BRIAN DEER: HARD SELL Page 6

No blame attaches to Elion for drug promotion - and she says she doesn’t even use allopurinol for her own gout. "That aspect of the marketing, I have nothing to do with," she explains. "Once the thing is established, sometimes they do things that are commercially feasible, and commercially important, and perhaps not medically important. And that's a decision that I don't have to make."

But exactly who is responsible isn’t easy to pin down. In London, Wellcome points to doctors and regulators who prescribe and rule on proper usage. Whether you talk with the commercial Wellcome plc, or the charitable Wellcome Trust, they take the position that it is neither company nor charity which decides on who gets what.

It is not surprising that they speak as one: it is what the founder, Henry Wellcome, had intended. In his will documents, filed in 1932, he stressed his belief in a co-ordinated approach, with marketing the name of the game.

"It is my special desire that there should be no material reduction in the proportional expenditure for publicity and other forms of propaganda of the several organisations,” he stipulated for his posthumous empire. “As I wish my trustees and the directors continuously to develop and increase the output and sale of the products of the industrial organisations of the Foundation throughout the world. The consistent pursuance of this policy will ultimately result in greatly increased profits."

But today the trust sponsors some of the most prestigious medical departments. It has an advisory system of more than 3,500 doctors and scientists. It owns one of the finest medical libraries and on-line retrieval systems. It has a multi-million pound research institute at its Euston Road headquarters. Its seven-person governing board includes a doctor and four professors. If it cannot evaluate its medicines’ profiles, then it is hard to know who could.

In a structure that distributes a share of its profits to researchers, moreover, there may be conflict of interest anxieties. When asked whether grant-seeking experts may feel inhibited from criticising Elion and Hitchings’ big four products because of the organisation's enormous reach, Dr Bridget Ogilvie, the trust’s director, did not refute the suggestion. She declined to comment.

This issue is sensitive, touching on ethics and propriety in an ever-more competitive world. Increases in research costs, and tight controls on public spending for science, mean that the trust is bombarded with requests for sponsorship - two thirds of which it refuses. Last year, even on the British government's Committee on the Safety of Medicines, 19 of the 21 members either worked in institutions which received Wellcome money, or were granted a share of it themselves.

The potential for a ménage between company, charity and experts, is a worrying feature of the founder’s legacy. Collusion was central to Henry Wellcome's thinking, with his will documents noting that some granted research money would produce "much of purely technical interest," but that even this "should also contribute to the discovery of remedies and curative agents and new methods of treatment which may be of practical interest and importance to the industrial organisations of the foundations".

In the United States, the Burroughs Wellcome Fund (of which Elion and Hitchings were for many years directors) has kept particularly close to this prescription. One of its biggest recent grants is a $350,000 award for "innovative methods in drug design and discovery", which in 1992 went to Dr Susan Amara in Oregon. Her work relates to brain chemicals which, according to the fund "may help physicians combat cocaine addiction". Meanwhile, Wellcome has a drug, bupropion, "undergoing clinical trials in the USA for the treatment of cocaine addiction".

In Britain, cross-fertilisation between company and trust has reached even the highest levels. One distinguished figure, whose profile has risen with Wellcome’s, is Sir Roy Calne of Cambridge University, one of the most accomplished transplant surgeons. As a young man, he helped Elion and Hitchings to develop azathioprine and, in the years that followed, was endowed by the charity with grants, research help and expenses.

Another example of how working with the company can be followed by trust support involves two professors: John Stenlake of Strathclyde University and James Payne of the Royal College of Surgeons. Both were key figures in developing atracurium, a top-selling Wellcome muscle-relaxant. Stenlake received trust grants for his work between the late 1960s, when atracurium's development began, and the mid-1970s. Payne got assistance in the early 1970s and the late 1980s.

Another instance recently is the case of Herman Waldmann, professor of therapeutic immunology at Cambridge, and a fellow of the Royal Society. With financial support from the trust, he advanced a revolutionary Wellcome product, Campath, the world's most developed monoclonal antibody. After assigning it to the company, he became an adviser to the charity and sought to obtain further sponsorship. This, however, was blocked last year - he believes on the advice of lawyers.

Nobody suggests impropriety by these respected figures, who are bound to seek funding where they can get it. And the trust would flatly deny that there is any quid pro quo when it offers its financial support. But it is clear that at least some collaborators hope for the trust’s rewards after furthering the company’s goals.

The money they get, of course, rarely goes into their pockets. The trust's help is to support research. But it is rarely cash in the bank that wins the hearts of people of the highest standing and influence in science. More often they are driven to advance medical progress, or to win peer-recognition. It’s a popular misconception, Elion says, that people like herself are primarily driven by their wallets.

"They think that we get some personal monetary reward out of it, and that really isn't what we want," she says of the many who misunderstand this point and assume she must be rich. "What we want is a chance to do research. A chance to, you know, get some additional people in our departments, and so on."

*****

While it is the trust which has handed out most of Wellcome’s money, the kind of opportunities to which Elion is referring can also come directly from the company. Both the Wellcome Foundation and Burroughs Wellcome in the US make major contributions to the medical money-go-round that is now a mainspring of the pharmaceutical industry.

During the last five years, Wellcome has courted particular controversy over its financial interventions in the field of Aids. People with this condition will often not only use AZT, but may also take acyclovir and Septrin as well: generating millions in profits to distribute. Recipients have ranged from the mighty US department of health ($5m), to countless small-time self-help groups.

Much of this money has created a climate to support trials of Wellcome products. In an American coast-to-coast test which won AZT its licence in 1987, for instance, one hospital, Massachusetts General, received $140,000 for data on just 19 patients. Other participants were also generously rewarded - and far from such payments guaranteeing good work, inspectors have discovered many flaws.

Another example concerns one of the most powerful medical figures: Dr Samuel Broder of the US National Cancer Institute. Broder is the person most associated with AZT's approval, and, crucially, was supported by Burroughs Wellcome. Although the money went to his laboratory, and not into his pocket, he accepted $55,000 at the time the company's product was under federal review.

Surprisingly, Aids activists, including the militant group Act-Up, have also been backed by the company. Among the group’s many high-profile protests in the epidemic's early years, Act-Up had even broken into Wellcome’s US offices. But in July 1992, only weeks before the trust floated a huge block of shares, Act-Up leaders appeared at a New York press conference to shake hands and accept $1m. Meanwhile, the British company spent £60,000 last year flying Act-Up supporters to a conference.

Even journalists and politicians are not overlooked, as Wellcome’s founder’s dream plays out. Writers are often helped to attend meetings in foreign locations, while even the European Community held a parliamentarians' conference last year that was sponsored by the Wellcome Foundation.

Such techniques - now common throughout drug-based medicine - provoke mirth from close observers. Sir James Black - Elion and Hitchings’ fellow Nobel prizewinner - smiles at mentions of the Wellcome Foundation, for which he used to work. "The industry as I've seen it, I think, takes the view that marketing drugs is the same as marketing anything," he says. "The promotional methods used by the pharmaceutical industry are no different from the promotional methods used in any other branch of the chemical industry."

Black addresses an issue he thinks the public still under-appreciates: the pressure of commercial imperatives. Wellcome's main board comprises much the same people who might run a bank or an oil company - and who do their job in much the same way. The difference lies in the reputation of medicine and science to assure us that they do their job well.

There have been no doubts about integrity at the top. Roger Gibbs, the chairman, has had wide business interests, including the London Clinic and the Arsenal football club. Another board member, Sir Peter Cazalet, is a former oil man and a prominent industrialist. But, in the legacy and structures set up by Henry Wellcome, the profit-sharing scheme, that continues to grow, may have acquired a life of its own.

Trying to control this has proved endlessly difficult, creating difficult management decisions. At least until 1984 (when such information ceased to be available), the trust invested in the British American Tobacco Corporation, as well as a string of breweries. Possibly good investments, but not free of controversy for a business which showcases support for health.

More important than such embarrassments, however, is how the trust and the company may be preparing for years to come. Both are deeply involved in biotechnology and genetic engineering - areas where error, or an excess of marketing, could lead to a catastrophe. As Wellcome’s empire grows, through its tax-exempt charitable arm, and the company's drug development programme, the medical money-go-round may lead to error that puts humanity itself into a spin.

Some doctors and scientists look forward with hope. Elion glances back with nostalgia. "When we first had people working on 6-mercaptopurine, allopurinol, Imuran, we didn't pay one cent for those studies," she remembers. "We didn't influence them in any way."

No doubt if her offspring had been children instead of drugs, she would have warned about candy from strangers.

[Vagaries of editing mean this version is different to what was printed in The Sunday Times. The second part of Hard Sell, referring to Elion and Hitchings, appeared under the heading "The Moneyspinners"]