New culture in the Zeneca lab

The drugs giant has led a revolution in R&D, writes Ian Griffiths
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The Independent Online
The Wilmington Trail Club is a friendly group of outdoor enthusiasts who meet regularly to share and appreciate the beauty of the Delaware countryside on the north-east coast of the US.

Warm greetings are a regular feature, but one witnessed a few weeks ago was, even by Trail Club standards, fulsome. "You have changed my life," a female member told the modest, bespectacled man in a kayak.

The man in question was Dr Peter Bernstein, a scientist at Zeneca's US research centre in Wilmington and one of the inventors of the pharmaceutical giant's revolutionary Accolate treatment for asthma.

Anyone who has asthma knows what a debilitating disease it is. The lady who so appreciated Dr Bernstein's endeavours used to have three different inhalers to counteract the disease. She could not exercise without taking medicine, experienced great discomfort and suffered from sleepless nights. Accolate changed all that. It is taken in pill rather than inhaler form. More importantly, it blocks the action of leukotrienes, chemicals in the body which contribute to breathing problems.

Accolate is the first drug in a new type of asthma therapy. It is a leukotrien receptor antagonist, the first new class of anti-asthma drugs introduced for over two decades.

The drug is the product of 16 years of diligent and painstaking work by Dr Bernstein and a 54-strong team of colleagues.

For him, part of the reward was the greeting at the Wilmington Trail Club. "There is nothing like that for someone like me who always wanted to be involved in drug discovery," Dr Bernstein says.

His reaction is typical of the scientists who work at Zeneca's research and development arm at Wilmington. While analysts back in London talk glibly of the "drugs pipeline", the Dr Bernsteins of this world live and breathe the science which they hope will take forward the fight against illness and disease.

There are about 15 million asthma sufferers in the US and over 5,000 deaths a year attributed to the disease. To someone like Dr Bernstein these are unacceptable figures.

This view is shared by Dr Edward Warawa, another Zeneca scientist who has spent over 20 years developing Seroquel, a new drug for the treatment of schizophrenia which goes on sale in the US later this month. This disease afflicts one in 100 Americans. The drug pioneered by Dr Warawa significantly reduces the side effects associated with earlier treatments, and is expected to help reduce significantly the annual $65bn (pounds 40bn) direct and indirect costs of caring for schizophrenics. With an estimated global market which will be worth nearly $4bn by the year 2000, the drug will also benefit Zeneca shareholders.

Dr Warawa personifies the understated commitment which seems to characterise the Zeneca culture. Much of his early work on Seroquel was done in his spare time. A less determined man would have given up years ago, but Dr Warawa was not prepared to quit.

Like Dr Bernstein he shuns any personal glory. Success is attributed to teamwork, hard work, patience and luck.

But other Zeneca insiders pay more fitting tributes to their genius, and to the contribution they have made to the credentials of the US R&D initiative.

The Wilmington R&D centre has a curious heritage. Originally Stewart Pharmaceuticals, it was subsumed into Atlas Chemicals until that company was bought by ICI. Wilmington has tended to be overshadowed by the research establishment at Alderley Park in north-west England. But when Zeneca was demerged from ICI, a conscious effort was made to give Wilmington greater prominence.

Many scientific breakthroughs were made in the US at that time. Research into genetics and developments in bio-chemistry demanded that Zeneca give more emphasis to its US R&D presence.

Accolate and Seroquel are the first two drugs to come on to the market out of the Wilmington stable under the Zeneca banner. That has contributed to the enormous pride felt right across the Wilmington establishment - a pride based on practical achievements and scientific excellence.

It is also a reflection of the new sense of identity which the workforce has developed since Zeneca's independence. But that independence has a cost. When rumours of a takeover bid for the group first surfaced they made front page headlines in the local newspaper. The workforce became unsettled. But familiarity bred contempt, and once the rumours became commonplace as well as unfounded they dropped from the front page of the local paper and were dismissed cheerfully by staff.

However, the rumours did highlight the importance of the company's share price; not because it boosted the wealth of the many worker/shareholders, but because it identified the outside investor, who in the end controls the company's destiny, as an important stakeholder in the business. This appreciation of the need to create shareholder value has been a critical factor in Zeneca's move to redefine its whole approach to R&D.

There would seem to be a glaring inconsistency between the servants of science and those who pay greater respect to the more material world. The white-coated boffins are more interested in finding the cure than funding the pension requirements of institutional investors.

So when in 1994 Zeneca put in place a review of its pharmaceutical research strategy, with a view to introducing a more managed approach, conflict seemed certain.

Dr Al Willard, vice-president of biomedical research, was at the heart of the review. A man who in his earlier years had worked with Dr Bernstein in pioneering Accolate now found himself advocating a more controlled approach to R&D.

The early efforts to manage the research rather than leave it to the scientists were met with distaste and disorder, but that soon gave way to a more considered response. "I have been amazed how quickly people have understood the importance of serving the needs of the business," Dr Willard says. "More interestingly, the scientists have also learned how to use management concepts to their own advantage."

The Zeneca approach may sound like a triumph for the bean counter over the bunsen burner, but in reality it has allowed the scientists to develop more fruitful research opportunities.

"Under the old system it was in the interests of the scientist to push a project as far as it would go," Dr Willard explains. "Now, while they may not always appreciate the judgement of management, they do recognise that they would rather be involved in a project which worked rather than one that yielded no practical benefit."

Under the new regime the research process has three distinct elements. The first is Target Selection, which allows the company to identify leading and competitive opportunities in the medical fields Zeneca has identified as important to its business. This combines internal research with external alliances. Next the process moves to Lead Identification, which uses the latest technology to screen compounds against the already defined molecular targets. Work which might have taken a lifetime can now be accomplished in days through the use of computers. Finally Zeneca goes to Lead Optimisation, which encourages more efficient choice of compounds which can be taken to the development stage.

It is methodical and efficient, yet it does not inhibit the natural drive of the scientists. The only lesson which they needed to learn is that the ambition to cure illness is not incompatible with the demand to add value for shareholders. The two masters can be served in parallel.

Indeed, the desire of the executives to expand the business has been of positive benefit to Zeneca's recent recruitment drive to increase its chemistry capability by 40 per cent.

Dr Dave Silberstein has been heading that recruitment drive on behalf of the Wilmington establishment. He has found that the target set by chief executive Sir David Barnes to grow sales at 15 per cent a year impresses potential employees. "In effect we are saying we will double the business in five years. To new recruits that suggests a commitment to science and a clear imperative to develop new drugs," Dr Silberstein says.

He joined Zeneca from Harvard, and academia remains a key hunting ground for new scientists. It is testimony to Zeneca's reputation that in his latest drive he has picked up five heads of laboratories from universities and attracted many more staff in the face of stiff competition from rival drugs firms. "They like our vision and they appreciate they will have the freedom to do science," Dr Silberstein concludes.

That will reassure those stock analysts who fret about Zeneca's "pipeline". What the Wilmington establishment shows - and this is no doubt repeated at the Alderley Park facility in the UK - is that Zeneca has the clear ability to regenerate its scientific capability. It has a culture and reputation founded on a commitment to scientific excellence which is rooted in history, but is capable of responding to technological change.

That technological change is most visible in the Lead Discovery department, where Dr Bob Hout can, at the flick of a switch, bring to life in glorious three-dimensional colour the interaction of different compounds. The cool whirring of the computer may not be quite as dramatic as the white heat of the laboratory, but it is highly efficient. The technology is not there to replace the laboratory, merely to help the scientists who work there to do their jobs better.

The old hands like to knock all the computer wizardry, but they do not really mean it. "The mouse used to sit in a cage, now it sits on a desk next to the computer," sighs one veteran. "Mind you, the one on the desk doesn't bite your fingers, and you need fewer of them before you get the answers you need."

The Zeneca culture dictates that it will remain at the forefront of technological developments in the field of drug research. Its scientists, certainly, would not want it any other way.