Karl Deisseroth says that one of his main influences while writing his first book Projections: A Story of Human Feeling was The Periodic Table, the cult book by chemist and poet Primo Levi that links personal stories with chemical elements, and which is considered one of best-written books on science of all time.
Deisseroth, born in 1971 in Boston, is professor of Bioengineering and Psychiatry and Behavioral Sciences at Stanford University, and has never hidden his passion for literature. It shines through in his recently published book, in which he mixes cases of patients he has met over the years as a psychiatrist with what optogenetics has taught him. The technique he has developed with his team since 2004 is the most revolutionary thing to happen to neuroscience in recent decades.
Optogenetics involves the very precise manipulation of neurons with light, and opens a new door to the mystery inside our heads. It has made blind people react to light, and has applications for autism, eating disorders, dementia and schizophrenia, advancing our understanding of psychiatry and mental illness.
One morning in July, Deisseroth met with EL PAÍS in his office in the Palo Alto lab where the technology that allows us to unravel the mysteries of our brain is still being developed.
Question. In addition to being a scientist, you are passionate about literature. Did you develop your love for literature while writing your first book?
Answer. That comes from when I was very small. I was reading literature and poetry long before I became a scientist. I was very interested in how a single word or a phrase in the right context could evoke or stir emotions in a very strong and precise way. It was something that struck me about poetry. A word without a semantic meaning in a sentence could be very powerful emotionally. But I did discover things about myself in writing this book.
Q. What led you to write it?
A. I wrote the first chapter 20 years ago, shortly after September 11, 2001. I had a patient who developed manic episodes right after [the terrorist attacks of] 9/11. He was someone who lived in the United States, but was not directly affected by the events of that day. He had never had – neither he nor anyone else in his family – a history of psychiatric episodes. Two weeks after the attacks he entered a state of bipolar disorder: he stopped sleeping, had a lot of energy, mood swings. He was retired and no longer the right age for it, but he kept writing letters to join the military. Then he went too far and became a risk to himself and his family, something that often happens in this type of patient. The case intrigued me because he was expressing and feeling more powerful and more potent emotions than he had ever felt before, but this was a problem. It raised some ethical and philosophical questions for me: How do you define a disease? How do you treat it? Why does something like this exist in humanity? And I wrote something about it.
We had always studied anxiety in animals, but the true connection to the human being is something we had not been able to develop
Q. Three years later you conducted the first optogenetics experiment, which is the most important thing to have happened to neuroscience in recent times. Did that help make it more understandable?
A. Optogenetics has always aroused a lot of curiosity in the majority of the public. There were stories in different newspapers around the world. It’s an accessible concept, but the connection with psychiatry had not been achieved, which opens up a whole new field of interest. We had always studied anxiety in animals, but the true connection to the human being is something we had not been able to develop. That is something very valuable that the book can do and scientific articles cannot.
Q. And you give it a sense of urgency by describing the technique as “supplanting the random hand of evolution.”
A. None of the findings would have come without a sense of urgency. I feel that part of it comes from psychiatry. There is so much need and suffering, but the understanding of them is very limited. We don’t have the same basic understanding of the brain as we do of the heart, for example. Now it seems obvious to us that the heart is a pump, but we have only known that for 400 or 500 years. We don’t have that basic level of understanding of the brain. Let’s think about a mental disorder: what is it, what does it look like physically, and why does it happen? We have to have a basic understanding in order to move forward. The brain is very interesting. It’s where mysterious and amazing things happen.
Q. But there have been advances. Optogenetics has been around for a decade...
A. Yes, it has revealed to us how our inner self is constructed, but to get to that point we had to build on 150 years of the most basic science, where people were experimenting with and poking at things they thought were interesting and wonderful. The deepest roots of this come from botany. This is very surprising to many people, that our understanding of ourselves as humans and animals actually comes from plants. A Russian scientist in the mid-1800s named Andrei Famintsyn was studying algae in a freshwater river. He noticed that single-celled algae could move. If you shone a bright light on it, it would move back a little bit to find the level of light that suited it most. The algae did that by using molecules that are ion channels, activated by light. In optogenetics we said: there is a protein that this plant has and it’s encrypted in its DNA. What would happen if we used that code and put it into a neuron or a group of neurons in a mammal? And we saw some cells that responded directly to light. Now we can light them up with fiber optics and manipulate the cells that have this algae gene. We can use this in models of psychiatric diseases: anxiety, addictions, high energy states, aggression. But nothing would have been possible without a 19th-century botanist observing algae.
We were able to implant a hallucination in a mouse by going into its visual cortex, the back part of the brain, the first to receive visual input
Q. You have reached a very precise level where you can control a single cell. What does that mean?
A. We got there in 2011 or 2012, but we hadn’t developed the technology to connect it to behavior, so that we could say, “These cells affect this behavior”. That took a long time. We achieved it in 2019 and published a series of papers showing that you could control one, or two, or 10 or 20 individual cells. We could play with a whole ensemble of cells and patterns and see how they affected behavioral choices in mammals. We saw competition between two basic drives like feeding and social behavior. You could activate cells of one or the other and see how they affected the choices one makes. This is very relevant to eating disorders.
Q. What other experiments have you done?
A. We were able to implant a hallucination in a mouse by going into its visual cortex, the back part of the brain, the first to receive visual input. Some cells only respond to visual stimuli in vertical shapes, and others only to horizontal shapes. We showed it vertical bars. Then we removed them completely and, using optogenetics, this animal immediately acted as if it was seeing the bars. That showed us, quantitatively, how perception can be introduced to the brain. That such a small number of cells affect the whole brain is very interesting and surprising.
Q. It has a great impact on the construction of self and reality.
A. It’s a theme that runs through many of the stories in Projections. The chapter on borderline personality disorder, the one on dementia, and the one on eating disorders. The construction of the self is something we all think about and would like to understand. And the construction of reality is also very interesting. It is present in the chapter on schizophrenia, the psychosis of altered reality. It is very interesting for many reasons related to philosophy and ethics. Everything comes from a group of cells in the brain and optogenetics gives us a window to see how it works.
Q. The technique has already begun to be applied in humans.
A. Ten years ago we started doing experiments, with my Swiss colleague Botond Roska, on retinas that had been removed from recently deceased cadavers. And just as it took us a while to get to control a single cell, this year Roska published a paper on living people suffering from retinal degeneration. The same principle worked and could confer a reaction to light from a person who was blind. As cool as this all sounds, one has to be cautious. A lot of people want to start doing all sorts of things now. The reason it was done first with the eye is that we know how it works and we know the cells we can use to affect vision. What works deeper in the brain is more mysterious. We must go further.