J R Soc Med 2002;95:411-416
doi:10.1258/jrsm.95.8.411
© 2002 Royal Society of Medicine
Medicines and men: Burroughs, Wellcome & Co, and the British drug industry before the Second World War
E M Tansey PhD MRCP(hon.)
Wellcome Trust Centre for the History of Medicine at UCL, 24 Eversholt
Street, London NW1 1AD, UK
E-mail:
t.tansey{at}ucl.ac.uk
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INTRODUCTION
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Britain in the final decades of the nineteenth century was a
vibrant market
place for purveyors of medicines, including,
inter alia, drug
peddlars and travelling quacks, dispensing
doctors and chemists, and
established compounding companies
such as Allen & Hanburys (est. 1715).
Regulation and control
of the manufacture, quality and efficacy of medicines
were practically
non-existent, and Weights and Measures and Poisons Acts were
the
principal relevant pieces of legislation.
During the same period, nationwide press and poster advertising, and the
easier country-wide distribution of goods opened up by the railroads,
contributed to the rise of the ‘branded’ commodity. Medicines,
pills potions and nostrums were not exempt, and products such as Friar's
Balsam, Wards Drop and Beechams Powders all achieved prominence and success in
the second half of the nineteenth century. One such manufacturer, Thomas
Holloway, was said to be spending £50 000 a year on advertising in 1883,
the year of his death.
In Europe however, especially in Germany and Switzerland and to a lesser
extent in France, several research-based scientific manufacturing companies
were emerging. The rise of the dye industry in Germany, itself a byproduct of
a coal-tar industry, provided a cadre of well qualified chemists whose
scientific investigations of dye products led to the recognition of medicinal
effects, and consequently to the creation of several pharmaceutical companies
including Hoechst, Bayer, Sandoz and
Ciba1. In Britain,
the only company to engage seriously in such research activities was
Burroughs, Wellcome & Co, founded in London in 1880 by two young American
pharmacists.
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ETHICAL PRODUCTS
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It was an opportune time for Silas Mainville Burroughs and Henry
Solomon
Wellcome to establish a pharmaceutical business in Britain,
initially
importing innovative American products including compressed
medicines, and
exporting medical goods to Europe and the British
Empire. From the beginning,
extensive advertising and promotion
in the pharmaceutical and medical press
was an important part
of their marketing strategy, although they were
obsessively
careful to avoid direct advertising to the public (which would
have
opened them, under the definitions of the Medicines Stamp Act,
to the
charge of being patent medicine suppliers). The young
company intended to
supply ethical products to the medical profession,
and so had to avoid any
dealings with quacks. In 1883 Burroughs,
Wellcome & Co moved into one of
the first commercial buildings
in the City to be lighted entirely by
electricity, and in the
same year they established a manufactory in
Wandsworth, South
London, to produce ‘Kepler’
products—cod-liver
oil and malt preparations. Because the Medicines
Stamp Act classified
imported medicines as patent medicines, they began to
manufacture
their own goods. Initially they marketed an electic range of
products
including shoe blacking, face cream, soda water, and pharmacists'
books
and apparatus, in addition to the compressed medicines of their
former
employers, McKesson and Robbins (Wellcome) and Wyeth
(Burroughs). From the
very beginning of their partnership, Kepler
malt extract and Kepler cod-liver
oil with malt were heavily
promoted in journal advertising and by their
travellers as nutritious,
palatable foodstuffs ideal for enhancing, promoting
and restoring
strength, vigour and health. Gradually the company's portfolio
became
more defined: books, equipment and blacking disappeared from
the lists,
and a wider range of medicinal compounds was offered.
In 1884 Wellcome registered the trademark ‘Tabloid’ to denote
some of their compressed products, although the word was never used
exclusively for pharmaceutical preparations—tea, bandages and
photographic chemicals being just some of the Tabloid products marketed.
Kepler goods, however, continued to be very much to the fore: some
advertisements reflected the company's scientific aspirations by the use of
microscopic illustrations (Figure
1); others used attractive artwork to catch the eye and attention
of doctors and pharmacists (Figure
2).
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BIOLOGICAL THERAPIES
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In 1895 Burroughs died unexpectedly after a short illness, and
Wellcome
became the proprietor of the company. Although disputes
with Burroughs' widow
caused some immediate difficulties, Wellcome's
new economic security soon
enabled him to indulge his wide interests
more extensively and roubstly than
previously. Inspired by his
personal passion for the history of
medicine—a subject
he interpreted broadly—he collected books,
manuscripts
and artifacts, supervised archaeological excavations, and created
medical
museums and a large personal
library
2. Of more
relevance to
the development of his business, he also established research
laboratories—the
Wellcome Chemical Research Laboratories (WCRL, founded
1896),
and the Wellcome Tropical Research Laboratories (WTRL, 1902).
These
were connected, to a lesser or greater degree, with the
main manufacturing
company, as was the first such venture, started
in 1894 whilst Burroughs was
still alive. Ultimately this became
known as the Wellcome Physiological
Research Laboratories (WPRL),
and comprised stabling for horses and a small
laboratory in
Central London, to produce the new biological therapy of serum
antitoxins.
The discovery in Germany, in 1890, that animals immunized against
diphtheria or tetanus produced antitoxins offered the hope of mass
immunization and treatment against a range of
infections3. The
therapeutic possibilities were rapidly recognised across Europe and the USA,
and in Britain, Burroughs Wellcome & Co were among the first to announce
successful production of serum antitoxin in November
18944. Preparations
of this sort would yield financial profit for many decades, but more important
in Wellcome's estimation was the prestige and reputation that his company
accrued from providing modern, scientifically produced, medicines.
Serum antitoxins were not the only biological to bring success and acclaim
to BW&Co. The company had also been amongst the first to market
‘animal substances’, including ‘extract of the supra-renal
glands’ (later called adrenaline) immediately after its discovery in
1894. Some of these achieved fame, almost royal patronage: in 1895, when the
London Figaro, commenting on the amount of weight lost recently by
the then Prince of Wales (later Edward VII), reported that Queen Victoria, who
was getting somewhat corpulent, was being urged to follow the same treatment.
Details of this marvellous remedy' soon followed—thyroid tabloids from
BW&Co5.
Wellcome was personally keen to extend the production and marketing of such
innovative therapies, emphasizing as early as 1895 that ‘it [is] very
important that we should be in the forefront with
this’6. By
1896 more laboratory space and stabling was needed and the WPRL moved to
larger premises, still in central London; four years later further expansion
was required, such was the demand for sera. In addition to increasing serum
production, Wellcome wanted to introduce routine biological testing and
standardization of a wide array of pharmaceutical products. This approach,
unique in Britain, involved use of animals in procedures regulated by the Home
Office under the 1876 Cruelty to Animals Act. Wellcome had applied for the
WPRL to be registered for such experiments in 1896, when the antitoxin work
began, but had been summarily rejected as a mere ‘tradesman’. In
1900 he applied again, precipitating a debate that lasted eighteen months.
Government officials, once more concerned that a commercial manufacturer
sought the privileges of professional men, consulted widely within medical and
pharmaceutical circles as to the desirability and advisability of granting the
request. Professional associations, including the medical Royal Colleges and
the Pharmaceutical Society, voiced their disapproval, although powerful
individuals (amongst them Lord Lister, Victor Horsley and Michael Foster)
supported Wellcome. Eventually the application was approved, the Home Office
being swayed by the economic argument that, if the BW&Co laboratories were
not registered, either they or other companies would undertake such work
abroad, and vital revenue and prestige would be lost to Britain. The officials
concerned did not tell the medical organizations directly of their
decision7.
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DALE AND BARGER
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The registration in September 1901 of the WPRL for animal experimentation
allowed
the company to employ staff to undertake original scientific
research,
and one of the earliest recruits was Henry (later
Sir Henry) Dale, who joined
in 1904. Dale had trained at the
Physiological Laboratory Cambridge and St
Bartholomew's Hospital
Medical School in London and was recommended to
Wellcome by
Ernest Starling, professor of physiology at University College
London,
with whom he had been working. But there was much prejudice
against
commerce and Dale was warned off by many colleagues,
although later recalling,
‘[I] never had a serious or
lasting reason to regret the change which I
had
made’
8.
Despite his training in the premier physiological laboratories of England,
Dale had no immediate research project of his own. He readily agreed therefore
to Wellcome's request that he study ergot of rye, a fungus long known for its
effects in promoting abortion and speeding up labour. Wellcome's curiosity was
commercially driven. Parke Davis & Co were marketing an ergot preparation
for obstetric use, claiming it was the active principle,
physiologically standardized. Wellcome had also employed a Cambridge trained
chemist, George Barger, and directed him towards the same subject. With a
competent chemist and an enthusiastic physiologist, a major research project
was about to begin at the WPRL, and, as Dale remembered,
‘on this basis we started a collaboration which was to last for the
next five years. To me it gave a scientific association of inestimable value,
and created the bonds of a personal friendship which grew ever closer in the
years that followed. It provided for me also the starting points for almost
all the investigations in which I have since been
concerned’9.
An early discovery was of an extract, ergotoxine, which promoted uterine
contractions and was enthusiastically marketed by the company. Despite this
encouraging beginning, this was not the obstetric active principle of
ergot of rye; another thirty years were to pass before ergometrine was finally
isolated by the young London obstetrician John Chassar Moir. Ergotoxine became
important in medical history, because Dale's observation that it inhibited
sympathetic nerve stimulation led him to the discovery of chemical
neurotransmission, for which he shared the 1936 Nobel Prize.
At the beginning of 1906, a conflict between scientific conventions and
commercial concerns loomed when Dale wished to publish work on ergotoxine and
its actions, and used the word ‘adrenaline’—a normally
accepted word within the British physiological community. However,
‘Adrenalin’ was a registered trade-mark of the American firm Parke
Davis & Co, and Dale's use raised several issues within the Wellcome
organization about apparently infringing another manufacturer's tradename. A
tremendous round of discussions and arguments ensued, between WPRL staff who
wanted to use ‘adrenaline’, and the rest of Wellcome's research
staff and the company's senior management who insisted on an alternative, such
as ‘physiologically active extract of the supra-renal gland’. J N
Langley, editor of the Journal of Physiology, gave an authoritative
opinion in support of the young physiologist. Dale hinted at resignation
should he be prevented, for commercial reasons, from using a word common
amongst his fellow scientists. Eventually, Wellcome bowed to academic
authority rather than commercial expediency, and sanctioned the disputed word.
It was an important decision—clearly positioning the company's
laboratories as research institutions run on scientific principles, rather
than routine production
facilities10.
Ergot of rye, a ‘treasure house for drugs’, continued to yield
important active compounds in the Wellcome
laboratories11. In
May 1909, Dale and Barger announced the identification of tyramine to the
Chemical Society and the Physiological Society. Just six weeks later, the
company advertised the chemical as another active principle of ergot; despite
hinting that it was the obstetric principle they gave no direct indication of
its usage. The speed with which tyramine was marketed provides a graphic
illustration of the ease with which compounds, reliable or dubious, tested or
otherwise, could be placed on the pharmacist's shelf. Ergot revealed further
constituents at the hands of the WPRL scientists, including histamine in 1907
and acetycholine in 1913, although neither provided immediately saleable
medicines. In 1914 Henry Dale joined the newly created Medical Research
Committee (later the Medical Research Council, MRC), having just been elected
a Fellow of the Royal Society—a striking indication of the quality of
his work done in laboratories owned by a ‘mere’ tradesman.
The quality of Dale's research work removed or prevented the type of
prejudice prevalent in America against ‘commercial’ enterprises.
The American attitude became obvious during Dale's candidacy for the Royal
Society, as indicated by one of his British supporters in a letter to
Professor John Abel of Michigan:
‘Please do not kick at Dale. He is of course with Burroughs W &
Co, but incurs no restrictions on that account here as he had done such
admirable work and does nothing whatever to aid the commercial side... I
merely want to point out that he is not quite in the same class as P. D.'s
[Parke Davis] men, as he has never represented the firm and never
‘writes up’ their products &c. except in the way that you or I
might
do’12.
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FIRST WORLD WAR
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With the outbreak of war in 1914 BW&Co, one of the few British
companies
with the research skills and manufacturing capacity to do so,
made
enormous contributions to the war effort. Drugs, especially
antitoxic sera,
were provided for military and domestic use,
and the company manufactured a
wide range of chemicals previously
imported largely from Germany. Among the
products of WCRL were
aspirin, chloroform (from alcohol), cholesterol,
cocaine, emetine
bismuthous iodide, flavine, hydroquinone, lanoline and
phenacetin.
An advertisement from 1916
(
Figure 3) emphasizes the
firm's
considerable contributions. The staff of the WPRL, in collaboration
with
the embryonic MRC, worked on developing substitutes for the
potent
antisyphilitic Salvarsan, as did May & Baker through
links with the French
company Poulenc Frères, although
both companies had recurrent
difficulties with production and
toxicity.
Serum production was greatly accelerated, mainly in response to military
needs—especially those of the British Expeditionary Force in Western
Europe. Vast amounts of antigonococcal, antimeningococcal, antitenanus and
anti-dysentery sera were prepared at the WPRL, and hundreds of horses passed
through the stables during this period. Although the company devoted time and
resources to the war requirements they did not neglect their domestic or
overseas civilian markets, continuing to push a wide range of products,
although the advertising was subtly altered to reflect the prevailing
circumstances (Figure 4).
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GROWTH AND COMPETITION
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At the end of the war, the enormous experience that BW&Co's
workforce
had developed in chemical and biological compounds
left them ideally placed to
take advantage of the major therapeutic
breakthroughs of the
1920s—notably insulin and vitamins—but
there were obstacles to
progress. The research and manufacturing
staff were exhausted and depleted;
and, of more lasting consequence,
the company was losing its pre-eminence.
Other companies had
followed Wellcome's lead in developing research
laboratories,
and after the war Allen & Hanburys, May & Baker, and
British
Drug Houses (BDH) were all snapping at BW&Co's heels (and
also
recruiting Wellcome staff to run their research programmes,
as did the MRC).
Allen & Hanburys and BDH collaborated to
produce the first marketable
insulin in Britain, although BW&Co
were only weeks behind. The
sophisticated marketing experience
of BW&Co, however, was apparent from
their advertisements—they
manufactured not only the insulin but also the
syringe with
which to administer it, and they soon added a urine-testing
kit
to their range, an early example of pharmaceutical added-value.
The discovery of vitamins by the Cambridge biochemist Frederick Gowland
Hopkins provided further stimulation to the growing British pharmaceutical
industry, especially Nathan & Co, who sold dried milk powder for babies
under the tradename ‘Glaxo’. Addition of vitamins to their
preparations necessitated the opening of research and development
laboratories, the basis of a major pharmaceutical
enterprise13.
BW&Co also produced their own vitamin products, and repositioned older
favourites such as Kepler cod-liver oil and Kepler malt preparations, now
marketed on the strength of their vitamin content and the company's expertise
in accurate measurement of these components
(Figure 5).
During the 1930s the innovative preparations marketed by BW&Co included
digoxin, a purified cardioactive glycoside derived from digitalis;
ergometrine, the obstetrically active principle of ergot, finally discovered
by Chassar Moir but developed by
BW&Co14;
sulphonamide preparations; and canine distemper vaccine (like ergometrine,
developed from research work undertaken at the National Institute for Medical
Research)15.
Digoxin was the last major drug before the war to be discovered and developed
completely ‘in-house’, the critical suggestion to examine
glycoside extracts of digitalis coming from Sir Thomas Lewis in a conversation
with a BW&Co representative (the only commercial person the cardiologist
would meet, because of the high scientific reputation of
BW&Co)16.
The start of the Second World War saw a very different state of
pharmaceutical affairs from that obtaining twenty-five years earlier. Some,
albeit limited, legislation was in place in the form of the Therapeutic
Substances Act, which provided basic safety standards for a limited range of
medicinal products. More research-based pharmaceutical companies existed,
which came to the fore when the Therapeutic Research Corporation (TRC) was
formed in 1941—a conglomeration of British manufacturers who agreed to
share research and development experience and costs in producing certain
drugs, especially penicillin. The founder members were Boots, BDH, Allen &
Hanburys, Glaxo and the Wellcome Foundation (the umbrella organization created
by Henry Wellcome in 1924 to include the different parts of his empire).
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THE WELLCOME LEGACY
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No longer was BW&Co alone. The unique position the company
had created
and spearheaded was now shared. Since its foundation
in 1880, however,
BW&Co had established an exceptional record
of achievement. The company
had pioneered the production and
marketing of safe, reliable medicines; led
the way in promoting
rational laboratory research within the company; and
broken
new ground in acquiring Home Office permission for animal
experimentation.
They produced numerous innovative chemical and biological
therapies,
and generated major scientific breakthroughs. But perhaps more
importantly
they trained men who contributed greatly to medical research.
By
the beginning of the Second World War former Wellcome staff
headed the
National Institute for Medical Research and four
of its departments, led the
research departments of four other
pharmaceutical companies, and occupied
chairs in a wide range
of medical and scientific subjects. Seventeen had
become Fellows
of the Royal Society, and one had gained the Nobel Prize for
Physiology
or Medicine.
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Acknowledgments
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This work is supported by a project grant to R A Church and
E M Tansey from
the Wellcome Trust. The Trust is a medical research
charity established by the
will of Sir Henry Wellcome, who died
in 1936. It is not directly associated
with any branch of the
pharmaceutical industry. I thank Mrs Wendy Kutner for
assistance
in the preparation of the paper and Mr Neil Weir, President
of the
History of Medicine Section, for inviting me to give
a talk on which it is
based.
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REFERENCES
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- Behring E von, Kitassato S. Ueber das Zustandekommen der
Diptheria-Immunität un der Tetanus-Immunität bei Thieren.
Dt Med Wschr1890; 16:113
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- Chemist and Druggist, 24 November1894
, p. 736
- Figaro, 3 January1895
- Wellcome Foundation Archives, Wellcome Library Archives and
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INTRODUCTION
ETHICAL PRODUCTS
