The present paper describes the results of a "Goldblum-type" ELISA to detect the putative anti-silicone antibodies in sera from mice and rats implanted with silicone elastomer for 6 months. The serologic results suggest that the binding of IgG to silicone is immunologically non-specific, consistent with well-recognised interactions between hydrophobic IgG molecules and hydrophobic surfaces such as silicone.
 
 

Both asymptomatic and symptomatic groups of women were reported to have statistically increased autoantibody production. 

In asymptomatic women, 5-15 different autoantibodies were increased. 

In the symptomatic women, 15-20 different autoantibodies were increased.

Although the above groups were matched for age, they differed with respect to the duration of their implants, and it remains possible that the development of autoantibodies may be related to implant duration.

Two questions arise from this study. The first is the genetic background of the patients and control women – for example, are they Ashkenazi or Sephardic Jews and does this significantly affect the results? The second question concerns the selection of patients, which was done through a lawyer dealing with breast implant liabilities – has this selection biased the results? As the results are very different from those reported in the paper by Karlson et al (reviewed above), this becomes an important issue.
 
 

Long term implantation was associated with an increased incidence arthritis following collagen + IFA treatment. IL-10 levels were also raised in these mice. The data suggest that long-term silicone implantation results in the production of autoantibodies to connective tissue antigens and increased susceptibility to an experimental model of autoimmune disease.
 
 

There are two editorials from both sides of the divide to accompany this article but neither sheds any particular light on the issues.
 
 

Methods
Intraperitoneal injection of 1) breast implant distillate shown by gas chromatography/mass spectrometry to comprise a mixture of cyclosiloxanes of different molecular weight and small traces of platinum 2) commercially available 99% pure, platinum-free octamethylcyclotetrasiloxane (CS-D4).

Results
After 5-8 days all receiving the distillate had died after a dose of 35g/kg and 20% after a dose of 17.5g/kg. For CS-D4 the LD50 at 5-8 days was 6-7 g/kg. Animals surviving 14 days showed interstitial pneumonitis and liver damage.

Comment
Apart from any difference in species specificity, these findings are unlikely to have relevance for human breast implantation in view of the large doses used and the route of administration that would produce systemic tissue levels, vastly in excess of those that could be achieved by escape from breast prostheses.

Methods
Aqueous emulsions of polysiloxanes and controls injected once (to study acute effects) or on six occasions (to study chronic effects) into the sides of Sprague Dawley rats. Popliteal and lumbar lymph nodes removed between 2 and 72 days later.

Results
In addition to resonance associated with polysiloxane injected, the NMR spectrum of lymph nodes showed new resonances attributed to partially hydrolised polysiloxanes and silica. Low molecular weight cyclic oligomers induced necrosis at the injection site but no tissue reaction was seen with polydimethylsiloxane or with a chloriform extract of a prosthesis.

Comments

The authors’ conclusion is that all polysiloxanes are biotransformed in lymph nodes but higher molecular weight polymers degrade slower than oligomers.

The presence of silica is of some concern. Silica has not yet been identified unequivocally around implant sites in humans (see papers 26 and 34) but has not been investigated in human lymph nodes.

The Laser-Raman Microprobe should be used to determine if silica is found in human lymph mode draining implants.

Methods
Raman scattering measurements undertaken on 44 breast implant capsular tissues with known types of implants.

Results
Polydimethylsiloxane demonstrated around all 44 implants, polyurethane around all four polyeurethane-coated implants and Dacron around all four Dacron patch gel filled implants. Talc was found in 8 out of 44 cases. The presence of amorphous or crystalline silica was not substantiated.

Comments

The technique looks useful for identifying materials in tissue in association with silicone breast implants.

No foreign materials were identified in this study but all implants studied were removed after only 4-6 months of use.

Studies on older implants are needed.

Methods
Raman-microprobe spectrometry of 5 explanted prostheses of 9-21 years duration.

Results
Capsular tissue contained calcium carbonate, calcium phosphate and starch. Polydimethylsiloxane found in the tissue from one patient with a history of rupture but no crystalline silica identified.

Comments
More studies on capsular tissues from longstanding implants needed.

Method
Silicone oil massage between index finger and thumb for one minute whilst wearing surgical gloves: a) containing talc from pre-1983 and b) containing calcium carbonate after 1983. Oil dabbed onto microscope slide and examined for talc by polarised light microscopy.

Results
Talc identified.

Comments
Not relevant to current debate on the effects of breast implants because:

Method
Standard histological examination of 47 consecutively removed sural nerve and muscle biopsies.

Results
Changes likely to be symptomatic in 7 (axonal neuropathy, granulomatous neuritis, myositis, diabetic neuropathy, hypertrophic onion ball neuropathy), minor morphological abnormalities of dubious significance in 11 and no abnormality in 28.

Comments
Highly selected patient population (33 were litigants)
Impossible to draw conclusions about any possible causal relationship between the implants and the pathological changes described.
 

The background for the articles is Marcia Angell’s seminal article published in 1996 in the New England Journal of Medicine, in which she attacked the decisions of American Courts which found in favour of plaintiffs. Several plaintiffs had succeeded in claims for damages on the basis that they had suffered serious systemic illnesses as a result of silicone gel breast implants.

A ruling was made at about the time the final papers for the collection of articles were being collated. The expert panel appointed by US District Judge Sam C. Pointer Jnr, who oversaw many thousands of breast implant cases, concluded that "women with silicone gel breast implants do not display a silicone induced systemic abnormality in the types or functions of cells in the immune system". As to local inflammation, the panel was less decisive.

The issues raised in the articles are summed up in the penultimate paragraph of the editorial note by Ronald Bayer, entitled "Science, Justice and Breast Implants". He poses a set of important questions to be addressed in the light of a series of court decisions in America (which have world-wide implications), the findings of the European Committee on Quality Assurance and Medical Devices, and the UK’s Independent Review Group.

The questions which the editor had hoped would be answered in the commissioned articles included the following:-

Although Stein asserts, in "Silicone Gel Implants: Epidemiological Evidence of Sequelae", that in the US, and not in other jurisdictions, it appears that "there is still room for reasonable doubt as to the supposed casual relationships", she concludes that the evidence presented in the article supports the view that silicone gel breast implants have not been proved guilty of causing connective tissue disorders.

Macklin’s article is entitled "Ethics Epidemiology and the Law". It concludes that the report of Judge Pointer’s panel could have an important impact on future cases involving silicone breast implants, as it has the standing of high level expert testimony in court, and "should succeed in granting to scientific evidence a rightful place in future judicial proceedings without compromising the interests of justice".

Fox begins the discussion in his article "Epidemiology and the New Political Economy of Medicine" with the comment that science, clinical judgement and money have recently become entwined in American healthcare law in ways that are "without precedent in the history of medicine". He describes the way in which, in the context of the silicone gel controversy, economic considerations in the healthcare are demanding more comprehensive epidemiological knowledge.

The most useful and informative article for the non-lawyer is the contribution by Annas entitled "Burden of Proof: Judging Science and Protecting Public Health in (and out of) the Courtroom". This commentary explains clearly the workings of the law, and the difference between causation in law and causation in science, defining the role of the law as not to determine truth, but rather to resolve disputes. Like the other contributors, Annas takes the view that scientific knowledge is essential in developing effective public health strategies, but that science cannot determine social and economic policies. He concludes, "the continuing challenge is to develop effective debate and democratic forums in which to debate and decide on policies that protect public health".

As the editorial by Bayer correctly suggests, it becomes clear from the articles that the courts were in error in terms of science, even though they arrived at their decisions in the course of embracing legal procedures that were fair. Marcia Angell is vindicated. The simple fact is that to satisfy a court in establishing a casual link between implants and systemic illness, it is only necessary to prove such a connection on a balance of probabilities. This means that there must be a 51% likelihood of a causal connection. By contrast, the test for acceptance of a scientific theory is far more rigorous – proof of causation is required at a much higher level, (close to 98%), and any publication must be peer-reviewed before it will be published in a reputable journal. In court, much depends upon the performance of expert witnesses under cross-examination, and it is accepted that a scientist who may not be regarded as reputable by his or her peers has the ability to convince a court of the accuracy of a hypothesis. This situation is compounded in America, where, unlike the situation in the UK, juries are used to decide civil cases. It is also necessary to bear in mind the fact that some experts behave like "hired guns", and regard their allegiances as resting with the party paying them.

Nothing startlingly new is being argued in the collected articles, but they do confirm the views stated by Marcia Angell in her various works, that reputable science (as opposed to junk science) ought to have a more assured place in the courtroom. The authors are ready to acknowledge the importance of epidemiology in the public health forum. As far the UK is concerned, the weight of scientific evidence is now even more firmly against the contention that systemic illness is caused by implants. Since the statement of Judge Pointer’s panel of experts and the findings of the IRG, there is now little prospect of any UK court being persuaded to arrive at a different conclusion to these two bodies on that point. The position of expert witnesses has been clarified in the UK by the introduction of new rules governing civil procedure in the spring of 1999. Under Part 35 of the Civil Procedure Rules, all expert witnesses must be aware that their primary duty is to the Court, and not to either party to the case in which they appear. Experts must now make a statement in their reports asserting the truth of the evidence.

The editorial sums up the position with the words: "it becomes necessary to assert that the claims of those who believed themselves aggrieved were ill-founded, and in the end, the needs of the most vulnerable will not be advanced or protected if the voice of reason or science is subverted in the name of compassion".
 
 

The date for The Bankruptcy Court in Bay City Michegan, to conduct its hearing to review the proposed plan was June 28^th 1999. The women who benefit from the plan could receive between 2,000 US dollars and 250,000 US dollars. They still have the alternative of bringing cases before the courts.

In the light of the articles reviewed above, and the recent developments concerning silicone gel breast implants, this appears to be incongruous. However, the Dow Corning settlement must be regarded as business decision which was made in the context of the earlier court rulings in America. Settlement was considered to be by far the cheapest option. The cost of fighting the large number of claims being made against it, would have been impossibly high, and a settlement was the only realistic alternative at the time the decision was made.