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‘He saved lives but didn’t touch anyone. He took medicine out of the lab and put it in society.'

So Conrad Keating describes the achievements of Professor Sir Richard Doll, the giant of Oxford medicine who helped determine the link between smoking and lung cancer, took on ‘Big Tobacco’, and continually showed the value of evidence-based medicine in guiding public health decisions to benefit the greatest number.

Conrad, writer in residence at the The Wellcome Unit for the History of Medicine at Oxford University, has just written the official biography of Doll (featured in last week's Oxford Times). And Conrad is clear: Doll was a revolutionary, not just in medicine but a social revolutionary too.

He wasn’t a hands-on doctor, he never saw patients – but he established evidence-based medicine as the pre-eminent tool in public health care. ‘The tools of his revolution were pencils and graphs,’ Conrad explains. ‘If you look at the papers in the British Medical Journal in the 1950s, none of them had any stats. Today they all have stats. Doll made doctors count.

‘With Richard, it was all about risk and how to evaluate it. It was a new approach to science, one of philosophical detachment and persuasion through numbers. Richard was always independent and went with the evidence.’

While Doll’s work on smoking and cancer is routinely described as having saved countless millions of lives, Conrad notes with a smile that Richard would probably say that he had ‘prevented premature death’, not ‘saved lives’.

Part biography, part British social history
But Conrad also feels that in writing Doll’s biography that he has written a social history of Britain. Despite Doll coming from a background that was solidly establishment, the suffering, social conditions and mass unemployment he witnessed as a young man in the 1930s radicalised him.

‘His politics pushed him towards public health medicine and doing the greatest good for the greatest number. He didn’t want to just look after the rich,’ says Conrad.

Doll went on the Jarrow march in 1936, when there was 80% unemployment among men in the North East, and treated the marchers’ blisters. He was at Dunkirk, and campaigned for the formation of the NHS – to the point of almost being ostracised from the medical establishment – despairing that only the rich could afford good doctors.

His antifascist politics in the 1930s also led to him joining the Communist party. ‘He described himself as a democratic communist,’ says Conrad. He was a member of the party until May 1957, by which time he had become disillusioned after Soviet tanks had rolled into Budapest and – characteristically – when he felt he could no longer believe or buy into the science coming out of the USSR at that time.

When Doll came to Oxford in 1969 as the Regius Professor of Medicine, some still didn’t want ‘Red Richard’. Yet they were soon won round by his science, Conrad says. Doll would also go on to accept a knighthood and appear as an expert witness for British Nuclear Fuels, showing his independence on every matter.

Smoking and lung cancer

Doll of course is primarily known for his work with Austin Bradford Hill that showed smoking was a cause of lung cancer. (It was an interesting relationship in many ways, Conrad says. Hill was an arch-Tory, but he still gave this young radical a job when he had been in danger of being ostracised from a full career in medicine.)

In 1950, lung cancer overtook TB as the biggest killer in the UK. It was a peculiarly British disease: Britain had the greatest rates of lung cancer and also the highest rates of smoking in the world. It’s hard to imagine now from a modern perspective how prevalent smoking was in Britain. In 1950, 80% of middle-aged men smoked. It was very difficult to find people who had never smoked: just 0.5% of middle-aged men could say they’d never touched a cigarette.

The idea that smoking might be harmful was met with disbelief by the general public in the 1950s. After all, it was their favourite habit. The medical community was also sceptical – smoking was similarly entrenched among doctors. It took 25 years for the media to start to get behind the idea and people’s minds began gradually to be changed.

Doll’s first investigation with Bradford Hill in 1948 into the British epidemic of lung cancer didn’t necessarily look for smoking as a possible cause. Doll even wondered if car exhaust fumes or tarmac might somehow be a cause of the disease. The two researchers gave questionnaires to patients in different wards in the hospital about their background, social class, where they lived and also whether they owned a car, ate tinned food, and many more. Of the 50 questions, only nine mentioned smoking. But they found that those patients with lung cancer were almost always smokers.

To really understand smoking’s role in lung cancer, they then wrote to every doctor in Britain in 1951 to ask them if they smoked, with the aim of following up later to see who developed lung cancer. It took them a year to open all the envelopes they got back. But their 1954 paper with the results is a landmark in evidence-based medicine, showing that smoking was a cause and an important cause of lung cancer.

Doll himself was a smoker for 19 years, stopping in 1949 when it became clear to him that smoking was likely to be damaging his health.

Doll continued to follow up with the British doctors for an incredible 50 years, showing that smokers on average lose 10 years in life span compared with non-smokers, but also showing that stopping smoking had immediate benefits. The results of the 50-year British doctor study were published 50 years to the day after the first paper, shortly before Doll’s 92nd birthday.

But it wasn’t just the effects of smoking that Doll studied. He led the first big study on asbestos in 1955, following stories of high rates of cancer among workers at an asbestos factory in Rochdale, the biggest factory at that time. He completed the first study of links between the contraceptive pill and thrombosis, and he looked at potential leukaemia clusters around the Sellafield nuclear power station.

‘He would say: ”On balance, this is what I think weighing everything up,”’ Conrad adds, explaining that Doll believed nuclear power, on balance, was a good thing. He felt that once the risks had been evaluated, it was down to society to decide on what was acceptable: for example, asbestos has saved thousands of lives through fire insulation, but taken thousands of lives as well through mesotheliomas. The contraceptive pill can have a small increased risk of thrombosis, but it has liberated women allowing them to control their destiny and has a preventative effect for certain cancers.

Much of this weighing up of evidence is evident in an interview he did with the BMJ in 1997.

Doll in person
‘One of the unnerving things about meeting him was that he truly listened to what people said,’ Conrad says. ‘This didn’t lead to easy conversations. He was a busy guy, there was a degree of intimidation in meeting him, and you needed to be on your game … He often didn’t have time for people on a personal level – he had a lot to do.’

Conrad first met Doll while working on a TV package for the BBC. Over lunch at Green College, Conrad says Doll became emotional while telling a story about the Jarrow march. Conrad hadn’t expected this vulnerability and saw a great opportunity.

‘It took a long time to persuade him [to agree to a biography being written],’ says Conrad. ‘He was a private man and a serious scientist.’

He tells me a story as an illustration. ‘We both loved Tolkein,’ says Conrad. After going to see one of Jackson’s films of the Lord of the Rings at the cinema, they drove back at night in Conrad’s ‘decaying’ 2CV to Doll’s house where Richard prepared a midnight feast of boiled eggs and tongue. Richard got them both a Ruddles beer. ‘After we clunked beers, Richard said to me: “This is almost like being friends,”’ laughs Conrad.

Doll never retired, continuing to work almost up to his death aged 92 in 2005. ‘He was uneasy when he wasn’t working,’ says Conrad. ‘On his 92nd birthday he gave a bravura performance at a public lecture in the John Radcliffe hospital to a huge audience.’

His legacy
Doll made Oxford a world centre for epidemiology, with his successors in Sir Richard Peto, Rory Collins at the Clinical Trial Service Unit and Valerie Beral at the Cancer Epidemiology Unit carrying on his work. But more than that, says Conrad, his techniques have been distilled to disciples that now run public health agencies across the world.

Oxford medicine owes more to Doll than anyone else in the 20th century, says Conrad. As well as all the academic achievements, he established five chairs at the University and founded Green College (now Green Templeton College). ‘He was one of Britain’s greatest ever medical investigators and wrote one of the indelible chapters in medicine.

Smoking kills: The revolutionary life of Richard Doll by Conrad Keating is available from Signal Books. A launch party for the biography will be held today for invitees at Green Templeton College.

Image credit: Rob Judges

Once he'd finished On the Origin of Species what did Darwin do with his vast collection of stuffed reptiles, mammals, fish and birds?

Have an office clear-out: or at least that's the amusing idea behind Darwin's Leftovers, a collection of stitched artworks created by over 60 knitters that's on display at the Oxford University Museum of Natural History [OUMNH] until 27 November. 

According to lead artist Liz Lancashire each element of the display celebrates a key part of Darwin's life and thinking: from the Galapagos iguanas and tortoises that showed how natural selection could cause new species to evolve to exploit new environments, to hummingbirds with their odd-shaped beaks giving an ultimate example of specialisation in nature.

She said: 'Charles Darwin had many hundreds of stuffed animals in his cupboard and I wanted to recreate some of the paraphernalia of his scientific collection and capture the day he had an office clear-out!'

All this month Liz will be helping the Museum run a series of workshops for both adults and children exploring the wide variety of 3D knitting and other textiles techniques used to create these curiosities.

It sounds like the perfect skill to learn in the run-up to Christmas: so if you see an iguana-shaped present nestling under your Christmas tree then you'll know you've got Mr Darwin to thank for it.

Darwin's Leftovers is on display in the main gallery of the Oxford University Museum of Natural History until 27 November

It’s the biggest problem in physics: the matter we can see in the universe accounts for just five per cent of the observed gravity that holds galaxies together.

The conventional explanation is that enormous amounts of invisible dark matter make up the missing 95 per cent but some have argued that it’s Einstein’s theory that’s at fault.

In a review in this week’s Science Pedro Ferreira of Oxford’s Department of Physics and Glenn Starkman of Case Western University assess how alternatives to dark matter are shaping up.

‘For over 25 years there has been a proposal that there is no dark matter, that we are simply misinterpreting the data and that what in fact is happening is that we don't understand gravity,’ Pedro tells me.

‘A rudimentary alternative was proposed in the early 80s but only recently were a few complete theories constructed that modify Einstein's theory of general relativity and that could in principle solve the dark matter problem without dark matter.’

Israeli physicist Mordehai Milgrom got the ball rolling in 1983 with a proposal that became known as modified Newtonian dynamics (MOND). Other alternatives build upon this work, such as Jacob Bekenstein’s TeVeS.

Pedro comments: ‘In the review we emphasize two main things. First of all that all of these theories seem to bring in something akin to dark matter through the back door. It is not that they need dark matter as well as modifications to gravity but that any attempt to modify gravity necessarily generates something dark.’

‘The second point is that, even though waters seem to be muddied, there should be observational tests which can distinguish between the two paradigms. By looking at how galaxies are distributed and how they distort any background light, it should be possible to pick out clues for modified gravity, i.e. to test whether Einstein was indeed correct.’

The hope is that galactic surveys, such as those carried out by the Joint Dark Energy Mission or Square Kilometre Array, will be able to see if the telltale signs predicted by these alternative theories really are out there.

Professor Pedro Ferreira is based at Oxford’s Department of Physics

A story earlier this week gave hope that a new method might be sensitive and reliable enough to help predict who will develop early memory problems that could later lead to dementia.

BBC News online reported that ‘memory and language tests can reliably reveal “hidden” early dementia’.

These tests aim to detect small slips in memory or slight loss of fluency in speech, and could help doctors monitor people coming to them with memory complaints.

It also could help researchers in this area, as Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust, points out in the BBC Online piece: ‘Being able to spot and measure the initial stages of dementia is a crucial challenge if we are to improve drug testing and lay the groundwork for prevention trials.’

Oxford University researchers in the Oxford Project to Investigate Memory and Ageing (OPTIMA) were behind this study, funded by the Alzheimer's Research Trust and others. They gave a group of 241 healthy elderly volunteers regular tests that were designed to measure their use of language and their learning and memory abilities. They did this for a very long period of time: 20 years.

By following the volunteers for this length of time, the study, published in the journal Neurology, was able to show that the results of the Cambridge Cognitive Examination could reliably predict when a healthy elderly person was likely to develop mild cognitive impairment, a frequent precursor to dementia.

Professor David Smith of the Department of Physiology, Anatomy and Genetics, who led the study, explains: ‘In normal elderly people, those who perform very slightly below average in two cognitive tests (use of language, and learning and memory) are likely to convert to a state called ‘mild cognitive impairment’ sooner than those who score just above average on the tests. People with mild cognitive impairment have a high risk of developing Alzheimer’s disease later on.’

91 of the participants developed mild cognitive impairment during the study. Older people and those scoring lower on the language or memory tests were more likely to develop mild cognitive impairment more quickly.

‘These sensitive tests indicate that some changes that are marked in Alzheimer’s disease actually occur many years before the disease is apparent,’ says Professor Smith. ‘This implies that the disease process goes on for many years, but it also allows us to detect the disease long before it can be diagnosed.’

‘These simple tests could be used in memory clinics to help predict when elderly people will become cognitively impaired,’ he adds. It also raises the prospect that, should preventive methods be developed for dementia in the future, these tests could be used to identify who would benefit from early treatment.

At Halloween our thoughts turn to spiders and all things scary but how about spiders and dinosaurs?

Martin Brasier of Oxford University's Department of Earth Sciences has shown that amber found by amateur dinosaur hunters contains threads of the world's oldest spider webs - webs that were spun 140 million years ago.

The Oxford team report their results in the latest issue of the Journal of the Geological Society.

Martin comments: ‘This amber is very rare. It comes from the very base of the Cretaceous, which makes it one of the oldest ambers anywhere to have inclusions in it.'

Their evidence shows that the webs these threads belong to would have graced lush prehistoric forests frequented by dinosaurs such as Iguanadon and Allosaurus.

The web-spinners in question were closely related to the modern day orb-web, or garden spider. ‘These spiders are distinctive and leave little sticky droplets along the spider web threads to trap prey,’ Martin explains.

‘We actually have the sticky droplets preserved within the amber. These turn out to be the earliest webs that have ever been incorporated in the fossil record to our knowledge.'

The cobwebs were preserved in tree sap, possibly emitted by trees in response to fire damage, which then fossilised into amber. To reconstruct the webs, the scientists focused through the amber at 40 different positions, tracing it through the layers and then splicing it together again using a computer technique called confocal microscopy.

As well as the amber, there are several other types of deposit at the site which are showing remarkable levels of preservation, including silica and phosphate minerals.

Martin adds: 'It’s part of a larger project which is yielding rich rewards. There’s still a lot more to find, and we have even more exciting things to report in the near future.'