Blog

Communication and common sense

by philippa.brice

The office is very quiet this week as a lot of staff are away - some on holiday, some on business (for example, Programme Director Hilary Burton is attending a meeting of the Public Health Genomics European Network (PHGEN) in Istanbul, Turkey. However, I’m really not at all jealous, because I went to an Information Conference on Monday, along with out Information Manager Simon Leese. As well as finding out lots of interesting stuff about using Web 2.0 to stay connected with funky tools such as delicious (you’ll be seeing that on our website in the near future, for sure), this included a very engaging session from a nice bloke called David Barker on how the colalife campaign came into being.

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, risks and rewards

by philippa.brice

Last week several of us attended the annual fund-raising lecture and dinner at our local hospital, for which the PHG Foundation was a sponsor. This year’s Addenbrookes Annual lecture was given by Professor Alastair Compston, and titled Treating multiple sclerosis: a modern saga. One of the undeniable benefits of Cambridge is the constant proximity to cutting-edge research in medicine and the biomedical sciences (yes, I suppose in a few other things as well - but research involving hadron colliders and all that just isn’t as much fun, to my mind). PHG Foundation headquarters is five minutes stroll from the Cambridge University Hospitals NHS Trust site, which incorporates both Addenbrookes and a whole bunch of major research centres.

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.

Ethical issues and newborn screening

by philippa.brice

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.