Wednesday, 12 December 2018

New neurons: astrocytes, gene therapy and the public fear of brain modification

Ever since the first cyberpunk novels of the early 1980s - and the massive increase of public awareness in the genre thanks to Hollywood - the idea of artificially-enhanced humans has been a topic of intense discussion. Either via direct augmentation of the brain or the development of a brain-computer interface (BCI), the notion of Homo superior has been associated with a dystopian near-future that owes much to Aldous Huxley's Brave New World. After reading about current research into repairing damaged areas of the brain and spinal cord, I thought it would be good to examine this darkly-tinged area.

Back in 2009 I posted about how science fiction has to some extent been confused with science fact, which coupled with the fairly appalling quality of much mainstream media coverage of science stories, has led to public fear where none is necessary and a lack of concern where there should be heaps. When it comes to anything suggestive of enhancing the mind, many people immediately fall back on pessimistic fictional examples, from Frankenstein to Star Trek's the Borg. This use of anti-scientific material in the consideration of real-world STEM is not an optimal response, to say the least.

Rather than working to augment normal humans, real research projects on the brain are usually funded on the basis that they will generate improved medical techniques for individuals with brain or spinal cord injuries. However, a combination of the fictional tropes mentioned above and the plethora of internet-disseminated conspiracy theories, usually concerning alleged secret military projects, have caused the public to concentrate on entirely the wrong aspects.

The most recent material I have read concerning cutting-edge work on the brain covers three teams' use of astrocytes to repair damaged areas. This is an alternative to converting induced pluripotent stem cells (iPSCs) to nerve cells, which has shown promise for many other types of cell. Astrocytes are amazing things, able to connect with several million synapses. Apparently Einstein's brain had far more of them than usual in the region connected with mathematical thinking. The big question would be whether this accumulation was due to nature or nurture, the latter being the high level of exercise Einstein demanded of this region of his brain.

Astrocyte research for brain and spinal cord repair has been ongoing since the 1990s, in order to discover if they can be reprogrammed as functional replacements for lost neurons without any side effects. To this end, mice have been deliberately brain-damaged and then attempts made to repair that damage via converted astrocytes. The intention is to study if stroke victims could be cured via this method, although there are hopes that eventually it may also be a solution for Parkinson's disease, Alzheimer's and even ALS (motor neurone disease). The conversion from astrocyte to neuron is courtesy of a virus that introduces the relevant DNA, although none of the research has as yet proven that the converted cells are fully functional neurons.

Therefore, it would seem we are some decades away from claiming that genetic manipulation can cure brain-impairing diseases. But geneticists must share some of the blame for giving the public the wrong impression. The hyperbole surrounding the Human Genome Project gave both public and medical workers a false sense of optimism regarding the outcome of the genome mapping. In the late 1990s, a pioneer gene therapist predicted that by 2020 virtually every disease would include gene therapy as part of the treatment. We are only just over a year short of this date, but most research is still in first phase trial - and only concern diseases that don't have a conventional cure. It turned out that the mapping was just the simplest stage of a multi-part programme to understand the complexities of which genes code for which disorders.

Meanwhile, gene expression in the form of epigenetics has inspired a large and extremely lucrative wave of pseudo-scientific quackery that belongs in the same genre as homeopathy, crystal healing and all the other New Age flim-flam that uses real scientific terminology to part the gullible from their cash. The poor standard of science education outside of schools (and in many regions, probably within them too) has led to the belief that changing your lifestyle can fix genetic defects or affect cures of serious brain-based illnesses.

Alas, although gene expression can be affected by environmental influences, we are ultimately at the mercy of what we inherited from our parents. Until the astrocyte research has been verified, or a stem cell solution found, the terrible truth is that the victims of strokes and other brain-based maladies must rely upon established medical treatments.

This isn't to say that we may in some cases be able to reduce or postpone the risk with a better lifestyle; diet and exercise (of both the body and brain) are clearly important, but they won't work miracles. We need to wait for the outcome of the current research into astrocytes and iPSCs to find out if the human brain can be repaired after devastating attacks from within or without. Somehow I doubt that Homo superior is waiting round the corner, ready to take over the world from us unenhanced humans…

Thursday, 29 November 2018

Setting low standards: bovine TB, badger culls and political pressure on science

If there's a single type of news story that's almost guaranteed to generate widespread sympathy across the British Isles it is one concerning the mistreatment of animals. Over the past five years, badger culls aimed at preventing the spread of bovine tuberculosis have generated much public debate, with opinions varying from those who think badgers are completely innocent victims to some who want to see the species eradicated anywhere domestic cattle are kept. Since the number of farmed cattle in the British Isles is close to ten million, this presumably means the no-badger zone is rather on the large size!

When debates concerning agriculture start to get overheated it usually reduces to a battleground between farmers and so-called townies, with mudslinging and emotive slogans taking precedence over the facts. In this particular case the badgers have an unusual ally in the form of rock musician and amateur astronomer Brian May, who has received much of the criticism usually reserved for tree huggers, animal rights' campaigners and environmentalist types in general.

As I've mentioned before, a species often receives support based more on its cuteness factor than anything else (I consider the irascible and curmudgeonly Mr Badger in Wind in the Willows as a fairly accurate representation of the true critter) so the farming community has seen fit to complain that ignorant, urban-based activists are unaware of the challenges Mother Nature throws at the agricultural sector.

Such stereotyping and reductionism does nothing to alleviate the issue, which other nations face in similar circumstances. New Zealand, for example, has a rapidly escalating battle over the use of 1080 to poison introduced predators. Even though many environmental organisations such as Forest and Bird proclaim it the most effective method the debate is far from settled, with the anti-1080 movement using emotive pleas in their campaign that at times combines hysteria and aggression in equal measure.

The UK's Department for Environment, Food and Rural Affairs (Defra) has funded an independent scientific review from Oxford University as to the efficacy of the cull, resulting in popular press reports that the evidence does not support it. Indeed, the high ratio of dead badgers in return for a 'modest' reduction in the disease has been given as a key reason to stop the culls. This might appear to be a nod towards animal welfare, until you read that other issues include their cost and complexity and a desire for the Government to gain in the opinion polls. A key scientific argument against the effectiveness of the culls come from rural vets, who support data suggesting even at maximum success, the reduction in new cases of cattle TB would only be 12-16% - in exchange for a culling of over 70% of local badger populations.

So what does this example say about humanity's attitude towards the environment and the use of science to reinforce that attitude? In terms of numbers of individuals, humans and our domesticated species (both livestock and household pets) vastly outnumber the inhabitants of the wilderness. The once diverse ecosystem has been vastly reduced, predominantly in the temperate regions suitable for intensive farming. But in return for this largely irreversible loss we have gained all-year round access to an incredible variety of inexpensive foodstuffs; clearly, our gastronomic gains take precedence over the wider ecosystem.

In the case of wild badgers as disease vectors, it isn't just the livelihood of individual farmers that are at stake. The European Union's threat to impose trade sanctions on the UK, such as a ban on the export of live cattle, must be considered as a potential loss at the national level. Little wonder then that the British Government implemented the cull after what has been termed 'a randomised trial period' or more impressively, 'over fifteen years of intensive research.' Even so, was the result of all this enough to justify the finality of the chosen method - or was the scientific data manipulated in the name of political expediency?

One telling example of how the culling might have been ordered due to political pressure rather than any scientific smarts was the use of evidence from other nations that are successfully controlling bovine TB. Australia and New Zealand have been held up as examples of how control of the disease vectors can vastly reduce or indeed remove the problem altogether. Except of course that those two nations don't have any badgers; it is the possum, a semi-arboreal marsupial, that is responsible for the spread of tuberculosis there. It seems to me that two creatures from such vastly different lineages should never have been seen as workable comparisons; the natural world just doesn't fall into the neat categories we would like it to. As a matter of fact, the UK Government has partly blamed the lack of success on the badgers themselves for failing to follow predicted behaviour. In 2013 the then Environment Secretary Owen Paterson stated that the animals had cheated by 'moving the goal posts'!

The Oxford University research reports that far more cases of bovine TB result from transmission between cattle rather than directly from badgers, explaining that farmers are not following Defra guidelines to minimise the spread. Even Defra itself states that there has been not nearly enough implementation of badger-proof feed storage and fencing, while its chief scientific adviser, Ian Boyd, has been quoted as admitting that badgers may only be responsible for as little as 6% of bovine TB! This incidentally comes from the man who in 2013 wanted complete control over what scientific results were reported to Government ministers, presumably so as to maintain a clear-cut, pro-STEM political lobby. Hmm, methinks I smell something fishy...

What can we conclude from these shenanigans? If scientific research doesn't provide reliable support for a method, shouldn't the mistake be admitted and a new approach implemented? Science is the sole invention of humanity with built-in error correction but when it gets embroiled in politics, unabashed use of political tools such as spin can prove fatal. In this particular case, the fatalities in the short term were the badgers. In the long run, an unbalanced ecosystem would have resulted. And we all know which species likes to think of itself as the pinnacle of creation. There's enough denial of scientific results as it is, without distortion for the sake of political convenience. Let's hope Defra has the courage to own up and try other tactics against the wily badger.