Glancing through the health headlines for news of any new developments in genomics and biomedical science this week, I saw little to get excited about. This was not particularly surprising - there were plenty of promising research findings published last month in this area. Whenever I see something about biomedicine reported in the news, my first thought is to wonder what it is all about and what the implications might be; my second, to wonder whether it is presented in such a way as to distort either or both of these things. Because sometimes it is seriously off-centre; blood pressure can seriously rise in our offices when, for example, a tiny preliminary study is reported with as much weight and gravitas as a massive long-term, international, scientifically rigorous one. Or when the potential implications of unconfirmed findings are extrapolated beyond the bounds of common reason (grr!).

A commentary piece in the New England Journal of Medicine this month examine this very issue. In Communicating medical news - pitfalls of health care journalism. The author raises the issue that reporters of news relevant to healthcare inevitably “deliver public health messages that can influence the behavior of clinicians and patients”. She gives some US examples; in the UK we need only recall the furore over the MMR vaccine raised by a single speculative paper in the Lancet proposing (though not in any way demonstrating) a possible link between vaccination and autism. The alarmist nature of reporting surrounding this paper led to massive public concern and a significant drop in uptake of the vaccine - and now we are seeing increased rates of measles infections as a result.

It is tempting to blame all this sort of thing on either the scientists, for over-hyping their own work in the first place, or on the journalists, for departing from measured reporting in favour of sensationalism. The author of this particular commentary concludes that journalists have a responsibility to adhere to higher standards of accuracy and balance when their reporting may influence patients or doctors, calling also for researchers to support these efforts. However, to a certain extent researchers are obliged to, if not over-hype, then at least strongly promote their own work; faint heart never won fair funding, in this respect. And journalists, whilst having an understandable preference for stories likely to interest the public, are often extremely skilled at interpreting and communicating new scientific findings for a general audience. However, it is not journalists but editors that have the final say over what goes out in final reports. So perhaps we should blame them?

I suspect the real problem is complex and goes deeper than merely a public lack of interest in measured, balanced reporting and the necessity of news vehicles to deliver material of public interest. The whole concept of what constitutes reliable evidence with respect to science and medicine is foreign to most, who seem to think it is all about sudden inspiration as opposed to long-term perspiration (perhaps efforts directed towards increasing public understanding of science should address this more). But in any case, an evidence-based approach to reporting just wouldn’t be as exciting; human nature being what it is, this may be an issue that we never manage to resolve.

There hasn’t been too much to report on recently in terms of activity of the PHG Foundation - not because there hasn’t been any, but because I have been a bit out of the loop thanks to a festive bout of viral grimness. Although I can officially reveal that the staff took a Christmas lunch break in the Cambridge branch of Wagamama (at their personal and individual expense, I should perhaps add). Things are warming up nicely for 2009, with the launch of some major reports quite a few national and international conferences where we shall have a presence, and some rounds of musical offices as we rearrange ourselves with the advent of new staff members..

So, what has December brought, besides a combination of seasonal cheer and seasonal infectious diseases? One thing that I have observed is a large number of new papers on genetic influences on in obesity and some related clinical measures, such as cholesterol levels. Obesity is of course a serious public health issue in the UK, a common topic in the news, and very relevant at a time of year that many of us are eating more than we should (actually, I always eat more than I should, but you know what I mean).

One interesting review paper that has caught my eye is called Is Obesity Our Genetic Legacy? by Alex Blakemore (Imperial College London) and Philippe Froguel (Pasteur institute, Lille). And the answer seems to be yes, to some extent it really is. The authors observe that rapid progress is being made in understanding some of the extremely complex genetic factors involved in the surprisingly high total genetic influence on obesity, estimated at around 70%. Despite being fairly well versed in genetics and health, I had not realised that genetics was thought to exert such a significant effect on weight regulation, although of course I knew that (as with any common complex condition), both genetic and environmental factors would be at play. Apparently obesity really may be, to some extent, our genetic heritage, although a genetic propensity towards disease does not mean that you will inevitably develop it.

The upshot of recent scientific progress in this area seems to be an increasing realisation that genetic information might one day inform and refine weight management for individuals, and perhaps also lead to some new therapeutic options; any additional measures to improve medical and public health intervention against obesity would be of great value, since attempting to modify the environment (fewer pies, more exercise) is, sadly, not always effective. Perhaps one day, medicine might offer me something that would make me voluntarily pass up on the pies. But for now, my main protection against moving from my current (shall we say, generously endowed) figure and complete sphericalness? On yer bike - literally. At least that’s feasible in Cambridge.

Now, colalife has no connection with genomics, and only an indirect connection with biomedical science, but on the other hand it has a great deal to do with innovation and taking good ideas forward, which we are very much in favour of at the PHG Foundation. And it certainly relates to population health. Basically, David Barker used to work in Africa and was struck by the fact that however remote his location, there always seemed to be somewhere that could supply him with a drink of Coca Cola. He was also struck by the alarming statistics on child mortality, whereby one in five children die before the age of five, many of them from treatable diarrhoeal diseases. And thus was born the idea “that Coca Cola use their distribution channels (which are amazing in developing countries) to distribute rehydration salts to the people that need them desperately” (see colalife website).

Now, we have no involvement in this campaign (unless watching their advert on YouTube whilst in the office counts as involvement, I suppose - all in the interests of engaging with Web 2.0, you understand), but it illuminates how simple innovations can potentially have major impacts. It is often assumed that public health genomics (and indeed genomics in general) has little to offer developing countries, where the outstanding need is more obviously for basic sanitation, healthcare and medicines. But whilst these things are badly needed, better understanding of genetics and disease can potentially benefit populations all over the world. For one thing, it can explain the underlying pathological disease mechanisms and allow the development of new treatments and preventative measures. Differences in genetic susceptibility and resistance to diseases between individuals from different ethnic groups are also of particular interest to researchers. But as well as lofty ambitions to map all this variation, there are some much more immediate common-sense approaches, too. For example, sharing Western knowledge about inherited disease with people and groups who understand the health needs and priorities of different countries can help shape basic services. Also, some of the new diagnostic tools and tests in development could actually be cheaper and/or more practical for use in less developed nations; for example, non-invasive prenatal testing that required only blood samples from the mother could be much easier to deliver to remote areas.

Should the benefits of human genome research be extended to everyone? You bet. Does this mean everyone will have to have their full genome sequenced before they can benefit? Fortunately not.

Multiple sclerosis or MS is not a disease that I have worked on, or indeed learned much about since studying pathology as a student quite a long time ago (Long in terms of biomedical research, anyway. OK then, it was 12 years ago), and so I was brought up to speed, in very general terms, with progress in understanding the molecular basis of the disease. Professor Compston and colleague Dr Alasdair Coles have also just produced a handy review on MS [Compston A, Coles A (2008) Lancet. 372(9648):1502-17], or for those who want to know more but in simpler terms, the UK MS society website has some information.

The main focus of the lecture was the story of Campath1 /alemtuzumab, the first humanised monoclonal antibody produced as a therapeutic agent (ie. treatment). Although it was originally produced with quite a different disease in mind, Professor Compston and colleagues reasoned that, since the neuronal damage in MS was the result of an inappropriate immune reaction (as with other forms of autoimmune disease), perhaps a drug that attacked immune cells might be an effective treatment. Some people with advanced forms of the disease received it, and showed significant initial improvement but didn’t do well longer term.

However, the researchers then tried the treatment in people in the early stages of the disease - when the insulating myelin sheath that normally protects neuronal cells and allows rapid transmission of impulses was being lost, but before the neurons themselves had been destroyed. It had some very grave side-effects, so that the trial of the treatment was truncated, with most patients not receiving the third planned administration of alemtuzumab. However, looking at the final results of the study it was shown that the patients who had received alemtuzumab had done much better than the control group who received standard therapy; not only had they had far fewer symptomatic attacks, but they generally also showed that their overall condition had improved over the course of the trial.

What struck me particularly was that the patients in this trial - whose enthusiastic personal endorsements of the striking benefits to their quality of life from the treatment could not fail to move even those of us for whom the key word in ‘fund-raising lecture and dinner’ had been ‘dinner’ - knew the risks of treatment. Quite a substantial proportion developed other types of autoimmunity and some, cancer; one patient died. But the adverse impact of MS on some patients before entering the trial had been very severe, and they had clearly thought it was worth the risk. Makes you think about the ethics of regulation of experimental treatments, really. I suppose the same patients would have been less enthusiastic had the treatment turned out to be unsuccessful. But it does seem to me that a certain degree of risk and bravery on the part of patients, clinicians, funders and regulators may be appropriate. Nothing ventured, nothing gained?

And if you think I should have said more about the genetics of susceptibility to MS, other researchers have just found the first genetic variant associated with disease risk to be expressed specifically in neurons, within the KIF1B gene: [Aulchenko YS et al. (2008) Nat Genet. Nov 9, epub ahead of print]. Gene variants previously associated with disease susceptibility have been involved in immune function.

Many PHG Foundation staff are also members of the Society for Genomics, Policy and Population Health (SGPPH), and attended the third annual general meeting (AGM) in London yesterday. Attendees came from a wide range of different backgrounds, from clinicians and laboratory scientists through to policy-makers and health commissioners, and the programme included perspectives on different forms of screening. Dr Jim Bonham, who spoke about newborn bloodspot screening, gave a very interesting historical background to the introduction of the practice. This included the story of how the genetic disorder phenylketonuria (PKU) was discovered in the twentieth century.

For those who have never heard of this recessively inherited genetic disorder, it prevents an enzyme involved in the normal metabolism of the amino acid phenylalanine from functioning, leading to gradual irreversible mental retardation due to the accumulation of phenylalanine. First characterised in 1934 by Norwegian doctor Asbjorn Folling - thanks in no small part to the efforts of the mother of two affected children - an effective treatment was determined by German doctor Horst Bickel in the 1950s. It was particularly diverting to hear how he not only placed an affected child (17-month old Sheila Jones) on a phenylalanine-free diet as an experimental treatment, but also checked his hypothesis by surreptitiously reintroducing a source of phenylalanine, leading poor Mrs Jones to return and report in distress that the child had ceased to make progress. Medical ethics has come on a long way since then!

It is sobering to reflect that this highly unethical experiment confirmed that careful restriction of dietary phenylalanine intake during infancy and childhood can prevent the mental retardation otherwise associated with PKU…Similarly, English doctor Edward Jenner is renowned for his discovery that vaccination with a related but relatively innocuous virus causing the disease cowpox was protective against the devastating disease smallpox. This began a process that eventually led to the development of a safe and effective vaccine, and the official global eradication of smallpox in 1980, a good day for public health. However, we would now consider Jenner’s method of testing his hypothesis (injecting a small boy with cowpox and subsequently exposing him to smallpox!) to be, in ethical terms, completely out of order.

Anyway, today in most developed countries, small bloodspot samples from newborn babies are screened for selected forms of genetic disease for which early diagnosis can prevent or ameliorate mortality (death) or morbidity (disease and disability). And yet ethical questions remain, some of which came up at the SGPPH meeting, based around the capacity of newborn screening to enact great good in terms of infant health, but potentially also some harm. For example, the issue of requiring informed parental consent for a procedure intended to benefit an infant; whose rights should be paramount here, those of the child, or of the parent? And is it ethical to test for conditions for which there is no effective treatment? There are arguments in favour of prompt diagnosis, if only to spare a child from extensive clinical investigations and inform the family in time for them to consider reproductive options for future children. Some countries, notably the US, include many more conditions on their panel of diseases for newborn screening than the UK does, but this could potentially lead to situations where the family know what is wrong with the child and a treatment exists - but is financially unaffordable.

On the whole, my own preference is for a society where we do give appropriate consideration to ethical issues in medicine; indeed, public health genomics emphasises the need for responsible applications of genomic knowledge to improve health. But I have to admit, it makes medical research and practice a whole lot more problematic.

The meeting attracted a much broader set of delegates than a purely scientific conference; advertised as appealing to “policy makers, academic researchers, industry, media and NGO representatives and citizens’ groups”, it was reported to be “full of social scientists”. So, what is it that interests social scientists in the area of genomics? Speed-dating: young researchers (anyone under 30, I would guess) were invited to participate in a special speed-dating networking exercise. Dr Sowmiya Moorthie reported having met a good mixture of researchers from all sorts of disciplines, not only the social sciences but also politics and international development, and they were found to have rather more social skills than your average scientist (not all that difficult).

For those to whom the social sciences are relatively unknown, try the illuminating explanation of What Social Scientists Do provided by the ESRC; it is, apparently, a “hectic but fulfilling” life! They define social science as the study of society and the manner in which people behave and impact on the world around us. More practically, it encompasses topics including sociology, psychology, political science and economics. More to the point for those of us with biological science backgrounds, it does not involve working with biohazardous materials or radioactivity, so that it is not incompatible with a tendency to suck your pen (really not a good idea in a laboratory). In fact, for any lab rats who are interested in science policy, regulation or related areas and looking for a career where they could drink coffee at their desk without violating health and safety regulations, you could do worse. Actually understanding the science is essential for a proper consideration of impact on society, and this really is a lot easier if you’ve done it.

For future opportunities to consider some of the social implications of genomics, coming up soon on 6^th November is the annual general meeting of the Society for Genomics, Policy and Population Health (SGPPH), where the PHG Foundation will again be well represented. This year’s topic is Genetic Screening: New Opportunities, New Challenges, New Attitudes, when we can expect to hear from speakers including Mark Henderson (Science editor of The Times and a serious contender with Ben Goldacre for the accolade Our Favourite Journalist) who will be speaking on Whole population genetic screening: fact or fiction? The SGPPH is another group that brings together geneticists and public health experts with lawyers, philosophers, social scientists and policy makers. Although as far as I am aware, it has yet to go into speed-dating.

Don’t get us wrong, we are not anti-science journalist; why, some of our best friends are science journalists, and they are often well informed (especially if they talk to us). True, not all that many are from a medical or scientific background originally (though Ben Goldacre himself is a practising doctor), but that isn’t a barrier to effective science journalism. Indeed, it may actively help in translating advances into terms that people without science training can easily comprehend. However, editors, it would seem - who generally don’t come from science backgrounds - are not too concerned with what is shown by reliable evidence to be true, but are very interested indeed by what makes good headlines. So, for example, the enduring furore over the MMR vaccine sparked by Andrew Wakefield’s highly questionable paper in the Lancet scored poorly in terms of supporting evidence, but highly in terms of provoking public concern. Similarly the assertion that vitamin C is superior to azathioprine (AZT) for the treatment of HIV infections (it isn’t).

Evidence, whilst of fundamental importance to scientists, is a concept that seems to be poorly understood in general. The bottom line is that all results are not equal; in fact they are very far from it. Any fool can conduct an experiment or gather a small series of cases and advance it as ‘evidence’ in support of a theory, but real evidence only comes from rigorous studies with reliable and reproducible results. These tend to include a selection of the following: independent studies, replicated findings, large numbers, good experimental design, respected scientists (with real and relevant qualifications - but don’t get me, or Ben Goldacre, started on that one…), and peer-reviewed literature. Contrast this with some bloke with a degree he bought over the internet doing dodgy experiments in his garden shed; he may be on to something, but it would be unwise to accept his theories without additional evidence.

The public can be seriously misled by reporting of science that fails to consider the quality of its sources. This is why consulting reputable (as opposed to self-styled) experts is always wise. Our take-home message today? We like evidence-based reporting, as well as evidence-based medicine. Oh, and Ben Goldacre.

Discussion apparently ranged from addressing practical issues such as how best to help people to make challenging choices or to increase awareness of genetics in health care, to philosophical questions on what it is to be human (something your average scientist or policy-maker hasn’t always considered in great detail, I would say).

Dr Moorthie, who is one of the more recent additions to the PHG Foundation staff, was struck by the requirements for getting promising biomedical innovations into practice in the health service, ranging from demonstration that the new technology is actually beneficial, to consideration of how to regulate it and to address issues it may raise with respect to societal and individual moral and ethical beliefs.

Overall, she reported that it had been a “very enlightening day, and a great way to meet lots of people from a wide range of societies and learn about inherited disorders I hadn’t known about before, how people are affected by them and how biomedical research can be of benefit to them”. Unfortunately, she also had a bad experience with a meat-based sandwich masquerading as vegetarian; but - as with engaging with ethical and social issues relating to genetics and health - we sometimes just have to step outside our comfort zones.

There has been a lot of media coverage about a new and safer form of antenatal testing for Down Syndrome this week. As devoted readers of the web pages about our work and / or our wonderful Genomics and Policy news will be aware, we have a major project in this area so we really do know what we’re talking about on this one.

What is all this about safer testing then? At present, diagnosis of genetic or chromosomal disease in an unborn fetus generally requires an invasive test (think big needles) to sample fetal cells from the placenta or the amniotic fluid that surrounds the fetus; DNA from these cells is then analysed in the laboratory. Not only is the whole big needle thing not hugely appealing (and requires an expert to perform it), but it also causes miscarriage in 0.5-2% of cases. So women who know the fetus is at high risk of having a specific disease and want to know whether or not it is affected have a difficult decision to make. However, ‘non-invasive’ testing from a sample of the mother’s blood would carry no risk of miscarriage and therefore be a much better option, although I’m told that waiting for the test results is the worst part, and that wouldn’t change.

The latest media attention is because of new research from Stanford University in the US, with the publication of a promising new approach to diagnosing Down Syndrome and similar chromosomal disorders from maternal blood. But others around the world (including in the UK) are working on different techniques, and investigating alternative uses for the test, such as identifying mutations associated with rare genetic diseases.

This is a great example of how innovation could produce medical benefits. But before we all go and get pregnant and rush to our doctors asking for testing, a note of warning: it needs a lot more evaluation yet to see whether it is reliable enough to use in routine care, and to consider the potential implications of using a different type of testing. Fortunately, we have a whole team here that has been working with the right people (doctors, midwives, geneticists, patient advocates and so on) to suggest a sensible way forward. More on this with our project report in January 2009! And meanwhile, back to the grindstone…

A recent editorial in the journal Science calls for decisive action from the scientific community to boost public support and involvement for health research in the way that climate change became an issue of general public concern and interest (see A Populist Movement for Health?), so perhaps public involvement will become the ‘in’ thing. Not before time, either - I don’t think that the general public knows enough about biomedical research, and it would be great counter that through increasing involvement as well as educational efforts, which can risk giving the impression of Nasty Science Homework. But who better to involve in efforts to improve public health than the public? As the authors say: “In part, the science community is responsible because we have not effectively helped the public realize that without a higher national and international priority for basic research, a crisis in human health is not far off”.

The programme of talks at the CRI evening emphasised the importance of translational research in delivering improved health and the need for funding in this area - which fitted in perfectly with our own position of calling for more resources for the ‘end-stage’ of translation - not translational research or even health-services research, but policy development and implementation planning. Translation often comes across less compelling than the pushing-the-boundaries-of-knowledge basic research reported, but it is absolutely crucial for delivering the benefits of scientific research, which at the end of the day is what the public wants to see: quicker diagnosis, more effective treatment, and better health.

Cambridge is a great place for top-level research, so unsurprisingly there were some interesting talks and stands, including groups hoping to recruit public volunteers to take part in various clinical trials. But my personal feeling was that the obesity researchers who had a selection of cakes on their stand ought to be done for unreasonable enticement.