Science and Science Fiction

Sherlock Holmes and the deductive paradigm of forensic epidemiology.

No blogs for ages, and then two in one week …

Deductive logic at its finest

Earlier this year, Dom Mellor was giving a talk to the epidemiology group at Glasgow, where he started by saying that, in his view, Sherlock Holmes represented the perfect example of forensic epidemiology. In a sense he was right, and at least some of you will know that it is commonly believed that the Holmesian forensic technique was based on Conan Doyle’s experiences as an Edinburgh medical student, where the medical doctor and University Professor Joseph Bell impressed the young student in his lectures. It was said that “all Edinburgh medical students remember Joseph Bell – Joe Bell – as they called him. Always alert, always up and doing, nothing ever escaped that keen eye of his. He read both patients and students like so many open books. His diagnosis was almost never at fault.” Sherlock Holmes most famous quote, taken from the Sign of the Four: “When you have eliminated the impossible, whatever remains, however improbable, must be the truth” is the iconic expression of deductive logic, and it could be said to be the ultimate goal of forensic epidemiology. I recall a colleague saying to me “Identify and eliminate the source of Infection, and you eliminate the epidemic”, apparently quoting from the highly respected veterinary epidemiologist, Prof. Mike Thrusfield at the Dick Vet School in Edinburgh, though I cannot comment on the accuracy of the quote. Of course, it is also well recognised that it would usually be impossible to be so sure as Sherlock Holmes in real life, but this nevertheless represents a sort of platonic ideal of forensics.

“Balance of probabilities, little brother” Mycroft Holmes, Hearse, Sign and Vow (from http://www.bbc.co.uk)

Move forward a century and more, and the hugely popular TV series ‘Sherlock’ presents a modern updating of the old stories, an updating which, to my great surprise, I have thoroughly enjoyed. In the third series, in the episode ‘Hearse, Sign and Vow’, Sherlock and his older, more intelligent brother Mycroft are engaged in a contest to characterise a man from only his woolly hat. In this contest Sherlock queries one of Mycroft’s “deductions”, when Mycroft replies “Balance of probabilities, little brother.” Now this statement is decidedly un-Holmesian – in the world of Arthur Conan Doyle’s Sherlock Holmes, probabilities have nothing to do with it. This statement is in fact, one of inductive logic. And it could be argued that the mathematical and statistical modelling of infectious diseases lies very much more in this inductive tradition. Not so much concerned with identifying the single chain of transmission, modelling traditionally concentrates on the identification of general, population level principles of transmission, and an overall ‘balance of probabilities’ of getting the right pattern.

These two traditions – that of the forensic epidemiologist and the mathematical/statistical epidemiologist do not sit easily together, and indeed it could be argued that much of the controversy over the 2001 Foot-and-mouth disease (FMD) epidemic in Great Britain can be attributed to precisely that clash of cultures.

Phylodynamic reconstruction of a foot-and-mouth disease (FMD) epidemic. (A) Identified likelihood that a particular infected premises was the source of another infected premises based on a space–time–genetic model. Circle size is proportional to the relative likelihood of that event. (B) Spatial relationships among premises in the dataset. Reproduced from Morelli et al. PLoS Pathogens 2012.

Phylodynamic reconstruction of a cluster of cases from the 2001 FMD epidemic in Great Britain. (A) Identified likelihood that a particular infected premises was the source of another infected premises based on a space–time–genetic model. Circle size is proportional to the relative likelihood of that event. (B) Spatial relationships among premises in the dataset. Adapted from Morelli et al. PLoS Pathogens 2012.

Now however, the integration of rapid high throughout sequencing of pathogens allows us to trace to a very fine scale the movement of pathogens from place-to-place, and even from individual-to-individual. Combined with mathematical models, this can often lead to very precise identification of likely sources of infection. The figure here is taken from a paper by Marco Morelli while he was working with Dan Haydon at Glasgow, illustrating precisely that kind of analysis using data from the 2001 FMD epidemic. Of course the most likely source under one model of transmission is not necessarily proof that the relationship is the true one (e.g. what if another model gives an equally strong but different prediction?) and there are many challenges still to be addressed. Despite these issues, the future is bright and it is just possible that, through these new technologies and approaches, we can at last approach that Holmesian ideal.

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Glasgow Science Festival – Zombies, Evolution and Science Sunday

Shaun Killen and Rowland Kao showing their knowledge of all things zombie.

‘Shaun of the Dead’ Killen and Rowland Kao showing their knowledge of all things zombie.

GlasgowSciFestThis past week has seen the opening of the ‘Glagsow Science Festival’ in which the Glasgow scientific community (largely but not entirely led by the University of Glasgow) presents itself to the general public. Offerings range from serious events highlighting the best science that our region has to offer (for example, in an opening night event celebrating Women in Science) to a ‘Whiskey-omics‘, event, which was a detailed study into the underlying molecular properties of Scotland’s favourite export led by Glasgow Polyomics.

Zara the Zombie

‘Zara the Zombie’ Gladman, former biodiversity PhD student and now Science Festival majordomo, shows her claws.

The Boyd Orr Centre was involved in two events. The first of these was an involvement in ‘Dead Sleazy‘, a celebration of all things zombie at Nice’n’Sleazy last Thursday night. It was originally conceived as a Boyd Orr Centre event, following on from other examples where zombies have been used to help inform people about science. A zombie apocalypse movie would be used to illustrate points about an epidemic, how it spreads and how it is controlled. At the suggestion of Deborah McNeill, the festival organiser, it was joined onto a Zombie Science lecture followed by a Q&A with Shaun Killen and myself, and a screening of Sam Raimi’s original Evil Dead movie. The modern zombie movie has largely evolved from George Romero’s ‘Night of the Living Dead’, and is now an amazingly popular movie genre.  Many zombie movies, such as with the ‘rage virus’ in 28 Days Later and its sequel, in I am Legend, or the TV series the Walking Dead, use viruses as the basis for zombie’ism, though there can be some controversy as to whether they really are about zombies (in I am Legend in particular, Richard Matheson’s original book and the movie Omega Man both considered the undead to be vampires, not zombies).  What were some questions we were asked? Are there any diseases that create zombies? Yes, according to Shaun there is a fungus that creates zombie ants. Which is worse – pandemic flu or the black death? Probably flu – with current antibiotics plague is treatable but vaccination against pandemic flu may not be fast enough. Are there any diseases that together could cause humans to behave like zombies? None that do it all (thankfully!) but rabies can induce behaviour changes and is transmitted by biting, while prion diseases (e.g. mad cow disease) impair motor control. Toxoplasmosis can cause rats to attack cats (apparently; I haven’t actually checked this one out). Why don’t zombies eat other zombies? We couldn’t answer that one – Katie Hampson provided the (now obvious) answer that its evolutionary selection – a zombie biting another zombie doesn’t help the virus survive! All in all, we had a really fun time with it, and the audience was excellent – many thanks to Zara Gladman and Deborah McNeill for organising it, and for Dr. Ian Smith of ZITS (the Zombie Institute for Theoretical Studies), who provided the excellent and informative introductory lecture before our Q&A.

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Caroline Millins (L) and Sej Modha (R) manning the Boyd Orr Centre stand and wearing their stylish Boyd Orr Centre T-shirts.

Last Sunday, the Boyd Orr Centre manned a display at the Science Sunday event, held in the Gilbert Scott Building. Many thanks to Sej Modha for working tirelessly to make it happen (together with Cat O’Connor who, despite a busy job fighting zoonoses at the HPA, provided support based on her efforts with the first Boyd Orr stand from last year) with help from Minnie Parmiter both in setting up and on the day, as well as stand volunteers Caroline Millins, Natalie Hutchinson, Michael Deason, Joaquin Prada, Joseph Crisp and Prof. Mike Stear. From playing the ‘sneeze game‘ to answering quiz questions about how Scotland would handle an infectious disease outbreak, we had a lot of interesting and interested visitors, including a knowledgeable 3 year old who knows what a rhinovirus is. EPIC (the Scottish Centre of Expertise for Animal Disease Outbreaks) and the Wellcome Trust provided some funding, including the prizes for the contests (the much coveted Boyd Orr Centre mugs for adults, soft toy viruses, bacteria and parasites for the kids). A series of posters illustrated our work, including a zombieSciencePoster by Jess Enright linking zombie night to our display. In quiet moments, there was also a chance to look around; the other stands at the Science Festival were excellent (though not as good as ours of course!). There was a chance to handle replica stone axes and play with a human skull. Visitors had a chance to use forensic science tools to find out ‘who dunnit?, learning about invasive species in Scotland, and race robots through mazes. Will we be back next year? Absolutely, and hopefully you will be there too.

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The Wellcome Trust, Depression, AT-AT’s and human locomotion

Sitting in Heathrow airport, just coming back from a meeting at the Wellcome Trust, which has been generous enough to funded my research over two fellowships and ten years. These meetings are designed to bring their funded fellows and investigators together. As the elements of the research I do (mathematical models, livestock diseases, social networks and infectious disease dynamics) each individually lie a bit on the edge of what the Trust funds, you can imagine that the combination of elements means I often feel slightly isolated in these meetings. Having said that, they do illustrate the diverse range of research funded by Wellcome, and you sometimes get a chance to see some really interesting stuff. We aren’t supposed to talk directly about the research we saw, as the intention is to have a free environment to discuss ongoing work. I can tell you about a couple of interesting people I met: Mark Williams is a clinical psychology professor from Oxford who works on depression and ways of alleviating it; one of the background points he made was that the proportion of years of work lost to depression, compared to other causes is very similar (and very high) across both developing and highly industrialised countries. I also met Jim Usherwood from the Royal Veterinary College, who works on various aspects of the mechanics of motion; he is very good at using lateral examples to illustrate his points, for example demonstrating how the movement of AT-AT’s atatin The Empire Strikes Back is unlike real motion; even crawling babies have moments of unstability as they wobble from stable point to stable point; in contrast, because the AT-AT scenes were done via the old magic of stop motion photography (rest in peace, Ray Harryhausen) and before CGI dominated movie-making, each position had to be stable. It really reminded me of how useful pop culture imagery can be to get your ideas across to your audience. Its all about connecting, without condescending. And maybe I’m not so isolated at Wellcome after all.