VIRUSMYTH HOMEPAGE
HARD SELL
By Brian Deer
The Sunday Times (London) 27 Feb. 1994
Were you to travel to London's Euston Road and stand outside the seven-storey
building at number 183, you would not think that you were close to anything of
note. The structure's white Portland stone facade and Greek-columned central
pavilion are reminiscent of nothing more than, say, a United States courthouse or a
down-sized Bank of England. It is a self-important but bland creation. To see it
once is to forget.
But if you sneaked through its revolving front door and up 12 cold steps to the
grand high-ceilinged lobby, you would find yourself in awesome spaces that shout
most loudly of money. Number 183 is the creation of the late Sir Henry Wellcome,
architect of the modern pharmaceutical industry; and the builders knew that this
meant they need not skimp on the job.
On the day it opened in 1932, only four years before Henry died, it was a point of
distinction that no wood or cheap metals should be visible anywhere. The floors,
walls and staircases were in fine imported marbles. The doors, windows and fittings
were exclusively of bronze. It was all to the taste of a president or a king a style to
suit the man.
Such hidden grandeur does perfect justice to the building's extraordinary role.
Number 183 is the headquarters of the Wellcome Trust the world's biggest private
medical research fund, a charity with assets worth more than £ 6 billion.
Though little known to the public, here is by far the United Kingdom's richest body
with the tax-breaks of charitable status. (It is twice as wealthy, for instance, as the
Church of England commissioners.)
From this building the trust controls a commercial drug company, the Wellcome
Foundation, one of the top pharmaceutical manufacturers in the world and, through
that, Burroughs Wellcome, its giant United States offshoot. Within these
operations, in turn, are the coffers that supply the Burroughs Wellcome Fund, one
of the 50 leading American foundations. At 183 is also based the Wellcome
Institute, a multi-million-pound centre that researches and shapes medicine's
history, politics and ideology.
From all of these through grants and sponsorship government agencies, universities
and hospitals are influenced everywhere. The trust alone distributes more money to
institutions than even the British government's Medical Research Council: some
£ 400m annually to doctors and scientists in Britain and around the world.
In offices on this building's first floor, decisions have been reached that have
affected lives and health on a scale that compares with minor wars. In the
conference room, set high above the street, and the meeting hall in the basement,
rulings in biotechnology and genetics are being handed down that will help to shape
the future of the human race itself.
If all of this is news to you, then at least some Wellcome products should be more
familiar. The Wellcome Foundation (which recently decamped to a tower-block at
160 Euston Road) most notably sells AZT, the controversial AIDS drug, which last
year commanded a market of £ 248m. Even more commercially noteworthy
is its herpes treatment acyclovir sold under the brand name Zovirax which grossed
£ 760m.
There are also over-the-counter cough and cold products, Sudafed and Actifed,
which brought in £ 141m; and some 50 other treatments ranging from an
antibacterial, marketed as Septrin, Septra or Septran, depending on the country, to
a gout remedy, allopurinol, known as Zyloric or Zyloprim. Total sales revenues are
more than £ 2billion annually.
Number 183, the citadel of this empire, is even more impressive today than
when it was constructed. In its sumptuous, galleried library on the second and third
floors, the quality of the furnishings is on a par with a five-star hotel. On the upper
ground floor, a high-tech science exhibition is like a cross between Disney World
and the toy department at Harrods. On every level there are old master paintings
and glossy publications.
The building's special place of honour, however, is below street level, where the
trust keeps a nominal shrine to the man who started it all. Here there are examples
of merchandise that got the company going; there are some of Henry's personal
items, medals and his soft-spined preacher-style Bible; and, by the staircase near
the entrance, there is an oil painting of the founder as he was in middle age with a
thick handlebar moustache that dominates his face.
On a winter evening among these things you can almost feel his ghostly presence.
This man, whose life was as controversial as his legacy, not only built the
formidable organisation which centres on this building and through it helped shape
the rise of 20th-century medicine but did so in a way that allows him to brood over
human health even from beyond the grave.
Shortly before the building was opened (and not long after he was knighted by
George V), Henry knew that he was approaching the end of his life and filed a
remarkable will. With it he included a lengthy handwritten memorandum. Together
these papers set out a detailed plan of how his empire would continue long after he
was gone.
Though you will not find them on display, or listed in the library, these documents
are held by the Charity Commission in London and, with Wellcome's inexorable
rise, have turned out to be among the most important papers in the history of
medicine.
What Henry set out was a blueprint for a philanthropic research body now the
Wellcome Trust with all the tax and image advantages that such entities enjoy. The
idea was that this charity would be the flagship for profit-making enterprises or, as
he called them, "industrial organisations" which today trade under the name of the
Wellcome Foundation Ltd.
So audacious and so successful was this scheme that, despite the efforts of some of
the most honest among Britain's "great and good" who have taken charge of both
enterprises over the years, it has placed the course of health and medicine into
Henry's posthumous grip.
Urging that there should be "frequent consultations" between the charitable and the
commercial parts of his empire, Henry revealed in the memorandum the scale of
his ambitions. "With the enormous possibility of development in chemistry,
bacteriology, pharmacy and allied sciences," he predicted, "if my desires and plans
are carried out in the way of research co-operation with the several industrial
organisations, there are likely to be vast fields opened for productive enterprise for
centuries to come."
The key exhibit at no 183 is Henry's personal Bible. For many years the trustees
who run his affairs have kept this black volume on display, open at one of the
passages he pencilled for special contemplation. "And thou shalt bestow that money
for whatsoever thy soul lusteth after," it says in the 26th verse from the 14th
chapter of the Old Testament's Deuteronomy. "For oxen, or for sheep, or for wine,
or for strong drink, or for whatsoever thy soul desireth."
If Henry's soul desirethed anything, it was power and wealth and the markings
suggest that he sought biblical authority for the quest on which he embarked. His
father, two of his uncles and his brother were all Christian ministers, and a deeply
felt religiousness was a constant theme in his life.
Henry Solomon Wellcome had been born in 1853 in the American Midwest and
grew up in Minnesota, where his father was a noted lectern-thumper of the Second
Adventist Church (then in some turmoil after an end-of-the-world prophecy had
expired in 1844). According to his faith, righteous people such as Henry presumed
himself to be would rise from the dead and live again when Christ returned to
earth.
From his father, Henry acquired not only a tough-minded religious fundamentalism
but also, most usefully, an evangelist's facility to persuade. For a while "Hank", as
he was then known, worked in a drugstore started by an uncle in the frontier
settlement of Garden City. It was there, when the future pharmaceutical millionaire
was just 16, that he came up with (an admittedly childish) sales ploy that set the
cast for what was to come.
Realising that it was not so much what a drugstore sold that made the money, but
the way that it went about selling it, Henry bottled what was probably lemon juice
and advertised it for invisible writing. "Wellcome's Magic Ink The Greatest Wonder
of the Age", he called this, his first foray into business. His pitch would have
shamed many a snake-oil salesman and continued in similar style. "This," it said, "is
something entirely New And Novel!"
There is no available record of this venture's success, but life in his uncle's
drugstore propelled Henry into pharmacy college, where he learned that the most
profitable involvements in health care were more to be found in marketing than
they were in medicine.
In 1880, at the age of 26, he moved to Britain and went into partnership with an
even better salesman than himself, one Silas Burroughs (who died in 1895); and the
pair put together a business which was to shape the pharmaceutical industry as it
affects our lives today.
Their most important inspirations lay in promotion and presentation. At the time
medicines were mainly prescribed as powders or liquids, so the two men set up a
European agency for new-fangled American tablets. With these, Henry prepared
attractive-looking chests containing such age-old remedies as ipecacuanha,
strychnine and quinine, and called the products "Tabloid" brand an expression
registered in 1884 as a catchword for Wellcome drugs (and still, in the fine print of
legality, the organisation's property).
The Tabloid chests (some of which are displayed at number 183) were often given
away to influential people and became the starting point for the modern industry's
much loved "freebies". Beginning as cartloads of complimentary first-aid kits,
hauled around London for the king, prime minister and other ruling-class figures,
the idea was soon widened to include foreign travel expenses and "tell your friends"
financial support for anyone else of use.
In particular, Henry became an ardent backer and no-charge supplier to his
close friend Sir Henry Stanley and other African explorers, who generated publicity
to bring glamour to his products.
The two partners were especially noted for pioneering door-to-door selling to
doctors. They had found that people who became physicians often did so mainly
for reasons of family, prestige or money and had little developed interest in the
drugs they prescribed. Burroughs was particularly adept at calling at their offices,
giving free samples and a smart sales pitch, pointing out the latest advertising and
departing with the knowledge that a new crop of patients had been won to the
brand.
Henry had comparable business acumen, but he also spent a great deal of time in
less commercially minded pursuits. Since he believed that the Bible was literally
true and therefore in conflict with evolution theory he spent huge sums hunting
throughout Africa for proof that white tribes existed in humanity's prehistory. In
Sudan he hired 4,000 people to scrape at the earth for four years in this inevitably
futile quest to overturn scientific progress.
During such bizarre ventures, the kind of individual that Henry really was came
dramatically to the fore. Donning the white pith helmet of the British imperial
explorer, he would distribute peacock feathers to workers who abstained from the
local drink (which he was convinced was the root cause of "all-night drunken
orgies"). He would also whip men caught asleep on watch at night.
These aspects of Henry's character have given headaches to those concerned ever
since with boosting Wellcome's image. Although the organisation pays homage to
its founder, information about him has been studiously controlled. Much of his
personal archive is claimed to have been destroyed, while a biography
commissioned in the 1940s from a staff member (who wrote of Henry's "inflexible
spirit of intolerance") was suppressed on its completion.
Nothing has been more problematic than one of the key chapters of Henry's life:
his marriage (in 1901) and subsequent divorce. His wife, Syrie Barnardo, daughter
of Britain's most celebrated child-care philanthropist, Dr Thomas Barnardo, was 27
years younger than her husband; and though they had a child together, their
relationship was not good. According to her friends, Syrie particularly disliked
Henry's persistent cruelty most notably that he beat her with a sjambok, a South
African cattle whip.
Perhaps in reaction, Syrie used Henry's absences looking for white tribes to court
other men in London. George Selfridge, the American-born department store
magnate, was one. Then, some time around 1911, she met and later had a sexual
relationship with the young Willie Somerset Maugham. He was England's most
celebrated playwright at the time and, awkwardly for her, gay.
Although Maugham and Syrie had a child together and later married, he mainly
needed her as a dinner-party escort; when Henry petitioned for divorce over the
adultery, the writer accepted it cheerfully. But according to the suppressed
Wellcome biography (which the trust refuses to make available, but was once
briefly seen by someone writing about Syrie) the effect of the affair on Henry
"soured his character for the remainder of his life". By the time he drafted the will
and memorandum that were to establish the Wellcome organisation as a dominant
force in medical science, the book concludes that the old man had lapsed "into a
morbid misery only to be soothed by a vicious preoccupation in his own interests".
If Henry's ghost is somewhere among the marble and bronze of 183 Euston
Road, he could only be of the conclusion that the God he looked to for comfort in
life was consoling him after death. At the time of the divorce, he could hardly bring
himself to think of Syrie's acts of alleged betrayal and of the homosexual
Maugham's lack of Christian morality. But with the passing of years, it was
precisely the conduct that had caused him misery which gave his empire its clout.
For there are no enterprises possibly excepting contraceptive pill manufacturers
which have profited as much as Wellcome has from changing attitudes to sex.
Before the 1960s "sexual revolution", which saw the annual number of gonorrhoea
cases jump 300% in a decade, the Wellcome company was an obscure
pharmaceutical house with a few bright scientists and a modest reputation in
cancer. But as the word "adultery" fell out of popular usage and promiscuity lost its
stigma, it was Henry's empire that was on the spot with drugs for the
accompanying complaints.
In the 1990s, the most high-profile of its products is AZT for AIDS, in the majority
of cases a sexually-transmitted disease. When this drug was first marketed in the
spring of 1987 it was hailed as a breakthrough, especially among gay men. Though
the company initially priced the treatment in America at more than $10,000 a year,
doctors and their patients seized on it as giving some brief last-ditch respite.
Such was the commercial success of AZT or zidovudine that a 20% block of
shares in the Wellcome Foundation sold by Henry's trust in 1986 at £ 1.20
each had soared to £ 12 each five years later. In the summer of 1992, when
the trust cashed in more fully on the drug's incredible publicity and sold another
40%, it grossed £ 2.2billion, while retaining a controlling interest. In London
it was the largest private flotation in the history of the Stock Exchange.
Unfortunately, the benefits of AZT have remained mired in controversy. First
synthesised in 1964 as a possible cancer treatment, it was abandoned for that
purpose because it could kill the patients before it killed their tumours. In people
with AIDS, who seemed likely to die anyway, scientists noticed that (possibly as
the sufferers' immune systems rallied against the chemical) it gave them a kind of
kick-start, often lasting only weeks or months, during which improvement was
sometimes apparent.
This small sad benefit, first revealed in a Sunday Times investigation in April 1989,
may justify a transitory role for some AIDS patients. But for others the drug's
severe side effects can prove disabling and sometimes fatal.
Had an organisation other than Wellcome developed AZT, it is possible (though by
no means certain) that it would have concentrated its efforts on targeting the drug
on particular kinds of patient. Henry's legacy, however, demanded that, whatever
the medical justification, selling was the first priority.
In a move which surprised some doctors, the company promoted the notion that
people who were HIV positive but had not quite developed AIDS should take the
drug; then those who showed no visible symptoms but whose immune systems
were weakened; and finally people who were HIV-positive, but who were
otherwise apparently well.
Although The Lancet, perhaps the world's most respected medical journal, warned
that "there is no evidence to suggest that clinicians should be encouraged to give
zidovudine to most symptom-free patients", Wellcome was drawn towards a
market that could be one hundred times bigger than just those diagnosed with
AIDS.
To pursue this avenue over which it is now facing a lawsuit in Britain Wellcome
mobilised the creative talents in its marketing departments. In a worldwide
campaign, medical journals were utilised for advertising and promotional articles;
doctors were bombarded with calls from sales representatives and with
independent-looking material; and, perhaps most worryingly, patients were targeted
with what seemed to be objective advice. The high profit margins on AZT thought
to be 70% net of all costs meant that the budgets available to push the product had
rarely been seen before.
The trust even installed a permanent exhibit for the drug at 183 Euston Road
perhaps thinking that a hard sell was what Henry would have wished.
Remembering the success of his Tabloid chest promotions, the founder had
instructed his successors in his will memorandum: "I consider it in the best interests
of the several industrial organisations and of all concerned that the publicity,
advertising and other propaganda shall be steadily increased as the output is
increased in volume and in profits."
Despite the hype around AZT, however, Wellcome's drug for herpes simplex
acyclovir or Zovirax is contributing three times as much to the company's turnover.
Surveys have shown that, while this condition is only rarely life-threatening, the
virus linked with it is at least 100 times more prevalent than the one associated with
AIDS. In America, an estimated one in five of the sexually active population is
infected with genital herpes and, though not all have symptoms, the number of
visits to doctors for such infections has jumped 16-fold in 20 years.
At the level of science, acyclovir was something of a landmark. Synthesised in
Wellcome's American laboratories in 1974, it was the first significant medicine that
could safely block a virus. Although acyclovir does not cure the often recurring
herpes it showed that, in principle, the smallest known infectious agents could be
pharmaceutically attacked. Since the drug's release in 1982 it has saved the lives of
many intensive-care and transplant patients who, due to immune suppression, are
at special risk from the disease.
Among people with the common genital condition, however, the picture is a lot less
clear. Key research (which took place a decade after the tests which established the
product on the market) reveals that, though acyclovir tablets can suppress
symptoms, the virus often continues to "shed", even in the presence of the drug.
This means that, although the blisters associated with herpes may not be visible, the
person may continue to be infectious and can therefore pass it on.
Thus, acyclovir (for which Wellcome charges $2,500 for six months' treatment in
the United States) may be lulling users into a false sense of security causing more,
not less, transmission.
Medical ethics might suggest that doctors should be loudly alerted to this problem in
order to warn their patients. But, instead of prioritising this, Henry's organisation
has used the sales techniques he pioneered in a worldwide campaign to boost the
product, including forms other than the tablets and for conditions other than herpes
simplex. In both situations, evidence suggests, the biggest gainer may be
Wellcome's accounts rather than public health.
The most visible aspect of this campaign is a reformulation of acyclovir as a
cosmetic lip cream for cold sores, or "herpes labialis". Though the company says its
research shows that this non-prescription product now advertised on television can
prevent attacks, the most authoritative independent report, published in the British
Medical Journal by two hospital teams, found that the plain cream base for the
medication may be just as good.
"As we have failed to show any therapeutic efficacy with this preparation and its
widespread use may encourage the development of strains of herpes simplex that
are resistant to acyclovir," they said, "we are reluctant to advocate its use in herpes
labialis."
Also open to question is another Wellcome initiative: to sell acyclovir for
chickenpox. This illness, which affects almost every child, which rarely has
complications and which may be a normal part of our body's training to fight
infections, is caused by another virus of the herpes family.
The biggest-ever published study in the New England Journal of Medicine showed
that taking acyclovir meant that children had, on average, 294 spots instead of 347
on a placebo. Acyclovir has no effect on the transmission of the virus, but could
net up to $150m a year for the company in the United States alone. The science
correspondent of America's NBC News has called the drug's use in these
circumstances an example of "irrationality and the quest for profits".
No better phrase, perhaps, could describe the dilemmas in the organisation which
hark back to Henry's time. For, while the efforts to push AZT and acyclovir will be
disturbing enough for some people, they are only among the more recent examples
of the company's general approach.
In response to inquiry, Wellcome presents its affairs in an unequivocal way.
Protesting to The Sunday Times about what it calls our "tendentious and frequently
alarmist generalisations", it said that the company took great care to comply with all
relevant procedures and requirements. "Products marketed by Wellcome over the
years have saved many lives and improved the quality of life for many patients," it
said.
But key issues remained unaddressed by the company and it is clear that, under the
controlling watch of a registered charity, the long-term business advantages of
Henry's empire may sometimes have been given a higher place than the health of
those consuming its products.
Its top-selling antibacterial, marketed as Septrin, Septra or Septran, is probably the
best example of how this can come about. Although, like acyclovir, it was rooted in
the brilliance of Wellcome's own researchers, saturation promotion which
accompanied it has been followed by associated deaths. Though grave worries have
been expressed about this for the best part of 20 years, little has been done.
Septrin is a mixture of a remarkably safe drug called trimethoprim (patented by the
company in 1957) and a more dangerous product called sulphamethoxazole, which
belonged to the Swiss pharmaceutical super-giant, Hoffman-La Roche. Both are
useful in certain diseases, but have been particularly popular in urinary tract
complaints which often are related to sexual activity and for some sexually
transmitted infections. Many people were prescribed the combination during the
1970s and 1980s for "non-specific urethritis".
That Septrin could injure or even kill emerged soon after it hit the market in 1969.
Reports appeared in journals and a survey by Britain's Committee on the Safety of
Medicines in the mid-1970s found a startling number of related deaths that were
not picked up by doctors.
In 1979, the company organised a conference at which some of these were
discussed but broadly dismissed as being either coincidental or outweighed by the
drug's benefits. In an interview with The Sunday Times, Dr Trevor Jones,
Wellcome's medical director, confirmed its commitment to the product. "Millions of
people have benefited significantly," he said. "I am very proud of the contribution
to health that Septrin has brought the world."
Nobody knows exactly how many deaths may have been associated with Septrin
(also marketed by Roche under the brand name Bactrim), but the compound was
the top anti-bacterial of its time (grossing more than $5billion) and so the figure
may run into thousands. Most problems have concerned older people suffering
from complaints which could mask the drug's side effects. Other reports, however,
have involved younger patients, including children. The company insists that,
although these followed use of the drug, causality should not be assumed. Although
government agencies have allowed the product to be marketed, Wellcome cannot
dispute that the sulphamethoxazole content of Septrin had a well-known record of
causing serious reactions. Nor that its combination with trimethoprim is hard to
justify for the treatment of most patients.
In 1973, a report warned about this in the journal Chemotherapy. In 1974, the
Annals of Clinical Research and the Journal of Clinical Pathology both made similar
points. In 1978, the advice was repeated in the British Medical Journal. In 1980, a
team summed up in The Lancet that, compared with Septrin "single therapy with
trimethoprim has the advantage of smaller tablets and fewer side effects, and it is
cheaper".
But even though powerful doubts had been raised about the product, Wellcome
remained loyal to Henry's ideas and sharpened its marketing. Such was the force of
its promotion to doctors, for instance, that from August 1981 the fortnightly
journal, World Medicine, carried a full-page colour Septrin advertisement in every
issue for a year. Other influential publications were similarly used, with the general
marketing slogan: "Today's antibacterial".
Considered alongside the controversy over AZT and acyclovir, the promotion of
Septrin may cause some to feel uncomfortable about Wellcome's sales approach.
Although Henry could never have dreamed of the sexual disease epidemics and
commercial advances that were to come, there is a common thread which starts
with him and runs through to the present day. While executives deny that there has
been excessive marketing, these stories raise questions about whether its greater
commitment is to fighting sickness or to maximising commercial success.
For the Wellcome Trust, which holds the reins and on whose reputation the
company trades, it can only prompt further inquiries about the scope of its
philanthropic intentions. How is it that a giant, respected organisation that is granted
charitable status to relieve human suffering and which is taking a commanding
position in medical science can be historically and financially rooted in the sale of
drugs which may be of trivial use and may be inappropriate or even dangerous?
The company says responsibility for prescribing and the patients' best protection is
firmly with the medical profession. There are also journals and government
regulations which have a special influence. The Wellcome Trust, its officers say,
has no involvement in the company's products, but promotes independent research.
In short, that most of what has been said so far is not true at all.
But as the Wellcome story unfolds, it is not hard to feel that the most worrying
thing about Henry's organisation is that in the structures he created and amid the
inevitable conflicts between commerce and sound medicine even the best efforts of
sincere people can produce perverse results.
It can also make you wonder whether, if the founder's ghost does wander the cold,
concealed splendour of number 183 Euston Road, he would be moaning over the
memory of his wife and Somerset Maugham. Or whether he would be chuckling at
the achievements of his empire and its drugs. *
VIRUSMYTH HOMEPAGE