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Tomorrow's People

Page 26

by Susan Greenfield


  These realistic applications of nanotechnology differ from that of the ‘grey-goo’ nightmare in that they exploit the small size of substances without challenging the non-negotiable principles of basic chemistry, or depending on solving the tricky riddles of energy or autonomy of agenda. The wilder aspirations of nanoscience assume that nanodevices will operate independently of the macroworld, and therein lies the problem. For the moment, however, nanoscience is increasingly integrated with the power and purpose of macrosystems, both biological and cybernetic, so it has truly turned into ‘the manufacturing technology of the 21st century’.

  Perhaps Haldane would have approved of nanotechnology as a satisfactory approach to his second question, on control ‘of matter as such’, not least because it could also have bearings on his third big challenge to the scientific imagination concerning man's control ‘of his own body and those of other living beings’. But it's time to leave the chemist of the future, perhaps in a more focused yet less speculative frame of mind than the physicist, and see how the biomedical scientists might perform in this third scientific arena – that of the body.

  A rather low-tech approach is currently taking off in 21st-century science that is conceptually innovative nonetheless in that it brings previously disparate branches of the biomedical sciences together: psychoneuroimmunology (PNI). PNI is based on the reasonable assumption that the three great control networks of the body – the immune, the nervous and the endocrine (hormonal) systems – are all interlinked. This arrangement makes intuitive sense, otherwise surely there would be biological anarchy. Moreover, we have known for a long time that any one of these systems can influence the other two. Dr Esther Sternberg, of the US National Institute for Mental Health, has pointed out that: ‘These notions that emotions have something to do with disease – that stress can make you sick, that believing can make you well – all of that has been around for thousands of years, embedded in the popular culture. And until very recently, we haven't had the scientific tools to prove these connections in a rigorous, scientific way.’

  That said, the medical profession in general, and PNI practitioners in particular, are amassing impressive but dispassionate documentation on the effects of stress on health; for example, a sample of hysterectomy patients at Guy's and St Thomas's Hospitals were played suggestive cassettes on the benefits of relaxing. Half of these patients were released one day after removal of their stitches, whilst of the rest of the patients, who had not listened to the cassettes, only 10 per cent were allowed home at that stage. It was a maxim of even late-20th-century collective wisdom that individuals reacting most to stress are at the highest risk of medical and mental illness. In fact, stress is a better predictor of heart disease than smoking or diet. One study tested the effects of behavioural, non-drug therapy for encouraging relaxation on some fifty patients receiving medication for hypertension; 59 per cent came off their medication altogether, and 35 per cent cut their intake by half. Meanwhile, melanoma patients receiving emotional support along with regular therapy have a staggering 60 per cent more immune cells within seven weeks than a group of patients receiving the therapy alone!

  As well as the widely documented effects of stress on health testifying to the robust and real link between mind and body, or more specifically between nervous and immune systems, there is the placebo effect. Taking its name from the Latin for ‘I shall please’, this well-known phenomenon consists of a significant improvement in health in the absence of any overt, active, external cause or substance. For example, as far back as forty years ago cardiologist Leonard Cobb showed that ‘sham’ surgery, in which he anaesthetized the patient and made appropriate incisions but didn't tie off two arteries to increase blood flow to the heart for angina, was just as successful as real surgery.

  No one is really surprised by this type of report. Everyone, patients and doctors alike, recognizes the placebo effect, so it was something of a shock when a recent study from Denmark came up with a counterclaim. In a meta-analysis, the authors of the study examined 130 different projects comparing placebos with untreated controls; the stark conclusion was that there was no difference after all, no placebo effect. But closer inspection showed that the survey included conditions such as genital herpes and anaemia following surgery, which might not be expected to be influenced by a placebo. The authors themselves admitted that if they considered only subjective conditions such as depression, then the placebo effect is actually significant. In fact, only recently a drug trial of a new antidepressant medication was halted because its beneficial effects were not proving any stronger than those of the placebo.

  And the notion of ‘subjective’ illness might be much broader than we think, where we include a factor, at least, that is ‘just psychological’. For example take Parkinson's disease, a neurological disorder where the radical loss of key brain cells that produce the transmitter dopamine results in an inability to generate movement – the problem is the real death of real neurons. Yet surprisingly, patients taking a placebo drug have displayed as much increased dopamine availability in their brains as those taking a drug that works directly on the neuronal chemistry to produce that effect. In another experiment the very real pain from wisdom-tooth extraction was relieved as much by fake ultrasound as by the real treatment, so long as both the patient and the therapist thought that the machine was on.

  These kinds of studies show that we cannot really draw a line between ‘objective’ and ‘subjective’ illnesses. Of course no amount of wishful thinking will mend a broken leg, but for many conditions, such as pain or even Parkinson's disease, the state of mind can certainly be an important factor. What is the all-important defining factor? Pain and Parkinsonism and certainly depression are, unlike a broken leg, intimately linked with the ongoing state of the brain. So what might be the actual mechanism whereby our neurons can exert such a powerful influence?

  One idea is that, just as Pavlov's famous dogs salivated upon hearing the sound of a bell that they associated with food, so the immune system could be conditioned. We now know that a rat's immune system can fail if conditioned to do so at the presentation of an otherwise harmless stimulus. Death could even be caused just by the sound of an otherwise neutral bell; perhaps such might be the basis for the effects of ‘the evil eye’ in the past. In any event, in humans, psychologist Angela Clow has demonstrated that negative and positive mood manipulations can have immediate but different effects on the immune system. Within minutes of smelling chocolate, for example, there is a measurable increase in the saliva of the chemical secretory immunoglobulin A (slgA), a sign that immune-system function has improved. One immediate, obvious and cheap application for the future would surely be to pipe the smell of chocolate through hospital wards! And as we understand more about which smells under which conditions can manipulate which aspects of our immune system, increasingly our environments may be set up to maximize health, and with it state of mind.

  On a less prosaic level, it is perhaps only in this century that science and the medical profession will begin to take the placebo effect seriously, along with the new interdisciplinary approach of PNI. PNI might well end up contributing not just to ‘tool-driven’ science, by enabling us to understand the link between the immune and nervous systems. In addition, along with the clinical value of developing novel ways to alleviate suffering, this new branch of science holds great promise for furnishing more conceptual insight into the actual physical mechanisms that enable our thoughts to influence our bodies, indeed eventually into the physical basis of thought itself.

  Already one study of placebos gives a hint of how the brain might be working in conjunction with the immune system. Subjects were given mild pain by a blood-pressure monitoring cuff applied to the arm. Not surprisingly this painful effect was abolished with morphine, and likewise with a placebo. However, the interesting point of the experiment was that, like the morphine itself, the placebo effect was cancelled out by a drug that blocks morphine, naloxone. Morphine works because t
here is a naturally occurring morphine-like hormone in our bodies, which the drug impersonates. The blocker naloxone will therefore act on this naturally occurring system; interestingly, it also blocks the placebo effect. The obvious interpretation of this result is that our naturally occurring morphine system, the enkephalins, mediate the placebo effect too.

  The results of a completely different type of study also fit this idea, that giving a placebo is not the same as giving nothing. Peak relief from pain typically comes an hour after giving the inert substance, as it would for a real painkiller. If the placebo effect were merely an effect of doing nothing, we would expect a more random time course of relief. The parallel time course of placebo response with that following painkillers suggests a final common conduit: the enkephalins, via drug simulation or via a process that we need to discover involving ‘thought’. A thought is, after all, just a neuronal event in the physical brain, albeit currently an unidentified one. But it seems reasonable that, whatever the details of the configuration of neurons and their mode of operation, a thought in a placebo situation would amount finally to a group of such cells releasing their own enkephalins into the body.

  The enkephalins belong to a particular class of chemicals in the body – peptides. Peptides are interesting because they could work trilingually, as hormones, as messenger molecules in the immune system and as transmitters in the brain: they could work on target cells by binding to special molecular targets (receptors) present in all three systems. The peptides would be ideally suited as intermediaries, allowing the three control systems of the body to communicate with each other. If the peptides do indeed act as molecular go-betweens, they could be released during conditioning experiments, or in real life according to certain states of mind. These states of mind arise from some kind of changing configuration in the neuronal landscape of the brain, where something, some holistic aspect of brain function, is ‘read out’ to the endocrine and immune systems; indeed read-out to the vital organs and rest of the body, via the peptides, would generate a cohesion between mind and body – a cohesion we call ‘feeling anxious’ or ‘being happy’ or even just ‘conscious’.

  Until as late as the 1980s scientists didn't really take the ‘problem’ of consciousness very seriously. It was, after all, the kind of subject over which philosophers wrangled; no one could really define it and worst of all it was, and still is of course, an utterly subjective experience. As such, consciousness has so far proved too slippery for the machinery of objective scientific methodology; one recent quip was that the whole area was, for scientists, a ‘CLM’ – a career-limiting move. But gradually things started to change. Very senior scientists who no longer needed to fret over the progress of their careers – a surprisingly large proportion of them Nobel laureates – started to tackle this fascinating issue: how might the physical brain, so banal in aspect, so unexciting in texture and colour, render to some mysterious inner observer, some disembodied ‘you’, the first-hand experience into which no one else can hack?

  Over these last few decades some scientists have looked up from the bench to stare out of the window, but still no single area of research has, or can claim, a monopoly on how to go about tackling this problem. Actually, scientists like myself, we neurobiologists who deal with the actual nitty-gritty of neurons, have been least conspicuous in contributing to the debate. But, confronted with the physical, inert brain on the one hand, and the elusive, intangible feel of being ‘you’ on the other, one of the biggest questions remaining for scientists of the future will be: how can we start to gain purchase on understanding the process by which the ‘water’ of neurons is turned into the ‘wine’ of subjective experience? This has become known as the ‘hard problem’. It will be a central question for 21st-century scientists.

  By the time the next generation or two of scientists inherits the hard problem it will be possible to range easily across different subject areas, cross-referencing and correlating different types of phenomena as part of the new ‘neuroinformatics’. What type of areas would they access? To start with the most macro-stage of all: the actual behaviour of the whole person in their environment. This is the approach that, among others, the evolutionary neurophysiologist William Calvin, cognitive psychologist and philosopher Dan Dennett and linguistic psychologist Steven Pinker are all currently adopting. In each case the evolutionary angle, and along with it consideration of how human thought and behaviour are different from that of the rest of the animal kingdom, can throw up enormously valuable insights into issues such as how genes differentially contribute in different species to respective behavioural repertoires. Moreover, we can start to appreciate just what kinds of behaviours and thoughts make us humans so special. But when it comes to consciousness itself, the kind of question we can ask relates not to the hard problem, the essence of consciousness, but instead to an ancillary problem, its evolutionary value: ‘Why and when did consciousness evolve?’ Or put even more bluntly: ‘What is the point of consciousness?’

  There is no doubting that the survival value of consciousness is worth thinking about. A favourite ploy is to try to work out what exactly you would not be able to do if you were not conscious but nonetheless the machine you are – with inputs from the senses and outputs of muscular contractions, but without any private inner world going on in between. It's actually virtually impossible to think immediately of any great loss, in terms of what actions and reactions would occur in the outside environment, but then we are talking about behaviours – and that is precisely the point. Consciousness is not a behaviour. It is an inner state, a subjective experience that can be dissociated from outward actions, the physical contractions of muscle. After all, someone lazing in the sun may not be moving at all, but is still conscious; by contrast there are numerous examples, as we saw in Chapter 3, of systems that are capable of sophisticated responses but are without any hinterland inner state. So it's pointless to approach the value of consciousness from the issue of behaviour.

  Perhaps instead we should start with consciousness and simply ask what it does for us, how it enhances our lives: the short and obvious answer is that it makes life worth living. Recall that when Tony Bland, the tragic victim of crushing in the Hillsborough football stadium, was deemed incapable of regaining consciousness, the courts eventually allowed food to be withheld until he died. The message here, then, is surely if you are not conscious, you might as well be dead. We survive to be conscious, rather than use consciousness as some optional extra to survival.

  What happens if we explore on a scale that is smaller and thus more detailed: the actual brain itself? This is the territory of the neuropsychologist. The aim is to explain impairments in consciousness, caused by brain damage or a contrived experimental paradigm, or both, to gain insight into how brain mechanisms might normally underpin consciousness. Using ingeniously devised tests, the skilled neuropsychologist can home in on the essence of the deficit, see how it compares with the known impairments of classic syndromes and, from there, extrapolate how the area of brain damage might match up to the problems or paradoxes being observed. Perhaps the most famous example of this approach is the definitively paradoxical-sounding blindsight.

  Sometimes a person can suffer damage to part of their brain relating to vision without necessarily being completely blind. Instead, they might have just a patch of blindness (a scotoma) that means that part of their visual world is black. For the last few decades, neuropsychologists have been fascinated by the fact that if an object is aligned so that it coincides with the black patch in a patient's vision, that patient will understandably claim that they cannot consciously see it, but they can point to it with an accuracy well above chance. The excitement for the scientists is that here is a situation where consciousness can apparently be dissociated from the subconscious workings of the brain. Moreover, the effect can be studied whilst imaging the brain and identifying the critical brain regions that are or, more tellingly, are not working.

  But although this type of stu
dy seems to offer an answer, the question is not so obvious. The philosopher John Searle has pointed out that when a blindsight patient tries to see something in their blind spot and fails, they are still just as conscious as they have been all along. So the central issue here, then, is about different conscious experiences, rather than the fundamental and more difficult question of how any subjective experience is generated in the first place.

  And the use of brain imaging as a technique for answering such a question can give us the impression of understanding more than we actually do. As we have seen previously, all any imaging technique will achieve is identification of the bits of the brain that are active and hard-working under certain experimental conditions. We can go a little further and see the difference in the configuration of brain regions when we are paying attention or not, or, as in the case of blindsight, when we admit that we cannot see something. But it does not follow that the area that then fails to light up is the ‘centre for consciousness’. Rather, that brain area will be playing some part in shifts of attention, not in the critical yet elusive physiological process that differentiates our brains from all other biological systems and synthetic objects and devices in the world. Indeed, if we do deprive the brain of consciousness, with anaesthesia, then multiple areas will shut down activity, not just one. In any case, the imaging techniques currently in use are incapable of showing the brain at work over the sub-second timescale over which consciousness occurs and at the same time displaying the dynamics of the shifting configurations of brain networks. And even if such a feat were possible, as it may be in the future, it would tell us only what was happening and where, not how a physical snapshot could be translated into a subjective sensation.

 

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