Monthly Archives: March 2009

Clive Cookson

The controversial all-in-one polypill – a cocktail of drugs to fight heart disease – has come through its biggest clinical trial so far with flying colours.

Two thousand middle-aged and elderly people in India took part in the trial. The results, published online by the Lancet, show that a polypill with five active ingredients works almost as well as the sum of its individual components. And the combination causes no unexpected side-effects.

Salim Yusuf of McMaster University in Canada and his Indian colleagues, who organised the trial, estimate that middle-aged people could roughly halve the chance of suffering a “cardiovascular event” – heart attack or stroke – by taking polypills regularly. For those at high risk, the benefits would be greater.

The polypill used in the Indian study contains a statin (simvastatin) to reduce cholesterol, aspirin to thin the blood and three antihypertensives (atenolol, ramipril and thiazide) to lower blood pressure. It is similar to the polypill originally advocated by two UK professors, Malcolm Law and Nick Wald, in the British Medical Journal in 2003.

Although there is nothing to stop a doctor prescribing the five polypill ingredients individually to patients, there is a strong psychological obstacle to taking so many pills at once every day. Much better to swallow them as a single capsule.

All the ingredients are off-patent, cheap and easy to produce. Indeed Indian generic drug companies are already gearing up to manufacture polypills.

Some experts have been concerned that adverse reactions between the ingredients might seriously reduce their effectiveness or even lead to new side-effects. The Indian study has allayed most of these fears, though more clinical evidence will be required before GPs – and regulators such as the US Food and Drug Administration – are convinced of the merits of the polypill. Issues such as dosing also need to be resolved.

A Lancet commentary by Christopher Cannon of Harvard Medical School, accompanying the research paper, raises another question: “Would the availability of a single magic bullet for the prevention of heart disease lead people to abandon exercise and appropriate diet? Would this make two of the major root causes of heart disease worse?” The medical profession would need to make sure that the answer is No.

Clive Cookson

This week is the 20th anniversary of what would have been the greatest scoop of my journalistic career – if it had been true. Sadly it is remembered mainly as a classic “bad science” story.

Cold fusion made its first public appearance on the front page of the FT on March 23, 1989, ahead of a press conference at the University of Utah at which two chemists, Martin Fleischmann and Stan Pons, were to announce a sensational discovery. They had created a potentially unlimited source of clean energy, by carrying out controlled nuclear fusion – the reaction that powers the sun and the H-bomb – in a simple electrochemical cell.

Not surprisingly, cold fusion aroused enormous media interest. And, despite widespread scepticism, physics and chemistry labs around the world raced to repeat the Fleischmann-Pons experiment. After all, the pair were not scientific charlatans but chemistry professors with respectable academic backgrounds.

Scientists and journalists gradually lost interest, as others failed to obtain evidence of nuclear reactions in their laboratories. Within a year cold fusion was generally regarded as a sad mistake.

Even now, however, cold fusion retains a small band of believers. Some of them are reporting positive results this week at a symposium organised by the American Chemical Society to coincide with the 20th anniversary of the original announcement. (The phenomenon has been renamed “low energy nuclear reactions” or LENR.) For instance, chemists at the US Navy Space and Naval Warfare Systems Centre in San Diego presented evidence of tracks left in a special plastic by neutrons originating in an electrochemical cell similar to the one used by Fleischmann and Pons.

Such results suggest that it may indeed be possible to induce a low level of nuclear fusion in an ordinary chemistry lab. But, if fusion is to become a serious energy source later this century, most scientists believe big special facilities will be needed, such as the $10bn ITER reactor to be built through an international collaboration at Cadarache in southern France.

Clive Cookson

Sometimes in science, persistence is rewarded. For more than 30 years Mark Pepys, professor of medicine at University College London, has concentrated on research into amyloidosis, an incurable disease that causes organ failure in tens of thousands of people a year worldwide.

Amyloidosis is caused by the build up of abnormal “amyloid” proteins in body tissues. Prof Pepys has long believed that the key to understanding the disease is a related blood protein called SAP, which sticks to amyloid fibres and stops enzymes removing them.

The FT has covered his work several times. My predecessor David Fishlock described in 1990 Prof Pepys’s discovery of a way to image SAP and amyloid fibres. I wrote in 1995 and 2002 about progress in developing a drug called CPHPC, which aimed to clear the destructive amyloid deposits from patients by removing the protective SAP from their blood.

Prof Pepys was working then in collaboration with Roche. But the Swiss pharmaceutical giant eventually pulled out.

“While we had promising early results [with CPHPC] they were not enough to benefit patients with advanced disease,” he says. “Something more dramatic is needed.”

That something turns out to a combination of CPHPC with an antibody – a molecular guidance system designed to seek out amyloid deposits in vital organs.

Now Prof Pepys has reached an agreement with another big pharmaceutical group, UK-based GlaxoSmithKline, to collaborate on producing a treatment for amyloidosis based on the CPHPC-antibody combination.

Although the details of this week’s deal are confidential, Prof Pepys says GSK will spend many millions of pounds working with UCL scientists, to convert their successful animal tests into an antibody-based drug for human use.

Mike Owen, GSK’s head of biopharmaceutical research, said it was realistic to aim for clinical trials within two years.

Symptoms of amyloidosis are very variable because the heart, kidneys, liver and almost any other organ can be affected. Every year 500 to 1,000 new cases are diagnosed in the UK, mainly in middle-aged and older people; their prognosis is poor.

Although amyloidosis is a rare disease, there are enough sufferers – an estimated 80,000 in the industrialised world – to bring in considerable revenues from an effective drug.

Prof Pepys points out that antibody-based medicines can sell for tens of thousands of pounds per patient, particularly if they treat a previously untreatable disease.

While staff at GSK’s research centre in Stevenage will look after the clinical development of the new medicine, “Prof Pepys will remain closely involved in the project,” says Pauline Williams, the company’s head of academic liaison. “It was critical for him to feel that he was not handing everything over to us.”

Clive Cookson

Whether to screen middle-aged men for prostate cancer is one of the most controversial issues in oncology.

Screening through the PSA blood test, which detects raised levels of “prostate specific antigen” associated with the disease, can reveal the presence of cancer before symptoms appear, enabling doctors to treat it early through surgery or radiation. In principle this should improve the prospects of a cure.

However the side-effects of treatment are often unpleasant, including impotence and incontinence. And prostate cancers often grow extremely slowly, causing no trouble till the patient dies of other causes.

Now the New England Journal of Medicine has published the results of two huge clinical trials of prostate cancer screening, which were supposed to give doctors better guidance about whether to give the PSA test to symptomless men.

Unfortunately the results are somewhat contradictory. But the overall conclusion seems to be that screening may save a small number of lives but will expose far larger numbers to unnecessary treatment and psychological stress.

A European study of 162,000 men, observed for an average of nine years, found a 20 per cent reduction in mortality among those given the PSA test. For every life saved, however, 1,400 men were screened and 48 men received treatment following a positive result. A US study of 77,000 men, followed for seven years, resulted in more detections of disease but no survival benefit from screening.

John Neate, chief executive of the UK-based Prostate Cancer Charity, says the research “highlights the critical importance of the development of a scientific test that can identify aggressive forms of prostate cancer and differentiate them from slow growing forms of the disease. Such a test would enable treatment to be focused on men for whom prostate cancer poses a serious risk to their health and avoid the over treatment of men with the harmless, slow growing forms of the disease.”

Until a much improved test is available, the middle-aged writer of this blog will decline any invitation to be screened for prostate cancer.

Clive Cookson

Financial mathematicians are unlikely to be impressed by Lord Turner’s review of the banking crisis. Their discipline features quite prominently in the first part of the report, looking at what went wrong, but hardly at all in subsequent sections that prescribe solutions.

Lord Turner, chairman of the Financial Services Authority, blames “misplaced reliance on sophisticated maths” for misleading banks’ top management into a false sense of security about the risks they were taking. That is unfair. As Tim Johnson of Heriot-Watt University puts it, the problem was that banks did NOT use sophisticated maths; their mathematical models were far too simple. They had no incentive to employ more complex and realistic models because the simple “single factor” models used for pricing gave an illusion of accuracy and precision – and lulled the market into believing banks had everything under control.

Putting it another way, the models were built to fit market prices. The result was that whacky prices were reinforced by an overlay of scientific respectability.

Lord Turner should have said that we need more and better maths for the future. In particular we require better models of the interdependency of different financial variables and of the risk of extreme events. That means more funding of research in financial mathematics, by the public and private sector.

Another priority, not mentioned by Lord Turner, is to educate bankers about the mathematical basis of their industry. It should no longer be acceptable for them to use models as “black boxes” without making any attempt to understand the underlying assumptions.

The world of research

The science blog is no longer updated but it remains open as an archive.

Clive Cookson, the FT's science editor, picks out the research that everyone should know about, in fields from astronomy to zoology. He also discusses key policy issues, from R&D funding to science education. He'll cover the weird and wonderful, as well as the serious side of science.

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