Milestones in European Thyroidology (MET)

Jean-Francois Coindet (1774 – 1834)

Jean-Francois Coindet A brief review of Jean-Francois Coindet and his experiences in treating goitre with iodine.

I. Introduction

“Coindet, a doctor in Geneva, introduced iodine into the treatment of goitre” (F. Merke)

This short factual sentence epitomises an important advance in medicine. It seemed to be of some interest to try to unravel how this breakthrough was conceptualised, prepared and implemented, and to review some of its early consequences. Iodine had only been discovered seven or eight years earlier, its role in thyroid physiology was completely unknown, and the cause of goitre was still conjectural, so it took imagination, intellectual courage and determination to complete such a study.


II. The man and some family information

Jean-François Coindet was born on July 12, 1774, in Geneva where his protestant family had settled. His family originated from nearby Annecy (currently in Haute-Savoie, France), where goitre was also commonplace. He died in Nice on February 11, 1834. He was the son of Jean Jacques Coindet and Catherine Gros. J-F Coindet married Catherine Walker, the daughter of Charles Walker, who owned a historic tavern in Writer's Court in Edinburgh and helped sponsor publication of Robert Burns' poems. One of JF Coindet's sons, Jean Charles Walker Coindet, who was born in Geneva on November 10, 1796, and died there July 1876, studied medicine in Edinburgh, like his father. The course in Materia Medica taught to students - both when father and son attended Edinburgh - included the use of burnt sponge as an effective treatment for struma or bronchocoele (as goiters were then called). J.-Ch. Coindet was elected the student president of the Royal Edinburgh Medical Society in March 1819, defended his thesis (De Renum Muneribus ie, About Renal Functions) in 1821, and returned to Geneva in 1823, where he was highly supportive of his father. He later became a psychiatrist who took care of such notables as Richard Wagner and the mistress of Franz Liszt. An uncle of Coindet, François Coindet became a familiar of J-J Rousseau in 1756 and is mentioned in the “Confessions”. Rousseau gave him responsibility for printing the engravings illustrating “La Nouvelle Héloïse”. Their association was ruptured in 1768 because Coindet interfered too much in Rousseau’s life and relationships. Coindet, however, had received from Rousseau the manuscript of “L’Emile” and his portrait by Latour, and in 1808 he gave them to his nephew.

Jean-François Coindet attended school at the Academy of Geneva, but went to Edinburgh in 1792 to study medicine. The Academy, founded when Calvin was alive, did not have a school of medicine, so that Genevans had to go abroad. The French Revolution, as well as the local “mini-terror” (1792-1794), meant young Genevans went to protestant countries, such as the Netherlands or the United Kingdom, particularly Edinburgh, which was more open to Calvinists than Cambridge or Oxford. Jean-François Coindet obtained his MD degree in 1797. His thesis “De Variolis” concerned a popular topic at that time in Edinburgh: there were 14 theses on the topic between 1781 and 1800. Jenner inoculated James Phipps with cowpox on May 14, 1796 and self-published his pamphlet “An inquiry into the causes and effects of variola vaccine…” in 1798. A century-long controversy about the safety of vaccination ensued, foreshadowing the controversy that followed Coindet's report on iodine.

In January 19, 1798, J-F Coindet published a detailed 32 page account of Elisabeth Fulhame’s book “An Essay on Combustion…” published in London in 1794, now considered the first experimental evidence for the concept of catalysis (30 Nivose, An V , Annales de Chimie, Citoyens Guyton, Monge, Berthollet…editors, Paris) (1). Coindet might have been acquainted with Elizabeth Fulhame's 10 year opus through her husband, who was in Edinburgh for at least 6 years after he obtained his doctorate there in 1784. Coindet's account of Mrs. Fulhame's various experiments reveals a solid knowledge of chemistry, which may have helped him years later, when he was confronted with the problems associated with various preparations of iodine.

After his return to Geneva in 1799, J-F Coindet obtained the position of Medecin-Chef in the Geneva Hospital, a position he held from 1809 to 1831. Interested in Public Health and Epidemiology, he became the medical authority responsible for the prisons and the epidemics after the annexation of Geneva to France in 1798, as the capital of the French Department du Leman. When Geneva regained independence from the French domination, he became a member of the Conseil Représentatif Genevoix (1814 – 1834). In 1801 he made a contribution concerning vaccination of a child in the Genevan "Bibliothèque Britanique" (later renamed the “Bibliothèque Universelle"), and in 1813 he was listed as a member of the Société de Vaccine. In 1817, J-F Coindet became the editor of "Bibliothèque Universelle des Sciences, Belles-Lettres et Arts, Sciences (Genève)" after the death of Louis Odier, another Edinburgh-trained physician who made the first French translation of Jenner's "Inquiry…" and who published it in the November and December 1798 issues of the Bibliothèque Britannique. In 1816, J.-F. Coindet won a contest organized by the Royal Society of Medicine of Bordeaux on "internal hydrocephaly", which was published in 1817 as: “Mémoire sur l’hydrocéphalie ou Céphalite interne hydrencéphalique" (2).

III. The treatment of goitre with iodine.

Coindet first communicated the results of his iodine treatment for goitre to the Société Helvétique des Sciences Naturelles in Geneva on July 21, 1820. His work became widely known from the three articles (1820-1821) he published in his Bibliothèque Universelle (Geneva). The first and the second articles also appeared in the Annales de Chimie et de Physique (Paris), the journal in which the discovery and the characteristics of iodine had previously been published, and they were widely translated.

The first paper(3) is a complete account of his research strategy, including a) the rationale for the use of iodine, b) the clinical presentation of various types of goitre including the “goitre de dedans” (endothoracic goitre) and compressive goitre, which were conditions that demonstrated some spectacular successes with iodine, c) a brief discussion of the uncertainties of the pathophysiology of goitres, d) the methods of preparation of the various solutions of iodine he used, e) the modalities of treatment, and f) the results (3). Despite his familiarity with chemistry, Coindet used iodide-iodine solutions from the Pharmacy of Le Royer and Tingry that were prepared by Jean Baptiste Dumas(4) , a poor 18 year-old boy who arrived barefoot from Alès in the south of France, but who later became Professor of Chemistry in Collège de France and a member of the French Academy. Coindet used three different preparations, a solution of potassium iodide, an iodide-iodine solution somewhat different from the one that Lugol later defined, and an alcoholic (tincture) solution that Coindet later was to recommend as the safest and easiest to use. Twenty drops of these solutions contained approximately 50 mg (one “French grain”) of iodine. Coindet routinely prescribed 10 drops three times a day for the first week, and then 15 drops thrice a day for the second week and 20 drops three times a day subsequently. He only rarely prescribed higher doses. The recommended duration of treatment was 8-10 weeks. Results of the treatment were spectacular: softening and shrinking of goitres occurred after 8 days, and disappearance or a significant improvement in disfiguring or uncomfortable goitres occurred later in many cases. In addition, he observed iodine had a general stimulating effect on the appetite, the uterus (?), acted as an aphrodisiac, and he concluded that, used with competence, iodine would become one of the most potent medication brought to medicine by modern chemistry !

IV. The Iodine Storm

Following Coindet's enthusiastic report on the efficacy of iodine, a craze for taking iodine rapidly developed in Geneva and elsewhere. The general public and more than a few physicians regarded it as a nostrum, and rapidly, ill-effects from taking iodine were observed (5) . Based on the sales of iodine in the pharmacies of Geneva, Coindet estimated that in 1821, 1000 people had taken iodine (6). In 1820, at a meeting of the Genevan Medico-Surgical Society, Dr. J.-P. Colladon (1769-1842), a well-known Geneva physician who had studied medicine in Edinburgh (and had been a strong proponent of vaccination) reported that among 9 patients he had treated with iodine, 6 had developed severe ill-effects, predominantly gastric pain and discomfort. He pointed out that in 1816, P. Orfila in his “Traité des Poisons" had characterized iodine as a "corrosive poison," based on experiments on dogs that employed gram quantities of iodine. At the same time, it became widely known that a lady from the high ranks of Geneva's society had died of a respiratory problem ascribed to 2 month's treatment with iodine(5). Colladon concluded that iodine should be considered as a poison, despite its initial beneficial effects (5).

In February 1821, J-F Coindet published an article concerning precautions and justification of iodine treatments (6). He reported that he himself had treated 150 patients, in robust health, and had not observed serious complications in any of them. Because of the public uproar about the ill-effects seen with iodine, in January of 1821 he requested the physicians, surgeons and pharmacists in Geneva to convene at City Hall to officially confirm that in these patients no serious ill-effects of iodine had been observed (6). Impressed by the aggressive effect of iodine on goitres, and recognising its potential danger, Coindet insisted that the dose of iodine be closely controlled, that patients be followed weekly and that the treatment be short-term. He also would not give iodine to subjects who were frail or nervous. Indeed, most of the complications which raised the iodine controversy – and discredited its use – had not occurred in Coindet’s patients, although his description of one of his own patients resembled what we would now consider a typical case of relapsing iodine-induced thyroiditis(6). Coindet noted that in several patients who had been given iodine by others and who had developed iodine-induced hyperthyroidism — his description being so classical that M. Greer suggested Jod-Basedow should be renamed Jod-Coindet – the symptoms improved rapidly after he treated them essentially by withdrawing iodine (6).

In January of 1821, the local authorities of Geneva called upon an assembly of physicians, surgeons and pharmacists to interdict the sale of iodine preparations in the absence of a medical prescription, a decision which they endorsed. At the same time, the editor of the Bibliothèque Universelle (Coindet himself) published the following advice to readers: “We have been sent various observations concerning the danger of the use of iodine, even when prescribed by careful physicians and with the appropriate precautions. From these observations it appears that some constitutions are severely affected at the same dose that other take without any untoward effect”. The advice concluded that, as long as more is not known “it is prudent to restrain ones opinion as well as the use of this remedy.”

To try to circumvent the gastric irritation due to iodine, Coindet proposed using an unguent containing iodine (1.9 g of potassium iodate in 45 g of hog lard) to be applied on the skin of the neck. Among 22 patients so treated, 50% were healed completely, the other 50% partially (7). In this last article, he provided a global assessment of his two-year experience with iodine treatment of over 200 patients in Geneva, not only with goitre but also with pathologies difficult to identify nowadays (“scrofulous” lymph nodes, various inflammatory, oedematous or cystic abnormalities of glands (lymph nodes), breasts or uterus, as well as in some syphilis complications). In the conclusion of the article, he recommended that iodine treatment be considered a research area and ended by quoting Boerhaave “at prudenter a prudente medico, si methodum nescis, abstine.”

Coindet was discouraged by the reports of failures and poor outcomes of some patients treated with iodine, although many of the cases reflected imprudence in the use of iodine, and in which he not been involved. He made no further publications on the subject. The statement “Coindet would not leave his house for fear of being stoned by his poisoned patients" (8) has been refuted (9). He remained a successful physician, numbering among his patients the French poet-politician Lamartine and his wife (10). In 1823, together with his son and four other physicians, he established the Medical Society of Geneva, which still exists today (5).

In contrast to the controversy that lingered in Geneva, Coindet received wide recognition for his work abroad. A thoughtful review in the Edinburgh Medical and Surgical Journal in 1824 stated : “…The physicians and surgeons of France, of Italy, of Germany, and of England have, since the publication of Dr. Coindet’s memoirs in 1820 and 1821, been zealously occupied, in hospital or in private practice, in ascertaining the powers of iodine, and observing its effects; and though, perhaps, in some respects, it has been misapplied, and in others its virtues have been overrated, it cannot be doubted that it possesses strong claims to the attention of the bold and judicious practitioner” (11). In 1831, J-F Coindet was awarded a major prize by the Paris Academy of Sciences.

V. No Idea is Completely Original

Iodine was discovered in Paris in 1811 by B. Courtois, the son of a saltpeter manufacturer from Dijon. During the extraction of sodium and potassium from the ashes of seaweed, in the presence of an excess of concentrated sulphuric acid, he noticed the release of a violet vapour which condensed on cold surfaces to form brilliant crystalline plates (12). With the chemist C.B. Désormes, Courtois reported the discovery in 1813. In 1813, H. Davy, who had been admitted to France with a special passport from Napoléon (despite the Continental Blockade) was given some iodine crystal by Gay-Lussac. Davy, perhaps unsportingly, competed with Gay-Lussac to be the first to report that iodine was a new element. Later during the same visit to the Continent, Davy spent 3 months in Geneva in 1814, where the discovery of iodine was widely discussed.

Marine sponges and other marine species had been used since antiquity to treat goitre. In 1815 – a time when Jean-Charles Coindet was an active member – Andrew Fyfe reported to the Royal Society of Edinburgh that sponge contained iodine. However, Fyfe did not publish his findings in the Edinburgh Philosophical Journal until 1819 (13). Coindet very carefully pointed out that he had an intuition that iodine could be the active anti-goitre substance contained in the ashes of marine sponge and seaweeds 6 months before the publication of Fyfe’s findings. However, it is not unlikely that his son Jean Charles had already told his father about Fyfe's findings in 1815. In 1816, Dr. William Prout, a British physician-chemist who had graduated from Edinburgh in 1811 and was practising in London, purportedly had been struck by Courtois' finding of iodine in seaweed, and after having taken potassium iodate himself without apparent consequence, suggested in 1816 that iodine could be a treatment for goitre. The suggested treatment was apparently adopted by J. Elliotson at St. Thomas’ Hospital in 1819, but not reported until 1834 (14). In December of 1819, J.C. Straub, Professor of Physics and Chemistry at the Agricultural Institute of Hofwyl, near Bern, reported that iodine was present in burnt sea sponge, and in February 1820 he published his observations in “Naturwissenschaftlicher Anzeiger der Allgeminer Schweizerischer Gesellschaft” (11, 15). Straub also claimed to have immediately suggested the use of iodine in medicine. Coindet, as the editor of Bibliothèque Universelle, duly reported Straub’s findings ... but in the issue that followed the one in which his own initial report was published.

Conclusion:

This historical appraisal illustrates the ways science and medicine were developing at the end of the 18th century. It is striking how a) there was intense interest in a broad range of scientific domains [Coindet’s initial 1820 article on the effects of iodine in the Annales de Chimie et Physique was preceded by an article on the role of the nervous system on the production of heat by CEJ Chossat, who in 1813 had been a theology student in Geneva and whose interest in science had been encouraged by JF Coindet, and it was followed by a classical paper by A. Ampère on the mutual effects of two electric currents]; b) there was widespread and rapid communication of new findings in the scientific community; and c) young people had access to the best scientific circles and journals. The actual relationship between iodine, goitre and the thyroid was not established until Baumann and Roos (Freiburg, Germany) reported their discovery that the thyroid gland contained a high level of iodine in 1896, which provided a start for more scientific clinical and animal research on the treatment and physiopathology of goitre. The problem of variability in the potency of various preparations of burnt sponge has been replaced nowadays by concerns about the stability of iodide preparations stockpiled in case of more nuclear reactor meltdowns. It has become clear that adding small amounts of iodine to the diet of children is less fraught with risk than administering larger dose to patients who already have multinodular goitres. We are only beginning to understand the reasons there can be wide inter-individual-variability between different patients' responses to a given dose of iodine, and the scientific basis for non-thyroidal effects of iodine. The use (and abuse) of iodine remain topical in today's medical literature.

J. Orgiazzi(1) and S. W. Spaulding(2)
(1) Lyon University and Hospices Civils de Lyon
(2) Buffalo VA Hospital and University at Buffalo, SUNY


Acknowledgement:

We are indebted to Professor J.-J. Dreifuss, from Geneva, for numerous insights concerning J.-F. Coindet and his family, as well as for his knowledge of the history of the medical life in Geneva. Professor Michel Vallotton kindly made available to us his collection of articles and books on the thyroid gland, iodine and goitre. Professor Albert Burger supported us actively in the early stages of the work. We heartily thank them. We also acknowledge the important role played by Google Advanced Search in increasing access to the world's literature.


References

1. Coindet JF. Extrait de l’ouvrage de Mme Fulhame, intitulé : « An essay on combustion… », Johnson, Robinson, Cadell, London, 182 pages, 1794, Annales de Chimie, 1798, 25, 58-85
2. Coindet JF. Mémoire sur l’hydrencéphalie, ou céphalite interne hydrencéphalite, J.J. Paschoud, libraire, Paris et Genève, 282 pages, 1817
3. Coindet JF. Découverte d’un nouveau remède contre le goitre. Bibliothèque Universelle, Sciences et Arts, Genève, 1820, 14, 190-198, and Annales de Chimie et de Physique (Paris), 1820, 15, 49-59
4. Le Royer A, Dumas JB. Naturwissenschaftlicher Anzeigefer allgemeinen Schweizerischen Gesellschaft für die gesammten Naturwissenschaften. Beylage zum Naturwissenschaftlichen Anzeigefer: Researches Pharmaceutics sur le nouveau reméde contre le goitre découvert par Mr. le Dr. Coindet. No. 3. September 1, 1820. pp. 1-4
5. Dreifuss JJ. Genève 1820-1836: l’Affaire de l’iode. Revue Médicale Suisse, 2005, 1, 2357-8
6. Coindet JF. Nouvelles recherches sur les effets de l’iode et sur les précautions à suivre dans le traitement du goitre par ce nouveau remède. Bibliothèque Universelle, Sciences et Arts, 1821, 16, 140-152 and Annales de Chimie et de Physique, 1821, 16, 252-66
7. Coindet JF. Notice sur l’administration de l’iode par friction et de l’application de ce médicament dans les scrofules et quelques maladies du système lymphatique. Bibliothèque Universelle des Sciences. Sciences et Arts, 1821, 16, 320-327
8. Zimmermann MB. Research on iodine deficiency and goiter in the 19th and early 20th centuries. J Nutr 2008, 138, 2060-2063
9. Pignot A., Iodisme in Dictionnaire Encyclopedique des Sciences Médicales, Vol. 52 , Dechambre A., ed. 1889, pp.146-212, G. Masson, Paris, France, cited in Carpenter KJ. David Marine and the Problem of Goiter. J Nutr, 2005, 135, 675-80
10. Dreifuss J.-J., personal communication
11. Anonymous. The Edinburgh Medical and Surgical Journal, 1824, 22, 210-219
12. Swain PA. Bernard Courtois (1777-1838), famed for discovering iodine (1811), and his life in Paris from 1798. Bull Hist Chem, 2005, 30, 103-111
13. Fyfe A. An account of some experiments, made with the view of ascertaining the different substances from which iodine can be procured. Edinburgh Philosophical Journal, 1819, 1, 245-258.
14. Rosenfeld L. William Prout: Early 19th Century Physician-Chemist. Clinical Chemistry, 2003, 49: 699-705
15. Merke F. A short history of endemic goitre, cretinism and goitre prophylaxis in Switzerland. A contribution to the 4th annual meeting of the European Thyroid Association, Bern, CIBA-GEIGY and Hans Huber Publishers, 1971.

Coindet
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