The Psychopharmacology of Grief

Aslan, C.S. Lewis’s lion, has meant many different things to many different readers at many different times. He means one thing to the scholar and another to the child. He is gentle, powerful, and disturbing. He is magical. He is the one Christological reference most schools include in their curriculums before anyone knows what the word “exegesis” means. But while Lewis is remembered for his lion, he will also be remembered for his contribution to the literature of grief, and perhaps the editors of the forthcoming Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders should consider not only the lion but also Lewis’s non-fiction work, A Grief Observed, before making their final decision as to how to define this condition. Condition, not illness. At least in most cases.


The New York Times Week in Review section gave great space to the consideration of loss this Sunday. There was Liesl Schillinger’s excellent piece on Christopher Hitchens, “Christopher Hitchens, Not Going Gently,” and there was the compelling, and admirably activist, opinion piece by Allen Frances, former chairman of psychiatry at Duke University. The latter was titled, simply, “Good Grief.” Both pieces are worth reading. Both attend to the twin anxieties experienced on either side of loss: the fear of dying, and so of being lost, on the one hand; and the devastation of loss, on the other. It was Lewis who tied these two things together.

“No one ever told me that grief felt so like fear,” Lewis wrote, in A Grief Observed. It is this fear that makes a mirror of death’s two sides, one for the dying and the other for the loved ones who are left behind. As Frances points out, there is a degree of pain/sadness that medication can—and should—assist. Yet the experience of losing someone we loved should not be cause, necessarily, for scientific intervention. Grief is part of being human. Grief reminds us that we love. Frances does not want grief to fall categorically into a drawer with other illnesses being alleviated. Grief might rather be something to be valued, even if it replicates the conditions of anxiety.

Lewis knew this. He embedded loss in his fiction far before he wrote about experiencing it in his own life.

Schillinger points out something different, but related: the idea that so many people now hope that the famously atheistic Christopher Hitchens will alleviate his pain not via medication but via belief. She writes:

This subject is one Mr. Hitchens has mulled over since childhood, when he decided, as he wrote in “God Is Not Great,” that it was “contemptible” to rely on religion just for comfort if it “might not be true.” As an adult whose hopes lay assuredly in the intellect, not in the hereafter, he concluded, “Literature, not scripture, sustains the mind and — since there is no other metaphor — also the soul.”

Is this true? What sustains us is what sustains us. We don’t want to let go, on either side. And it is this Not Wanting to Let Go that often leads us to Something to Hold Onto: God, literature, God as represented in a work of literature. Reading through these two pieces (though neither one mentioned him), Lewis came to mind.  As did Aslan. Judge not, the lion might say. But then shouldn’t we trust our doctors and our scientists and our religious leaders to know what we need? Or our novelists?

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But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.

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