Antonio Meno Ortega (R) is cared for by his parents Juana (L) and Antonio (C) in November 2010. He has been in a persistent vegetative state since a botched nose operation in 1989. Photo: Getty Images
Show Hide image

Reading the minds of those trapped in their own bodies, unable to ask for help

Thousands remain trapped between life and death. Three scientists are working to free them. Roger Highfield reports.

“Imagine you wake up, locked inside a box,” says Adrian Owen. “It’s only just big enough to hold your body but sufficiently small that you can’t move.

“It’s a perfect fit, down to every last one of your fingers and toes. It’s a strange box because you can listen to absolutely everything going on around you, yet your voice cannot be heard. In fact, the box fits so tightly around your face and lips that you can’t speak, or make a noise. Although you can see everything going on around the box, the world outside is oblivious to what’s going on inside.

“Inside, there’s plenty of time to think. At first, this feels like a game, even one that is strangely amusing. Then, reality sets in. You’re trapped. You see and hear your family lamenting your fate. Over the years, the carers forget to turn on the TV. You’re too cold. Then you’re too hot. You’re always thirsty. The visits of your friends and family dwindle. Your partner moves on. And there’s nothing you can do about it.”

Owen and I are talking on Skype. I’m sitting in London, UK, and he’s in another London three-and-a-half thousand miles away at the University of Western Ontario, Canada. Owen’s reddish hair and close-cropped beard loom large on my screen as he becomes animated describing the torment of those with no voice: his patients.

People in a ‘vegetative state’ are awake yet unaware. Their eyes can open and sometimes wander. They can smile, grasp another’s hand, cry, groan or grunt. But they are indifferent to a hand clap, unable to see or to understand speech. Their motions are not purposeful but reflexive. They appear to have shed their memories, emotions and intentions, those qualities that make each one of us an individual. Their minds remain firmly shut. Still, when their eyelids flutter open, you are always left wondering if there’s a glimmer of consciousness.

A decade ago, the answer would have been a bleak and emphatic no. Not any longer. Using brain scanners, Owen has found that some may be trapped inside their bodies yet able to think and feel to varying extents. The number of patients with disorders of consciousness has soared in recent decades, ironically, because of the rise and success of intensive care and medical technologies. Doctors have steadily got better at saving patients with catastrophic injuries, though it remains much easier to restart a heart than restore a brain. Today, trapped, damaged and diminished minds inhabit clinics and nursing homes worldwide - in Europe alone the number of new coma cases is estimated to be around 230,000 annually, of which some 30,000 will languish in a persistent vegetative state. They are some of the most tragic and expensive artefacts of modern intensive care.

Owen knows this only too well. In 1997, a close friend set off on her usual cycle to work. Anne* had a weak spot on a blood vessel in her head, known as a brain aneurysm. Five minutes into her trip, the aneurysm burst and she crashed into a tree. She never regained consciousness.

The tragedy left Owen numb, yet Anne’s accident would shape the rest of his life. Owen began to wonder if there was a way to determine which of these patients were in an unconscious coma, which were conscious and which were somewhere in between?

That year, he had moved to the Medical Research Council’s Cognition and Brain Sciences Unit in Cambridge, where researchers used various scanning techniques. One, positron emission tomography (PET), highlights different metabolic processes in the brain, such as oxygen and sugar use. Another, known as functional magnetic resonance imaging (fMRI), can reveal active centres in the brain by detecting the tiny surges in blood flow that take place as a mind whirrs. Owen wondered whether he could use these technologies to reach out to patients, like his friend, stuck between sensibility and oblivion. At the core was a deceptively simple question: how do we know that another person is conscious?

Half a century ago, if your heart stopped beating you could be pronounced dead even though you may have been entirely conscious as the doctor sent you to the morgue. This, in all likelihood, accounts for notorious accounts through history of those who ‘came back from the dead’. As a corollary, those who were fearful of being buried alive were spurred on to develop ‘safety coffins’ equipped with feeding tubes and bells. As recently as 2011, a council in the Malatya province of central Turkey announced it had built a morgue with a warning system and refrigerator doors that could be opened from the inside.

What do we mean by ‘dead’? And who should declare when an individual is dead? A priest? A lawyer? A doctor? A machine? Owen discussed these issues at a symposium in Brazil with the Dalai Lama and says he was surprised to find that they both agreed strongly on one point: we need to create an ethical framework for science that is based on secular, rather than religious, views; science alone should define what we mean by death.

The problem is that the scientific definition of ‘death’ remains as unresolved as the definition of ‘consciousness’. Much confusion is sowed by the term ‘clinical death’, the cessation of blood circulation and breathing. Even though this is reversible, the term is often used by mind-body dualists who cling to the belief that a soul (or self) can persist separately from the body. Today, however, being alive is no longer linked to having a beating heart, explains Owen. If I have an artificial heart, am I dead? If you are on a life-support machine, are you dead? Is a failure to sustain independent life a reasonable definition of death? No, otherwise we would all be ‘dead’ in the nine months before birth.

The issue becomes murkier when we consider those trapped in the twilight worlds between normal life and death - from those who slip in and out of awareness, who are trapped in a ‘minimally conscious state’, to those who are severely impaired in a vegetative state or a coma. These patients first appeared in the wake of the development of the artificial respirator during the 1950s in Denmark, an invention that redefined the end of life in terms of the idea of brain death and created the specialty of intensive care, in which unresponsive and comatose patients who seemed unable to wake up again were written off as ‘vegetables’ or ‘jellyfish’. As is always the case when treating patients, definitions are critical: understanding the chances of recovery, the benefits of treatments and so on all depend on a precise diagnosis.

Pioneering work to understand and categorise disorders of consciousness was carried out in the 1960s by neurologist Fred Plum in New York and neurosurgeon Bryan Jennett in Glasgow. They were the odd couple. Jennett - or ‘BJ’, as he was known to colleagues - was reserved and gentlemanly, with an unusually penetrating and analytical mind. Plum was larger than life, commanding and an inspiring teacher who was famous for his idiosyncratic ways of diagnosing neurological conditions. ‘Fred Plum stories’ abound: he would diagnose hemispatial neglect (where damage in one cerebral hemisphere makes a person behave as if their opposite side does not exist) by seeing if the patient could tell if his glasses were askew and one arm pulled out of a sleeve of his coat.

Plum coined the term ‘locked-in syndrome’, in which a patient is aware and awake but cannot move or talk. With Plum, Jennett devised the Glasgow Coma Scale to rate the depth of coma, from a minimum of 3 to a maximum of 15, and Jennett followed up with the Glasgow Outcome Scale to weigh up the extent of recovery, from death to mild disability. Together they adopted the term ‘persistent vegetative state’ for patients who, they wrote, “have periods of wakefulness when their eyes are open and move; their responsiveness is limited to primitive postural and reflex movements of the limbs, and they never speak”. In 2002, Jennett was among a group of neurologists who chose the phrase ‘minimally conscious’ to describe those who are sometimes awake and partly aware, who show erratic signs of consciousness so that at one time they might be able to follow a simple instruction and another they might not. In this way, Plum’s yin and Jennett’s yang launched the field of coma science. Even today, however, we’re still arguing over who is conscious and who isn’t.

§

Adrian Owen has a well-honed routine he uses at public events. A confident performer - helped no doubt by spending 14 years as the lead singer of a band called You Jump First - he asks the audience to raise their left arms. They obey. After a pause, he asks them to raise their right arms. Once again, they comply. “I know you’re conscious because you’ve all got your hands up,” he declares.

The same sort of test features in countless medical dramas, when the doctor clasps the hand of a seemingly unconscious patient and says, “Squeeze if you can hear me”. A tightening grip would represent an act of will. That basic interaction between two conscious minds is the only real signature of being both aware and awake, says Owen. But what if the patient does not squeeze? What is a doctor supposed to think then?

The public perception of coma (from the Greek koma, meaning ‘deep sleep’) is of a patient lying peacefully, eyes shut, without a glimmer of arousal or consciousness, eventually awakening to make a full recovery. The images of films such as Hable con Ella (Talk to Her) and While You Were Sleeping are a long way from the intubations, double incontinence and uncertainty of the reality: a person cannot be awakened, does not respond to pain, light or sound, and does not undergo a normal cycle of sleep and wakefulness.

Kate Bainbridge, a 26-year-old schoolteacher, lapsed into a coma three days after she came down with a flu-like illness. Her brain became inflamed, including the primitive region atop the spinal cord, the brain stem, which rules the sleep cycle. A few weeks after her infection had cleared, Kate awoke from the coma but was diagnosed as being in a vegetative state. Luckily, the intensive care doctor responsible for her, David Menon, was also a Principal Investigator at the newly opened Wolfson Brain Imaging Centre in Cambridge, where one Adrian Owen then worked.

Menon wondered if elements of cognitive processing might be retained in patients in a vegetative state and discussed with Owen how to use a brain scanner to detect them. In 1997, four months after she had been diagnosed as vegetative, Kate became the first patient in a vegetative state to be studied by the Cambridge group. The results, published in 1998, were unexpected and extraordinary. Not only did Kate react to faces: her brain responses were indistinguishable from those of healthy volunteers. Her scans revealed a splash of red, marking brain activity at the back of her brain, in a part called the fusiform gyrus, which helps recognise faces. Kate became the first such patient in whom sophisticated brain imaging (in this case PET) revealed ‘covert cognition’. Of course, whether that response was a reflex or a signal of consciousness was, at the time, a matter of debate.

The results were of huge significance for science but also for Kate and her parents. “The existence of preserved cognitive processing removed the nihilism that pervaded the management of such patients in general, and supported a decision to continue to treat Kate aggressively,” recalls Menon.

Kate eventually surfaced from her ordeal, six months after the initial diagnosis. She described how she was indeed sometimes aware of herself and her surroundings. Each day she woke up, she fell asleep, but like all such patients she could not respond to people’s questions. Worse, she had a raging thirst that was never slaked.

“They said I could not feel pain,” she says. “They were so wrong.” Sometimes she’d cry out, but the nurses thought it was just a reflex. She felt abandoned and helpless. Hospital staff had no idea how much she suffered in their care. Kate found physiotherapy scary: nurses never explained what they were doing to her. She was terrified when they removed mucus from her lungs. “I can’t tell you how frightening it was, especially suction through the mouth,” she has written. At one point, her pain and despair became so much that she tried to snuff out her life by holding her breath. “I could not stop my nose from breathing, so it did not work. My body did not seem to want to die.”

Kate says her recovery was not so much like turning a light on but a gradual awakening. It took her five months before she could smile. By then she had lost her job, her sense of smell and taste, and much of what might have been a normal future. Now back with her parents, Kate is still very disabled and needs a wheelchair. Twelve years after her illness, she started to talk again and, though still angry about the way she was treated when she was at her most vulnerable, she remains grateful to those who helped her mind to escape.

She sent Owen a note.

Dear Adrian,
Please use my case to show people how important the scans are. I want more people to know about them. I am a big fan of them now. I was unresponsive and looked hopeless, but the scan showed people I was in there.
It was like magic, it found me. 

§

When you are awake, your brain has to make sense of a flood of information from your senses. To make the most of its limited data-processing resources, our ancestors evolved a brain that can focus on that approaching spear or lurking lion rather than a broad sweep of savannah landscape. One can think of it as a spotlight of attention that illuminates key sensory information in the brain, which then enters into conscious awareness. This is the mind’s spotlight on the outside world, with awareness at its focus and the degree of wakefulness tuning its intensity.

Steven Laureys, who leads the Coma Science Group at the University of Liège in Belgium, is one of those seeking the source of this illumination. He sits before me clutching a little plastic brain. There are islands of blue on the surface, one at the front and one at the back. He divides it in two, revealing a further blue dot deep inside. This is the thalamus, a two-sided structure that sits atop the brain stem and acts as a relay station for incoming sensory information. “There is no such thing as a ‘consciousness region’ in the brain,” he explains. But subtract the fMRI scans of vegetative patients who are awake and unaware from the scans of those who are awake and fully aware and you find the difference boils down to an ‘awareness network’, the areas marked in blue on his plastic brain.  

Laureys describes a thought experiment. “If I use a scalpel to remove the blue regions you would still be awake, breathe and move but you would not be aware.” Similar networks exist in other mammals to varying extents, he explains, and the traditional idea that we alone are conscious while all other animals are automata is unlikely to be true. “Given our studies of vegetative patients, we have tended to underestimate consciousness in the past,” he says.

This idea of an awareness network chimes with various theories of consciousness, such as the ‘global workspace’ first proposed by Amsterdam-born neurobiologist Bernard Baars. In essence, it suggests that awareness emerges from neurons distributed throughout the cortex in a network that blends sensory information and filters out contradictory or unnecessary information to create a unified picture of reality.

This view complements the work of Nicholas Schiff at Weill Cornell Medical College in New York. A neurologist, he started out as a disciple of Fred Plum’s school. Schiff’s working life is a balancing act between putting the interests of his patients and their families first and keeping true to the science as he wrestles with disorders of consciousness. “There’s a lot we don’t know,” he admits. “Frankly, I am wrong a lot of the time.”

Schiff started to piece together this neural circuitry, building on pioneering experiments conducted on cats in the 1940s. These showed how the animals could be revived from anaesthesia by stimulating the thalamus, which plays a crucial part in the brain’s complex orchestra. Studies suggest that a key population of nerve cells (intralaminar thalamic neurons), radiating from this hub to the outer rind (the cortex) and every corner of the brain, have a central role in arousal and waking up. By the same token, they have a central role in coma too: they are more vulnerable than other nerve cells to harm, such as oxygen starvation, which helps to explain why brain damage can lead to unconsciousness.

Schiff is interested in how the relay post that is the thalamus links with a surrounding structure called the striatum and with the frontal cortex. And among these deeper brain regions is an area dubbed the posterior medial complex, a network whose activity is impaired in vegetative brains.

Illustration: Bret Syfert/Wellcome Images (CC-BY)

The thalamus and frontal lobe are also more active in conscious and locked-in patients. Together, Schiff and Laureys have identified three broad brain circuits - those in the thalamus, the frontal lobe and the posterior medial complex - that are key to consciousness. 

At scientific meetings, Schiff has outlined a more detailed version of this neural structure, called the ‘mesocircuit’, which actually consists of two circuits linking the thalamus to the cortex. Some of the connections involved in the mesocircuit stimulate nerve activity, others reduce or prevent it. Overall, higher-level consciousness emerges as a dynamic coalition of these two parallel interactive brain networks. This theory, which he and Laureys are putting to the test, also reveals a way in which one might jump-start a stalled brain. Over the years, a remarkable series of experiments have shown how a mind might be coaxed back into awareness.

§

In 1995, Schiff studied an 81-year-old woman with a disordered consciousness. As a result of an acute stroke, she had suffered hemispatial neglect. She was unable to identify her right hand as her own. Ice-cold water was squirted into her ear, as a standard test to see the extent to which her responses were lopsided. To Schiff’s amazement, the water reversed almost all her symptoms: “That’s my hand!” she cried out. Schiff believed that the chill had stimulated her inner ear, which controls the sense of balance through the vestibular system, and, in turn, her thalamus, knitting together the networks that had been disrupted by the stroke. Four minutes later, when the water had warmed, she lost her hand once again.

The case helped him work up the basic neuroscience of how to increase awareness in a brain stalled in limbo by stimulating the thalamus. Armed with this understanding, Schiff has provided insight into the paradoxical discovery that some patients in vegetative states can be awoken with a sedative, zolpidem. One of the best-known cases is the South African Louis Viljoen, who had been left vegetative by a road accident. One day in 1999, Wally Nel, a GP working near Johannesburg, gave Louis the drug to ease the way that he clawed at his mattress. Instead of being relaxed, Viljoen sat bolt upright, smiled, and said: “Hello Mum. Am I in hospital?” Schiff believes that the drug dampens down so-called ‘medium spiny neurons’ in the part of the mesocircuit that links the striatum, the globus pallidus and the thalamus. Because these neurons inhibit the thalamus, quelling their activity can actually boost awareness. Just as a little alcohol can initially stimulate a buzz, so zolpidem can help “turn the brain on rather than off”, says Schiff.

A study by Schiff and Laureys shows how slow waves of nerve activity, of the kind seen in sleep or anaesthesia, wash over the brain before the drug is given, but afterwards sluggish synchronicity gives way to the crackle of high-frequency brain waves typically seen in conscious patients. PET images tell the same story, revealing how the drug ramps up brain metabolism. Similar effects are caused by another compound, the anti-Parkinson’s drug amantadine. Laureys’s team in Liège finds that about half of patients in a minimally conscious state show mild improvement in awareness as a result of receiving the drug.

The awareness network can be electrically roused. Laureys and his colleagues recently tested transcranial direct-current stimulation (tDCS), in which scalp electrodes are used to pass a weak direct current through the skull to alter the excitability of underlying brain tissue. The Liège team applied tDCS for 20 minutes to part of the mesocircuits of 55 people who were in a minimally conscious or vegetative state. They found that 15 showed glimmers of consciousness as a result. Some showed responses to commands, even though it was several years after they had been declared minimally conscious. Most dramatic, for two patients who had been declared minimally conscious a few months earlier, tDCS enabled them to nod or move their eyes in response to six questions.

The method offers a powerful way to probe which circuits have to be manipulated to awaken a silent brain. “In theory, at least, tDCS offers another way to reactivate circuits to help a damaged brain to recover some functionality, even several years after suffering severe damage,” Laureys explains. However, the results are not as remarkable as those seen in a case where the thalamus was stimulated directly.

In 2005, Schiff applied his emerging understanding of the circuits of consciousness to Jim*, a 38-year-old man who had been beaten and robbed and was left minimally conscious. Jim’s eyes had mostly remained shut. He showed no sign of awareness that his family could detect. His plight seemed hopeless. Eventually, Jim’s mother gave a ‘do not resuscitate’ order to doctors. Schiff thought different.

Schiff had earlier scanned Jim with fMRI, in 2001. His team had played subjects, including Jim, an audiotape in which a relative or loved one reminisced. Jim showed near-normal patterns in the language-processing areas of his brain and this told Schiff that some of Jim’s neural networks were still working. In detailed fMRI scans, Jim had shown that, despite having a very underactive brain, he had strongly preserved large-scale language networks. When he heard a story that meant something to him, his brain lit up. This encouraged Schiff to revive the idea he had mulled over for a decade. What if they activated Jim’s thalamus by deep brain stimulation?

A brain pacemaker was implanted into Jim. Thanks to the regular pulses of electricity it delivered to his thalamus, he was able to use words and gestures, respond reliably to requests, eat normally, drink from a cup, and carry out simple tasks such as brushing his hair. Schiff believes that once a brain re-engages with the world, it accelerates processes of repair. For the next six years, before Jim died of unrelated causes, he kept his mind above the minimally conscious state. “He could converse in short sentences reliably and consistently and make his wishes known,” says Schiff. “He could chew and swallow and eat ice cream and hang out. His family told us that they had him back.” The case made the front page of the New York Times. “I prayed for a miracle,” his mother told me at the time he was brought back. “The most important part is that he can say ‘Mummy and Pop, I love you’. God bless those wonderful doctors. I still cry every time I see my son, but it is tears of joy.”  

In a forested campus south of Liège, Steven Laureys studies vegetative patients in research that dates back decades. Working there as part of the Cyclotron Research Centre in the 1990s, he was surprised when PET brain scans revealed that the patients could respond to a mention of their own name: meaningful sounds produced a change in blood flow within the auditory primary cortices. Meanwhile, on the other side of the Atlantic, Nicholas Schiff was finding that within catastrophically injured brains lay partially working regions, clusters of remnant neural activity. What did it all mean?

At that time, doctors thought they already knew the answers: no patient in a persistent vegetative state was conscious. Never mind that staring at images made the brain light up, they carped: you can do that in a sedated monkey. Based on previous experience, a brain starved of oxygen as a result of a heart attack or a stroke was unlikely to recover if it didn’t in the first few months. These patients had suffered a fate that many people regarded as worse than death itself: they were functionally brainless. Undead. Doctors, with the best intentions, thought it was perfectly acceptable to end the life of a vegetative patient by starvation and the withdrawal of water. This was the age of what Laureys calls “therapeutic nihilism”.

What Owen, Laureys and Schiff were proposing was a rethink of some of the patients who were considered vegetative. A few of them could even be classed as being fully conscious and locked-in. The establishment was doggedly opposed. “You cannot imagine the environment in the late 1990s,” says Schiff. “The hostility we encountered went well beyond simple scepticism.” Looking back, Laureys pauses and smiles thinly: “Medical doctors do not like to be told they are wrong.” Schiff, Laureys and Owen cut lonely and isolated figures at academic conferences, desperately trying to explain their findings to their peers, who remained unconvinced, even antagonistic. The trio’s ideas were condemned as a waste of time.

Then came 2006. Owen and Laureys were trying to find a reliable way to communicate with patients in a vegetative state, including Gillian*. In July 2005, this 23-year-old had been crossing a road, chatting on her mobile phone. She was struck by two cars. Yet, though she had been diagnosed as vegetative, there was something about her that caught the attention of Martin Coleman of the University of Cambridge Impaired Consciousness Research Group, who submitted her for study by Owen.

Five months later, a strange stroke of serendipity allowed Gillian to unlock her box. The key arose from a systematic study Owen started with Laureys in 2005. They had asked healthy volunteers to imagine doing different things, such as singing songs or conjuring up the face of their mother. Then Owen had another idea. “I just had a hunch,” he says. “I asked a healthy control to imagine playing tennis. Then I asked her to imagine walking through the rooms of her house.” Imagining tennis activates part of the cortex, called the supplementary motor area, involved in the mental simulation of movements. But imagining walking around the house activates the parahippocampal gyrus in the core of the brain, the posterior parietal lobe, and the lateral premotor cortex. The two patterns of activity were as distinct as a ‘yes’ and a ‘no’. So, if people were asked to imagine tennis for ‘yes’ and walking around the house for ‘no’, they could answer questions via fMRI.

Gazing into Gillian’s ‘vegetative’ brain with the brain scanner, he asked her to imagine the same things - and saw strikingly similar activation patterns to the healthy volunteers. It was an electric moment. Owen could read her mind.

Gillian’s case, published in the journal Science in 2006, made front-page headlines around the world. The result provoked wonder and, of course, disbelief. “Broadly speaking, I received two types of email from my peers,” says Owen. “They either said ‘This is amazing - well done!’ or ‘How could you possibly say this woman is conscious?’”

As the old saw goes, extraordinary claims require extraordinary evidence. The sceptics countered that it was wrong to make these ‘radical inferences’ when there could be a more straightforward interpretation. Daniel Greenberg, a psychologist at the University of California, Los Angeles, suggested that “the brain activity was unconsciously triggered by the last word of the instructions, which always referred to the item to be imagined”. 

Parashkev Nachev, a neurologist now at University College London, says he objected to Owen’s 2006 paper not on grounds of implausibility or a flawed statistical analysis but because of “errors of inference”. Although a conscious brain, when imagining tennis, triggers a certain pattern of activation, it does not necessarily mean that the same pattern of activation signifies consciousness. The same brain area can be activated in many circumstances, Nachev says, with or without any conscious correlate. Moreover, he argues that Gillian was not really offered a true choice to think about playing tennis. Just as a lack of response could be because of an inability to respond or a decision not to cooperate, a direct response to a simple instruction could be a conscious decision or a reflex. Nachev says that he is weary of stating, as he has time and again to the media, that profound conceptual issues with the techniques used to redefine this penumbra of consciousness remain unresolved.

What is needed is less philosophising and more data, says Owen. A follow-up study published in 2010 by Owen, Laureys and colleagues tested 54 patients with a clinical diagnosis of being in a vegetative state or a minimally conscious state; five responded in the same way as Gillian. Four of them were supposedly in a vegetative state at admission. Owen, Schiff and Laureys have explored alternative explanations of what they observed and, for example, acknowledge that the brain areas they study when they interrogate patients can be activated in other ways. But the 2010 paper ruled out such automatic behaviours as an explanation, they say: the activations persist too long to signify anything other than intent. Owen is grateful to his critics. They spurred him on, for instance to develop a method for asking patients questions that only they would know how to answer. “You cannot communicate unconsciously - it is just not possible,” he says. “We have won that argument.” 

Since Owen’s 2006 Science paper, studies in Belgium, the UK, the USA and Canada suggest that a significant proportion of patients who were classified as vegetative in recent years have been misdiagnosed - Owen estimates perhaps as many as 20 per cent. Schiff, who weighs up the extent of misdiagnosis a different way, goes further. Based on recent studies, he says around 40 per cent of patients thought to be vegetative are, when examined more closely, partly aware. Among this group of supposedly vegetative patients are those who are revealed by scanners to be able to communicate and should be diagnosed as locked-in, if they are fully conscious, or minimally conscious, if their abilities wax and wane. But Schiff believes the remainder will have to be defined another way altogether, since being aware does not necessarily mean being able to use mental imagery. Nor does being aware enough to follow a command mean possessing the ability to communicate.

In 2009, Laureys’s team asked one of the original group of 54 patients that he and Owen had studied - patient 23 - a series of yes-or-no questions. It was the usual drill: imagine playing tennis for yes, navigating the house for no. The Liège patient, who had been in a vegetative state for five years, was able to answer five of six questions about his earlier life - and all of those were correct. Had he been on holiday to a certain place prior to his injury? Was such-and-such his father’s name? It was an exciting moment, said Laureys. “We were stunned,” adds Owen, who helped independently score the tests. “By showing us that he was conscious and aware, patient 23 moved himself from the ‘do not resuscitate’ category to the ‘not allowed to die’ category. Did we save his life? No. He saved his own life.”

§

“This is your big chance. Just do your best.” Owen gazed down at 39-year-old Scott Routley, lying on a gurney. Scott had studied physics at the University of Waterloo, Ontario, but his promising career in robotics came to an end when, aged 26, he collided with a police vehicle. Since that accident, on 20 December 1999, Scott had been diagnosed as being in a vegetative state by a well-seasoned neurologist, Bryan Young, and in 2012 his diagnosis was confirmed by Owen’s team, again using traditional methods.

As Owen talked to him, Scott’s mouth remained wide open, apparently unaware, the same way that he’d been in the 12 years since the accident. This encounter was filmed by a crew from the BBC. Reporter Fergus Walsh was there to witness the moment that Owen attempted to reach inside Scott’s mind. Owen admits now that he was sceptical that the scans would reveal anything at all.

The team scanned Scott several times. To their surprise, the pattern of brain activity showed Scott knew exactly who he was, where he was and that he was actively choosing to answer the team’s questions. “My heart stopped when we asked if, after 12 years, Scott was in pain,’’ Owen recalls. “Thankfully, the answer was no.”

Although Owen’s colleague, Lorina Naci, recounts how the experience of telling the Routley family the news was “quite emotional”, the BBC crew were surprised at their relative lack of celebrations. Not Owen. Scott’s parents, Jim and Anne, and his brother, Ritch, had always been convinced that he was conscious. They insisted he could lift a thumb or move his eyes to indicate as much, even though standard tests had always reached the same gloomy conclusion: Scott was unresponsive.

Scott had the same neurologist - Young - for more than a decade and had appeared vegetative in every assessment, including more than a dozen separate assessments by Owen’s own team. Perhaps the family discerned subtle signs of consciousness that were almost undetectable, even to the trained eye. Or perhaps they had deceived themselves, as many families do for comfort. “Either way, it was the word of the family against that of my team, and their word against an army of specialists over many years,” says Owen. Where the family saw a sign of cognition, the doctors saw only wishful thinking. “The scans showed that they were right, perhaps for the wrong reasons - we will never know - but Scott’s story teaches us the value of objective measures. And the need for a little humility.” 

There’s anecdotal evidence that when contact is re-established with the occupant of a living box they are understandably morose, even suicidal. They have been ground down by frustration at their utter powerlessness, over the months, even years, it can take to recognise their plight. Yet the human spirit is resilient, so much so that they can become accustomed to life in this twilight state. In a survey of patients with locked-in syndrome, Laureys has found that when a line of communication is set up, the majority become acclimatised to their situation, even content (again, these insights took some time to be accepted by the medical and scientific establishment - and even to be published in a scientific journal - reflecting the prevailing unease about the implications for hospitals and care homes).

The important question is detecting the extent to which such patients are conscious. Studies of large numbers of patients with brain injuries, and how they fare over the years, show that it makes a huge difference to the chance of recovery if a patient is minimally conscious rather than vegetative. The former have fragmentary understanding and awareness and may recover enough to return to work within a year or two. Yet there are still surprises, such as the case of New York fireman Don Herbert, who awoke after a decade from a minimally conscious state caused by a severe brain injury suffered while fighting a fire in 1995. In the past year, Schiff has recommended withdrawing care from a man who had lain in a coma for eight weeks after a cardiac arrest. “I was wrong,” he says. “This man is now back at work.” Schiff has used a technique called diffusion tensor imaging to show how a brain can rewire itself even decades after an injury.

It is important too not to lose sight of the impact on the families. Take Jamel, a 41-year-old construction worker left unconscious after a cardiac arrest. His family became convinced he had a glimmer of awareness and, fighting against the doctor’s stark diagnosis, spent almost 14,000 euros transporting him to Liège and Steven Laureys’s team for a detailed diagnosis. Sadly, their scans revealed no signs of consciousness. The family took the news badly. His sister Leila insists that Jamel can hear what they are saying. He was tired out by travel and surgery before he had his scan, she explains. The family has vowed to gather video evidence to show Laureys.A patient’s story

Parashkev Nachev has not changed his view since he first criticised Owen’s work and has spelt out the basis of his unease in a more detailed paper published in 2010. “For every relative of a living PVS [persistent vegetative state] patient given (probably false) hope, another is burdened with the guilt of having acquiesced in the withdrawal of treatment from someone who - he has been led to believe - may have been more alive than it seemed,” he says. “There are moral costs to false positives as well as to false negatives.” 

“I find the whole media circus surrounding the issue rather distasteful,” he told me. “The relatives of these patients are distressed enough as it is.”

Laureys, Owen and Schiff spend a great deal of time with the families and understand these sensitivities only too well. Owen counters that, from his years of experience dealing with the families, they are grateful that doctors and scientists take an interest and are doing everything that they can. “These patients have been shortchanged over the years,” he insists. A recent study showed that many people would grant more ‘moral rights’ to a corpse than to someone in a vegetative state. This surprising finding emerged when a team from the University of Maryland and Harvard University asked 201 people to read accounts of a car accident in which the protagonist lived, died or sank into a persistent vegetative state. The latter was regarded as worse than death.

Owen is adamant that doctors have a moral duty to provide a correct diagnosis, even if the results do cause guilt, unease or distress. “We must give every patient the best chance of an accurate diagnosis, so we can give them the appropriate care that goes along with that diagnosis.”

Under the umbrella classification of ‘vegetative’ lies a vast array of different brain injuries and, as a result, even some of the most vocal critics accept that some vegetative patients are not as diminished as traditional measures suggest. Lynne Turner-Stokes chairs a group for the Royal College of Physicians that is revising UK guidelines on ‘Prolonged Disorders of Consciousness’. She remains unconvinced that the exceptional cases identified by Owen, Laureys and Schiff are particularly common or that enough has been done to establish brain scanners as a standard tool for routine diagnosis, particularly when the cost and convenience of these methods are taken into account. When it comes to extending these tests to all patients in a vegetative states as standard practice, “the evidence is just not there yet,” she says.

Despite all the hard work done since the pioneering research of Plum and Jennett, there’s still a need for basic spadework to harmonise standards, tools and timescales of assessment for these patients, says Turner-Stokes. More has to be done to ensure that a vegetative patient in, say, the UK is assessed in the same way as one in the USA, and to close gaps in understanding of this very complex group of patients, notably how their brains can change and heal over time. But she stresses that she is simply being cautious, not sceptical, describing the work of Owen, Laureys and Schiff as “important and exciting”.

“We are only just beginning to scratch the surface,” she says. “But I have no doubt [these techniques] will have a place, eventually, in the evaluation of patients.” 

§

The art of mind reading is constantly being refined. Owen and Lorina Naci have come up with a more reliable way to communicate with patients by getting them to focus their attention while in the scanner. First, a yes/no question is asked, and then a recording is played of the word ‘yes’ repeated several times interspersed with distracting, random numbers, and a similar recording with ‘no’. The participant has to count how many of the correct answer they hear and ignore the incorrect answer. This mental effort (‘selective auditory attention’) shows up distinctively when Naci and Owen examine the brain scans, so they can decode the responses correctly based on activity changes within the attention network of the brain.

In follow-up studies using this method, Scott Routley showed he knew his own name, as distinct from another, and that he was in a hospital rather than elsewhere, indicating he possessed a higher level of self-awareness. “This not only further corroborated that he was, indeed, consciously aware but also revealed that he had far richer cognitive reserves than could be assumed based on his diagnosis as being vegetative,” says Owen. “He had autobiographical knowledge and awareness of his location in time and space.” 

Yet there are many issues left to resolve. After the initial diagnosis, relatively little effort is made to systematically explore brain function in these patients, says Schiff. There are also minimally conscious patients who may not be able to imagine tennis and so on, when a few exceptional vegetative patients can. Schiff’s team has encountered a patient who had remained vegetative, or in a very low-level minimally conscious state, for more than one year, who had not responded to fMRI, but later regained the ability to make conversation (though, of course, whether they had truly been vegetative is another question). And a 2014 study by Laureys’s group suggests that PET could be better than fMRI at predicting the likelihood that a patient may wake up. It also estimates that the standard diagnostic procedure misses signs of responsiveness in around a third of patients classed as minimally conscious - which Owen notes is consistent with his and Schiff’s findings.

Indeed, other limitations are caused by the use of medication during trials or the huge diversity of the patients that are usually collapsed into groups (to spare doctors from carrying out the same procedures on the same patient again and again). When it comes to younger patients, there is a limit to the number of PET scans they can have in a given period because a radioactive tracer has to be injected into the body. fMRI is also hindered by the fact that huge, multimillion-dollar imaging machines - confining and magnetic - are unsuitable for patients whose bodies are affected by spasticity or have been rebuilt with screws, plates, pins and other metal.

But more convenient alternatives are in development. Laureys is studying pupil dilation, which is linked with thought (the wider the pupil, the higher a patient’s emotional arousal, while more subtle dilations have been linked to mental functions such as decision making). Another method implants fine electrodes in the hand of a patient to measure ‘sub-threshold’ muscle activity triggered when they are asked to move. 

Perhaps the most promising alternative is electroencephalography (EEG), which detects crackles of electrical activity in the brain through electrodes attached to the scalp. This is cheap, relatively portable and fast (with milliseconds of lag, compared with 8 seconds for fMRI), meaning that a research team can ask up to 200 questions in 30 minutes. This method can also cope with patients who twitch and move, or who have been reconstructed with implants. “This is a vulnerable patient population, and moving them is never easy,” says Owen, whose team have equipped a jeep. “We pack our gear in our ‘EEJeep’ and visit them instead.”

A bedside EEG consciousness detector has been tested in Addenbrooke’s Hospital, Cambridge, and in the University Hospital of Liège. It looks promising but doubts remain, even among the believers, with Schiff’s team sceptical whether one particular EEG methodology used with the detector really works. “One has to be careful of the dead salmon effect,” admits Laureys, referring to an apparently frivolous study of a deceased fish that made a serious point about the limitations of fMRI. The methodology struggled to distinguish real brain activity from background ‘noise’, suggesting that the dead Atlantic salmon that had been put in the scanner was actually thinking. “We don’t want to get excited about dead fish,” says Laureys, “but, on other hand, we do not want to be so conservative and demanding of statistics that we miss things.” The dispute has caused some tensions - though united against their critics, the groups are still competitive - but Schiff stresses that it is all for the greater good: “We are all funded on [a] multinational grant to cross-validate and share methods and agree that they work. That is why we pushed our criticisms hard and in the end it was better for everybody.”

§

Today it is normal to think of the transition between life and death as a question of ‘how the brain is’ rather than ‘how the heart is’. A patient in a persistent vegetative state still has a functioning brain stem and can breathe unaided. They may possess some degree of consciousness and have a slim chance of recovering. By comparison, a PET scan of a brain-dead person reveals a black void within the skull, a barren neural landscape with no chance of sparking back into activity again: their body cannot survive without artificial help.

Though they are becoming rarer, there are still chilling stories that apparently blur the boundaries between life and death. In October 2009, Colleen Burns was admitted to St Joseph’s Hospital Health Center in New York after a drug overdose. Doctors pronounced the 39-year-old dead while she was in a drug-induced coma. Fortunately for Burns, she woke minutes before the first incision was to be made to harvest her organs. “Remember that not a single patient who showed clinical criteria of brain death has ever recovered consciousness,” says Laureys. “Whenever a brain-dead patient does manage this feat, it turns out they were not properly examined and the criteria for brain death not properly applied.”

Schiff believes that a combination of devices, drugs and cell therapies, laying the foundations for a new generation of diagnostics and treatments, will illuminate the penumbra between conscious and unconscious. “We’re not quite there yet,” he stresses. Much of the work to date has demonstrated the value of brain scans on populations of patients but, ultimately, they need dependable methods that will work on a patient-by-patient basis, which means precise definitions and standards. They need ways to deal with false positives and false negatives, and to make sense of the impact of a bewildering array of brain injuries, from oxygen starvation to blows and bullet wounds. “We are going to have to do some amazing small-scale studies to show what is possible in one or two subjects before everyone gets simple things done that can help them today,” Schiff says. Eventually, he believes there will be a “cultural shift”. Laureys thinks we may need to start with the language used to describe these patients - he wants replace the loaded term ‘vegetative’ with the neutral ‘unresponsive wakefulness’.

Despite the scepticism, the difficulties in dealing with such diverse groups of patients, and the challenges of standardising diagnosis, the research is moving forward. It is already making a difference, enabling a few patients to tell their doctors whether they need pain relief. 

Back on Skype, Owen smiles, considering whether to tell me what he is planning next. Owen’s partner, Jessica Grahn, also a neuroscientist, became pregnant at the start of 2013. What happens when consciousness winks on in the developing brain?

He emails me a video of their unborn child, a montage of fMRI slices through their baby’s head, as it twists and turns in Jessica’s womb. “My colleagues have been doing fMRI on my wife’s tummy every week for a few weeks now to see if we can activate the fetus’s brain,” he writes. “It is AMAZING.”  

Scott Routley died in September 2013 with his family by his side.

Adrian Owen’s friend Anne remains in a vegetative state.

Adrian Owen and Jessica Grahn’s baby boy, Jackson, was born on 9 October 2013.

* Some names have been changed to protect identities.

This article was commissioned by Mosaic, a new digital publication from the Wellcome Trust dedicated to exploring all strands of the science of life. It is reproduced under a Creative Commons Attribution 4.0 International Licence.

Photo: ANDREW TESTA/THE NEW YORK TIMES/ EYEVINE
Show Hide image

Interview: Nicola Sturgeon's Scottish referendum dilemma

In a candid interview, the First Minister discusses Theresa May’s coldness, Brexit and tax rises – and why she doesn't know when a second referendum will be held. 

Nicola Sturgeon – along with her aides, who I gather weren’t given much choice – has taken up jogging in the verdant country­side that lies to the east of the Scottish Parliament. “The first time was last week,” she says, when we meet in her large, bright Holyrood office. “Loads of people were out running, which made me a bit self-conscious. But it was fine for ages because everybody’s so focused. Then, suddenly, what must have been a running group came towards me. I saw one of them look and as they ran past I turned round and all of them were looking.” She winces. “I will eventually get to the point where I can run for more than 100 yards at a time, but I’m not at the stage yet where I can go very far. So I’m thinking, God, they’re going to see me stop. I don’t know if I can do this.”

This is a very Nicola Sturgeon story – a touch of the ordinary amid the extraordinary. She may have been a frontbencher for almost two decades, a cabinet minister for half of that and the First Minister since 2014, but she retains that particularly Scottish trait of wry self-mockery. She is also exceptionally steely, evident in her willed transformation over her adult life from a shy, awkward party member to the charismatic leader sitting in front of me. Don’t be surprised if she is doing competitive ten-kilometre runs before the year is out.

I arrived at the parliament wondering what frame of mind the First Minister would be in. The past year has not been especially kind to her or the SNP. While the party is still Scotland’s most popular by a significant margin, and Sturgeon continues to be its dominant politician, the warning lights are flashing. In the 2015 general election, the SNP went from six seats out of 59 to 56, a remarkable result. However, in Theresa May’s snap election in June this year, it lost 21 of those seats (including those of Angus Robertson, the SNP leader at Westminster, and Alex Salmond), as well as half a million votes. Much of the blame has been placed on Sturgeon and her call for a second independence referendum following the vote for Brexit. For critics, it confirmed a suspicion that the SNP only cares about one thing and will manipulate any situation to that end. Her decision also seemed a little rushed and desperate, the act of a woman all too aware of the clock ticking.

But if I expect Sturgeon to be on the defensive, maybe even a little downbeat, I’m wrong. Having just come from a feisty session of First Minister’s Questions, where she had the usual barney with her Tory opposite number, Ruth Davidson, she is impressively candid. “When you come out [of FMQs], your adrenaline levels are through the roof,” she says, waggling a fist in my direction. “It’s never a good idea to come straight out and do an interview, for example.” Adrenalised or not, for the next hour, she is thoughtful, frank, funny and perhaps even a little bitchy.

Sturgeon’s office is on the fourth floor, looking out over – and down on – Holyrood Palace, the Queen’s official residence in Edinburgh. As we talk, a large artistic rendering of a saltire adorns the wall behind her. She is similarly in blue and white, and there are books about Burns on the shelves. This is an SNP first minister’s office.

She tells me that she and her husband, Peter Murrell, the party’s chief executive, took a summer break in Portugal, where his parents have a share in an apartment. “We came home and Peter went back to work and I spent a week at home, just basically doing housework…” I raise an eyebrow and an aide, sitting nearby, snorts. She catches herself. “Not really… I periodically – and by periodically I mean once a year or once every two years – decide I’m going to dust and hoover and things like that. So I did that for a morning. It’s quite therapeutic when you get into it. And then I spent a week at home, reading and chilling out.”

In a recent Guardian interview, Martin Amis had a dig at Jeremy Corbyn for having “no autodidact streak”. Amis said: “I mean, is he a reader?… It does matter if leaders have some sort of backing.” One of Sturgeon’s great strengths is that she is a committed bibliophile. She consumes books, especially novels, at a tremendous rate and raves to me about Gabriel Tallent’s astonishing debut, My Absolute Darling, as well as Bernard MacLaverty’s Midwinter Break. She has just ploughed through Paul Auster’s daunting, 880-page 4 3 2 1 (“It was OK. I don’t think it should be on the Booker shortlist.”) She also reread the works of Chimamanda Ngozi Adichie before interviewing her onstage at the Edinburgh International Book Festival in August.

The First Minister is now reading What Happened, Hillary Clinton’s book about her defeat by Donald Trump. “I’ve never been able to read any of her [previous] books because literally every word is focus-grouped to the nth degree,” Sturgeon says. “This one, there are moments of frankness and raw honesty and passages where it’s victimhood and self-pity, but that’s kind of understandable and very human. The thing that fascinates me about Hillary, apart from the politics, is just her sheer bloody resilience.  Given what she’s gone through and everything that’s been chucked at her, I genuinely don’t know how she keeps coming back.”

***

Speaking of resilience, does she have any fellow feeling for Theresa May, humiliated by the electorate and, for now, kept in No 10 like a racoon in a trap by colleagues who are both power-hungry and biding their time? “At a human level, of course,” she says. “When you’ve got an insight into how rough and tough and, at times, downright unpleasant the trade of politics can be, it’s hard not to feel some personal sympathy. Her position must be pretty intolerable. It’s tempered, though, by the fact that nobody made her call an election and she did it for purely party-political interest.”

How does she get on with May – who is formal and restrained, even off-camera – in their semi-regular meetings? Sturgeon starts laughing. “The Theresa May that the country ended up seeing in the election was the one I’ve been dealing with for however long she’s been Prime Minister. This is a woman who sits in meetings where it’s just the two of you and reads from a script. I found it very frustrating because David Cameron, whose politics and mine are very far apart, always managed to have a personal rapport. You could sit with David and have a fairly frank discussion, agree the things you could agree on and accept you disagree on everything else, and have a bit of banter as well.

“I remember just after May came back from America [in January], when she’d held Trump’s hand [Sturgeon starts laughing again], she’d also been to Turkey and somewhere else. This was the Monday morning. We sit down, it’s literally just the two of us, and I say, ‘You must be knackered.’ She said, ‘No! I’m fine!’ And it was as if I’d insulted her. It was just impossible to get any human connection.”

Given this, and the weaknesses exposed during the election, Sturgeon is scathing about how the Conservatives fought the campaign, putting May’s character and competence front and centre. “The people around her must have known that vulnerability,” she says. “God, we all make mistakes and we all miscalculate things, so this is not me sitting on high, passing judgement on others, but don’t build a campaign entirely around your own personality when you know your personality’s not capable of carrying a campaign… Even if you can’t see that yourself, somebody somewhere around you should have.”

Sturgeon might not be in May’s beleaguered position but she has problems. Her demand in March, at a press conference at Bute House, Edinburgh, for a second independence referendum by spring 2019 was a serious mistake and it has left a dent in what had seemed her impermeable personal popularity. Polls show support for the SNP and independence now share a similar downward trajectory. Over the next three years, the First Minister must persuade a sceptical electorate that her party deserves a fourth consecutive term in government.

Does she regret demanding another vote on separation?

Here she gets as close as she will go to a mea culpa. “Obviously I’m thinking pretty deeply about it. I think Brexit is a complete and utter car crash – an unfolding disaster. I haven’t changed my views on that, and I think it’s deeply wrong for [Scotland] to be taken down that path without the ability to decide whether that’s right or not.

“I recognise, as well – and it’s obviously something I have reflected on – that understandably people feel very uncertain about everything just now, partly because the past few years have been one big decision after another. That’s why I said before recess that I will not consider any further the question of a second referendum at this stage. I’m saying, OK, people are not ready to decide we will do that, so we have to come back when things are clearer and decide whether we want to do it and in what timescale.”

Will she attempt to hold a second referendum? Could it be off?

“The honest answer to that is: I don’t know,” she says. Her expression of doubt is revealing.

Would she, however, support a second EU referendum, perhaps on the final separation package? “I think it probably gets more and more difficult to resist it,” she tells me. “I know people try to draw lots of analogies [between the EU and independence referendums], and there are some, but whatever you thought of the [Scottish] white paper, it was there and it was a fairly detailed proposition.

“One of the beautiful things about the independence referendum was the extent to which ordinary folk became experts on really technical, big, macro­economic positions. Standing on a street corner on a Friday morning, an ordinary working-class elderly gentleman was talking to me in great detail about lender of last resort and how that would work. You can say the white paper was crap, or whatever, but it was there, people were informed and they knew what they were voting for.

“That was not the case in the EU referendum. People did not know what they were voting for. There was no proposition put forward by anyone that could then be tested and that they could be held to account on. The very fact we have no idea what the final outcome might look like suggests there is a case for a second referendum that I think there wasn’t in 2014. It may become very hard to resist.”

Sturgeon hasn’t found the Brexit process “particularly easy”, especially when the government at Westminster is in the grip of what is becoming an increasingly vicious succession battle. The SNP administration has repeatedly clashed with the relevant ministers at Westminster, whom it says have given little care to Scotland’s particular needs. Sturgeon’s view of David Davis, Liam Fox and Boris Johnson is not rosy.

“Probably not a day goes by where I don’t look at them and think, ‘What the hell’s going on?’” she says. “That’s not meant as a personal comment on their abilities – although [with] some of them I would have personal question marks over their abilities. But they’re completely paralysed, and the election has left them in a position where you’ve got a Prime Minister who has no control over the direction of her government, and you have other senior ministers who are prepared to keep her there only because it’s in their short-term interests to do it. If you’re sitting on the European side of the table now, how can you have a negotiation with a government where you don’t actually know what their position is, or whether the position you’re being told across the table is one that can carry support back at home? It’s a shambles and it’s increasingly going to be the case that nothing other than Brexit gets any bandwidth at all. It’s really, really not in the interests of the country as a whole.”

***

This is an accusation that is directed at the SNP, too – that the national interest takes second place to its constitutional imperative. It is undoubtedly something that Sturgeon considered over the summer as she sought to rebalance her administration. As a result, the programme for government unveiled earlier this month was impressively long-term in places: for example, its promise to create a Scottish national investment bank, the setting of some ambitious goals on climate change and the commitment to fund research into a basic income.

Most striking, however, was Sturgeon’s decision to “open a discussion about… responsible and progressive use of our tax powers”. With the Scotland Act 2016, Westminster passed control over income tax to Holyrood, and Sturgeon intends to use this new power.

“For ten years,” she says, “we have done a pretty good job of protecting public services as best we can in a period of austerity, while keeping the taxes that we’ve been responsible for low. We’re now at a stage where austerity’s continued, we’re going to have economic consequences from Brexit, we all want good public services, we want the NHS to continue to have strong investment, we want our public-sector workers to be paid more, we want businesses to have the right infrastructure. How do we progressively and responsibly, with the interests of the economy taken strongly, fund our public services going forward? Most people would think right now that there is a case for those with the broadest shoulders paying a little bit more.”

I wonder whether the success of Jeremy Corbyn has influenced her thinking – many expect that a revival of Scottish Labour would force the SNP to veer left (it will also be interesting to see how Westminster reacts to Scotland raising the top rate of income tax). “It’s not particularly Corbyn that’s made me think that,” she insists, a little unconvincingly.

Isn’t Sturgeon concerned that making Scotland the highest-taxed part of the UK could undermine its competitiveness, its attraction as a place to live and as a destination for inward investment? “We should never be in a position where we don’t factor that kind of thing into our thinking, but you talk to businesses, and tax – yes, it’s important, but in terms of attracting investment to Scotland, the quality of your infrastructure matters. Businesses want good public services as well, so it’s the whole package that determines whether Scotland is an attractive place to live and invest in and work in,” she tells me. “It’s seeing it in the round. The competitiveness of your tax arrangements are part of what makes you attractive or not, but it’s not the only part.”

As for the immediate future, she is upbeat. She believes that Ruth Davidson, her main rival, is overrated. “I think Ruth, for all the many strengths people think she might have, often doesn’t do her homework very well,” she tells me. “From time to time, Ruth slips up on that… Quite a bit, actually. I know what I want to do over the next few years, and I’m in a very good place and feeling really up for it. After ten years in office, it’s inevitable you become a victim of your own success. What’s more remarkable is that, after ten years, the SNP still polls at least 10 and usually 10-15 points ahead of our nearest rivals.”

Author's note: Shortly after this interview went to print, the SNP got in touch to say that Nicola Sturgeon’s comment, ‘the honest answer to that is: I don’t know’, was about the timescale of the next independence referendum and not whether there would be one. The misinterpretation was mine.

Chris Deerin is the New Statesman's contributing editor (Scotland).