Neuroscientist Karl Deisseroth: ‘Coronavirus has changed us all’


The coronavirus pandemic has been a disorienting kind of emergency. It is a generation-defining cataclysm, but for many of us the day-to-day reality has been lonely, even dull. It is a call to action, but the most useful thing most of us can do is stay at home. Covid-19 is a disease that attacks the lungs, but it has also worsened mental health while causing a drastic reduction in patients seeking care for depression, self-harm, eating disorders and anxiety. Whatever path the pandemic takes from here, says Karl Deisseroth, the pioneering American neuroscientist, psychiatrist, bioengineer and now author, “Coronavirus has affected us all and it has changed us all. There’s no doubt about that.”

Deisseroth, 49, is talking in the lush, squirrel-filled garden of his house in Palo Alto, northern California, where he has spent much of the pandemic looking after his four young children. But he has had much else on his mind. He has been finishing his book, Connections: A Story of Human Feeling, an investigation into the nature of human emotions. He has been meeting with psychiatric patients over Zoom as well as putting in night shifts as an emergency hospital psychiatrist. And he has fitted all of this around his day job, which is using tiny fibre-optic cables to fire lasers into the brains of mice that he has infected with cells from light-sensitive algae and then observing what happens, millisecond by millisecond, when he turns individual neurons on or off.

This is the basic methodology of optogenetics, a technique that Deisseroth pioneered in 2005 with his team at what is now the Deisseroth Lab at Stanford University. It has been widely recognised as one of the great scientific breakthroughs of the 21st century. In essence, he found a way to activate or deactivate individual brain cells with incredible precision – which in turn has brought about a revolution in neuroscience. Optogenetics is now its own field, its techniques and principles used in hundreds of laboratories across the world to advance understanding of the circuits of the brain and the consequences of conditions such as schizophrenia, autism and dementia. Mostly this is done by running experiments on animals – literally dialling up or down the circuits that control aggression, for example; however, the possibilities appear almost endless. Last month, the Swiss neurologist Botond Roska published a study that showed how he had used optogenetic principles on a human retina to partially restore the sight of a blind person.

Deisseroth has another great leap forward on his CV, too: see-through brains. In 2013, his team figured out a way to drain away the opaque fatty matter in a mouse brain and instead suspend all the brain cells in a scaffold of hydrogel, a transparent, jelly-like substance that allows for extraordinarily detailed brain imaging – a significant leap forward from the standard fMRI scan. He came up with the concept while changing a nappy.

Shaggy-haired and unhurried, Deisseroth more resembles a bassist in a west coast rock band than a leading scientist – and the way he tells it, all of his hi-tech questing grew out of his childhood ambition to be a poet. “That was my first love and vocation – I wanted to be a writer,” he says. He once crashed his bicycle as he was attempting to read a volume of Gerard Manley Hopkins while pedalling. “I was always intrigued by how words stir emotions, how they can lift us up and bring us down, how they serve as very potent symbols. If you look at it, one route to understanding how those symbols are transformed into feelings might be looking at how the brain works. So I got very interested in neuroscience.”

But he arrived at neuroscience via psychiatry. The two fields are usually seen as distinct – brain v mind – but the insights gained in consultations with patients have seeded many of Deisseroth’s experiments. “Anybody can read a diagnostic manual and see a list of symptoms, but what really matters to the patient is a different story,” he says. “It’s what allows me to think: what are the correspondences that we can do in the laboratory? How can inspiration flow both ways?”

Connections is Deisseroth coming “full circle”, he says, back to his “original and greatest love” – writing. It is a revelatory book. Peppered with quotes from Jorge Luis Borges and Toni Morrison, it leaps from wasp evolution to autism, the origins of mammalian fur to self-harm in borderline personality disorder patients, music to dementia, casually blowing apart any crude arts-science dichotomies as it does so. At times, it recalls the case histories of Oliver Sacks, at times the sweep of Yuval Noah Harari’s Sapiens – though Deisseroth says a closer model is The Periodic Table by the poet-chemist Primo Levi. He writes with an evident love of words – but also, with a lucid line of scientific inquiry. What are feelings? How do they work? Why do we have them? How do new feelings evolve? And why are they so often maladapted to our circumstances?

“Feelings are responses to information in the world – but as we all know, they follow th
eir own trajectory,” Deisseroth says. “They coalesce and disappear with time. Sometimes we’re not even conscious of them.” While we are still far from even a sketchy understanding of the physical nature of feelings, optogenetics is beginning to give us a handle on how and why they arise. “We can not only record from the activity of tens of thousands of neurons while the processes that correspond to feelings are happening – we can directly turn up and turn down the representation of these feelings with great precision. We can make an animal more or less anxious or aggressive or maternal or hungry or thirsty. And all of that neurobiology maps on to this fundamental question of what a feeling is.”

There are many moments where Deisseroth’s case histories echo the strange times we are living through. One of the more perplexing stories concerns Alexander, a wealthy, well-adjusted American man with no history of mental illness whose retirement happened to fall around the time of 9/11. Alexander was nowhere near New York when the attack happened and knew no one involved. But two weeks afterwards, while on holiday in Greece, he began to display “classic mania”. He was extraordinarily joyful; he drastically cut down on his sleep (he felt no need); he had increased libido. When he returned home, he volunteered for the US Navy and started training for war, climbing trees, practising his aim, reading military strategy, insisting to his baffled wife and children that he was better than he had ever been.

For Deisseroth, the case was a sort of parable (Alexander turned out OK, by the way). “Why does this susceptibility to mania exist? Is there a value to it – if not to the person, then to the community, or to the species? Is that something that was more valuable at a different time in the long march of evolution?” He speculates that the manic state – “in some ways the highest expression of what a human can be” – was a circuit in the brain waiting to be tripped; and perhaps such states have helped humans cope with war, famine, climate emergency or pandemics in the past. What we think of as mental illness may be an evolutionary adaptation – or an attempt at an adaptation – that helped past communities survive. “Nothing in biology makes sense except in the light of evolution,” as the great geneticist Theodosius Dobzhansky wrote.

This leads Deisseroth to ponder the case of Joan of Arc in medieval France – a female teenage peasant who, like Alexander, appeared to be an inappropriate vessel for such mania, but nevertheless managed to make a national impact. “The altered state has been…



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