Introduction

Medicines have been made from plants, animal tissues and minerals, and possibly date back to and conceivably predate the earliest human cultures. Some animals, e.g. cats, are known to seek out certain plants when not well. Hints of herbal or medicinal practice are thought to date back to about 25 000 BC. Early hieroglyphics suggest that Egyptians and Babylonians practised surgery and medicine at least 2500 years ago. Evidence for herbal medicine in Pakistan has been dated back to about 3000 BC and Ayuverdic medicine in India is at least 2000 years old. The Chinese have been practising herbal medicine and acupuncture for at least 5000 years and are known to have practised inoculation against smallpox before 200 BC. Hippocrates (about 460–370 BC), however, is generally accepted in the west as the father of modern medicine, although arguably the most influential early practitioners were the Arab doctors and pharmacists of the first millennium AD, who laid the foundations for the sciences of, for example pharmacology, modern surgery and the quantification of drug effects. Europe, alas, sank into a mediaeval ‘Dark Age’ of medicine, where for centuries the leech and bloodletting reigned supreme until the Enlightenment of the eighteenth century. The science of the alteration and manipulation of natural resources to create new chemical compounds is relatively recent in human medical history, and is due mainly to advances in chemical synthesis and medical knowledge. Notable examples include the development of the smallpox and rabies vaccines, and the chemical synthesis of aspirin and its subsequent marketing by the German company Bayer towards the end of the nineteenth century. The discovery and identification of insulin by Banting and Best and their colleagues in the 1920s in Canada marked the birth of endocrinology as a science in its own right, and the consequent saving of thousands, if not millions, of patients with diabetes. Another very significant advance of the twentieth century was the discovery of the effects of the mould Penicillium species on bacteria by Alexander Fleming in 1928, and the subsequent development of penicillin by Florey and Chain in the 1940s. During that decade the introduction of the BCG (Bacille Calmette–Gu erin) vaccine and streptomycin offered the first effective treatment for tuberculosis and, in 1944, the first successful heart operation was performed on a baby born with a congenital heart problem, thus ending the previously fatal ‘blue baby’ birth. The 1950s saw a rapid growth in the development of newer antibiotics and for the first time effective pharmacological tools were available to treat psychiatric patients. Perhaps the discovery most blessed by patients and healthcare professionals alike was that of the general anaesthetic. Surgery is arguably as old as humanity and so, presumably, is the search for a means of blocking pain during the procedure. The oldest recorded use of morphine for anaesthesia was found in the Egyptian Ebers Papyrus around 1552 BC, and from then to the nineteenth century morphine was the mainstay until the discovery of the anaesthetic gases. Analgesia, too, has its roots in the development of biological materials such as morphine and willow bark and the identification of salicylic acid, which eventually led to the synthesis of aspirin. This was followed by a rapid growth of the biological sciences and, of particular relevance to this book, those concerned with amino acids, proteins, RNA, DNA, the elucidation of the genetic code and recombinant DNA technology. Of equal importance was the discovery of the bacterial plasmid, which has become an indispensable tool in the development of many of the new biological therapeutic agents, and also of the structure and function of bacteria and viruses.

Contents

① Introduction to genetic manipulation 1
Nucleotides and the genetic code 3
Recombinant DNA technology 4
The tools used for recombinant DNA technology 5
Mass production of insulin: an example 9
Knockout mice 10
Multiple choice questions 11
Further reading 12

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② Vaccines 13
Definition of a vaccine 13
A brief history 13
Miniglossary 14
Immunity 15
Mechanism of action of vaccines 17
Production of vaccines 17
Modern production methods 17
Paradigm of a coordinated response to the threat
of an influenza pandemic 19
Some examples of specific vaccines 20
Multiple choice questions 25
References 27
Further reading 27

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③ Hormone-related drugs 29
Brief history 30
Thyroid hormones 31
Adrenal hormones 35
The sex hormones 40
Biological drugs and cancer chemotherapy 41
Calcitonin 42
Parathyroid hormone 42
Insulin 43
Growth hormone 48
The incretins 50
Multiple choice questions 51
Further reading 52

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④ The nature of inflammation and mediators of inflammation 53
Hypersensitivity 54
Mechanisms and chemical mediators of the inflammatory response 57
The interferons 62
Multiple choice questions 71
Further reading 73

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⑤ Autoimmunity and autoimmune diseases 75
Autoimmunity 75
Immunological tolerance 79
Low-level autoimmunity 80
Triggers and mechanisms of autoimmune reactions 80
Some cellular mechanisms implicated in loss of self-tolerance
and onset and maintenance of autoimmune states 83
Transplant rejection 84
Multiple choice questions 85
Further reading 86

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⑥ Treatment of rheumatoid arthritis and other inflammatory
disorders with biological drugs 89
Rheumatoid arthritis 90
Administration of biological drugs 94
Psoriasis 97
Systemic lupus erythematosus 99
Crohn's disease 100
Multiple choice questions 101
Reference 102
Further reading 102

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⑦ Development of biological antineoplastic drugs 103
Mechanisms and targets for biological antineoplastic drugs 104
Some biological antineoplastic drugs currently in use or development 108
Effectiveness of the biological treatments for cancer 109
viii | Contents
Multiple choice questions 112
Further reading 113

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⑧ Stem cell therapy 115
The nature of stem cells 115
Embryonic stem cell cultures 117
Preparation of stem cells from the blastocyst 117
Prospects and the future for regenerative medicine 119
References 121
Further reading 121

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