10 Page single spaced Research paper

Turner, Chakaela | Fort Valley State University| BIOL 4254K | November 28, 2017

Autism THE TRUE CAUSE OF AUTISM

Autism Turner

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Introduction

Vaccines have been a controversial topic on social media and in the headlines in the past

year. The purpose of a vaccine is to guard individuals to work with the immune system to

avoid disease. A vaccine is an item that produces resistance from an ailment and can be

administered through shots, orally, or by airborne.

Many people are now turning to natural approaches to heal the body rather than using

medications and vaccines. Top-rated causes of Autism Spectrum Disorder (ASD) were

genetics, brain structure, will of God, toxins in vaccines, and environmental pollutions

(Goin-Kochel, Mire, & Dempsey, 2014). However, in the result of receiving vaccines,

many parents believe that their children were showing signs of autism due to toxins in the

vaccines. In the summer of 2017, doctors diagnosed my youngest nephew Dylan with

high-functioning autism, ADHD, and hypotonia. Autism is one of three disorders part of

the Autism Spectrum Disorder (ASD); it is a range of states portrayed through social

skills, tedium behaviors, speech, and nonverbal correspondence (Autism Speaks, 2017).

Children who possess autism have restricted interests or repetitive behaviors with

difficult transitions. Paul Eugen Bleuler coined the term autism in 1912. Its origin derived

from the Greek word autos, meaning "self" (Blake, Hoyme, & Crotwell, 2013).

"Spectrum" refers to the variation in challenges and strengths possessed by each person

with autism (Autism Speaks, 2017). The subgroups recognized within ASD include

autistic disorder, Asperger syndrome and pervasive developmental disorder not otherwise

classified. (Blake, Hoyme, & Crotwell, 2013). Moreover, there are two types of

symptom onsets of ASD: regressive onset and early onset. Children with a regressive

autism demonstrate a loss of previously established skills in the first 24 months of life.

Early onset displays ASD symptoms in the first year of life, but no forfeiture of skills

characterizes symptom onset (Goin-Kochel, Mire, & Dempsey, 2014).

There are several types of vaccinations. Those include: live, attenuated vaccines;

inactivated vaccines; subunit vaccines; toxoid vaccines; conjugate vaccines; DNA

vaccines; and recombinant vector vaccines. Moreover, vaccinations such as Thimerosal-

containing vaccine and the measles, mumps, and rubella (MMR) vaccine are two

vaccines that have caused the most controversy in whether they result in autism. MMR is

a live attenuated vaccine; in other words, the microbe is weakened in the lab to prevent

disease and is the closest thing to a natural infection. They elicit strong cellular and

antibody responses and often confer lifelong immunity with only one or two doses.

Individuals with weakened immune systems cannot be administered live vaccines

(National Institute of Health, 2012).

Thimerosal, however, contains ethylmercury; ethylmercury prevents the growth of

bacteria in vaccines. Once thimerosal enters the body, the body can break it down to

ethylmercury and thiosalicylate, which are eliminated without trouble (Centers for

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Disease Control and Prevention, 2015). Thimerosal was once used in some childhood

vaccines, but in 2001 thimerosal was removed from vaccines. Today thimerosal only

exists in flu vaccines packaged in multidose vials. Thimerosal-free alternatives are also

available for flu vaccines (Centers for Disease Control and Prevention, 2015). Thimerosal

had never been utilized within MMR since antimicrobial agents are not utilized within

live vaccines (The College of Physicians of Philadelphia, 2017). Since the 1990s, a

various amount of studies have been done that indicate a thimerosal-containing vaccine, a

thimerosal-free vaccine, and an MMR vaccine does not cause autism. However, many

tests are still being done by researchers to determine if this still stands true for any

vaccine, including flu vaccines or if genetics plays a role.

Methodology/Description/Genetics

Various studies were done over the decades to determine whether the MMR vaccine, a

thimerosal-containing vaccine, or genetics played a role in an individual being diagnosed

with autism. The myth that vaccines caused autism started an anti-vaccine movement; it

was the result of a TV documentary titled DTP: Vaccine Roulette shown on WRC-TV, an

NBC affiliate in Washington D.C., on April 19, 1982, linking pertussis (whooping cough)

vaccine to severe reactions in children (Blake, Hoyme, & Crotwell, 2013). Three studies

are referred to below:

METHOD

MMR vaccine

All children born on January 1, 2001, to December 31, 2007, were included in the

database. These children were registered in a health care plan from birth to at least five

years of age and who also had an older sibling enrolled in a health care plan for at least

six months between the beginning and end of the study period. Siblings had to be at least

between 6 months and 17 years older than the index child to be included in the study.

ASD in index children and older siblings was determined using a claims-based algorithm

with a positive predictive value of 87% that required two or more claims on separate

dates of service with an International Classification of Diseases, Ninth Revision, Clinical

Modification diagnosis code in any position for autistic disorder, other specified

pervasive developmental disorder including Asperger syndrome, or unspecified Pervasive

developmental disorder.

Relative risks included children receiving one dose of MMR at ages 2, 3, 4, and 5 years

and two doses at age five years vs. those who were unvaccinated at those ages. Separate

relative risks were estimated for children with older siblings with and without ASD. Age

since birth was utilized as a time scale and included MMR receipt as a time-varying

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covariate assigning follow-up time to either the unvaccinated group, the 1-dose group, or

the 2-dose group, depending on immunization standing at any given age.

Fixed covariates included in the models were gender of the index child, parents’ age at

index child’s birth, geographic position defined by the four U.S. Census regions, mental

health assistance, index childbirth year, occurrence of seizures, presence of vaccination-

associated allergies, preterm birth, modified Childhood Chronic Conditions score (CCC)

parents’ educational level, household income, and race/ethnicity.

Statistical significance testing of unadjusted rate proportions was conducted utilizing the

Yates χ2 test; statistical significance testing of hazard ratios was conducted using Wald

χ2 statistics. All analyses were two-sided and were performed using SAS statistical

software (Jain et al., 2015).

Thimerosal-containing vaccine

From 1970 on, the only thimerosal-containing vaccine in the program was the whole-cell

pertussis vaccine. The same vaccine was reformulated without thimerosal and used

January 1, 1997, when it was replaced with an acellular pertussis vaccine. The whole cell

vaccine was administered at five weeks, nine weeks, and ten months from 1970 and until

it was replaced. The thimerosal formula comprised 50 µg of thimerosal (~25 µg of

ethylmercury) in the first dose and 100 µg (~50 µg of ethylmercury) in each of the

following two doses.

Since April 1968, all citizens of Denmark were given a unique identification number. The

scientists constructed a cohort consisting of all children born in Denmark in the period

from January 1, 1990, to December 31, 1996. The identification numbers were used to

link information on vaccinations, diagnoses of autism, diagnoses of other ASDs, other

relevant diagnoses, and potential confounders to the children in the cohort. Doses

administered before June 1, 1992, were considered to contain thimerosal, and doses

administered after June 1, 1992, were deemed thimerosal-free.

Data were obtained on possible confounding factors from the Danish Civil Registration

System and the Danish Medical Birth Registry. Factors are as follow: child's gender,

child's birth-place, weight at birth, 5-minute Apgar score, how far along the pregnancy is,

mother's age at birth of the child, and mother's country of birth.

Children within the cohort contributed time to follow-up from one year of age or January

1, 1991, whichever occurred last, until ASD, 11 years of age, or until December 31, 2000,

whichever occurred first. Follow-ups were done at one year of age due to evaluations for

ASD done after one year of age. Vaccination history was considered a time-varying

variable. Rate ratios were adjusted for age and calendar period.

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Brain Study

Colombia University researcher Guomei Tang analyzed brain tissue from 26 children and

young adults affected by autism. 13 of the children were between the ages of 2 and 9

when they died. 13 were between ages 13 and 20. For comparison, she also examined

donated postmortem tissue from 22 children and teens who did not have autism. Tang

measured the abundance of synapses in a small section of the cortical tissue from each

brain (Autism Speaks, 2014).

DESCRIPTION

MMR Vaccine

In 1998, Wakefield and associates published a study in The Lancet claiming that the

MMR vaccine was linked to autism even though they could not demonstrate a

relationship between MMR and autism. His paper was retracted in February 2010.

However, years after the study many other research experiments were carried out.

A reflective cohort study was directed utilizing a managerial claims database associated

with a significant U.S. health plan (the Optum Research Database). The database

included more than 34 million individuals each year, containing both commercially

insured individuals and Medicare managed care enrollees.

The MMR vaccine should be administered twice: once at age 12 to 15 months and once

and the age 4 to 6 years. Decreased vaccination rates could threaten public health and

reduce both individual and community protection. The belief that MMR is linked to

ASD, in collection with knowing that younger siblings of children with ASD are already

at higher genetic risk for ASD, may alert parents to avoid vaccinating their younger

children. According to the survey, out of the 486 parents of children with ASD,

approximately 20% had declined or deferred MMR immunization in the younger siblings

(Jain et al., 2015).

Thimerosal-containing vaccine

Mercuric compounds are nephrotoxic (toxic to the kidneys) and neurotoxic (toxic to the

nervous system) at high doses. Thimerosal, a preservative, contains ethylmercury. Many

believe that the vaccine is related to autism. 467450 children born in Denmark from

January 1, 1990, until December 31, 1996, were used in the study, comparing children

treated with a thimerosal-containing vaccine with children treated with a thimerosal-free

formulation of the same vaccine (Hviid, Stellfeld, Wohlfahrt, & Melbye, 2003).

Brain Study

A recent brain-tissue study proposes that children affected by autism have an excess

number of synapses or connections between neurons. The surplus is due to the decreased

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amount of regular pruning that occurs during brain growth. The scientist found that in

mice, the medication rapamycin not only aided in normal synaptic pruning but also

reduced autism-like behaviors. Their goal is to eventually use the medication to treat

autism in humans (Autism Speaks, 2014).

During regular brain development, an eruption of synapse formation arises in infancy.

The formation is noticeable in the cortex, which is essential to thought and processing

information from the senses. But by late adolescence, pruning eradicates about half of

these synapses. Also, many genes linked to autism are known to affect the development

or function of brain synapses (Autism Speaks, 2014).

GENETICS

Autism is fundamentally a genetic disease. A study done by scientists at Cold Spring

Harbor Laboratory in New York suggests that autism traces to one of 200 gene-disabling

mutations found in the child but neither parent. These mutations completely disable genes

that are crucial to early brain development. Also, they appear to be more common among

people who are severely disabled by autism versus those who are only mildly affected.

De novo, or new mutations first occur in the mother's egg, the father's sperm or early in

embryonic development. These variations also contain disruptive variants, which have

biased transmission: they are more often transmitted from mother to child affected with

ASD. Biased transmission is seen more frequently in affected children of lower IQ.

(Iossifov, et al., 2015).

These mutations are seen in higher rates of autism among children of older parents.

Mutations, however, are also based on environmental exposures (Iossifov et al., 2015).

These mutations can include deletions or duplications, also known as copy number

variations. To look at the changes in DNA between parent and child, another group of

scientists at Stanford School of Medicine used a CGH array to look for significant DNA

changes in a person's DNA all at once (Stanford School of Medicine Department of

Genetics, 2013). Of the discovered genes, 49 play a role in chromatin remodeling, RNA

processing or building connections between neurons (Gholipour, 2017).

Results/Research Data

MMR vaccine

Out of 95727 children in the study, 1929 (2.02%) had an older sibling with ASD. Overall,

994 (1.04%) children in the cohort had ASD diagnosed during follow-up. Among the

individuals who had an older sibling with ASD, 134 (6.9%) were diagnosed with ASD,

compared with 860 (0.9%) diagnosed with ASD among those with siblings without ASD

(P < .001). The MMR vaccination rate (at least one dose) for the children with unaffected

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siblings was 84% (n = 78549) at two years of age and 92% (n = 86063) at age five years

of age. On the contrary, the MMR vaccination rates for children who had siblings with

ASD were lower (73% at age two years of age [n = 1409] and 86% [n = 1660] at age five

years of age) (Jain et al., 2015).

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Thimerosal-containing vaccine

Out of 2,986,654 individuals, there were 440 identifiable autism cases and 787 cases of

other autistic-spectrum disorders. The average age for diagnosis of autism was

approximately four-and-a-half years and six years for other autistic-spectrum disorders.

In the cohort, only 20755 (4.4%) of children did not receive any whole-cell pertussis

vaccine, 446695 (95.6%) were vaccinated at least once, 416081 (89%) were vaccinated

twice, and 293186 (62.7%) received three doses of whole-cell pertussis vaccine. In those

receiving at least one dose of whole-cell pertussis vaccine, there were 407 cases of autism

and 751 cases of other autistic-spectrum disorders (303 receiving thimerosal-free and 321

receiving the thimerosal-containing vaccine). Furthermore, there was no evidence of a

dose-response association between the dose of ethylmercury received and ASD.

The danger of autism and other autistic-spectrum disorders did not vary significantly

between children vaccinated with thimerosal-containing vaccine and children treated with

the thimerosal-free vaccine (RR, 0.85 [95% confidence interval {CI}, 0.60-1.20] for

autism; RR, 1.12 [95% CI, 0.88-1.43] for other autistic-spectrum disorders). Moreover,

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no evidence was found of a dose-response association (increase in RR per 25 µg of

ethylmercury, 0.98 [95% CI, 0.90-1.06] for autism and 1.03 [95% CI, 0.98-1.09] for other

autistic-spectrum disorders) (Hviid, Stellfeld, Wohlfahrt, & Melbye, 2003).

Brain Study

After measuring the abundance of synapses, by late childhood, the density had decreased

50% in the brain tissue unaffected by autism. By contrast, the density had reduced by

16% in the brain from individuals who had autism. Likewise, evidence was found as to

what may have caused the lack of pruning. The neurons from the individuals with autism

were filled with damaged parts, and deficient in signs of a normal breakdown pathway

called autophagy.

Scientists traced the pruning defect to a protein called mTOR (mammalian Target of

Rapamycin). When mTOR is overactive, the brain cells lose much of their self-pruning

ability. Thus, the brain cells show an overabundance of synapses. The researchers

restored normal autophagy and synaptic pruning in the mice by administering rapamycin

– a drug that inhibits mTOR. Treatment eliminated the mice’s autism-like behaviors. The

treatment remained effective even when given to older mice. Further evidence showed

that large amounts of overactive mTOR were found in the postmortem brain tissue of

individuals with autism. Countless genes have been linked to autism, but a portion of

them affect the mTOR/autophagy pathway (Autism Speaks, 2014).

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Discussion

MMR vaccine

The data and results were depended on privately insured children with an extended period

of continuous enrollment in a single health plan. Observations concluded that there was

no association between the MMR vaccination and increased ASD risk among privately

insured children. No evidence was found regarding either one or two doses of the MMR

vaccination was associated with an increased risk of ASD among children who had older

siblings with ASD.

As the occurrence of diagnosed ASD rises so does the number of children who have

siblings diagnosed with ASD. Even though there were no statistically substantial rate

ratio estimates indicating increased ASD risk at any age in those whose older siblings had

or did not have ASD, the statistically significant interactions in the final model suggested

differences in the rate ratio by both age and older sibling ASD status.

This study used a large administrative claims dataset spreading a recent 11-year period to

observe the relationship between MMR immunization status and ASD risk in the United

States. The administrative claims database permitted the estimation of associations free

from potential recall bias. The directorial claims, however, do demonstrate some

significant research boundaries. The MMR immunization rates were 4% to 14% lower

than rates stated in the National Immunization Survey. Therefore, children in the study

who were considered unvaccinated may have received vaccines in public health clinics or

schools in which claims were not submitted. Many children with ASD did not receive

care during the study time frame. However, a quantitative bias analysis was done to

evaluate the potential impact of these measurement errors; these errors did not strongly

influence the findings of the study (Jain et al., 2015).

Thimerosal-containing vaccine

There is no proof of a relationship between thimerosal-containing vaccine and autism in

children who received the thimerosal-containing vaccine vs. children who received the

thimerosal-free vaccine. Ethylmercury, on the other hand, is believed to have a shorter

lifespan in the body than methylmercury; no controlled research of low-dose

ethylmercury toxicity has yet been conducted in the human body. The concentration of

mercury in the stool, urine, and blood of infants who were administered the vaccine was

measured; the vaccine did not raise the blood concentration of mercury above safe limits,

and ethylmercury was eliminated rapidly via the stools (Hviid, Stellfeld, Wohlfahrt, &

Melbye, 2003).

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Brain Study

Rapamycin is an FDA-approved antibiotic and immunosuppressant. This drug inhibits

the activity of mTOR, which in turn inhibits the process called autophagy. Autophagy

allows a cell to break down its molecules and other components that are no longer

needed. In other words, rapamycin inhibits mTOR and promotes autophagy. Rapamycin

also helps nerve cells break down, hence why pruning is important (Liou, 2010).

Conclusion

Vaccines are safe and effective. They work with the immune system to prevent disease

and protect individuals and the community (U.S. Department of Health and Human

Services, 2011); they reduce the risk of infection by working with the body's natural

defenses to help safely develop immunity to diseases. Vaccines help build resistance by

imitating infection, but it does not cause infection. When someone in a community has

been vaccinated, the spread of a virus/disease decreases. Vaccination does not eliminate

an unvaccinated person from getting infected, but it does lower the risk.

There is no evidence to prove that the measles-mumps-rubella vaccine and a thimerosal-

containing vaccine cause autism. While vaccines have been proven not to cause autism,

studies show that autism is genetic due to mutations in the child. Genetics plays a major

role in autism, specifically as a mutation. Other causes of autism include excess

cerebrospinal fluid and infections in mothers during pregnancy but little evidence has

been found.

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