An acute talent for innovation -

Sir James Black places his walking stick on one side, eases himself into a plump yellow sofa atthe Royal Society of Medicine’s headquarters in London and begins to talk in a soft voice. But heis soon working himself up into a passion. He becomes agitated when discussing a Harvard Business Review article from 2008 by Jean-Pierre Garnier, the former chief executive of on the future of drugdevelopment. He agrees with the prognosis, but is fundamentally at odds over the prescriptionfor change. “In this time of gloom, the pharmaceutical companies ought to be doing extremely well,” he saysin his Scottish lilt. “There is no market as unique as drugs; when people are distressed, theirdesire for relief pre-empts all others; and the industry has a reputation for being good atdevelopment. The trouble is that it keeps making promises.” Still working, debating and writing in his 83rd year, long after mostof his peers have quietly retired, Sir James has plenty ofrecommendations for improvement in an industry that has sufferedfrom a flagging product pipeline, and still more thoughts on whathas gone wrong. He has no time for classic industry clichés such as “blockbuster”medicines; no truck with the modern approach to peer review; andno patience with any re-writing of history to suggest a more complexcontemporary era of drug discovery has replaced one of “low-hanging fruit” in the past. This is no idle chatter from an armchair pontificator, nor an academic divorced from the pressures of business. He is a distinguished scientist, the recipient of the Nobel Prize for Medicine in 1988, not to mention a Royal Medal and an award from the Lasker Foundation. But his rare skill – reflected late last year in the lifetime achievement award he received from Medical Futures, a British organisation established to commercialise doctors’medical ideas – is to have bridged the divide between university and business. He was pivotal in the development of two of the most successful blockbuster medicines that thepharmaceutical industry has ever developed: propranolol, the first beta-blocker to treathypertension; and cimetidine for stomach ulcers. Both transformed the lives of millions ofpatients and saved health systems enormous costs.
Raised in Fife, the fourth of five boys in a “staunch Baptist home”, Sir James says he was adaydreamer in school, and it was only in the “forbidding” atmosphere of St Andrew’s University,where he studied medicine, that disciplined study took over. He researched and taught in Singapore and then Glasgow, but was soon drawn into industryafter a friend working in ICI’s marketing division suggested that he contact the chemicalcompany’s pharmaceutical unit to co-operate in his research on beta blockers. To hisastonishment, they invited the academic outsider on a site visit to their new laboratories inAlderley Edge. “They said it would be much easier if I did the work in their labs. They were justheaven compared with anything I’d worked in before.” His approach highlighted one aspect that he believes is key to successful drug development:entrepreneurial teams of up to about 25 people, allowed to operate at arms’ length from the restofthe company. “Lab researchers have an insatiable appetite for growth. But we were small. Ihad a chemist and a technician, and off we went. I had to fight, but I could chat up the head ofR&D. We knew everyone by their first name.” He raises his eyes skywards when he discusses last week’s $68bn ( €53bn £48bn) takeover by the world’s largest pharmaceutical group, of and says the restructuring to comewill sap both teams. “Will they never learn? They will completely exhaust each others’ energiesfor two years.” Even in ICI in the 1960s – the pharmaceutical division of which is now part of AstraZeneca, theproduct of a mega-merger a decade ago – he began to feel too much bureaucracy and too muchdrift towards conformity for someone who considers himself “an inventor, not a discoverer”. “They wanted me to concentrate on development,” he says, recalling with horror a seniorcolleague who was increasingly distracted from his research, forced instead to spend “two days aweek meeting anaesthetists for talks and then eating and drinking their heads off”. Keen to begin work on a different field – antihistamines – when a friend at SmithKline andFrench asked if he could recommend people to hire, he put forward himself.
The result was his second blockbuster, generating billions of pounds in revenues. But he winces at the word, a symbol of what has gone wrong in drug development. “It’s a kind of obscenity.
Very few of the drugs classified as blockbusters retrospectively were designed in that way. Thepeople who know about markets can’t even predict what next year will do.” He points out that the sales forecasts for propranolol were £250,000 a year, and those forcimetidine £5m. The reality in both cases was orders of magnitude greater. “All you can do isplan for something which will fulfil a need. Being first is most important.” Sir James questions how far research can be successfully managed and quantified in advance.
He is scathing of pharmaceutical executives’ focus on bonuses and incentives. “I remembervividly the managing director of ICI pharmaceuticals saying to me that he would pay to do hisjob, he enjoyed it so much. Now apparently we have to bribe people.” He also recalls a senior researcher at the Wellcome Foundation – where he then moved butwhich subsequently merged with his former employer to become GlaxoSmithKline – whochanged his research targets each year because he could not show results in the short term. “Isaid, ‘you pick one and we’ll stick with it’.” The result was a new type of anti-convulsant. He rejects any suggestion that drug discovery was easier in the past. “I never found it easy.
People say I was lucky twice but I resent that. We stuck with [cimetidine] for four years with noprogress until we eventually succeeded. It was not luck, it was bloody hard work.” On the contrary, he suggests that the growing use of new technologies and techniques, frommolecular biology to genomics, has proved a mixed blessing. “The techniques have gallopedahead of the concepts. We have moved away from studying the complexity of the organism;from processes and organisation to composition.” Sir James was not able to repeat his own blockbuster success a third time, either at Wellcome,at subsequent academic posts, in the James Black Foundation that he founded after retirement,or in his continuing research today. But, given the uncertainties of science, even a single successis more than most drug developers can ever hope for.
He believes that for true innovation, researchers’ projects should not be assessed prospectivelyby their peers but on their promise demonstrated in the past and over longer cycles. “I believeyou should be judged by what you have done,” he says. On those grounds, no one can questionhis contribution to medicine over the past century.
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