In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 03-0632V

Originally filed September 28, 2015

Refiled in redacted form May 23, 2016

 For Publication

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

*

R.K., on behalf of A.K., a Minor, * Autism; Entitlement;

* Mitochondrial

Petitioners, * Disorder;

* Influenza Vaccine;

* Diagnosis; ASD

SECRETARY OF THE DEPARTMENT *

OF HEALTH AND HUMAN SERVICES, *

*

Respondent. *

*

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

John F. McHugh, New York, N.Y. for petitioners.

Heather L. Pearlman, U.S. Department of Justice, Washington, DC, for respondent.

DECISION1

Vowell, Special Master:

On March 26, 2003, petitioners [ * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * 

* * * * * ] filed a Short-Form “Petition for Vaccine Compensation”2for compensation

under the National Vaccine Injury Compensation Program, 42 U.S.C. §300aa-10, et

1

[* * * * * * * * * * * * * * * * * * * * * This ruling was originally issued on September 28, 2015. In this 

public Ruling, the family name of the petitioners has been redacted, pursuant to their request.]

2 By electing to file a Short-Form Autism Petition for Vaccine Compensation, petitioners alleged that:

[a]s a direct result of one or more vaccinations covered under the National Vaccine Injury

Compensation Program, the vaccine in question has developed a neurodevelopmental

disorder, consisting of an Autism Spectrum Disorder or a similar disorder. This disorder

was caused by a measles-mumps-rubella (MMR) vaccination; by the “thimerosal”

ingredient in certain Diphtheria-Tetanus-Pertussis (DTP), Diphtheria-Tetanus-acellular

Pertussis (DTaP), Hepatitis B, and Hemophilus Influenza Type B (HIB) vaccinations; or

by some combination of the two.

Autism General Order #1, filed July 3, 2002, Exhibit A, Master Autism Petition for Vaccine Compensation

at 2.
2

seq3[“Vaccine Act” or “Program”] on behalf of their son [“A.K.”], thereby joining the

Omnibus Autism Program [“OAP”]. An amended petition was filed on February 28,

2011, and a second amended petition [hereinafter “2d Am. Pet”], which now constitutes

the operative petition for petitioners’ vaccine injury claim on behalf of A.K., was filed on

April 17, 2013, just days prior to the causation hearing.

In their second amended petition,4 petitioners claimed that A.K.’s two influenza

vaccinations “either resulted in an encephalopathy or significantly aggravated an

existing condition related to prior vaccinations or otherwise.” Petition at 1 (ECF No.

237). In ¶¶ 74-76, petitioners specified that the “existing condition” is a mitochondrial

disorder.

Petitioners here, like the petitioners in the vast majority of the autism spectrum

disorder [“ASD”] cases on my docket since 2007, have a firm, fixed belief that

vaccinations have caused or significantly aggravated their child’s neurodevelopmental

disorder. Since the OAP test case decisions were issued (and affirmed on appeal),5

most of the petitioners who elected to proceed on new theories (or old theories

readdressed) have eschewed the autism diagnoses that appear in their children’s

medical records, asserting that their children have various other conditions which

resulted in behavioral symptoms that led to or looked like ASD, using terms like

“encephalopathy” or “encephalitis” as euphemisms for ASD. They have also asserted

that their children have metabolic or mitochondrial disorders that either look like an ASD

or to explain that, notwithstanding the test case decisions, their children were vulnerable

3 The National Vaccine Injury Compensation Program [“Vaccine Program”] is set forth in Part 2 of the

National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended,

42 U.S.C. § 300aa-10 et seq. (2012). All citations in this decision to individual sections of the Vaccine Act

are to 42 U.S.C. § 300aa.

4 Hereinafter, unless the context clearly indicates otherwise, any references to “petition” are to this

Second Amended Petition.

5 Decisions in each of the three test cases pertaining to the first theory of causation [“Theory 1”] presented

by the Petitioners’ Steering Committee [“PSC”] rejected the petitioners’ causation theories. Cedillo v.

Sec’y, HHS, No. 98-916V, 2009 WL 331968 (Fed. Cl. Spec. Mstr. Feb. 12, 2009) aff’d, 89 Fed. Cl. 158

(2009), aff’d, 617 F.3d 1328 (Fed. Cir. 2010); Hazlehurst v. Sec’y, HHS, No. 03-654V, 2009 WL 332306

(Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d 88 Fed. Cl. 473 (2009), aff’d, 604 F.3d 1343 (Fed. Cir. 2010);

Snyder v. Sec’y, HHS, No. 01-162V, 2009 WL 332044 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed.

Cl. 706 (2009). Decisions in each of the three “test cases” pertaining to the PSC’s second theory

[“Theory 2”] also rejected the petitioners’ causation theories, and the petitioners in each of those three

cases chose not to appeal. Dwyer v. Sec’y, HHS, No. 03-1202V, 2010 WL 892250 (Fed. Cl. Spec. Mstr.

Mar. 12, 2010); King v. Sec’y, HHS, No. 03-584V, 2010 WL 892296 (Fed. Cl. Spec. Mstr. Mar 12, 2010);

Mead v. Sec’y, HHS, No. 03-215V, 2010 WL 892248 (Fed. Cl. Spec. Mstr. Mar. 12, 2010). These “test

case” decisions were deliberately written comprehensively, in anticipation that the evidence set forth

therein would be available to resolve the thousands of cases remaining in the OAP. They thus analyzed

in detail all of the evidence presented on both sides. The three test case decisions in Theory 1 totaled

more than 600 pages of detailed analysis, and were solidly affirmed in many more pages of analysis in

three different rulings by three different judges of the United States Court of Federal Claims, and in two

rulings by two separate panels of the United States Court of Appeals for the Federal Circuit. The three

decisions concerning Theory 2 were similarly comprehensive; no motions for review were filed. Thus, 11

lengthy written rulings by the special masters, the judges of the U.S. Court of Federal Claims, and the

panels of the U.S. Court of Appeals for the Federal Circuit unanimously rejected the petitioners’ claims.
3

to the side effects of a vaccine by virtue of these underlying genetic conditions. Thus,

they have claimed that various vaccines significantly aggravated these underlying

conditions, resulting in an ASD diagnosis.

For nearly nine years, several of my colleagues and I have had the unenviable

task of hearing these heart-wrenching cases.6If sympathy alone could provide a basis

for judgment in their favor, they would have that judgment. This case is rendered even

more difficult because of the severity of A.K.’s condition and because petitioner [ R.K.

* * * * ] is a well-respected attorney who appears frequently in Vaccine Act cases,

including many similar to A.K.’s.

Nevertheless, I am charged with deciding this causation in fact case based on

the requirements of the Vaccine Act and the binding precedents of the Federal Circuit

interpreting the Act’s provisions. The Act requires preponderant evidence that a

vaccine actually caused or significantly contributed to A.K.’s condition before

compensation may be awarded. Petitioners failed to produce preponderant evidence

that the two influenza vaccinations they now claim were responsible7 can or did cause

or significantly aggravate A.K.’s condition. Their petition is therefore dismissed.

I. Abbreviated Procedural History.

This case has had a long and complicated procedural history. Indeed, petitioners

initially advanced this case as a test case for the OAP with regard to the second

causation theory – i.e., that thimerosal-containing vaccines cause autism. Ultimately,

petitioners withdrew as an OAP test case and filed an amended petition which changed

6 A small minority of the autism petitioners have elected to continue to pursue their cases, seeking other

causation theories and/or other expert witnesses. All of the causation in fact and significant aggravation

decisions issued to date have rejected petitioners’ claims that vaccines played a role in causing their

child’s autism. See, e.g., Holt v. Sec’y HHS, No. 05-136V, 2015 WL 4381588 (Fed. Cl. Spec. Mstr. June

24, 2015) (mitochondrial disorder), Miller v. Sec’y HHS, No. 02-235V, 2015 WL 5456093 (Fed. Cl. Spec.

Mstr. Aug. 18, 2015) (encephalopathy and mitochondrial disorder), Nuttall v. Sec’y, HHS, No. 07-810V,

2015 WL 4934583 (July 31, 2015), Brook v. Sec’y, HHS, No. 04-405V, 2015 WL 3799646 (Fed. Cl. Spec.

Mstr. May 14, 2015) (autoimmune encephalopathy), Blake v. Sec’y, HHS, No. 03-31V, 2014 WL 2769979

(Fed. Cl. Spec. Mstr. May 21, 2014) (autism not caused by MMR vaccination); Henderson v. Sec’y, HHS,

No. 09-616V, 2012 WL 5194060 (Fed. Cl. Spec. Mstr. Sept. 28, 2012) (autism not caused by

pneumococcal vaccination); Franklin v. Sec’y, HHS, No. 99- 855V, 2013 WL 3755954 (Fed. Cl. Spec.

Mstr. May 16, 2013) (MMR and other vaccines found not to contribute to autism); Coombs v. Sec’y, HHS,

No. 08-818V, 2014 WL 1677584 (Fed. Cl. Spec. Mstr. Apr. 8, 2014) (autism not caused by MMR or

varicella vaccines). In addition, some causation autism claims have been rejected without trial, at times

over the petitioner’s objection, in light of the failure of the petitioner to file plausible proof of vaccinecausation. See, e.g., Waddell v. Sec’y, HHS, No. 10-316V, 2012 WL 4829291 (Fed. Cl. Spec. Mstr. Sept.

19, 2012) (autism not caused by MMR vaccination); Geppert v. Sec’y, HHS, No. 00-286V, 2012 WL

2500852 (Fed. Cl. Spec. Mstr. Sept. 6, 2012); Fesanco v. Sec’y, HHS, No. 02-1770, 2010 WL 4955721

(Fed. Cl. Spec. Mstr. Nov. 9, 2010); Fresco v. Sec’y, HHS, No. 06-469V, 2013 WL 364723 (Fed. Cl. Spec.

Mstr. Jan. 7, 2013); Pietrucha v. Sec’y, HHS, No. 00-269V, 2014 WL 4338058 (Fed. Cl. Spec. Mstr. Aug.

22, 2014). Judges of this court have affirmed the practice of dismissal without trial in such a case. E.g.,

Fesanco v. Sec’y, HHS, 2011 WL 1891701 (May 16, 2011) (Judge Braden). No judge or special master

has found, post the test case decisions, that any vaccine can contribute to or cause autism.

7 When this claim was filed, the influenza vaccines they now claim were causal were not on the Vaccine

Injury Table, and thus no claim of injury caused by them could be brought. See 42 C.F.R. § 100.3(c)(6)

(“Trivalent influenza vaccines (Item XIV of the Table) are included on the Table as of July 1, 2005”).
4

their theory to allege that two doses of A.K.’s influenza vaccination were the cause of

his injury.8

The history of this case is also noteworthy for a dismissal of the petition in 2011

for failure to prosecute and failure to comply with court orders and a granted motion to

reconsider the dismissal; scattershot and untimely filing of medical literature; and a

number of motions in limine filed on the eve of the entitlement hearing. Thus, due to the

unusually protracted procedural history in this case, I have issued a separate ruling

addressing the numerous motions and evidentiary issues raised prior to and after

hearing. See Motions Ruling, filed on Sept. 28, 2015 (ECF No. 319). A more complete

procedural history of this case appearing in that ruling is incorporated here by reference.

Only those matters necessary to the understanding of events at the hearing and the

entitlement determination process will be repeated here. This abbreviated procedural

history is provided to place the lengthy delays leading to resolution of this 12-year-old

claim in context.

By filing their short-form petition, petitioners opted into the OAP.9 Cases in the

OAP remained “on hold” for an extended period at petitioners’ request, while discovery

proceeded. In early 2008, A.K.’s case was identified as one of the three test cases to

be heard on the second theory of causation in the OAP. This theory was that

thimerosal-containing vaccines caused ASD.

While this case was one of the test cases, petitioners filed some expert reports

and medical records.10 They also filed some of A.K.’s medical and school records.

See, e.g., filings of Feb. 14, 2008.

On April 10, 2008, approximately a month before the OAP was to begin,

petitioners filed a motion requesting to withdraw A.K.’s case as a test case and to

withdraw from the OAP.11 They explained that they intended to pursue another theory

of causation not addressed in the OAP, while specifically reserving the right to present

evidence on the thimerosal theory along with their new theory. See Motion, filed Apr.

10, 2008. Respondent did not object and I granted petitioners’ motion. See Order, filed

8 At the time the original petition was filed in this case, other vaccines were alleged as causal. The

influenza vaccine was not added to the Vaccine Injury Table, 42 C.F.R. § 100.3, until 2005.

9 A detailed explanation of the creation of the OAP and the effects of opting into it can be found in Dwyer,

2010 WL 892250, at *3.

10These expert reports by Drs. Elizabeth Mumper, Richard Deth, Sander Greenland, and H. Vasken

Aposhian were filed in support of the thimerosal causation theory. With the exception of Dr. Mumper’s

report, they were not tailored to A.K.’s specific case, and presented only general causation evidence. In

Dwyer, 2010 WL 892250, based on these same reports and subsequent testimony, I rejected the

hypothesis that thimerosal-containing vaccines can cause ASDs.

11 In a status conference on November 3, 2008, petitioners indicated their desire to return the case to the

OAP, largely because I was pressing them to obtain and file an expert report on causation and, as the

OAP test case decisions were still pending, they would have the benefit of the extended period of delay

afforded to the OAP petitioners until the test case decisions were finalized. I directed them to file a

written motion so requesting. See Order filed November 7, 2008. Petitioners never filed such a motion.
5

Apr. 15, 2008. By withdrawing from the OAP, petitioners signaled their intent to

proceed to a causation hearing on their new theory.12

However, soon after the withdrawal, it became apparent that petitioners were not

yet prepared to proceed to a hearing. Petitioner [R.K.* * * ] was substituted as the

attorney of record for his son. Order, filed May 23, 2008. Although [R.K. * * * * ] 

represented that he was actively seeking another attorney to pursue A.K.’s claim (see

Order, filed Jun. 17, 2008) and that he was pursuing medical testing and opinions on

causation, a new attorney, or did not enter an appearance for about 19 months. On

January 5, 2010,13 Mr. John McHugh filed a motion to be substituted in as counsel in

this case.

On January 20, 2010, I held a status conference with the parties to discuss the

next steps in this case. During this phone call, Mr. McHugh informed me he had not yet

met with petitioners or familiarized himself with the case. See Order, filed Jan. 20,

2010, at 1. Over the next two months, there was little progress on the case, but in

March 2010, Mr. McHugh informed me that he was reviewing A.K.’s medical records,

that Dr. Marcel Kinsbourne had been retained as an expert,14 and suggested that in 90

days, he would be able to participate in a status conference to set a schedule for further

proceedings.

On June 8, 2010, I held a status conference with the parties. Reporting that

financial constraints were hampering their ability to obtain experts, petitioners indicated

they intended to file a request for interim costs. I directed that the interim fee

application be filed by July 23, 2010, and that petitioners inform me of their progress in

retaining additional experts by August 9, 2010. Order, Jun. 8, 2010. Petitioners did not

file an interim fee application.

Instead, they filed an out of time15 status report on August 13, 2010. In their

status report, petitioners informed me that: (1) Dr. Kinsbourne was unable to complete

his expert report as he was awaiting further diagnostic tests; (2) Dr. Kinsbourne could

not specify when his expert report would be completed; and (3) petitioners were

pursuing another unnamed expert as Dr. Kinsbourne might not be testifying in the case.

12 It later became apparent that their new theory was based on what they perceived as having happened

in another OAP case. That case, Poling v. Sec’y, HHS, No. 02–1466V, is discussing in detail in Sections

VIII.A.2-3, below, and in the motions ruling in this case. Petitioners here have asserted that the

respondent is “judicially estopped” from contesting A.K.’s case based on how the Poling case was

handled. See Motions Ruling, filed on Sept. 28, 2015 (ECF No. 319), at Section II.B.6.

13 Mr. McHugh filed a defective motion to substitute on December 2, 2009.

14 Doctor Kinsbourne, a frequent witness for Vaccine Act petitioners, had testified in both the Theory 1 and

Theory 2 test cases. Snyder, 2009 WL 332044, at *11-12 (referencing Dr. Kinsbourne’s participation 

in Cedillo, 2009 WL 331968, at *23 and Dwyer, 2010 WL 892250, at *16).

15Petitioners’ status report was due on August 9, 2010. Petitioners were reminded how to request

additional time under Vaccine Rule 19(b) and warned that future out of time filings would be struck from

the record. See Order, filed Aug. 18, 2010, at 1, n.1.
Status Report, filed Aug. 13, 2010, at 1-2. Petitioners suggested that they file monthly

status reports until their expert reports were filed. Id. at 2.

I rejected this suggestion and, instead, ordered petitioners: (1) to identify their

potential new expert and outline the steps taken to contact him or her; (2) to file a status

report informing me when Dr. Kinsbourne had received the medical records he needed

and when his report could be filed; and (3) if Dr. Kinsbourne could not file his report

within 75 days, to file a letter from Dr. Kinsbourne explaining why and giving a date

when his report would be completed. Order, filed Aug. 18, 2010, at 1-2. The deadline

set in this order was August 27, 2010.

My August 18 order, I was very clear that some progress in obtaining an expert

report had to be demonstrated if the case was to continue, as the records filed to date

had failed to suggest vaccine causation of A.K.’s condition. I noted that the geneticist

who had been seeing A.K. had specifically recommended that he continue to receive

vaccinations and indicated that he was a “good candidate” to receive seasonal

vaccinations, such as influenza. Petitioners’ Exhibit [“Pet. Ex.”] 34, p. 6.16 At this point,

Dr. Kinsbourne had been reviewing A.K.’s case for about five months. The fact that no

opinion from Dr. Kinsbourne had yet been filed, coupled with the suggestion that he

might not be testifying, signaled to me that he was either unable or unwilling to opine

favorably in A.K.’s case.

Petitioners failed to reply to both this order and likewise ignored an Order to

Show Cause issued on September 3, 2010. Therefore, I dismissed the petition on

October 13, 2010. However, petitioners filed a motion for reconsideration on October

26, 201017 which I granted on November 12, 2010.18

I subsequently ordered petitioners to file a status report informing me of the date

a report from their new expert, Dr. Frye, would be filed and to file an “amended petition

clarifying their theory of causation.” Order, filed Nov. 15, 2010, at 1. In response,

petitioners filed a motion requesting an enlargement of time to file their amended

petition and seeking an award of interim costs in the amount of $5,00019 to be paid as a

16 In this decision, pin citations to medical records are made using a page number format. E.g., “Pet. Ex.

34, p. 6.” Pin citations to other documents, including affidavits, expert reports, medical journal articles,

briefs, etc., are made using an “at” format. E.g., “Pet. Ex. 23 at 3.” Because medical journal articles are

often publically available, citations to journal articles are usually made using the page numbers integral to

the published article, rather than the page numbers assigned by counsel. The public has no access to

articles filed by a party. See § 12(d)(4)(A).

17 With their motion for reconsideration, petitioners also filed the much-delayed report from Dr. Marcel

Kinsbourne, along with other evidence. See Pet. Exs. 37-56.

18 Petitioners also filed motions requesting redaction of the October 13, 2010 decision and November 24,

2010 order granting the motion for reconsideration. See Motions, filed Oct. 29 and Nov. 24, 2010. I

granted redaction of A.K.’s name and the medical references identified by petitioner but denied redaction

of petitioners’ names. Order, filed Jan. 10, 2011, at 3, 5.

19 This amount was based on an hourly rate of $500 and thus constituted payment for ten hours of work.

To the best of my knowledge, this decision was the first time any special master had authorized advance

payment for an expert.

6
7

retainer to Dr. Frye. On January 28, 2011, I granted the motion for additional time to file

an amended petition and awarded interim costs in the amount of $5,000.20

On February 28, 2011, petitioners informed me that Dr. Frye would not be

opining in this case as he was changing institutions and “would no longer be able to

provide services as an expert witness.” Motion, filed Feb. 28, 2011, at 1.

In March 2011, petitioners identified their new expert, Dr. Yuval Shafrir, and

requested an additional sixty days to file his report. Status Report, filed Mar. 9, 2011. I

granted petitioners’ unopposed request for additional time, ordering them to file Dr.

Shafrir’s expert report by May 9, 2011. Order, filed Mar. 9, 2011, at 1. Petitioners

received one more enlargement of time before filing Dr. Shafrir’s expert report on July 7,

2011.21 See Order, filed Jun. 30, 2011.

Between July and December 2011, petitioners filed the report of an additional

expert, Dr. Fran Kendall, and respondent filed a supplemental Vaccine Rule 4 report and

several expert reports. At a January 13, 2012 status conference, petitioners indicated

that they were looking for two additional experts, one in pediatric development 

and one in oxidative stress. As the report of petitioners’ mitochondrial disease specialist

had not been filed until December 21, 2011, I provided a new deadline for the report of

respondent’s mitochondrial disorder specialists. I indicated that, notwithstanding the

indications that more expert reports were expected, the parties should confer on hearing

dates, with a hearing to begin between November 2012 and February 2013.

The parties having eventually agreed to a hearing for the last two weeks of

February 2013, on February 13, 2012, I set this case for a hearing on February 17-27,

2013 in Washington, DC. Additional experts were identified and reports filed between

March and July 2012.22

On July 31, 2012, notwithstanding that the February 2013 hearing date had been

set a year in advance, petitioners informed me that the hearing date would have to be

moved. Petitioners explained that their attorney was lead counsel in an unrelated civil

case in which the trial judge had “set a firm trial date” which conflicted with the hearing

date for this case. Status Report, filed Jul. 31, 2012, at 1.

20 On February 7, 2011, respondent filed a motion for reconsideration which I denied. See Order, filed

Feb. 23, 2011, at 5. However, I withdrew my decision awarding interim costs on February 28, 2011 after

petitioners informed me that Dr. Frye was no longer opining in this case. See Order, filed Feb. 28, 2011.

21Petitioners did not seek interim fees for Dr. Shafrir until shortly before the hearing.

22 On March 13, 2012, respondent filed expert reports from Bruce Cohen, M.D. and Kendall B. Wallace,

Ph.D. Petitioners informed me that A.K.’s pediatrician, Dr. Heddy Zirin, would be testifying in this case

but they still were seeking a medical expert in oxidative stress. Status Report, filed Jun. 1, 2012, at 1. On

July 31, 2012, petitioners filed a status report, informing me that Richard Deth, Ph.D. would be testifying

as an expert in oxidative stress and Mary Megson, M.D. would be testifying as a developmental

pediatrician.
8

On August 1, 2012, I held a status conference to discuss this issue. See Order,

filed Aug. 1, 2012, at 1. I reminded petitioners that I “deliberately set the hearing a year

in advance to give the large number of experts who are expected to testify ample time

to make the necessary arrangements in their clinical practices and research schedules

to permit their presence at the hearing.” Id. Furthermore, I “expressed my concern that

petitioners’ counsel failed to inform the trial judge of our previously set firm hearing date

in this case when the jury trial date was being discussed.” Id. (emphasis in the original).

I ordered the parties to file a joint status report, discussing whether the entitlement

hearing could be held from February 25, 2013 through March 5, 2013 and if a fact

hearing could be scheduled in December 2012 or January 2013. Id.

Instead of a joint report, the parties filed separate status reports on August 15,

2012 indicating their preferred schedules. I then set a fact hearing in New York City,

N.Y. from December 12-13, 2012 to take testimony from petitioners and fact testimony

from two of A.K.’s treating physicians, Drs. Boris and Zirin (fact testimony only).

Ultimately, only [A.K.’s parents] testified at the fact hearing. For reasons never clearly

articulated, Dr. Zirin never testified; Dr. Boris appeared at the entitlement hearing as

both a fact and as an expert witness.

I set the entitlement hearing for April 22-30, 2013. Order, filed Aug. 16, 2012, at

1. I also ordered petitioners to file all expert reports by September 14, 2012 and

respondents to file all expert reports by November 13, 2012.23

This time the entitlement hearing went off as scheduled, notwithstanding a

number of late filings by petitioners, including expert reports, motions, a second

amended petition, and medical journal articles. Post-hearing, petitioners sought to file

more medical journal articles, and requested and received several extensions for their

post-hearing briefs. I declared the evidentiary record closed in 2013 (Order, issued

Nov. 15, 2013 (ECF No. 282)), but petitioners filed many more medical journal articles

thereafter, some of which I allowed and some of which I ordered to be stricken from the

record. See Motions Ruling, filed on Sept. 28, 2015 (ECF No. 319), at Section II.C.

Although petitioners had requested the opportunity to present the testimony of

either Dr. Megson or another physician with expertise in developmental pediatrics,

ultimately they decided to rely on Dr. Megson’s report. They withdrew their requests to

file another expert report and conduct another session of the entitlement hearing.

Motion in Limine, filed Apr. 8, 2013 (ECF No. 227). With the filing of the last posthearing briefs on June 16, 2014, this case became ripe for resolution.24

23 Once again, the deadlines had to be extended. Petitioners filed expert reports from Drs. Megson and

Boris on September 26, 2012 and from Dr. Deth on October 29, 2012. Since I had extended petitioners’

deadlines at their request, I also adjusted respondent’s deadline, ordering her to file all expert reports by

December 13, 2012. See Order, filed Sept. 26, 2012.

24After this date, petitioners and respondent filed additional documents addressing various motions,

which are discussed in greater detail in the in the motions ruling. See Motions Ruling, filed on Sept. 28,

2015 (ECF No. 319), at Section II.C.1.
9

The subsequent sections begin with a brief summary of the reasons for the

decision in this case (Section II) followed by a summary of A.K.’s medical history

(Section III). More detailed information about A.K.’s medical history is provided in the

later sections dealing with A.K.’s diagnoses and the analyses of the various theories

presented by petitioners’ experts (Sections VI-IX).

II. Summary of Decision.

Although petitioners present multiple theories, this crux of all of them is whether

A.K.’s two influenza vaccinations in November and December of 2001 significantly

aggravated A.K.’s alleged underlying mitochondrial disorder, thereby causing-in-fact

ASD or an encephalopathy presenting as ASD.

Because petitioners are not raising a “Table” injury claim, they must show by

preponderant evidence a medical theory causally connecting the vaccinations to the

injury, a logical sequence of cause and effect showing that the vaccination was the

reason for the injury, and a showing of a proximate temporal relationship between the

vaccinations and the injury.

After considering the record as a whole, I hold that petitioners have failed to

establish by preponderant evidence that A.K.'s condition was caused or significantly

aggravated by a vaccine or any component thereof. The evidence presented was both

voluminous and extraordinarily complex. After careful consideration of all of the

evidence, it was abundantly clear that petitioners' theories of causation were speculative

and unpersuasive. Respondent's experts were far more qualified, better supported by

the weight of scientific research and authority, and simply more persuasive on nearly

every point in contention.

Petitioners have failed to show that A.K. had an underlying mitochondrial

disorder. They have also failed to show that the onset of A.K.’s ASD was in any way

related to his influenza vaccinations. Indeed, respondent persuasively presented

significant evidence indicating that A.K.’s ASD onset predated his vaccinations. Nor did

petitioners establish by preponderant evidence that A.K. experienced any regression of

skills related to his ASD or his vaccinations. Thus, petitioners have failed to establish

as a factual matter that either of A.K.’s two influenza vaccines of November and

December 2001 either caused or aggravated his ASD or any other neurological

condition. Moreover, even if I accepted petitioners’ interpretation of the factual record,

petitioners failed via their multiple theories to even establish that an influenza vaccine

could have caused the type of injury they have alleged.

Therefore, I deny their petition for compensation.

III. Summary of A.K.’s Medical History.

Most of A.K.’s medical history is not in dispute. The portions that are in dispute

primarily concern whether certain behaviors displayed on videos, and sometimes

mentioned in medical records or other evidence, constituted early symptoms of ASD,

when symptoms of developmental delay or ASD arose, the symptoms he displayed

prior to and after the allegedly causal vaccinations, and whether some of the diagnoses
10

appearing in his records are correct. These contested issues are addressed in some

detail in Sections VI – IX below. Thus, only an abbreviated medical history is provided

below.

A.K. was born in early November 1999, after an uneventful pregnancy. See

generally, Pet. Exs. 15, 19. He was a large baby, weighing about 10 1⁄2 pounds, and

because of his size, he was delivered early by caesarian section. Pet. Ex. 19, pp. 7-8.

His Apgar scores were 9 and 9, reflective of a healthy newborn.25 Id. A slight heart

problem was noted before he was discharged from the hospital, but a pediatric

cardiology consultation found no pulmonary stenosis.26 Pet. Exs. 61, p. 178.

In his first 18 months of life, A.K. received the usual childhood vaccinations,

without apparent ill effects.27 These vaccinations are reflected on a handwritten

summary sheet appearing in the records of Woodbury Pediatrics Associates

[“Woodbury Pediatrics”], where A.K. received most of his primary care from his

25 The Apgar score is a numerical assessment of a newborn’s condition (with lower numbers indicating

problems), usually taken at one minute and five minutes after birth. The score is derived from the infant’s

heart rate, respiration, muscle tone, reflex irritability, and color, with from zero to two points awarded in

each of the five categories. See DORLAND’S ILLUSTRATED MEDICAL DICTIONARY (32d ed. 2012)

[“DORLAND’S”] at 1682 (all citations to DORLAND’S will be to the 32d ed., unless otherwise noted).

26 Subsequent evaluations in 2000 and 2001 also found that the murmur was essentially benign. See

Pet. Ex. 61, pp. 176-77.

27 A.K. received his initial hepatitis B vaccination on November 15, 1999, with subsequent doses on

December 30, 1999 and May 2, 2000. Pet. Ex. 61, p. 4. This series of vaccinations was completed. His

other vaccinations appear to have been spaced out to avoid receipt of more than two vaccinations at any

one time. He received his first diphtheria, tetanus and acellular pertussis [“DTaP”] on December 20, 1999

when he was about six weeks old and his first Haemophilus influenza type B [“Hib”] and inactivated polio

[“IPV”] vaccinations on January 27, 2000, when he was about two and one half months old. Pet. Ex. 61,

p. 4. A.K. received a second DTaP on February 29, 2000, at not quite four months of age, and his

second Hib and IPV vaccines on March 30, 2000 at not quite five months of age. The year of this Hib

vaccination is incorrectly reflected on the summary sheet (Pet. Ex. 61, p. 4) as 2001, but it appears on

another summary sheet and the vaccine administration record as 2000. See id., p. 106; Pet. Ex. 16, p.

131. A.K. received his third DTaP vaccine on May 2, 2000 and his third Hib vaccination on June 6, 2000,

when he was six and seven months of age, respectively. Pet. Ex. 61, p. 4. He did not begin receiving

Prevnar vaccinations until September 20, 2000, when he was over 10 months of age, but this was likely

because Prevnar was not licensed until February 2000. Id.; see also the vaccine administration schedule

for 2001, cited below. The measles, mumps, and rubella [“MMR’] vaccines are ordinarily administered in a

combined MMR vaccination, but A.K. received his in three separate vaccinations administered on

December 1, 2000 (mumps); December 19, 2000 (measles), and January 2, 2001 (rubella), when he was

between 13-14 months of age. Id. A.K. received his final Hib vaccination (the last in the four-shot series)

and his second Prevnar vaccination on February 17, 2001and his last DTaP vaccination (short of

completing the vaccine series) on May 9, 2001, along with his third Prevnar vaccination. Id. He received

his last IPV vaccination on May 24, 2001, when he also received his only varicella vaccination. Id. At the

time of these last vaccinations, A.K. was 18 months of age. The childhood vaccination schedule

recommended by the Centers for Disease Control and Prevention [“CDC”] may be found at the following:

http://www.cdc.gov/vaccines/schedules/past.html (listing recommended childhood vaccinations and time

frames for administration for the years in question) (last visited Sept.14, 2015). The vaccination schedule

in place in 2000 and 2001 indicates that a fourth dose of DTaP should have been administered between

15-18 months of age; as well as a fourth dose of Prevnar about six months after the last dose.
11

pediatrician, Dr. Marvin Boris.28 See Pet. Ex. 61, p. 4 (summary sheet); see also id., p.

106 (American Academy of Pediatrics standard vaccine administration record). The

dates of administration on the summary sheet are clearer and more complete than

those on the vaccine administration record; therefore, most citations will be to the

summary sheet.

Most vaccinations were also reflected in the pediatric visit notes (see e.g., Pet.

Ex. 61, pp. 93, 98, 99, 100, 101, 105), but not the two influenza vaccinations,29

administered on November 2, 2001 and December 3, 2001, that petitioners claim are

causal. These two influenza vaccinations are not reflected on the vaccine

administration record (Pet. Ex. 61, p. 106) or in any office visit notes from Woodbury

Pediatrics. A record of the second influenza vaccination was located in [A.K.’s 

mother’s] medical records some time prior to the December 12, 2012 fact hearing and 

was filed on that date as Pet. Ex. 118.30

Notwithstanding the somewhat unusual pattern of vaccine administration

reflected in n.27, supra, A.K. had routine well-child visits. See, e.g., Pet. Ex. 61, pp. 96

(six month well child visit), 98 (four month well-child visit), 100 (well-child visit at two and

one half months of age) 101 (two month well child visit at seven weeks of age). At his

twelve month well-child visit, he was in the 95th percentile for height and weight.

Furthermore, he was noted to play “pat-a-cake,” wave bye-bye, bang two blocks

together, imitate vocalizations, say “Mama” and Dada,” understand “no,” cruise and

stand alone for 2-3 seconds. Id. at 78.

A.K. was also seen and treated for various childhood illnesses, including

conjunctivitis (Pet. Ex. 61, pp. 103), an upper respiratory infection [“URI”] (p. 98),

congestion (p. 94), cough, congestion, and possible allergies (pp. 90-91), loose bowel

movements (p.89), rash (p. 85), presumed viral infection (p. 82) and possible otitis

media (p. 80), during his first year of life. When he received the rubella vaccination on

January 2, 2001, the medical record from that date included a complaint that he had just

experienced “5 miserable days” and an impression of “rhinitis, teething.” Pet. Ex. 61, p.

75. Later in January 2001, A.K. vomited, had loose stools, was running a high fever,

28Woodbury Pediatrics records were originally filed as Pet. Ex. 2. The copy of the immunization summary

sheet in those records is blotchy and difficult to read. An updated (and clearer) copy of the Woodbury

Pediatrics records was subsequently filed as Pet. Ex. 61, p. 4 in the updated version of the Woodbury

records.

29These were the next two vaccinations chronologically on the summary sheet after the varicella

vaccination. They are the only two on the summary sheet (Pet. Ex. 61, p. 4) for which there are no

pediatric records ordering administration. Neither appears on the vaccine administration record (id., p.

106). The summary sheet lists November 2, 2001 for the first vaccination, but only the month and year

(“12/01”) for the second. Id., p. 4.

30 Doctor Boris, who served as one of A.K.’s pediatricians during A.K.’s first year, left Woodbury Pediatrics

in January 2001 to start his own practice treating “adults and children with allergies or immunological

conditions and children with developmental problems.” Pet. Ex. 47 at 2. Doctor Boris also served as

[A.K.’s mothers’] pediatrician since the age of three years old and he is married to her father's cousin. Tr.

at 16.
12

had a runny nose, was holding his ears, and was constipated with a decreased appetite.

Id. at 74.31

His medical records also reflect several telephone calls by his parents to the

pediatric practice and returned calls by the practice to his parents. See, e.g., Pet. Ex.

61, pp. 87 (loose stools, diarrhea, and diet), 95 (teething advice and diet), 97 (eye

discharge and teething). Although his parents reported low grade fevers after his

vaccinations, no record of such fevers appears in A.K.’s medical records. Pet. Exs. 45

at 20; 46 at 3; Tr. 61-62. There was a report on May 11, 2001 that A.K. had redness at

the injection site for his Prevnar and DTaP vaccinations, which he had received two

days earlier. Pet. Ex. 61, p. 64. On June 4, 2001, after having received his only

varicella and third polio vaccinations on May 24, 2001, he was he was diagnosed with

pharyngitis (inflammation of the throat). Pet. Ex. 61, p. 63. Under the section titled

physical exam, it was noted that A.K. was febrile at the time of the examination but his

exact temperature was not recorded.32 Id.

There are several telephone calls pertaining to fevers, but none in close proximity

to his many vaccinations. See, e.g., Pet. Ex. 61, pp. 72 (fever and reported partial

recovery around February 2001), 81 (two phone calls regarding fever in late October

2000, with the closest prior vaccination administered on September 20, 2000) (id., p. 4).

A.K.’s growth and development during his second and third year of life (from 12-

36 months of age) are in dispute and are thus addressed elsewhere in this decision. He

continued to have childhood illnesses during this period. They included a URI and

some sleep problems, loose stools, and teething in July 2001. Pet. Ex. 61, p. 59. Both

A.K. and his mother contacted a stomach virus in early September 2001. Id., p. 58. On

October 5, 2001, A.K. was diagnosed with a protracted URI after suffering from a cold

for ten days. Id., p. 57. He was prescribed amoxicillin and noted to be much better by

October 9, 2001. Id.

As indicated above, the vaccine summary sheet reflected that A. K. received a

vaccination for influenza on November 1, 2001. See Pet. Ex. 61, p. 4. However, there

is no record of a visit on that date in the medical records from Woodbury Pediatrics.33

31 A.K was also seen by Dr. Heddy Zirin at Woodbury Pediatrics. Tr. at 16. Doctor Zirin had been [A.K.’s

mother’s] pediatrician since she was a teenager. Id.

32 I note that the medical records from Woodbury Pediatrics did not contain entries giving actual

temperatures or respiratory rates. These records often are unsigned or signed with a J or P, neither of

which is indicative of A.K.'s pediatrician at that time, Dr. Boris.

33 On February 24, 2011, petitioners filed additional medical records from Woodbury Pediatrics. These

records covered the period from November 6, 2002 until August 29, 2007 and included an updated record

of vaccinations. See Pet. Ex. 61. However, there is no notation of an office visit or this influenza

vaccination administered on November 2, 2001 in the earlier medical records from Woodbury Pediatrics.

Petitioners explained that A.K. received his second dose of the influenza vaccine from Dr. Boris at his 

new practice due to Woodbury Pediatrics’ shortage of vaccine. See infra n.34. However, they indicated

he received his first influenza vaccination on November at Woodbury Pediatrics. See, e.g., Pet. Ex. 46 at

3 (Declaration of [A.K.’s mother]).
See Pet. Exs. 2; 61. There are notes, perhaps reflecting telephone calls, on Oct 23,

2001 (reflecting that A.K. had a copiously runny nose) and on November 16, 2001

(reflecting nasal congestion and ear rubbing). According to Pet. Ex. 118, Dr. Boris

administered influenza vaccinations to petitioners and both of their children on what

appears to be “12/3/01.” The date on the form was written over, and may have initially

read “12/1/01,” which was a Saturday. 34

A.K.’s influenza vaccinations, and the events surrounding them, are discussed in

greater detail in Sections VII.C.2-3, below. Petitioners claim that after A.K.'s second

influenza vaccination, he became fatigued, irritable, unresponsive, and exhibited

regression in his speech. Pet. Ex. 46 at 7; Petition at 13, 15, 18-22 (ECF 237). Over

the course of late December 2001 through February 2002, A.K. suffered from a

protracted URI, rhinitis, bilateral otitis media (infections in both ears), and experienced

some fever for approximately three nights. Pet. Ex. 61, p. 49-52, 54.35

A.K. was formally diagnosed with ASD by a pediatric neurologist, Dr. Isabel

Rapin, on April 22, 2004, at about four and a half years of age. Pet. Ex. 11, p. 3.

However, Dr. Boris’ records indicate his impression that A.K. had ASD on September

12, 2002. Pet. Ex. 3 at 142. Issues surrounding A.K.’s diagnosis, as well as A.K.’s

speech delay are discussed in greater detail in Section VII.

Both before and after his formal ASD diagnosis by Dr. Rapin, A.K. received a

variety of therapies and treatments for his condition, including a 2002 colonoscopy.

During this period (2002-04), he primarily saw Dr. Boris and Dr. Arthur Krigsman.36

34 In a declaration filed in this case, [A.K.’s mother] indicated that sometime during the week of December

3, 2001, Dr. Boris, a relative and former pediatrician of both A.K. and his mother, accommodated the

whole [ * * * * * * *] family by providing influenza vaccinations when Woodbury Pediatrics ran out of vaccine.

Pet Ex. 46 at ¶¶ 14-16. Petitioners subsequently filed a single page of medical records from Dr. Boris

recording that flu vaccines were administered to each of the members of the [* * * * *] family. Pet Ex.

118. Exhibit 118 is a page from [A.K.’s mother’s] pediatric record. Tr. 190-91. Doctor Boris explained

that when he left Woodbury Pediatrics to begin his allergy practice, he carried over the medical files for

relatives who had been his patients, including [A.K.’s mother]. Id. He indicated that he recorded the

influenza vaccinations in [A.K.’s mother’s] file, because he did not have a file for A.K. at that time. Tr.

157-58. There was no mention of this record in Dr. Boris’s declaration filed in this case in October of

2010 (see Pet Ex. 47) and the medical record was not filed until years later on December 12, 2012 (see

Pet Ex. 118), the day of the fact hearing in this case. Doctor Boris indicated that he recalled the

existence of the record only after petitioners’ counsel suggested he may have recorded the vaccinations

in someone else’s file. Tr. 157. As a result of this, the question of whether A.K. received his second dose

of influenza vaccine as alleged remained a disputed issue at the time of the hearing in this case. See

Respondent’s Prehearing Submission Regarding Disputed and Undisputed Issues (ECF No. 226) at 2.

Subsequently, respondent amended her position, contending that although petitioner maintains the

burden of establishing that the vaccinations occurred, the issue was no longer disputed. Tr. 942; ECF

No. 295 at fn. 1.

35 Doctor Zirin, A.K.'s primary pediatrician at that time, explained that the December 17, 2001 entry is

from a telephone call with [A.K.’s mother]. Pet. Ex. 108, filed Sept. 26, 2012, at 3.

36 Doctor Krigsman was an expert witness for petitioners in the Theory 1 OAP test cases. While he was

an attending physician at Lenox Hill Hospital in New York from 2000–2004, the hospital became

concerned that he was performing medical procedures on autistic children for research purposes, rather

than for medical necessity. He sued the hospital for what he viewed as a restriction on his privileges. He

testified that the pathology findings supported his decision to perform the colonoscopies. His professional

13
14

Doctor Krigsman treated A.K. for various gastrointestinal problems in 2002-03.

See generally, Pet. Ex. 8. He performed a colonoscopy in November 2002 for

“abdominal pain and diarrhea.” Id., pp. 60-61.

Over the course of his treatment of A.K., Dr. Boris ordered a wide variety of tests.

See generally, Pet. Ex. 3, pp. 148-398. Doctor Boris treated him with intravenous

gammaglobulin infusions [“IVIG”] (see, e.g., pp. 320),37 secretin infusions (p. 142),

glutathione and vitamins (p.140), chelating agents (pp. 138-39 (prescribing a chelating

agent and noting completion of first chelation course)) and methylcobalamin injection (p.

137). Doctor Boris recorded many different diagnoses, including communication delay,

allergic rhinitis, hypotonia, ASD, autoimmune neurological disorder, autism, colitis,

metabolic/nutritional disorder, malabsorption, toxic metals, “allergic autism,” and

“chronic inflam[matory] neuropathy,” among others. See, e.g., id., pp. 120, 125, 128,

144, 146. According to Dr. Boris’ notes, virtually every treatment resulted in

improvement, but overall, A.K.’s condition remained about the same, according to

therapy records. See, e.g., Pet. Exs. 17 (Early Intervention Records 2002); 18 (school

records from Roslyn School in 2003); 14 (School for Language and Communication

Development records from January to June 2003).

A brain MRI ordered by Dr. Boris in 2004 was read as “unremarkable.” Pet. Ex.

3, p. 264. A test measuring A.K.’s “skeletal age” as “approximately six years” was

performed in September 2005, when A.K. was not quite six years of age. Id., p. 237. A

number of urine tests for toxic metals were performed by Doctors’ Data laboratory during

A.K.’s treatment by Dr. Boris. See, e.g., id., pp. 259, 354-55, 359-60, 367, 372. 

The results varied widely. For example, A.K.’s tin levels varied from 2.6 to 30 to 86 μg/g

creatinine in tests performed just months apart. Id., pp. 359-60, 367, 372.

Doctor Boris continued to treat A.K. through 2006. Tr. 170. None of the

treatments he pursued appear to have been particularly successful in addressing A.K.’s

behavioral symptoms, although therapies for some of his gastrointestinal problems may

have provided some relief.

During the December 2012 fact hearing, [A.K.’s mother] testified that A.K. 

continued to currently experience gastrointestinal problems, including severe

constipation a n d a diagnosis of colitis from Dr. Krigsman, which required that he

maintain a very 

record also reflected a 2005 fine imposed by the Texas State Board of Medical Examiners for an

advertisement that he was available to see patients at a time before he was licensed to practice medicine

in Texas. Snyder, 2009 WL 332044 at *16.

37 Funding for these IVIG infusions was denied by A.K.’s insurance in March 2003 as there was no

evidence that he had low immunoglobulin levels or immunodeficiency. Pet. Ex. 3, pp. 340-43. An appeal

was denied in April 2003, as the stated basis for use of IVIG (mercury and lead poisoning), did not meet

the criteria for use of IVIG. Id., pp. 324-25. In June 2003, Dr. Boris wrote a letter supporting a further

appeal, stating that A.K. had evidence of “an autoimmune neuropathy,” “positive autoantibodies to the

thyroid and active colitis. He also fails to respond to measles vaccinations, not producing any antibodies.

This is a selective immunodeficiency.” Id., p. 316. As A.K. had only one measles vaccination, the plural

“measles vaccinations” was incorrect. This appeal was denied as well. Id., p. 311
15

restrictive diet. Tr. 20-21. [ A.K.’s mother] testified that “A.K. does not speak. He's had

speech return and disappear several times through the years.” Id. at 52. She also

testified that A.K. is currently being homeschooled because of his constantly changing

condition. Id. at 80. A.K. plays the piano and takes musical therapy. Id. at 52, 81.

IV. Legal Standards Applying to Off-Table Causation Claims.

When petitioners allege an off-Table injury, eligibility for compensation is

established when, by a preponderance of the evidence, petitioners demonstrate that the

vaccinee received, in the United States, a vaccine appearing on the Table and

sustained an illness, disability, injury, or condition caused by the vaccine or experienced

a significant aggravation of a preexisting condition. They must also demonstrate that

the condition has persisted for more than six months.38 Vaccine Act litigation rarely

concerns whether the vaccine appears on the Table, the geographical location of

administration, or whether the symptoms have persisted for the requisite time. In the

very small minority of Vaccine Act cases that proceed to a hearing, the most common

issue to be resolved by the special master is whether the injury alleged was caused by

the vaccine.

To establish legal causation in an off-Table case, Vaccine Act petitioners must

establish by preponderant evidence: (1) a reliable medical theory causally connecting

the vaccination and the injury; (2) a logical sequence of cause and effect showing that

the vaccination was the reason for the injury; and (3) a proximate temporal relationship

between vaccination and injury. Althen v. Sec’y, HHS, 418 F.3d 1274, 1278 (Fed. Cir.

2005); see de Bazan v. Sec’y, HHS, 539 F.3d 1347, 1351-52 (Fed. Cir. 2008); Caves v.

Sec’y, HHS, 100 Fed. Cl. 119, 132 (2011), aff’d per curiam, 463 Fed. Appx. 932 (Fed.

Cir. 2012) (specifying that each Althen factor must be established by preponderant

evidence). Where a petitioner in an off-Table case is seeking to prove that a

vaccination aggravated a pre-existing injury, petitioners must establish three additional

factors. See Loving v. HHS, 86 Fed. Cl. 135, 144 (Fed. Cl. 2009) (combining the first

three Whitecotton factors for claims regarding aggravation of a Table injury with the

three Althen factors for off table injury claims to create a six-part test for off-Table

aggravation claims); see also W.C. v. HHS, 704 F.3d 1352, 1357 (Fed. Cir. 2013)

(applying the six-part Loving test.). The additional Loving factors require petitioners to

demonstrate aggravation by showing: (1) the vaccinee’s condition prior to the

administration of the vaccine, (2) the vaccinee’s current condition, and (3) whether the

vaccinee’s current condition constitutes a “significant aggravation” of the condition prior

to the vaccination. Id.

The applicable level of proof is the “traditional tort standard of ‘preponderant

evidence.’” Moberly v. Sec’y, HHS, 592 F.3d 1315, 1322 (Fed. Cir. 2010) (citing de

Bazan, 539 F.3d at 1351; Pafford v. Sec’y, HHS, 451 F.3d 1352, 1355 (Fed. Cir. 2006);

Capizzano v. Sec’y, HHS, 440 F.3d 1317, 1320 (Fed. Cir. 2006); Althen, 418 F.3d at

1278). Although special masters are not bound by the formal rules of evidence

38 Section 13(a)(1)(A). This section provides that petitioner must demonstrate “by a preponderance of the

evidence the matters required in the petition by section 300aa–11(c)(1) . . . .” Section 11(c)(1) contains

the factors listed above, along with others not relevant to this case.
16

generally applicable in federal courts, they are required to find evidence reliable before

they may consider it. Knudsen v. Sec’y, HHS, 35 F.3d 543, 548-49 (Fed. Cir. 1994)

(Petitioner has the burden to present a reliable and reputable medical theory, which

must be “legally probable, not medically or scientifically certain.”); Daubert v. Merrell

Dow Pharmaceuticals, 509 U.S. 579, 590 (1993) (holding that scientific evidence and

expert opinions must be reliable to be admissible). The preponderance standard

“requires the trier of fact to believe that the existence of a fact is more probable than its

nonexistence.” In re Winship, 397 U.S. 358, 371 (1970) (Harlan, J., concurring)

(internal quotation and citation omitted).

Another formulation of the causation requirement in off-Table cases is the “Can it

cause?” and “Did it cause?” inquiries used in toxic tort litigation. These queries are also

referred to as issues of general and specific causation. Prong 1 of Althen has been

characterized as an alternative formulation of the “Can it cause?” or general causation

query. Prong 2 of Althen, the requirement for a logical sequence of cause and effect

between the vaccine and the injury, has been characterized as addressing the “Did it

cause?” or specific causation query. See Pafford v. Sec’y, HHS, No. 01-165V, 2004 WL

1717359, at *4 (Fed. Cl. Spec. Mstr. July 16, 2004), aff’d, 64 Fed. Cl. 19 (2005), aff’d,

451 F.3d 1352 (2006). Prong 3 of Althen, the requirement that the injury sustained

occur within a medically appropriate interval after vaccination, is subsumed into the

other inquiries. Even if a particular vaccine has been causally associated with an injury,

petitioner must still establish facts and circumstances that make it more likely than not

that this vaccine caused the particular injury. Timing may be one of those

circumstances.

Whether a case is analyzed under Althen or the “Can it cause?” formulation,

petitioners are not required to establish identification and proof of specific biological

mechanisms, as “the purpose of the Vaccine Act’s preponderance standard is to allow

the finding of causation in a field bereft of complete and direct proof of how vaccines

affect the human body.” Althen, 418 F.3d at 1280. Petitioners need not show that the

vaccination was the sole cause, or even the predominant cause, of the injury or

condition; showing that the vaccination was a “substantial factor”39 in causing the

condition, and was a “but for” cause, are sufficient for recovery. Shyface v. Sec’y, HHS,

165 F.3d 1344, 1352 (Fed. Cir. 1999); see also Pafford, 451 F.3d at 1355 (petitioners

must establish that a vaccination was a substantial factor and that harm would not have

occurred in the absence of vaccination). Petitioners cannot be required to show

“epidemiologic studies, rechallenge, the presence of pathological markers or genetic

disposition, or general acceptance in the scientific or medical communities to establish a

logical sequence of cause and effect” (Capizzano, 440 F.3d at 1325), but the special

master may certainly consider such evidence when filed. Andreu v. Sec’y, HHS, 569

F.3d 1367, 1379 (Fed. Cir. 2009) (Special masters may consider medical literature and

39 The Restatement (Third) of Torts has eliminated “substantial factor” in the factual cause analysis. § 26

cmt. j (2010). Because the Federal Circuit has held that the causation analysis in the Restatement

(Second) of Torts applies to off-Table Vaccine Act cases (see Walther v. Sec’y, HHS, 485 F.3d 1146,

1151 (Fed. Cir. 2007); Shyface, 165 F.3d at 1352), this change does not affect the determination of legal

cause in Vaccine Act cases: whether the vaccination is a “substantial factor” is still a consideration in

determining whether it is the legal cause of an injury.
17

epidemiological evidence, when it is submitted, in “reaching an informed judgment as to

whether a particular vaccine likely caused a particular injury.”). Causation is determined

on a case by case basis, with “no hard and fast per se scientific or medical rules.”

Knudsen, 35 F.3d at 548. Close calls regarding causation must be resolved in favor of

petitioners. Althen, 418 F.3d at 1280; but see Knudsen, 35 F.3d at 550 (when evidence

is in equipoise, the party with the burden of proof fails to meet that burden).

In Vaccine Act cases, special masters are frequently confronted by expert

witnesses with diametrically opposing positions on causation. When experts disagree,

many factors influence a fact-finder to accept some testimony and reject other contrary

testimony. As the Federal Circuit noted, “[a]ssessments as to the reliability of expert

testimony often turn on credibility determinations, particularly in cases . . . where there

is little supporting evidence for the expert’s opinion.” Moberly, 592 F.3d at 1325-26.

Objective factors, including the qualifications, training, and experience of the expert

witnesses; the extent to which their proffered opinions are supported by reliable medical

research and other testimony; and the factual basis for their opinions are all significant

factors in determining what testimony to credit and what to reject. Lalonde v. Sec’y,

HHS, 746 F.3d 1334, 1340 (Fed. Cir. 2014) (noting that “as the finder of fact, the special

master was responsible for assessing the reliability of [the expert’s] testimony by looking

for reliable medical or scientific support” (citing Moberly, 592 F.3d at 1324-25)).

Congress contemplated that special masters would weigh and evaluate opposing

expert opinions in determining whether petitioners have met their burden of proof.

Congress clearly specified petitioners’ burden of proof in off-Table cases as the

preponderance of the evidence standard. It directed special masters to consider the

evidence as a whole, but stated that special masters are not bound by any particular

piece of evidence contained in the record.40 In weighing and evaluating expert opinions

in Vaccine Act cases, the same factors the Supreme Court has considered important in

determining their admissibility provide the weights and counterweights. See Kumho

Tire Co. v. Carmichael, 526 U.S. 137, 149-50 (1999); Terran v. Sec’y, HHS, 195 F.3d

1302, 1316 (Fed. Cir. 1999). As the Supreme Court has noted, a trial court is not

required to accept the ipse dixit of any expert’s medical or scientific opinion, because

the “court may conclude that there is simply too great an analytical gap between the

data and the opinion proffered.” Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997).

Although special masters are not bound by the formal rules of evidence generally

applicable in federal courts, the Federal Rules of Evidence and cases interpreting them

can guide special masters in their decisions. Daubert, which interpreted Rule 702 of the

Federal Rules of Evidence provides a useful framework for evaluating scientific

evidence in Program cases. Terran, 195 F.3d at 1316 (concluding that it was

reasonable for the special master to use Daubert to evaluate the reliability of an expert’s

testimony); Cedillo, 617 F.3d at 1339 (noting that special masters are to consider all

40See § 13(a)(1)(A) (preponderance standard); § 13(a)(1) (“Compensation shall be awarded . . . if the

special master or court finds on the record as a whole . . . .” ); § 13(b)(1) (indicating that the court or

special master shall consider the entire record in determining if petitioner is entitled to compensation and

special master is not bound by any “diagnosis, conclusion, judgment, test result, report, or summary”

contained in the record).
18

relevant and reliable evidence filed in a case and may use Daubert factors in their

evaluation of expert testimony); Davis v. Sec’y, HHS, 94 Fed. Cl. 53, 67 (2010)

(describing the Daubert factors as an “acceptable evidentiary-gauging tool with respect

to persuasiveness of expert testimony already admitted . . . by special masters in

vaccine cases”); see also Snyder, 88 Fed. Cl. at 718 (quoting Ryman v. Sec’y, HHS, 65

Fed. Cl. 35, 40-41 (2005) (special masters perform gatekeeping function when

determining “whether a particular petitioner’s expert medical testimony supporting

biological probability may be admitted or credited or otherwise relied upon” and as a

“trier-of-fact [a special master] may properly consider the credibility and applicability of

medical theories”)).

The special master’s use of Daubert’s factors to evaluate the reliability of expert

opinions in Vaccine Act cases has been cited with approval by the Federal Circuit more

recently in Andreu, 569 F.3d at 1379 and Moberly, 592 F.3d at 1324. See also

Vaughan v. Sec’y, HHS, 107 Fed. Cl. 212, 222 (2012) (“The Federal Circuit has

repeatedly stated that the Special Master may refer to Daubert to assess reliability of

expert testimony in vaccine cases.”). Special masters decide questions of credibility,

plausibility, probability, and reliability, and ultimately determine to which side the

balance of the evidence is tipped. See Pafford, 451 F.3d at 1359.

Bearing all these legal standards in mind, I now turn to the causation evidence

presented in this case, beginning with the qualifications of the experts and a summary

of their opinions.

V. Expert Testimony.

In this case I heard extensive expert testimony from eleven witnesses. These

experts have diverse qualifications and represent a number of different scientific or

medical disciplines, including psychology, pediatric neurology, immunology,

biochemistry, and pharmacology. While the experts’ opinions cover the breadth of

issues in this case, they do so in overlapping and conflicting ways. Certain aspects of

these expert opinions will be highlighted because they illuminate the analysis to follow,

but each expert’s opinion was carefully considered in full. In this section, I will therefore

separately summarize each expert’s qualifications and opinions.

A. Petitioners’ Experts.

Petitioners presented three expert witnesses, and one witness who testified as a

treating physician, fact witness, and expert, Dr. Marvin Boris.41 The first of the three

expert witnesses to testify was Dr. Frances Kendall, a pediatrician and biochemical

geneticist who has focused much of her career on diagnosing and treating mitochondrial

disorders. Doctor Kendall argued that A.K. has a mitochondrial disorder and presented

a theory that such disorders can be aggravated by oxidative stress from the influenza

vaccine. She was joined by Dr. Shafrir, a pediatric neurologist, and Dr. Deth, a

pharmacologist. Doctor Shafrir argued that A.K.’s ASD resulted from the combined

41 Doctor Boris’s expert opinions are discussed in conjunction with Dr. Shafrir’s causation theory with

regard to Dr. Shafrir’s reliance on A.K.’s MTHFR polymorphisms as well as Dr. Shafrir’s contention that

A.K. had an abnormal immune system. See Sections VIII.B.2.b and B.2.c, below.
19

effects of an autoimmune attack coupled with other vulnerabilities, such as A.K.’s

alleged mitochondrial disorder and “MTHFR” (i.e., methylenetetrahydrofolate reductase)

mutation. Doctor Deth postulated a mechanism whereby the influenza vaccine could

create injurious oxidative stress in the manner suggested by Drs. Kendall and Shafrir.

1. Frances Kendall, M.D.

a. Doctor Kendall’s Qualifications.

Doctor Kendall has been practicing medicine with a special attention to

mitochondrial diseases for 20 years. Pet. Ex. 65 at 1. She was trained at Harvard

Medical School and Boston Children’s Hospital before she started Horizon Molecular

Medicine, a laboratory dedicated to the molecular and enzymatic diagnosis of

mitochondrial patients. Pet. Ex. 65 at 1; Tr. 236-37. She considers herself one of “only a

handful” of mitochondrial experts in the country. Pet. Ex. 65 at 1; Tr. 416.

Doctor Kendall received a biology degree from Temple University before

attending medical school. Pet. Ex. 232 at 1; Tr. 237. She completed her residency in

pediatrics at Thomas Jefferson University Hospital and fellowships in genetics at the

Children’s Hospital in Boston and Harvard Medical School. Id. Doctor Kendall has past

university affiliations with Harvard and Emory Universities and has been on the staff of

Boston Children’s Hospital as well as director and chairman of the genetics department

at Scottish Rite Children’s Hospital. Pet. Ex. 232 at 1-3; Tr. 237, 241. She is currently

on staff at the Children’s Hospital of Atlanta. Id.

For approximately the last five years, Dr. Kendall has operated her own private

practice. Tr. 241. Her current practice, Virtual Medical Practice, is devoted to the care of

patients with mitochondrial and other rare genetic disorders. Pet. Ex. 65 at 1. She

estimates that she has over one thousand patients and that at least one hundred of them

have both autism and mitochondrial disorders. Tr. 373. Her patients come to her both

for diagnosis and for ongoing management of their symptoms. Tr. 372-73. She recently

published an article in the JOURNAL OF PEDIATRIC BIOCHEMISTRY that sets out an overview

of mitochondrial disease and testing and which has been submitted in this case. Tr. 238;

Pet. Ex. 172.

b. Doctor Kendall’s Opinion.

Doctor Kendall’s opinions extended to A.K.’s diagnosis and causation of his

injury. She opined that A.K. met the diagnostic criteria for a mitochondrial disorder.

She also opined that immunizations can act as metabolic stressors that can cause a

child with a mitochondrial disorder to decompensate or regress. In A.K.’s case, she

contended that his influenza vaccinations of November and December of 2001

aggravated his underlying mitochondrial disorder, triggering an autistic regression.

She explained that there is no “gold standard” test for diagnosis of mitochondrial

disease that can be applied in every case, and that each diagnosis depends on the

expertise of the clinician, who must look at a collection of different data points. Tr. 248-

49, 425-27. A mitochondrial diagnosis is typically made by considering biochemical,

genetic, and clinical features. Tr. 249-51. Although there is no universally accepted

diagnostic standard for mitochondrial disorders, she opined that A.K. exhibited enough
20

signs and symptoms of mitochondrial dysfunction to be so diagnosed.42 Pet. Ex. 65 at

7; Tr. 285.

Specifically, Dr. Kendall felt that A.K.’s biochemical tests showed elevated levels

of lactate and “AST” that are consistent with mitochondrial disease.43 Tr. 244. She also

noted A.K.’s enzymology indicated a “Complex I” defect.44 Tr. 250-51. She contended

that these findings, combined with his clinical presentation of autistic features,

developmental delays, dysautonomia (i.e., temperature intolerance), gastrointestinal

issues, fatigability, and hypotonia, were sufficient to support a diagnosis of

mitochondrial disease. Id. She acknowledged that there were no genetic findings in

A.K.’s case to support her diagnosis. Tr. 251; see also Pet. Ex. 33.

Having concluded that A.K. had a mitochondrial disease, Dr. Kendall further

opined that this left him susceptible to mitochondrial regression following episodes of

metabolic (or oxidative) stresses. Tr. 253-54. Doctor Kendall opined that, based on her

own experience, A.K.’s influenza vaccine could have been such a stressor. Tr. 253-54.

Based on her interpretation of A.K.’s complete medical history, the onset of his

developmental delays and ASD-like symptoms were temporally related to the two doses

of influenza vaccine he received in November and December of 2001.45 Tr. 285.

42 In her report, Pet. Ex. 65 at 1, Dr. Kendall explained that her diagnosis of A.K. was based on the

“Bernier” criteria. See F. Bernier, et al., Diagnostic criteria for respiratory chain disorders in adults and

children, NEUROL. 59(11):1406-11 (2002), filed as Pet. Ex. 90, Res. Ex. SS, Tab 1, and Res. Ex. UU, Tab 1

[hereinafter “Bernier, Pet. Ex. 90”]. Application of the Bernier criteria results in diagnoses at different

confidence levels, rated as definite, probable, or possible. Pet. Ex. 90 at 1407. She opined that based on

these criteria, A.K.’s mitochondrial diagnosis could be considered “definitive or highly probable.” Pet. Ex.

65 at 7. However, after being questioned extensively by respondent’s counsel about her application of 

the Bernier criteria to A.K.’s case, Dr. Kendall acknowledged that A.K.’s diagnosis is not “definitive” under

that criteria and instead characterized it as “probably probable.” Tr. 317-19. On further questioning, Dr.

Kendall became somewhat critical of the Bernier criteria, arguing that they are “not comprehensive” and

stressing that there are other, more recent diagnostic criteria available, and that there is no consensus on

what criteria to use. Tr. 423-25. She re-emphasized this point in her supplemental report filed on October

3, 2013. See Pet. Ex. 269.

43 According to Dr. Kendall, “AST” is a liver function test, but she contended that AST elevation can be a

sign of a mitochondrial disorder. Tr. 244-45. “AST” stands for “aspartate aminotransferase,” an enzyme

“found in very high concentrations within highly metabolic tissue.” When injury or disease occurs in these

tissues, the serum level of AST rises, remaining elevated for several days after injury. If the “injury is

chronic, levels will be persistently elevated.” K. Pagona & J. Pagona, MOSBY’S MANUAL OF DIAGNOSTIC

AND LABORATORY TESTS (5th ed. 2014) at 119 [hereinafter “MOSBY’S LABS”].

44 Mitochondria function via five protein complexes (typically numbered with Roman numerals) which

make up what is called the electron transport chain or respiratory chain. These concepts are discussed in

greater detail in Section VI.A, below. Doctor Kendall acknowledged that the muscle biopsy enzymology

findings were open to debate. She indicated that the lab that tested A.K.’s tissue for respiratory chain

function did not perform calculations designed to account for the difficulty of measuring function of

Complex I of the respiratory chain in tissue. Tr. 247-48. She argued, however, that there is no single

standard by which to evaluate the validity of the results, and, at least initially, considered the results valid.

Id. This issue is discussed in more detail in Section VI.C.1, below.

45 I questioned Dr. Kendall’s recitation of the facts of A.K.’s medical history within her report, noting that

her report was misleading regarding his medical history at several points. Tr. 341-55. Doctor Kendall’s

testimony was also confused about A.K.’s medical history. On direct examination she contended that

video clips of A.K. at about 18-19 months of age supported her view regarding the temporal association
21

Doctor Kendall was not aware of any study that found that the influenza vaccine

could aggravate a mitochondrial disorder or cause regression. Tr. 332. Nonetheless,

citing to three medical journal articles (Poling, Shoffner, and Weissman),46 she

contended that these “recent studies have documented the association of

developmental regression and autism in patients with mitochondrial disease following

exposure to immunizations.” Pet. Ex. 65 at 7-8; Tr. 376-78. When challenged, Dr.

Kendall acknowledged that A.K.’s presentation did not fit within the parameters of these

studies, but contended that the studies establish that “there are other factors that impact

these children that can cause autistic regression.”47 Tr. 369-71. She argued that they

established a “precedent” for an association between A.K.’s influenza vaccinations and

his condition. Pet. Ex. 65 at 8; Tr. 288-90. She therefore opined, particularly in the

absence of any other explanation, that the two doses of influenza vaccine more likely

than not caused A.K.’s condition. Id.

2. Yuval Shafrir, M.D.

a. Doctor Shafrir’s Qualifications.

Doctor Yuval Shafrir received his medical degree from the Sackier School of

Medicine in Tel Aviv, Israel, in 1982. Pet. Ex. 62 at 1. From 1982 to 1992, Dr. Shafrir

continued post graduate medical training, including pediatric residencies with a

neonatology rotation, as well as fellowships in pediatric neurology and pediatric

neurophysiology and epileptology. Id. Doctor Shafrir is currently licensed to practice in

the state of Maryland. He has previously been licensed in Israel, Virginia, Oklahoma,

Pennsylvania, and the District of Columbia. Id. at 2. Doctor Shafrir is board certified in

between the onset of A.K.’s condition and his influenza vaccines. Tr. 270-72. During subsequent

questioning, however, she appeared unsure whether the video had any significance, stating that “I looked

at that with a question mark. You know, does this mean anything?” Tr. 411.

46 Three medical journal articles are addressed extensively in the analysis below. The first, J. Poling, et

al., Developmental Regression and Mitochondrial Dysfunction in a Child with Autism, J. CHILD NEUROL.,

21(2):1-3 (2006), was filed as Pet. Exs. 40; 63, Ref. 18; 91 and as Res. Exs. MM, Tab 14 and UU, Tab 9

[hereinafter “Poling, Res. Ex. MM, Tab 14”]. The second, J. Shoffner, et al., Fever Plus Mitochondrial

Disease Could Be Risk Factors for Autistic Regression, J. CHILD NEUROL., 25: 429-434 (2010), filed as

Pet. Exs. 42; 63, Ref. 15; 92 and as Res. Exs. MM, Tab 16 and UU, Tab 10 [hereinafter “Shoffner, Res.

Ex. MM, Tab 16”]. The third extensively discussed article, J. Weissman, et al, Mitochondrial Disease in

Autism Spectrum Disorder Patients: A Cohort Analysis, PLoS ONE 3(11): e3815 (2008) was filed as Pet.

Exs. 39 and 63, Ref. 3 and as Res. Exs. MM, Tab 15; SS, Tab 18, and UU, Tab 14.[hereinafter

“Weismann, Pet. Ex. 39”]. Doctor Kendall did not cite the Weissman paper in her report, although it was

discussed to some extent during her testimony. The Poling and Shoffner articles were cited in Dr.

Kendall’s report, Pet. Ex. 65, as references 26 and 27. My usual practice is to cite to petitioners’ exhibit

numbers when an article is filed by both parties. However, during the hearing, I indicated that the copy of

the Shoffner article filed with Dr. Kendall’s report was incomplete and that I intended to rely on a copy of

that article filed by respondent as Exhibit MM, Tab 16. The copies of the Poling article filed as petitioners’

exhibits were an on-line version; I therefore cite to the print publication version filed by respondent.

Because the evidence filed in this case is not publically available, I cite to these (and other) journal

articles by the page numbers that appear in the published versions of the article to enable any readers to

more easily find the references that appear throughout this decision

47 During the hearing I questioned Dr. Kendall closely regarding her exaggeration of the findings of the

Shoffner study in her report. Tr. 369-71. The Shoffner study and what Dr. Kendall claimed about it are

discussed in more detail in Section VIII.A.2.a, below.
22

neurology and clinical neurophysiology and was formerly board certified in pediatrics.48

Pet. Ex. 62 at 2; Tr. 450.

Doctor Shafrir has held several clinical positions, including attending child

neurologist at Georgetown University Hospital from 1995 to 1999 and at Oklahoma

University Health Science Center from 1999 to 2000. Pet. Ex. 62 at 3. In addition, he

has held assistant professorships in neurology and pediatrics at the U.S. University of

the Health Sciences, Georgetown University, and the University of Oklahoma. Pet. Ex.

62 at 3; Tr. 451. Since 2000 Dr. Shafrir has operated a full-time private practice in

pediatric neurology where he sees about 60 patients a week. Tr. 451-52. He estimated

that in private practice he has treated at least 1,000 children with autism. Tr. 452. In

addition to his private practice, Dr. Shafrir also serves as a clinical assistant professor at

the University of Maryland. Tr. 451.

Doctor Shafrir’s curriculum vitae listed seven journal articles relating to child

neurology, none of which were related to autism or mitochondrial disorders, three letters

to the editor, ten abstracts, and numerous conference lectures.49 Pet. Ex. 62 at 4-8.

However, he is not a member of any professional societies and does not review for any

professional journals. Pet. Ex. 62 at 3; Tr. 517-18.

b. Doctor Shafrir’s Opinion.

Although he does not believe that autism itself is genetically caused, Tr. 481-84,

Dr. Shafrir opined that A.K. had genetic factors that left him vulnerable to

environmentally induced autistic regression.50 Pet. Ex. 63 at 12, 16-18; Tr. 554-55.

That is, Dr. Shafrir argued that the presence in A.K. of both a Complex I mitochondrial

disorder51 and a double mutation in the MTHFR gene left A.K. susceptible to

mechanisms of brain injury including apoptosis, oxidative stress, and other unspecified

mechanisms. Pet. Ex. 63, p. 18-19. On cross examination, Dr. Shafrir conceded that

there is no basis for contending that either the mitochondrial disorder or the MTHFR

gene mutation actually caused A.K.’s autism. Tr. 547, 560-61. Rather, he opined that

each of these conditions was a “risk factor” for autistic regression. Id.

Doctor Shafrir contended that, when A.K. received his influenza vaccinations,

these genetic factors, combined with an “abnormal, rare, genetically determined

48 Doctor Shafrir’s curriculum vitae was last updated in 2005. He confirmed during the hearing that his

certifications in neurology and neurophysiology are not time limited, but that he opted not to renew his

board certification in pediatrics when it expired in 2005. Tr. 450, 515-18.

49 At the hearing, Dr. Shafrir indicated that he had published one additional article since his curriculum

vitae was last updated in 2005. Tr. 517-18. The article, on the subject of spinal cerebral ataxia type 2,

was published in NEUROLOGY in 2011. Id.

50 Doctor Shafrir contended that autism and autistic regression were overlapping, but distinct, entities. 

Pet. Ex. 63 at 12; Tr. 519-22. I have previously rejected this contention (see Dwyer 2010 WL 892250, *37

and Synder, 2009 WL 332044, *39) and do so here as well, for the reasons set forth in Section VIII.B.1,

below.

51 Significantly, while Dr. Shafrir assumed the presence of a mitochondrial disorder for purposes of his

theory, he noted that he is not a mitochondrial expert and deferred to the other experts in this case

regarding the question of whether A.K. in fact had any mitochondrial disorder. Tr. 513-14, 546.
structure of his immune system,”52 resulted in an autoimmune attack on A.K.’s brain

which caused an encephalopathy leading to autistic regression. Pet. Ex. 63 at 15-16;

Tr. 458, 556. Doctor Shafrir contended that what happened to A.K. was an example of

the “triple hit theory,” which he said explains the relationship between genetic and

environmental factors in autism. Pet. Ex. 63 at 18; Tr. 549-54. He argued by analogy

that abnormal immune responses in cases regarding chicken pox, Guillain-Barre

Syndrome [“GBS”], acute disseminated encephalomyelitis [“ADEM”], and narcolepsy

showed that a vaccine could activate a neuroimmune reaction among vulnerable

populations. Pet. Ex. 63 at 14-16; Tr. 484-89, 502-04, 542.

Significantly, however, Dr. Shafrir acknowledged that there is no evidence in this

case that A.K. experienced any immune reaction within his brain. Tr. 541-42. Instead,

he argued that his theory is supported by the nature and timing of A.K.’s autistic

regression, which he claimed demonstrated a clear challenge-rechallenge response53 to

the two doses of influenza vaccine at issue in this case.54 Tr. 491, 502-04. In that

regard, although he cautioned that regression is a process and cannot necessarily be

pin-pointed, Dr. Shafrir placed the onset of A.K.’s autistic regression at about two years

of age. Tr. 528.

Initially, Dr. Shafrir opined that “there is excellent documentation of appearance

of regression of language and behavioral changes typical for the autistic regression such

as loss of eye contact appearing after the first, and worsening after the second influenza

vaccine.” Pet. Ex. 63, p. 12. At the hearing, however, Dr. Shafrir indicated 

that A.K.’s medical records were “sketchy” (Tr. 461), and added that it was difficult to

rely on A.K.’s pediatric records alone, particularly with regard to his speech development

(Tr. 529-30). He explained that his opinion was based on a combined 

reading of A.K.’s medical records and [the affidavits of A.K.’s parents], which he said

indicated that A.K. had some speech prior to vaccination which he lost after the

vaccination. Tr. 531, 534, 538-39. He contended that there is no evidence in the record

to suggest that A.K. was not developmentally normal up until November 9, 2001. Tr.

528-29. Doctor Shafrir argued in particular that video clips of A.K. shown during the

hearing demonstrated a dramatic change in behavior between November 9, 2001, and

November 10, 2001.55 Tr. 470-71, 478-79. He testified that A.K.’s regression was

apparent, because A.K. acted “more or less normal” in the first video, but his autistic

symptoms were “absolutely striking” in the second.56 Tr. 470-73.

52 Doctor Shafrir’s claim that A.K. has an abnormal immune system appears to be based on his diagnosis

at three years of age with Hashimoto Thyroiditis, a type of autoimmune hypothyroidism. Tr. 556-57.

53 A challenge-rechallenge event occurs when a patient who had an adverse reaction to a vaccine suffers

worsened symptoms after an additional injection of the vaccine.” Cappizano, 440 F.3d at 1322. This

concept is discussed in greater detail in Sections VII.D and VIII.B.3.b, below.

54 Doctor Shafrir also contended that A.K.’s regression occurred within the medically accepted time frame

for an autoimmune reaction, as evidenced by the recognized time frame for other adverse immune

reactions such as GBS. Pet. Ex. 63 at 15; Tr. 478-79.

55 Doctor Shafrir had not yet viewed the videos at the time he wrote his report for this case. Tr. 458-59.

56 Despite drawing this comparison, Dr. Shafrir testified that you cannot diagnosis a child with autism from

video footage. Tr. 467-69. In particular he indicated that he “really feel[s] that you cannot make

23
24

3. Richard Deth, Ph.D.

a. Doctor Deth’s Qualifications.

Doctor Richard Deth is a professor of pharmacology at Northeastern University in

Boston, Massachusetts, a position which he has held since 1976. Tr. 599-600; Pet Ex.

117 at 4. He received his undergraduate degree in Pharmacy at the State University of

New York at Buffalo in 1970, and earned a Ph.D. in Pharmacology from the University

of Miami in 1975. Tr. 599; Pet. Ex. 95 at 1. He also completed one year of postgraduate training at the University of Leuven in Belgium. Id.

Doctor Deth claimed more than eighty peer-reviewed publications, including a

monograph entitled “Molecular Origins of Human Attention: The Dopamine-Folate

Connection.” Pet. Ex. 95 at 4-11. He also serves as a journal referee for a number of

publications, including the JOURNAL OF PHARMACOLOGY, EXPERIMENTAL THERAPEUTICS,

CIRCULATION RESEARCH, SCIENCE MAGAZINE, and MOLECULAR PSYCHIATRY. Tr. 604; Pet.

Ex. 95 at 3. He is a member of the Society for Neuroscience, the International Society

for Autism Research, the American Society of Pharmacology and Experimental

Therapeutics, and the Society for Biological Psychiatry. Pet. Ex. 95 at 1.

Doctor Deth’s professional history is noteworthy in that his original background

and training focused on the cardiovascular system rather than the neurological system.

Tr. 601. He did not begin his current research focus on oxidative stress and brain

disorders until approximately 1998. Tr. 608. Doctor Deth testified that for the past eight

to ten years he has focused his attention on studying autism and working with autism

support groups. Tr. 601-02. In 2008, Dr. Deth testified in the Vaccine Program’s

Omnibus Autism Proceeding with regard to the theory that the thimerosal component of

certain vaccines could cause autism. Tr. 609.

b. Doctor Deth’s Opinion.

Doctor Deth summarized his opinion in this case57 thusly: “vaccinations promote

inflammation and oxidative stress as integral components of the immune response, and

individuals with limited capacity to recovery are at higher risk of long term adverse

consequences, including developmental regression in the case of young children.” Tr.

comments about thing[s] that you expect to see but you don’t see.” Tr. 470. Doctor Shafrir’s argument

appears to be that analysis of video footage is not ordinarily a valid method of diagnosis, but that it can be

used in this case to determine the timing of A.K.’s regression due primarily to the presence of “dramatic”

features of autism in the second video which cannot be seen in the first video, marking a stark contrast

between the two. Tr. 467-69, 537-38. In that regard, Dr. Shafrir’s assessment of the first video seemed to

hinge on the argument that there was no “obvious evidence for autistic behavior.” Tr. 473 (emphasis

added). It is noteworthy then that Dr. Shafrir’s stance on this issue appears to be largely informed by the

fact that he was highly pessimistic about the efficacy of autism evaluation guidelines (Tr. 495-98, 522-24)

and in fact rejected the idea that “subtle” signs of autism should even be considered for diagnostic

purposes at all, regardless of whether they appear on video. Tr. 473-74, 483-84.

57 Petitioners’ counsel indicated that petitioners did not intend for Dr. Deth’s opinion to be considered as a

separate causation theory, but rather that he was opining with regard to the mechanism by which A.K.’s

injury might have occurred. Tr. 597. I found Dr. Deth’s testimony to be highly problematic and not at all

helpful in resolving this case. A more detailed discussion of the problems with Dr. Deth’s testimony is

contained in Section IX, below.
25

751. That is, Dr. Deth argued that “oxidative stress” is one phenomenon that can

impact gene expression, and ultimately human development, through epigenetic

regulation.58 Tr. 615-16.

As Dr. Deth explained, oxidative stress can occur when cells metabolize oxygen

via mitochondrial function. Tr. 640-41. In mitochondrial oxygen metabolism, electrons

are lost and harmful “reactive oxygen species” [“ROS”] molecules are created. Id.

Under normal conditions, cells use existing antioxidants to provide additional electrons

in order to neutralize the ROS and maintain balance (i.e., a normal “redox” state). Tr.

640-42. When cells lack sufficient antioxidants to neutralize the harmful ROS, oxidative

stress results. Tr. 642.

Two antioxidants central to Dr. Deth’s theory, methionine59 and cysteine,60 are

amino acids that are absorbed through the terminal ilium of the small intestine. Tr. 713-

15. Doctor Deth argued that inflammation of the intestinal tract, and the terminal ilium in

particular, depresses the uptake of these antioxidants due to the presence of a proinflammatory cytokine called “tissue necrosis factor alpha” [“TNF-α”]. Tr. 707, 713, 723.

According to Dr. Deth, TNF-α has been shown to both inhibit methionine synthase and

reduce the uptake of cysteine. Tr. 708-09. Thus, Dr. Deth contended that since the

terminal ilium of the intestinal tract is the primary source of these antioxidants,

inflammation of the gastrointestinal [“GI”] tract can lead to a whole body deficit of

antioxidants and increase susceptibility to oxidative stress.61 Tr. 715-16, 721-23.

In A.K.’s case, Dr. Deth argued that evidence of terminal ilium inflammation upon

endoscopy, coupled with multiple findings of low cysteine and the presence of

antibodies to gliaden, casein, and casomorphin, supported the conclusion that A.K.

experienced a depressed antioxidant status and an abnormal immune response. Tr.

58 Doctor Deth contended that epigenetics, i.e., the impact of non-genetic factors on gene expression (see

n. 288, infra), is key to understanding autism in that autism is caused by a combination of genetic and

environmental factors. Tr. 613, 621, 644-46. Although he acknowledged that epigenetics operates in all

phases of human development from pre-conception through adulthood, Dr. Deth stressed that epigenetic

changes occurring in earlier development have a larger impact. Tr. 628-31, 813-14. In particular, he

argued that epigenetic changes occurring in early childhood, when significant brain and immune

development is occurring, were the most critical. Tr. 628-31. He maintained that the acute inhibition of

deoxyribonucleic acid [“DNA”] methylation (a process whereby enzymes control gene expression by

attaching single carbon molecules to specific DNA sites) by oxidative stress could have long-term

consequences for growth and development. Tr. 622-25.

59 Doctor Deth identified the enzyme methionine synthase as being one of the enzymes that controls DNA

methylation. He stressed that it is particularly sensitive to oxidative stress. Tr. 646-48.

60 Doctor Deth contended that while the neuronal activity of the brain is of a higher-energy and demands

a higher rate of aerobic metabolism than the rest of the body, the cerebral spinal fluid surrounding the

brain is particularly low in antioxidants. Tr. 659-61. Thus he opined that the brain is particularly

dependent upon cystine (the oxidized form of cysteine) crossing the blood/brain barrier. Tr. 663-66.

61 I warned at multiple points during the hearing that Dr. Deth’s opinions regarding the impact of

inflammation on the intestinal tract were beyond his area of expertise. See, e.g., Tr. 747, 751. Doctor

Deth is not a physician, and has no training in gastroenterology or immunology, and thus many of his

opinions are entitled to little weight.
26

745-749. He therefore contended that A.K. was at a higher risk of experiencing longterm adverse consequences due to oxidative stress.62 Tr. 751.

Doctor Deth also opined that vaccines create increased metabolic need as a

result of the activation of “T cells” to initiate an immune response, requiring additional

antioxidants. Tr. 733-34. Doctor Deth claimed that, as a result of additional

inflammatory responses created by the aluminum adjuvant in vaccines, TNF-α is

released, possibly in the brain; methylation is decreased; and available antioxidant

pathways are modified.63 Tr. 737, 741-44. That is, Dr. Deth claimed that vaccines both

increase metabolic need and decrease the availability of the antioxidants necessary to

counteract the reactive oxygen species generated by that excess metabolic activity.

Thus, Dr. Deth contended that among those—like A.K., allegedly—who have

difficulty maintaining redox, the result is neural inflammation which can ultimately lead to

encephalopathy or other brain injury. Tr. 744-45. He argued that the brain is

particularly susceptible to changes brought about by oxidative stress64 and that studies

have linked signs of oxidative stress within the brain to autism. 65 Tr. 705-08; Pet. Ex.

117 at 12. More specifically, he hypothesized that when the brain is subjected to

oxidative stress, it impairs the development of “D4” dopamine receptors, which he

argued are necessary to the “gamma” frequency brain activity associated with the

capacity for attention. Tr. 686-87. He argued that the decreased gamma activity is a

characteristic of autism. Tr. 686-89. Significantly, however, Dr. Deth’s opinion in this

case was severely limited in that he has acknowledged that he does not know how

much oxidative stress is created by an influenza vaccination, nor the amount of

oxidative stress necessary to cause autism or how long the onset period would be. Tr.

773-74.

4. Marvin Boris, M.D.

a. Doctor Boris’s Qualifications.

62 Doctor Deth also argued that A.K.’s MTHFR polymorphism was an additional factor contributing to

A.K.’s vulnerability in that it, too, leads to impaired methylation. Tr. 721-23, 749-50.

63 Doctor Deth acknowledged, however, that the effect of vaccination on methylation “has not been

extensively studied,” and indicated that “that’s a serious problem.” Tr. 736.

64 For example, he contended that the presence of oxidative stress would determine epigenetically

whether brain development favored the growth of neurons or astrocytes. Tr. 651-54. And again, as noted

above, he stressed that the cerebral spinal fluid surrounding the brain is relatively antioxidant poor. 

Tr. 660-61.

65 Doctor Deth presented his own post-mortem brain study which he described as showing lower levels of

the messenger RNA [“mRNA”] necessary for creating methionine synthase among autistic individuals. Tr.

705-07. He posited that the messenger RNA was inhibited by TNF-α. Tr. 708. On cross-examination, he

acknowledged that the post-mortem study did not find that the hydroxyl guanosine biomarker for oxidative

stress was elevated in the autistic population. Tr. 781-82. On redirect, Dr. Deth explained that he 

thought that the low levels of methionine synthase mRNA is evidence of a coping mechanism which

allowed the autistic individuals to keep the biomarkers of oxidative stress low. Tr. 827.
27

Related to [A.K.’s mother] by marriage, Dr. Boris treated A.K. and interacted with

his family socially.66 He originally was scheduled to testify at both the fact and

entitlement hearings. Due to scheduling difficulties, petitioners opted instead to have Dr.

Boris testify at the entitlement hearing as both a factual and expert witness. See Status

Report, filed Nov. 16, 2012 (ECF No. 185).

In 2010, petitioners filed a declaration containing factual assertions from Dr. Boris

as an attachment to their motion for reconsideration. See Pet. Ex. 47. His expert opinion

was filed on September 26, 2012, and he testified about the manifestation and cause 

of autism during the entitlement hearing. Tr. at 146-48. He opined as to the 

cause of A.K.’s autism in his declaration. See Pet. Ex. 47 at 8-9.

Doctor Boris earned his medical degree from the New York University, College of

Medicine in 1958. Tr. at 142, 145; Pet. Ex. 47 at 10. His post graduate medical training

included a one year internship at Bellevue Hospital and residency at New York Hospital,

Cornell Medical Center, both in New York City. Tr. at 142-43. He then spent two years

at the CDC in Atlanta, Georgia, in the Epidemic Intelligence Service. When he left the

CDC, he entered private practice in the areas of pediatrics, allergy and immunology. Tr.

at 143.

Doctor Boris is board certified in both pediatrics and allergy and immunology. Tr.

at 143-44; Pet. Ex. 47 at 10. He has held teaching positions at Cornell University,

School of Medicine and the New York University, School of Medicine and has published

approximately 28 articles regarding infectious disease, allergy, immunology and autism.

Tr. at 144. He is a member of the American College of Allergy Immunization, American

Board of Allergy, American Academy of Pediatrics and Defeat Autism Now! (DAN!).67 Tr.

at 144-45; Pet. Ex. 47 at 10.

While affiliated with Woodbury Pediatrics, he was the pediatrician for A.K.’s sister

and A.K. for the first year of A.K.’s life. Tr. at 149, 154-55; Pet. Ex. 47 at 1-2. In early

2001, he left Woodbury Pediatrics to focus on allergy and immunology. Tr. at 154; Pet.

Ex. 47 at 1-2. During this period, however, Dr. Boris still saw [A.K.’s family] socially. Tr.

at 149; Pet. Ex. 47 at 2. He and petitioners testified that he administered influenza

vaccinations to all family members in early December 2001 after Woodbury Pediatrics

ran out of the vaccine.68 Tr. at 156-57.

66 Doctor Boris’s wife is a second cousin of [A.K.’s mother’s] father. Tr. at 148; Pet. Ex. 47 at 2. When

she was a child, [A.K.’s mother] was a patient of Dr. Boris’s. Tr. at 148. Doctor and Mrs. Boris socialized

with [A.K.’s family], along with A.K.’s grandparents, on multiple occasions (Tr. at 149) and Dr. Boris’s wife

is A.K.’s godmother (Tr. at 151).

67 Defeat Autism Now [“DAN!”] physicians subscribe to treatment protocols developed by the Autism

Research Institute. These treatments may include chelation and other therapies not vetted as efficacious

by controlled clinical studies. Dwyer, 2010 WL 892250 at *20, 178.

68 A. K. received his first vaccination for influenza on November 1, 2001. See Pet. Ex. 61, p. 4.

According to Pet. Ex. 118, Dr. Boris administered influenza vaccinations to petitioners and both of their

children on what appears to be “12/3/01.” The date on the form was written over, and may have initially

read “12/1/01,” which was a Saturday.
28

Doctor Boris described his practice as “80 percent allergy immunology, and 20

percent developmental” (Tr. at 209) consisting of “30 percent children and 70 percent

adults” (Tr. at 210). He testified that he has treated over two thousand patients who

have been diagnosed with autism or autistic-like symptoms. Tr. at 146. When he began

treating A.K. again in June 2002, he used treatments he employed with other autistic

children such as a gluten-free, casein-free diet and chelation of heavy metals. Tr. at

207-209. I regarded Dr. Boris as a treating physician, factual witness, and expert.

b. Doctor Boris’s Opinion.

Doctor Boris described his opinion as “personal” indicating it was based on his

experience with over two thousand autistic patients. Tr. at 146. Labeling autism’s

cause as “a biomedical reason secondary to genetics,” Dr. Boris testified that he

believes autism develops in an individual with a genetic biomedical defect who

experiences an immunological insult, “environmentally or otherwise.” Tr. at 146. He

emphasized that both the genetic defect and environmental trigger were required for

autistic symptoms to manifest. Tr. at 147-48.

The only specific cause mentioned by Dr. Boris was a MTHFR deficiency which

he claimed was more prevalent in autistic children. He testified that, along with a noted

specialist in the field, Dr. Jill James, he found “a higher statistical preponderance of this

MTHFR deficiency in autistic children.”69 Tr. at 166-67. He theorized that this

deficiency could cause autism or at least make the person who is unable to methylate

properly more susceptible. Tr. at 167.

In his declaration, Dr. Boris attributed A.K.’s autism to the two doses of the

influenza vaccine he received in November and December 2001. He theorized that

A.K. exhibited the phenomena termed challenge-rechallenge when he suffered adverse

effects after each dose of the influenza vaccine. Pet. Ex. 47 at 8-9. In making this

assertion, Dr. Boris relied on the “close temporal proximity” of A.K.’s symptoms to

vaccination. Id. at 9. During his testimony, however, Dr. Boris indicated he did not see

evidence of challenge-rechallenge in A.K.’s medical records. Tr. at 165. After further

questioning from petitioner’s counsel, he noted the speech problem reported in A.K.’s

medical records in mid-November 2001 as evidence of an adverse effect following the

first influenza dose. Tr. at 165; see also Pet. Ex. 2, p. 20.

Most of Dr. Boris’s testimony concerned the manifestation of A.K.’s symptoms.

He maintained that A.K. was “a perfectly developing, normal boy” during his first year of

life receiving all childhood vaccinations and suffering only normal childhood illnesses.

Tr. at 154-55; accord. Pet. Ex. 47 at 2-3. After leaving Woodbury Pediatrics, Dr. Boris

still saw A.K. on social occasions and saw no evidence of any developmental issues.

He described him as acting like a normal developing child, reacting, and coming when

called. Tr. at 155-56, 183-84. In particular, he indicated nothing struck him as

abnormal when, as a favor to petitioners, he administered the second dose of the

influenza vaccine to A.K. in his office in early December 2001. Tr. at 158; Pet. Ex. 47 at

69 See, Pet. Ex. 55, M. Boris, et al, Association of MTHFR Gene Variants with Autism, J. AM. PHYSICIAN &

SURGEONS, 9(4): 106-08 (2004) filed as Pet. Ex. 55 [hereinafter “Boris, Pet. Ex. 55,”]. This article is

addressed in Section VIII.B.2.b, below.
29

4-5. Doctor Boris could not remember many of the details associated with that visit, but

he did remember speaking to each family member including A.K. Although he testified

that he did not remember the content of these conversations (Tr. at 191-195), he

indicated in his declaration that he remembered [A.K.’s mother] telling him “that she had

developed in the previous weeks some concerns about [A.K.’s] speech.” Pet. Ex. 47 at

5.

Doctor Boris next saw A.K. at a Hanukkah party at A.K.’s grandparent’s house in

early December 2001. Tr. at 158-59. After observing A.K. not responding to his name,

not speaking, not smiling, and not reacting to others, Dr. Boris told [A.K.’s mother] that

A.K.’s behavior was abnormal and recommended she get A.K.’s hearing tested. 70 Tr.

at 159. On cross examination, Dr. Boris could not recall many of the details regarding

the party and clarified that he did not feel A.K.’s behavior warranted a visit to the

hospital. Tr. at 198-200.

Over the next six months, he communicated with [A.K.’s mother] on multiple

occasions regarding A.K.’s abnormal behavior. Tr. at 202; Pet. Ex. 47 at 5. After

learning A.K.’s hearing test results were normal,71 Dr. Boris encouraged [A.K.’s mother]

to bring A.K. in for an evaluation. Tr. at 202; Pet. Ex. 47 at 5. [ A.K.’s mother] did so in

late June 2002 and Dr. Boris assessed him as hypotonic and a typical autistic child. Tr.

at 160, 202; see also Pet. Ex. 47 at 5. Doctor Boris claimed A.K. had indicators of

metabolic problems “as well as problems related to immune function and autoimmunity.”

Pet. Ex. 47 at 5. In his testimony, he cited abnormal lab results, he claimed showed

abnormal metabolism and thyroid function. Tr. at 173.

Doctor Boris recommended a gluten-free, casein-free diet for A.K. and began

therapies such as chelation, supplements to counteract the effects of his MTHFR gene

defect, and autoimmune medications. Tr. at 168-69. He testified that A.K. “did not

respond very well to most of the treatments [he] administered.” Tr. at 169. During cross

examination, Dr. Boris was unable to produce the low immunoglobulin G [“IgG”]) level he

thought he had seen prior to administering intravenous immunoglobulin [“IVIG”]

treatment to A.K. (Tr. at 215-221) and agreed that “there was no real definite

immunoglobulin deficiency” (Tr. at 231).72 In his declaration, Dr. Boris indicated he

continues to treat A.K. “for his developmental problems and various other symptoms.”

Pet. Ex. 47 at 2.

B. Respondent’s Experts.

70 He testified that it was Mrs. Boris who noticed A.K.’s behavior and prompted him to make his

observations. Tr. 199; Pet Ex. 47 at ¶12.

71 Doctor Boris did not remember exactly how he learned A.K.’s hearing test results were normal. Tr. at

201.

72 Doctor Boris originally testified that A.K. did not have an “ordinary common variable immunodeficiency,

but [fell] into that category” indicating that he based his assessment on a low IgG level. Tr. at 215. When

asked to find this test result, Dr. Boris could point only to a test result showing deficiencies of “the side

chains of Kappa Lambda and Kappa Lambda combinations.” Tr. at 220 (referencing Pet. Ex. 3, p. 375).

He indicated that record was the only one which supported the immunodeficiency he diagnosed in A.K.

Tr. at 220-21.
Respondent presented testimony by seven experts. Doctor Judith Miller, a

psychologist, addressed the onset and diagnosis of A.K.’s ASD, arguing that the onset

of this condition predated the implicated vaccinations. Doctor Kendall Wallace, a

biochemist, disputed the laboratory data upon which A.K.’s diagnosis of mitochondrial

disorder was based, while Dr. Bruce Cohen, a pediatric neurologist and mitochondrial

disease specialist, disputed the overall diagnosis of mitochondrial disorder, including

both the laboratory results and clinical symptoms. Doctor Christine McCusker opined,

contrary to Dr. Shafrir’s theory, that A.K.’s immunological status was normal, and Drs.

Gerald Raymond, Dean Jones, and Jeffrey Johnson, with expertise in neurology and

genetics, biochemistry, and pharmacology respectively, each countered various aspects

of Dr. Deth’s presentation.

1. Judith Miller, Ph.D.

a. Doctor Miller’s Qualifications.

Doctor Judith Miller received an M.S. in Psychology from the University of Utah in

1996, followed by a Ph.D. in Clinical Child and Family Psychology from the same

institution four years later in 2000. Tr. 849; Respondent’s Exhibit [“Res. Ex.”] PP at 1.

After graduation, she completed a postdoctoral fellowship at the Emery Autism

Resource Center at Emory University in Atlanta, Georgia. Id. Thereafter, Dr. Miller

served as an assistant professor of Psychiatry at the University of Utah from 2002 to

2008 and as an associate professor from 2008 to 2010, before moving to her current

position with the Children’s Hospital of Philadelphia [“CHOP”]. Tr. 849-50; Res. Ex. PP

at 1.

Currently, Dr. Miller is the Clinical Training Director and Co-Director at the Center

for Autism Research at CHOP. Tr. 847-48; Res. Ex. PP at 1. In that capacity she

oversees an assessment clinic that completes diagnostic assessments of between 15-

20 children per week who are suspected of having autism. Tr. 847. In addition, Dr.

Miller serves as Autism Director for Leadership Education in Neurodevelopment

Disabilities [“LEND”], an interdisciplinary training program at CHOP, and as Planning

Manager for CHOP’s Autism Integration Committee. Tr. 848-49; Res. Ex. PP at 1.

Doctor Miller is licensed in both Utah and Pennsylvania. Res. Ex. PP at 2. She

is a founding member of the Autism Council of Utah and maintains membership in both

the American Psychological Association and the International Society for Autism

Research. Tr. 850-52; Res. Ex. PP at 2. In addition to being a regular reviewer for

PEDIATRICS and the JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY (id.), her curriculum

vitae listed 29 peer reviewed research publications which deal almost exclusively with

subjects relating to autism spectrum disorders. Res. Ex. PP at 4-7. She is also a

frequent lecturer. Tr. 851-52; Res. Ex. PP at 3-4.

b. Doctor Miller’s Opinion.

Doctor Miller testified at length regarding the diagnosis and assessment of

autism spectrum disorders.73 Tr. 860-95. In particular, she described the proper

73 In their post-hearing brief, petitioners argued that Dr. Miller’s testimony in this case should be stricken

in its entirety because it lacked foundation. See, Pet. Post Hearing Brief (ECF No. 297) at 31, n.17. I

30
31

application of standard diagnostic tools such as the Autism Diagnostic Interview [“ADI”]

and Autism Diagnostic Observation Schedule [“ADOS”], which correspond to the

Diagnostic and Statistical Manual of Mental Disorders [“DSM”] criteria for autism

spectrum disorders.74 Tr. 857-95. Doctor Miller concluded that A.K. met 11 of the 12

DSM-IV criteria, far more than necessary, for diagnosing ASD.75 Tr. 937-38.

Doctor Miller opined that the early signs and symptoms of A.K.’s autism could be

observed long before he received either of his influenza vaccinations and that he did not

experience any regression after them.76 Tr. 939; Res. Ex. OO at 2. Specifically, Dr.

Miller noted that there were references in A.K.’s early pediatric record which suggested

early signs of autism that were not recognized as such at the time.77 Tr. 928-37. She

testified at length about signs of ASD in video footage of A.K. as early as 14 months of

age. Tr. 896-919. Doctor Miller stressed that, even if the videos occasionally showed

“good” moments, “based on the totality, he has extremely few moments that look good,

and at his age and across the number of hours of video we have, we should see

hundreds of examples of that kind of moment that we saw maybe two or three of.” Tr.

1041-42.

Significantly, Dr. Miller specifically disagreed with Dr. Shafrir’s contention that the

video footage in this case showed a dramatic change in A.K.’s behavior between

November 9 and 10, 2001. Tr. 907. Doctor Miller described distraction, limited social

interaction, and object focus during the November 9 footage, which she argued were

“the same exact behaviors” that A.K. demonstrated in the video footage of the next

ruled against petitioners on this issue. See Motions Ruling, filed on Sept. 28, 2015 (ECF No. 319), at

Section II.F.4.

74 At the time of Dr. Miller’s testimony (April 25, 2013), the DSM was in its fourth edition [“DSM-IV-TR”].

Doctor Miller noted in her testimony, however, that the fifth edition of the DSM [“DSM-V”] was soon to be

released. Tr. 889. Doctor Miller explained the changes coming in the DSM-V (Tr. 889-95) and opined

that A.K. met the criteria for ASD under either version (Tr. 895-96).

75 According to Dr. Miller, A.K.’s symptoms included: limited eye contact, lack of facial expressions or

gestures to communicate, failure to initiate or share social interaction, appearing as if “in his own world,”

not responding to or having emotional reciprocity, delayed language, lack of conversational approximation,

having repetitive sounds, lack of pretending or imitating, circumscribed interest, 

mannerisms such as ear holding or hand flapping, and preoccupation with objects or parts of objects. Tr.

937-38. Doctor Miller did not observe any rigid routines, which is the one DSM-IV criteria she noted was

absent. Tr. 938.

76 Although there are parental reports of regression of certain skills in the medical records, Dr. Miller

argued that there was no indication that A.K. ever developed these skills “to any kind of significant level”

such that they could be considered to have been lost and noted that these regressions were first

documented in the records at age 3 years and 5 months. Tr. 938-39; Res. Ex. OO at 2.

77 Doctor Miller did not fault A.K.’s pediatricians for not recognizing these signs. Rather, her critique

spoke to the state of the field of autism assessment and diagnosis during the period at issue in this case.

That is, she argued that the available screening techniques have improved significantly since that time.

Tr. 1036-38, 1047-50. At the time A.K. was diagnosed, children were not routinely referred for autism

evaluations until about three or four years of age. Tr. 1048. Now, however, reliable and stable diagnosis

of autism is possible at two years of age. Tr. 870-71. Much of the change has to do with a better

understanding of social and non-verbal communication skills which should develop before speech. Tr.

871-72.
32

day,78 Tr. 904-07, albeit that the November 10 video was a more dramatic presentation

of A.K.’s relative abnormality in behavior given that, due to the setting, A.K.’s behavior

stood out starkly when compared to the other children.

2. Kendall Wallace, Ph.D.

a. Doctor Wallace’s Qualifications.

Kendall Wallace, Ph.D., is a professor of biochemistry and molecular biology at

the University of Minnesota School of Medicine. Tr. 1057; Res. Ex. VV at 1. He earned

a B.S. in Biochemistry from Michigan State University in 1975, followed by an M.S. and

Ph.D. in Physiology from the same university in 1977 and 1979 respectively. Tr. 1056;

Res. Ex. VV at 1. From 1979 to 1981, he completed a two year postdoctoral fellowship

in toxicology at the University of Iowa. Id.

Doctor Wallace has been a professor at the University of Minnesota at Duluth

since 1981. Tr. 1056; Res. Ex VV at 1. Prior to joining the Department of Biochemistry

and Molecular Biology in 1996, he was a professor of pharmacology and director of

graduate studies for the school’s toxicology program. Ex VV at 1. He was also director

of the school’s Chemical Toxicology Research Center. Id. In his current position, Dr.

Wallace teaches courses in mitochondrial biology and molecular regulation, cardiac

pharmacology and clinical toxicology, as well as conducting clinical training on

differential diagnosis. Tr. 1057.

Doctor Wallace’s primary role, however, is laboratory-based research. Tr. 1059.

He has published 100 peer-reviewed publications, including five book chapters. Tr.

1059-60; Res. Ex. VV at 17-23. Doctor Wallace indicated that the majority of his

publications were based on his own laboratory research relating to mitochondrial

biology and toxicology. Tr. 1060. He is also a reviewer for a number of academic

journals, including the JOURNAL OF PHARMACOLOGY and EXPERIMENTAL THERAPEUTICS,

CANCER RESEARCH, MITOCHONDRION, TOXICOLOGICAL SCIENCES, and TOXICOLOGY AND

APPLIED PHARMACOLOGY. Id. He has been a co-editor of the journal TOXICOLOGY since

2001. Tr. 1060; Res. Ex VV at 9.

Doctor Wallace is board certified in toxicology by the American Board of

Toxicology and is a fellow of the Academy of Toxicological Sciences. Tr. 1061; Res. Ex

VV at 7. He is a member and past president of both the Society of Toxicology and the

Mitochondrial Research Society. Tr. 1061; Res. Ex. VV at 7-8.

b. Doctor Wallace’s Opinion.

Doctor Wallace opined that the metabolic, biochemical and genetic laboratory

test results generated in A.K.’s case did not support a diagnosis of mitochondrial

78 Doctor Miller also disagreed with Dr. Shafrir’s broader criticism of using videos to diagnosis ASD. She

testified that studies have shown that home video footage can be used to assess a child in his or her

home environment to identify early signs of autism that are more difficult to observe clinically. Tr. 919-21.

She also noted that this is a practice currently used by clinicians. Tr. 921. In this case, Dr. Miller noted

that although the medical records do include some “red flags,” the nature of developmental screening at

that time was such that A.K.’s social behaviors prior to age two were not well documented. Tr. 921-22.

She observed that the videos illustrated behaviors not noted in the medical records. Tr. 922.
33

disorder.79 Tr. 1064; Res. Ex. UU at 19. Specifically, Dr. Wallace reviewed the findings

of Dr. John Shoffner’s 2008 evaluation of A.K., see Pet. Ex. 32, and concluded that “the

original diagnosis of a Complex I defect by Dr. Shoffner on November 20, 2008, was, in

my opinion, tentative and contingent on confirmation by subsequent genetic tests, all of

which were negative and not supportive of the original diagnosis.”80 Res. Ex. UU at 19;

Tr. 1115.

After reviewing Dr. Shoffner’s enzymology results, Dr. Wallace contended that

the raw data for the two Complex I enzyme assays presented should have been

normalized over citrate synthase, and that when that calculation was performed, the

assay results fell within the normal range to a 95% confidence level.81 Tr. 1106-07.

Doctor Wallace also noted that Dr. Shoffner further supported his Complex I finding by

citing “correlative protein chemistry changes.”82 Tr. 1113; Pet. Ex. 32, p. 3. He

explained that the protein chemistry changes were tested using a method called

“Western blot” and argued that, although Dr. Shoffner listed a “possible” decrease in the

ND6 subunit within Complex I, the actual numbers generated by the Western blot

support a “normal” finding for ND6. Tr. 1077, 1112. Doctor Wallace further noted that

Dr. Shoffner’s interpretation of the ND6 finding as potentially decreased was not

supported by subsequent genetic testing which found no mutation to the ND6 gene. Tr.

1113-15.

Moreover, even taking the reported enzymology values at face value, Dr.

Wallace argued that Dr. Shoffner’s respirometry results—a measure of the functioning

of the complete respiratory chain rather than a single enzyme complex—were

equivocal, meaning the results were insufficient to demonstrate an abnormality. Tr.

1110-11. Doctor Wallace contended that this finding cast doubt on Dr. Shoffner’s

diagnosis, even in the face of a depressed Complex I finding, because the respirometry

results showed that the mitochondria were functioning “just fine” overall and that the

79 Doctor Wallace was careful to note that he is not a physician or a clinician and that his opinion does not

extend to A.K.’s overall clinical diagnosis. Tr. 1072.

80 Significantly, Dr. Wallace indicated that he was not challenging the underlying data gathered by Dr.

Shoffner. Tr. 1115.

81 Doctor Wallace acknowledged, as Dr. Kendall asserted, that there was no agreement among

laboratories regarding the proper interpretation of enzyme assays. Tr. 1120-22. He did not know why Dr.

Shoffner chose not to normalize over citrate synthase and characterized it as “his professional judgment.”

Tr. 1125. Nonetheless, Dr. Wallace was clearly of the opinion that normalizing the Complex I results over

citrate synthase was a superior approach. He argued that because Complex I enzymes are the most

unstable enzymes, normalization over citrate synthase is an important means to narrow the resulting

variations among different laboratories when handling the enzyme. Tr. 1102-04. To the extent that he

acknowledged that citrate synthase is also difficult to accurately measure, he noted that Complex I can

also be normalized over Complex II as an alternative approach. Tr. 1104-05. Significantly, Dr. Wallace

further noted that the Bernier criteria upon which Dr. Kendall relied (see, e.g., n. 42, supra.) recommend

normalizing Complex I assays over either citrate synthase or Complex II. Tr. 1100-01. He contended that

A.K.’s results would remain normal within a 95% confidence level if normalized over Complex II rather

than citrate synthase. Tr. 1108-09.

82 Additional protein chemistry findings relating to Complexes II and IV were reported as “reduced” (Pet.

Ex. 32, p. 36), but Dr. Shoffner did not report any correlating Complex II or IV defects among his

enzymology results (Pet. Ex. 32, p. 35).
34

respirometry results were consistent with the blood, urine and cerebral spinal fluid

metabolic profile. Id. Doctor Wallace also observed that Dr. Shoffner’s own findings

indicated that blood, urine, and cerebral spinal fluid tests showed metabolites that were

within a normal range.83 Tr. 1097-98.

To the extent Dr. Kendall pointed to instances of elevated lactic acid as an

indication of mitochondrial disorder, Dr. Wallace noted that although there was one

instance of elevated lactic acid on one occasion within A.K.’s medical records, testing

on five additional occasions resulted in normal or below normal lactic acid.84 Tr. 1116.

Doctor Wallace therefore argued that the weight of the evidence was against a finding

of elevated lactic acid. Id. He also pointed out that A.K.’s medical records included four

reports showing normal urine organics and nine reports of normal acylcarnitines. Tr.

1118-19. He disputed Dr. Kendall’s contention that AST and ALT, bio-indicators of liver

dysfunction, could be considered evidence of a mitochondrial disorder. Tr. 1116-17.

3. Bruce Cohen, M.D.

a. Doctor Cohen’s Qualifications.

Bruce Cohen, M.D., earned his undergraduate degree in Chemistry from

Washington University in St. Louis, Missouri, in 1978 and his M.D. at the Albert Einstein

College of Medicine at Yeshiva University in New York, New York, in 1982. Res. Ex. TT

at 1; Tr. 1134. After medical school, Dr. Cohen completed both a pediatric residency

and a pediatric neuro-oncology fellowship at the Children’s Hospital of Philadelphia as

well as a pediatric neurology residency at Columbia Presbyterian Medical Center. Res.

Ex. TT at 1.

Currently, Dr. Cohen serves as the director of neurology at the Children’s

Hospital Medical Center of Akron and as a professor of pediatrics at Northeast Ohio

Medical University where he specializes in mitochondrial disease, brain tumors, and

chemotherapy complications. Res. Ex. TT at 2; Tr. 1134-35. His practice is “heavily

weighted towards mitochondrial disease,” an area in which he first became interested in

1983. Tr. 1135-36. He estimated that he has evaluated over 2,000 patients with

suspected mitochondrial diseases. Tr. 1137.

Doctor Cohen is also a member of the medical consulting staff for the department

of pediatrics at Hillcrest Hospital, part of the Cleveland Clinic Health System. Res. Ex.

TT at 2. Previously, Dr. Cohen served as staff physician for the Neurological Institute of

the Cleveland Clinic and as chairman of the Cleveland Clinic’s pediatric neurology

section. Id. He was a professor at Case Western Reserve University for approximately

22 years. Tr. 1139-40; Res. Ex. TT at 2.

Doctor Cohen is licensed to practice medicine in the state of Ohio. Res. Ex. TT

at 2. He is a fellow of the National Board of Medical Examiners and the American

83 The results were characterized by Dr. Shoffner as “unremarkable.” Pet. Ex. 32, p. 1.

84 Doctor Wallace noted that elevated lactate—or lactic acidosis—can be a marker for a number of

metabolic disorders. He also stressed that its instability makes accurate measurement difficult. For that

reason, he noted that elevated lactic acid was normalized by reporting it as a ratio to pyruvate. Tr. 1115-

16.
Board of Psychiatry and Neurology with special competence in child neurology. Res.

Ex. TT at 2; Tr. at 1134. He is a member of the American Academy of Neurology, the

Child Neurology Society, Professors of Child Neurology, the Mitochondrial Research

Society, and the Mitochondrial Medicine Society. Res. Ex. TT at 3; Tr. 1141-42. He is a

past president of both the Professors of Child Neurology and the Mitochondrial Medicine

Society. Id. He has served on a multitude of committees and advisory groups both

nationally and at the Cleveland Clinic and is on the editorial board of seven academic

journals, including NEUROLOGY and MITOCHONDRIAN. Res. Ex. TT at 3-5. Doctor Cohen

listed numerous peer-reviewed and frequently cited articles on his curriculum vitae, as

well as 29 peer-reviewed book chapters and an edited journal volume. Res. Ex. TT at

33-40. He co-authored several of the medical journal articles extensively discussed in

this case.

b. Doctor Cohen’s Opinion.

Like Dr. Kendall, Dr. Cohen acknowledged that there was disagreement among

experts regarding the diagnosis of mitochondrial disorders. Res. Ex. SS at 13. He

agreed with her that there was no single test to confirm a mitochondrial diagnosis and

that such diagnoses are made in the judgment of clinicians looking at a number of

factors. Tr. 1179-80, 1319-23. He cited the Bernier criteria, however, as an

authoritative standard that brings some certainty to the analysis and stressed that a firm

diagnosis requires “a lot” of evidence supported by a patient’s medical records. Id.

Applying these standards, Dr. Cohen disagreed with Dr. Kendall’s ultimate conclusion

that A.K. had a mitochondrial disorder, and further disagreed that A.K.’s influenza

vaccinations would have aggravated that disorder.85 Res. Ex. SS at 16; Tr. 1147-48,

1220.

Doctor Cohen disagreed with both Dr. Kendall and Dr. Shafrir’s assessments of

A.K.’s clinical history. Res. Ex. SS at 15-16. He argued that A.K.’s clinical course was

consistent with the classic pattern of autism and was not consistent with mitochondrial

encephalopathy. Res. Ex. SS at 9-10. In particular, he noted that the video footage in

evidence in this case showed signs of autism as early as 15 or 16 months of age and

did not support parental reports of regression. Res. Ex. SS at 6, 8; Tr. 1383-87. He

further pointed out that the records of A.K.’s medical treatment in the months

immediately following A.K.’s vaccinations (i.e., November and December of 2001) did

not include any expressing of concern regarding regression and did not reflect a course

of treatment consistent with such a concern.86 Moreover, Dr. Cohen contended that

85 To the extent petitioners argued that A.K.’s medical records showed opinions by other mitochondrial

specialists, including Drs. Korson, Sims and Alvarez, Dr. Cohen argued that his opinion should still

control. Tr. 1330. He said that there is insufficient evidence to show that either Drs. Sims or Alvarez

conducted any independent assessment of A.K. Tr. 1222-23, 1323. Rather, he contended they simply

reiterated Dr. Shoffner’s conclusion, which he challenged. Id. He also argued that, although Dr. Korson

did a thorough exam of A.K., his report did not reflect any analysis of A.K.’s medical records or the video

footage filed in this case. Tr. 1326-27. For those reasons, Dr. Cohen argued that his opinion is better

informed. Tr. 1330.

86 More specifically, Dr. Cohen contended that a sudden and complete loss of speech such as petitioners

are alleging would constitute a medical emergency for which immediate diagnostic tests such as MRI,

EEG or spinal tap would be necessary. Tr. 1154-55, 1369-70. Doctor Cohen indicated that possible

35
36

A.K.’s clinical features of fatigue, autism, developmental delay, and gastrointestinal

problems—relied upon by Dr. Kendall in her diagnosis—were too non-specific, absent

additional findings, to be indicative of mitochondrial disorder.87 Tr. 1182-91. He also

questioned the validity of notations indicating that A.K. experienced autonomic

dysfunction and hypotonia. Tr. 1190-91, 1193-94.

Like Dr. Wallace, Dr. Cohen also challenged the significance of Dr. Shoffner’s

enzymology results and disputed his resulting diagnosis of mitochondrial

encephalomyopathy.88 Tr. 1220-21. Echoing Dr. Wallace, Dr. Cohen asserted that

normalizing the Complex I assay result over citrate synthase was preferable and noted

that when that calculation was performed, the results were normal. Res. Ex. SS at 13;

Tr. 1206-12. He additionally noted that the normal finding for the combined Complex I

and III measurement cast significant doubt on the separate Complex I finding, Res. Ex.

SS at 13; Tr. 1212, as it was unlikely the combined finding would be normal where one

of its components was decreased. Moreover, he stressed that the combined Complex I

and III measure was considered a more robust finding and is more commonly used. Id.

Taking the rest of Dr. Shoffner’s findings into account, which were either normal or

equivocal, Dr. Cohen argued that a diagnosis could not be made based on the Complex

I finding alone, since it represented incongruent data at best. Id. He stated that the test

results for lactic acid, AST, or ammonia, conducted on other occasions did not have any

diagnostic significance. Tr. 1197-1206.

Doctor Cohen disagreed with the assertions by both Dr. Kendall and Dr. Shafrir

that A.K.’s influenza vaccine could be linked to a regression through several papers.89

Doctor Cohen argued that these papers did not stand for the proposition that vaccines

causes for abrupt speech loss could include stroke, seizure, or meningitis. Tr. 1369-70. Doctor Cohen

further testified that, even if one were to consider a regression occurring over the course of two months, a

full battery of tests would still be advisable for detection of other disorders, such as Landau-Kleffner

Syndrome, which also result in lost speech. Tr. 1155-56. Doctor Cohen noted in his expert report that

those presenting with mitochondrial regression often present with acute or sub-acute loss of function,

ataxia, blindness, loss of speech, and other symptoms that “result in a shocking change to parents and

physicians.” Res. Ex. SS at 9-10. Doctor Cohen indicated, however, that such presentations typically

result in emergency evaluation, including neuroimaging. Res. Ex. SS at 10.

87 Doctor Cohen claimed that the type of GI distress usually associated with mitochondrial disorders was

a type of non-physical intestinal blockage called a “pseudo-obstruction,” which A.K. did not have. Tr.

1186-88. Although he indicated that some mitochondrial patients do exhibit constipation, Dr. Cohen

argued that a course of alternating diarrhea and constipation, such as A.K. experienced, would not be

diagnostic of a mitochondrial disorder absent other classic mitochondrial disorder findings such as large

fiber neuropathy, cardiac conduction defect, or other clinical or laboratory findings not present in A.K.’s

history. Tr. 1188, 1303-04. Doctor Cohen opined that A.K.’s GI distress was more likely linked to his

autism than to any mitochondrial disorder. Tr. 1220-21.

88 To the extent Dr. Shoffner’s assessment is based on his clinical summary in addition to his own test

results, Dr. Cohen noted that there is no evidence to suggest Dr. Shoffner conducted any independent

clinical evaluation. Rather, Dr. Cohen argued that it appears that Dr. Shoffner reported a clinical

summary provided to him by Dr. Boris. Tr. 1220-21. In any event, Dr. Cohen stated, in essence, that it

was not a lab technician’s place to make an overall clinical diagnosis. Tr. 1221-22; Res. Ex. SS at 12.

89 Referring to the Shoffner, Res. Ex. MM, Tab 16; Weissman, Pet. Ex. 39, R. Hass, Autism and

Mitochondrial Disease, Dev. Disabil. Res. Rev., 16:144-53 (2010), filed as Pet. Ex. 63, Ref. 17 and as

Res. Ex. MM, Tab 13 [hereinafter “Hass, Pet. Ex. 63, Ref. 17”]; and Poling, Res. Ex. MM, Tab 14, papers.
37

incited mitochondrial regression that petitioners’ experts contended they do, and that

even if they did, the studies were not good evidence of such a link, because they were

not controlled studies and had other methodological flaws.90 Res. Ex. SS at 15; Tr.

1226-30, 1356-59.

4. Christine McCusker, M.D.

a. Doctor McCusker’s Qualifications.

Christine McCusker, M.D., received her M.S. and her M.D. from McMaster

University in Hamilton, Ontario, in 1988 and 1993, respectively. Res. Ex. RR at 1; Tr.

1396. From 1993 to 1999 she completed a residency training program in pediatrics and

a clinical fellowship in allergy and immunology at McGill University in Montreal, Quebec.

Res. Ex RR at 2; Tr. 1396.

Currently, Dr. McCusker is an associate professor of allergy and immunology in

the department of Pediatrics at the Montreal Children’s Hospital and McGill University.

Res. Ex. RR at 3; Tr. 1396-97. She is also a research director for Meakins-Christie

Laboratories and a staff physician and director of the Clinical Immunology Laboratory at

Montreal Children’s Hospital. Res. Ex. RR at 4; Tr. 1397. Additionally, Dr. McCusker

serves on a number of committees, including the Hereditary Angioedema Society and

Primary Immunodeficiency Network, the Canadian Immunodeficiency Patient

Organization Scientific Advisory Committee, and the Examination Committee for Allergy

and Immunology of the Royal College of Physicians and Surgeons of Canada. Res. Ex.

RR at 13. She is Co-Chair of the Immunology Interest Section of the Canadian Society

for Allergy and Clinical Immunology. Id.

As well as being licensed by the Medical Council of Canada, Dr. McCusker is

board certified by the American Board of Pediatrics. Res. Ex. RR at 2; Tr. 1397. She is

a Fellow of the Royal College of Physicians and Surgeons of Canada, recognized in

pediatrics as well as allergy and immunology. Res. Ex. RR at 3. She is licensed by the

Collège des Médecins du Québec. Res. Ex. RR at 2-3; Tr. 1397. Doctor McCusker is

also a member of the Canadian Medical Protective Association, the Federation of

Medical Specialists of Quebec, the Quebec Allergy and Immunology Association, and

the Clinical Immunology Society. Res. Ex. RR at 14.

In addition to her clinical and teaching duties, Dr. McCusker is an active

researcher, listing numerous research grants on her curriculum vitae as well as three

pending patent applications. Res. Ex. RR at 17-19. Doctor McCusker has published 25

90 Doctor Cohen’s testimony regarding methodological flaws of the Weissman article was particularly

noteworthy in that he was a listed author of that study. Tr. 1227-29. Among Dr. Cohen’s concerns

regarding that paper are the fact that the authors did not know how many patients were ultimately

screened to arrive at the study’s population, leaving them without any “denominator” to assess the

significance of their findings. Tr. 1357-59. He was also concerned that some potential subjects were

screened out of the study based on the results of chromosomal microarray, but that this test was not

consistently conducted on all of the subjects. Tr. 1356-57. Perhaps most significantly, Dr. Cohen

indicated that he objected to the inclusion of the Poling case within the report. Id. He indicated that this

objection resulted in negotiated language among the authors stating that the Poling case did not prove

causation. He further argued that this article does not otherwise speak to vaccination, as the focus was a

cohort analysis regarding mitochondrial disorders and autism. Tr. 1227-29, 1356-57, 1379-80.
38

articles and one book chapter on topics relating to allergy and immunology. Id. at 19-

22. She is also a reviewer for a number of academic journals, including the JOURNAL OF

IMMUNOLOGY, the JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, CLINICAL AND

EXPERIMENTAL ALLERGY, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, and IMMUNOBIOLOGY.

Tr. 1400; Res. Ex. RR at 12.

b. Doctor McCusker’s Opinion.

Doctor McCusker opined, based on a review of A.K.’s medical history,91 that

there is no evidence that A.K. had any immune disorder or deficiency. Tr. 1401, 1426-

27. Rather, contrary to the opinions of Drs. Boris and Shafrir, she opined that A.K. has

a normal immune system. Tr. 1426-27. She explained that A.K. had only “usual

childhood illnesses” during his first two years of life, from which he recovered well, and

that the isolated finding of antibodies, such as the myelin basic protein antibodies found

in A.K., did not support any finding of immune dysregulation in the absence of

correlating clinical symptoms. Res. Ex. QQ at 3; Tr. 1402, 1411, 1439-40. She also

disputed that there was any evidence to suggest that A.K. had an abnormal adverse

reaction to his influenza vaccines or that these vaccines contributed to his

developmental delays.92 Res. Ex. QQ at 3-5; Tr. 1411-12, 1426-27.

Doctor McCusker testified that the laboratory results relied upon by Dr. Boris to

diagnose A.K. with common variable immunodeficiency [“CVID”] did not support that

diagnosis, as they showed normal immunoglobulin levels. Tr. 1404 (evaluating Pet. Ex.

3, p. 375). She further opined that, even if A.K. did have low immunoglobulin, a

diagnosis of CVID also required a corresponding functional deficiency, which A.K did

not demonstrate. Id. That is, a definitive feature of CVID is that patients cannot

produce antibodies when their immune system is stimulated. A.K., however, did form

antibodies, as evidenced by the testing of the response to his mumps vaccine.93 Tr.

1403-04, 1406.

In addition, Dr. McCusker disputed both Dr. Shafrir’s contention that A.K. had

autoimmune hypothyroidism as well as his assertion that such a condition was

indicative of an abnormal immune system. Res. Ex. QQ at 3; Tr. 1407-08, 1410-11.

Doctor McCusker explained that autoimmune hypothyroidism occurs where the

formation of autoantibodies against the thyroid gland prevent the production of thyroid

hormones such as “T4”. Res. Ex. QQ at 3; Tr. 1407. Looking at A.K.’s lab results, Dr.

McCusker acknowledged that A.K. did show autoantibodies, but noted that his thyroid

91 Doctor McCusker did not review the video footage filed in this case. Tr. 1401.

92 Although Dr. McCusker acknowledged that [A.K.’s mother] reported that A.K. experienced a low grade

fever following his influenza vaccination, she stressed that there is no indication of any abnormal immune

response. Res. Ex. QQ at 4; Tr. 1412. She testified petitioners’ reliance on the immunological concept of

challenge-rechallenge and the so called “triple hit” theory to explain how A.K.’s vaccines could have led to

developmental delays was misplaced. Res. Ex. QQ 3-5; Tr. 1419-26, 1440-41.

93 Although Dr. McCusker acknowledged that A.K.’s test results were equivocal with regard to his

immunity to measles and mumps, she noted that he did not receive the recommended second “booster”

vaccine against the diseases. Tr. 1406. Doctor McCusker stated that although a booster could have

improved his protection against these diseases, A.K.’s results show that he did make antibodies in

response to vaccines. Tr. 1407.
function tests showed levels of T4 and TSH that were both normal. 94 Id. She argued

that absent an abnormal T4 finding, A.K.’s tests did not support a diagnosis of

autoimmune hypothyroidism. Tr. 1408. Moreover, occurring at a rate of eight per one

thousand males per year, Dr. McCusker stated that autoimmune hypothyroidism is “not

an uncommon problem” and is not an indication of general immune dysfunction. Tr. at

1411; Res. Ex. QQ at 3.

5. Gerald Raymond, M.D.

a. Doctor Raymond’s Qualifications.

Doctor Gerald Raymond earned his undergraduate degree in biology from

Fairfield University in 1980. He subsequently earned an M.D. from the University of

Connecticut in 1984 and completed postdoctoral training from 1984 to 1993, including

an internship and junior residency in pediatrics at Johns Hopkins Hospital and a

neurology residency at Massachusetts General Hospital. He also completed

fellowships in developmental neuropathology and genetics and teratology. Res. Ex. NN

at 1; Tr. 1442-43.

Currently, Dr. Raymond is director of pediatric neurology and a professor of

neurology at the University of Minnesota School of Medicine in Minneapolis where he

maintains a clinical practice devoted to neurology and genetics. Tr. 1443-46; Res. Ex.

NN at 1. Prior joining that faculty, he was a professor of neurology at Johns Hopkins

University, director of neurogenetics research at the Kennedy Krieger Institute, and a

staff physician in pediatrics and neurology at Johns Hopkins Hospital. Res. Ex. NN at

1-2; Tr. 1443.

Doctor Raymond is licensed to practice medicine in both Minnesota and

Maryland and was previously licensed to practice in Massachusetts. Res. Ex. NN at 11.

He is board certified in both clinical genetics and neurology, with special qualifications in

child neurology, and was formerly board certified in pediatrics. Res. Ex. NN at 11; Tr.

1444. Doctor Raymond is a reviewer for a number of peer-reviewed academic journals,

including the ANNALS OF NEUROLOGY, NEUROLOGY, LANCET, TERATOLOGY, the AMERICAN

JOURNAL OF HUMAN GENETICS, and the AMERICAN JOURNAL OF MEDICAL GENETICS. Res.

Ex. NN at 12; Tr. 1446. His curriculum vitae listed 98 peer-reviewed original articles,

one book, and 16 book chapters. Res. Ex. NN at 2-6, 9-11.

b. Doctor Raymond’s Opinion.

Doctor Raymond’s opinion in this case focused principally on the epigenetic

aspects of Dr. Deth’s theory as well as the significance of A.K.’s MTHFR mutation,

which was raised by both Dr. Deth and Dr. Shafrir.95 Although it is undisputed that A.K.

94 Doctor McCusker did note that A.K. occasionally showed mildly elevated TSH. She indicated,

however, that such mild elevations could happen transiently and were not concerning unless

accompanied by elevated T4. She explained that TSH is a signal for the production of more thyroid

hormone. Tr. 1407-08.

95 Doctor Raymond’s report was the first to be filed by respondent as among respondent’s testifying

experts. Tr. 1447-49. His report also spoke to broader issues in this case that were subsequently

addressed by other of respondent’s experts and which were not addressed during his direct examination.

39
40

has two variants in his gene coding for MTHFR, a heterozygous C677T alteration and a

heterozygous A1298C alteration, Dr. Raymond disputed that these gene variants could

have had the impact on A.K.’s condition that petitioners claim. Pet. Ex. 3, p. 301; Tr.

1449, 1454-57. He also contended that Dr. Deth’s theory was implausible and premised

on a fundamentally flawed understanding of the different ways in which epigenetic

changes manifest in prenatal and postnatal development. Tr. 1460, 1464-69, 1472-

73.

According to Dr. Raymond, the specific MTHFR alterations at issue are known as

“polymorphisms,” because they are found in a significant portion of the general

population. Tr. 1450. Most people who have these polymorphisms have no issues

related to the condition and are “perfectly fine.” Tr. 1452-53. Among those who are

impacted, the chief concern is a slowing of metabolic processes resulting in elevated

homocysteine. Res. Ex. MM at 4; Tr. 1453-55. He explained that these metabolic

consequences appear among those with nutritional folate deficiency and can ultimately

lead to vascular health concerns later in life, but these polymorphisms are not linked to

autism. Tr. 1455-57. Although Dr. Raymond acknowledged that some medical

literature has posited an association between the MTHFR polymorphisms and

conditions such as autism, Down syndrome and other developmental delays, these

studies have been “all over the place” and did not present reliable evidence of a causal

relationship. Res. Ex. MM at 5; Tr. 1456-57. Doctor Raymond also noted that the

reports were only looking at prenatal embryonic development. Id.

Doctor Raymond had very definite and focused disagreements with Dr. Deth’s

presentation on epigenetics. Doctor Deth contended that early childhood is an

important period for epigenetic regulation, but Dr. Raymond noted that Dr. Deth ignored

the critical distinction between pre- and postnatal development.96 Doctor Raymond

explained that during early prenatal development, epigenetic activity occurs in the

context of cell differentiation, regulating the process by which early cells begin to create

different kinds of tissue. Tr. 1461-64. At that stage, epigenetic changes resulting from

methylation can be carried on by the further replicating cells. Id. Postnatally, however,

when epigenetic regulation acts on non-dividing cells, the changes are not carried

forward as they would have been during early prenatal development. Tr. 1464-68.

Doctor Raymond therefore asserted that Dr. Deth’s theory was implausible, because the

type of disruption in methylation Dr. Deth described—occurring at around 2 years of age

on non-dividing neural cells—would have to be systematic to have such a significant

impact to the brain. Id. Doctor Deth could not account for the “impossible” chance

occurrence necessary for the methylation disruption he posits to impact a specific

phenotype in the context of that type of systemic whole body deficit. Tr. 1467-68. That

My summary of his opinion will address his more focused testimony. I do note, however, that Dr.

Raymond indicated that despite the apparent reduction in the scope of his opinion, he still maintained that

Dr. Deth’s theory overall was “a striking oversimplification of a number of biochemical pathways” and that

he had “numerous issues” with Dr. Deth’s theory aside from its epigenetic aspects. Tr. 1474-75.

96 Although Dr. Raymond agreed that epigenetic regulation occurs throughout life, he noted that

epigenetic activity is critically important from conception through the second trimester of gestation. Tr.

1457-59.
41

is, Dr. Raymond asserted that Dr. Deth could not explain how his theory would result in

autism, and only autism, without impacting other body tissues.97 Tr. 1468-69.

6. Dean Jones, Ph.D.

a. Doctor Jones’ Qualifications.

Dean Jones, Ph.D., is a professor at Emory University in the department of

medicine with appointments in the departments of biochemistry, ophthalmology, and

pediatrics. Res. Ex. YY at 1; Tr. 1610. In addition, he is the director of the Emory

Clinical Biomarkers Laboratory and co-director of the Center for Clinical and Molecular

Nutrition. Res. Ex. YY at 1. Doctor Jones focuses his research on two areas—personal

medicine and oxidative stress—and considers himself an expert in oxidative stress. Tr.

1611-12. He listed a number of currently active research grants on his curriculum vitae,

including three National Institutes of Health [“NIH”] grants for research on reactive

oxygen species and antioxidants. Res. Ex. YY at 3; Tr. 1610. He has been affiliated

with Emory University since 1979. Res. Ex. YY at 37; Tr. 1608.

Doctor Jones earned his undergraduate degree with majors in chemistry and

biochemistry from the University of Illinois Champaign-Urbana, in Urbana, Illinois, in

1971. Res. Ex. YY at 2; Tr. 1608. Five years later, he earned a Ph.D. in biochemistry

at the Oregon Health Sciences University in Portland, Oregon. Id. Thereafter, Dr.

Jones completed a postdoctoral fellowship in nutritional biochemistry at Cornell

University in Ithaca, New York. Id. He spent a further two years as a guest scientist in

biochemical toxicology at the Korolinksa Institute department of forensic medicine in

Stockholm, Sweden, and as a postdoctoral research associate in physiological

chemistry at the Oregon Health Sciences University School of Medicine. Id.

Doctor Jones is a member of several academic societies, including the Society of

Toxicology, the Society for Free Radical Biology and Medicine, and the Association for

Advancement of Science. Res. Ex. YY at 2. He serves as a peer reviewer for a number

journals, and provides special expertise in oxidative stress as a member of the National

Institutes of Health Basic Mechanisms of Center Therapeutics Study Section.

Res. Ex. YY at 37; Tr. 1609. He listed 270 peer-reviewed original publications on his

curriculum vitae, over half of which he estimated are on subjects relating to oxidative

stress, as well as numerous reviews and book chapters. Res. Ex YY at 11-36; Tr. 1612.

97 Doctor Raymond argued in particular that Dr. Deth’s reliance on a recently published medical journal

article was misplaced. See C. Wong, et al., Methylomic analysis of monozygotic twins discordant for

autism spectrum disorder and related behavioral traits, MOL. PSYCHIATR., 23 April 2013 (advance online

publication) [hereinafter “Wong, Pet. Ex. 240”]. is misplaced. Tr. 1470. While Dr. Deth relied on this

paper to support a relationship between epigenetics and autism (Tr. 621), Dr. Raymond pointed out that

the article addresses epigenetic changes occurring during very early embryonic development (Tr. 1470-

74), because the studies were done on blood. The primogenitor cells that result in the cells that create

blood are formed in the first few days or weeks of gestation. For an epigenetic difference between

identical twins to occur and be identified in blood cells, it must have occurred when the blood producing

cells were generated. Doctor Raymond argued that the paper therefore does not support the idea of

vaccine-caused epigenetic dysregulation. Tr. 1470. I note that the study was filed after the deadline I

imposed for filing medical literature, but because it was published April 23, 2013, I allowed it to be

considered as evidence.
42

In addition, he has edited two books and registered six patents with an additional patent

pending. Res. Ex. YY at 36.

b. Doctor Jones’ Opinion.

Doctor Jones asserted that Dr. Deth’s testimony and written opinion relied on an

outdated understanding of the concept of “oxidative stress” and advanced a more

nuanced understanding of the term. Thiol is the most reduced form of sulfur in the

biological system, common in proteins. The traditional way of thinking about oxidative

stress—as any imbalance in redox state favoring oxidation—failed to capture the reality

that the different “thiol systems”98 (such as cysteine vs. glutathione) do not exist in

equilibrium with one another, but rather in “a nonequilibrium steady state.” Tr. 1613-17.

Any discussion of an overall whole-body redox balance is inadequate. Id. He noted the

necessary role of oxidation in healing and immune responses. He explained that

vaccinations do produce oxidation, but only to the extent of impacting redox signaling as

part of the normal immune response. Vaccinations do not cause oxidative damage. 99

Tr. 1621, 1679-80. Doctor Jones pointed out that Dr. Deth’s own study100 showed that

there is no association between markers of oxidative stress and autism. The study

showed that markers of oxidative stress were not significantly different between subjects

with autism and a control group.101 Tr. 1651.

With regard to A.K.’s case specifically, Dr. Jones testified that Dr. Deth’s theory

lacked evidence to support four key components of the causal mechanism he

proposed,102 Tr. 1633-34, 1661,: (1) there is no credible evidence of oxidative stress; (2)

no evidence of neuro-inflammation from oxidative stress,103 see Res. Ex. ZZ at 2-6; Tr.

1650-52, 1659-61; (3) no evidence of impaired sulfur amino acid metabolism; and (4) no

98 I note that “thiol” is misspelled throughout the transcript as “thial.” I will use the correct spelling within

this decision, but will not further address each misspelling within the record.

99 Doctor Jones questioned the thinking that oxidative stress is a central mechanism to understanding

human disease. In this regard, Dr. Jones noted that studies have shown that administering antioxidants

does not give a health benefit. Tr. 1617-18. He noted that, in addition to ill effects, “oxidative stress” also

encompasses necessary redox signaling. Tr. 1620-21. Therefore not all oxidative stress is bad or 

causes damage. Id.

100 Pet. Ex. 135, C. Muratore, et al, Age-Dependent Decrease and Alternative Splicing of Methionine

Synthase mRNA in Human Cerebral Cortex and an Accelerated Decrease in Autism, PLOS ONE 8(2):

e56927 (2013) [hereinafter ”Muratore, Pet. Ex. 135”]. Doctor Deth was the last listed author on this

journal article, the position usually used to designate the senior researcher.

101 I note that, for his part, Dr. Deth confirmed that his study did not show elevated biomarkers for

oxidative stress among autistic individuals. Tr. 827. He expressed surprise at that outcome, but

hypothesized (without apparent support) the presence of a coping mechanism to explain the results. Id.

102 Doctor Jones’s hearing testimony refined his opinion in light of Dr. Deth’s testimony. Tr. 1624, 1633-

34. Therefore, I focus primarily on his hearing testimony.

103 No test ever measured inflammatory cytokines in A.K., and that to the extent A.K. showed clinical

signs of inflammation over the course of his medical history, such as upper respiratory infections, or

coughing and sneezing, these kinds of symptoms are not indicative of neuroinflammation in particular.

Tr. 1659-61.
43

evidence of impaired methionine synthase activity,104 see Res. Res. Ex. ZZ at 6-8; Tr.

1657-59.

According to Dr. Jones, Dr. Deth relied solely on a finding of no detectable level

of cystine in A.K.’s cerebral spinal fluid as evidence of the presence of oxidative stress.

Tr. 1651-52. However, oxidative stress is associated with elevated cystine, and not low

cystine, as Dr. Deth indicated. Tr. 1648-49. Moreover, regardless of its significance, Dr.

Jones stated that the result of no detectable cystine was a misnomer in that the normal

range for cystine in CSF was below the detection limits of the test used. Tr. 1643-45.

Measurements of cystine are incredibly unreliable absent specific protocols, and cystine

values vary by both time of day and diet. Tr. 1645-48. For these reasons, as well as

the absence of information regarding the lab’s handling of the samples, Dr. Jones did

not trust the reported cystine values. Thus, even under Dr. Deth’s erroneous view of

low cysteine as a marker for oxidative stress, this test was inadequate as supporting

evidence.105 Id.

With regard to the claim of impaired sulfur amino acid metabolism, Dr. Jones

contended that such an impairment could manifest in one of two ways. If an impairment

occurred at the level of conversion of homocysteine to methionine, then one would

expect to see a build-up of homocysteine. Alternatively, if impairment occurred at the

level of the transsulfuration pathway, then one would expect to see an increase in

methionine along with a decrease in both cystathionine and taurine. Tr. 1638-39.

Doctor Jones pointed out, however, that in A.K.’s case, testing showed that all four of

these components were normal. Tr. 1639, 1642-43. Moreover, Dr. Jones noted that Dr.

Deth’s own citation106 indicated that the impact of vaccination on transsulfuration and

methylation was only a fraction of the impact demonstrated between fasting and fed

subjects. Thus, Dr. Jones noted that the capacity of the vaccine to impact sulfur amino

acid metabolism is actually quite small. Tr. 1639-42.

With regard to the claim of impaired methionine synthase activity, Dr. Jones

indicated that Dr. Deth was wrong to characterize the EAAT3 transporter107 as the

primary transporter for cysteine and cystine in the intestine. Tr. 1654-57. While he was

unable to state whether EAAT3 is the primary transporter in the brain, Dr. Jones testified

that EAAT3 does not appear to be a major transporter for cysteine in the intestine and,

thus, questioned the validity of Dr. Deth’s focus on that transporter. Tr. 1655-56.

104 In addition, for reasons similar to respondent’s other experts, Dr. Jones also thought there was

insufficient evidence to show that A.K. had any mitochondrial dysfunction. Tr. 1626-33.

105 In rebuttal testimony, Dr. Deth argued that Dr. Jones has no basis to discount the reported cystine

values. He did not, however, specifically address Dr. Jones’s actual criticisms. Instead, he simply argued

that Dr. Jones was “shooting the messengers.” Tr. 1743.

106 Pet. Ex. 132, S. Mercier, et al., Methionine Kinetics are Altered in the Elderly Both in the Basal State

and After Vaccination, AM J. CLIN. NUTR 83:291-98 (2006) [hereinafter “Mercier, Pet. Ex. 132”].

107 In Dwyer, I explained the EAAT3 transporter’s function thusly: “Cysteine, like other amino acids, is

transported across cell membranes by transporter proteins.” Dwyer, 2010 WL 892250, at *121, n.517.

Quoting Dr. Deth’s testimony in that case, “in neurons, the transport is accomplished by the excitatory

aminio acid transporter-3 [“EAAT3”], which also transports glutamate, the primary excitatory amino acid.”

Id. (citations omitted).
44

Doctor Jones also indicated that an impairment in methionine synthase activity would

increase levels of homocysteine. Tr. 1653-54. Turning again to Dr. Deth’s own

study,108 however, Dr. Jones noted that, contrary to Dr. Deth’s hypothesis in this case,

homocysteine was lower among subjects with ASDs. Tr. 1652-54.

7. Jeffrey Johnson, Ph.D.

a. Doctor Johnson’s Qualifications.

Jeffrey Johnson, Ph.D., is a professor of pharmaceutical sciences at the

University of Wisconsin, Madison School of Pharmacy. The majority of his time there is

spent engaged in laboratory research focused on “molecular aspects in regulation of

gene transcription and neurodegeneration.” Res. Ex. WW at 1; Tr. 1688-1690. More

specifically, his research addresses redox biology in the context of chronic

neurodegenerative diseases. Res. Ex. XX at 1. Prior to his appointment at the

University of Wisconsin, Dr. Johnson was an assistant professor in the department of

pharmacology, toxicology and therapeutics at the University of Kansas Medical Center

in Kansas City, Kansas. Res. Ex. WW at 1.

In 1984, Dr. Johnson completed an undergraduate degree with a major in biology

at the University of Minnesota, Duluth. Res. Ex. WW at 2; Tr. 1688-89. He later

completed a master’s degree in pharmacology at the same institution in 1986 before

pursuing his Ph.D. in molecular environmental toxicology at the University of Wisconsin,

Madison, from 1986 to 1992. Res. Ex. WW at 2; Tr. 1689. Doctor Johnson then

completed a three-year postdoctoral fellowship in molecular neuroscience at the

University of Washington in Seattle, Washington. Tr. 1689.

Doctor Johnson listed 82 peer-reviewed articles, seven reviews, and two book

chapters on his curriculum vitae, along with numerous invited lectures. Res. Ex. WW at

2-12; Tr. 1690-91. He is a reviewer for numerous academic journals and currently holds

three NIH grants. Tr. 1691. In addition, he is a member of the NIH study section on

Neural Oxidative Metabolism and Death and an ad hoc member of the NIH study section

on Neurotoxicology and Alcohol. Res. Ex. WW at 4; Tr. 1692. He is chair of the

external advisory committee for Emory University’s Parkinson’s Disease-Collaborative

Environmental Research Center and serves on multiple grant review panels. Res. Ex.

WW at 4.

b. Doctor Johnson’s Opinion.

Doctor Johnson disputed Dr. Deth’s claim that vaccinations can cause

neuroinflammation leading to oxidative stress and inhibited methionine synthase activity

resulting in autism. Tr. 1732-33. Focusing on several specific studies cited by Dr. Deth,

he contended that “there are a number of significant issues with the way these data

were generated and interpreted” and that ultimately “Dr. Deth’s hypothetical mechanism

for how vaccines cause autism is fatally flawed” and lacks sufficient evidence. Res. Ex.

XX at 3, 7.

108 Muratore, Pet. Ex. 135.
45

Addressing Dr. Deth’s citation of a study by Waly,109 (Dr. Deth was a co-author of

this study), Dr. Johnson contended that the study, which he characterized as “the whole

foundation of Dr. Deth’s theory,” had a number of significant issues and had not been

corroborated by any other laboratory.110 Res. Ex. XX at 3-5. In addition to pointing out

several technical deficiencies, Dr. Johnson asserted that the study failed to produce

statistically valid data, and failed to test what impact, if any, the subject compounds had

on global methylation. Id. at 5. He also noted that the study failed to actually examine

neuronal methionine synthase activity and oxidative stress generation, both of which

were “primary end points” for the paper’s hypothesis. Res. Ex. XX at 3, 5; Tr. 1694.

Doctor Johnson argued, therefore, that the hypothesis Dr. Deth based on the study

lacks any sound scientific support. Res. Ex. XX at 5. Moreover, he noted that as a

study based on neuroblastoma cells, any conclusion drawn from the test would be

relevant only to the cell line and would not be indicative of actual neuronal activity. Id.

at 3. These were all criticisms directed against the study in the OAP Theory 2 test

cases and were cited there as reasons for rejecting Dr. Deth’s opinions on how mercury

in vaccines caused oxidative stress.

Doctor Johnson was also critical of Dr. Deth’s attempt to rely on a study by

James, et al.,111 to link markers of oxidative stress among children with autism to

vaccines. He noted that another study by Dr. Jill James112 showed that these subjects

have the same metabolic patterns as their mothers, strongly suggesting that the findings

cited by Dr. Deth could not be attributable to vaccination. Tr. 1696-98.

In addition, Dr. Johnson pointed out that Dr. Deth selectively presented the

results of his own study on methionine synthase mRNA splicing, and stated that the

study actually presented contradictory data suggestive of a technical failure. Tr. 1708-

14. Although Dr. Deth presented charts showing a lifetime decrease of MS “Cob”

mRNA and MS “Cap” mRNA to zero by about age 70, Dr. Johnson pointed out that a

figure from Dr. Deth’s study showing the results of an ethidium113 bromide-stained PCR

gel showed that in a 76 year old patient, 95% of the MS mRNA was full length. Tr.

1708-10. Because the decrease of Cob and Cap to zero, as suggested by Dr. Deth,

would require the deletion of those domains from the full mRNA, the finding of 95% full

length mRNA in an aged subject was contradictory both to Dr. Deth’s findings and to his

hypothesis of a difference in methionine synthase activity between old, young and

109 Pet. Ex. 117, Ref. 9, M. Waly, et al., Activation of methionine synthase by insulin-like growth factor-1

and dopamine: a target for neurodevelopmental toxins and thimerosal, MOL. PSYCHIATR 9(4):358-370

(2004) [hereinafter “Waly, Pet. Ex. 117, Ref. 9”].

110 This paper was discussed extensively in the OAP theory 2 test cases and is addressed in more detail

in Section IX.C.

111 Pet. Ex. 117, Ref. 38, S.J. James, et al, Metabolic endotype and related genotypes are associated with

oxidative stress in children with autism, AM. J. MED. GENET. B. NEUROPSYCHIATR. GENET.; 141B(8): 947-56

(2006) [hereinafter, “James, Pet. Ex. 117, Ref. 38”].

112 Pet. Ex. 117, Ref. 36, S.J. James, et al, Abnormal transymethlation/transsfulfuration metabolism and

DNA hypomethylation among parents of children with autism, J. AUTISM DEV. DISORD.; 38(10:1966-1975

(2008) [hereinafter “James, Pet. Ex. 117, Ref. 36”].

113 Misspelled in the transcript as “epithidium.”
46

autistic. Id. Moreover, to the extent that Dr. Deth suggested that the presence of TNF-α

explained how inflammation caused oxidative stress and inhibited methionine synthase

activity, Dr. Johnson pointed out that Dr. Deth’s underlying data, published elsewhere

and not presented to the court, showed that the effects of TNF-α on methionine

synthase activity were reversed within six hours, suggesting that the TNF-α has little-tono long-term effect on methionine synthase activity.114 Tr. 1714-19.

Finally, Dr. Johnson noted that the Wong study, Pet. Ex. 240, also contradicted

Dr. Deth’s theory. While Dr. Deth posited that autism is caused by depressed

methylation, the Wong study showed that twins discordant for autism showed no overall

difference in methylation. In fact, the study demonstrated that the discordant twins were

variously over or under methylated. Doctor Johnson argued that Dr. Deth’s theory

cannot account for that outcome and that, contrary to Dr. Deth’s hypothesis of

depressed methylation, the Wong study showed that methylation was either increased

or decreased among autistic subjects with a majority of the genes of the autistic twins

becoming over-methylated. Tr. 1719-24, 1726. The Wong study showed that of the ten

genes in the autistic twins with the largest changes in methylation, only three

demonstrated decreased methylation. Tr. 1724.

VI. Petitioners Have Not Established That A.K. Actually Has an Underlying

Mitochondrial Disorder or Dysfunction.

Petitioners’ claim is that “one or more vaccines significantly aggravated an

underlying mitochondrial disorder.” 2d Am. Pet (ECF No. 237), ¶ 74. This petition, filed

April 17, 2013, alleged that “the medical evidence establishing mitochondrial disorder . .

. establishes that [A.K.] was vulnerable to vaccine injury, either directly due to oxidative

stress caused by the vaccine or indirectly due to oxidative stress caused by the fever(s)

which accompanied most of A.K.’s vaccinations.” Id., ¶ 73. Moreover, petitioners

explicitly stated in their post-hearing brief that “petitioners’ claim relies on a diagnosis of

A.K. with a mitochondrial defect based on enzyme assays of a muscle biopsy and other

biomarkers.” ECF No. 297 at 4. All three of petitioners’ medical experts rely, inter alia,

on the fact of A.K.’s mitochondrial disorder diagnosis. See, e.g., Pet. Exs. 65 at 7-8;

117 at 2-3; 63 at 18. 115

114 Moreover, Dr. Johnson further noted that the method of that study—i.e., directly injecting TNF-α into

cells—resulted in a concentration of TNF-α an “order of magnitude” greater than one would see in

cerebral spinal fluid after a vaccination. Thus, Dr. Johnson noted that if such a direct injection cannot

produce a sustained inhibition of methylation, then a vaccine would not be able to produce enough

oxidative stress to inhibit methylation. Tr. 1727.

115 There is some uncertainty as to whether Dr. Deth considered a pre-existing mitochondrial disorder to

be a condition precedent to his opinion. Despite his discussion of mitochondrial dysfunction, he indicated

during cross-examination that he would still opine that A.K.’s injury was vaccine caused “with or without” a

mitochondrial disorder being present, stating that he could still make “90% of the same connections.” Tr.

799-800. This led respondent to state in her post-hearing brief that “evidence of impaired mitochondrial

function is apparently not ‘important’ to Dr. Deth in this case.” ECF No. 295 at 74. Petitioners argued in

response that respondent mischaracterized Dr. Deth’s opinion and that while oxidative stress is the

damage-causing agent in Dr. Deth’s theory, “mitochondrial malfunction adds to this mix.” ECF No. 302 at

21. In arguing against the consideration of evidence from the OAP test cases, petitioners contended that

this case is distinct from the OAP test cases precisely because it involves mitochondrial disease and “the
47

Thus, whether A.K. had a mitochondrial disorder is a threshold issue in this case.

Petitioners contended that A.K.’s medical records established the mitochondrial disorder

diagnosis, one made by multiple treating physicians. They also presented expert

testimony by Dr. Kendall that A.K. meets accepted standards for a mitochondrial

disorder diagnosis. Respondent countered with presentations by Drs. Cohen and

Wallace, who both disputed the laboratory data on which A.K.’s mitochondrial disorder

diagnosis was based. Additionally, Dr. Cohen’s testimony disputed Dr. Kendall’s

interpretation of A.K.’s clinical history.

For the reasons discussed below, I find that respondent has made the more

persuasive case and that petitioners have not established, more likely than not, that

A.K. had any mitochondrial disorder or dysfunction.

A. Explaining Mitochondrial Disorders.

Mitochondria are small organelles (structures inside cells) that turn food and

oxygen into the body’s supply of chemical energy. According to the experts in this case,

mitochondria’s role within a cell can be analogized to the power plants that provide

electricity to a city or the internal combustion engine that drives a car. Tr. 258-60, 1161-

64. In addition to energy production, mitochondria are also responsible for maintaining

proper functioning of various organs. See e.g., Bast v. Sec’y, HHS, No. 01-565V, 2012

WL 6858040 at *24 (Fed. Cl. Spec. Mstr. Dec. 20, 2012), aff’d, 117 Fed. Cl. 104 (2014).

Mitochondria use oxygen and food to produce adenosine triphosphate [“ATP”],

the primary source of energy for all bodily functions, through a process labeled “the

respiratory chain” or “electron transport chain” [“ETC”]. Res. Ex. UU at 6. Problems with

energy production in the ETC can occur as the result of genetic defects in either the

mitochondria’s own DNA [“mtDNA”] or in the DNA found in the nucleus of cells

themselves [“nuclear DNA”or “nDNA”]. Tr. at 1165; see also Res. Ex. UU at 8-11. The

sole function of the mtDNA is to make proteins that are components of the ETC. Tr. at

1069-70; see also Res. Ex. UU at 6-7. The activity of the ETC, which takes place largely

on the inner of the two membranes comprising the outer part of the mitochondria,

consists of five protein complexes (Complexes I-V). Ex. UU at 6. A different biochemical

step in the conversion of nicotinamide adenine dehydrogenase to ATP takes place in

each complex. Id. This conversion process is referred to as “oxidative phosphorylation”

or “OXPHOS.” Id.

role of oxidative stress in causing mitochondrial decompensation.” Id. at 10. Notwithstanding this

argument, Dr. Deth’s testimony in this case, as well as the slides he used to illustrate it, overlapped

considerably with his testimony and the slides he used in the OAP. Petitioners argued that Dr. Deth’s

hypothesis is supported, inter alia, by “extensive research establishing clear connections between

mitochondrial disease and autism.” Id. at 11. However, petitioners have also stated that Dr. Deth’s

opinion in this case does not constitute a separate theory of causation, but rather an explanation of the

mechanism supporting their theory of the case, which is that A.K.’s underlying mitochondrial disorder was

aggravated by his vaccinations. Tr. 597; 2d Am. Pet (ECF No. 237) ¶¶ 73-74. In that regard, I note that

Dr. Deth characterized his opinion as answering the questions of “how a vaccine causes oxidative stress”

and “how such oxidative stress can cause injury to a child with a mitochondrial disorder.” Pet. Ex. 117 at

2. Thus, despite Dr. Deth’s testimony on cross-examination, the centrality of a mitochondrial disorder to

petitioner’s claim is indisputable.
48

“Mitochondrial disease is not a single entity but, rather, a heterogeneous group of

disorders characterized by impaired energy production due to genetically based

oxidative phosphorylation dysfunction.” Res. Ex. SS, Tab 6, R. Haas, et al,

Mitochondrial Disease: A Practical Approach for Primary Care Physicians, PEDIATR..,

120(6) 1326-33, (2007) at 1326 [hereinafter “Haas, Res. Ex. SS, Tab 6”]. There is no

“definitive biomarker that characterizes mitochondrial disease in all patients.” Id. at

1331. “Mitochondrial diseases are usually progressive and multisystemic,” typically

affecting organs with “a high energy demand, including skeletal and cardiac muscle,

endocrine organs, kidney, nonmucosal components of the intestinal tract, retina, and

the central nervous system.” Id. at 1327.

When a DNA defect results in clinical symptoms, a person is said to have a

“primary” mitochondrial disease or defect. Other bodily processes including metabolic

disorders, hypoxia, and some drugs may also affect the ETC, causing diminished ETC

function, producing “secondary mitochondrial dysfunction.” Tr. at 1165; see also Res.

Ex. UU at 9. In the absence of an identified genetic defect or the presence of clusters of

symptoms fitting a known mitochondrial syndrome, diagnosing a mitochondrial disorder

is difficult.116 See e.g., Pet. Ex. 65 at 4-7 (expert report of Dr. Kendall); Res. Ex. SS at

11-14 (expert report of Dr. Cohen).

In this case, the allegation that A.K. has a mitochondrial disorder stems primarily

from a report by Dr. John Shoffner, the medical director of a laboratory known as

Medical Neurogenetics. See Pet Ex. 32. Doctor Shoffner completed what he termed

“an oxidative phosphorylation disease evaluation,” which included metabolic studies

from blood, urine and cerebral spinal fluid as well as light microscopy of skeletal muscle,

enzymology testing from muscle biopsy, and genetic testing. Pet Ex. 32, pp 1-2. He

offered a diagnosis of “probably mitochondrial encephalomyopathy,” based on an

enzymology finding of a Complex I defect with correlative protein chemistry changes on

Western Blot testing. Pet Ex. 32, p. 3. Although there is no evidence to suggest that Dr.

Shoffner conducted any evaluation of A.K.’s medical history, his diagnosis was also

116 I have discussed mitochondrial disorders extensively in other recent decisions. See Holt v. HHS, 2015

WL 4381588, No. 05-236v (Fed. Cl. Spec. Mstr. June 24, 2015); Miller v. HHS, 2015 WL 5456093, No.

02-235v (Fed. Cl. Spec. Mstr. August 18, 2015). I note in particular that in Holt, a significant issue was the

question of whether studies related to mitochondrial disorders or diseases (terms that can be used

interchangeably) could be applied to a claim of mitochondrial dysfunction. In Holt, petitioner alleged that

her minor child had mitochondrial dysfunction that did not rise to the level of severity of an actual

mitochondrial disease or disorder. Holt, 2015 WL 4381588, *22-23. In this case, petitioners were

consistent in their amended petition in alleging that A.K., having been diagnosed with mitochondrial

encephalomyopathy, had a mitochondrial disorder that was aggravated by his vaccinations. See 2nd Am.

Pet, (ECF No. 237), passim. In their post-hearing brief, petitioners referred variously to mitochondrial

disorder (ECF No. 297 at 8), disease (ECF No. 297 at 39), susceptibility (ECF No. 302 at 25), defect

(ECF No. 297 at 4), diagnosis (ECF No. 297 at 32, n.18), malfunction (ECF No. 302 at 21), and

dysfunction (ECF No. 302 at 21). I find no instance in this case where petitioners have asserted or

explained any intended distinction among those terms. In any event, the issue arose in Holt because

respondent’s expert conceded that there was laboratory evidence suggestive of a mitochondrial

dysfunction, but that such dysfunction was not responsible for any of the petitioner’s clinical symptoms,

meaning no mitochondrial disorder was present. Holt, 2015 WL 4381588, *79. For the reasons described

below, I have found that no such laboratory evidence exists for A.K. I find that A.K. had neither 

a mitochondrial disorder nor any mitochondrial dysfunction.
49

based on reported clinical symptoms including ASD, gastrointestinal dysfunction and

pain, fatigue, and heat and cold intolerance. Ex. 32, p. 1. Genetic and metabolic tests

were all “unremarkable.” Ex. 32, pp. 1-2. As discussed below, petitioners contend that

Dr. Shoffner’s findings were subsequently confirmed by multiple treating physicians.

B. Diagnostic Standards for Mitochondrial Disorders.

Both of the clinical mitochondrial experts in this case (Drs. Kendall and Cohen)117

agreed that the diagnosis of mitochondrial disorders involves the analysis of a number

of signs and symptoms, including biochemical, genetic and clinical features. Tr. 248-51,

1322-23. Both also agreed that there is a great deal of uncertainty regarding the

diagnosis of mitochondrial disorders and that the field has failed to standardize

adequately the diagnostic criteria.118 See, e.g., Tr. 248-49, 1351. Each of these experts

has published a review of other articles in which they address their own interpretations

of the diagnostic criteria for mitochondrial disorders. See Ex SS, Tab 2,

B. Cohen, et al, The clinical diagnosis of POLG disease and other mitochondrial DNA

depletion disorders, METHODS, 51: 364-73 (2010); Pet. Ex. 172, F. Kendall, et al,

Mitochondrial disorders: Overview of diagnostic tools and new diagnostic trends, J.

PEDIATRIC BIOCHEM., 2: 193-203 (2012).

Nonetheless, Dr. Kendall relied on the Bernier criteria,119 at least initially. Both

parties agreed that the Bernier criteria were useful in diagnosing mitochondrial

disorders. In her report, Dr. Kendall explained that:

Because the diagnosis of mitochondrial disease is complicated and often

required a multitude of clinical and laboratory findings for confirmation, a

number of groups have developed diagnostic criteria to assist in

evaluating suspected mitochondrial patients. In 2002, Bernier et al

outlined these diagnostic criteria for respiratory chain disorders in adults

and children in the journal Neurology.

Pet. Ex. 65 at 7 (citing Bernier, Pet. Ex. 90).

Although Dr. Kendall acknowledged that there are “other similar criteria,” she

used only the Bernier criteria in her expert report, concluding that “a review of [A.K.]’s

clinical features and laboratory data collected to date provide support for a definitive or

highly probable mitochondrial disease utilizing these diagnostic criteria. Pet. Ex. 65 at

7; see also Tr. 308. Doctor Cohen agreed that the Bernier criteria are authoritative,

117 Petitioners’ experts, Drs. Shafrir and Deth, discussed mitochondrial disorders as part of their opinions,

but both indicated that they deferred to other experts on the diagnosis of mitochondrial disorders. Tr.

513-14, 796. In addition, although respondent elicited testimony from two other experts (Drs. Wallace

and Jones) regarding mitochondrial biology and supporting laboratory evidence, these experts indicated

that they are not clinicians and that their opinions do not extend to the diagnosis of mitochondrial

disorders. Tr. 1072, 1625-26.

118 Doctor Cohen noted that some specific phenotypes of mitochondrial disorder are not subject to

uncertainty, in that they have clearly identifiable genetic markers and accompanying clinical

presentations, but he agreed that not all mitochondrial disorders can be so identified. Tr. 1319-22. In

A.K.’s case, there is no genetic evidence of a mitochondrial disorder. Tr. 251.

119 Bernier, Pet Ex. 90.
50

testifying that using the criteria “assigns a level of certainty to the diagnosis” where

there is otherwise no certainty by requiring significant substantiated evidence. Tr. 1319-

22. He characterized the Bernier criteria as a useful diagnostic tool and indicated that

he uses them in his own practice. Tr. 1179-80. However, he disagreed with Dr. Kendall

that, applying these criteria to the facts of A.K.’s case, he had a mitochondrial disorder.

Tr. 1220.

On cross examination, Dr. Kendall was forced to acknowledge that she could not

reach a “definite” mitochondrial disorder diagnosis by applying the Bernier criteria. On

redirect, she began to question the efficacy of the Bernier criteria, implying that more

recent diagnostic criteria, such as the Morava criteria,120 were more diagnostically

accurate. Tr. 317-19, 423-25. She also indicated that the Bernier criteria were less

comprehensive than her own published criteria in terms of listing specific clinical

symptoms, rather than broader categories. She then contended that A.K. had a

mitochondrial disorder diagnosis under her own diagnostic criteria, based on his autistic

features, developmental delays, dysautotonomia, hypotonia, gastrointestinal

problems/dismotitlity, and fatigability. Tr. 423-24.

Doctor Cohen agreed that the Bernier criteria have been supplanted to some

degree by other diagnostic methods, particularly the use of molecular genetics.

However, he opined that these criteria remain a useful diagnostic tool—and one that he

used in his own diagnostic practice. Tr. 1179-80. Moreover, he noted that, to the extent

there are problems with the Bernier criteria, it is that the criteria are over-sensitive,

rather than under-sensitive. Thus, application of the Bernier criteria will result in a

mitochondrial disorder diagnosis for patients who actually have other identifiable

disorders. The over-diagnosis using the Bernier criteria is something Dr. Cohen 

testified that he had experienced. Id.

Doctor Kendall did not address the over-inclusivity of the Bernier criteria in her

testimony. She did testify that the reason for using the “basket” of clinical features that

comprise various diagnostic criteria is to avoid false positives. Tr. 307.

Following the hearing in this case, I filed the “Nijmegen” or “Wolf” criteria121 as

Court Exhibit I and instructed the parties to submit supplemental reports regarding that

article. See Order, 9/3/2013 (ECF No. 277). In response to my order, Dr. Cohen

submitted a report indicating that he did not believe that A.K.’s case would even warrant

120 Referring to E. Morava, et al, Mitochondrial disease criteria: Diagnostic applications in children,

NEUROL. 67:1823-26 (2006), filed as Res. Ex. SS, Tab 11, hereinafter simply “Morava” or “Morava

criteria.” This article was filed in conjunction with Dr. Cohen’s expert report. The name of the principal

author is incorrectly spelled in the transcript as “Morave.” Tr. 424.

121 N. Wolf & J. Smeitink, Mitochondrial disorders, A proposal for consensus diagnostic criteria in infants

and children, NEUROL. 59 (9): 1402-05 (2002), filed as Court Ex. I; also filed as Res. Ex. SS, Tab 19. This

study was a product of the Nijmegen Center for Mitochondrial Disorders, Nijmegen, the Netherlands,

hence the shorthand reference to it as the “Nijmegen criteria.” As I have previously noted, the Morava

criteria are, in effect, the Nijmegen criteria, the Morava study having been performed to address the

specificity of the Nijmegen criteria in identifying children with mitochondrial disorders established through

genetic screening while screening out those with multi-system disease with other, non-mitochondrial

genetic diagnoses. Miller, 2015 WL 5456093, *28.
full testing under the Nijmegen criteria. Res. Ex. KKK at 1. Nonetheless, applying the

“scoring” system under the Nijmegen standards, Dr. Cohen opined that A.K.’s history

would only generate one point, which makes a mitochondrial disorder diagnosis

“unlikely.”122 Id. at 4. For his part, Dr. Wallace stressed that both the Nijmegen and

Bernier criteria achieve “very similar results” in terms of diagnosing respiratory chain

disorders. Res. Ex. LLL at 2-3. Ultimately, both of respondent’s mitochondrial disorder

experts opined that consideration of the Nijmegen criteria did not change their opinions

originally rendered using the Bernier criteria. Res Ex. KKK at 5; Res. Ex. LLL at 3.

In her supplemental expert report (Pet. Ex. 269), Dr. Kendall explicitly argued

that the Nijmegen criteria cannot be used to evaluate A.K.’s case. Specifically, Dr.

Kendall noted that the Nijmegen criteria includes scoring based on additional

biochemical tests not completed in A.K.’s case. Pet Ex. 269 at 1. Doctor Kendall

stressed that the Bernier criteria fall short of a “gold standard,” but noted again – as she

did in her initial report – that the Bernier criteria were used to screen patients for

inclusion in the only current clinical trial for mitochondrial patients. Pet. Exs. 269 at 2;

65, p. 7. Thus, although Dr. Kendall has been consistent in maintaining the lack of any

gold standard diagnostic tool for mitochondrial disorders, her half-hearted references to

other diagnostic criteria (made only after being challenged on the facts of this case) do

not conceal her clear acceptance of, and reliance on, the Bernier criteria.

I am familiar with the other criteria for diagnosing mitochondrial disorders that

have been cited, and indeed, I have addressed those criteria in other cases. See, e.g.,

Holt v. HHS, 2015 WL 4381588; Miller v. HHS, 2015 WL 5456093, No. 02-235v (Fed.

Cl. Spec. Mstr. Aug. 18, 2015). In this case, however, petitioners have come forward

with no expert opinion or other medical evidence analyzing the particulars of A.K.’s case

under any generally accepted diagnostic rubric other than Bernier.123 Although Dr.

Kendall raised the existence of the Morava criteria, she did not actually opine that A.K.

fit that criteria, and she argued explicitly against the application of the Nijmegen criteria.

Moreover, her application on redirect examination of criteria from her own review article

was cursory at best.124

122 Similar to the Bernier criteria described in greater detail below, Nijmegen seeks to categorize

mitochondrial disorder diagnoses based on level of certainty, describing a diagnosis as either unlikely,

possible, probable, or definite. Court Ex. I at 1403. Nijmegen “scores” patients based on clinical,

metabolic, imaging, histopathologic and biochemical criteria. Id. at 1403. To avoid overemphasizing

individual diagnostic categories, three general categories (clinical presentation, metabolic investigation

and imaging, and histopathology) are capped at four points each. Id. at 1402-03. According to Dr.

Cohen, whereas a probable or definite diagnosis ranges from five to twelve points, A.K.’s single point

makes a diagnosis “unlikely.” Rex. Ex. KKK at 5.

123 As described in Section VI.D below, petitioners point to mitochondrial diagnoses contained in A.K.’s

medical records as evidence that he does have a mitochondrial disorder. I note that none of those

records reflect the use of any diagnostic instrument that reflects a systematic evaluation of A.K.’s

documented clinical symptoms. Even Dr. Shoffner, the physician who first diagnosed A.K. with a

probable mitochondrial encephalomyopathy (see Pet. Ex. 32, p. 3), did not identify the diagnostic criteria

upon which his diagnosis was based (id.). Most of these later references merely repeat the history of an

earlier diagnosis by Dr. Shoffner, rather than reaching an independent diagnosis.

124 Although Dr. Kendall identified a number of symptoms she viewed as relevant, she did not specify how

A.K.’s clinical history conformed to the symptoms she had identified within her own article. Although her

51
Ultimately Dr. Kendall testified that there is no diagnostic methodology that

enjoys consensus and that each diagnosis depends on the particular experience of the

diagnosing physician, opining in sum that the diagnosis of mitochondrial disorders is “as

much an art as it is a science.” Tr. 426. This alternative framing is wholly insufficient.

“[I]t should be obvious to petitioner[s] that a scientific theory that lacks any empirical

support will have limited persuasive force.” Caves, 100 Fed. Cl. at 134 (quoting Gen.

Elec. Co. v. Joiner for the proposition that “Daubert does not require a trial court ‘to

admit opinion evidence that is connected to existing data only by the ipse dixit of the

expert.’”).

In his expert report, Dr. Cohen also indicated that published diagnostic criteria

“are not meant to account for all clinical and laboratory outcomes” and that “it is up to

the clinician to offer a final determination if the laboratory data taken as a whole justify

the diagnosis of a mitochondrial disorder or not.” Ex. SS at 12. Nonetheless, he also

indicated that the diagnostic criteria “compliment the opinion of the clinician.” Id. In that

regard, I stress that I am not adopting a strict application of the Bernier criteria in lieu of

accepting Dr. Kendall’s opinion, but rather assessing the credibility and persuasiveness

of her opinion regarding the appropriate diagnosis for A.K. in light of, inter alia, her

claimed application of the Bernier criteria. Where Dr. Kendall went too far is in

expressing, by virtue of comparing diagnosis to an art, that there are no credible or

limiting diagnostic standards whatsoever.

125 The lack of an agreed upon “gold

standard” is not the same as having no standard at all.

Whatever the shortcomings of the Bernier criteria, the parties in this case agree

that it is a valid diagnostic tool and that there is in fact no gold standard to be followed.

Moreover, petitioners have provided no significant analysis under any other objective

standard from which one could conclude A.K. in fact has a mitochondrial disorder.

126

Thus, my analysis will focus much of its attention on the Bernier criteria.

article contains a chart of “possible” mitochondrial disease symptoms, which she cited in her testimony,

neither the chart nor her testimony discuss what tests or thresholds are necessary to consider whether

those symptoms match the typical presentations seen in mitochondrial disease, nor what number or

combination of “possible” symptoms is supportive of a mitochondrial disease diagnosis under her

particular criteria. Tr. 423; Pet. Ex. 172, at 195 (Table 1). For example, her chart lists “gastrointestinal

problems,” but does not define them. Other criteria, including Nijmegen, Morava, and even Bernier,

require specific gastrointestinal symptoms reflective of dysmotility and that the gastrointestinal symptoms

be unexplained. Her lack of detail may have been an attempt to avoid an extensive cross-examination

similar to what she experienced when she was questioned in detail about whether A.K.’s clinical data in

fact matched the Bernier criteria. See Tr. 308-319.

125 Being careful not to reduce Dr. Kendall’s entire opinion to one unfortunately worded utterance, I note

that Dr. Kendall’s suggestion that mitochondrial disorder diagnosis is “as much an art as it is a science”

implied the lack of precision which is emblematic of her approach to this case. At multiple points, I found

Dr. Kendall’s grasp of the facts of this case to be tenuous or vague and her application of her own theory

both cursory and problematic.

126 The Bernier criteria are derived from adult diagnostic criteria, although they have been applied to

pediatric patients. In contrast, the Nijmegen criteria were developed specifically to create a diagnostic

standard more finely tailored to children and infants. The Wolf article noted, for example, that “[m]ost

infants and children present with a nonspecific clinical picture, having neither histopathologic hallmarks

like ragged red or COX-negative fibers nor mtDNA mutations. Applying a less restrictive approach to

complex clinical pictures, we enabled nonclassic pediatric clinical presentations to achieve maximum

52
53

C. Applying the Diagnostic Criteria to A.K.’s Case.

The Bernier criteria were developed in an attempt to find consensus in diagnosis

of mitochondrial disorders. Pet. Ex. 90 at 1406. A mitochondrial disorder diagnosis

under these criteria is based on an aggregation of positive findings among clinical

features, histology, enzymology, function (i.e. ATP synthesis rates), molecular

pathogenicity, and metabolic indicators of impaired respiratory function. Pet. Ex. 90 at

1407, Table 1 & 2. Specific levels of impairment are specified for testing (i.e., “>3 SD

[standard deviations] below mean” to consider fibroblast ATP synthesis rates as

evincing a mitochondrial problem). For each type of feature (except metabolic features),

“major” and “minor” diagnostic criteria are identified.127 Id. Based on these indicators, a

diagnosis can be characterized as either definite, probable, or possible.128 Id. at 1407.

Doctor Cohen contended that A.K. does not fit any of the Bernier criteria, major or

minor. Tr. 1219-20. By contrast, Dr. Kendall initially argued that application of the

Bernier criteria produced a diagnosis of a definite mitochondrial disorder. Pet. Ex. 65 at

7; Tr. 308.

During cross-examination, Dr. Kendall conceded that A.K. did not exhibit a

number of the features listed under Bernier that she had previously scored as present.

Tr. 308-14. These concessions ruled out any of the “major” criteria for clinical

presentation, histology, function or molecular pathogenicity in A.K. Id. Ultimately, Dr.

Kendall conceded that she could not reach the conclusion that A.K.’s diagnosis was

“definite” under Bernier and instead argued that his diagnosis would be considered

“probable” based on enzymology, metabolic indicators of impaired respiratory chain

function, and clinical features compatible with a respiratory chain defect.129 Tr. 314,

317-19.

scoring.” Court Ex. I at 1404. However, based on Dr. Kendall’s reliance on Bernier, and her explicit

statement that the Nijmegen criteria were inapplicable, and Dr. Cohen’s concession to the application of

the Bernier criteria, I will evaluate the experts’ opinions and the facts of the case in the context of the

Bernier criteria. Although the Nijmegen standard appears to be more applicable to the diagnosis of a

child, to the extent it can be viewed as a more stringent standard, using it over petitioners’ expert’s

objection is not warranted. And, it is unnecessary to consider the more specific and tailored Nijmegen

criteria here, because I conclude that petitioners have not even established that A.K. has a mitochondrial

disorder under the broader Bernier criteria.

127 Metabolic indicators of impaired respiratory chain function are a minor finding only. Court Ex. I at

1404.

128 A definite diagnosis requires a finding of either two major criteria or one major plus two minor criteria. A

probable diagnosis includes either one major plus one minor criterion or at least three minor criteria. A

possible diagnosis requires either a single major criterion or two minor criteria, at least one of which is

clinical. Pet. Ex. 90 at 1407.

129 Although she did not specify why she altered her diagnosis, Dr. Kendall’s change from a definite to a

probable diagnosis under Bernier was likely an indication that she did not believe that A.K. met the

threshold for a “major” enzymology finding under Bernier. That is, having contended that A.K.

demonstrated minor findings in two categories – clinical features and metabolic indicators – a major

finding in enzymology would have been sufficient for her to maintain her position that A.K.’s diagnosis

was definite. A minor enzymology finding, however, would support only a “probable” diagnosis, providing

minor findings in three categories. In this regard it is also worth noting that, as described in more detail
54

Thus, the critical questions are whether Dr. Kendall’s interpretation of A.K.’s

enzymology results, clinical features and metabolic indicators can withstand scrutiny as

a general matter and, if so, to what extent those features match the thresholds

established by the Bernier criteria. For the reasons discussed below, I find that the Dr.

Kendall’s analysis largely falls short in both regards.

1. Enzymology.130

Under the Bernier criteria, enzymology results will support a mitochondrial

disorder diagnosis as a “major” finding if the results show less than 20% of normal (i.e.

mean) activity in any respiratory chain complex in a tissue, less than 30% of any

respiratory chain complex in a cell line, or less than 30% of activity of the same

respiratory chain complex in two or more tissues. Pet. Ex. 90 at 1407, Table 1.

Enzymology will constitute a “minor” finding if the same tests show results of 20-30% for

tissue or 30-40% for either a cell line or two or more tissues. Pet. Ex. 90 at 1407, Table

2.

In A.K.’s case, his enzymology results from Dr. Shoffner indicated results of 41

and 76 in two different assays (n-decyl CoQ and CoQ1)131 of Complex I against means

of 85 and 246.132 Pet. Ex. 32, p. 35. This calculates to activity levels of approximately

48% and 31% of the reported mean respectively. Based on these figures, Dr. Shoffner

concluded that a Complex I defect “appears likely.” Id. These are the figures and

conclusion on which Dr. Kendall relied when she claimed that A.K.’s enzymology results

satisfied the Bernier diagnostic criteria. Tr. 245-48. Clearly, however, these results,

though falling below the mean, do not fall low enough to be considered an abnormal

finding under Bernier, either major or minor.133

below, even using Dr. Kendall’s preferred approach, Dr. Shoffner’s enzymology results do not reach the

threshold for a major finding under Bernier.

130 Enzymology is a process of measuring the enzyme activity of an individual mitochondrial complex in

isolation from the rest of the respiratory chain. Tr. 1078. The process involves mechanically breaking

apart the mitochondria to extract the individual complex. The sample is then placed in a substrate

medium optimized to that complex’s function. Id. As time elapses the sample processes the surrounding

substrate as it would within the respiratory chain. Id. The test results in a measure of velocity, or the rate

of that processing over time. Tr. 1080-81. The concentration of substrate in the testing medium is

increased until the velocity rate reaches maximum velocity, the point at which the concentration of the

substrate is no longer a limiting factor. This leaves the complex itself as the limiting factor. Tr. 1083-84.

131 Complex I’s natural substrate is ubiquinone, also called CoenzymeQ or “CoQ”). Res. Ex. UU, Tab 6,

D. Kirby, et al, Biochemical Assays of Respiratory Chain Complex Activity, Chapter 4, METHODS IN CELL

BIOL., 80: 93-119 (2007), at 103 [hereinafter “Kirby, Res. Ex. UU, Tab 6”]. The most common form of

CoQ in mammals is CoQ10; however, it is largely insoluble in aqueous assays. Id. Short chain

coenzyme Q analogs, which are soluble, provide more reliable assays. Id. However, Dr. Shoffner’s

report did not explain why he used n-decyl CoQ and CoQ1. Pet. Ex. 32, p. 35.

132 The unit of measure for enzyme activity is “nanomoles of substrate/minute/mg mitochondrial protein.”

Pet. Ex. 32, p. 35.

133 The result for the CoQ 1 assay at 31% (based on the raw data) is very close to the 30% threshold for a

minor finding under Bernier. The Bernier authors cautioned that there is “no clear cut-off between normal

and abnormal activities” and that these percentages are “arbitrary.” Pet. Ex. 90 at 1409. Doctor Cohen

likewise acknowledged the “arbitrariness” of these figures, but noted that they generally conform to the
55

But even if Dr. Shoffner’s raw data did fall below the Bernier threshold, there is a

further issue with applying Dr. Shoffner’s raw data to the Bernier criteria. The Bernier

threshold is not based on raw numbers; it calls for an adjusted figure that is normalized

against one of two other enzyme assays typically performed, either citrate synthase or

Complex II. Pet. Ex. 90 at 1407, Tables 1-2. After performing that calculation, both Drs.

Wallace and Cohen pointed out that that A.K.’s enzymology results are much higher

than reflected in the raw data and would be considered normal under Bernier (within the

95% confidence interval) when the raw data is normalized over the citrate synthase

finding. Tr. 1107-08, 1206-08. Although Dr. Kendall maintained that the use of raw

numbers is a valid approach, she acknowledged on cross examination that the

distinction means that A.K. did not, strictly speaking, meet the Bernier enzymology

standard. Tr. 311-12.

The question of whether to normalize raw enzymology results is a professional

judgment and one for which there is no consensus in the field. Tr. 1211-12.

Respondent’s experts, however, have persuasively argued that normalization is the

superior approach and that it yields a more accurate result in this case in particular, in

addition to being the methodology required under Bernier. Tr. 1100-04, 1210-11. They

described Complex I as being the most complicated of the five respiratory (electron

transfer) chain complexes, and the one most difficult to extract from the mitochondria.

Tr. 1102-05, 1210-11. They indicated that as a result of that difficulty, Complex I assays

often produce unreliable or highly variable raw data. Id. By measuring the Complex I

results against citrate synthase (a water soluble enzyme of the Krebbs cycle),

laboratories can account for the degree of loss caused by the extraction process. Id.

This normalization provides more consistent results among different laboratories. Id.

Doctor Cohen further explained that because citrate synthase is universally present in

living cells and critically important to cellular function, it remains a good proxy for

establishing how successful the extraction process was in any given case. Tr. 1210-11.

Both Drs. Cohen and Wallace opined that the results are more reliably interpreted when

normalized over citrate synthase and that in A.K.’s case those normalized results show

no Complex I defect in A.K. Tr. 1107-08, 1209-12.

Doctor Kendall relied on the lack of consensus on the proper approach to

interpreting enzymology results, but she did not advance any argument as to why using

the raw data – in this case or in any case – would be a better approach.134 Doctor

level which divides symptomatic from non-symptomatic patients. Tr. 1208-09. Thus, he stated that he

would still consider 31% as a result outside the abnormal range under Bernier. Tr. 1210.

134 Doctor Kendall asserted that Dr. Shoffner reported raw data because of his position that the citrate

synthase levels can be falsely decreased, making the normalized results unreliable. Tr. 312. She did 

not, however, explicitly adopt, defend or substantiate that view. In contrast to Dr. Kendall’s apparent

deference to the absent Dr. Shoffner, respondent’s argument in favor of interpreting the enzymology in

light of citrate synthase is supported not only by both Dr. Wallace and Dr. Cohen’s explanations, but also

by multiple studies in evidence in this case. See, e.g., Bernier, Pet. Ex. 90; F. Gellerich, et al, The

problem of interlab variation in methods for mitochondrial disease diagnosis: enzymatic measurement of

respiratory chain complexes, MITOCHONDRION 4: 427-39 (2004), filed as Res. Ex. UU, Tab 3; Kirby, Res.

Ex. UU, Tab 6. Each of these papers recommends using results calculated against citrate synthase. And

it is, of course, highly significant that among these is the very Bernier criteria that Dr. Kendall relied upon

and cited in her expert report.
56

Wallace did acknowledge that normalizing over citrate synthase is not a perfect

approach in that citrate synthase can also be lost in the extraction process. Tr. 1104-

5. He also noted, however, that the instability of citrate synthase can be accounted for

by additionally or alternatively normalizing the enzymology results over Complex II and

that when he performed that calculation in this case, A.K.’s results, when normalized

over Complex II, still remain normal. Tr. 1104-05, 1108-09.

Furthermore, looking at the specifics of A.K.’s results in particular, respondent’s

experts also point out that, when compared to other findings made by Dr. Shoffner, the

reported Complex I defect looks more like an aberration than a true defect, lending

further credibility to the argument that the normalized results, which show no defect, are

more accurate in this case. Specifically, Dr. Cohen pointed out that, even as a raw

figure, A.K.’s assay measuring a combined Complex I and Complex III showed no

abnormality. Tr. 1212. He argued that if Complex I activity was truly decreased, one

would expect a combined figure including Complex I to likewise show a decrease. Id.

Indeed, Dr. Cohen, pointed out that many laboratories report only the combined

Complex I and III results as a proxy for the Complex I results, finding it to be a more

“robust assay.” Id.

Another significant point is that A.K.’s respirometry results – a measure of the

functioning of the entire mitochondrial respiratory chain – were equivocal. As with the

Combined Complex I and III results, Dr. Wallace argued that if there was a true

Complex I defect, its impact should be evident in the broader respirometry results. Tr.

1110-11. The fact that this result is equivocal suggests that the respiratory chain as a

whole is functioning normally – or at least not functioning in a demonstrably abnormal

way – and that there is therefore an insufficient basis to argue the presence of a defect.

Id. Doctor Cohen likewise stressed that the equivocal finding indicates that Dr. Shoffner

did not find anything supportive of a Complex I defect on respirometry. Tr. 1212-13. In

that regard, I note that Dr. Shoffner himself indicated that “high resolution respirometry

may more closely reflect the in vivo state of the respiratory chain and oxidative

phosphorylation function.” Pet. Ex. 32, p. 45.

Doctor Wallace also noted that Dr. Shoffner supported his Complex I finding by

citing “correlative protein chemistry changes” shown on a “Western blot” test. Tr. 1113;

Pet. Ex. 32, p. 3. He pointed out that, although Dr. Shoffner listed a “possible” decrease

in the ND6 subunit within Complex I, the actual numbers generated by the Western blot

support a “normal” finding for ND6. Tr. 1077, 1112. Doctor Cohen agreed that the

finding for Complex I was normal, and that such a finding is incongruent with the

enzymology result. Tr. 1213-14. Doctor Wallace further noted that Dr. Shoffner’s

interpretation of the ND6 finding as potentially decreased was not supported by

subsequent genetic testing which found no mutation to the ND6 gene. Tr. 1113-15.

Doctor Kendall did not delve into the details of Dr. Shoffner’s report. Pet. Ex. 65

at 3, 7. She offered no rebuttal to any of these points, aside from simply reciting Dr.

Shoffner’s findings. In fact, by the time of her testimony, Dr. Kendall indicated that she

couldn’t even remember if respirometry had been performed. Tr. 314.

Thus, respondent’s experts persuasively argued that the best interpretative

approach, normalizing over citrate synthase and/or Complex II, indicated that A.K.’s
57

enzymology testing showed no defect in Complex I. Moreover, even if I accepted the

Dr. Shoffner’s finding of a Complex I defect at face value, respondent’s experts

established that, in light of the overall results reported by Dr. Shoffner, the “defect” was

better characterized as an incongruent finding, rather than evidence of a respiratory

chain defect or dysfunction.

2. Metabolic Indicators.

The Bernier paper did not define what constituted a finding of a metabolic

indicator of impaired respiratory chain function, beyond noting that a number of subjects

were given such a coding based on a finding of elevated lactic acid in either blood or

cerebral spinal fluid. Pet. Ex. 90 at 1409. In her expert report, Dr. Kendall indicated

that “persistent, significant elevations in lactate,” constitute an indicator of mitochondrial

disorders.135 Pet. Ex. 65 at 5. Doctor Cohen similarly noted that evidence of

persistently elevated lactate is necessary for the lactate level to be considered indicative

of a mitochondrial disorder. Tr. 1199-1200.

Doctor Cohen explained that a problem with using elevated lactate levels as a

metabolic indicator of a mitochondrial disorder is the difficulty in collecting blood under

conditions that do not artificially elevate lactate. Another problem is the lack of

specificity of elevated lactate, which can be indicative of factors other than mitochondrial

defects, including such common occurrences as exercise.136 Res. Ex. SS, at 11; Tr.

1199-1200. He stressed that the question for mitochondrial patients is whether there is

a chronic elevation of lactic acid and indicated that one test for lactic acid is never

indicative of a mitochondrial disorder. Tr. 1199-1200. Doctor Kendall also

acknowledged that lactate tests are subject to collection errors and that lactate findings

should be confirmed either through multiple tests showing a persistent elevation or by

considering the lactate finding as a ratio to pyruvate.137 Tr. 357-59. Although she

indicated that she would not “completely discount” an otherwise unconfirmed elevation

in lactate, Dr. Kendall did agree that it would “raise an indicia of suspicion that the

elevated lactate might be a collection artifact.” Tr. 358. She seemed to acknowledge

135 Doctor Kendall also noted in her expert report that decreased plasma carnitine, increased blood

alanine, generalized aminoaciduria, and findings of Kreb cycle intermediates, tiglygylcine, and 2-

oxoadipic acid on organic acid analysis are also biochemical markers supportive of a mitochondrial

disorder. Pet. Ex. 65 at 7, 12 (table 2). She did not, however, indicate that any such findings were made

in A.K.’s case. As part of his evaluation of A.K., Dr. Shoffner did a metabolic work up, including blood,

urine and cerebral spinal fluid testing, and found no abnormalities whatsoever. Pet. Ex. 32, p. 1.

136 For this point, Dr. Cohen cited R. Hass, et al., The In-depth Evaluation of Suspected Mitochondrial

Disease: The Mitochondrial Medicine Society’s Committee on Diagnosis, MOL. GENET. METAB. 94(1): 16-

37 (2008) (unedited prepublication manuscript), filed as Res. Ex. SS, Tab 7 [hereinafter “Haas, Res. Ex.

SS, Tab 7”]. This paper indicated that “spurious elevation of plasma lactate is indeed the most common

cause, resulting from either a patient (usually a child) struggling or the prolonged use of a tourniquet

during sample collection.” Res. SS, Tab 7 at 3. Another article by Hass, Pet. Ex. 63, Ref. 17, contains a

table titled “Causes of Plasma Lactate Elevation,” listing a variety of reasons for elevated lactate. Id.,

Table 2, at 147.

137 There has been no suggestion in this case that A.K.’s elevated lactate was confirmed via computation

of a lactate/pyruvate ratio. For example, when Dr. Shoffner ran his tests in August of 2008, A.K. showed

normal lactate and pyruvate. Pet. Ex. 32, pp. 17-21. And on July 1, 2002, when A.K. did test high for

lactate, pyruvate does not appear to have been measured. Pet. Ex. 3, p. 375.
that reliance on “one or two lactate levels” as demonstrative of mitochondrial

dysfunction would be subject to challenge. Tr. 362.

Doctor Kendall contended that A.K.’s lactate tests evidenced a mitochondrial

disorder, because they showed “elevated lactate levels on a number of occasions.” Pet.

Ex. 65 at 7; Tr. 250. This position was not supported by the facts. Petitioners identified

only one instance in which A.K. had elevated lactate (see Pet. Ex. 3, p. 375), while

respondent pointed to multiple instances of normal or near normal lactate levels138 Pet.

Exs. 3, pp. 303, 333; 32, p. 17. Moreover, in the one instance of elevated lactate, the

pyruvate level was not reported. Pet. Ex. 3, p. 375. Even if this instance did not involve

a collection artifact or some benign reason for elevation, Dr. Kendall acknowledged that

a single instance of elevated lactic acid compared to multiple instances of normal

findings would not be indicative of persistent, significant elevation, which is what she

opined was necessary for lactate levels to be evidence of a mitochondrial disorder.

Compare Pet. Ex. 65, p. 5 with Tr. 316.

Thus, Dr. Kendall, in an apparent retreat from her claim of multiple instances of

elevated lactic acid, ultimately opined that in A.K.’s case his elevated AST/ALT ratio139

was “more of a biomarker” than his lactate levels, because that elevation was

persistent. Tr. 402-03. Doctor Kendall has not, however, substantiated her opinion that

elevated AST or an elevated AST/ALT ratio is a biomarker for mitochondrial disorders.

Although she listed elevated AST values as an indicator of mitochondrial disorder

in her expert report, Dr. Kendall provided no accompanying citation. Pet. Ex. 65, p. 4.

In her testimony, she indicated that “Richard Kelley has published some information

about if the ratio is elevated between the two of them [referring to AST and ALT] that

can be indicative. It’s a biomarker for mitochondrial disease.” Tr. 362. Doctor Kendall

provided no specific citation, however, nor did I find any article authored by Richard

Kelley cited in her report or filed anywhere in the extensive record of this case. Indeed,

in discussing Dr. Kendall’s assertion in their post-hearing brief, petitioners cited Pet. Ex.

40,140 rather than any publication by Dr. Kelley. ECF No. 297 at 73. This citation was

138 Doctor Cohen, who routinely uses Dr. Shoffner’s lab, noted that he believed Dr. Shoffner’s measures

of both lactate and pyruvate to be very accurate. Tr. 1197-98. Doctor Shoffner found A.K.’s lactate and

pyruvate levels to be normal when he conducted his complete metabolic analysis. Pet. Ex. 32, pp. 17-21.

139 See n.43 (defining “AST”). “ALT” stands for “alanine aminotransaminase.” ALT is found

predominantly in the liver, and ALT elevations are most often caused by liver dysfunction, including

hepatitis and cirrhosis. MOSBY’S LABS at 39-40. The ratio between the two tests is used to differentiate

viral hepatitis from other liver diseases. Id. Diagnosis of mitochondrial disorders is not listed as one of

the conditions for which this test has clinical significance. Id. at 40.

140 Petitioners referred to this Brief Communication, published in the JOURNAL OF CHILD NEUROLOGY, as

the “Zimmerman mitochondrial regression report.” ECF No. 297 at 110. This labeling was disingenuous.

Doctor Zimmerman is listed as the senior researcher (the last listed author) on the case report. See Pet.

Ex. 40, Developmental Regression and Mitochondrial Dysfunction in a Child With Autism, J. CHILD

NEUROL. 21(2):1-3 (2006). However, the principal author was Jon Poling, and another author was John

Shoffner, the clinician who performed the mitochondrial disorder testing on A.K. Id .at 2. Most journal

articles are cited by the name of the first author or by all authors, rather than by the name of the senior

researcher alone. A perusal of Pet. Ex. 40 reveals that the exhibit is the same as the Poling article, Res.

Ex. MM, Tab 14, and also filed as Pet. Ex. 63, Ref. 18 and as Pet. Ex. 91 (the clearer of the latter two

copies). This, in turn, is the same article criticized by the editor in chief of the journal in which it appeared

58
misplaced, in that this citation to Dr. Kelley’s unpublished research in Pet. Ex. 40 did not

involve using the AST/ALT ratio as a marker for mitochondrial dysfunction; rather, Dr.

Kelley’s unpublished work was cited for use of the alanine to lysine ratio as a surrogate

for pyruvate measurements. Pet. Ex. 40 at 1.

Although the authors of Pet Ex. 40 speculated that findings of elevated AST on a

retrospective evaluation of laboratory records might be suggestive of abnormal

mitochondrial function, that conclusion was not actually supported by the findings. Pet.

Ex. 40 at 2. Rather, they reported elevated AST, but not ALT, among subjects with

autism, not mitochondrial defects, as compared to typically developing controls. Id.

Moreover, the authors cautioned that even this retrospective evaluation lacked the data

necessary to rule out false-positives. Id.

Petitioners further cited Weissman, Pet. Ex. 39, a cohort analysis of 25 children

with mitochondrial disorder and ASD diagnoses, as evidence that AST/ALT is a marker

of mitochondrial disorder. ECF No. 297 at 9. Doctor Cohen was one of this study’s

authors. The Weismann study provided scant support for this contention. The

researchers conducted “a chart review of the biochemical, genetic and histopathological

findings in 25 patients with ASD who had unequivocal evidence of a disorder of

oxidative phosphorylation,” i.e., a respiratory chain defect: Id. at 1. These were

children with an ASD diagnosis “referred for genetic and/or metabolic evaluation of

autism, but not specifically for evaluation for mitochondrial disease.” Id. at 2. Thus, the

study was not composed of randomly selected ASD patients; something in their medical

history or clinical picture suggested that additional screening for a genetic or metabolic

problem was recommended. As a part of that screening the Weismann researchers

looked at AST/ALT results, but did not list these results as a part of the biochemical

evidence of mitochondrial dysfunction, listing only “increased blood lactate and pyruvate

levels, elevated plasma alanine level, and increased urinary levels of Krebs cycle

intermediates or 3-methylglutaconate.” Id. at 2.

Although 52% of subjects showed some abnormality of AST and/or ALT, the

authors did not indicate why they considered the AST/ALT ratio at all, much less

indicating that it was a marker of mitochondrial disease. Weismann, Pet. Ex. 39 at

e3815. To the extent that liver dysfunction can be seen in mitochondrial disease (see

Bernier, Pet. Ex. 90 at 1407, Table 1, listing the hepatic organ system as one of the

possible symptoms in which mitochondrial disorder symptoms might present), perhaps

the Weismann researchers were looking for evidence of liver problems.

Doctor Wallace testified that, despite researching the question, he could not find

any peer-reviewed literature indicating that either AST or ALT was considered a marker

for mitochondrial disease. Tr. 1116-17. Similarly, Dr. Cohen indicated based on his

own observations of an ongoing 30-subject clinical trial he is conducting, that there was

for the failure of the authors to disclose that Dr. Poling was the father of the child whose case was

reported. See n.216, infra. in Section VIII.A.3.a, where I discuss the reasons this article, regardless of

name, has little evidentiary value in terms of petitioners’ theory of causation.

59
no correlation between AST or ALT and mitochondrial disorders.141 Tr. 1203-04.

Doctor Cohen also pointed out that there are other simple explanations for elevated

AST levels that have nothing to do with mitochondrial disorders. Tr. 1203-04.

Doctor Cohen testified that elevated AST is an indicator of muscle breakdown,

which may be seen in active children. Tr. 1203-04. He opined that if A.K.’s elevated

AST was the result of a chronic process, rather than the result of activity, elevated

creatine kinase [“CK”] would be present as well. Tr. 1202. Both the Weissman paper

and the Poling case report (Pet. Exs. 39 and 40, respectively) cited by petitioners

reported the AST/ALT levels in conjunction with CK values. Pet. Ex. 39 at 3; Pet. Ex. 40

at 2. Doctor Cohen noted, however, that A.K. did not have elevated CK, which

suggested that his AST/ALT ratio results were not significant as an indicator of a

mitochondrial problem. Tr. 1202.

Finally, there was also some suggestion by petitioners that elevated ammonia

levels could also be considered a marker of mitochondrial disorders. Doctor Kendall

never actually opined that elevated ammonia was an indicator of mitochondrial

dysfunction, never cited elevated ammonia when discussing the signs of mitochondrial

disorder in A.K.’s case, and declined to even opine that the finding of elevated ammonia

in A.K.’s case was genuine.142 Tr. 244-47, 249-51, 317, 400. Respondent’s experts

also disputed that elevated ammonia is itself an indicator of mitochondrial disease. Tr.

1127-28, 1204-06. In particular, Drs. Cohen and Wallace both noted that ammonia can

be elevated for many reasons, including digestion, lack of sleep, illness or other

stresses. Id. Doctor Cohen indicated that it is a “very nonspecific marker,” and both

opined that it would not be of any clinical significance to a mitochondrial disorder without

a corresponding elevation in glutamine, which A.K. did not have.143 Id.

141 I add that I did not give much weight to Dr. Cohen’s testimony about his on-going, but unpublished,

research but did not discount it entirely, as experts frequently use their own clinical experiences in

forming opinions.

142 Doctor Boris, A.K.’s pediatrician, testified that he believed the elevated ammonia was an indicator of

abnormal metabolism. Tr. 172-73. Similarly, in his expert report, Dr. Deth also indicated that elevated

ammonia is suggestive of a mitochondrial dysfunction. Pet. Ex. 117 at. 5. Neither of these doctors,

however, is qualified to diagnose a mitochondrial disorder. Indeed, as previously indicated, Dr. Deth

explicitly deferred to the other experts in this case on that subject. Tr. 796. In their post-hearing brief,

however, petitioners juxtaposed Dr. Kendall’s above-discussed opinion regarding lactate and AST with

the additional fact of A.K.’s elevated ammonia (see, e.g., ECF No. 297, p. 54) before ultimately arguing

that “Dr. Deth and Dr. Kendall both testified that all of these findings taken in totality are suggestive of

metabolic disorder.” ECF No. 297, p. 74. This is a disingenuous attempt to bring their argument

regarding the significance of the elevated ammonia under the imprimatur of Dr. Kendall, their only

mitochondrial expert in this case. The only time Dr. Kendall ever actually discussed the elevated

ammonia findings, she explicitly indicated that it “might not be” of any significance and cautioned that

ammonia in particular needs to be handled carefully. She specifically testified that she “can’t tell” if the

elevation was genuine. Tr. 400. I resolve the conflict between the opinions of Drs. Deth and Boris that

the presence of high ammonia is significant to the diagnosis of mitochondrial disorders and the opinion of

Dr. Cohen that it is not, in favor of Dr. Cohen’s position.

143 In a prior decision I noted that “In individuals with urea cycle disorders, an illness (or dehydration due

to an illness) may produce an excess of ammonia in the body, termed “hyperammonemia,” resulting in a

metabolic decompensation.” See Holt, 2015 WL 4381588, *24. Doctor Kendall, however, specifically

noted that A.K. does not have a urea cycle disorder. Tr. 359-60.

60
61

Thus, contrary to petitioners’ argument, none of the testifying mitochondrial

experts in this case assigned any significance to the finding or elevated ammonia. Nor

have petitioners established that AST, ALT, or the ratio of the two, represents a

hallmark of mitochondrial disorder. And although the experts agree that chronic or

persistent elevation of lactic acid is an indicator of mitochondrial disorder, the evidence

in this case does not establish any such persistent elevation, showing at most only one

instance of elevated lactic acid.

3. Clinical Features.

Doctor Kendall identified a number of clinical features of mitochondrial disorders,

Pet. Ex. 65 at 11, Table 1 and argued that, among those features, A.K.’s medical history

is significant for the following: ASD, developmental delay, hypotonia144, gastrointestinal

problems, fatigue, and temperature instability/autonomic dysfunction.145 Tr. 249-51,

252. These are the same clinical features included in Dr. Shoffner’s brief clinical

summary. Pet. Ex. 32, p. 1. Doctor Cohen agreed as a general matter that these

symptoms can be present with mitochondrial disorders; however, he characterized them

as “nonspecific findings.” Tr. 1173-1176; Pet. Ex. FFF at 2-3. Absent confirmation from

history, physical examination, or laboratory results, Dr. Cohen did not find these clinical

presentations diagnostic of a mitochondrial disorder. Tr. 1186. Rather, citing Haas,

Res. Ex. SS, Tab 6,146 Dr. Cohen argued that A.K. does not have any of the “classic”

mitochondrial phenotypes or “red flags.” Tr. 1169-73; Res. Ex. SS, Tab 6 at 1327

(Table 1), Red-Flag Findings in Mitochondrial Disease.

Doctor Kendall did not address the distinction between clinical symptoms that

would be considered diagnostic “red flags” versus nonspecific findings. Her table of

mitochondrial disorder symptoms within her expert report is not so divided and in her

testimony she merely states that “clinically, [A.K.] has a number of features that you

certainly see in mitochondrial disease.” Pet. Ex. 65 at 11; Tr. 249. Her table reflects a

kitchen sink list of symptoms, few of which appear on Dr. Haas’ “Red Flag” Table 1.

Res. Ex. SS, Tab 6, at 1327.

Her argument seems to be that having a sufficient number of relevant clinical

symptoms – regardless of which particular symptoms – is a basis for putting a patient

“into that basket,” i.e., diagnosing a mitochondrial disorder. Tr. 250. This is consistent

with her review article on mitochondrial disorder diagnosis, which indicates that the

144 The transcript reflects that on direct examination, Dr. Kendall indicated that “hypertonia” was an

indication that A.K. had a mitochondrial disorder. In her expert report, however, Dr. Kendall indicated that

A.K. was “hypotonic” (Pet. Ex. 65 at 2) and that low muscle tone was a sign of mitochondrial disease (Pet.

Ex. 65 at 4.) Moreover, on later questioning, Dr. Kendall referenced “low tone” when reiterating which

clinical indicators she believed to be relevant to A.K.’s diagnosis. Tr. 363. Thus, this reference to

hypertonia is likely a typographical or transcription error. I can find no other instance where Dr. Kendall

sought to link hypertonia to mitochondrial disease.

145 Doctor Kendall also indicated that regression was another factor in her clinical diagnosis. Tr. 252. For

the reasons discussed in Section VII.C, below, however, I have found that A.K. did not experience a

regression as petitioners alleged.

146 Doctor Cohen was a co-author of this article, as was Nicole Wolf, one of the co-authors of Court Ex. I,

the article establishing the Nijmegen diagnostic criteria.
62

presence of “widespread, seemingly unrelated multisystem problems” is itself “highly

suggestive of mitochondrial disease.” Pet. Ex. 172 at 195.

According to the Haas article, “some symptoms and signs truly are more

suggestive of a mitochondrial disorder than others.” Ex. SS, Tab 6 at 1327. So-called

“red flag” findings “warrant the initiation of a baseline diagnostic evaluation for

mitochondrial disease” while “nonspecific” symptoms (such as A.K. has) “frequently

occur in infants and children with mitochondrial disease but have a broad differential

diagnosis, and more often lead to other clear diagnoses.” Id. Thus, Dr. Cohen noted,

that the presence of ASD and developmental delays, which were key clinical findings for

Dr. Kendall, also occur in children with other types of neurological conditions. Tr. 1186.

A study by Oliviera, et al,147 found that only a small percentage of children with ASD had

evidence of mitochondrial disorder.148 Tr. 1184-85. Even Dr. Kendall acknowledged,

for example, that mitochondrial disorders cannot explain the imbalanced male-female

ratio in ASD. Tr. 260. Thus, autism should not be considered a “red flag” for a possible

mitochondrial disorder. Even if mitochondrial disease occurs in the ASD population at a

higher rate than in the general population, the vast majority of ASD cases do not have

the co-morbid mitochondrial diagnosis, much less a causal relationship between the two

diagnosis. Perhaps this explains why Dr. Cohen does not believe that a child with

A.K.’s presentation, and most notably his ASD, warrants screening for ASD.

Given the lack of evidence of mitochondrial disorder in this case in terms of

histology, function, molecular pathogenicity, genetics, enzymology, and metabolic

indicators, the lack of any red flag findings in A.K. is highly significant. Although Dr.

Cohen could not rule out the possibility that one could have a mitochondrial disorder

without any manifestation of the “red flag” findings (Tr. 1170-73), that is an issue

different from the one presented here—petitioners’ burden to demonstrate that A.K.

actually has such a disorder. In that regard, Dr. Cohen opined that, by today’s

standards, a patient with A.K.’s clinical features (most notably ASD) would not even be

screened for a mitochondrial disorder, absent multiple positive findings on blood and

urine testing. Tr. 1183. And indeed, Dr. Kendall was unable to opine based on clinical

features alone that A.K. in fact had any mitochondrial disorder based on the Bernier

147 Pet. Ex. 38, G. Oliveira, et al, Epidemiology of autism spectrum disorder in Portugal: prevalence,

clinical characterization, and medical conditions, DEVELOP. MED. & CHILD NEUROL. 49: 726-733 (2007)

[hereinafter “Oliveira, Pet. Ex. 38”].

148 Doctor Cohen indicated that the Oliveira study showed that 7% of the studied population had evidence

of mitochondrial dysfunction based on electron transport chain testing. Tr. 1185. In fact, the study

indicated that approximately 4% of ASD cases had co-morbid mitochondrial disorder diagnoses. Pet. Ex.

38 at 730 (Figure 1). The authors indicated that 102 idiopathic cases of autism were evaluated and of

those, five patients were classified as having a definite mitochondrial disorder. Id. at 730. Nonetheless,

the authors noted that this represented an “unexpectedly high rate” of respiratory chain disorders. Id. at

726. Significant to Dr. Cohen’s point, however, after screening these subjects for related conditions

including mitochondrial disorders, the study found that 80% of cases were still considered idiopathic. Id.

at 730 (Figure 1).
63

criteria. At most he would satisfy only one minor criteria, which is insufficient for a

diagnosis.149 Pet. Ex. 90 at 1406-07.

Moreover, in reviewing Dr. Kendall’s expert report, testimony, and her own

review article, I do not see any indication that Dr. Kendall would diagnose a

mitochondrial disorder based on clinical features alone. For example, even in regard to

a well-defined mitochondrial disease with a clear constellation of symptoms, such as

seen in Leigh disease, Dr. Kendall still indicated that a diagnosis must be confirmed by

at least “minimal” testing. Pet. Ex. 172 at 196. Where those clinical features, while

consistent with mitochondrial disorder, are not red flags for or, in Bernier’s terms,

“essentially pathognomonic” for a respiratory chain disorder, and, in fact, more often

lead to other diagnoses, a diagnosis based on clinical features alone would be

overreaching. Haas, Res. Ex. SS, Tab 6 at 1327; Bernier, Pet. Ex. 90 at 1407 (Table

1).

Additionally, Dr. Cohen challenged certain aspects of Dr. Kendall’s clinical

summary. For example, he questioned whether A.K. in fact had hypotonia, noting that

while Dr. Boris recorded hypotonia in his notes, Dr. Rapin instead identified “loose

joints.” Doctor Cohen argued that loose joints, an unrelated condition not associated

with mitochondrial disorders, is frequently misdiagnosed as hypotonia, noting that he

himself has made the error. Tr. 1193-94. He also drew a distinction between

alternating constipation and diarrhea such as A.K. had, with pseudo-obstruction, which

is a non-physical blockage often requiring hospitalization. Although Dr. Cohen noted

that he has seen mitochondrial disorder patients with constipation, he stressed that only

a pseudo-obstruction would constitute a classic phenotype for a mitochondrial disorder,

and indicated that A.K.’s constipation was more likely to be associated with his ASD,

than indicative of a mitochondrial disorder. Tr. 1186-89, 1220-21; Ex. FFF at 3. Doctor

Cohen observed that if A.K.’s constipation was related to a mitochondrial disorder, one

would expect to see some “red flag” findings, such as “findings in the classic

mitochondrial phenotype description.” Tr. 1304. Nothing in Dr. Kendall’s testimony

directly rebutted any of these points.

D. A.K.’s Medical Records Do Not Establish that A.K. has a Mitochondrial Disorder.

In addition to Dr. Kendall’s opinion, petitioners also argued that A.K.’s

mitochondrial disorder was evidenced by the diagnoses and opinions of several treating

physicians. They therefore assert that A.K.’s medical records are sufficient to meet their

burden of proof on the question of A.K.’s mitochondrial disorder diagnosis. ECF No.

297 at 17. Indeed, petitioners claim that “the medical evidence, both diagnostic and

clinical establishing that A.K. has a mitochondrial disorder, is overwhelming.” Id.

Specifically, petitioners highlight the laboratory findings of Dr. Shoffner, which they

argue were “reviewed and affirmed by several other practitioners expert in or familiar

149 As previously indicated, Dr. Kendall testified that she could not opine that A.K.’s clinical symptoms met

the requirements for a major finding under Bernier. Specifically, she conceded that A.K. does not have a

clinically complete respiratory chain encephalomyopathy and that she could not identify a “progressive

clinical course with episodes of exacerbation” as would be necessary to alternatively conclude that he 

had a mitochondrial cytopathy. Tr. 309-10. Doctor Kendall testified that she did not see any evidence of

any progression or worsening of A.K.’s mitochondrial disorder. Tr. 325.
64

with mitochondrial disorder.” Id. at 11. Those practitioners are Drs. Sims, Korson,

Hoffman, and Alvarez-Altalef.150 Id. at 11-15.

Although petitioners’ argument encompassed both the fact of these treating

physicians’ diagnoses as affirmation of their claim, as well as the underlying clinical data

on which the physicians relied, this section deals exclusively with the significance of the

alleged diagnostic statements themselves. In the preceding section, I have already

addressed the most pertinent underlying clinical data addressed by Dr. Kendall and

found it lacking. None of these treating physicians’ reports provide any additional

evidence bearing on the validity of—or, more accurately, the significance of the data to a

correct and accurate—mitochondrial disorder diagnosis. Moreover, although these

records contain extensive clinical histories, the physicians who took the histories largely

declined to assign diagnostic significance to the clinical symptoms reported. This is

unsurprising, in that these records do not represent the independent diagnoses that

petitioners claim they do.

Although contemporaneous records from treating physicians are normally given

considerable weight,151 petitioners dramatically overstated the significance of the record

notations made in this case. As an initial matter, the “diagnosis” made by Dr. Shoffner

is of dubious provenance, something that would not be apparent to a treating physician

simply informed of the diagnosis or even one who read the summarized report. For the

reasons described in Section VI.C, above, there are considerable problems with Dr.

Shoffner’s diagnosis of a Complex I defect, based on both on his own testing and on

symptomology reported by petitioners. Even Dr. Kendall acknowledged the problems

evident in Dr. Shoffner’s diagnosis.

To the extent a mitochondrial diagnosis requires clinical evaluation in addition to

laboratory findings, there is no evidence to suggest that Dr. Shoffner had access to

A.K.’s complete medical history or conducted any physical examination of A.K to

150 Petitioners also cited a consultation report by Dr. Marcel Kinsbourne as further confirmation of A.K.’s

diagnosis (Pet. Ex. 48; ECF No. 297 at 16-17). This report was filed as a part of petitioners’ efforts to

buttress their motion for reconsideration (ECF No. 100) of my decision dismissing their petition for failures

to prosecute and comply with court orders (ECF No. 99), a motion I subsequently granted (ECF No. 106).

Doctor Kinsbourne’s report selectively summarized the medical records and affidavits and concluded that

“investigations have substantiated [A.K.]’s diagnosis of mitochondrial disorder.” Pet. Ex. 48 at 2. Doctor

Kinsbourne was neither a treating physician nor a testifying expert in this case. Moreover, unlike

neurologists who testified as experts in this case, there is no evidence in the record to suggest that he 

has any special competency in diagnosing mitochondrial disorders. In any event, Dr. Kinsbourne’s report,

which contains a discussion of A.K.’s case that is cursory at best, is effectively a restatement of

petitioners’ contention that Dr. Shoffner’s findings were accepted by other treating physicians. Pet. Ex. 48

at 2. The report does nothing to further substantiate that claim or otherwise elucidate the diagnostic issues

presented.

151 See, e.g., Cucuras v. HHS, 993 F.2d 1525 (Fed. Cir. 1993) (noting that “medical records, in general,

warrant consideration as trustworthy evidence. The records contain information supplied to or by health

professionals to facilitate diagnosis and treatment of medical conditions. With proper treatment hanging in

the balance, accuracy has an extra premium. These records are also generally contemporaneous to the

medical events.”); see also Capizzano, 440 F.3d at 1326 (noting that “treating physicians are likely to be in

the best position to determine whether ‘a logical sequence of cause and effect show[s] that the

vaccination was the reason for the injury’”).
65

substantiate the histories provided to him. I have found that Dr. Shoffner’s opinion that

A.K. “probably” had mitochondrial encephalomyopathy (Pet. Ex. 32, p. 3) is not reliable,

as his test results were not normalized as required by the Bernier diagnostic criteria,

and were based on reports of symptoms that did not meet the diagnostic strictures of

that criteria.152 Thus, to the extent Drs. Sims, Korson, Hoffman, and Alvarez-Altalef

have based their own diagnoses on Dr. Shoffner’s report, and depended on his

underlying finding of a Complex I defect, their resulting reports would be of equally

dubious evidentiary value.153

But in any event, petitioner’s argument that each of these doctors “accepted” Dr.

Shoffner’s finding of probable “mitochondrial encephalomyopathy” begs the question of

whether that acceptance was critical or passive.154 To the extent that any of these

reports reflected a diagnosis of mitochondrial disorder, they do not reflect any

independent application of the diagnostic standards or any interpretive analysis of Dr.

Shoffner’s findings.155

It is not uncommon for treating physicians to rely on a diagnosis supplied by

another specialist, and to simply accept that diagnosis at face value. Doctor Kendall

suggested as much, indicating during questioning that she saw patients for symptom

152 Doctor Cohen, in particular, argued that Dr. Shoffner overstepped in reaching such a diagnosis. Tr.

1220-22.

153 The issue of this reliance is distinct from any issue regarding the qualifications of these physicians, a

separate point which petitioners have stressed.

154 I find it significant that petitioners are inconsistent in the phrasing of their argument. At some points

they argue that these physicians “concluded” that A.K. had a mitochondrial disorder. See, e.g., ECF No.

297 at 57. At other points in their brief, however, they merely argue that these physicians had “accepted”

Dr. Shoffner’s findings. See, e.g., ECF No. 297 at 74.

155 The significant issue here is one of interpretation rather than accuracy. As treating physicians, these

doctors each had an incentive to be accurate in their diagnosis and no reason to mold their records to a

particular outcome, as is often a concern in litigation. That makes their records “trustworthy.” See

Cucuras, supra. The testifying experts in this case have made it clear, however, that there is

disagreement among practitioners in this field regarding the proper interpretation of laboratory results and

have submitted their analysis of those results to the scrutiny of the court. In the present context, that

detailed analysis simply outweighs any competing, yet unexplained, view of A.K.’s treating physicians.

See, e.g., Snyder v. HHS, 88 Fed. Cl. 706, 745 n. 67 (2009) (emphasizing that a statement of a treating

physician is not “sacrosanct” and can be rebutted). I also note that Dr. Shoffner’s testing and diagnosis

can be viewed as ones sought primarily for the purposes of this litigation. The testing was requested and

performed shortly after the entitlement decision in the Poling case was issued and publicized. See Res.

Ex. MM, Tab 17, R. Brumback, The Appalling Poling Saga, J. CHILD NEUROL., 23(9): 1090-1091 (Sept.

2008) [hereinafter “Brumback, Res. Ex. MM, Tab 17”]. Petitioners explicitly withdrew their case as an

OAP test case in order to pursue a new theory of causation at around the same time the Poling case

became public knowledge. ECF No. 40 (motion to Withdraw, filed Apr. 10, 2008); ECF No. 45 (status

report filed July 1, 2008, reflecting that petitioners were pursing “additional medical evaluation and testing

for [A.K.} to determine the extent to which theories of causation in addition to the thimerosal theory are

applicable.”); ECF No. 54 ( status report, filed Mar. 3, 2009 (reflecting that their “new theory” was the

impact of vaccinations on a child with mitochondrial DNA defects). They sought testing from one of the

authors of the Poling case report. The testing performed, the symptoms recorded and relied upon, and

the conclusions reached by Dr. Shoffner (see Pet. Ex. 32, filed Jan. 16, 2009).have significant

shortcomings, as explained by the testimony and reports of Drs. Cohen, Wallace, and at least some of

which were acknowledged by Dr. Kendall. See Sections VI.C.1-3, supra.
66

management that she has not herself diagnosed.156 Tr. 372. Moreover, respondent’s

expert, Dr. Cohen, likewise indicated that he believes it is not uncommon for physicians

in this context to accept a prior doctor’s statement as true without necessarily arriving at

an independent conclusion. Tr. 1223, 1324-25. In fact, Dr. Cohen and Dr. Kendall both

indicated that in their own practices they will guide patients through symptom

management on a provisional or presumptive basis even where they do not necessarily

believe the patient’s testing was positive for a mitochondrial disease.157 Tr. 249, 1223-

25.

Doctor Cohen did not believe that the records in this case showed evidence of

any independent conclusion by these treating physicians. Tr. 1223. Similarly, Dr.

Kendall acknowledged with regard to Dr. Sims’s report, for example, that she could not

tell from the report whether Dr. Sims had independently reached a diagnosis or simply

reported a prior diagnosis. Tr. 354-55.

Doctor Sims noted in her report158 that A.K. was “recently diagnosed with a type I

mitochondrial disorder” and that “the family presents today to initiate management of his

mitochondrial disorder.” Pet. Ex. 35, p. 13. There is nothing, however, to indicate that

Dr. Sims had separately analyzed, let alone agreed with, that diagnosis. In fact,

although Dr. Sims specifically noted Dr. Shoffner’s findings, she explicitly characterized

his data as “incomplete” and indicated in her treatment plan that “we have asked for

more complete records particularly the Shoffner mitochondrial work-up detail.” Pet. Ex.

35, pp. 13-14. These notations are directly contrary to petitioners’ argument that Dr.

Sims and the other treating physicians “affirmed” Dr. Shoffner’s findings and raise the

question of whether any of the doctors were even provided with Dr. Shoffner’s complete

findings.

Similarly, with regard to Dr. Alvarez-Altalef, petitioners argued that, “based upon

her own examination of A.K., her review of A.K.’s history and record and ‘extensive

workup,’ including A.K.’s laboratory reports and the objective findings therein, and a

review of the objective findings of Dr. Shoffner, Dr. Alvarez-Altalef concluded that A.K.

had a mitochondrial disorder.” ECF No. 297 at 15. There is no statement in Dr.

156 Specifically, I asked Dr. Kendall “what are the primary reasons that children with mitochondrial

disorders and autism come to you? Is it to have the mitochondrial disorder diagnoses?” She responded

that “It can be that. It depends on where they are in the process of being evaluated, but it certainly can be

for diagnosis, number one, and then the other can be again symptomatic management.” Tr. 372

(emphasis added). I note that Dr. Kendall has also appeared frequently as the petitioners’ expert in 

cases alleging vaccines cause “mitochondrial autism,” and has provided expert reports in many more

cases that have not yet involved hearings.

157 Doctor Cohen in particular stressed that a patient’s clinical problems still need to be treated regardless

of whether they are a manifestation of a mitochondrial disorder. He therefore indicated that there is no

harm in acting on a “working” or unsubstantiated mitochondrial disorder diagnosis so long as it does not

impede investigation of other potential diagnoses. Tr. 1223-25; see also R. Frye, et al, Treatments for

mitochondrial dysfunction associated with autism spectrum disorders, J. PEDIATR. BIOCHEM. 2: 241-249

(2012), filed as Pet. Ex. 186, at 242 (noting that treatment of mitochondrial disorders relies primarily on

precautions to prevent decompensation, vitamin supplements, and modification of diet).

158 The report was actually prepared by a resident, Dr. Robin Ryther, under Dr. Sims’s direction. Pet. Ex.

35, p. 14.
67

Alvarez-Altalef’s report, however, that would indicate that she arrived at any

independent conclusion regarding A.K.’s mitochondrial disorder diagnosis. All of the

language cited by petitioners in support of their argument (see ECF No. 297 at 14-15

quoting Pet. Ex. 36, pp. 1, 3) is contained in Dr. Alvarez-Altalef’s recitation of A.K.’s

prior history, which indicates that he was previously diagnosed with mitochondrial

disorder (see Pet. Ex. 36, pp. 1-4).159 Moreover, it appeared that Dr. Alvarez-Altalef

may have viewed A.K.’s prior mitochondrial diagnosis as being a working or provisional

diagnosis only. She stated in her report that A.K.’s work up yielded “at this point” a

diagnosis of mitochondrial disorder.160 Pet. Ex. 36, p. 1.

Doctor Hoffman’s report161 is also ambiguous. Although it is true, as petitioners

argued, that the report reflects an evaluation of A.K., it is unclear the extent to which the

report was focused on diagnosis as opposed to symptom management. The report

reflected that A.K. and his family approached Dr. Hoffman precisely because they

already believed A.K. had a mitochondrial disorder. The beginning of the report stated

that “[A.K.] and his family came to us today in order to discuss his history and how to

move forward in terms of taking care of his mitochondrial disease and optimizing his

care.” Pet. Ex. 34, p. 1. To the extent that Dr. Hoffman’s report indicated in the

summary that she believed A.K. to have a mitochondrial disorder, the particular

phrasing, stating that A.K. “is felt to have mitochondrial disease,” obscured whether she

was referring to her own diagnosis or a prior diagnosis. Pet. Ex. 34, p. 5-6.

The very fact of these treating physician reports does provide some support for

petitioner’s argument of a mitochondrial diagnosis. However, the evidence of

mitochondrial disorder diagnosis contained in A.K.’s medical records is far more

equivocal than petitioners suggested. Petitioners portrayed the record as reflecting

multiple independent diagnoses of mitochondrial disorder, but I do not find these claims

of “independence” to be substantiated in the records. Moreover, all of these alleged

instances of diagnosis ultimately relied on Dr. Shoffner’s initial laboratory assessment

and are predicated on Dr. Shoffner’s finding of enzyme abnormalities, an interpretation

which I have rejected.

159 Doctor Kendall indicated during her testimony that she did not believe that Dr. Alvarez-Altalef is

known to be among the country’s small number of mitochondrial specialists. Tr. 421-22.

160 Petitioners have emphasized testimony by Dr. Kendall indicating that working diagnoses are common

in this field due to the unusual level of uncertainty in mitochondrial disorder diagnosis. ECF No. 297 at 58

(quoting Tr. 426).

161 Petitioners characterized Dr. Hoffman as an assistant to Dr. Korson and her report as one from a joint

evaluation conducted by both Dr. Hoffman and Dr. Korson. ECF No. 297 at 13. Doctor Hoffman was a

geneticist at the Floating Hospital for Children at Tufts Medical Center in the Division of Genetics and

Metabolism while Dr. Korson was the Chief of Metabolism. Pet. Ex. 34, p. 1. Doctor Hoffman’s report to

Dr. Zirin, A.K.’s pediatrician, noted the additional involvement of Dr. Korson in the medical treatment of

both A.K. and his sister, but is not explicit in describing what, if any, involvement Dr. Korson had in the

evaluation discussed. Pet. Ex. 34. Moreover, even if Dr. Korson did participate in the evaluation, there is

no statement indicating that he reviewed or approved the report itself. Thus, to the extent petitioners

attempted to characterize the report as reflecting the views of Dr. Korson as a mitochondrial expert (e.g.,

ECF No. 297 at 57), that argument is not supported by the report itself. In that regard, it is also worth

noting that while it is undisputed that Dr. Korson is well respected in the field of mitochondrial disorders

(Tr. 417-18, 1326-27), his actual qualifications are not a part of this record.
68

E. Conclusions and Finding of Fact Regarding A.K.’s Mitochondrial Diagnosis.

There are significant issues with Dr. Kendall’s interpretation of A.K.’s clinical

history. She has relied on non-specific clinical findings to diagnose A.K. with

mitochondrial disease. The reliance by A.K.’s treating physicians on Dr. Shoffner’s

report appears to have shaped their diagnostic impressions and their diagnostic

conclusions thus rise or fall based on the reliability of Dr. Shoffner’s diagnosis. Treating

A.K. for a mitochondrial disorder is not confirmation that he actually has that diagnosis,

for such treatment is without significant side effects. Tr. 249, 372, 1223-25.

Mitochondrial disorders are difficult to diagnose—a point on which the experts for

both sides agree. A.K.’s clinical symptoms, to the extent they are interpreted as signs

of mitochondrial disorder, cannot be matched up to other key findings such as

enzymology, metabolic testing, histology, or genetics, for all of the reasons described

above. He does not reach the “possible diagnosis” level under Bernier, let alone the

probable or definite diagnosis classification posited by Dr. Kendall. Indeed, the Bernier

criteria would characterize A.K.’s case as “unlikely.” Pet. Ex. 90 at 1406. Doctor

Kendall herself stressed that a mitochondrial disorder diagnosis must be made in light of

the totality of evidence, including laboratory data, with “enough data points” favoring

such a diagnosis. Tr. 249. She argued that in A.K.’s case “when you look at all of it . . .

I say to myself, well, that looks like it’s probably a mitochondrial disease based on all of

the different points of data that come together.” Tr. 251.

But, for all of the reasons discussed above, I do not find that most of these data

points exist, much less “come together,” in the manner Dr. Kendall suggested. Thus,

while it have been reasonable for A.K.’s treating physicians to engage in symptom

management based on the suspicion of a mitochondrial disorder, such a suspicion does

not meet petitioners’ burden of proof here. That is, considering the record as a whole, I

do not find that it is more likely than not that A.K. actually has either a mitochondrial

disorder or dysfunction.

VII. The Onset of A.K.’s ASD is Not Temporally Related to his Vaccinations and

the Course of A.K.’s ASD is Inconsistent with Petitioners’ Theories.

Regardless of the mechanism, petitioners allege that A.K.’s influenza

vaccinations ultimately led to his ASD.162 As indicated above, Dr. Shafrir’s and Dr.

Kendall’s causation opinions rely heavily on the supposition that the onset of A.K.’s

ASD, or ASD-like symptoms, is temporally related to A.K.’s two administrations of

162 Petitioners have been inconsistent in describing the exact nature of A.K.’s injury. They have variously

described A.K.’s injury as consisting of “epigenetic changes in his brain, evidenced by autistic symptoms”

(ECF No. 297 at 105) or as “a regressive encephalopathy with features of autism spectrum disorder” (2d

Am. Pet at ¶ 74). They have also argued more directly that A.K.’s ASD itself is a vaccine-caused injury,

noting that “petitioners maintain [the] position that the flu vaccinations caused A.K.’s condition, including

autism.” ECF No. 297 at 128. Regardless of how they characterize the injury, however, petitioners have

been clear in asserting that there is a temporal relationship between the onset of A.K.’s symptoms,

inclusive of his ASD symptoms, and his vaccinations, arguing that “A.K.’s medical records and the

testimony of his parents and Dr. Boris establish not just an association between the vaccinations and the

onset of symptoms, but indeed, challenge re-challenge.” ECF No. 297 at 124.
69

influenza vaccine. Thus, determining the timing of that onset is critical to assessing

petitioners’ causation claim. Not surprisingly, petitioners expended considerable efforts

in an attempt to discredit the primary witness who placed onset of A.K.’s ASD prior to

administration of these vaccinations, Dr. Miller.

There is no dispute in this case that the onset of A.K.’s ASD predated his first

explicit ASD diagnosis by years. A.K. was first diagnosed with ASD by Dr. Rapin on

April 22, 2004, at about four and a half years of age. Pet. Ex. 11, p. 3. At that point, Dr.

Rapin indicated that “there is no doubt that [A.K.] is a child on the autistic spectrum.” Id.

An earlier evaluation on July 10, 2002, using the Childhood Autism Rating Scale

[“CARS”], had found that A.K. was not autistic. Pet. Ex. 5, p. 3. However, that

evaluation showed that, at 32 months of age, he was not functioning at the appropriate

age level in cognitive, language, adaptive, and social development skills. Pet. Ex. 5, p.

7.

Petitioners’ expert in pediatric neurology, Dr. Shafrir, expressed doubt regarding

the earlier CARS evaluation’s conclusion. Tr. 526-27. He opined that the substance of

that report reflected ASD, even if that ultimate conclusion was not expressed. Tr. 527.

And, although respondent’s expert in autism, Dr. Miller, did not specifically discuss the

accuracy of the July 10, 2002 CARS evaluation, she did note that in 2002, ASD

screening techniques were not sophisticated enough to reliably identify ASD before

about ages three to four, older than A.K. was at the time of the CARS evaluation. Tr.

1037-38. Doctor Miller also noted that, even today, with more advanced and proactive

approaches to ASD diagnosis, it can still take families “years” to get a diagnosis. Tr.

860-61. Thus, the parties agree that A.K.’s 2004 diagnosis in itself does not pinpoint

the onset of his ASD.

Unsurprisingly, however, petitioners and respondent have very different

perspectives regarding the time by which A.K.’s ASD actually manifested. Petitioners

have alleged that “there is no evidence . . . in this record that A.K. was autistic prior to

the administration of the influenza vaccinations. There is ample evidence, moreover,

that A.K. became autistic in November and December 2001, after the administration of

the vaccinations.” ECF No. 297 at 131. Petitioners further argue the

November/December onset of A.K.’s ASD represented the beginning of a clear

regression. See, e.g. ECF No. 297 at 102-03.

Respondent disagrees. Respondent argues, primarily through the expert opinion

of Dr. Miller, that A.K. showed clear signs of his ASD as early as 14 months of age, well

before he received the two doses of influenza vaccination implicated in this claim, and

that there is no credible evidence of regression. See, e.g. ECF No. 295 at 24-25.

For the reasons described below, I find that respondent has established that

A.K.’s ASD became evident prior to his influenza vaccinations and that there is

insufficient evidence in the record to suggest that he regressed as petitioners contend.

A. Respondent’s Primary Expert on ASD Diagnosis, Dr. Miller, Was Highly Persuasive.

The question of when A.K.’s ASD first manifested was most extensively

addressed by Dr. Miller on behalf of respondent and by Dr. Shafrir on behalf of
70

petitioner. 163 In their post-hearing brief, petitioners raised objections to Dr. Miller’s

testimony and I have addressed those objections in my prior ruling in which I declined to

strike her testimony. See Motions Ruling, filed on Sept. 28, 2015 (ECF No. 319), at

Section II.F. Here I note that Dr. Miller’s presentation regarding the proper screening

and diagnosis for ASD is not only acceptable, it was in fact far more extensive, better

supported, and far more credible than Dr. Shafrir’s testimony on the same topics.164

163 Petitioners also filed an expert report (Pet. Ex. 107) by Dr. Mary Megson, a developmental

pediatrician, primarily to address the significance of the video evidence filed in this case. Id. at 2.

Although I address Dr. Megson’s report below, I note here that she was unable to testify in this case.

164 I stress that although I have considered all of petitioners’ objections to Dr. Miller’s testimony, I have not

only found that they are without merit; in many instances, they are deliberate misrepresentations of Dr.

Miller’s testimony. For example, in their response to respondent’s post-hearing brief, petitioners argued

that Dr. Miller had criticized Dr. Rapin for not following “appropriate medical protocol” in arriving at her

diagnosis. ECF No. 302 at 7. Petitioners’ counsel engaged in a protracted cross-examination of Dr.

Miller on this point, during which Dr. Miller was quite clear in stating that petitioners’ counsel was incorrect

in summarizing Dr. Miller’s testimony as being critical of Dr. Rapin for using insufficient diagnostic criteria

in A.K.’s case. Tr. 983-84. Rather, Dr. Miller testified that Dr. Rapin likely relied at least in part on

parental reports and that it is not standard medical practice to fact-check parental reports. Tr. 984-85.

Petitioners characterize this as “ironic,” because Dr. Miller’s own diagnostic tools rely on parental reports

(ECF No. 302 at 8), but there was nothing ironic in Dr. Miller’s testimony. She simply offered what should

be an uncontroversial observation – that parental reports can provide important information, but that not

all parental reports are equally reliable. In that regard, Dr. Miller explained that parental reports can be

assessed for their reliability by “drilling down” with follow up questions that call for concrete examples and

by matching up parental claims to what is observed clinically. Tr. 948-950. Contrary to petitioners’

argument, Dr. Miller did not testify that this was not done in A.K.’s case, only that it cannot be confirmed

and therefore the reliability of those reports is an open question. This issue is addressed in more detail in

Section VII.C.3, below.

In another example of overreaching, petitioners argued that Dr. Miller should be discredited on the basis

that she indicated that A.K.’s influenza vaccinations were not recorded in his “official” immunization record. 

Petitioners claim that this statement demonstrated Dr. Miller’s lack of familiarity with pediatric 

practice. ECF No. 297 at 27-28. The point that Dr. Miller made in her report is quite clear: she wrote that

she could find no notation of A.K.’s first influenza vaccination in either his “official” vaccine record, 

referring to the page of A.K.’s medical records constituting his “vaccine administration record” (Res. Ex.

OO at 2 (citing Pet. Ex. 2, p. 2.), nor in the progress note for the visit at which he received the vaccine

(Res. Ex. OO at 2 (citing Pet Ex. 2, p. 21.) Instead, she pointed out, the influenza vaccine is only noted in

a summary of vaccinations. Res. Ex. OO at 2 (citing Pet. Ex. 2, p. 1. and Pet. Ex. 61, p. 4). Unlike the

administration record, the vaccine summary lacks parental signatures or an administrator signature and/or

initials. Compare Pet. Ex. 2, p. 1 and p. 2. Particularly in light of Dr. Miller’s clear citation to the precise

record she was characterizing as “official,” petitioners’ belaboring of Dr. Miller’s word choice is not a

persuasive argument regarding Dr. Miller’s fitness as an expert witness. The extent of the testimonial

evidence than no vaccine record can be considered “official” was Dr. Shafrir’s general umbrage at the 

idea that any “official” immunization record could even be thought to exist. Doctor Shafrir was obviously

disdainful of Dr. Miller as a non-pediatrician or even a physician, and it was this attitude, rather than any

actual misunderstanding of Dr. Miller’s reference to the records. Tr. 506-510. And, Dr. Miller was not

wrong in contending that there is an “official” vaccination record. See § 300aa-25 (requiring that each

health care provider who administers a vaccination shall record in a permanent medical record or office

log the date of administration, the manufacturer and lot number, the name and address of the health care

provider, and other information required by regulation). Even if I thought that Dr. Miller’s word choice was

a poor one, there is no question as to what her underlying point was and no evidence to suggest that Dr.

Miller was confused regarding the nature of the records she reviewed.
Doctor Miller extensively described the ASD diagnostic methods available,

explaining that ASD diagnosis is based on observable behaviors listed in the DSM and

describing the diagnostic criteria under both the DSM IV and DSM V. Tr. 889-95. She

explained in detail the stages of inquiry, beginning with general monitoring, or

surveillance, through more specific assessments known as screening, and ultimately

leading to diagnosis. Tr. 857-59.

Doctor Miller explained that an ASD diagnosis is based primarily on

developmental history and clinical observation. Tr. 861-62. She indicated that the “gold

standard” for ASD diagnostics are the Autism Diagnostic Interview, Revised [“ADI-R”]

and the ADOS. Tr. 862-64. These are commercially available screening tools, but

training is required to establish that the practitioner is statistically reliable. Tr. 863.

Doctor Miller has not only completed such training, she is herself responsible for

supervising that training. Tr. 863-64. Doctor Miller also addressed the different agebased modules of the ADOS. Tr. 865-69. She explained how the different modules

correspond, not only to the DSM autism criteria, but also to CDC recommendations

regarding social milestones. Tr. 872-73; Res. Ex. DDD.

Significant to this case, Dr. Miller noted that the ADOS includes a module for one

to two year olds that accounts for the fact that children of that age are less verbal. Tr.

866-69; Res Ex. CCC at 9. She explained that in the absence of fully developed

speech, practitioners can screen for ASD by evaluating a number of features. These

include: joint attention (where the child is aware that both he and another person are

looking at the same object); imitation (which involves both re-creating actions and being

able to “pretend” an object is something else); eye contact and facial expressions; play

(both functional and pretend); responding to name; social interest and reciprocity (i.e.

when the child gets excited, is the attention fixated on an object or is the affect shared

with others); and stereotyped behaviors (unusual movements or fixations). Id.

Doctor Miller also explained that the ability to reliably screen toddlers at about 2

years of age is a more recent development. Petitioners were very critical of Dr. Miller’s

testimony, in part, because she did not accept the clinical observations of Dr. Boris or

Dr. Zirin. ECF No. 297 at 31-32. Doctor Miller observed, however, that at the time A.K.

experienced the onset of his ASD, screening techniques for one to two year olds were

not yet available. Tr. 1047-50. She explained that early screening became possible

because of research into nonverbal social communication which has found that certain

behaviors “come online” even before a child speaks his first word. Tr. 871-72. The

American Academy of Pediatrics released screening recommendations for 18 to 24

months in approximately 2007 or 2008. Tr. 1048. Because the pediatric records at

issue in this case were generated in the 2001 to 2002 timeframe, Dr. Miller observed

that A.K.’s pediatricians would not have had screening questions available to them that

would have led to an earlier ASD diagnosis. Tr. 1037-38. She observed that, at the

time that Drs. Boris and Zirin would have been observing A.K.’s development and noting

any concerns, children were not routinely referred for ASD evaluations prior to age three

or four.165 Tr. 1048.

165 Petitioners are quite vociferous in their objections to this aspect of Dr. Miller’s testimony. They argue

that Dr. Miller “does not know Dr. Boris or his practices” and that “Dr. Miller’s opinion that Dr. Boris would

71
72

In contrast, Dr. Shafrir offered a polemic decrying the state of autism knowledge

generally, and the DSM diagnostic parameters in particular. He argued that knowledge

of the cause or causes of autism has not advanced since the 1980’s and that in the face

of what he calls an “epidemic” of autism, attempts to understand the condition via study

of psychology and genetics are failures. Tr. 481-84. He argued that attempts to

develop guidelines for the assessment and treatment of autism are self-serving, if not

fraudulent, attempts by academics to earn fame and promotion. Tr. 496. He believes

that recommendations are being made “without any practical information” and that this

is “sad” and “shocking.” Tr. 497. And ultimately, he opined that approaching autism

diagnosis from a psychiatric perspective based on observable behaviors is a

fundamental flaw in thinking on autism. Tr. 522-24. Apparently he believes that

because ASD cannot be cured, studying how it presents is useless.

Doctor Miller’s testimony thoroughly rebutted Dr. Shafrir’s claim that ASD

assessment guidelines are being made without basis and without “any practical

information.” Tr. 496-97. Although Dr. Shafrir was correct in noting that we do not yet

know the cause of ASD, Dr. Miller has clearly shown that ASD assessment is based on

an understanding of the ways in which the ASD population deviates from expected

social development milestones. Indeed, when asked to define ASD himself, Dr. Shafrir

offered a description that is utterly consistent with Dr. Miller’s explanation of the ADOS

module for one to two year olds. He testified that autism is “a child who has impairment

in communication, in socialization, and in imagination, which means that they . . . have

primitive play without any use of imagination with the play. They can communicate

verbally or non-verbally. They [sic] most traumatic one is they don’t relate to other

people.” Tr. 580.

In addition to his testimony that essentially no progress in understanding the

causes of autism has been made since the late 1980’s (Tr. 495-98), he also opined that

there has been little progress in screening and diagnosis as well (Tr. 525-26). However,

not recognize the early signs of autism is both outrageous and inadmissible.” ECF No. 297 at 102. They

also contend that “Dr. Miller’s entire testimony concerning the observations and diagnoses of A.K.’s

physicians was predicated on speculation.” ECF No. 302 at 7. Protracted questioning of Dr. Miller on recross-examination suggests that petitioners fundamentally misconstrued the nature of Dr. Miller’s

testimony. Tr. 1045-55. She did not testify that A.K.’s physicians, nor Dr. Boris in particular, made

diagnostic errors in A.K.’s case. She testified that their findings must be understood in the context of the

state of ASD screening knowledge at the time. That is, to the extent that Dr. Boris’s records indicate no

developmental concern, a conclusion contrary to the contemporary video evidence in this case, Dr. Miller

explained that this fact is less significant than it otherwise would be, because the prevailing practices at

the time would tend to suggest that Dr. Boris could not reasonably be expected to have made such an

observation. Screening practices simply were not sensitive to many behaviors at that time. This is not 

the “speculation” petitioners decry. It is much-needed context from an expert in such matters. Indeed, by

raising this objection, in effect petitioners argue that Dr. Boris’s observations and professional judgments

were not merely unassailable, but actually not even constrained by the medical community’s

understanding of ASD. Although Dr. Boris testified to having some familiarity with ASD, nothing in his

testimony indicated that he was unusually positioned to be able to pick up on early autistic behaviors. He

did not testify that he actually looked for and ruled out the presence of any of the behaviors Dr. Miller

noted as present on the videos. Petitioners’ outrage over Dr. Miller’s testimony is completely misplaced.

That she saw things AK’s doctors did not is not an indictment of their expertise or observational skills; it is

that she observed AK’s behavior with the benefit of advancements in the understanding of ASD and how

it may present, as well as hindsight.
73

Dr. Miller’s testimony regarding the increased ability to diagnose ASD, even in toddlers,

which has developed within the last ten years, suggests that Dr. Shafrir’s assessment of

the diagnostic standards is either outdated or overly pessimistic. In that regard, I note

that when asked about his specialized training in autism, Dr. Shafrir cited experience

ending in 2000, well before the developments Dr. Miller described. Tr. 525. Moreover,

as I indicated in Section VIII.B.1, below, I found Dr. Shafrir’s attempt to distinguish

between autism and autistic regression to be unsupported and damaging to his

credibility.166

B. The Video Footage Filed In This Case Supports Respondent’s Argument that A.K.’s

ASD Predated His Vaccinations.

The biggest point of contention between the parties in terms of identifying the

onset or first manifestation of A.K.’s ASD stems from a series of videos filed in this

case, some of which were presented to the experts during the hearing. Two of

respondent’s experts, Drs. Miller and Cohen, experts in child psychology and pediatric

neurology respectively, opined that the videos collectively show signs of ASD well

before A.K.’s second birthday.167 In contrast, Dr. Shafrir, petitioners’ expert in pediatric

neurology, contended that the videos show no signs of ASD prior to November 10,

2001, and that the November 10 footage shows a dramatic overnight change compared

to footage recorded the day before on November 9, 2001.168 Drs. Kendall and Megson

(a non-testifying expert) similarly, but less forcefully, opined that although A.K.

experienced some prior speech delays, the period following his second birthday

166 In their response to respondent’s post-hearing brief, petitioners state that “petitioners recognize that 

Dr. Miller is well credentialed in her field of clinical psychology. She is not, however, a medical doctor and

should not be given license to substitute her judgments most, if not all of which, are based on conclusory

statements and speculation, without any support in the record, for the observations of highly experienced

medical doctors.” ECF No. 302 at 8-9. I note, however, that Dr. Miller’s testimony is being considered

solely with regard to the onset of A.K.’s ASD which is, in fact, a matter falling within the practice of clinical

psychology. Doctor Shafrir, for example, decried the fact that the diagnosis of ASD under the DSM “has

nothing to do with medical practice” because “we let psychiatrists run the show.” Tr. 522-24. Thus, Dr.

Shafrir himself has separated his medical expertise as a pediatric neurologist from ASD diagnosis and

has undercut petitioners argument that Dr. Miller’s status as a non-medical doctor has any bearing on her

opinion regarding the application of the DSM. See, e.g. King S, 2010 WL 892296, at *79 (noting that

“autism is considered a neurologic and a psychiatric disorder” and that “psychologists are also often

specialists who diagnose autism.”); see also Synder, 2009 WL 332044, at*32 (noting that “[a]ll of the

disorders falling within the autism spectrum are defined by a collection of symptoms or behaviors. With

the exception of Rett’s disorder, all ASDs are diagnosed by comparing behavioral symptoms exhibited by

a child against an established set of broad diagnostic criteria. The diagnosis is made by direct

observation, videos of the child, and from parental reports, as there is no biochemical test for ASD.”).

167 In the interest of brevity, Dr. Cohen’s testimony regarding the video footage was limited to confirming

his agreement with Dr. Miller’s testimony and noting that in his opinion the video footage in totality shows

a slow evolution of abnormal findings beginning prior to two years of age rather than any abrupt change as

petitioners allege. Tr. 1148-49. Doctor Cohen’s opinion regarding the videos is otherwise contained in 

his expert report. See Res. Ex. SS.

168 This marked a change from Dr. Shafrir’s report wherein he indicated that A.K.’s loss of speech was the

first indication of A.K.’s alleged regression. Pet Ex. 63 at 11-14. However, Dr. Shafrir had not seen the

videos when he wrote his expert report. Tr. 458-59. He testified that he still opined there was a loss of

speech, but that the behavior change seen in the videos is “much more dramatic.” Tr. 530-31. Doctor

Shafrir’s assertion regarding speech loss is addressed in Section VII.C, below.
74

presented more pronounced developmental problems. Tr. 283-84; Pet Ex. 107 at 6.

For the reasons described below, I find respondent’s interpretation of the videos more

persuasive.

1. Doctor Shafrir’s Interpretation of the November 9 and 10 Videos Was Not

Persuasive.

The November 10, 2001169 video shows A.K. at his second birthday party

surrounded by many other children of various ages. Pet. Ex. 236, 64KV. For much of

the video, A.K. wandered throughout the large room, which appeared to be an activity

room at a community center or similar facility. He does not interact with the other

children and does not engage with the adults who attempt to get his attention, nor does

he participate in the activities presented for the children. For example, when the other

children sat in a circle and used sticks to tap along to a song, A.K. wandered the

perimeter of the room and twirled the sticks. Id. The experts all agreed that A.K.’s

behavior at this party shows clear signs of ASD. See, e.g., Res. Ex. SS at 7-8; Tr. 471,

900-02. Doctor Shafrir, in particular, described the autistic features on display in this

video as “absolutely striking.” Tr. 471.

In contrast, the November 9 video depicts a family gathering in [A.K.’s * * *] home

to celebrate A.K.’s second birthday. The more intimate in-home setting marks a

contrast to the larger, louder party of November 10. The clip played during the hearing

shows A.K. unwrapping and receiving presents, including an “Elmo” toy and a train set,

and having “happy birthday” sung to him. Pet. Ex. 236, 63KV. According to Dr. Shafrir,

this clip shows that as a matter of personality A.K. is quiet and less outgoing than his

sister, but that he is “more or less normal.” Tr. 472-73. Doctor. Shafrir stressed that the

video showed that A.K. could engage in interaction and could show enthusiasm.170 Tr.

473.

According to Dr. Miller, the November 9 video, just as the November 10 video,

largely shows A.K. wandering around without paying much attention to the people

around him. Tr. 904-07. She indicated that the video showed that it was difficult for

169 The videos were originally filed by petitioners on eight CDs marked Pet. Exhibits 109- 116. Petitioners

subsequently refiled the footage in reduced “clips” that extracted the footage specifically pertaining to A.K.

These reduced clips were filed as Exhibit 236, with individual clips identified by number with the initials

“KV.” The November 9 video of A.K. was resubmitted for presentation at the hearing as Exhibit 236,

63KV, and the November 10 video as Exhibit 236, 64KV.

170 The video clearly showed A.K. smiling and responding when his family began singing “Happy

Birthday.” Importantly, Dr. Miller noted that even though that represented a social response, A.K. did not

voluntarily seek out affection. Tr. 904. She acknowledged that the video footage in this case does show

occasional “good” moments of appropriate social interaction. Her testimony was that those moments

were far, far fewer than would otherwise be expected. Tr. 1041-42. In contrast, Dr. Shafrir rejected the

idea that anything less than “striking” features of autism should be considered significant. Tr. 473-74.

Doctor Shafrir appeared to opine that the fact that A.K. could be induced to interact or become

enthusiastic at all, was an indication that he was not autistic. Tr. 474-75. In this regard, Dr. Shafrir

attempted to use the presence of behaviors present in typically developing children to “rule out” ASD, but

ASD cannot be ruled out because particular behaviors are “normal” or not diagnostic of ASD. It is the

presence of the abnormal behaviors that leads to the ASD diagnosis; but the concurrent presence of other

behaviors that are present in typically developing children does not nullify the diagnosis.
75

people to get A.K.’s attention, noting in particular his lack of interest in his sister’s

dancing. Tr. 904. She also pointed out that A.K. remained focused on or distracted by

his toy train cars. Tr. 905-07.

Doctor Miller explained that, at two years of age, A.K. should have had the

cognitive ability to recognize that a wrapped birthday present was for him and that it

would contain something intended for him. Tr. 905. However, A.K. did not stay

engaged in opening the present, and that when he was participating, he seemed

focused on the wrapping paper itself, not what it contained. Id. His face did not register

any emotional change when the new toy was revealed. Id.

Specifically, Dr. Miller pointed out that A.K. initially failed to recognize the Elmo

doll as a depiction of the Elmo character, and instead became fixated on the toy doll’s

eyeball. This is similar to the behavior he exhibited on November 10. When A.K. met

the costumed Elmo character, he became fixated on the fur of the costume, rather than

interacting with the character. Tr. 902-03.

In addition, Dr. Miller noted that the November 9 video showed A.K. banging the

toy train cars together as mere objects rather than playing with them as parts of a toy

train. Tr. 905. This behavior appears akin to the manner in which A.K. interacted with

the sticks at the larger November 10 party: he was unable or unwilling to use the sticks

in accordance with the organized activity.

These behaviors are consistent with the signs and symptoms Dr. Miller discussed

from the ADOS module for the appearance of ASD behaviors in children one 

to two years of age. See, e.g., Res. Ex. CCC at 9. Although the setting and the 

obvious dichotomy between A.K. and other children made A.K.’s behavioral differences

more obvious in the November 10 video, the parallel between the two videos in terms of

A.K.’s reaction to Elmo is striking, as is A.K.’s propensity in both videos to separately

bang or twirl the sticks and train cars without apparent interest in the others in the room.

In both videos, A.K. demonstrated a lack of imaginative play (an inability to recognize a

“pretend” Elmo) and instead engaged in object-focus regarding Elmo’s eyeball on

November 9 and fur on November 10. While sitting in his box and banging the train cars

on November 9, A.K. failed to respond to his father calling his name three or four times. 

Pet. Ex. 263, 63KV. He similarly failed to respond to his name in the November 

10 video. Tr. 903; Pet Ex. 236, 64KV. A child’s failure to respond to his own name is

specifically noted as a warning sign in the ADOS. See, e.g., Res. Ex. CCC at 9. In fact,

Dr. Miller testified that failing to respond to one’s name is specific to autism, constituting

a “big red flag.” Tr. 1007-08. A.K.’s failure to respond to his name in the November 9

video, when in a familiar environment with fewer distractions, may be of more

significance than the similar failure on November 10, when in a less familiar

environment with more distractions.

Dr. Miller also noted that the November 9 video shows A.K. holding his ear. Tr.

904. This is a behavior that Dr. Miller noted across many of the videos, including the

November 10 video, as well as in a subsequent video from March 2003, a time after

which it is undisputed that A.K. was symptomatic for ASD. See, e.g., Tr. 897, 901, 904.

Significantly, the ear holding could also be seen in videos as early as about 14 months

of age. Tr. 916. Doctor Miller opined that A.K.’s ear holding, which is shown
76

consistently throughout the videos, is a mannerism consistent with ASD. Tr. 932-33.

Although A.K.’s medical records do note A.K.’s ear holding as a possible symptom of

teething (e.g. Pet Ex. 61, p. 56), Dr. Miller noted that A.K. does not appear to be holding

his ear out of pain, and that the consistency over time of his habit of ear holding

suggests it is not related to teething (Tr. 932-33).

Moreover, in addition to Dr. Miller’s competing opinion, Dr. Shafrir’s interpretation

of the videos is undercut by the fact that petitioners’ other experts did not appear to find

the same significance in the November 9 and 10 videos. Whereas Dr. Shafrir testified

that the November 9 and 10 videos displayed an “amazing change” constituting “the

most dramatic appearance of behavior change I’ve seen in my career” (Tr. 528), neither

Dr. Kendall nor Dr. Megson expressed any similar opinions. Although Dr. Kendall

indicated that A.K.’s second birthday party represented the time when A.K. began losing

his social connectedness, she did not specifically cite the distinction between the

November 9 and 10 videos. Tr. 281-84. Indeed, Dr. Kendall did not offer any testimony

regarding the November 9 video at all. For her part, Dr. Megson, like Dr. Miller,

highlighted the fact that on November 9, A.K. retreated to his blue box to hold his two

train cars and did not vocalize much. Pet. Ex. 107 at 5. At no point in her report did Dr.

Megson draw any specific contrast between the November 9 and November 10 videos.

Instead, Dr. Megson contrasted A.K.’s behavior at the larger birthday party with his

behavior in early videos from September of that year.171 Id.

Doctor Shafrir contended that the November 9 video, when contrasted with the

November 10 video, showed a dramatic and overnight change. Tr. 470. In my viewing

the two videos, both at and after the hearing, it is clear that the November 10 video

places A.K.’s behavior in stark and startling contrast to the behavior of the other

children. However, in the November 10 video, the focus of the camera is almost

exclusively on A.K. in a setting where his behavior is qualitatively and dramatically

different from that of the other children present. In contrast, the November 9 video is

not so exclusively focused on A.K., and he is not in a place where the presence of other

children and activities could be overwhelming. When viewing the two videos at and

after the hearing, I found Dr. Miller’s description of A.K.’s behavior in the November 9

video as showing features of ASD to be accurate and convincing. I noted what she

testified about—that the difference between the two videos does not reflect a distinction

in A.K.’s behavior so much as the larger, louder party puts that same behavior in a

context which makes it appear more obvious. Tr. 907. I agree with Dr. Miller’s

interpretation. I find that the November 9 and November 10 videos do not evince the

dramatic change in A.K.’s behavior that Dr. Shafrir contends they do. Rather, I find that

171 Doctor Megson’s ultimate conclusion was that A.K.’s developmental problems began to become more

pronounced after his second birthday, citing November 9, 2001, as the key date. Pet. Ex. 107 at 6. At

first blush, this would appear to directly contradict Dr. Shafrir’s contention that A.K.’s behavior on

November 9 was “more or less normal.” I note, however, that Dr. Megson incorrectly indicated that both

of A.K.’s birthday parties occurred on November 9. Pet. Ex. 107 at 5. Although this error makes her

precise meaning unclear, the resulting ambiguity underscores the fact that, unlike Dr. Shafrir, she did not

describe any clear contrast between the two videos and did not seek to distinguish between the two.

Indeed, Dr. Megson’s opinion was that the critical period of regression occurred in December 2001. Id.
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both the November 9 and November 10 videos show behaviors consistent with A.K’s

later ASD diagnosis.172

2. Earlier Videos and Medical Records Also Demonstrate Behaviors Consistent

with ASD Much Earlier than A.K.’s Influenza Vaccinations.

In addition to noting the presence of ASD features in the November 9, 2001

video, Dr. Miller also opined that videos dating as far back as January 2001, when A.K.

was approximately 14 months old, also show A.K. exhibiting behavior indicative of ASD,

at a time long before he received the influenza vaccines at issue in this case. Doctor

Miller also pointed out notations in A.K.’s pediatric records that point to an earlier onset

of ASD than petitioners claim.

In a video dated August 26, 2001, A.K. was at a restaurant with his grandmother.

Pet. Ex. 236, 58KV. According to Dr. Miller, this video shows A.K. failing to respond to

his name several times, and only responding to his grandmother’s prompts once she is

extremely close, close enough to be felt. Tr. 907. Failing to respond to one’s name is

“a big red flag” in terms of ASD screening. Res. Ex. CCC at 9; Tr. 1007-08. Doctor

Miller also suggested a lack of appropriate social interaction in this video segment.

Although Dr. Megson’s characterized A.K. as “extremely responsive” to his grandmother

in this video (Pet. Ex. 107 at 4), Dr. Miller noted that A.K. did not maintain the interaction

and instead appeared to simply watch the movement of his grandmother’s mouth. Tr.

908-09, 1008-10. She did agree, however, that he smiled. Id. According to Dr. Miller,

even accounting for his language delay, A.K should have been reflexively mimicking his

grandmother’s motions. Tr. 909. Absent that type of response, Dr. Miller opined that

this is not actually a social interaction.173 Tr. 909.

In a video from June 2001, when A.K. was about 19 months old, A.K. was shown

at home with his family, spending much of his time in the video playing with a bat. Pet.

Ex. 236, 53KV. In this video, A.K. did not appear to demonstrate age-appropriate,

purposeful play with the bat, according to Dr. Miller. Tr. 910. Rather, he appeared to

simply flip it around while pacing or wandering. Id. This behavior with the bat was quite

similar to his behavior at the birthday party depicted on the November 10 video, where

he was twirling the sticks while wandering. I note the similarity in these behaviors in

172 To the extent that Dr. Shafrir has contended that A.K. was “more or less normal” appearing during the

November 9 video (Tr. 472-73) and would attribute the different interpretations to his assertion that “you

cannot make comments about thing[s] that you expect to see but don’t see” in videos” (Tr. 470), I stress

that upon my viewing of these videos I find the ASD-like behaviors described by Dr. Miller to be readily

observable. I add that video evidence is frequent filed in contested cases alleging vaccine causation of

ASD, and I have viewed video evidence in at least 30 cases, including the OAP test cases.

173 During the hearing, Dr. Shafrir was shown this August 2001 video in conjunction with the November 9,

2001 video. Tr. 472. It is obvious from his overall testimony that he believed that, like the November 9

video, it showed A.K. as being “more or less normal,” but he did not offer any testimony specific to this

video. Tr. 471-75. Doctor Kendall testified that this clip showed A.K. making eye contact and being

interactive. Tr. 282-83. Doctor Miller noted that it was difficult to tell if there was any eye contact because

A.K.’s grandmother was wearing sunglasses. Tr. 1008. I agree with Dr. Miller’s impression that A.K.’s

gaze appeared to be on his grandmother’s mouth and not as far up as her eyes, perhaps because A.K.’s

grandmother was exaggerating her pronunciation and facial movements while repeating the words “ball”

and “pencil.”
light of Dr. Shafrir’s testimony that A.K. displayed a classic ASD presentation on the

November 10 video. The flipping and twirling of the bat and sticks represents

circumscribed interests, a DSM symptom of ASD, according to Dr. Miller. Res. Ex. CCC

at 18.

Moreover, as in the other videos, at 19 months of age, A.K. showed a lack of

appropriate social interaction. Tr. 910-12. Doctor Miller testified that he mostly kept a

neutral facial expression, wandered back and forth in a repetitive manner, and failed to

keep interactions going. Id. For example, during an attempt at playing peek-a-boo with

a blanket, A.K. did not look at his mother and instead simply hit the blanket with his bat.

Tr. 910. A.K. enjoyed a sensory activity, being tickled, but did not keep the interaction

going. Tr. 911. Once again, he failed to respond to his name after multiple prompts.

Tr. 910. These types of behaviors reflect a lack of nonverbal communication, a lack of

social sharing, and a lack of emotional reciprocity, all indications of ASD under the

DSM. Res. Ex. CCC at 18.

In another clip from June 2001, Dr. Miller noted that A.K. was being prompted by

the phrase “diggly do.” Tr. 912-14; Res. Ex. 114, file 1. Doctor Miller opined that “diggly

do” is representative of “jargon.”174 Tr. 912-14. She noted that jargoning is distinct from

babbling and jargon is common among children with ASD. Id. She explained that

specialists refer to “jargon” as a technical diagnostic term distinct from “babbling.” Tr.

927-28, 1038-40. Babbling constitutes the beginning of speech and will ultimately lead

to proper speech, but jargon has none of the inflection of babbling. It does not lead to

proper speech, but is rather a form of self-stimulating behavior symptomatic of ASD. Tr.

1038-40. Once again, Dr. Miller asserted that A.K.’s use of stereotyped language is a

symptom of ASD appearing in the DSM. Res. Ex. CCC at 18. She also noted that this

video showed that A.K. was not engaging in a functional way with the objects he

encountered and that he did not initiate any interaction with anyone, and that a child of

his age would be expected to display those behaviors. Tr. 912-14.

According to Dr. Miller, a video from February 22, 2001, when A.K. was about 15

months old, shows a good moment where A.K. responded to his name (though not on

the first try) and smiled. Res. Ex. 113, file 1; Tr. 914-16. She noted, however, that that

interaction did not persist and that for the remainder of the video there was no more

social interaction. Id. At that age, there should be “hundreds” of such moments of

interaction. Id. Similarly, a video from about a month earlier, on January 15, 2001,

showed some good signs, such as the potential beginning of pretend play as A.K. lifted

a phone to his ear. Pet. Ex. 236, 22KV; Tr. 916-17. Nonetheless, there were numerous

indicators of ASD in the same clip. For example, Dr. Miller indicated that A.K. failed to

respond to his name.175 Tr. 916. He appeared to be exploring his toys in a non174 Although this clip only shows A.K.’s parents using the term “diggly do” and not A.K. himself, Dr. Miller

testified that based on the parents’ use of the phrase, she believed it was fair to infer that A.K. used it as

well. Tr. 1042-43. She also testified that she did recall A.K. using the phrase himself on another video,

though she did not specify what video. Id. Tr. 1042-43. But in any event, A.K.’s use of jargon is not in

dispute. Petitioners’ expert Dr. Megson indicated in her expert report that A.K. could be heard jargoning

in videos as early as 15 months of age and as late as three and a half years of age. Pet Ex. 107, at 3.

175 She observed that an alternate explanation of A.K.’s lack of response in both the 14 month and 15

month videos was that A.K. may have been distracted by the television. Tr. 915-16.

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79

functional way, failed to maintain interaction, engaged in hand flapping and repetitive

behavior, and paced in the same manner as in other videos. Tr. 917-18. According to

Dr. Miller, the whole “the lack of responding when other people are trying to get his

attention and the lack of other functional play all comes together to indicate that this

[behavior].is not typical”176 Tr. 919.

Although Dr. Megson’s report indicated that A.K.’s developmental “slow-down”

increased “markedly” following his vaccinations, she nonetheless noted that “from 16-24

months of age, he seems to plateau in his level of alertness, and processing language.”

Pet. Ex. 107 at 6. Thus, in some degree, one of petitioners’ own experts confirms Dr.

Miller’s opinion that A.K. showed signs of difficulty prior to his vaccinations, albeit while

disagreeing as to the ultimate significance of those observations. Doctor Megson

opined that “the video shows repeated instances of excellent social engagement and

normal interaction” prior to age 24 months, but also noted instances of behavior

seemingly consistent with Dr. Miller’s observations. For example, Dr. Megson observed

that A.K. appeared “somewhat self-absorbed” in videos from about age 19-20 months

and “a little less aware of his environment” just a couple of months prior to his

vaccinations. Pet. Ex. 107 at 3-4. She also noted several points at which A.K. was

jargoning. Id.

On the whole, however, I attach less weight to Dr. Megson’s report than I do to

Dr. Miller’s testimony because Dr. Megson’s characterizations of the videos run counter

to what I observed while viewing them. For example, while Dr. Miller clearly

demonstrated at the hearing that A.K. was hand-flapping, playing with his ears and

failing to respond to his name as early as 14 months of age, behaviors I was able to

observe first-hand while the videos played, Dr. Megson intimated that these behaviors

first appeared after his influenza vaccinations. Pet. Ex. 107 at 5. Based on Dr. Miller’s

testimony, as well as my own observation of the videos, I find that Dr. Megson’s

assertions are simply incorrect. Similarly, Dr. Megson described the above-discussed

August 26, 2001 video of A.K. with his grandmother as showing A.K. was “extremely

responsive” and specifically noted that he “turns in immediate response to her.” Pet.

Ex. 107 at 4. Having viewed these videos myself, I do not find these characterizations

accurate. While there is clearly some room for disagreement regarding the level of

interaction between A.K. and his grandmother, it is very clear that Dr. Megson’s

description of A.K. turning “in immediate response” is a mischaracterization. In fact, as

176 On cross-examination, Dr. Miller was also shown video clips from October and May 2001. Tr. 1008-

22; Pet Ex. 236, 60KV, 40KV. The October 2001 video, in particular, was one that Dr. Kendall described

as showing purposeful play and engagement with A.K.’s sister. Tr. 283. However, Dr. Miller disputed 

that the video showed A.K. playing with his sister. Rather, she noted that he was focused on his toy and

that the two were just playing “near” each other, known as “parallel play,” a type of play significant for its

lack of interaction. Tr. 1010-11. She felt that the October 2001 video – showing A.K. and his mother with

a bat and ball – showed a lack of social interaction, although it did show that A.K. was capable of

establishing some level of routine. Tr. 1014-17. Counsel questioned Dr. Miller extensively regarding

moments of the film that may have shown A.K. making eye contact with his mother, but she felt the video

was inconclusive about eye contact, in that A.K.’s mother was out of view. Tr. 1017-22. She also

commented on how A.K. viewed the ball, asserting that it was unusual in that A.K. had been playing with

it for some time, but suddenly focused his gaze on it. Tr. 1022.
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noted above, A.K. failed to respond to his grandmother calling his name twice before he

turned to look at her.

Moreover, despite having noted at least some delay or plateau in both A.K.’s

language and alertness prior to age two, Dr. Megson’s report seems to strain to

minimize the significance of A.K.’s pre-vaccination behavior. That is, she noted similar

behaviors occurring both pre and post-vaccination, but sought to characterize only those

behaviors relative to the post-vaccination footage as symptomatic of ASD. For 

example, she noted that A.K. was seen “wandering about” in videos at both 15 months

of age and also at about age four and a half, but only ascribed a lack of social interest to

that wandering in connection with the later, post-vaccination, video. Pet. Ex. 107 at 3-4.

Having viewed these videos, I find no basis for the failure to treat similar behavior as

symptomatic of ASD.177

I also note that Dr. Miller’s opinion was fully corroborated by Dr. Cohen’s report.

Res. Ex. SS. Although Dr. Cohen did not testify in detail about the videos, he was

present in the hearing room during her testimony, and expressed his complete

agreement with that testimony. Tr. 1148-49. His report included his conclusions based

on the video footage, conclusions that are substantially similar to Dr. Miller’s

observations. Res. Ex. SS at 5-8. Like Dr. Miller, he opined that “the video recordings

of A.K. demonstrate a child who began showing signs of atypical developmental

behavior sometime between January and March 2001. By March 2001, there was

marked impairment of social skills and by June 2001, A.K. was evidencing problems

with expressive language skills . . . the video recordings made during and after June

2001, and up through October 31, 2001, before his first influenza vaccine, clearly

demonstrate a child who showed behavior as seen in autism.” Res. Ex. SS at 8.

In contrast, Dr. Shafrir did not offer any opinion or testimony specific to any of

these videos. His only response to Dr. Miller’s opinion regarding these early videos was

to generally assert that it is error to attempt to identify what he considers to be “subtle”

early signs of autism. Tr. 473-74. However, Dr. Shafrir never substantiated his opinion

that all features of ASD must necessarily be striking or dramatic. Doctor Shafrir testified

that “autism is not a subtle condition” and that “everybody can make a diagnosis of

autism.” Tr. 483. But these statements completely beg the question of any distinction

between actual onset and perceived onset, early symptoms and those that manifest at a

point when “everybody” can agree that an autism diagnosis is appropriate. They reveal

Dr. Shafrir’s lack of understanding regarding the screening techniques Dr. Miller

177 Although she did not specifically identify these videos as she did with other examples, Dr. Megson

appears to have been comparing a video from either February or March 2001 in which A.K. is at home

during a birthday party for his sister (she noted he was wandering around with a piece of bread) to a

video from A.K.’s fourth birthday party. Pet. Ex. 113, files 1 and 2. Although there is a moment in the

earlier video where A.K. accepted a cup of juice from his mother, at no point did he seek out any

interaction with anyone. In fact, at one point during the video A.K. appeared completely oblivious to his

sister, who was poking him. I do note that there are moments in the earlier video where A.K. appeared to

be laughing or smiling, although not at or with anyone. For example, at one point he laughed when

shown a party favor. This does contrast with the later video in which A.K.’s expression appeared more

disinterested. Overall, however, both videos appear consistent with the type of wandering and lack of

interest that Dr. Miller noted during her testimony.
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explained in detail. They may also reflect Dr. Shafrir’s own experience in that his

patients are referred to him for ASD diagnosis — a point when other have recognized

already that a child may be autistic.

In effect, Dr. Shafrir contended that autism is not autism until its appearance is so

obvious that even a lay person can recognize it. As Dr. Miller explained, the

appearance that ASD is worsening stems from the fact that when a child with ASD

plateaus in development, the absence of skills becomes more pronounced over time

because the gap between the condition of the child with ASD and the expected

development curve for a typically developing child becomes wider as more milestones

are missed. Tr. 998-99. As Dr. Shafrir would have it, however, early indications of

developmental problems should not be viewed prospectively as indicators of autism

unless or until the condition is obvious. Tr. 483. At no point, did Dr. Shafrir address the

question of whether such developmental problems, when viewed in hindsight, can be

linked to autism once a stable ASD diagnosis has been confirmed. Doctor Miller did

address this question in detail, and her testimony regarding the early video footage is

very persuasive.

Doctor Miller linked her analysis of the video footage to A.K.’s medical records.

Although the experts on both sides expressed the view that A.K.’s earlier pediatric

records were of limited use in determining the true nature of his development (Tr. 461,

921-22), Dr. Miller pointed out that some of these records include notations that reflect

“red flags” (Tr. 921-22). For example, Dr. Miller pointed out that on April 4, 2001, when

A.K. was approximately 17 months old, a health care provider characterized him as a

“fearless Wildman.” Tr. 928-29; Pet. Ex. 61, p. 68. She noted that it is an unusual

notation for a pediatric record. Tr. 929. Doctor. Miller acknowledged that this phrase in

isolation is subject to multiple interpretations, but stressed that particularly in light of the

videos, it may well be an indication that A.K. lacked social or safety awareness. Id.

That is, it may indicate that he was susceptible to wandering without “checking in” with

his parents. Id.

Doctor Miller also noted that at two years of age, A.K.’s pediatric record

described him as “self-sufficient.” Tr. 933-35; Pet. Ex. 61, p. 55. A record from

December 17, 2001, described him as “very focused.” Pet. Ex. 61, p. 54. Doctor Miller

opined that these notes were unusual and not age-appropriate. Tr. 933-37. In her

opinion, they were indicative of A.K.’s general propensity in the videos to wander and

not respond, i.e. to “be in his own world.” Id. Again, this evidences a lack of social

sharing or emotional reciprocity. Res. Ex. CCC at 18. In addition, as noted above, Dr.

Miller explained that the references in A.K.’s pediatric records to ear rubbing, though

attributed to teething at the time, likely show evidence of a mannerism or stereotyped

behavior related to his ASD. Tr. 932-33; Res. Ex. CCC at 18; Pet. Ex. 61, p. 56.

3. Petitioners’ Arguments against Consideration of the Video Footage Are

Without Merit.

Finally, the most basic issue raised by petitioners with regard to the videos is

whether it respondent should be permitted to rely on the video footage at all. In raising

this point, petitioners seek to use the video footage both as a shield and a sword. On

the one hand, they affirmatively rely on the videos, arguing repeatedly that their own
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testimony, as well as the opinions of both Drs. Shafrir and Kendall, is corroborated by

the videos. ECF No. 297 at 18, 21, 40, 48, 56. Yet, to the extent respondent’s experts

noted that the video evinced behaviors contrary to petitioners’ description of onset, they

then assert that “the video record provides mere intermittent snippets of A.K. The video

is not a clear chronology fully depicting A.K.’s life. The video record is an insufficient

evidence source from which to draw diagnostic conclusions.” ECF No. 297 at 86. In

particular, Dr. Shafrir testified that it is “profoundly wrong” to review video footage for

signs of autism. Tr. 467. He testified that “I don’t think anybody can make a diagnosis

of autism based on a few minutes of videotape. . . . You can see behaviors and identify

behaviors that you see in autistic children, but can you say that you can make the

diagnosis of autism using videotapes, it’s just ludicrous.” Tr. 467.

In making this argument, both petitioners and Dr. Shafrir mischaracterized the

nature of Dr. Miller’s testimony and evinced a misunderstanding of the scientific bases

for the utility of videos in the diagnosis of ASD. At no point did Dr. Miller indicate that

she was “diagnosing” A.K. based on the video footage alone. Rather, Dr. Miller testified

that her opinion that A.K. has ASD was based on the complete medical record,

including contemporaneous evaluations, “supplemented” by the videos. Tr. 896; Res.

Ex. OO at 3-5. Due to the state of screening techniques available at the time A.K.’s

ASD manifested, the medical records did not address enough behaviors to support a

diagnosis on their own. It was significant for her testimony that the videos and the

records together “point[ed] toward the same direction.” Tr. 921-22. She indicated that

she could see “a lot more behaviors in the videos than are in the record before the age

of two” but noted that the medical records did raise “some pretty significant red flags.”

Id.

Thus, petitioners’ criticism is misplaced. As noted above, Dr. Shafrir himself

acknowledged that on video “you can see behaviors and identify behaviors that make

you worried, you can see behaviors that you see in autistic children.” Tr. 467. That is

exactly what Dr. Miller did. As noted in the prior section, there is a difference between

engaging in diagnosis and recognizing with the benefit of hindsight that certain signs or

symptoms are indicative of a subsequently diagnosed condition. Indeed, Dr. Miller

testified that stable diagnosis of ASD is possible only at about two years of age. Tr.

870-71. Thus, the question is not whether the videos are diagnostic of A.K.’s ASD in

themselves, but whether A.K.’s behavior in the videos is consistent with or contrary to

petitioners’ description of the timeline of onset.

Moreover, Dr. Miller was convincing when she explained as a general matter that

videotapes are useful diagnostic tools. Tr. 919-21. She noted that, beginning about 10-

15 years ago, studies were conducted to see whether home videos could be used to

provide diagnostic consistency in the face of inconsistent or unreliable parental

reports.178 Tr. 920-21. She indicated that those studies found that additional social

178 Some of these studies were filed as exhibits in this case. See, e.g., Res Ex. C, A. Mars, et al,

Symptoms of pervasive developmental disorders as observed in prediagnostic home videos of infants

and toddlers, PEDIATR., 132(3): 500-04 (1998) (finding that children later diagnosed with PPD could be

differentiated from typically developing peers on the basis of specific anomalies, such as a lack of joint

attention, observed in home video footage); Res. Ex. D, E. Werner, et al, Brief Report: Recognition of

Autism Spectrum Disorder Before One Year of Age: A Retrospective Study Based on Home Videos, J.
83

behaviors indicative of ASD, that otherwise would have been missed, were present on

the videos. Tr. 920. For example, a journal article filed with Dr. Miller’s expert report

found that parental reports are particularly unreliable with regard to non-language

behaviors, and that such parental reports benefit from confirmation by supplemental

sources such as videos. See Res. Ex. OO, Tab 1, W. Goldberg, et al, Use of Home

Videotapes to Confirm Parental Reports of Regression in Autism, J. AUTISM DEV.

DISORD., 38: 1136-1146 (2008). Another study filed with Dr. Miller’s report found that

“there is low agreement between parent report and home video” and suggested that

“later aberrant patterns of development likely stand out to parents because of their

alarming nature, proximity in time to the interview, and consistent with their child’s

current presentation.” Res. Ex. OO, Tab 4, S. Ozonoff, et al, Onset Patterns in Autism:

Correspondence Between Home Video and Parent Report, J. AM. ACADEMY CHILD &

ADOLES.T PSYCHIATRY, 50(8): 796-806 (2011) [hereinafter “Ozonoff, Res. Ex. OO, Tab

4”]. Doctor Miller also pointed out that home videos are especially useful in that they

depict a child in a familiar environment, allowing the clinician to account for behaviors

that should be attributed to the clinical setting. Tr. 920-21. She further noted that home

videos remain a diagnostic tool in current use by practitioners, particularly with regard to

the emergence of early behaviors that cannot be fully observed during clinical

observation. Tr. 921.

By contrast, Dr. Shafrir failed to provide any substantial basis for his rejection of

videotapes as an aid screening for ASD. With hyperbole typical of his testimonial

criticism of mainstream medical approaches to ASD, he characterized the use of

videotapes in autism diagnosis as “one of the blackest chapters of pediatrics.” He then

focused the brunt of this criticism on the moral implications of using videotapes to

screen foreign adoptees for signs of autism. Tr. 467-69. While such a practice may be

troubling, Dr. Shafrir’s testimony on that practice was a non sequitur. The use of videos

in the instant case does not have any of the moral implications Dr. Shafrir decried.

Moreover, nothing in Dr. Shafrir’s testimony indicated any basis for claiming that use of

videos as part of ASD screening would be inaccurate or ineffectual. In fact, Dr. Shafrir

indicated that he was unaware of any of the studies regarding the use of videotapes to

aid in diagnosing autism. Tr. 570-71. While Dr. Shafrir cautioned with regard to video

footage that, “I really feel that you cannot make comments about thing[s] that you

expect to see but don’t see,” he also conceded that “you can identify autistic behaviors

or behavior that are frequently found in autistic children in a videotape.” Tr. 470. Thus,

Dr. Shafrir’s harangues aside, he did not actually opine that the use of video would lead

to inaccurate diagnosis or wrong conclusions.179

AUTISM & DEV. DISORD., 30(2): 157-62 (2000) (a study finding that early onset ASD can be detected on

video as early as 8-10 months of age and noting that failing to response to one’s name is a particularly

evident feature of early onset ASD) Res. Ex. E, E. Werner, et al, Validation of the Phenomenon of Autistic

Regression Using Home Videotapes, ARCH. GEN. PSYCHIATRY, 62(8): 889-895 (2005) (study concluding

that parental reports of regression on the ADI-R can be validated using home video footage.)

179 In fact, when viewed in the full context of his testimony, Dr. Shafrir’s attempt to distinguish between

affirmative signs of autism observable on video and “things you expect to see but don’t” appears to be

more of a semantic distinction than anything. Despite attempting to discredit Dr. Miller’s opinion on that

basis, Dr. Shafrir’s opinion regarding the contrast between the November 9 and November 10 videos was

entirely predicted on the fact that in the November 10 videos A.K. was not relating to or being social with
84

Petitioners advanced that particular argument themselves, contending that “the

testimony and evidence interpreting the tapes is fraught with inconsistency, as is

demonstrated by the inconsistent and at times polar opinions of the various experts who

testified concerning their respective interpretations of segments of the tapes.” ECF No.

297 at 86. That experts disagree is no basis for rejecting expert testimony. Petitioners’

concern does not implicate the usefulness of the videos themselves, which constitute

objective evidence, so much as the quality of the expert testimony in this case. The

qualifications of respondent’s witnesses to diagnosis ASD were far superior to those of

the experts upon whom petitioners relied. Inconsistencies among the experts’ opinions

actually make the videos all the more valuable as evidence, because it provides a

benchmark against which to assess the reliability and credibility of these experts. As

described above, I found Dr. Miller’s descriptions of the videos to be highly persuasive

in no small part because her observations tracked most closely to my own impression of

the videos whereas Dr. Shafrir’s description of a dramatic overnight change was

inconsistent with what I saw while watching the video footage.

Petitioners are also unconvincing in arguing that the videos are of little value

because they constitute only “intermittent snippets” of A.K.’s life. ECF No. 297 at 86.

Even accounting for the fact that the footage of A.K. himself is far less than the whole of

what was initially filed, multiple hours of video showing A.K.’s behavior were filed in this

case.180 In that regard, Dr. Miller was clear in explaining that in her opinion the available

video footage was in itself, without extrapolation, sufficient to demonstrate a 

clear deficit in A.K.’s social development. Tr. 1041-42. That is, Dr. Miller acknowledged

that there are instances in the videos which show A.K. engaging in developmentally

appropriate interaction, such as making eye contact (Tr. 1026-28), but stressed that

“based on the totality, he has extremely few moments that look good, and at his age

and across the number of hours of video we have, we should see hundreds of examples

of that kind of moment that we saw maybe two or three of.” Tr. 1042.

In any event, even if these videos were mere “snippets,” petitioners have

conspicuously stopped short of arguing that the clips are aberrations from A.K.’s overall

behavior. To the contrary, to the extent they assert that the footage corroborates their

own testimony and their experts’ opinions that A.K. was developmentally normal prior to

receiving his vaccinations, petitioners implicitly argued that these videos actually are

representative of A.K.’s overall behavior. ECF No. 297 at 18, 21, 40, 48, 56. And even

if there were times when A.K.’s behavior was substantially different (an unsubstantiated

others in the room or being incited to happiness. Tr. 476. Doctor Shafrir characterized this as dramatic

self-directed behavior, but one could easily characterize it as a lack of expected social interactions.

Indeed, Dr. Shafrir specifically cited A.K.’s failure to laugh, smile or clap his hands as distinguishing

features of the November 10 video. Tr. 478. Moreover, Dr. Shafrir testified that a September 2002 video

of A.K. showed “a traumatic severe classic autism” despite also testifying that in the same video “you

don’t see any positive autistic symptoms.” Tr. 476-77 (citing Pet. Ex. 236, 74KV). Thus, it is not really

clear in what way Dr. Shafrir’s approach to analyzing these videos actually differs in practice from Dr.

Miller’s, other than that Dr. Miller’s conclusions differed from his..

180 For her part, Dr. Miller estimated that there were approximately three to four hours of video of A.K.

prior to two years of age. Tr. 1043-44. Petitioners similarly estimated that 20-30% of the 12 hours of

footage originally filed is of A.K., which would amount to about three hours. ECF No. 297 at 86.
85

supposition181), Dr. Miller and Dr. Shafrir both made the point that ASD symptoms do

not have to exist at all points in time to be consistent with an ASD diagnosis. Tr. 478,

1005-08. The fact would still remain that the videos clearly show A.K. demonstrating

ASD-like behaviors at an age when petitioners contend that he was not.

In any child diagnosed with ASD, there was a point in time at which parents or

caregivers became concerned about the child’s behavior. They may have chosen to

acknowledge their misgivings and seek help or advice from physicians, therapists, or

friends. They may have chosen to engage in watchful waiting. They may simply have

put aside their concerns until they were confronted with something that they could not

ignore. The point at which their awareness that their child’s behavior differed

substantially from that of other children crystalized does not necessarily include a

regression or mark the first instance of abnormal behavior. It simply marks the point at

which excuses could no longer be made or that they finally became aware that

something was truly wrong. This does not mean that symptoms of ASD were not

present at earlier points in time.

C. Neither the Video Footage nor the Contemporaneous Medical Records Support

Petitioners’ Claim of a Speech Regression.

Notwithstanding the compelling evidence that A.K.’s ASD manifested far earlier

than A.K.’s second birthday, petitioners contend that A.K. experienced an autistic

regression that was most clearly evidenced by a loss of speech. Petitioners

acknowledged that prior to receiving his influenza vaccinations, A.K. may have

demonstrated “subtle” developmental delay that consisted of a slowing in A.K.’s speech

progress, but they argued that his loss of words following vaccination was distinct. ECF

No. 297 at 130. Doctor Shafrir initially relied very heavily on the idea that the onset of

A.K.’s condition was most clearly evidenced by his loss of speech. Pet. Ex. 63 at 11.

And although, he later opined that there was a more dramatic change in behavior visible

in the video footage discussed above, he still maintained that A.K.’s condition was

evidenced by a loss of speech following his November 2001 vaccination. Tr. 530-31.

Specifically, Dr. Shafrir indicated in his expert report that “the most crucial

dramatic and clearly defined component [of A.K.’s autistic regression] was the fact that

he stopped talking. This is a highly specific and unusual phenomenon in children, which

always imply [sic] brain injury, either permanent or transient.” Pet. Ex. 63 at 11. In

terms of timing, Dr. Shafrir testified that there was excellent documentation of A.K.’s

loss of language following his first dose of the influenza vaccine which worsened after

his second dose. Pet. Ex. 63 at 12. Specifically, Dr. Shafrir cited a December 17, 2001

notation indicating that A.K. had “no spontaneous speech” as indicating that A.K.

experienced a critical event that stopped all of his speech. Pet. Ex. 63 at 14. Doctor

Shafrir contended that record “is decisive and does not leave room for alternate

interpretation.” Id.

181 For example, petitioners’ own expert made a point of stressing that it is reasonable to view the videos

as representative of A.K.’s overall behavior. With regard to the behavior he observed during the

November 10 footage, which he pegged as the beginning of A.K.’s “dramatic” autistic behavior, Dr. Shafrir

colorfully quipped that somebody could tell him that A.K. “recited the Declaration of Independence”

between video clips, but that absent such information, the videos are what we have to go on. Tr. 478.
86

I do not find his interpretation of the record dispositive or credible. Doctor

Shafrir’s opinion is belied by the fact that A.K. began to show signs of speech difficulty

as early as 18 months of age. The record as a whole does not support the claim that

A.K. experienced a sudden loss of speech. Rather, as respondent’s experts suggested,

it appears more likely than not that A.K. experienced a speech impairment beginning at

about 18 months of age that became more concerning as A.K. fell further behind

developmental milestones and his ASD became more pronounced.182

1. The Onset of A.K.’s Speech Delay Was at about 18 Months of Age.

In their expert reports, both Drs. Kendall and Shafrir characterized A.K.’s 18

month well visit as reflecting normal language development. Doctor Kendall stressed

that A.K. was noted as having “short phrases,” while Dr. Shafrir indicated that A.K. was

reported as having a vocabulary of “about 20 words.” Pet. Ex. 65 at 2; Pet. Ex. 63 at 3.

Neither of these characterizations, however, is accurate. There is not much detail in the

18-month well visit record regarding A.K.’s development, but it does indicate that A.K.

was able to say “oh, look.” Pet. Ex. 61, p. 65. It also appears to indicate that A.K. was

using the words “yes,” “no,” and “more,” could point for needs, and was using

“jargon.”183 Id. There is nothing in that record, however, to indicate a broader

182 Petitioners argued in their post-hearing brief that A.K.’s onset of speech delay at 18 months is

irrelevant, because speech delay was removed from the DSM-V criteria for ASD. ECF No. 297 at 127-28.

Petitioners are partially correct, but effectively wrong. The DSM-IV-TR diagnostic criteria for autistic

disorder had three categories of behavior (social interaction, communication, and restricted repetitive and

stereotyped behavior), with diagnosis requiring qualitative impairments in each of the three categories.

Speech delay was a specific criterion in DSM IV-TR, under the category of communication. DSM -IV-TR

at 70-71, 75. The DSM V merged the communication and social interaction categories to create a

category called social communication and social interaction but there are no specific symptoms that must

exist, simply a non-exhaustive list of examples. Although speech delay is no longer listed as one of the

examples in the new DSM (DSM-V at 50), it remains a symptom of ASD. In a section of DSM-V’s chapter

on ASD, under the heading “Diagnostic Features,” the following explanation appears:

Verbal and nonverbal deficits in social communication have varying manifestations,

depending on the individual’s age, intellectual level, and language ability, as well as other

factors such as treatment history and current support. Many individuals have language

deficits, ranging from complete lack of speech through language delays, poor

comprehension of speech, echoed speech, or stilted and overly literal language.

DSM-V at 53. See also Tr. 890-91 (Dr. Miller explaining that while “the essence of everything that was in

DSM-IV is still in DSM-V,” language delay was removed as a listed diagnostic criterion in DSM-V because

it is not specific to autism.)

The explanation quoted above, along with Dr. Miller’s testimony, establishes that speech delay or loss

of speech remain symptoms of ASD, although they are less specific in pointing toward a diagnosis than

the repetitive mannerisms or restricted patterns of interest that A.K. also displayed. More importantly,

petitioner’s argument misses the point. The onset of A.K.’s speech delay is not significant merely

because it indicates that A.K. might have autism. It is significant because it speaks to the question of

A.K.’s overall language development. That is, it is evidence supporting respondent’s contention that A.K.

struggled to develop language skills in the first instance, rather than experiencing the type of sudden loss

of previously acquired skills that petitioners suggest. Regardless of whether it is a symptom of ASD,

petitioners have specifically argued that the pattern of A.K.’s speech development is evidence that their

experts’ theories of causation are correct. ECF No. 302 at 18-19.

183 As noted above, Dr. Miller indicated that specialists refer to “jargon” as a technical diagnostic term

distinct from “babbling,” in that it does not have intonation or lead to speech. Tr. 927-28, 1038-40. She
vocabulary beyond the three to four words explicitly mentioned, nor is there any

indication of additional phrases beyond “oh, look.” Indeed, Dr. Kendall acknowledged

this latter point when I questioned her about it. Tr. 345. Prior pediatric records do

indicate additional words A.K. had used. For example, at his 15-month visit, A.K. was

noted to say “good,” “dada,” and “ah.” Pet. Ex. 61, p. 69. But even taking these prior

records into account, I still do not see evidence in the pediatric records that A.K. had a

20 word vocabulary as Dr. Shafrir contended.184

Doctor Miller opined that although the 18-month record does not note any

concerns, the data recorded actually reflects language development that is “minimal for

this age.” Res. Ex. OO at 3. She did not necessarily believe the record reflected a

state of development likely to generate a high level of concern, as there was “some”

development. Tr. 930-31. Nonetheless, she felt the record showed language skills that

are “not great.” Tr. 931. Specifically, she noted that the record is insufficient to indicate

that A.K. had any of this vocabulary in any permanent sense. Rather, she interpreted it

as reflecting that the parents had reported that he said each word “at least once.” Tr.

930. She also cautioned that the reference to the phrase “oh, look” should not actually

be assumed to be the use of a phrase. Tr. 930-31. To be considered a phrase or

simple sentence, there would need to be evidence that A.K. was additionally using the

words “oh” and “look” separately. Id. There is nothing in the records to indicate that he

was doing so.

In contrast to Dr. Miller’s close reading of the record, both Dr. Kendall and Dr.

Shafrir seem to base their interpretation of the record as reflecting normal development

on expansive inferences drawn from these sparse notations. For example, Dr. Kendall

indicated that she reported A.K. as having multiple simple phrases on the assumption

that the notation of a single short phrase was intended as an example of the fact that

A.K. was generally capable of forming phrases. Tr. 345. More broadly, Dr. Shafrir

relied on the lack of any specific indication of a developmental concern as evidence that

no developmental problem was present. Tr. 493. When asked about his opinion

regarding A.K.’s speech development, however, Dr. Shafrir indicated that it was difficult

to develop such an opinion, because “the pediatric records are pretty sketchy.” Tr. 461.

He repeated later the point that because the pediatrician was “very, very brief in his [sic]

writing” it was “very difficult” to use the medical records to determine A.K.’s language

development. Tr. 530. This acknowledgement, coupled with Dr. Kendall’s and Dr.

Shafrir’s overstatements regarding the contents of the 18 month record, suggest that

these experts are straining to interpret A.K.’s earlier records, not as merely silent or

inconclusive, but as affirmatively reflecting normal speech development.

did not feel there was a basis, however, to conclude that A.K.’s pediatrician was making that distinction,

suggesting that references in A.K.’s medical records to jargon are likely more accurately interpreted as

babbling. Tr. 927-32. That interpretation would seem to be consistent with [A.K.’s mother’s] testimony as

well. [ A.K.’s mother] described both babbling and jargon as steps leading to speech. Tr. 28-29.

184 Years later, in 2004, Dr. Rapin took a history wherein A.K. was reported by his parents as having 20

words at two years of age. Ex. 11, p. 1. Nonetheless, she still characterized A.K. as having delayed

speech at two years of age. Id.

87
Moreover, petitioner’s own experts conceded that the video footage filed in this

case supported Dr. Miller’s interpretation that A.K. was experiencing speech delay by 18

months of age. That is, Dr. Kendall conceded that A.K. demonstrated speech delay in

the videos at 18 months of age, notwithstanding what the medical records reflected. Tr.

272-74, 283-84. Specifically, she acknowledged that, contrary to her initial report which

indicated A.K. was developmentally normal until November 2001, the videos taken

when A.K. was 18-19 months of age showed a lack of spontaneous or expressive

speech that was indicative of a speech delay.185 Tr. 290-92. Doctor Kendall declined to

identify a cause of A.K.’s early speech delay, but she conceded that it could be caused

by ASD.186 Tr. 292. Doctor Megson, a non-testifying petitioners’ expert in child

development, likewise indicated her report the videos of A.K. show “a very subtle

language delay emerge at 15 to 16 months, when [A.K.]’s vocabulary fails to increase

and two-word phrases are heard only sporadically.” Pet. Ex. 107 at 6. Although he

disputed its significance, Dr. Shafrir also acknowledged that the videos showed “very

little language.” Tr. 462.

Ultimately, Dr. Shafrir indicated that he believed the parental reports to be more

reliable in this case than either the video or the medical records. Tr. 529-32. In that

regard, it is significant that both [of A.K.’s parents], despite attributing a vocabulary to

A.K. of between 20 to 30 words,187 testified that they were concerned about A.K.’s

speech by the time of this 18 month visit. [ A.K.’s mother] repeatedly testified that she

first had concerns regarding A.K.’s speech when he was between 15 to 18 months

old.188 Tr. 33-34, 81. [A.K.’s father] similarly testified that he became concerned 

regarding A.K.’s speech at about 18 months. Tr. 99. Consistent with Dr. Miller’s 

interpretation of A.K.’s medical record, [A.K.’s father] testified that they were not

“especially concerned” about A.K.’s speech delay at that point, but that it was 

noticed.189 Tr. 100. Consistent with Dr.

185 During the hearing, Dr. Kendall viewed and discussed a video from March 2001 marked as Ex. 236,

clip 29KV. Tr. 260-63. She testified regarding clip 58 from August 26, 2001, clip 60 from October 2001,

and clips 64 and 66, from A.K.’s second birthday on November 10, 2001. Tr. 270, 275-76, 282-83. She

indicated, however, that her opinion reflected her impression of all 88 videos filed in this case. Tr. 283-

84.

186 In subsequent testimony Dr. Kendall did backtrack a bit insofar as she expressed doubt about the

significance of what she observed on the 18-19 month video when contrasted with the record of A.K.’s 18

month well visit. Tr. 411. However, she maintained her contention that the video showed a lack of

spontaneous speech. Id.

187 [A.K.’s mother] testified that A.K. had over 30 words. Tr. 63-64. [ A.K.’s father] testified that A.K. never

had more than 20 words. Tr. 112.

188 I note that this timing tracked with the allegations in this case when it was still an OAP test case. At

the time the petition was filed, the influenza vaccine which is now alleged to be causal was not a vaccine

covered by the Program. Influenza vaccine was not added to the Vaccine Injury Table until 2005, about

three years after the original petition was filed.

189 In their second amended complaint, petitioners argued that their early speech development concerns

were “unfounded,” because the concern was based, incorrectly, on the idea that A.K. should have

developed speech on a similar pace as his older sister. 2

nd Am. Pet. at ¶ 30. I note, however, that neither

of [A.K.’s parents] attempted to disclaim those concerns during their hearing testimony, beyond noting

that they were reassured by doctors that it was normal for boys to develop speech slower than girls. Tr.

32-34, 99-100. But in any event, [A.K.’s parents’] recollections are significant for the fact of what

they observed, not the significance they ascribed to those events. Neither of [A.K.’s parents] have any

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89

Miller’s interpretation of the medical record, [A.K.’s mother] testified that she raised her

concern about A.K.’s speech during that time period, but was told it was not a significant

concern.190 Tr. 33-34.

A.K.’s speech delay was first explicitly noted in his medical records at his 2 year

well child visit on November 21, 2001, approximately three weeks following his first

dose of influenza vaccine.191 Pet. Ex. 61, p. 55. His medical record described him as

jargoning and having the “beginnings or ends of words.” Id. At that point his

pediatrician recommended observation only. Id. To the extent [A.K.’s parents]described

that A.K. was speaking less, a concern which they raised at that visit with Dr. Zirin,

[A.K.’s father] testified that the diminution was “not dramatic.” Tr. 103. [A.K.’s] mother]

confirmed in her testimony that Dr. Zirin “did not seem at all concerned” about the

speech delay. Tr. 39. In fact, although [A.K.’s mother] testified that A.K. had stopped

speaking a few days after his first influenza vaccination (Tr. 64), there was no mention

of speech concerns when she called Dr. Zirin’s office on November 16, 2001 (Pet. Ex. 2,

p. 21). Rather, [A.K.’s mother] testified that, as of November 16, A.K. had other physical

symptoms related to nasal congestion and teething which she considered more

worrying. Tr. 65-67. In any event, [A.K.’s mother] described the loss of speech she was

concerned about as a lack of response or that he “wasn’t speaking spontaneously.” Tr.

64. In other words, it appears to be precisely the type of concern the experts in this

case observed when watching the videos dating back to 18 months of age.192

2. A.K.’s Subsequent Course is Consistent with a Continuation or Progression of

His Earlier Speech Delay.

Subsequently, on or about December 3, 2001, [A.K.’s] family visited Dr. Boris’s 

office for administration of influenza vaccines – the second dose for A.K. Tr. 40, 156-57.

[ A.K.’s mother] described A.K.’s speech as being “plateaued” at this point, neither

worsening nor improving in terms of his ongoing speech delay and lack of spontaneous

speech. Tr. 72. Doctor Boris testified that he recalled A.K. as appearing to be “a normally

functioning child” and indicated that he observed nothing “abnormal.” Tr. 158. On crossexamination, however, Dr. Boris indicated that he could not recall any of the

special competency in child development, but their observation that A.K.’s speech appeared delayed to

them is consistent with the considered opinions of experts on both sides of this case.

190 I note that A.K.’s pediatrician, Dr. Zirin, signed a declaration indicating that “prior to November 21,

2001, I made no observation of [A.K.] or notations in the medical record showing that he had any

developmental problem whatsoever.” Pet. Ex. 108 at ¶ 8. [ A.K.’s mother] testified that another partner

in the pediatric practice, Dr. Weindorf, discussed A.K.’s speech delay with her. Tr. 34.

191 To the extent that Dr. Shafrir relies at least in part on this notation as proof that A.K. lost speech after

his first dose of influenza vaccine (Tr. 531-33), I note that Dr. Shafrir indicated that he believes that

speech “delay” is a misnomer and a hedge for what he believes is more accurately termed speech

“impairment.” (Tr. 462-64.) Doctor Shafrir indicated that he believed pediatricians routinely hesitate to

document developmental delays and stressed that a notation of speech delay does not indicate when the

condition started or how severe it is. Id. Thus, Dr. Shafrir criticized his own reliance on that record.

192 [A.K.’s mother] asserted that A.K. lost vocabulary at that time, but was unable to give specifics beyond

noting that she believed he was “reduced to his basic beginning words,” and stressed that her concern

related to frequency. Tr. 64-65. She indicated that “I don’t remember the variety, but the frequency

diminished greatly.” Tr. 65.
99

details of his interactions with any of the four family members present for vaccinations.

Tr. 191-95. Moreover, in a prior declaration, Dr. Boris indicated that he did not conduct

a speech evaluation of A.K. despite being told by [A.K.’s mother] that the family had

concerns regarding A.K.’s speech. Pet. Ex. 47 at ¶ 11. At best, I take Dr. Boris’

testimony as an indication that he did not recall anything grossly abnormal about A.K.

(or anyone else in the family) at that visit. The record of this vaccination appears in

[A.K.’s mother’s] medical records, and it simply records that the vaccinations were

administered. Pet Ex. 118, p. 1; Tr. 190-91.

Approximately a week later, at a social function on December 9, 2001, Dr. and

Mrs. Boris had an opportunity to observe A.K. for an extended period. Tr. 198-200.

Mrs. Boris observed A.K. was playing, but was not nonresponsive to what was

happening around him, and brought the issue to Dr. Boris’s attention. That prompted

Dr. Boris to observe A.K. for the remainder of the afternoon. Tr. 199-200. Although Dr.

Boris indicated he believed there was a “marked” change in A.K. based on his prior

limited observations, he seemed to indicate that it was no cause for alarm, testifying that

he recommended that A.K. go for a hearing test, a normal first step, rather than believing

the situation warranted an emergency necessitating a hospital visit. 193 Tr.

199-201.

As Dr. Boris had recommended, A.K. had his hearing tested on December 12,

2001. Pet. Ex. 31, pp. 2-6. His hearing was within normal limits. Id.

At a pediatric visit on December 17, 2001, Dr. Zirin noted for the first time that

A.K. had “no spontaneous speech.” Pet. Ex. 61, p. 54. This is the record that Dr.

Shafrir characterizes as decisive evidence of a dramatic event that implies brain injury.

Pet. Ex. 63 at 11, 14. Contrary to Dr. Shafrir’s contention, however, the above timeline

suggests that the notation of “no spontaneous speech” on December 17 is simply the

culmination of an evolving understanding of A.K.’s lack of speech development.

Both of [A.K.s’ parents] testified that they were aware of delayed speech as early

as 18 months and had reported the same on multiple occasions and as recently as two

to three weeks prior to this alleged dramatic event. Moreover, [A.K.’s mother]

specifically indicated that her concerns regarding A.K.’s speech encompassed, by no

later than November 21, the issue of a lack of spontaneous speech. And indeed, the

videos filed in this case, as interpreted by the experts, confirmed a prior lack of

spontaneous speech. In particular, petitioners’ own expert, Dr. Kendall, specifically

193 Although Dr. Boris was A.K.’s pediatrician for the first year of life, Dr. Boris left the Woodbury pediatric

practice after that first year, and Dr. Zirin became A.K.’s pediatrician during the period when A.K.’s 

speech delay began at about 18 months of age. Tr. 37. Although Dr. Boris indicated that he continued to

see A.K. at social functions in the year following his departure from Woodbury pediatrics (Tr. 155-56), he

was not able to provide any specifics and could not recall the details of any interaction with A.K. (Tr. 178-

83). And, to the extent he had the opportunity to observe A.K. on December 3, he acknowledged that he

did not do any developmental or speech evaluation of A.K. at that office visit. But in any event, it is also

worth noting that it was not Dr. Boris, but Mrs. Boris, who noticed A.K.’s lack of responsiveness. I do not

draw from this testimony that A.K. was therefore markedly different from how he behaved previously.

Since Dr. Boris only noticed A.K’s behavior in this one instance when prompted, there is no reason to

assume he would have noted A.K.’s developmental condition on prior occasions. The fact is that Dr.

Boris never independently recognized A.K.’s developmental delay regardless of the timing of onset.
indicated that the videos showed a lack of spontaneous speech dating back to 18

months. In light of this history, none of the notations in A.K.’s contemporary medical

records actually indicated any worsening, much less a dramatic or sudden one, of A.K.’s

speech. Thus, Dr. Zirin’s notations of “speech delay” on November 21 and her

subsequent note of “no spontaneous speech” on December 17, are both consistent with

the previously noted concerns.194

There is also good reason to doubt Dr. Shafrir’s interpretation from a medical

perspective. Respondent’s expert in pediatric neurology, Dr. Cohen, opined that, when

viewed together, the medical records and video footage in this case show a slow

evolution of abnormal findings and no evidence of the type of dramatic change Dr.

Shafrir described. Tr. 1149; Res. Ex. SS at 7-9. Doctor Cohen testified that if A.K.

experienced the type of sudden loss of speech Dr. Shafrir alleged – a loss of speech

that would implicate a brain injury – then there should be evidence in the

contemporaneous records of urgent concern among A.K’s physicians about a

neurologic emergency. Res. Ex. SS at 10. Doctor Cohen stressed that A.K.’s

subsequent medical records showed no such concern. In particular, he noted that

medical records from A.K.’s December 12 hearing test, the December 17 visit with Dr.

Zirin, and his December 31 sick-child visit, do not note any regression or major

developmental change. Nor do they express any urgent concerns. Tr. 1157-59; Pet.

Ex. 3, pp. 2-6; Pet. Ex. 61, pp. 52-54. Doctor Boris testified that, although he felt he

was observing an acute change, he did not believe A.K. was in any immediate danger

which belies a concern about any brain injury. Tr. 229-30.

On direct examination, Dr. Shafrir took issue with Dr. Cohen’s contention that his

descriptions of the December event constituted an emergency situation. Tr. 464-67,

504-05. He maintained that the complete loss of speech in a two year old does not

indicate an acute neurological event, such as stroke, as it would in an older individual

and stressed that children with regressive autism are not routinely sent to the

emergency room. Tr. 466-67. Doctor Cohen explained, however, that a sudden

regression or loss of speech occurring over a period of weeks, or especially over a

period of days as alleged here, would be a medical emergency in the sense that the

proper standard of care would require testing, to include an MRI.195 EEG,196 and

194 Doctor Shafrir’s interpretation of Dr. Zirin’s notations as reflecting a loss of speech between November

and December, i.e., a progression from mere “speech delay” on November 21 to a more serious “no

spontaneous speech” on December 17, is further contradicted by Dr. Zirin’s subsequent records. As

described below, Dr. Zirin reverted to referring to A.K.’s condition as “speech delay” in June 2002. Pet.

Ex. 61, p. 42. If Dr. Zirin had intended for her notation of “no spontaneous speech” to supplant her prior

notation of “speech delay” as indication of a distinctly worsened condition inclusive of a loss of speech,

one would not expect her to continue referring to A.K.’s condition merely as “speech delay” in later

records. Moreover, even taking those differing notations at face value, respondent’s expert, Dr. Cohen,

still disagreed with Dr. Shafrir’s interpretation, opining that “in the context of the variability and ups and

downs in a child’s life, I don’t know that to be a significant change.” Tr. 1372-73.

195 A magnetic resonance imaging (MRI) is “a method of visualizing soft tissues of the body by applying

an external magnetic field that makes it possible to distinguish between hydrogen atoms in different

environments.” DORLAND’S at 916.

196 An electroencephalogram (EEG) is “a recording of the potentials on the skull generated by the currents

emanating spontaneously from nerve cells in the brain. . . . [f]luctuations in potential are seen in the form

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92

possibly a spinal tap (lumbar puncture), over the succeeding weeks in order to rule out

serious conditions that can cause loss of speech in a child, including seizure disorders

or epileptic conditions such as Landau-Kleffner syndrome. Tr. 1154-56.

And indeed, his incredulity in testimony notwithstanding, Dr. Shafrir‘s own report

conveyed a sense of medical emergency. He stated that “the fact that [A.K.] stopped

talking, is dramatic and well documented. It is seen only with acute macroscopic

structural brain injury such as stroke, certain rare epilepsies such as Landau-Kleffner

Syndrome or autistic regression.” Pet. Ex. 63 at 12. Despite raising these conditions as

potential causes in his expert report, Dr. Shafrir offered no explanation for why there

would be no need to rule them out in A.K.’s case. Thus, Dr. Shafrir ultimately

acknowledged on subsequent questioning that a sudden and severe regression would

be a neurological emergency. Tr. 577.

The medical records subsequent to Dr. Boris’s December 9 observation evince

an investigation of the type of ongoing speech concern that had already been

recognized, rather than any urgent concern reflective of an emergent neurological

condition. Although Dr. Shafrir’s expert report identified potential causes of speech loss

that constituted serious medical conditions, Dr. Shafrir’s acknowledgment that a routine

hearing test was the appropriate next step (Tr. 465) belied his characterization of the

comments of Dr. Boris and Dr. Zirin as indicative of a dramatic neurologic event. It

suggests that this characterization may have been yet one more example of the

hyperboles Dr. Shafrir frequently employed.

Concerns about A.K.’s speech were not mentioned in his pediatric records again

until April 29, 2002, (Pet. Ex. 61, p. 46) and he did not see a speech specialist until July

2002, after Dr. Kovacs, a pediatrician from whom [A.K.’s family] sought a second 

opinion, made the referral in June 2002 (Pet. Exs. 26, p. 2; 21, pp. 4 (speech therapy

intake in June), 14 (summary sheet reflect first speech therapy session on July 24,

2002 ). At that point – consistent with Dr. Miller’s opinion that A.K. never developed

true speech – Dr. Kovacs characterized the chief complaint for A.K.’s visit as “child [the

word “still’ lined through] not talking yet.” Pet. Ex. 26, p. 2. Around that same time, on

June 24, 2002, Dr. Zirin completed a health status report for the early intervention

program which, once again, characterized A.K.’s issue as “speech delay.” Pet. Ex. 61,

p. 42. None of these records mentioned speech regression or loss of speech.

3. Noncontemporaneous Parental Reports of Regression Are Not Persuasive.

The subsequent evolution of the parental reports of regression is evident in the

records. On June 17, 2002, A.K.’s intake form for early intervention indicates that [A.K.’s 

parents] reported that “child has few words” and that he “used to have some words that 

he doesn’t use unless prompted now. (ex – will say dog only when sees one now).” Pet. 

Ex. 21, p. 1. That same record characterized [A.K.’s mother’s] concern as being “speech 

delay” possibly caused by the fact that A.K.’s nanny was Spanish- speaking. Id. During

a July 10, 2002, speech and language evaluation, [A.K.’s mother] characterized A.K.’s as

having “very limited spontaneous language.” Pet. Ex. 21, p. 32.

of waves, which correlate well with different neurologic conditions and so are used as diagnostic criteria.”

DORLAND’S at 600.
93

She indicated that as he developed, A.K. had steady progress in vocalization, but that

his verbal abilities were “very inconsistent.” Id. A.K.’s evaluation showed that his verbal

abilities were “not progressing on an age appropriate level” and that his vocabulary

contained “a very limited repertoire of true words.” Pet. Ex. 21, p. 33.

In August 2002, Dr. Boris reflected the extent of A.K.’s speech ability with less

precision, noted that he “had some words” and that they were lost “after developing

them.” Pet. Ex. 3, p. 144. A month later, in September 2002, Dr. Boris recorded that

A.K.’s parents were reporting “normal development until 16-18 months, including

speech,” that A.K. had about 10 words, and that A.K.’s parent noted a loss of speech

and eye contact at about 22-24 months. Pet. Ex. 3, p. 141. A.K. was 22 months of age

in September 2001 and 24 months of age in November 2001.

By the time A.K. was evaluated by Dr. Rapin in April 2004, about a year after the

original petition was filed in this case, A.K.’s parents were explicitly reporting that A.K.

had experienced a “language regression.” Pet. Ex. 11, p. 1. The history recorded by

Dr. Rapin reflected that A.K.’s language “was delayed in that he had had only about 20

words at age 2 years when parents became aware that he had in fact regressed, that he

mostly did not speak at all and had lost his sociability.” Pet. Ex. 11, p. 1.

Doctor Rapin appeared to accept that a regression had occurred (Pet. Ex. 11, pp.

2-3), however, the contrast between this report and the contemporaneous records is

striking. None of A.K.’s records from the first report of speech delay in November 2001

to his early intervention evaluation in July 2002 contain any reference to any regression.

To the extent there are references to a “loss” of some words, it is to the extent of noting

a lack of spontaneous speech, something which [A.K.’s mother] characterized as late

as July 2002 as limited and inconsistent throughout A.K.’s speech development. All of

these records characterized A.K.’s issue as speech “delay” and Dr. Kovacs’ record

explicitly indicated that the chief complaint at that visit was a lack of any language

development in the first instance. Moreover, as late as August 2002, A.K.’s parents

were still reporting that A.K.’s language had always been very limited. At that time, they

estimated he had 10 words before they became concerned. By 2004, they were

reporting to Dr. Rapin that A.K. had, at some unspecified point, developed 20 words. At

the fact hearing in this case, [A.K.’s mother] inflated A.K.’s prior vocabulary further,

testifying that prior to his influenza vaccines A.K. had over 30 words. Tr. 63-64.

Thus, the record clearly reflects that as time passed, [A.K.’s parents’] 

recollection of these events deviated ever more significantly from the medical records

themselves.197 Their testimony and their later parental reports regarding regression do

not have sufficient indicia of reliability to be credited over the contemporaneous medical

records and their own earlier statements, which do not show speech regression. See,

e.g., Reusser v. Sec'y, HHS., 28 Fed. Cl. 516, 523 (1993) (“[W]ritten documentation

recorded by a disinterested person at or soon after the event at issue is generally more

197 As I note, infra, with regard to the Shoffner study’s (Res. Ex. MM, Tab 16) reliance on parental reports

of regression, in the OAP test cases considerable doubt about the validity of later-reported regressions

was noted, particularly in view of the widespread information about the purported link between MMR

vaccines and onset of autistic symptoms or loss of skills. Dwyer, 2010 WL 892250, at *36, n.163, *169;

Snyder, 2009 WL 332044, at *44, *137.
94

reliable than the recollection of a party to a lawsuit many years later.”); Vergara v. HHS,

08-882V, 2014 WL 2795491,*4 (Fed. Cl. Spec. Mstr May 15, 2014) (“Special Masters

frequently accord more weight to contemporaneously-recorded medical symptoms than

those recorded in later medical histories, affidavits, or trial testimony.”) See also

Cucuras, 993 F.2d at 1528 (noting that “the Supreme Court counsels that oral testimony

in conflict with contemporaneous documentary evidence deserves little weight.”).)

198

In sum, the totality of the record, including A.K.’s contemporaneous medical

records, videos, and parental testimony, suggests that A.K. showed signs of language

difficulty as early as 18 months and that this language difficulty became more

pronounced as he aged. The record does reflect, however, any sudden or severe loss

of language. Subsequent claims by A.K.’s parents of a clear regression are not

supported by the contemporaneous records or videos.

D. Conclusion and Findings of Fact: A.K. Did Not Experience an Autistic Regression or

a Challenge-Rechallenge Reaction Following His Vaccinations.

Although the expert testimony regarding a possible regression focused primarily

on the question of whether A.K. lost speech (see, e.g. Tr. 498-500, 993, 1154), Dr.

Shafrir did testify about other signs of autism – including lack of social interaction – as

part of what he characterized as A.K.’s autistic regression. Tr. 479-80. Based on the

history provided by A.K.’s parents, Dr. Rapin similarly noted that A.K.’s alleged

regression at about age two included a loss of sociability. Pet. Ex. 11, p. 1. Petitioners’

claim that the onset of his ASD was sudden and included a loss of previously achieved

milestones, including but not limited to speech. Indeed, Dr. Shafrir opined that the

videos showed that the change occurred “overnight.”

As noted in the preceding sections, however, I have found that A.K.’s ASD

manifested much earlier than petitioners’ contend. I also noted that the signs of ASD

found on the video footage include a clear lack of social development, including, most

glaringly, the repeated failure to respond when called by name. These symptoms were

visible in videos dating as far back as January 2001 when A.K. was approximately 14

months of age.199

I find that what A.K. experienced was a gradual manifestation of ASD which

could be observed long before he was administered either of the two doses of influenza

198 To be sure, “it must [also] be recognized that the absence of a reference to a condition or

circumstance is much less significant than a reference which negates the existence of the condition or

circumstance. Since medical records typically record only a fraction of all that occurs, the fact that

reference to an event is omitted from the medical records may not be very significant.” Murphy v. HHS,

23 Cl. Ct. 726, 733 (Fed. Cl. 1991), aff’d 968 F.2d 1226 (Fed. Cir. 1992)). Here, however, the

contemporaneous medical records do not simply fail to report regression, they are inconsistent with

regression. Moreover, a loss of language would be highly significant and not likely to go unreported for

so long if actually present.

199 To the extent Dr. Shafrir also cited symptoms such as malaise, weakness or hypotonia occurring after

vaccination, he acknowledged that, like the alleged regression in speech, these symptoms were reflected

only in much later parental reports and not in the contemporaneous medical records. Tr. 534-37. But in

any event, he did not establish that these were symptoms of ASD or autistic regression.
95

vaccine in the fall and winter of 2001.200 Had there been a dramatic change on

November 10, I find the parental inaction to such a change, and their failure to mention

it at subsequent visits, inexplicable. As indicated above, Dr. Miller explained that often

the appearance that ASD is worsening stems from the fact that a child with ASD falls

further from the typical development curve as he ages. Tr. 998-99. To the extent that

petitioners’ experts have opined that there was a marked increase in A.K.’s ASD-like

behavior following his vaccinations, each of these opinions was predicated on that

expert’s related opinion that A.K. appeared, in the words of Dr. Shafrir, “more or less

normal” prior to vaccination. That is, the opinion that A.K. was markedly worse was

expressed relative to apparently normal behavior prior to the vaccinations. Since I have

declined to accept those observations, finding them to be inaccurate, then the

correlative statement that he was therefore “worse” in the later videos necessarily fails

as well.

This also eliminates, as a factual matter, the possibility that A.K. experienced a

challenge-rechallenge reaction.201 As noted in Section VIII.B.3.b, below, challengerechallenge is not even a relevant concept in this case. Indeed, [A.K.’s mother]

testified that A.K. has had his speech disappear and reappear several times over the

years without any suggestion that it was associated with vaccination. Tr. 52.

Nonetheless, I note that the record as a whole does not support the contention that

A.K. experienced two distinct reactions to his vaccinations.

Contrary to petitioners’ claim, the above analysis shows that the onset of A.K.’s

ASD predated his first vaccination. Although the first notation of speech delay in the

medical record was recorded during the period between his two vaccinations, I find it

more likely than not that this notation was reflective of an ongoing concern that was first

noted by A.K.’s parents at about 18 months of age. Moreover, there is no credible

evidence to suggest that A.K.’s condition actually worsened following the first

vaccination. To the extent A.K.’s parents testified that there was a worsening in A.K.’s

spontaneous speech, they themselves acknowledged that it was “not dramatic,” and

that concern itself is consistent with what was observed in the video footage prior to his

200 I do not reach the question of whether A.K.’s onset of ASD at 14 months would itself constitute a

regression, because even if it did occur, it obviously would not be temporally related to his vaccinations.

201 The “challenge-rechallenge” concept has been addressed in numerous cases within the Vaccine

Program. Most notably, the Federal Circuit succinctly summarized the theory by explaining that “a

rechallenge event occurs when a patient who had an adverse reaction to a vaccine suffers worsened

symptoms after an additional injection of the vaccine.” Capizzano, 440 F.3d at 1322. More specifically,

the Institute of Medicine defines a rechallenge case as one in which “an adverse event occurred after

more than one administration of a particular vaccine in the same individual. Each rechallenge, however,

must meet the same attributes of reasonable latency, documentation of vaccination receipt, and clinician

diagnosis of the health outcome.” Pet. Ex. 223, K. Stratton, et al, Adverse Effects of Vaccines: Evidence

and Causality, Institute of Medicine of the National Academies (2011), p. 46 [hereinafter 2011 IOM Report,

Pet. Ex. 223]; see also Tr. 1419-20 (Dr. McCusker describing rechallenge as a function of adaptive

immune response). Thus, to successfully establish a challenge-rechallenge theory, a petitioner 

must show a temporal relationship between the occurrence of petitioner’s symptoms and multiple vaccine

administrations. See, e.g. Doe v. HHS, 95 Fed. Cl. 598, 609 (Fed. Cl. 2010)(affirming the decision of the

special master and noting that “the special master found that petitioner had not established causation by

a preponderance of the evidence because neither of his expert’s proposed ‘challenge events’ had the

necessary temporal connection to the first or second dose of the vaccine.”)
96

vaccination. In addition, for the reasons described above, I have declined to accept Dr.

Shafrir’s characterization that the two birthday videos document a dramatic overnight

change from November 9 to November 10.

Nor is there any credible evidence in the record to support the idea that A.K.’s

condition worsened again following the second influenza vaccine. This claim is based

on Dr. Boris’s observations and upon Dr. Zirin’s notation of “no spontaneous speech” in

late December of that year. Doctor Zirin’s notation is fully consistent with the ongoing

concern present before the vaccinations. Moreover, Dr. Boris’s testimony about a

change between December 3 and December 9 is simply not persuasive. He

acknowledged that he did not look for speech or development concerns on December 3

and that he could not remember any details of that encounter. I also note that none of

A.K.’s medical records, even those later records in which A.K.’s parents eventually

reported a prior regression, indicated that A.K. experienced that regression in two

distinct phases. The testimony of A.K.’s parents] appears to be colored by the passage

of time. Their testimony portrays more development prior to A.K.’s vaccines than is

supported by the actual medical records (e.g., they contemporaneously reported that

A.K. had only 10 words, but testified that he had 20-30 word).

Thus, I find that the onset of A.K.’s ASD was not temporally associated with

A.K.’s influenza vaccinations. Nor is there any evidence to suggest that the subsequent

course of A.K.’s ASD was in any way aggravated by his vaccinations or, indeed, in any

way consistent with petitioners’ theories of causation.

VIII. The Causation Theories of Dr. Kendall and Dr. Shafrir Lack Sufficient Indicia

of Reliability and are Unpersuasive.

Assuming, arguendo, that A.K. has a mitochondrial disorder or dysfunction, the

divergent theories advanced by Drs. Kendall and Shafrir must be considered and

evaluated. Petitioners summarized their theory as contending that “oxidative stress,

exacerbated by inflammation from the influenza vaccination, in A.K., who suffered from

a mitochondrial malfunction further impairing his aerobic system, increasing oxidative

stress, caused epigenetic changes in his brain, evidenced by autistic symptoms.” ECF

No. 297 at 105. Put more simply elsewhere in their brief, they argue that “A.K. has

been diagnosed with a mitochondrial defect that renders him particularly susceptible to

oxidative stress, which was activated by the two doses of trivalent influenza vaccine,

thereby causing his decompensation and severe developmental regression.” ECF No.

297 at 4. For the reasons described in Section VI, above, I have concluded that A.K.

likely does not have any mitochondrial disease or defect. Moreover, for the reasons

discussed in Section VII, I have concluded that A.K.’s ASD is not temporally related to

his vaccinations. Nonetheless, even assuming, arguendo, that he did have a

mitochondrial disease or defect and further assuming that the onset of his ASD was

consistent with vaccine causation, I would still find that petitioners’ theory lacks

sufficient indicia of reliability to meet the Althen requirement for preponderant evidence

of a reliable medical theory.

With the testimony of Dr. Kendall and Dr. Shafrir in this case, petitioners take two

distinct approaches to explaining how the influenza vaccines caused A.K.’s condition.
97

Doctor Kendall proposed a direct causal link between vaccines and developmental

regression manifesting as ASD in mitochondrial disorder patients. Doctor Shafrir’s

approach was much more convoluted. He posited that A.K. had a mélange of factors,

including mitochondrial disease, MTHFR polymorphisms, and an abnormal immune

system that, combined with his influenza vaccinations during a vulnerable period in

A.K.’s development, caused a brain injury resulting in his current condition.

These theories, conjoined only by the necessary presence of a mitochondrial

disorder, were further supported by Dr. Deth’s presentation regarding the epigenetic

consequences of inflammation and oxidative stress. Doctor Deth’ s testimony purported

to explain in further detail how A.K.’s mitochondrial and other alleged vulnerabilities

could result in the type of injury petitioners alleged. Petitioners have stressed, however,

that Dr. Deth’s presentation goes to the question of what biological mechanism is at

work. They therefore argue, since they are not obligated to prove any biological

mechanism, that they can meet their burden even without Dr. Deth’s testimony. Tr. 597.

I first address Dr. Kendall’s and Dr. Shafrir’s opinions before separately addressing Dr.

Deth’s presentation in a later section of this decision. For the reasons described below,

however, I do not find either Dr. Kendall’s or Dr. Shafrir’s theory persuasive, with or

without Dr. Deth’s presentation.

A. Doctor Kendall’s Theory.

In her report, Dr. Kendall contended that “recent studies have documented the

association of developmental regression and autism in patients with mitochondrial

disease following exposure to immunizations.” Pet. Ex. 65 at 7. Building on this

association, she asserted that “if mitochondrial dysfunction, from either a primary

genetic abnormality or secondary inhibition of oxidative phosphorylation by other

factors, is present at the times of infections and immunizations in young children that the

added oxidative stresses from immune activation on cellular metabolism are likely to 

be very critical for the highly energy dependent central nervous system.” Id. at 7-8.

Thus, in light of her assumptions that A.K. had a mitochondrial disorder and that he

experienced a developmental regression with onset temporally related to his influenza

vaccines, Dr. Kendall opined that A.K.’s two doses of influenza vaccine aggravated his

underlying mitochondrial disease “with subsequent onset of clinical symptoms and

regression.” Pet. Ex. 65 at 8. Doctor Kendall argued that the type of regression A.K.

experienced was documented in two articles which noted “a precedent for this

association,” referring to the Poling and Shoffner articles discussed in more detail

below. Id.

Doctor Kendall’s theory is based on the understanding that mitochondrial

disorder patients may experience periods of decompensation or deterioration that can,

at least sometimes, be linked to particular stresses. This understanding is not

contested. But, in arguing that vaccines have been demonstrated to be a stressor that

can trigger decompensation, she went beyond that general understanding. The

evidence that mitochondrial deterioration can be linked to generally to vaccines is

largely anecdotal, and the evidence that mitochondrial decompensation looks like ASD

is nearly non-existent. While mitochondrial disease and ASD diagnoses can be comorbid, the former is generally a progressive and degenerative condition and the latter
98

condition is not. Although those with ASD may experience plateaus and occasional

deteriorations in development and behavior, those with ASD typically continue learning

and improving, albeit not at the same trajectory as their typically developing peers. See

DSM V at 56; See also Res. Ex. RML 123, DSM IV at 73. See also Pet. Ex. 172, F.

Kendall, et al, at 193 (mitochondrial disorders “are often progressive and degenerative

in nature.”); Res. Ex. SS, Tab 6, Haas, et al (“mitochondrial diseases are usually

progressive and multisystemic.”).

1. The Context for Dr. Kendall’s Theory.

Doctor Kendall’s theory builds on an observed characteristic of mitochondrial

disorders that is not particularly controversial, even if it has not been well studied or

documented. That is, the condition of individuals with mitochondrial disorders often

worsens over time. This may occur gradually, or there may be abrupt regressions or

decompensations that result in illness and/or the inability to perform motor or cognitive

tasks once mastered. Tr. 253-55, 257-58, 1167-69, 1373-75.

These regressions may occur without any apparent cause or may be temporally

related to events such as viral or febrile illness, dehydration, or surgery. Tr. 253-55,

327, 444, 1168-69, 1304-06, 1373-75. Some of those who experience decompensation

or regression return to baseline, some plateau, and in many, the loss of skills signals a

downward spiral in the progression of mitochondrial disease. Tr. 253, 1373-75.

A correlation has been drawn between metabolic stressors, such as illnesses

and surgery, and periods of regression in those with mitochondrial disease, based on

the temporal relationship between such stressors and a regression or decline in health.

No one knows, however, exactly how or why this occurs. Doctor Kendall indicated that

the amount of stress necessary to cause this damage is unknown and likely dependent

on a “constellation of factors.” Tr. 257-58. Fever, in particular, has been recognized as

a stressor that can possibly aggravate a mitochondrial disorder though how and why it

does so is not well understood. Tr. 1304-05.

The lack of both specificity and strength in the association between illness and

decompensation or regression has contributed to the uncertainty about the causal

mechanism—that is, what is it about a fever or illness that causes the loss of skills? Not

all individuals with mitochondrial disorders experience periods of decompensation with

such stresses, and many experience such periods of decompensation even in the

absence of metabolic stress. In the face of this already uncertain understanding of

mitochondrial regression, petitioner’s theory that a vaccine can aggravate a

mitochondrial disorder leading to an ASD-like developmental regression significantly

extends what is generally accepted about mitochondrial disorders. That is, Dr.

Kendall’s claim that a vaccine, not just an illness, can exacerbate, aggravate, or trigger

regression or deterioration goes well beyond the above-described foundation, which is,

itself, not well understood. Moreover, she asserted that a mitochondrial

decompensation can result in ASD. Her opinions on these matters are based almost

exclusively on a wildly overreaching interpretation of two papers discussed below.

2. Doctor Kendall Drastically Overstated the Support Provided by the Shoffner

and Poling Papers.
99

The two articles Dr. Kendall cited in support of her opinion that vaccines

themselves can cause developmental regression and autism in mitochondrial disease

patient are Poling, Res. Ex. MM, Tab 14 and Shoffner, Res. Ex. MM, Tab 16. In her

expert report, Dr. Kendall claimed that these two papers “have documented the

association of developmental regression and autism in patients with mitochondrial

disease following exposure to immunizations.”202 Pet. Ex. 65 at 7. An examination of

the two articles demonstrates that they do not establish the association that Dr. Kendall

claimed they did.

a. The Shoffner Study.

The Shoffner study looked retrospectively at 28 patients with co-morbid

diagnoses of autism and mitochondrial disease, via a “chart review,” ostensibly to

examine whether a relationship between autistic regression and fever existed.

Shoffner, Res. Ex. MM, Tab 16, at 429-30. The article was vague concerning whether

the diagnosis of ASD or the mitochondrial disease diagnosis came first; it contains data

about the age of the patients “at the time of evaluation of mitochondrial disease,” which

ranged from 1.5 to 19.3 years of age, but no data about the age at which ASD was

diagnosed. Id. at 430.

About 61% (17 of 28) of the children studied were said to have experienced an

“autistic regression” (“defined as the loss of developmental skills that included speech,

receptive skills, eye contact, and social interests in individuals”)—a higher percentage of

regression than commonly reported in those with ASD, which the authors estimated at

25%.203 Shoffner, Res. Ex. MM, Tab 16, at 430-31. Significantly, the Shoffner study

does not explain how the authors determined that a regression occurred; whether it was

contemporaneously reported or appeared in later histories; or what standard was used

to evaluate the presence of regression at the time it was reported. As I noted in Snyder:

Documentation of the nature and extent of skill loss in children with autistic

disorder or PDD-NOS is complicated by the retrospective nature of case

ascertainment in most studies, concerns about possible reporting bias in

202 Although she did not specifically reference these studies during her direct examination, Dr. Kendall

also testified that she believed vaccines were among the various stressors generally “known” to be

capable of causing a deterioration or regression in a mitochondrial disease patient. Tr. 254, 285-86.

203 The article cites two articles (references 22 and 23) for the percentage of those with ASD who

experience a regression or loss of skills. The article at reference 22 was filed in this case. See Pet. Ex. 

F, S. Rogers, Developmental Regression in Autism Spectrum Disorders, MENT. RETARDATION & DEV.

DISAB. RES. REV., 10(2): 139-43 (2004). Rogers reported that about one-third to one-half of the children

with autism show some regression and loss of skills, a number higher than the 25% rate for which this

article was cited. Id. at 140. The Taylor study (reference 23) was not filed in this case, but was discussed

in the Rogers literature review (Res. Ex. F at 142) and in the OAP test case decisions (see, e.g., Dwyer,

2010 WL 892250 at *39), where it was cited in connection with estimates of the prevalence of regression

in autism. The prevalence rates in all studies discussed in Dwyer ranged from 15%-50%. Estimates of

regression in the Theory 1 test cases (see Snyder, 2009 WL 332044 at * 42, and n.115) ranged from 5%-

50%. Thus, the 61% with regression reported by Shoffner is higher than the upper levels reported in the

studies examined in the test cases. Given the small number of children in the Shoffner study, the

difference between the rates of regression reported there and those in other studies is not as significant as

it might appear from the 25% rate of regression reported by the Shoffner researchers.
parental observations, and the lack of a standard measurement for

regression. There is general agreement that some children with autistic

disorders experience a loss of previously acquired skills, usually at 15-24

months of age. Loss of language skills is most frequently observed, but

skill loss may also occur in nonverbal areas of development. . . . The

range of estimates may be affected by recall bias, as parental interviews,

conducted months or years after the onset of symptoms, were often the

only method available to investigators to classify children as having

experienced regression.

Snyder, 2009 WL 332044 at *42 (internal citations omitted). Thus, the omission of

information concerning how regression was assessed and whether the reports were

contemporaneous or made years after the event, the nature of the skills lost, or indeed,

any details at all about the regression reported, in a study intended to determine a

relationship between autistic regression and fever, are significant omissions.

Significantly more detail concerning the mitochondrial disorder manifestations and

testing appear in this article than discussions of the nature of the regression.

The authors also reported that 12 of the 17 children experienced an autistic

regression within two weeks of a febrile episode. Shoffner, Res. Ex. MM, Tab 16, at

431. Vaccination, without any associated fever, was not associated with regression. Id.

The authors of the Shoffner article explicitly stated that: “No individual [studied] showed

regression with vaccination unless a febrile response was present.” Id. The authors

concluded that “[i]n our patients with mitochondrial disease and autistic spectrum

disorders, the vaccines did not appear related to the neurologic regression.” Id. at 432.

I note that the two siblings in this case, who regressed frequently with idiopathic fevers,

did not regress after vaccination.204 Id.

Thus, at best, Shoffner, Res. Ex. MM, Tab 16, supported the temporal

relationship between a febrile episode and some loss of skills, a phenomenon known to

exist in some mitochondrial disorders in some patients some of the time.205

204 The study contained two siblings, both of whom were reported to have experienced:

multiple episodes of neurologic regression, all with febrile episodes. Fever was typically

idiopathic, with no infectious source identified. The length of time required for recovery

lengthened with each febrile event. Regression in these siblings could last for weeks or

even several months before they would begin regaining skills. Both brothers received a

complete vaccination schedule without incident.

Shoffner, Res. Ex. MM, Tab 16 at 431.

205 Although Dr. Kendall indicated that A.K. had experienced post-vaccination fevers in her recitation of

A.K.’s medical history (Pet. Ex. 65 at 2), there is no contemporaneous or reliable evidence of fever after

the influenza vaccinations. Indeed, Dr. Kendall acknowledged on cross-examination that she could not

cite to any medical record in support of that assertion. Tr. 294, 342. Although respondent conceded that

A.K. received his first influenza vaccine on November 2, 2001, there is no contemporaneous record of its

administration. The vaccination is listed in his immunization summary. Pet. Ex. 61, p. 4. In her

declaration, [A.K.’s mother] indicated that for about 10 days prior to his November 2 vaccination, A.K. had

been experiencing symptoms of an upper respiratory problem, including a runny nose, but that he did not

at that time have any fever. Pet. Ex. 46 ¶ 10. [ A.K.’s] mother indicated she had concerns about giving

A.K. a vaccination while he was still symptomatic. Id. In her declaration, [A.K.’s mother] indicated that

A.K. ran a “low grade” fever in the days following his vaccination. Pet. Ex. 46 ¶ 11. At the hearing,

however, her

100
101

Significantly, the authors did not specify whether this regression marked the first

manifestation of ASD or whether symptoms of ASD were already extant in the children

studies.

b. The Poling Case Report and Study.

The Poling paper contains both a study and a single case report. The case

report involved a child who regressed after receiving vaccines at 19 months of age and

who was subsequently diagnosed with both ASD and a mitochondrial disorder. Res.

Ex. MM, Tab 14, at 171-72. It also included a retrospective analysis of159 children with

autism compared to 94 patients with neurological disorders other than ASD. The

testimony regarding A.K.’s condition following that vaccination did not include fever. Tr. 38. She listed

symptoms such as irritability and listlessness. Id. She did not mention any fever until prompted by her

declaration on cross-examination. Tr. 62. She characterized the fever as “slight.” Id. I note that this

declaration was written in October 2010, almost nine years after the events in question.

A.K.’s medical records in the weeks following his vaccination reflect that on November 16, 2001, A.K.

had two nights of waking with nasal congestion. Pet. Ex. 61, p. 56. A.K. was seen for his 2 year checkup less than a week later on November 21, 2001. Pet. Ex. 61 at 55. The notes for that visit indicate that

A.K. had rhinitis and [A.K.’s mother] testified that A.K.’s pediatrician felt he likely had a virus. Pet. Ex. 61,

p. 55; Tr. 39, 65. In addition, A.K. had elevated lymphocytes as of November 21. Pet. Ex. 61 at 54.

None of the records during this period contain any mention of a fever. Pet. Ex. 61, pp. 55-56.

A.K. received his second influenza vaccine on December 3, 2001. Pet. Ex. 118. [ A.K.’s mother]

testified that after that vaccination A.K. was again listless and had stomach difficulties. Tr. 40-43. She

described a dramatic change and indicated that she called the doctor and was told A.K. probably had a

virus. Id. There is no record of that call in any medical record. [ A.K.’s mother] initially described A.K. as

slightly warm at that point, but later indicated that he had not been feverish until December 9, 2001. Tr.

42, 74. [ A.K.’s mother] indicated that December 9 he was “warm and sweaty, not burning hot.” Tr. 74.

She reported that he otherwise had no symptoms of illness. Id. For his part, [A.K.’s father] testified that

he had no independent recollection, but that [A.K.’s mother] may have mentioned that A.K. felt warm. Tr.

109, 133.

The next notation in A.K.’s pediatric record is from about a week later on December 17, 2001. Pet. Ex.

61, p. 54. It indicated that A.K. had cold symptoms. Id. Subsequently, on December 31, 2001, A.K. was

diagnosed with a “protracted” upper respiratory infection. Pet. Ex. 61, p. 52.

When considering a medical history “it must be recognized that the absence of a reference to a

condition or circumstance is much less significant than a reference which negates the existence of the

condition or circumstance. Since medical records typically record only a fraction of all that occurs, the fact

that reference to an event is omitted from the medical records may not be very significant.” Murphy v.

Sec’y, HHS, 23 Cl. Ct. 726, 733 (Fed. Cl. 1991), aff’d 968 F.2d 1226 (Fed. Cir. 1992). However, medical

records do “warrant consideration as trustworthy evidence.” Cucuras, 993 F.2d at 1528. Accordingly

where subsequent testimony conflicts with contemporaneous medical records, special masters frequently

accord more weight to the medical records. See, e.g., Reusser, 28 Fed. Cl. at 523 (“[W]ritten

documentation recorded by a disinterested person at or soon after the event at issue is generally more

reliable than the recollection of a party to a lawsuit many years later.”).

Here, there is no documentation of any fever temporally related to A.K.’s vaccinations despite the fact

that [A.K.’s mother] was in contact with A.K.’s doctor following both vaccinations due to general concerns

regarding illness. This casts doubt on the report of fever. Moreover, even if I did accept that the fevers

had occurred, A.K.’s complete medical history reveals other possible, if not more likely, explanations for

the alleged fevers. Significantly, [A.K.’s mother] herself indicated that in both instances A.K.’s treating

physicians attributed the symptoms to a viral illness and there was no reference to any vaccine as a

contributor to the symptoms. Therefore, petitioners have not established, more likely than not, that A.K.

experienced any fevers attributable to the two half doses of influenza vaccine implicated by this claim.
102

specific types of the “other disorders: were not mentioned. The study compared results

for some of the same tests performed on the Poling child, finding elevated levels of AST

were elevated in the ASD group as compared to the children with other neurological

disorders, and a suggestion that the creatine kinase levels were also elevated in those

with ASD, although there were too few results available from the “other neurological

disorders” group to allow for comparison. The specific numbers of children with AST

results available in each group were not reported. Id. at 171-72. The authors

suggested that, in view of the AST and creatine kinase levels, some of the children with

ASD might possibly have a mitochondrial disorder as well. Id. at 172. However, in

terms of documenting developmental regression with subsequent development of

enough behavioral symptoms to qualify as ASD and diagnosis of a mitochondrial

disorder, the Poling article presents only a single case report. Moreover, as the Poling

child also experienced a fever following her immunizations (id. at 171) this case report

falls squarely within the parameters of the Shoffner study findings, which implicated

fever as a trigger for mitochondrial decompensation, not simply vaccination.206

A close examination of the symptoms reported for the Poling child in the case

report do not reflect the loss of language or social skills within days or even two weeks

of the vaccination. The symptoms reported within 48 hours of the immunizations

included a fever, “inconsolable crying, irritability, and lethargy and [a refusal] to walk.”

Res. Ex. MM, Tab 14 at 171. Four days after the vaccinations, she was “waking up

multiple times in the night, having episodes of opisthotonus,[207] and could no longer

normally climb stairs.” Id. She developed a rash 10 days after immunization, and was

apparently seen by her pediatrician, who thought the rash was due to her varicella

vaccination. Id. The precise timing of later symptoms is difficult to discern; the report

indicates that: “For 3 months [the start time is not identified, but is presumably the

vaccination], the patient was irritable and increasingly less responsive verbally, after

which the patient’s family noted clear autistic behaviors, such as spinning, gaze

avoidance, disrupted sleep/wake cycle, and perseveration on specific television

programs.” Id. at 171. The report does not identify when the language loss began,

reporting only that the child lost “[a]ll expressive language” by 22 months of age. Id.

However, she began speaking again about a month later, before any mitochondrial

treatments were administered. Id.

Thus, it appears that the Poling child lost motor skills within a short period after

the vaccination, but any loss of language or social skills was gradual and did not occur

within days or a few weeks of the vaccination. This gradual loss of language may

properly be termed an autistic regression, but the behavioral manifestations the study

described are quite consistent with the way ASD appears.

206 It is also noteworthy that Dr. Shoffner is listed as an author on both papers. Compare Res. Ex. MM,

Tab 14 and Res. Ex. MM, Tab 16. Doctor Kendall thus stretched the facts when she claimed that

“several groups” have documented this alleged association. See Pet. Ex. 65 at 8. Although Dr. Shoffner

was one of multiple authors of each paper, the fact that the two papers share a common author suggests

that these reports were not independent research, as Dr. Kendall seemed to imply in her report.

207 Opisthotonus is a “form of spasm consisting of extreme hyperextension of the body; the head and the

heels are bent backward and the body bowed forward.” DORLAND’S at 1330.
103

3. Analysis of Dr. Kendall’s Claims Regarding Vaccination as a Trigger.

When cross-examined, Dr. Kendall conceded both that Poling paper is not really

a study but a single case report (albeit one augmented by attempts to find similar test

results in other autism patients), and that the Shoffner study did not find that a

vaccination was temporally associated with autistic regression in the absence of fever.

Tr. 331-32.

When I expressed my concern to Dr. Kendall that she may have exaggerated the

nature of the findings in the Shoffner paper and that her report misrepresented the

Poling and Shoffner articles as implicating vaccines as causal, she backtracked on her

claim that these papers claimed any association between regression and vaccination.

She confirmed that her intent in citing these papers was only to show that “other factors”

could impact children with mitochondrial disorders generally, and not to claim that A.K.

fit the pattern presented by either the Shoffner or Poling papers. Tr. 368-71. That is,

Dr. Kendall contended that she cited the Poling and Shoffner papers merely for the

proposition that metabolic stressors generally could cause a regression and not for the

more specific contention they claimed that vaccines can act as such a stressor. Tr.

331-32. That distinction is critical, because it is only the latter and not the former point

that is disputed in this case.208

As described above, Dr. Cohen likewise acknowledged that fever or other illness

appears to be capable of triggering a regression in a mitochondrial disorder patient. He

stressed, however, that although the mitochondrial community has generally accepted

the idea that fevers can be temporally associated with mitochondrial deterioration in

some but not all cases – that is they “appear” to be capable of triggering such

regression – no one yet knows why. Tr. 1343-46. Doctor Cohen indicated that most

instances of regression actually take place with no identifiable stressor. Tr. 1305.

Doctor Cohen further explained that even in cases of viral illnesses, which have

been associated with mitochondrial regression and do tend to include fever, it is still is

not understood what, if any, impact the fever itself has on that process. Id. Other

factors associated with viral illness such as anorexia and dehydration may, in fact, have

a closer temporal association to subsequent deterioration than does the fever. Id.

Indeed, as Dr. Cohen testified, there is no evidence that a fever causes a person

to be in a state of oxidative stress. Tr. 1346. Doctor Deth opined similarly that fever

208 In that regard it is also significant that Dr. Kendall acknowledged that under her theory she cannot rule

out A.K.’s contemporaneous respiratory illness (see e.g., n. 205, above) as a contributing stressor. Tr.

286-87. Indeed, Dr. Kendall testified that “sometimes it’s hard to determine what’s going to be the

appropriate combination that’s going to lead to problems in a given individual. But certainly, multiple

impacts or multiple problems at a given time could have a cumulative effect on them.” Tr. 287. She

indicated that it is difficult to know the impact of the illness, because she does not know how significant it

was or whether A.K. was “back to his baseline” at the time of his vaccination. Tr. 286. Although Dr.

Kendall is clearly of the opinion that the vaccination contributed to A.K.’s condition, it is significant that Dr.

Kendall did not describe any basis to exclude A.K.’s illness as the sole cause of his condition. Although

she felt it was significant that A.K. tolerated prior instances of vaccination or illness (Tr. 328-29), she also

testified that intercurrent illnesses cause oxidative stress with or without an associated fever. Tr. 382.
104

itself does not cause oxidative stress, but rather should be considered a symptom of

other conditions, such as inflammation, that may cause oxidative stress.209 Tr. 808.

Thus, absent an understanding of how or why fever can cause a mitochondrial

deterioration, the conclusions one can draw from the temporal association suggested by

the Shoffner article are severely limited, a point that goes to the heart of Dr. Kendall’s

reliance on the Poling and Shoffner articles. That is, to the extent that Dr. Kendall

posited that vaccines aggravate mitochondrial disorders by causing oxidative stress,

neither the Poling nor Shoffner papers in themselves actually established that any of the

subjects who experienced a fever were in a state of oxidative stress. Thus, Dr.

Kendall’s assertion that the association between fever and deterioration illustrated by

Shoffner and Poling offers a “precedent” for her suggestion that vaccines, by virtue of

being a source of oxidative stress, can do the same, is actually unsupported

speculation.210

a. The Shoffner and Poling Papers Are Weak Evidence.

Even evaluating these two papers for the point which they actually make – that a

fever, vaccine-induced or otherwise, may trigger a decompensation or regression – I

note that they still provide scant evidence that the regression will be an autistic

regression or otherwise constitute the first symptom of ASD. The Shoffner study relied

upon a very small sample, making it difficult to assign it much weight. Indeed, the

Shoffner authors themselves stressed that their data “emphasize the need for larger

studies investigating the role of fever, plus coexisting metabolic abnormalities.”211 Res.

Ex. MM, Tab 16 at 432.

209 Doctor Cohen, in turn, testified that, based on the antigen load involved, that a post-vaccine

inflammatory response would be far less than inflammation caused by a viral illness. Tr. 1311.

210 Doctor Kendall’s causation opinion did not directly implicate oxidative stress as a causal mechanism

for regression, nor did she directly assert that vaccines create oxidative stress. That aspect of the theory

was addressed by Dr. Deth’s presentation. Doctor Deth attempted to explain the presence of oxidative

stress more broadly in terms of various sources of inflammation. These points are addressed in later

sections of this decision. The point here is that the Shoffner and Poling papers do not establish the

scientific “precedent” that Dr. Kendall claims.

211 In recent Vaccine Act cases, Federal Circuit judges have expressed concern about special masters’

reliance on small studies involving rare events, perhaps because the studies may not be sufficiently

powered to detect the events being studied. Paluck v. Sec’y, HHS, 786 F.3d 1373, 1384-86 (Fed. Cir.

2015) (finding that the special master erred in determining a period of onset for symptoms of

neurodegeneration using only articles and a case study containing very few participants); Koehn v. Sec’y,

HHS, 773 F.3d 1239, 1243 (Fed. Cir. 2014) (questioning the special master’s reliance on a study

insufficiently powered “to produce statistically significant results”). The “power” of a study to detect events

is one factor in determining how much weight to give such studies. Reference Manual on Scientific

Evidence, Federal Judicial Center, 2011(3d ed.) at 218-19. The concern about small studies expressed

by the Circuit judges is one shared by special masters. However, in the traditional toxic tort case, plaintiffs

rarely prevail without epidemiological evidence showing a relative risk (odds ratio) of 2 or

greater, both to establish general causation (the “can it cause?” query) and that the toxic substance is

more likely than not the responsible agent in the case at bar (the did it cause?” query) by preponderant

evidence. Id. at 217 n.14 (citing McClain v. Metabolife Int’l, Inc., 401 F.3d 1233, 1244 (11th Cir. 2005)

(additional internal citations omitted)). Toxic tort cases are very similar to Vaccine Act cases in the

scientific subject matter, the lack of definitive proof of a substance’s effects on the human body, and in

the application of the preponderant evidence standard. Unlike toxic tort litigation, a study involving an
105

Additionally, the lack of explanation of the methodology used makes reliance on

the Shoffner study problematic. The Shoffner paper did not clearly indicate when

mitochondrial disease was diagnosed in the patients; thus, it is impossible to determine

if the autistic regression occurred prior to or after the onset of the mitochondrial disorder

symptoms or diagnosis. Nor did the Shoffner study indicate whether the regression was

reported contemporaneously, was pulled from later histories in the participants’ medical

records, or was elicited from interviews of the study participants’ parents.212 It appears

odds ratio of 2 or greater is rarely, if ever, seen in contested Vaccine Act causation in fact cases.

Respondent routinely concedes causation or settles at close to full value in cases where the epidemiology

is far less definitive. For example, cases involving influenza vaccine and Guillain Barré syndrome do not

have epidemiology showing a relative risk greater than 2, but the vast majority of such cases are settled.

See, e.g., Jones v. Sec’y, HHS, No. 14-1007V, 2015 WL 2359064, at *1 (Fed. Cl. Spec. Mstr. Apr. 23,

2013) (typical of settlements routinely seen in influenza-Guillain Barré cases). Respondent has agreed to

settle cases where the available proof of vaccine causation is even lower. See, e.g., Tompkins v. Sec’y,

HHS, No. 10-261V, 2013 WL 3498652, at *2 (Fed. Cl. Spec. Mstr. June 21, 2013), motion for rev. denied,

117 Fed. Cl. 713 (2014) (recounting the procedural history of the execution of a settlement agreement in

the case (rendered void by the death of the vaccinee from unrelated causes)). Tompkins later proceeded

to hearing on petitioner’s causation in fact claim, and in the subsequent decision, I ruled that petitioner 

had failed to produce preponderant evidence, based in part on the epidemiological evidence regarding

both influenza and tetanus vaccines and the lack of a causal association of the tetanus vaccine with

Guillain Barré syndrome.

In a Program where Daubert is not used to exclude evidence or experts, causation of rare conditions is

often alleged and there is little evidence on general and specific causation, other than opinions. Special

masters often discuss the evidence filed and relied upon by a party as a part of their statutory mandate to

consider the record as a whole. They may accept less definitive epidemiology as some support for a

causation opinion, but rarely does a special master rely upon epidemiology alone. Evidence from small

studies may be the only evidence available to support or undercut an opinion on causation. When there

is no support for a causation theory other than the expert’s own ipse dixit, a judge in another court may

refuse to admit the testimony (Joiner, 522 U.S. at 146) (citing Daubert, 509 U.S. at 589), but a special

master is not similarly constrained by the rules of evidence. In the OAP test cases, the special masters

heard evidence from the petitioners on theories that other state and federal courts refused to admit,

based on Daubert and Frye v. United States, 293 F. 1013 (D.C. Cir. 1923). See Blackwell v. Wyeth, 971

A.2d. 235 (2009); Doe v. Ortho-Clinical Diagnostics, Inc. 440 F. Supp. 2d. 465 (M.D. N.C. 2006); Redfoot

v. B.F. Ascher & Co., No. C 05-2045 PJH, 2007 WL 1593239 (N.D. Cal. June 1, 2007).

I emphasize that I am not requiring either party to produce epidemiological evidence in this (or any

other) case, but I must consider the epidemiological evidence the parties filed as part of the statutory

requirement to consider the evidence as a whole. When two well-qualified experts testify contradictory to

one another on vaccine causation, support (or lack thereof) in the scientific literature is one factor

identified in Daubert itself as a matter to consider in deciding if the expert testimony is reliable. Daubert,

509 U.S. at 596.

212 In the OAP test cases, considerable doubt about the validity of later-reported regressions was noted,

particularly in view of the widespread information about the purported link between MMR vaccines and

onset of autistic symptoms or loss of skills. Dwyer, 2010 WL 892250, at *36, n.163, *169; Snyder, 2009

WL 332044, at *44, *137. In this case, several medical journal articles were filed that discussed

discrepancies in parental reporting as compared to contemporaneous evidence such as videos. See,

e.g., Ozonoff, Res. Ex. OO, Tab 4, at 802-03 (finding parental recall of behavior patterns and onset

conflicted with video evidence from the same periods, and noting that this was seen even when parents

were interviewed as little as a year or two after the events recalled).

In my own experience as a special master, with close to 1700 autism cases on my docket in 2007, I

have read medical records of many children who reportedly experienced an autistic regression at a

particular time, usually proximate to a vaccination, as reported in a later history, the petition, or affidavits.
106

from comments about the group with fever that either a records review or some form of

interview was conducted.213 Res. Ex. MM, Tab 16 at 431. Perhaps even more

significantly, the study made no claim that the regression caused the ASD diagnosis.214

The authors of the Shoffner study acknowledged some limitations themselves.

As previously indicated, they “did not investigate changes that could be important in the

induction of regression such as dehydration, hypoglycemia, decreases in substrate

ability to oxidative phosphorylation, and other metabolic abnormalities such as fatty acid

oxidation dysfunction.” Res. Ex. MM, Tab 16, at 432. Moreover, the authors also

commented: “In our patients with mitochondrial disease and autism spectrum disorders,

the vaccines did not appear related to the neurological regression.” Id. Indeed, the two

siblings in the study, both of whom had frequent regressions in response to metabolic

When the contemporaneous medical records and histories more proximate to the events in question were

examined, the regression, if any, did not occur as reported in the vast majority of cases. See Hodges v.

Sec’y, HHS, 9 F. 3d 958, 961 (Fed. Cir. 1993) (noting that Congress contemplated the special masters

would use their accumulated expertise in the field of vaccine injuries to judge the merits of individual

claims). Conflation of events to place their occurrence close in time to a possible cause has been quite

common in the OAP cases, although, with rare exceptions, it does not appear that the conflation was

deliberate. Using parental recall to establish that a regression occurred instead of contemporaneous

medical records reporting such a regression casts doubt upon the validity of the reports of regression, as

well as the temporal connection. Based on the information provided in the Shoffner paper, it is impossible

to determine what the authors relied on to determine that a regression had occurred in close temporal

proximity to a febrile episode.

213 The reference to the degree of fever included the qualifier “as reported by parents,” which could mean

interviews as a part of the study, a review of contemporaneous records, or a review of later histories in

the medical records. However, the authors also commented that the “precise fever duration was difficult

to ascertain because patients were usually managed in the home.” Shoffner, Res. Ex. MM, Tab 16, at

431. This comment suggests that the presence or absence of fever around the time of regression was

based on parental recall.

214 Regression is not required for an autism diagnosis. Loss of skills is not listed as a diagnostic criterion

in the DSM V. See DSM V at 50-51 (listing diagnostic criteria); 53-55 (diagnostic features discussion).

Regression or loss of skills is mentioned only in the section titled “Development and Course.” Id. at 55-

56. Comments pertaining to regression include:

The pattern of onset description might include information about early developmental

delays or any losses of social or language skills. In cases where skills have been lost,

parents or caregivers may give a history of gradual or relatively rapid deterioration in

social behaviors or language skills. Typically, this would occur between 12 and 24

months of age and is distinguished from the rare instances of developmental regression

occurring after at least 2 years of normal development (previously described as childhood

disintegrative disorder). . . .Some children with autism spectrum disorder experience

developmental plateaus or regression, with a gradual or relatively rapid deterioration in

social behaviors or use of language, often during the first 2 years of life. Such losses are

rare in other disorders and may be a useful ‘red flag’ for autism spectrum disorder. Much

more unusual and warranting more extensive medical investigation are losses of skills

beyond social communication (e.g., loss of self-care, toileting, motor skills) or those

occurring after the second birthday.

Id. at 55. Thus, even if a fever or other inciting event triggered a loss of skills in a child with an underlying

mitochondrial disorder, the regression would not necessarily constitute the triggering of an ASD or be

causal of that condition. And, in a child who already exhibited ASD symptoms, a regression or loss of

skills in social behavior or language would appear to be consistent with the natural course of ASD.
107

stressors, did not report any problems after vaccinations. Thus, this article is a thin reed

upon which to hang Dr. Kendall’s opinion that vaccines, with or without fever, can trigger

onset or aggravate a mitochondrial disorder.

The Poling case report is also weak support.215 The Poling case study is merely

a single instance consistent with the conclusion stated in the Shoffner study. A single

case study in isolation is not significant proof of an association because what happened

could easily be entirely due to chance. That is, a single instance of something occurring

is by definition not evidence of a pattern.

Although case reports are not completely without evidentiary value, in this case

such an isolated report is especially weak in that Dr. Kendall herself indicated that

metabolic disorder patients live in a fragile state where “anything can just cause them to

tip over fairly quickly.” Tr. 255. She indicated that “lots of different things” can cause

them to decompensate, including dehydration, not eating well, surgery, infections or

other illnesses. Tr. 255, 327. Indeed, she noted that a mitochondrial disorder patient

can experience a deterioration even in the absence of any stressor. Tr. 253-54, 444.

Nevertheless, I have considered this case report, but decline to place much

reliance upon it. See Paluck v. Sec'y, HHS, 104 Fed. Cl. 457, 475 (2012) (noting that

although “case reports ‘do not purport to establish causation definitively, and this

deficiency does indeed reduce their evidentiary value’.... ‘the fact that case reports can

by their nature only present indicia of causation does not deprive them of all evidentiary

weight.’” (quoting Campbell v. Sec'y, HHS, 97 Fed. Cl. 650, 668 (2011)); Bast, 2012 WL

6858040, at *24, *28 (discussing the limited value of case reports); The Reference

Manual on Scientific Evidence, Federal Judicial Center, 2011(3d ed.) at 724 (noting that

in determining medical causation, case reports “are at the bottom of the evidence

hierarchy,” largely because they lack controls and thus do not provide the level of

information or detail found in epidemiologic studies; nevertheless, they “may be the first

signals of adverse events or associations that are later confirmed with larger or

controlled epidemiological studies”). Id. “[S]ome courts have suggested that attempts

to infer causation from anecdotal reports are inadmissible as unsound methodology

under Daubert.” Id. at 217 n.14 (citing McClain v. Metabolife Int’l, Inc., 401 F.3d at

1244) (additional internal citations omitted).

215 I am aware of the recent Federal Circuit decision in Paluck, 786 F.3d at 1384-86, in which the panel

relied in part on the Poling case report. In that case, however, the Federal Circuit’s actual consideration 

of the Poling report was limited to the fact that, despite describing a young girl experiencing an apparent

regression following vaccination, the report does not purport to establish any definitive time frame for the

onset of a neurological regression. Any discussion of the significance of the Poling report in terms of

petitioner’s theory of causation was preempted because respondent conceded the plausibility of the

petitioner’s causation theory in that case. Indeed, the Federal Circuit’s decision in Paluck does not

address the validity of the petitioners’ theory, but rather whether the special master had properly

construed that theory for purposes of determining whether the Paluck’s child, K.P., had a medical history

consistent with the expected time frame stated by the theory. In this case, unlike Paluck, respondent is

contesting petitioner’s theory that a vaccine can cause a regression (as well as petitioners’ assertions that

the Poling case settlement constituted a concession that vaccines could cause a regression (see Motions

Ruling, filed on Sept. 28, 2015 (ECF No. 319), at Section II.B.3.d)). In the motions ruling in this case, I

already addressed why respondent is not constrained by her prior concession in the Poling case or,

indeed, any case.
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If Poling was the first signal that vaccines, accompanied by fever, might serve as

the trigger for a Table encephalopathy or even actual causation of “mitochondrial

autism,” the only followup study filed, the Weissman study (discussed in more detail

below), failed to find any incidences of vaccinations alone triggering autistic-type

regression in children with mitochondrial disorders.

There are other reasons to give this case report scant weight. Doctor Poling, the

lead author, wrote the report about the experience of his infant daughter.216 The child

experienced a developmental regression within 48 hours of a DTaP vaccination and

within five to 15 days of a measles vaccination administered at 19 months of age. Res.

Ex. MM, Tab 14 at 171 (factual presentation). The onset of neurological symptoms was

within the periods for a DTaP Table encephalopathy (72 hours) and a measles Table

encephalopathy (five to 15 days). See 42 C.F.R. § 100.3(a)(II)(B) and (a)(III)(B)(2011)

(Vaccine Injury Table identifying encephalopathy as an associated injury for DTaP and

measles vaccines and setting forth the time periods required). The child was eventually

diagnosed with both autism and a mitochondrial disorder. Res. Ex. MM, Tab 14, at 171-

72; see also Poling v. Sec'y, HHS, No. 02–1466V, 2011 WL 678559, at *1 (Fed. Cl.

Spec. Mstr. Jan. 28, 2011) (fees and costs decision, noting that the case was

compensated as a Table injury).

It is noteworthy then that the Poling child’s condition arose after she received

multiple vaccinations including diphtheria, tetanus and pertussis and measles mumps

rubella (Res. Ex. MM, Tab 14, at 171), two vaccines that carry a presumption of causing

216 The familial relationship was not disclosed by Dr. Poling in the case report. See Brumback, Res. Ex.

MM, Tab 17. In this short commentary, Dr. Brumback, the editor in chief of the JOURNAL OF CHILD

NEUROLOGY (the journal in which the Poling article was published) noted that the authors of the Poling

article disclosed no conflict of interest at the time the article was submitted for publication or in the 12

months that passed prior to actual publication, in spite of a pending claim filed by Dr. Poling on behalf of

his daughter in the Vaccine Injury Program. He commented:

To any journal editor, this is an appallingly troubling issue. Openness and transparency

related to any and all potential conflicts of interest is critical to maintaining the integrity of

science in general and of journal quality in particular. Whether the manuscript would

have been accepted for publication if the authors had disclosed earlier the conflict of

interest is not a moot point, but this does not excuse the behavior of the authors in not

disclosing the conflict of interest at the time, despite their current [apologies]. . . .[M]edia

linkage of the published article to the legal outcome implies scientific support from [the

Journal of Child Neurology] for this legal opinion (referring to the special master’s opinion

awarding compensation).

Id. at 1090. Doctor Brumback noted that this event provoked a change in policy; all authors’ statements

regarding potential conflicts of interest would be published. He also observed that “no written statement

can substitute for honesty, good faith, and integrity on the part of authors. Id. at 1091.

As Dr. Brumback also observed, disclosure of possible conflicts of interest is expected when submitting

a medical journal article for publication. Conflicts of interest are a matter to be considered when applying

Daubert. In its opinion on remand in Daubert, the Ninth Circuit considered whether the matters an expert

proposed to testify about flowed from research conducted independently of involvement in the litigation in

question, noting that this factor provides objective proof that the research was conducted for scientific

purposes. Daubert v.Merrell Dow Pharmaceuticals, 43 F.3d 1311, 1317 (9th Cir. 1995); see also Exxon

Shipping Co. v. Baker, 128 S. Ct. 2605, 2626 n.17 (2008) (declining to consider research funded in part

by a party to the litigation).
109

that condition in this program under the Vaccine Injury Table. The same cannot be said

of the influenza vaccines at issue in this case. See also the discussion of the Poling

vaccine injury case in the ruling on motions in this case (Motions Ruling, filed on Sept.

28, 2015 (ECF No. 319), at Section II.B.1-2).

b. The Weissman Article Does Not Support Petitioners’ Theory.

Although Dr. Kendall did not specifically rely on it in her report or direct

testimony, on redirect examination, petitioners’ counsel questioned Dr. Kendall about

the Weissman article, Pet. Ex. 39. Tr. 375-82. The study is not about vaccinations;

however, it does contain one short passage that addresses the subject of vaccine

causation. Weissman, Pet. Ex. 39 at 4. Specifically, petitioners’ counsel drew Dr.

Kendall’s attention in particular to a statement wherein the authors indicate that there

“might” be no difference between vaccinations and childhood diseases in terms of

inflammatory or catabolic stress. Id.; Tr. 378. Doctor Kendall indicated that the

statement was consistent with her clinical experience. Tr. 378.

Even in isolation, with its use of the word “might,” the statement is far from a

strong statement regarding vaccine causation and is, at best, equivocal on the issue.

Moreover, quoting the relevant passage in full reveals a much different picture, one that

indicated that the Weissman authors would not be likely to agree with Dr. Kendall’s

theory. They stated that:

Recently, there has been increased concern regarding a possible

causative role of vaccinations in autistic children with an underlying

mitochondrial cytopathy. For one of our 25 patients, the child’s

autism/neurodevelopmental deterioration appeared to follow vaccination.

Although there may have been a temporal relationship of the events in this

case, such timing does not prove causation. That said, there might be no

difference between the inflammatory or catabolic stress of vaccinations

and that of common childhood diseases, which are known precipitants of

mitochondrial regression. Large, population-based studies will be needed

to identify a possible relationship of vaccination with autistic regression in

persons with mitochondrial cytopathies.

Pet. Ex. 39 at 4 (internal citations omitted).

Based on this passage, the Weissman authors clearly do not believe that a 1- in25 occurrence of deterioration following vaccination is sufficient to conclude that

vaccines can cause autism or neurodevelopmental deterioration. Doctor Cohen, one of

the participating authors, testified that the passage was intended by the authors to

stress that the temporal relationship present in that one case is not proof of causation.

Tr. 1228-29. In other words, despite the statement cherry-picked by petitioners, the

passage as a whole is intended to convey that no causal association between

vaccinations and decompensation was recognized.

Moreover, the one child in Weissman who experienced a deterioration following

vaccination was the Poling child, the subject of the above-discussed Poling case study.

This was confirmed not only by the citation to the Poling case report, but also by Dr.
110

Cohen’s testimony. Pet. Ex. 39 at 4 (citing to reference 12, which is the Poling case

study); Tr. 1227-29. Thus, not only does the Weissman article not actually bring any

additional evidence to bear, it also casts further doubt on the value of the Poling case

study.

Like the Shoffner study, the Wiessman study is, of course, very small. In fact,

petitioners’ counsel noted during his redirect that, assuming there is no overlap217, the

population between the two studies was a mere 53 subjects (28 in Shoffner and 25 in

Weissman). Tr. 378-79. Moreover, Dr. Cohen cautioned that the Weissman study was

not case-controlled, and therefore not capable of determining statistical significance. Tr.

1227-29. Nonetheless the study does add some broader context to the Poling case

study tending to suggest that the Poling report is less significant than petitioners claim.

That is, although the Weissman study does not identify how many patients were

screened to arrive at the 25 test subjects, Dr. Cohen did indicate that such a screening

process occurred. Tr. 1378. In addition, the article itself states that the subjects were

drawn from investigators at major institutions across the country such as the Cleveland

Clinic, Massachusetts General Hospital and Kennedy Krieger Institute, suggesting a

relatively broad scope. Pet. Ex. 39 at 2. Moreover, the above-quoted passage

indicates that the authors considered the potential temporal association between

vaccination and deterioration among the subjects. Yet, despite this, the Poling case still

remains an isolated case study. While very far from conclusive given the size of the

study population and the unknowns regarding the screening process, this does bear to

some degree on the weight to be accorded the Poling report as it increases the

likelihood that the temporal relationship in Poling was actually a chance occurrence.218

4. The Lack of Substantiation.

Doctor Kendall testified that she was not aware of any reports regarding the

specific question of whether vaccines act as stressors among metabolic patients.219 Tr.

365-66. Similarly, she also testified that she was not aware of any evidence that the

influenza vaccine in particular can cause regression or significantly aggravate a

mitochondrial disorder. Tr. 332. Rather, she confirmed during my questioning that the

only evidence she had to support her claim of an association between vaccination and

mitochondrial regression were the Poling and Shoffner papers discussed above. Tr.

367-68. Absent her initial reliance on those studies, Dr. Kendall ultimately testified that

she was unaware of any medical literature supporting an association between

217 This may not be a safe assumption given that both studies sought out patients who had already been

diagnosed with both mitochondrial disorders and ASD, a small population, and did so within two years of

each other.

218 I stress again that the Weissman study is very small and was not intended as a study of vaccines or

vaccine reactions. As such I am not indicating that it negates the Poling case report. See n.211, supra,

regarding reliance on studies insufficiently powered to detect rare events. Nonetheless, it shows that the

Poling case remains the only specifically identified case of a temporal relationship between a vaccination

(accompanied by fever) and a regression.

219 I note that Dr. Shafrir separately cited some additional articles regarding mitochondrial disorders and

autism that are discussed in Section VIII.B.2.a, below. None of those articles, however, provide any

further support for Dr. Kendall’s theory.
111

vaccination and regression.220 Tr. 371. Nonetheless she indicated, without further

elaboration, that she was taught as a general matter during fellowship training that

immunizations can act as stressors for children with inborn errors of metabolism. Tr.

365-66.

Doctor Kendall testified that some of her own patients had some problems

subsequent to vaccination. Tr. 255. She agreed, however, that metabolic disorder

patients live in a fragile state where “anything can just cause them to tip over fairly

quickly.” Tr. 255. She indicated that “lots of different things” can cause them to

decompensate, including dehydration, not eating well, surgery, infections or other

illnesses. Tr. 255, 327. Indeed, she noted that a mitochondrial disorder patient can

experience a deterioration even in the absence of any stressor. Tr. 253-54, 444. She

offered no specifics regarding these anecdotal instances from her own practice of

vaccination aggravating a mitochondrial disorder and did not indicate if any other

potential stressors were also present in these patients. In his competing experience,

Dr. Cohen testified that he had never seen a vaccination aggravate a mitochondrial

disorder. Tr. 1306-07.

B. Doctor Shafrir’s Theories.

Although Dr. Shafrir identified A.K.’s alleged mitochondrial disorder as a relevant

factor in his analysis, there was otherwise no discernable overlap between his theories

and Dr. Kendall’s. Doctor Shafrir argued more broadly that A.K. had a “highly specific

and extremely rare constellation of independent, genetically determined factors . . .

combining in a vulnerable time in his development, to produce an unusual brain

dysfunction, which was clearly triggered by the vaccine.” Pet. Ex. 63 at 12. He

contended that A.K. had a mitochondrial disorder, a MTHFR polymorphism, and a

genetically-determined abnormal immune system, all of which, when combined with his

influenza vaccination, caused an autoimmune brain injury (encephalopathy) which

manifested as an autistic regression. Pet. Ex. 63 at 14-18. Doctor Shafrir relied on the

so called “triple hit” hypothesis to explain how these factors would come together. Pet.

Ex. 63 at 18; Tr. 549-54.

The “triple hit” hypothesis that Dr. Shafrir referenced was raised in an article by

Dr. Manuel Casanova, written as a part of a symposium on the neurobiology of

autism.221 See Casanova, Pet. Ex. 63, Ref. 22, at 422-23. According to Dr. Casonova,

220 I do note that a great deal of literature was filed in this case, and some of it does address the broader

context from which Dr. Kendall’s theory derives, namely the possible link between autism, mitochondrial

disorders and oxidative stress. Doctor Kendall was clear, however, in explaining that only the Shoffner

and Poling papers supported her proposed extension of that understanding to include vaccinations as a

trigger for decompensation in a child with a mitochondrial disorder.

221 Doctor Shafrir’s reference 22 was an article by M. Casanova, The Neuropathology of Autism, BRAIN

PATHOL. 17:422-33 (2007) [hereinafter “Casanova, Pet. Ex. 63, Ref. 22”]. Doctor Casanova’s earlier work

on minicolumnar pathology of the brain in ASD was cited with approval in Snyder, 2009 WL 332044 at

n.142 (“Doctor Rust's testimony about minicolumn differences in autistic brains is supported by the

research of Dr. M. Casanova”). His expert report was filed in that case, but he was not called to testify by

respondent. Dwyer, 2010 WL 892250 at n.186. He reiterated his earlier work on minicolumnar pathology

in Pet. Ex. 63, Ref. 22, at 426-27.
112

the triple hit hypothesis suggests that autism is caused by a combination of “(i) a critical

period of brain development, (ii) an underlying vulnerability, and (iii) exogenous

stressor(s).” Pet. Ex. 63; Ref. 22, at 423 (setting forth the triple hit factors); Pet. Ex. 63

at 18 (Dr. Shafrir asserting the applicability of the triple hit hypothesis to A.K.’s case).

For the reasons described below, however, Dr. Shafrir has failed to establish any

of these three factors are either present in A.K. or contributed to his ASD. To the extent

that he relied on either an autoimmune encephalopathy or challenge-rechallenge to

establish that the influenza vaccine could cause A.K.’s condition, his reliance was

misplaced. There is no evidence, other than Dr. Shafrir’s opinion, that ASD is caused

by an autoimmune reaction or that there was a challenge-rechallenge scenario under

the facts of this case.

1. A Critical Period in Brain Development.

Although Dr. Shafrir disavowed that “regressive autism” could be caused by

genetics (see Pet. Ex. 63 at 13),222 Dr. Casanova wrote that while autism is not

monogenetic in nature, “current clinical consensus regards autism as a multifactorial

trait as opposed to an oligogenic or polygenic disorder. Studies suggest the presence

of multiple susceptibility and protective genes that modify the risk of developing the

condition.” Casanova, Pet. Ex. 63, Ref. 22 at 432. Casanova also noted that

“epidemiological studies, including twin studies done in separate or conserved

environments, strongly support the presence of heritable factors. Autism in

monozygotic twins is stated to be 12 times higher than in the normal population” and

that the rate for dizygotic (fraternal) twins is four times higher than in the general

population. Id. at 422.

Unlike Dr. Shafrir, Dr. Casanova acknowledged that genetics plays a significant

role in the etiology of autism. While Dr. Casanova’s triple hit hypothesis posited the

three factors Dr. Shafrir argued were present in A.K.’s case (a critical period in brain

development, an underlying vulnerability, and exogenous stress or stressors), Dr.

Shafrir simply ignored the portions of Dr. Casanova’s work that indicated that the critical

period in brain development was prenatal, not postnatal. Pet. Ex. 63, Ref. 22 at 423-28.

Doctor Shafrir contended that this period of vulnerability extended into childhood

and that A.K. was in a state of vulnerability at the time he received his influenza

vaccines at around two years of age, because the brain is still developing in infancy and

222 Indeed, Dr. Shafrir also stated that “[t]he notion that autism is a genetic disease is not supported by

evidence.” Pet. Ex. 63 at 13. He argued that the increasing prevalence of autism belies a genetic cause.

Id. He noted that “worldwide genetic studies have failed to identify an ‘autism gene’ and yielded only a

very small number of patients with genetic defects,” and claimed that most children with ASD-associated

abnormal genes do not experience regression. Id. (internal citations omitted). He claimed that the

“current view of the genetic component in autism is that it represents an inherited vulnerability to

environmental factors,” but did not cite any supporting medical literature for this proposition. Id. It is thus

not clear whether he contends that regressive autism is not genetically caused or whether all autism is not

genetically caused. He does clearly assert that autistic regression is somehow etiologically different 

from early onset autism, claiming that regression “is seen only with acute macroscopic structural brain

injury such as stroke, certain rare epilepsies such as Landau-Kleffner Syndrome or autistic regression. It

cannot be explained by anything else, but a pathological process affecting the brain.” Id. at 12.
113

childhood. Pet. Ex. 63 at 18. During cross-examination, respondent’s counsel asked

Dr. Shafrir a series of questions relating to specific examples listed in the Casanova

article. Tr. 549-54. Doctor Shafrir acknowledged that all of the examples supporting a

period of vulnerability related to prenatal events, but nonetheless maintained that the

theory could be applied to environmental or exogenous stressors occurring either

prenatally or postnatally. Id.

The Casanova article reflects that mostly likely vulnerable period is confined to

the first trimester of gestation. Specifically, the article concludes by noting that “several

studies suggest that birth complications in autism are the result of preexisting prenatal

abnormalities. The literature indicates that underlying brain alterations in autism occur

well before symptom expression. Most evidence favors the first trimester of gestation

as providing a time window of susceptibility.” Pet. Ex. 63, Ref. 22, at 9-10.223

This conclusion is consistent with and further supported by another much more

recent study filed by petitioners.224 That study looked at the small number of identical

twins who are discordant for ASD (only one of the twin pair having an ASD diagnosis).

Although identical twins share identical DNA, about 10% of such twin pairs are

discordant. The fact that monozygotic twins are not 100% concordant has been used

as an argument that ASD is not caused by genetics alone—that “something else” must

play a role. The Wong study examined whether epigenetics might be that “something

else” to account for the discordance. Epigenetics involves the process by which genes

are “turned on” or “turned off” through the methylation of DNA. Pet. Ex. 240 at 1.

Although the study was small, with just 32 twin pairs, the authors stressed that

“the use of disease-discordant MZ [i.e.,monozygotic (identical)] twins represents a

powerful strategy in epigenetic epidemiology because identical twins are matched for

genotype, age, sex, maternal environment, population cohort effects and exposure to

many shared environmental factors.” Pet. Ex. 240 at 1, 8.

Respondent’s expert on genetics, Dr. Raymond, argued that the Wong study was

significant because it showed that the epigenetic changes occur very early in embryonic

development. Tr. 1470-74. Although Dr. Raymond did not dispute petitioners’ evidence

223 Two other expert reports, filed while A.K.’s case was still identified as a Theory 2 test case, also

provide support for the prenatal origins of ASD. See Res. Exs. U (expert report of Dr. Thomas Kemper)

and EE (expert report of Dr. Patricia Rodier). Their work was referenced in Casanova, Pet. Ex. 63, Ref.

22, at 431-33 (internal references 10, 65, and 107). Doctor Kemper did some of the early work

demonstrating specific differences between the brains of typically developing individuals and those with

ASD through autopsy studies, and concluded that most of the differences occurred at early stages of

brain development in utero, with the only postnatal change being an arguable increase in head

circumference beginning shortly after birth. See generally, Res. Ex. U. Doctor Rodier, a teratologist who

has studied the toxic effects of mercury, as well as the stages of brain development when autism is

thought to arise, opined that autism arises early in gestation, based on known environmental risk factors,

histological studies of brains of those with autism, and from the co-occurring craniofacial abnormalities in

some children with autism. See Res. Ex. EE at 2-8.

224 See Wong, Pet. Ex. 240. Although the article was filed by petitioners during the course of the hearing,

I excused the late filing because the study represented newly discovered evidence. Because the article

was filed after Dr. Shafrir testified, he did not address it. I note that Dr. Shafrir did not testify in rebuttal,

although Dr. Deth did.
114

that epigenetic changes continue to occur postnatally, he argued that petitioners

overlooked a critical distinction between pre and postnatal epigenetics. Tr. 1459. He

testified that only prenatal epigenetic changes, occurring while fetal cells are still

dividing to create different types of tissues, can carry forward errors in a system-wide

manner. Tr. 1461-68.

Doctor Raymond noted that the Wong study drew its epigenetic profile from

blood samples as a proxy for each subject’s brain profile. Tr. 1470-74. In order for the

epigenetic changes to be discordant among the twins and yet observable in the blood

sample, Dr. Raymond observed that the epigenetic change at issue must have occurred

sometime after the twins “split,” but before the developing fetus had differentiated blood

and brain tissues. Id. He pointed out that this would place the change “at a very, very

early stage” of fetal development. Tr. 1472. More generally, and consistent with the

Casanova paper, Pet. Ex. 63, Ref. 22, Dr. Raymond also noted that the most critical

period of development epigenetically is from conception through the second trimester.

Tr. 1458.

Although the earlier Casanova paper indicated that “the exact mechanisms of

interaction remain unknown,” it indicated that the suggested “window of vulnerability in

autism” is supported by, inter alia, a “strong association to neuro-embryological

dysfunction” among those exposed in utero to thalidomide. Pet. Ex. 63, Ref. 22, at 423

(citing to work by Dr. Rodier). Doctor Casanova indicated that those subjects

developed certain ear abnormalities in addition to autism. He therefore indicated that

“timing of these ‘minor’ malformations and the supposition that autism may have arisen

during the same stage of development suggests a time window of vulnerability early in

gestation (20-24 days).” Id. He further noted that “the first trimester is the time of

development for multiple congenital anomalies that include autism as one of their

manifestations.” Id.

Doctor Raymond’s interpretation of the Wong study is therefore particularly

compelling. It appears that the Wong study extended and corroborated Dr. Casanova’s

opinion that a vulnerable period exists during the first trimester of pregnancy, and

particularly very early (20-24 days) within that period. Although Dr. Casanova did not

posit an exact mechanism, Wong suggested that very early prenatal epigenetics may

explain the interplay between genetics and in utero “environmental” factors in the

development of autism. The relevant vulnerable period that Dr. Shafrir posited is

postnatal and that timing is not supported by the literature in this case. His reliance on

the “triple hit” mechanism posited by Casanova to explain how A.K.’s ASD emerged

after the allegedly causal influenza vaccines at around two year of age is therefore

misplaced.225

225 On cross-examination, petitioners’ counsel posed the question to Dr. Raymond of whether the prenatal

epigenetic changes suggested by the Wong study could create a latent susceptibility to later postnatal

environmental insults. Doctor Raymond said he could not completely rule out that possibility, but noted

that it is highly unlikely. He again noted that the Wong article shows that the epigenetic changes are

happening across all tissues, and so there is no basis to speculate that these changes would cause a

vulnerability that would impact the brain and only the brain. Tr. 1514-19.
115

In his expert report, Dr. Shafrir contended (as did petitioners in the OAP Theory 1

and Theory 2 test cases)226 that children who experience an autistic regression

constitute a distinct phenotype with an etiology distinct from others with ASD. He

asserted that autistic regression “cannot be explained by anything else, but a

pathological process affecting the brain.” Pet. Ex. 63 at 12. But, like his unsupported

extension of the Casanova triple hit theory into the postnatal period, this claim is

likewise without apparent basis.

A.K. was diagnosed as having ASD by his treating neurologist, Dr. Rapin, in April

of 2004. Pet. Ex. 11, pp. 1-4. In addition, Dr. Miller, a child psychologist with significant

qualifications and background in the diagnosis of ASD, offered extensive and

compelling testimony explaining how A.K. fit into the standard diagnostic criteria for

ASD. Indeed, she testified that A.K. met 11 of the 12 DSM-IV criteria for diagnosing

ASD.227 Tr. 937-38. Doctor Shafrir did not appear to dispute these points.

Doctor Shafrir testified that he had no reason to disagree with A.K.’s ASD

diagnosis by Dr. Rapin, who he described as “the most famous person in autism until

recently.” Tr. 526-27. And indeed, he appeared to express doubt about an earlier

evaluation that failed to result in an ASD diagnosis. Id. Moreover, he testified

extensively about A.K.’s evident autism, at one point noting that a particular video clip of

A.K. showed “a traumatic severe classic autism.” Tr. 476, 526-27. Nonetheless, Dr.

Shafrir argued extensively in his expert report that what A.K. experienced was an

autistic regression, which, he contended, is distinct from autism itself and remains

unexplained. Pet. Ex. 63 at 12-13.

This, of course, was an issue that was addressed at length as part of the OAP.

As part of the Theory 1 test cases in the OAP (the MMR or MMR plus thimerosal theory)

all three OAP special masters addressed the question of whether regressive autism –

children with an ASD diagnosis who experience a loss of previously acquired skills –

represented a distinct phenotype with a distinct cause. Synder, 2009 WL 332044, *39;

see also Cedillo, 2009 WL 331968; Hazlehurst, 2009 WL 332306. This issue was again

further explored in the Theory 2 test cases, which involved the thimerosal causation

theory also raised in this case by Dr. Deth. Dwyer, 2010 WL 892250; King, 2010 WL

892296; Mead, 2010 WL 892248.

Significantly, the reason regressive autism was discussed in the OAP was

because the petitioners sought to argue that symptoms appearing later in development,

contemporaneous to vaccination, could be explained by an external environmental

trigger rather than being genetically predetermined. See, e.g. Synder, 2009 WL 332044

at *40 (noting that petitioners’ MMR theory contended the temporal relationship between

226 See Snyder, 2009 WL 332044, at *40; Dwyer, 2010 WL 892250, at *29, 36-40.

227 According to Dr. Miller, A.K.’s symptoms included: limited eye contact, lack of facial expressions or

gestures to communicate, failure to initiate or share social interaction, appearing as if “in his own world,”

not responding to or having emotional reciprocity, delayed language, lack of conversational approximation,

having repetitive sounds, lack of pretending or imitating, circumscribed interest, 

mannerisms such as ear holding or hand flapping, and preoccupation with objects or parts of objects. Tr.

937-38. Doctor Miller did not observe any rigid routines, which is the one DSM-IV criteria she noted was

absent. Tr. 938.
116

the vaccine and regression was evidence of causation). This is exactly the argument

that Dr. Shafrir advanced in this case, arguing that what he characterizes as autistic

regression “cannot be explained by anything else, but a pathological process affecting

the brain.” Pet. Ex. 63 at 12.

The conclusions in the OAP test cases, however, were exactly opposite to what

Dr. Shafrir argued in his expert report. Although a subset of children with ASD

experience regression of skills, the evidence was insufficient to conclude that these

children have a distinct phenotype or have a distinct etiology with a separate cause or

“trigger.” Specifically, I noted in Synder that “neuropathologic findings, coupled with the

association of autism with certain prenatal exposures, strongly indicate that autism has

a prenatal onset. The evidence for autism's genetic basis and prenatal origin renders

petitioners' MMR theory of causation improbable, as a vaccination in the second year of

life is unlikely to generate the brain structure changes seen in ASD. Petitioners have

not demonstrated that their postulated regressive autism phenotype is etiologically

distinct from other forms of ASD.” Synder, 2009 WL 332044 at *52. These conclusions

were also expressed in the Kemper and Rodier expert reports. See Res. Exs. U and

EE.

Doctor Shafrir simply offered no support, other than his opinion that it must be so,

for regressive autism constituting a separate phenotype. Although he argued as a

general matter that his theory was supported by medical literature, he provided no

citation to support his assertion that autistic regression is distinct from autism.228 Pet.

228 Doctor Shafrir has cited several studies which suggest that “mitochondrial autism,” i.e., a dual diagnosis

of autism and mitochondrial disease, may come to be known as a separate phenotype of ASD which 

in turn can be associated with neurologic or mitochondrial regression. See, e.g., Weissman, Pet. Ex. 

63, Ref. 16;Pet. Ex. 63, Ref. 17, Haas, Pet. Ex. 63, Ref. 17. I stress, however, that this constitutes

speculation, not a reliable theory that “mitochondrial autism” is different from other forms of autism with or

without regression. In the seven years since the Weismann study suggested that mitochondrial autism

might be a separate diagnostic entity, the evidence that those with both a mitochondrial disorder and an

ASD diagnosis might constitute an etiologically, clinically, or genetically distinct group remains lacking.

ASD has many co-morbid conditions—seizure disorders, tuberous sclerosis, intellectual disability, anxiety

disorders, and psychiatric disorders, only a few of which may be related to the ASD diagnostic symptoms.

See DSM V at 58-59; Casanova, Pet. Ex.63, Ref. 22, at 422. A number of parallels can be drawn

between co-morbidity in ASD and mitochondrial disorders and comorbidity between ASD and tuberous

sclerosis, a genetic disorder in which tubers in the body, and in particular in the brain, can cause mental

retardation and seizures (see DORLAND’S at 397). Casanova noted that a substantial percentage of

patients with tuberous sclerosis (estimates ranging from 17%-68%) also have an ASD diagnosis. but only

a small percentage of ASD patients also have tuberous sclerosis. Id. at 423. In the case of ASD and

mitochondrial disorders, the presence of ASD-associated developmental delays and/or regression are

clinical symptoms used in the mitochondrial disorder diagnosis as well. For example, pertinent to the

instant discussion, Casanova suggested that the presence of comorbidities such as mitochondrial 

disorder should not be exclusionary from an ASD diagnosis. The co-morbidity underscores the

heterogeneity of ASD generally, and supports “the possibility that autism originates early in the first

trimester of gestation.” Pet. Ex. 63, Ref. 22, at 422. In any event, whether mitochondrial autism is a

distinct phenotype is a separate question from whether regressive autism is itself a distinct phenotype

caused by a distinct trigger. And ultimately that is a question that leads back to Dr. Kendall’s abovediscussed theory which in turn fails to link vaccination to mitochondrial regression. In that regard, I note

that while the Shoffner study examined a possible link between fever and autistic regression, they

specifically noted that “autistic regression occurs prior to 3 years of age in approximately 25% of children

with autism, in whom developmental abnormalities were previously unrecognized. The etiology of this
117

Ex. 63 at 12-13; Tr. 520. This is, of course, a striking contrast to the extensive

exploration of the issue during the OAP. Nor did he suggest that the scientific

community’s understanding of autism has changed in the six years since the first OAP

test cases were decided. Indeed, Dr. Shafrir actually argued that our understanding of

the causes of autism has been stalled since the 1980’s. Tr. 495-98. When specifically

asked during cross-examination about the distinction he drew in his report between

autism and autistic regression, Dr. Shafrir admitted that there are no published medical

criteria defining autistic regression. Tr. 524. He also stated that what he considers

autistic regression overlaps with autism in about 95% of cases. Tr. 521.

Despite this, Dr. Shafrir speciously maintains that autistic regression and autism

are separate entities, based on what he characterized as short-comings of the “official”

definition of autism contained in the DSM, a definition he viewed as overly broad. Tr.

520-24 (Dr. Shafrir’s general, unsupported critique of the DSM is discussed in Section

VII.A, above). Doctor Shafrir essentially argued that regressive autism is too “major” of

an entity to ignore.229 But such an argument does not actually address the question of

whether autistic regression has a distinct etiology. In that regard, it is particularly

noteworthy that Dr. Shafrir contended that the cause of autistic regression is completely

unknown. Pet. Ex. 63 at 13. Thus, even taking Dr. Shafrir’s criticism of the DSM at face

value, it is still not actually an argument that necessarily separates autism from autism

with regression.

Despite his strong (and laudable) desire to find a cause for ASD, Dr. Shafrir

acknowledged that no clear cause has been identified. Tr. 580. His frustration

notwithstanding, Dr. Shafrir has not articulated how, in the absence of a clear etiology,

autism should be diagnosed other than by observable behaviors. Indeed, when asked

to define autism himself, Dr. Shafrir characterized it entirely in terms of observable

features, testifying that autism is “a child who has impairment in communication, in

socialization, and in imagination, which means that they . . . have primitive play without

any use of imagination with the play. They can communicate verbally or non-verbally.

The most traumatic one is they don’t relate to other people.” Tr. 580. Moreover, several

of the studies cited by Dr. Shafrir screened their subjects for ASD using the DSM-IV

criteria and the screening tools described by Dr. Miller, and did so without noting any

criticisms similar to those raised by Dr. Shafrir.230

It is understandable that Dr. Shafrir, a neurologist who sees many children with

ASD as patients, would be eager to discover a clear neurological cause of autism and I

regression is unknown.” Res. Ex. MM, Tab 16, at 429-30. See n.203 supra, reflecting that the actual

number of children with ASD who experience a loss of skills is higher than 25%. And in any event, even if

mitochondrial autism is a separate phenotype, that still cannot explain A.K.’s ASD since I have concluded

he did not have mitochondrial disease and therefore he would not fall within that very hypothetical

phenotype.

229 I note that Dr. Kinsbourne made precisely the same argument in the Theory 1 test cases. Snyder,

2009 WL 332044 at *41.

230 See, e.g., Shoffner Res. Ex. MM, Tab 16; Weissman, Pet. Ex. 39; Haas Pet. Ex. 63, Ref. 17; Poling,

Res. Ex. MM, Tab 14.
118

am sure his intensity derives from a sincere desire to help his patients, but his attacks

are leveled without apparent support and are therefore very damaging to his credibility

in this case. Faced with a clear ASD diagnosis which he does not dispute, Dr. Shafrir

unconvincingly strained to discredit the generally-accepted ASD diagnostic approach in

favor of an understanding of autistic regression derived from his own ipse dixit. He

redefined autism to require a “trigger” that fit his theory. He sought, without apparent

basis, to extend the so called “triple hit” theory beyond the prenatal development

despite the above-cited contradictory evidence in the record of this case. Thus,

regardless of whether the alleged vulnerabilities Dr. Shafrir cites actually have the

significance he claims, the fact remains that Dr. Shafrir’s entire theory stems from an

unsupported and likely false premise, namely that an environmental insult at two years

of age could cause the type of fundamental changes within the brain evidenced in

autism.

2. A.K.’s Alleged Genetic Vulnerabilities Either Do Not Exist or Do Not Have the

Significance Dr. Shafrir Claims.

Assuming, arguendo, that Dr. Shafrir has established that A.K.’s autism results

from a brain injury caused at about two years of age, I address Dr. Shafrir’s claims that

the injury occurred because separate genetic conditions made him vulnerable to

adverse effects of the influenza vaccine: mitochondrial disease, a genetic polymorphism

(the MTHFR polymorphism) and an abnormal immune system which may be

genetically based. These conditions represent the second prong of the triple hit

hypothesis. Although the core of Dr. Shafrir’s theory is that A.K. experienced an

autoimmune reaction, he argued that these genetic vulnerabilities “enhanced” the insult

to A.K.’s brain. Pet. Ex. 63 at 18. And, although Dr. Shafrir does not explain in any

detail how such an enhancement might occur – instead deferring to Dr. Deth in that

regard – it is quite clear that Dr. Shafrir alleges that these conditions are “risk factors”

associated with ASD. Thus, the second critical issue raised by Dr. Shafrir’s theory is

whether the vulnerabilities he cites actually exist in A.K., and if so, whether they have

the significance to autism causation that he claims.

For the reasons described in Section VI above, I have found that A.K. does not

have any mitochondrial disease or defect. Doctor Shafrir’s reliance on that alleged

vulnerability is therefore misplaced. Nonetheless, I note that his reliance on that

condition to explain A.K.’s alleged injury suffers the same shortcomings as Dr. Kendall’s

opinion. And, although it is undisputed that A.K. does have MTHFR polymorphisms,

contrary to Dr. Shafrir’s contention, I do not find a significant association between

MTHFR polymorphisms and autism. The evidence that he has an abnormal immune

system is scant, and largely conclusory in nature.

a. Mitochondrial Disorder.

In claiming that A.K.’s alleged mitochondrial disorder played a role in A.K.’s

autistic regression, Dr. Shafrir relied on the same articles that Dr. Kendall cited –

Shoffner and Poling. Pet. Ex. 63 at 16-17. He also cited the above-discussed

Weissman article, as well as Haas, Pet. Ex. 63, Ref.17 (a review article by Hass). Id.
119

Doctor Shafrir’s reliance on the Shoffner, Poling and Weissman articles is

misplaced for the same reasons discussed above with regard to Dr. Kendall’s theory.

The Haas article, Pet. Ex. 63, Ref. 17, does not provide any additional support.

This review article’s discussion of a causal role for immunizations is limited to a

recitation of the Poling case report and the Shoffner study, which are noted in the

review to be in contrast to several other studies which failed to show any association

between immunization and autism. Pet. Ex. 63, Ref. 17, at 149. Figure 2 of the article

obviously played into Dr. Shafrir’s theory, positing “a hypothesis for the role of

inflammation and mitochondrial dysfunction in the pathogenesis of ASD regression.” Id

at 150. Figure 2 illustrated the theory: the response to a nonspecific stressor

(infection/immunization/fever) in the presence of a genetic autistic predisposition and

mitochondrial disease or dysfunction, followed by an abnormal immune response or an

abnormal metabolic response (or perhaps both), resulting in regression. Id. (Fig. 2).

Doctor Haas then reviewed literature pertaining to metabolic and immunologic

abnormalities in ASD. However, he also noted that regression was not more common

after administration of MMR vaccine (15.6%) than before it (18.4%), in spite of the live

viral nature of the vaccine and the enhanced nature of some types of immune response

to the vaccine over those of the wild type measles infection. Moreover, although the

Haas article does discuss co-morbidities in mitochondrial disorders and ASD, the article

ultimately concludes that “the underlying mechanisms of mitochondrial involvement in

ASD are unknown, but likely involve neuroinflammation, glial activation and cytokine

release.” Pet. Ex. 63, Ref. 17, at 151.

Significantly then, just as Dr. Kendall did, Dr. Shafrir acknowledged on crossexamination that he had no basis to claim that the Shoffner study reflected what

happened to A.K. Tr. 560-61. Rather, he indicated that “the only thing I said is

mitochondrial disorder is a risk factor for autistic regression. I didn’t make any other

claim, not about the vaccination or about anything else.”231 Tr. 561. Ultimately, Dr.

Shafrir argued that the Shoffner study supported an association between mitochondrial

disease and autistic regression. Tr. 564-66.

Linking ASD and mitochondrial disorders together as possible comorbidities,

however, is insufficient to demonstrate that one causes the other. For example,

Casanova, on whom Dr. Shafrir relied regarding the triple hit theory, suggested that the

presence of comorbidities such as mitochondrial disorder should not be exclusionary

from an ASD diagnosis, but rather that they underscore the heterogeneity of ASD

generally and may actually support “the possibility that autism originates early in the first

231 In his expert report, Dr. Shafrir cited James, Pet. Ex. 117, Ref. 38 (which was also filed as Pet. Ex. 63,

Ref. 19) and argued that this paper described how A.K.’s alleged mitochondrial disorder “made him

vulnerable to apoptosis and other forms of permanent structural changes in the brain as a result of the

activation of the brain immune system induced by the vaccine.” Pet. Ex. 63 at 18. Doctor Shafrir

described the paper as indicating that “children with autism have been found to have high plasma levels

of homocysteine and a biochemical profile of reduced methylation capacity.” Id. This assertion is best

discussed in light of Dr. Deth’s presentation, particularly because Dr. Deth discussed the same paper, 

and Dr. Shafrir acknowledged that he is neither a metabolic specialist nor an expert in oxidative stress

and therefore can do no more than cite what he saw as a “significant relationship” reflected in the medical

literature. Tr. 547-49.
120

trimester of gestation.” Pet. Ex. 63, Ref. 22, at 422. Ultimately all the Haas and

Weissman papers cited by Dr. Shafrir demonstrate is that mitochondrial disorders

appear in the autistic population with greater frequency than in the general population.

“Comorbid” is not the same as “causal.”232

b. MTHFR Gene Polymorphism.

The 5, 10-Methylenetetrahydrofolate reductase (MTHFR) gene is involved in

folate metabolism. See Botto, Res. Ex. MM, Ref. 21, at 1.233 “Normal MTHFR activity

may help maintain the pool of circulating folate and methionine and possibly prevent a

buildup of homocysteine.” Id. The MTHFR gene is involved in the process of DNA

methylation. Pet. Ex. 63 at 17; Tr. 1451-52.

It is undisputed that A.K. has two MTHFR gene alterations or variations known as

polymorphisms. Pet. Ex. 63 at 17-18; Res. Ex. MM at 3. Specifically, A.K. is

heterozygous for a C677T alteration as well as for an A1298C alteration234, meaning

that he has one common and one less common allele at each site. Pet. Ex. 3, p. 301.

Doctor Shafrir contended that the presence of these two polymorphisms is

significant, because they are more common among the ASD population than in the

general population. Pet. Ex. 63 at 18. He posited that these polymorphisms reduce

enzyme activity and, in children with ASD, ultimately lead to reduced methylation

capacity, leaving them vulnerable to oxidative stress and brain injury.235 Id. Ultimately,

however, Dr. Shafrir acknowledged that he could not say that A.K.’s MTHFR

polymorphisms caused A.K.’s autism, only that the polymorphisms are associated with,

or are a risk factor for, autism. Tr. 547. I note that there is a wide gulf between

“association” and “risk factor.” More children with ASD have intellectual disabilities than

the general population and in that sense these two conditions are “associated,” but

intellectual disability is not a risk factor for autism.

Respondent’s experts challenged Dr. Shafrir’s contentions that these MTHFR

polymorphisms are associated with, or are a risk factor for, ASD, pointing out that this

232 In any event, Dr. Shafrir’s reliance on the role of a mitochondrial disorder as a contributing factor in his

development of ASD is further misplaced to the extent that I have concluded that A.K. does not have any

mitochondrial disorder or defect. See Section VI, above.

233 Res. Ex. MM, Tab. 21, L. Botto, et al, 5, 10-Methylenetetrahydrofolate reductase Gene Variants and

Congenital Anomalies: A Huge Review, AM. J. EPIDEMIOL. 151(9): 862-877 (2000) [hereinafter “Botto, Res.

Ex. MM, Ref. 21”]/

234 The alpha-numeric names refer to two different alleles of the MTHFR gene. Res. Ex. MM, Ref. 21, at

862. An allele is “one of the two or more alternative forms of a gene that can occur at a particular

chromosomal locus and that determine alternative characters in inheritance. In humans and other diploid

organisms there are two alleles, identical or differing, for each specific locus of an autosomal

chromosome, one on each chromosome of a homologous pair.” DORLAND’S at. 51.

235 The mechanism by which this allegedly occurs was explained by Dr. Deth and is addressed in Section

IX, below. It is worth noting, however, that to the extent Dr. Shafrir suggested that the polymorphisms

resulted in autism by virtue of causing reduced methylation capacity, such supposition actually runs

counter to the Wong study, Pet. Ex. 240, which found no overall difference in methylation between twins

discordant for ASD. See Tr. 1719-24, 1726 (testimony of Dr. Johnson).
association is not supported by medical literature. Res. Exs. MM at 5; XX at 2. Doctor

Raymond characterized the literature on MTHFR polymorphisms and developmental

disorders, including autism, as “all over the place” and that “any association between

MTHFR polymorphisms and autism is unproven.” Tr. 1456-57; Res. Ex. MM at 5.

Initially, Dr. Shafrir agreed with Dr. Raymond, but then asserted that there is such an

association. Tr. 500-01. That is, when asked whether the association between MTHFR

polymorphisms and autism is “unproven” as Dr. Raymond asserted, Dr. Shafrir’s

testimony was confusing. He stated: “I mean, I think it’s unproven, but I think that some

serious people said that there is a relationship.” Thus, Dr. Shafrir conceded that the

studies are mixed, but he relied on the studies that showed an association. However,

the studies filed with Dr. Shafrir’s own expert report were contradictory of one another.

For example, Dr. Boris, one of A.K.’s treating physicians, was the principal author

of a 2004 study that looked retrospectively at 168 children with confirmed ASD

diagnoses and compared them against a control population of over 5,000

Caucasians.236 Boris, Pet. Ex. 55 at 106-07. The dual 677CT/1298AC heterozygous

polymorphism that A.K. has was present in 25% of the ASD subjects but in only 15% of

the controls. Id. at 106. Five years later, however, another study looked at a much

larger population in an attempt to determine if specific autistic behaviors could be linked

to the MTHFR gene.237 These authors found that the genotype distributions for the ASD

subjects were comparable to the general U.S. white population. Goin-Kochel, Pet. Ex.

51 at 105-06. The Goin-Kochel article specifically noted that these findings were in

conflict with the prior Boris study and noted that the findings did not support the

relationship suggested by Boris.238 Id. at 106. The authors argued that the question of

an association remained open and urged even larger studies. Id.

Another study cited by Dr. Shafrir indicated that the frequency of compound

heterozygous MTHFR 677CT/1298AC only reached “borderline significance” among its

sample of autistic children. James, Pet. Ex. 117, Ref. 38.239

236 Boris, Pet. Ex. 55. Doctor Shafrir did not cite this article in his expert report, but confirmed during his

testimony that he believed it demonstrated the link he proposed between MTHFR polymorphisms and

autism. Tr. 579.

237 Pet. Ex. 51, R.. Goin-Kochel, et al, The MTHFR 677C→T Polymorphism and Behaviors in Children

With Autism: Exploratory Genotype-Phenotype Correlations, AUTISM RESEARCH 2: 98-108 (2009)

[hereinafter [“Goin-Kochel, Pet Ex. 51”]. Doctor Shafrir did not cite this article in his expert report, but

confirmed during his testimony that he believed it demonstrated the link he proposed between MTHFR

polymorphisms and autism. Tr. 579.

238 Pertinent to this case, the Goin-Kochel authors speculated that the Boris findings could be attributable

to the greater presence of those having reported autistic regression among the Boris population. They

cautioned, however, that Boris (Pet. Ex. 55) did not identify how regression was “operationally defined”

and that a non-standardized approach may have inflated the frequency of regressive cases. GoinKochel, Pet. Ex. 51 at 106. This note of caution is similar to the issue I mentioned relative to the Shoffner

paper regarding reliance on parental reporting of regression. See, e.g., n.212, supra.

239 In addition, Pet. Ex. 63, Ref. 21, N. Mohammad, et al, Aberrations in folate metabolic pathway and

altered susceptibility to autism, PSYCHIATR. GENETICS, 19:171-76 (2009), found the frequency of the

MTHFR 677T-allele was higher among autistic children than non-autistic children while the 1298C-allele

occurred with similar frequency in both groups. However, P. Pasca, et al, One carbon metabolism

disturbance and the C677T MTHFR gene polymorphism in children with autism spectrum disorders, J.

121
122

Moreover, the experts on both sides in this case acknowledge that these MTHFR

polymorphisms are common in the general population.240 Pet. Ex. 63 at 18; Tr. 1449-

50. Indeed, Dr. Raymond stressed that not only do many individuals in the general

population share A.K.’s MTHFR variances, the majority of them experience no adverse

effect from the polymorphism.241 Tr. 1452-53. This creates an additional interpretative

hurdle in finding some causal significance for A.K.’s polymorphisms. Thus, the Boris

study cautions that “the high natural prevalence of MTHFR variants in the absence of

autistic symptoms could be interpreted in various ways.” Pet. Ex. 55 at 107. In

addition, the Goin-Kochel study also noted that the distribution of MTHFR varied by

many other factors as well, including geographical location, race, and ethnicity. Pet. Ex.

51 at 105. Even Dr. Shafrir, while arguing that an epidemiological relationship exists,

nonetheless conceded that the significance of that association is arguable. Tr. 501.

Thus, although there is some literature positing a connection between the

MTHFR polymorphisms and ASD, the evidence does not preponderate in favor of an

association. The studies in the record are in conflict on that very point, and even if I

concluded that an association exists, its significance would remain speculative. Doctor

Shafrir himself acknowledged that the fact of the association is as far as he can opine.

Moreover, the presence of this polymorphism in the general population, variable by

other factors such as race and geographic location, makes any potential significance of

an association particularly difficult to establish.

c. Immune System Abnormalities.

Although Dr. Shafrir concludes in his expert report that A.K. has an “abnormal,

rare, genetically determined structure of his immune system” (Pet. Ex. 63 at 18), he

never actually identified what that supposed genetic structure is or how it was evinced.

Nor does he cite any specific abnormality evident in A.K.’s immune system. The closest

he came to explanation in his expert report was his broad (and largely unsubstantiated)

claim was: “I do not think that there are many physicians and researchers who doubt

that a particular expression of an infection in a host, its severity and complication, and at

the same token, the severity of immune reaction with its complication and severity (for

example they range from fever and irritability to severe devastating and even lethal

encephalopathy) are genetically determined.” Pet. Ex. 63 at 16.

CELLULAR MOL. MED., 13(10): 4229-4238 (2009), Pet. Ex. 117, Ref. 33, showed a normal distribution of

the C677T polymorphism in children with ASD. Finally, Pet. Ex. 63, Ref. 20, X. Lui, et al, Population- and

Family-Based Studies Associate the MTHFR Gene with Idiopathic Autism in Simplex Families, J. AUTISM

& DEVEL. DISORD., 41:938-944 (2011), indicated that the MTHFR gene polymorphisms were elevated

among families with only a single instance of autism, but that those results could not be replicated among

a group of families with a history of instances of autism.

240 In fact, that is why these alterations are known as “polymorphisms” rather than “mutations.” Tr. 1449-

50.

241 In this regard, Dr. Raymond also distinguished between those who have a homozygous polymorphism,

which is thought to be more likely to result in a clinical impact, and a heterozygous polymorphism such as

A.K. has, which is viewed as much milder. Tr. 1453-54. Doctor Raymond opined that a heterozygous

polymorphism is unlikely to have any metabolic consequences. Tr. 1454. He did note, however, that with

the combination of C677T and A1298C variations, A.K. might arguably be considered “somewhat

intermediate.” Tr. 1454.
123

Although he cited G. Poland, et al, Adversomics: The Emerging Field of Vaccine

Adverse Events Immunogenetics, PEDIATR INFECT DIS J., 28(5): 431-32 (2009), filed as

Pet Ex. 63, Ref. 12 [hereinafter “Poland, Pet. Ex. 63, Ref. 12”] as support, this paper is

not a study or even a literature review. Instead, it is a short opinion piece, advocating

for more study of the emerging field of vaccine adverse event immunogenetics or

“adversomics.” Id. at 1.242 This call to explore a possible role for genetics in accounting

for variations in immune reaction and adverse events following vaccination can hardly

be said to constitute the general acceptance that Dr. Shafrir claimed. Citing prior work

on the role of genetics in susceptibility to infectious disease, the authors indicated that

they desire to “further that construct” and “have hypothesized that adverse reactions

and events may not be random, but may in fact be, in part, genetically predetermined.”

Pet. Ex. 63, Ref. 12, at 1. Although the manuscript referenced some prior studies which

examined genetic susceptibility to intensified or decreased reactions in Native American

populations, the article primarily advocated looking for genetic susceptibilities to certain

recognized vaccine reactions, such as the causal relationship between idiopathic

thrombocytopenia purpura and the MMR vaccine. Id. at 2. Nothing in the article

appeared directly relevant to A.K.’s case.

During his direct examination, however, Dr. Shafrir equated the “abnormal

immune regulation” he had cited to A.K.’s purported Hashimoto thyroiditis diagnosis.

Hashimoto thyroiditis is a type of autoimmune disease, and one which Dr. Shafrir

claimed is an “extremely rare condition for a child of this age.”243 Tr. 501. During crossexamination, Dr. Shafrir acknowledged that this condition constitutes the only evidence

in A.K.’s medical records supporting the presence of an autoimmune disease. Tr. 556-

57. However, he contended that this condition indicated that “there was something

unusual about [A.K.’s] immune system” and that the presence of that condition provides

“some support,” albeit “not strong support,” for his contention that A.K. experienced an

autoimmune reaction to his influenza vaccinations. Id.

Respondent’s immunology expert, Dr. McCusker, disagreed. Doctor McCusker,

who is far more qualified in this area than is Dr. Shafrir, opined that there is no evidence

in A.K.’s medical history indicating that he had any immune deficiency or disorder.244

Tr. 1401. More specifically, Dr. McCusker disputed that A.K. actually has autoimmune

hypothyroidism.

242 The filed copy was an “author manuscript” four pages in length. Citations are to the page numbers

appearing in the upper right hand corner of each page of the author manuscript. The citation reflects that,

when reformatted to the journal pagination, the article is only two pages long (pp. 431-32 of the cited

volume (28(5)).

243 Hashimoto thyroiditis, or “Hashimoto disease,” is a “progressive type of autoimmune thyroiditis with

lymphocytic infiltration of the gland and circulating anti-thyroid antibodies; patients have goiter and

gradually develop hypothyroidism. DORLAND’S at 542.

244 Although Dr. Shafrir urged an “immunogenetic” understanding of A.K.’s condition, he acknowledged

that he is expert in neither immunology nor genetics. Tr. 540-41, 546-47. To the extent Dr. Shafrir

argues that his overall theory remains in his wheel-house by virtue of his clinical experience in

neuroimmune diseases (Tr. 540-41), that does not qualify him to speak to A.K.’s immunological status

overall, particularly not where he bases his opinion regarding the presence of an autoimmune process on

a thyroid condition which, obviously, is outside of his area practice area of neurology.
124

She explained that autoimmune hypothyroidism occurs when autoantibodies

formed against the thyroid gland impede the production of the T4 hormone normally

produced by the thyroid. Tr. 1407. In A.K.’s case, however, although there is evidence

that he had these autoantibodies, multiple thyroid function tests showed normal levels of

the T4 hormone.245 Id. Doctor McCusker explained that the ability to produce

autoantibodies is inherent to the immune system and is on some level expected even in

healthy immune systems. Tr. 1408-1411. Thus, she noted that the presence of antithyroid antibodies is not uncommon (occurring in one per 8,000 males per year) and is

not in itself evidence of immune dysregulation. Tr. 1410-11. Thus, Dr. McCusker

argued that A.K.’s laboratory results are not diagnostic of autoimmune hypothyroidism.

Tr. 1407 (citing Pet. Ex. 3, p. 330).

During redirect Dr. Shafrir also raised the fact that on one occasion A.K. tested

positive for myelin basic protein antibodies. Tr. 578-79 (citing Pet. Ex. 3, p. 331).

Doctor Shafrir argued that this is objective evidence of an autoimmune reaction aimed

against A.K.’s nervous system. Tr. 579. Doctor McCusker again disagreed with Dr.

Shafrir’s conclusions. In addition to her earlier testimony that the presence of

autoantibodies is not evidence of immune dysregulation, she testified that “the isolated

finding of antibodies in and of itself does not support anything.” Tr. 1411. Doctor

McCusker stressed that myelin basic protein antibodies can be indicative of multiple

disorders, including multiple sclerosis. Tr. 1439-40. These antibodies may be

supportive of a diagnosis when accompanied by clinical correlates, but are not in

themselves diagnostic. Id.

Ultimately, although he did maintain that the autoantibodies were evidence of

autoimmune activity, Dr. Shafrir conceded that “I don’t’ think anybody can say that we

understand the significance of the presence of those [antimyelin] antibodies.” Tr. 585.

Doctor McCusker also addressed an issue raised by Dr. Boris, but not by Dr.

Shafrir. During his testimony, Dr. Boris was asked about the common variable

immunodeficiency [“CVID”] diagnosis he made of A.K. He indicated that he believed

A.K. fell “into that category,” but stopped short of characterizing it as a diagnosis. Tr.

215. He testified that the “diagnosis” was based on laboratory results from July of 2002

which indicated that A.K. had deficiencies in immunoglobulin A [“IgA”] “side chains of

Kappa Lambda and Kappa Lambda combinations.” Tr. 220 (citing Pet. Ex. 3, p. 375).

Doctor Shafrir mentioned these results in his expert report, but did not explain their

significance, if any, without explanation. Pet. Ex. 63 at 6. Doctor Boris indicated that

this was his sole basis for indicating that A.K. has CVID. Tr. 220.

Doctor McCusker testified that CVID is a condition that represents a “grab bag” of

different problems associated with antibody formation. Tr. 1403. She indicated that

there are clear diagnostic standards for CVID which include at least two findings of

below normal immunoglobulin levels and a failure to produce antibody when stimulated.

245 Doctor McCusker did note that there is some evidence in the record that A.K. occasionally had “mildly

elevated” TSH (Thyroid Stimulating Hormone). She explained, however, that TSH is a signal to produce

more T4 and elevated TSH is not considered a concern unless T4 is also abnormal. Tr. 1407-08. But in

any event, Dr. McCusker characterized A.K.’s TSH as normal overall. Tr. 1407.
125

Id. She also noted that it is characterized clinically by recurrent ear, nose and throat

conditions. Id. She opined that A.K.’s medical records do not support a CVID

diagnosis. Tr. 1404. One set of results relied on by Dr. Boris actually showed normal

immunoglobulin levels, a point which Dr. Boris conceded. Tr. 220, 1404; Pet. Ex. 3, p.

375. Moreover, she noted that A.K. did not have any functional deficiency, a necessary

part of any CVID diagnosis. Tr. 1404. A.K.’s records show that he developed

antibodies in response to his MMR vaccine.246 Pet. Ex. 3, pp. 380-81. And, A.K.’s

medical history over his first two years of life showed only the “usual childhood

illnesses.” Tr. 1401-02. Neither would be likely in a child with CVID.

Thus, Dr. Shafrir’s contention that A.K. had a genetically determined abnormal

immune system is without support. Doctor McCusker, a pediatric immunologist with far

more training and experience than Dr. Shafrir, eviscerated the basis for Dr. Shafrir’s

conclusions about Hashimoto’s thyroiditis or CVID as evidence of a dysfunctional

immune system or a genetic propensity to develop autoimmune disease.

3. Doctor Shafrir Has Not Established That the Influenza Vaccine Could Cause

an Autoimmune Reaction Resulting in A.K.’s Condition.

The core of Dr. Shafrir’s theory was that A.K. had an “abnormal, rare, genetically

determined structure of his immune system which produced an immune reaction within

his brain to the influenza vaccine.” Pet. Ex. 63 at 18. To the extent that Dr. Shafrir

relied on this abnormal immune system as a condition precedent to his contention that t

A.K. experienced a “brain insult induced by the immune system” (id), his theory of

causation lacks that necessary predicate. Doctor Shafrir’s relied on an abnormal

immune system to explain how A.K.’s two doses of influenza vaccine acted as an

exogenous or environmental stressor per the third prong of the triple hit hypothesis.

He conceded that there was no direct evidence in A.K.’s case of any abnormal

immune reaction. Tr. 545. Indeed, he acknowledged that there is no evidence in the

record of this case demonstrating any immune reaction in A.K., abnormal or otherwise,

to his influenza vaccinations. Tr. 541-42. Rather, Dr. Shafrir appears to surmise the

existence of an autoimmune process triggered by the influenza vaccine based on three

circumstantial factors – (1) that A.K. had an abnormal immune system in the first place,

(2) that the influenza vaccine is capable of causing neurological injury generally, and (3)

that in A.K.’s case, the temporal association between A.K.’s two vaccinations and his

regression constitute a challenge-rechallenge response, an immunological concept that

demonstrates causation. Looking at these points collectively, Dr. Shafrir argued that

despite being unable to identify an “exact immune abnormality” or an “exact mechanism

for immune abnormality” it nonetheless “all fits.” Tr. 502. Doctor Shafrir fails, however,

to persuasively establish any of these three points. The evidence (or lack therof) for an

abnormal immune system was addressed in Section VIII.B.2.c, above. The remaining

two points are addressed in turn below.

a. Ability of the Influenza Vaccine to Cause A.K.’s Condition.

246 Doctor McCusker did note that A.K.’s antibody response to the MMR vaccine was “equivocal,” but

attributed that fact to his lack of any booster dose. She found the antibody response normal under that

circumstance. Tr. 1406.
126

Assuming A.K. was vulnerable to an autoimmune attack, Dr. Shafrir further

contended that such an attack can be surmised from the fact that the influenza vaccine

is capable of causing a neurological autoimmune injury. To establish this point, Dr.

Shafrir cited a number of studies related to recognized autoimmune conditions and to

some he claimed were autoimmune in nature: acute disseminated encephalomyelitis

[“ADEM”], transverse myelitis [“TM”], Guillain-Barre Syndrome [“GBS”], and narcolepsy.

See Pet. Ex. 63, Refs. 7-11; Exs. 124, 126, 127.247 Although he conceded that A.K. did

not have any of those disorders (Tr. 542), he argues that the results can be carried over

by analogy to A.K.’s condition (Pet. Ex. 63 at 15; Tr. 582-83).

Doctor Shafrir’s argument amounted to a “one size fits all” approach to

autoimmune reactions. While his analogy may hold at the most superficial level, looking

at the details of these conditions makes it impossible to say that what happens in one

context carries forward to the context of this case. At the heart of his unestablished

assumptions is that A.K.’s ASD is the result of an autoimmune brain injury.

Doctor Shafrir acknowledged that “in order to demonstrate an autoimmune

reaction you have to find the actual antibody to isolate it and to show that this antibody

is capable of producing the disease.” Tr. 584. And, in arguing that A.K. experienced a

challenge-rechallenge event, Dr. Shafrir actually quoted language in his expert report

from a case report regarding ADEM which specifically associated the symptomology to

“production of greater amounts of antibodies to myelin after each vaccination” (emphasis added). Pet. Ex. 63 at 16, quoting Pet. Ex. 63, Ref. 8. With the exception of

narcolepsy, all of the conditions cited by Dr. Shafrir as analogous are demyelinating

conditions. See generally, Pet. Ex. 63, Refs. 7-11. Doctor Shafrir conceded that A.K.’s

his MRI was normal, effectively ruling out a demyelinating brain injury. Pet. Ex. 63 at

12; Tr. 545. Although he stressed that a normal MRI does not completely rule out any

brain injury (Tr. 545), Dr. Shafrir did rule out demyelination as a cause of A.K.’s

regression (Pet. Ex. 63 at 12).

These studies are therefore of very little relevance to this case. It would be

completely speculative to argue that evidence linking the influenza vaccine to

demyelination is also evidence that the same process would be the cause other nondemyelinating injuries. In fact, the Immunization Safety Review Committee Report cited

247 Pet. Ex. 63, Ref 7, K. Stratton, et al, IMMUNIZATION SAFETY REVIEW: INFLUENZA VACCINES AND

NEUROLOGICAL COMPLICATIONS (2004), [“IOM 2004 Influenza Report”]; Pet. Ex. 63, Ref. 8, K. Lapphra, et

al, Adverse Neurologic Reactions After Both Doses of Pandemic H1N1 Influenza Vaccine with Optic

Neuritis and Demyelination, PEDIATR INFECT DIS J., 30(1): 84-86 (2011); Pet. Ex. 63, Ref. 9,.C. Wells, A

Neurological Note on Vaccination Against Influenza, BRIT MED J., 3:755-56 (1971); B. Willi, et al,

Encephalitis after vaccination against H1N1 influenza virus, EUROP J PAEDIATR NEUROL., 15: 276-277

(2011); C. Poser, Neurological complications of swine influenza vaccination, Acta. Neurol. Scandinav.,

66: 413-431 (1982); Pet. Ex. 124, M. Partinen, et al, Increased Incidence and Clinical Picture of Childhood

Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland, PLOS ONE 

7(3): e33723 (2012) [hereinafter “Partinen, Pet. Ex. 124”]; Pet. Ex. 126, E. Miller, et al, Risk of narcolepsy

in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine:

retrospective analysis, BMJ, 346:f794doi: 10.1136/bmj.f794 (2013) hereinafter “Miller, Pet. Ex. 126”]; Pet.

Ex. 127, Swedish Medical Products Agency publishes report from a case inventory study on Pandemrix

vaccination and development of narcolepsy with cataplexy, EURO SURVEILL, 16(26): 19904 (2011)

[hereinafter “Pandemrix Vaccination Study”].
127

by Dr. Shafrir, indicated that, even if one accepts a causal relationship between the

influenza vaccine and GBS and the other demyelinating conditions specifically studied,

“the committee concludes that the evidence is inadequate to accept or reject a causal

relationship between influenza vaccine and other demyelinating neurological disorders.”

Pet. Ex. 63, Ref. 7, at 17. Thus, the sources cited by Dr. Shafrir do not advocate that

evidence of cause of one demyelinating condition constitutes evidence of a causal role

for influenza in other demyelinating conditions, let alone an extension to other

conditions in which demyelination is not the mechanism of injury.

Moreover, Dr. Shafrir’s citations regarding demyelinating disorders do not even

necessarily provide strong support for the general proposition that the influenza vaccine

causes a neurologic autoimmune reaction. None of the papers cited by Dr. Shafrir

actually concluded that the adverse neurological events caused by the influenza

vaccine were autoimmune. For example, although the IOM 2004 Influenza Report

acknowledged that molecular mimicry and bystander activation, mechanisms cited by

Dr. Shafrir as possibly applicable in AK’s case, are possible as causal mechanisms, it

characterizes the evidence in favor of those mechanisms as “weak.” Pet. Ex. 63, Ref.

7, at 13. Doctor Shafrir himself has acknowledged that “the systematic assessment of

the risk for neurological complications from influenza vaccine has multiple barriers” and

that “no systematic study controlled in any way was performed in very large population.”

Pet. Ex. 63 at 14.

Doctor Shafrir cited to an article by Toplak, et al,248 for the proposition that “there

are studies showing the appearance of autoantibodies in certain individuals after

influenza vaccine.” Pet. Ex. 63 at 16. That study concluded, however, that “influenza

vaccination did not increase the percentage of positive autoantibodies in the general

healthy adult population.” Pet. Ex. 63, Ref. 13, at 138. Only 7 out of 92 study

participants had persistently elevated levels of autoantibodies after influenza

vaccination. Id. The authors concluded that “there were no statistically significant

differences” in the percentage of positive antibodies. Pet. Ex. 63, Ref. 13, at 134.

Thus, to the extent Dr. Shafrir has not established that demyelinating disorders,

mismatched to the facts of this case as they are, even constitute autoimmune injuries in

the first instance, his analogy does not hold up on even the most basic level.

Perhaps recognizing these short-comings, on cross examination, Dr. Shafrir

stressed his comparison of A.K.’s condition to narcolepsy. Tr. 542. He noted that

narcolepsy is “very different from ADEM and GBS” and implied that it is more closely

aligned to A.K.’s condition “because it’s less acute, it’s lifelong, it’s disabling, it’s very

different. And it has no acute presentation.” Id. Doctor Shafrir’s reliance on the

narcolepsy studies, however, is equally misplaced.

Although the Partinen article noted that prior research suggested an autoimmune

etiology for narcolepsy (Pet. Ex. 124 at 2), none of the studies cited by Dr. Shafrir

actually studied that question. See generally, Partinen, Pet. Ex. 124; Miller, Pet. Ex.

126; Pandemrix Vaccination Study ,Pet. Ex. 127. Nor do they contain sufficient

248 Pet. Ex. 63, Ref. 13, N. Toplak, et al, Autoimmune response following annual influenza vaccination in

92 apparently healthy adults, AUTO IMMUN REV, 8: 134-38 (2008).
128

discussion of the prior research to allow for evaluation of that contention. Rather, each

study sought only to establish an association between onset of narcolepsy and

vaccination. Id. Thus, contrary to Dr. Shafrir’s assertion, the narcolepsy studies do not

in themselves show that the disorder is autoimmune in nature. Tr. 582-83. They

therefore do not establish, as Dr. Shafrir argues, the capacity of the influenza vaccine to

cause a neurological autoimmune injury.

Doctor Shafrir also acknowledged that the findings of the narcolepsy studies

were specific to the particular vaccine in question (“Pandemrix” H1N1) and the results

were not replicated in non-epidemic influenza vaccines. Tr. 543-44. Although one of

the cited articles intimated that the adjuvant contained in that particular vaccine might

have been causal, even that point was not widely accepted. Pet. Ex. 126 at 5.

Regardless of the cause, however, Dr. Shafrir acknowledged that the implicated vaccine

was specific to northern European countries. Tr. 543. There is no evidence to suggest

that A.K. ever received the vaccine studied.

Nonetheless, Dr. Shafrir argued that notwithstanding the fact that the narcolepsy

studies spoke to a vaccine and injury that are not at issue in this case, he “presented a

mechanism that is identical to what we have here in another situation and it can

definitely be applied here under the same mechanism that this child developed autism

in the same way those kids developed narcolepsy.” Tr. 489. His assertion was fervent,

but without any support.

Even if narcolepsy is a neurological autoimmune disorder, it does not

automatically follow that Dr. Shafrir’s analogy holds. As with GBS and ADEM,

narcolepsy appears to be caused by factors not relevant to this case. Partinen noted

that narcolepsy is typically characterized by a lack of hypothalamic hypocretin

production. Pet. Ex. 124 at 2. There has been no suggestion that hypothalamic

hypocretin problems are present in either ASD generally or in A.K. in particular.

Partinen also suggested that narcolepsy was strongly associated with specific genetic

polymorphisms not at issue in this case (HLA DR15 (DR2) and DQBI*0602). Id. Thus,

even if the narcolepsy studies established as a general matter the type of correlation

between genetic susceptibility and vaccination that Dr. Shafrir suggested was present in

A.K., neither the genetic vulnerability nor the ultimate neurological impact can be

matched up to this case. That is, even if the narcolepsy studies showed that a specific

influenza vaccine caused some type of neurological injury, they do not establish that

ASD is that type of neurological injury, or that A.K. received the type of vaccine that was

causal of narcolepsy.

Doctor Shafrir ‘s theory is predicated on the presence of a specific, unknowable,

antigen being present in A.K.’s influenza vaccine that would interact with his immune

system in this particular way. Tr. 554-56. Doctor Shafrir gave an example from his

training at St. Louis Children’s Hospital wherein 30-40 children presented with cerebral

ataxia following chicken pox. Tr. 502-03. He indicated that no one could explain why

those particular children succumbed to that particular complication of chicken pox,

noting that the immune system is “unique for every person on the face of the earth.” Tr.

503. Thus, he argued in effect that the only way to know what happened to those

children was to know that cerebral ataxia was a known immune reaction that was
129

associated with varicella infection. Id. Given this framing by Dr. Shafrir himself, it is

unclear by what basis Dr. Shafrir contends that the results of the narcolepsy study, or

any study using a different vaccine and resulting in a different injury, can be carried over

to A.K.’s case by way of analogy, as ASD is not a known complication of or reaction to

influenza or influenza vaccine.

b. Doctor Shafrir’s Reliance on Challenge-Rechallenge.

Finally, Dr. Shafrir argues with regard to adverse neurologic reactions to the

influenza vaccine that “their temporal association with the vaccine, when there is a lack

of other plausible cause, [is] a convincing argument for causality.” Pet. Ex. 63 at 15.

Specifically, Dr. Shafrir relies on the concept of challenge-rechallenge to show that A.K.

fits a pattern whereby his condition worsened after each of two doses of vaccine,

thereby strongly suggesting causation. Pet. Ex. 63 at 16. Although I addressed

whether the facts of A.K.’s case in particular fit the challenge-rechallenge model in

Section VII.D, above (and find that they do not), I note here that Dr. Shafrir’s reliance on

the challenge-rechallenge model in this context is conceptually inapt.

The “challenge-rechallenge” concept has been addressed in numerous cases

within the Vaccine Program. Most notably, the Federal Circuit succinctly summarized

the theory by explaining that “a rechallenge event occurs when a patient who had an

adverse reaction to a vaccine suffers worsened symptoms after an additional injection

of the vaccine.” Cappizano, 440 F.3d at 1322. To successfully establish a challengerechallenge theory, a petitioner must show a temporal relationship between the

occurrence of petitioner’s symptoms and multiple vaccine administrations. See, e.g.,

Doe, 95 Fed. Cl. at 609 (affirming the decision of the special master and noting that “the

special master found that petitioner had not established causation by a preponderance

of the evidence because neither of his expert’s proposed ‘challenge events’ had the

necessary temporal connection to the first or second dose of the vaccine.”)

Doctor McCusker explained, however, that challenge-rechallenge is

fundamentally an immunological concept. Tr. 1419-20, 1440-41. What the challengerechallenge scenario requires is problems associated with an adaptive immune

response. The expectation is that an immune reaction will be more muted at the first

dose and more pronounced on the second dose as the adaptive immune system’s

memory allows for a more rapid formation of antibodies. Tr. 1420. Doctor Shafrir

described the concept similarly. Tr. 491. Indeed, Dr. Shafrir cited language from a case

study regarding ADEM which indicated that “the patient’s neurologic symptoms

occurred shortly after the first dose of vaccine and resolved and additional symptoms

occurred shortly after the second dose of vaccine.” Pet. Ex. 63 at 16 quoting Pet. Ex.

63, Ref. 8.

The IOM noted, however, that “[i]t is possible that one or more of the ‘challenges’

in an individual case patient reporting is related to a coincidental exposure” and that the

value of rechallenge reports as evidence of causation “is much greater for monophasic

conditions (events that typically happen only once, e.g. vasculitis) than for relapsingremitting conditions, such as multiple sclerosis or rheumatoid arthritis.” 2011 IOM

Report, Pet. Ex. 223, at 46-47 [hereinafter” 2011 IOM Report”]. I also noted during my

questioning of Dr. Shafrir that the idea of challenge-rechallenge depends on the
130

condition at issue being monophasic. That is, that multiple occurrences of a symptom

or condition are only suggestive of causation if they would not otherwise be expected to

recur. Tr. 574-75. Doctor Shafrir conceded that he hadn’t considered that, but that

“there is something in it.” Tr. 575.

In this case, Dr. Shafrir relied solely on a parental report that A.K. lost speech

after the first dose of vaccine, experienced some improvement in speech, and then

demonstrated other symptoms of ASD subsequent to the second vaccine. Pet. Ex. 63

at 3-4. Doctor Shafrir also made a point, however, of noting that speech development is

a complex issue and that a notation of “speech delay” only indicates that the milestone

is “not happening now” and the ultimate significance of that delay, whether it is mere

delay or truly an impairment, usually becomes evident only later. Tr. 462-64. Doctor

Miller also intimated that children go through a period of development where they have

language – have uttered words – but have not yet progressed to using those words

consistently or reliably. Tr. 990-93. And, indeed, [A.K.’s mother] testified that A.K. has

had his speech disappear and reappear several times over the years without any

suggestion that it was associated with vaccination. Tr. 52.

In that regard, the variability in A.K.’s speech, which respondent’s experts

indicated may not even have been developed in any meaningful way in the first

instance, is a very tenuous indicator that A.K. experienced two distinct immune

responses to his vaccinations. Indeed, Dr. McCusker disputes that loss of speech could

be considered a manifestation of challenge-rechallenge at all. Tr. 1441.

The problem becomes more obvious when looking at Dr. Shafrir’s actual

explanation of autistic regression. In his expert report he indicates that some autistic

regression patients recover within a few months or years and others “progress to

develop various neurodevelopmental syndromes with variable degree of autistic

characteristics.” Pet. Ex. 63 at 12. With regard to A.K. in particular, he indicated that

“there is excellent documentation of appearance of regression of language and

behavioral changes typical for the autistic regression such as loss of eye contact

appearing after the first and worsening after the second influenza vaccination.” Id. He

stressed during his testimony, however, that a regression is a process that cannot be

pinpointed and that he could not say when exactly it started. Tr. 528. He also testified

that “autistic behavior fluctuates over time. It’s not something [where] a child behaves

like this and tomorrow is going to behave exactly the same way.” Tr. 478.

Thus, by Dr. Shafrir’s own explanation A.K.’s worsening condition, whether

identified by delayed or variable speech attainment or onset of other ASD symptoms, is

explained by the fact that he was experiencing a variable, yet ongoing condition. Doctor

Shafrir stresses that his condition worsened after the second vaccine, but that outcome

would have been expected by virtue of his autism with or without the second vaccine.

The fact that it happened is therefore not evidence that the vaccine was responsible.

C. Doctor Deth’s Presentation Does Not Otherwise Support Either Dr. Kendall or Dr.

Shafrir’s Theories.

Doctor Kendall’s opinion in this case was never more specific than to say that

vaccines create oxidative stress and are therefore metabolic stressors capable of
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causing a metabolic decompensation. In terms of substantiating that assertion, she

offered no proof or explanation beyond asserting that the Shoffner and Poling papers

demonstrated a” precedent” for the claimed association. Doctor Shafrir, likewise,

ultimately relied in part on mechanisms of neuroinflammation, oxidative stress, and DNA

methylation that he did not fully explain. Thus, as indicated above, in addition to Dr.

Kendall and Dr. Shafrir’s testimony, petitioners have also offered a presentation by Dr.

Deth which purported to explain a mechanism by which their respective theories may

operate.

Given that the causes of mitochondrial deterioration are not well studied or well

understood, Dr. Deth’s presentation could have been a viable vehicle for petitioners to

prove their theory. That is, if Dr. Deth presented a sound explanation for how a vaccine

could be expected to act in the manner Dr. Kendall and Dr. Shafrir each suggested, that

might provide sufficient support for one or both of their causation opinions. For the

reasons described in Section IX below, however, I have found that Dr. Deth’s opinion is

fundamentally flawed in a number of key regards and cannot be credited.

Of course, petitioners are not obligated to prove the mechanism of injury as part

of their burden of proof. Knudsen, 35 F.3d at 549. Nor am I requiring such proof.

Nonetheless, “causation in fact requires proof of a logical sequence of cause and effect

showing that the vaccination was the reason for the injury. A reputable medical or

scientific explanation must support this logical sequence of cause and effect.” Grant v.

Sec’y, HHS, 956 F.2d 1144, 1148 (Fed. Cir. 1992). It is therefore significant that the

mechanism proposed by Dr. Deth is in itself biologically implausible. See, e.g. Moberly

v. Sec’y HHS, 85 Fed. Cl. 571, 606 (Fed. Cl. 2009), aff’d 592 F.3d 1315 (Fed. Cir. 2010)

(holding that the Federal Circuit’s Knudsen decision “does not mean that a special

master cannot consider the reliability and soundness of theories of biological

mechanisms of causation that are proposed by parties.”).

Ultimately, all three of petitioners’ experts failed to present any sound scientific

explanation supporting petitioners’ theory. Therefore, the implausibility of Dr. Deth’s

proposed mechanism, particularly when coupled with the relative dearth of any other

supporting evidence, actually tends, if anything, to suggest that Dr. Kendall’s and Dr.

Shafrir’s theories are less likely to be valid.249

D. Conclusions Regarding Dr. Kendall’s and Dr. Shafrir’s Theories.

As indicated above, the context for Dr. Kendall’s theory is that there appears to

be a generally accepted correlation between metabolic stressors, such as illnesses and

surgery, and periods of regression in mitochondrial disorder patients, based on a

temporal relationship between such stressors and a regression or decline in health. Yet

no one knows exactly how or why this occurs, a point which Dr. Kendall herself

acknowledged. In the face of that uncertainty, Dr. Kendall has sought to extrapolate a

concrete and very specific cause and effect relationship between vaccines and

mitochondrial regression that simply lacks evidentiary support.

249 I do note, however, that based on the preceding analysis I would find that Dr. Kendall’s and Dr.

Shafrir’s theories were insufficiently supported even in the complete absence of Dr. Deth’s presentation.
132

Doctor Kendall has pointed to no medical literature that actually speaks to this

alleged relationship. Rather, the two articles she cited – Shoffner and Poling –

suggested only that fever might play a role in mitochondrial decompensation or

deterioration. Such a finding is fully consistent with the current state of scientific

understanding regarding mitochondrial disorders, but does not establish that any fever,

a common event in children, produces a condition that looks like ASD in general or

autistic regression in particular. All of the reports of mitochondrial regression in the

literature filed, and in the expert reports and testimony in this case, were quite vague

regarding the presentations of a mitochondrial decompensation. No one, not Dr. Shafrir

and not Dr. Kendall testified that they had seen a mitochondrial decompensation or

regression that looked like ASD. The Shoffner paper explicitly disclaimed any

connection between vaccination and neurological regression. Moreover, these studies,

which are particularly small, are weak evidence in themselves, that autistic regression

occurred more often in those with comorbid ASD and mitochondrial disorder conditions.

Contrary to petitioners’ claims, vaccines have not been shown to be metabolic

stressors at a level sufficient to trigger a metabolic or mitochondrial decompensation or

regression. To the extent Dr. Kendall argued that studies positing a temporal

connection between fever and regression establish a precedent for such a claim,

petitioners have not shown that such a finding could be translated to other potential

stressors based on current knowledge. In the absence of such an established

connection, petitioners have further failed to convincingly explain how such a

connection might otherwise be explained biologically. For these reasons, I find that I

cannot credit Dr. Kendall’s theory of causation.

For his part, Dr. Shafrir cited the very same purported relationship between

mitochondrial regression and vaccination and his argument presented the same

weaknesses. In addition, his application of the “triple hit” hypothesis failed on every

prong. He failed to demonstrate that A.K. had a genetically-based vulnerability from an

abnormal immune system. He failed to demonstrate that MTHFR polymorphisms are

associated with ASD or would cause an aberrant immune response to influenza

vaccine. Thus, there was nothing unique to A.K. which could have enhanced any

reaction to his influenza vaccine.

Doctor Shafrir contended that A.K.’s ASD – which he argued was an etiologically

distinct condition of autistic regression – was the result of a brain injury that was

autoimmune in nature. He failed to produce any evidence that A.K. had a brain injury

caused by a vaccine reaction, that ASD (or autistic regression) is an autoimmune

condition, or that A.K. had an autoimmune reaction to his two influenza vaccinations..

Doctor Shafrir acknowledged that there was no evidence of an autoimmune reaction in

this case. His attempts to circumstantially demonstrate the capacity of the influenza

vaccine to cause such a reaction were not only circular, they utterly failed.

Finally, and most critically, Dr. Shafrir also failed to demonstrate that two years of

age represents the “vulnerable period” that the “triple hit” hypothesis contemplates. The

available evidence in this regard has not changed since the OAP test cases were

decided. Doctor Casanova’s triple hit hypothesis squarely places the “vulnerable

period” prenatally, not at or near two years of age.
133

Thus, for all these reasons, I find that the theories espoused by Dr. Shafrir are

unreliable, and that the factual predicates for those theories are not present in A.K.’s

case.

IX. Dr. Deth Has Not Presented a Plausible Biological Mechanism for Either

Theory Advanced.

Doctor Deth’s presentation added little to petitioners’ case. Had Dr. Deth

presented a plausible biological mechanism explaining how A.K.’s influenza

vaccinations could have contributed to his alleged injury, his testimony theoretically

could have alleviated at least some of the above-discussed shortcomings of Dr.

Kendall’s and Dr. Shafrir’s theories. Though difficult to summarize, Doctor Deth’s

opinion is that “vaccinations promote inflammation and oxidative stress as integral

components of the immune response, and individuals with limited capacity to recovery

are at higher risk of long term adverse consequences, including developmental

regression in the case of young children.” Tr. 751.

That is, Dr. Deth opined that individuals with inhibited ability to produce

antioxidants are susceptible to injury due to the metabolic demand created by the

inflammation and oxidative stress associated with the immune response to vaccination.

He posited that this inflammation and oxidative stress impacts the transsulfuration

activity of the body’s sulfur metabolism to cause epigenetic changes (i.e. alterations in

gene expression) associated with autism. Pet Ex. 117 at 10-13. He identified A.K.’s

alleged mitochondrial disorder, his MTHFR polymorphisms, and alleged gastrointestinal

inflammation as vulnerabilities leading to a whole-body antioxidant deficit that left A.K.

at risk for such injury. Id. at 3.

Doctor Deth’s presentation, however, was ultimately unable to answer the key

question of how a vaccination could have produced an injurious level of oxidative stress.

In addition, as with Dr. Kendall’s and Dr. Shafrir’s opinions, his theory was predicated

on alleged vulnerabilities that simply do not exist in A.K.’s case or the significance of

which was not established. And, even if I did accept the presence and significance of

those vulnerabilities, Dr. Deth’s hypothesis was still implausible from both an epigenetic

and metabolic standpoint.

I note in particular that, despite my cautions that I did not intend to permit relitigation of the same evidence presented in the OAP test cases, much of Dr. Deth’s

presentation merely recycled a theory of sulfur metabolism that was rejected during the

OAP theory 2 test cases. Moreover, the entirety of Dr. Deth’s presentation was

undercut by his clear lack of candor and credibility.

A. Even Accepting Dr. Deth’s Theory as Valid, He Has Not Established That Any

Vaccine Could Have Contributed to A.K.’s Injury.

Doctor Deth’s presentation in this case did not provide any meaningful support to

either Dr. Kendall or Dr. Shafrir’s theories. In his expert report, Dr. Deth characterized

his opinion as ultimately answering the questions of “how a vaccine causes oxidative

stress” and “how such oxidative stress can cause injury to a child with a mitochondrial

disorder.” Pet. Ex. 117 at 2; Pet. Ex. 239 at 2-3. Even if I accepted all of Dr. Deth’s
134

underlying reasoning, he has failed to satisfactorily answer the threshold question of

how the vaccination itself would have contributed to the injury.

Importantly, with regard to oxidative stress, the question is not whether

vaccinations produce any oxidative stress at all, but rather whether they produce

sufficient oxidative stress to be injurious. Doctor Jones, a witness with far greater

expertise in oxidative stress than Dr. Deth, explained that oxidative stress is, in

essence, an ever present part of life and that, in moderation, it is not harmful. Tr. 1613-

21. Doctor Jones asserted that the term “redox biology” is more descriptive of what

happens in the body than the term “oxidative stress.” Res. Ex. ZZ at 1. He noted that

common daily occurrences such as exercise, eating and exposure to sunlight create

oxidative stress. Tr. 1620. An active infection produces a “respiratory burst” that

produces ROS (reactive oxygen species) to kill the infecting microorganism, but Dr.

Jones explained that the lesser immunological response to a vaccination produces ROS

only to the extent of the normal physiological signaling process known as “redox

signaling.” Tr. 1620-21.

Doctor Deth agreed with Dr. Jones’s basic description of redox biology. Tr. 639-

40. That is, in his own presentation he explained the distinction between harmful ROS

and ROS merely necessary to redox signaling. Id. Moreover, he conceded that

“vaccination has not been extensively examined with regard to its effects on redox and

methylation events.” 250 Tr. 736. He characterized that as a “serious problem.” Id.

Ultimately, Dr. Deth conceded during cross-examination that he did not know: (1)

how much oxidative stress was created by an influenza vaccine; (2) the threshold level

of oxidative stress necessary to cause autism under his theory; and (3) what level of

oxidative stress would be insignificant as a brain insult. Tr. 773. He agreed that

transitory oxidative stress, such as that caused by the exercise of a skeletal muscle,

does not impact the brain. Tr. 807. Thus, despite his lengthy presentation, Dr. Deth

250 Although Dr. Deth did not address it, I note that petitioners did file an additional study purporting to

show that a live attenuated influenza vaccine produced measurable biomarkers of oxidative stress. See

Pet. Ex. 97, M. Phillips, et al, Effect of influenza vaccination on oxidative stress products in breath, J.

BREATH RES. 4: 026001, pp 1-8 (2010) [hereinafter “Phillips, Pet. Ex. 97”]. However, the study’s results,

which are limited to the detectability of the oxidative stress produced by inhalation of a live, attenuated

influenza vaccine, do not support Dr. Deth’s theory in any meaningful way or otherwise advance

petitioners’ case. Nonetheless I asked Dr. Jones about the paper during the hearing. He noted the

significant distinctions between administration of a live viral vaccine directly into the lungs and a killed

virus administered intramuscularly. Tr. 1676-77. Consistent with Dr. Jones’s testimony regarding the

distinction between active infection and vaccination, the study authors hypothesized that the live

attenuated influenza vaccine in their study impacted oxidative stress by producing reactive oxygen

species in the same manner as the body’s response to viral pneumonia. Phillips, Pet. Ex. 97 at 3. This

suggests that the distinction between a live attenuated and killed influenza vaccine is significant. In

testifying that a vaccine does not have the same ability to generate a whole body response as a live

infection, Dr. McCusker stressed that a killed virus in a vaccine cannot replicate or spread and cannot

enter and activate the body’s cells. Tr. 1414-17. Given that the only live, attenuated influenza

vaccination was not approved for use until 2003 (PHYSICIAN’S DESK REFERENCE at 1689 (66th ed.

2012)), and A.K.’s influenza vaccinations were administered in 2001 (see Pet. Ex. 61, p. 4; Pet. Ex. 118),

he could not have received a live viral vaccination.
ultimately conceded that he was unable to opine that A.K.’s influenza vaccines were

capable of contributing to his ASD via a theory of harmful oxidative stress.251

Notwithstanding these significant problems for his proposed biological

mechanism for injury, his opinions regarding the role of inflammation in enhancing the

oxidative stress impact of vaccination, ultimately leading to brain injury, is also faulty.

Doctor Deth contended that “vaccination produces an inflammatory response that

includes changes in antioxidant and methylation pathways, along with increased

formation of TNF-α. In concert with the effects of aluminum (and mercury), TNF-α

promotes neuroinflammation in the brain and migration of activated monocytes to the

brain, especially during the postnatal years. An infectious challenge coupled with

immune/inflammatory stimulation increases the adverse consequences for the brain. In

combination these events represent an encephalopathy.” Pet. Ex. 239 at 96.

The most basic issue is that Dr. Deth’s hypothesis was based on an unsupported

principle. That is, he contended that the immune system is capable of impacting the

brain via the pro-inflammatory cytokine TNF-α (Pet. Ex. 239 at 91-92) and that vaccines

have an effect “similar to the effect of TNF-alpha” (Pet. Ex. 239 at 86). He therefore

posited, without any apparent support, that the immune response generated by a

vaccine must necessarily impact the brain.252 This argument does not account for the

significant differences in immune system challenges presented by vaccines as

compared to natural infections.

Dr. McCusker explained that vaccines produce only a transient immune

response. Tr. 1417-18. She noted that if a peripheral immune event such as a

vaccination created a significant central nervous system response, then one would

expect to see specific types of cytokines, known as endogenous pyrogens, acting on

the hypothalamus, which would generate a “very high” fever. Tr. 1417. To the extent

A.K. experienced any fever at all, petitioners were consistent in characterizing it as

“slight” or “low-grade.” See n. 205, supra. Doctor Cohen testified, consistent with Dr.

McCusker’s opinions, that the reduced antigen load of a vaccine made it unlikely that

the vaccine could produce sufficient inflammation to cause a mitochondrial

decompensation. Tr. 1311-12. Doctor Deth admitted that he could not opine that an

influenza vaccine has an antigen load comparable to an infection. Tr. 792-94.

Moreover, Dr. McCusker also pointed out that Dr. Deth’s hypothesis was based

in large part on a misreading of the work of Staci Bilbo regarding the effects of immune

251 Doctor Deth also indicated that he did not believe there is a specific amount of oxidative stress

generated by a vaccine, opining instead that he believed the level of oxidative stress caused by a vaccine

would vary from person to person. Tr. 824.

252 To the extent Dr. Deth’s hypothesis relied on the presence of aluminum adjuvant, it was inapplicable to

A.K.’s case. Doctor McCusker’s testimony that there was no aluminum adjuvant in the 2001-2002

influenza vaccine was unrebutted. Tr. 1418. Although Dr. Deth speculated that any other adjuvant would

have the same effect (Tr. 829-31), there was no evidence in this case that the influenza vaccines A.K.

received contained any adjuvant.

135
response on brain development. Doctor Deth cited Bilbo & Schwarz,253 a review article,

for the proposition that peripheral immune activation with or without infection could

impact brain development during the first three to five years of life.254 Tr. 742-43.

Doctor McCusker pointed out that Dr. Bilbo’s work focused on the effects of maternal

cytokine inflammation on the fetus. Tr. 1421-26. Doctor McCusker quoted the

statement that “these data [referring to data regarding the lack of any impact from

infection in later development] indicate that early infection-induced vulnerability is

specifically a developmental effect and not a general sensitizing event that can occur at

any time. Tr. 1425 (quoting Bilbo & Schwarz, Pet. Ex. 143 at 5). Indeed, the graphic

from this paper included in Dr. Deth’s presentation explicitly stated that it was reflecting

a “neonatal immune challenge.” Compare Pet. Ex. 239 at 93 and Bilbo & Schwarz, Pet.

Ex. 143 at 7, Figure 2. I also note that this review article noted that cytokines in the

brain, including TNF-α, are produced in the brain, involved with synapse formation and

neurogenesis, and with both injury and repair. Bilbo & Schwarz, Pet. Ex. 143, at

abstract.

Doctor Deth cited a study by Mercier, et al,255 purporting to show that, consistent

with this theory, vaccinations ultimately decrease methylation. Tr. 736-37; Pet. Ex. 239

at 86. Doctor Jones pointed out, however, that to the extent the study showed that the

vaccinations studied increased transsulfuration and decreased methylation, the actual

impact of the vaccinations was less significant than the difference between fasting and

fed subjects, suggesting that the impact is extremely small. Tr. 1639-42 (citing Pet. Ex.

132). It would, therefore, be impossible to differentiate between the impact of a

vaccination and skipping a meal.

Doctor Deth also cited his own study looking at the pro-inflammatory cytokine

TNF-α.256 See R. Deth, et al., Age-Dependent Decrease and Alternative Splicing of

Methionine Synthase mRNA in Human Cerebral Cortex and an Accelerated Decrease in

Autism, PLOS ONE, 8(2): e56927 (2013), filed as Pet. Ex. 135 [hereinafter “Deth, Pet.

Ex. 135”]; 257 Tr. 706-08; Pet Ex. 239 at 68. He contended that the study demonstrated

that TNF-α “strongly” decreased the amount of methionine synthase mRNA (“MS

mRNA”).258 Pet. Ex. 239 at 68; Tr. 708. Doctor Johnson pointed out, however, that Dr.

253 Pet. Ex. 143, S. Bilbo & J.Schwarz, Early-life programming of later-life brain and behavior: a critical

role for the immune system, FRONTIERS BEHAV.NEUROSCIENCE, 3(14): 1-14 (Aug. 2009) [hereinafter “Bilbo

& Schwarz, Pet. Ex. 143].

254 On cross-examination Dr. Deth refused to specify which of the studies discussed in the Bilbo &

Schwarz review supported his theory. Tr. 789-92.

255 Mercier, Pet. Ex. 132.

256 This is the same study discussed in Section IX.D, below as the post-mortem brain study. Here, Dr.

Deth refers to a different aspect of that study conducted not with post mortem brain samples, but with SHSY5Y neuroblastoma cells which were treated with 30 ng/ml of TNF-α. Pet Ex. 135 at 7; Tr. 708.

257 Citations will be to the machine-generated page numbers assigned by petitioners, as the actual

article’s pages are not numbered.

258 The significance of this finding, per the text of the study, is that “it can be inferred that TNF-α-mediated

inflammation is a candidate for causing lower levels of MS mRNA in autism.” Deth, Pet Ex. 135 at 11.

MS [methionine synthase] mRNA is a redox-responsive multi-domain enzyme that acts as part of the

transsulfuration pathway. Deth, Pet Ex. 135 at 1. Within the post-mortem aspect of the study, Dr. Deth

136
Deth’s underlying data, published elsewhere and not presented by Dr. Deth at this

hearing, showed that the effects of TNF-α on methionine synthase activity were

reversed within six hours, suggesting that TNF-α has little to no long-term effect on

methionine synthase activity. Tr. 1714-19.

Doctor Johnson further noted that the study methodology – i.e. directly injecting

TNF-α into cells – results in a concentration of TNF-α an “order of magnitude” greater

than one would see in cerebral spinal fluid after a vaccination. Thus, Dr. Johnson

contended that if such a direct injection cannot produce a sustained inhibition of

methylation, then a vaccine would not be able to produce enough oxidative stress to

inhibit methylation. Tr. 1727.

In light of Dr. Johnson’s testimony, Dr. Deth conceded that the impact of TNF-α

on methionine synthase is transient. Tr. 1750-51. Moreover, he indicated that reversal

of the decrease in methionine synthase is expected, to the extent that cells have the

ability to adapt to external stresses in order to maintain homeostasis. Tr. 1750-52. He

speculated, however, that there is an unspecified epigenetic “price to be paid” as a

result of the transient stress.259 Tr. 1752-53.

Finally, respondent’s experts stressed that there is no evidence in A.K. of either

neuroinflammation or oxidative stress and no evidence to suggest that A.K. had an

abnormal immune response to his influenza vaccines. Tr. 1412, 1651-52, 1659-61.

B. Doctor Deth Has Not Established that A.K.’s GI Issues Have Any Significance.

Doctor Deth never actually opined that A.K.’s vaccination alone was sufficient to

cause his injury. Like Dr. Shafrir, Dr. Deth asserted that A.K. was vulnerable to the

impact of his vaccination due to a number of factors, including both a mitochondrial

disorder and MTHFR polymorphisms, which I have already addressed in Section VIII

above. In addition, Dr. Deth also relied heavily on the idea that A.K. had gastrointestinal

problems leading to a whole-body deficit in antioxidants. For the reasons described

purported to show that individuals with autism have lower levels of MS mRNA. See Deth, Pet Ex. 135 at 

6; Pet Ex. 239 at 65; Tr. 706. He also posited that “factors affecting MS activity, such as oxidative stress,

can be a source of risk for neurological disorders across the lifespan via their impact on methylation

reaction, including epigenetic regulation of gene expression.” Deth, Pet Ex. 135 at 1. This theory

regarding the possible impact to the transsulfuration pathway recycles Dr. Deth’s OAP theory 2

presentation and is discussed further in Section IX.C below. The validity of Dr. Deth’s post-mortem study

is also discussed further below.

259 This is one of multiple examples (see sections IX.D.2 and E.2, below) of Dr. Deth changing or confusing

his theory on rebuttal. In his expert report and in his initial presentation, Dr. Deth asserted that the

presence of the TNF-α directly caused an epigenetic change by lowering cysteine uptake, increasing

transsulfuration, and inhibiting methylation. Pet. Ex. 117, p. 9; Pet. Ex. 239 at 68; Tr. 708. That is, he

testified that “what TNF-α is doing, it’s actually shifting the flow of cysteine away from the growth factor

regulated EAAT3 pathway, it’s decreasing that, whereas it’s increasing the alternative transsulfuration

pathway, which is usually low in the brain.” Tr. 710. Thus, he concluded that the TNF-α is “taking away

some of the characteristic features of the brain.” Id. But once forced to concede that the impact he

identified was transient and not as strong as he appeared to suggest, Dr. Deth then contended that it was

not the presence of the TNF-α itself that caused a lasting impact, but rather somehow the indirect result of

the cell’s actual demonstrated ability to clear the stressor that Dr. Deth had identified.

137
138

below, I find that Dr. Deth’s presentation regarding gastrointestinal inflammation is

wholly unpersuasive.

Specifically, Dr. Deth opined that that “to me, in my expert opinion, the perhaps

most critical feature predisposing and making [A. K.]’s case a special one of higher risk

for vaccination injury is his gut inflammation which has been documented.” Tr. at 745.

He opined that A.K. had “leaky gut syndrome” and that he was impacted by the

presence of gliadomorphin and casomoprhin, food-derived opiate peptides. Id. at 745,

818. Ultimately, Dr. Deth opined that the terminal ilium is critical for the uptake of 260

cysteine via the EAAT3

uptake.261 Tr. 715-18.

transporter and that inflammation of the GI tract inhibits that

The evidence that A.K. has any chronic GI problem is very limited. A.K. was

seen by his pediatrician on August 10, 2000, for a chief complaint of loose stools. His

diagnosis was “AGE.”262 Pet. Ex. 61, p. 88. A few days later on August 13, 2000,

A.K.’s continued loose stools were the subject of a telephone consultation. Pet. Ex. 61,

p. 87. Subsequent notations indicate a report of three weeks of diarrhea as of August

14, 2000, and a “long diet discussion” on September 9, 2000. Id. Subsequent records

show periodic reports of “loose stool.” Pet. Ex. 61, pp. 74, 70, 62. On June 26, 2001,

A.K. was seen for an apparent “gastro” complaint, including “liquid diapers” and

dehydration.263 Pet. Ex. 61, p. 61.

On November 12, 2002, A.K. had an intestinal biopsy analyzed by Dr. Harry

Ioachim at Lenox Hill Hospital.264 Pet. Ex. 3, pp. 322-23; Pet. Ex. 61, pp. 129-32. On

260 Doctor Deth contended that EAAT3 is the major source of cysteine for the brain. Tr. 666-68. Doctor

Jones, however, noted that there are multiple cysteine transporters and questioned Dr. Deth’s focus on

EAAT3 in particular. Tr. 1654-56. Doctor Deth’s focus on EAAT3 appears to stem from the fact that he

believes EAAT3 can be associated with both the uptake of cysteine in the GI tract as well as the delivery

of cysteine to the brain. Tr. 716-17. That is, he contends that GI inflammation can, via its impact on the

EAAT3, ultimately impact the brain. Tr. 713-18. In the Theory 2 test cases, Dr. Deth focused on the

EAAT3 transporter because he thought it was the only cysteine transporter available to neurons. That

assertion was incorrect, as Dr. Jones demonstrated. See Dwyer, 2010 WL 892250 at *121, n.517. Here,

as in Dwyer, in a matchup between Dr. Deth and Dr. Jones, Dr. Deth fares poorly.

261 It is worth noting that Dr. Jones challenged Dr. Deth’s assertion that EAAT3 is the primary transporter 

of cysteine in the intestine. Tr. 1654-57. However, since I have concluded that Dr. Deth is not qualified to

opine regarding the significance of A.K.’s alleged GI inflammation, it is not necessary to reach the 

question of whether Dr. Deth or Dr. Jones is correct on that specific point.

262 “AGE” is a commonly used abbreviation for “acute gastroenteritis.” See, e.g., N. Davis, MEDICAL

ABBREVIATIONS: 32,000 CONVENIENCES AT THE EXPENSE OF COMMUNICATION AND SAFETY (15th ed.), at 40.

263 Petitioners interpret that handwritten diagnostic impression as “AGI” which they indicate stands for

“acute gastrointestinal symptoms.” ECF No. 297 at 6. It may also say “AGE.” Pet. Ex. 61, p. 61.

Regardless of the interpretation it is clear that this visit reflects that A.K. had a gastrointestinal complaint

of some kind.

264 Petitioners stress that Dr. Iochim found that “A.K.’s intestinal cells showed the presence of ‘multiple

reactive hyperplastic lymphoid follicles’ in three sites in the ilea muscosa, ‘fecal mucosa with reactive

lymphoid follicles,’ ‘seven sites with nodular or diffuse inflammatory infiltrates of lymphocytes’ and more.”

ECF No. 297 at 9. They argue that these findings are “all indicative of marked gastrointestinal disease.”

Id. I note, however, that Dr. Levy, the director of the Children’s Digestive Health Center at the New York
139

that same date, he had a colonoscopy exam conducted by gastroenterologist Dr. Arthur

Krigsman.265 Pet. Ex. 8, pp. 59-61. Doctor Krigsman found, inter alia, that A.K.’s

terminal ileum was “moderately lymphonodular.” Pet. Ex. 8, p. 61. Following the biopsy

and colonoscopy, Dr. Boris noted lymph node hyperplasia and that A.K. was positive for

colitis. Pet. Ex. 3, pp. 133-35. I note that Drs. Boris and Krigsman had offices adjacent

to one another, based on their office addresses. See Pet. Exs. 3, p. 389 (listing Dr.

Boris’ office as “77 Froehlich Farm Blvd”); 8, pp. 28, 57 (listing Dr. Krigsman’s office as

“Woodbury Pediatrics Assoc., 75 Froehlich Farm Blvd” and as simply the same address

without the Woodbury Pediatrics reference).

Looking at an image of A.K.’s distal ileum from the November 2002 colonoscopy,

and comparing it to a “normal” example, Dr. Deth testified that “so just for contrast, a

normal gut epithelium is on the left here. We can see kind of a clean vascular surface,

lots of nice mucus, but none of the sort of bulbous lymphoid, which mean, of course,

immune cells, white cells. There’s some kind of inflammation happening there which I

would have to say does not look like it’s favorable for the processes that I’ve just

reviewed, the absorption in that area.” Tr. 721-22 (discussing Pet. Ex. 13, p 1.). Doctor

Deth initially described the reported GI inflammation as “severe,” before admitting that

the colonoscopy report actually indicated that the inflammation was “moderate.” Tr.

760.

Dr. Deth characterized this piece of evidence as “striking” and “obviously

relevant.” Tr. 721. However, nothing in Dr. Deth’s background, training, or experience

suggest that he is qualified to offer any opinion regarding the nature of the inflammation

depicted, nor its significance in terms of GI function. He conceded that he is neither a

pathologist nor a gastroenterologist. Tr. 722. I note again that Dr. Deth holds a Ph.D.,

not a medical degree.

In that regard, I sought to clarify the nature of Dr. Deth’s reliance on this

colonoscopy. Specifically, I asked him if he was relying on Dr. Krigsman’s expertise

and ultimate diagnosis or whether he was offering his own opinion. Tr. 721. At first, Dr.

Deth confirmed he was relying on Dr. Krigsman’s impression of lymphonodular

hyperplasia, but then continued to offer his own interpretation of the image, noting as

described above that the depicted inflammation “does not look like it’s favorable” to the

uptake of cysteine. Tr. 721-22.

Presbyterian Children’s Hospital of New York characterized the biopsy findings only as “suggestive of

mild colitis.” Pet. Ex. 61, p. 123. In any event, Dr. Deth did not at any point cite these findings as

supportive of his opinion.

265 Significantly, Dr. Krigsman testified regarding the possible connection between gut disorders and

regressive autism during the OAP. Synder, 2009 WL 332044, *83-86. Based on a review of his own

patients, Dr. Krigsman testified regarding a concept he referred to as “autistic entercolitis.” Respondent’s

experts rebutted this concept by noting, inter alia, that there is no diagnosis of “autistic entercolitis”

recognized in gastroenterology and that epidemiological evidence does not support the contention that

children with regressive autism experience inflammatory bowel disease more frequently than those

without regression. Id.
140

In light of his insistence, I again gave Dr. Deth an opportunity to cite something –

anything – to support his argument that the depicted inflammation would result in this

particular loss of function. Tr. 722. Doctor Deth then claimed that he is “a

knowledgeable scientist” in the relevant field and that he knows “enough about GI

epithelial function in regard to cysteine uptake.” Tr. 722. Despite this protest, he

nonetheless conceded that he could not cite anything to support his claim and instead

stated that generally speaking “without being too concrete about that . . . the cell’s

normal function will be impaired when it’s inflamed. So I’d have to leave it at that.” Tr.

722-23.

Doctor Deth attempted to further link his claim regarding A.K.’s GI inflammation

to A.K.’s overall medical record, indicating that “there’s other evidence to that effect

including a medical history of GI problems, and those problems could be related to his

other metabolic abnormalities affecting the terminal ileum because that is the place that

was most inflamed.” Tr. 745. Doctor Deth also offered opinions that the GI

disturbances noted in earlier portions of A.K.’s medical history “seemed not to be at the

same level of importance” as subsequent findings. Tr. 804. He claimed to know the

significance of a finding regarding “irritable bowel disease.”266 Tr. 803. When

challenged regarding his analysis of A.K.’s medical history, Dr. Deth conceded only that

he has no expertise relative to the timing of the cited GI inflammation, but insisted that

he was nonetheless qualified to speak to its potential impact. Tr. 747.

His testimony regarding the significance of GI inflammation in A.K.’s medical

history was confusing and inconsistent. In his expert report, Dr. Deth indicated that

A.K.’s alleged GI dysfunction was a factor predisposing him to harm from his

vaccinations. Pet. Ex. 117 at 14. In his subsequent trial presentation, however, Dr.

Deth indicated that A.K. developed GI inflammation after his vaccinations. Pet. Ex. 239

at 98. When I questioned Dr. Deth regarding the discrepancy, he acknowledged that

the reference to the inflammation being after the vaccine was based on the fact that the

266 On cross-examination, Dr. Deth was asked whether A.K.’s testing negative for “irritable bowel disease”

would affect his opinion. Tr. 803. This appears to be a reference to inflammatory bowel disease (“IBD”).

Doctor Deth clarified that respondent’s counsel was not referring to irritable bowel syndrome (“IBS”)

before indicating that a negative finding for irritable bowel disease would not change his opinion. Id.

Significantly, however, Dr. Deth cited a review paper on Crohn’s disease, a type of IBD, to support his

contention that TNF-α is responsible for the type of GI inflammation A.K. experienced. Pet. Ex. 239 at 77

(citing Pet. Ex. 260, S. Peake, et al, Mechanisms of Action of Anti-tumor Necrosis Factor α Agents in

Crohn’s Disease, INFLAM. BOWEL DIS., 19: 1546-55 (2013) [hereinafter “Peak, Pet Ex. 260”]. When Dr.

Johnson indicated that this paper had nothing to do with autism and was not relevant to his theory (Res.

Ex. JJJ at 3), Dr. Deth replied that the article indicated that “the proinflammatory cytokine TNF-alpha

contributes to GI inflammation. GI inflammation has to do with autism and with [A.K.].” ECF No. 281 at 5.

Doctor Deth’s citation, however, indicated that TNF-α has been examined in Crohn’s disease because it 

is a regulator of the innate immune response and the chronic gut inflammation of inflammatory bowel

diseases such as Crohn’s disease or ulcerative colitis is known to occur via an immunopathogenic

mechanism. Peake, Pet. Ex. 260 at 1546. To the extent Doctor Deth’s statement was that the presence

or absence of IBD would not alter his opinion, this suggests that he is not aware of that distinction.

Indeed, during his initial presentation Dr. Deth indicated that TNF-α is broadly implicated in many forms of

GI inflammation. Tr. 724-25. That statement goes well beyond the Peake article, which is the only cite 

he provided for that assertion. Although A.K. may have had some signs of colitis, he did not have

ulcerative colitis. Pet. Ex. 61, p. 124; Tr. 96.
141

colonoscopy, the only explicit evidence of inflammation cited, occurred over a year after

the vaccinations in question. Tr. 746. He then suggested that earlier notations in A.K.’s

medical records were indicative of prior inflammation, before finding himself unable to

cite any specific notations and ultimately acknowledging that he did not have the

expertise to so opine. Tr. 746-47. He also indicated that the question of whether A.K.’s

inflammation occurred before or after the vaccine was important, but nonetheless

seemed to opine, quite unconvincingly in light of the above, that he could reconcile

either scenario with his theory. Tr. 747.

Doctor Deth also cited urine samples showing gliadomorphin and casomorphin

peptides as evidence that A.K. has “leaky gut syndrome.” Pet. Ex. 117 at 13. “Leaky

gut syndrome,” also known as “autistic enterocolitis” is not a recognized diagnosis.

Rather, it is a hypothesis initially advanced by the now-discredited Andrew Wakefield.

See, e.g., Synder, 2009 WL 332044 at *79-87. Moreover, Dr. Deth’s own expert report

indicated that these peptides are, if anything, diagnostic of celiac disease, not irritable

bowel syndrome or inflammatory bowel disease. Pet. Ex. 117 at 14. To the extent Dr.

Deth claimed that his own research has shown that these same peptides inhibit EAAT3,

his only citation is to one of his own publications: Autism: A Neuroepigenetic Disorder,

filed as Pet. Ex. 117, Ref. 46.267 Although the article is best characterized as a review

article, Dr. Deth nonetheless referenced his own original research within the text,

without reporting any of his actual data. Particularly in light of his selective presentation

of his other studies (see Section IX.D, below), this is not a persuasive piece of

evidence.

I also note that one of A.K.’s own treating gastroenterologists, Dr. Levy,

expressed serious doubts about the pursuit of a “leaky gut” “diagnosis.” Pet. Ex. 61, p.

124. Doctor Levy, writing in April of 2003, specifically noted that as of that date A.K.

was negative for serological markers of celiac disease and cautioned against pursuing

the “leaky gut” theory to connect A.K.’s autism to either food allergies or immunizations.

Id. In contrast, Dr. Deth’s sole citation in support of his claim that A.K. had

gliadomorphin and casomorphin peptides was a much later hand written notation by Dr.

Boris from January of 2005. Pet. Ex. 117 at 13 (citing Pet. Ex. 3, p. 45). Neither Dr.

Deth nor petitioners have cited any testing to substantiate that notation. Moreover, I

find the notation Dr. Deth relied upon (Pet. Ex. 3, p. 45) to be illegible.

Doctor Deth also cited a finding in A.K. of low cystine in August of 2008 as

evidence that A.K. had a deficit of antioxidants caused by his GI inflammation. Tr. 749;

Pet. Ex. 239 at 101. The actual result was not characterized as low; it was

characterized as below the detection limit of the test, according to Dr. Jones. Tr. 1643-

45. Moreover, Dr. Jones noted that measurements of cystine are incredibly unreliable

absent specific protocols, and cystine values vary by both time of day and diet. Tr.

1645-48. For these reasons, as well as the absence of information regarding the lab’s

handling of the samples, Dr. Jones did not trust the reported cystine values. Id. In his

rebuttal testimony, Dr. Deth did not address any of Dr. Jones’s concerns, but stated only

that Dr. Jones’s concerns “struck me as shooting the messengers if you don’t like the

267 AUTISM SCIENCE DIGEST: THE JOURNAL OF AUTISMONE, 3:8-19. The filed copy of the article indicates

that it is reprinted with permission, but does not identify the source document or the year of publication.
142

delivery of the package” before stating without any apparent support that “there’s no

reason to disparage the validity of those results and they speak for themselves.” Tr.

1743.

The fact that Dr. Deth’s testimony strayed a bit from his precise area of expertise

is not, in itself, highly significant. I note that many of the respondent’s experts

occasionally did the same. Indeed, there is an extent to which the interconnectedness

of these topics requires it. See, e.g., Dr. Johnson briefly discussing the immunologic

topic of the impact of vaccines versus active infection as it related to neurotoxicity. Tr.

1732. But Dr. Deth’s testimony is unique in this case both for the significant extent to

which his opinion is ultimately built upon this overreaching, as well as the extent to

which he has attempted to assert – without any apparent basis – sufficient knowledge in

the area of gastroenterology to opine knowledgeably and reliably, despite his lack of

credentials. Indeed, Dr. Deth asserted that A.K.’s purported GI inflammation was the

“most important” piece of evidence regarding the presence of oxidative stress in A.K.’s

case. Tr. 801. He also persisted in claiming expertise regarding the impact of

gastrointestinal inflammation, despite being unable to provide any supporting source for

his assertions and his tenuous grasp on what the medical records actually reflected. 268

The wide latitude afforded to an expert “is premised on an assumption that the expert’s

opinion will have a reliable basis in the knowledge and experience of his discipline.”

Daubert, 509 U.S. at 592.269 This assumption does not apply when an expert is opining

outside of his discipline.

During the OAP I observed that while Dr. Deth has a Ph.D. in pharmacology

most of his research prior to 1998 focused on hypertension and cardiovascular

problems, not neurotoxicology, neuropharmacology, autism, or sulfur metabolism.

Dwyer, 2010 WL 892250 at *108. I found that respondent’s competing experts offered

more persuasive testimony in part because, unlike Dr. Deth, they carefully restricted

their testimony to their areas of expertise. Id. The same dynamic plays out in the

instant case. Doctor Deth’s credibility in this case is greatly reduced by his unapologetic

attempts to testify well beyond his expertise. See, e.g., Tr. at 628-29 (toxicology), 722

(pathology and gastroenterology), 733-34 (immunology). As described herein, this

tendency was particularly pronounced with regard to Dr. Deth’s claims regarding

gastroenterology. Indeed, as noted above, I felt compelled to challenge Dr. Deth’s

overreach on this subject numerous times (Tr. 722-23, 747, 751),and, after he had

opined that the two influenza vaccinations were responsible for A.K.’s “neuro

developmental injury,” “regressive encephalopathy,” and “severe early developmental

regression,” I commented that Dr. Deth’s diagnoses and causation opinions constituted

268 Interestingly, despite his forays into gastrointestinal diagnosis, Dr. Deth acknowledged that upon his

review of A.K.’s medical records, he did not recognize the importance of “AGE” notations. Tr. 753. Even

[ A.K.’s father], a lay witness, testified that he understood what the abbreviation “AGE” meant. Tr. 94-95.

While not terribly significant in itself, this does provide a tidy illustration of why I am highly skeptical of Dr.

Deth’s claimed, yet un-credentialed and unsubstantiated, knowledge of gastrointestinal function.

269 The Federal Circuit has approved the use of the Daubert factors by special masters in evaluating the

reliability of and the weight assigned to expert opinions in Vaccine Act cases. See Moberly, 592 F.3d at

1324 (Fed. Cir. 2010); Andreu, 569 F.3d at 1379; Terran, 195 F.3d at 1316.
143

“practicing medicine without a license” (Tr. 751).270 Doctor Deth’s medical opinions

regarding A.K.’s gastrointestinal inflammation and its purported relationship to two

vaccinations were outside his expertise and unsupported by other evidence. I find them

inherently unreliable based on Dr. Deth’s lack of qualifications to diagnose this child and

to opine on the cause of a neurodevelopmental condition.

C. Doctor Deth’s Opinion Remains Predicated on Concepts Rejected During the OAP.

The remainder of Dr. Deth’s presentation largely recycled concepts and ideas he

previously presented during the OAP theory 2 test cases, particularly with regard to

sulfur metabolism. During the OAP, all three special masters who heard him found his

testimony lacked sufficient indicia of reliability to be credited.271 King, 2010 WL 892296

at *54-61; Dwyer, 2010 WL 892250 at *108-142; Mead, 2010 WL 892248 at *64-80.

In the OAP Theory 2 cases, Dr. Deth hypothesized a biochemical process by

which mercury can produce an oxidizing environment in the brain, described the

biochemical processes involved in neuroinflammation, and explained that only a small

fraction of children vaccinated with TCVs develop autistic symptoms because of

“genetic and epigenetic differences between individuals.” Dwyer, 2010 WL 892250 at

*108. He testified “that ‘the most critical problem in autism’ involves maintaining a

normal ‘redox’ status in cells” and attempted to explain the underlying cellular

metabolism relating to this problem. Id. He also asserted that children with autism have

an impaired ability to handle oxidative stress. Id.

Then-Special Master Campbell-Smith “found that the particular limitations that

Dr. Deth recognized in his own testimony significantly diminished the weight that could

be accorded to the theory he presented.” Mead, 2010 WL 892248 at *6. Special

Master Campbell-Smith also found Dr. Deth’s own research to be of questionable

reliability. Id. at *73-74. Special Master Hastings similarly, but more forcefully, stated

270 In light of petitioners’ arguments against consideration of Dr. Miller’s testimony, I find it ironic that they

proffered the testimony of a pharmacologist with no background in gastroenterology, neurology, or

immunology to opine in all three fields. While toxicology is certainly grounded in biochemistry and related

to pharmacology, it does constitute a separate discipline. I am certainly not requiring that a witness have

a medical degree in order to offer an opinion in a Vaccine Act case. Indeed, I have permitted,

considered, and credited the testimony of Ph.D. witnesses who lack a medical degree in the past. See,

e.g. Synder, 2009 WL 332044 at *17, *20-21 (crediting the testimony of, inter alia, Dr. Thomas

MacDonald, a Ph.D. specialist in gastroenterology; Dr. Michael McCabe, a Ph.D. toxicologist, Dr. Steven

Bustin, a Ph.D. molecular geneticist.) Here, however, Dr. Deth’s opinions were so far outside his areas of

education, training, research, and experience to be per se unreliable. Had this been a jury trial, I would

not have let him testify, based on the requirements of Daubert. Unlike Dr. Deth, Dr. Miller clearly

possessed the education, training, and expertise necessary to opine on the matters about which she

testified.

271 The OAP special masters were not the only judicial officers to express concerns about the reliability of

Dr. Deth’s opinions based on his lack of expertise to opine. In one of the autism cases tried outside the

Vaccine Program, Maryland Circuit Court Judge Berger found Dr. Deth’s testimony inadmissible because

“his opinion ‘that exposure to mercury [from] thimerosal-containing vaccines causes autism,’ would have

required him to delve into fields of toxicology, epidemiology, neurology, and genetics—all fields with

which he had little or no expertise.” Blackwell v. Wyeth, 408 Md. 575, 625-26 (2009). The highest court

of Maryland upheld this ruling. Id. at 630.
144

that the testimony of Dr. Deth “was not persuasive in any event.” King, 2010 WL

892296 at *28. He observed that Dr. Deth “did not explain his opinion well, and relied

heavily on questionable in vitro experiments and on his own laboratory’s work, part of it

unpublished.” Id. at *55. I stressed that “the scientific studies upon which [Dr. Deth]

relied provided, at best, only tangential support for his hypothesis” and that his own

research was “poorly performed and scientifically implausible.” Dwyer, 2010 WL

892250 at *109. I also noted that “in the course of the hearing, nearly every premise of

his causation theory, other than that of the ubiquity of mercury exposure in children

(with or without autism), was seriously undermined, where not completely demolished.”

Id. at *110.

In Dwyer, I summarized Dr. Deth’s theory in pertinent part as contending that

mercury depletes glutathione levels, which in turn increased oxidative stress. Oxidative

stress turns off methionine synthase activity, resulting in less methionine. Lowered

methionine levels result in reduced “SAM” production and that leads to fewer

methylated products available for DNA methylation. 272 It also impacts the D4 dopamine

receptor on neuronal cells, decreasing synchronization for neuronal activity. According

to Dr. Deth, both impaired methylation and the negative impact on dopamine receptor

can produce autistic symptoms. Dwyer, 2010 WL 892250 at *113.

Except for mercury as the trigger for oxidative stress, this is the same process

Dr. Deth described in this case. Doctor Deth testified that ultimately the most important

aspect of his present theory is the level and state of glutathione oxidation in the brain.

Tr. 772. He opined that “a decrease in [methionine synthase] activity inhibits

methylation reactions by lowering the SAM/SAH ratio” and that “any factor that

significantly alters [methionine synthase] activity will exert significant epigenetic effects.”

Pet. Ex. 117 at 8. He also opined, as he did in the OAP, that the reduction in

methionine synthase activity results in both a decrease in D4 receptor phospholipid

methylation and DNA methylation, which both in turn lead to autism. Tr. 689; Pet. Ex.

239 at 55.

Indeed, Dr. Deth made the overlap with his OAP testimony quite clear when he

indicated during his presentation in this case that his current theory is reflected in his

2008 review article. Tr. 646; Pet. Ex. 239 at 24; Pet. Ex. 117 at 9, 12 (citing Pet. Ex.

117, Ref. 11, R. Deth, et al, How environmental and genetic factors combine to cause

autism: A redox/methylation hypothesis, NEUROTOXICOL. 29: 190-201 (2008). In Dwyer,

I noted that at the time of his participation in the OAP, this review article was Dr. Deth’s

only publication on oxidative stress. Dwyer, 2010 WL 892250 at *108, n. 456. The

problems with the article and the theory behind it were discussed extensively in Dwyer,

272 “SAM” refers to S-adenosylmethionine, a methyl donor. Pet. Ex. 117 at 8. As in the OAP, Dr. Deth

contended here that the level of methionine synthase has a direct relation to the level of SAM while being

inverse to “SAH” or S-adenosylhomocysteine. Id. That is, he contended that increased methionine

synthase activity promotes methylation by increasing the SAM/SAH ratio while decreased methionine

synthase activity inhibits methylation by lowering the SAM/SAH ratio. Id. Methylation of DNA is

responsible for alterations in gene expression, producing the epigenetic changes that Dr. Deth

referenced. Pet Ex. 117 at 7.
145

and like much of Dr. Deth’s other testimony, was given very little weight. Dwyer, 2010

WL 892250 at *111, 113, 114, 116, 121, 133, 135, 140.

During the OAP, I discussed Dr. Deth’s peculiar views regarding both the

methionine-methylation cycle and his D4 receptor methylation hypothesis. Dwyer, 2010

WL 892250 at *115-19. I discussed at length the short-comings of Dr. Deth’s own study

regarding the D4 receptor (the Waly study) on which he relied heavily.273 Doctor Deth

claimed to have discovered an unusual extracellular methylation cycle at the D4

receptor. Dwyer, 2010 WL 892250 at *118-19. Based on the profound flaws of that

study, coupled with Dr. Deth’s unsupported extrapolation of its findings, I found the

evidentiary value of this paper to be essentially nil.274 Id. Despite continuing to rely on

that same study, Dr. Deth has presented very little new information on these points in

this case and has failed to remedy any of the deficiencies I identified.275 See, e.g., Pet.

Ex. 117 at 9 (Dr. Deth’s expert report’s reliance on the conclusions from the Waly study

as a basis for much of his later work). And, his opinion and his underlying research

work were, once again, thoroughly and extensively rebutted by Dr. Johnson. See Res.

Ex. XX at 6-9 (Dr. Johnson’s expert report, identifying twelve flaws with the Waly paper

before concluding, “[t]his single paper, the whole foundation of Dr. Deth’s theory in this

case, has no data on either oxidative stress or methylation. This lack of data indicates

that, once again, Dr. Deth’s hypothesis is simply speculation without scientific

foundation.”).

But perhaps the most glaring flaw Dr. Deth has carried forward from his

discredited OAP theory is the concept of the cystathionine block. As noted above, Dr.

273 Waly, Pet. Ex. 117, Ref. 9. For some reason, the actual paper was filed in the OAP but, in the present

case, the on-line early release version was filed. In comparing page number citations to the article in the

two proceedings, the present case’s page 1 corresponds to page 358 in Dwyer. Since the Waly paper

continues to play an important role in Dr. Deth’s opinion in the present case, I take note that this original

paper was rejected by three journals before it was published by a fourth. Dwyer, 210 WL 892250 at *108

n.457.

274 In Dwyer, I described the Waly paper as having two distinct parts, one related to the effects of insulinlike growth factor 1 and dopamine on methionine synthase activity and one related to the inhibitory effects

of heavy metals on DNA methylation. See Dwyer, 2010 WL 892250 at * 116-17, 119. My focus here is

primarily on the first part.

275 Although he did cite the Waly study multiple times in his expert report (see Pet. Ex. 117 at 8-9), Dr.

Deth attempted to gloss over his reliance on the study during his testimony. He presented a slide

depicting “the D4 receptor that our lab discovered,” but then stated that “while I’ve published a number of

papers about this, I don’t recount them here.” Tr. 684. He also tried to deflect the criticisms of his work

by claiming that the critique offered by Dr. Johnson constituted an attempt to redo the peer-review

process, stating that “at this point in time I find it inappropriate as well as off target to some extent to

review the way we did our experiments and to suggest other controls that we could have done. There

was a time for that, but that time was when the paper was published, and if somebody wants to pick up

and add to our data and test it, that’s what science is.” Tr. 764-65. Such an argument is, of course,

absurd. By Dr. Deth’s logic, all peer-reviewed literature is of precisely equal quality and value simply by

virtue of having met the minimum criteria for publication. That is clearly not true. Moreover, Dr. Jones

pointed out that the peer-review process is not perfect and that results in works of variable quality. Tr.

1664-65. I also note, for example, that Dr. Cohen, in contrast to Dr. Deth, was quite forthright in testifying

regarding his opinion that a paper for which he was a participating author had significant methodological

flaws. See, e.g., Tr. 1227-29, 1356-59.
146

Deth has indicated that his theory is ultimately based on how the body supplies

glutathione to the brain. Tr. 772. Respondent’s experts have noted, however, that the

human brain has compensatory systems, that the transsulfuration pathway does not

operate via a single transporter, and that it is not plausible for the mechanism that Dr.

Deth described to impact the brain and only the brain. See, e.g., Tr. 1514-19, 1728-32,

1654-57. In that regard, Dr. Deth relied on what he characterized as the “cystathionine

block” in the human brain to explain both that the brain is uniquely susceptible to

oxidative stress and dependent upon the EAAT3 transporter to provide cysteine. Tr.

666-68.

Cystathionine is the first of the two intermediate steps on the transsfulfuration

pathway, between homocysteine at one end and glutathione on the other. Cysteine is

the second intermediate step, failing between cystathionine and glutathione. Dwyer,

2010 WL 892250 at *197, n.520; Tr. 668-69. As in the OAP, Dr. Deth cited a 1958

study showing that the human brain has a much higher level of cystathionine than other

species, such as monkeys, rats and ducks.276 Dwyer, 2010 WL 892250 at *121-22; Tr.

669-70; Pet. Ex. 239 at 37. He contended that this study shows that “evolution has

gradually tightened the noose around transsulfuration, has gradually reduced the ability

of homocysteine to be converted into cysteine, thereby gradually increasing the

importance of the EAAT3-mediated cysteine uptake pathway.” Tr. 669-70.

But, as in the OAP, Dr. Deth’s description of a cystathionine block remains

completely unsupported. See, e.g., Tr. 1735-36. As I noted in Dwyer, “Dr. Deth jumped

from high cystathionine levels to the conclusion that there was a blocked metabolic

process without any data that such a block actually exists. He did not rely on any

measurements of lower cysteine and glutathione levels in human brains; he simply

concluded that they must be low as a result of high cystathionine levels. It is equally

likely that cysteine and glutathione levels are also higher in humans.” Dwyer, 2010 WL

892250 at *122. Indeed, Dr. Deth still has not offered any explanation as to why one

would even expect a duck to have the same level of cystathionine in the brain as a

human such that any explanation was called for in the first place. In the OAP Dr.

Johnson also challenged the study’s finding. In this case, Dr. Deth claimed that he had

recently replicated the findings of this 1958 study (Tr. 669-70), but did not cite to any

specific study, much less one that had been published.

While I am mindful of the fact that the results from the OAP test cases are not

binding on any other litigant currently or formerly in the OAP, I cautioned petitioners’

counsel on several occasions that I did not intent to permit Dr. Deth to present anew

here what he presented (and I rejected) in the OAP, absent new evidence. Here, Dr.

Deth’s theory in this case simply shares too many similarities with his prior discredited

testimony to ignore. See Hodges, 9 F.3d at 961 (noting that Congress contemplated

276 Pet. Ex. 117, Ref. 15, H. Tallan, et al., L-cystathionine in human brain, J. BIOL. CHEM., 230(2):707-716

(1958).
147

the special masters would use their accumulated expertise in the field of vaccine injuries

to judge the merits of individual claims).277

Petitioners argue in effect that Dr. Deth’s prior OAP testimony should not be a

factor in my decision. ECF No. 302 at 9-10. They note that “Dr. Deth’s testimony in the

OAP focused on mercury and its effect on oxidative stress, hardly the issue herein.”278

Id at 10. And while it may be true, as petitioners stress, that “the OAP cases did not

involve mitochondrial disease or the influenza vaccine” (id.), the fact remains that Dr.

Deth’s opinion still focuses on oxidative stress and relies on the same flawed

understanding of sulfur metabolism and on many of the same concepts and studies.

Indeed, upon my review of the record of this case, it appears as though Dr. Deth

ultimately posited the same core mechanism as in the OAP, merely substituting a new

source of oxidative stress in place of his previously discredited theory regarding

thimerosal.279 Petitioners’ argument that this case involves mitochondrial disease rather

than mercury misses the point. There was substantial overlap in Dr. Deth’s two

presentations.

Petitioners stress that in the five years that have passed since the OAP “an

overwhelming abundance of medical literature has emerged supporting Dr. Deth’s

medical theory of causation.” ECF No. 302 at 10. And while it is no doubt true that

further studies have been published since the time of the OAP, Dr. Deth has simply

failed to establish that any subsequent literature actually supports his view in any

meaningful way.

277 Petitioners have argued that OAP evidence should be barred, because consideration of expert

witnesses and evidence not before the Court in the instant case violates the confrontation clause. See,

e.g., ECF No. 302 at 10. While I previously addressed that objection in my prior ruling on motions (See

Motions Ruling, filed on Sept. 28, 2015 (ECF No. 319), at Section II.D), I note here that this argument is

particularly misplaced with regard to Dr. Deth’s testimony. My analysis is focused on the weaknesses

inherent to Dr. Deth’s own opinion and Dr. Deth has, of course, testified in both cases. Indeed, the critical

point is that Dr. Deth’s testimony in this case remains flawed, a problem which petitioners had ample

opportunity to address. Although the OAP results are not binding, the analysis it contains remains highly

persuasive, and moreover, was equally available to both sides, as both the OAP documents and

testimony remain publically available. Petitioners have long been on notice that claims that merely repeat

the theories presented during the OAP will not be compelling. Moreover, three of the same experts

arrayed against Dr. Deth during the OAP theory two cases (Drs. Jones, Johnson, and Mailman) submitted

reports in this case as well, and two of those three (Drs. Jones and Johnson) also testified.

278 However, in withdrawing from the OAP, petitioners specifically reserved the right to present evidence

on the mercury causation theory. See Motion to Withdraw as a Test Case, April 10, 2008, (ECF No. 40),

at 1.

279 In fact, Dr. Deth’s presentation in the instant case is so similar to his OAP presentation that he failed to

even completely eliminate references to mercury as a causal agent. References remain two of the

PowerPoint slides used in this case. See Pet. Ex. 239 at 89, 96. Moreover, Dr. Deth raised mercury

several times in his testimony. See, e.g., Tr. at 740 (irreversible binding to thioredoxin reductase), 744

(three factors at play here: mercury, TNF-alpha, and aluminum); 783-85 (influence of mercury on 

oxidative stress); 786-89 (elevated mercury levels in one of A. K.’s tests), and 829 (additive effect with

other stressors). Petitioners cannot present evidence on the mercury theory, against my express orders,

and without notice to the court and opposing counsel and then bar my consideration of evidence refuting

it.
148

For example, immediately following his veiled reference to the above-discussed

Waly study, Dr. Deth referenced three subsequent studies which he claimed confirm his

hypothesis. Tr. 685-86; Ex. 239 at 51. In a supplemental report280, however, Dr.

Johnson pointed out that the three studies discuss the dopamine D4 receptor only as it

relates a completely different point, and not with regard to the methylation activity Dr.

Deth was discussing. Res. Ex. JJJ at 2. Doctor Johnson commented that Dr. Deth’s

testimony regarding dopamine D4 receptor-mediated methylation remains “complete

speculation.” Id. In response, Dr. Deth admitted in his own supplemental rebuttal report

that his theory of dopamine-stimulated phospholipid methylation has “not been proven,”

but argued that the observations of the studies were nonetheless somehow relevant to

his theory. ECF No. 281 (incorrectly filed as Pet. Ex. 239) at 4.

Indeed, Dr. Johnson’s supplemental report persuasively established that much of

the late-filed literature by Dr. Deth was simply irrelevant or not related to Dr. Deth’s

theory in the manner that Dr. Deth suggested.281 See Res. Ex. JJJ, passim. For the

most part, Dr. Deth’s responses to Dr. Johnson’s criticisms confirmed, either directly or

indirectly, that the literature was only related to his theory in the broadest of senses and

did not offer any significant confirmation of his ideas. ECF No. 281, passim; Posthearing Order, filed Sep. 9, 2013 (ECF No. 278). For example, where Dr. Johnson

pointed out that an article Dr. Deth relied upon was “not physiologically relevant” in that

its results “would never be achieved in vivo,” Dr. Deth responded only that the study

illustrated as a general manner that “enzymes are modified by glutathionylation.” ECF

No. 281 at 3. When Dr. Johnson criticized Dr. Deth’s reliance on a study to show that

autism is epigenetically caused, Dr. Deth responded that the relationship in question is

“complex and currently not completely understood,” but that the article is relevant

because epigenetics is considered a driver of development generally. Id. Neither these

responses, nor Dr. Deth’s presentation overall, persuade me that Dr. Deth’s theory in

this case has any better grounding in the relevant science than did his OAP theory. 282

280 Due to the fact that Dr. Deth included references to many medical and scientific journal articles in his

hearing presentation that had not been cited in his report nor previously filed into the record—in violation

of my prehearing order (see Prehearing Order, February 21, 2013 (ECF No. 199)) and my letter to each

of the experts (including Dr. Deth) that all journal articles they expected to rely upon must be filed before

the hearing—I afforded respondent the opportunity to address those studies in writing. See Scheduling

Order, filed Jun. 6, 2013 (ECF No. 270).

281 Doctor Deth’s penchant for citing a study for a matter that it did not support was abundantly clear

during the Theory 2 test cases and it is precisely why I required petitioners to file the studies referenced

on Dr. Deth’s slide presentation (see Pet Ex. 239) and allowed respondent the opportunity to respond to

Dr. Deth’s numerous citations in his hearing presentation in writing after the hearing.

282 It is worth noting that as a general matter, Dr. Deth was either unable or unwilling to directly answer

many of the challenges to his theory raised by respondent’s experts. For example, Dr. Johnson

questioned Dr. Deth’s reliance on a particular study regarding oxidative stress, noting that he felt the

results were more consistent with acute damage or injury and not a chronic or delayed process such as

autism. Res. Ex. JJJ at 2 (citing Pet. Ex. 239 at 23; Pet. Ex. 246, T.R. Hurd, et al, Complex I Within

Oxidatively Stressed Bovine Heart Mitochondria is Glutathionylated on Cys-531 and Cys-704 of the 75-

kDa Subunit: Potential Rolse of CYS Residues in Decreasing Oxidative Damage, J. BIOL. CHEM.:

283(36)(September 5): 24801-24815.). Rather than actually address the point raised by Dr. Johnson, Dr.

Deth replied that “once again Dr. Johnson rejects a scientific finding because it supports a theory that he

does not support. The finding obviously supports a theory whereby mitochondrial activity is regulated by
149

D. Doctor Deth was Not a Credible Witness.

It is also highly significant that whatever the advances in the relevant fields since

the OAP, and whatever the alterations to Dr. Deth’s original hypothesis, he remains an

inherently unreliable witness. There are numerous instances in this case where I found

that Dr. Deth had attempted to gloss over information which further complicated, if not

disproved, his underlying hypotheses. These examples further undermine the basic

premise of Dr. Deth’s theory, but perhaps more importantly, they also undermine his

credibility as a witness. This was most egregious with regard to Dr. Deth’s own postmortem study.

During the OAP, Dr. Deth described unpublished post-mortem brain studies

conducted by his lab as the strongest piece of evidence in favor of his opinion. Dwyer,

2010 WL 892250 at *109. Significant concerns were raised regarding the quality and

reliability of the data generated.283 Dwyer, 2010 WL 892250 at *126. The study was

published by the time of this hearing. See Deth, Pet. Ex. 135;284 see also Tr. 695-706;

Pet. Ex. 239 at 62-65 (discussions of the study and findings). Nothing in the present

testimony cleared up any of the concerns from the OAP.

1. Doctor Deth Selectively Presented the Results of His Own Study on mRNA

Splicing.

As Dr. Deth described it, the post-mortem study showed that, among

neurotypical subjects, mRNA for methionine synthase in the brain decreased 500-fold

over the course of a lifetime.285 Tr. 702. Despite this, the study also showed that the

level of protein produced by the mRNA remained constant during the life span. Id.

Doctor Deth described the finding as “surprising,” but offered the interpretation that an

age-dependent slowing of metabolism resulted in the production of less new protein

with an accompanying longer longevity for the proteins produced. Tr. 702-03.

oxidative stress status. Simply because Dr. Johnson doesn’t support a theory, however, does not provide

a basis to reject sound science.” ECF No. 281 at 3. Doctor Deth’s very unhelpful “shoot the messenger”

comment in response to Dr. Jones’s concerns regarding the collection and measurement of cystine would

be another similar example. Tr. 1743. In yet another instance, Dr. Deth responded to a challenge

regarding the relevance of an illustration he pulled from a study by focusing first and foremost on Dr.

Johnson’s use of the word “cartoon” to describe the graphic. ECF No. 281 at 5. “Cartoon” is a term

frequently used to distinguish graphics or diagrams (as opposed to photographs or charts) used to

illustrate concepts or points, and is not pejorative. Doctor Johnson’s use of the term “cartoon” was clearly

not intended to be derogatory, and he used the same term to describe a graphic in his own expert report.

See Res. Ex. UU at 5. The lack of substantive response to Dr. Johnson’s criticisms is telling.

283 Many of the illustrations and charts presented in Dwyer and the other Theory 2 test cases were

replicated in the article.

284 Citations will be to the machine-generated page numbers assigned by petitioners, as the actual

article’s pages are not numbered.

285 Doctor Deth explained that his study looked at mRNA as a substitute for actually measuring

methionine synthase activity, because he felt that the enzyme could not be measured reliably in the postmortem brain. Tr. 778-81.
150

In subsequent testimony, however, Dr. Johnson explained the significance of the

alternative RNA splicing aspect of Dr. Deth’s study. Tr. 1698-1708. He noted that

portions of Dr. Deth’s study, which Dr. Deth did not mention in his testimony (referring

specifically to a figure showing the epithelium bromide-stained gel data), showed that

95% of methionine synthase mRNA was retained in older subjects and that there was

no difference in methionine synthase protein levels between the different groups,

indicating that the total methionine synthesis activity between the groups was the same.

Tr. 1708-14. He contended that the data that Dr. Deth omitted constituted contradictory

data, possibly suggestive of a technical failure. Tr. 1712. He further indicated that he

did not find Dr. Deth’s explanation – that proteins among the aged simply stop

degrading - to be viable, noting that it is inconsistent with aging. Tr. 1713-14.

Doctor Deth’s chief response in rebuttal was to claim that the criticism is

irrelevant, because the data Dr. Johnson cited is not data from the autistic group.286 Tr.

1754. This response is simply inadequate. Doctor Deth’s ultimate conclusion regarding

the autistic group was couched as a comparison to the neurotypical group, so data

calling those results into question is relevant to his ultimate conclusion. Moreover,

regardless of which aspects of the study on which Dr. Deth ultimately relied, he testified

about the results in the neurotypical group. By failing to mention the contradictory data

he implicitly overstated the viability of the data about which he testified. And finally,

regardless of Dr. Deth’s intentions, to the extent Dr. Johnson contended that the data

reflected a technical failure, that calls into question the overall quality of the study and

the weight it should be accorded.

In sum, Dr. Deth failed to mention that data he was presenting was potentially

contradicted by other findings within the same study.

2. Doctor Deth’s Claim of a “Compensating” Mechanism to Explain Away His

Inconsistent Results is Unsubstantiated Speculation and Not Credible.

In discussing the significance of his post-mortem study with regard to the autistic

group, Dr. Deth testified that this group had lower levels of the mRNA necessary for

creating methionine synthase. Tr. 705-07. From this result he concluded that “levels of

methionine synthase mRNA are lower in autism, consistent with a premature

progression to a more oxidized state.” Pet. Ex. 239 at 65. On cross-examination,

however, Dr. Deth acknowledged that despite testing for markers of oxidative stress, the

post-mortem study did not find any elevation of any markers of oxidative stress in the

autistic population (specifically noting hydroxyl guanosine). Tr. 781-82. Providing

further detail, Dr. Jones noted that this study found no difference in GSH, GSSG,287

cysteine, cystine, or their respective ratios, the markers of oxidative stress used in other

studies. Tr. 1651.

286 Doctor Deth also claimed that the criticism is not valid because the sample was normalized for

“product” rather than for brain material. Tr. 1754. He stopped short, however, of explaining how that

distinction could account for the contradictory data Dr. Johnson revealed.

287 GSH refers to the reduced thiol form of glutathione and GSSG to the oxidized disulfide form.

DORLAND’S at 809.
On redirect, Dr. Deth acknowledged that Dr. Jones was correct in his

interpretation of the lack of oxidative stress markers, testifying that: “we were, I would

say, somewhat surprised, to not find the biomarker that we used for oxidative stress to

be elevated, and in fact many of the metabolites that we thought might be abnormal

were not abnormal, but we then appreciated that the large changes in the mRNA that

we observed are probably compensating successfully for the otherwise expected

oxidative stress.” Tr. 827. That is, he speculated that “the large decrease in autism

subjects of methionine synthase was how they accommodated or adapted to the

oxidative stress and probably relieved their oxidative stress sufficiently so that they

didn’t have biomarkers, but what they did have was lower levels of methionine synthase

messenger RNA.” Id.

Doctor Deth’s later testimony suggests that he was attempting to mislead in his

initial testimony that this study supported his theory. He presented the depressed

mRNA levels as “consistent with” a state of increased oxidation (i.e. “a progression to a

more oxidized state”). Pet. Ex. 239 at 65. Yet, on cross-examination he first admitted

that the study failed to show that autistic brains had that increased oxidative state (Tr.

781-82) and on rebuttal, acknowledged that the study included findings contradictory to

his hypothesis and that they came as a “surprise.” Tr. 827. On direct examination Dr.

Deth indicated that decreased mRNA is “consistent with a premature progression to a

more oxidized state;” in rebuttal he actually speculated, in complete contradiction to his

initial presentation, that the decreased mRNA is actually a sign of the subject’s ability to

relieve or cope with oxidative stress.

This is not an insignificant point. Doctor Deth indicated that “I think the evidence

for epigenetics being related to oxidative stress and oxidative stress being a common

feature of autism, make the persuasive argument that is certainly a reasonable

hypothesis if not the primary most logical explanation that’s at hand right now.” Tr. 758.

Although this study was not the only basis by which Dr. Deth contended that markers of

oxidative stress are associated with autism, it does undercut his hypothesis to a

significant degree.

It appears that Dr. Deth’s study simply failed to generate results consistent with

his initial hypothesis. The fact that he posited an untested after-the-fact hypothesis to

explain away the discrepancy does not excuse his unqualified statement in his initial

presentation that the mRNA levels are themselves indicative of “a more oxidized state,”

a statement which he knew to be incomplete.

E. Doctor Deth’s Theory is Implausible from an Epigenetic Standpoint.

Epigenetics is the bedrock of Dr. Deth’s theory.288 That portion of his theory was

not well-developed in the Theory 2 test cases, and his epigenetics presentation in this

288 “Epigenetic” is defined as the alteration of “the activity of genes without changing their DNA

sequence.” DORLAND’S at 632. Alternatively, it can be described as something that affects phenotype

without changing the genotype. Id. Epigenetics is “the study of heritable changes in the function of

genes that occur without changes in the DNA sequence, occurring during development and cell

proliferation and including mechanisms such as DNA methylation, histone modification, and RNA

interference. Id.; Tr. at 1457. Epigenetics helps explain how identical twins can differ with respect to

diseases that are considered genetic in nature, but not related to a single gene. By affecting gene

151
152

case was one of the few areas where his testimony was different and new. He stressed

that knowledge about epigenetics has increased greatly in the past decade. Tr. 620;

Pet. Ex. 239 at 8. Yet, even if I accepted that A.K. had all of the vulnerabilities Dr. Deth

relied upon, and even if I accepted as accurate his explanation of sulfur metabolism,

oxidative stress and inflammation as they relate to vaccination, his hypothesis would still

not make sense from an epigenetic standpoint.

Doctor Deth posited that ASD is an epigenetic disorder wherein environmental

factors impact gene expression. Tr. 613, 617-18. Asserting that children with ASD

show evidence of decreased DNA methylation, he reasoned that DNA methylation,

which is particularly sensitive to oxidative stress, was altered by oxidative stress. Tr.

625, 639, 689-92. Petitioners summarized his testimony as describing “the mechanism

by which a vaccine administered to a two year old child could and did cause epigenetic

changes in the child’s brain giving rise to autistic-like symptoms . . .” ECF No. 297 at

63.

Respondent’s experts challenged his assertion that there is an association

between autism and depressed DNA methylation as well as arguing that other evidence

suggests that a post-natal/early childhood insult resulting in epigenetic changes is

unlikely.

1. Doctor Deth’s Theory is Not Plausible as a Postnatal Occurrence.

Although he indicated that epigenetics operates in all phases of human

development from pre-conception through adulthood, Dr. Deth stressed that epigenetic

changes occurring in earlier development have a larger impact. Tr. 628-31, 813-14. In

particular, he contended that epigenetic changes occurring in early childhood, when

significant brain and immune development is occurring, are the most critical. Tr. 628-

31. He maintained that the acute inhibition of DNA methylation (a process whereby

enzymes control gene expression by attaching single carbon molecules to specific DNA

sites) by oxidative stress can have long-term consequences to growth and

development. Tr. 622-25.

Doctor Raymond noted that petitioners’ theory ignores the critical distinction

between pre- and postnatal development.289 Doctor Raymond explained that during

early prenatal development, epigenetic activity occurs in the context of cell division,

regulating the process to create different kinds of tissue. Tr. 1461-64. At that stage,

epigenetic changes from methylation can be carried on by the further replicating cells.

Id. Postnatally, when epigenetic regulation acts on non-dividing cells, the changes are

not carried forward (heritable) as they would have been during early prenatal

development. Tr. 1464-68.

expression, but not the underlying DNA structure of the gene, epigenetic changes can produce significant

differences, and differences that can be inherited. Methylation turns genes on or off (or partially on or

off).

289 Although Dr. Raymond agreed that epigenetic regulation occurs throughout life, he asserted that the

most significant epigenetic activity occurs from conception through the second trimester of gestation. Tr.

1457-59.
153

Doctor Raymond therefore contended that, even though it is undisputed that

epigenetic changes occur throughout a person’s lifetime, Dr. Deth’s theory is

implausible, because the type of disruption in methylation he describes – occurring at

around 2 years of age on non-dividing neural cells – would have to be systematic to

have such a significant impact to the brain. Tr. 1464-68. That is, the likelihood that only

the genes necessary to cause autism would be activated postnatally and that they

would be activated uniformly throughout the brain (e.g., to remove all Purkinje cells) is

“not plausible.” 290 Tr. at 1461, 1467-68. Thus, Dr. Raymond maintained that Dr. Deth

cannot account for the “impossible” chance occurrence necessary for the methylation

disruption he posited to impact a specific phenotype in the context of that type of

systemic whole body deficit. Tr. 1467-68. That is, Dr. Raymond contended that Dr.

Deth cannot explain how his theory would result in autism, and only autism, without

impacting other body tissues.291 Tr. 1468-69.

And indeed, Dr. Deth effectively conceded Dr. Raymond’s point, testifying that “if

that disturbance of development in methylation occurs early it’s going to have a larger

impact because the earliest cells give rise to whole pathways, whole regions of

development, whereas later in life, later in development, abnormalities can be expected

to have a more discrete I’ll call it localized impact. This is evident by the comparison

between let’s say fetal abnormalities, which again can be related to epigenetic

consequences, as opposed to let’s say postnatal or even adolescent abnormalities,

which while they might result in disease certainly have a more limited repertoire of

outcomes compared to earlier defects.” Tr. 628.

Nonetheless, Dr. Deth contended without apparent basis that “different organs

have different vulnerability to epigenetic insult” and that the brain is unique in that it is

“restrained from development until the postnatal period.” Tr. 629-30. His citations

regarding epigenetics and brain development, however, actually contradict his ultimate

conclusion. For example, Dr. Deth cited DNA methylation signatures in Development

and Aging of the Human Prefrontal Cortex by Numata et al., from THE AMERICAN

JOURNAL OF HUMAN GENETICS, but that study found that “the fastest changes occur

during the prenatal period” and “slow down markedly after birth.”292 He also cited an

290 Doctor Raymond noted in particular that Dr. Deth’s reliance on Wong, Pet. Ex. 240, is misplaced. Tr.

1470. In Wong’s methylomic manuscript, the profiles were gathered from blood samples. Tr. at 1471. In

order for the blood profiles to correspond to the expected autistic methylation profiles in the brain, the

methylation events that resulted in the triggering of autism would have to occur early on, before the stem

cells differentiated. Tr. at 1472. Doctor Raymond describes the Wong paper as “a stellar paper... It has

limitations, but it clearly makes the point that [the epigenetic event that results in autism is] way back

there” in prenatal development. Tr. 1473.

291 On cross-examination, Dr. Deth indicated that under his theory there would be oxidative stress in the

whole body, but that because A.K. had a neurological injury, his focus was on the brain. Tr. 772-73.

Doctor Deth did not explain what impact he would expect on the rest of the body under his theory. Nor

did he attempt to show that A.K. experienced any other medical issues beside his ASD that were

potentially explained by this whole-body oxidative stress.

292 See Pet Ex. 242, Numata, et al, DNA methylation signatures in Development and Aging of the Human

Preffrontal Cortex, AM. J. HUM. GENET. 90(2)(Feb. 10, 2012): 260-72. Doctor Deth included this article

in his slide presentation but had not previously submitted it into the record. It was subsequently filed by

petitioners on May 31, 2013, but no exhibit number was assigned at filing. See ECF No. 260. Upon my
154

author manuscript by Colantuoni, et al, titled Temporal dynamics and genetic control of

transcription in the human prefrontal cortex, which likewise indicated that “the rate of

expression change during fetal development is much faster than at any other stage in

human life.” 293 Clearly, these studies do not support Dr. Deth’s assertion that from an

epigenetic perspective the postnatal period is the most critical phase of brain

development.

Ultimately, Dr. Deth cited 13 studies which he indicated all have findings

“indicative of body-wide oxidative stress” among children with autism. Pet. Ex. 117 at

12. Further describing those studies, Dr. Deth opined that “we have these two partners,

oxidative stress, impaired methylation, that were yoked together by their shared

metabolic pathways as being very common and evident in autism. This implies that

factors which cause oxidative stress and impaired methylation are primary suspects, or

misfactors, or targets for causation of autism and should be investigated as such.” Tr.

692. Yet, when discussing the role of environmental insults in epigenetic development

of developmental disorders in his expert report, Dr. Deth cited a review article limited

exclusively to prenatal environmental exposures. See Pet. Ex. 117, Ref. 7, F. Perera,

Prenatal Environmental Exposures, Epigenetics, and disease, REPROD. TOXIOCOL., 31:

363-273 (2011). Thus, Dr. Deth’s attempt to extend these epigenetic concepts to the

onset of ASD in early childhood remains unsupported and speculative.

Doctor Johnson also cast further doubt on the significance Dr. Deth ascribed to

the claimed association between autism and oxidative stress. Doctor Johnson pointed

out that among the 13 studies Dr. Deth cited to link autism and oxidative stress as a

general matter, at least one of those studies, one by James, et al,294 showed that both

the autistic and control subjects had the same metabolic patterns as their mothers,

strongly suggesting that contrary to what Dr. Deth implied, there is no relationship

between this state of oxidative stress and post-natal environmental factors such as

vaccines. Specifically, to the extent Dr. Deth contended that the studies show that

“factors which cause oxidative stress and impaired methylation are primary suspects, or

misfactors, or targets for causation of autism,” Dr. Johnson pointed out that the James

study suggests that the metabolic profile Dr. Deth described is a genetically determined

“baseline” for these individuals and not likely associated with vaccines. Tr. 1692, 696-

98.

In rebuttal, Dr. Deth contended that “the assumption here that Dr. Johnson

seemed to be making is all of it – sort of the causative factor for autism lies within the

metabolic features of their parents, and I think this is . . . not true.” Tr. 1759-60. Doctor

Deth opined that Dr. Johnson was overstating the role of genetics and not accounting

sufficiently for the environmental factors that also contribute. Tr. 1760. Consistent with

Dr. Raymond’s testimony, however, the James paper highlighted by Dr. Johnson

order, petitioners’ subsequently filed an updated exhibit list identifying this article as Pet. Ex. 242. See

Exhibit List, June 25, 2013 (ECF No. 271).

293 See Pet Ex. 243, C. Colantuoni, et al, Temporal Dynamics and Genetic Control of Transcription in the

Human Prefrontal Cortex, NATURE 478 (7370)(2012):519-23. As with the Numata study, this document

was not given an exhibit designation at the time of filing. See n. 292, supra.

294 James, Pet. Ex. 117, Ref. 36.
155

indicated that to the extent the authors saw their results as supportive of an epigenetic

theory of autism causation, they felt the results were suggestive of epigenetic alterations

occurring during fetal development. James, Pet. Ex. 117, Ref. 36, at 1971. Thus,

regardless of whether Dr. Johnson overstated the role of genetics or not, this James

paper – cited by Dr. Deth himself – undermines his theory with regard to the timing of

the epigenetic changes he asserts.

2. Doctor Deth’s Theory Is Predicated on an Unproven Association Between

Hypomethylation and Autism.

Doctor Deth further opined that “during oxidative stress [methionine synthase]

activity is inhibited, resulting in a decrease of SAM/SAH and inhibition of all methylation

reactions, including DNA methylation.” Pet. Ex. 117 at 8. Thus, he concluded that “any

factor that promotes oxidative stress has the potential to cause a significant decrease in

global DNA methylation, disrupting the normal pattern of epigenetic regulation.” Id.

Doctor Deth cited the Wong study,295 as evidence supporting the link between

epigenetics and autism, noting that “this paper did show that the degree of changes in

DNA methylation of epigenetic regulation was associated with differences in the severity

of the autism.” Tr. 621; Ex. 239 at 9.

Doctor Johnson noted, however, that the Wong study actually contradicted Dr.

Deth’s theory with regard to the expected methylation outcome. That is, while Dr. Deth

posited that autism is caused by depressed methylation, the Wong study showed that

twins discordant for autism showed no overall difference in methylation and in fact that

different genomes are variously over or under methylated. Doctor Johnson contended

that Dr. Deth’s theory cannot account for that outcome and that, contrary to Dr. Deth’s

hypothesis of depressed methylation, the Wong study shows that methylation is either

increased or decreased among autistic subjects with a majority of the genes becoming

over-methylated. Tr. 1719-24, 1726. That is, Dr. Johnson noted that the Wong study

showed that of the ten genes experiencing the largest change, only three experienced

decreased methylation. Tr. 1724.

In rebuttal, Dr. Deth initially stated that his theory of hypomethylation was still

consistent with the Wong article, because the manuscript only looked at gene and

promoter methylation, which accounted for less than 5% of the genome. He concluded

that, looking at the entire genome would show that hypomethylation was still present.296

Tr. 1757-58. Doctor Deth was incorrect in this statement, however, as the article clearly

indicates that changes in global methylation were not found to be correlated with

autism. Wong, Pet. Ex. 240 at 3.

Subsequently, Dr. Deth seemed to acknowledge that the Wong paper indicated

that there was no consistent pattern of global hypomethylation among the autistic

subjects. Tr. 1765-66. He then completely backtracked on his claim that decreased or

hypomethylation was required for autism, stating that “I would say that changes in or

295 Wong, Pet. Ex. 240.

296 Doctor Deth also stressed a distinction between blood DNA and brain DNA, but he could not explain

the difference. Tr. 776-77, 1764.
156

dynamic changes over time in DNA methylation is a more accurate term to use rather

than essentially trying to paint me into a box here of saying, oh, it has to be

hypomethylation, and I never said that it has to be hypomethylation, and indeed, even if

I did, I’ll say here that changes in the pattern, the normal pattern of methylation are

sufficient to have epigenetic effects rather than simply always being hypomethylation.

Tr. 1766.

This admission, however, completely undermines Dr. Deth’s entire presentation.

Contrary to his later rebuttal testimony, Dr. Deth was quite clear in asserting that he was

relying on studies which he claimed showed a 28% decrease in the SAM/SAH ratio

among autistic subjects, which he argued was evidence of impaired methylation. See,

e.g., Pet. Ex. 239 at 59. He was also clear in stating that it was the relationship between

oxidative stress and impaired methylation, and the fact that they could both be

associated with autism, that supported his theory. Id. Specifically, he testified that “we

have these two partners, oxidative stress, impaired methylation, that were yoked

together by their shared metabolic pathways as being very common and evident in

autism. This implies that factors which cause oxidative stress and impaired methylation

are primary suspects, or misfactors, or targets for causation of autism and should be

investigated as such.” Tr. 692.

This is highly significant, because Dr. Deth’s opinion ultimately was that “any

factor that promotes oxidative stress has the potential to cause a significant decrease in

global DNA methylation, disrupting the normal pattern of epigenetic regulation.” Pet.

Ex. 117 at 8. Absent the alleged association between autism and impaired DNA

methylation, it is not clear how Dr. Deth purports to complete his connection between

oxidative stress and autism. Even if he established that reduced methionine synthase

activity could create some form of epigenetic consequence, he would have no basis to

conclude that the outcome would be autism. Indeed, as described above, Dr.

Raymond’s testimony regarding prenatal versus postnatal epigenetics makes that

outcome unlikely.

F. Conclusion and Findings Regarding Dr. Deth’s Presentation.

For all of the above reasons, I decline to credit Dr. Deth’s testimony in this case.

Doctor Deth failed to candidly address the science underlying his hypothesis; attempted

to testify beyond his expertise; and relied to a significant degree on previously

discredited concepts and ideas. Snyder, 88 Fed. Cl. at 718 (quoting Ryman, 65 Fed.

Cl. at 40-41(special masters perform gatekeeping function when determining “whether a

particular petitioner’s expert medical testimony supporting biological probability may be

admitted or credited or otherwise relied upon” and as a “trier-of-fact [a special master]

may properly consider the credibility and applicability of medical theories”)).

Moreover, even accepting Dr. Deth’s testimony as at least minimally credible, he

still has not presented a plausible theory. By his own admission his opinion stops short

of actually contending that vaccines cause harmful oxidative stress. Moreover, his

theory is fundamentally flawed in its understanding of basic metabolic and epigenetic

concepts. And, in any event, the mechanism proposed by Dr. Deth is predicated on the
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existence of vulnerabilities not present in this case. Thus, even considering Dr. Deth’s

presentation at face value, it remains highly unpersuasive.

X. Analysis under Althen, Pafford and Loving.

A. Althen Prong 1: A Reliable Theory.

Althen requires that a petitioner in an off-Table causation case present a reliable

medical theory by explaining how the vaccines administered can cause the injury in

question. Althen, 418 F.3d at 1278. This first prong of Althen’s three part causation test

has also been characterized as the equivalent of the “Can it cause?” inquiry used in

toxic tort litigation. See Pafford, 2004 WL 1717359, at *4.

The medical theory must be a reputable one, although it need only be “legally

probable, not medically or scientifically certain.” Knudsen, 35 F.3d at 548-49. The

Supreme Court’s opinion in Daubert likewise requires that courts determine expert

opinions to be reliable before they may be considered as evidence. “In short, the

requirement that an expert’s testimony pertain to ‘scientific knowledge’ establishes a

standard of evidentiary reliability.” 509 U.S. at 590 (footnote omitted). The Federal

Circuit has stated that a “special master is entitled to require some indicia of reliability to

support the assertion of the expert witness.” Moberly, 592 F.3d at 1324.

Here, petitioners’ experts strained to stretch the idea of mitochondrial regression

to encompass vaccines as triggers of such regression. As described above, that

extension is completely unsupported by any scientific literature; it was presented in this

case almost entirely through the opinion of Dr. Kendall, supported by one case report

(Poling, Res. Ex. MM, Tab 14). Doctor Kendall’s and Dr. Shafrir’s further reliance on

the Shoffner and Weissman papers was misplaced and their opinions that vaccines can

act as triggers of mitochondrial regression were unpersuasive.

Evidence that regression in ASD, a well-described phenomenon involving the

loss social communication and behavior, “looks like” mitochondrial regression was also

nearly non-existent. “Mitochondrial autism” may someday be accepted as a descriptor

for co-morbid autism and mitochondrial disorder diagnoses, but there is little evidence

that autism itself is caused by such disorder, and no evidence that autism causes

mitochondrial disorders. While Dr. Kendall is one of the few mitochondrial disorder

specialists in the U.S., her opinion that vaccines can trigger either onset of a

mitochondrial disorder with symptoms looking like ASD, or ASD via a mitochondrial

regression are insufficiently supported and remain speculative.

To the extent Dr. Shafrir alternatively sought to establish that A.K.’s condition

could be explained by a constellation of vulnerabilities contributing to an autoimmune

reaction, he failed to demonstrate that any of the alleged vulnerabilities have the

significance he maintains. He failed to articulate any basis for claiming that an influenza

vaccination could lead, via autoimmunity, to the type of injury A.K. experienced. He

also failed in his attempts to extend the so called “triple hit” hypothesis beyond the prenatal context. Contrary to Dr. Shafrir’s theory, there is no basis upon which to argue

that regressive autism can be linked to a postnatal environmental factor. Moreover, his

reliance on challenge-rechallenge is not persuasive in the context of this case wherein
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A.K. was experiencing an ongoing and continuous condition (i.e. ASD) with a variable

course.

To the extent petitioners attempted to otherwise establish a causal relationship

through Dr. Deth’s presentation regarding oxidative stress and inflammation – intended

to establish a plausible biological mechanism – they failed. Doctor Deth’s opinion

suffered far too many serious flaws to be credited. Notably, having acknowledged that

not all oxidative stress is injurious, Dr. Deth conceded that he could not opine what level

of oxidative stress is created by a vaccination or what level of oxidative stress would be

necessary to cause the type of neurological injury he described. Respondent’s experts

persuasively addressed these same questions, contending that the oxidative stress

created by a vaccination is likely to be quite small. In any event, Dr. Deth also failed to

credibly or persuasively address those aspects of his theory based on gastrointestinal

function, epigenetics, and sulfur metabolism. To the extent Dr. Deth’s presentation

appeared coherent at a superficial level, it simply collapsed at the slightest challenge.

B. Althen Prong 2: A Logical Connection.

Even if petitioners had provided a theory which satisfied the first prong, to satisfy the

second prong of the Althen test, petitioners must establish a “logical sequence of cause

and effect showing that the vaccination was the reason for the injury.” Althen, 418 F.3d

at 1278. In other words, petitioners must show that the received vaccine did, more

likely than not, cause the injury in the case at bar. Pafford, 451 F.3d at 1356. The

sequence of cause and effect need only be “‘logical’ and legally probable, not medically

or scientifically certain.” Knudsen, 35 F.3d at 548-49; accord Capizzano, 440 F.3d at

1326. Evidence from a treating physician may assist petitioner in meeting her burden of

proof under the second Althen prong. Capizzano, 440 F.3d at 1326.

Most significant to Althen Prong 2, there is strong evidence in the record

suggesting that A.K.’s condition predated his vaccinations. A.K. was showing signs of

both ASD and speech delay well before receiving either dose of his two dose series of

influenza vaccinations. Moreover, the actual timeline of events do not support

petitioners’ claim of a regression. This is fatal to both Dr. Kendall’s and Dr. Shafrir’s

opinions in that each relied on fact of a temporal relationship between the onset of

A.K.’s ASD and his vaccinations as proof of vaccine causation. Doctor Shafrir, in

particular, sought to rely on a challenge-rechallenge response as evidence that A.K.’s

vaccines caused his condition. Absent such a reaction, Dr. Shafrir acknowledged that

there was no other evidence upon which to causally link A.K.’s vaccinations to his

alleged injury.

Additionally, all of petitioners’ experts relied at least in part on the fact that A.K.

was vulnerable to vaccine injury due to his alleged mitochondrial disorder. For the

reasons described above, however, I have determined that that reliance was in error.

Although petitioners’ cited Dr. Shoffner’s finding of a Complex I defect in A.K.’s medical

history, as well as clinical reports by multiple treating physicians referencing that finding,

these medical records did not provide support for petitioners’ contention, particularly in

light of respondent’s presentation of multiple expert witnesses who interpreted Dr.

Shoffner’s findings as tentative, based on the need for further testing, and showing on
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their own no abnormality. This finding is fatal to Dr. Kendall’s opinion in this case and

also highly significant to Dr. Shafrir’s opinion as well.

Moreover, contrary to the opinions of Drs. Shafrir, Deth and Boris, I have also

found that A.K. did not have an abnormal immune system. Doctor McCusker fully

rebutted Dr. Shafrir’s claims regarding Hashimoto’s thyroiditis and myelin basic protein

antibodies as well as Dr. Boris’s specious diagnosis of common variable

immunodeficiency. Dr. Deth likewise failed to establish that A.K.’s gastrointestinal

complaints are significant to his immune status or otherwise contributed to the cause of

A.K.’s autism.

Additionally, A.K.’s MTHFR polymorphisms have not been shown to cause or

contribute to autism as several of petitioners’ experts claimed. Although some studies

have suggested a possible association between MTHFR polymorphisms and autism,

respondent’s expert, Dr. Raymond, noted that the overall body of studies on the subject

have generated conflicting findings. Moreover, Dr. Raymond also noted that most

people with these polymorphisms experience no ill-effect, and that the only established

consequence of these polymorphisms relates to cardiovascular health.

C. Althen Prong 3: A Proximate Temporal Connection.

Merely showing a proximate temporal connection between a vaccination and an

injury is insufficient, standing alone, to establish causation. Grant, 956 F.2d at1148. A

proximate temporal relationship, even when coupled with the absence of any other

identified cause for the injury, is not enough to demonstrate probable cause under the

Vaccine Act’s preponderance standard. Moberly, 592 F.3d at 1323 (citing Althen, 418

F.3d at 1278). Therefore, since petitioners have failed to establish Althen prongs 1 and

2, they cannot prevail even if they did establish a temporal connection. Nonetheless, I

note again that, as described above, respondent has established that A.K.’s speech

delay and autism predated his vaccinations. Moreover, I have determined that A.K. did

not regress following his vaccinations. These findings preclude any temporal

relationship between the onset of A.K.’s ASD and his influenza vaccinations.297

D. Loving Factors: Significant Aggravation.

Although the above analysis is itself dispositive, since petitioners’ claim is that

“one or more vaccines significantly aggravated an underlying mitochondrial disorder”

(Petition (ECF No. 237) ¶ 74), I will briefly address the additional Loving factors

necessary to proving such a claim. To demonstrate aggravation of a pre-existing

297 In their post-hearing brief, faced with respondent’s evidence regarding the onset of A.K.’s ASD,

petitioners alternatively cite earlier vaccinations administered in May of 2001 as potentially causal. ECF

No. 297 at 125. Notwithstanding the fact that these vaccines were mentioned in the operative petition,

this after-the-fact argument is patently insufficient. Petitioners cite to no medical opinion by any expert or

treating physician in support of this claim. Moreover, the focus of this case has clearly been on A.K.’s two

influenza vaccines in November and December of 2001. Indeed, petitioners’ experts not only failed to

opine that these earlier vaccines contributed to A.K.’s condition, they explicitly based their causation

opinions on the temporal relationship they believed was present between the November and December

2001 influenza vaccines and A.K.’s alleged regression. In fact, Dr. Shafrir explicitly confirmed during the

hearing that he was not opining that the May 2001 vaccines were casual. Tr. 527-28.
case, Banks v. Sec’y, HHS, No. 02-738V, 2007 WL 2296047 (Fed. Cl. Spec. Mstr. Jul. 20, 2007),

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condition, petitioners must show: (1) the vacinee’s condition prior to the administration

of the vaccine, (2) the vacinee’s current condition, and (3) whether the vacinee’s current

condition constitutes a “significant aggravation” of the condition prior to the vaccination.

See Loving, 86 Fed. Cl. at 144 (combining the first three Whitecotton factors for claims

regarding aggravation of a Table injury with the three Althen factors for off table injury

claims to create a six-part test for off Table aggravation claims); see also W.C., 704

F.3d at 1357 (applying the six-part Loving test).

Petitioners claim fails under this analysis first and foremost, because petitioners

have failed to establish that A.K. had any mitochondrial disease or defect at all. That is,

they have failed to show that A.K. even had the condition they allege to have been

aggravated. Moreover, to the extent petitioners claim that the aggravation ultimately

resulted in ASD with onset post-dating his vaccinations, respondent has established

that A.K.’s ASD predated his vaccinations. Thus, petitioners have failed to establish

both of the first two Loving factors relating to A.K.’s condition before and after the

vaccination. That is, petitioners have failed to establish that A.K. was in two distinct

states before and after the vaccination rather than experiencing an ongoing disorder,

albeit one with a naturally variable course.298

Moreover, even if A.K. did have a mitochondrial disorder, petitioners still would

have failed to show that A.K.’s current condition constitutes a significant aggravation of

that disorder. As noted above, there is insufficient evidence to suggest that

mitochondrial decompensation results in autism or autism-like features. Moreover, as

noted in the Althen analysis above, there is no evidence demonstrating that any of

A.K.’s vaccinations would have been the cause of such aggravation.

XI. Conclusion.

ASD can be a devastating injury, and that is certainly true in A.K.’s case. Only a

heartless individual could remain unmoved by the testimony of petitioners in this case.

If sympathy alone were a basis to award compensation, such an award would certainly

issue in this case.

It is not. Petitioners, like every other petitioner to claim that vaccines cause or

substantially contributed to a condition that led to an ASD diagnosis, have been unable

to muster preponderant evidence in support of vaccine causation. As such, I have no

choice but to dismiss their vaccine injury claim.299

298 To the extent petitioners argue in the alternative that A.K. may have had minor pre-existing

developmental delays that were subsequently exacerbated by his influenza vaccines (ECF No. 297 at

128-30), I further note that I have found that A.K. did not regress in the manner petitioners alleged.

299 I am aware of two cases in which petitioners have prevailed on a Table injury theory, where the child in

question developed an acute encephalopathy meeting the strict Table definition of that condition, within the

requisite time frame after administration of specific vaccinations. One is the Poling case, discussed at

length in the motions ruling in this case and in this decision, in which respondent conceded the Table

injury. The other is a recent decision I issued in Wright v. Sec’y, HHS, No. 12-423V (Fed. Cl. Spec. Mstr.

Sept. 21, 2015) (ECF No. 83), in which respondent contested the presence of a Table injury. In another
This case is dismissed. The Clerk shall enter judgment accordingly.

IT IS SO ORDERED.

s/Denise K. Vowell

Denise K. Vowell

Special Master

petitioners prevailed on their theory that the viral vaccine administered to the child caused encephalitis,

which manifested with symptoms sufficient to warrant an ASD diagnosis. None of those cases resemble

the facts and theories proposed in this case.

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