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Posted by on Nov 5, 2008 in Ethics, Neuropsychiatry, Toxicology

Op Ed-Plus: Further Commentary on the Work of Mark and David Geier

Op Ed-Plus: Further Commentary on the Work of Mark and David Geier

When examining the work of Mark and David Geier (and by extension, the work of their various coauthors), it becomes readily apparent that their rationales for administering Lupron and chelation therapy to children with autism are, at best, flimsy and, at worst, products of fantasy. It amounts to, in my mind, the twisted end-result of a highly convoluted, technically dense wish fulfillment that rests on these disturbing claims: 

  1. That autism remains a consequence of mercury toxicity (despite a lack of evidence or, in fact, an abundance of contrary evidence);
  2. That mercury toxicity can be indirectly established by measuring certain urinary porphyrins (on the basis of rat data and a pilot study in Mexican dental workers);
  3. That questionable values of thiols indicate a reduced capacity to eliminate heavy metals generally and mercury specifically (on the basis of rat and crustacean data);
  4. That mercury is bound up with testosterone in the human body (on the basis of an in vivo condition not found in living organisms); and
  5. That children with autism demonstrate central precocious puberty* (in the absence of acknowledging and publicly documenting the diagnostic criteria for the condition).

At this blog, the values of some thiol levels in autistic children published by the Geiers have been questioned in a series of postsperhaps too many (see, for example, here, here, here, here, here, here, and here). These questionable values undermine the validity of at least one of the Geiers’ claimsnamely, that thiol levels in autistic children (as the Geiers’ indicators of a “reduced detoxification capacity”) are significantly different from those in control children.

In a kind of preemptive rebuttal to this very legitimate concern, Geier et al wrote in their recently published article in the Journal of the Neurological Sciences:

It was observed, when comparing the actual numeric values from the current study with previous studies, that there were some differences in the actual values measured for the different metabolites examined. This may reflect differences in the exact methods employed in measuring various blood levels of transsulfuration metabolites [ie, thiol levels], but given the consistency observed between the studies, helps to indicate the overall validity of the observations.

In other words, Geier et al acknowledge that some of their thiol levels are inconsistent with those in other published sourcesalthough they do not admit specifically that their values for plasma cysteine, oxidized glutathione (GSSG), and total sulfate are different by 1, 2, or 3 orders of magnitude from those in the cited literature. They also fail to note that at least 2 of their assay references provide very different values for plasma cysteine and total sulfate, respectively.

But, because Geier et al found statistical differences between autistic children and control childrenlike those in the work of James et al, for instancethey defend the validity of their findings. This is like saying that, although my measurements of blood pressure are 12/8 mm Hg or 1200/800 mg Hg, instead of 120/80 mm Hg, findings of statistical difference are still validwhich is, of course, rubbish.

And in cases in which the Geiers’ thiol levels in autistic children fall within published reference ranges, they nevertheless appear eager to find statistical differences between these levels and those in control childrenwhich violates the spirit of the null hypothesis. Generally such conclusions must be offered extremely cautiously and should require independent reproducibility before recommending costly diagnostic tests or therapies.

In addition, the published drawbacks of thiol testing in human plasma also raise concerns about the validity of the Geiers’ conclusions. For instance, the reliability of measuring reduced glutathione (GSH) and GSSG in human plasma has been called into question. Values of these substances are relatively very low in human plasma and can vary substantially on the basis of specimen handlingfor instance, they are reported to vary considerably with even minor hemolysisOne laboratory source indicates that it is not possible to distinguish between GSH and GSSG in serum or plasma, owing to their very low levels.

On a related note, there may be confusion about the presentation of values for blood GSH and those for plasma GSH in the Geiers’ published work. In “A case series of children with apparent mercury toxic encephalopathies manifesting with clinical symptoms of regressive autistic disorder,” which was published in the Journal of Toxicology and Environmental Health, Part A last year, the Geiers measured blood GSH in 5 children (age range, 4-9 years) and reported values from 18 to 28 mg/dL. This range is the same range reported for plasma GSH in 10 children by the Geiers in their 2006 Hormone Research article. To aid further examination of the Geiers’ published values for blood or plasma GSH, these results are tabulated along with values from other sources (including other studies written by the Geiers). (Note that values, when necessary, are converted to units of μmol/L [molecular weight of GSH = 307.43 μg/μmol].)

Source

Blood GSH,
μmol/L

Plasma GSH,
μmol/L

Geier et al, 2008 (n = 28)

3.1 ± 0.53
(control, 4.2 ± 0.72)

Geier et al, 2008 (n = 38)

3.14 ± 0.56
(control, 4.2 ± 0.72)

TAP et al, 2008 (international patent application) (n = 2)

651*
(lab ref, >1041)

ALPCO, 2008

620-970

Geier and Geier, 2007 (n = 5)

585-911
(lab ref, >1041)

Geier and Geier, 2007 (n = 1)

0.933
(lab ref, >2)

Rossi et al, 2006 (n = 4)

1323-1392

Geier and Geier, 2006
(n = 10)

585-911
(control, 911-1431)

James et al, 2006 (n = 80)

1.4 ± 0.5
(control, 2.2 ± 0.9)

Melnyk et al, 1999 (n = 11)

6.9 ± 0.5

Michelet et al, 1995 (n = 13)

3.57 ± 0.74

Andersson et al, 1993
(n = 10)

3.4 ± 0.9

Curello et al, 1987 (n = 27)

4.2

* This value (originally reported in mg/dL) is not specified to be from plasma in the patent application, but it is presented along with other plasma thiol levels.

The 5 blood GSH values (585-911 μmol/L) reported by the Geiers in their 2007 case series are reasonably consistent with reference values for blood GSH in the literature, and the reference value for plasma GSH in the 10-year-old boy (>2 μmol/L) is also reasonably consistent with the relevant literature (if plasma values of GSH are reliable at all). But the data also suggest that the plasma GSH values (585-911 μmol/L) reported by the Geiers in Hormone Research in 2006 and the GSH values provided in the international patent application may well be blood GSH values.

In the 2007 case series and the Hormone Research study, GSH values were measured at the dubious Great Smokies Diagnostic Laboratory, aka Genova Diagnostics in Asheville, NC. In a curious case of indirect self-reproach, Mark Geier more or less dismissed this laboratory in his recorded June 2007 speech in front of the CDC (@ the 3:26 mark on YouTube), approximately 1 year after his Hormone Research article was published and 1 month after his case series was published.

* And this is without even discussing the Geiers’ use of Lupron in autistic children during timely puberty. 

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.