Expertos, juicios y crimen: Pere Mata (1811-1877) y el veneno de María Bonamot / Experts, trials and crimes: Pere Mata (1811-1877) and Maria Bonamot's poison

El siglo XIX fue un periodo en el que se produjo un creciente interés por los venenos y los crímenes por envenenamiento a pesar de no ser formas habituales de homicidio. La nueva toxicología pretendía ofrecer herramientas para combatir este tipo de crímenes. Sin embargo, fueron precisamente los debates surgidos durante los procesos judiciales, los que ayudaron a configurar la toxicología del siglo XIX. Alejados de las pautas ofrecidas en los manuales y ante la necesidad de mostrar a un juez carente de formación en estas materias, la presencia o ausencia del veneno, los toxicólogos del siglo XIX pusieron en juego todas sus estrategias para vencer a otros expertos y convencer a los profanos. A mediados de 1844 se produjo en Madrid un caso de envenenamiento que llamó la atención tanto de la prensa médica como de la prensa periódica española. Dos factores contribuyeron a su popularidad: las fechas en las que se produjo (tan solo un año después de la creación de la cátedra de Medicina Legal en las Facultades de Madrid y Barcelona); y la participación como peritos de algunos de los personajes españoles más influyentes en la medicina legal y toxicología española como es el caso de Pere Mata i Fontanet (1811-1877). Pere Mata desempeñó una labor importante en los tres terrenos que contribuyeron decisivamente a la homogeneidad de la comunidad de toxicólogos: la formación universitaria, la literatura académica y la organización profesional. El análisis de un caso de envenenamiento como el que se desarrolla en este trabajo, permite considerar muchas de las cuestiones relacionadas con la toxicología en el siglo XIX: la constitución de una nueva disciplina académica, la creación de una comunidad de expertos, las controversias públicas y la gestión de las pruebas periciales en los tribunales

The XIXth century saw a growing interest in poisons and crimes by poison although these are not usual ways of murder. New technology aspired to offer tools to combat this type of crimes. However, it was precisely the debates that arose during trials that helped to configure XIXth century toxicology. Far from the guidelines offered in manuals and facing the need to demonstrate to a judge, lacking In training in these subjects the presence or absence of the poison, XIXth century toxicologists used all of their strategies to beat other experts and convince the layperson. In the middle of 1844 there was a case of poisoning in Madrid that caught the attention of both the medical press and the Spanish newspapers. Two factors contributed to its popularity: the date that it happened 8only a year after the creation of the chair of Forensic Medicine at the faculties in Madrid and Barcelona); and the participation as experts of some of the most influential Spaniards in forensic medicine and Spanish toxicology such as Pere Mata I Fontanet (1811-1877). Pere Mata carried out important work in the three fields which decisively contributed to the homogeneity of the community of toxicologists: university training, academic literature and the professional organization. The analysis of a case of poisoning as the one developed in this work permits the consideration of many issues related totoxicology in the XIXth century: the constitution of a new academic subject, the creation of a community of experts, public controversies and the management of expert evidence at trials

Soma, food of the immortals according to the Bower Manuscript (Kashmir, 6th century A.D.).

ETHNOPHARMACOLOGICAL RELEVANCE: Food is medicine and vice versa. In Hindu and Ayurvedic medicine, and among human cultures of the Indian subcontinent in general, the perception of the food-medicine continuum is especially well established. The preparation of the exhilarating, gold-coloured Soma, Amrita or Ambrosia, the elixir and food of the 'immortals'-the Hindu pantheon-by the ancient Indo-Aryans, is described in the Rigveda in poetic hymns. Different theories regarding the botanical identity of Soma circulate, but no pharmacologically and historically convincing theory exists to date. We intend to contribute to the botanical, chemical and pharmacological characterisation of Soma through an analysis of two historical Amrita recipes recorded in the Bower Manuscript. The recipes are referred therein as panaceas (clarified butter) and also as a medicine to treat nervous diseases (oil), while no exhilarating properties are mentioned. Notwithstanding this, we hypothesise, that these recipes are related to the ca. 1800 years older Rigvedic Soma. We suppose that the psychoactive Soma ingredient(s) are among the components, possibly in smaller proportions, of the Amrita recipes preserved in the Bower Manuscript. MATERIALS AND METHODS: The Bower Manuscript is a medical treatise recorded in the 6th century A.D. in Sanskrit on birch bark leaves, probably by Buddhist monks, and unearthed towards the end of the 19th century in Chinese Turkestan. We analysed two Amrita recipes from the Bower Manuscript, which was translated by Rudolf Hoernle into English during the early 20th century. A database search with the updated Latin binomials of the herbal ingredients was used to gather quantitative phytochemical and pharmacological information. RESULTS: Together, both Amrita recipes contain around 100 herbal ingredients. Psychoactive alkaloid containing species still important in Ayurvedic, Chinese and Thai medicine and mentioned in the recipe for 'Amrita-Prâsa clarified butter' and 'Amrita Oil' are: Tinospora cordifolia (Amrita, Guduchi), three Sida spp., Mucuna pruriens, Nelumbo nucifera, Desmodium gangeticum, and Tabernaemontana divaricata. These species contain several notorious and potential psychoactive and psychedelic alkaloids, namely: tryptamines, 2-phenylethylamine, ephedrine, aporphines, ibogaine, and L-DOPA. Furthermore, protoberberine alkaloids, tetrahydro-ß-carbolines, and tetrahydroisoquinolines with monoamine oxidase inhibitor (MAO-I) activity but also neurotoxic properties are reported. CONCLUSIONS: We propose that Soma was a combination of a protoberberine alkaloids containing Tinospora cordifolia juice with MAO-I properties mixed together with a tryptamine rich Desmodium gangeticum extract or a blending of Tinospora cordifolia with an ephedrine and phenylethylamine-rich Sida spp. extract. Tinospora cordifolia combined with Desmodium gangeticum might provide a psychedelic experience with visual effects, while a combination of Tinospora cordifolia with Sida spp. might lead to more euphoric and amphetamine-like experiences.

The pharmacology of medieval sedatives: the "Great Rest" of the Antidotarium Nicolai.

ETHNOPHARMACOLOGICAL RELEVANCE: Past practices of compound drugs from different plant ingredients enjoyed remarkable longevity over centuries yet are largely dismissed by modern science as subtherapeutic, lethal or fanciful. AIM OF THE STUDY: To examine the phytochemical content of a popular medieval opiate drug called the "Great Rest" and gauge the bioavailability and combined effects of its alkaloid compounds (morphine, codeine, hyoscyamine, scopolamine) on the human body according to modern pharmacokinetic and pharmacodynamic parameters established for these compounds. CALCULATIONS AND THEORY: We reviewed the most recent studies on the pharmacodynamics of morphine, codeine, hyoscyamine and scopolamine to ascertain plasma concentrations required for different physiological effects and applied these findings to dosage of the Great Rest. RESULTS: Given the proportional quantities of the alkaloid rich plants, we calculate the optimal dose of Great Rest to be 3.1±0.1-5.3±0.76 g and reveal that the lethal dose of Great Rest is double the therapeutic concentration where all three alkaloid compounds are biologically active. CONCLUSION: This study helps establish the effective dose (ED50), toxic dose (TD50) and lethal dose (LD50) rates for the ingestion of raw opium, henbane and mandrake, and describes their probable combined effects, which may be applied to similar types of pre-modern pharmaceuticals to reveal the empirical logic behind past practices.

Early drug discovery and the rise of pharmaceutical chemistry.

Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history.

Khat in the Horn of Africa: historical perspectives and current trends.

AIM OF THE STUDY: This article looks at the history of the expansion of khat consumption from the traditional chew regions to Western countries and assesses the implication of possible international control for its use and trade in the Horn of Africa. MATERIALS AND METHODS: Ten months of initial field work in Ethiopia, three follow up field work, archival work in Ethiopia and Europe, as well as study of available relevant literature. RESULTS: The debut of khat in the West in the 1980s was initially greeted with disdain and indifference. Authorities dismissed it on grounds that the mode of consumption, chewing the leaves for an extended period of time to extract a miniscule amount of the active ingredient, would not be appealing to Western users. Following the Mogadishu debacle of 1993, as depicted in the movie Black Hawk Down, authorities in the West began to express concern that khat was a new drug of abuse. Its trade was increasingly linked with terrorism because of its association with immigrants from the traditional khat use countries in the Horn of Africa and the Arabian Peninsula. Amid hysteria and moral panic, many Western countries classified khat as a highly potent controlled substance, rendering its possession, cultivation, and trade illegal. CONCLUSION: This article argues that more and more Western governments, out of panic rather than definitive evidence of harm, will be instituting national laws banning the leaves, but khat will not be placed under international control because the scientific evidence of harm is unlikely to rise to a critical mass that would justify its illegalization. States in the source countries would continue to tolerate khat because banning it would be disastrous from an economic and social welfare standpoint. Because of its ambiguous legal position and the unstable nature of its active ingredient, cathinone, khat would not be successfully commoditized as a global commodity or transformed into a highly concentrated illicit drug. In this situation, khat would continue to be chewed in the traditional-use areas of the Red Sea littoral marketed by local syndicates who work with a large network of petty commodity traders.

Beginnings of drug therapy: drug therapy in ancient India.

Four thousand years ago, the medical knowledge of the Indian subcontinent was codified into a system called the Ayurveda. Ayurveda remains a vital system of medicine and drug therapy in India and elsewhere. Plant alkaloids are the primary active ingredients of Ayurvedic drugs. Today the pharmacologically active ingredients of many Ayurvedic medicines are being identified and their usefulness in drug therapy being determined.

Xylocain (lidocaine, lignocaine), its discovery and Gordh's contribution to its clinical use.

Hans v. Euler, while investigating how genes and enzymes were chemically related in some chlorofylldefective mutants of barley, isolated gramine, an indole. Erdtman synthetized isogramine and found it to have weak anesthetic properties. He then together with Löfgren synthetized other amino-amides, but no one of them could compete with the existing local anesthetics of the ester-type, derivatives of para-aminobenzoic acid, e.g. procaine. Later Löfgren and Lundqvist followed up these studies and found an amid compound lidocaine (2-dimethylaminoacet-2, 6-xylidide). Lidocaine represented such a significant advance over procaine in clinical tests preformed by T. Gordh that it was introduced for clinical use. It has now during a half century been the standard local anesthetic drug. All local anesthetics are neurotoxic in high enough doses. Xylocain, however, has had an excellent record of safety. Only during the last years have there been reports on possible toxic irritation and damage by Xylocain used for spinal anesthesia. The aetiology is still not clear In this connection two early observations by Gordh and his coworkers are discussed.

[Witches' ointments and love-potions: a contribution to the cultural history of nightshades]. / Hexensalben und Liebestranke: ein Beitrag zur Kulturgeschichte der Nachtschattengewachse.

The nightshades (solanaceae) were used as intoxicants since the ancient civilizations and are still in use today. Their alkaloids, atropine and scopolamine, were the major active substances of the ointments of witches, of medieval "anaesthetics", and of modern poisons for murder. In a medium dose-range the predominant symptoms are hallucinations and illusions. This explains the use of nightshades in fortune-telling and religious rituals. In higher doses the alkaloids produce coma and apnea. Scopolamine enjoyed a particular popularity as a poison for murder. In the 19th century the nightshade alkaloids were also in clinical use. This article focusses on the medical history of the psychosis due to intoxication with solanaceae.

The discovery of alkaloids.

This paper presents the history of the discovery of the first alkaloids. Isolation of alkaloids is connected with the study of the active principles of medicines of plant origin, for example opium and cinchona bark. Sertürner described morphine as a plant alkali and claimed that it was capable of neutralizing free acids yielding salts. The recognition of alkaloids as a new class of compounds was an important step at that time because of the dogmatic denial of the possible existence of plant bases. Isolation of alkaloids is a significant event from the point of view of chemistry, physiology and medicine. The discovery caused essential conceptual changes in chemistry. Priority claims with reference to the discovery of the alkaloids are also reviewed.

Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review.

The use by the Khoisan of South Africa of Sceletium plants in psychoactive preparations has often been alluded to in the literature. However, much of it is fragmentary and contradictory. The current review reassembles the historical data recorded over a 300-year period, describes techniques for the preparation and use of "kougoed' from plants of Sceletium and documents the subjective experiences of a number of contemporary users. Apart from chewing the dried product, after "fermentation', there are reports of uses as tinctures for sedation and analgesia, chewing the material directly and smoking the residue after chewing. The symbolic connections of Sceletium with eland antelopes, the "trance animals' par excellence of the San hunter-gatherers is noted. Observations by Paterson (1789) and reports of contemporary users indicate a synergism and potentiation with smoked Cannabis. There is no evidence to support the view that "kougoed' or Sceletium alkaloids are hallucinogenic. The alkaloid distribution in Sceletium and other members of the family Mesembryanthemaceae are considered. Chemical studies have indicated as many as nine alkaloids in Sceletium which fall into three distinct structural categories. Mesembrine, the alkaloid first isolated and named is not the dominant constituent of plants and is weakly narcotic. Evidence is assembled to suggest that traditional and contemporary methods of preparation serve to reduce levels of potentially harmful oxalates, which are found in Sceletium and other Mesembryanthemaceae. It is concluded that there is a need for further pharmacological studies on these alkaloids, based on their narcotic-anxiolytic properties, strong synergism with other psychomimetics, moderate toxicity and anti-cancer activity.

Historical perspectives on inotropic agents.

Although early experiments in animals and humans suggested that digitalis glycosides increased cardiac output only in the failing heart, later studies showed that these cardiotonic agents increase intraventricular systolic pressure and decrease relaxation time in the normal animal. The controversy concerning the peripheral vascular or direct cardiac effects of digitalis was finally resolved when new methods were applied to the study of the effects of this drug on intraventricular pressures and cardiac contractile force. Other positive inotropic agents, such as the adrenergic agonists, have also been tested for the treatment of heart failure. However, during long-term oral or intravenous therapy, the effectiveness of these drugs appears to diminish. Clinical studies of glucagon, a polypeptide with positive inotropic and chronotropic effects, have revealed its potential for causing side effects and its reduced activity in patients with chronic heart failure. With the discovery of several new types of inotropic agents, i.e., the bipyridines and the imidazole and benzimidazole derivatives, interest in revising our therapeutic approach to congestive heart failure has increased. This review discusses recent developments in this area.

Hunting poisons of the North Pacific Region.

The hunting poisons of the North Pacific region are discussed. The most important one used by the Ainu was based on Aconitum species (surku or suruku): on Hokkaido, to some extent A. japonicum Thumb. but probably mainly A. yezoense Nakai and A. sachalinense Fr. Schm.; on southern Sakhalin, perhaps A. fischeri Reichb., A. maximum Pall. ex DC., and/or A. sachalinense Fr. Schm.; and on the Kuril Islands, A. maximum Pall. ex DC. Poison from the Japanese stingray Dasyatis akajei (Müller et Henle) (aikor chiep) was also much used, alone or mixed with aconite, and was believed by some Ainu to be better than aconite. Adjuvants to these poisons were numerous and varied in each locality. Daphne kamtschatica Maxim. var. yezoensis (Maxim.) Ohwi (ketuhas) was used in hunting walrus. The use of Cynanchum caudatum (Miq.) Maxim. (penup) enabled birds to be caught. Juglans ailanthifolia Carr (nesko) was a fish poison. A critical evaluation of the accounts by Krasheninnikov, Steller, Harms, and others, indicates that the inhibitants of the Kamchatka Peninsula, the Kamchadal (Itelmen), hunted with a poison derived from Aconitum maximum Pall. ex DC. This same species was almost certainly used in the Aleutian Islands and the Kodiak Island region, principally for hunting whales. There is some evidence that the inhabitants of the far north-eastern part of Siberia and of the Alaskan coasts opposite may also have used poison in hunting. The chemistry and toxicology of the poisons are briefly considered.