Arsenic, Familicide, and Female Physiology in Nineteenth-Century America.

Sarah Jane Whiteling was accused of fatally poisoning her husband and two children in Philadelphia in 1888. The case prompted public outrage over the appearance that Ms. Whiteling's motive was to collect life insurance. It was evident, however, that she was disturbed, raising a question of culpability. Dr. Alice Bennett, the first female physician in charge of an asylum, provided the defense with expert testimony on the defendant's mental state. Dr. Bennett, who had little forensic but much clinical experience, proposed a physiological theory of insanity among women with reproduction-related derangements. At that time, cultural ideas about "female poisoners" colored popular and journalistic perceptions of Ms. Whiteling. Familicide was considered unconscionable because a mother's duty was to nurture and protect her family. When Ms. Whiteling was convicted and sentenced to death, Dr. Bennett undertook a campaign for commutation. Her unsuccessful efforts to reduce culpability were followed by Ms. Whiteling's hanging in 1889, the first execution of a woman in Philadelphia since colonial times. This article recounts the Whiteling case, Dr. Bennett's involvement in it, and how it relates to what is known about familicide. It is argued here that Dr. Bennett was a pioneer in applying medical expert testimony to effect individualized mitigation.

Poisoning histories in the Italian renaissance: The case of Pico Della Mirandola and Angelo Poliziano.

Giovanni Pico della Mirandola and Angelo Poliziano were two of the most important humanists of the Italian Renaissance. They died suddenly in 1494 and their deaths have been for centuries a subject of debate. The exhumation of their remains offered the opportunity to study the cause of their death through a multidisciplinary research project. Anthropological analyses, together with documentary evidences, radiocarbon dating and ancient DNA analysis supported the identification of the remains attributed to Pico. Macroscopic examination did not reveal paleopathological lesions or signs related to syphilis. Heavy metals analysis, carried out on bones and mummified tissues, showed that in Pico's remains there were potentially lethal levels of arsenic, supporting the philosopher's poisoning theory reported by documentary sources. The arsenic concentrations obtained from analysis of Poliziano's remains, are probably more related to an As chronic exposure or diagenetic processes rather than poisoning.

Long-term neurological and neuropsychological complications of sulfur mustard and Lewisite mixture poisoning in Chinese victims exposed to chemical warfare agents abandoned at the end of WWII.

In August 2003, 44 victims were poisoned by chemical warfare agents (CWAs) leaked from five drums that were excavated at a construction site in Qiqihar, Northeast China. The drums were abandoned by the former Japanese imperial army during World War II and contained a mixture of Sulfur mustard (SM) and Lewisite. We carried out a total of six regular check-ups between 2006 and 2014, and from 2008 we added neurological evaluations including neuropsychological test and autonomic nervous function test in parallel with medical follow-up as much as was possible. Severe autonomic failure, such as hyperhidrosis, pollakiuria, diarrhoea, diminished libido, and asthenia appeared in almost all victims. Polyneuropathy occurred in 35% of the victims and constricted vision occurred in 20% of them. The rates of abnormal response on cold pressor test (CPT), active standing test (AST), Heart rate variability (CVR-R), performed in 2014, were 63.1%, 31.6%, and 15.9%, respectively. On neuropsychological testing evaluated in 2010, a generalized cognitive decline was observed in 42% of the victims. Memories and visuospatial abilities were affected in the remaining victims. Finally, a 17-item PTSD questionnaire and the Beck Depression Inventory evaluated in 2014 revealed long-lasting severe PTSD symptoms and depression of the victims. Our findings suggest that an SM/Lewisite compound have significant adverse consequences directly in cognitive and emotional network and autonomic nervous systems in the brain.

The history of arsenical pesticides and health risks related to the use of Agent Blue.

Arsenicals in agriculture. Beginning in the 1970s, the use of arsenic compounds for such purposes as wood preservatives, began to grow. By 1980, in the USA, 70% of arsenic had been consumed for the production of wood preservatives. This practice was later stopped, due to the US Environmental Protection Agency (EPA) ban of the arsenic-and chromium-based wood preservative chromated copper arsenate. In the past, arsenical herbicides containing cacodylic acid as an active ingredient have been used extensively in the USA, from golf courses to cotton fields, and drying-out the plants before harvesting. The original commercial form of Agent Blue was among 10 toxic insecticides, fungicides and herbicides partially deregulated by the US EPA in February 2004, and specific limits on toxic residues in meat, milk, poultry and eggs, were removed. Today, however, they are no longer used as weed-killers, with one exception - monosodium methanearsonate (MSMA), a broadleaf weed herbicide for use on cotton. Severe poisonings from cacodylic acid caused headache, dizziness, vomiting, profuse and watery diarrhea, followed by dehydration, gradual fall in blood pressure, stupor, convulsions, general paralysis and possible risk of death within 3-14 days.The relatively frequent use of arsenic and its compounds in both industry and agriculture points to a wide spectrum of opportunities for human exposure. This exposure can be via inhalation of airborne arsenic, contaminated drinking water, beverages, or from food and drugs. Today, acute organic arsenical poisonings are mostly accidental. Considerable concern has developed surrounding its delayed effects, for its genotoxic and carcinogenic potential, which has been demonstrated in epidemiological studies and subsequent animal experiments. Conclusions. There is substantial epidemiological evidence for an excessive risk, mostly for skin and lung cancer, among humans exposed to organic arsenicals in occupational and environmental settings. Furthermore, the genotoxic and carcinogenic effects have only been observed at relatively high exposure rates. Current epidemiological and experimental studies are attempting to elucidate the mechanism of this action, pointing to the question whether arsenic is actually a true genotoxic, or rather an epigenetic carcinogen. Due to the complexity of its effects, both options remain plausible. Its interactions with other toxic substances still represent another important field of interest.

Managing uncertainty in the academy and the courtroom: normal arsenic and nineteenth-century toxicology.

This essay explores how the enhanced sensitivity of chemical tests sometimes produced unforeseen and puzzling problems in nineteenth-century toxicology. It focuses on the earliest uses of the Marsh test for arsenic and the controversy surrounding "normal arsenic"--that is, the existence of traces of arsenic in healthy human bodies. The essay follows the circulation of the Marsh test in French toxicology and its appearance in the academy, the laboratory, and the courtroom. The new chemical tests could detect very small quantities of poison, but their high sensitivity also offered new opportunities for imaginative defense attorneys to undermine the credibility of expert witnesses. In this context, toxicologists had to dispel the uncertainty associated with the new method and come up with arguments to refute the many possible criticisms of their findings, among them the appeal to normal arsenic. Meanwhile, new descriptions of animal experiments, autopsies, and cases of poisoning produced a steady flow of empirical data, sometimes supporting but in many cases questioning previous conclusions about the reliability of the chemical tests. This challenging scenario provides many clues about the complex interaction between science and the law in the nineteenth century, particularly how expert authority, credibility, and trustworthiness were constructed, and frequently challenged, in the courtroom.

Arsenic exposure and toxicology: a historical perspective.

The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.

The medical mystery of Napoleon Bonaparte: an interdisciplinary exposé.

Napoleon Bonaparte (1769 to 1821) is one of the most studied historical figures in European history. Not surprisingly, amongst the many mysteries still surrounding his person is the cause of his death, and particularly the suspicion that he was poisoned, continue to intrigue medical historians. After the defeat of the Napoleonic Army at the battle of Waterloo in 1815, Napoleon was exiled to the small island of Saint Helena in the South Atlantic, where he died 6 years later. Although his personal physician, Dr François Carlo Antommarchi, stated in his autopsy report that stomach cancer was the cause of death, this diagnosis was challenged in 1961 by the finding of an elevated arsenic concentration in one of Napoleon's hair samples. At that time it was suggested that Napoleon had been poisoned by one of his companions in exile who was allegedly supported by the British Government. Since then Napoleon's cause of death continues to be a topic of debate. The aim of this review is to use a multidisciplinary approach to provide a systematic and critical assessment of Napoleon's cause of death.

[Spina bifida occulta associated with environmental arsenic exposure in a prehispanic sample from northern Chile]. / Evaluación de la frecuencia de espina bífida oculta y su posible relación con el arsénico ambiental en una muestra prehispánica de la Quebrada de Camarones, norte de Chile.

BACKGROUND: The Camarones River Valley, located in the extreme north of Chile, is characterized by high environmental arsenic levels and an arid desert. It has been inhabited by humans for the past 7,000 years. Evidence exists for chronic arsenic poisoning in both prehispanic and present populations residing in the area. Chronic arsenic exposure causes multi-systemic problems and can induce congenital malformations, in particular neural tube development defects such as spina bifida. AIM: To study the prevalence of spina bifida among prehispanic mummies of the area. MATERIAL AND METHODS: One hundred and twenty prehistoric adult individuals were analyzed for evidence of spina bifda occulta of the sacrum in skeletal samples from the sites of Camarones 8, Camarones 9, Azapa 140 and Lluta 54, held in repository at the Museo Universidad de Tarapacá de Arica- San Miguel de Azapa. A diagnosis was considered positive when at least S1, S2 or S3 were affected. As controls, mummies of individuals that resided in Lluta and Azapa valley, with a low arsenic exposure, were analyzed. RESULTS: The frequency of spina bifida occulta among samples from the Camarones coast and Lluta and Azapa Valley were 13.5 and 2.4% respectively. CONCLUSIONS: Considering these were contemporaneous samples, and are believed to have had no other differences in diet or other factors, the differential exposures to arsenic could have produced the observed differences in spina bifida frequencies.

Evaluación de la frecuencia de espina bífida oculta y su posible relación con el arsénico ambiental en una muestra prehispánica de la Quebrada de Camarones, norte de Chile / Spina bifida occulta associated with environmental arsenic exposure in a prehispanic sample from northern Chile

Background: The Camarones River Valley, located in the extreme north of Chile, is characterized by high environmental arsenic levels and an arid desert. It has been inhabited by humans for the past 7,000 years. Evidence exists for chronic arsenic poisoning in both prehispanic and present populations residing in the area. Chronic arsenic exposure causes multi-systemic problems and can induce congenital malformations, in particular neural tube development defects such as spina bifda. Aim: To study the prevalence of spina bifda among prehispanic mummies of the area. Material and Methods: Onehundred and twenty prehistoric adult individuals were analyzed for evidence of spina bifda occulta of the sacrum in skeletal samples from the sites of Camarones 8, Camarones 9, Azapa 140 and Lluta 54, held in repository at the Museo Universidad de Tarapacá de Arica- San Miguel de Azapa. A diagnosis was considered positive when at least S1, S2 or S3 were affected. As controls, mummies of individuals that resided in Lluta and Azapa valley, with a low arsenic exposure, were analyzed. Results: The frequency of spina bifda occulta among samples from the Camarones coast and Lluta and Azapa Valley were 13.5 and 2.4 percent respectively. Conclusions: Considering these were contemporaneous samples, and are believed to have had no other differences in diet or other factors, the differential exposures to arsenic could have produced the observed differences in spina bifda frequencies.

Metallurgy, environmental pollution and the decline of Etruscan civilisation.

BACKGROUND, AIM AND SCOPE: The Etruscans were justifiably famous in antiquity for their advanced metallurgy and for the rich mineral resources of their region (including La Tolfa, the Colline Metallifere, Mont'Amiata and Elba). We offer a new perspective on certain Iron Age and Archaic (ca. 1,000-480 BC: ) Etruscan industrial and habitation sites, and on the problem of heavy metal poisoning, still being investigated today, coincidentally in some of the same areas that originally saw Etruscan mines and workshops. MATERIALS AND METHODS: This study investigates ancient sources, including literature and excavation reports, in the light of modern studies of heavy metal poisoning on human beings, plant and animal life. Furthermore, it is the first to use non-invasive Niton X-ray fluorescence analysis of samples of Etruscan (strictly ethnically Faliscan) hair (c. 350 BCE: ). RESULTS: The findings show the strong likelihood of heavy metal poisoning in areas of Etruscan metallurgical activity with the effects of this being responsible for or contributing to the abandonment of a number of these sites around the 6th century BC: . No thoroughly satisfactory explanation of this phenomenon has previously been offered. However, findings suggest that Faliscan women, represented by sample CG 2004-6-2, were not exposed to high levels of arsenic in life, which is not perhaps surprising for an urban aristocratic woman of the mid-4th century BC: . DISCUSSION: The reasons for the abandonment of several flourishing settlements are without doubt complex, and include political and social change. We suggest heavy metal contamination as an additional stimulus to the noted phenomenon of the peaceful abandonment, at the beginning, and at the end of the 6th century BC: , of sites in southern and northern Etruria such as Marsiliana d'Albegna (late 7th c.), Lago dell'Accesa, Acquarossa and Poggio Civitate-Murlo (late 6th c.). CONCLUSIONS: While the historical truth of the demise of Etruscan civilisation is much more complex, an interim set of related events, the desertion of several important settlements during and at the end of the Archaic period, might actually have been stimulated by the consequences of industrial pollution and arsenic poisoning. RECOMMENDATIONS AND PERSPECTIVES: We call for archaeologists and curators to test any available human and animal remains in their museums and collections for evidence of heavy metal poisoning, taking due caution and consideration of course to the relevance of the aristocracy, and urge the application of analytical techniques developed in response to this serious modern problem, to provide additional insights into the ancient situation.

Multielemental analysis of tissues from Cangrande della Scala, Prince of Verona, in the 14th century.

Cangrande della Scala, Prince of Verona (Italy), died suddenly shortly after his triumph in the battle of Treviso (July 18, 1329). Thus, in the frame of a multidisciplinary paleo-pathological study, we carried out a multielemental analysis on the Prince's tissue specimens, including hair, liver, muscle, and bone, in order to characterize a multitissue profile of metallic elements in a nobleman of the 14th century. Biological specimens were analyzed by inductively coupled plasma-mass spectrometry. We were able to rule out arsenic poisoning as the primary cause of death. High levels of gold and silver in both hair and liver samples were probably due to prolonged contact of the mummy with precious metals in the funeral garments. High lead concentrations in both liver and bone tissue can be traced back to the ingestion of contaminated food and alcoholic beverages. Most of the essential elements were in the normal range of values for contemporary living people. The low arsenic and chromium levels in the Prince's tissues as compared to modern people would be suggestive of raised concentrations of both the elements in the present era, which are likely due to industrial pollution.

Arsenic: a beneficial therapeutic poison - a historical overview.

Arsenicals have been used since ancient Greek and Roman civilizations and in the Far East as part of traditional Chinese medicine. In Western countries, they became a therapeutic mainstay for various ailments and malignancies in the 19th and early 20th centuries. Fowler's potassium bicarbonate-based solution of arsenic trioxide (As2O3)solution was the main treatment of chronic myeloid leukaemia until the 1930s. After a decline in the use of arsenic during the mid-20th century, arsenic trioxide was reintroduced as an anticancer agent after reports emerged from China of the success of an arsenic trioxide-containing herbal mixture for the treatment of acute promyelocytic leukaemia. Arsenic trioxide was first purified and used in controlled studies in China in the 1970s.Subsequently, randomised clinical trials performed in the United States led to FDA approval of arsenic trioxide in the treatment of patients with relapsed or refractory acute promyelocytic leukaemia.

Arsenic in food and water--a brief history.

Arsenic has been used for millenia. Although it has been known for many years that arsenic is soon fatal when ingested at high doses, the effects of low dosages became apparent in the 1980s. The full societal implications are only now becoming clear. It is now known to pose the highest calculated risk of any substance regulated by the US Environmental Protection Agency (EPA); high concentrations have been found in drinking water in many countries. In Bangladesh, in particular, the number of people suffering from over exposure vastly exceeds the number affected by the catastrophic accident at Chernobyl. This article shows the development of the human understanding about chronic arsenic poisoning with Bangladesh as a particular example.