# Hall v. Baxter Healthcare Corp.

> District Court, D. Oregon · December 18, 1996 · 947 F. Supp. 1387

URL: https://www.frixlaw.com/law-library/cases/1453782

## Case

- **Full name:** Leaann D. HALL, Plaintiff, v. BAXTER HEALTHCARE CORP.; Et Al., Defendants; Tammy JOHNSTON; Robert Johnston; Laura Bentley; Ralph Bentley; Susan Eisele; Darrell Dwayne Eisele; Michelle Tytlar; Jeffrey Tytlar, Plaintiffs, v. BRISTOL-MYERS SQUIBB COMPANY, Et Al., Defendants; Debra SHERVEY, Plaintiff, v. BRISTOL-MYERS SQUIBB COMPANY, Et Al., Defendants
- **Court:** District Court, D. Oregon
- **Decided:** December 18, 1996
- **Citations:** 947 F. Supp. 1387; 46 Fed. R. Serv. 26; 1996 U.S. Dist. LEXIS 18960; 1996 WL 730693
- **Precedential status:** Published
- **Opinion:** Opinion by Jones
- **Judges:** Jones
- **Cited by:** 68 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/1453782

## How later opinions describe it (automated extraction)

- finding that “case reports and case studies are universally regarded as an insufficient scientific basis for a conclusion regarding causation because case reports lack controls”; hence, they do not supply scientific knowledge upon which an opinion can be based under Daubert
- finding a Rule 403 analysis applicable but unnecessary in making its decision to exclude testimony
- holding that differential diagnosis cannot establish general causation because the method “assumes that general causation has been proven”

## Opinion text

OPINION AND ORDÉR
ROBERT E. JONES, District Judge:
1.
INTRODUCTION
Currently pending in this court are a number of silicone breast implant cases brought by or on behalf of the plaintiffs against various breast implant manufacturers.
1
Plaintiffs seek damages for injuries they claim to have suffered as a result of implantation with silicone gel breast implants.
Among other things, the plaintiffs assert that silicone from the implants has migrated and degraded in their bodies and has caused a systemic syndrome or illness, which they generally refer to as “atypical connective tissue disease” (ACTD). In essence, plaintiffs claim a “unique constellation of symptoms” consisting of hundreds of symptoms commonly experienced by the general population.
2
This opinion addresses the defendants’ motions in limine to exclude testimony by plaintiffs’ experts concerning any causal link between silicone breast implants and the alleged systemic disease - or syndrome.
3
To resolve these motions, the court, in its role as “gatekeeper”
(see Daubert v. Merrell Dow Pharmaceuticals, Inc.,
509 U.S. 579 , 113 S.Ct. 2786 , 125 L.Ed.2d 469 (1993) (hereinafter
Daubert I),
initiated proceedings under Federal Rule of Evidence 104. The process through which the court has endeavored to ■ resolve the pending motions, a process the
*1392
court believes to be unique in federal practice to date, is described below.
II.
FACTS AND PROCEDURAL BACKGROUND
The breast implant cases at issue here were either filed initially in this court or removed from state court. The cases were then transferred to the Judicial Panel for Multidistrict Litigation,
In re Silicone Gel Breast Implant Products Liability Litigation,
MDL No. 926, 1994 WL 114580 , where they have been managed expeditiously under the watchful eye of the transferee judge, Chief Judge Sam C. Pointer, Jr. In 1995 and 1996, Judge Pointer remanded a number of cases to Oregon for trial.
All breast implant cases remanded to Oregon, federal district court have been assigned to this judge. After a series of status conferences involving all interested parties and counsel, I determined that, at least initially, similar cases should grouped for trial. I designated the following three trial groups:
Plaintiffs Defendants)
Group 1
4
Hall Pope Stern Preskey Baxter
Group 2
5
. Andrews , Johnston Eisele Bentley Tytlar Bristol-Myers Squib
Group 3
6
Shervey Zingarelli Adamson D. Hall Young Mitchel Bristol-Myers and Medical Engineering Corp.
After initial trial dates were set, the court instructed counsel for Groups 1 and 2 to provide a list of all lay and expert witnesses to be called at trial, together with a narrative statement of each witness’ proposed testimony. The court also instructed counsel to summarize each expert witness’ opinion, to identify all the materials upon which each expert would rely for his or her opinions, and to submit transcripts of any testimony given by the witness in similar cases.
Once the witness materials were duly filed, in July 1996, defendants jointly filed a series of motions in limine to exclude plaintiffs’ experts’ testimony concerning causation.
7
To address these motions, I scheduled an integrated hearing under Rule 104(a) on the admissibility of the scientific evidence. All interested parties and counsel were invited to attend the hearing, which I set for August 1996.
In view of the complicated scientific and medical issues involved and in an effort to effectively discharge my role as “gatekeeper” under
Daubert I,
I invoked my inherent authority as a federal district court judge to appoint independent advisors to the court.
8
See, e.g., Goetz v. Crosson,
967 F.2d 29, 37 (2d Cir.1992) (VanGraafeiland, J., concurring and dissenting) (citing
Scott v. Sponger Bros., Inc.,
298 F.2d 928 (2d Cir.1962));
see also
1972 Advisory Committee Notes to FRE 702. Pursuant to that inherent authority, I began a search to find technical advisors with the necessary expertise in the fields of epidemiology, immunology/toxicology, rheumatology,
*1393
and chemistry to assist in evaluating the reliability and relevance of the scientific evidence.
9
Dr. Richard Jones, M.D., Ph.D.,
10
assisted the court by screening dozens of potential appointees and ultimately selecting four totally unbiased and uncommitted experts in the necessary fields, which the court approved and appointed. The technical ad-, visors and their fields of expertise are: Mer-wyn R. Greenlick, Ph.D. (epidemiology); Robert F. Wilkens, M.D. (rheumatology); Mary Stenzel-Poore, Ph.D. (immunology/toxicology); and Ronald McClard, Ph.D. (polymer chemistry). .
With the exception of Dr. McClard, whom I appointed shortly after the initial Rule 104 hearing terminated, the technical advisors reviewed the parties’ voluminous materials in preparation for the hearing and observed most of the testimony in court. After his appointment, Dr. McClard reviewed all of the relevant materials and the videotaped arguments of counsel, and participated in all subsequent proceedings.
I structured the Rule 104 hearing according to subject matter, with plaintiffs presen^ • ing their experts in a particular field, followed by defendants’ witnesses in the same field. All participating parties stipulated to the experts’ qualifications under Rule 702. Because in proceedings pursuant to Rule 104(a) the court is not bound by rules of evidence, except those that pertain to privileges I ruled that no evidentiary objections would be permitted.
11
At the hearing, which spanned four intense days (August 6-8, 1996),
12
experts on both sides were questioned by counsel, the court, and the technical advisors. The parties then submitted videotaped summations, which the court and all technical advisors reviewed.
13
The court also asked the parties to submit proposed questions to guide the technical advisors in evaluating the testimony and preparing their reports. After considering the parties’ proposed questions, the court prepared and submitted the following questions to the advisors:
1. Is the expert’s opinion supported by scientific reasoning and methodology that is generally accepted in the expert’s particular scientific community or otherwise qualified as stated in
Daubert II,
as quoted above?
14
*1394
2. Is the expert’s opinion based upon scientifically reliable data?
3. If epidemiological studies have not been done or are inconclusive, what other data, such as animal studies, biophysical data, clinical experience in the field, medical records, differential diagnosis, preliminary studies, general scientific knowledge, and medical literature can justify, to a reasonable medical probability, a conclusion concerning the cause of the syndrome or disease at issue?
4. Do the methodology and data support the expert’s conclusions?
5. Does the scientific data relied upon by the expert apply to the syndrome or disease in issue in these cases? For instance, are epidemiological studies directed at other typical or classical diseases relevant to an atypical disease?
The court also submitted almost all of the parties’ proposed questions
15
to the technical advisors for their consideration, with this instruction:
We are also enclosing suggested questions and references provided by counsel. Do not feel obligated to answer all of counsel’s questions, but respond to those that you feel are relevant and that you feel will be helpful to the court in discharging our “gatekeeping” role. For instance, the defense contends that the record of the hearing does not reflect the plaintiffs’ reconstruction of their witness’ testimony. We leave that issue to you.
16
The technical advisors submitted their reports to the court in September 1996,
17
and on September 13, 1996, the court gave counsel on both sides an opportunity to question them. Following this hearing, the court expressed preliminary concerns that plaintiffs’ position could not be sustained and asked defense counsel to submit proposed findings of fact and conclusions of law. Plaintiffs then filed objections and proposed alternative findings, and the defendants filed a further response.
Having fully reviewed the entire record and the reports of the advisors, I am now prepared to rule on the pending rule 104 hearing motions in limine. For the reasons explained below, the defendants” motions in limine to exclude plaintiffs’ expert testimony concerning causation of any systemic disease or syndrome are GRANTED.
I note, however, that while this court was in the midst of the Rule 104 proceedings, Judge Pointer appointed a national panel of experts pursuant to FRE 706 to assist in a similar evaluation of the scientific evidence in the MDL. As recognized by Senior Judge Jack B. Weinstein and Judge Harold Baer, Jr., in their recent joint opinion in breast implant cases pending in the Southern and Eastern Districts of New York (see
In
re
Breast Implant Cases
(Amended Preliminary Memorandum Oct. 23,1996)), it will probably be some time before the national panel completes its important work.
18
In view of the ongoing national proceedings and the potential for further scientific developments during their pendency, the court will defer the effective date of this opinion until the findings of the national Rule 706 panel are available.
19
Depending on the court’s evaluation of those findings, plaintiffs
*1395
in these cases may seek reconsideration, if appropriate, of this decision. Plaintiffs’ motion to add the national Rule 706 panel members to the witness lists in Groups 2 and 3
20
is also deferred pending completion of the panel’s work.
III.
ADMISSIBILITY STANDARDS
A.
Rule 702 and Rule 104(a)
The Federal Rules of Evidence govern in diversity cases, except in the rare circumstance where a state rule of evidence is “ ‘intimately bound up’ with the rights and obligations being asserted * *
Wray v. Gregory,
61 F.3d 1414, 1417 (9th Cir.1995) (quoting
Erie R.R. Co. v. Tompkins,
304 U.S. 64, 78 , 58 S.Ct. 817, 822 , 82 L.Ed. 1188 (1938)). With respect to the issues presently before the court, no state evidence rule supplants the federal rules.
21
Rule 702 is the starting point for any evaluation of the admissibility of expert testimony.
Daubert I,
509 U.S. at 589 , 113 S.Ct. at 2794-95 (Rule 702 is the “primary locus” of the expert screening “obligation”). Rule 702 provides:
If the scientific, technical or other specialized knowledge will assist the trier of fact to understand the evidence or to determine a fact in issue, a witness qualified as an expert by knowledge, skill, experience, training, or education, may testify thereto in the form of an opinion or otherwise.
The assessment of whether proffered expert testimony is admissible under Rule 702 is a preliminary question for the court under Rule 104(a).
Daubert I,
509 U.S. at 592 , 113 S.Ct. at 2796 . Rule 104(a), which provided the framework for the hearing in this case, states:
Preliminary questions concerning the qualification of a person to be a witness, the existence of a privilege, or the admissibility of evidence shall be determined by the court, subject to the provisions of subdivision (b). In making its determination it is not bound by the rules of evidence except those with respect to privileges.
22
The Ninth Circuit recently emphasized that the proponent of the expert testimony bears the burden of proving admissibility under Rule 104.
Lust v. Merrell Dow Pharmaceuticals, Inc.,
89 F.3d 594 , 598 (9th Cir.1996) (“[i]t is the proponent of the expert who has the burden of proving admissibility”);
see also Daubert v. Merrell Dow Pharmaceuticals, Inc.,
43 F.3d 1311, 1316 (9th Cir.1995) (hereinafter
Daubert
II) (“the party presenting the expert must show that the expert’s findings are based on sound science”). In this case, the plaintiffs, as proponents of the evidence, have the burden of establishing admissibility by a preponderance of the evidence.
Daubert I,
509 U.S. at 592 n. 10, 113 S.Ct. at 2796 n. 10.
In determining whether the plaintiffs have met their burden of establishing the admissibility of their expert evidence, the court is guided by Rule 702 and the recent
*1396
Supreme Court and Ninth Circuit decisions interpreting it, particularly
Daubert I
and
Daubert II.
In
Daubert I,
the Supreme Court clarified that adoption of Rule 702 displaced the traditional Frye
23
test, which made “general acceptance” in the relevant scientific community the prerequisite to admissibility.
Daubert I,
509 U.S. at 589 , 113 S.Ct. at 2794-95 . Instead, under
Daubert I,
which. focused closely on the language of Rule 702, expert scientific opinion is admissible if it qualifies as “scientific knowledge” and is therefore sufficiently “reliable.”
Daubert I,
509 U.S. at 589-90 , 113 S.Ct. at 2795 ;
see also Lust,
89 F.3d at 597.
According to
Daubert I,
“the adjective ‘scientific’ implies a grounding in the methods and procedures of science,” and “the word ‘knowledge’ connotes more than subjective belief or unsupported speculation.” 509 U.S. at 590 , 113 S.Ct. at 2795 . The Court explained that
in order to qualify as “scientific knowledge,” an inference or assertion must be derived by the scientific method. Proposed testimony must be supported by appropriate
validation
— i.e., “good grounds,” based on what is known.
Id.
The requirement that an expért’s testimony pertain to “scientific knowledge” “es^ tablishes a standard of evidentiary reliability,”
i.e.,
trustworthiness. 509 U.S. at 590 and n. 9, 113 S.Ct. at 2795 and n. 9.
The Supreme Court charged district courts with the duty to act as “gatekeepers,” to ensure that any and all scientific testimony or evidence admitted is not only relevant, but reliable.
Daubert I,
509 U.S. at 597-98 , 113 S.Ct. at 2798-99 . Thus, the court must determine at the outset, pursuant to Rule 104(a), “whether the expert is proposing to testify to (1) scientific knowledge that (2) will assist the trier of fact to understand or determine a fact in issue.”
Id.
at 592-93 , 113 S.Ct. at 2796 . This determination “entails a preliminary assessment of whether the reasoning or methodology underlying the testimony is scientifically valid and of whether that reasoning or methodology properly can be applied to the facts in issue.”
Id.
The task before this court, then, is two-pronged. First, the court must determine whether plaintiffs’ experts’ testimony reflects “scientific knowledge,” constitutes “good science,” and was “derived by the scientific method.”
Daubert II,
43 F.3d at 1316 . Second, the court must ensure that the proposed testimony “fits,” that is, that the testimony is “‘relevant to the task at hand’ ” in that it “logically advances a material aspect of the proposing party’s ease.”
Id.
at 1315 (quoting
Daubert I,
509 U.S. at 597 , 113 S.Ct. at 2798-99 ).
1.Reliability.
Daubert I
and
Daubert II
list several factors to guide federal courts in deciding the first prong, whether the expert testimony is scientifically valid and therefore reliable. These factors, which may or may not apply in a particular case, include:
1. Whether the theory or technique employed by the expert, is generally accepted in the scientific community;
2. Whether the theory has been subjected to peer review and publication;
3. Whether the theory can be and has been tested;
4. Whether the known or potential rate of error is acceptable; and
5. Whether the experts are. proposing to testify about matters growing naturally or directly out of research, or whether they have developed their opinions expressly for purposes of testifying.
24
*1397
Daubert I,
509 U.S. at 593-94 , 113 S.Ct. at 2796-97 (first four factors);
Daubert II,
43 F.3d at 1316-17 (adding fifth factor). The list is illustrative, not exhaustive.
Daubert II,
43 F.3d at 1317 .
As mentioned earlier, with respect to the first listed factor, whether the expert’s theory or method is generally accepted, the Ninth Circuit explained in
Daubert II
that in certain circumstances it may be sufficient if a minority in the scientific community accepts the methods employed, but only if the proponent demonstrates in “some objectively verifiable way that the expert has both chosen a reliable scientific method and followed it faithfully.”
Daubert II,
43 F.3d at 1319 n. 11.
2. Fit.
Even if the proponents meet their burden of establishing that an expert’s testimony qualifies as scientific knowledge, the court must still exclude the evidence if it does not “fit” the matters at issue in the case.
Daubert I,
509 U.S. at 591 , 113 S.Ct. at 2795-96 . As the Ninth Circuit in
Daubert II,
explained, to “fit,” testimony must “logically advance a material aspect of the proposing party’s case.”
Daubert II,
43 F.3d at 1315 ;
see also In re Paoli R.R. Yard PCB Litigation,
35 F.3d 717, 743 (3d Cir.1994) (hereinafter
Paoli
II
25
). In
Paoli II,
Judge Becker described the “fit” requirement as follows:
For example, animal studies may be methodologically acceptable to show that chemical X increases the risk of cancer in animals, but they may not be methodologically acceptable to show that chemical X increases the risk of cancer in humans.
Daubert
explains that, “‘[f]it’ is not always obvious, and scientific validity for one purpose is not necessarily scientific validity for other, unrelated purposes.” * * * Thus, even if an expert’s proposed testimony constitutes scientific knowledge, his or her testimony will be excluded if It is not scientific knowledge
for purposes of the case.
“Rule 702’s ‘helpfulness’ standard requires a valid
scientific
connection to the pertinent inquiry as a precondition to admissibility.” * * * For example, in order for animal studies to be admissible to prove causation in humans, there must be good grounds to. extrapolate from animals to humans, just-as the methodology of the studies must constitute good grounds to reach conclusions about the animals themselves. Thus, the requirement of reliability, or “good grounds,” extends to each step in an expert’s analysis all the way through the step that connects the work of the expert to the particular case.
Paoli II,
35 F.3d at 743 (citations omitted; emphasis in original).
As the defendants correctly point out in their proposed findings and conclusions, the issue before the court, as in the Bendectin litigation considered in
Daubert II,
is causation. In
Daubert II,
the Ninth Circuit concluded that the plaintiffs in that case failed to make any objective showing of admissibility under the first prong of Rule 702. Because the plaintiffs had submitted their expert materials while
Frye
was the law of the circuit, however, rather than remand the case to permit the plaintiffs to augment the record, the court proceeded to reach the second prong, or “fit” requirement, of the
Daubert I
analysis.
Daubert II,
43 F.3d at 1320 . In doing so, the court explained that in assessing whether proffered expert testimony “will assist the trier of fact” in resolving the causation issue, the court must look to the substantive standard — in that case, California tort law. The court commented:
California tort law requires plaintiffs to show not merely that Bendectin increased
*1398
the likelihood of injury, but that it more likely than not caused their injuries. * * * In terms of statistical proof, this means that plaintiffs must establish not just that their mothers’ ingestion of Ben-dectin increased somewhat the likelihood of birth defects, but that it more than doubled it—only then can it be said that Bendectin is more likely than not the source of their injury. Because the background rate of limb reduction defects is one per thousand births, plaintiffs must show that among children of mothers who took Bendectin the incidence of such defects was more than two per thousand.
Id.
at 1320 (citation omitted).
26
The substantive standard under Oregon tort law is quite similar to the California standard. Under Oregon law, the plaintiffs in this litigation must prove not merely the possibility of a causal connection between breast implants and the alleged systemic disease, but the medical probability of a causal connection.
See Harris v. Kissling,
80 Or. App. 5, 9 , 721 P.2d 838 (1986);
see also Griffin v. K.E. McKay’s Market of Coos Bay, Inc.,
125 Or .App. 448, 451-52, 865 P.2d 1320 (1993), in which the court stated:
[The plaintiff] must introduce evidence which affords a reasonable basis for the conclusion that it is more likely than not that the conduct of the defendant was a substantial factor in the result. A mere possibility of such causation is not enough * * * (Citation omitted.)
27
Under this substantive standard, if an expert cannot state the causal connection in terms of probability or certainty, the expert’s testimony must be excluded under the second prong of Rule 702. In
Daubert II,
for example, the Ninth Circuit affirmed the district court’s exclusion of certain of plaintiffs’ experts’ opinions, reasoning that:
As the district court properly found below, “the strongest inference to be drawn for plaintiffs based on the epidemiological evidence is that Bendectin could
possibly
have caused plaintiffs’ injuries.” * * * The same is true of the other testimony derived from animal studies and chemical structure analyses—these experts “testify to a possibility rather than a probability.” * * * Unlike these experts’ explanation of their methodology, this is not a shortcoming that could be corrected on remand; plaintiffs’ experts could augment their affidavits with independent proof that their methods were sound, but to augment the substantive testimony as to causation would require the experts to change their conclusions altogether. Any such tailoring of the experts’ conclusions would, at this stage of the proceedings, fatally undermine any attempt to show that these findings were ‘derived by the scientific method.’ Plaintiffs’ experts must, therefore, stand by the conclusions they originally proffered,
rendering their testimony inadmissible under the second prong of Fed. R.Evid. 702.
Daubert II,
43 F.3d at 1322 (citation omitted; emphasis added).
28
*1399
3. Methodology v. Conclusions.
The plaintiffs insist that this court must focus solely on the expert’s methodology and may not consider the experts’ conclusions in any respect. Certain language in
Daubert I
can be read, superficially, to support plaintiffs’ position. The
Daubert I
Court wrote:
The inquiry envisioned by Rule 702 is, we emphasize, a flexible one. Its overarching subject is the scientific validity — and thus the evidentiary relevance and reliability— of the principles that underlie a proposed submission.
The focus, of course, must be solely on principles and methodology, not on the conclusions that they generate.
Daubert I,
509 U.S. at 595 , 113 S.Ct. at 2797 (emphasis added).
Since
Daubert I
was decided, however, courts and commentators have wrestled with the methodology/eonclusion distinction, concluding that the distinction is of limited practical import. In
Paoli II,
for example, Judge Becker offered the following cogent analysis:
Plaintiffs are correct, of course, that
Dau-bert
requires the judge’s admissibility decision to focus not on the expert’s conclusions but on his or her principles and methodology. * * * But we think that
this distinction has only limited practical import.
When a judge disagrees with the conclusions of an expert, it will generally be because he or she thinks that there is a mistake at some step in the investigative or reasoning process of that expert. If the judge thinks that the conclusions of some other expert are correct, it will likely be because the judge thinks that the methodology and reasoning process of the other expert are superior to those of the first expert. This is especially true given that the expert’s view that a particular conclusion “fits” a particular case must itself •constitute scientific knowledge — a challenge to “fit” is very close to a challenge to the expert’s ultimate conclusion about the particular, case, and yet it is part of the judge’s admissibility calculus under
Dau-bert.
35 F.3d at 746 (emphasis added). In a footnote, Judge Becker added that:
The methodology/eonclusion distinction remains of some import, however, to the extent that there will be cases in which a party argues that an expert’s testimony is unreliable because the conclusions of an expert’s study are different from those of other experts. In such eases, there is no basis for holding the expert’s testimony inadmissible.
35 F.3d at 746 n. 15 (citations omitted).
In
Claar v. Burlington Northern R. Co.,
29 F.3d 499 (9th Cir.1994), the Ninth Circuit emphasized that a district court is “both authorized and obligated to scrutinize carefully the
reasoning
and methodology” underlying the expert’s proffered testimony. 29 F.3d at 502 (emphasis added). According to the court in
Claar :
This requirement means that the court had to determine that [the experts] arrived at their conclusions using scientific methods and procedures, and
that those conclusions were not mere subjective beliefs or unsupported speculation.
29 F.3d at 502 (emphasis added).
29
More recently, in
Lust v. Merrell Dow Pharmdceuticals, Inc., supra,
the Ninth Circuit acknowledged that a district court need not ignore an expert’s anomalous conclusions in determining admissibility under Rule 702. In
Lust,
plaintiff’s expert, Dr. Done, proposed to testify that ingestion of the drug Clomid causes a substantial increase in the probability of all birth defects on the ground that human epidemiological studies and animal studies show an association between the drug and a wide variety of problems. Un-contradicted testimony from defendant’s expert, however, indicated that Done’s chief
*1400
premise — that if there is evidence of a positive association between an agent and a wide variety of birth defects in human epidemiological and animal studies, then the agent substantially increases the probability of all types of birth defects — was not espoused by a relevant minority of teratologists.
Lust,
89 F.3d at 596.
The Ninth Circuit held that the district court properly excluded Done’s testimony. Responding to Done’s contention that the district court “violated Daubert’s command that “ ‘[t]he focus ... must be solely on principles and methodology, not on the conclusions that they generate,’ ” the court stated:
Done’s conclusions did arouse the district court’s suspicion, but that is to be expected. When a scientist claims to rely on a method practiced by most scientists, yet presents conclusions that are shared by no other scientist,
the district court should be wary that the method has not been faithfully applied.
It is the proponent of the expert who has the burden of proving admissibility. To enforce this burden,
the district court can exclude the opinion if the expert fails to identify and defend the reasons that his conclusions are anomalous.
Lust,
89 F.3d at 598 (emphasis added; citation omitted).
In a recent law review article evaluating the admissibility of scientific evidence after
Daubert,
the author suggests the following approach to the methodology/conclusion debate:
Rule 702 seeks to ensure that there is a valid scientific connection to the pertinent inquiry, and scientific validity for one purpose is not necessarily scientific validity for other purposes. * * * In a case where a plaintiff alleges personal injury from exposure to a substance, the issue at hand is not whether the agent can potentially cause that injury. Rather, the issue is whether the agent caused the particular plaintiffs injury.
To return to the animal study hypothetical, the court should not simply ask whether the type of animal study relied on by the expert can be validly used to determine whether Bendectin is a teratogen, but should also ask whether scientists reasonably rely on that type of animal study to prove that Bendectin is a teratogen in humans. If the answer is yes, the court should ask whether the animal study provides sufficient information to allow a scientist to reasonably rely on it to prove that Bendectin caused a birth defect in a particular individual.
Finally, assuming those questions are answered to the court’s satisfaction, the ■ court must determine whether the expert’s principles and methodology are sound.
In other words, has the expert properly extrapolated from the animal study at issue, or is her reasoning flawed?
Some have argued that Daubert forbids courts to ask this question. * * *
This reasoning is wrong-headed. When Daubert forbids courts to examine an expert’s conclusions, it is obviously alluding to the Frye rule. Some courts used Frye to exclude novel expert testimony if it conflicted with the established view in the scientific community, regardless of the soundness of the expert’s methodology and reasoning. That is no longer permissible after Daubert.
But Daubert does demand that courts assess the scientific validity of the expert’s testimony. Daubert demands that in reviewing the expert’s principles and methodology, a court should determine whether “the principle supports what is purports to show.” * * *
Daubert therefore not only allows, but requires, courts to determine whether an expert’s extrapolations from underlying studies or data are proper, or whether the expert has committed scientific or mathematical errors.
David E. Bernstein,
The Admissibility of Scientific Evidence After Daubert v. Merrell Dow Pharmaceuticals, Inc.,
15 Cardozo L.Rev. 2139, 2165-66 (1994) (emphasis added; footnotes omitted).
In
Paoli II,
35 F.3d at 745 , Judge Becker noted that
Daubert’s requirement that the expert testify to scientific knowledge — conclusions supported by good grounds for each step
*1401
in the analysis — means that
any
step that renders the analysis unreliable under the
Dauberb factors renders the expert’s testimony inadmissible. This is true whether the step completely changes a reliable methodology or merely misapplies that methodology.
(Emphasis in original; footnote omitted.)
There appears to be no clear demarcation between scientific methodology and the conclusions it generates.
Daubert I
acknowledged this much, recognizing that science is a process, not “an encyclopedic body of knowledge.” 509 U.S. at 590 , 113 S.Ct. at 2795 (citation omitted). This court need not and should not ignore any step in that process, but must ensure that in each step, from initial premise to ultimate conclusion, the expert faithfully followed valid scientific methodology. In other words, this court need not accept, as scientifically reliable, any conclusion thát good science does not permit to be drawn from the underlying data but which, instead, constitutes “unsupported speculation,” or, in the words of Dr. Stenzel-Poore, a “leap of faith.” The Ninth Circuit requires no less.
See Claar,
29 F.3d at 502 ;
see also Lust,
89 F.3d at 598.
Accordingly, in resolving the pending issues before me, this court will examine the evidence to ensure, as Judge Becker noted in
Paoli II,
that
every
step in the expert’s reasoning process, including the expert’s formulation of conclusions, are grounded in good science.
IY.
FINDINGS AND CONCLUSIONS
Physicians have used silicone
30
products in the human body for various purposes since the 1950s. Medical devices made from hard silicone include shunts, finger joints, hip joints, and heart valves. In addition, the United States and Japan experimented with injecting liquid silicone' directly into the human body in the 1950s and 1960s. However, the FDA eventually classified silicone liquid directly injected as a drug and has approved it only for experimental investigations. The silicone- gel breast implants involved in this litigation consist of 80 to 90 percent liquid silicone combined with 10 to 20 percent silicone gel, contained in a silicone rubber shell.
Plaintiffs’ theory of causation — or, as they refer to it, bioplausibility — begins with the premise that silicone from breast implants is released into a woman’s body, either through implant rupture or through “gel bleed,” the slow but continuous release of very small droplets (“mierodroplets”) of silicone gel through the silicone rubber implant cover. Once released into the body, plaintiffs assert, silicone migrates throughout the body, either by diffusing through cell membranes or by being carried by macrophages, the cells in a person’s body that devour and eliminate invading foreign bodies and wastes. In the process, the silicone degrades, or is chemically converted, into more reactive molecules such as silanols. The released silicone and the reactive products of silicone degradation purportedly elicit an autoimmune response from the woman’s immune system, essentially turning her immune system against her. The result, plaintiffs conclude, is general, systemic disease and particular signs and symptoms such as muscle and joint pain, headaches, rashes, and an inability to concentrate.
*1402
Plaintiffs’ theory of causation thus brings four general areas of science into play: epidemiology; rheumatology; immunology/toxicology; and polymer chemistry. As has been described, the Rule 104 hearings and many of the parties’ arguments have been generally structured around these scientific fields. Thus, while I am mindful that the motions in limine actually address the exclusion of particular expert witnesses, my findings and conclusions will track the various disciplines at issue.
A. Atypical Connective Tissue Disease
Plaintiffs premise many of their claims on the existence of a variously-titled atypical connective tissue disease (ACTD).
31
This “disease” allegedly manifests itself through a constellation of various symptoms
32
and is allegedly caused by an autoimmune response to silicone from breast implants. Plaintiffs have offered Dr. Eric Gershwin and Dr. Kip Kemple as experts in rheumatology' to testify that silicone exposure is the probable cause of plaintiffs’ atypical constellation of symptoms.
By definition, ACTD is not one of the classical autoimmune diseases, such as lupus, scleroderma, or rheumatoid arthritis. In addition, plaintiffs’ expert Dr. Goldsmith testified that ACTD does not exist even as a hypothesis yet. “Epidemiologically, the question that you have asked me twice is where we are with these atypical diseases. And I am telling you we are back at the beginning of formulating studiable hypotheses to test. We are really at the beginning of that.” TRANS. Of Pretrial Hearings before the Honorable Robert E. Jones (hereinafter Portland Trans.), Aug. 6, 1996, at 164:23 to 165:2. A silicone research group has proposed criteria for this alleged disease, but these criteria have not yet been tested, nor does the rheumatology community generally accept the existence of ACTD. Dr. Gershwin has acknowledged that he would not rely on these criteria as authoritative for his medical opinion. Portland Trans., Aug. 5, .1996, at 78:25 to 79:23. He also admitted that there is no specific diagnostic test for this alleged disorder. Portland Trans., Aug. 5,1996, at 88:1-4,15-19. Finally, women who allegedly have ACTD do not uniformly exhibit the same signs and symptoms, and there is no “signature” disorder to suggest either that the cause is silicone exposure or that the cause is the same for all women showing this constellation of symptoms.
33
Instead, the asserted constellation of symptoms comprising ACTD overlaps significantly with those comprising chronic fatigue syndrome and fibromyalgia.
34
,
Because ACTD is at best an untested hypothesis, there is no scientific basis for any expert testimony as to its causes and presence in plaintiffs. Therefore, defendants’ motions are GRANTED as regards any expert testimony relating to the existence and causation of any atypical, silicone-caused, autoimmune disorder.
With the possible exception of plaintiff LeaAnn Hall, moreover, plaintiffs have not been diagnosed as having classical autoimmune disorders. Therefore, the rest of this
*1403
opinion will address expert testimony in regards to plaintiffs’ individual signs and symptoms.
B. Epidemiology
Plaintiffs offer Dr. David Goldsmith as an expert to testify that there is epidemiological and other scientific data showing that women with silicone breast implants have significantly elevated probability of suffering from classical diseases when compared to women without breast implants.
35
In contrast, plaintiffs offer Dr. Shanna Swan, through transcripts of her previous testimony in other cases, to testify that no valid epidemiological studies regarding the relationship of silicone breast implants and disease have been completed as of August 1996.
Epidemiology is the medical science devoted to determining the causes of disease in human beings. Epidemiologists compare control groups of unexposed individuals to groups of individuals exposed to a hypothetical cause of the disease being studied to determine whether exposed individuals have a greater risk of manifesting that disease. In epidemiological terms, any difference in risk of getting the disease between the two groups is the exposed individuals’ relative risk. The existence or nonexistence of relevant epidemiology can be a significant factor in proving general causation in toxic tort cases.
Daubert II,
43 F.3d at 1320-21 ;
Brock v. Merrill-Dow Pharmaceuticals, Inc.,
874 F.2d 307, 311-13 (5th Cir.1989).
To support admissible expert opinions, epidemiological evidence must fit the legal as well as the substantive issues of the case. Because this is a diversity action, Oregon substantive standards of law must apply.
Erie Railroad Co. v. Tompkins,
304 U.S. 64 , 58 S.Ct. 817 , 82 L.Ed. 1188 (1938).
36
As discussed above, under Oregon law, a plaintiff seeking to prove causation must “ ‘introduce evidence which affords a reasonable basis for the conclusion that it is more likely than not that the conduct of the ■ defendant was a substantial factor in the result.’”
Griffin v. K.E. McKay’s Mkt.,
125 Or.App. at 451-52 , 865 P.2d 1320 (quoting
Eitel v. Times, Inc.,
221 Or. 585, 594 , 352 P.2d 485 (1960)). This burden requires plaintiffs to demonstrate that exposure to breast implants more than doubled the risk of their alleged injuries.
Daubert II,
43 F.3d at 1320 .
In epidemiological terms, Oregon’s standard of proof means that plaintiffs must be able to show a relative risk of greater than 2.0:
The threshold for concluding that an agent was more likely the cause of a disease than not is relative risk greater than 2.0. Recall that a relative risk of 1.0 means that that agent has no effect on the incidence of disease. When the relative risk reaches 2.0, the agent is responsible for ah equal number of cases of disease as all other background causes. . Thus, a relative risk of 2.0 implies a 50% likelihood that an exposed individual’s disease was caused by the agent.
Bailey,
et al.,
Reference Guide on Epidemiology, REFERENCE MANUAL ON SCIENTIFIC EVIDENCE at 168. The Ninth Circuit has reached a similar conclusion under California’s standard of proof, which is very similar to Oregon’s, holding that “[f]or an epidemiological study to show causation under a preponderance standard,, ‘the relative risk of [the condition at issue] arising from the epidemiological data ... will, at minimum, have to exceed “2”.’ ”
Daubert II,
43 F.3d at 1321 (quoting
DeLuca v. Merrell Dow Pharmaceuticals,
911 F.2d 941 , 958 (3d Cir.1990)).
*1404
Although, as discussed above, epidemiological studies showing a relative risk of less than 2.0 might be relevant under some circumstances, here, as in
Daubert II,
“plaintiffs’ experts did not seek to differentiate these plaintiffs from the subjects of the statistical studies. The studies must therefore stand or fall on their own.”
Id.
at 1321 n. 16.
Plaintiffs’ experts base their proffered expert opinions on the sixteen epidemiological studies
37
assessing the relationship of silicone breast implants to classical connective tissue disease. In addition, plaintiffs have called this court’s attention to the 1996 Liang-Schottenfeld abstract recently presented at a meeting of the American College of Rheumatology that reports a relative risk of 2.27 for Undifferentiated Connective Tissue Diseases (UCTD).
38
Dr. Goldsmith testified in the proceedings before this court that he was not willing to testify, based on the 16 then-available studies, that silicone more likely than not could cause disease in women. That testimony was as follows:
DR. GREENLICK: You were asked a question if you had an opinion on causality based on whatever other evidence was left, case studies, other animal evidence. I think there is a sense that when you talked about there was a suggestion from some of the things that would mean you had a very low certainty of causality and that causality could go from saying, “We don’t know if there’s any link at all,” all the way to saying, “We are really quite certain, short of randomly implanting women, we are very certain.”
Given the fact that there is no epidemiological data on this, where would you say your sense of certainty of your causality is? How close to zero as opposed to 100 percent are you? Are you in certainty with your opinion that there is a causal relationship with breast implants and atypical connective tissue disease?
*1405
DR. GOLDSMITH: Let me also make sure that I give you an answer that I think is reflective of the — of the question in front of us. I don’t believe it should go from zero to — to fully sure. I think it’s also possible that breast implants could, in fact, be negatively related to those atypical syndromes as well.
DR. GREENLICK: Right. I was just starting from a zero, yes, could you have gone all the way from they are highly protective through no relationship, all the way to certain causality.
But let’s just — I assume you don’t — you are not suggesting that the current data would tell you they are protective against atypical disease. So let’s start from zero at “I have no certainty whatever there’s a relationship,” all the way to “I am absolutely certain there’s a relationship from the existing data given no epidemiological data.” I was wondering where you would—
DR. GOLDSMITH:
At the moment, I must suggest to you that the evidence looks to me as if it’s just that, that it’s a possibility, and I would have to characterize it as less than 50 percent.
That would be where I am at the moment.
But where the new evidence is going to show that there is or is not an association, I think we have to wait for the science to tell us. We have to wait for the epidemiology.
PORTLAND Trans., Aug. 6, 1996, at 241:14 to 243:4 (emphasis added).
With the release of the Liang-Schottenfeld abstract, Dr. Goldsmith now indicates a willingness to testify that such causation is “more likely than not.”
39
This court cannot accept his proffered change in testimony because it finds the methodology supporting this changed testimony unreliable under
Daubert I
and
Daubert II.
First, none of the- 16 epidemiological studies found that women with silicone breast implants faced a relative risk of classical diseases or disease signs and symptoms of anywhere near 2.0. Indeed, only one study — the Hennekens study — found any statistical relationship between the presence of silicone breast implants and disease, and there the relative risk was only 1.24. Therefore, these studies cannot support expert testimony that silicone “more likely than not” causes disease or signs and symptoms of disease in women.
Second, the Liang-Schottenfeld abstract cannot in itself support Dr. Goldsmith’s change in testimony. The abstract is not yet published, nor is a full write-up of the study, including the supporting data, yet available. Indeed, Dr. Goldsmith admitted in his New York testimony that his only knowledge of the details of the study came from a telephone inquiry. New YorK Trans., at 71:17-24. According to the abstract, moreover, the study included only three women with breast implants, calling its epidemiological significance severely into question. In addition, the abstract explicitly concludes that “silicone breast implants were not significantly associated with UCTD,” suggesting that silicone gel breast implants are
not
associated with disease. In contrast, the abstract concludes overall that, “[ajmong all types of implanted devices, including breast implants, both those containing silicone * * * and those that did not contain silicone * * * were significantly associated with UCTD.” This apparent internal contradiction within the abstract’s conclusions calls the value of this study further into question. In light of these shortcomings
40
and in the face of the other 16 studies, which Dr. Goldsmith has already admitted do not support expert testimony that silicone “more likely than not” causes
*1406
disease in women, this court GRANTS defendant’s motion to exclude Dr. Goldsmith’s epidemiological testimony.
41
As for defendants’ motion to exclude Dr. Swan’s proffered testimony, the motion must be GRANTED because Dr. Swan’s testimony is unreliable and no longer “fits” plaintiffs’ theory of the case. I first note that several courts have rejected Dr. Swan’s testimony and her “reanalysis” approach as unreliable.
42
Dr. Swan’s reanalysis of the silicone epidemiology has never been subjected to peer review.
Merlin
HEARING TRANS., at 73-76. Moreover, her theory has not been espoused by any other scientist whose work has been subjected to the peer review process.
Merlin
Hearing Trans., at 73-74. Peer review and publication weigh heavily in the calculus of the reliability of expert testimony because such peer review “increases the likelihood that substantive flaws in methodology will be detected.”
Daubert I,
509 U.S. at 594 , 113 S.Ct. at 2797 . Thus, the lack of peer review for Dr. Swan’s theories weighs heavily against the admissibility of Dr. Swan’s testimony.
In addition, Dr. Swan’s testimony involves only her opinions and criticisms of others’ work; as such, it is-not based on any technique that can be scientifically tested. Moreover, her criticisms of the existing epidemiology for silicone gel breast implants have not been generally accepted. In fact, they have not been accepted at all.
Merlin
Hearing Trans., at 92-93. In contrast, Dr. Swan admits that no studies have established a causal link of any scientific significance between silicone breast implants and disease,
Merlin
Hearing Trans., at 82, and this is the reeog-nized consensus of the relevant scientific community.
As the Supreme Court stated, “widespread acceptance can be an important factor in ruling particular evidence admissible, and a known technique that has been able to attract only minimal support within the community may properly be viewed with skepticism.”
Daubert I,
509 U.S. at 594 , 113 S.Ct. at 2797 . Many courts have recognized that an unexplained conflict with the generally accepted methodology or theories in a given scientific field can be a basis for excluding proffered expert testimony.
See Turpin v. Merrell Dow Pharmaceuticals, Inc.,
959 F.2d 1349, 1360 (6th Cir.),
cert. denied,
506 U.S. 826 , 113 S.Ct. 84 , 121 L.Ed.2d 47 (1992) (finding no scientific basis for testimony of a causation expert who did “not testify on the basis of the collective view of his scientific discipline^ nor [did] he take issue with his peers and explain the grounds for his difference”);
O’Conner v. Commonwealth Edison Co.,
807 F.Supp. 1376, 1398 (D.Ill.1992),
aff'd
13 F.3d 1090 (7th Cir.),
cert. denied
— U.S. -, 114 S.Ct. 2711 , 129 L.Ed.2d 838 (1994) (holding that “an expert opinion that
actually contradicts directly
the scientific consensus is inadmissible”);
Conde v. Velsicol Chem. Corp.,
804 F.Supp. 972, 1024 (S.D.Ohio 1992),
aff'd
24 F.3d 809 (holding that “when an expert expresses an opinion which is not generally accepted within the medical and scientific communities, he has an obligation to provide a reasoned explanation of why his methodology and opinions differ”). In addition to not being peer-reviewed and to being untestable, Dr. Swan’s proffered testimony inexplicably conflicts with the general con
*1407
sensus of the epidemiological community. Thus, it is unreliable and hence inadmissible.
In addition, Dr. Swan’s testimony has no “fit.” As discussed above, even if the proponents of expert testimony establish that that testimony is reliable scientific knowledge, the court must still exclude the evidence if it does not fit the issues to be decided in the case.
Daubert I,
509 U.S. at 591 , 113 S.Ct. at 2795-96 . In the Ninth Circuit, testimony only “fits” a ease if it logically advances a material aspect of the proponent party’s case.
Daubert II,
43 F.3d at 1315 . Here, Dr. Swan seeks to testify that current epidemiology regarding the relationship of silicone breast implants and classical disease is invalid. However, this court has already determined that the proffered testimony based on that epidemiology is inadmissible, and it will determine, see discussion below, that plaintiffs cannot base their entire case on differential diagnosis. In addition, to the extent that plaintiffs intended to use Dr. Swan’s testimony to support their argument that silicone breast implants can cause ACTD, I have already ruled that no- testimony regarding ACTD will be permitted. Therefore, Dr. Swan’s testimony is now a stepping stone that leads nowhere; it no longer “fits” plaintiffs’ case.
There is no doubt but that Dr.- Swan has impressive credentials, as Justice Black-mun himself recognized in
Daubert I,
509 U.S. at 583 n. 2, 113 S.Ct. at 2792 n. 2 (noting that Dr. Swan has “a master’s degree in biostatics from Columbia University and a doctorate in statistics from the University of California at Berkeley, is chief of the section of the California Department of Health and Sciences that determines causes of birth defects, and has served as a consultant to the World Health Organization, the Food and Drug Administration,, and the National Institutes of Health.”) However, as Judge Wein-stein noted in the Agent Orange litigation, the jury should “not be permitted to be misled by the glitter of an expert’s accomplishments outside the courtroom” if the expert opinion is based on “untrustworthy” data or is otherwise not reliable.
43
,
In re “Agent Orange” Product Liability Litigation,
611 F.Supp. 1223, 1245 (E.D.N.Y.1985) (citations omitted). As in that ease, “‘the speculation and unfounded assumptions underlying [the] testimony [of Dr. Swan] decrease its probative value, perhaps to the level of the gossamer.’ ”
Id.
at 1256 (quoting
American Bearing Co. v. Litton Indus., Inc.,
729 F.2d 943 , 950 n. 14 (3d Cir.1984)). In this litigation, Dr. Swan’s well-traveled opinions are no more than educated guesses dressed up in evening clothes. Therefore, for all of the above reasons, I GRANT defendants’ motions to exclude Dr. Swan’s testimony.
C. Immunology and Toxicology
Plaintiffs have offered Dr. Eric Gershwin as an expert in immunology to testify that silicone is capable of causing plaintiffs’ constellation of symptoms because (1) silicone in contact with human tissue results in chronic inflammation through immune activation and cellular reactions; (2) silicone is an immune adjuvant and thus can produce enhanced immune responses when in the presence of a triggering condition and exacerbate existing
*1408
immune-mediated conditions; and (3) the surface of silicone changes or degrades
in vivo
into silanol groups and/or silica. He relies on the epidemiological studies discussed above, his own clinical experience, biomarker, immune activation, and toxicological studies,
44
and the work of the Harvard
*1409
NMR Center on the degradation of silicone as the bases of his proffered opinion.
Plaintiffs also offer Dr. Kip Kemple to testify that silicone can produce an immunological response in women. Dr. Kemple relies on immunological studies showing that autoantibodies are elevated in women with breast implants
45
and his own study of anti-ganglioside antibodies in women with breast implants.
The court submitted immunological/toxicological issues to its expert, Dr. Mary Stenzel-Poore,
46
who specifically looked at the adju-vant potential of silicone gel implants, the potential for immune stimulation of T cells by silicone gel implants, altered natural, killer cell activity, and immune system cancer formation in rodents. She opined that the studies relied upon by plaintiffs’ experts justified the following conclusions regarding silicone gel adjuvant potential:
la. Silicone gel
emulsified with antigen
may act as an adjuvant in humoral and cell-mediated immune responses in rodents.
lb. Silicone oils that are both linear and low molecular weight,
emulsified with antigen
do not act as adjuvants in rodents.
le. Silicone oils that are low molecular weight and cyclic (D4)
emulsified with antigen
may act as adjuvants.
Appendix D, at 2. However, “[djirect attempts to demonstrate that immunization with these agents emulsified with ‘auto-antigens’ or given in the absence of antigens failed to show evidence of autoimmune disease despite obvious disease induction by Freund’s adjuvant,” except in a genetic strain of rat developed to have a high susceptibility of developing arthritis.
Id.
Thus,
in rodents only,
“enhanced immune responses are not found if the antigen is not emulsified with the silicone agents * *
Id.
at 2-3 (citations omitted).
Dr. Stenzel-Poore 'further stated that “[fjorming the conclusion that elicitation of autoimmune and/or inflammatory disease occurs in women with SBI based on the evidence that silicone gel acts as an adjuvant
when emulsified with antigen
is unsupported by the data since peer-reviewed, studies failed to show evidence of any autoimmune-mediated disease.” Appendix D, at 3. Although “[t]he scientific methodology used in the aforementioned studies is generally sound,” -
Dr. Gershwin’s opinion regarding the adju-vant properties of silicone gel
requires a substantial leap of faith
since it is undeter.mined from these studies whether silicone gel breast implants would lead to adjuvant actions, much less autoimmune responses or systemic inflammation; indeed, studies designed to test this hypothesis argue
*1410
against such an outcome. Thus, the position of Dr. Gershwin is not well-supported by the data available in the published scientific literature nor is it derived from valid conclusions of the studies cited above.
Id.
(emphasis added).
With regard to T-cell stimulation, Dr. Stenzel-Poore opined that “[t]he view that SBIs stimulate antigen-specific T cell mediated responses in vivo is not well substantiated by the experimental studies reported in the literature.” Appendix D, at 4. Moreover, although “[s]everal studies have been performed attempting to establish a link between silicone breast implantation in women and silicone-specific T-cell responses,” “these studies have a number of methodological shortcomings and thus should not form the basis of an opinion.”
Id.
at 5. As a result,
those opinions of Dr. Gershwin regarding the role of silicone gel breast implants in stimulating specific T cell immunity and thereby providing a plausible mechanism of autoimmune induction are not upheld by the literature discussed above. The position of Dr. Gershwin is simply not well-supported by studies available in the published scientific literature nor is it derived from appropriate conclusions regarding the studies cited above.
Id.
at 8.
Dr. Stenzel-Poore also examined the literature regarding changes in natural killer cell function. . She noted that “[c]hanges in natural killer (NK) cell function have been reported to be associated with silicone gel exposure in rodents and humans.” Appendix D, at 9. Such an association could be significant because “changes in NK cells have also been associated with increased susceptibility to pathogens and tumor formation.”
Id.
However, “[g]iven the concerns raised by the degree of irreproducibility and fluctuations in time and dose-dependency [in the silicone gel/NK cell studies], conclusions made regarding the suppressive effect of silicone gel on NK function based on these studies are premature.”
Id.
Moreover, “although the data indicate that 50% of symptomatic women with implants had lower NK activity prior to removal of the implant, it is misleading since the degree of variation is not shown in the implanted women, or in women without implants. It is invalid to conclude that silicone-gel breast implants in women lead to a depressed NK cell activity that is reversible with explanation.”
Id.
at 10.
Finally, in evaluating the studies evaluating the development of immune system cancer in response to silicone, Dr. Stenzel-Poore stated that “Dr. Gershwin’s opinions regarding the development of immune system cancers in women with silicone breast implants is unwarranted” from the current studies, which are all animal studies. Appendix D, at 11. “There is no conclusive evidence to date that this model of tumor formation in mice has any human correlate.”
Id.
I agree with and accept Dr. Sten-zel-Poore’s assessments of Dr. Gershwin’s scientific methodology in fight of legal standards for
Daubert
hearings. As a preliminary matter, I note that most if not all of the studies that Dr. Gershwin and Dr. Kemple rely upon are animal studies (generally involving rodents), case reports or collections of case reports, and/or studies involving crystalline silica. Extrapolations of animal studies to human beings are generally not considered reliable in the absence of a scientific explanation of why such extrapolation is warranted.
See Viterbo v. Dow Chemical Co.,
826 F.2d 420 (5th Cir.1987) (excluding the evidence where there was only a single animal study of picloram and it showed a link to a disease completely different than plaintiffs diseases);
Richardson v. Richardsort-Merrell, Inc.,
857 F.2d 823, 830 (D.C.Cir.1988) (excluding animal studies of Bendeetin because of the overwhelming body of contrary epidemiological evidence and the admissions of the expert that animal studies merely raise a suspicion of causation in humans);
Lynch v. Merrell-National Laboratories,
830 F.2d at 1194 (excluding animal studies of Bendeetin where they stood in the face of significant contrary epidemiological data);
Turpin v. Merrell Dow Pharmaceuticals, Inc.,
959 F.2d at 1360 (excluding testimony where the record failed to make clear how the animal studies were sufficient to show that Bendeetin causes birth defects more probably than not). Plaintiffs offer no explanation of why extrapolations from the rodent
*1411
studies their experts rely upon to humans are warranted here.
Similarly, case reports and case studies are universally regarded as an insufficient scientific basis for a conclusion regarding causation because case reports lack controls.
Casey v. Ohio Medical Products,
877 F.Supp. 1380 (N.D.Cal.1995);
Muzzey v. Kerr-McGee Chemical Corp.,
921 F.Supp. 511, 519-20 (N.D.Ill.1996);
In re Three Mile Island Litigation Cases Consolidated II,
911 F.Supp. 775, 795-96 (M.D.Penn.1996);
Grimes v. Hojfmann-LaRoche, Inc.,
907 F.Supp. S3, 35 n. 2 (D.N.H.1995). Therefore, these cannot be the basis of an opinion based on scientific knowledge under
Daubert.
Third, as will be discussed below, studies based on crystalline silica cannot support the testimony of plaintiffs’ experts because plaintiffs make no showing that silicone breast implants are associated with the presence of crystalline silica in women. In other words, the purported disease-causing agent in the silica studies has not been show to be scientifically relevant regarding the purported disease-causing agent — namely, silicone gel — in these cases.
Finally, Daubert’s establishment of the court as gatekeeper requires that proffered scientific expert opinions that make too great a leap of faith from the scientific knowledge currently available be excluded. As . discussed above, an evaluation of whether scientific methodology is valid for
Daubert
purposes should include an examination of how the proffered conclusions relate to the bases upon which the expert relies. The court’s neutral technical advisor has advised that Dr. Gershwin — and, by implication, Dr. Kemple, who relies on most if not all of the same studies as Dr. Gershwin — has made too great a leap from the underlying data to his conclusions. In other words, those conclusions are themselves not the result of the faithful application of valid scientific methodology. Therefore, defendants’ motions to exclude Dr. Gershwin’s and Dr. Kemple’s testimony on these issues is GRANTED.
D. Chemistry
Plaintiffs offer Dr. Christopher Batich as an expert in chemistry to testify that: (1) silicone migrates out of breast implant capsules; (2) there is an increase in surface area of silicone from gel breast implants to which the body reacts over time; (3) silicone changes in the body and forms bioreactive silanol groups on its surface; (4) silicone degrades into silica in the body; and (5) there is similar surface chemistry in all silox-ics (silicones, silicates, and silicas) that make the siloxics reactive in humans. In addition, plaintiffs offer Dr. Harold Alexander, a biom-aterials engineer, to testify that: (1) silicone microdroplets and/or particles are released from breast implants through gel bleed or rupture and have a high potential to cause inflammatory reactions in body tissues, and (2) the small size-’ of silicone microdroplets and/or particles allows them to migrate through the body via microphages and other migrating cells, and' their low molecular weight allows them to diffuse through tissue.
The court’s technical advisor for polymer chemistry, Dr. Ronald McClard, carefully reviewed the question of whether the scientific evidence supports Dr. Batich’s and Dr. Alexander’s proffered testimony that silicone degrades to silica
in mvo.
47
In reviewing the plaintiffs’ main scientific support for silica-induced biological reactions, a paper published by B. Razzaboni and P. Bolsaitis in
Environmental Health
Perspectives,
48
Dr. McClard stated that:
The Razzaboni article * * * clearly attempts to offer a biochemical explanation for the silica-caused hemolytic process. This article seems scientifically sound. If silicones are converted to silica then this article seems relevant to the issue at hand.
I am unaware that any of the papers that I reviewed clearly demonstrated the conversion of silicone to silica (most likely amorphous forms thereof),
though the process seems possible given the known chem
*1412
istry of silicon.
The link between silicones and the Razzaboni article is a prospective one.
Appendix E, at 11 (emphasis added). In other words, the opinions plaintiffs’ experts proffer regarding the
in vivo
degradation of silicone to silica are currently unsupported by the scientific literature. As with the immunological/toxieological conclusions discussed above, plaintiffs’ experts again make too great a leap of faith in their proffered testimony that silicone gel from breast implants degrades to silica. This is especially true for any testimony that silicone gel degrades
in vivo
to crystalline, as opposed to amorphous, silica. Therefore, I hereby GRANT defendants’ motions as pertains to such testimony.
In addition, because there is no scientifically valid evidence to support the conclusion that silicone gel degrades to silica in the human body, any other immunological or toxicological studies involving the inhalation, ingestion, or absorption of crystalline, silica cannot “fit” the issue of whether silicone breast implants can cause signs or symptoms of disease in women. Therefore, as discussed above, I must also exclude testimony based on this evidence under the “fit” prong of
Daubert I
and
Daubert II.
■ Dr. McClard also had several strong reservations about the other chemical studies upon which Dr. Batich and Dr. Alexander rely. Nevertheless, Dr. McClard consistently reported that these studies are supported by. valid scientific reasoning and methodology. Moreover, while plaintiffs’ experts’ opinions are, in his view, “controversial,” he concluded that those opinions are generally scientifically valid in that they properly may be derived from the chemical studies:
It’s a bit like two doctors looking at a chest X-ray (having both agreed that a chest X-ray was the correct diagnostic procedure to use) and disagreeing, sometimes heatedly, over the interpretation of a shadow on the film and perhaps how long the exposure should have been. I have no doubt that all of the chemical studies examined in these hearings are based on appropriate methods, whether or not there are serious questions about fine points of technique or far-reaching conclusions. Indeed some of the work is inadequately documented and of clearly debatable value, but that is really not for me to decide, to be sure.
Appendix E, at 12.
I find Dr. McClard’s exposition of the numerous methodological flaws in the other chemical studies troubling. Nevertheless, I need not decide whether this evidence is admissible on the basis of valid scientific methodology because the evidence now does not “fit” plaintiffs’ case, as
Daubert I,
509 U.S. at 594 , 113 S.Ct. at 2797 , and
Daubert II,
43 F.3d at 1315 , require. Testimony as to how silicone behaves chemically inside the human body cannot, in itself, establish that silicone gel breast implants cause signs and symptoms of disease in women in the absence of any epidemiological, rheumatological, or immunological/toxicological evidence linking those breast implants to disease. Thus, such testimony no longer logically advances a material aspect of the proponent party’s case.
Daubert II,
43 F.3d at 1315 . Therefore, I hereby GRANT defendants’ motions to exclude the testimony of Dr. Batich and Dr. Alexander.
E. Differential Diagnosis
Plaintiffs have offered Dr. Robert Bennett, M.D., both to testify that silicone gel breast implants can cause disease in women and to testify as a case-specific expert in
LeaAnn Hall v. Baxter
Healthcare.
49
Dr. Bennett is plaintiff Hall’s treating physician and is prepared to testify, on the basis of differential diagnosis, that plaintiff Hall suffers from systemic sclerosis sine scleroderma, manifested by her pulmonary fibrosis, as a result of having silicone gel breast implants.
As has been noted, the issue before me in this
Daubert
hearing is silicone gel’s ability to cause disease in women with breast implants. Courts, however, have recognized two levels of causation: general causation
*1413
(la, whether silicone gel can cause disease in anyone) and specific causation
(ie.,
whether silicone gel breast implants caused disease, in this plaintiff).
In Re: Silicone Gel Breast Implants Products Liability Litigation,
887 F.Supp. 1469 , 1477 (N.D.Ala.1995);
Jones v. United States,
933 F.Supp. 894, 900 (N.D.Cal.1990);
DeLuca v. Merrell Dow Pharmaceuticals, Inc.,
911 F.2d at 958;
Rutigliano v. Valley Business Forms,
929 F.Supp. 779, 783 (D.N.J.1996).
Differential diagnosis is a patient-specific process of elimination that medical practitioners use to identify the “most likely” cause of a set of signs and symptoms from a list of possible causes. However, differential diagnosis does not by itself
prove
the cause, even for the particular patient. Nor can the technique speak to the issue of general causation. Indeed, differential diagnosis
assumes
that general causation has been proven for the list of possible causes it eliminates:
The process of differential diagnosis is undoubtedly important to the question of “specific causation.” If other possible causes of an injury cannot be ruled out, or at least the possibility of their contribution to causation minimized, then the “more likely than not” threshold for proving causation may not be met.
But, it is also important to recognize that a fundamental assumption underlying this method is that the final, suspected “cause” remaining after this process of elimination must actually be capable of causing the injury.
That is, the expert must “rule in” the suspected cause as well as “rule out” other possible causes. And, of course, expert opinion on this issue of “general causation” must be derived from scientifically valid methodology.
Cavallo v. Star Enterprise,
892 F.Supp. 756, 771 (E.D.Va.1995) (emphasis added),
aff'd on this ground, rev’d on other grounds
—100 F.3d 1150 (4th Cir.1996).
Testimony regarding specific causation in a given patient is irrelevant unless general causation is established.
DeLuca,
911 F.2d at 958;
Jones,
933 F.Supp. at 900 ;
Rutigliano,
929 F.Supp. at 783 ;
Grimes,
907 F.Supp. at 38.
Hopkins v. Dow Corning Corp.,
33 F.3d 1116 (9th Cir.1994), does not require a different conclusion for differential diagnosis. First, nothing in
Hopkins
indicates that any witness used differential diagnosis to establish
any
level of causation, let alone both general and specific causation.
50
Second, even if the expert’s medical examination of the plaintiff in
Hopkins
were a differential diagnosis (and that is far from clear), it was not, as would be the case here, the
only
evidence of causation proffered. Although the court concluded “that Hopkins’ experts based their opinions on the types of scientific data and utilized the types of scientific techniques relied upon by medical experts' in making determinations regarding toxic causation where there is no solid body of epidemiological data to review,”
id.
at 1124 , this data was collective ánd included: toxicological experience; reviews of medical records; reviews of Dow’s studies; “general scientific knowledge of silicone’s ability to cause immune disorders as established by animal studies and biophysical data”; published scientific studies; personal research; “participation in a preliminary epidemiological study involving over 200 women”; animal studies; clinical experience; “preliminary results of an epidemiological study”; medical literature;
and
an examination of the plaintiff.
Id.
at 1125 . Most of- this information; as this
Daubert
hearing has demonstrated, would have been offered to establish general causation — that is, the issue of whether silicone gel breast implants can cause disease in anyone.
Finally, the
Hopkins
court, because of the timing of the case, was reviewing a pre-
Daubert
district court decision to admit the
*1414
expert testimony. As a result, the district court had reached that decision on a record not shaped by Daubert’s elucidation of the court’s gatekeeping function, nor did the Ninth Circuit delve into the methodology underlying the scientific data upon which Hopkins’ experts relied. Because I have done so and have excluded all proffered testimony regarding general causation, Dr. Bennett’s testimony now stands in isolation — an evi-dentiary predicament substantially different from that in
Hopkins .
Plaintiffs have consistently claimed that this court has jumped the gun in stating that plaintiffs cannot make out a prima facie case. Plaintiffs assert that they have more evidence to present at trial in the nature of differential diagnosis as well as pursuing their theory of “bioplausibility.” The fact of the matter is that plaintiffs cannot resort to these purported additional arrows in their legal quiver because neither differential diagnosis nor their bioplausibility theory can make out a prima facie case to prove specific causation of a systemic disorder or particular signs and symptoms absent proof of general causation. Moreover,, plaintiffs cannot use Dr. Bennett’s testimony, by itself, as part of their proof of general causation because a single differential diagnosis is a scientifically invalid methodology for such a purpose. Therefore, I must exclude Dr. Bennett’s testimony for all cases to the extent that plaintiffs proffer it to prove general causation.
Nor is Dr. Bennett’s testimony admissible to prove specific causation in LeaAnn Hall’s case, and for two reasons. General causation issues aside, an expert must rule out other potential causes of the patient’s condition in order for differential diagnosis testimony to be admissible.
Conde v. Velsicol Chemical Corp.,
24 F.3d 809, 814 (6th Cir.1994);
Paoli II,
35 F.3d at 759 . Here, Dr. Bennett has not testified as to how he eliminated other potential causes of Ms. Hall’s disease. Moreover, ■ his conclusion is inconsistent with the epidemiology for classical diseases. Therefore, his testimony is unreliable and exclusion of it is warranted on that basis.
See Conde v. Velsicol Chemical Corp.,
24 F.3d at 814 (upholding the district court in excluding doctors’ opinions purporting to link plaintiffs health problems to ehlordane exposure when they failed to exclude other potential causes for the symptoms and their theories were inconsistent with the scientific literature).
In addition, in the absence of proof of general causation, Dr. Bennett’s testimony regarding his differential diagnosis does not “fit” LeaAnn Hall’s case because there will be no evidence that silicone gel breast implants are a legitimate possible cause of Ms. HalTs disease.
51
Therefore, for all of the above reasons, I hereby GRANT defendants’ motions to exclude the testimony of Dr. Bennett.
V.
CONCLUSION
For the reasons stated above, those portions of defendants’ motions in limine (## 69, 70, 72, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, and 95 (filed in Group 2)) that seek exclusion of any expert testimony concerning a general causal link between silicone gel breast implants and ACTD or any systemic illness or syndrome are GRANTED. The remaining portions of the above-listed motions are MOOT, with leave to refile as necessary in further pretrial proceedings.
In light of these rulings, the court will sever plaintiffs’ local injury claims
52
from their claims for ACTD or any systemic illness or injury. The eases that do proceed to trial will do so on a much more restricted basis than Judges Weinstein and Baer may even contemplate in the New York litigation.
53
Specifically, I will exclude as irrelevant any testimony or evidence of the following: ACTD; any systemic illness or syndrome or autoimmune disorder of any kind; any emotional distress claims arising out of any alleged fear of developing any
*1415
systemic disease or injury or fear of cancer.
54
Finally, as stated earlier, I will defer the effective date of this decision pending the reports of the national Rule 706 panel, and likewise will defer plaintiffs’ motion to incorporate the panel members as witnesses. Nonetheless, I wish to make it abundantly clear that while I will evaluate the Rule 706 panel reports before finalizing my decision, I am unlikely to amend these findings and conclusions absent substantial and compelling developments in the scientific arena.
I am mindful that this opinion goes farther in evaluating and in eliminating plaintiffs’ claims than any other opinion in breast implant litigation pending in this country. However, litigation over the ability of silicone gel breast implants to cause disease in women has been chaotic in its results, in part because, as
Hopkins
demonstrates, the interjection of the
Daubert
standards into the screening process for proposed scientific evidence has substantially heightened the scrutiny through which such evidence must pass. In my opinion,
Daubert I
and
Daubert II
and their progeny command this disposition. Postscript: It should be noted, as a matter of
ease management in mass toxic tort litigation, that at the outset of proceedings after remand from the MDL, counsel for all sides presented an all-day “tutorial” to the court on the complex science involved in these cases. The tutorial demonstrated the need for and prompted the court to appoint the technical advisors. It should also be noted that Judge Sam Pointer appointed Dr. Richard Jones to serve with Professor Margaret Berger, Chair, on the national Rule 706 selection panel.
APPENDIX A
Jonathan M. Hoffman, OSB # 75418
MARTIN, BISCHOFF, TEMPLETON
LANGSLET & HOFFMAN
3100 First Interstate Tower
1300 SW Fifth Avenue
Portland, OR 97201-5667
Telephone: (503)’224-3113
Fax: (503)224-9471
Mary A. Wells
WELLS, ANDERSON & RACE LLC
1700 Broadway, Suite 1850
Denver, CO 80290
Telephone: (303) 830-1212
Fax: (303)830-0898
Kelly P. Corr
BOGLE & GATES
Two Union Square, 51st Floor
601 Union Street
Seattle, WA 98101
Telephone: (206)682-5151
Fax: (206) 621-2660
Of Attorneys for Defendants,
BAXTER. HEALTHCARE .CORPORATION and BAXTER INTERNATIONAL INC.
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF OREGON
LeaAnn DeGraw Hall, Plaintiff, v. Baxter Healthcare Corporation, et al., Defendants.
Case No. CV 92-182-JO-LEAD .
94-892-JO
94 — 903-JO
94-907-JO
PROPOSED QUESTIONS REGARDING . METHODOLOGY UTILIZED BY PLAINTIFFS’ EXPERT ORGANIC CHEMIST, CHRISTOPHER BATICH, Ph.D.
Defendants, Baxter Healthcare Corporation and Baxter International Inc., Bristol-Myers Squibb, and 3M, propose the following questions regarding the methodology utilized by plaintiffs’ expert organic chemist, Christopher Batich, M.D.:
*1416
QUESTION 1
Are Dr. Batich’s opinions that silicone degrades into silica in the human body supported by scientifically rehable methodologies?
QUESTION 2
Even if it is biologically plausible that silicone degrades in the human body, is that sufficient evidence to support scientifically a conclusion that silicone breast implants cause “atypical” connective tissue disease as described by Drs. Gershwin, Bennett, or Kem-ple?
QUESTION 3
Does the potential rate of error associated with the methodology employed by Dr. Ba-tich render unreliable his conclusion that silicone degrades to silicates or silica in the human body?
QUESTION 4
Is Dr. Batich qualified to opine that silicone degradation results in disease in implanted women?
QUESTION 5
Does the methodology employed by Dr. Batich support his conclusion that silicone degrades to silanol groups, converts to silica, and results in disease in implanted women?
QUESTION 6
Is any portion of Dr. Batich’s opinion that silicone gel degrades into silica which leads to disease in implanted women based on speculation, hypotheses, or assumptions?
QUESTION 7
Does the underlying methodology in the Garrido Nuclear Magnetic Resonance (NMR) spectroscopy studies, and the conclusions therein, relied upon by Dr. Batich, support his conclusion that silicone degrades to silicates or silica resulting in disease in implanted women?
QUESTION 8
What “fit” (or relevancy) do the Batich opinions have if the opinions of Drs. Gershwin, Bennett, and Kemple are not founded on accepted scientific methodology?
DATED this 16th day of August, 1996.
MARTIN, BISCHOFF, TEMPLETON, LANGSLET & HOFFMAN
By: /s/ Jonathan Hoffman
Jonathan Hoffman, OSB # 75418
WELLS, ANDERSON & RACE
By: /s/ Mary Wells
Mary Wells, Pro Hac Vice
Of Attorneys for Defendants,
BAXTER HEALTHCARE CORPORATION
and BAXTER INTERNATIONAL INC.
TOOZE, SHENKER, HOLLOWAY & DU-DEN
By: -
Paul Duden, OSB # 66035
Of Attorneys for Defendant, BRISTOL-MYERS SQUIBB
MILLER, NASH, WIENER, HAGER & CARLSEN, LLP
By: -
William Crow, OSB # 61018
Of Attorneys for Defendant,
MINNESOTA, MINING & MANUFACTURING COMPANY (3M)
Jonathan M. Hoffman, OSB # 75418
MARTIN, BISCHOFF, TEMPLETON
LANGSLET & HOFFMAN
3100 First Interstate Tower
1300 SW Fifth Avenue
Portland, OR 97201-5667
Telephone: (503)224-3113
Fax: (503)224-9471
Mary A. Wells
WELLS, ANDERSON & RACE LLC
1700 Broadway, Suite 1850
Denver, CO 80290
Telephone: (303) 830-1212
Fax: (303)830-0898
Kelly P. Corr
BOGLE & GATES
Two Union Square, 51st Floor
601 Union Street
Seattle, WA 98101
Telephone: (206) 682-5151
Fax: (206)621-2660
*1417
Of Attorneys for Defendants, BAXTER HEALTHCARE CORPORATION and BAXTER INTERNATIONAL INC.
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF OREGON
Leaann DeGraw Hall, Plaintiff, v. Baxter Healthcare Corporation, et al., Defendants.
Case No. CV 92-182-JO-LEAD
94-892-JO
94-903-JO
94-907-JO
PROPOSED QUESTIONS REGARDING METHODOLOGY UTILIZED BY PLAINTIFFS’ BIOMATERIALS EXPERT, HAROLD ALEXANDER, Ph.D.
Defendants, Baxter Healthcare Corporation and Baxter International Inc., Bristol-Myers Squibb, and 3M, state that plaintiffs have failed to satisfy their burden of proof concerning the admissibility of the testimony of Dr. Harold Alexander. Plaintiffs did not submit any briefing in opposition to defendants’ motion to exclude the testimony of this witness, nor did plaintiffs submit an affidavit from any expert supporting the methodology utilized by this witness in forming his opinions. Therefore, defendants request that this Court grant their motion
in limine
and exclude the testimony of Dr. Alexander.
To assist the Court in making its decision, defendants propose that the following questions be considered regarding the methodology utilized by Dr. Alexander.
QUESTION 1
Based upon his own research, as well as the generally accepted definition of biocom-patibility, is "it scientifically sound for Dr. Alexander to conclude that silicone as used in silicone breast implants is not bioeompatible?
QUESTION 2
Is the methodology utilized in Dr. Alexander’s research regarding silicones associated with an unreasonably high rate of error? QUESTION 3
Is Dr. Alexander’s research regarding sil-icones consistent with the published scientific literature on the biocompatibility of silicones? QUESTION 4
Based upon his research as well as the generally accepted bioeompatibility testing methodology standards, is it scientifically sound for Dr. Alexander to conclude that silicone has not been adequately tested for biocompatibility?
. DATED this 16th day of August, 1996.
MARTIN, BISCHOFF, TEMPLETON, LANGSLET & HOFFMAN
By: /s/ Jonathan Hoffman
Jonathan Hoffman, OSB # 75418
WELLS, ANDERSON & RACE
By: /s/ Mary Wells
Mary Wells, Pro Hac Vice
Of Attorneys for Defendants,
BAXTER HEALTHCARE CORPORATION
and BAXTER INTERNATIONAL INC. TOOZE, SHENKER, HOLLOWAY & DU-DEN
By: -
Paul Duden, OSB # 66035
Of Attorneys for Defendant,
BRISTOL-MYERS SQUIBB
MILLER, NASH, WIENER, HAGER & CARLSEN, LLP
By:-
William Crow, OSB # 61018
Of Attorneys for Defendant,
MINNESOTA, MINING & MANUFACTURING COMPANY (3M)
Jonathan M. Hoffman, OSB # 75418
MARTIN, BISCHOFF, TEMPLETON
LANGSLET & HOFFMAN
3100 First Interstate Tower
1300 SW Fifth Avenue
Portland, OR 97201-5667
*1418
Telephone: (50B) 224-3113
Fax: (503)224-9471
Mary A. Wells
WELLS, ANDERSON & RACE LLC
1700 Broadway, Suite 1850
Denver, CO 80290
Telephone: (303) 830-1212
Fax: (303)830-0898
Kelly P. Corr
BOGLE & GATES
Two Union Square, 51st Floor
601 Union Street
Seattle, WA 98101
Telephone: (206) 682-5151
Fax: (206)621-2660
Of Attorneys for Defendants,
BAXTER HEALTHCARE CORPORATION and BAXTER INTERNATIONAL INC.
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF OREGON
LeaAnn DeGraw Hall, Plaintiff, v. Baxter Healthcare Corporation, et al., Defendants.
Case No. CV 92-182-JO-LEAD
94-892-JO
94-903-JO
94-907-JO
PROPOSED QUESTIONS REGARDING METHODOLOGY UTILIZED BY PLAINTIFFS’ EXPERT PATHOLOGIST, NANCY HARDT, M.D.
Defendants, Baxter Healthcare Corporation and Baxter International Inc., Bristol-Myers Squibb, and 3M, state that plaintiffs have failed to satisfy their burden of proof concerning the admissibility of the testimony of Dr. Nancy Hardt. Plaintiffs did not submit any briefing in opposition to- defendants’ motion to exclude the testimony of this witness, nor did plaintiffs submit an affidavit from any expert supporting the methodology used by this witness in forming her opinions. Therefore, defendants request that this Court grant their motion
in limine
and exclude the testimony of Dr. Hardt.
To assist the Court in making its decision, defendants propose that the following questions be considered regarding the methodology utilized by Dr. Hardt:
QUESTION 1
Have plaintiffs established by the greater weight of the evidence that Dr. Nancy Hardt’s opinion, that silicone migrates through the breast capsule, is based on valid scientific methodologies?
QUESTION 2
Given that Dr. Nancy Hardt has not examined tissue slides from any portion of the anatomy of the four
Andrews
plaintiffs other than the breast capsule, is her opinion that silicone has migrated outside the breast capsule in these women based on accepted scientific or medical practices or methodologies? QUESTION 3
Is any portion of Dr. Hardt’s opinions as described in her witness statement based on speculation, hypotheses, or assumptions?
QUESTION 4
Is Dr. Hardt qualified to testify as to any alleged chemical interaction between silicone and protein?
DATED this 16th day of August, 1996.
MARTIN, BISCHOFF, TEMPLETON, LANGSLET & HOFFMAN
By: /s/ Jonathan Hoffman
Jonathan Hoffman, OSB # 75418
WELLS, ANDERSON & RACE
By: /s/ Mary Wells
Mary Wells, Pro Hac Vice
Of Attorneys for Defendants,
BAXTER HEALTHCARE CORPORATION
and BAXTER INTERNATIONAL INC.
TOOZE, SHENKER, HOLLOWAY & DU-DEN
By: -,-
/s/Paul Duden, OSB # 66035
Of Attorneys for Defendant, BRISTOL-MYERS SQUIBB
*1419
MILLER, NASH, WIENER, HAGER & CARLSEN, LLP
By: -
William Crow, OSB # 61018
Of Attorneys for Defendant,
MINNESOTA, MINING & MANUFACTURING COMPANY (3M)
Michael L. Williams, OSB # 78426
Gayle L. Troutwine, OSB # 83106
Kathleen M. Dailey, OSB # 88188
Kathryn A. Stebner, OSB # 93126
WILLIAMS & TROUTWINE, P.C.
1001 S.W. Fifth Avenue, Suite 1900
Portland, Oregon 97204
(503) 295-2924
Of Attorneys for Plaintiffs
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF OREGON
In re Breast Implant Litigation Pending in the United States District Court, District of Oregon (Group 1)
Case Nos.
Group 1: 92-182-JO LEAD
94-892-JO
94-903-JO
94-907-JO
PLAINTIFFS’ PROPOSED QUESTION REGARDING NMR TECHNOLOGY AND THE PUBLISHED PEER-REVIEWED STUDIES OF DR. GARRI-DO AND OTHERS
Plaintiffs propose the following question regarding nuclear magnetic resonance (NMR) technology:
QUESTION
Is nuclear magnetic resonance (NMR) technology, as used by Leoncio Garrido and his colleagues and other groups conducting research on silicone, a scientifically valid method to identify and monitor the presence of silicon compounds in tissue and blood and to detect changes in the chemical composition of silicone after it has been introduced into animals and humans when:
A. Results have been published in three different peer-reviewed journals on eight different occasions between 1991 and 1995, as follows:
1. Garrido, L., Mark, J.E., Sun, C.C., Ackerman, J.L., Chang, C.,
NMR Characterization of Elastomers Reinforced With In Situ Precipitated Silica,
24(14) Macromolecules, 4067-72 (1991).
2. Pfleiderer, B., Ackerman, J.L., Garrido, L.,
In Vivo1
H
Chemical Shift Imaging of Silicone Implants,
29(5) Magnetic Resonance in Medicine 656-6549 (1993).
3. Garrido, L., Pfleiderer, B., Papisov, M.; Ackerman, J.L.,
In Vivo Degradation of Silicones,
29(6) Magnetic Resonance op Medicine, 839-843 (1993).
4. Pfleiderer, B., Ackerman, J.L., Garri-do, L.,
In Vivo Localized Proton NMR Spectroscopy of Silicone,
30 Magnetic Resonance in Medicine 149-154 (1993).
5. Pfleiderer, B., Ackerman, J.L., Garri-do, L.,
Migration and Biodegradation of Free Silicone Gel-Filled Implants after Long-Term Implantation,
30 Magnetic Resonance in Medicine 534-543 (1993).
6. Garrido, L., Pfleiderer, B., Jenkins, B.G., Hulka, C.A., Kopans, D.B.,
Migration and Chemical Modification of Silicone in Women with Breast Prostheses,
31 Magnetic Resonance in Medicine 328-330 (1994).
7. Pfleiderer, B., Xu, P., Ackerman, J.L., Garrido, L.,
Study of Aging of Silicone Rubber Biomaterials with NMR,
29 JJBiomedical Materials' Research 1129-MO (1995).
8. Pfleiderer, B., Garrido, L.,
Migration and Accumulation of Silicone in the Liver of Women with Silicone Gelr-Filled Breast Implants,
33(1) Magnetic Resonance in Medicine 8-17 (1995).
B. Additional abstracts have been published or presented to colleagues at scientific conferences, as follows:
1. Garrido, L., Pfleiderer, B., Ackerman, J.L., Moore, J.,
Characterization of Biom-aterials with NMR,
Materials Research Society Symposium Proceedings, 217:49-54 (1991).
2. Pfleiderer, B., Moore, J., Ackerman, J.L., Garrido, L.,
Study of the Aging Pro
*1420
cess of PDMS Implants In Vivo and Ex Vivo by Nuclear Magnetic Resonance Spectroscopy and Imaging,
330 PolymeR PREPRINTS (published by the American Chemical Society) 767-768 (1992).
3. Garrido, L., Pfleiderer, B., Ackerman, J.L., Brady, T.J.,
Detection of Silicone Migration and Biodegradation with NMR,
Abstract Presented at the National Institutes of Health Immunology of Silicones Workshop, Bethesda, Maryland, Mar. 13-14,1995.
C. Data is the result of a collaborative effort of multiple scientists at the NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School;
D. Data is the result of numerous tests run on animal and human tissue and blood samples;
E. Other scientists in the field, including those who work for the Center for Devices and Radiological Health, FDA, use almost identical methods to identify silicone in tissue and blood;
1
,
2
F. Local NMR specialist, Dr. David Pey-ton, from Portland State University agrees that Dr. Garrido is most likely seeing a real silicone signal, even in the one study that is being questioned by Dr. Peter Macdonald.
3
G. Only one paper exists that criticizes a single conclusion made by Dr. Garrido’s group when they used a single NMR technique
4
to identify silicone levels in the blood but which does not address any other conclusions made, the appropriateness of NMR techniques to identify molecule structure in general
5
or other NMR techniques used by Dr. Garrido in identifying or analyzing silicone in any other circumstance;
6
and has
*1421
only used one set of samples in attempting to confirm the work of Dr. Garrido and his colleagues;
H. Even the study which allegedly brings Dr. Garrido’s methodology into question confirms Dr. Garrido’s ultimate conclusions.
7
DATED this 13th day of July, 1996.
Respectfully Submitted,
WILLIAMS & TROUTWINE, P.C.
/s/ [Signature]
Michael L. Williams, OSB # 78426
Gayle L. Troutwine, OSB # 83106
Kathleen M. Dailey, OSB # 88188
Kathryn A. Stebner OSB # 93126
Of Attorneys for Plaintiffs
Mike L. Williams, OSB # 78426
Gayle L. Troutwine, OSB # 83106
Kathleen M. Dailey, OSB # 88188
Kathryn A. Stebner, OSB # 93126
WILLIAMS & TROUTWINE, P.C.
1001 SW 6th Avenue, Suite 1900
Portland, OR 97204
Telephone: (503) 295-2924
Of Attorneys for Plaintiffs
Pursuant to L.R. 120-l(e), a complete list of all counsel submitting this document for filing appear on the signature page to this motion.
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF OREGON
In re Breast Implant Litigation Pending in the United States District Court, District of Oregon (Group 1)
Case Nos.
Group 1: 92-182-JO-LEAD;
94-892-JO
94-903-JO;
94-907-JO
PLAINTIFFS’ PROPOSED QUESTIONS REGARDING CHEMISTRY AND PLAINTIFFS’ EXPERT CHEMIST
Plaintiffs propose the following questions regarding chemistry and expert chemist, Christopher D. Batich, Ph.D.
QUESTION 1
Have plaintiffs established by the greater weight of evidence that Dr. Batich used a scientific methodology to arrive at his conclusion that silicone liquid, in the form of micro-droplets, as well as isolated small molecules, diffuse through the thin silicone elastomer and migrate throughout the body, by using the following methodology?
A. Reviewing the medical literature that demonstrates silicone fluids injected into animals are picked up by macrophages and migrate throughout the body? (Ex. C, # 1, 2, 3)
B. By reviewing the medical literature on migration of silicone in women:
*1422
(1) Dr. Nancy Hardt’s studies; (Ex. A # 100,162,163)
(2) Dr. Garrido’s studies on migration in animals; Ex. C, # 4, 5, 6, 7, 8)
(3) Dr. Garrido’s studies on migration in women; (Ex. A, # 3, 6)
(4) The FDA abstract confirming migration of silicone to the liver of women using NMR techniques; (Ex. A, #80)
(5) Published studies showing elevated levels of silicon in tissue and blood of implanted women. (Ex. A, # 97, 98, 166,167; Ex. C, # 9)
C. By reviewing internal Dow Corning reports showing migration of silicone in animals to distant parts of the body; (Ex. C, # 10; Ex. B, Le78.DC, La68, K087, Cu85, Re67, Tr88)
D. By conducting his own studies showing that silicone leaves the implant and migrates to the brains of animals; (Ex. C, # 11)
E. By reviewing the literature indicating that the 80% liquid constituting the bulk of the silicone gel materials inside an implant steadily depolymer-izes, forming new low molecular weight silicone chains as the earlier formed ones bleed out and diffuse into the body; (Ex. C, # 13; Ex. B, MC87-DC)
F. By conducting his own peer-reviewed, published gel bleed study? (Ex. C, #12)
QUESTION 2
Have plaintiffs established by the greater weight, of the evidence that Dr. Batich used scientific methodology to arrive at his conclusion that silicone is chemically changed in the body in ways that would make it more biologically active?
A. By reviewing internal Dow Corning studies on metabolism of silicone compounds in animals? (Ex. C, # 14, 15)
B. By reviewing published reports in the scientific literature, and sworn expert testimony of Dow Corning chemists, on the degradation of silicones into silica in the environment? (Ex. C, #16, 17; Ex. B, An94-Dc; Ex. B, Vo82, Ge82 & Ma83)
C. By reviewing published reports in the scientific literature showing that silicone physical properties decline over time when exposed to the body’s environment? (Ex. A, # 18; Ex. C, # 22, 23)
D. By reviewing internal Dow Coming studies showing that in people who accidentally inhaled vapors of silicone, the methyl groups were chemically removed before the material was excreted in urine? ■ (Ex. B, An80-Dc)
E. By conducting his own experiment with his masters student, Mr. DePal-ma, using contact angle measurements to estimate the rate of change to a hydrophilic surface, (i.e., rate of formation of silanol groups on silicone surfaces in the body), and by reviewing the Dow Coming (Kennan) study which confirmed thé DePalma data? (Ex. C, # 20,21)
F. By reviewing studies which show that the toxic effects of both crystalline and amorphous silica derive from the surface chemistry of silanol group formation on particles inside cells, indicating that there is no qualitative difference, only a quantitative difference, between the cellular toxicity of amorphous and crystalline silica? (Ex. A, # 30, 40, 45, 115,112; Ex. B, Zh87a, Le78de, Ra90)
G. By conducting his own research to conclude that the surface area of silicone mierodroplets exposed to the body’s chemical machinery greatly increases over time? (Ex. A, # 45)
H. By reviewing published, peer reviewed studies demonstrating silicone degradation in animals? (Ex. B FE70, FE67; Ex. C, 19)
I. By reviewing published, peer-reviewed articles containing evidence of silicone degradation in
in vitro
experiments, animals and humans? (Ex. A #43, 169; Ex. B Ga93a, COc76, SP80-dc)
*1423
Respectfully submitted, this 13th day of August, 1996.
WILLIAMS & TROUTWINE, P.C.
By /s/ [Signature]
Michael L. Williams OSB # 78426
Gayle L. Troutwine, OSB # 83106
Kathleen M. Dailey, OSB # 88188
Kathryn A. Stebner, OSB # 93126
Of Attorneys for Plaintiffs
EXHIBIT A
1. Smalley, D.L.;, D.R.; Hall, M.F.; Stevens, M.V.; Hanissian, A.; “Immunologic Stimulation of T Lymphocytes by Silica After Use of Silicone Mammary Implants”,
The FASEB Journal,
9:424-427 (March 1995).
2. Ciapetti, G.; Granchi, D.; Stea, S.; Cenni, E.; Schiavon, P.; Giuliane, R.; Pizzoferrato, A.; “Assessment of Viability and Proliferation of In Vivo Silicone-Primed Lymphocytes after In Vitro Re-Exposure to Silicone”,
Journal of Biomedical Materials Research,
29:583-590 (1995).
3. Ojo-Amaize, E.A; Conte, V.; Bin, HC; Brueker, R.F.; Agopian, M.S.; Peter, J.B.; “Silicone-Specific Blood Lymphocyte Response in Women with Silicone Breast Implants”,
Clinical and Diagnostic Laboratory Immunology,
l(6):689-695 (November 1994).
4. Narini, P.P.; Semple, J.L.; Hay, J.B.; “Repeated Exposure to Silicone Gel Can Induce Delayed Hypersensitivity”,
Plastic and Reconstructive Surgery,
96(2):371-380 (August 1995).
5. Wolf, L.E.; Lappe, M.; Peterson, E.D.; Ezrailson, E.G.; “Human Immune Response to Polydimethylsilox-ane (Silicone): Screening Studies in a Breast Implant Population”,
The FA-SEB Journal,
7:1265-1268 (October 1993).
6. Heggers, J.; Kossovsky, N.; Parsons, R.W.; Robson, M.C.; Martin, E.; Pel-ley, R.P.; Raine, T.J.; “Biocompatibility of Silicone Implants”,
Annals of Plastic Surgery,
2(l):38-45 (July 1983).
Kossovsky, N.; Heggers, J.P.; Parsons, R.W.; Robson, M.C.; “Analysis of the Surface Morphology of Recovered Silicone Mammary Prostheses and Discussion by Anderson, J.M.”,
Plastic and Reconstructive Surgery,
71(6):795-804 (June 1983). 7.
8. Kossovsky, N.; Heggers, J.P.; Robson, M.C., “Experimental Demonstration of the Immunogenicity of Silicone-Protein Complexes”,
Journal of Biomedical Materials
'
Research,
21:1125-1133 (1987).
9. Kossovsky, N.; Heggers, J.P.; Robson, M.C.; The Bioreaetivity of Sil- ■ icone”,
CRC Critical Review of Bior-eactivity,
3(l):53-85 (1987).
10. Kossovsky, N.; Freiman, C.J.; Stassi, J.B.; Mena, E.; “Cytokine Expression in Response to Biomaterials”,
Immu-nomethods,
343 — 49 (1993).
11. Kossovksy, N.; “Death of the NonSpecific Foreign Body Reaction”,
Trends in Polymer Science,
1(7):190-191 (1993).
12. Kossovsky, N.; Freiman, C.J.; “Silicone Breast Implant Pathology”,
Archives of Pathology and Laboratory Medicine,
118:686-693 (July 1994).
13. Kossovsky, N.; Gelman, A., Hnatysz-yn, H.J.; Rajguru, S.; Mena, E.A., Crowder, J.; Torres, M.; Zemanovich, G.; “Abstract — Adjuvant Effect of Silicone on the Formation of Anti-Insulin and Anti-Fibronectin Antibodies”,
Presentation at the American College of Rheumatology Meeting,
No. 668 (1994).
14. Kossovsky, N.; Freiman, C.J.; “Review-Physicochemical and Immunological Basis of Silicone Pathophysiology”,
Journal of Biomaterials Science ^Polymer Edition,
7(2):101-113 (1995).
]g Kossovsky, N.; Heggers, J.P.; Parson, R.W.; Robson, M.C.; “Acceleration of Capsule Formation Around Silicone Implants in a Guinea Pig Model with Discussion by Anderson, J.M.”,
Plastic and Reconstructive Surgery,
73(1):91-96 (January 1984).
*1424
16. Kossovsky, N.; Zeidler, M.; Chun, G.; Nguyen, A.; Rajguru, S.; Stassl, J.; Gehnan, A.; Sponsler, E.; “Surface Dependent Antigens Identified by High Binding Avidity of Serum Antibodies in a Subpopulation of Patients with Breast Prostheses”,
Journal of Applied Biomaterials,
4:281-288 (1993).
17. McDonald, A.H.; Medical College of Wisconsin; Weir, K; Sanger, J.R.; “Silicone-Induced T Cell Proliferation in Mice”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 189-198,1996.
18. Potter, M.; Morrison, S.; Wiener, F.; Zhang, S.K.; Miller, F.W.; “Induction of Plasmacytomas with Silicone Gel in Genetically Susceptible Strains of ■. Mice”,
Journal of the National Cancer Institute,
86(14):1058-1065 (July 1994).
19. Claman, H.; Robertson, A.D.; “Antinuclear Antibodies and Breast Implants”,
Western Journal of Medicine,
160:225-228 (1994).
20. Bar-Meir, E.; Teuber, S.S.; Line, H.C.; Alosacie, L.I.; Goddard, G.; Terybery, J.; Barka, N.; Shen, B.; Peter, J.B.; Blank, M.; Gershwin, M.E.; Shoenfeld, Y.; “Multiple Au-toantibodies in Patients with Silicone Breast Implants”,
Journal of Autoimmunity,
8:267-277 (1995).
21. Teuber, S.S.; Yoshida, S.H.; Gershwin, M.E.; “Immunopathologic Effects of Silicone Breast Implants”,
Western Journal of Medicine,
162(5):418-425 (May 1995).
22. Rowley, M.J.; Cook, A.D.; Teuber, . S.S.; Gershwin, M.E.; “Antibodies to Collagen: Comparison Epitope Mapping in Women with Silicone Breast Implants, Systemic Lupus Erythema-tosus and Rheumatoid Arthritis”,
Journal of Autoimmunity,
7:775-789 (1994).
23. Yoshida, S.H.; Teuber, S.S.; German, J.B.; Gershwin, M.E.; “Immunotoxici- . ty of Silicone: Implications of Oxidant Balance Towards Adjuvant Activity,
Fd.Chem.Tox.,
32(11):1089-1100 (1994).
24. Yoshida, S.H.; Chang, C.C.; Teuber, S.S.; Gershwin, M.E.; “Silicon and Silicone: Theoretical and Clinical Implications of Breast Implants”,
Regulatory Toxicology and Pharmacology,
17(1):3-18 (February 1993).
25. Yoshida, S.; Gershwin, M.E.; “Autoimmunity and Selected Environmental Factors of Disease Induction”,
Seminars in Arthritis and Rheumatism,
22(6):339-419 (June 1993).
26. Yoshida, S.H.; Swan, S.; Teuber, S.; Gershwin, M.E.; “Silicone Breast Implants: Immunotoxic and Epidemiologic Issues”,
Life Sciences,
56(16):1299-1310 (1995).
27. Dobke, M.K.; Svahn, J.K.; Vastine, V.L.; Landon, B.N.; Stein, P.C.; Parsons, C.L.; “Characterization of Microbial Presence at the Surface of Silicone Mammary Implants”,
Annals of Plastic Surgery,
34(6):563-571 (June 1995).
28. Su, C.W.; Dreyfuss, D.A.; Krizek, T.J.; Leoni, K.J.; “Silicone Implants and the Inhibition of Cancer with Discussion by Brody, G.S.”,
Plastic and Reconstructive Surgery,
96(3):513-520 (September 1995).
29. BLANK
30. Shanklin, D.R.; Smalley, D.L.; “Quantitative Aspects of Cellular Responses to Silicone”,
International Journal of Occupational Medicine and Toxicology,
4(1):99 — 111 (1995).
31. Robinson, G.O.; Bradley, E.L.; Wilson, D.S.; “Analysis of Explanted Silicone Implants: A Report of 300 Patients”,
Annals of Plastic Surgery,
34(l):l-6 (January 1995).
32. deCamara, D.L.; Sheridan, J.M.; Kammer, B.A.; “Rupture and Aging of Silicone Gel Breast Implants”,
Plastic and Reconstructive Surgery,
21(5):828-834 (April 1993).
33. Vojdani, A.; Brautbar, N.; Campbell, A.; “Immunologic and Biologic Markers for Silicone”,
Journal of Toxicolo
*1425
gy and Industrial Health,
10(Jé):25-42 (1994).
34. Hess, E.V.; “Editorial — Environmental Lupus Syndromes”,
British Journal of Rheumatology,
34(7):597-599 (1995).
35. Goldblum, R.M.; Pelley, R.P.; O’Donnell, A.A.; Pyron, D.; Heggers, J.P.; “Antibodies to Silicone Elastomers and Reactions to Ventriculoperitoneal Shunts”,
The Lancet,
340:510-513 (1992).
36. Pfleiderer, B.; Garrido, L.; “Migration and Accumulation of Silicone in the Liver of Women with Silicone Gel-Filled Breast Implants”,
Magnetic Resonance in Medicine,
33:8-17 (1995).
37. Garrido, L.; Pfleiderer, B.; Papisov, M.; Ackerman, J.L.; “In Vivo Degradation of Silicones”,
Magnetic Resonance in Medicine,
29(6):839-843 (June 1993).
38. Pfleiderer, B.; Ackerman, J.L.; Garri-do, L.; “Migration and Biodegradation of Free Silicone Gel-Filled Implants after Long-Term Implantation”,
Magnetic Resonance in Medicine,
30:534-543 (1993).
39. Garrido, L.; Pfleiderer, B.; Jenkins, B.G.; Hulka, C.A; Kopans, D.B.; “Migration and Chemical Modification of Silicone in Women with Breast Protheses”,
Magnetic Resonance in Medicine,
31:328-33- (1994).
40. Picha, G.J.; Goldstein, J.A; “Analysis of the Soft-Tissue Response to Components used in the Manufacture of Breast Implants: Rat Animal Model”,
Plastic and Reconstructive Surgery,
87(3):490-500 (March 1991).
41. Claman, H.N.; Robertson, AD.; “Antinuclear Antibodies in Apparently Healthy Women with Breast Implants”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs 265-268 (1996).
42. Hill, S.L.; Landaver,. G.; Rose, N.R.; “The Adjuvant Effect of Silicone Gel and Silicone Elastomer Particles in Rats”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 123-137 (1996).
43. Garrido, L.; Bogdanova, A.; Cheng, L.L.; Pfleiderer, B.; Todareva, E.; Ackerman, J.L.; Brady, T.J.; “Detection of Silicone Migration and Biode-gradation with NMR”,
Current Topics in Microbiology and
Immunology—
Immunology of Silicones,
Potter, M. and Rose, N.; Editors, Springer-Ver-lag, Heidelberg, pgs. 49-58 (1996).
44. Meyers, C.A.; Seheibel, R.S.; Forman, A.D.; “Persistent Neurotoxicity of Systemically Administered Interferon-Alpha”,
Neurology,
41:672-676 (1991).
45. Batich, C.; Depalma, D.; Marotta, J.; Latorre, G.; Hardt, N.S.; “Silicone Degradation Reactions”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, Springer-Verlag, Heidelberg, pgs. 13-23 (1996).
46. Airing, C.R.; Wassef, N.M.; Potter, M.; “Antibodies to Cholesterol: Biological Implications of Antibodies to Lipids”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 181-186 (1996).
47. Felix, K.; Janz, S.; Pitha, J.; Williams,' J.A; Mushinski, E.B.; Bornkamm, G.W.; Potter, M.; “Cyto-toxicity and Membrane Damage In Vi-tro by Inclusion Complexes Between Gamma-Cyelodextrin and Siloxanes”,
Current Topics in Microbiology and Immunology-Immunology of Sil-icones,
Potter, M.; and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 93-99,1996. ,
48. Raso, D.S.; Green, W.B.; Vesely, J.J.; Willingham, M.C.; “Light Microscopy Techniques for the Demonstration of Silicone Gel”,
Archives of Pathology &
*1426
Laboratory Medicine,
118:984-987 (1994). :
49. .Langer, A.M.; Nolan, R.P.; “Physioco-chemieal Properties of Quartz Controlling Biological Activity”,
Silica, Silicosis, and Cancer
— Surface
Properties,
pgs. 125-135.
50. Nicholson, J.J.; Wong, G.E.; Frondo-za, C.G.; Rose, N.R.; “Silicone Gel and Octmethylcyclotetrasiloxane Po-tentiate Antibody Production to Bovine Serum Albumin in Mice”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 139-144,1996.
51. ' Pavol, M.A.; Meyers, C.A.; Rexer, J.L.; Valentine, A.D.; Mattis, P.J.; Talpaz, M.; “Pattern of Neurobeha-vioral Deficits Associated with Interferon Alfa Therapy for Leukemia”, '
Neurology,
45:947-950. (May 1995).
52. Naim, J.O.; Ippolito, K.M.L.; Lanza-fame, R.J.; van Oss, C.J.; “Induction of Type II Collagen Arthritis in the DA Rat Using Silicone Gel as Adju-vant”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, Nó. 210, Springer-Verlag, Heidelberg, pgs. 106-111,1996.
53. Wall, W.; Martin, L.; Fritzler, M.J.; Edworthy, S.; “Letter — Non-fasting Chylomicronaemia in Breast Implant Patients”,
The Lancet,
345:1380 (May 27,1995).
54.. Harbut, M.; “Speaker Abstract — An Occupational Medicine Approach to the SBI Patient”,
Presentation at Conference Sponsored by The Institute for Occupational & Environmental Medicine,
Cobo Hall, Detroit MI (September 28,1995).
55. Boley, W.F.; LeVier, R.; “Immunological Enhancing Activities of Organosili-con Compounds and Nonfunctional Fluids”,
Dow Coming Internal Study,
(October 1974).
56. Lake, R.S.; Radonovich, M.F.; “Action of Polydimethylsiloxanes on the Reti-culoendothelial System of Mice: Basic Cellular Interactions and Structure-Activity Relationships”,
Dow Coming Internal Study,
(October 30,1975).
57. Haustein, U.F.; Ziegler, V; “Environmentally Induced Systemic Sclerosis-Like Disorders”,
International Journal of Dermatology,
24(3):147-151 (April 1985).
58. Haustein, U.F.; Ziegler, V.; Hermann, K.; Mehlhorn, J.; Schmidt, C.; “Silica-Induced Scleroderma”,
Journal of the American Academy of Dermatology,
22(3):444-448 (March 1990).
59. Koeger, A-C; Marre, ' J-P; Rozenberg, S.; Gutmann, L.; Bourgeois, P.; “Maladies Auto-Immunes Apres' Expositions Inhabituelles a’ la Sílice ou aux Silicones”,
Ann.Med.In-teme.,
143(3):165-170 (1992).
60. Burrell, R.; “Immunological Aspects of Silica”,
Health Effects of Synthetic Silica Particulates,
pages 82-93. Symposium sponsored by ASTM Committee E-34 on Occupational Health and Safety and the Industrial Health Foundation, Spain, Nov. 5-6,1979.
61. Naim, J.O.; Lanzafame, R.J.; van Oss, C.J.; “The Adjuvant Effect of Silicone-Gel on Antibody Formation in Rats”,
Immunological Investigations,
22(2):151 — 161 (1993).
62. Naim, J.O.; Ippolito, K.M.L.; Lanza-fame, R.J.; van Oss, C.J.; “The Effect of Molecular Weight and Gel Preparation on Humoral Adjuvancy of Silicone Oils and Silicone Gels”,
Immunological Investigations,
24(3):537-547 (1995).
63. Naim, J.O.; Lanzafame, R.J.; van Oss, C.J.; “The Effect of Silicone-Gel on the Immune Response”,
Journal of Biomaterial Science Polymer Edition,
7(2):123-132 (1995).
64. Ojo-Amaize, E.A.; Lawless, O.J.; Peter, J.B.; “Abstract — Elevated Plasma concentrations of Interleukin — 1 Beta and Interleukin — 1 Receptor Antagonist in Women with Silicone Breast Implants” (1995).
*1427
65. Sun, L.; Alexander, H.; Lattarulo, N.; Blumenthal, N.; Wu, J.; Rieei, J.; Chen, G.; “Conformational Change and Denaturation of Proteins by Cyclic Silicone”, Abstract submitted to the Fifth World Biomaterials Congress, May 29-June 2,1996, Toronto.
66. Rosenstreich, D.L.; Farrar, J.J.; Dougherty, S.; “Absolute Macrophage Dependency of T Lymphocyte Activation by Mitogens”,
Journal of Immunology,
116:131-139 (1976).
67. Hedfors, E.; Holm, G.; Pettersson, D.; “Activation of Human Peripheral Blood Lymphocytes by Concanavalin A Dependence of Monocytes”,
Clinical Experimental Immunology,
22:223-229 (1975).
68. Bradley, S.G.; White, K.L. Jr.; McCay, J.A.; Brown, R.D.; Mus-grove, D.L.; Wilson, S.; Stern, M.; Luster, M.I.; Munson, A.E.; “Immu-notoxicity of 180 Day Exposure to Po-lydimethylsiloxane (Silicone) Fluid, Gel and Elastomer and Polyurethane Disks in Female B6C3F1 Mice”,
Drug and Chemical Toxicology,
17(3):221-269 (1994).
69. Campbell, A.; Brautbar, N.; Vojdani, A.; “Suppressed Natural Killer Cell . Activity in Patients with Silicone Breast Implants: Reversal Upon Explanation”,
Toxicology and Industrial Health,
10(3):149-154 (1994).
70. Kyle, R.A.; “Benign’ Monoclonal Gam-mopathy — After 20 to 35 Years of Follow-Up”
Mayo Clinic Proceedings,
68:26-36 (1993).
71. Diamond, D.J.; Szalay, P.; Symer, D.; Hao, P.; Shin, H.S.; Dintzis, H.M.; Reinherz, E.L.; Siliciano, R.F.; “Major Histocompatibility Complex Independent T Cell Receptor-Antigen Interaction: Functional Analysis Using Fluorescein Derivatives”,
Journal of Experimental Medicine,
174:229-241 (July 1991).
72. Ganju, R.K.; Smiley, S.T.; Bajorath, J.; Novotny, J.; Reinherz, E.L.; “Similarity Between Fluorescein-Specific T-Cell Receptor and Antibody in Chemical Details of Antigen Recognition”,
Proceeding of the National Academy of Sciences, USA,
89:11552-11556 (December 1992).
73. Bommer, J.; Ritz, E.; Waldherr, R.; Gastner, M.; “Letter — Silicone Cell Inclusions Causing Multi-Organ Foreign Body Reaction in Dialysed Patients”,
The Lancet,
p. 1314 (June 13, 1981).
74. Leong, AS.-Y.; Disney, A.P.S.; Gove, D.W.; “Letter — Retractile Particles in Liver of Haemodialysis Patients”
The Lancet,
p. 889-890 (April 18, 1981).
75. Kenik, J.; Radiographs of silicone sy-novitis in R first metatarsophalangeal joint 4 years after silastic arthroplasty, submitted as a clinical image to
Arthritis and Rheumatism,
October 1995.
Granchi, D.; Cavedagna, D.; Ciapetti, G.; Stea, S.; Schiavon, P.; Giulani, R.; Pizzoferrato, A.; “Silicone Breast Implants: The Role of Immune System on Capsular Contracture Formation”,
Journal of Biomedical Materials Research,
29:197-202 (1995).
77’ Goldsmith, J.R.; Goldsmith, D.F.; “Fiberglass or Silica Exposure and Increased Nephritis or ESRD (End-Stage Renal Disease),
American Journal of Industrial Medicine,
23873-881 (1993).
Steenland, K.; Brown, D.; “Mortality Study of Gold Miners Exposed to Silica and Nonasbestiform Amphibole Minerals: An Update with 14 More Years of Follow-up”,
American Journal of Industrial Medicine,
27:217-229 (1995).
79. Ueki, A; Yamaguehi, M.; Ueki, H.; Watanabe, Y.; Ohsawa, G.; Kinugawa, K.; Kawakami, Y.; Hyodoh, F.; “Poly-clonal Human T-Cell Activation by Silicate In Vitro”,
Immunology,
82:332-335 (1994).
gQ_ Rajan, S.S.; Clauw, D.J.; Grossman, L.W.; Myers, K.J.; Patt, R.H.; “Breath-Hold MRS for the Detection of Silicone Migration to the Liver”, Abstract presented at Proceedings of
*1428
the Society of Magnetic Resonance and the European Society for Magnetic Resonance in Medicine and Biology. August 19-25,1995, Nice, France.
81. Yoshino, S.; “Silicone-Induced Arthritis in Rats and Possible Role for T Cells”,
Immunobiology,
192:40-47 (1994).
82. Duvic, M.; Moore, D.; Menter, A; Vonderheid, E.C.; “Cutaneous T-Cell Lymphoma in Association with Silicone Breast Implants”,
Journal of the American Academy of Dermatology,
32(6)939:942 (June 1995).
83. Young, V.L.; Nemecek, J.R.; Schwartz, B.D.; Phelan, D.L.; Schorr, M.W.; “HLA Typing in Women with Breast Implants”,
Plastic and Reconstructive Surgery,
96(7):1497-1520 (December 1995).
84. Cuellar, M.L.; Gluck, 0.; Molina, J.F.; Gutierrez, S.; Garcia, C.; Espinoza, R.; Silicone Breast Implant-Associated Musculoskeletal Manifestations”,
Clinical Rheumatology,
14(6):667-672 (1995).
85. Leong, A. S-Y; Gove, D.W.; “Pathological Findings in Silicone Spallation In Vitro Studies”,
Pathology,
15:189-192 (1983).
86. Thomsen, J.L.; Christensen, L.; Nielsen, M.; Brandt, B.; Breiting, V.B.; Felby, S.; Nielsen, E.; “Histologic Changes and Silicone Concentrations in Human Breast Tissue Surrounding Silicone Breast Prostheses”,
Plastic and Reconstructive Surgery,
85(1):38-41 (January 1990).
87. Sluis-Cremer, G.K.; Hessel, P.A.; Nizdo, E.H.; Churchill, A.R.; Zeiss, E.A.; “Silica, Silicosis, and Progressive Systemic Sclerosis”,
British Journal of Industrial Medicine,
42:838-843 (1985).
88. Winding, 0.; Christensen, L.; Thom-sen, J.L.; Nielsen, M.; Breiting, V.; Brandt, B.; “Silicon in Human Breast Tissue Surrounding Silicone Gel Prostheses”,
Scandinavian Journal of Plastic and Reconstructive Surgery,
22:127-130 (1988).
89. Gedalia, A.; Cuellar, M.L.; Espinoza, L.R.; “Skin Rash and Anti-Ro/SS-A Antibodies in an Infant From A Mother With Silicone. Breast Implants”,
Clinical and Experimental Rheuma-tology,
13:521-523 (1995).
90. Klockars, M.; Koskela, R-S.; Jarvi-nen, E.; Kolari, P.J.; Rossi, A.; “Silica Exposure and Rheumatoid Arthritis: A Follow Up Study of Granite Workers 1940-81”,
British Medical Journal,
294:997-1000 (April 18,1987).
01 Koeger, A-C; Lang, T.; Alcaix, D.; Milleron, B.; Rozenberg, S.; Chaibi, P.; Arnaud, J.; Mayaud, C.; Camus, J-P; Bourgeois, P.; “Connective Tissue Disease Associated with Silicone Alveolitis Due to Silicone Spray. A Prospective Series”,
Abstract presented at the American College of Rheu-matology Annual Meeting,
October 1995, San Francisco, ACR Supplement, 8(9), Abstract No. 1136.
Wilson, S.D.; Munson, A.E.; “Silicone-Induced Modulation of Natural Killer Cell Activity”,
Current Topics in Microbiology and Immunology
— Im
munology of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 199-208 (1996).
93. Silverman, S.; Vescio, R.; Silver, D.; Renner, S.; Weiner, S.; Berenson, J.; “Silicone Gel Implants and Monoclonal Gammopathies: Three Cases of Multiple Myeloma and the Prevalence of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 367-374 (1996).
„, Garland, L.L.; Ballester, O.F.; Vasey, F.B.; Benson, K.; Moscinski, L.C.; Farmelo, M.J.; Rodriguez, M.J.; Ra-paport, D.P.; “Multiple Myeloma in Women with Silicone Breast Implants. Serum Immunoglobulin and Interleukin-6 Studies in Women at Risk”,
Cur
*1429
rent Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, Springer-Verlag, Heidelberg, pgs. 361-366 (1996).
96.Rabkin, C.S.; Silverman, S.; Tricot, T.; Garland, L.L.; Ballester, 0.; Potter, M.; “The National Cancer Institute Silicone Implant/Multiple Mye-loma Registry”,
Current Topics in Microbiology and Immunology
— Im
munology of Silicones,
Potter, M. and Rose, N.; Editors, Springer-Ver-lag, Heidelberg, pgs. 385-387 (1996).
96. Potter M.; Morrison, S.; “Plasmacyto-ma Development in Mice Injected with Silicone Gels”,
Current Topics in Microbiology and Immunology
— Immu
nology of Silicones,
Potter, M. and Rose, N.; Editors, Springer-Verlag, Heidelberg, pgs. 397-407 (1996).
97. Peters, W.; Smith, D.; Lugowski, S.; McHugh, A.; Baines, C.; “Do Patients with Silicone-Gel Breast Implants Have Elevated Levels of Blood Silicon Compared with Control Patients?”,
Annals of Plastic Surgery,
34(4):343-347 (April 1995).
98. Peters, W.; Smith, D.; Lugowski, S.; McHugh, A.; MacDonald, P.; Baines, C.; “Silicon and Silicone levels in Patients with Silicone Implants”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 39-48 (1996).
99. O’Hanlon, T.P.; Ikada, S.; Love, L.A.; Dick, G.; Young, V-L; Miller, F.W.; “Immunohistopathology and T Cell Receptor Gene Expression in Capsules Surrounding Silicone Breast Implants”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, No. 210, Springer-Verlag, Heidelberg, pgs. 237-242 (1996).
100. Hardt, N.S.; Emery, J.A.; Latorre, G.; Batieh, C.; Winter, W.E.; “Macrophage-Silicone Interactions in Women with Silicone Breast Prostheses”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; Editors, Springer-Verlag, Heidelberg, pgs. 245-252 (1996).
101. Hennekens, C.H.; Lee, I-H; Cook, N.R.; Hebert, P.R.; Karlson, E.W.; LaMotte, F.; Manson, J.E.; Buring, J.E.; “Self-Reported Breast Implants and Connective-Tissue Diseases in Female Health Professionals”,
JAMA,
275(8):616-621 (February 28,1996).
102. Sanchez-Guerrero, J.; Colditz, G.A.; Karlson, E.W.; Hunter, D.J.; Speizer, F.E.; Liang, M.H.; “Silicone Breast Implants and the Risk of Connective-Tissue Diseases and Symptoms”,
The New England Journal of Medicine,
332(25):1666-1670 (June 22,1995).
103. Gabriel, S.E.; O’Fallon, M.; Kurland, L.R.; Beard, C.M.; Woods, J.E.; Melton, L.J.; “Risk of Connective-Tissue Diseases and Other Disorders after Breast Implantation”,
The New England Journal of Medicine,
330(24):1697-1702 (June 16,1994).
104. .Steenland, K.; Goldsmith, D.F.; “Silica Exposure and Autoimmune Diseases”,
American Journal of Industrial Medicine,
28:603-608 (1995).
105. Sanchez-Roman, J.; Wichmann, L; Saiaberri, J.; Varela, J.M.; , Nunez-Roldan, A.; “Multiple Clinical and Biological Autoimmune Manifestations in 50 Workers After Occupational Exposure to Silica”,
Annals of Rheumatic Diseases,
52:534-538 (1993).
106. Bridges, A.J.; Anderson, J.D.; Burns, D.E.; Kemple, K.; Kaplan, J.D.; Lar-den, T.; “Autoantibodies in Patients with Silicone Implants”,
Current Topics in Microbiology and Immunology
— Immunology
of Silicones,
Potter, M. and Rose, N.; editors, No. 210, Springer-Verlag, Heidelberg, pgs. 277-290 (1996).
107. Marosok, R.; Washburn, R.; Indorf, A.; Solomon, D.; Sherertz, R.;- “Contribution of Vascular Catheter Material to the Pathogenesis of Infection: De
*1430
pletion of Complement by Silicone Elastomer In Vitro”,
Journal of Biomedical Materials Research,
30(2):245-250 (February 1996).
108. Borenstein, D.; “Silieonosis: A Spectrum of Illness”,
Seminars in Arthritis and Rheumatism,
24(1) (Supplement 1):l-7 (August 1994).
109. Solomon, G.; “A Clinical and Laboratory Profile of Symptomatic Women with Silicone Breast Implants”,
Seminars in Arthritis and Rheumatism,
24(1) (Supplement 1):29 — 87 (August 1994).
110. Freundlich, B.; Altman, C.; Sandorfi, N.; Greenberg, M.; Tomaszewski, J.; “A Profile of Symptomatic Patients With Silicone Breast Implants: A Sjo-grens-like Syndrome”,
Seminars in Arthritis and Rheumatism,
41(1) (Supplement l):44-53 (August 1994).
111. Conrad, K.; Mehlhorn, J.; Lüthke, K.; Dorner, T.; Frank, K-H.; “Systemic Lupus Erythematosus After Heavy Exposure to Quartz Dust in Uranium Mines: Clinical and Serological Characteristics”,
Lupus,
5:62-69 (1996).
112. Daniel, L.N.; Mao, Y.; Williams, AO.; Saffiotti, U.; “Direct Interaction Between Crystalline Silica and DNA — A Propo

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