J R Coll Physicians Edinb 2005; 35:258–260
2005 Royal College of Physicians of Edinburgh
Goat's rue – French lilac – Italian fitch –Spanish sainfoin: gallega officinalis andmetformin:The Edinburgh connection
DR HaddenHon. Consultant Physician, Royal Victoria Hospital Belfast, IrelandABSTRACT The hypoglycaemic drug metformin is derived from galegine, which is Correspondence to Professor DR
found naturally in Goat’s rue (gallega officinalis). This plant is speading northwards
Hadden, Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6BA Northern Ireland KEYWORDS metaformin tel. +44 (0)2890 667110 DECLARATION OF INTERESTS No conflict of interest to declare. fax. +44 (0)2890 310111 e-mail [email protected] i.nhs.uk
If you need a good reference book on eighteenth century
brief description of Goat’s Rue as galegus officinalis under
botany, it is worth consulting a series of large volumes in
genus 10 (leguminosae) still stands today.
the College library. When Sir John Hill produced hismagnum opus on The Vegetable System in 26 volumes,
‘This is a perennial, native of Spain, and Italy; of
between 1759 and 1775, he was partially financed by the
Greece and Africa. A specious plant, of a yard high,
then Earl of Bute, who subsequently (after Hill died
that flowers in August. The stalk is juicy, and green:
penniless in 1775) presented them to the College, of
the leaves are of a fine fresh green: the flowers are
purple; sometimes white.’ (Figures 2A, 2B).
College rare books librarian, identified Goat’s Rue inVolume XX1, page 54, as a full page colour plate.
Goat’s Rue, also known as French Lilac or Italian Fitch, isthe natural source of galegine which is a precursor of
Although Linnaeus had admired the plates he also is said
metformin, now a very widely used oral antidiabetic agent.
to have wept at the lack of science, nevertheless Hill’s
The story of its discovery, dismissal and rediscovery on
FIGURE 1A Title page of The vegetable system.13 FIGURE 1B Page 54 of Volume XXI, The vegetable system.13 FIGURE 2A Galegus officinalis growing in the Chelsea Physic FIGURE 2B Goat’s Rue. Plate 54, The Vegetable System.13
Garden in London, June 2004. (Reproduced by kind
(Reproduced from the copy in the Library of the RCPE by
two occasions makes a useful comment on the problems
biguanide), and the friendly approach of the only
of the pharmaceutical industry, with some Edinburgh
representative of the Rona organisation, who was also
the managing director of the UK company. Perhaps forthat reason, metformin found an understanding reception
METFORMIN – THE ROAD TO ACCEPTANCE
in Belfast and in Edinburgh, and our clinical experiencegradually supported the rather meagre scientific
Pharmaceutically, metformin is an interesting substance,
background to the drug. (One suggested explanation of
and at times those working on it might have diverted into
its action was biophysical rather than biochemical – it
the antimicrobial actions of the biguanides – germicidal,
was a mild cell poison that made holes in the cell
antiviral and antimalarial – the most widely used of these
membrane and allowed glucose to enter without the
compounds is hexamethyl bischlorophenyl biguanide, or
need for insulin!) In the south of England it was not
chlorhexidine, a useful germicide and disinfectant.1 The
widely used, and it was never marketed in the USA at
history of the early researchers has been extensively
that time. A number of clinical studies by Dr B Clarke
reviewed under the auspices of the pharmaceutical firms
and Dr L Duncan at the Royal Infirmary of Edinburgh, and
Lipha and Merck, who now with Bristol-Myers Squibb
others in Belfast, demonstrated the efficacy and safety of
continue to produce metformin for use as an oral
hypoglycaemic agent.2 This continues under the watchful
Campbell and Dr H Howlett more recently produced an
scientific eye of Dr H Howlett, who served his time in the
important meta-analysis at a time when the use of
ethical pharmaceutical industry with metformin, and after
metformin in Type 2 diabetes was becoming less popular
many years of involvement in clinical research studies was
and other types of drugs were being widely promoted.7
elected a Fellow of the Royal College of Physicians ofEdinburgh in 2002.
All this has changed in the past decade since the outcomeof the UK Prospective Diabetes Study, where metformin
Metformin first became available in the UK National
had been included as a primary randomisation (although
Formulary in 1958, and the earliest clinical reports of its
only for the obese sub-group).8 Metformin (also known
effectiveness in maturity-onset (now Type 2) diabetes
by its trade name Glucophage) is now the most widely
date to that time – including one in French from the
prescribed oral antidiabetic medication throughout the
world, with a new understanding of its mode of action as
company, Aron, which marketed metformin under an
even smaller UK subsidiary, Rona, was at a commercialdisadvantage, and I well remember as a junior doctor the
GOAT’S RUE IN THE UK
difference in the sales pitch between that of the largeinternational company with pharmaceutical
Traditional plant medicines have been recorded as
representatives who supported phenformin (another
treatments for diabetes since the Ebers papyrus in 1550
J R Coll Physicians Edinb 2005; 35:258–260
BC, which recommended a high fibre diet of wheat grainsand ochre.9 Goat’s Rue, as galega officinalis is known in theUK, is now becoming increasingly common as a wildflower in this country. Look out for this member of thepea family (leguminosae) ‘a medium-tall, erect, oftenhairless perennial to 1·5 m. Flowers pinkish-lilac or white,12–15 mm with five bristle-like sepal-teeth, in stalkedspikes June–September. Pods rounded, short to 3 cm. Increasingly naturalised in waste, usually grassy, places’.10The new atlas of 10 km squares of botanical distributionin the UK indicates that the spread of this species is veryrecent. Although introduced into cultivation in England in1568, and first recorded in the wild in 1640, it was notmapped at all in 1962. Now, it is found in 75% of the 10km squares in London, and is widely distributed in thehome counties. It has even been officially recorded inEdinburgh, but not yet in Ireland (see figure 3).11 So watchout for this tall lilac pea-like flower on your walks: if youor your patient mislay your metformin tablets, rememberthe galegine-containing seeds of Goat's Rue – but bewareof the side effects, which might even be hypoglycaemic!
FIGURE 3 Distribution of gallega officinalis in the British Isles
The final irony has been pointed out by Clifford Bailey in
(2002), from the New Atlas 10 km Census Dataset.11
Birmingham,12 that galega officinalis is classed as a class AFederal Noxious Weed in 35 states of the USA, andappears on the database of poisonous plants, recalling the
John Dallas, rare books librarian at the College kindly
observation of Paracelsus (1493–1541) that ‘the right
provided the reproduction from the large volumes of Sir
dose differentiates a poison from a useful medicine’.
John Hill (1772). Clifford Bailey has done more than mostto reveal the interesting botanical background to this
plant, originally prized in the English garden but nowbecoming a weed. It has invaded Scotland, and I await its
I am grateful to the staff of the Chelsea Physic Garden in
first sighting across the Irish sea.
London for their interest and enthusiasm in cultivatingthis plant and for the photograph taken in June 2004. REFERENCES 4:25–8.
Campbell I, Howlett H. Worldwide experience of metformin as aneffective glucose-lowering agent: a meta-analysis. Diabetes Metab
Bell PM, Hadden DR. Metformin. Endocrinol Metab Clin North Am.Rev 1995; 11:557–62.
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Pasik C (editor). Glucophage (1957–1997): Serving diabetology for
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Bailey CJ, Day C. Traditional plant medicines as treatments for
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10 Blamey M, Fitter R, Fitter A. Wild Flowers of Britain and Ireland.
metformin treatment on weight and blood glucose response of
Preston CD, Pearman DA, Dures TD. New Atlas of the British and
uncontrolled obese diabetics. Lancet 1968; 1:123. Irish Flora. Oxford: Oxford University Press 2002;CD-ROM.
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uncontrolled by diet. BMJ 1977; 2:1576–8.
13 Hill J. The Vegetable System, or the Internal Structure and the Life of
Rigas AN, Bittles AH, Hadden DR, Montgomery DAD. Circadian
variation of glucose, insulin and free fatty acids during long-termuse of oral hypoglycaemic agents in diabetes mellitus. BMJ 1968;
J R Coll Physicians Edinb 2005; 35:258–260
Pane al pane.vino al vino. “Non sarà quella là la baita?” chiedo preoccupata all’idea di camminare finlassù, lassù tra i pini sfavillanti di stille aggrappate ai verdi aghi edilluminati da un timido raggio di sole. “No, non preoccuparti siamoarrivati”. “Per fortuna” penso che quelle parole siano incoraggianti. Ilcane pastore avvisa, con il suo abbaiare lento e calmo, il Mario
SCAR FORMATION KEY FIGURES: This chapter gives background information about the scarring process. Treatment options for problematic scars are also discussed. Normal Course of Scar Maturation Scar tissue is never as strong as normal, uninjured skin. For the first3–4 weeks after injury, the wound can easily be reopened by minimaltrauma. By 6 weeks, the scar has attained approximately 5