a 18 yr old son just now getting on the protocol. I also have NT 3 year old daughter and NT 9 month old son. (Kansas, January 26, 2007)
[same mother, three days later on another list]
If you don’t live in his area – I believe he is in Maryland, will he treat long distance or guide your doctor on treatment?
Yes! He is in Maryland, and I am in Kansas. (Kansas, January 29, 2007)

In spite of the participation of other doctors in their research, Dr. and Mr. Geier do not identify their co-investigators or their study sites.

Apparent failure to obtain valid legally effective parental permission and assent from minor research subjects

With a telling misspelling, Dr. and Mr. Geier state that “informed consistent [sic] was obtained from each patient.” It is doubtful whether any consent they obtained is truly “informed,” given the many erroneous scientific claims in their patent applications and public presentations. Such claims include the fantasy that testosterone and mercury bond in vivo to form poisonous, chelation-resistant “sheets” in the brain.

It is known in the art that mercuric chloride binds and forms a complex with testosterone in subjects. (USPTO patent application, September 13, 2005)
[David Geier] And even more than that, we discovered that testosterone and mercury complexed classically in the body. You’re looking at your testosterone here – that’s these folded, sheety things. They form long strands, like little threads. And what mercury does, that’s these blackened-in balls here, it comes in and binds one string of testosterone to another one. So you take something that was a linear string and make it two-dimensional, so now it’s in effect a testosterone-mercury sheet. And this is something that makes for the idea of when you do chelation, or for build-up of testosterone in the body, shows that it’s going to be very tough to get rid of both of them. There should be testosterone in the body, and lots of mercury embedded in that.
[Mark Geier] And incidentally, this was seen by x-ray crystallography. It’s the ultimate way of seeing things. It’s a way of seeing molecules. It’s the same way they got the structure of DNA. So that’s really what it looks like. (David Geier, Dr. Mark Geier, May 2005)

Dr. and Mr. Geier’s “discovery” did not occur in their own laboratory, but in their erroneous interpretation of data from A. Cooper et al., The Crystal Structure and Absolute Configuration of the 2:1 Complex between Testosterone and Mercuric Chloride (Acta Crystallographica, Part B, July 15, 1968). The authors of that study did not conclude that “testosterone and mercury complex classically in the body,” that is, under physiological conditions; rather, they conducted an x-ray crystallographic analysis of crystals formed by dissolving mercury and testosterone in hot benzene. Although Dr. and Mr. Geier have ceased to refer to “mercury-testosterone sheets” in their public presentations and papers since being publicly criticized by other scientists for doing so, their claims persist in audio and video recordings made in 2005 and early 2006, both freely available and offered for purchase online.

Dr. and Mr. Geier have courted parents with the erroneous assertion that the majority of autistic children experience precocious puberty, and that treatment with Lupron can “make autism virtually disappear.”

If you look at these children, most of them have signs and symptoms of precocious puberty… You can treat them by lowering their testosterone and removing the mercury, and we’ve had unbelievable success… Why don’t you treat the precocious puberty because it makes the autism virtually disappear.” (Dr. Mark Geier, June 23, 2006)

Informed consent cannot be obtained when investigators represent speculative procedures as “therapy,” and conflate treatment with research, in violation of the ethical principles enumerated in the Belmont Report.

We are doing something between a treatment and a study. That is, we’re studying all the biochemical parameters of the children we’re seeing. We’re not doing a double blind placebo matched control because we can’t get any parents who want to do that. They want the therapy… We’re doing a study, but we’re also doing a treatment. (Dr. Mark Geier, November 2005)

Neither can informed consent be obtained when both investigators and the parents of research subjects are uncertain regarding basic matters such as the duration and cost of children’s participation in a study.

I don’t know how long she needs to stay on this drug. (Illinois, March 16, 2006)
Make sure you get your insurance on board. We didn’t. We forgot to ask how much. Labcorp didn’t tell us how much. Until we got the bill. For one kid, right around 7 grand. No new truck this year. (California, July 4, 2006)
The only thing that I can think, that I’m not sure of is, I don’t know how long I have to keep treating these kids, if I stop treating them will they go back to the way they were? That I don’t know. (Dr. Mark Geier, June 23, 2006)
The doc (Geier) didn’t say to chelate or not. I haven’t really spoken with him. Just his son called. (California, June 6, 2006)
I took my 2 sons to the Geiers this time last year. When we had our initial consult I was almost convinced but being an OB nurse I wanted to ask around about Lupron. When we went back to get our lab results and find out what our sons treatment protocol would be I was surprised and a little skeptical. First of all Dr. Mark Geier was not in the room the son was giving us the lab results and the treatment protocol. As a nurse I found that to be odd because the son is not the M.D. therefore I felt this was practicing medicine without a license. I was concerned about the Lupron being covered by insurance and I had a few other questions that David Geier could not answer. To date (1 year later) I am still trying to get the labs that they ordered to be paid by my insurance BCBS. So I did not start their protocol because if I couldn’t get their help with getting the labs paid (which is thousands of dollars) then I figured I was not going to get the Lupron paid which is what? $1500/shot. Has anyone else had this problem with them? […] Labcorp is billing me thousands of dollars because my insurance BCBS is not paying for them. When I spoke with Dr. Geiers office about it I haven’t gotten much help. I spoke with Eleanor and David Geier about it and they just keep telling me that the codes that they used are the correct codes and they are the codes they use for everyone. My insurance company is not paying because they say it is coded under educational. (Virginia, December 11, 2006)

These last two posts raise the disturbing possibility that David Geier has interpreted laboratory results and offered medical advice in his father’s absence, without the benefit of a medical education.

Inadequate disclosure of materials and methods that expose a vulnerable population to excessive risk

Dr. and Mr. Geier describe the criteria for autistic children’s entry into their study as “exposure to mercury in their medical history” and “evidence of elevated testosterone, serum/plasma DHEA, or serum androstenedione” (p. 834). They describe subjecting every prospective research subject to an extensive battery of blood, urine and imaging tests intended to identify genetic disorders, metabolic problems, environmental exposures, and neurological issues. The copious blood draws and laboratory tests they order are administered by personnel of LabCorp, Inc., a commercial enterprise with offices throughout the United States. They claim to have ordered over thirty tests for any child considered for enrollment in their study, and biweekly monitoring of all children subjected to the “Lupron protocol”; however, they do not reveal the total number of applicants for their study, and do disclose whether or how they monitor the quality of venipuncture performed. In a March 2007 radio interview, Dr. Geier stated that he had evaluated approximately 300 children, and medicated approximately 120 of them.

Dr. and Mr. Geier do not discuss their criteria for determining whether any given child has been exposed to dangerous levels of mercury or determining all possible sources of mercury exposure. They do not discuss their criteria for determining whether androgens are “elevated” in any given child. Although Dr. and Mr. Geier superficially acknowledge the importance of genetic factors in the genesis of autism, and although they subject potential research subjects to tests for known genetic syndromes, they do not discuss the possibility that autism might be associated with previously-unidentified genetic factors for which tests have not been developed.

Dr. and Mr. Geier refer to intramuscular injection of Lupron Depot using the passive voice – i.e., “the children were then administered an intramuscular injection” (p. 834). Although their research subjects are geographically dispersed, and although Dr. Geier is only licensed to practice medicine in Maryland and Virginia, they do not reveal where and by whom these injections were administered. If parents of research subjects performed this task, it would be appropriate to report how and by whom they were trained to do so.

Yesterday, we gave R[…] her second Depo shot (intramuscularly, with the big, 2-inch needle) in her buttocks. We did this one while she was awake, by holding her down while she lay on her belly. We were able to hold her still for the injection by sitting/straddling her back, while my wife held her legs still. This was necessary to keep her from moving around too much, which would bend the needle and cause bruising. But it worked. (Illinois, May 22, 2006)
My son is about the same age as your boy and we have been using Lupron on him (and chelating) for about 10 months now… The monthly Lupron shots are NOT like MB12 shots. They are big shots and the boy needs to be held very still when giving. (New Jersey, January 16, 2007)

Dr. and Mr. Geier do not reveal how parents acquired intramuscular injections of Lupron Depot for home administration to their children. Many major insurance providers in the United States cover pediatric intramuscular injections as a medical benefit rather than a pharmacy benefit, and require that they be administered in a doctor’s office by a licensed medical professional to minimize the possibility of harm to children.

Dr. and Mr. Geier describe administration of a “test-dose” of subcutaneous leuprolide three days before administration of a 15mg Lupron Depot injection (p. 834). This differs significantly from the examples of the “Lupron Protocol” included in their September 2005 patent applications. According to these descriptions, eight year old “Child X” (Rev. Sykes’ son) and six year old “Child Y” were initially administered intramuscular injections of the 22.5mg, 3-month form of Lupron Depot, with no preliminary testing (WIPO application, pp. 39 and 46). Dr. and Mr. Geier also state that they administered a second injection of 3-month Lupron Depot to both “Child X” and “Child Y” approximately nine weeks after the first.

Table 1 indicates that the eleven research subjects ranged from six to fourteen years of age (p. 835). By transforming this data into a “median age of nine years,” Dr. and Mr. Geier imply that there is no need to distinguish between pre-pubertal children and adolescents – children at extremely different stages of hormonal development. They do not disclose the numbers or percentage of study participants who are older than eleven years, the age beyond which Lupron’s label recommends discontinuation of the drug.

Dr. and Mr. Geier refer to daily administration of subcutaneous injections of LUPRON®, displaying the proprietary product’s registered trademark and manufacturer name, but provide no rationale for preferring a reference-listed drug over the readily-available, therapeutically-equivalent and less-costly generic leuprolide (p. 834). Newsgroup posts indicate that generic leuprolide is in fact the drug dispensed by pharmacies to parents of research subjects, since neither insurance providers, Medicaid nor parents paying out-of-pocket are willing to pay for the more costly proprietary product.

[TAP’s patent on Lupron expires in May 2006. The question is whether the [Geiers] will switch to a cheaper alternative.]
Actually, they already do for the sub-cutaneous daily shots. That brand is called “Leuprolide” and not made by TAP. TAP makes the Depo shots (28 day intramuscular injections) that we only use once a month. The Depo shot is used to quickly lower testosterone… and the daily shots prevent the testosterone from coming back up as the Depo shot wears off a few or three weeks later. My insurance carrier has an in-house specialty pharmacy that I go through. I pay $10/month for a co-pay. (Illinois, April 26, 2006)
My trial prescription costs over $500 for 1/2 month and says Leuprolide Acetate Injection/Leuprolide – Generic Lupron and is prescribed at 1.4mL subcutaneously every day. (January 14, 2007)

Dr. and Mr. Geier characterize their baseline dose of 50mcg/kg of leuprolide – administered as a combination of Lupron Depot and daily subcutaneous leuprolide, for a minimum of 31 injections per month – as “compatible with that observed by Tanaka et al as a dose of LUPRON® that would significant [sic] reduce androgen levels” (p. 834). The study to which they refer, however – T. Tanaka et al., A dose finding study of a super long-acting luteinizing hormone-releasing hormone analog in the treatment of central precocious puberty (Endocrinologia Japonica, August 1991) – specifically discusses administration of Lupron Depot to a subject pool consisting of 36 children diagnosed with central precocious puberty. Only two of these children were boys. The investigators did not measure “androgen levels” but gonadotropin levels (that is, levels of follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), with clinical effectiveness defined as regression of secondary sexual characteristics – that is, physicial maturation, not behavior modification. This study utilized only Lupron Depot, not depot and daily formulations together.

Dr. and Mr. Geier do not disclose any adverse events associated with the “Lupron protocol,” either generally or with respect to their research subjects. Newsgroup posts by parents and doctors, however, include reports of adverse events, as well as reports of “no progress” that do not factor into Dr. and Mr. Geier’s discussion of their work.

We worked with the Geiers for several months and then have stopped since Lupron did nothing but make my son irritable (we saw no additional metal excretion). Before we started with Lupron, he did seem to have slightly high testosterone although no other signs of precocious puberty. Now, after we have stopped, it has gone back into the normal range – not sure why. (Virginia, January 20, 2006)
I know 2 kids who have been at this over a year with very little change. (Location unknown, February 5, 2006)
We worked with the Geiers when my son did their protocol. I think that the first few patients were diagnosed with precocious puberty. My son’s testosterone levels were as high as these kids but he didn’t have the other signs of precocious puberty that they had. He did have a lot of aggression so we decided to try it. We gave it a 2 month trial but my DAN and I did not think it was healthy to stop testosterone on an 8 yr old boy that is not having prec. puberty. Also, we did not see any changes in behavior or chelation output. (New York, January 4, 2006)
I now have 7 patients who have received ongoing Lupron injections not from me or from my recommendation. None of these boys show any difference in behavior or anything else I can observe. The parents have reported some mixed results but so far I can’t confirm any responses. It is a painful injection and all of the parents report considerable resistance in administering it. (Dr. Lawrence Leichtman, Virginia, January 14, 2007)

Dr. and Mr. Geier describe the chelation portion of the “Lupron Protocol”:

Three days following starting of the LUPRON Depot® and the subcutaneous daily LUPRON®, children were begun on an oral dose of CHEMET® [succimer] 100 mg capsules (CHEMET® (meso-2, 3-dimercaptosuccinic acid – DMSA, McNeil Consumer Products Company) at 10 mg/kg bodyweight. This dose was administered three times per day in the morning, mid-day, and night and repeated every other day throughout the treatment period. This level was selected to be similar to that observed by Bradstreet et al. as a dose of DMSA that would significantly increase urinary heavy metal excretion (6). If severe gastrointestinal disturbances (i.e. severe diarrhea or severe constipation) were observed following oral CHEMET®, trans-dermal DMSA was to be administered according to the same treatment schedule as the oral CHEMET®… Patients assessed in the present study were on the therapy for a minimum of 2 months and a maximum of 7 months.” (pp. 834-5)

Even the minimum duration of treatment described here reflects a radical departure from the recommended use of succimer, whose only FDA-approved pediatric indication is acute lead toxicity. The product information for CHEMET® warns that “[t]he safety of uninterrupted dosing longer than three weeks has not been established and is not recommended.” Dr. and Mr. Geier cite Bradstreet et al., A Case-Control Study of Mercury Burden in Children with Autistic Spectrum Disorders (Journal of American Physicians and Surgeons, Fall 2003) as the basis for their dosing schedule, obscuring the fact that they were co-investigators on that study. (Like Dr. Geier, Dr. Bradstreet serves as an expert witness for plaintiffs in the Omnibus Autism Proceeding, and has himself been a vaccine-injury plaintiff). Although they openly acknowledge the high risk to children of gastrointestinal distress posed by oral succimer, and refer to their use of transdermal DMSA as an alternate treatment, they fail to specify the number of their research subjects who experienced adverse effects from succimer, or the number administered transdermal DMSA. They do not reveal that transdermal DMSA is not an FDA-approved product, and do not identify the compounding pharmacy that prepared it or the manufacturer of the chemicals used.

Dr. and Mr. Geier also do not disclose their use of another chelation drug, DMPS (2,3-Dimercaptopropane Sulfonic Acid), on at least two of their research subjects. In their patent applications, Dr. and Mr. Geier state that both “Child X” and “Child Y” “received a 1.5 transdermal DMPS dose/kg bodyweight every other day,” and that seven weeks later, each “received 7.5 mg DMSA/kg bodyweight, three times per day of the oral DMSA every other day, on the days when he was also being administered transdermal DMPS” (WIPO application, pp. 40,46-7). Like transdermal DMSA, transdermal DMPS is not approved by the FDA for marketing in the United States; due to safety concerns, DMPS is not approved by the FDA for marketing in any form.

Dr. and Mr. Geier further indicate that after follow-up testing, certain children were “supplemented with subcutaneous injections of LUPRON® dosing… as clinically necessary” (p. 835). They fail to specify any measure of “clinical necessity” for such supplementation over their baseline regimen of 31+ injections per month, beyond a vague reference to “clinical/laboratory signs of increased androgens.” Although they imply that this increase in dosage is exceptional, newsgroup posts suggest that Dr. and Mr. Geier’s patient/subjects now routinely receive two subcutaneous injections per day and biweekly intramuscular depot injections, for a total burden of 62+ injections per month.

[I] think the protocol for most is a IM shot every two weeks by a professional and then small shots daily that you do at home. (Ohio, December 20, 2006)
My daughter receives bimonthly Depo injections, as well as daily subcutaneous injections. (Illinois, January 25, 2007)

This escalation in routine dosage recommendations for Lupron further renders Dr. and Mr. Geier’s research subject to FDA regulations for INDs.

Dr. and Mr. Geier state that certain other children “were supplemented with… oral ANDROCUR® 100 mg capsules (cypterone [sic] acetate, Schering AG) as clinically necessary” (p. 835) Schering AG’s product information for Androcur (cyproterone acetate) lists a single, non-pediatric indication – treatment of inoperable prostate cancer. Only an immediately life-threatening condition warrants administration of a drug associated with a high risk of hepatic toxicity. In contrast to their specific reference here to 100 mg capsules – the highest dose of Androcur manufactured – Dr. and Mr. Geier’s patent applications indicate that their first two research subjects were administered 50 mg tablets three times per day (WIPO application, pp. 40 and 47). Curiously, Dr. and Mr. Geier fail to disclose how they obtained for use in pediatric research in the United States a drug no longer FDA-approved or legally available in this country. A recent statement attributed to Dr. Geier suggests that parents of research subjects purchase the drug from Canadian mail-order pharmacies.

I have also prescribed Androcur a drug available from Canada in some of my patients. (January 25, 2007)

As mentioned previously, the FDA’s database contain no evidence that either Dr. or Mr. Geier has ever filed an IND with the FDA for research on transdermal DMSA, DMPS, Androcur, or for the use of Lupron in behavior modification, in doses exceeding those recommended on the product label for the treatment of central precocious puberty.

Dr. and Mr. Geier state that their study participants “were on the therapy for… a maximum of seven months,” alternately represented in Table 1 as a “median number of 111 days’ enrollment” (p. 835). However, in a radio interview broadcast in July 2006 – when Dr. and Mr. Geier submitted A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders for publication – IRB member Rev. Lisa Sykes publicly acknowledged that her son had been “on the therapy” continuously since November 2004 – that is, for over a year and a half. Newsgroup posts suggest the likelihood that many of Dr. and Mr. Geier’s patient/subjects have been administered Lupron, DMSA, Androcur and other additions to the “Lupron Protocol” for considerably longer than seven months.

My son is 11 and was kid #10 on the protocol, and is still on it… The Geiers are now viewing this as something that is likely to be a maintenance treatment – not a cure… How long to leave him on it (forever? a couple of more years?) is a major question in my mind. (California, December 19, 2006)
My son is 15 and we are on the Geier’s protocol. […] We have been doing this since the end of April 2005. He was on the DMSA from May 2005 to Oct 2005 with great results and is still on the lupron shots. (California, January 11, 2007)

If by “on the therapy for a maximum of seven months” Dr. and Mr. Geier mean that they have analyzed a maximum of seven months’ worth of data for any given child, they should disclose this specifically, and give an accurate account of the total duration of administration of drugs to each child enrolled in their study – not just the children chosen for inclusion in this paper.

Dr. and Mr. Geier state that “Autism Treatment Evaluation Checklist (ATEC) evaluations were conducted prior to beginning the protocol on each child and at the end of the study period for each child. The ATEC quantitatively evaluates (using a numeric scoring system) skills in a number of areas” (p. 836). They do not initially disclose who performed these evaluations; in the Discussion section, however, they indicate that the reports were completed by the parents of research subjects (p. 837). Their reference to “quantitative evaluation” inaccurately implies that the ATEC is a precise and appropriate tool for assessing outcomes in pharmaceutical research. Although the ATEC is a useful starting point for organizing parental observations about individual children’s behavior and their temporal association with various clinical interventions, one cannot reasonably use it as a measure of pharmaceutical efficacy. Neither can a small, heterogeneous cohort of eleven research subjects serve as an adequate basis from which to draw any meaningful scientific conclusions. Nonetheless, in Table 2 (p. 835), Dr. and Mr. Geier aggregate and analyze ATEC scores and seek to persuade their readers that their subjects’ every developmental gain can be attributed to the patent-pending “Lupron Protocol.” The caption “An evaluation of the effects of treatment on skills in the study group of children,” provides a succinct example of the post hoc fallacy.

Dr. and Mr. Geier report increases in urinary elimination of metals consistent with the described pharmacological activity of chelation drugs, and decreases in testosterone consistent with the described pharmacological activity of GnRH agonists and anti-androgens (pp. 837-8). Although reported behavioral changes are consistent with children’s maturation, access to effective teachers and teaching techniques, and the infusion of parental optimism that often accompanies initiation of a treatment promoted with extreme claims of efficacy, Dr. and Mr. Geier fail to consider the extent to which behavioral improvements might be attributable to non-pharmaceutical factors.

With Figure 1 (p. 836), Dr. and Mr. Geier suggest that meaningful generalizations might be derived from teacher evaluations of a single child’s in-school behavior over little more than two months. Table 4 (p. 837) presents data from evaluations of Rev. Sykes’ son. The 2003-2004 and 2004-2005 evaluation results are simplistically divided by the annotation, “Treatment Initiated,” with no discussion of personnel, curriculum, family or other changes contemporaneous with the transition from “0 Skills Mastered” to “Many Skills Mastered.” In contrast to the extensive attention dedicated to educators’ accounts of two children’s in-school behavior, the results of subjects’ toxicology and serum testosterone tests are each discussed in a single sentence.

Dr. and Mr. Geier claim that the simultaneous administration of chelators and hormonal suppressants to autistic children and teenagers “resulted in minimal significant adverse effects,” and refer to various tests of mineral metabolism and organ function that purportedly confirm this finding (p. 837). However, they fail to specify when these tests were conducted, a point worth addressing given their subjects’ wide age range, and the wide range of their subjects’ duration of participation in the study. They claim that a 2005 paper by T. Tanaka et al., Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate (Journal of Clinical Endocrinology and Metabolism, March 2005), reported “no adverse effects on future reproductive function” after long-term administration of Lupron. Tanaka and his colleagues did not claim the ability to predict the future; rather, they determined that menarche or remenarche had occurred in 96.8% of 63 girls in their study by the time they reached 14½ years of age, and that each of 13 boys attained normal serum testosterone levels within three years of cessation of treatment. Although reassuring, these results can hardly be interpreted as a guarantee that these children will not suffer reproductive complications in adulthood.

Neither Tanaka nor Dr. and Mr. Geier discuss any of the other documented adverse effects of Lupron; these include osteoporosis, pituitary infarction, autoimmune thyroiditis, neutropenia, anemia, emotional lability, irritability, fatigue, and impaired cognition.

Dr. and Mr. Geier also do not address the potential for injection site reactions, nerve injury, bruising and infection, or the potential for psychological trauma to developmentally disabled, communicatively-impaired children forced to submit to daily injections, a process often requiring physical restraint.

Inadequate peer review and editing and potential conflicts of editorial interest

One cannot reasonably expect scientific editors and reviewers to be sufficiently familiar with online discussions on autism parents’ groups to recognize when subjects’ accounts of research differ significantly from those offered to the scientific community by investigators. However, it is reasonable to expect reviewers of papers describing pharmaceutical products to be sufficiently familiar with those products to recognize when they are being administered in a manner that differs significantly from their generally-accepted use. It is reasonable to expect reviewers of scientific papers to be sufficiently familiar with internationally-accepted standards for research involving human subjects to recognize when those standards have not been met. It is reasonable to expect reviewers of papers in any academic field to be sufficiently familiar with the elements of logic to recognize when authors engage in fallacious reasoning.

One cannot generally expect scientific editors and reviewers to be sufficiently familiar with a researcher’s previous work to recognize when they are engaging in “salami publication” (that is, publishing findings from a single study in numerous journals), recycling their old prose, contradicting themselves, or modifying previous claims. However, it appears that at least one member of the Editorial Board of Neuroendocrinology Letters has previously published work by Dr. and Mr. Geier. Dr. George Stefano of SUNY Neuroscience Research Center is also editor of the journal Medical Science Monitor, which in August 2005 published Dr. and Mr. Geier’s paper, A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis (Medical Science Monitor, April 2005). Shortly after its publication, Frank DeStefano, M.D., Captain of the U.S. Public Health Service and Acting Director of the Immunization Safety Office of the U.S. Centers for Disease Control (CDC), wrote a letter to Dr. Stefano, expressing his concern about extensive similarities that existed between it and an early draft of a study on which he had been co-author, and expressing his doubts about the legitimacy of Dr. and Mr. Geier’s claim to have conducted the analysis they described in their paper. (The “Two-Phased Study” also contains numerous passages apparently derived from an earlier paper by Dr. and Mr. Geier.) I obtained a copy of Dr. DeStefano’s letter and subsequently confirmed that one of Dr. Stefano’s staff members phoned the CDC to acknowledge receiving it. In spite of Dr. DeStefano’s documented allegations, the CDC has never received a substantive response to Dr. DeStefano’s letter, and no response has ever been published in Medical Science Monitor.

Dr. Stefano subsequently published another paper by Dr. and Mr. Geier, An assessment of downward trends in neurodevelopmental disorders in the United States following removal of Thimerosal from childhood vaccines (Medical Science Monitor, June 2006). The Introduction and Discussion sections of this paper are substantially similar to the corresponding sections of Dr. and Mr. Geier’s Early Downward Trends in Neurodevelopmental Disorders Following Removal of Thimerosal-Containing Vaccines (Journal of American Physicians and Surgeons, Spring 2006), published just three months earlier.

In view of the seriousness of the unaddressed allegations of plagiarism in a work written by Dr. and Mr. Geier and published by Dr. Stefano, it would be appropriate for the Editorial Board of Neuroendocrinology Letters to disclose whether Dr. Stefano played any role in reviewing A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders for publication.

It would also be appropriate to disclose whether any of the peer reviewers responsible for vetting this paper are serving plaintiffs in vaccine-related litigation. Expert witnesses to plaintiffs in the Omnibus Autism Proceeding and other vaccine-injury cases, professionals paid by the U.K. Legal Services Corporation for their service to plaintiffs in the now-terminated MMR litigation, and recipients of funding from organizations promoting the interests of vaccine-injury plaintiffs include:

Mohamed Abou-Donia, M.D. 2
James Adams Ph.D. 1,3,5,6
Kenneth Aitken, M.D. 2
Andrew Anthony, F.R.C.P. 2,7
Paul Ashwood, Ph.D. 2,7
Harland Austin, D.Sc. 1
Sidney Baker, M.D. 5
David Baskin, M.D. 1,5
Teresa Binstock 5
Marvin Boris, M.D. 5
Jeffrey Bradstreet, M.D. 1,2,3,5
Thomas Burbacher, Ph.D. 3
Harold Buttram, M.D. 4
Vera Byers, M.D. 2
Stephanie Cave, M.D. 4
Richard Deth, Ph.D. 1,3,5
Peter Fletcher, Ph.D. 2
Mark Geier, M.D. 1,2,4
M. Eric Gershwin, M.D. 1
Phillippe Grandjean, Ph.D. 1
John Green, M.D. 5
Sander Greenland, Dr.P.H. 1
Boyd Haley, Ph.D. 1,2,5
Richard Halvorsen, M.D. 2
Robert Hirsch, Ph.D. 1
Amy Holmes, M.D. 5
Mady Hornig, M.D. 3
S. Jill James, Ph.D. 3
Marcel Kinsbourne, M.D. 2,4
Arthur Krigsman, M.D. 1,2
Cathy Lally, M.P.H. 1
W. Ian Lipki