Drugs in sport 7th edition

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Contents

6.6 6.7

vii

Summary 95 References 95

7 The role of Athlete Support Personnel in drug use in sport

99

NEIL CHESTER, MARK STUART AND DAVID R. MOTTRAM

7.1 7.2 7.3 7.4 7.5 7.6 7.7

Introduction 99 Athlete Support Personnel 99 Medical support personnel and athlete therapy 105 The World Anti-Doping Code and Athlete Support Personnel 106 Education and support for Athlete Support Personnel 111 Summary 111 References 112

8 Medical and pharmacy services for international games

114

MARK STUART

8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 8.10 8.11 8.12 8.13 8.14 8.15

Introduction 114 Medical services at sporting venues 114 The games polyclinic 115 Polyclinic services 116 Role of healthcare professionals in anti-doping 117 Medical workforce and training 117 Drug administration to athletes 118 Prescribing prohibited substances to athletes 118 Medicines governance 119 Selection of medicines for athlete treatment at games 120 Patterns of drug use 121 Importation of drugs for team use 123 Anti-doping support for local healthcare services 124 Summary 124 Bibliography 124

SECTION 2

Substances and methods prohibited in sport

127

9 Anabolic agents

129

NEIL CHESTER

9.1 9.2 9.3 9.4 9.5

Introduction 129 Anabolic androgenic steroids 130 Pharmacology of anabolic androgenic steroids 131 Clinical uses of anabolic androgenic steroids 134 Anabolic androgenic steroids as performance- and image-enhancing agents 134

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Contents

9.6 9.7 9.8 9.9 9.10 9.11 9.12 9.13 9.14 9.15 9.16

Adverse effects following anabolic androgenic steroid use 136 Use of anabolic androgenic steroids in sport 138 Prevalence of anabolic androgenic steroid use 141 Designer steroids 143 Prohormones 143 Detection of anabolic androgenic steroids 144 Selective Androgen Receptor Modulators 145 Beta-2 agonists 145 Tibolone 146 Summary 146 References 146

10 Peptide hormones, growth factors and related substances

151

DAVID R. MOTTRAM AND NEIL CHESTER

10.1 Introduction 151 10.2 Erythropoiesis-stimulating agents 152 10.3 Hypoxia-inducible factor (HIF) stabilizers 156 10.4 Chorionic gonadotrophin (CG) 156 10.5 Luteinizing hormone (LH) and its use in sport 157 10.6 Corticotrophins 158 10.7 Growth hormone (GH) 158 10.8 The abuse of growth hormone in sport 160 10.9 Growth hormone releasing factors (GHRFs) 163 10.10 Detection of growth hormone abuse 163 10.11 Growth factors 165 10.12 Prevalence of peptide hormone use in sport 166 10.13 Peptide hormones as potential targets for gene doping 167 10.14 Summary 167 10.15 References 168 11 Beta-2 agonists

173

NEIL CHESTER AND DAVID R. MOTTRAM

11.1 11.2 11.3 11.4 11.5 11.6 11.7

Introduction 173 What are beta-2 agonists? 173 Clinical uses of beta-2 agonists 174 The illicit use of beta-2 agonists in sport 179 Beta-2 agonists and the WADA Prohibited List 183 Summary 184 References 184

12 Hormone and metabolic modulators NEIL CHESTER

12.1 Introduction 188 12.2 Hormone and metabolic modulators and the WADA Prohibited List 188

188

Contents

12.3 12.4 12.5 12.6 12.7 12.8 12.9

ix

Aromatase inhibitors 189 Selective Oestrogen Receptor Modulators 190 Other anti-oestrogenic substances 191 Agents modifying myostatin function(s) 192 Metabolic modulators 193 Summary 196 References 196

13 Diuretics and masking agents

199

DAVID R. MOTTRAM

13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8

Introduction 199 What are diuretics? 199 Action and use of diuretics in sport 199 Action and uses of masking agents in sport 202 History of diuretics and masking agents in sport 203 WADA classification of diuretics and masking agents 206 Summary 208 References 208

14 Manipulation of blood and blood components

210

YORCK OLAF SCHUMACHER

14.1 14.2 14.3 14.4 14.5 14.6 14.7

Introduction 210 Blood transfusions 211 Erythropoiesis stimulating agents 212 New developments in erythropoietic drugs 213 Blood substitutes 215 Summary 217 References 217

15 Chemical and physical manipulation

219

DAVID R. MOTTRAM

15.1 Introduction 219 15.2 Current (2017) WADA regulations with respect to chemical and physical manipulation 219 15.3 Prevalence of chemical and physical manipulation in sport 220 15.4 Institutionalised manipulation of the doping control process 223 15.5 Techniques for identifying chemical and physical manipulation 225 15.6 Summary 226 15.7 References 226 16 Gene doping DOMINIC J. WELLS

16.1 Introduction 228 16.2 What is gene doping? 228

228

x

Contents

16.3 16.4 16.5 16.6 16.7 16.8

Clinical uses of gene therapy 230 History of gene doping in sport 234 Action and use of gene doping in sport 234 Gene doping and the WADA Prohibited List 235 Summary 236 References 237

17 Stimulants

242

DAVID R. MOTTRAM

17.1 17.2 17.3 17.4 17.5 17.6

Introduction 242 Types of stimulants and their modes of action 242 The use of stimulants in sport 245 Stimulants and the WADA Prohibited List 256 Summary 259 References 259

18 Narcotics

263

DAVID R. MOTTRAM

18.1 18.2 18.3 18.4 18.5 18.6 18.7 18.8

Introduction 263 What are narcotics? 263 Clinical uses of narcotic analgesics 263 The history of narcotics in sport 265 The action and use of narcotics in sport 268 Narcotics and the WADA Prohibited List 269 Summary 270 References 270

19 Cannabinoids

271

DAVID R. MOTTRAM

19.1 19.2 19.3 19.4 19.5 19.6 19.7

Introduction 271 What are cannabinoids? 271 History of cannabis in sport 274 Cannabinoids in sport 275 Cannabinoids and the WADA Prohibited List 277 Summary 280 References 280

20 Glucocorticoids NICK WOJEK

20.1 Introduction 283 20.2 Clinical uses, side effects and mode of action 284 20.3 Physiological and pharmacological effects 286

283

Contents

xi

20.4 Anti-doping regulations 290 20.5 Summary 293 20.6 References 294 21 Alcohol

298

DAVID R. MOTTRAM

21.1 21.2 21.3 21.4 21.5 21.6 21.7

Introduction 298 Mode of action of alcohol 298 Adverse effects of alcohol 300 Alcohol use in sport 301 Alcohol and the WADA Prohibited List 304 Summary 305 References 305

22 Beta blockers

307

DAVID R. MOTTRAM

22.1 22.2 22.3 22.4 22.5 22.6 22.7 22.8

Introduction 307 What are beta blockers? 307 Clinical uses of beta blockers 309 History of beta blockers in sport 310 The action and use of beta blockers in sport 311 Beta blockers and the WADA Prohibited List 312 Summary 315 References 315

SECTION 3

Substances and methods permitted in sport

317

23 Non-steroidal anti-inflammatory drugs

319

NICK WOJEK

23.1 23.2 23.3 23.4 23.5 23.6 23.7

Introduction 319 What are NSAIDs? 319 Clinical uses and efficacy 320 Adverse effects 322 Prevalence of use and ethical issues of NSAID use within sport 323 Summary 324 References 325

24 Sports supplements and herbal preparations NEIL CHESTER

24.1 Introduction 328 24.2 What are sports supplements? 328

328

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Contents

24.3 Why do athletes use supplements? 329 24.4 The prevalence of supplement use 330 24.5 The risks associated with supplement use 331 24.6 Herbal supplementation 335 24.7 Anti-doping violations involving the use of sports supplements 339 24.8 Safeguarding athletes against inadvertent doping through supplement use 340 24.9 Summary 342 24.10 References 342 25 Caffeine

346

NEIL CHESTER

25.1 Introduction 346 25.2 Pharmacology 347 25.3 Mechanisms of action 348 25.4 Performance-enhancing properties 349 25.5 Caffeine combinations 354 25.6 Therapeutic actions 355 25.7 Adverse side effects 355 25.8 Caffeine use and WADA regulations 357 25.9 Summary 358 25.10 References 358 SECTION 4

Evolving issues concerning drug use in sport

365

26 Drug use in society and the impact on the anti-doping movement

367

NEIL CHESTER AND JIM MCVEIGH

26.1 26.2 26.3 26.4 26.5 26.6

Introduction 367 Recreational psychoactive drug use 367 Performance- and image-enhancing drug use 369 Performance-enhancing drug use in recreational/non-elite athletic groups 371 Human enhancement technology 372 The normalisation of drug use in society and the impact on the anti-doping movement 374 26.7 Summary 375 26.8 References 376 27 Governance and corruption in sport with respect to doping NEIL KING

27.1 Introduction 379 27.2 The evolution of anti-doping policy: an overview 380

379

Contents

xiii

27.3 The anti-doping governance infrastructure 381 27.4 Case study: doping in Russia and the McLaren reports 382 27.5 Building an effective governance infrastructure and anti-doping policy 384 27.6 Discussion: at a crossroads – doping as a test case for sport governance 390 27.7 Summary 391 27.8 References 391

Index

395

Figures

1.1 Some physiological effects of adrenaline mediated through the five principal classes of adrenergic receptors 1.2 Drugs used socially or recreationally that are subject to WADA regulations and the number of adverse analytical findings, for each class of drug, reported by WADA laboratories in 2015 2.1 Time-line for significant events related to sport, doping and anti-doping 3.1 Sports with the highest number of ADRVs 4.1 A schematic representation of the structure of anti-doping within the context of the World Anti-Doping Code 5.1 Normal haematological profile depicting the haematological markers 5.2 Example of a blood passport indicating the abuse of an erythropoietic stimulant such as EPO 5.3 Flow chart of the evaluation process for the assessment of blood profiles in the Athlete’s Biological Passport (adapted from Schumacher and d’Onofrio, 2012) 5.4 A flow diagram illustrating the chain of events with respect to sample provision, analysis and potential sanctioning following the confirmation of an adverse analytical finding 7.1 The various roles that individuals fulfil to support the athlete 7.2 Range of suspension periods (in years) for the Athlete Support Personnel listed as suspended by WADA on 10 April 2017 9.1 The formation of testosterone and its derivatives 9.2 The molecular structure of testosterone illustrating the major sites of modification in the formation of synthetic anabolic androgenic steroids 10.1 Results of the detection of erythropoiesis stimulating agents obtained using isoelectric focusing and chemiluminescence.

Image courtesy of the World Anti-Doping Agency 10.2 Results of the detection of erythropoiesis stimulating agents obtained using SDS-PAGE. Image courtesy of the World Anti-Doping Agency

9

15 22 44 54 74 74

76

79 100 110 132

133

153

154

List of figures

11.1 Numbers of adverse analytical findings for beta-2 agonists in Summer and Winter Olympic sports for 2015 17.1 The inter-relationship between the various nervous systems of the body 19.1 Percentage of all adverse analytical findings from WADA anti-doping testing figures that relate to cannabinoids, for the years from 2003 to 2015 19.2 The sports within which AAFs for cannabinoids were most frequently recorded in 2015 20.1 Simplified scheme of the synthesis, secretion and actions of glucocorticoids 22.1 Sports in which beta blockers were identified through WADA test results, for 2015 23.1 Biosynthesis of prostaglandins and the mode of action of NSAIDs 25.1 Chemical structure of naturally occurring methylxanthines

xv

180 243

278 279 284 313 320 348

Tables

1.1 1.2 1.3 1.4 1.5 1.6 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 2.10 2.11 2.12 2.13 2.14 2.15 3.1 3.2 3.3 3.4

WADA Prohibited List, January 2017 Examples of the classification and description of drugs by their names Examples of the classification of drugs by their mechanism of action and use Examples of dosage forms for drugs used in sport Side effects associated with some drugs that are commonly misused in sport Medical conditions for which athletes may require drug treatment involving drugs that appear on the WADA Prohibited List Major changes to the IOC Prohibited List 1967–2003 German Democratic Republic doping programme (1970s and 1980s) Ben Johnson case (1988) The Festina affair (1998) Ross Ribagliati case (1998) Alain Baxter case (2002) Major changes to the WADA Prohibited List 2004–2012 Major changes to the WADA Prohibited List 2013–2017 The BALCO affair (2003) Operación Puerto (2006) Lance Armstrong case (2012) Significant changes introduced in the 2015 World Anti-Doping Code Key findings of the McLaren Independent Person 1st Report Some key findings of the McLaren Independent Person 2nd Report Maria Sharapova case (2016) Adverse and atypical findings, for all sports, by WADA-accredited laboratories from 2003–2015 Substances identified as AAFs in each drug class (all sports) by WADA-accredited laboratories from 2003–2015 Summary of WADA Anti-Doping Rule Violation (ADRV) Reports for 2013–2015 Profile of Anti-Doping Rule Violations (ADRVs) as a result of an adverse analytical finding (AAF)

4 4 5 5 10 13 24 25 26 28 28 29 30 31 32 33 33 35 35 36 36 41 42 43 44

List of tables

6.1 6.2 6.3 6.4 7.1 7.2 7.3 7.4 8.1 8.2 9.1 9.2 9.3 10.1 10.2

11.1 11.2 11.3 12.1 12.2 13.1 13.2 13.3 13.4 15.1

Examples of prohibited substances that may be taken inadvertently Reports on the extent of supplement use by elite athletes Definition of “No fault or negligence” and “No significant fault or negligence” Summary of WADA’s ineligibility sanctions Profile of non-analytical Anti-Doping Rule Violations (ADRVs) (including Athletes and Athlete Support Personnel) Profile of non-analytical Anti-Doping Rule Violations (ADRVs) by type of violation Non-analytical ADRV cases committed by Athlete Support Personnel classified according to the nationality of the ASP Country of origin for the 148 Athlete Support Personnel listed as suspended by WADA on 10 April 2017 (WADA, 2017) Most commonly prescribed medicines during the London 2012 Olympic Games period Some results of sports injuries and illnesses at London 2012 Olympic Games Class S1 of the 2017 WADA list of prohibited substances and methods Categorisation of AAS according to their route of administration and their structural modification from testosterone Prohibited anabolic agents identified by WADA-accredited laboratories in 2015 The list of peptide hormones, growth factors, related substances and mimetics on the WADA Prohibited List (January 2017) WADA statistics for the number of positive results for substances classed as peptide hormones, growth factors and related substances (2009–2015) Selective beta-2 agonists WADA statistics for the number of adverse analytical findings for substances classed as beta-2 agonists (2006–2015) WADA Prohibited List (2017) regulations relating to beta-2 agonists Class S4 of the 2017 WADA List of prohibited substances and methods Prohibited hormone and metabolic modulators identified

by WADA-accredited laboratories in 2015 Classification of diuretics and their major clinical uses Substances used as masking agents in sport WADA statistics for the number of positive results for substances classed as diuretics and other masking agents (2009–2015) List of substances included under diuretics and other masking agents in the WADA Prohibited List, 2017 WADA Prohibited List (2017) regulations relating to chemical and physical manipulation

xvii

84 90 92 93 107 107 108 109 122 123 130 134 141 151

167 174 179 180 188 189 200 202 204 207 219

xviii

List of tables

15.2

Adverse analytical findings (AAFs) relating to chemical and physical manipulation from WADA statistics 2003–2015 Statistics from WADA-accredited laboratories for adverse analytical findings (AAFs) for substances classed as stimulants (2008–2015) Stimulants that appear on the WADA Prohibited List and which are commonly found in supplements WADA (2017) regulations regarding stimulants WADA statistics for the number of adverse analytical findings for substances classed as narcotics (2006–2015) WADA (2017) Prohibited List regulations with respect to in-competition use of narcotics Incidences of glucocorticoids reported as adverse analytical findings by WADA-accredited laboratories from 2009–2015 Demonstrable effects of alcohol at different blood alcohol concentrations Particular sports in which alcohol was prohibited, according to the WADA Prohibited List (2017) WADA statistics for the annual number of adverse analytical findings for alcohol The main tissues and organs of the body (other than the brain) that contain β-adrenoceptors and the pharmacological effects produced by beta blockers Beta blockers and their receptor selectivity The main clinical conditions for which beta blockers are used 2017 WADA regulations for beta blockers WADA statistics for the number of adverse analytical findings for beta blockers (2006–2015) Examples of selective and non-selective COX inhibitors available in the UK (data obtained from the following medicine databases: Medicines.org.uk and MHRA.gov.uk, 2017) Caffeine content of selected beverages and OTC products Examples of pharmacological agents used to enhance performance and image

17.1 17.2 17.3 18.1 18.2 20.1 21.1 21.2 21.3 22.1

22.2 22.3 22.4 22.5 23.1

25.1 26.1

220 246 254 256 266 269 292 300 304 305

308 308 309 313 314

321 346 373

Boxes

6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 6.10 6.11 6.12 8.1 10.1 10.2 10.3 10.4 11.1 11.2 11.3 11.4 11.5 13.1 13.2 13.3 13.4 15.1 15.2 15.3 15.4 15.5

Alberto Contador (2010) Nick Delpopolo (2012) Andreea Raducan (2000) Timo Hoffmann (2013) Nicklas Backstrom (2014) Frankie Dettori (2012) Abdur Rehman (2012) Richard Gasquet (2009) Gil Richards (2016) Evi Sachenbacker-Stehle (2014) Dieter Baumann (1999) Justin Gatlin (2006) Prescription procedure for prohibited substances at international games Lance Armstrong (2012) Johannes Duerr (2014) Terry Newton (2010) Nikolay Marfin and Vadim Rakitin (2012) Ian Sibbit (2009) Simon Yates (2016) The “Festina affair” (1998) Jessica Hardy (2008) Alberto Contador (2010) Pedro Delgardo (1988) 8th Swimming World Championships, Australia (1998) World Nordic Skiing Championships, Finland (2001) Zach Lund (2006) Katrina Krabbe (1992) Michelle de Bruin (née Smith) (1998) Galabin Boevski (2003) Rebecca Gusmao (2007) Olga Yegorova (2008)

85 85 86 87 87 88 89 89 89 91 91 91 119 155 155 164 165 181 181 183 183 183 205 205 205 206 221 221 221 222 222

xx

17.1 17.2 17.3 17.4 17.5 17.6 17.7 17.8 17.9 18.1 18.2 18.3 18.4 18.5 18.6 19.1 19.2 19.3 19.4 19.5 22.1

List of boxes

Tommy Simpson (1967) Kelli White (2003) Andreea Raducan (2000) Alain Baxter (2002) Martina Hingis (2007) Richard Gasquet (2009) Frankie Dettori (2012) Vitalijs Pavlovs, William Frullani and Evi SchenbacherStehle (2014) Asafa Powell (2013) “Pot Belge” Festina affair (1998) Cahors affair (2005) Christophe Brandt (2004) Ambesse Tolossa (2007) Kate Reed (2008) Ross Ribagliati (1998) Tomas Enge (2002) Michael Phelps (2009) Nicholas Delpopolo (2012) Jake Humphries (2016) Kim Jong-Su (2008)

248 249 251 251 252 252 253 255 256 265 267 267 267 267 268 274 274 275 275 275 311

Contributors

Susan H. Backhouse is Director of Research and Professor of Psychology and Behavioural Nutrition in the Carnegie School of Sport at Leeds Beckett University, UK. Kelsey Erickson is a Research Fellow in the Carnegie School of Sport at Leeds Beckett University, UK. Neil King is Senior Lecturer in Sport in the Sport Studies and Sports Development Department at Edge Hill University, UK. Jim McVeigh is Director of the Public Health Institute at Liverpool John Moores University, UK. Yorck Olaf Schumacher is Sports Medicine Physician at Aspetar Sports Medicine Hospital, Qatar.

Mark Stuart is Clinical Lead for Pharmacy, Nursing and Allied Healthcare at the British Medical Journal, UK. Dominic J. Wells is Professor in Translational Medicine at the Department of Comparative Biomedical Sciences, Royal Veterinary College, UK. Nick Wojek is Head of Science and Medicine at UK Anti-Doping.

Section 1

The use, misuse and regulation of drugs in sport

Chapter 1

Drugs and their use in sport David R. Mottram

1.1 Introduction In this chapter we will review what is meant by the term “drug”. Having established how drugs exert their effects and side effects within the body, we will reflect on the various circumstances by which athletes may take drugs. Finally, we will consider why drugs are used by athletes for the purpose of performance enhancement.

1.2 What is a drug?

Definition of a drug The branch of science investigating drug action is known as pharmacology. Drugs are chemical substances which, by interaction with biological targets, can alter the biochemical systems of the body. For example, drugs such as ephedrine can lead to an increase in the force and rate of beating of the heart; amphetamines can produce changes in mood and behaviour; drugs such as insulin interact with metabolic processes in the treatment of disorders such as diabetes.

Banned drugs in sport In this chapter, frequent reference is made to drugs that appear on the World Anti-Doping Agency (WADA) Prohibited List (http://list.wada-ama.org). The 2017 list is presented in Table 1.1.

Mazzoni et al. (2011) have provided a comprehensive description of the structure, review and update processes for the WADA Prohibited List. Each class of drug is described in detail in Section 2 of this book.

Classification and description of drug names Drugs are variously classified and described by their: •• •• ••

generic name (International Non-proprietary Name: INN) proprietary name (manufacturer’s name) mechanism of action

The generic name (INN) is the internationally recognised name of the drug and should normally be used when describing the drug. However, when a pharmaceutical company first

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David R. Mottram

Table 1.1 WADA Prohibited List: January 2017 Substances and methods prohibited at all times (in- and out-of-competition) Prohibited substances S.0 Non-approved substances S.1 Anabolic agents S.2 Peptide hormones, growth factors, related substances and mimetics S.3 Beta-2 agonists S.4 Hormone and metabolic modulators S.5 Diuretics and masking agents Prohibited methods M.1 Manipulation of blood and blood components M.2 Chemical and physical manipulation M.3 Gene doping Substances and methods prohibited in-competition Categories S.0 to S.5 and M.1 to M.3 plus: S.6 Stimulants S.7 Narcotics S.8 Cannabinoids S.9 Glucocorticoids Substances prohibited in particular sports P.1 Alcohol P.2 Beta blockers Source http://list.wada-ama.org/

develops a new drug, it patents the drug under a proprietary name. When the patent expires, other pharmaceutical companies may produce the same drug under their own proprietary name. Some examples of the classification and names of drugs which appear on the WADA Prohibited List are presented in Table 1.2.

Drugs may be classified by their mechanism of action (pharmacology) or by the therapeutic use for which the drug is designed. Examples are given in Table 1.3.

Development of new drugs Over the centuries, herbalists and apothecaries have extracted drugs from plant and animal sources. For example, morphine is extracted from the opium poppy and digoxin from the Table 1.2 Examples of the classification and description of drugs by their names Class of drug

Generic name

Proprietary name

Anabolic androgenic steroids Diuretics Beta-2 agonists Narcotics Beta blockers Human growth hormone

Nandrolone Furosamide Terbutaline Morphine Atenolol Somatropin

Deca-Durabolin Lasix Bricanyl Sevredol Tenormin Humotrope

Drugs and their use in sport

5

Table 1.3 Examples of the classification of drugs by their mechanism of action and use Class of drug

Pharmacological action

Therapeutic use in:

Diuretics

Prevention of re-absorption of water from the kidneys Bronchodilation through stimulation of beta-2 adrenoreceptors Agonist on opioid µ receptors Antagonists on beta adrenoreceptors

Heart failure; Hypertension

Beta-2 agonists Morphine Beta blockers

Asthma; Chronic obstructive pulmonary disease Severe pain Angina; Hypertension; Cardiac arrhythmias; Anxiety

foxglove plant. However, the majority of drugs are produced by pharmaceutical companies through chemical synthesis. Current research into gene technology is revolutionising the development of new drugs.

Drug development is monitored by government agencies who evaluate the activity and safety of new drugs before awarding a Product Licence which states the therapeutic purpose(s) for which the drug may be used. The development of new drugs can take between 10 and 12 years and have a cost of several hundred million dollars. The WADA Prohibited List includes a class S.0, Non-approved Substances, which includes drugs that are still under development. The pharmaceutical industry is ideally placed to identify the doping potential of new medicines and to support early development of detection methods (Elliott and Leishman, 2012).

Dosage forms for drug delivery to the body There are many different dosage forms through which drugs can be administered to the body. Some examples for drugs that are subject to restrictions in sport are presented in Table 1.4.

Table 1.4 Examples of dosage forms for drugs used in sport Generic drug name

Dosage forms

Testosterone (anabolic androgenic steroid)

Oral capsules Intramuscular injection Transdermal patches Aerosol inhaler Oral tablets Syrup Injection Oral tablets Injection Ear/eye drops Cream/ointment Oral tablets Injection

Terbutaline (beta-2 agonist)

Hydrocortisone (glucocorticoid)

Pethidine (narcotic analgesic)

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David R. Mottram

The absorption, distribution, metabolism and elimination of drugs For a drug to exert its effect it must reach its site of action. This will involve its passage from the site of administration to the cells of the target tissue or organ. The principal factors which can influence this process are absorption, distribution, metabolism and elimination, known as the pharmacokinetics of drug action.

Absorption The absorption of a drug is, in part, dependent upon its route of administration. Most drugs must enter the bloodstream in order to reach their site of action and the most common route of administration for this purpose is orally, in either liquid or tablet form.

Where a drug is required to act more rapidly, or is susceptible to breakdown in the gastrointestinal tract, the preferred route of administration is by injection. The main routes of injection are subcutaneous (under the skin), intramuscular (into a muscle) and intravenous (directly into the blood stream via a vein).

Some drugs can be applied topically for a localised response. This may take the form of applying a cream, ointment or lotion to an area of skin for treatment of abrasions, lesions, infections or other such dermatological conditions. Topical applications may also involve applying drops to the eye, the ear or the nose. Drugs administered by a topical route are not normally absorbed into the body to the same extent as drugs administered orally.

Consequently, the WADA regulations regarding some prohibited drugs take into account the route of administration.

Distribution Apart from topical administration, a significant proportion of a drug will reach the blood stream. Most drugs are then dissolved in the water phase of the blood plasma. Within this phase some of the drug molecules may be bound to proteins and thus may not be freely diffusible out of the plasma. This will affect the amount of drug reaching its target receptors.

An additional obstruction to the passage of drugs occurs at the “blood–brain barrier” which comprises a layer of cells which covers the capillary walls of the vessels supplying the brain. This barrier effectively excludes molecules which are poorly lipid soluble.

The blood–brain barrier is an important factor to be considered in drug design since a drug’s ability to cross this barrier can influence its potential for centrally-mediated side effects.

Metabolism The body has a very efficient system for transforming chemicals into safer molecules which can then be excreted by the various routes of elimination. This process is known as metabolism and many drugs which enter the body undergo metabolic change.

There are several enzyme systems which are responsible for producing metabolic transformations. These enzymes are principally located in the cells of the liver but may also be found in other cells. They produce simple chemical alteration of the drug molecules by processes such as oxidation, reduction, hydrolysis, acetylation and alkylation.

Drugs and their use in sport

7

The consequences of drug metabolism may be seen in a number of ways: 1 2 3 4

An active drug is changed into an inactive compound. This is the most common means for the termination of the activity of a drug.

An active drug can be metabolised into another active compound. The metabolite may have the same pharmacological action as the parent drug or it may differ in terms of higher or lower potency or a different pharmacological effect.

An active drug can be changed into a toxic metabolite.

An inactive drug can be converted into pharmacologically active metabolites. This mechanism can be used for beneficial purposes where a drug is susceptible to rapid metabolism before it reaches its site of action. In this case a “prodrug” can be designed which is metabolised to an active drug on arrival at its target tissue.

Generally speaking, the metabolism of drugs results in the conversion of lipid soluble drugs into more water-soluble metabolites. This change affects distribution, in that less lipidsoluble compounds are unable to penetrate cell membranes. The kidneys are able to excrete water-soluble compounds more readily than lipid-soluble molecules since the latter can be reabsorbed in the kidney tubules and therefore re-enter the plasma.

Metabolism is a very important factor in determining a drug’s activity since it can alter its intrinsic activity, its ability to reach its site of action, and its rate of elimination from the body.

Many drugs are completely metabolised before being excreted in the urine. The WADA testing procedures in doping control detect both the parent drug and its metabolite(s), where appropriate.

Elimination There are many routes through which drugs can be eliminated from the body: •• •• •• •• •• ••

Kidneys (urine) Salivary glands (saliva) Sweat glands (sweat) Pulmonary epithelium (exhaled gases) Mammary glands (mammary milk) Rectum (faeces)

The most important route for drug excretion is through the kidneys into the urine. Urine sampling is therefore the principal method used in dope testing. The methods available for detecting drugs and their metabolites are extremely sensitive and capable of determining both the nature and the concentration of the drug and/or metabolite present.

Pharmacological means have been used in an attempt to mask illegal drug taking.

Diuretics have also been used to mask drug taking by accelerating urine excretion.

Effect of exercise on pharmacokinetics Under most circumstances exercise does not affect the pharmacokinetics of drug action.

During severe or prolonged exercise, blood flow within the body will be altered, with a decrease in blood supply to the gastrointestinal tract and to the kidneys. However, there is

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David R. Mottram

little documentary evidence to suggest that such changes significantly affect the pharmacokinetics of the majority of drugs.

Drugs and their targets Ideally, a drug should interact with a single target to produce the desired effect within the body. However, all drugs possess varying degrees of side effects, largely dependent on the extent to which they interact with sites other than their primary target. During a drug’s development, pharmaceutical companies ensure that it undergoes a rigorous evaluation in order to maximise therapeutic effects and minimise side effects. “Designer” drugs, produced by “back-street” laboratories to supply the illicit sport market, will not have undergone such rigorous testing for safety.

The sites through which most drug molecules interact are known as receptors, which are normally specific areas of cell membranes. Receptors are present within cells to enable naturally occurring substances, such as neurotransmitters, to induce their biochemical and physiological functions within the body. We exploit the fact that receptors exist, by designing drugs to stimulate (agonists) or block (antagonists) these receptors and thereby intensify or reduce biochemical processes within the body.

The interaction between a drug (ligand) and a receptor is the first step in a series of events which eventually leads to a biological effect. The drug–receptor interaction can therefore be thought of as a trigger mechanism.

There are many different receptor sites within the body, each of which possesses its own specific arrangement of recognition sites. The more closely a drug can fit into its recognition site the greater the triggering response and therefore the greater the potency of the drug on that tissue.

Agonists and antagonists A drug which mimics the action of an endogenous biochemical substance (i.e. one which occurs naturally in the body) is said to be an agonist. The potency of agonists depends on two parameters: •• ••

Affinity – The ability to bind to receptors.

Efficacy – The ability, once bound to the receptor, to initiate changes which lead to effects.

Antagonists have the ability to interact with receptor sites (affinity) but, unlike agonists, do not trigger the series of events leading to a response. The pharmacological effect of antagonists is produced by preventing the body’s own biochemical agents from interacting with the receptors and therefore inhibiting particular physiological processes.

A typical example of this can be seen with beta blockers. They exert their pharmacological effect by occupying beta receptors without stimulating a response, but prevent the neurotransmitter, noradrenaline (norepinephrine), and the hormone, adrenaline (epinephrine), from interacting with these receptors. Beta blockers therefore reduce heart rate under stress conditions or in exercise.

Many receptor classes can be sub-classified. This can be illustrated by looking at how adrenaline (epinephrine) interacts with adrenergic receptors. We know that there are at least five subclasses of adrenergic receptors, known as alpha-1 (α1), alpha-2 (α2), beta-1 (ß1), beta-2 (ß2) and beta-3 (ß3). Adrenaline can interact with all of these receptors, producing

Drugs and their use in sport

9

Figure 1.1 Some physiological effects of adrenaline mediated through the five principal classes of adrenergic receptors

a variety of physiological effects, examples of which are shown in Figure 1.1. Some drugs have selectivity for particular sub-classes of receptors. For example, the drug Salbutamol was developed to have a selective effect on beta-2 receptors. It therefore produces bronchodilation, without the other effects associated with adrenaline. As such it is a first-line drug in the treatment of asthma. The selective nature of Salbutamol, Salmeterol and Formoterol is recognised by the WADA who permit their use in sport, subject to certain specific restrictions, whilst other less selective sympathomimetics are totally banned.

Side effects of drugs All drugs produce side effects. Some of these side effects occur at normal, therapeutic dose levels whilst other side effects are experienced only at higher doses. In many instances, where athletes misuse drugs for doping, they take doses far in excess of those required for therapeutic purposes and in so doing increase the risk of toxic side effects. Predictable side effects associated with some of the drugs that are commonly misused in sport are shown in Table 1.5.

Non-predictable toxicity can occur following the administration of therapeutic or even sub-therapeutic doses of drugs. An example of this is idiosyncrasy where a drug produces an unusual reaction, normally genetically determined and often due to a biochemical deficiency. This over-reaction to the drug may be due to an inability to metabolise the drug.

A second type of non-predictable toxicity is drug allergy. Patients will only exhibit allergic reactions after previous exposure to the drug or a closely related chemical which sensitises the patient. The drug combines with a protein within the body to produce an antigen, which,

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David R. Mottram

Table 1.5 Side effects associated with some drugs that are commonly misused in sport Class of drugs

Side effects

Amphetamines

Restlessness; irritability; tremor; insomnia; cardiac arrhythmias; aggression; addiction (Knopp et al., 1997) Tremor; tachycardia; cardiac arrhythmias; insomnia; headache (Prather et al., 1995) Constipation; respiratory depression; addiction Acne; hypertension; mania; depression; aggression; liver and kidney tumours In females: masculinisation; cliteromegaly In males: testicular atrophy; gynaecomastasia (Tucker, 1997) Dehydration; muscular cramp (Caldwell, 1987) In children: gigantism In adults: acromegaly (hypertension; diabetes; muscular weakness; thickening of the skin) (Healy and Russell-Jones, 1997) Flu-like symptoms; hypertension; thromboses (Drug and Therapeutics Bulletin, 1992)

Beta-2 agonists Narcotic analgesics Anabolic androgenic steroids

Diuretics Human growth hormone Erythropoietin

in turn, leads to the formation of other proteins called antibodies. Subsequent exposure to the drug will initiate an antigen-antibody reaction. This allergic reaction can manifest itself in a variety of ways. An acute reaction is known as anaphylaxis and normally occurs within one hour of taking the drug. This response frequently involves the respiratory and cardiovascular systems and is often fatal. Sub-acute allergic reactions usually occur between one and twenty-four hours after the drug is taken and the most common manifestations involve skin reactions, blood dyscrasias, fever and dysfunctions of the respiratory, kidney, liver and cardiovascular systems. Examples of drugs known to produce such allergic responses are aspirin and some antibiotics including penicillins and cephalosporins.

Complex drug reactions Complex reactions may occur during long-term usage of a drug or where more than one drug is being taken simultaneously.

If the frequency of administration exceeds the elimination rate of a drug, then drug cumulation occurs thereby increasing the likelihood of toxicity reactions. The reason for a slow elimination may be related to a slow metabolism, a strong tendency to plasma protein binding or an inhibition of excretion such as occurs in patients with kidney disease.

The opposite response to cumulation is seen in patients with drug resistance, which may be genetically inherited or acquired. Inherited resistance is not common in humans, though it is an increasing problem in antibacterial therapy where pathogenic microbes can develop genetic changes in their structure or biochemistry which renders them resistant to antibiotic drugs. Acquired resistance to drugs, also known as tolerance, can develop with repeated administration of a drug. Where tolerance occurs, more drug is needed to produce the same pharmacological response. A very rapidly developing tolerance is known as tachyphylaxis.

This is usually caused by a slow rate of detachment of the drug from its receptor sites, so that subsequent doses of the drug are unable to form the drug-receptor complexes which are required to produce an effect.

Drugs and their use in sport

11

A number of drugs acting on the central nervous system, particularly narcotic analgesics, produce tolerance which is accompanied by physical dependence. This is a state in which an abrupt termination of the administration of the drug produces a series of unpleasant symptoms known as the abstinence syndrome. These symptoms are rapidly reversed after the readministration of the drug. A further manifestation of this problem involves psychogenic dependence in which the drug taker experiences an irreversible craving, or compulsion, to take the drug for pleasure or for relief of discomfort.

Where more than one drug is being taken there is a possibility for a drug interaction to occur. Less commonly, drugs may interact with certain foodstuffs, particularly milk products in which the calcium can bind to certain drugs and limit their absorption. The effects of interactions can range from minor toxicity to fatality.

Drugs and the law The manufacture and supply of drugs is subject to legal control. This legislation may vary from country to country but the principles are the same.

The definition of a medicinal product Medicinal product means any substance which is manufactured, sold, supplied, imported or exported for use in either or both of the following ways: (a) Administered to human beings or animals for medicinal purposes (b) As an ingredient in the preparation of substances administered to human beings or animals for medicinal purposes “Medicinal purpose” means any one or more of the following: (a) Treating or preventing disease (b) Diagnosing of disease or physiological condition (c) Contraception (d) Inducing anaesthesia (e) Otherwise preventing or interfering with the normal operation of physiological function Classes of medicinal products In many countries, there are three classes of medicinal products: (1) General sale list medicines (GSL) (2) Pharmacy medicines (P) (3) Prescription-only medicines (POM) The law of the country dictates which medicines may be purchased and which can only be obtained through a prescription. In general these laws are similar from country to country but exceptions do occur. Regrettably, most drugs can be obtained legally or illegally, without professional advice, through internet sources.

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David R. Mottram

Patients can obtain prescription-only medicines (POMs) from medical practitioners in a hospital, clinic or community practice. Prescriptions are then dispensed by a pharmacist or, in some cases, by a dispensing doctor. Once the prescription has been dispensed, the medicine becomes the property of the patient.

Over-the-counter (OTC) medicines are available for purchase, without a prescription.

These medicines are normally only available from a pharmacy (P medicines) although some medicines, such as aspirin and other analgesics, may be obtained in small pack sizes from other retail outlets (GSL medicines). OTC drugs pose particular problems for athletes, since a number of drugs subject to WADA regulations are available in OTC preparations.

Controlled drugs (CDs), normally those drugs with addictive properties, are subject to more extensive legal restrictions. In most countries CDs include: •• •• •• ••

Hallucinogenic drugs (e.g. LSD and marijuana) Opiates (narcotic analgesics e.g. morphine, heroin) Amphetamines Cocaine

For these drugs, the law states that it is illegal to possess such drugs, except where the user is a registered addict and has obtained their drug legally on prescription.

In some countries anabolic androgenic steroids, clenbuterol and some polypeptide hormones are classed as CDs as a further deterrent to their misuse in sport and in body building.

1.3 Why might athletes take drugs?

There are many reasons why sportsmen and women may take drugs. These can be broadly categorised as: •• •• ••

Legitimate therapeutic use for the treatment of medical conditions (prescription drugs or self-medication) Social or “recreational” use (legal and illegal) Performance enhancement

Within each of the above categories there are drugs which appear in the WADA Prohibited List (see Table 1.1). Both the deliberate and inadvertent use of prohibited drugs carries significant consequences for athletes. Athletes should always carefully consider the specific need for taking a drug and the full implications of their action.

Therapeutic use of drugs for the treatment of medical conditions Like any other person, an athlete is liable to suffer from a major or minor illness that requires treatment with drugs. A typical example might involve a bacterial or fungal infection necessitating the use of an antibiotic or antifungal agent. Apart from side effects such treatment would be unlikely to affect an athlete’s ability to compete and most drugs are not subject to WADA restrictions. However, there are a number of medical conditions for which athletes may require drug treatment, involving drugs that appear on the WADA Prohibited List.

Examples of these conditions are shown in Table 1.6.

For each condition, the more commonly used classes of drugs are listed, with those classes of drugs subject to WADA regulations highlighted.

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DANCE ON STILTS AT THE GIRLS’ UNYAGO, NIUCHI

Newala, too, suffers from the distance of its water-supply—at least the Newala of to-day does; there was once another Newala in a lovely valley at the foot of the plateau. I visited it and found scarcely a trace of houses, only a Christian cemetery, with the graves of several missionaries and their converts, remaining as a monument of its former glories. But the surroundings are wonderfully beautiful. A thick grove of splendid mango-trees closes in the weather-worn crosses and headstones; behind them, combining the useful and the agreeable, is a whole plantation of lemon-trees covered with ripe fruit; not the small African kind, but a much larger and also juicier imported variety, which drops into the hands of the passing traveller, without calling for any exertion on his part. Old Newala is now under the jurisdiction of the native pastor, Daudi, at Chingulungulu, who, as I am on very friendly terms with him, allows me, as a matter of course, the use of this lemon-grove during my stay at Newala.

FEET MUTILATED BY THE RAVAGES OF THE “JIGGER” (Sarcopsylla penetrans)

The water-supply of New Newala is in the bottom of the valley, some 1,600 feet lower down. The way is not only long and fatiguing, but the water, when we get it, is thoroughly bad. We are suffering not only from this, but from the fact that the arrangements at Newala are nothing short of luxurious. We have a separate kitchen—a hut built against the boma palisade on the right of the baraza, the interior of which is not visible from our usual position. Our two cooks were not long in finding this out, and they consequently do—or rather neglect to do—what they please. In any case they do not seem to be very particular about the boiling of our drinking-water—at least I can attribute to no other cause certain attacks of a dysenteric nature, from which both Knudsen and I have suffered for some time. If a man like Omari has to be left unwatched for a moment, he is capable of anything. Besides this complaint, we are inconvenienced by the state of our nails, which have become as hard as glass, and crack on the slightest provocation, and I have the additional infliction of pimples all over me. As if all this were not enough, we have also, for the last week been waging war against the jigger, who has found his Eldorado in the hot sand of the Makonde plateau. Our men are seen all day long—whenever their chronic colds and the dysentery likewise raging among them permit—occupied in removing this scourge of Africa from their feet and trying to prevent the disastrous consequences of its presence. It is quite common to see natives of this place with one or two toes missing; many have lost all their toes,

or even the whole front part of the foot, so that a well-formed leg ends in a shapeless stump. These ravages are caused by the female of Sarcopsylla penetrans, which bores its way under the skin and there develops an egg-sac the size of a pea. In all books on the subject, it is stated that one’s attention is called to the presence of this parasite by an intolerable itching. This agrees very well with my experience, so far as the softer parts of the sole, the spaces between and under the toes, and the side of the foot are concerned, but if the creature penetrates through the harder parts of the heel or ball of the foot, it may escape even the most careful search till it has reached maturity.

Then there is no time to be lost, if the horrible ulceration, of which we see cases by the dozen every day, is to be prevented. It is much easier, by the way, to discover the insect on the white skin of a European than on that of a native, on which the dark speck scarcely shows. The four or five jiggers which, in spite of the fact that I constantly wore high laced boots, chose my feet to settle in, were taken out for me by the all-accomplished Knudsen, after which I thought it advisable to wash out the cavities with corrosive sublimate. The natives have a different sort of disinfectant—they fill the hole with scraped roots. In a tiny Makua village on the slope of the plateau south of Newala, we saw an old woman who had filled all the spaces under her toe-nails with powdered roots by way of prophylactic treatment. What will be the result, if any, who can say?

The rest of the many trifling ills which trouble our existence are really more comic than serious. In the absence of anything else to smoke, Knudsen and I at last opened a box of cigars procured from the Indian store-keeper at Lindi, and tried them, with the most distressing results. Whether they contain opium or some other narcotic, neither of us can say, but after the tenth puff we were both “off,” three-quarters stupefied and unspeakably wretched. Slowly we recovered—and what happened next? Half-an-hour later we were once more smoking these poisonous concoctions—so insatiable is the craving for tobacco in the tropics.

Even my present attacks of fever scarcely deserve to be taken seriously. I have had no less than three here at Newala, all of which have run their course in an incredibly short time. In the early afternoon, I am busy with my old natives, asking questions and making notes. The strong midday coffee has stimulated my spirits to

an extraordinary degree, the brain is active and vigorous, and work progresses rapidly, while a pleasant warmth pervades the whole body. Suddenly this gives place to a violent chill, forcing me to put on my overcoat, though it is only half-past three and the afternoon sun is at its hottest. Now the brain no longer works with such acuteness and logical precision; more especially does it fail me in trying to establish the syntax of the difficult Makua language on which I have ventured, as if I had not enough to do without it. Under the circumstances it seems advisable to take my temperature, and I do so, to save trouble, without leaving my seat, and while going on with my work. On examination, I find it to be 101·48°. My tutors are abruptly dismissed and my bed set up in the baraza; a few minutes later I am in it and treating myself internally with hot water and lemon-juice.

Three hours later, the thermometer marks nearly 104°, and I make them carry me back into the tent, bed and all, as I am now perspiring heavily, and exposure to the cold wind just beginning to blow might mean a fatal chill. I lie still for a little while, and then find, to my great relief, that the temperature is not rising, but rather falling. This is about 7.30 p.m. At 8 p.m. I find, to my unbounded astonishment, that it has fallen below 98·6°, and I feel perfectly well. I read for an hour or two, and could very well enjoy a smoke, if I had the wherewithal—Indian cigars being out of the question.

Having no medical training, I am at a loss to account for this state of things. It is impossible that these transitory attacks of high fever should be malarial; it seems more probable that they are due to a kind of sunstroke. On consulting my note-book, I become more and more inclined to think this is the case, for these attacks regularly follow extreme fatigue and long exposure to strong sunshine. They at least have the advantage of being only short interruptions to my work, as on the following morning I am always quite fresh and fit.

My treasure of a cook is suffering from an enormous hydrocele which makes it difficult for him to get up, and Moritz is obliged to keep in the dark on account of his inflamed eyes. Knudsen’s cook, a raw boy from somewhere in the bush, knows still less of cooking than Omari; consequently Nils Knudsen himself has been promoted to the vacant post. Finding that we had come to the end of our supplies, he began by sending to Chingulungulu for the four sucking-pigs which we had

bought from Matola and temporarily left in his charge; and when they came up, neatly packed in a large crate, he callously slaughtered the biggest of them. The first joint we were thoughtless enough to entrust for roasting to Knudsen’s mshenzi cook, and it was consequently uneatable; but we made the rest of the animal into a jelly which we ate with great relish after weeks of underfeeding, consuming incredible helpings of it at both midday and evening meals. The only drawback is a certain want of variety in the tinned vegetables. Dr. Jäger, to whom the Geographical Commission entrusted the provisioning of the expeditions—mine as well as his own—because he had more time on his hands than the rest of us, seems to have laid in a huge stock of Teltow turnips,[46] an article of food which is all very well for occasional use, but which quickly palls when set before one every day; and we seem to have no other tins left. There is no help for it—we must put up with the turnips; but I am certain that, once I am home again, I shall not touch them for ten years to come.

Amid all these minor evils, which, after all, go to make up the genuine flavour of Africa, there is at least one cheering touch: Knudsen has, with the dexterity of a skilled mechanic, repaired my 9 × 12 cm. camera, at least so far that I can use it with a little care.

How, in the absence of finger-nails, he was able to accomplish such a ticklish piece of work, having no tool but a clumsy screw-driver for taking to pieces and putting together again the complicated mechanism of the instantaneous shutter, is still a mystery to me; but he did it successfully. The loss of his finger-nails shows him in a light contrasting curiously enough with the intelligence evinced by the above operation; though, after all, it is scarcely surprising after his ten years’ residence in the bush. One day, at Lindi, he had occasion to wash a dog, which must have been in need of very thorough cleansing, for the bottle handed to our friend for the purpose had an extremely strong smell. Having performed his task in the most conscientious manner, he perceived with some surprise that the dog did not appear much the better for it, and was further surprised by finding his own nails ulcerating away in the course of the next few days. “How was I to know that carbolic acid has to be diluted?” he mutters indignantly, from time to time, with a troubled gaze at his mutilated finger-tips.

Since we came to Newala we have been making excursions in all directions through the surrounding country, in accordance with old habit, and also because the akida Sefu did not get together the tribal elders from whom I wanted information so speedily as he had promised. There is, however, no harm done, as, even if seen only from the outside, the country and people are interesting enough.

The Makonde plateau is like a large rectangular table rounded off at the corners. Measured from the Indian Ocean to Newala, it is about seventy-five miles long, and between the Rovuma and the Lukuledi it averages fifty miles in breadth, so that its superficial area is about two-thirds of that of the kingdom of Saxony. The surface, however, is not level, but uniformly inclined from its south-western edge to the ocean. From the upper edge, on which Newala lies, the eye ranges for many miles east and north-east, without encountering any obstacle, over the Makonde bush. It is a green sea, from which here and there thick clouds of smoke rise, to show that it, too, is inhabited by men who carry on their tillage like so many other primitive peoples, by cutting down and burning the bush, and manuring with the ashes. Even in the radiant light of a tropical day such a fire is a grand sight.

Much less effective is the impression produced just now by the great western plain as seen from the edge of the plateau. As often as time permits, I stroll along this edge, sometimes in one direction, sometimes in another, in the hope of finding the air clear enough to let me enjoy the view; but I have always been disappointed.

Wherever one looks, clouds of smoke rise from the burning bush, and the air is full of smoke and vapour. It is a pity, for under more favourable circumstances the panorama of the whole country up to the distant Majeje hills must be truly magnificent. It is of little use taking photographs now, and an outline sketch gives a very poor idea of the scenery. In one of these excursions I went out of my way to make a personal attempt on the Makonde bush. The present edge of the plateau is the result of a far-reaching process of destruction through erosion and denudation. The Makonde strata are everywhere cut into by ravines, which, though short, are hundreds of yards in depth. In consequence of the loose stratification of these beds, not only are the walls of these ravines nearly vertical, but their upper end is closed by an equally steep escarpment, so that the

western edge of the Makonde plateau is hemmed in by a series of deep, basin-like valleys. In order to get from one side of such a ravine to the other, I cut my way through the bush with a dozen of my men.

It was a very open part, with more grass than scrub, but even so the short stretch of less than two hundred yards was very hard work; at the end of it the men’s calicoes were in rags and they themselves bleeding from hundreds of scratches, while even our strong khaki suits had not escaped scatheless.

NATIVE PATH THROUGH THE MAKONDE BUSH, NEAR MAHUTA

I see increasing reason to believe that the view formed some time back as to the origin of the Makonde bush is the correct one. I have no doubt that it is not a natural product, but the result of human occupation. Those parts of the high country where man—as a very slight amount of practice enables the eye to perceive at once—has not yet penetrated with axe and hoe, are still occupied by a splendid timber forest quite able to sustain a comparison with our mixed forests in Germany. But wherever man has once built his hut or tilled his field, this horrible bush springs up. Every phase of this process

may be seen in the course of a couple of hours’ walk along the main road. From the bush to right or left, one hears the sound of the axe— not from one spot only, but from several directions at once. A few steps further on, we can see what is taking place. The brush has been cut down and piled up in heaps to the height of a yard or more, between which the trunks of the large trees stand up like the last pillars of a magnificent ruined building. These, too, present a melancholy spectacle: the destructive Makonde have ringed them— cut a broad strip of bark all round to ensure their dying off—and also piled up pyramids of brush round them. Father and son, mother and son-in-law, are chopping away perseveringly in the background—too busy, almost, to look round at the white stranger, who usually excites so much interest. If you pass by the same place a week later, the piles of brushwood have disappeared and a thick layer of ashes has taken the place of the green forest. The large trees stretch their smouldering trunks and branches in dumb accusation to heaven—if they have not already fallen and been more or less reduced to ashes, perhaps only showing as a white stripe on the dark ground.

This work of destruction is carried out by the Makonde alike on the virgin forest and on the bush which has sprung up on sites already cultivated and deserted. In the second case they are saved the trouble of burning the large trees, these being entirely absent in the secondary bush.

After burning this piece of forest ground and loosening it with the hoe, the native sows his corn and plants his vegetables. All over the country, he goes in for bed-culture, which requires, and, in fact, receives, the most careful attention. Weeds are nowhere tolerated in the south of German East Africa. The crops may fail on the plains, where droughts are frequent, but never on the plateau with its abundant rains and heavy dews. Its fortunate inhabitants even have the satisfaction of seeing the proud Wayao and Wamakua working for them as labourers, driven by hunger to serve where they were accustomed to rule.

But the light, sandy soil is soon exhausted, and would yield no harvest the second year if cultivated twice running. This fact has been familiar to the native for ages; consequently he provides in time, and, while his crop is growing, prepares the next plot with axe and firebrand. Next year he plants this with his various crops and

lets the first piece lie fallow. For a short time it remains waste and desolate; then nature steps in to repair the destruction wrought by man; a thousand new growths spring out of the exhausted soil, and even the old stumps put forth fresh shoots. Next year the new growth is up to one’s knees, and in a few years more it is that terrible, impenetrable bush, which maintains its position till the black occupier of the land has made the round of all the available sites and come back to his starting point.

The Makonde are, body and soul, so to speak, one with this bush.

According to my Yao informants, indeed, their name means nothing else but “bush people.” Their own tradition says that they have been settled up here for a very long time, but to my surprise they laid great stress on an original immigration. Their old homes were in the south-east, near Mikindani and the mouth of the Rovuma, whence their peaceful forefathers were driven by the continual raids of the Sakalavas from Madagascar and the warlike Shirazis[47] of the coast, to take refuge on the almost inaccessible plateau. I have studied African ethnology for twenty years, but the fact that changes of population in this apparently quiet and peaceable corner of the earth could have been occasioned by outside enterprises taking place on the high seas, was completely new to me. It is, no doubt, however, correct.

The charming tribal legend of the Makonde—besides informing us of other interesting matters—explains why they have to live in the thickest of the bush and a long way from the edge of the plateau, instead of making their permanent homes beside the purling brooks and springs of the low country.

“The place where the tribe originated is Mahuta, on the southern side of the plateau towards the Rovuma, where of old time there was nothing but thick bush. Out of this bush came a man who never washed himself or shaved his head, and who ate and drank but little.

He went out and made a human figure from the wood of a tree growing in the open country, which he took home to his abode in the bush and there set it upright. In the night this image came to life and was a woman. The man and woman went down together to the Rovuma to wash themselves. Here the woman gave birth to a stillborn child. They left that place and passed over the high land into the valley of the Mbemkuru, where the woman had another child, which

was also born dead. Then they returned to the high bush country of Mahuta, where the third child was born, which lived and grew up. In course of time, the couple had many more children, and called themselves Wamatanda. These were the ancestral stock of the Makonde, also called Wamakonde,[48] i.e., aborigines. Their forefather, the man from the bush, gave his children the command to bury their dead upright, in memory of the mother of their race who was cut out of wood and awoke to life when standing upright. He also warned them against settling in the valleys and near large streams, for sickness and death dwelt there. They were to make it a rule to have their huts at least an hour’s walk from the nearest wateringplace; then their children would thrive and escape illness.”

The explanation of the name Makonde given by my informants is somewhat different from that contained in the above legend, which I extract from a little book (small, but packed with information), by Pater Adams, entitled Lindi und sein Hinterland. Otherwise, my results agree exactly with the statements of the legend. Washing?

Hapana—there is no such thing. Why should they do so? As it is, the supply of water scarcely suffices for cooking and drinking; other people do not wash, so why should the Makonde distinguish himself by such needless eccentricity? As for shaving the head, the short, woolly crop scarcely needs it,[49] so the second ancestral precept is likewise easy enough to follow. Beyond this, however, there is nothing ridiculous in the ancestor’s advice. I have obtained from various local artists a fairly large number of figures carved in wood, ranging from fifteen to twenty-three inches in height, and representing women belonging to the great group of the Mavia, Makonde, and Matambwe tribes. The carving is remarkably well done and renders the female type with great accuracy, especially the keloid ornamentation, to be described later on. As to the object and meaning of their works the sculptors either could or (more probably) would tell me nothing, and I was forced to content myself with the scanty information vouchsafed by one man, who said that the figures were merely intended to represent the nembo—the artificial deformations of pelele, ear-discs, and keloids. The legend recorded

by Pater Adams places these figures in a new light. They must surely be more than mere dolls; and we may even venture to assume that they are—though the majority of present-day Makonde are probably unaware of the fact—representations of the tribal ancestress.

The references in the legend to the descent from Mahuta to the Rovuma, and to a journey across the highlands into the Mbekuru valley, undoubtedly indicate the previous history of the tribe, the travels of the ancestral pair typifying the migrations of their descendants. The descent to the neighbouring Rovuma valley, with its extraordinary fertility and great abundance of game, is intelligible at a glance—but the crossing of the Lukuledi depression, the ascent to the Rondo Plateau and the descent to the Mbemkuru, also lie within the bounds of probability, for all these districts have exactly the same character as the extreme south. Now, however, comes a point of especial interest for our bacteriological age. The primitive Makonde did not enjoy their lives in the marshy river-valleys.

Disease raged among them, and many died. It was only after they had returned to their original home near Mahuta, that the health conditions of these people improved. We are very apt to think of the African as a stupid person whose ignorance of nature is only equalled by his fear of it, and who looks on all mishaps as caused by evil spirits and malignant natural powers. It is much more correct to assume in this case that the people very early learnt to distinguish districts infested with malaria from those where it is absent.

This knowledge is crystallized in the ancestral warning against settling in the valleys and near the great waters, the dwelling-places of disease and death. At the same time, for security against the hostile Mavia south of the Rovuma, it was enacted that every settlement must be not less than a certain distance from the southern edge of the plateau. Such in fact is their mode of life at the present day. It is not such a bad one, and certainly they are both safer and more comfortable than the Makua, the recent intruders from the south, who have made USUAL METHOD OF good their footing on the western edge of the CLOSING HUT-DOOR plateau, extending over a fairly wide belt of country. Neither Makua nor Makonde show in their dwellings anything of the size and comeliness of the Yao houses in the plain, especially at Masasi, Chingulungulu and Zuza’s. Jumbe Chauro, a Makonde hamlet not far from Newala, on the road to Mahuta, is the

most important settlement of the tribe I have yet seen, and has fairly spacious huts. But how slovenly is their construction compared with the palatial residences of the elephant-hunters living in the plain.

The roofs are still more untidy than in the general run of huts during the dry season, the walls show here and there the scanty beginnings or the lamentable remains of the mud plastering, and the interior is a veritable dog-kennel; dirt, dust and disorder everywhere. A few huts only show any attempt at division into rooms, and this consists merely of very roughly-made bamboo partitions. In one point alone have I noticed any indication of progress—in the method of fastening the door. Houses all over the south are secured in a simple but ingenious manner. The door consists of a set of stout pieces of wood or bamboo, tied with bark-string to two cross-pieces, and moving in two grooves round one of the door-posts, so as to open inwards. If the owner wishes to leave home, he takes two logs as thick as a man’s upper arm and about a yard long. One of these is placed obliquely against the middle of the door from the inside, so as to form an angle of from 60° to 75° with the ground. He then places the second piece horizontally across the first, pressing it downward with all his might.

It is kept in place by two strong posts planted in the ground a few inches inside the door. This fastening is absolutely safe, but of course cannot be applied to both doors at once, otherwise how could the owner leave or enter his house? I have not yet succeeded in finding out how the back door is fastened.

MAKONDE LOCK AND KEY AT JUMBE CHAURO

This is the general way of closing a house. The Makonde at Jumbe Chauro, however, have a much more complicated, solid and original one. Here, too, the door is as already described, except that there is only one post on the inside, standing by itself about six inches from one side of the doorway. Opposite this post is a hole in the wall just large enough to admit a man’s arm. The door is closed inside by a large wooden bolt passing through a hole in this post and pressing with its free end against the door. The other end has three holes into which fit three pegs running in vertical grooves inside the post. The door is opened with a wooden key about a foot long, somewhat curved and sloped off at the butt; the other end has three pegs corresponding to the holes, in the bolt, so that, when it is thrust through the hole in the wall and inserted into the rectangular opening in the post, the pegs can be lifted and the bolt drawn out.[50]

MODE OF INSERTING THE KEY

With no small pride first one householder and then a second showed me on the spot the action of this greatest invention of the Makonde Highlands. To both with an admiring exclamation of “Vizuri sana!” (“Very fine!”). I expressed the wish to take back these marvels with me to Ulaya, to show the Wazungu what clever fellows the Makonde are. Scarcely five minutes after my return to camp at Newala, the two men came up sweating under the weight of two heavy logs which they laid down at my feet, handing over at the same time the keys of the fallen fortress. Arguing, logically enough, that if the key was wanted, the lock would be wanted with it, they had taken their axes and chopped down the posts—as it never occurred to them to dig them out of the ground and so bring them intact. Thus I have

two badly damaged specimens, and the owners, instead of praise, come in for a blowing-up.

The Makua huts in the environs of Newala are especially miserable; their more than slovenly construction reminds one of the temporary erections of the Makua at Hatia’s, though the people here have not been concerned in a war. It must therefore be due to congenital idleness, or else to the absence of a powerful chief. Even the baraza at Mlipa’s, a short hour’s walk south-east of Newala, shares in this general neglect. While public buildings in this country are usually looked after more or less carefully, this is in evident danger of being blown over by the first strong easterly gale. The only attractive object in this whole district is the grave of the late chief Mlipa. I visited it in the morning, while the sun was still trying with partial success to break through the rolling mists, and the circular grove of tall euphorbias, which, with a broken pot, is all that marks the old king’s resting-place, impressed one with a touch of pathos.

Even my very materially-minded carriers seemed to feel something of the sort, for instead of their usual ribald songs, they chanted solemnly, as we marched on through the dense green of the Makonde bush:—