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Handbook on Opium
This page intentionally left blank
Handbook on Opium
History and Basis of Opioids in Therapeutics

Vasantha K. Kumar, MD
Delta Pain Consultants, Columbus, OH, United States
Academic Press is an imprint of Elsevier
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as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our
understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any
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The illustration shows three legendary figures in medicine (from left to right): Apollo holding a bow, Aesculapius holding
a serpent-entwined staff, and Hippocrates holding a skull and all three examining a poppy plant. Putti at the steps hold
Materia Medica and a box of various chemicals, while the section on the right shows drugs being produced in the labora-
tory. Oil painting by Johannes Prey (c. 1791 CE) from Wellcome Collection. https://wellcomecollection.org/works/ju4rytva

v
This page intentionally left blank
 Dedication

To my parents, Sara and Kay, for the trail

To my wife Jo and son Barrett for the journey
This page intentionally left blank
Contents

About the Author xiii 3.2 Ancient Egypt 22

Preface xv 3.2.1 Cultivation of poppy 22
Acknowledgments xvii 3.2.2 Papyrus of Ebers 23
3.3 Classical history 24
3.3.1 Hippocrates of Cos 25
Part I 3.3.2 Theophrastus 27
3.3.3 Mithridates of Pontus 28
Plant 3.4 Dawn of common era 29
3.4.1 Scribonius 29
1. Botanical aspects 3.4.2 Celsus 29
1.1 Plant 3 3.4.3 Pliny the Elder 30
1.1.1 Overview 3 3.4.4 Dioscorides 32
1.1.2 Cultivation 3 3.4.5 Galenus 33
1.2 Latex 4 3.5 Synopsis 35
1.2.1 Laticifers 4 References 35
1.2.2 Capsule 5
1.2.3 Extraction of opium 7
4. Postclassical history
1.3 Opium alkaloids 8
1.3.1 Poppy sources 8 4.1 Late Antiquity 39
1.3.2 Nonpoppy sources 9 4.2 Islamic Renaissance 40
1.4 Synopsis 9 4.2.1 Medical glossators 40
References 9 4.2.2 Rhazes 42
4.2.3 Age of addiction 43
4.2.4 Avicenna 44
Part II 4.3 Eastern opium 46
History 4.4 Synopsis 46
References 47
2. Prehistory
2.1 Paleobotanical evidence 13 5. Modern history
2.2 Archaeological evidence 14
5.1 European Renaissance 49
2.2.1 Early humans 14
5.1.1 Paracelsus 49
2.2.2 Artifacts 14
5.1.2 Early theories on opium 50
2.3 Genetic evidence 14
5.2 Early modern 51
2.3.1 Origins of poppy 14
5.2.1 Thomas Sydenham 51
2.3.2 Spread of poppy 15
5.2.2 Opiologia 52
2.4 Evolutionary milestones 16
5.2.3 Thomas Dover 52
2.5 Synopsis 16
5.2.4 Opium experiments 53
References 17
5.3 Opium intemperance 54
5.3.1 Opium romantics 54
3. Ancient history 5.3.2 OTC opium 54
3.1 Opium in antiquity 19 5.4 Opium in the East 54
3.1.1 Mesopotamia 19 5.4.1 Opium in China 54
3.1.2 Clay tablets of Nineveh 21 5.4.2 Opium in India 55

ix
x Contents

5.5 Late modern 55 9. Opioids

5.6 First opioid epidemic 57
5.7 Chronology of opium 60 9.1 The family 99
5.8 Synopsis 60 9.1.1 Structure of morphinans 99
References 60 9.1.2 Chemical classes of opioids 99
9.2 Structure-activity relationships 99
9.2.1 Phenanthrenes 100
6. Contemporary history
9.2.2 Piperidines 102
6.1 Wars and anesthesia 63 9.2.3 Diphenylheptanes 102
6.1.1 Wars and opium 63 9.2.4 Benzomorphans 103
6.1.2 Opium and surgery 63 9.3 Common opioids 103
6.2 Second opioid epidemic 64 9.3.1 Diacetyl morphine 103
6.3 Synopsis 66 9.3.2 Codeine and hydrocodone 103
References 66 9.3.3 Oxycodone 103
9.3.4 Meperidine 103
9.3.5 Fentanyl 103
Part III 9.3.6 Methadone 104
9.3.7 Buprenorphine 104
Trade 9.3.8 Nalorphine 104
9.3.9 Naloxone 105
7. Business of opium 9.3.10 Naltrexone 105
7.1 Before Common Era 71 9.4 Unique formulations 105
7.2 Religion, free trade, and 9.4.1 Extended release 105
colonialism 71 9.4.2 Abuse deterrent 105
7.2.1 Indian opium 71 9.4.3 PAMORA 106
7.2.2 Chinese opium 74 9.4.4 Novel synthetics 106
7.2.3 Opium Wars 75 9.5 Milestones in opioid synthesis 106
7.2.4 Other opium 77 9.6 Synopsis 106
7.3 Commercialization 78 References 106
7.4 Licit trade 79
7.5 Illicit trade 80
7.6 Legislation 82 Part V
7.6.1 International efforts 83
7.6.2 Efforts in the United States 83
Molecular basics
7.6.3 Future perspectives 85
7.7 Synopsis 85
10. Receptors
References 85 10.1 Overview 111
10.1.1 Discovery 111
10.1.2 Receptor diversity 111
Part IV 10.1.3 Opioid genes 112
10.2 Endogenous opioid peptides 113
Alkaloids 10.3 Opioid receptor terminology 114
10.4 Ligand characteristics 114
8. Opiates 10.4.1 Message-address sequence 114
8.1 Discovery 91 10.4.2 Agonist/antagonist 115
8.2 Synthesis 93 10.5 Receptor structure 115
8.2.1 Extraction 93 10.5.1 Structural basics 116
8.2.2 Biosynthetic pathway 93 10.5.2 Binding pocket 116
8.3 Opium alkaloids 94 10.5.3 Orthosteric and allosteric sites 116
8.3.1 Major alkaloids 95 10.6 Kinetics of conformational changes 117
8.3.2 Minor alkaloids 96 10.7 Distribution of opioid receptors 119
8.4 Synopsis 96 10.7.1 Central distribution 119
References 96 10.7.2 Peripheral distribution 120
 Contents xi

10.8 Milestones 120 13.3 Transmission pathways 148

10.9 Synopsis 120 13.3.1 Peripheral nerves 148
References 121 13.3.2 Dorsal root ganglion 149
13.3.3 Dorsal horn 149
11. Effectors 13.3.4 Ascending fibers 151
13.3.5 Descending fibers 152
11.1 Overview 125
13.4 Perception and modulation 152
11.2 Heterotrimeric G proteins 125
13.4.1 Supraspinal mechanisms 152
11.2.1 Structure 125
13.4.2 Spinal modulation 153
11.2.2 Basal coupling with GPCR 126
13.5 Opioid analgesia 153
11.3 G protein/GPCR complex 126
13.5.1 Supraspinal and spinal
11.3.1 Activation 126
mechanisms 153
11.3.2 Termination of action 127
13.5.2 Molecular mechanisms 154
11.4 G protein-dependent pathways 127
13.6 Synopsis 154
11.4.1 Adenylyl cyclase and Gα
References 154
pathways 128
11.4.2 Effectors of Gβγ subunit 129
11.5 G protein-independent pathways 130 14. Adverse effects
11.5.1 Structure of arrestins 130 14.1 Overview 157
11.5.2 Arrestin-mediated pathways 131 14.2 Respiratory 157
11.5.3 Receptor trafficking 132 14.2.1 Respiratory control 157
11.6 Molecular mechanisms of opioid 14.2.2 Opioid-induced respiratory
effects 132 depression 158
11.6.1 Gα effects 133 14.3 Gastrointestinal 158
11.6.2 Gβγ effects 133 14.3.1 Opioid receptors and bowel
11.6.3 Arrestin effects 133 control 158
11.6.4 Heterologous sensitization 133 14.3.2 Opioid-induced bowel
11.6.5 Effector pathways database 134 dysfunction 158
11.7 Synopsis 134 14.3.3 Nausea and vomiting 159
References 134 14.4 Integumentary 159
14.4.1 Pruritus 159
14.5 Genitourinary 159
Part VI 14.5.1 Urinary retention 159
Benefits and harms 14.5.2 Sexual dysfunction 160
14.6 Neurological 160
12. Metabolism 14.6.1 Cognitive effects and
sedation 160
12.1 Overview 139 14.6.2 Myoclonus and seizures 160
12.1.1 Receptor-specific functions 139 14.6.3 Sleep disruption 161
12.1.2 Systemic effects 139 14.7 Cardiovascular 161
12.1.3 Supraspinal effects 139 14.7.1 Opioid receptors in
12.1.4 Spinal and peripheral effects 139 cardiovascular function 161
12.2 Opioid metabolism 141 14.7.2 Arrhythmogenesis 161
12.2.1 Absorption 141 14.7.3 Cardioprotective functions 161
12.2.2 Distribution 141 14.8 Endocrine and reproductive 162
12.2.3 Metabolism 142 14.8.1 Effects on HPG axis 162
12.2.4 Elimination 144 14.8.2 Effects on HPA axis 162
12.3 Synopsis 144 14.9 Mood disorders 163
References 145 14.10 Neuroinflammation 163
14.11 Angiogenesis and tumorigenesis 164
13. Analgesia 14.12 Tolerance 165
13.1 Overview of pain 147 14.12.1 Overview 165
13.2 Nociceptors 147 14.12.2 Mechanisms 166
xii Contents

14.13 Withdrawal 166 15.7 Other issues 195

14.13.1 Overview 166 15.7.1 Overdose 195
14.13.2 Mechanisms 167 15.7.2 Neonatal opioid withdrawal
14.14 Opioid-induced hyperalgesia 167 syndrome 196
14.14.1 Overview 167 15.7.3 Falls and crashes 196
14.14.2 Mechanisms 168 15.7.4 Infection 196
14.15 Dependence 170 15.8 Synopsis 196
14.15.1 Overview 170 References 197
14.15.2 Mechanisms 170
14.16 Other adverse effects 172 16. Advances and prospects
14.17 Synopsis 172
References 172 16.1 Opium production 205
16.1.1 Breeding techniques 205
16.1.2 Metabolic genetic engineering 205
Part VII 16.2 Overview of therapeutic advances 206
Therapeutic utility 16.3 Abuse-deterrent formulations 206
16.4 Peripheral selectivity 207
16.4.1 Peripheral receptors 207
15. Uses and issues
16.4.2 Nanocarrier delivery 208
15.1 Opioids in therapeutics 181 16.4.3 pH-dependent activation 208
15.2 Therapeutic principles 181 16.5 Molecular targets 208
15.2.1 Utility and safety 181 16.5.1 Overview 208
15.2.2 Relative potency and equivalence 182 16.5.2 Modification of endogenous
15.3 Therapeutic predicament 184 opioids 209
15.4 Acute pain 185 16.5.3 Multifunctional ligands 209
15.4.1 Perioperative use 185 16.5.4 Allosteric modulation 210
15.4.2 Nonsurgical use 186 16.5.5 Biased agonism 210
15.5 Chronic pain 187 16.5.6 Nonopioid receptor targets 211
15.5.1 Taxonomy 187 16.5.7 Receptor-independent selective
15.5.2 Chronic cancer pain 188 modulators 214
15.5.3 Chronic noncancer pain 189 16.6 Gene therapy 215
15.6 Opioid use disorder 192 16.7 Synopsis 215
15.6.1 Taxonomy 192 References 215
15.6.2 Medical use of opioids 193
15.6.3 Nonmedical use of opioids 193
15.6.4 Treatment of dependence 193
15.6.5 Guidelines 195 Index 221
About the Author
Vasantha K. Kumar, MD, completed medical school
at Madurai Medical College, Madurai, India, and served
for five years as Captain in Army Medical Corps. After
this tenure, he earned MD in Aerospace Medicine in
1986 from the Indian Air Force Institute of Aerospace
Medicine, Bangalore, India. He was National Research
Council Research Fellow at NASA Johnson Space Center,
Houston, Texas, from 1988 to 1990 and conducted human
trials on decompression sickness supporting extravehicu-
lar activities for the Space Shuttle program. He continued
this research as Supervisor of Environmental Physiology
Laboratory with a subcontractor at NASA Johnson Space
Center, Houston, Texas, until 1996. He later completed
an anesthesiology residency at the University of Texas,
Galveston, Texas, in 2000 and a pain medicine fellowship
at the University of Cincinnati, Cincinnati, Ohio, in 2001.
Since then, he has practiced comprehensive pain care in
various clinical settings.
Dr. Kumar has authored or presented more than 70 pa-
pers on topics such as decompression sickness, historical
perspectives, and chronic pain. He was awarded the “Silver
Snoopy” medal in 1996 by NASA astronauts for his con-
tribution to the Space Shuttle program. He also served on
the Editorial Board of the journal Aviation, Space, and
Environmental Medicine between 1996 and 1998. He is
Board Certified in Anesthesiology and Pain Medicine from
the American Board of Anesthesiology and a member of
several professional organizations. In addition to his profes-
sional activities, Dr. Kumar has a special interest in histori-
cal biographies and epistemology.
xiii
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Preface
Those about to study medicine, and the younger Physicians,
should light their torches at the fires of the Ancients.
Carl von Rokitansky (c. 1846 CE)
Opium has always held a polysemic relationship and sig-
nificance in society. One of the earliest known drugs in the
history of humanity, its use has spanned contexts, cultures,
and continents across the globe. From the earliest find in
the funerary sites of Europe, it has proven to be a dominant
sociocultural factor in medicine, geopolitics, and economy.
Cautiously advocated by Hippocrates and ardently favored
by great minds such as Galen, Avicenna, and Paracelsus,
and commodified by colonial interests, opium has always
evoked dualistic attributes of remedy and poison in history.
After Serturner’s discovery of morphine almost
200 years ago, unbridled enthusiasm and use resulted in
the first opioid epidemic during the Industrial Age. Global
antiopium movement of this period assigned stricter con-
trols and limited use of opioids in medicine. Since then, a
quest for enhancing remedial effects of opium poppy has
thrust research on poppy and its products to a higher level,
unimagined by polymaths of the bygone era. Our compre-
hension of the plant and its potential has grown leaps and
bounds over the past century, and it is difficult to keep pace
with the flood of information. However, the use of opioids
for chronic pain in the 20th century, in its characteristic du-
alism, has either endorsed or queried its use during the cur-
rent opioid epidemic.
Aware of public health emergency during the current
opioid epidemic, I focused on doing the right thing by im-
plementing guidelines proffered by medical societies and
regulatory bodies that I only vaguely acknowledged histori-
cal events. About 5 years ago, I stumbled upon a book that
was tucked behind the counter in a dingy little bookstore
at the airport, where I was waiting for my flight home. The
book that piqued my interest, A Concise History of Hong
Kong by John Carroll (Rowman & Littlefield Publishers,
Inc., 2007), recounts the history of Hong Kong Island from
its tumultuous founding to its emergence as a major finan-
cial center of the East. I was thrilled with what the book had
to offer and sat wide-eyed through the long flight. I was fas-
cinated, but nescient, about the turn of events in the glorious
age of sail and the ignominious basis for this critical piece
of history—opium. It was a fortuitous moment, as it set me
on a quest to learn and retell the history of poppy as it was
scripted over the years.
Many therapeutic dilemmas posed by opioid use during
the current epidemic are not new, as these issues have chal-
lenged physicians for centuries. Ironically, several factors
that led to the first opioid epidemic of the Industrial Age
share common features with the second opioid epidemic of
modern times. However, we missed the opportunity to learn
from historical works and events while getting mired in de-
tails of the current opioid epidemic. As I waded through his-
torical documents on opium, I realized that history has the
answers to provide perspectives for research, therapeutics,
and policy-making for the future.
I must admit that I am neither a historian nor a linguist,
and my medical training stopped short of educating me on
drugs, “guidelines,” and how to use them in practice. This
book is an effort to bridge history and therapeutics. This book
trails poppy from prehistory to present history, as advocated,
analyzed, and advanced by the great minds in medicine. As
such, it is a synthesis of botany, chemistry, physiology, and
molecular biology interlaced with historical vignettes in the
spirit of great encyclopedists before me.
What started as a venture of self-education in history led
to a more complex palimpsest that poppy truly is. I have at-
tempted to present readers with a comprehensive knowledge
base on opium poppy, starting with the plant, its history, com-
merce, medical use, current status, and future perspectives.
It is my fervent hope that this endeavor serves as a resource
for anyone wishing to explore the world of opium poppy or at
least awakens interest in history as it has done for me.
Proceed then as you have begun.
Robert Brady (c. 1670 CE) in “Epistle to Thomas Sydenham”
Vasantha K. Kumar
Columbus, OH, United States
xv
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Acknowledgments
This work is a tribute to the deliberations of numerous
protagonists and adversaries, struggles of transcribers and
glossators, and trials and labors of those researchers on
opium throughout history. Pictures tell stories better than
words, and I would like to acknowledge the contribution
by public domain figures and open source articles from
the United States National Library of Medicine, RCSB
Protein Data Bank, GPCRdb, Reactome, Wikimedia,
Wellcome Collection, and numerous other institutions.
All illustrations in this book are by the author, unless
otherwise indicated. This compilation is a work of
passion and personal endeavor, and the author received
no financial support for research, authorship, graphics,
drafting, and/or publication of this book. Particular
thanks are due to my team at Elsevier for bringing this
project to fruition.
xvii
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Part I

Plant
This page intentionally left blank
Chapter 1
Botanical aspects
And he bowed his head to one side like a poppy that in a garden is
laden with its fruit and the rains of spring.
Homer in Iliad (c. 630 BCE)
1.1 Plant
1.1.1 Overview
Plants included in the family Papaveraceae are a group
of herbaceous flowering plants found primarily in the
Northern Hemisphere, which prefer a temperate climate
and have more than 100 subspecies. However, Papaver
(Latin: poppy) is also cultivated in some tropical areas
in the Southern Hemisphere. Many varieties grow in the
wild, including Poppy of Troy, Papaver setigerum (Latin:
bristly), some plants like Papaver rhoeas (Greek: red or
to fall) are grown for ornamental purposes, and Papaver
somniferum (Greek: to induce sleep) is the only species
acclaimed as a distinctive medicinal plant for pain relief
and maligned as the source of addictive drug all over the
world.
1.1.2 Cultivation
Papaver is a self-pollinating, multipurpose species. It is a
valuable food source for humans and also serves as animal
fodder (Bernath, 1998; Duke, 1983; Kapoor, 1995; Lim,
2013). It has a glaucous stem, sessile leaves with dentate
margins with peduncle, and drooping buds (Fig. 1.1). Poppy
flowers come in various shades of color, including white,
pink, violet, and red.
After poppy blooms, leaves fall within a week, and a
poppy pod or a capsule with its characteristic calyces forms
a prominent part of the plant (Fig. 1.2). The capsule size
may vary depending on the cultivar and geographical distri-
bution, from broad oval to cylindrical.
Poppy seeds are the most edible part of the plant and
kidney shaped and also vary in color from gray, white
to blue. They are usually harvested after the poppy cap-
sule has dried out, and they are used as a food additive to
Handbook on Opium. https://doi.org/10.1016/B978-0-323-90903-7.00018-1
Copyright © 2022 Elsevier Inc. All rights reserved.
provide texture, flavor, and caloric value (100 g of poppy
seeds provides approximately 500 cal). The seeds contain
linoleic acid (up to 60%) and are a great source of calcium,
niacin, thiamine, and tocopherols (Knutsen et al., 2018).
Poppy seed oil can be used without refining for cooking,
lubrication, or lamps, where they burn longer and cleaner
than olive oil. Poppy seed oil is expensive; its production
slowly reduced in the late 18th century, after which it was
completely stopped.
The vegetation period of cultivated poppy varies from
region to region, from 120 to 250 days, based on agrotech-
nical methods used and whether sown in spring or fall.
It is usually cultivated by the end of the rainy season in
Southeast Asia (Fig. 1.3). Usually, about a pound of poppy
seeds is required to sow one acre of land (Drug Enforcement
Administration (DEA), 1992).
Six distinct developmental stages are observed in the
growth of poppy (Bernath, 1998; Duke, 1983; Lim, 2013):
Phase 1: Embryo phase, when seeds are in the soil or
dormant (for up to 6 years).
Phase 2: Germination phase, when first leaves appear
(15–20 days).
Phase 3: Leaf rosette phase, the longest stage of leaf
formation (50–60 days for summer varieties and 180–
220 days for winter varieties).
Phase 4: Branching phase, lasts until blossoming
(20–30 days).
Phase 5: Blossoming and capsule formation phase, when
flowers bloom briefly for a day and green capsules take
another 10 days to mature (20–30 days).
Phase 6: Capsule ripening is the final phase when dry,
rattling poppy capsules are ready for seed harvesting
(15–25 days).
All phases of growth require careful tendering to en-
sure good capsule formation and may be adversely af-
fected at any stage by environmental factors such as light,
temperature, and moisture (Bernath, 1998). However, it
is labor-intensive once the capsule forms and is ready for
tapping.
3
4 PART | I Plant
FIG. 1.1 Poppy plant. Parts of Papaver somniferum by Otto Thome
(c. 1885 CE) including A, leaves; 1, longitudinal section of flower; 2,
­stamen; 3, pistil; 4, cross-section of ovary; 5, poppy capsule; 6, poppy
seeds. (Credit: Thome, O. W. (1885) from Wikimedia. https://commons.
wikimedia.org/wiki/File:Illustration_Papaver_somniferum0.jpg.)
FIG. 1.2 Green poppy capsule. Capsules may vary from oval to
cylindrical in shape. (Credit: Pixabay. https://pixabay.com/photos/
poppy-poppy-capsules-seeds-2502046/.)
1.2 Latex
1.2.1 Laticifers
Laticifers are an elongated, anastomosing network of cells
found in the cortex of the entire poppy plant from roots to
the capsule (Bird, Franceschi, & Facchini, 2003; Liscombe
& Facchini, 2008; Mahlberg, 1993). In the capsule, ­laticifers
are found within 2–4 cm of capsular surface (Fig. 1.4).
These laticifers are formed by resorption and coalescence
of cell walls, resulting in an elongated tubular system run-
ning throughout the plant.
It has been shown that biosynthetic enzymes are synthe-
sized in companion cells. They are then transported to sieve
elements where alkaloid biosynthesis occurs. Alkaloids of
poppy are stored as latex in vacuoles (Fig. 1.5), formed
from localized dilatation of endoplasmic reticulum within
the laticifer networks (Bercu, 2012; Lee, Hagel, & Facchini,
2013; Liscombe & Facchini, 2008). Latex particles of
opium alkaloids are suspended in these vacuoles (Fig. 1.6)
and located just below the capsular surface (Beaudoin &
Facchini, 2014; Griffing & Nessler, 1989; Nessler, Allen, &
Galewsky, 1985; Nessler & Mahlberg, 1976).
Modern techniques, such as immunofluorescent label-
ing, have enabled us to identify key enzymes in the bio-
synthesis of opium alkaloids. Furthermore, molecular
genetic techniques have aided in cell-specific localization
of alkaloid synthesis in Papaver somniferum (Beaudoin
& Facchini, 2014; Chalise, 2015; Liscombe & Facchini,
2008).
Results of these studies showed that synthesis of al-
kaloids of poppy occurs in the adjacent companion cells
and sieve elements and then they accumulate in latici-
fers (Bird et al., 2003; Harvest, 2011; Weid, Ziegler, &
Kutchan, 2004). It is difficult to produce morphine in
Papaver somniferum cell cultures, possibly due to the ab-
sence of a naturally occurring laticifer system in cultured
cells (Bird et al., 2003). Multiple levels of regulation ex-
ist in the synthesis of alkaloids from naturally occurring
amino acid l-tyrosine in the plant. Details of morphine
synthesis are dealt with in another section (please refer
to Section 8.3).
Box 1.1 Laticifer
Marcello Malpighi (1628–1694 CE), a renowned Italian
physician biologist (Fig. 1.7), called the milky latex exu-
date of plants “vasa propria.” His contemporary Nehemiah
Grew (1641–1712 CE), an English physician and the
“Father of Plant Anatomy” (Fig. 1.8), used a microscope to
describe the structure of the laticiferous system in plants,
which contain the milky sap, and also noted that this exu-
date coagulated (like blood) after extraction from the plant
(Arber, 1941).
 Botanical aspects Chapter | 1 5

RAINY SEASON COLD SEASON

Land
Prep Germination
15 days Leaf Rosette
60 days Branching
Flowering Capsule formation
30 days
30 days & ripening
30 days

FIG. 1.3 From cotyledons to capsules. Duration of each stage of growth varies depending on the subspecies, region, and environmental factors.

phloem
xylem

phloem

xylem

Current Opinion in Biotechnology

FIG. 1.4 Laticifers in poppy plant. Cross section of phloem shows pairing of laticifers (yellow), sieve elements, and companion cells (red) in aerial
parts, compared with roots of poppy. (With permission from Liscombe, D., & Facchini, P. (2008). Elsevier. https://doi.org/10.1016/j.copbio.2008.02.012.)

1.2.2 Capsule
Latex juice is found in all parts of the poppy plant, with
the highest concentration in the capsule, while its pres-
ence is negligible or absent in seeds (Knutsen et al.,
2018). Latex juice containing psychoactive alkaloids
increases in concentration as the capsule matures in the
final phase (Fig. 1.9). Final alkaloid concentration is in-
fluenced by a host of environmental factors, including
ambient light, water supply, temperature after flowering,
nutrients, infection by fungi, and enzymatic degradation
(Bernath, 1998).
6 PART | I Plant

FIG. 1.5 Cross section of laticifer in poppy. Enzymes are synthesized

in companion cells (cc), transported to sieve elements (se) for alkaloid
synthesis and stored in laticifers (la) in phloem parenchyma (pp). Other
structures shown include vascular cambium (vc) and xylem vessels (xy)
in xylem parenchyma (xp). (From Lee, E., Hagel, J. M., & Facchini, P. J.
(2013). https://doi.org/10.3389/fpls.2013.00182.)

FIG. 1.7 Marcello Malpighi. He was the first to describe the milky sap
of plants. (Credit: Wellcome Collection. https://wellcomecollection.org/
works/svekkc2e.)

FIG. 1.6 Electron micrograph of laticifer. Alkaloids of poppy are seen

suspended within vesicles (v) in the sieve (s) tubules. (With permission FIG. 1.8 Nehemiah Grew. He demonstrated the laticiferous system in
from Nessler, C. L., Allen, R. D., & Galewsky, S. (1985). https://doi. plants by microscopy. (Credit: Wellcome Collection. https://wellcomecol-
org/10.1104/pp.79.2.499.) lection.org/works/axt8asec.)
 Botanical aspects Chapter | 1 7

25

20

15
Percent

10

0
1
10
15
20
25
30
40
Number of Days after Flowering

FIG. 1.9 Alkaloid content in poppy capsule. With maturation, the al-
kaloid content of poppy increases after 3 weeks and starts to decrease
by 4 weeks. (Data from Bernath, J. (1998). Cultivation of poppy under
tropical conditions. In J. Bernath (Ed.), Poppy: The Genus Papaver (pp.
237–248). Harwood Academic Publishers.)
1.2.3 Extraction of opium
Opium alkaloids may be extracted from green poppy cap-
sules by excoriating superficially with a sharp and shallow
blade by hand, vertically or horizontally, so its milky white
sap is extruded (Fig. 1.10). The sap is allowed to dry for a
day or two, after which it is carefully scraped off the pods
and collected into wooden bowls (Fig. 1.11). Then, the
pod is ready for its next round of excoriation (Krikorian &
Ledbetter, 1975).
The green poppy pod secretes for about 10 days of
its annual cycle and may be tapped as much as six times
during this period. The concentration of opium reduces if
it is tapped more often. This process is labor-intensive, as
the poppy capsule is individually tapped repeatedly over
10 days. On average, the yield is approximately 80 mg
of raw opium per pod, and an acre of poppy provides
FIG. 1.11 Dried poppy latex. The dried milky sap contain-
ing opium is scrapped manually from each capsule. (With per-
mission from Couperfield@123rf.com. https://www.123rf.com/
photo_81603467_detail-of-harvesting-of-raw-opium-on-poppy-field.
html?downloaded=1.)
less than 6 kg of raw opium (DEA, 1992; Krikorian &
Ledbetter, 1975).
The raw opium may be “cooked” in boiling water to
remove all plant contaminants and then strained through
cheesecloth. This liquid opium may be re-heated in low
flame to yield a sticky brown paste (suitable for smoking or
eating). The collected opium is then air-dried before being
packaged into cubes or balls for shipment.
Another source of extracting opium is the naturally
dried pods of poppy capsules after harvesting their seeds
(Fig. 1.12). These dry capsules, called “poppy straw,” are
a common source for commercial production of opium,
which still contain opium alkaloids albeit at a lower
concentration.

FIG. 1.10 Excoriation of poppy capsule. Each excoriation re-
sults in milky exudate over 1–2 days. (With permission from
Couperfield@123rf.com. https://www.123rf.com/photo_81603489_
detail-of-cutting-poppy-heads-with-knife-to-harvest-opium-latex.
html?downloaded=1.)
FIG. 1.12 Poppy straw. Dry poppy capsules with seeds consti-
tute the “straw.” (Credit: Pixabay.com. https://pixabay.com/photos/
seeds-dried-poppy-poppies-flower-4461737/.)
8 PART | I Plant

1.3 Opium alkaloids

1.3.1 Poppy sources
The word “opium” is used to define latex juice of the
poppy and is most likely derived from the Greek word
“opos” (c. 100 CE). Natural opium is blackish brown
in color with a characteristic bitter taste. It contains as
much as 80 ­alkaloids (10%–30% of content), sugars
(20%), water (20%), and meconic acid (5%) (Chalise,
2015). The alkaloids belong to several groups: phen-
anthrene derivatives, which include the morphinan
alkaloids (morphine, codeine, thebaine, oripavine),
benzylisoquinolines (papaverine, reticuline, laudanine),
phthalideisoquinolines (noscapine or narcotine, narcoto-
line, narceine), protoberberines (berberine), and ben- FIG. 1.13 Maker of dreams. Morpheus with poppy in hand. Oil painting
zophenanthridines (sanguinarine) (Lim, 2013; Mishra by Jean-Bernard Restout (c. 1771 CE). (Credit: https://www.clevelandart.
et al., 2013; Schiff, 2002). org/art/1963.502.)
Psychoactive morphinan alkaloids (morphine, co-
deine, thebaine, oripavine) are the predominant reason
for its cultivation (Gupta, 2016). Many plants in Papaver
species have minimal quantities of opium and of no com-
mercial value. Morphinan alkaloid concentration may
range from 20% to 30% in Papaver somniferum, 10%
to 15% in Papaver setigerum, and minimal or none in
other Papaver species. In Papaver orientale, primary al-
kaloids are oripavine (20%) and thebaine (9%), while in
Papaver bracteatum, 90% of alkaloid content is thebaine
(Hosztafi, 2014; Khanna & Shukla, 1986). The alkaloid
sanguinarine, widely used for its antibacterial and antiin-
flammatory effects, especially in toothpaste, is found in
the root, stem, and leaves, but not in the poppy capsule.
A new variety of poppy developed in Australia called
top1 specifically accumulates thebaine and oripavine, in-
stead of morphine (Beaudoin & Facchini, 2014; Hosztafi,
2014).

Box 1.2 Hypnos and Morpheus

In Greek mythology, Hypnos (Somnus in Roman mythol-
ogy—hence Papaver somniferum) was the God of sleep
(Fig. 1.14), who tricked Zeus into sleep twice at the be-
hest of Hera during the Trojan War to favor Greek vic-
tory. His parents were Nyx (Goddess of night) and Erebus
(God of darkness), his twin brother was Thanatos (God
of death), and his wife was Pasithea (Goddess of relax-
ation). Dreams were created by the children of Somnus
and Pasithea, called “Oneiroi” comprising of four broth-
ers. Morpheus (Greek morphe = to form) was the most
powerful and in charge of dreams (Fig. 1.13), with the
assistance of his brothers Phobetor (who created pho-
bic nightmares), Phantasus (who created illusions), and
Ikelos (who created prophecy). Morpheus had wings to
take him into anyone’s dreams, including those of other
Gods, and slept in a cave surrounded by poppy fields
(Gottler, 2018).
FIG. 1.14 God of sleep. Greeks called him Hypnos (sculpture in the British
Museum), and Romans called him Somnus. (Credit: Wikimedia. https://com-
mons.wikimedia.org/wiki/File:Hypnos,_British_Museum_No._267.JPG.)
Naturally occurring opioids from Papaver somniferum
are morphine (from the Greek God “Morpheus”), codeine
(Greek: “kodeia” or poppy head), thebaine (Greek: “Thebai,”
city in Egypt where it was grown), and minor alkaloid of
importance oripavine. The major alkaloid of opium, mor-
phine, was identified in 1804 CE (Schmitz, 1985), codeine
in 1832 CE, thebaine in 1835 CE (Wisniak, 2013), and al-
most 100 years later, oripavine in 1935 CE (Hosztafi, 2014).

1.3.2 Nonpoppy sources
Interestingly, some of the naturally occurring peptides are
found related to opioids—alkaloid mitragynine from south
Asian plant Mitragyna speciosa or kratom, terpenoid sal-
vinorin A from central American plant Salvia divinorum
used in Shamanistic rituals, and dermorphin and deltorphin
from the skin of certain South American frogs. Mitragynine
also has psychoactive properties, salvinorin A is a potent
hallucinogen, and dermorphin has low therapeutic potential
(Ivanovic, 2017; Zjawiony et al., 2019).
Box 1.3 Entheogen
Salvinorin A is a natural hallucinogen found in Salvia divi-
norum, used by Mazatec shamans of Mexico as an entheo-
gen (Greek: entheos, root for enthusiasm) in rituals. Salvia
was first recorded by anthropologist Jean Basset Johnson
(1915–1944 CE), while studying native Mazatecs in 1939 CE
as a graduate student from California. Along with his wife
Irmgard Weitlaner, he made numerous field trips to study the
Mazatecs. His research was interrupted by World War II, and
he died at the age of 29 while serving in Tunisia. His father-
in-law, Roberto Weitlaner (1883–1968 CE), was an Austrian
engineer, who worked in several US steel companies before
turning to anthropology while residing in Mexico. He is well
known for the re-discovery of psilocybin mushrooms in 1936
CE and also wrote extensively on ethnic and linguistic as-
pects of indigenous Americans of the region.
Incidentally, Finnish chemist Adolf Arppe discovered a
product in 1845 CE that “turned from white to green on stand-
ing” by heating morphine with sulfuric acid. Later in 1869
CE, Augustus Matthiessen and Charles Alder Wright named
it “apomorphia” (Auffret, Drapier, & Vérin, 2018). Although
pharmacological similarities were noted with morphine, it
was found to be “no more like morphine than sawdust is like
sugar” (Dent, 1934). In addition to its emetic and sedative
effects, it has dopaminergic excitatory properties and is used
as an anti-Parkinsonian drug to treat hypomotility.
1.4 Synopsis
The Papaveraceae family has numerous plants, but Papaver
somniferum is the major medicinal plant of interest. Poppy
is grown in tropical as well as temperate climates over a
period of 6–7 months. It is a multipurpose plant with leaves
and seeds that serve as an edible food source, while the la-
tex of poppy capsule is of great medicinal value. Alkaloids
of poppy (numbering 80) are synthesized in the laticiferous
system of the plant and found abundantly in capsules, com-
pared with the rest of the plant. Morphinan alkaloid con-
centration varies from 20% to 30% in Papaver somniferum,
while thebaine is a major alkaloid in Papaver bracteatum.
Extraction of opium by an excoriation of capsules is known
for centuries and labor-intensive. Some peptides from
Botanical aspects Chapter | 1 9
n­ onpoppy sources (kratom, salvia) are also chemically re-
lated to opium. Dry poppy capsules (poppy straw) are now
a major commercial source for opium globally.
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Part II

History
This page intentionally left blank
Chapter 2
Prehistory
Soul-soothing plant! that can such blessings give,
By thee the mourner bears to live!
By thee the hopeless die!
Charlotte Smith in Ode to the Poppy (c. 1795 CE)
For most part of their existence (almost 95%), modern
humans survived by “foraging” or “hunting and gather-
ing.” Although preagricultural diet consisted of meat, fruits,
nuts, and roots, early farming of cereals developed approxi-
mately 10 thousand years ago or KYA (Greek: chilioi or
kilo, meaning thousand) (i.e., around 8000 BCE) (Nielsen
et al., 2017; Trinkaus, 2005). When humans began to ex-
periment with the domestication of plants, mostly out of
necessity, they would have naturally used plants found in
surroundings with beneficial properties. It is entirely pos-
sible that humans knew about poppy even before the era of
farming. The story of origin and spread of poppy around the
world makes an interesting inquiry. In this short review, we
look at palaeobotanical and archaeological clues, followed
by recent interpretation using genomic analysis (Nielsen
et al., 2017).
2.1 Paleobotanical evidence
Poppy is considered indigenous to Asia Minor in the
Mediterranean region (Carod-Artal, 2013; Duke, 1983;
Gabra, 1956). It is generally accepted that Papaver se-
tigerum is phylogenetically earlier than Papaver som-
niferum (Gabra, 1956). The “dump-heap theory” of Edgar
Anderson proposes an interesting line of reasoning for the
advent of farming in general (Stebbins, 1978). It proposes
that dump or rubbish heaps of prehistoric human camp sites
enabled vigorous growth of plants and that humans used
this observation to grow specific plants they found useful.
This concept also offers an attractive explanation for the
origin of poppy cultivation by humans.
Handbook on Opium. https://doi.org/10.1016/B978-0-323-90903-7.00010-7
Copyright © 2022 Elsevier Inc. All rights reserved.
Box 2.1 Edgar Anderson
Edgar Anderson (1897–1969 CE), a great American bota-
nist who recognized genetic variation in plants, said that
“if we are to learn anything … we must reduce the prob-
lem to the simplest terms.” His popular book “Plants,
Man and Life” published in 1952 CE is an exploit of his
research laced with philosophical and historical views
on plants. Incidentally, he briefly worked with two great
­geneticist-statisticians in Britain: R.A. Fisher, a distinguished
mathematician-­ geneticist who founded modern statisti-
cal science, and J.B.S. Haldane, an illustrious evolutionary
biologist-geneticist-statistician, who, among numerous
other contributions, also proposed that sickle cell disease
offered immunity to malaria.
Palaeobotanical evidence indicates that opium poppies
were cultivated in the Near East region and then spread into
Europe along the Mediterranean coast into Spain. Seeds of
Papaver somniferum were discovered in a submerged vil-
lage called La Marmotta at the bottom of volcanic Lake
Bracciano near Rome, Italy, in the early 1990s (Merlin,
2003). This site is considered to be a farming community,
dating back to the early Neolithic (c. 5700 BCE) period
(Fig. 2.3). Poppy seeds were found stored in utensils, along
with cereals, indicating possible cultivation of poppy dur-
ing this period. It is the earliest known association of poppy
with humans (Harris, 2015; Merlin, 1984, 2003).
Poppy seeds were found in several funerary sites and settle-
ments dating to the middle Neolithic (c. 4200 BCE) and late
Neolithic (c. 3000 BCE) periods. Fossilized poppy seeds were
discovered in several human settlements in Central Europe and
Swiss Foreland during this period as well (Fig. 2.3). Although
poppy seeds were frequently found in early Neolithic sites,
find of poppy capsules in a funeral site at Cueva de los
Murcielagos (Spain) dated much later (c. 2500 BCE). These
sites were reviewed at great length by ethnobotanist Mark
Merlin (University of Hawaii at Manoa) (Merlin, 1984).
13
14 PART | II History
Based on palaeobotanical evidence, it appears that
poppy had a significant place in daily life with seeds as
a food source and possibly used for its oil (Merrillees,
1979). However, poppy capsules were not a common find,
and evidence for processing of poppy capsules or their use
as a mind-altering drug during Neolithic period is lacking
(Boekhoud, 2003; Lillios, 2010; Merlin, 2003; Merrillees,
1989).
2.2 Archaeological evidence
2.2.1 Early humans
Archaic humans existed since two million years ago (MYA)
in various forms, including Neandertals and Desovians, un-
til Homo sapiens evolved around 200 thousand years ago
or KYA (kilo or thousand years ago). It is presumed that
modern humans interacted with archaic humans during this
period (Trinkaus, 2005). Modern humans then emerged
from Africa in two waves: one around 60 KYA via Arabia,
southeast Asia to Australia, and another around 45 KYA
via the Levant to Europe. The last major wave of migration
was around 15 KYA from Siberia across Beringia into the
Americas (Manco, 2013; Nielsen et al., 2017; Pääbo, 2014).
Chimpanzees and bonobos share high similarity with
the human genome (Seaman & Buggs, 2020) and are our
closest relatives along with archaic humans. Chimpanzees
are omnivores; fruits and seeds consist almost 60% of their
food source. They are also known to preferentially eat cer-
tain plants of value that are not part of their staple. Their
knowledge would have passed onto archaic and later mod-
ern humans. We could only surmise that after migration out
of Africa, poppy (indigenous to Asia Minor) was carried by
early migrants into other areas in Europe.
2.2.2 Artifacts
The earliest poppy artifacts discovered include late Bronze
age necklaces with poppy capsule pendants (c. 1550 BCE)
and paintings with poppy gardens in the tombs of Egyptian
Kings in Thebes, including that of Tutankhamun (Rosso,
2010; Veiga, 2016). In one of these paintings, Meritaton,
daughter of Pharaoh Akhenaton and Queen Nefertiti, was de-
picted offering poppy to her husband Pharaoh Semenkhare
(c. 1400 BCE) (Rosso, 2010). Gold poppy-shaped earrings
were found in the tomb of Queen Tausret, the last Pharaoh
of the Nineteenth Dynasty, in whose time it is believed that
Troy was taken (Veiga, 2016). These paintings, offerings, and
ornaments suggest that poppy was an object fit for Egyptian
Royals or used by them for their psychedelic effects.
In the Aegean, Minoan (c. 2100 BCE), Mother Earth
Goddess, and her descendent Demeter, Greek Goddess of
Agriculture, are often depicted in various reliefs holding
grains and poppy capsules (Carod-Artal, 2013; Merrillees,
1962). Artifacts with poppy capsule engraved gold pins and
pendants dating to the Mycenaen period (c. 1500 BCE)
were unearthed in Crete. Other finds included terracotta
idols of “Poppy Goddess” and hairpins resembling opium
poppy in Crete and multiple items of daily use such as jars,
ivory pipe for smoke, and numerous clay jugs shaped like
opium poppy in Cyprus (c. 1200 BCE) (Gabra, 1956; Guo
et al., 2018). Numerous artifacts excavated in this region
showed widespread use and trading of poppy in the Aegean
(Boekhoud, 2003; Lillios, 2010; Merlin, 1984). Poppy was
probably a valuable commodity with medicinal and recre-
ational values during this period.
The first evidence for the presence of opium (morphine,
codeine, noscapine) and poppy oil from Papaver som-
niferum was found in a juglet (c. 1550 BCE) from Egypt
in the British Museum (Gabra, 1956; Merrillees, 1962).
The chemical presence of other opium alkaloids (papaver-
ine and thebaine) was recently confirmed in a Cypriot ju-
glet from this period as well (Smith, Stacey, Bergström, &
Thomas-Oates, 2018). These findings suggest that opium
was possibly known and extracted from poppy during this
period.
Based on archaeological evidence, Kritikos et al. pos-
tulated that the Minoans in Crete (c. 2100 BCE) and
later Mycenaeans in Greek mainland (c. 1400 BCE) used
poppy for “oil, healing powers, euphoria, sleep and death”
(Askitopoulou, Ramoutsaki, & Konsolaki, 2002; Kritikos
& Papadaki, 1967). These findings are also suggestive of
religious use of opium poppy dating up to the Common Era
(Veiga, 2016).
2.3 Genetic evidence
The advent of molecular genetic techniques and whole-­
genome analysis has provided us with innovative techniques
to evaluate existing evidence. Genetic studies on poppy are
a recent effort, and immense advances have been made over
the past couple of years.
2.3.1 Origins of poppy
Opium poppy belongs to the Papaveraceae family of flow-
ering eudicot plants of the ancient order Ranunculales. The
taxonomy of Papaveraceae has changed over the years, and
it was included in the order Ranunculales around 1993 CE.
The Papaveraceae family represents a higher evolutionary
level in this order based on the evolution of benzylisoquino-
line alkaloids (BIA) (Mihalik, 1999). Phylogenomic analy-
sis of Papaver origin has only recently been accomplished
using whole-genome sequence assemblies (Guo et al.,
2018; Li, Winzer, He, & Graham, 2020).
Phylogenetically, S-norcoclaurine (1-benzylisoquinoline)
is the earliest alkaloid, estimated to be present in the
­order Ranunculales around 122 MYA, and protoberberine

FIG. 2.1 Phylogenetic clade of Papaver alkaloids. Alkaloid S-norcoclaurine is the earliest phylogenetically, while morphinans recent in evolution.
a­ lkaloids appearing between 122 MYA and 110 MYA. It is
estimated that the next group of benzophenanthridine alka-
loids appeared before the Papaveraceae family split in the
order Ranunculales around 77 MYA. It was followed by the
evolution of phthalideisoquinoline alkaloids noscapine and
thebaine. Morphinan alkaloids, to which morphine belongs,
evolved around 18 MYA after a major whole-genome du-
plication (WGDa) event in Papaver during the evolutionary
process (Fig. 2.1). Thus, morphinans represent the highest
order of alkaloid evolution in Papaver (Li et al., 2020).
2.3.2 Spread of poppy
Tracing the origin and migration of humans through vast
continents is a monumental task since 99% of human devel-
opment occurred in “prehistory” before any form of written
documents were kept. Our understanding of evolution was
mainly dependent on archaeological and paleontological
information in the past. Data acquired from mitochondrial
DNA since the 1980s was limited in scope, as it represented
only female inheritance and not the whole genome. A ­major
a. WGD is the process of spontaneous doubling of all chromosomes,
whereby a duplicated gene is allowed to mutate, while the original gene
remains unchanged. This major event in evolution enables us to trace phy-
logenetic origin and changes.
Prehistory Chapter | 2 15
breakthrough occurred when the full human genome was
decoded in 2003 CE. Advances in sequencing and other
techniques are helping us to understand and reevaluate
earlier data (Stewart & Chinnery, 2015). Thus, the shift
from artifact-based archaeology (“pots are not people”) to
­technology-based archaeology has been valuable in tracing
human stories.
With the advent of farming around 10 KYA, poppy was
probably cultivated for its nutritional value. This is borne
out by bowls containing poppy seeds (along with other
grains) found in La Mormotta site in Italy (Harris, 2015;
Merlin, 2003), which dates closer to 8 KYA—earliest evi-
dence of poppy use by modern humans (Fig. 2.2). Recent
genetic studies confirmed a common source for two pat-
terns of spread of agriculture (including poppy) into Europe
during the Neolithic period. One spread in southern Europe
called Cardial Pottery Culture along the Mediterranean
coastline into Iberia, and another called Linearbandkeramik
(LBK or Linear Pottery Ceramic) Culture along the Danube
into Central Europe (Olalde et al., 2015; Salavert, 2017).
Opium poppy seeds were found along with ancient cereals
(wheat, barley), pulses (chickpeas), and oleaginous plants
(flax, poppy) in several of these cultural sites (Merlin,
1984; Salavert, 2017). Thus, there is considerable ­evidence
to ­support the concept that poppy was cultivated in the
Neolithic period in Europe, probably one of the earliest
16 PART | II History
FIG. 2.2 Possible routes of poppy spread. Patterns of poppy spread possibly follow the same line of the spread of agriculture into Europe.
crops to be cultivated by humans, and followed the spread
of farming into Western Europe (Salavert et al., 2020).
2.4 Evolutionary milestones
The evolution and spread of poppy from the Near East to
other parts of the world followed, mostly along human mi-
gration lines, and these main events are depicted in Fig. 2.3.
In summary, evolutionary milestones in history started
with mammals (200 MYA) to Homo sapiens who evolved
almost 100 million years after poppy and the earliest find-
ing of poppy in a human settlement around 7500 years ago.
Genetic studies have shown that morphinan alkaloids were
present in poppy for at least 18 million years before mod-
ern humans, with higher-order morphinans being the last to
evolve.
For an interesting description of human migration in
general and specifically European migration, based on an
interdisciplinary mix of history, archaeology, genetics,
and linguistics, we recommend Jean Manco’s Ancestral
Journeys (2013). For key discussions on the spread of
a­griculture, refer to Olalde et al. (2015), regarding the
spread of poppy, refer to Salavert et al. (2020), and for ge-
netic studies on poppy, refer to Li et al. (2020).
2.5 Synopsis
Tracing the use of poppy by early humans is a difficult
endeavor. Palaeobotanical and archaeological evidence
(as early as 8 KYA) points to its use in diet, its popularity
as jewelry, and its use as an artifact in funeral sites and
possibly a recreational drug. Recent phylogenetic evalu-
ations, using new tools such as whole-genome analysis,
indicate that poppy as a plant existed at least 100 MYA,
and morphinans evolved approximately 18 MYA before
modern humans. Evidence also indicates that the poppy
plant is indigenous to the Near East region. It probably
spread along the Mediterranean coastline and Swiss
Forelands into Europe during human migration in the
Neolithic period. New tools such as genome analysis,
hopefully, will bring new vistas on opium use by early
humans.

FIG. 2.3 Milestones in human and poppy evolution. Evolution of morphinan alkaloids preceded human evolution.
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Chapter 3

Ancient history

she cast into the wine of which they were drinking a drug,
to quiet all pain and strife, and bring forgetfulness of every ill.
Homer in Odyssey (c. 8th century BCE)

3.1 Opium in antiquity

3.1.1 Mesopotamia
The story of opium in recorded history (c. 4000 BCE)
starts in Egypt and the Fertile Crescent of the Middle
East. It is generally assumed that Assyrian and Egyptian
cultures co-existed in recorded history dating as early as
4000 BCE (Langdon, 1921). The people of Mesopotamia
included Sumerians in the south, Akkadians in the middle,
and Assyrians in the north. Egyptian Dynasties were a con-
stant threat to the Levant during this period. Campaigns of
Assyrian Kings Esarhaddon (c. 673 BCE–671 BCE) and
his son Ashurbanipal (c. 667 BCE–663 BCE) leading to
the sack of Thebes and plunder of its riches are well docu-
mented (Kahn, 2006). It could therefore be assumed that
Assyrians probably knew about the cultural and medical use
of poppy by Egyptians.
The history of Mesopotamian civilization was largely
unknown until recent times. The earliest recognition of
Babylonian ruins by Pietro della Valle in 1616 CE (Fig. 3.1) FIG. 3.1 Pietro della Valle. Pietro journeyed from Italy to India between
led to excavations by the vicar Abbe Beauchamp more than 1614 CE and 1626 CE and also brought back cuneiform writings from
a century later (Ben-Zaken, 2009; Blunt, 1953; Gurney, Mesopotamia to Europe. (Portrait by Gilliam van der Gouwen (n.d.) in
2011; Stone, 2014). This was followed by British East India Wikimedia. https://commons.wikimedia.org/wiki/File:Portret_van_Pietro_
Company’s Claudius James Rich in 1811 CE and numerous della_Valla,_RP-P-1909-4464.jpg.)
others (Budge, 1920).
archeology, he was also an ethnographer and composer and
wrote theoretical dissertations on music. His journey makes
Box 3.1 Pietro’s journey interesting reading for anyone interested in history.
The yearnings of biblical hermeneutics took the Italian
Nobleman Pietro della Valle from Rome all the way through However, a big breakthrough on Babylonian civiliza-
Levant, Mesopotamia, Iran to India and back. During his visit tion occurred in 1847 CE, more than 200 years after Pietro,
to the city of Hillah, Iraq in 1616 CE, he identified ruins of with the discovery of clay tablets in King Ashurbanipal’s
Babylon from his knowledge of the scriptures and also brought Library by Austen Layard (Fig. 3.2) and Hormuzd Rassam
back the first inscribed bricks with cuneiform writings. Besides (Fig. 3.3).

Handbook on Opium. https://doi.org/10.1016/B978-0-323-90903-7.00015-6

Copyright © 2022 Elsevier Inc. All rights reserved. 19
20 PART | II History
FIG. 3.2 Sir Austen Henry Layard. Layard discovered clay tablets in the
Library of Ashurbanipal containing Sumerian inscriptions. (Photography
by Caldesi Blandford & Co. (n.d.) in Wellcome Collection. https://­
wellcomecollection.org/works/e29pdsr7.)
FIG. 3.3 Hormuzd Rassam. Rassam was an archeologist and co-­
discoverer of Assyrian clay tablets. (Portrait by Philip Henry Delamotte
(c. 1854 CE) in Wikimedia. https://commons.wikimedia.org/wiki/
File:Hormuzd.Rassam.reclined.jpg.)
Box 3.2 Assyrian archeologists
On his way to Sri Lanka looking for a British Civil Service
job, Austen Henry Layard (1817 CE–1894 CE) explored
ruins of Assyria in 1847 CE and 1849 CE and discovered
several monuments including Ashurbanipal’s Library (c. 700
BCE) in the city of Assur. Layard and his assistant Hormuzd
Rassam (1826 CE–1910 CE) unearthed thousands of clay
tablets in ruins of Kouyunjik mounds of Nineveh on the out-
skirts of Mosul in modern Iraq. The drawings on the ruins by
Layard are as fascinating as his excavations (Layard, 1867).
He later turned to politics, investigated the Indian Mutiny of
1857 CE, and was British Under-Secretary for Foreign Affairs
for years.
Rassam had an illustrious career as well and discovered
numerous cylinders and clay tablets with inscriptions, in-
cluding the Epic of Gilgamesh. He also served briefly as
a British diplomat before resuming his archeological work
with numerous other discoveries throughout the rest of his
career (Reade, 1993).
The clay tablets were written in Sumerian or Akkadian
on numerous topics, including the earliest known story
of the region “Poor Man of Nippur” and the earliest liter-
ary work “Epic of Gilgamesh.” Most of these clay tablets
were fragmented and partially baked from fire and de-
struction by invading forces. These epics were later trans-
lated by the printer-turned-archeologist George Smith in
1872 CE.
Clay tablets found in the Ashurbanipal’s Library
(c. 600 BCE) consisted of several Babylonian texts includ-
ing approximately 1594 literary and scientific texts, other
religious, historical, and medical topics, and archival texts
totaling more than 3500 tablets dating as early as 1500 BCE
(Reade, 1993). Of these, approximately 81 tablets are de-
voted to plants and medicine (Fincke, 2003).
Furthermore, ancient bas reliefs excavated in Nimrud
(near Nineveh) showed figures holding a plant with a cap-
sular head. It was argued by some that this plant ­represented
poppy, while other researchers considered it to be pome-
granate (Krikorian, 1975). Based on these figures and other
cuneiform writings, the view that Sumerian culture knew
about the medicinal use of poppy was proposed and propa-
gated by earlier experts on this subject (Kramer, 1963;
Kritikos & Papadaki, 1967; Thompson, 1924). However,
this idea was challenged by other Sumerian experts
subsequently.
The change in views on poppy in Sumerian culture
arises primarily from early difficulties in reading and inter-
preting ancient Sumerian writings. Sumerian is a “language
isolate” with no relationship to other languages, includ-
ing Akkad (the earliest Semitic language) and its dialects
(Assyrian, Babylonian) (Jastrow, 1915). Translation of
these writings was complex and attempted by many, but
credit for early breakthrough goes to British Army Officer
Sir Henry Rawlinson (Fig. 3.4).

FIG. 3.4 Sir Henry Rawlinson. As a young captain in British East India
Company, Rawlinson copied trilingual inscriptions on Mount Behistun in
1837 CE. (Photograph by Lock & Whitfield (n.d.) in Wikimedia. https://
commons.wikimedia.org/wiki/File:Sir_Henry_Rawlinson.jpg.)
Box 3.3 Holy trinity of cuneiform
Cuneiform script, originally developed by Sumerians,
was used in Mesopotamia until about 100 BCE when it
was replaced by an alphabetic script. Major contribution
for deciphering cuneiform script was provided by British
East India Company Army officer Sir Henry Creswicke
Rawlinson (1810 CE–1895 CE). While stationed in Persia,
Rawlinson found trilingual (old Persian, Elamite, and
Babylonian) cuneiform inscriptions on a cliff 300 feet
above ground level in Mount Behistun. He diligently
copied these, by hanging from a ladder often held pre-
cariously on the hill by an aide or using a telescope, inter-
preted and published the old Persian part of inscriptions in
1837 CE (Rawlinson, 1898).
Rawlinson’s early transcription, along with scholarly
work by Rev Edward Hincks and Franco-German Jules
Oppert, often called “holy trinity of cuneiform,” paved the
way for deciphering complex Babylonian scripts by 1857
CE. An online dictionary of the Akkadian language was
completed in 2010 CE by the University of Chicago.
3.1.2 Clay tablets of Nineveh
Clay tablets from Nineveh (dating to 1500 BCE) con-
taining the first ever recorded “Pharma” were found
Ancient history Chapter | 3 21
in two Sumerian tablets, one with a single prescrip-
tion and the other with 15 prescriptions. In his tran-
scription on plants and herbals “The Assyrian Herbal,”
Campbell Thompson interpreted the words “HUL GIL”
and “PA-PA” to connote poppy plant (Thompson, 1924).
As these words were found numerous times in the tab-
lets, poppy was advanced as a popular Assyrian medici-
nal plant. In an extension of his translation, Thompson
again identified “poppy” in at least three prescriptions
(Thompson, 1924, pp. 12–13 and 23), which helped to
propagate the concept that poppy was known and used
in Sumerian Pharma.
Box 3.4 Transcribing Assyrian
Reginald Campbell Thompson (1876 CE–1941 CE), a British
Assyriologist, in addition to being involved in the excava-
tions in Nineveh (in 1904 CE and later in 1923 CE), was
Assistant Professor of Semitic Languages in the University
of Chicago (1907–1909 CE), served as Intelligence Officer
in First World War, wrote fiction and books on Assyriology,
and often performed trapeze as a hobby.
Samuel Noah Kramer (1897 CE–1990 CE), whose fam-
ily emigrated from Ukraine region to the United States in
1905 CE, took interest in Assyriology when he was 30 years
old, participated in excavations in Iraq, worked on Assyrian
Dictionary at University of Chicago, and spent most of his
career transcribing Sumerian tablets until his death (Kramer,
1988).
However, in later transcriptions of these tablets, no
word in Sumerian or Akkadian was definitely identified as
poppy by etymologists (Kramer, 1963; Krikorian, 1975;
Merrillees, 1979). In his authoritative treatise, Samuel
Noah Kramer goes over layers of confusion to clarify the
archeological history of Sumerians. The prescriptions from
Sumerian Pharma contained materials from plants such as
thyme, mustard, figs, plum, pear, willow, fir, pine, processed
with vegetable oil, beer, and wine. He concluded that there
is no definitive mention of pain or poppy in these prescrip-
tions (Kramer, 1963).
The Chicago Assyrian Dictionary (CAD) now reads
“HUL GIL” as “UKUS”, interpreted as a cucumber;
“PA-PA” or “ARARU” or “IRRU,” now read as “TIGILLU”
and interpreted as melon (Krikorian, 1975). Many of the
words interpreted in “The Assyrian Herbal” by Campbell
Thompson are now considered either obsolete or inter-
preted differently.
In a review of these works, it is concluded by Krikorian
that there is no evidence that poppy was cultivated or used
by Sumerians, Babylonians, or Assyrians (Krikorian,
1975). Thus, contrary to popular writings, it appears that
the medicinal use of poppy was largely unknown in ancient
Mesopotamia.
22 PART | II History

3.2 Ancient Egypt

3.2.1 Cultivation of poppy
Ancient Egypt, dating back to its predynastic period (5000
BCE), was a land of a great civilization and known for its
sciences including architecture, religion, and medicine.
There is evidence for cultivation and use of poppy during
the XVIII Dynasty (c. 1500 BCE) of the Pharaonic civiliza-
tion of Egypt. Poppy was cultivated in Thebes during this
period and inspired the name “thebaine” to one of the major
alkaloids of poppy (Bryan, 1930). Poppies were shown fre-
quently in bouquets along with mandrake and cornflowers
in Egyptian paintings, including the tomb of Tutankhamun
(Rosso, 2010).
Several Egyptian papyri in Hieretic script (Greek:
Hieros = sacred; Hieretic is a cursive and shorthand form
of Hieroglyphics), such as Edwin Smith and Ebers papyri
(both dating to 1500 BCE), were discovered in the 18th
century. However, their interpretation remained an onerous
task until the discovery of the Rosetta Stone (Fig. 3.5) and
subsequent transcription by Thomas Young (Fig. 3.6) and
Jean-Francois Champollion (Fig. 3.7).

FIG. 3.6 Thomas Young. Physician polymath who deciphered Rosetta

Stone, credited as the “last man who knew everything.” (Mezzotint by G.R.
Ward (c. 1855 CE) in Wellcome Collection. https://wellcomecollection.org/
works/xv69yyrp.)

FIG. 3.7 Jean-Francois Champollion. Champollion, an accomplished

FIG. 3.5 The Rosetta Stone. Trilingual inscriptions on the Rosetta philologist who completed the decipherment of Rosetta Stone, is known
Stone with Hieroglyphics in the upper third panel. (Unknown author as “Father of Egyptology.” (Painting by Leon Cogniet (1831 CE) in
(n.d.) in Wikimedia Commons. https://commons.wikimedia.org/wiki/ Wikimedia. https://commons.wikimedia.org/wiki/File:Jean-Francois_
File:Rosetta_Stone_BW.jpeg.) Champollion,_by_Leon_Cogniet.jpg.)
 Ancient history Chapter | 3 23

Box 3.5 Hieroglyphics

Egyptian Hieroglyph (Greek for “holy word”) was a system
of pictorial writings dating to 3000 BCE, until its decline by
the third century CE, when the Coptic (based on Greek al-
phabet) language was adapted in Egypt. Hieroglyphics was
lost in time, and the earliest work to interpret Hieroglyphics
was published, almost six centuries after its disuse, by
Arabian Egyptologist Ibn Wahshiyya (Kitab al-Mustaham)
in 982 CE.
However, complete interpretation of Hieroglyphics re-
mained difficult until the discovery of the Rosetta Stone.
This inscription (c. 196 BCE) was discovered in 1799 CE by
Pierre Francois Xavier Bouchard, an officer of Napoleon’s
army in the city of Rashid. The stone contained trilingual
inscriptions (Hieroglyphic, Demotic, and Greek) of the
same message; it was seized by the British in 1801 CE af-
ter Napoleon’s defeat and currently resides at the British
Museum in London.

Box 3.6 Race for Rosetta

The Rosetta Stone was deciphered by two great minds
with fierce competition. It was initially cross-interpreted
FIG. 3.8 Page from Ebers Papyrus. Poppy was mentioned in Ebers
from Demotic script by English physician Thomas Young. It
Papyrus as a component of several remedies. (U.S. National Library of
was later fully deciphered in 1820 CE by the charismatic Medicine (c. 1500 BCE). http://resource.nlm.nih.gov/101436767.)
Frenchman Jean-Francois Champollion.
Thomas Young (1773–1829 CE) was a physician poly-
math who mastered ancient languages by 14 years of age,
established wave theory of light, worked on physiology
of optics, formulated several biophysical characteristics
(Young’s modulus of elasticity, Young-Laplace equation of
capillary pressure, Young’s rule for calculating drug dose
for children), and laid foundation for interpreting Rosetta
Stone. He was called “the last man who knew everything”
(Robinson, 2005).
Champollion (1790–1832 CE), youngest of seven chil-
dren in his family, mastered ancient oriental languages,
Latin and Greek, by 16 years of age, became a professor
of history by age 20, served as a curator of Egyptian collec-
tion in Louvre Museum by 36 years of age, and took part in
Franco-Tuscan expedition to Egypt. He died early by age 41
of stroke; he is hailed as “Father of Egyptology” (Robinson,
2012).

3.2.2 Papyrus of Ebers

Papyrus of Ebers (c. 1500 BCE) listed multiple preparations
along with spells and incantations for dealing with ailments, in
accordance with the theory of diseases of the times (Fig. 3.8).
It is a medical compendium in Hieratic with 811 prescrip-
tions and lists multiple diseases and several plant remedies,
including parts of poppy plant, berries, and seeds as constit-
uents in several prescriptions (Bryan, 1930; Nunn, 1996). FIG. 3.9 Georg Moritz Ebers. Ebers was a German novelist who came
Ebers Papyrus is a historic discovery and landmark in the across a set of medical papyrus in Egypt (1874 CE),which now bears his name.
(Wikimedia (n.d.). https://commons.wikimedia.org/wiki/File:Georg_Ebers.jpg.)
history of medicine.
24 PART | II History
Box 3.7 Egyptian papyri
Edwin Smith (1822–1906 CE) from Connecticut was an
Egyptologist and dealer of antiquities. He lived for almost
two decades in Egypt, and in 1862 CE, came across two sets
of papyri in Luxor. He kept the first set of papyrus, while
the second set was temporarily in his possession until 1869
CE, after which its whereabouts unknown. The first set of
papyrus was donated by his daughter (after his death) to
New York Historical Society. Its significance was not real-
ized until analyzed by historian James Breasted in 1930 CE.
Edwin Smith Papyrus is the oldest known treatise on cranial
and spinal cord injuries (Hughes, 1988; Van Middendorp,
Sanchez, & Burridge, 2010).
Georg Mortiz Ebers (1837–1898 CE) was a German
novelist (Fig. 3.9), who popularized Egyptian folklore
through historical romantic novels in Germany. The sec-
ond set of papyrus was purchased by Ebers, when it sur-
faced again in Luxor in the winter of 1874 CE. It was
wrapped in old mummy clothes and perfectly preserved,
and consisted of a scroll 20 meters long containing 108
columns of text, dated at the reign of Amenophis I (1536
BCE) (Bryan, 1930). Ebers Papyrus is a compendium of
medical knowledge of the day written in Hieratic, trans-
lated into German with great devotion by physician
Egyptologist Hans Joachim, and into English (1930 CE) by
physician Cyril Bryan.
Opium poppy is mentioned in the Ebers Papyrus as “Spn”
(Rosso, 2010) and is the earliest known record on opium. There
is frequent mention of poppy in Ebers Papyrus as a compo-
nent of several remedies used for headache to stop crying in
children and abdominal discomfort (Fig 3.10). Treatment of
headache in the medical papyri was analyzed by Karenberg
and Leitz (2001), including a few prescriptions that in-
cluded poppy as a component (Karenberg & Leitz, 2001).
FIG. 3.10 Poppy prescriptions in papyri. Examples of prescriptions in papyri containing poppy as one of the ingredients.
However, poppy was not the only ingredient for the treat-
ment of pain or any other ailments in the papyri (Bryan,
1930; Hobbs, 1998; Rosso, 2010). These findings indicate
that although soporific and analgesic effects of poppy were
known, other medicinal or addictive potentials were prob-
ably unrecognized during this time.
3.3 Classical history
Pharmacopeia of ancient Egypt was eagerly studied
by Greek physicians and formed the basis of several
therapeutics in Greek medicine. The earliest reference
­
to poppy in Greek writings is attributed to Linear B
Mycenaean tablets of Pylos (c. 1400 BCE), discovered by
British Archeologist Arthur Evans in 1939 CE. Several ref-
erences to the Greek Goddess Demeter were found in these
tablets (Janke & Solca, 2018). Linear B equivalent of the
word “I-DA-MA-TE” in the Minoan A tablets is often con-
sidered equivalent to “DAMATE” in the Mycenean B tab-
lets and interpreted as Demeter in classic Greek. Demeter
was usually depicted as the Goddess of Harvest, with cere-
als and poppy in her hand in ancient Greece. It was inferred
from this depiction that poppy was known and used during
those times in ancient Greece.
Box 3.8 Linear B script
Sir Arthur John Evans (1851–1941 CE), a British journalist-
archeologist and adventurer-statesman, unearthed the
Palace of Knossos on Crete. He was instrumental in delin-
eating Minoan civilization (c. 2700–1600 BCE) that pre-
dated Mycenaean (c. 1600–1100 BCE) based on artifacts.
In addition, he also found 3000 clay tablets in two different
scripts—Linear A and Linear B dating to the Minoan period
that gave insight into their civilization (Evans, 1950). One of

his school friends was Francis Maitland Balfour, a renowned
biologist and Darwinian. For a general description and cata-
log of ancient languages of Levant and Mediterranean, refer
to website Mnamon (www.mnamon.sns.it).
The first reference to poppy in the literature is attributed
to early Greek poets (c. seventh century BCE), Hesiod and
Homer. Hesiod in “Theogony” described a banquet scene at
the city of Mekone near Corinth. Homer described “droop-
ing head” of poppy in “Iliad,” and a drug “to lull all pain
and anger” called nepenthe in “Odyssey” that Helen of
Troy obtained from an Egyptian noble. It is postulated that
Mekone was named after the field of poppies, and nepenthe
may have been opium (Kritikos & Papadaki, 1967).
No further information on poppy is available until the
start of the classical Greek period around fifth century
BCE. Eminent writings of Hippocrates, Aristotle, and
Theophrastus at the dawn of Greek medicine renewed inter-
est in the medical use of opium poppy.
3.3.1 Hippocrates of Cos
Hippocrates of Cos (c. 460 BCE–370 BCE), known as “Father
of Clinical Medicine” was a great influence on Medicine
(Craik, 2014; Jones, 1923; Jouanna, 1999; Fig. 3.11), and
FIG. 3.11 Hippocrates of Cos. Poppy was mentioned in Hippocratic
Corpus multiple times but was not the primary component of these reme-
dies. (Lithograph by Lanta, J. (c. 1835 CE) in Wellcome Collection. https://
wellcomecollection.org/works/uhdx4jrn.)
Ancient history Chapter | 3 25
collection of his works is known as “Hippocratic Corpus.”
Remedies described by Hippocrates for diseases included
parts of several plants (numbering 200, including poppy),
mostly mixed with other ingredients (such as old wine,
cumin, honey, pepper, silphium or asafetida, celery, fen-
nel, goat cheese, castor oil, black hellebore, bark of pome-
granate, acacia, and anise, among others) (Elliott, 1914;
Prioreschi, Heaney, & Brehm, 1988). Poppy is referred to
as “mekon” in various texts of Hippocratic Corpus (Cilliers
& Retief, 2000; Coxe, 1846; Retief & Cilliers, 2010). In
Fistulae, Hippocrates recommends “white meconium”
(white poppy) for anal inflammation and protrusion when
other measures fail. Poppy extracts and seeds (in mixtures
with several other substances) were prescribed by him for
gynecological ailments including leukorrhea (Astyrakaki,
Papaioannou, & Askitopoulou, 2010).
Box 3.9 Corpus Hippocraticum
The works of Hippocrates II of Cos (460–357 BCE), written
in Ancient Greek and numbering 60, are collectively known
as “Corpus Hippocraticum” (these works are listed in Craik,
2014). English translation of complete works of Hippocrates
is not available—most are taken from Latin translations of
Foesius (1624 CE), Haller (1775 CE), Gardeil (1801 CE), or
Kuhn (1825 CE).
Hippocrates is a descendent of Hippolochus, son of
Podalirius Esculapius, grandson of Apollo—line of great phy-
sicians of their times. Similar to the Pythagorean philosophy
of four elements (water, earth, wind, and fire), Hippocrates
believed that the body consisted of four humors (black bile,
yellow bile, phlegm, and blood) and four elements (cold,
hot, dry, and moist). In the case of diseases, healing is done
by restoring the balance of these humors and elements by
using four methods such as bleeding, emetics, purgatives,
and surgery. Hippocratic Oath has a Pythagorean influence
of four fundamentals including duty, justice, respect, and se-
crecy (Jouanna, 1999). Pythagorean philosophy, propagated
by Empedocles (493–433 BC) who believed in reincarna-
tion, was founded by the legendary Pythagoras.
In an extensive review of the Hippocratic Corpus from the
compendium by Maloney and Frohn (1986), Prioreschi et al.
found direct reference to poppy for relief of pain in only three
passages (Maloney & Frohn, 1986; Prioreschi, 1993). These
passages are quoted below, where page numbers refer to the
work by Maloney & Frohn (1986):
For the pain of the uterus … a soup of white poppy seeds and
nettle seeds.
(On Women’s Diseases, II, ccvi, Littre, VIII, p. 400)
hypochondria are also painful, an enema is to be given and, on
an empty stomach, a drink of birthwort, hyssop, cumin, laser
wort, white poppy, flowers of copper, honey, vinegar, and Water.
(On Diseases, III, xvi, Littre, VII, pp. 146–148)
26 PART | II History

If sudden, intense pain develops and there is faintness, make Box 3.10 Vivisectionists
pills of one drachma with rose leaves, cinnamon, pure myrrh,
Erasistratus served briefly as a court physician of Seleucus
oil of bitter almonds, and poppy sap. Put them on a pitcher
Nikator of Syria and later practiced in Alexandria and
shard and, when it is red, use for fumigation. Antioch. Famed story of Erasistratus diagnosing the son
(On Women’s Diseases, II, ccvi, Littre, VIII, p. 400) of Seleucus, Antiochus, as love sick with his young step-
mother Stratonice, was later immortalized by several artists.
They also found that poppy was used (with other ingredi- Seleucus was gracious to offer his young wife to his son,
ents) in 13 other passages to treat symptoms associated with which healed future King Antiochus’ sickness.
pain, but in the majority of conditions with pain (at least 81 Erasistratus, along with the great Anatomist Herophilus
different painful conditions discussed by Hippocrates), poppy (330–260 BCE), studied anatomy by human vivisection
was not at all prescribed. Overall, poppy was included in ap- on (alive) criminals (Bay & Bay, 2010). Both distinguished
proximately 20% of these remedial mixtures for pain in the separate neural pathways for sensory and motor function.
Hippocratic Corpus (Prioreschi et al., 1988). Given these Herophilus, often called “Father of Anatomy,” made great
findings, it may be inferred that there was no separation of contributions to the anatomy of the brain and vascular
system and was a major influence on Galen. Human vivi-
treatment of pain from general treatment of diseases in the
section was abandoned after them until the 16th century
Hippocratic Corpus. Forever a cautious physician, Hippocrates (Dobson, 1925; Pearce, 2013; von Staden, 1992).
said in the Oath, “I will give no deadly medicine to anyone if
asked, nor suggest such counsel” (Jouanna, 1999). It is widely held that Alexander the Great (356–323
The first herbal “Rhizotomika” was written by Greek BCE), a pupil of Aristotle (384–322 BCE), introduced
physician Diocles of Carystus (c. 350 BCE), known as opium to the people of Persia and India (Holt, 2003)
“younger Hippocrates.” Most of his work is fragmen- (Fig. 3.12). Aristotle himself was interested in medicine and
tary and deduced from quotes of later physicians such as
Galen, Celsus, and Oribasius. In description of medici-
nal plants, Diocles included poppy and its effects on the
body. His work is also considered to be the first to include
pictures of plants in prescriptions (van der Eijk, 2000).
There is some indication that Diagoras of Cyprus
(c. 300 BCE), “skilled at sorting the medicinal herbs”
(quoted in De materia medica, 4.64.5–6), disapproved
the use of opium (Osbaldeston & Wood, 2000). He is fre-
quently mentioned in writings of later physicians (such as
Dioscorides, Erasistratus, and Oribasius) as a prominent
­oculist and is credited with preparation of the “rose col-
lyrium” for severe pain in the eye:
“Fresh roses without the white part of the petals 72 drach-
mas (weight), kadmeía 25 drachmas, krókos (saffron) 6
drachmas, opium 3 drachmas, … myrrh 3 drachmas, …”
(quoted by Oribasius, 3.141).

Grant (1997) and Tsoucalas et al. (2018)

Diagoras was concerned with adulteration of poppy in

his preparation, which was harmful to the eye. It is also
claimed that Diagoras said that it was “better to suffer pain
than to become dependent on opium” (Booth, 1996).
It is mentioned that Erasistratus of Ceos (c. 325–250
BCE) treated snake bites with a mixture of opium and cas-
toreum (Billinger, 1876). However, Erasistratus did not
recommend poppy juice for other illnesses or pain (Tibi,
2005). Most of his works are quoted by Galen, and it is al-
leged that Erasistratus may have killed himself using opium FIG. 3.12 King Porus and Alexander the Great. Alexander vanquished
Porus in Western Punjab and then made him a satrap of his empire. This
(Pearce, 2013). It is unclear if Diagoras and Erasistratus encounter may have introduced opium poppy to India. (Engraving by
were concerned about opium due to adulterants in the prep- Alonzo Chappel (1865 CE) in Wikimedia. https://commons.wikimedia.org/
aration, or due to consideration as a poison or both. wiki/File:Surrender_of_Porus_to_the_Emperor_Alexander.jpg.)
Another random document with
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back; accordingly, on the following morning, he was seen coming along the
beach alone, "and when he had arrived within good gun-shot, they
commenced firing at him; without changing his pace, he continued to
advance, and drawing his cutlass, called out to Paine to stop firing and he
would make peace with him; Paine, however, continued to fire, and, at the
third or fourth discharge, Comstock fell lifeless upon his face, a ball having
pierced his heart. Fearing that he might not be quite dead, and perhaps would
get up again, Paine ran up to him with an axe, and cut off the back of his
neck. He was buried close to the tent, in the manner he had often expressed a
wish to be, with all his clothes on, and his cutlass hung to his side. Upon first
landing, he had fixed upon a site for a town, and amongst other public
buildings that he contemplated erecting, was a church, for which he had
selected what he considered an eligible situation.

"The natives were all the time so very friendly, that we were not in the
least afraid of them. A great many of them came to our tent every day, and
some of them were there day and night, eating, drinking, and sleeping with
us. Paine had a girl that he brought from another islet, who did not like to
stay with us, and would run away whenever she got an opportunity; he fired
muskets at her several times, and at last, used to keep her by putting her in
irons.

A few days after the ship ran away, some of the natives, who had been at
the tent, stole from us a number of tools. Paine gave four or five of our
people muskets without cartridges, and sent them to the natives, a great
many of whom were assembled not far off, for the stolen articles. The
natives refused to give them up, and soon began to throw stones at our
people, who, knowing that they had not the means of resisting, began to
retreat; the natives pursued them, throwing stones, and one of the party,
Rowland Jones, either fell or was knocked down by his pursuers, who came
up immediately afterwards and killed him. When the party returned to the
tent, Paine, who had taken the command after Comstock's death, ordered all
the muskets brought to him, and locked them up. We were all in or about the
tent, when a few hours afterwards the natives came there as usual, but in
greater numbers. After they had been there a little while, some one
remarked, 'I am afraid they are going to kill us; they have all got spears, or
stones, or sticks in their hands.' Upon this, Paine said he believed we were
all taken, but that he was safe. The words were scarcely out of his mouth,
when the natives commenced the massacre, knocking our people on the head
with stones and clubs, and sticking spears in them. An old man and his wife
laid hold of me, one on each side, and led me a little way off in the bushes,
where, I thought they were going to kill me, but where they only held me
fast and protected me from the violence of several who came and wanted to
kill me. I saw two of the natives lead Paine off a little way, and thought they
were going to save his life; but they proceeded only a few yards, when one
of them took up a stone and struck him on the head; he attempted to run, but
a second blow brought him down, and they immediately afterwards killed
him. Oliver, I did not see; but the natives told me that he ran a short distance,
when he was overtaken and killed in the bushes. A Sandwich Islander that
was with us, got to the water, and was overtaken and killed there."

"Were there any women at the massacre?"

"Oh, yes, and children too. The women seemed to take as active a part as
the men. I saw one old woman run a spear in the back of one man, who was
held by two natives, with a degree of violence that seemed far beyond her
strength. I thought that all but myself were killed until the following
evening. I had been taken to the islet where your schooner is anchored, and
where all the chiefs were assembled, when they brought Huzzy, to show me
that there was one living besides myself. After an interview of a few hours,
Huzzy was taken away to live with Lugoma, who had saved his life, and I
was taken to live with the old man who had saved mine. He was so very
poor that I scarcely ever got enough to eat of the coarsest native food. I had
to labour very hard, although I suffered constantly from hunger, which soon
made me weak and extremely wretched. At last, the high chief took
compassion upon me, and made me live with him; after which, I had always
plenty to eat, and was at liberty to work or not, as I pleased. He was very
kind to me in every respect. They have always brought Huzzy to me, or
taken me to see him once a fortnight, or once a month, and suffered us to
pass the day together."

Here Lay's narrative ended. Huzzy told us, that during his residence with
Lugoma, his time had been spent principally on the water, going with him in
his canoe, which required two to work it. Lugoma was a great fisherman,
and distinguished amongst the chiefs for his industry and enterprising
character. He would always have enough to eat, if he had to steal it. When
Huzzy would complain to him of the hard and laborious life that he led,
Lugoma would always reply, that if he would eat he must work. There seems
to be no doubt, that the natives saved the lives of these young men from no
other motive than that of making them slaves, and availing themselves of the
advantage of their labour.

At the dawn of day, we prepared to depart for the schooner, and in

getting up our anchor, which was a kedge, weighing upwards of a hundred
pounds, we found that it was hooked to a bunch of coral at the bottom, from
which all our efforts failed to move it. As soon as Lugoma saw our
difficulty, he told his son to go down and clear the anchor. The little fellow
jumped into the water, which was about three fathoms deep, and in a few
moments came up, making motions for us to haul away. He had disengaged
the kedge, and we had no further trouble in getting it up. It is a universal
practice amongst the natives, whenever they wish to anchor, to take a line
from the end of the canoe, and tie it to a tree of coral at the bottom.

The chief persisted in his desire to leave us, saying he was still afraid I
would kill him; and as I had no object in taking him with me against his will,
I consented to his departure, presenting him with some seeds, the culture of
which I caused to be explained to him, as also the value of the fruit. Our
return on board was welcomed by every body. We had now accomplished
the object of our visit, and the islands were altogether so void of interest,
except for their novel formation, and the singular habits of the natives, that
we were well content to leave them and return to some other place more
congenial to the feelings of civilized men. Before we left, however, we
wished to see the chiefs, and after representing the impropriety of their
conduct toward the white men who had sought an asylum upon their islands,
point out the course they must in future pursue towards such as might again
visit them. On the morning of December the first, none of the chiefs or
people residing upon the islet abreast of us having returned, the mother of
the high chief was directed to send for her son to come back, and bring with
him the rest of the chiefs, without delay. I made a visit to the chief's village,
where I found but few inhabitants, most of whom were women and children.
It was situated on the side of the island opposite to us, and bordering upon
the inland sea. It was not extensive, but a beautiful and romantic spot; the
grove of cocoa-nut and bread-fruit trees, through which were scattered the
huts of the natives, ran about a hundred yards back from the inland sea to a
wild thicket that passes through the centre of the islet, in length two or three
hundred yards. Here I found the largest canoe that I had yet seen. It was
large enough to carry fifty men, but being old, leaked so badly, that the high
chief was compelled to leave it behind, in his flight, with all the rest.

Near the high chief's hut, we came to consecrated ground. It was the
place of burial for the royal dead. It was but a small space, comprehended
within the circumference of a few yards, and at the head of each grave stood
a cocoa-nut tree, bound round with dry leaves,—a mark that prohibited the
use of the fruit. We were accompanied by a son of the high chief, a child
about twelve years old, who desired us not to tread on the graves of his
ancestors. Two graves were pointed out, as those of chiefs, who had been
highly distinguished, beside which stood the aged trunks of cocoa-nut trees,
that indicated the period of their demise to have been very distant. At one of
the huts we saw a domestic fowl, which, when I expressed a wish to
purchase, the chief's son, whose name was Ladro, immediately presented
me. We afterwards saw a number of others running wild in the thickets. They
were small, and looked like what is called the bantam. The natives never eat
them, giving, as the reason for it, that they are not cleanly in their food. On
our return, Lay took me to a place, where, after the massacre, he had buried
a Spanish dollar. It was still there, and he took it with him as a memento of
his captivity. We passed several springs of water, to which the women are
banished at a certain period.

We met with a native, whom Lay knew, and who, assuming the native
dress, went through the violent motions and gestures of a Mulgrave man,
engaged in battle. It was an indescribable mixture of the frightful and
ludicrous. I was apprehensive that it would offend the native: but he laughed
with us at the representation, and said, it was very good. On the following
morning, December the second, we were disappointed in not seeing the
chiefs. The captain went again to the high chief's mother, who made some
excuse for their not appearing, and declared, that they would positively be up
that night by moonlight. He told her to send to them again, and say, if they
were not there on the morrow, he would go after them, and the consequence
might be serious. The old woman seemed very much alarmed at hearing
such language, and promised a faithful compliance on the part of her son. It
had the desired effect, as on the following morning, December the third, the
chiefs all presented themselves on the shore, near our anchorage. The
captain, taking Lay and Huzzy with him, went on shore to meet them. They
told him, by way of opening the interview, that they were in his power, and
ready to obey all his commands. He required of them to restore a whale boat
that belonged to the Globe, a swivel, they had taken from the white men, and
Lay's musket, to all of which they cheerfully assented. He then gave them, as
a proof of his friendship, some cotton handkerchiefs, axes, and a variety of
other articles, of much more value to them than those he had taken. He told
them, that white men would never come there to hurt them, and that they
must always be kind and friendly to them, whenever ships should hereafter
visit their island. That, if other white men should ever be similarly situated
to those they had killed, they must take care of them, and at some future time
they would be rewarded for it. They promised faithfully to do all that they
were told, and regretted having killed our countrymen. We gave them a pair
of pigs, male and female, which we told them to take great care of, and
increase the number as much as possible, forbidding them, on pain of our
displeasure, to kill any until we should again return, which might be at no
very distant period, although it was uncertain when. The surgeon's grave was
made a sacred spot by the high chief, and every thing about it was to be held
in the same reverence as the burial-place of his forefathers. The high chief
was instructed, through the interpreters, in the manner of cultivating the
fruits and vegetables, the seeds of which we had given him in great variety.
Some we planted, and all was to be under his especial care. The use of the
various kinds was explained to him, as well as their importance to ships, that
might visit his islands, which would give him in return for them, axes, or
whatever else was most valuable to him.

On the fourth of December, I obtained a boat, and set off on a visit to

Lugoma, who, contrary to his promise, had not yet been on board. I took
Huzzy with me, knowing that it would delight the chief to see him. We met
with a variety of obstacles in our passage, through the inland sea, and did not
arrive at the islet of the chief until the second day after our departure. We
stood into his bay in the midst of a heavy shower, notwithstanding which, as
soon as he saw us, himself and son ran down to the shore to meet us, and
waded up to the middle in the water, extending their arms towards us, full of
roasted fish, of which he had taken a large quantity on the preceding day.
Both of them called to Huzzy, with repeated expressions of their happiness
at seeing him, and, in a moment after we struck the shore, the whole tribe of
old women welcomed us, with their joyful exclamations. As soon as we
were out of the boat, each one in turn clung round Huzzy's neck, and
embraced him in the kindest manner. In several different huts were large
piles of fish, amounting to some thousands, which had been roasted to
preserve them. Lugoma offered at once to accommodate us for the night,
saying, he had an abundance of room in his huts for us to sleep, and plenty
of fish for us to eat. The weather was squally and wet, which induced me to
accept his offer. I wished, also, to witness the manner in which he caught
fish in such quantities, and another opportunity might not offer before I left
the islands.

As soon as the shower was over, which lasted for two or three hours,
Lugoma went out, and employed himself busily collecting and breaking up
dry wood, and arranging his ovens of stones, that all might be in readiness to
cook the fish as soon they were taken out of the water. There was a
considerable shoal extending out from the shore, opposite to his huts, upon
which the fish, in their migrations along the islets came in great numbers. At
the outer edge of this shoal he had sunk, a few feet below the surface of the
water, a long line of cocoa-nut leaves, which were dry, and of a reddish
colour. One end of the line of leaves was taken to the shore, and made fast,
where there was a pen, built of stone. The line was then taken round upon
the shoal semi-circularly, encompassing a considerable portion of it, and the
space between the other end of the line and the shore left quite open. When a
school of fish is seen, the natives intercept them, driving them through this
open space, and, pressing forward, finally into the stone pen, from which
they are taken with nets. After all the arrangements were made, Lugoma and
another native, waded out beyond the line of leaves, to watch the schools of
fish, but, unfortunately, he allowed them all to escape; and, as well as
ourselves, seemed to be a good deal disappointed with his bad success. What
appeared to be most remarkable about this method of catching fish, is that,
after they are inclosed, they will not pass under the cocoa-nut leaves,
although there is a depth of several feet water between them and the bottom.
Lugoma took me to the place where he had planted the water-melon seeds, I
gave him at the time of our parting. He had cleared and mellowed the ground
with care, preparatory to planting the seeds, which were already up, and
looked thrifty. I bestowed upon him a great deal of praise, and planted a
variety of other seeds, of fruit and vegetables, of which he promised to have
an abundant supply for me, when I should again return. When night came,
and the hour of repose was at hand, I was perplexed with the difficulty of
providing for our security against surprise or treachery, without giving
Lugoma reason to suppose that we did not confide in his friendship, which I
knew he would infer, from any particular watchfulness on our part. I did not
believe that we had reason to apprehend danger from Lugoma or any one
else, but as we were exposed to it, and had the means of security, I was
determined not to run any risk. Three of the men were sent to sleep in the
boat, anchored off a short distance from the shore, and which Lugoma was
told no one must approach. The rest were directed to bring their arms on
shore, and keep a lookout through the night, in rotation. When the
arrangement was made, and we had all lain down, except the man that was
standing sentry, Lugoma saw him, and asked, if there was not room enough
for him to lay down. We answered evasively several times, with a view to
satisfy the uneasiness he expressed, lest he should be thought wanting in any
respect in hospitality; but were at last obliged to tell him, that the man was
keeping watch, to see that no one came to hurt us. His mortification was
evident, as he remarked, in reply, that no one would come to his island to
hurt us. We expressed our full confidence in his friendship, giving him the
further information, that it was our custom always to have some one on the
look-out. Lugoma arranged mats upon the floors of his huts for us all, and
invited me to lay down on one side of him, having his wife and daughter on
the other side. It blew and rained hard all night, but the morning was clear
and pleasant. We set off on a visit to an islet a few miles beyond that of
Lugoma. He offered to go with us, and dive for a large shell-fish, found
there; but as we could not take him, without incommoding ourselves, we
declined his company. The islet was so uninteresting, as hardly to repay us
for the trouble of going to it. It was covered with a thick growth of hard red
wood, common to most of the low islands, and wild bup. We soon took our
departure from it, and returned to Lugoma's islet, at an early hour of the day.

For the first time, at the Mulgraves', I observed, in one of Lugoma's huts,
a drum, resembling those of Nooaheeva, but of small dimensions. I supposed
it was an instrument of music, and in compliance with my request, Lugoma
readily consented to play on it. Calling his daughter to him, he bade her
thump upon it with her hands, whilst he sung, in time with the music, a few
short lines, throwing himself in a variety of attitudes, alternately extending
one arm, with great vigour, and drawing the other to his breast. Upon
inquiring what was the subject of his song, he told me, through Huzzy, that it
was the massacre of the white men,—a rudeness, I did not expect,—even
from the untutored Lugoma. I declined any further display of his musical
powers. When we were preparing to return on board, Lugoma came to me
several times, saying, that I might just as well cut his throat, as to lake Huzzy
away from him. "I have no one," said he, with a distressed look, "that is
equally capable of assisting me, to work my canoe, and now, he is going
away with his musket, my enemies can come and kill me." Finding, at last,
that he could not prevail upon us to leave Huzzy, he said, we must bring him
back very soon. That, if we were long absent, we should not find him living.
He said, that we must bring him clothes, like ours; guns and axes; and that
we should share the government of his islet with him, promising to have an
abundant supply for us, of all the fruits and vegetables we had planted.

When he and the old women had taken an affectionate leave of Huzzy,
he requested me to take two or three females in my boat, with their baskets
of fish, which were intended as a present to the high chief, and land them
upon the islet where he lived. We consented to do so, and, after landing
them, arrived on board late in the afternoon, the schooner having run down
to the Globe's anchorage, where she was now lying.

On the following morning Lugoma made his appearance on the beach,

with his little son, having landed with his canoe upon the opposite side of the
narrow islet. A boat was sent to bring them off. The chief stared wildly
round, astonished, and wondering at every thing he saw. He was very timid,
and, notwithstanding our kind reception, appeared to feel extremely doubtful
of his safety. His confidence was in a measure gained, however, when we
gave him an axe, a piece of cotton handkerchiefs, and some other trifles; and
he left us, reminding me of my promise to return. Not long after his
departure we got underway, and ran back to the residence of the chiefs,
where, at ten, A.M., we came to in our old anchorage.

The captain went on shore, and at two, P.M., December the eighth,
returned on board with the high chief, and two others. They were shown
every thing about the deck, but without awakening much apparent curiosity.
We then beat to quarters, and let them see what a formidable appearance we
made, arrayed for battle,—an appearance, truly ridiculous to one accustomed
to the imposing effect of a fine ship of war, and calculated to excite our
risibility, notwithstanding the seeming gravity we assumed for the occasion.
The captain asked the high chief, if he did not wish to hear one of the cannon
fired, to which he answered evasively, unwilling, I suppose, to acknowledge
his fears, as he had been a great warrior in his time. The captain then told
him, that he would have one of them fired, if he was not afraid, which
brought the chief to a confession, that he dared not hear it. The chiefs
brought a number of presents for the Tamon,[10] as they called the captain,
consisting principally of mats.

When they became tired of remaining on board, and expressed a wish to

be sent on shore, we gratified them, and got underway. The high chief's son,
who had visited me a number of times before, and to whom I had made
presents of trifling value, but important to him, came on board with his
father, and expressed a wish to go with me. His father gave his consent,
being perfectly willing that he should go; but as there was great probability
an opportunity would never offer for him to return, I thought it would be
cruel to take him from his native islands, where, in his father's inheritance,
he would be so well provided for.

It was late in the evening when we got underway, at the Mulgraves, for
the last time. We had surveyed all that part of the islands intervening
between our first anchorage and the Globe's landing, and now steered to the
eastward by the bearings we had previously taken. Squalls of wind and
heavy rain coming on, we soon lost sight of the land. The loud roaring of the
surf, off the extreme north-eastern point, as well as the heavy swell that set
in immediately afterwards, apprised us that we had cleared the group. The
land was in sight from the mast-head, in the morning, when we ran down for
the eastern end of the island, where we had first anchored, and at a
convenient distance run along upon the weather side, taking hearings at the
end of every base of three or four miles. Near the centre of the windward
part of the group we passed a wide opening into the inland sea, not far from
which was a reef of considerable extent, where a very high surf was
breaking. Within a short distance of the reef, we saw the bottom plainly in
ten fathoms water. There was no place on the weather side of the islands,
where it was possible to land with any degree of safety. After passing the
extreme northern point we steered off, with the trending of the land W. by S.;
and, at sun-down, were up with the island, from whence I had taken Lay,
having sailed nearly round the group. Here we hove to for the night.
 The group of Mulgrave Islands, as they are called, form a circular chain
of narrow strips of land, which are no where more than half a mile wide,
inclosing within the circle an inland sea, one hundred and forty miles in
circumference, filled with shoals and reefs of coral. It is every where
bounded on the sea-side, by a bank of coral, that protects it from the violence
of the ocean. This bank generally extends but a short distance from the
shore, when it goes off into unfathomable water. At the chief's islet, where
we buried the surgeon, it was wider than at any other place about the group,
being upwards of a cable's length, which, for a low coral island, may be
considered good anchorage. The whole circle is broken alternately into
clumps, a few feet above the water, of level and low coral reefs, some of
which are above high-water mark, and some sufficiently low to afford a
passage for boats. The clumps vary in length, but none of them are more
than two miles long, without an interruption of a dry or drowned reef. They
are covered with a thick growth of bushes, and trees of small size, except
where the cocoa-nut and bread-fruit trees rear their tall heads, and wide-
spreading branches. Wherever these grow, the underwood disappears, and
the place has the appearance of an old forest, cleared for a pleasure ground,
where a few trees have been left standing, for the advantage of their shade.

The bread-fruit tree is of two kinds. One is the same as that, which is
found at the Society, Sandwich, and many other islands of the Pacific. This
has no seed, and can only be produced by cuttings from the tree, or shoots,
that spring up from the roots. The other kind is seminal, and very much
superior to the first. It was not the bread-fruit season, when we were at the
Mulgraves, and much to our regret, we could not obtain any of the seeds of
this rare and valuable plant. This tree, in general, attains a size considerably
larger than that of the common bread-fruit. The leaf of the bread-fruit tree
strongly resembles that of the fig, and any one, who has seen the latter,
would immediately recognise it, by the resemblance, and the fine rich
foliage it bears, when growing luxuriantly. This is by far the most important
production of the Mulgrave Islands. When the fruit is not blasted, as
sometimes happens, there is a great plenty for the inhabitants. It lasts,
however, only for a few weeks; and it is to be presumed, that the natives
have no way of preserving it, in a dried or baked state, as is practised with
many of the South Sea Islanders, none having been seen by us during our
stay. The cocoa-nut tree is next in value to the natives. Of this food there is
an ample supply, unless the fruit is blasted. When the bread-fruit and cocoa-
nut, both fail in the same year, the natives experience great distress, and are
reduced to the necessity of living upon a fruit, they call bup. It is commonly
used by the poorest people, and in small quantities by the chiefs at all times.
It grows upon almost all the islands in the West Pacific; but, when wild, is
much inferior to that growing on the trees, which have a clear open space
around them.

Lay lived upon the wild bup for a considerable time after the massacre,
when residing with the poor old man, who saved his life, and before the high
chief took compassion on him. It has a sweet taste, like the juice of a green
corn-stalk. Bread-fruit, cocoa-nuts, and bup, is the only food of the
inhabitants of the Mulgrave Islands, except at the season of the year, when
great numbers of fish are taken. The industrious and enterprising have an
abundant supply at that period; but it is only whilst the season lasts, as they
are not in the practice of preserving them. The bup-tree is the most
remarkable of all the vegetable productions of the Mulgrave Islands. To
shipwrecked seamen, it might be the means of sustaining life, when no other
food could be found, and, as it is a never-failing resource, it ought to be
generally known amongst those, who navigate the Pacific Ocean. The tree
generally grows from twenty to thirty feet high,—sometimes singly, but
more frequently in small clusters. The diameter of the body rarely exceeds
six inches. It has a hard thick bark, but the wood is spongy, like that of the
cocoa-nut tree. It stands on from half a dozen to a dozen roots or prongs, by
which it is propped up two or three feet from the ground. The fruit is an
exact resemblance of a pine-apple. Its smell, when ripe, is at first agreeable,
but, so powerful, that it soon becomes offensive. The taste of the ripe fruit
has much the same effect—agreeable at first, like a mellow, sweet apple, but
cloying and nauseous to the stomach, when taken in any quantity. The ripe
fruit is never eaten by the natives of the Mulgraves. When green, it is not
considered in a state to be eaten, until a beard, which grows out alongside of
the stem, has acquired a length of four or five inches. It may then be taken
from the tree, and eaten raw, or roasted between hot stones. The soft part of
the seeds (if I may so call them) is alone palatable, the other part being hard
and tough. The manner of eating it is, to twist the soft part off with the teeth,
whereby the juice is expressed. There was but little about the islands that
would excite the interest of either the botanist or naturalist. We saw but few
flowers or plants. The islands were swarming with a species of small rat, that
had a tuft of hair upon its tail. The natives spoke of them as being very
troublesome. By throwing a small quantity of food upon the ground, near
one of the huts, dozens of them could be collected together in a few
moments.

When one of the natives is sick, the friends collect at the hut, where he is
lying, and chant over him, to appease the offended spirit that has afflicted
him. The same prescription is given for all diseases, which is a tea, made
from an herb found upon the island. If death takes place, the friends of the
deceased assemble, and mourn over the body, keeping it until it becomes
very offensive. Frequently, in the midst of their most bitter mourning and
lamentation, some of the mourners will intentionally say or do something
calculated to excite mirth, when they all burst out into immoderate laughter,
as if their mourning were the affectation of children, and as soon as the
humorous excitement has passed over, again relapse into their mournful
strain of howling and chaunting. When the body can be kept no longer, and
the day of interment arrives, the grave is dug, and the corpse taken upon
sticks, and carried to it by the friends of the deceased, followed by a large
concourse, who move along without order, and some one occasionally
breaks in upon their solemnity by a humorous trick, which gives rise to
others, and sets them all laughing. This is soon again succeeded by
mourning. The body is lowered into the grave, and covered up, when a little
canoe, with a sail to it, and laden with small pieces of cocoa-nut or other
food, having been previously prepared, is taken to the sea-shore on the
leeward part of the island, and sent off, with a fair wind, to bear far away
from the island the spirit of the deceased, that it may not afterwards disturb
the living. This ceremony is considered indispensably necessary, and is
never neglected. At the head of the grave a cocoa-nut is planted, the tree that
springs from which, is held sacred, and its fruits never eaten, in times of the
greatest famine. Their burial places are usually a short distance back of the
houses, and the females are strictly prohibited from going to them.

Their marriages are conducted with but little ceremony. If a man fancies
a female for his wife, he makes the proposal to her, which, if agreeable, he
applies to her friends. They meet, and hold a consultation, as to the propriety
of the match, and decide whether it shall take place. If the man's suit is
denied, nothing more is said on the subject. When united, they are said to be
very faithful, and jealous of each other's chastity. Lay or Huzzy related an
occurrence, that took place during their residence on the islands, which
shows how keenly a sense of injury is felt by them, and that jealousy
sometimes inspires them with the most ferocious and deadly revenge. A
young man had taken a young woman for a wife, whom he supposed to be a
virgin. In a very short time after she went to live with him, however, it was
evident that she was pregnant, and before the period which nature has
prescribed had elapsed, gave birth to a child. The indignant husband took the
infant from its mother's arms, and in her presence dashed its head upon a
stone in front of his hut. It was an act for which, under other circumstances,
he would have suffered death, by a custom of the islands, forbidding the
destroying of human life; and, as the female was of superior rank to the man,
being the daughter of a chief, it was believed that he would be punished. Her
friends were loud in their calls for justice upon the offender, until a council
of the chiefs was called, and the matter brought before them.

After an investigation, the chiefs were satisfied, that the woman had
grossly imposed upon her husband, whom they suffered to depart without
censure. It is permitted to the men to have as many wives as they can get;
but as food is very scarce, and they find it difficult to support one, there are
few, even of the chiefs, who have more. The high chief was the only
exception to this remark at the time of our visit. He had six, one of whom
was a particular favourite.

Latuano, the high chief of the Mulgraves, was called the greatest warrior
that the islands had produced for a long time. He told us that in one of his
wars he was driven from his islands, and remained (I think) fourteen days at
sea in his canoe, most of the time out of sight of land. He steered for an
island, which, according to the tradition of his countrymen, lay to the west of
the Mulgraves, and, after a great deal of suffering, arrived there in safety.
The high chief of this isle (south Pedder's Island) received him with
kindness, and after he had visited thirteen different islands of the group,[11]
sent him back to the Mulgraves with a fleet of canoes, and a great many
men. He arrived there in safety, conquered his enemies, and at the time of
our visit was tributary to the chief of Pedder's Island, who had given him a
daughter or grand-daughter in marriage. They told us that every few years
the chief of Pedder's Island, who is very powerful and very wise, sends a
fleet of canoes to the Mulgraves, for tribute. Lay and Huzzy were to have
been sent to him, as also the Globe's whaleboat and swivel. I was
particularly struck with Latuanos' strong resemblance to General Bolivar.
His stature was about the same, and his face bore the same marks of care and
serious thought, when his attention was not awakened to any particular
thing; and, when animated by conversation, the same vivid expression
beamed from his fine features, and sparkling black eyes. I could not but
think, when I was looking at him, that if he and General Bolivar could be
placed near to each other, similarly dressed, it would be difficult to tell
which was the Indian chief, and which the patriot hero.

The high chief is absolute in his authority, but, in the administration of

justice, particularly where the life of an individual is concerned, he is
influenced in passing judgment by the opinion of the chiefs of most
consequence.[12] Like all other men, whether civilized or uncivilized, they
have different grades of rank in their society, from the high chief down to the
farthest remove of relationship to royalty. The different islets that are
inhabited, are partitioned off to different chiefs, who acknowledge their
subordination to the high chief, by sending him a part of whatever grows, or
is taken within the limits of their government. They send him a portion of
their cocoa-nuts, bread-fruit, and bup, and of the fish or birds, that may be
caught by themselves or any of their people. The high chief requires this for
the support of his numerous family. Besides his wives and children, he
usually keeps a large number of men about him, who go in his canoe, and
perform other essential duties in his service. Several of the principal chiefs
are also in attendance, and live with him constantly. In his family, there is no
ceremony, to remind the common people of their lowly condition. They all
eat, drink, and sleep alike. In dress, there is nothing to distinguish the chiefs
from the common people, except that the former sometimes wear a mat that
comes down to the knee, of straw, and finely wrought. This, however, I
believe, is only worn upon particular occasions.

The men wear bunches of grass hanging down before and behind, such
as I have described at our first anchorage, being about the size and
appearance of a horse's tail. Those in most common use, were of a reddish
colour; but a few of them were white. The bark of which they are made is
taken from a long running vine. The boys go quite naked until they are ten or
twelve years old, when a dress similar to that of the men is put on them.
Their ornaments consist of shell bracelets and necklaces, and sometimes a
string of thorn is put round the head; flowers, when they can be obtained, are
often used instead of shells. Many of the men, and some of the women have
large slits in their ears, through which they put rolls of leaves from one to
two inches in diameter. The women wear beautiful white straw mats, of
elegant workmanship, about two feet square, and sometimes larger, bordered
round the edge, from one to two inches, with black diamond figures, worked
in with coloured straw, died with the husk of the cocoa-nut. They usually
wear two of these mats, one of which is behind and the other before, tied
round the waist with a beautiful round cord of braided straw. The ornaments
of the women are the same as those worn by the men. They have no manner
of worship. They acknowledge the existence of a Great Spirit whom they
call Kenneet, and who, they say, can make them sick and kill them: they
look for nothing good from him, and, so far as I could learn, have no idea of
rewards and punishments after death. They have a sort of conjurers amongst
them, for whose art they entertain great reverence, and in whom they place a
strict reliance. To them they apply in all cases of great emergency. Their art
consists in having a large bunch of straws, which they fold double and tie in
a great many different ways; if, after the straws are thus folded, doubled, and
tied, they can be drawn out without being in any manner entangled the one
with the other, the omen is propitious; but otherwise, the contemplated
undertaking is relinquished. On the following morning it is again resorted to,
and so on until success is promised. It must never be tried but in the
morning, and only once on the same day. The morning I took Lay from the
natives, the chiefs had recourse to this art before they would allow him to
speak to us; they were promised good fortune, otherwise he would have been
concealed from us. He who cannot perform the mysteries of this art, is not
allowed to drink from the same cup with him who can.
 They had a great aversion to hearing us whistle, particularly in their
houses, and would invariably run up to any of our people when they were
whistling, and with a fearful look, beg them to stop; saying, it would bring
spirits about the house that would make them sick and kill them. If one of
them has wronged another who has died, or if they were enemies, he never
eats without throwing away a portion[13] of his food to appease the ghost
of the departed.

At a meeting we had with the chiefs on shore, the captain remarked an

old man in the circle, whose name and character he asked of Lay or Huzzy;
being replied to, he said, in a stern manner that he did not like his face,
meaning that he looked like a bad man. The old fellow, seeing himself the
subject of conversation, asked the interpreter what the captain was saying
about him. On being told, his countenance expressed the utmost dismay,
and in a day or two afterwards, he died. There was not a native on the
islands with whom Lay or Huzzy conversed, that did not believe the
captain's dislike killed the old man. They seemed to entertain the most
singular notions of the captain's supernatural powers.

For the purpose of ascertaining what idea the high chief entertained of a
God, the captain asked him several questions, to which his answers were
vague and unsatisfactory. He thought he had conceived the right one, when
he asked the chief who he thought made it thunder. After a moment's
hesitation, he looked at the captain and replied, "I suppose you can make it
thunder." This was as satisfactory as any thing he could be made to express.
Thunder he believed was produced by the agency of a being superior to
himself, and the captain he conceived to be infinitely his superior.

Not long after the massacre of the white men, the natives were visited
by a disease that caused their limbs to swell, and produced great distress
amongst them; it was before unknown, and they ascribed it to Lay and
Huzzy, who, they believed, had the power to afflict them in that manner,
and had done it to be revenged for the death of their countrymen. They
finally charged them with it, and threatened to kill them, which, in all
probability they would have done, but for their superstitious fear of some
greater evil.
 Their huts are not, generally, more than ten by fifteen feet, and from ten
to fifteen feet high. They are divided into two apartments, upper and lower;
the lower is open all round, without any thatching; the floor is raised a little
above the adjacent ground, and covered over with small pieces of the
cleanest and whitest coral that can be found. The rafters and small sticks
that are laid across them for the thatching, are secured by twine made from
the outer husk of cocoa-nut, with which the thatching is also secured. The
thatch is the leaves of palm or cocoa-nut. The ceiling of the lower room is
generally so low, that one must bend almost double to get into it, and if you
remain, it must be in a lying or sitting posture. The garret has a floor of
sticks thickly interwoven with leaves; it is higher than the ground floor, and
has an air of comfort. The natives keep their provisions in it, and all such
things as they would preserve from the rats. They also sleep there in wet
weather. In the floor, a hole is left just large enough for a person to crawl
through, and so far from the sides that the rats cannot get to it.

Their canoes display the greatest ingenuity, and I have no doubt, that in
a civilized country, they would be ranked amongst the rarest specimens of
human industry, unassisted but by the rudest implements. The model is
most singular, and differs from all that I have ever seen in use, either in the
European or American world. Its construction is so remarkable, and in
many respects so inconvenient, that it seems improbable the model should
have had its origin in any other cause than the want of suitable timber for a
more perfect structure. The depth of a Mulgrave canoe, of common size, is
four or five feet; its length from thirty to forty. It is so narrow that a man
can scarcely stand in it; perfectly flat on one side, and round on the other. It
is sharp at both ends. The mast is from twelve to twenty-five feet long, and
the sail, (a straw mat,) which is bent to a small yard, is very large in
proportion to the canoe. They always sail on the flat side, and have the mast
a little inclined forward. It is supported by shrouds and a guy at either end,
which is used at pleasure to give the mast its proper inclination. In beating
to windward, instead of tacking as we do, and presenting the other side of
the boat to the wind, they bring the other end of the boat to it, making that
the bow which was before the stern. Amidships there are several light spars
extending about ten feet over the round side, and four over the other. Across
these are smaller sticks, which are securely lashed above and below, and
over them is made a platform. Upon that part of it which extends over the
flat side, they have a small thatched cabin, in which they store whatever
they wish to preserve from getting wet, or would conceal from observation.
The other part of the platform is intended to keep the canoe from being
upset; and when hard pressed with carrying sail, several men will
sometimes get on it, to keep the canoe upright. They move through the
water with astonishing velocity, and, in turning to windward, no boats can
surpass them. Although the natives had no other tools to work with than
what they made of shells, previous to the visit of the Globe, every article of
their workmanship is neat, and as highly polished as though it had been
wrought with steel. In the construction of their canoes, the keel-stern and
sternpost are solid pieces of hard wood, upon which they are built up of
small pieces laid one above the other, and closely seized on with the line of
cocoa-husk. The seams are neither caulked or payed, and the canoe
consequently leaks so much as to require one man to bail constantly. The
steerage is very laborious; they have no rudder, and the only means by
which they steer, is with a long flat paddle held in the hands of the
helmsman. To steer a large canoe in blowing weather, requires the utmost
strength of six or eight men. Upon the outriggers or platforms, and along
the masts, they arrange their spears, which are always taken with them,
even upon the most ordinary occasions. The canoes are also always
ballasted with a quantity of round stones, weighing about a pound each,
which forms a material part of their armament. Our carpenter was several
days at work upon the canoe of the high chief, caulking and graving her.
When he had completed his work, the high chief, after expressing his
gratification, earnestly solicited the captain to leave him on the island; he
said that he would always provide him an abundance to eat, and that no one
should ever hurt him. This, according to the high chief's standard, was the
most ample reward that he could promise for useful services.

The people of the Mulgraves are in general of moderate stature, and

well made. Their complexion is not so dark as that of the natives of the
Duke of Clarence and Byron's Island, and their features more comely. They
appeared to us like a different race of men. They have not the flat noses and
thick lips of the low islanders, except that two or three persons we saw
would come under that description. Their hair is long and invariably
combed out with great neatness, and tied on the top of their heads. Their
deportment is modest and manly, and after one becomes a little accustomed
to their dress, they have always an air of gentility. They have a fine majestic
walk, which one would hardly suppose, when it is considered that their way
is everywhere paved with sharp coral.

After we had given them the pigs, it was amusing to see with what
apparent pleasure they carried them about in their arms, nursing them with
as much care and tenderness, as though they had been children, whilst the
pigs, unused to such treatment, were kicking and scratching the naked
bodies of the poor natives, and squealing away most lustily. We had to
interfere to keep the pigs from being killed with kindness, and finally
prevailed upon the chief to forbid their being petted in this style. It is not
improbable that, in a few years, the whalers that may have occasion to
cruise, in the vicinity of these islands, will find an abundant supply. It is
hoped, however, that until they become numerous, no navigator who may
chance to touch there, will encourage the natives to diminish their number.

At 4, A.M., on the 9th of December, we took our departure from the

Mulgrave Islands, and stood to the westward. At daylight, we had lost sight
of the group, and at 10, A.M., made South Pedder's Island. Having stood a
little too far to the southward, we were all day beating up to weather the
N.E. point, where, at sun-down, we hove to in the hope that on the
following morning we should be able to effect a landing, and get a sight of
the great chief, so celebrated amongst the people we had just left. On the
11th of December, having passed all the early part of the day searching in
vain for anchorage, we hove to, a little after meridian, opposite to a
considerable bay, upon the shore of which was a native village, and large
forests of cocoa-nut trees. The captain took Huzzy in the gig, and, followed
by another boat, pulled in over a wide coral bank to the village. A few
people were attracted to the shore by the appearance of our boats. They
immediately conducted the captain to the chief, who was seated on a mat in
the open air, in front of his hut. He seemed but little moved at the
unexpected appearance of his visitors. He was a very old man, and had a
long white beard that came down upon his breast. The natives stood round
in respectful silence, as the old chief addressed the captain, whom he soon
distinguished as the person of highest rank amongst the strangers. He spoke
the same language as the inhabitants of the Mulgraves, and Huzzy was
forbidden to let him know that he was understood, but to listen attentively
to what he was saying to those around him. For a time his intercourse with
the captain was carried on by signs, and Huzzy overheard him say to the
natives, standing by, "Don't disturb them yet. Wait until to-morrow, and see
what they are going to do. They will look round here to see what they can
find, trade a little, and go on board of their vessel, to sleep, and to-morrow
they will come again." When the captain told Huzzy to address some
questions to the chief in his own language, it seemed to operate as quickly
as an electric shock upon the natives, who stared wildly around at him, and
at each other, with looks of the utmost astonishment. The chief partially lost
his gravity in the sensation it produced, being not less surprised than his
subjects. He asked Huzzy, before answering the question put to him, where
he had learned to speak the language of Pedder's Island. Huzzy replied, that
he had learned it at the Mulgrave Islands, where he had been for two years.
The old chief said, that he had been informed of two white men being there,
and was then fitting out a fleet of canoes to send after them. He expressed a
great deal of disappointment, that we had taken them away, saying, he
would have had them brought to his own island, and treated them well. He
asked, if Lay was also on board of the vessel. The captain had taken on
shore a present for the chief, and a number of trifles, that he thought might
be acceptable to the natives. Our people endeavoured to obtain a quantity of
cocoa-nuts and bup, of which there was the greatest abundance; but the
natives parted with their fruit very reluctantly. When finally the captain
addressed the chief, upon the subject of giving or selling us a supply, he
said,—No! that his island was thickly inhabited, and produced no more
food than was necessary for his people. That, if we were in want of cocoa-
nuts and bup, there were other islands, not far to the westward, where there
was an abundance, and but few people, and he advised our going there as
speedily as possible. Upon being asked, if he had ever seen white men
before, he replied,—Yes; that a long time ago there came a large vessel, in
which there were white men, who brought their forge on shore, where they
remained for several days. This, he said, was the only instance. The young
women were all sent away, and concealed in the thickets, or upon a distant
part of the island, where they remained during the whole day.

Amongst other presents made by the captain to the high chief, was a
battle-axe,—to him an article of the greatest value. He received it, however,
with reluctance, expressing his regret, that he had it not in his power to