Théodore Nicolas Gobley

Gobley's family originated from the small city Fulvy in the Yonne region, a very rural hilly area of Burgundy. His father had settled at the end of the 18th century as a wine broker in Paris, marrying a young lady in a family long established (since at least the beginning of the 17th century) in that trade in the capital city of France. That family, Boutron, was registered in the 17th and 18th centuries as one of the 12 suppliers of wines to the King's Court.

Wine trading had strong links with alcoholic distillation, some close kin of the Boutron family were indeed spirits distillers, and it is likely this environment that led Gobley to studies in chemistry and pharmacy.

Indeed, an historical study conducted in 1957 by P. et C. Chatagnon on the early steps of brain tissues chemical structure studies mentions that Gobley effected a stay as apprentice by one of his parents named Guerin, indicated as pharmacist (actually, his brother-in-law, Denis Guerin (1798–1888), pharmacist in Paris for a few years in the early 1830s, but more well known as mayor of the city of Fontainebleau during close to 30 years, from 1843 till 1871, and so far as known, not related to the Boutron family).

Whatever the initial lead, further on Gobley entered full grade studies in pharmacy and in the early 1830s attended courses delivered by one of the great figures of French pharmaceutical and chemistry arts of that time, Pierre Jean Robiquet, of whom he became a close collaborator, and ultimately his son-in-law, through marrying Laure Robiquet, one of the daughters of his master and mentor.

Robiquet (1780–1840), a long-standing professor at the Ecole de Pharmacie in Paris (since 1811) was a very prominent, respected and honoured player among the French chemists/pharmacists community of the first half of the 19th century: member of the "Société de Pharmacie" later on designated as the "Académie Nationale de Pharmacie" (1817), of which he was Secretary General then President, (1817 till his death) (see (http://www.shp-asso.org/)), member of the "Académie de Médecine" (1820), member of the Académie des Sciences, distinguished with the order of Légion d'Honneur, author of numerous studies and pioneering work in the research of complex molecules in natural bodies, either plants or animals, who had isolated such fundamentals products, as caffeine, cantharidin, and most of all the alizarin, a powerful and stable red dye that was to become one of the first dyes to be mass-produced through a pure chemical synthesis path.

Gobley qualified as a pharmacist in 1835, married Laure Robiquet in 1837, and established himself as pharmacist in Paris (60 rue du Bac; the place had been run down when Boulevard Saint Germain was opened some 30 years later); in parallel to his trade, in his personal lab he conducted his research, and followed a path very similar to that of his father-in–law (demised in 1840): he entered the Ecole de Pharmacie as professor in 1842 (he quit in 1847), became a member of the Académie Nationale de Pharmacie in 1843, of which he became president in 1861, and was admitted as a member of the Académie de Médecine that same year.

While conducting various works on a very diversified range of topics very much like most pharmacist/chemists of the 19th century, Gobley singled himself out by a somehow unique lifelong pursuit in the study of lipids in the living animals reign, whereby he demonstrated the universal presence of a fundamental substance, which he named lecithin, and the exact composition of which he pursued during thirty years.

Gobley was also a philanthropist, and he was involved in the management of a local administration office for the housing of poorer people in the "Département de la Seine" (today, the greater Paris area including districts 75, 78, 91, 92, 93, 94, 95).

One of Gobley's daughters married composer Paul Collin. Gobley died on 1 September 1876 in the Pyrenean thermal resort of "Bagnères-de-Luchon, where he was on a family trip. His burial place lies at "cimetière Montparnasse" in southern Paris.

In the course of the first half of the 19th century, several French chemists had initiated some tries at the chemical components of brain tissues, but tools and methods for analysis were poor and results fairly unsatisfactory; however they had consistently obtained through different methods, mostly through dissolution in warm alcohol of brain matter, a lipidic substance of more of less stable composition which they had diversely called "matière blanche" (Louis-Nicolas Vauquelin), "cérébrote" (J. P. Couërbe), acide cérébrique (Edmond Frémy).

Obviously, the brain tissues were not solely composed of that, and confusion was high as to their actual composition, with especially Edmond Fremy holding, based on his work on "acide cerebrique", for a blend of neutral lipids such as olein and phosphoric acid.

Gobley found a masterly solution to this question in a series of careful incremental steps. Building on a succession of biological tissue models : egg yolk (1846–1847), carp fish eggs (1850), carp fish roe (1850), brain matter of sundry higher class vertebrae such as chicken, and ultimately man, fat matters in human fluids: blood (1852), bile (1856), Gobley, in a series of works assiduously pursued over a span of more than 30 years, classified the several fat matters from a variety of biological tissues, characterized their several properties, identified their respective structure, established bridges between wide apart categories (seminal matter, brain) and branches of zoology (birds, fish, mammals), shed light on similarities of tissues build-up and specified their differences depending on their function (1874).

The identification and chemical breakdown of lecithin, the first of phospholipids, 1848–1874

In the course of the next three years 1848–1850, Gobley extended the scope of his research in parallel over egg yolk, carp fish eggs, fish roe, and brain tissue.

In 1850 ("Recherches chimiques sur les œufs de carpe"), he evidenced the presence of his "matière phosphorée", with identical properties, in carp fish eggs; he proposed for it the name of lecithin which history upheld, from the Greek lekithos (egg yolk) (Journal de Pharmacie et de Chimie, Paris, 1850, 17, 401), thus underlining the clear link with his early studies.

And in its wake he demonstrated that lecithin, however obtained (from egg yolk, carp fish eggs, fish roe, human brain), and even though not totally purified, always yields a mix of oleic acid, margaric acid and glycerophosphoric acid when hydrolyzed, and under no circumstances whatsoever anything like phosphoric acid which would have been expected if ordinary fat matter acids, such as phospho-oleic acid, had been involved ("Recherches chimiques sur la laitance de carpe." Journal de Pharmacie et de Chimie 1851, t19, 406).

Conversely, he demonstrated that the non phosphoric fraction of egg yolk, that he had called "cérébrine" is absolutely identical in chemical breakdown and reactive properties to the "acide cérébrique" identified by Edmond Frémy and M. R. D. Thompson in the brain.

In 1852, he evidenced the presence of lecithin in veinous blood (Recherches chimiques sur les matières grasses du sang veineux de l'homme), and in 1856, in bile as well (Recherches sur la nature chimique et les propriétés des matières grasses contenues dans la bile).

However, he still lacked one brick for a complete breakdown of lecithin's structure.

That brick was found during the 1860s by parallel work conducted mainly in Germany, that identified yet a new component of biological fat matters, choline, first in the liver-produced bile by the German chemist Adolph Strecker (Ann. Chem. Pharm. 1868, 148, 77), then shortly afterward in the human brain through the research of Oscar Liebreich in Berlin (who believing he had identified a different matter named it initially "nevrin") and in his wake complementary contributions by Dibkowsky, Baeyer and Wurtz.

Using these additions to his own work, Gobley in 1874 crowned this long, patient and unyielding series of steps through a final proposal of a complete structure for lecithin, whose hydrolysis yields exactly one oleic acid, one margaric acid, one glycerophosphoric acid and one choline ("Sur la lécithine et la cérébrine", Gobley J Pharm Chim 1874, 19, 346).

Fig 1. 1 example of variant phosphatidylcholine, palmitoyl-oleyl-sn-phosphatidylcholine.

Later studies expanded the egg yolk lecithin into a wide family of lecithins answering to this structure, combining with a choline head and glycerophosphoric acid a variety of fatty acids. In general, a lecithin, or more precisely a phosphatidylcholine is obtained using a saturated fatty acid, in the example here palmitic acid or hexadecanoic acid H₃C-(CH₂)₁₄-COOH (margaric acid identified by Gobley in egg yolk, now named heptadecanoïc acid H₃C-(CH₂)₁₅-COOH, belongs to that class) and an unsaturated fatty acid, here oleic acid or 9Z-octadecenoic acid as in Gobley's original egg yolk lecithin).

In parallel, Gobley developed a number of additional threads of research of a more mainstream type:

In cooperation with a French doctor, member of the Academie de Medecine, Jean-Léonard-Marie Poiseuille, he published some results on urea in blood and urine.

In liaison with his commitment in public health matters and institutions, he involved himself in various studies on toxics, human nutrition and health, and the safety of industrial processes: thus he successively investigated toxins in toadstools (Recherches chimiques sur les champignons vénéneux, 1856), medicinal real or supposed properties of diverse plants, herbs and preparations, toxicity of lead in widespread tins used for cooking utensils, poisonous effects of rye.

In the tradition of the methods of Robiquet, from the natural vanilla fruit, he obtained in 1858 the very first samples of pure vanillin, its active flavoring principle. Gobley lived just long enough to see this breakthrough bring about the advent of artificial industrial vanillin synthesis, in a process based on glycosides extracted from the sap of pine trees (1874), opening the path to the extraordinary expansion of the use of that very popular flavour. Incidentally that also brought about the complete collapse of the growing of natural vanilla and the related industry, but that was probably not intended by Gobley.

• "Sur l'existence des acides oléique, margarique et phosphoglycérique dans le jaune d'oeuf. Premier Mémoire: Sur la composition chimique du jaune d'oeuf"; par M. Gobley. (Extrait). C R hebd Acad Sci 1845, 11, 8

66

• "Recherches chimiques sur le jaune d'oeuf de poule"; par M. Gobley. Deuxième Mémoire. C R hebd Acad Sci 1845, 21, 988
• "Recherches chimiques sur le jaune d'oeuf - Examen comparatif du jaune d'oeuf et de la matière cérébrale". Journal de Pharmacie et de Chimie 1847, t11, 409 et 412
• "Recherches chimiques sur les oeufs de carpe". Journal de Pharmacie et de Chimie 1850, t17, 401, et t18, 107
• "Recherches chimiques sur la laitance de carpe". Journal de Pharmacie et de Chimie 1851, t19, 406
• "Recherches chimiques sur la matière grasse du sang veineux de l'homme". Journal de Pharmacie et de Chimie 1852, t21, 241
• "Recherches sur la nature chimique et les propriétés des matières grasses contenues dans la bile". Journal de Pharmacie et de Chimie 1856, t30, 241
• "Recherches chimiques sur le cerveau; par M. Gobley". Journal de Pharmacie et de Chimie 1874,4ème série, t19, p. 346–354
• "Sur la lécithine et la cérébrine"; par M. Gobley". Journal de Pharmacie et de Chimie 1874,t20, 98–103, 161–166
• "Note sur l'Elaïomètre, nouvel instrument d'essai pour les huiles d'olive". M. Gobley. J Pharm Chim 1843, 4, 285
• "Recherches sur la nature chimique et les propriétés des matières grasses contenues dans la bile", par M. Gobley. Journal de Pharmacie et de Chimie, 1856
• "Recherches physiologiques sur l'urée (avec Mr le docteur Poiseuille)", par M. Gobley. Comptes rendus de l'Académie des Sciences et Gazette hebdomadaire de médecine et de chirurgie, 1859
• "Recherche sur le principe odorant de la vanille", par M.Gobley. Journal de Pharmacie et de Chimie 1858

• Pierre Jean Robiquet
• Eugène Chevreul
• Louis-Nicolas Vauquelin
• Théophile-Jules Pelouze
• Edmond Frémy
• Oscar Liebreich
• Jean Léonard Marie Poiseuille
• Strecker amino acid synthesis

• Dossier de Légion d'Honneur (base LEONORE des Archives Nationales, cote L1157072)
• Dossier biographique à la bibliothèque interuniversitaire de pharmacie
• Eloge funèbre par Mr Jean Baptiste Chevallier (1793–1879), membre de l'Académie de Pharmacie
• L'étude chimique des constituents du tissu cérébral au cours du XIXème siècle, Les pionniers français (III): Théodore-Nicolas GOBLEY (1811–1874),par Mlle C.Chatagnon et P.Chatagnon, extrait des Annales Médico-Psychologiques, n°2, juillet 1957
• Bernard F. Szuhaj, "Lecithins", The American Oil Chemists Society, 1989
• Richard L. Myers, Rusty L. Myers, "The 100 Most Important Chemical Compounds", Greenwood Publishing Group, 2007
• Donald Bayley Tower, Michel-Augustin Thouret, "Brain Chemistry and the French Connection, 1791-1841: An Account of the Chemical Analyses of the Human Brain by Thouret", Raven Press, 1994
• Adolf Strecker, "Isolement de la lécithine de l'oeuf" Académie de Münich, 1869, t2, 269
• J.L.W Thudichum "Die chemische Konstitution des Gehirns des Menschen und der Tiere", Tübingen, Verlag von Franz Pietzcker, 1901
• J.F. John, "Chemische Schriften, vol 4, n°31, p228
• J.F. John, "Zoochemische Tabellen", T.I.A, 1814, p12
• O. Liebreich, Ann.Chem., 1864,134,29

• La Création de l'Ecole de Pharmacie (in French)
• Académie Nationale de Pharmacie (in French)
• Portrait of Robiquet at The Ecole de Pharmacie, Salle des actes (in French)
• Fontainebleau streets denomination, origin (in French)