Dental amalgam has been embroiled in controversy for long periods during the 160 years since its introduction. The fact that it is still in use tends to be regarded as evidence that it has actually passed the equivalent of a very long clinical trial. This conclusion may not be well founded. The methods of medical research are not very sensitive when the problem is to assess the long-term safety of a substance to which a large proportion of the population are exposed. The difficulties encountered in such situations are particularly well illustrated by the history of research on tobacco and health, but other examples can be found in cancer research.
The epidemiology of chronic diseases is in itself a difficult field of study because of the relatively long interval between the induction and the manifestation of such diseases. The classical critera of causality known as Koch's Postulates are often hard to apply in non-infectious, non-acute disorders . But there is also a structural problem in science itself, which in many cases tends to prolong the process of coming to a conclusion. Research operates within a kind of adversarial system. This is inevitable as there would be no growth of knowledge without a battle of ideas. If scientists were perfect people who were only motivated by love of truth, there would be no great problem. Personal ambition may be a disturbing factor, but this is nothing compared to the effects of various corporate interests on the process of scientific inquiry.
The scientific community has at long last reached consensus on the seemingly interminable question of smoking and disease. The tobacco industry has not given up yet, but their rearguard action is no longer a serious threat to the integrity of science. Asbestos has been banned, as well as a fairly large number of other carcinogens. Are we winning the war on cancer? Unfortunately not. The partial victories just mentioned have not been enough, and they have furthermore been much delayed by the influence of corporate interests on the scientific process. Robert N. Proctor's book "Cancer Wars"  is a great source on this rather unflattering chapter in the history of science.
The research process is very vulnerable to situations where "for every Ph.D. there is an equal and opposite Ph.D." Trade associations know this and act accordingly. Some 30 years ago the following appeared in an internal document produced by a cigarette company :
"Doubt is our product since it is the best means of competing with the 'body of fact' that exists in the mind of the general public. It is also the means of establishing a controversy. If we are successful at establishing a controversy at the public level, then there is an opportunity to put across the real facts about smoking and health."
I am not suggesting that the dental organizations are as cynical as the tobacco industry, but when they make pronouncements on the safety of amalgam we should not forget that they enjoy the privilege of being regarded as more or less scientific bodies. Everybody knows that the tobacco industry is protecting its own commercial interests, but so is every guild from time immemorial. The dental associations have it in their power to retard the growth of knowledge about the side effects of amalgam. In my view, the only decent attitude is to assist the critics of amalgam in every way in their efforts to reveal the truth. This does not mean that a great deal of active professional help will be needed, since the work will mainly be done by researchers from medical fields such as neurology, psychiatry, gastro-enterology, immunology, and several more. If indeed amalgam has non-trivial side effects, this is an old, neglected problem of both medicine and dentistry. We have inherited this from previous generations of scientists, and our liability is clearly limited to the consequences of any avoidable delays in the process of uncovery, once the suspicion has taken root.
Dental amalgam entered the scene during the Industrial Revolution. This was an era of unbridled environmental pollution. Chimneys spewed out smoke from coal fires which brought fresh mercury into the global circulation . Mercury compounds were in widespread medical use. Many of the so-called diseases of civilisation probably emerged, or became common, during this era. There is a general lack of reliable information on changes in the incidence of various diseases over such long periods of time, and medical researchers often hesitate to draw any conclusions from historical data. Parkinson's disease, which is easily recognized in typical cases, was first described in 1817. Alzheimer's disease was described in 1906 as a relative novelty among people below the age of 60. Multiple sclerosis has a geographic distribution with a higher incidence in the temperate zones in which industrialization started. Its epidemiology shows interesting parallels to that of dental caries . These are examples of diseases in which a role for mercury and amalgam has been suggested.
In my own specialty, psychiatry, two important diseases, schizophrenia and major depression, are historically remarkable for possible long-term changes of incidence. Schizophrenia got its modern name in 1911, but it can be clearly recognized in 19th century sources back to 1809. It has proved quite hard to find even earlier descriptions of this very severe, common disease, which of course suggests that it was relatively rare before that time. In the 19th century it was often taken for granted that the rise of "insanity" was a real phenomenon, and a cause for great concern . The infamous eugenic movement, which arose 100 years ago, was motivated by a perceived decline of the mental health of Western populations.
There is epidemiological evidence of a quite remarkable rise in the incidence of depressive disorders during recent decades. Anxiety disorders have probably also become more common .
Cancer is a complex field, but several forms of malignancies have certainly increased in incidence during the present century. Asthma and allergies in young people show an almost explosive rise at the present time.
The causes of the diseases mentioned above are largely unknown. It is interesting that genetic contributions appear to be fairly well substantiated in many of them, but of course this does not explain why they have become more common. The fact that something "runs in families" is relatively easy to demonstrate, but the crucial factor may nevertheless be environmental. If the environment deteriorates, genetic factors of resistance and susceptibility will often become decisive at the individual level. Tuberculosis tends to run in families, but still the solution of this very serious health problem proved to be environmental. As long as we don't have an obvious chief suspect, genetics may be playing the role of a red-herring, as in cancer research .
Why are the causes of many of the major killers and disablers of humanity unknown? A difficult question, but two partial answers were suggested at the beginning of this paper:
The second of those
explanations is clearly relevant to cancer research, including the tobacco story
But why should the sensitivity be too low?
Important discoveries don't grow on trees. There is always an element of surprise in new knowledge, and we have heard about such things as Serendipity, and the importance of having a Prepared Mind. On the other hand we tend to think of "the scientific method" as composed of rigorous procedures and accepted routines, which is a quite different angle on the subject. In medicine many relatively simple problems have been solved, but the complex ones remain. It may be that our methods will have to be made more flexible in order to tackle this.
The traditional medical attitude implies that we should rather throw away a few babies with the bath-water than accept a spurious causal relationship. This may look like a prudent and responsible attitude, worthy of a true scientist, but it may in fact be too conservative for today's problems. We all, collectively, pay a price if the rules are too rigid and confining, first of all by having to wait longer than necessary for a solution, but also more directly by supporting research that is handicapped by mistaken methodological notions. In my opinion medical research will have to draw some general conclusions from the tobacco story.
It is important to realize that research is not objective in such a way that the truth will force itself upon you, willy-nilly, if you just abide by the rules. That is of course one reason why money from the tobacco industry is not welcome in the world of science . But irrespective of the source of funding, it is a waste of both time and money when people are looking for something they rather hope not to find, as can be the case with serious side effects of dental amalgam. This simply won't work in actual practice, and scientific progress would be much better served if we gave all the money to researchers who are biased against amalgam! No amount of research can ever prove that a foreign substance which is implanted in the body will have no adverse effects.
Even the least toxic of drugs have serious side effects in some cases, so why should mercury be an exception? If none have been found so far, we shall probably have to change our approach to the problem. A first step in this direction would be to start collecting case reports of suspected side effects, as is routinely done with drugs. There is traditionally a disdainful attitude to "anecdotal evidence" in medicine. However, the safety of drugs and medical interventions cannot be monitored without an input of anecdotal material. This very important function would be paralysed if controlled studies were to be required as evidence throughout. There is little or no discussion about these things, but the necessity of case reports is tacitly accepted by everyone concerned.
Side effects of drugs usually appear rather promptly, which makes them relatively easy to recognize. When the drug is discontinued, the side effect will fade away, which confirms that there was a causal relationship. Catching and reporting a side effect is often as simple as that. With amalgams the time scale is rather different, and it is often impossible to establish any significant temporal relationship between amalgam placement and the emergence of symptoms. The research problems are therefore quite similar to those of carcinogenesis, but if amalgam effects are reversible, we still have the opportunity to observe what happens after amalgam removal. This is where the defenders of amalgam have invoked placebo effects in order to explain the very numerous reports of remarkable results in cases with long-standing symptoms.
The placebo concept came into prominence after WWII and seems to have been accepted without much resistance as a kind of universal principle that would apparently account for a very wide range of phenomena for which medicine lacks a scientific explanation. There is a diffuse medical tradition which tells of the remarkable powers of placebo, and the need to be critical of such stories is rarely recognized. Some of the original work on placebo has turned out to be of very doubtful quality . However, nobody could seriously maintain that a mere placebo treatment is enough to bring about permanent improvements in any illness of long duration, except in very rare cases. There is simply no scientific basis for this. The placebo argument has the added disadvantage of being a patronizing insult to the intelligence of those people who have recovered from serious illness.
Nobody knows exactly what the effects might be of chronic low-dose mercury exposure in sensitive individuals. Today dental amalgam is a dominant source of such exposure in the West. In my opinion medicine and dentistry will both have to change their attitudes to this problem. The scientific debate has been much too defensive. It cannot yet be ruled out that mercury from amalgam is partly responsible for some of the health problems which have emerged as so-called "diseases of civilisation" during the last 150 years. This is a scientific problem of the highest order, and our treatment of this will be of crucial importance for the future goodwill of the health sciences.
 Dalén, P.
(1969) Causal explanations in psychiatry: A critique of some current concepts.
Brit J Psychiat 115, 129-37. I am offering this old reference because to my
knowledge the discussion of Koch's postulates has not changed very much since
I wrote this paper.
 Basic Books, New York, 1995. See also an on-line interview with Dr. Proctor at http://www.trimaris.com/~ussw/bc/bcwars.html.
 Proctor 1995, page 110.
 Goldwater, L.J. (1971) Mercury in the environment. Scientific American 224(5), 15-21; Airey, D. (1982) Contributions from coal and industrial materials to mercury in air, rainwater and snow. Sci Total Environ 25, 19-40; Lindqvist, O & Rodhe H (1985) Atmospheric mercury - a review. Tellus 37B, 136-59.
 Craelius, W. (1978) Comparative epidemiology of multiple sclerosis and dental caries. J Epid Comm Hlth 32, 155-65.
 Torrey, E.F. (1980) "Schizophrenia and Civilisation", New York, Jason Aronson; Hare, E.H. (1988) Schizophrenia as a recent disease. Brit J Psychiat 153, 521-31.
 Hagnell, O. et al. (1982) Are we entering an age of melancholy? Psychol Med 12, 279-89.
 Proctor, op. cit., ch 10.
 See for instance several indignant comments (editorial, news, letters) on a proposed donation of tobacco money to Cambridge University (British Medical Journal vol 312, No. 7027, 23 March 1996). The editorial started as follows: "Most people would agree that Cambridge University would be ill advised to launder money for a Colombian cocaine cartel."
 Kienle, G.S. (1995) "Der sogenannte Placeboeffekt", Stuttgart, New York; Schattauer.
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