I shall trace the history of the terms “human pharmacology” and “applied

pharmacology” and discuss how they are related to each other.

In doing so I shall develop a model of pharmacology showing the

inter-relations of human and applied pharmacology.

1

There is no dichotomy between basic pharmacology and clinical pharmacology.

They form a seamless scientific weave, and numerous bridges link their

various aspects. However, some of those bridges need to be strengthened.

2

The Oxford English Dictionary allows you to trace the histories of words,

their etymologies, and their previous and current uses.

3

The definition of “pharmacology” is non-controversial, but includes a surprising

obsolete usage. The first citation in the list of quotations illustrating the

uses of the word is the earliest known instance in English.

4

The time line (1700-1850) of the first recorded instances of various ologies

shows that, after anatomy, pathology, physiology, and therapeutics,

pharmacology is the oldest medical science. Materia medica and

toxicology also precede all other ologies.

5

Most later ologies first appeared in the English language between 1850 and

1950. Since neonatology (1960) we have had omics, not ologies.

6

Of course, the word “pharmacology” dates back much earlier than its use in

English—in fact, it existed in Greek. As did the term “materia medica”,

in its Greek equivalent.

7

8

Pedakios Dioscorides, from the island of Anasarbos, published his

five-volume treatise on herbal medicine “Peri hules iatrikes” (literally

“about medical stuff”) in the first century AD. The Codex Vindobonensis

(512 AD) is the earliest version still extant.

9

In this parallel text version (Greek on the left, Latin on the right) the title

is translated into Latin as “De medica materia”, a direct translation of

the original Greek.

10

The term “materia medica” first entered English in the 17th century,

but not in its current meaning.

11

In the 18th century “materia medica” came to mean the study of therapeutic

medications. Tobias Smollett, himself a doctor (MD Aberdeen 1750),

referred to it in his medical novel “The Expedition of Humphry Clinker”,

mentioning its theoretical and practical connections.

12

After that, the term “materia medica” was used in the titles of many textbooks

of therapeutics, a small selection of which is shown here. John Mitchell

Bruce’s text, first published in 1884, later became “Dilling’s Clinical

Pharmacology”.

13

This is the 11th edition of 1918. Dilling went on to become Professor of

Materia Medica and Therapeutics in Edinburgh.

This is Louis Lewin, whom some have called the father of toxicology

(see Aronson JK. Louis Lewin—Meyler's predecessor. In: Side Effects

of Drugs, Annual 27. Amsterdam: Elsevier, 2005: xxv-xxix).

14

In 1881 Lewin published his textbook on the adverse effects of drugs,

subtitled “Pharmakologisch-klinisches Handbuch”, the first time, to my

knowledge, that the words “clinical” and “pharmacological” had been

juxtaposed. [This is a later edition (1899).]

15

16

The German physician Paul Martini also used the adjectival term

“pharmakologisch klinisches” (see Shelley & Baur. Lancet 1999; 353:

1870-3), but the US physician Harry Gold was the first to bear the title

“Professor of Clinical Pharmacology”.

17

In 1953, John Gaddum, Professor of Materia Medica and Pharmacology

in Edingburgh, gave his Dixon Memorial Lecture to the Section of

Experimental Medicine and Therapeutics. The physician and pharmacologist

Gladwin Buttle was President of the Section at the time.

18

Gaddum explained how he had to come to call his lecture “Clinical pharmacology”.

His paper contained a wealth of dose-response curves based on human studies.

19

In 1958 a symposium was held in London on the topic of quantitative

methods in human pharmacology and therapeutics. In 1959 the proceedings

were published, edited by Desmond Laurence, of the Department of

Applied Pharmacology, in University College, London.

20

Gold contributed and it seems that at that time the terms “clinical

pharmacology”, “human pharmacology”, and “applied pharmacology”

were vying for supremacy.

21

The term “clinical pharmacology” prevailed, when Stanley Alstead published

“Dilling’s Clinical Pharmacology” in 1960. This is the edition that I used as a

medical student in Glasgow University in the 1960s, when I studied what at

that time was still called “materia medica”.

22

In the same year (1960) Desmond Laurence published the first edition of

his textbook “Clinical Pharmacology”. Here we see Desmond during the

1970s, carrying the papers for a meeting of the Committee on Safety of

Medicines, packed in four large green bags.

So much for the terms. Now for the bridges.

23

Vannevar Bush was a US engineer turned science administrator. In late

1944, President Roosevelt wrote to Bush, asking him to give his

recommendations on four areas of scientific research.

24

The second point about which the President was concerned was how to

organize a program of research in medicine and related sciences following

the Second World War.

25

Bush wrote a forty-page report, which included several appendices from

committees that he had marshalled to discuss and answer the President’s

points. In his report he stressed the importance of basic science.

26

This led to the view that medical research is linear. In the “scientific push”

model curiosity drives basic research, which in turns leads to practical

developments. In the “market pull” model basic research may be necessary

or may already be available.

27

The development of the atom bomb in the USA during the Second World War

is a good example of linear research. It started with basic, curiosity-driven

(“blues skies”) research, but led to a practical outcome.

28

But in 1958, Jewkes et al. published their thorough study of 61 important

scientific discoveries or inventions, analysing how they had come about.

They concluded that linear models did not fully explain the genesis of

scientific innovations. [This is a later edition (1965).]

29

Since then there have been several studies of the role of linear models

in scientific innovations and of the supposed relative contributions of

basic and applied science.

30

This is the biggest and most impressive study, although it has been subjected

to some criticism (See, for example, Smith R. Comroe and Dripps revisited.

Br Med J (Clin Res Ed) 1987; 295: 1404-7).

31

Previous studies had gone back only 20-50 years; Comroe and Dripps

looked back much further. This is illustrated here, in part of one of the

tables that they prepared on the history of ten important advances in

cardiorespiratory medicine that they chose to study.

32

With the help of many colleagues they identified key papers in the

development of those advances and classified them as basic or not,

clinically oriented or not. The basic studies were more frequent.

This work was later used as evidence in favour of funding basic science.

33

What can we learn from the conflicting results of all these studies?

Two lessons emerge. First, there is no one model that fits all types of

scientific developments. Secondly, asking whether basic or applied science

is more important is a non-question; there is no dichotomy.

34

This is the German philosopher Immanuel Kant (1724-1804).

35

In his “Lectures on Logic” Kant reminded us of the importance of

polytomy (considerering a problem in all its aspects) and decried

dichotomy (analysing a problem into two opposing parts, e.g. Type

A/Type B or on-target/off-target effects), seductive though it may be.

36

37

Let’s start with a linear model of pharmacology, from principles to practice,

from molecules to medicines, from human pharmacology to applied

pharmacology, from bench to bedside. This reminds us of the

components of the subject, but does not show their interactions.

To develop the model further, we turn to the US political analyst,

Donald Stokes, who considered more complex models of scientific

development in his book “Pasteur’s Quadrant” (1997).

38

He described three models: the quest for fundamental understanding

(pure basic research, as practised by Niels Bohr); utility only (pure

applied research, as practised by Thomas Edison); a combination

of the two (use-inspired basic research, as practised by Louis Pasteur).

39

The empty fourth quadrant is unsatisfactory, so we can discard it and

rearrange the other three quadrants, as shown. Now we can see how

existing understanding and technology can be translated into improved

understanding and improved technology.

40

This model takes an analogous approach to pharmacology. The top two

ovals show the major core topics in human pharmacology (left) and applied

pharmacology (right), and the bottom two show the practical applications

in individuals (left) and populations (right).

41

We can now add in the essential bridges that interconnect the different

sections in different ways. Only some of the bridges and the topics that

form them are shown. Others can be imagined. The components of

preclinical pharmacology (top) need to be expanded.

42

There is no dichotomy between basic pharmacology and clinical pharmacology.

All aspects of basic pharmacology, whether in animal or human cells, tissues,

or organs, are relevant to and inform clinical practice.

43