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 (retired) 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 www.bbc.co.uk)

“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.

 

Back to the badgers – the evidence base for bovine Tuberculosis control policies in England and Wales

Wildlife reservoirs for disease make control difficult.

Badgers are just one of many wildlife reservoirs for bovine Tuberculosis around the world.

So the badgers are back in the news, along with cats, of course. The Secretary of State for the Environment, Food and Rural Affairs, Owen Paterson, presented a government statement on strategy for eradication of bovine TB. In brief, his statement acknowledged the severity of the problem facing farmers, the rapid increase in the number of herds affected, the cost of the epidemic as well as the issues associated with any single control measure, none of which present a ‘magic bullet’ solution. As such, multiple measures are being pursued simultaneously, including cattle vaccination trials following EFSA recommendations that are scheduled to start in the near future, badger vaccination already being tested in the field, and programmes to enhance on-farm biosecurity. And of course badger culling.

Mr. Paterson’s statement pointed out that, in countries with a serious wildlife problem, reduction in cattle disease has followed from comprehensive approaches tackling the disease in both the wildlife reservoir and cattle, and indeed, it is likely that such an approach in England and Wales provides the best chance of achieving control. Proper consideration much also be given to the social, cultural and economic factors influencing the epidemic, including both the farming community and the wider public, and with a fuller appreciation of the ecological context of any single control measure, or suite of measures. An intriguing aspect of the problem is the role of legislation governing international trade that represents a considerable cost at the national level, was largely developed in the context of countries seeking eradication when human cases were a greater issue, but now many decades old. How this legislation will stand up in the face of increased evidence of wildlife problems across multiple EU nations including Spain and France and of tuberculosis caused by Mycobacterium caprae in Austria remains to be seen.

Consideration of bovine TB control in England and Wales must consider many inter-related factors

Consideration of bovine TB control in England and Wales must consider many inter-related factors

What makes the control of the problem particularly difficult in England and Wales is the now well accepted evidence that badger culling has the potential to result in both a positive and negative impact on cattle disease. To my knowledge, this makes it considerably different from known wildlife problems in other countries such as New Zealand or for that matter, in the Republic of Ireland, where no such perturbation problem has been observed. While well studied in the context of the randomised badger culling trial or RBCT, whether or not culling results in a positive or negate outcome is likely to be dependent in a complex and as yet poorly understood way on the underlying badger density, existing human interventions (illicit culling, sett disturbance, etc.), the as yet poorly quantified relationship between badger infection prevalence and cattle disease, and the impact of the disease in cattle on the badger population, and possibly other factors. These complex factors mean that any attempt to confidently extrapolate the results of the RBCT at a national scale are at best problematic.

So is there a solution? The statement by Mr. Paterson suggested control of bTB by 2038 would be viewed as success. In order to achieve even such a long term goal, continued investment in not just tackling the problem but understanding it is essential. Policy of course cannot wait for science to come up with definitive answers, but must be sufficiently nimble to respond when scientific evidence changes – the badgers may not have moved the goal posts, but not knowing where those posts are makes scoring that goal even more difficult.

Return of the blog – Boyd Orr Centre members at Buckingham Palace

Dear All,

Neither gone nor forgotten, just buried under a mountain of obligations. Sorry for the gap in blog posts, hope that these will resume with greater regularity as I finally find a bit of clear water through the myriad of responsibilities that too sadly mirror what many of my friends and colleagues experience.

Last Thursday, a group of ten members of the University of Glasgow attended the awards ceremony for the Queen’s Anniversary Prize at Buckingham Palace. As well as our Chancellor (Prof. Sir Kenneth Calman) and Vice-Chancellor (Prof. Anton Muscatelli), were myself, two key founding members of the Centre (Barb Mable and Richard Reeve), as well as five younger scientists who represent the engine of our research, the postdoctoral scientists (Richard Orton and Sunny Townsend) and Ph.D. students (Minnie Parmiter, Joaquin Prada, and Caroline Millins). After gathering in front of the Palace we were led in for the main ceremony where two individuals (for Glasgow, Anton Muscatelli and myself) received the award and a scroll from the Queen and Prince Phillip. I’m not exactly a monarchist, but neither am I a republican, and I do have a healthy respect for the role that the titular head of state has to play, and the usefulness (indeed importance) of separating out the ceremonial function of the head of state from the operational requirements of its “chief executive”. Plus I’m a sucker for a bit of history (so maybe I am a monarchist, of sorts). Monarchist or republican, there is no denying the grandeur one is presented with when entering Buckingham Palace, or the impact of being ushered into the room in which we received the award. Afterwards there was an informal meet and greet with the Queen and all the members of our group (where our good Dr. Orton somehow managed to promote the admittedly excellent work at Imperial College on SARS, rather than his own equally excellent work on FMD virus :) ). The Queen seemed particularly impressed at the breadth of research going on, with every person she was introduced to working on yet another disease with real impact on human and animal health. Remarkably the Palace made what was a very formal occasion quite relaxed, a trick that takes real skill. Following the reception, the group of Boyd Orr Centre members gathered outside the palace for a few photos. It was a decidedly enjoyable day, one that was made so by the fact that it occurred amongst colleagues and friends.

Boyd Orr Centre members at Buckingham Palace for the Queen's Anniversary Prize Ceremony. From L to R, Joaquin Prada, Dan Haydon, Caroline Millins, Minnie Parmiter, Barb Mable, Richard Reeve, Rowland Kao, Sarah Cleaveland, Richard Orton, Sunny Townsend, Tiziana Lembo, and Louise Matthews.

Boyd Orr Centre members at Buckingham Palace for the Queen’s Anniversary Prize Ceremony. From L to R, Joaquin Prada, Dan Haydon, Caroline Millins, Minnie Parmieter, Barb Mable, Richard Reeve, Rowland Kao, Sarah Cleaveland, Richard Orton, Sunny Townsend, Tiziana Lembo, and Louise Matthews.

As noted in the last blog post, the QAP award is given for both excellence of research but also the impact that research has on the real world, and this is a combination that the Boyd Orr Centre excels at. The brief citation read out as we entered to receive the prize said:

The Boyd Orr Centre is recognized for the scientific excellence and
global impact of its work on infectious diseases to benefit the health
and livelihoods of agricultural communities and wildlife conservation.

This work goes on through the combined efforts of all of its members, from the least experienced student or technician, to the increasingly grey heads of those who lead it. A small group and only recently formed, its impact has been remarkable and it is a group that I am very proud to be a part of. This blog  also seems a very good place to ‘officially’ announce my stepping down as Director of the Centre, effective as of now. The award of the prize is indeed an excellent book end to my tenure. Its been a fantastic experience, but I’ve been acting as Director of the Centre for long enough and its time for others to inject some new energy into it. One of the things I’d like to see more of are initiatives that improve the linkages across Garscube and Gilmorehill. Considering the difficulties that even such small distances present for communication and collaboration, I don’t think we do too badly but, like marriages, is something that in my view should not be taken for granted, always needs to be worked on, and could always be done better. One way to do so is by expanding the responsibilities – being based largely at Garscube I often feel like I don’t know enough about what happens at Gilmorehill and thus some ‘directorial’ responsibilities across both campuses would have some benefits. Coherent with a consensus of the principal investigators of the Centre, a new leadership based on a co-Directorship between Richard Reeve and Louise Matthews will provide tangible, novel benefits to the Centre. They are both founding members and have been committed to the Boyd Orr Centre from the start, and thus if a joint Directorship is going to work they are in a good place to make it so as Louise (based at Garscube) and Richard (at Gilmorehill) both already expend a considerable effort keeping up an active presence in both campuses. While I shall continue to work on behalf of the Centre (including a commitment to continue this blog), I and others are confident that this new co-directorship will bring the Centre forward in a substantial way.