Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
December 12, 2009
In a 2006 review about metallothioneins [MTs] and mercury (1), Michael
Aschner includes a passage about ethylmercury (eHg; 2). Dr. Aschner's
paragraph about eHg stands in stark contrast to an ethylmercury summary
presented by Geier et al (3). A comparison of the two articles'
sections about ethylmercury is instructive and prompts concern: Why, as
a professor and researcher seemingly qualified to write intelligently
about ethylmercury, did Michael Aschner write inaccurately and
misleadingly about eHg?
First, consider Dr. Aschner's first sentence of the section entitled,
"Ethylmercury and MTs". He wrote, "Studies have yet to be performed to
address the effects of EtHg, a vaccine preservative containing 50%
EtHg, on MTs in brain." Here's a minor quibble. That sentence states
that EtHg is a vaccine preservative "containing 50% EtHg". More
accurate would have been to write that, Thimerosal is used as a vaccine
preservative and is approximately 50% mercury by weight.
More significantly, the rest of his paragraph about "Ethylmercury and
MTs" conveys the impression of Not To Worry about thimerosal. Dr.
Aschner wrote:
"EtHg decomposes faster than MeHg. Because passage through the
blood-brain barrier favors small molecules and MeHg is actively
transported, Hg concentrations in the brain are higher following
exposure to MeHg. Hg also clears faster after administration of EtHg
versus MeHg. Because metabolic rates (basic metabolism, rates of loss
from the body burden) are related to the fractional power of body
weight (allometric relationship), Hg clears faster from infants, thus
blood Hg concentrations for MeHg underestimate the safe exposure range
for EtHg... These observations suggest, but have yet to be verified,
that MT induction upon EtHg is most likely relatively small in
comparisons to Hg0 and even inorganic mercury in the form of Hg2+."
(1)
However, injected ethylmercury may not be as benign as Dr. Aschner's
rhetoric suggests. Consider an ethylmercury summary by more thorough
reviewers, who describe ethylmercury-brain findings in a primate model
(21) published two years before Dr. Ashner's 2006 review:
"Researchers evaluated infant monkeys following oral
administration of methyl-Hg hydroxide or injected doses of thimerosal,
sodium ethyl-Hg thiosalicylate, comparable to the dosing schedule
(weight- and ageadjusted) that US children received during the 1990s...
They determined that the maximum Hg content in the brains of the
thimerosal-treated infant monkeys averaged about 40-50
parts-per-billion. In addition, they calculated that the half-life for
organic Hg in the brain of the infant monkeys examined was about 14
days. By contrast, they determined that maximum Hg content in the
brains of methyl-Hg treated infant monkeys averaged about 80-120
parts-per-billion. In this case, they calculated that the half-life for
organic Hg in the brain of the infant monkeys examined was about 58
days. Based on these results, it was demonstrated that infant low-dose
organic Hg exposure, mimicking the Hg exposure received by US children
through the 1990s immunization schedule, was able to induce significant
levels of Hg in the monkey brain, and that this organic Hg was present
in the brain for several weeks postdosing.
"In addition, post-dosing-schedule testing found the
concentration of Hg2+ (formed from the ethyl-Hg entering the brain)
averaged 16 parts-per-billion in the brains of the thimerosal-treated
infant monkeys (all had a measurable level), whereas methyl-Hg treated
infant monkeys had significantly less than half as much Hg2+ (almost
half had a level below the method’s detection limit). Moreover, the
half-life of Hg2+ in the monkeys’ brains was too long to estimate from
the available data (no significant measurable decline was detectable by
120 days). Additionally, it was previously reported that, as a result
of the significant Hg2+ fraction of Hg observed in the brain following
injection of thimerosal, a longer biological time was observed for the
Hg in the brain from ethyl-Hg than for the Hg from methyl-Hg..." (3)
Initial conclusion: After being injected by a physician or nurse,
thimerosal's ethylmercury is not as benign as Dr. Aschner would have us
believe if we rely upon his 2006 essay.
Furthermore, the levels of eHg present in healthy human infants after
vaccination with a thimerosal-containing vaccine (4) are sufficiently
high so as to alter methionine synthase (5). This finding has
additional significance because Dr. Pichichero's sample size was small
(4) and, by utilizing healthyinfants, the study may not
have included infants with increased susceptibility (eg, 6-7) and did
not include infants who - at the time of deliberate thimerosal
injection - were sick or had been recently sick. Importantly,
thimerosal inhibits glutathione function (8).
A diligent reader of thimerosal literature might overlook one study's
perfunctory and misleading summary about ethylmercury (eg, 1), but for
Dr. Aschner, whitewashing adverse effects of thimerosal has been
repeated (reviewed in 9).
Furthermore, despite news media summaries that tell us how safe
physician- and nurse-injected thimerosal is, a growing number of
findings indicate that thimerosal injections are associated with an
increased need for special education services (10), with an increased
rate of autism (11), with mitochondrial dysfunction (eg, 12-14).
Moreover, the ethylmercury in thimerosal may interact additively,
cumulatively, or synergistically with airborne mercury (eg, 15-17) and
with other toxicants (eg, pesticides; 18-19).
Fortunately, a thorough review about thimerosal has been written by
Geier and colleagues and is free online (20).
References:
1. Metallothioneins:
mercury species-specific induction and their potential role in
attenuating neurotoxicity
Aschner M, Syversen T, Souza DO, Rocha JB.
Exp Biol Med (Maywood). 2006 Oct;231(9):1468-73.
{free online}
http://www.ebmonline.org/cgi/reprint/231/9/1468
2. EtHg is the traditional acronym for ethylmercury, but I prefer the
shortened abbreviation, eHg, which is easily differentiated from mHg,
which can be an abbreviation for methylmercury.
3. A comprehensive
review of mercury provoked autism
Geier DA, King PG, Sykes LK, Geier MR.
Indian J Med Res. 2008 Oct;128(4):383-411.
{free online}
http://www.icmr.nic.in/ijmr/2008/october/1004.pdf
4. Mercury
concentrations and metabolism in infants receiving vaccines containing
thiomersal: a descriptive study
Pichichero ME, Cernichiari E, Lopreiato J, Treanor J.
Lancet. 2002 Nov 30;360(9347):1737-41.
BACKGROUND: Thiomersal is a preservative containing small amounts of
ethylmercury that is used in routine vaccines for infants and children.
The effect of vaccines containing thiomersal on concentrations of
mercury in infants' blood has not been extensively assessed, and the
metabolism of ethylmercury in infants is unknown. We aimed to measure
concentrations of mercury in blood, urine, and stools of infants who
received such vaccines. METHODS: 40 full-term infants aged 6 months and
younger were given vaccines that contained thiomersal
(diptheria-tetanus-acellular pertussis vaccine, hepatitis B vaccine,
and in some children Haemophilus influenzae type b vaccine). 21 control
infants received thiomersal-free vaccines. We obtained samples of
blood, urine, and stools 3-28 days after vaccination. Total mercury
(organic and inorganic) in the samples was measured by cold vapour
atomic absorption. FINDINGS: Mean mercury doses in infants exposed to
thiomersal were 45.6 microg (range 37.5-62.5) for 2-month-olds and
111.3 microg (range 87.5-175.0) for 6-month-olds. Blood mercury in
thiomersal-exposed 2-month-olds ranged from less than 3.75 to 20.55
nmol/L (parts per billion); in 6-month-olds all values were lower than
7.50 nmol/L. Only one of 15 blood samples from controls contained
quantifiable mercury. Concentrations of mercury were low in urine after
vaccination but were high in stools of thiomersal-exposed 2-month-olds
(mean 82 ng/g dry weight) and in 6-month-olds (mean 58 ng/g dry
weight). Estimated blood half-life of ethylmercury was 7 days (95% CI
4-10 days). INTERPRETATION: Administration of vaccines containing
thiomersal does not seem to raise blood concentrations of mercury above
safe values in infants. Ethylmercury seems to be eliminated from blood
rapidly via the stools after parenteral administration of thiomersal in
vaccines.
5. Activation of
methionine synthase by insulin-like growth factor-1 and dopamine: a
target for neurodevelopmental toxins and
thimerosal
Waly M et al.
Mol Psychiatry. 2004 Apr;9(4):358-70.
{free online}
http://www.nature.com/mp/journal/v9/n4/pdf/4001476a.pdf
Methylation events play a critical role in the ability of growth
factors to promote normal development. Neurodevelopmental toxins, such
as ethanol and heavy metals, interrupt growth factor signaling, raising
the possibility that they might exert adverse effects on methylation.
We found that insulin-like growth factor-1 (IGF-1)- and
dopamine-stimulated methionine synthase (MS) activity and
folate-dependent methylation of phospholipids in SH-SY5Y human
neuroblastoma cells, via a PI3-kinase- and MAP-kinase-dependent
mechanism. The stimulation of this pathway increased DNA methylation,
while its inhibition increased methylation-sensitive gene expression.
Ethanol potently interfered with IGF-1 activation of MS and blocked its
effect on DNA methylation, whereas it did not inhibit the effects of
dopamine. Metal ions potently affected IGF-1 and dopamine-stimulated MS
activity, as well as folate-dependent phospholipid methylation: Cu(2+)
promoted enzyme activity and methylation, while Cu(+), Pb(2+), Hg(2+)
and Al(3+) were inhibitory. The ethylmercury-containing preservative
thimerosal inhibited both IGF-1- and dopamine-stimulated methylation
with an IC(50) of 1 nM and eliminated MS activity. Our findings outline
a novel growth factor signaling pathway that regulates MS activity and
thereby modulates methylation reactions, including DNA methylation. The
potent inhibition of this pathway by ethanol, lead, mercury, aluminum
and thimerosal suggests that it may be an important target of
neurodevelopmental toxins.
6. Homozygous gene
deletions of the glutathione S-transferases M1 and T1 are associated
with thimerosal sensitization
Westphal GA et al.
Int Arch Occup Environ Health. 2000 Aug;73(6):384-8.
7. Metabolic
endophenotype and related genotypes are associated with oxidative
stress in children with autism
James SJ et al.
Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141B(8):947-56.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610366/pdf/nihms68264.pdf
Autism is a behaviorally defined neurodevelopmental disorder usually
diagnosed in early childhood that is characterized by impairment in
reciprocal communication and speech, repetitive behaviors, and social
withdrawal. Although both genetic and environmental factors are thought
to be involved, none have been reproducibly identified. The metabolic
phenotype of an individual reflects the influence of endogenous and
exogenous factors on genotype. As such, it provides a window through
which the interactive impact of genes and environment may be viewed and
relevant susceptibility factors identified. Although abnormal
methionine metabolism has been associated with other neurologic
disorders, these pathways and related polymorphisms have not been
evaluated in autistic children. Plasma levels of metabolites in
methionine transmethylation and transsulfuration pathways were measured
in 80 autistic and 73 control children. In addition, common polymorphic
variants known to modulate these metabolic pathways were evaluated in
360 autistic children and 205 controls. The metabolic results indicated
that plasma methionine and the ratio of S-adenosylmethionine (SAM) to
S-adenosylhomocysteine (SAH), an indicator of methylation capacity,
were significantly decreased in the autistic children relative to
age-matched controls. In addition, plasma levels of cysteine,
glutathione, and the ratio of reduced to oxidized glutathione, an
indication of antioxidant capacity and redox homeostasis, were
significantly decreased. Differences in allele frequency and/or
significant gene-gene interactions were found for relevant genes
encoding the reduced folate carrier (RFC 80G > A), transcobalamin II
(TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A),
methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A >
C), and glutathione-S-transferase (GST M1). We propose that an
increased vulnerability to oxidative stress (endogenous or
environmental) may contribute to the development and clinical
manifestations of autism.
8. Inhibition of the
human erythrocytic glutathione-S-transferase T1 (GST T1) by
thimerosal
Muller M et al.
Int J Hyg Environ Health. 2001 Jul;203(5-6):479-81.
9. Michael Aschner
& Sandra Ceccatelli: Sins of Omission Regarding
Thimerosal
Teresa Binstock
here
10. Hepatitis B
triple series vaccine and developmental disability in US children aged
1-9 years
Gallagher C, Goodman M. Toxicol Environ Chem 2008 90(5):997-1008.
{free online}
http://fourteenstudies.org/pdf/hep_b.pdf
This study investigated the association between vaccination with the
Hepatitis B triple series vaccine prior to 2000 and developmental
disability in children aged 1-9 years (n = 1824), proxied by parental
report that their child receives early intervention or special
education services (EIS). National Health and Nutrition Examination
Survey 1999-2000 data were analyzed and adjusted for survey design by
Taylor Linearization using SAS version 9.1 software, with SAS callable
SUDAAN version 9.0.1. The odds of receiving EIS were approximately nine times
as great for vaccinated boys (n = 46) as for unvaccinated boys
(n = 7), after adjustment for
confounders. This study found statistically significant evidence to
suggest that boys in United States who were vaccinated with the triple
series Hepatitis B vaccine, during the time period in which vaccines
were manufactured with thimerosal, were more susceptible to
developmental disability than were unvaccinated boys.
11. Hepatitis B
vaccination of male neonates and autism
[conference abstract as published]
CM Gallagher, MS Goodman, Graduate Program in Public
Health, Stony Brook University Medical Center, Stony Brook, NY
Annals of Epidemiology, p659
Vol. 19, No. 9 Abstracts (ACE) September 2009: 651–680
PURPOSE: Universal newborn immunization with hepatitis B vaccine was
recommended in 1991; however, safety findings are mixed. The Vaccine
Safety Datalink Workgroup reported no association between hepatitis B
vaccination at birth and febrile episodes or neurological adverse
events. Other studies found positive associations between hepatitis B
vaccination and ear infection, pharyngitis, and chronic arthritis; as
well as receipt of early intervention/special education services (EIS);
in probability samples of
U.S. children. Children with autistic spectrum disorder (ASD) comprise
a growing caseload for EIS. We evaluated the association between
hepatitis B vaccination of male neonates and parental report of ASD.
METHODS: This cross-sectional study used U.S. probability samples
obtained from National Health Interview Survey 1997–2002 datasets.
Logistic regression modeling was used to estimate the effect of
neonatal hepatitis B vaccination on ASDrisk amongboys age 3–17 years
with shot records, adjusted for race, maternal education, and
two-parent household.
RESULTS:Boyswho received the hepatitis B vaccine during the first month
of life had 2.94 greater odds for ASD (nZ31 of 7,486; OR Z 2.94; p Z
0.03; 95% CI Z 1.10, 7.90) compared to later- or unvaccinated boys.
Non-Hispanicwhite boys were 61% less likely to have ASD(ORZ0.39;
pZ0.04; 95% CIZ0.16, 0.94) relative to non-white boys.
CONCLUSION: Findings suggest that U.S. male neonates vaccinated with
hepatitis B vaccine had a 3-fold greater risk of ASD; risk was greatest
for non-white boys.
12. Biochemical and
molecular basis of thimerosal-induced apoptosis in T cells: a major
role of mitochondrial pathway
Makani S et al.
Division of Basic and Clinical Immunology, University of California
Genes Immun. 2002 Aug;3(5):270-8.
http://www.nature.com/gene/journal/v3/n5/abs/6363854a.html
The major source of thimerosal (ethyl mercury thiosalicylate) exposure
is childhood vaccines. It is believed that the children are exposed to
significant accumulative dosage of thimerosal during the first 2 years
of life via immunization. Because of health-related concerns for
exposure to mercury, we examined the effects of thimerosal on the
biochemical and molecular steps of mitochondrial pathway of apoptosis
in Jurkat T cells. Thimerosal and not thiosalcylic acid (non-mercury
component of thimerosal), in a concentration-dependent manner, induced
apoptosis in T cells as determined by TUNEL and propidium iodide
assays, suggesting a role of mercury in T cell apoptosis. Apoptosis was
associated with depolarization of mitochondrial membrane, release of
cytochrome c and apoptosis inducing factor (AIF) from the mitochondria,
and activation of caspase-9 and caspase-3, but not of caspase-8. In
addition, thimerosal in a concentration-dependent manner inhibited the
expression of XIAP, cIAP-1 but did not influence cIAP-2 expression.
Furthermore, thimerosal enhanced intracellular reactive oxygen species
and reduced intracellular glutathione (GSH). Finally, exogenous
glutathione protected T cells from thimerosal-induced apoptosis by
upregulation of XIAP and cIAP1 and by inhibiting activation of both
caspase-9 and caspase-3. These data suggest that thimerosal induces
apoptosis in T cells via mitochondrial pathway by inducing oxidative
stress and depletion of GSH.
13. Mitochondrial
mediated thimerosal-induced apoptosis in a human neuroblastoma cell
line (SK-N-SH)
Humphrey ML, Cole MP, Pendergrass JC, Kiningham KK.
Neurotoxicology. 2005 Jun;26(3):407-16.
Environmental exposure to mercurials continues to be a public health
issue due to their deleterious effects on immune, renal and
neurological function. Recently the safety of thimerosal, an ethyl
mercury-containing preservative used in vaccines, has been questioned
due to exposure of infants during immunization. Mercurials have been
reported to cause apoptosis in cultured neurons; however, the signaling
pathways resulting in cell death have not been well characterized.
Therefore, the objective of this study was to identify the mode of cell
death in an in vitro model of thimerosal-induced neurotoxicity, and
more specifically, to elucidate signaling pathways which might serve as
pharmacological targets. Within 2 h of thimerosal exposure (5 microM)
to the human neuroblastoma cell line, SK-N-SH, morphological changes,
including membrane alterations and cell shrinkage, were observed. Cell
viability, assessed by measurement of lactate dehydrogenase (LDH)
activity in the medium, as well as the
3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)
assay, showed a time- and concentration-dependent decrease in cell
survival upon thimerosal exposure. In cells treated for 24 h with
thimerosal, fluorescence microscopy indicated cells undergoing both
apoptosis and oncosis/necrosis. To identify the apoptotic pathway
associated with thimerosal-mediated cell death, we first evaluated the
mitochondrial cascade, as both inorganic and organic mercurials have
been reported to accumulate in the organelle. Cytochrome c was shown to
leak from the mitochondria, followed by caspase 9 cleavage within 8 h
of treatment. In addition, poly(ADP-ribose) polymerase (PARP) was
cleaved to form a 85 kDa fragment following maximal caspase 3
activation at 24 h. Taken together these findings suggest deleterious
effects on the cytoarchitecture by thimerosal and initiation of
mitochondrial-mediated apoptosis.
14. Thimerosal
induces neuronal cell apoptosis by causing cytochrome c and
apoptosis-inducing factor release from
mitochondria
Yel L et al.
Int J Mol Med. 2005 Dec;16(6):971-7.
There is a worldwide increasing concern over the neurological risks of
thimerosal (ethylmercury thiosalicylate) which is an organic mercury
compound that is commonly used as an antimicrobial preservative. In
this study, we show that thimerosal, at nanomolar concentrations,
induces neuronal cell death through the mitochondrial pathway.
Thimerosal, in a concentration- and time-dependent manner, decreased
cell viability as assessed by calcein-ethidium staining and caused
apoptosis detected by Hoechst 33258 dye. Thimerosal-induced apoptosis
was associated with depolarization of mitochondrial membrane,
generation of reactive oxygen species, and release of cytochrome c and
apoptosis-inducing factor (AIF) from mitochondria to cytosol. Although
thimerosal did not affect cellular expression of Bax at the protein
level, we observed translocation of Bax from cytosol to mitochondria.
Finally, caspase-9 and caspase-3 were activated in the absence of
caspase-8 activation. Our data suggest that thimerosal causes apoptosis
in neuroblastoma cells by changing the mitochondrial
microenvironment.
15. Environmental
mercury release, special education rates, and autism disorder: an
ecological study of Texas
Palmer RF et al.
Health Place. 2006 Jun;12(2):203-9.
16. Autism spectrum
disorders in relation to distribution of hazardous air pollutants in
the san francisco bay area
Windham GC et al.
Environ Health Perspect. 2006 Sep;114(9):1438-44.
17. Proximity to
point sources of environmental mercury release as a predictor of autism
prevalence
Palmer RF et al.
Health Place. 2009 Mar;15(1):18-24.
18. Paraoxonase
[PON1] gene variants are associated with autism in North America, but
not in Italy: possible regional specificity in gene-environment
interactions
D'Amelio et al.
Mol Psychiatry. 2005 Nov;10(11):1006-16.
Organophosphates (OPs) are routinely used as pesticides in agriculture
and as insecticides within the household. Our prior work on Reelin and
APOE delineated a gene-environment interactive model of autism
pathogenesis, whereby genetically vulnerable individuals prenatally
exposed to OPs during critical periods in neurodevelopment could
undergo altered neuronal migration, resulting in an autistic syndrome.
Since household use of OPs is far greater in the USA than in Italy,
this model was predicted to hold validity in North America, but not in
Europe. Here, we indirectly test this hypothesis by assessing
linkage/association between autism and variants of the paraoxonase gene
(PON1) encoding paraoxonase, the enzyme responsible for OP
detoxification. Three functional single nucleotide polymorphisms, PON1
C-108T, L55M, and Q192R, were assessed in 177 Italian and 107
Caucasian-American complete trios with primary autistic probands. As
predicted, Caucasian-American and not Italian families display a
significant association between autism and PON1 variants less active in
vitro on the OP diazinon (R192), according to case-control contrasts
(Q192R: chi2=6.33, 1 df, P<0.025), transmission/disequilibrium tests
(Q192R: TDT chi2=5.26, 1 df, P<0.025), family-based association
tests (Q192R and L55M: FBAT Z=2.291 and 2.435 respectively,
P<0.025), and haplotype-based association tests (L55/R192: HBAT
Z=2.430, P<0.025). These results are consistent with our model and
provide further support for the hypothesis that concurrent genetic
vulnerability and environmental OP exposure may possibly contribute to
autism pathogenesis in a sizable subgroup of North American
individuals.
19. Maternal
residence near agricultural pesticide applications and autism spectrum
disorders among children in the California Central
Valley
Roberts EM et al.
Environ Health Perspect. 2007 Oct;115(10):1482-9.
20. A review of
Thimerosal (Merthiolate) and its ethylmercury breakdown product:
specific historical considerations regarding safety and
effectiveness
Geier DA, Sykes LK, Geier MR.
J Toxicol Environ Health B Crit Rev. 2007 Dec;10(8):575-96.
http://www.informaworld.com/smpp/ftinterface~content=a787584924~fulltext=713240930
21. Comparison of blood and brain mercury levels in infant
monkeys exposed to methylmercury or vaccines containing
thimerosal
Burbacher TM... Clarkson T.
Environ Health Perspect. 2005 Aug;113(8):1015-21.
{free online}
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280342/pdf/ehp0113-001015.pdf
Thimerosal is a preservative that has been used in manufacturing
vaccines since the 1930s. Reports have indicated that infants can
receive ethylmercury (in the form of thimerosal) at or above the U.S.
Environmental Protection Agency guidelines for methylmercury exposure,
depending on the exact vaccinations, schedule, and size of the infant.
In this study we compared the systemic disposition and brain
distribution of total and inorganic mercury in infant monkeys after
thimerosal exposure with those exposed to MeHg. Monkeys were exposed to
MeHg (via oral gavage) or vaccines containing thimerosal (via
intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total
blood Hg levels were determined 2, 4, and 7 days after each exposure.
Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days
after the last exposure. The initial and terminal half-life of Hg in
blood after thimerosal exposure was 2.1 and 8.6 days, respectively,
which are significantly shorter than the elimination half-life of Hg
after MeHg exposure at 21.5 days. Brain concentrations of total Hg were
significantly lower by approximately 3-fold for the thimerosal-exposed
monkeys when compared with the MeHg infants, whereas the average
brain-to-blood concentration ratio was slightly higher for the
thimerosal-exposed monkeys (3.5 +/- 0.5 vs. 2.5 +/- 0.3). A higher
percentage of the total Hg in the brain was in the form of inorganic Hg
for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate
that MeHg is not a suitable reference for risk assessment from exposure
to thimerosal-derived Hg. Knowledge of the toxicokinetics and
developmental toxicity of thimerosal is needed to afford a meaningful
assessment of the developmental effects of thimerosal-containing
vaccines.
Contact Teresa Binstock by email
Return to index of essays by Teresa Binstock
|