R.K. v. the Secretary of Health and Human Services

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”2 for 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.

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.

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

4 Hereinafter,

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.

2

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.6 If 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

6A 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 vaccine-

causation. 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”).

3

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.

9A 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.

10 These 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.

11In 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.

4

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).

15 Petitioners’

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.

5

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

16In 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.

18Petitioners 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 Thisamount 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

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.

20On 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.

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

22On 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.

7

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 post-

hearing 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.

24 After

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.

8

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

9

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 ½ 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

25The 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).

26Subsequent 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.

10

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,

28 Woodbury 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.

29 These 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.

11

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.

32I 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]).

12

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

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

14

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

38Section 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.

15

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

39The 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.

16

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

40 See§ 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).

17

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

41Doctor 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.

18

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

19

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.

45I 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

20

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

47During 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.

21

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

48Doctor 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.

50Doctor 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.

51Significantly, 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.

22

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.

53A 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.

54Doctor 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.

56Despite 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

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 post-

graduate 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.

24

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 pro-

inflammatory 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.

60Doctor 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.

25

745-749. He therefore contended that A.K. was at a higher risk of experiencing long-

term 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.

62Doctor 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.

63Doctor 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.

64For 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.

26

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).

67Defeat 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.

68A. 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.

27

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

69See, 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.

28

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.

70He 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.

71Doctor Boris did not remember exactly how he learned A.K.’s hearing test results were normal. Tr. at

201.

72Doctor 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.

29

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

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.

74At 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).

75According 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.

76Although 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.

77Doctor 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.

31

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

78Doctor 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.

32

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

79Doctor 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.

80Significantly, 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.

82Additional 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).

33

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.

84Doctor 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.

34

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.

86More 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

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.

89Referring 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.

36

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

90Doctor 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.

37

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.

92Although 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.

93Although 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.

38

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.

94Doctor 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.

95Doctor 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

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.

96Although 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.

40

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.

97Doctor 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.

41

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.

99Doctor 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.

100Pet. 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.

101I 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.

102Doctor 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.

103No 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.

42

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.

104In 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.

105In 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).

43

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.” R

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