Papaver somniferum in seventeenth century (Italy): archaeotoxicological study on brain and bone samples in patients from a hospital in Milan

Abstract

In this paper, we present the results of toxicological analyses of preserved brain tissue and bone samples from the remains of the seventeenth century patients of the Ospedale Maggiore, the main hospital in Milan and one of the most innovative hospitals in Europe from the Renaissance period. Beneath it, the crypt functioned as the burial place for the deceased of the hospital. In this multidisciplinary study of the remains, toxicological analyses in particular were performed with HPLC-MS/MS on different biological samples from nine individuals. Anthropological, paleopathological, histological, radiological examinations and radiocarbon dating were also carried out. As a result, archeotoxicological analyses revealed the presence of codeine, morphine, noscapine and papaverine, derived from Papaver somniferum, a plant present in the hospital pharmacopeia used as a narcotic, analgesic, astringent, coagulant, and antitussive agent. Such analyses have shed light on the pharmacological therapies administered to the patients near the time of death and have implemented our knowledge of medical treatment and drug administration in the 1600's.

Figure 1

Signs of tertiary syphilis on cranium MI CG 21 O-US 4-I 39 (red arrow), both photographs and CT image.

Figure 2

(a) Left lateral view of cranium MI CG 21 O-US 4-1003. Ante-mortem trauma of the left parietal bone (arrow), followed probably by trepanation and long term healing; (b) superior-lateral view of ante-mortem trauma on cranium MI CG 21 O-US 4-1003.

Figure 3

Radiological imaging of MI CG 21 O-US 4-1003. From (a–h), left lateral view of cranium. (a) X-rays imaging (green arrow: ante-mortem trauma). (b) CT image without signs of antemortem trauma. From (c–g), CT images of antemortem trauma probably followed by trepanation on left parietal bone. (h) CT image without signs of antemortem trauma. (i) Three-dimensional representation of cranium from superior lateral view of the left side.

Figure 4

Chromatographic spectrum (upper lane) and mass spectral ion ratio (lower lane) of morphine detected in C4.

Figure 5

Chromatographic spectrum (upper portion) and mass spectral ion ratio (bottom portion) of codeine detected in PBT5.

Figure 6

Chromatographic spectrum (upper raw) and mass spectral ion ratio (lower portion) of papaverine detected in C3.

Figure 7

Chromatographic spectrum (upper portion) and mass spectral ion ratio (bottom raw) of noscapine detected in PBT1.

Figure 8

Preserved brain tissue referred to cranium MI CG 21 O-US4-155.

Figure 9

Sampling sites of brain MI CG 21 O-US4-1000 for histological investigation. Square named as 1 referred to the frontal cortex; square labeled as 2 was the occipital brain area, and square called 3 referred to parietal brain area.