Published in North America as Projections: A Story of Human Emotions

Dr. Karl Deisseroth is a Renaissance man: He is a psychiatrist with a special interest in autism and treatment-resistant depression; he has a Ph.D. in neuroscience; and he is a professor of bioengineering at Stanford, where he spends much of his time running a lab. His interactions with patients who are challenged by a range of psychiatric or neurological issues raise provocative questions and inform his work in the lab. He’s also a lover of literature, which he regards as important for “understanding patients” and which can “at times provid[e] a window into the brain [that is] more informative than any microscopic objective.” Deisseroth is a proponent of cross-fertilization between disciplines—the humanities, engineering, and various scientific fields. Ideas and influences from unexpected directions can be transformative, he says, and if science is too biased towards solving disease-related questions, innovation is curtailed. Projections reflects its polymathic author’s philosophy. It’s a rich, fascinating, and exciting amalgam of stories of patients with particular psychiatric diseases and symptoms, including mania, paranoia, multi-infarct dementia, autism, borderline personality disorder, eating disorders, and depressive illness. The narratives are offered with the view that the broken can provide insight into the unbroken—abnormal function helps us understand what is normal. Deisseroth’s book also contains elements of personal memoir and scientific expository writing about genetics, evolution, and the role that a technology called optogenetics can play in exposing the complex neural circuitry and components involved in certain emotional states and diseases.

Unlike other medical specialists who can use a range of diagnostics—including blood work and imaging—to home in on and identify disease, psychiatrists are reliant on patient history and clinical presentation. Deisseroth writes: “The challenge of trying to perceive and experience unconventional realities from the patient’s perspective is the heart of psychiatry, working through the distortions of both the observer and the observed.” To practise well, he intimates, psychiatrists have to have a measure of self-awareness. They must be careful not to over-identify with patients and be mindful not to ascribe their own emotions or experiences to those they are treating. Sometimes, however, psychiatric diagnoses can be reached when the clinician notes the feelings a patient evokes in him. For example, in dealing with borderline patients, who are “maestros” at eliciting emotion in others—bringing forth powerful positive or negative feelings that approach patients’ own intense states—Deisseroth has found it useful to be attentive to the “rising tingle” up his back “in that sensation of defensive rage that we feel in our skin when personal boundaries are violated.”

Physicians are trained to see brains as biological objects. With psychiatric illnesses, however, the organ itself is not obviously damaged, and there are few explanations for why patients are suffering and what their diseases mean in a biological sense. A new technology called optogenetics (much of it developed in Deisseroth’s own Stanford bioengineering lab) is changing that. This technology allows scientists to see specific nerve cells firing as well as activity patterns in brain “circuits” created by the “projections”—the axons (extensions or threads)—of neurons across the brain.

Optogenetics involves taking genes responsible for making light-responsive proteins from such microorganisms as ancient algae and delivering them to specific neurons in laboratory animals, usually mice. Amazingly, this genetic material can be carried to its target by a virus. Once it reaches the intended nerve cell, the microbial DNA provides instructions so that the mammalian neuron can now produce a light-sensitive protein called a rhodopsin. Later, scientists can administer laser light to the transformed neuron by means of thin flexible fibers of glass (fiber optics). The genetically-altered lab animal’s neuron fires in response to that light—it’s excited or inhibited. Throughout the process, the animal brain is left intact; researchers are able to study the components that give rise to neurological function without taking the system apart. Deisseroth’s team has also developed and employed another technology called hydrogel-tissue chemistry, which helps to turn the normally dense and opaque brain into a state which permits light to pass through freely. This allows high-resolution visualization of the physical components of certain brain functions and emotional states.

Deisseroth explains early in his book that optogenetics technology has allowed scientists to learn that emotional states typically involve several brain areas. (Knowledge gained through this method may ultimately lead to treatments for afflictive states.) Anxiety, for example, begins in a region of the brain called the bed nucleus of the stria terminalis (BNST), an extension of the amygdala (a part of the brain involved with experiencing emotion). Threads from the BNST radiate out and activate several other brain areas. One projection travels to the parabrachial nucleus in the pons, which is part of the brainstem. When activated, this area increases the breathing rate of an anxious individual. The risk aversion (fearful avoidance) we see in an anxious person is controlled by a different thread, one travelling from the BNST to the lateral hypothalamus. Finally, the negative feeling or “valence” associated with anxiety is handled by a third projection, which extends to the ventral tegmental area, a part of the mammalian brain’s reward-and-motivation network.

Projections is organized around patient stories. Deisseroth walks the reader through the symptomatology of each condition, what is known about its genetics, and the ways in which optogenetics has shed light on what is going on. The author often considers the social context in which the patient’s illness has developed, whether it be the ruptured early family life of a borderline patient or the state-sponsored persecution of a patient from a Uyghur community in China. I appreciated his reminder that “nothing in biology makes sense, except in the light of evolution.” If something does not matter for survival, it disappears. It’s very possible, then, that what we now consider psychiatric illness once served a purpose. For example, the elevated state of being that we see in mania may have allowed some people to lead others in past times of existential threat; the euphoria of the manic individual may have uplifted and inspired his fellows. The decreased need for sleep, the abundant energy, and the intense commitment to projects may have served ancient societies well in times of migration or rebuilding. On the other hand, humans may have had periods during which the conservation of energy was critical for survival. The roots of depression may lie there.

Deisseroth acknowledges that there are ethical concerns about how new technologies like optogenetics are used. Neuroscience can target specific cells and connections to make animals more or less aggressive, defensive, energetic, sexual, social, hungry, thirsty, or sleepy. To what extent might these findings ultimately be applied to transform dysfunctional or suffering humans? Which changes are socially and morally acceptable and which are not? Deisseroth opines that the scientific community has a duty to explain its work to the general public, who must become engaged in the discussions about how new neuroscientific technologies are applied.

I am grateful to Random House for approving my Net Galley request for an early review copy of Karl Deisseroth’s book. It is one of the most stimulating works I’ve read in some time. I think other motivated readers interested in the workings of the brain will find it very rewarding, too. ( )

Dr. Karl Deisseroth is a Renaissance man: He is a psychiatrist with a special interest in autism and treatment-resistant depression; he has a Ph.D. in neuroscience; and he is a professor of bioengineering at Stanford, where he spends much of his time running a lab. His interactions with patients who are challenged by a range of psychiatric or neurological issues raise provocative questions and inform his work in the lab. He’s also a lover of literature, which he regards as important for “understanding patients” and which can “at times provid[e] a window into the brain [that is] more informative than any microscopic objective.” Deisseroth is a proponent of cross-fertilization between disciplines—the humanities, engineering, and various scientific fields. Ideas and influences from unexpected directions can be transformative, he says, and if science is too biased towards solving disease-related questions, innovation is curtailed. Projections reflects its polymathic author’s philosophy. It’s a rich, fascinating, and exciting amalgam of stories of patients with particular psychiatric diseases and symptoms, including mania, paranoia, multi-infarct dementia, autism, borderline personality disorder, eating disorders, and depressive illness. The narratives are offered with the view that the broken can provide insight into the unbroken—abnormal function helps us understand what is normal. Deisseroth’s book also contains elements of personal memoir and scientific expository writing about genetics, evolution, and the role that a technology called optogenetics can play in exposing the complex neural circuitry and components involved in certain emotional states and diseases.

Unlike other medical specialists who can use a range of diagnostics—including blood work and imaging—to home in on and identify disease, psychiatrists are reliant on patient history and clinical presentation. Deisseroth writes: “The challenge of trying to perceive and experience unconventional realities from the patient’s perspective is the heart of psychiatry, working through the distortions of both the observer and the observed.” To practise well, he intimates, psychiatrists have to have a measure of self-awareness. They must be careful not to over-identify with patients and be mindful not to ascribe their own emotions or experiences to those they are treating. Sometimes, however, psychiatric diagnoses can be reached when the clinician notes the feelings a patient evokes in him. For example, in dealing with borderline patients, who are “maestros” at eliciting emotion in others—bringing forth powerful positive or negative feelings that approach patients’ own intense states—Deisseroth has found it useful to be attentive to the “rising tingle” up his back “in that sensation of defensive rage that we feel in our skin when personal boundaries are violated.”

Physicians are trained to see brains as biological objects. With psychiatric illnesses, however, the organ itself is not obviously damaged, and there are few explanations for why patients are suffering and what their diseases mean in a biological sense. A new technology called optogenetics (much of it developed in Deisseroth’s own Stanford bioengineering lab) is changing that. This technology allows scientists to see specific nerve cells firing as well as activity patterns in brain “circuits” created by the “projections”—the axons (extensions or threads)—of neurons across the brain.

Optogenetics involves taking genes responsible for making light-responsive proteins from such microorganisms as ancient algae and delivering them to specific neurons in laboratory animals, usually mice. Amazingly, this genetic material can be carried to its target by a virus. Once it reaches the intended nerve cell, the microbial DNA provides instructions so that the mammalian neuron can now produce a light-sensitive protein called a rhodopsin. Later, scientists can administer laser light to the transformed neuron by means of thin flexible fibers of glass (fiber optics). The genetically-altered lab animal’s neuron fires in response to that light—it’s excited or inhibited. Throughout the process, the animal brain is left intact; researchers are able to study the components that give rise to neurological function without taking the system apart. Deisseroth’s team has also developed and employed another technology called hydrogel-tissue chemistry, which helps to turn the normally dense and opaque brain into a state which permits light to pass through freely. This allows high-resolution visualization of the physical components of certain brain functions and emotional states.

Deisseroth explains early in his book that optogenetics technology has allowed scientists to learn that emotional states typically involve several brain areas. (Knowledge gained through this method may ultimately lead to treatments for afflictive states.) Anxiety, for example, begins in a region of the brain called the bed nucleus of the stria terminalis (BNST), an extension of the amygdala (a part of the brain involved with experiencing emotion). Threads from the BNST radiate out and activate several other brain areas. One projection travels to the parabrachial nucleus in the pons, which is part of the brainstem. When activated, this area increases the breathing rate of an anxious individual. The risk aversion (fearful avoidance) we see in an anxious person is controlled by a different thread, one travelling from the BNST to the lateral hypothalamus. Finally, the negative feeling or “valence” associated with anxiety is handled by a third projection, which extends to the ventral tegmental area, a part of the mammalian brain’s reward-and-motivation network.

Projections is organized around patient stories. Deisseroth walks the reader through the symptomatology of each condition, what is known about its genetics, and the ways in which optogenetics has shed light on what is going on. The author often considers the social context in which the patient’s illness has developed, whether it be the ruptured early family life of a borderline patient or the state-sponsored persecution of a patient from a Uyghur community in China. I appreciated his reminder that “nothing in biology makes sense, except in the light of evolution.” If something does not matter for survival, it disappears. It’s very possible, then, that what we now consider psychiatric illness once served a purpose. For example, the elevated state of being that we see in mania may have allowed some people to lead others in past times of existential threat; the euphoria of the manic individual may have uplifted and inspired his fellows. The decreased need for sleep, the abundant energy, and the intense commitment to projects may have served ancient societies well in times of migration or rebuilding. On the other hand, humans may have had periods during which the conservation of energy was critical for survival. The roots of depression may lie there.

Deisseroth acknowledges that there are ethical concerns about how new technologies like optogenetics are used. Neuroscience can target specific cells and connections to make animals more or less aggressive, defensive, energetic, sexual, social, hungry, thirsty, or sleepy. To what extent might these findings ultimately be applied to transform dysfunctional or suffering humans? Which changes are socially and morally acceptable and which are not? Deisseroth opines that the scientific community has a duty to explain its work to the general public, who must become engaged in the discussions about how new neuroscientific technologies are applied.

I am grateful to Random House for approving my Net Galley request for an early review copy of Karl Deisseroth’s book. It is one of the most stimulating works I’ve read in some time. I think other motivated readers interested in the workings of the brain will find it very rewarding, too. ( )