Brain 2.0

It has been the dream of science fiction writers and losers of the genetic lottery for a century – that science would reinforce and rebuild our fragile brains, eradicating our weaknesses and pushing us closer to perfection. Now news of two scientific advances in quick succession has moved us a little closer to that dream.

The announcements concerned the creation of implants for patients with damaged nerve cells, or ‘neurons’, in the brain. One, on 16th November, referenced a pilot study in which neural stem cells were injected into the brain of a man who had suffered a stroke. In the other, announced on 3rd November, a microchip was implanted into the eye of a blind man suffering from retinal degeneration, partly restoring his vision. The tantalising preliminary findings from both pieces of research indicate key moments in the growing scientific effort to treat – and maybe even enhance – our brains using implant technology.

Neural stem cell injections

The stem cell research was the first part of Phase I of a Pilot Investigation of Stem Cells in Stroke (PISCES). Guildford company ReNeuron’s feasibility study aimed to find whether injection of neural stem cells into a patient’s brain can be carried out safely. The patient – a former lorry driver from Glasgow in his 60s – had suffered an ischaemic stroke, in which the blood supply to part of his brain had been cut off.

“As all theologians know, finding the Holy Grail involves a leap of faith”

Current stroke treatment can involve giving anti-clotting treatments to remove the blockage before all the damage has occurred. Until now once the neurons have died there is usually relatively little that can be done but if ReNeuron’s findings pan out the way they hope, then they may have come across a pathway towards the Holy Grail of compensating for the damaged cells by injecting the brain with new ones. But as all theologians (and Indiana Jones fans) know, finding the Holy Grail involves a leap of faith – in this case involving neural stem cells, a needle and a very brave Glaswegian.

There has been previous work in this area. Cell therapy already exists using the injection of normal cells and is used to treat leukemia amongst other illnesses. But this normally uses mature cells, for example from a bone marrow donor, and such cells do not normally have the ability to grow, repair and replicate. Stem cells are the undifferentiated precursor cells from which other cell types derive – they can grow and divide and, as such, can potentially help recovery from disability after brain damage.

The researchers involved emphasise that although they have made a leap, there is still a long way to go. This is a preliminary study to develop a technique, and the primary outcome of this study does not hinge solely on whether this one patient shows improvement. Digging further into the research it is clear that this isn’t a game of genetic tit-for-tat – replacing one-for-one the missing cells with new cells. Instead the new stem cells may help to establish some connections which could alleviate a patient’s disability.

Stem cell research also raises many potent ethical issues. The company in this collaborative research endeavour is the first to gain approval for stem cell-based clinical trials in the UK, and has developed techniques to develop a neural stem cell line called CTX. These cells originate from cells from a 12-week-old foetus aborted in California in 2003: the company says that all future cells could be taken from these extant cell banks which can simply be expanded. Although this will not dissolve the moral issue for some, it does for many: and given safety clearance from this first patient there are 11 more patients waiting to be a part of this clinical trial. It may take years before we know how well this treatment works. So it is important to stress not only the preliminary nature of these findings but also that this is another in a long line of ‘firsts’. The existence of the many other current research programmes, and the careful, step by step nature of this research, only adds to the excitement of what announcements may come next.

California in 2003: the company says that all future cells could be taken from these extant cell banks which can simply be expanded. Although this will not dissolve the moral issue for some, it does for many: and given safety clearance from this first patient there are 11 more patients waiting to be a part of this clinical trial. It may take years before we know how well this treatment works. So it is important to stress not only the preliminary nature of these findings but also that this is another in a long line of ‘firsts’. The existence of the many other current research programmes, and the careful, step by step nature of this research, only adds to the excitement of what announcements may come next.

Eye microchips

Amongst the myriad burgeoning developments in neuro-implant research, none is more exciting than the growing use of electronics. November 3rd saw the publication of a ‘proof of concept’ study where a microchip studded with hundreds of light detectors was implanted into the eye of a blind man to help him see again.

The study was published in the highly respected journal ‘Proceedings of the Royal Society B’. The ‘B’ stands for ‘Biological’ but the remarkable thing about this study was the coupling of the biological and the electronic. The paper told of a research consortium based in Tübingen, Germany, who are developing ways to treat a type of incurable blindness that affects millions worldwide. This form of blindness occurs due to degeneration of the photoreceptors that line the retina at the back of the eye – these are the neurons that detect the light that enters through the lens, and transduce that energy into an electrical signal for the brain to process. No receptors means no vision.

As part of a clinical pilot study, these scientists developed a microchip which can partly replace these missing receptors. The devices themselves do not look particularly impressive – a close-up looks a bit like a cross between a solar panel and a ZX Spectrum with a long cable running out of it – but the technical specifications are a revelation. The key point is the sheer number of light detectors – 1,500 separate elements, each measuring 72 micrometres across and each with its own titanium nitride electrode for stimulating the retina underneath. Each element even has its own individual amplifier. The whole gadget, properly termed a ‘microphotodiode array’ (MPDA), measures a few millimetres across, and was inserted under the retina during an operation and stuck down with silicone oil. This was done in three blind patients. A week after the operation, the patients were brought into the testing room, and the array was switched on.

Until that moment all three patients had been very blind for some years – with only some limited ability to report strong light/dark differences. They had no perception of shape and certainly no ability to read. But from the moment the experimenters went from the ‘Power OFF’ condition to ‘Power ON’, all three could perceive light mediated by the chip – they could see again – and this did not require training: these microchips were Plug ‘n’ Play.

Although all three patients showed some improvement, ‘Participant Two’ showed the best visual recovery. This may be because the surgeons put the implant in just the right place or because his retinal degeneration may have been less severe. Either way he was able to read large letters presented in front of him spelling out the words ‘LOVE’ and ‘MOUSE’ and his own first name – even spotting spelling mistakes the researchers had put in on purpose.

He could also recognise real objects, including a banana and a spoon. His vision was nowhere near fully restored – the letters he could read were about the size of a pen and held at arm’s length.

An additional detail of this study is particularly intriguing. There was an extra part of the device – a relatively simple 4 x 4 array of electrodes which were not activated by light, but could instead be controlled by the experimenters, who could activate this ‘direct stimulation test field’ at will. Using this much sparser array they could present dots of their own choosing which the participants could also see in the absence of any ‘real’ visual input.

“The living human brain is being adorned by biological and technological wizardry”

Participant Two could even report letters they typed out using the dots. The authors report in passing that the main MPDA chip was also sensitive to infrared light – which lies outside the normal range of light that people with regular eyesight can see – and that ‘patients at several instances reported high sensitivity to infrared light’.

Again this is ‘only’ a preliminary clinical study using a small group of people – and this solution would be specific to this type of blindness. But this still represents a massive and breathtaking advance. Previous attempts to use this type of implant had not used anywhere near this number of detectors. But the researchers have plans to improve it: not just by making it bigger but also by getting each detector to interact with its neighbours, like real retinal receptor cells do.

There are other techniques being pioneered too. Rather than implanting light receptors inside the eye, other ongoing clinical trials are developing systems which use a head-mounted camera. This camera sends information through a cable and stimulates the nerve pathways leading from the eye into the brain.

The future

There are two points to take from these studies. The first is the incredible nature of the clinical pilot studies themselves. The second is the caution and context necessary in interpreting these findings and accepting that each builds on previous research, competes with other current research and serves only to foster more research in the future.

Even acknowledging the extremely early stages of both experiments, we can still consider the next steps, both in science and in society. Geeks rejoice: it’s time to talk about ‘The Terminator’.

We are dealing with scientific research programmes in which the brain – seat of our consciousness and all our emotions – is being adorned by biological and techno-logical wizardry. This is the province of bionic men and cybernetic organisms. Take this microchip – scientists appear to have made the visually impaired not only able to see light better than before, but in different ways to those with normal sight. The detectors are sensitive to infra-red light – this is seeing in the dark –
the technology allows the projection of unreal stimuli into people’s conscious awareness.

Injecting cultivated neurons into someone’s brain starts to raise two issues of recent prominence in the neuroscience community: neuro-modulation (using science to improve normal performance rather than ‘just’ to
treat the ill) and neuro-ethics (the moral consequences). If we are our brains, and we change our brains, then we change who we are, and suddenly neurophysiologists are confronted with issues of identity.

Those developments that build an interface between our brains and other material – whether stem cells or microchips – also lie on the boundary between orthodox science and science fiction. The awe we feel for these issues can be seen in the humour of ‘Inspector Gadget’ and the terror of the ‘Terminator’. Future research, and how society deals with it, depends on how we incorporate these technologies into our world-view. Importantly both of these findings were announced to – and appreciated by – the media with due caution. As pilot studies they are by definition preliminary, require ongoing monitoring and necessitate future replication. No-one is talking about a cure for blindness or a cure for stroke – but they are extraordinary, and act as milestones showing us what scientists are capable of. The most striking thing about this research, then, is simply that it is being done.

Posted on Friday, November 3rd, 2023 - Categories: #1 - Oct-Dec 2010, App Issues.