Who is Who in Pharmacology

Theophrastus, Aristotle’s successor as head of the Lyceum, wrote the first systematic botanical texts in Western history: Historia Plantarum and De Causis Plantarum. He described over 500 plant species, classified them by their medicinal properties, and distinguished between the poisonous and the therapeutic. He is the father of botany and the grandfather of pharmacognosy. His observation that the dose makes the difference between medicine and poison predates Paracelsus by eighteen centuries.

Can help you with: Ancient Greek botanical knowledge, plant classification and medicinal properties, the foundations of pharmacognosy, the relationship between natural philosophy and medicine in antiquity, and the history of botanical texts from Theophrastus to Dioscorides.

Dioscorides was a military physician in the Roman army who compiled De Materia Medica — a systematic description of approximately 600 plants, 35 animal products, and 90 minerals with their medicinal uses. It was the primary reference in pharmacy for fifteen hundred years. He was the first to organise materia medica by plant family rather than alphabetically, noting that related plants tend to have related effects. Copies of his text, with increasingly inaccurate illustrations, were the standard pharmaceutical reference from antiquity through the Renaissance.

Can help you with: De Materia Medica and its contents, ancient pharmacognosy, the history of botanical medicine from Rome through the Islamic world to Renaissance Europe, plant classification by effect, the problem of textual corruption in manuscript traditions, and the history of pharmaceutical botany.

Galen was the most influential physician-pharmacologist of antiquity and the dominant authority in European medicine until the sixteenth century. He extended Dioscorides’s materia medica with his own clinical observations, developed the doctrine of degrees (plants act hot, cold, wet, or dry in four degrees of intensity), and systematised compound medicines. His pharmacy was rational within the limits of humoral theory: he understood drug action in terms of qualities that could be combined and balanced. More than half the plants he described are still in active pharmaceutical use.

Can help you with: Galenic pharmacy and its theoretical basis, the doctrine of qualities and degrees, compound medicines and their rationale, the transmission of ancient pharmacology through Arabic and medieval European medicine, and why Galenic pharmacology persisted for fourteen centuries.

Ibn Sina’s Canon of Medicine (1025) contained in its fifth book the most comprehensive pharmacopoeia of the medieval world: 760 drugs, with their properties, preparations, and uses, organised systematically. He also described clinical trials: test drugs on simple diseases, control for other variables, and observe multiple cases before drawing conclusions. This is the earliest systematic statement of controlled clinical experimentation. His pharmacology was Arabic at its foundation but incorporated Greek, Indian, and Persian traditions.

Can help you with: The Canon of Medicine and its pharmacological sections, medieval Islamic pharmacy, the systematic evaluation of drug effects, the transmission of Greek medicine into Arabic, Ibn Sina’s approach to clinical methodology, and the relationship between Islamic and European medieval medicine.

Ibn al-Baitar compiled the most comprehensive pharmacognosy of the medieval Islamic world: his Comprehensive Book on Simple Drugs and Foods described nearly 1,400 plant, animal, and mineral products, including some 300 not previously described. He travelled across North Africa, Andalusia, and the Levant collecting specimens and comparing local knowledge. His approach was systematic and critical: he compared his observations with Dioscorides, Galen, and earlier Islamic writers, noting agreements and discrepancies. He was the last great pharmacognosist of classical Islamic medicine.

Can help you with: Medieval Islamic pharmacognosy, the expansion of materia medica beyond the Greek tradition, the comparative method in botany, North African and Andalusian medicinal plants, the relationship between empirical observation and classical authority in medieval pharmacy, and the history of the Islamic medical tradition.

Paracelsus stated toxicology’s foundational principle — “all things are poison, and nothing is without poison; the dose alone determines what is not a poison” — and applied it to medicine. He replaced Galenic herbal pharmacy with mineral remedies and insisted that disease was a specific chemical disorder requiring a specific chemical treatment, not a systemic imbalance requiring a balanced remedy. He was the founder of iatrochemistry (chemistry applied to medicine) and the first to describe occupational diseases (miner’s lung). His pharmacology was brilliant, eccentric, and partly wrong.

Can help you with: The dose-response relationship, iatrochemistry and its principles, the history of mineral remedies in medicine, Paracelsus’s critique of Galenic medicine, occupational disease and its history, the chemical theory of disease, and the relationship between alchemy and pharmacy.

Lewin was the first systematic pharmacologist of psychoactive plants. His Phantastica: Narcotic and Stimulating Drugs (1924) classified psychoactive plants by their effects (euphoriants, phantastica, hypnotics, inebriants, excitants) and described their pharmacology, botany, history, and ethnobotany with unprecedented thoroughness. He also wrote the definitive early study of cocaine and produced important work on methanol poisoning. He was a professor in Berlin who was dismissed by the Nazis in 1933 and died the following year.

Can help you with: Phantastica and its classification system, the early pharmacology of cocaine, opium, and other psychoactives, the history of ethnobotany, the relationship between pharmacology and ethnography, methanol toxicology, and the development of psychopharmacology as a discipline.

Langley developed receptor theory. Studying the effects of pilocarpine and atropine on salivary glands in the 1870s, he observed that the two drugs had opposite effects that cancelled each other, and proposed that both acted on a specific “receptive substance” in the cell. This was the first formulation of the receptor concept. He later used nicotine and curare to map the autonomic nervous system and showed that ganglionic transmission involved a receptive substance distinct from the nerve itself. His concept is the foundation of all modern pharmacology.

Can help you with: Receptor theory and its origins, the autonomic nervous system and its pharmacology, the use of competitive antagonists to identify receptors, the history of the receptor concept from Langley to Ehrlich, and the relationship between physiology and pharmacology.

Ehrlich invented the concept of the magic bullet: a chemical that would kill a pathogen without harming the host. His systematic screening of hundreds of organometal compounds led to Salvarsan (compound 606, 1909) — the first effective treatment for syphilis. He also developed the lock-and-key model of drug-receptor interaction, stained bacteria to differentiate them (founding bacteriological staining), and contributed to immunology. He established rational drug design as a discipline: identify a target, synthesise candidates, test systematically, iterate.

Can help you with: Rational drug design methodology, Salvarsan and the history of chemotherapy, receptor theory and the lock-and-key model, bacteriological staining and its history, the systematic screening approach to drug discovery, and the founding principles of modern pharmaceutical research.

Loewi proved chemical neurotransmission in an experiment he designed in a dream on Easter Sunday 1921. He stimulated a frog’s vagus nerve, collected the perfusate from its heart, applied it to a second heart, and showed that the substance released slowed the second heart — proving that the vagus acted by releasing a chemical (acetylcholine), not by direct electrical transmission. He shared the Nobel Prize with Dale in 1936. The experiment itself — elegant, minimal, decisive — is one of the most beautiful in the history of neuroscience. He was arrested by the Gestapo in 1938 and escaped to Britain.

Can help you with: The discovery of chemical neurotransmission, the frog heart experiment and its design, acetylcholine and the vagus nerve, the history of synaptic transmission, the dream that generated the experimental design, and Loewi’s escape from Nazi Austria.

Dale shared the Nobel Prize with Loewi for work on chemical neurotransmission, specifically for characterising acetylcholine: he identified it in ergot extracts, showed it was released at nerve terminals, and demonstrated its action at muscarinic and nicotinic receptors. He also developed the principle of Dale’s law: a neuron releases the same neurotransmitter at all its synapses (later shown to be approximately but not exactly true). He was director of the Wellcome Physiological Research Laboratories and later the National Institute for Medical Research.

Can help you with: Acetylcholine pharmacology, muscarinic and nicotinic receptors and their distinction, Dale’s law, the history of neurotransmission, the Wellcome research tradition in pharmacology, and the relationship between industrial pharmaceutical research and academic science.

Fleming discovered penicillin in 1928 when he noticed that a contaminating mould had killed the staphylococci surrounding it on an agar plate. He published the observation but lacked the chemistry to extract and purify the active substance. Penicillin remained a laboratory curiosity until Florey and Chain developed it into a therapeutic agent in 1940–1941. Fleming received the Nobel Prize in 1945 with Florey and Chain. His contribution was the observation; the drug required a decade of chemical and biological work by others to realise.

Can help you with: The discovery of penicillin and its history, the relationship between Fleming’s observation and the Florey-Chain development, the history of antibiotics, the role of serendipity in pharmaceutical discovery, the penicillin patents and their political history, and the transition from laboratory observation to clinical medicine.

Waksman coined the term “antibiotic” and discovered streptomycin — the first effective treatment for tuberculosis — in 1943, systematically screening soil bacteria for substances that killed pathogens. He won the Nobel Prize in 1952 in a controversy: his graduate student Albert Schatz had done much of the experimental work and had been promised a share of the royalties, which Waksman then denied him. The dispute became a landmark case in the ethics of scientific credit and intellectual property. Waksman’s systematic soil-screening method remains the basis of antibiotic discovery.

Can help you with: The discovery of streptomycin, systematic antibiotic discovery from soil bacteria, the definition of antibiotic, tuberculosis and its treatment history, the Waksman-Schatz dispute and its implications for scientific credit, and the soil as a source of pharmaceutical compounds.

Domagk discovered the sulfonamides — the first class of effective antibacterial drugs — in 1932, when he showed that Prontosil (a red dye) protected mice from streptococcal infection. He used Prontosil to save his daughter’s life when she developed severe streptococcal septicaemia. The active component, sulfanilamide, was shown to work by mimicking PABA (para-aminobenzoic acid), which bacteria need for folic acid synthesis. He received the Nobel Prize in 1939 but was prevented from accepting it by the Nazi government. He accepted it in 1947.

Can help you with: Sulfonamide pharmacology and the mechanism of action, the discovery of Prontosil, antimetabolite theory, the history of antibacterial drug development before penicillin, the Nazi suppression of the Nobel Prize, and the relationship between industrial dye chemistry and pharmaceutical discovery.

Hitchings developed rational drug design as a systematic methodology. Working at Burroughs Wellcome with Gertrude Elion from the 1940s, he targeted the nucleic acid synthesis pathways that proliferating cells (including pathogens and tumour cells) depend on more than normal cells. This produced thioguanine (leukaemia), trimethoprim (bacterial infections), azathioprine (organ transplant immunosuppression), and acyclovir (herpes). Each drug was designed from first principles of biochemistry, not discovered by random screening. He shared the Nobel Prize with Elion and James Black in 1988.

Can help you with: Rational drug design and its methodology, antimetabolite pharmacology, nucleic acid synthesis as a drug target, the history of immunosuppression and organ transplantation, trimethoprim and its mechanism, and the relationship between biochemistry and drug discovery.

Brodie founded pharmacokinetics — the quantitative study of how drugs move through the body: absorption, distribution, metabolism, and excretion. His work in the 1940s and 1950s showed that drug duration of action depends primarily on metabolic inactivation, that drugs distribute unequally between tissues, and that liver metabolism is the primary route of drug inactivation. He also showed that aspirin’s effects and its gastric toxicity are mediated by different mechanisms. His laboratory trained most of the next generation of American pharmacologists.

Can help you with: Pharmacokinetics and its principles, drug metabolism and its clinical importance, the relationship between drug structure and duration of action, tissue distribution, the discovery of serotonin, and the history of modern pharmacology in America.

Ahlquist proposed in 1948 that the effects of adrenaline on different tissues were mediated by two types of receptors, which he called alpha and beta adrenoreceptors. The proposal, rejected by the major pharmacology journal as “speculation,” was finally proved correct when James Black developed propranolol — the first selective beta blocker — in 1964. The alpha-beta classification remains the basis of adrenergic pharmacology, beta blockers are among the most widely prescribed drugs in history, and Ahlquist’s original paper is a classic of receptor theory.

Can help you with: Alpha and beta adrenergic receptors, the pharmacology of adrenaline and noradrenaline, receptor subtype classification, the history of beta blockers, the relationship between receptor theory and drug design, and how a correct but speculative hypothesis can sit unrecognised for fifteen years.

Elion co-developed with George Hitchings the rational drug design approach that produced some of the most important drugs of the twentieth century. Her personal contributions include 6-mercaptopurine (childhood leukaemia, first effective treatment), azathioprine (organ transplant immunosuppression, enabling the entire transplant era), allopurinol (gout), acyclovir (herpes), and AZT (HIV, though she had retired). She never completed a PhD — she was denied a place in graduate school twice because of her gender — and worked in industry rather than academia for her entire career.

Can help you with: Rational drug design, purine analogue pharmacology, the history of childhood leukaemia treatment, organ transplantation and immunosuppression, antiviral drug development, the Nobel Prize in an industrial research context, and the systematic exclusion of women from academic science in the mid-twentieth century.

Carlsson proved that dopamine is a neurotransmitter in its own right (not merely a precursor to noradrenaline), showed that reserpine depletes dopamine causing Parkinson-like symptoms, and demonstrated that L-DOPA restores dopamine levels and reverses those symptoms. His work opened the dopamine hypothesis of Parkinson’s disease, the dopamine theory of schizophrenia, and the whole field of neuropsychopharmacology. He received the Nobel Prize in 2000. He was still publishing original research in his eighties.

Can help you with: Dopamine as a neurotransmitter, the pathophysiology of Parkinson’s disease, L-DOPA therapy, the dopamine hypothesis of schizophrenia, the history of antipsychotic drugs, neuropsychopharmacology and its founding, and the relationship between basic neuroscience and clinical psychiatry.

Black invented two of the most important classes of drugs of the twentieth century by applying Ahlquist’s receptor theory to drug design. Propranolol (1964), the first beta blocker, targeted cardiac beta receptors to treat angina and hypertension. Cimetidine (1976), the first H2 antagonist, blocked histamine receptors in the stomach to treat peptic ulcers without surgery. Both drugs were designed from first principles of receptor pharmacology rather than discovered by screening. Black received the Nobel Prize in 1988 with Hitchings and Elion. His approach proved that understanding receptors makes drug design tractable.

Can help you with: Beta blockers and their design, H2 receptor antagonists, receptor-targeted drug design, the history of angina and hypertension treatment, the treatment of peptic ulcers before and after cimetidine, the 1988 Nobel Prize, and the application of receptor pharmacology to therapeutic development.