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Quest for a cure
Media Watch
Radio Quest for a cure 2005 saw pharmaceutical giants Pfizer, GlaxoSmithKline, and Merck and Co generate revenues in excess of US$100 billion (£55 billion). In its depiction of a murderous drugs company brutally exploiting impoverished Kenyans, the Oscar-winning film The constant gardener tapped into growing public disenchantment with the industry. Yet it costs an estimated US$800 million (£450 million) to bring a new drug to the marketplace, money that has to be recouped from somewhere. Veteran BBC journalist Peter Day spent 5 years with one of the largest pharmaceutical companies, tracking the progress of a potential new therapy for HIV/AIDS. Quest for a cure is his fascinating insight into the controversial and secretive world of “big pharma”. The ancient Kent town of Sandwich is the incongruous setting for Quest for a cure. A stopping point for Thomas A Beckett on his flight from Henry II, and for Richard the Lionheart after the Crusades, it now houses Pfizer’s biggest facility outside the USA. It was here that Viagra was invented (ironically researchers were actually looking for a treatment for heart trouble), a site employing 3000 people, two-thirds of whom are highly qualified scientists. The front-line in the attempt to create the next generation of drugs. This is an arena where failure is the norm—Wilma Keithley, senior director of Discovery Technologies at Sandwich, considers that to work on one or two marketed drugs in an entire career would be “lucky”. We follow the journey taken by compound number 107543 from Pfizer’s refrigerated storeroom of millions of chemical entities, through its refining over the course of 3 years and 11 000 modifications into a drug known as UK427857, and the final stages of further testing and the eventual production of a pale blue tablet called Maraviroc, still awaiting approval from the US regulatory authorities. The experience of those involved with Maraviroc is not atypical. After the emergence of AIDS in the 1980s, Pfizer spent from 1988 to 1995 engaged in a fruitless search for an antiviral. The discovery by the US National Institutes of Health (Bethesda, MA, USA) of the CCR5 coreceptor radically changed matters and Pfizer started to work on developing a CCR5 antagonist. The testing of hundreds of thousands of chemical compounds began, and by 1997 the high throughput screening process (thousands of glass slides pitted with ink wells, each with a tiny drop of the chemical to be automatically tested) had yielded a handful of compounds of interest. Next, animal
http://infection.thelancet.com Vol 6 June 2006
testing, and by late 2001 the drug was ready for human volunteers. The tortuous wait for approval followed. This latter part is particularly expensive; the drug has to be ready for immediate distribution, necessitating an outlay of US$100 million on manufacture, purchasing starting chemicals, and producing the launch supplies. And for every drug that makes it to the marketplace ten fail, some of which have already entered the costly stage of human clinical trials. John LaMattina, president of Pfizer Global Research and Development, eagerly tells of enormous headway in the field. He explains the scarcely credible “rat hotplate test” that constituted cutting-edge research in the 1970s. A rat, injected with a painkiller, was placed on a hotplate. The object was to find a drug that delayed the moment at which the unfortunate rodent leapt from the heated surface. LaMattina goes on to promise a “golden age of drug discovery” spurred on by the technological and scientific breakthroughs of the past 20 years (for him the golden age is right now—according to Forbes Magazine, LaMattina’s 2005 earnings were a very healthy US$3·38 million). Harvard Medical School’s Jerry Avorn disputes LaMattina’s buoyant assessment, pointing out that only 13% of revenues are put back into research and development, that the industry’s rate of discovery has “slowed to a crawl”, and that publicly funded establishments such as universities and hospitals are now responsible for the major scientific advancements. Campaigner James Love agrees, suggesting an alternative method of financing drug discovery: a generous prize fund to be divided between companies behind the most important innovations. Hank McKinnel, the chairman and chief executive officer of Pfizer, is, unsurprisingly, scornful of the idea. “I think that worked in the British navy in the 17th century” he says cryptically before defending the free market with a mangled misquote from Winston Churchill. There are omissions. Africa is not so much as mentioned, nor does Day question Pfizer executives about “orphan illnesses” (diseases where the number of sufferers worldwide are insufficient for drugs companies to invest in developing a cure). But in its detailing of the painstaking everyday work of the industry, Quest for a cure is truly revelatory.
Quest for a cure was broadcast on BBC Radio 4 in March–April 2006. An archive of this series can be found at http://www.bbc. co.uk/radio4/questforacure/
Talha Burki [email protected]
333
Radio Quest for a cure 2005 saw pharmaceutical giants Pfizer, GlaxoSmithKline, and Merck and Co generate revenues in excess of US$100 billion (£55 billion). In its depiction of a murderous drugs company brutally exploiting impoverished Kenyans, the Oscar-winning film The constant gardener tapped into growing public disenchantment with the industry. Yet it costs an estimated US$800 million (£450 million) to bring a new drug to the marketplace, money that has to be recouped from somewhere. Veteran BBC journalist Peter Day spent 5 years with one of the largest pharmaceutical companies, tracking the progress of a potential new therapy for HIV/AIDS. Quest for a cure is his fascinating insight into the controversial and secretive world of “big pharma”. The ancient Kent town of Sandwich is the incongruous setting for Quest for a cure. A stopping point for Thomas A Beckett on his flight from Henry II, and for Richard the Lionheart after the Crusades, it now houses Pfizer’s biggest facility outside the USA. It was here that Viagra was invented (ironically researchers were actually looking for a treatment for heart trouble), a site employing 3000 people, two-thirds of whom are highly qualified scientists. The front-line in the attempt to create the next generation of drugs. This is an arena where failure is the norm—Wilma Keithley, senior director of Discovery Technologies at Sandwich, considers that to work on one or two marketed drugs in an entire career would be “lucky”. We follow the journey taken by compound number 107543 from Pfizer’s refrigerated storeroom of millions of chemical entities, through its refining over the course of 3 years and 11 000 modifications into a drug known as UK427857, and the final stages of further testing and the eventual production of a pale blue tablet called Maraviroc, still awaiting approval from the US regulatory authorities. The experience of those involved with Maraviroc is not atypical. After the emergence of AIDS in the 1980s, Pfizer spent from 1988 to 1995 engaged in a fruitless search for an antiviral. The discovery by the US National Institutes of Health (Bethesda, MA, USA) of the CCR5 coreceptor radically changed matters and Pfizer started to work on developing a CCR5 antagonist. The testing of hundreds of thousands of chemical compounds began, and by 1997 the high throughput screening process (thousands of glass slides pitted with ink wells, each with a tiny drop of the chemical to be automatically tested) had yielded a handful of compounds of interest. Next, animal
http://infection.thelancet.com Vol 6 June 2006
testing, and by late 2001 the drug was ready for human volunteers. The tortuous wait for approval followed. This latter part is particularly expensive; the drug has to be ready for immediate distribution, necessitating an outlay of US$100 million on manufacture, purchasing starting chemicals, and producing the launch supplies. And for every drug that makes it to the marketplace ten fail, some of which have already entered the costly stage of human clinical trials. John LaMattina, president of Pfizer Global Research and Development, eagerly tells of enormous headway in the field. He explains the scarcely credible “rat hotplate test” that constituted cutting-edge research in the 1970s. A rat, injected with a painkiller, was placed on a hotplate. The object was to find a drug that delayed the moment at which the unfortunate rodent leapt from the heated surface. LaMattina goes on to promise a “golden age of drug discovery” spurred on by the technological and scientific breakthroughs of the past 20 years (for him the golden age is right now—according to Forbes Magazine, LaMattina’s 2005 earnings were a very healthy US$3·38 million). Harvard Medical School’s Jerry Avorn disputes LaMattina’s buoyant assessment, pointing out that only 13% of revenues are put back into research and development, that the industry’s rate of discovery has “slowed to a crawl”, and that publicly funded establishments such as universities and hospitals are now responsible for the major scientific advancements. Campaigner James Love agrees, suggesting an alternative method of financing drug discovery: a generous prize fund to be divided between companies behind the most important innovations. Hank McKinnel, the chairman and chief executive officer of Pfizer, is, unsurprisingly, scornful of the idea. “I think that worked in the British navy in the 17th century” he says cryptically before defending the free market with a mangled misquote from Winston Churchill. There are omissions. Africa is not so much as mentioned, nor does Day question Pfizer executives about “orphan illnesses” (diseases where the number of sufferers worldwide are insufficient for drugs companies to invest in developing a cure). But in its detailing of the painstaking everyday work of the industry, Quest for a cure is truly revelatory.
Quest for a cure was broadcast on BBC Radio 4 in March–April 2006. An archive of this series can be found at http://www.bbc. co.uk/radio4/questforacure/
Talha Burki [email protected]
333